**Coronary CT Angiography and the Napkin-ring Sign Indicates High-Risk Atherosclerotic Lesions**

Lucia Agoston-Coldea, Carmen Cionca and Silvia Lupu

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61393

#### **Abstract**

Coronary computed tomography angiography (CCTA) is used extensively nowa‐ days as a non-invasive imaging method for the evaluation of patients suspected of coronary artery disease, providing data on calcium burden, the presence of coro‐ nary artery stenoses, but also, more recently, on coronary atherosclerotic plaque morphology and composition. Plaque morphology analysis by CCTA aims to accu‐ rately identify vulnerable plaques, in an attempt to reduce the number of ischemic events triggered by high-risk atherosclerotic lesions. Recent research provides CCTA descriptions of vulnerable plaques and a particular radiological sign shows promising perspectives. The napkin-ring sign refers to a rupture-prone plaque in a coronary artery, comprising a necrotic core covered by a thin cap fibro-atheroma. The napkin-ring sign is described on CCTA in cross-sectional images of coronary arteries as a central low-attenuation area surrounded by an open ring area of high attenuation, having a high specificity and positive predictive value for the presence of advanced lesions. These lesions have been designated as vulnerable plaques, in‐ dicating an increased probability of rupture, and were shown to correlate with a higher incidence of cardiovascular events. In acute coronary syndromes, the loca‐ tion of the napkin-ring sign was shown to correspond to the culprit lesions. The aim of the current paper is to provide an overview of the current literature on available methods for quantitative measurement of atherosclerotic plaque features from CCTA and to discuss the clinical implications of the napkin-ring sign as detected by CCTA.

**Keywords:** Coronary computed tomography angiography, Coronary artery plaque, Napkin-ring sign, Plaque quantification, Plaque characterization

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **1. Introduction**

The development of atherosclerosis by lipoprotein storage, inflammation, muscle cell prolif‐ eration, necrosis, apoptosis, calcification, and fibrosis in the arterial wall triggers important changes in the coronary vessels, leading to coronary artery disease (CAD). In fact, atheroscle‐ rosis is the main etiology of CAD, and plaque rupture followed by intraluminal thrombosis is the most common cause of acute coronary events, including sudden coronary death [1, 2]. For that reason, the early and accurate characterization and quantification of atherosclerotic plaques is valuable for preventing and managing acute coronary syndrome (ACS) [3]. In everyday clinical practice, major acute ischemic cardiac events involve plaque rupture in thincap fibroatheromas, which are considered vulnerable plaques; these rupture-prone athero‐ sclerotic lesions usually contain a high level of lipids and have a large necrotic core, numerous inflammatory cells, and a thin, vulnerable fibrotic cap [4]. Vulnerable atherosclerotic plaques can be characterized by several invasive and non-invasive methods that are either fully validated, pending validation, or still under scrutiny for clinical practice. Among non-invasive methods, coronary computed tomography angiography (CCTA) by multi-detector computed tomography (MDCT) is currently the preferred modality for evaluating the extent of CAD, providing the advantage of accurate assessment of coronary atherosclerotic plaque morphol‐ ogy and composition. In two recent multicenter trials [5, 6], CCTA was shown to have excellent sensitivity (95–99%) and negative predictive value (97–99%), although rather low specificity (64–83%) for identifying patients with at least one coronary artery stenosis among individuals at low to intermediate risk for CAD. Moreover, CCTA imaging of atherosclerotic plaques was found to correlate well with invasive assessment by intravascular ultrasound (IVUS) [7, 8, 9].

#### **2. Role of MDCT in the detection of plaque morphology and composition**

#### **2.1. Plaque characteristics**

#### *2.1.1. Plaque morphology and composition*

Pathophysiologically, a subendothelial accumulation of lipoproteins generates inflammatory responses involving macrophages and T-cells, leading to the further development of athero‐ sclerotic lesions [10]. Initially, atherosclerotic lesions were classified as fatty streaks, fibroa‐ theromas [11], and advanced plaques, complicated with hemorrhage, calcification, ulceration, and thrombosis [12]. Over the years, this classification became more complex and six types of atherosclerotic lesions have been defined by the American Heart Association (AHA) Consen‐ sus Group: type I - characterized by adaptive intimal thickening; type II - fatty streak; type III - transitional or intermediate lesions; type IV - advanced plaques (atheromas); type V fibroatheroma or atheroma with thick fibrous cap; and type VI - complicated plaques with denudated surface, and/or hematoma/hemorrhage, and/or thrombosis [13]. The earliest lesions are represented by adaptive intimal thickening (AHA type I) and fatty streaks or intimal xanthoma, which are basically foam cell collections (AHA type II) [13]. AHA type III transi‐ tional lesions, described as pathological intimal thickening, represent the earliest stage of the progressive plaques and are considered precursor lesions of more advanced fibroatheroma. This type of lesions consists of multiple layers of proliferating smooth muscle cells near the lumen, with an increased quantity of lipids on the intimal medial border. Intimal xanthomas are lesions containing a large amount of foamy macrophages but without lipid acumulation outside the cell [14]. Type IV AHA, also called fibrous cap atheromas, are the first of the advanced lesions of coronary atherosclerosis [15] and are characterized by the presence of a necrotic core with a high amount of lipids surrounded by a fibrous cap containing smooth muscle cells, collagen, and proteoglicans, as well as inflammatory cells such as macrophages and lymphocytes. This type of lesion can cause significant artery stenosis and may be submit‐ ted to complications, namely surface disruption, thrombosis, and calcification. Fibrous cap plaques may be more or less prone to complications depending on the thickness of the cap: fibroatheromas are more stable due to the rather thick fibrous cap, while thin-cap fibroather‐ omas characterize the typycal "vulnerable plaques" [15].

**1. Introduction**

114 Coronary Artery Disease - Assessment, Surgery, Prevention

**2.1. Plaque characteristics**

*2.1.1. Plaque morphology and composition*

The development of atherosclerosis by lipoprotein storage, inflammation, muscle cell prolif‐ eration, necrosis, apoptosis, calcification, and fibrosis in the arterial wall triggers important changes in the coronary vessels, leading to coronary artery disease (CAD). In fact, atheroscle‐ rosis is the main etiology of CAD, and plaque rupture followed by intraluminal thrombosis is the most common cause of acute coronary events, including sudden coronary death [1, 2]. For that reason, the early and accurate characterization and quantification of atherosclerotic plaques is valuable for preventing and managing acute coronary syndrome (ACS) [3]. In everyday clinical practice, major acute ischemic cardiac events involve plaque rupture in thincap fibroatheromas, which are considered vulnerable plaques; these rupture-prone athero‐ sclerotic lesions usually contain a high level of lipids and have a large necrotic core, numerous inflammatory cells, and a thin, vulnerable fibrotic cap [4]. Vulnerable atherosclerotic plaques can be characterized by several invasive and non-invasive methods that are either fully validated, pending validation, or still under scrutiny for clinical practice. Among non-invasive methods, coronary computed tomography angiography (CCTA) by multi-detector computed tomography (MDCT) is currently the preferred modality for evaluating the extent of CAD, providing the advantage of accurate assessment of coronary atherosclerotic plaque morphol‐ ogy and composition. In two recent multicenter trials [5, 6], CCTA was shown to have excellent sensitivity (95–99%) and negative predictive value (97–99%), although rather low specificity (64–83%) for identifying patients with at least one coronary artery stenosis among individuals at low to intermediate risk for CAD. Moreover, CCTA imaging of atherosclerotic plaques was found to correlate well with invasive assessment by intravascular ultrasound (IVUS) [7, 8, 9].

**2. Role of MDCT in the detection of plaque morphology and composition**

Pathophysiologically, a subendothelial accumulation of lipoproteins generates inflammatory responses involving macrophages and T-cells, leading to the further development of athero‐ sclerotic lesions [10]. Initially, atherosclerotic lesions were classified as fatty streaks, fibroa‐ theromas [11], and advanced plaques, complicated with hemorrhage, calcification, ulceration, and thrombosis [12]. Over the years, this classification became more complex and six types of atherosclerotic lesions have been defined by the American Heart Association (AHA) Consen‐ sus Group: type I - characterized by adaptive intimal thickening; type II - fatty streak; type III - transitional or intermediate lesions; type IV - advanced plaques (atheromas); type V fibroatheroma or atheroma with thick fibrous cap; and type VI - complicated plaques with denudated surface, and/or hematoma/hemorrhage, and/or thrombosis [13]. The earliest lesions are represented by adaptive intimal thickening (AHA type I) and fatty streaks or intimal xanthoma, which are basically foam cell collections (AHA type II) [13]. AHA type III transi‐

In fact, thin-cap fibroatheromas are very likely to lead to plaque rupture. Although they are not included as individual entities in the AHA consensus classification, plaque erosion and calcified nodules are also prone to coronary thrombosis. Erosions may occur on intimal thickening or fibroatheroma, whereas the notion of calcified nodules refers to eruptive fragments of calcium that protrude into the lumen, causing a thrombotic event [16]. Also, plaque ruptures may heal by wide accumulation of proteoglycans, having more reduced necrotic cores and more extensive areas of calcification. In their study on early coronary lesion progression near branch points, Nakashima et al. provided evidence endorsing the hypothesis that intimal thickening lesions with macrophages are more advanced [17].

Macrophage infiltration in lipid pools rich in cholesterol and the deterioration of the extrac‐ ellular matrix believed to be induced by matrix metalloproteinase activity suggest early stages of the necrosis process and should be recognized. This particular feature, combined with macrophage destruction as a consequence of an anomalous phagocytic clearance of apoptotic cells, may contribute to the development of late plaque necrosis. In addition to that, an extended necrotic core is a strong predictor of complications [17, 18].

Thin-cap fibroatheromas are highly prone to plaque rupture due to their rather large necrotic core and thin, inflamed fibrous cap (<65 μm). The accumulation of an increased number of macrophages at the level of the cap is characteristic, although exceptions may occur. However, as a significant number of fatal coronary events are triggered by plaque rupture due to the impairment of the fibrous cap followed by thrombosis, early recognition of thin-cap fibroa‐ theromas is crucial. The fibrous cap mainly contains type I collagen, variable numbers of macrophages and lymphocytes, and rather few alpha-actin positive smooth muscle cells. Fibrous cap disruption exposes the lipid-rich necrotic core, favoring the formation of local thrombi by platelet accumulation. Most plaque ruptures are reported in the proximal segments of the coronary arteries, near branch points, with the left anterior descending coronary artery being the most frequently affected, followed by the right and left circumflex coronary arteries [19]. Although the mechanisms behind plaque rupture are far from being fully understood, the increased activity of matrix metalloproteinases, excessive enzyme secretion by inflamma‐ tory cells, high shear stress, macrophage calcification, and iron build-up are recognized as implicated factors. Data are also beginning to pool on different gene expression in stable and unstable atherosclerotic plaques [20]. For instance, in one study, differential expression of 18 genes coding for metalloproteinase ADAMDEC1, retinoic acid receptor responser-1, cysteine protease legumain (a potential activator of matrix metalloproteinases), and cathepsins was shown to contribute to increased lesion vulnerability [20]. As previously mentioned, the extension of the necrotic core is also a main factor in plaque complication development, and intraplaque hemorrhage was shown to favor the accumulation of free cholesterol provided by red blood cells in these lesions [21]. As atherosclerotic lesions expand, more vasa vasorum infiltrate the plaque and become leaky, triggering intraplaque hemorrhage [22]. Morphologic studies have suggested that repeated ruptures are responsible for plaque progression beyond 40–50% cross-sectional luminal stenoses [23]. Three hystological types of lesions have been described in association with acute coronary events: rupture, erosion, and calcified nodule [13]. Ruptured coronary atherosclerotic plaques folowed by intraluminal thrombosis are the most common cause of acute myocardial infarction [24]. In fact, two-thirds of luminal thrombi in acute events result from ruptured atherosclerotic lesions characterized by a necrotic core covered by a thin layer of fibrous cap [4]. Ruptured plaques are characterized by a lipid-rich necrotic core (>40% of the total volume of the plaque), surrounded by a thin, fibrous cap with active inflammation (increased number of monocytes, macrophages, and sometimes even Tcells), endothelial denudation leading to superficial platelet aggregation, and the presence of hemodynamically significant coronary artery stenosis (>90%) [19]. Vulnerable plaques prone to rupture share most of the morphological characteristics with ruptured plaques, showing a large necrotic core, macrophage infiltration, and often an increased number of intraplaque vasa vasorum [4], but an intact, thin fibrous cap [13]. These lesions—called thin-cap fibroa‐ theromas—are considered to be at high risk for rupture and subsequent ischemic events [4].

The destruction of the endothelium exposes the minimally inflammed intima containing smooth muscle cells and proteoglycans to circulating platelets, favoring thrombus formation. In a post-mortem study of 20 patients who died with acute myocardial infarction, plaque ruptures were found in 60% of lesions with thrombi, while the remainder of 40% only revealed superficial erosion [16]. Plaque erosion refers to the lack of endothelial cells on the luminal surface beneath the thrombus. Kramer et al. showed in their study that, when plaque erosion was the incriminated lesion, the thrombus was limited to the luminal portion of the plaque, and no ruptures were identified following serial sectioning of these lesions. In the same study, more than 85% of thrombi in erosions showed evidence of healing, such as acute inflammatory cell lysis, invasion by smooth muscle cells and/or endothelial cells, or organized layers of smooth muscle cells and proteoglycans with varying degrees of platelet/fibrin layering. By contrast, only half of the ruptured plaques showed signs of healing [25].

Beyond histopathological description, a clinically relevant definition of vulnerable plaques refers to the risk of developing future major cardiac events, which may also involve the presence of "vulnerable blood" (prone to hypercoagulability) or "vulnerable myocardium" (susceptible to arrhythmia), either due to acute or pre-existing ischemia and/or non-ischemic electrophysiological anomalies. The presence of one or more of these elements elevates the individual risk of the patients for cardiovascular events, turning them into "vulnerable patients".

tory cells, high shear stress, macrophage calcification, and iron build-up are recognized as implicated factors. Data are also beginning to pool on different gene expression in stable and unstable atherosclerotic plaques [20]. For instance, in one study, differential expression of 18 genes coding for metalloproteinase ADAMDEC1, retinoic acid receptor responser-1, cysteine protease legumain (a potential activator of matrix metalloproteinases), and cathepsins was shown to contribute to increased lesion vulnerability [20]. As previously mentioned, the extension of the necrotic core is also a main factor in plaque complication development, and intraplaque hemorrhage was shown to favor the accumulation of free cholesterol provided by red blood cells in these lesions [21]. As atherosclerotic lesions expand, more vasa vasorum infiltrate the plaque and become leaky, triggering intraplaque hemorrhage [22]. Morphologic studies have suggested that repeated ruptures are responsible for plaque progression beyond 40–50% cross-sectional luminal stenoses [23]. Three hystological types of lesions have been described in association with acute coronary events: rupture, erosion, and calcified nodule [13]. Ruptured coronary atherosclerotic plaques folowed by intraluminal thrombosis are the most common cause of acute myocardial infarction [24]. In fact, two-thirds of luminal thrombi in acute events result from ruptured atherosclerotic lesions characterized by a necrotic core covered by a thin layer of fibrous cap [4]. Ruptured plaques are characterized by a lipid-rich necrotic core (>40% of the total volume of the plaque), surrounded by a thin, fibrous cap with active inflammation (increased number of monocytes, macrophages, and sometimes even Tcells), endothelial denudation leading to superficial platelet aggregation, and the presence of hemodynamically significant coronary artery stenosis (>90%) [19]. Vulnerable plaques prone to rupture share most of the morphological characteristics with ruptured plaques, showing a large necrotic core, macrophage infiltration, and often an increased number of intraplaque vasa vasorum [4], but an intact, thin fibrous cap [13]. These lesions—called thin-cap fibroa‐ theromas—are considered to be at high risk for rupture and subsequent ischemic events [4].

116 Coronary Artery Disease - Assessment, Surgery, Prevention

The destruction of the endothelium exposes the minimally inflammed intima containing smooth muscle cells and proteoglycans to circulating platelets, favoring thrombus formation. In a post-mortem study of 20 patients who died with acute myocardial infarction, plaque ruptures were found in 60% of lesions with thrombi, while the remainder of 40% only revealed superficial erosion [16]. Plaque erosion refers to the lack of endothelial cells on the luminal surface beneath the thrombus. Kramer et al. showed in their study that, when plaque erosion was the incriminated lesion, the thrombus was limited to the luminal portion of the plaque, and no ruptures were identified following serial sectioning of these lesions. In the same study, more than 85% of thrombi in erosions showed evidence of healing, such as acute inflammatory cell lysis, invasion by smooth muscle cells and/or endothelial cells, or organized layers of smooth muscle cells and proteoglycans with varying degrees of platelet/fibrin layering. By

Beyond histopathological description, a clinically relevant definition of vulnerable plaques refers to the risk of developing future major cardiac events, which may also involve the presence of "vulnerable blood" (prone to hypercoagulability) or "vulnerable myocardium" (susceptible to arrhythmia), either due to acute or pre-existing ischemia and/or non-ischemic electrophysiological anomalies. The presence of one or more of these elements elevates the

contrast, only half of the ruptured plaques showed signs of healing [25].

Identifying vulnerable plaques is currently a major challenge, although recent progress in cardiovascular imaging raises new possibilities. As vulnerable plaques are prone to rupture and rapid evolution towards the development of ACS, [26, 27, 28] finding reliable imaging characteristics that could help detect unstable plaques are of the utmost importance. Early identification of such plaques could facilitate timely initiation of adequate primary prevention measures, thus diminishing the incidence of acute coronary events [29]. For this purpose, several imaging methods have been proposed, including IVUS, optical coherence tomography (OCT), magnetic resonance imaging (MRI), or MDCT (Table 1), with variable success [30, 31, 32]. However, the use of many of these methods is mainly confined to experimental studies and has not yet been validated for everyday clinical practice.




**Table 1.** Methods for the Identification and Characterization of Vulnerable Plaques

**Non-invasive imaging methods Advantages Limitations**

Invasive

resolution

Invasive

Invasive

Invasive

Invasive

resolution

Invasive

surface

Invasive

Invasive

resolution

differences

Prolonged duration

Cardiac motion

Limited tissue penetration

Limited tissue penetration and spatial

The cooling effect of the blood leads to underestimated temperature

Limited tissue penetration and spatial

Limited temporal resolution Limited spatial resolution prevents thin cap fibroatheroma quantification Low accuracy for detecting plaque composition by gray scale IVUS

Limited spatial resolution Artefacted by cardiac motion

Limited spatial resolution

Limited tissue penetration and spatial

Limited tissue penetration; however, the most relevant morphologic findings are primarily localized within the first 500 μm under lumen

Quantifies stenoses accurately

remodeling, and neovascularization Characterizes plaque morphology and

and plaque (fibrous plaques are stiffer than lipid-rich ones); high strain regions describe

plaques, calcified, and non-calcified plaques

Allows accurate quantification of the fibrous

Highest spatial resolution of all imaging

Can identify thin fibrous caps <65 μm The only technique for eroded plaques

Accurate detection of plaque composition

chemical structure, temperature and inflammation of the plaque

Detects plaque inflammation and


118 Coronary Artery Disease - Assessment, Surgery, Prevention

Standard Quantifies plaque volume, vascular

composition

IVUS elastography Measures the local strain rate of vessel wall

Virtual histology Identifies the necrotic core, fibro-lipidic

Angioscopy Identifies lipid plaques, plaque rupture,

OCT Provides microscopic characterization of

plaque

methods

detection

Spectroscopy Identifies the lipid core and evaluates the

neoangiogenesis



more vulnerable plaques

erosion, and thrombosis

plaque morphology

Identifies macrophages presence



A possible imaging method for coronary artery plaque assessment is IVUS, which has been used to measure lumen area, plaque burden, and vascular remodeling [33, 34]; plaque burden and positive remodeling, in particular, can identify high-risk, thin-cap fibroatheromas during follow-up [34, 35, 36]. As suggested by IVUS-based studies, a vulnerable plaque is character‐ ized by the presence of an extensive necrotic core surrounded by a thin-cap fibrous with macrophage infiltration, a large lipid pool, and several more specific traits such as positive remodeling or spotty calcifications [37, 38]. When such characteristics occur, there is an increased risk of fibrous rupture, exposing the thrombogenic lipid core, which leads to thrombus formation and the development of ACS. A more detailed analysis of coronary plaque composition has been provided by virtual histology (VH)-IVUS studies [39, 40, 41].

Another recently developed method for the assessment of coronary artery plaques quantifi‐ cation is intracoronary OCT that provides the advantage of very high resolution (approxi‐ mately 10 to 20 μm), which is about 10-fold higher than that of IVUS [42, 43]. Unlike some other imaging methods, including CCTA [27, 44, 45], OCT can be used for measuring fibrous cap thickness and for detecting lipid content, which makes it useful for in vivo identification of thin-cap fibroatheromas and for evaluating plaque vulnerability [46]. For the time being, the correspondence between OCT- and IVUS-derived characteristics of thin-cap fibroathero‐ mas, as well as the angiographic stenosis severity, is yet to be established.

As advanced coronary artery plaques have a high level of complexity, basic classifications that include non-calcified plaques, calcified plaques, and mixed plaques are rather crude and of limited use for establishing the potential risk for acute ischemic clinical events of individual lesions [4, 26, 47]. For that reason, some authors have attempted to provide more detailed descriptions of vulnerable plaques and to establish correlations between CCTA imaging characteristics (Figure 1) of the lesions and the risk for acute events. Motoyama et al. suggested that vulnerable plaques are characterized by positive remodeling, low attenuation plaque and spotty, limited calcification [44]. In later research, non-calcified plaques were more extensively characterized by modern MDCT and several authors described a ring-like attenuation of the non-calcified portion of the coronary atherosclerotic lesion, which is now called the napkinring sign [48, 49, 50]. The description of the napkin-ring sign has changed current classifications of non-calcified plaques, which are now classified in three categories: homogenous plaques, non-napkin-ring sign heterogeneous plaques, and napkin-ring sign heterogeneous plaques [49]. The napkin-ring sign corresponds to a morphological type of vulnerable plaque described on coronary CCTA (thin-cap fibroatheromas) comprising a necrotic, low attenuation core surrounded by a thin area of higher attenuation, which some believe may represent the thin peripheral fibrous cap (Figure 2) [26, 47]. However, in vulnerable plaques, the fibrous cap has extremely reduced thickness [48, 51], which makes it indistinguishable by non-invasive imaging methods; by contrast, the necrotic core may be visualized and quantified on thin sections (<0.6 mm) on modern CCTA [52, 53]. As the presence of the napkin-ring sign was shown to have a high predictive value for future cardiac events and is considered a valuable correlate of unstable plaques [49, 27, 20, 54, 55], its detection could add specificity to the CCTA assessment of vulnerable plaques.

**Figure 1. Different Types of Coronary Plaques by CCTA**. The 3 main types of coronary plaques are shown: calcified plaques (A, D), non-calcified plaques (B, E) and partially calcified plaques (C, F), illustrated in curved planar reformat‐ ted and cross-sectional views.

**Figure 2. Representative CCTA Images with Napkin-ring Signs**. An atherosclerotic plaque with positive remodeling, low attenuation plaque, and a napkin-ring sign in the proximal left anterior descending artery on computed tomogra‐ phy angiography. The boxed area indicates cross-sectional images of atherosclerotic plaque showing a napkin-ring sign.

However, in studies conducted over the last decade, CCTA was also shown to have excellent sensitivity for detecting, and particularly, for excluding coronary atherosclerosis in patients with symptoms suggesting either stable or acute CAD [56]. In addition to that, data from large prospective registries support the use of CAD absence/presence and extension evaluation by CCTA for prognostic purposes [53, 57, 58, 59, 60]. Recent studies conducted with more advanced scanners having 64 to 320 detector rows, and higher spatial (230 to 625 μm) and temporal (75 to 175 ms) resolution focused on identifying vulnerable coronary artery plaques and on establishing correlation between plaque characteristics and ischemic events [61]. Currently available spatial resolution of CCTA scanners approach the spatial resolution provided by invasive methods such as IVUS (100 μm) and invasive coronary angiography (200 μm). Moreover, spatial resolution reaching 0.3 mm in-plane in modern CCTA scanners allows a more accurate discrimination of the non-calcified portion of the plaques [62].

Some researchers [63, 64, 65] attempted to distinguish lipid-rich from fibrous plaque by CCTA based on attenuation criteria, as expressed by Hounsfield Units (HU), but conflicting results have been obtained. In addition to that, HU values cannot accurately discriminate between the types of plaques, mostly due to the small dimensions of the plaque, insufficient spatial resolution of CCTA, and reduced contrast difference between lipid-rich and fibrous plaques. In these studies, certified methods of coronary artery plaque quantification (such as IVUS and histology) were used for comparison to CCTA [63, 64, 65].

Despite current technical limitations, progress has been made in the non-invasive imaging assessment of coronary artery lesions by CCTA. Data from recent studies suggest that low attenuation (<30 HU) is more common to culprit lesions in acute coronary events, as well as to high-risk, vulnerable plaques [26, 27, 47, 66]. Currently, there is not enough data to support a valid assumption on the accuracy of CCTA for detecting non-calcified coronary plaques at high risk. Small studies comparing CCTA to IVUS reported sensitivities and specificities between 80 and 90% for the detection of coronary artery segments with plaque [8, 9, 67, 68]. Other studies demonstrated significant correlations between measurements of plaque crosssectional area, volume of single plaques, and plaque volume per coronary segment on CCTA and IVUS [8, 69, 70, 71]. However, despite significant and quite high correlation coefficients, the limits of agreement were typically large in most studies, which betrays the limitations of CCTA, mainly imposed by the spatial resolution of the method. Plaque quantification is particularly challenging when plaques have low thickness. Reported interobserver variability is also unusually high (30% variability for plaque volume quantification) [9, 72, 73] and is very much influenced by image quality. In a research on 41 patients, the interobserver variability was 17±10% for the left anterior descending coronary artery, which was best, visualized with fewer artifacts, but escaladed to 29±13% for the left circumflex and 32±10% for the right coronary artery [73].

#### *2.1.2. Low CT attenuation plaques*

on coronary CCTA (thin-cap fibroatheromas) comprising a necrotic, low attenuation core surrounded by a thin area of higher attenuation, which some believe may represent the thin peripheral fibrous cap (Figure 2) [26, 47]. However, in vulnerable plaques, the fibrous cap has extremely reduced thickness [48, 51], which makes it indistinguishable by non-invasive imaging methods; by contrast, the necrotic core may be visualized and quantified on thin sections (<0.6 mm) on modern CCTA [52, 53]. As the presence of the napkin-ring sign was shown to have a high predictive value for future cardiac events and is considered a valuable correlate of unstable plaques [49, 27, 20, 54, 55], its detection could add specificity to the CCTA

**Figure 1. Different Types of Coronary Plaques by CCTA**. The 3 main types of coronary plaques are shown: calcified plaques (A, D), non-calcified plaques (B, E) and partially calcified plaques (C, F), illustrated in curved planar reformat‐

**Figure 2. Representative CCTA Images with Napkin-ring Signs**. An atherosclerotic plaque with positive remodeling, low attenuation plaque, and a napkin-ring sign in the proximal left anterior descending artery on computed tomogra‐ phy angiography. The boxed area indicates cross-sectional images of atherosclerotic plaque showing a napkin-ring

assessment of vulnerable plaques.

120 Coronary Artery Disease - Assessment, Surgery, Prevention

ted and cross-sectional views.

sign.

In CCTA studies investigating patients with ACS, several features of high-risk plaques have been described, such as low attenuation plaque, positive remodeling, and spotty calcification [74, 54]. Recent studies have also described a specific CCTA aspect of coronary artery lesions

called the napkin-ring sign consisting of a low attenuation area surrounded by a rim-like area of higher CCTA attenuation [22, 47]. Speculations were made on the histological substrate of this aspect, as it was believed to be given by either a central lipid core within a fibrous cap, deep micro-calcifications, neo-vascularization, or the presence of intramural thrombus [22, 27]. Current criteria for the definition of the napkin-ring sign include the presence of a high attenuation ring around a certain coronary artery plaque and higher CCTA attenuation of the ring by comparison to the adjacent plaque, but no greater than 130 HU, in order to differentiate from calcium deposits [27, 47]. Plaques with rich necrotic core have been described as plaques of low attenuation; low attenuation areas were shown to correlate strongly with echolucent areas in IVUS [75]. In a large prospective study on more than 1000 patients, low attenuation plaques and positive remodeling were shown to correlate with the development of acute coronary events. In this group, 45 patients had both CCTA characteristics and 10 of them (22%) experienced an acute coronary event vs. only 4 (0.5%) of the patients who did not exhibit neither positive remodeling nor low attenuation plaques. Patients with normal CCTA did not have any coronary events at all (p<0.001). In this study, positive remodeling and/or low attenuation plaques were independent predictors of acute coronary events (hazard ratio: 23, 95% confidence interval: 7 to 75, p<0.001) [74].

A limitation of CCTA in quantifying atherosclerotic plaques may have its origin in the fact that intravascular attenuation significantly influences the attenuation of the plaques. Cademartiri et al. performed a phantom test that supports this hypothesis [76, 77] and Schroeder et al. also obtained similar results in their study [78]. Comparative studies between CCTA density and IVUS or histopathology suggest that lipid-rich plaques have lower CCTA density than fibrous plaques. However, low CCTA attenuation is not a constant finding in lipid-rich plaques, raising controversy over its ability to discriminate between lipid-rich and fibrous plaques. As mentioned above, some studies have reported that luminal density influences neighboring structures CCTA attenuation. Some authors reported that, when contrast medium is not used for examination, significant overlaps can occur between CCTA attenuation values of lipid-rich and fibrous plaques.

CCTA resolution is defined in terms of spatial, contrast and temporal resolution. Although significant technological progress has been made in CCTA, the spatial resolution of CCTA (0.5 mm) is still inferior to that of cardiac catheterization or IVUS. The 0.5 resolution is suboptimal, considering the fact that the average diameter of a coronary artery is 3–4 mm. CCTA density is influenced by the partial volume effect and contrast resolution has not improved despite other technological advances in MDCT [27]. CCTA attenuation values, measured in HU, are given by the amount of radiation absorbed by tissue in the voxel and density is directly proportional to the attenuation coefficient. A CCTA value of –1,000 HU corresponds to air, while 0 HU corresponds to water. Most soft tissues CCTA averages have values of 50 HU. Some tissues, such as bone, calcified tissues, or the iodine-rich tissue of the thyroid gland are >100 HU, whereas fat or fatty mixed tissue and lung tissue are <0 HU. If the value for a tissue type, with the exception of calcified or fatty tissues, deviates from the soft tissue attenuation, artifacts should be considered, particularly if contrast is used and the beam hardening effect is suspected; another element of confusion may be the presence of a near-by area of calcification or fat that may induce a partial volume effect. MIn addition to that, motion artifacts should be considered. CCTA values can also be influenced by tube voltage [27].

#### *2.1.3. Spotty calcium in plaques*

called the napkin-ring sign consisting of a low attenuation area surrounded by a rim-like area of higher CCTA attenuation [22, 47]. Speculations were made on the histological substrate of this aspect, as it was believed to be given by either a central lipid core within a fibrous cap, deep micro-calcifications, neo-vascularization, or the presence of intramural thrombus [22, 27]. Current criteria for the definition of the napkin-ring sign include the presence of a high attenuation ring around a certain coronary artery plaque and higher CCTA attenuation of the ring by comparison to the adjacent plaque, but no greater than 130 HU, in order to differentiate from calcium deposits [27, 47]. Plaques with rich necrotic core have been described as plaques of low attenuation; low attenuation areas were shown to correlate strongly with echolucent areas in IVUS [75]. In a large prospective study on more than 1000 patients, low attenuation plaques and positive remodeling were shown to correlate with the development of acute coronary events. In this group, 45 patients had both CCTA characteristics and 10 of them (22%) experienced an acute coronary event vs. only 4 (0.5%) of the patients who did not exhibit neither positive remodeling nor low attenuation plaques. Patients with normal CCTA did not have any coronary events at all (p<0.001). In this study, positive remodeling and/or low attenuation plaques were independent predictors of acute coronary events (hazard ratio: 23,

A limitation of CCTA in quantifying atherosclerotic plaques may have its origin in the fact that intravascular attenuation significantly influences the attenuation of the plaques. Cademartiri et al. performed a phantom test that supports this hypothesis [76, 77] and Schroeder et al. also obtained similar results in their study [78]. Comparative studies between CCTA density and IVUS or histopathology suggest that lipid-rich plaques have lower CCTA density than fibrous plaques. However, low CCTA attenuation is not a constant finding in lipid-rich plaques, raising controversy over its ability to discriminate between lipid-rich and fibrous plaques. As mentioned above, some studies have reported that luminal density influences neighboring structures CCTA attenuation. Some authors reported that, when contrast medium is not used for examination, significant overlaps can occur between CCTA attenuation values of lipid-rich

CCTA resolution is defined in terms of spatial, contrast and temporal resolution. Although significant technological progress has been made in CCTA, the spatial resolution of CCTA (0.5 mm) is still inferior to that of cardiac catheterization or IVUS. The 0.5 resolution is suboptimal, considering the fact that the average diameter of a coronary artery is 3–4 mm. CCTA density is influenced by the partial volume effect and contrast resolution has not improved despite other technological advances in MDCT [27]. CCTA attenuation values, measured in HU, are given by the amount of radiation absorbed by tissue in the voxel and density is directly proportional to the attenuation coefficient. A CCTA value of –1,000 HU corresponds to air, while 0 HU corresponds to water. Most soft tissues CCTA averages have values of 50 HU. Some tissues, such as bone, calcified tissues, or the iodine-rich tissue of the thyroid gland are >100 HU, whereas fat or fatty mixed tissue and lung tissue are <0 HU. If the value for a tissue type, with the exception of calcified or fatty tissues, deviates from the soft tissue attenuation, artifacts should be considered, particularly if contrast is used and the beam hardening effect is suspected; another element of confusion may be the presence of a near-by area of calcification

95% confidence interval: 7 to 75, p<0.001) [74].

122 Coronary Artery Disease - Assessment, Surgery, Prevention

and fibrous plaques.

Besides plaque density (Figure 3), other CCTA features such as positive remodeling and spotty calcification can suggest plaque vulnerability. Positive remodeling is appreciated by referral to the remodeling index; obviously, expanded plaques have higher remodeling index, above the cut-off values, but borderline values can hamper interpretation, considering the narrow lumen of the coronary arteries, which barely averages 4 mm; a difference of 10% is less than 1 pixel on the CCTA image. Consequently, when the set cut-off value is near one, plaque expansion may be erroneously measured as positive. Also, the presence of spotty calcification can lead to overestimation of plaque expansion. As the presence of more calcium is considered to be an element of increased atherosclerotic plaque stability, low calcification plaques are regarded as more vulnerable [27].

**Figure 3. Curved Planar Reformation of the Coronary Artery in CCTA**. The curved planar reformatted computed to‐ mography angiography image of the right coronary artery demonstrates two large, predominantly non-calcified athe‐ rosclerotic plaques with spotty calcification (arrowheads) in the proximal segment and mild of the right coronary artery.

However, pathological studies concluded that calcium is commonly encountered in ruptured plaques causing sudden cardiac death and that a few scattered small calcium deposits are often present in the fibrous cap of fibroatheromas [79]. The development of scattered small calcium around the necrotic core is believed to be triggered by osteogenic changes under the influence of inflammatory factors and oxidized lipids [80, 81]. The presence of spotty calcifications seems to induce mechanical instability at the interface with non-calcified plaque components [82]. Clinical studies have shown that: spotty calcification has been associated with an increased incidence of ischemic cardiovascular events [83] and, more accurately, that patients with ACSs have a different pattern of calcification when compared to those with stable angina [84]; spotty calcifications are more likely to be found in culprit lesions in patients with myocardial infarction than in patients with stable angina [38]; spotty calcification are more commonly encountered in patients with accelerated disease progression [85]; ruptured coronary plaques are associated with spotty calcification, particularly in deep locations and the number of deep calcium deposits is an independent predictor of culprit plaque ruptures in patients who had ACSs [84]; and superficial spotty calcifications in IVUS are associated with very late stent thrombosis after bare-metal stent implantation [86]. A possible caveat in CCTA imaging may be the fact that microcalcifications under the detection level of CCTA seem to induce very high plaque instability. However, the presence of calcification increases CCTA values, which seems to contradict the finding that low attenuation plaques are unstable.

#### **2.2. Plaque quantification**

Currently, MDCT with at least 64 detectors allows nearly motion-free visualization of the coronary arteries and accurate detection of significant stenosis, comparing well to coronary angiography at low heart rates [8, 87]. Contrast-enhanced scans are performed by injecting intravenously 80–100 ml of contrast agent at a flow rate of 6 ml/s followed by 70 ml of saline. The delay time is previously established using the bolus tracking technique with a region of interest positioned in the ascending aorta; a manually triggered threshold of 100 HU is specified for the main scanning. All scans are performed during a single breath-hold.

Non-contrast CCTA is also useful for atherosclerotic plaque description, allowing the calcu‐ lation of the coronary artery calcium (CAC) score. The CAC is validated as a good marker of atherosclerotic burden and high values are associated with increased cardiovascular risk [88], However, despite relatively easy quantification, the CAC is hindered by several disadvantag‐ es, including the inability to identify small, scattered calcifications in non-calcified plaques, which may lead to the underestimation of disease severity and cardiovascular risk. Also, plaque morphology cannot be described on native calcium scans.

Quantitative measurements of coronary plaques aim to assess global atherosclerotic burden and provide detailed and specific descriptions of plaque morphology that could accurately evaluate the risk for cardiovascular events [70, 89, 90]. However, volumetric measurements of coronary artery plaques with manual tracing contours is strenuous and time-consuming; current software, such as AUTOPLAQ (APQ; Cedars-Sinai Medical Center, Los Angeles, CA), allow semi-automated quantification of both calcified and non-calcified plaques that has reduced the examination time and was shown to correlate very well to the IVUS assessment of the coronary plaque volume

[91]. Dey et al. [92] evaluated the accuracy of APQ and compared semi-automated quantifi‐ cation on CCTA using APQ to IVUS with manual tracing of the coronary artery plaque. Average examination time was significantly reduced by automated quantification. Manual IVUS required the longest processing time (15 to 35 minutes), followed by manual CCTA (5 to 15 minutes), while automated plaque segmentation and quantification took less than 20 seconds. There were no significant differences in plaque volumes calculation between IVUS compared with APQ, or between manual CCTA quantification and APQ. Interestingly, APQ quantification revealed smaller absolute differences from IVUS results than CT manual quantification. APQ has also been shown to have reliable interscan reproducibility of quanti‐ tative plaque measurements. Schuhbaeck et al. evaluated total plaque volume, volume of calcified and non-calcified plaque, and maximal remodeling index by performing CCTAs twice in consecutive patients; using APQ there were no significant differences in any of the measurements between scans [93].

Another CCTA automated software for plaque quantification, QAngio (Medis, Netherland), has been developed and compared with IVUS. In their study, Boogers et al. [90] evaluated the accuracy of CCTA automated plaque quantification using a single algorithm to co-register CT and IVUS after having previously established anatomical markers; slice-by-slice comparisons of each location along the transverse axis of the coronary arteries have been made. The compared parameters included the percent lumen area stenosis, plaque burden, the degree of remodeling at the level of minimal lumen area, and the mean plaque burden for the whole coronary plaque. The study revealed significant correlations between the two methods regarding the quantification of lumen area stenosis, plaque burden at the level of the minimal lumen area, as well as mean plaque burden. However, CCTA failed to quantify all parameters as accurately as IVUS, underestimating minimal lesion area and overestimating lumen area stenosis. Moderate correlations were established between the two methods regarding coronary plaque remodeling. Automated plaque quantification methods are expected to reduce interobserver variability by comparison with manual quantification techniques. Several studies were conducted in order to assess the reproducibility of the results. Papadopoulou et al. [94] reported little inter- and intraobserver variability for lumen and vessel areas. Also, in an additional study inter- and intraobserver relative differences for lumen, vessel, plaque area, and plaque burden did not reach statistical significance. Automated plaque quantification proved, however, less reliable for compositional measurements of plaque attenuation values, demonstrating high inter-observer variability (12%), which is an important limiting factor. Despite this drawback, automated softwares can be used for evaluating coronary artery sclerosis progression, as demonstrated by Papadopoulou et al [95]. In another study, Blackmon et al. [96] tested the accuracy and interobserver variability for volumetric measurement of noncalcified lesions of another automated postprocessing software algorithm. Very strong correlations were found between manual measurements performed by highly experienced examiners and automated plaque volumetry, and interobserver variability was reduced when using the plaque analysis algorithm. As demonstrated by the aforementioned studies, automated softwares provide the major advantage of higher reproducibility, while also allowing faster quantifications, which make them elligible for more widespread use. CCTA is very accurate for stenosis detection [97] and for the measurement of calcified plaque burden [98, 99]. The amount of coronary calcification quantified by CCTA is a strong predictor of CAD [100, 101], but fails to accurately identify the site of stenosis. Moreover, even in modern CT scanners, spatial resolution is not sufficient to provide an accurate analysis of the fibrous cap by CCTA [102]. Also, histopathologically-based studies suggest that vulnerable plaques are enlarged in all three spatial dimensions [103] and that average measurements of the necrotic core, such as length and area [104] are beyond the plaque detection threshold for CCTA [105].

#### **2.3. Functional plaque characteristics**

encountered in patients with accelerated disease progression [85]; ruptured coronary plaques are associated with spotty calcification, particularly in deep locations and the number of deep calcium deposits is an independent predictor of culprit plaque ruptures in patients who had ACSs [84]; and superficial spotty calcifications in IVUS are associated with very late stent thrombosis after bare-metal stent implantation [86]. A possible caveat in CCTA imaging may be the fact that microcalcifications under the detection level of CCTA seem to induce very high plaque instability. However, the presence of calcification increases CCTA values, which seems

Currently, MDCT with at least 64 detectors allows nearly motion-free visualization of the coronary arteries and accurate detection of significant stenosis, comparing well to coronary angiography at low heart rates [8, 87]. Contrast-enhanced scans are performed by injecting intravenously 80–100 ml of contrast agent at a flow rate of 6 ml/s followed by 70 ml of saline. The delay time is previously established using the bolus tracking technique with a region of interest positioned in the ascending aorta; a manually triggered threshold of 100 HU is

Non-contrast CCTA is also useful for atherosclerotic plaque description, allowing the calcu‐ lation of the coronary artery calcium (CAC) score. The CAC is validated as a good marker of atherosclerotic burden and high values are associated with increased cardiovascular risk [88], However, despite relatively easy quantification, the CAC is hindered by several disadvantag‐ es, including the inability to identify small, scattered calcifications in non-calcified plaques, which may lead to the underestimation of disease severity and cardiovascular risk. Also,

Quantitative measurements of coronary plaques aim to assess global atherosclerotic burden and provide detailed and specific descriptions of plaque morphology that could accurately evaluate the risk for cardiovascular events [70, 89, 90]. However, volumetric measurements of coronary artery plaques with manual tracing contours is strenuous and time-consuming; current software, such as AUTOPLAQ (APQ; Cedars-Sinai Medical Center, Los Angeles, CA), allow semi-automated quantification of both calcified and non-calcified plaques that has reduced the examination time and was shown to correlate very well to the IVUS assessment

[91]. Dey et al. [92] evaluated the accuracy of APQ and compared semi-automated quantifi‐ cation on CCTA using APQ to IVUS with manual tracing of the coronary artery plaque. Average examination time was significantly reduced by automated quantification. Manual IVUS required the longest processing time (15 to 35 minutes), followed by manual CCTA (5 to 15 minutes), while automated plaque segmentation and quantification took less than 20 seconds. There were no significant differences in plaque volumes calculation between IVUS compared with APQ, or between manual CCTA quantification and APQ. Interestingly, APQ quantification revealed smaller absolute differences from IVUS results than CT manual quantification. APQ has also been shown to have reliable interscan reproducibility of quanti‐ tative plaque measurements. Schuhbaeck et al. evaluated total plaque volume, volume of calcified and non-calcified plaque, and maximal remodeling index by performing CCTAs

specified for the main scanning. All scans are performed during a single breath-hold.

to contradict the finding that low attenuation plaques are unstable.

plaque morphology cannot be described on native calcium scans.

**2.2. Plaque quantification**

124 Coronary Artery Disease - Assessment, Surgery, Prevention

of the coronary plaque volume

Recently, some techniques have been developed for the purpose of analyzing functional parameters, as well as anatomical structures. CT-based fractional flow reserve (FFR-CT) and CT perfusion allow the non-invasive hemodynamic assessment of coronary stenoses and increase the specificity of CCTA, which may greatly influence the management of CAD patients in the future [106].

#### *2.3.1. Endothelial Shear Stress (ESS)*

ESS refers to the tangential stress that is applied on the endothelial surface of the arterial wall by flowing blood friction and is expressed in units of force/unit area [107]. ESS is influenced by blood viscosity and the spatial gradient of blood velocity at the wall. When a fluid passes through a tube, its flow is influenced by the characteristics of the tube walls such as surface irregularities or obstructions. Fluid flow may be laminar or turbulent. Laminar flows are streamlined and may be either completely smooth ("undisturbed flows") or "disturbed", with areas of reversed flow. In turbulent flow, velocities vary continuous‐ ly in a certain point in space [108]. The presence of low ESS favors the formation and development of coronary artery plaques, as well as their progression to high-risk, vulnera‐ ble plaques. Local blood hemodynamics can influence atherosclerosis development for better or for worse. Therefore, an accurate in vivo quantification of plaque characteristics, local ESS, and vascular remodeling response would facilitate a better understanding of the mechanisms behind CAD progression, as well as clinical decision making regarding possible pre-emptive local interventions [109]. The evolution of each coronary artery plaque is individual and considerably influenced not only by the progression of atherosclerosis, but also by vascular remodeling. Extensive remodeling leads to the development of vulnera‐ ble plaques and is triggered by ESS. Persistent ESS favors local lipid build-up, inflamma‐ tion, oxidative stress, and matrix breakdown, with subsequent plaque progression and further remodeling [109]. Advanced plaques in areas of severe stenosis are submitted to considerable shear stress that promotes plaque destabilization [110].

#### *2.3.2. Fractional Flow Reserve (FFR)*

FFR is calculated as the ratio between the maximum blood flow within a diseased coronay artery and the theoretical maximum flow in a normal coronary artery. An FFR of 1.0 is considered normal, while values of less than 0.75–0.80 are acknowledged by most as associated with myocardial ischemia [111]. FFR values >0.8 but <1 are considered indica‐ tive of a hemodinamically unsignificant stenosis, while values <0.75 reflect significant stenoses. In earlier works, values between 0.75–0.80 represented a grey area and were interpreted according to the clinical context. Investigators estimated that the cut-off value for FFR could be extended to 0.80, thus improving sensitivity without significantly compromising specificity. The cut-off value of 0.80 was already used in the FAME 1 and FAME 2 trials and proved to be clinically valid [112, 113]. This is now the recommended ischemic reference standard for the invasive assessment of myocardial ischemia [114]. Invasive coronary angiography is the established clinical standard for coronary artery disease assessment, with IVUS providing the advantage of intramural and transmural coronary artery imaging. OCT offers an even more accurate visualization of the coronary arteries [115]. The use of these additional invasive imaging methods can facilitate therapeut‐ ical decisions regarding revascularization and help guide percutaneous coronary interven‐ tions, leading to better postprocedural results. However, in current clinical practice, the reported rates of use for these techniques in assessing intermediate (40–70%) coronary stenoses are fairly low, 20.3% for IVUS and 6.1% for FFR [116].

CT perfusion allow the non-invasive hemodynamic assessment of coronary stenoses and increase the specificity of CCTA, which may greatly influence the management of CAD

ESS refers to the tangential stress that is applied on the endothelial surface of the arterial wall by flowing blood friction and is expressed in units of force/unit area [107]. ESS is influenced by blood viscosity and the spatial gradient of blood velocity at the wall. When a fluid passes through a tube, its flow is influenced by the characteristics of the tube walls such as surface irregularities or obstructions. Fluid flow may be laminar or turbulent. Laminar flows are streamlined and may be either completely smooth ("undisturbed flows") or "disturbed", with areas of reversed flow. In turbulent flow, velocities vary continuous‐ ly in a certain point in space [108]. The presence of low ESS favors the formation and development of coronary artery plaques, as well as their progression to high-risk, vulnera‐ ble plaques. Local blood hemodynamics can influence atherosclerosis development for better or for worse. Therefore, an accurate in vivo quantification of plaque characteristics, local ESS, and vascular remodeling response would facilitate a better understanding of the mechanisms behind CAD progression, as well as clinical decision making regarding possible pre-emptive local interventions [109]. The evolution of each coronary artery plaque is individual and considerably influenced not only by the progression of atherosclerosis, but also by vascular remodeling. Extensive remodeling leads to the development of vulnera‐ ble plaques and is triggered by ESS. Persistent ESS favors local lipid build-up, inflamma‐ tion, oxidative stress, and matrix breakdown, with subsequent plaque progression and further remodeling [109]. Advanced plaques in areas of severe stenosis are submitted to

considerable shear stress that promotes plaque destabilization [110].

FFR is calculated as the ratio between the maximum blood flow within a diseased coronay artery and the theoretical maximum flow in a normal coronary artery. An FFR of 1.0 is considered normal, while values of less than 0.75–0.80 are acknowledged by most as associated with myocardial ischemia [111]. FFR values >0.8 but <1 are considered indica‐ tive of a hemodinamically unsignificant stenosis, while values <0.75 reflect significant stenoses. In earlier works, values between 0.75–0.80 represented a grey area and were interpreted according to the clinical context. Investigators estimated that the cut-off value for FFR could be extended to 0.80, thus improving sensitivity without significantly compromising specificity. The cut-off value of 0.80 was already used in the FAME 1 and FAME 2 trials and proved to be clinically valid [112, 113]. This is now the recommended ischemic reference standard for the invasive assessment of myocardial ischemia [114]. Invasive coronary angiography is the established clinical standard for coronary artery disease assessment, with IVUS providing the advantage of intramural and transmural coronary artery imaging. OCT offers an even more accurate visualization of the coronary arteries [115]. The use of these additional invasive imaging methods can facilitate therapeut‐ ical decisions regarding revascularization and help guide percutaneous coronary interven‐

patients in the future [106].

*2.3.1. Endothelial Shear Stress (ESS)*

126 Coronary Artery Disease - Assessment, Surgery, Prevention

*2.3.2. Fractional Flow Reserve (FFR)*

In the Percutaneous Coronary Intervention of Functionally Non-significant Stenosis (DEFER) Study [117], investigators evaluated 181 patients with stable ischemic heart disease and FFR > 0.75 across an intermediate stenosis. These patients were randomized to either percutaneous coronary interventions or to deferral of percutaneous coronary interventions with medical treatment. At 5-year follow-up, patients in the deferred group had a significantly decreased (less than half) rate of death or myocardial infarction by comparison with the percutaneous coronary interventions group. In the Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) trial [113], 1,005 patients with multivessel disease were randomized to either FFR- or angiography-guided percutaneous coronary interventions. In patients with FFR-guided interventions, the composite rate of death, MI, or repeated revas‐ cularization at 1 year was significantly lower (13.2% vs. 18.3%, P<0.02). The Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) trial [113] compared the outcomes of FFR-guided percutaneous coronary interventions with optimal medical therapy against optimal medical therapy alone in a group of 888 patients with stable ischemic heart disease. In this trial, unlike in others such as COURAGE, only patients having at least one lesion with FFR <0.80 were enrolled [118].

FFR assessment of lesions with 50% to 70% diameter narrowing revealed that only 35% of the lesions were hemodynamically significant. Interestingly, in severe lesions with 71% to 90% diameter stenoses, 20% were not hemodynamically significant based on FFR and did not require percutaneous coronary interventions. These results endorse the hypothesis that FFR can have essential clinical implications regarding revascularization decisions even in more severe angiographic stenoses and, particularly when noninvasive data is discordant with coronary angiography [119]. In patients with multivessel coronary artery disease, FFR can be performed, allowing an accurate determination of the Functional SYNTAX Score, and subsequently, a better selection of patients that could benefit from percutaneous coronary intervention rather than being submitted to coronary artery by-pass graft [120]. The use of CCTA for non-invasive anatomic assessment has increased considerably and the method is considered an accurate tool for detecting or excluding CAD [6, 5]. FFR-CT is a recently developed method based on computational fluid dynamics to calculate coronary blood flow, pressure, and FFR based on routinely acquired CCTA datasets [121, 122, 123, 124, 125, 126, 127, 128, 129].

## **3. Clinical implications of napkin-ring sign plaque for prognosis and management**

Recent research has shown that the napkin-ring sign is associated with future cardiac events, frequently corresponding to the culprit lesion in ACS [53]. In the study by Otsuka et al., 895 patients were evaluated by CCTA and followed up for 2.3±0.8 years; in this popula‐ tion, the presence of the napkin-ring sign on CCTA was strongly associated with ACS events: 24 patients (2.6%) experienced ACS events, of which 41% developed plaques with napkin-ring sign during the follow-up period [53]. Kashiwagi et al. conducted a CCTAbased study on 273 patients with either ACS or stable angina. In their research, the authors described the napkin-ring sign as the presence of a ring of high attenuation and the CT attenuation of a ring presenting higher than those of the adjacent plaque and no greater than 130 HU. The napkin-ring sign was more frequently encountered in culprit lesions (12.7% vs. 2.8%, p<0.01). Moreover, napkin-ring sign plaques were associated with a higher remodeling index and lower CT attenuation (1.15 ± 0.12 vs. 1.02 ± 0.12, p<0.01 and 39.9 ± 22.8 HU vs.72.7 ± 26.6 HU, p<0.01) [50]. Similar results were obtained in another study in which the napkin-ring sign was more common in patients developing ACS than in those with stable angina [28].

Besides the napkin-ring sign, other imaging characteristics such as large plaque volume, low CT attenuation, positive remodeling, and spotty calcification were proved to be correlated with a higher risk of acute events [130]. Motoyama et al. found that positive remodeling and low attenuation correlated best with the development of ACS, [74] which is consistent with results from other studies [131, 132]. Considering the results of the previously mentioned studies, one can conclude that the identification of CCTA aspects suggesting vulnerable lesions may be useful for several reasons. Firstly, although statins are known to reduce the incidence of acute cardiovascular events [133], proving their effect on a certain individual is challenging. CCTA may help identify coronary artery lesions regression, but, as it is not routinely performed, there is not enough data to support this hypothesis. Risk stratification in asymptomatic individuals has also been taken into account as a possible use for CCTA, but the actual ability of MDCT for detecting small nonstenotic plaques is yet to be established [134].

In conclusion CCTA is used extensively nowadays as a non-invasive imaging method for the evaluation of patients suspected of CAD and the napkin-ring sign described on CCTA has been designated as a valid element for identifying vulnerable plaques, indicating an increased probability of rupture, and was shown to correlate with a higher incidence of cardiovascular events.

#### **Author details**

Lucia Agoston-Coldea1,2, Carmen Cionca2 and Silvia Lupu3


#### **References**

tion, the presence of the napkin-ring sign on CCTA was strongly associated with ACS events: 24 patients (2.6%) experienced ACS events, of which 41% developed plaques with napkin-ring sign during the follow-up period [53]. Kashiwagi et al. conducted a CCTAbased study on 273 patients with either ACS or stable angina. In their research, the authors described the napkin-ring sign as the presence of a ring of high attenuation and the CT attenuation of a ring presenting higher than those of the adjacent plaque and no greater than 130 HU. The napkin-ring sign was more frequently encountered in culprit lesions (12.7% vs. 2.8%, p<0.01). Moreover, napkin-ring sign plaques were associated with a higher remodeling index and lower CT attenuation (1.15 ± 0.12 vs. 1.02 ± 0.12, p<0.01 and 39.9 ± 22.8 HU vs.72.7 ± 26.6 HU, p<0.01) [50]. Similar results were obtained in another study in which the napkin-ring sign was more common in patients developing ACS than in those

Besides the napkin-ring sign, other imaging characteristics such as large plaque volume, low CT attenuation, positive remodeling, and spotty calcification were proved to be correlated with a higher risk of acute events [130]. Motoyama et al. found that positive remodeling and low attenuation correlated best with the development of ACS, [74] which is consistent with results from other studies [131, 132]. Considering the results of the previously mentioned studies, one can conclude that the identification of CCTA aspects suggesting vulnerable lesions may be useful for several reasons. Firstly, although statins are known to reduce the incidence of acute cardiovascular events [133], proving their effect on a certain individual is challenging. CCTA may help identify coronary artery lesions regression, but, as it is not routinely performed, there is not enough data to support this hypothesis. Risk stratification in asymptomatic individuals has also been taken into account as a possible use for CCTA, but the actual ability of MDCT for detecting small non-

In conclusion CCTA is used extensively nowadays as a non-invasive imaging method for the evaluation of patients suspected of CAD and the napkin-ring sign described on CCTA has been designated as a valid element for identifying vulnerable plaques, indicating an increased probability of rupture, and was shown to correlate with a higher incidence of

and Silvia Lupu3

1 Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

2 Hiperdia Diagnostic Imaging Center, Cluj-Napoca, Romania

3 University of Medicine and Pharmacy of Targu Mures, Romania

with stable angina [28].

128 Coronary Artery Disease - Assessment, Surgery, Prevention

cardiovascular events.

**Author details**

stenotic plaques is yet to be established [134].

Lucia Agoston-Coldea1,2, Carmen Cionca2


phy: A prospective, multicenter, multivendor study. J Am Coll Cardiol. 2008;52:2135-2144. DOI: 10.1016/ j.jacc. 2008.08.058.


[14] Nakashima Y, Wight TN, Sueishi K. Early atherosclerosis in humans: Role of diffuse intimal thickening and extracellular matrix proteoglycans. Cardiovasc Res. 2008;79:14-23. DOI: 10.1093/cvr/cvn099.

phy: A prospective, multicenter, multivendor study. J Am Coll Cardiol.

[7] Pundziute G, Schuijf JD, Jukema JW, Decramer I, Sarno G, Vanhoenacker PK, Boers‐ ma E, Reiber JH, Schalij MJ, Wijns W, Bax JJ. Evaluation of plaque characteristics in acute coronary syndromes: Non-invasive assessment with multi-slice computed to‐ mography and invasive evaluation with intravascular ultrasound radiofrequency da‐

[8] Achenbach S, Moselewski F, Ropers D, Ferencik M, Hoffmann U, MacNeill B, Pohle K, Baum U, Anders K, Jang IK, Daniel WG, Brady TJ. Detection of calcified and non‐ calcified coronary atherosclerotic plaque by contrast-enhanced, submillimeter multi‐ detector spiral computed tomography: A segment-based comparison with intravascular ultrasound. Circulation. 2004;109:14-17. DOI: 10.1161/01.CIR.

[9] Petranovic M, Soni A, Bezzera H, Loureiro R, Sarwar A, Raffel C, Pomerantsev E, Jang IK, Brady TJ, Achenbach S, Cury RC. Assessment of nonstenotic coronary le‐ sions by 64-slice multidetector computed tomography in comparison to intravascular ultrasound: Evaluation of nonculprit coronary lesions. J Cardiovasc Comput To‐

[10] Duewell P, Kono H, Rayner KJ, Sirois CM, Vladimer G, Bauernfeind FG, Abela GS, Franchi L, Nuñez G, Schnurr M, Espevik T, Lien E, Fitzgerald KA, Rock KL, Moore KJ, Wright SD, Hornung V, Latz E. NLRP3 inflammasomes are required for athero‐ genesis and activated by cholesterol crystals. Nature. 2010;464:1357-1361. DOI:

[11] Stary HC, Chandler AB, Glagov S, Guyton JR, Insull W Jr, Rosenfeld ME, Schaffer SA, Schwartz CJ, Wagner WD, Wissler RW. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Le‐ sions of the Council on Arteriosclerosis, American Heart Association. Circulation.

[12] Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, Rosenfeld ME, Schwartz CJ, Wagner WD, Wissler RW. A definition of advanced types of athe‐ rosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Arterioscler Thromb Vasc Biol. 1995;15:1512-1531. DOI:

[13] Virmani R, Kolodgie FD, Burke AP, Farb A, Schwartz SM. Lessons from sudden cor‐ onary death: A comprehensive morphological classification scheme for atherosclerot‐ ic lesions. Arterioscler Thromb Vasc Biol. 2000;20:1262-1275. DOI: 10.1161/01.ATV.

ta analysis. Eur Heart J. 2008;29:2373-2381. DOI: 10.1093/eurheartj/ehn356.

2008;52:2135-2144. DOI: 10.1016/ j.jacc. 2008.08.058.

mogr. 2009;3:24-31. DOI: 10.1016/j.jcct.2008.12.005.

1994;89:2462-2478. DOI: 10.1161/01.CIR.89.5.2462.

0000111517.69230.0F.

130 Coronary Artery Disease - Assessment, Surgery, Prevention

10.1038/nature08938.

10.1161/01.ATV.15.9.1512.

20.5.1262.


PW; PROSPECT Investigators. A prospective natural-history study of coronary athe‐ rosclerosis. N Engl J Med. 2011;364:226-235. DOI: 10.1056/NEJMoa1002358.

[24] Arbustini E, Dal Bello B, Morbini P, Burke AP, Bocciarelli M, Specchia G, Virmani R. Plaque erosion is a major substrate for coronary thrombosis in acute myocardial in‐

[25] Kramer MC, Rittersma SZ, de Winter RJ, Ladich ER, Fowler DR, Liang YH, Kutys R, Carter-Monroe N, Kolodgie FD, van der Wal AC, Virmani R. Relationship of throm‐ bus healing to underlying plaque morphology in sudden coronary death. J Am Coll

[26] Maurovich-Horvat P, Hoffmann U, Vorpahl M, Nakano M, Virmani R, Alkadhi H. The napkin-ring sign: CT signature of high risk coronary plaques? J Am Coll Cardiol

[27] Tanaka A, Shimada K, Yoshida K, Jissyo S, Tanaka H, Sakamoto M, Matsuba K, Ima‐ nishi T, Akasaka T, Yoshikawa J. Non-invasive assessment of plaque rupture by 64 slice multidetector computed tomography—comparison with intravascular

[28] Pflederer T, Marwan M, Schepis T, Ropers D, Seltmann M, Muschiol G, Daniel WG, Achenbach S. Characterization of culprit lesions in acute coronary syndromes using coronary dual-source CT angiography. Atherosclerosis. 2010;211:437-444. DOI:

[29] Aziz K, Berger K, Claycombe K, Huang R, Patel R, Abela GS. Noninvasive detection and localization of vulnerable plaque and arterial thrombosis with computed tomog‐ raphy angiography/positron emission tomography. Circulation. 2008;117:2061-2070.

[30] Youssef G, Budoff M. Role of Computed Tomography Coronary Angiography in the Detection of Vulnerable Plaque, Where Does it Stand Among Others? Angiol.

[31] Vancraeynest D, Pasquet A, Roelants V, Gerber BL, Vanoverschelde JL. Imaging the vulnerable plaque. J Am Coll Cardiol. 2011;57:1961-1979. DOI: 10.1016/j.jacc.

[32] Toutouzas K, Stathogiannis K, Synetos A, Karanasos A, Stefanadis C. Vulnerable atherosclerotic plaque: From the basic research laboratory to the clinic. Cardiology.

[33] Hong MK, Mintz GS, Lee CW, Kim YH, Lee SW, Song JM, Han KH, Kang DH, Song JK, Kim JJ, Park SW, Park SJ. Comparison of coronary plaque rupture between stable angina and acute myocardial infarction: A three-vessel intravascular ultrasound study in 235 patients. Circulation. 2004;110:928-933. DOI: 10.1161/ 01.CIR.0000139858.

[34] Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, Parise H, Templin B, White R, Zhang Z, Serruys

farction. Heart. 1999;82:269-272. DOI:10.1136/ hrt.82.3.269.

Cardiol. 2010;55:122-132. DOI: 10.1016/j.jacc.2009.09.007.

Img. 2010;3:440-444. DOI: 10.1016/j.jcmg.2010.02.003.

10.1016/j.atherosclerosis.2010.02.001.

132 Coronary Artery Disease - Assessment, Surgery, Prevention

DOI: 10.1161/CirculationAHA.106.652313.

2013:1:2. DOI: 10.4172/2329-9495.1000111.

2012;123:248-253. DOI: 10.1159/000345291.

2011.02.018.

69915.2E.

ultrasound. Circ J. 2008;72:1276-1281. DOI: 10.1253/circj.72.1276.


frequency ultrasound. Am J Cardiol. 2000;85:641-644. DOI: 10.1016/ S0002-9149(99)00825-5.


ring sign indicates advanced atherosclerotic lesions in coronary CT angiography. JACC Cardiovasc Imaging. 2012;5:1243-1252. DOI:10.1016/j.jcmg.2012.03.019.

[50] Kashiwagi M, Tanaka A, Shimada K, Kitabata H, Komukai K, Nishiguchi T, Ozaki Y,Tanimoto T, Kubo T, Hirata K, Mizukoshi M, Akasaka T. Distribution, frequency and clinical implications of napkin-ring sign assessed by multidetector computed to‐ mography. J Cardiol. 2013;61:399-403. DOI: 10.1016/j.jjcc.2013.01.004.

frequency ultrasound. Am J Cardiol. 2000;85:641-644. DOI: 10.1016/

[43] Kume T, Akasaka T, Kawamoto T, Watanabe N, Toyota E, Neishi Y, Sukmawan R, Sadahira Y, Yoshida K. Assessment of coronary intima media thickness by optical co‐ herence tomography: comparison with intravascular ultrasound. Circ J.

[44] Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, Inoue K, Okumura M, Ishii J, Anno H, Virmani R, Ozaki Y, Hishida H, Narula J. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am

[45] Hoffmann U, Moselewski F, Nieman K, Jang IK, Ferencik M, Rahman AM, Cury RC, Abbara S, Joneidi-Jafari H, Achenbach S, Brady TJ. Noninvasive assessment of pla‐ que morphology and composition in culprit and stable lesions in acute coronary syn‐ drome and stable lesions in stable angina by multidetector computed tomography. J

[46] Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, Bouma B, Bruining N, Cho JM, Chowdhary S, Costa MA, de Silva R, Dijkstra J, Di Mario C, Du‐ dek D, Falk E, Feldman MD, Fitzgerald P, Garcia-Garcia HM, Gonzalo N, Granada JF, Guagliumi G, Holm NR, Honda Y, Ikeno F, Kawasaki M, Kochman J, Koltowski L, Kubo T, Kume T, Kyono H, Lam CC, Lamouche G, Lee DP, Leon MB, Maehara A, Manfrini O, Mintz GS, Mizuno K, Morel MA, Nadkarni S, Okura H, Otake H, Pietra‐ sik A, Prati F, Räber L, Radu MD, Rieber J, Riga M, Rollins A, Rosenberg M, Sirbu V, Serruys PW, Shimada K, Shinke T, Shite J, Siegel E, Sonoda S, Suter M, Takarada S, Tanaka A, Terashima M, Thim T, Uemura S, Ughi GJ, van Beusekom HM, van der Steen AF, van Es GA, van Soest G, Virmani R, Waxman S, Weissman NJ, Weisz G. International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT). Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: A report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol. 2012;59:1058-1072. DOI: 10.1016/j.jacc.2011.09.079.

[47] Kashiwagi M, Tanaka A, Kitabata H, Tsujioka H, Kataiwa H, Komukai K, Tanimoto T, Takemoto K, Takarada S, Kubo T, Hirata K, Nakamura N, Mizukoshi M, Imanishi T, Akasaka T. Feasibility of noninvasive assessment of thin-cap fibroatheroma by multidetector computed tomography. J Am Coll Cardiol Img. 2009;2:1412-1419. DOI:

[48] Narula J, Garg P, Achenbach S, Motoyama S, Virmani R, Strauss HW. Arithmetic of vulnerable plaques for noninvasive imaging. Nat Clin Pract Cardiovasc Med. 2008;5

[49] Maurovich-Horvat P, Schlett CL, Alkadhi H, Nakano M, Otsuka F, Stolzmann P, Scheffel H, Ferencik M, Kriegel MF, Seifarth H, Virmani R, Hoffmann U. The napkin

Coll Cardiol. 2007;50:319-326. DOI:10.1016/j.jacc.2007.03.044.

Am Coll Cardiol. 2006;47:1655-1662. DOI:10.1016/j.jacc.2006.01.041.

S0002-9149(99)00825-5.

134 Coronary Artery Disease - Assessment, Surgery, Prevention

10.1016/j.jcmg.2009.09.012.

Suppl 2:S2-10. DOI: 10.1038/ncpcardio1247.

2005;69:903-907. DOI:10.1253/circj.69.903.


[70] Otsuka M, Bruining N, Van Pelt NC, Mollet NR, Ligthart JM, Vourvouri E, Hamers R, De Jaegere P, Wijns W, Van Domburg RT, Stone GW, Veldhof S, Verheye S, Dudek D, Serruys PW, Krestin GP, De Feyter PJ. Quantification of coronary plaque by 64 slice computed tomography: A comparison with quantitative intracoronary ultra‐ sound. Invest Radiol. 2008;43:314-321. DOI: 10.1097/RLI.0b013e31816a88a9.

[60] Abdulla J, Asferg C, Kofoed KF. Prognostic value of absence or presence of coronary artery disease determined by 64-slice computed tomography coronary angiography a systematic review and meta-analysis. Int J Cardiovasc Imaging. 2011;27:413-420. DOI:

[61] Voros S. What are the potential advantagesand disadvantages of volumetric CT scan‐ ning? J Cardiovasc Comput Tomogr. 2009;3:67-70. DOI: 10.1016/j.jcct.2008.12.010. [62] Kristanto W, van Ooijen PM, Greuter MJ, Groen JM, Vliegenthart R, Oudkerk M. Non-calcified coronary atherosclerotic plaque visualization on CT: Effects of con‐ trast-enhancement and lipid-content fractions. Int J Cardiovasc Imaging.

[63] Becker CR, Nikolaou K, Muders M, Babaryka G, Crispin A, Schoepf UJ, Loehrs U, Reiser MF. Ex vivo coronary atherosclerotic plaque characterization with multi-de‐ tector-row CT. Eur Radiol. 2003;13:2094-2098. DOI: 10.1007/ s00330-003-1889-5.

[64] Pohle K, Achenbach S, Macneill B, Ropers D, Ferencik M, Moselewski F, Hoffmann U, Brady TJ, Jang IK, Daniel WG. Characterization of non-calcified coronary athero‐ sclerotic plaque by multi-detector row CT: Comparison to IVUS. Atherosclerosis.

[65] Schroeder S, Kuettner A, Wojak T, Janzen J, Heuschmid M, Athanasiou T, Beck T, Burgstahler C, Herdeg C, Claussen CD, Kopp AF. Non-invasive evaluation of athero‐ sclerosis with contrast enhanced 16 slice spiral computed tomography: Results of ex

[66] Nakazawa G, Tanabe K, Onuma Y, Yachi S, Aoki J, Yamamoto H, Higashikuni Y, Ya‐ gishita A, Nakajima H, Hara K. Efficacy of culprit plaque assessment by 64-slice mul‐ tidetector computed tomography to predict transient no-reflow phenomenon during percutaneous coronary intervention. Am Heart J. 2008;155:1150-1157. DOI: 10.1016/

[67] Leber AW, Becker A, Knez A, von Ziegler F, Sirol M, Nikolaou K, Ohnesorge B, Fayad ZA, Becker CR, Reiser M, Steinbeck G, Boekstegers P. Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coro‐ nary system: A comparative study using intravascular ultrasound. J Am Coll Cardi‐

[68] Sun J, Zhang Z, Lu B, Yu W, Yang Y, Zhou Y, Wang Y, Fan Z. Identification and quantification of coronary atherosclerotic plaques: A comparison of 64-MDCT and intravascular ultrasound. Am J Roentgenol. 2008;190:748-754. DOI: 10.2214/AJR.

[69] Schepis T, Marwan M, Pflederer T, Seltmann M, Ropers D, Daniel WG, Achenbach S. Quantification of noncalcified coronary atherosclerotic plaques with Dual Source Computed Tomography: Comparison to intravascular ultrasound. Heart.

vivo investigations. Heart. 2004;90:1471-1475. DOI:10.1136/hrt.2004.037861.

10.1007/s10554-010-9652-x.

136 Coronary Artery Disease - Assessment, Surgery, Prevention

j.ahj.2008.01.006.

07.2763.

2013;29:1137-1148. DOI 10.1007/s10554-012-0176-4.

2007;190:174-180. DOI: 10.1016/j.atherosclerosis.2006.01.013.

ol. 2006;47:672-677. DOI:10.1016/j.jacc.2005.10.058.

2010;96:610-615. DOI: 10.1136/hrt.2009.184226.


segments using nondecalcifying methodology. J Am Coll Cardiol. 1998;31:126-133. DOI: 10.1016/S0735-1097(97)00443-9.

[89] Brodoefel H, Burgstahler C, Sabir A, Yam CS, Khosa F, Claussen CD, Clouse ME. Coronary plaque quantification by voxel analysis: Dual-source MDCT angiography versus intravascular sonography. AJR Am J Roentgenol. 2009;192:W84-89. DOI: 10.2214/AJR.08.1381.

[79] Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syn‐ dromes: The pathologists' view. Eur Heart J. 2013;34:719-728. DOI: 10.1093/eurheartj/

[80] Aikawa E, Nahrendorf M, Figueiredo JL, Swirski FK, Shtatland T, Kohler RH, Jaffer FA, Aikawa M, Weissleder R. Osteogenesis associates with inflammation in earlystage atherosclerosis evaluated by molecular imaging in vivo. Circulation.

[81] Flammer AJ, Gössl M, Widmer RJ, Reriani M, Lennon R, Loeffler D, Shonyo S, Simari RD, Lerman LO, Khosla S, Lerman A. Osteocalcin positive CD133þ/CD34-/KDRþ progenitor cells as an independent marker for unstable atherosclerosis. Eur Heart J.

[82] Johnson RC, Leopold JA, Loscalzo J. Vascular calcification: Pathobiological mecha‐ nisms and clinical implications. Circ Res. 2006;99:1044-1059. DOI: 10.1161/01.RES.

[83] Watabe H, Sato A, Akiyama D, Kakefuda Y, Adachi T, Ojima E, Hoshi T, Murakoshi N, Ishizu T, Seo Y, Aonuma K. Impact of coronary plaquecomposition on cardiac tro‐ ponin elevation after percutaneous coronary intervention in stable angina pectoris: a computed tomography analysis. J Am Coll Cardiol. 2012;59:1881-1888. DOI: 10.1016/

[84] Fujii K, Carlier SG, Mintz GS, Takebayashi H, Yasuda T, Costa RA, Moussa I, Dangas G, Mehran R, Lansky AJ, Kreps EM, Collins M, Stone GW, Moses JW, Leon MB. In‐ travascular ultrasound study of patterns of calcium in ruptured coronary plaques.

[85] Kataoka Y, Wolski K, Uno K, Puri R, Tuzcu EM, Nissen SE, Nicholls SJ. Spotty calcifi‐ cation as a marker of accelerated progression of coronary atherosclerosis: Insights from serial intravascular ultrasound. J Am Coll Cardiol. 2012;59:1592-1597. DOI:

[86] Yumoto K, Anzai T, Aoki H, Inoue A, Funada S, Nishiyama H, Tanaka S, Kowase S, Shirai Y, Kurosaki K, Nogami A, Daida H, Kato K. Calcified plaque rupture and very late stent thrombosis after bare-metal stent implantation. Cardiovasc Interv Ther.

[87] Nieman K, Cademartiri F, Lemos PA, Raaijmakers R, Pattynama PM, de Feyter PJ. Reliable noninvasive coronary angiography with fast submillimeter multislice spiral computed tomography. Circulation. 2002;106:2051-2054. DOI: 10.1161/01.CIR.

[88] Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, Schwartz RS. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery

Am J Cardiol. 2005;96:352-357. DOI: 10.1016/j.amjcard.2005.03.074.

2011;26:252-259. DOI: 10.1007/s12928-011-0070-3.

2007;116:2841-2850. DOI: 10.1161/CIRCULATIONAHA.107.732867.

2012;33:2963-2969. DOI: 10.1093/eurheartj/ehs234.

ehs411.

138 Coronary Artery Disease - Assessment, Surgery, Prevention

0000249379.55535.21.

j.jacc.2012.01.051.

10.1016/j.jacc.2012.03.012.

0000037222.58317.3D.


nary angiography in patients with an intermediate pretest likelihood for coronary artery disease. Eur Heart J. 2007;28:2354-2360. DOI: 10.1093/eurheartj/ehm294.


gions is associated with loss of compensatory remodeling. Circulation. 2003;108:17-23. DOI: 10.1161/01.CIR.0000078637.21322.D3.

[108] Feldman CL, Ilegbusi OJ, Hu Z, Nesto R, Waxman S, Stone PH. Determination of in vivo velocity and endothelial shear stress patterns with phasic flow in human coro‐ nary arteries: A methodology to predict progression of coronary atherosclerosis. Am Heart J 2002; 143:931-939. DOI: 10.1067/mhj.2002.123118.

nary angiography in patients with an intermediate pretest likelihood for coronary

artery disease. Eur Heart J. 2007;28:2354-2360. DOI: 10.1093/eurheartj/ehm294.

Am Coll Cardiol. 1990;15:827-832. DOI:10.1016/0735-1097(90)90282-T.

s00330-008-1095-6.

140 Coronary Artery Disease - Assessment, Surgery, Prevention

0b013e3181e0a541.

[98] Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J

[99] Oudkerk M, Stillman AE, Halliburton SS, Kalender WA, Möhlenkamp S, McCol‐ lough CH, Vliegenthart R, Shaw LJ, Stanford W, Taylor AJ, van Ooijen PM, Wexler L, Raggi P. Coronary artery calcium screening: Current status and recommendations from the European Society of Cardiac Radiology and North American Society for Cardiovascular Imaging. Eur Radiol. 2008;18:2785-807. DOI: 10.1007/

[100] Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individ‐

[101] Vliegenthart R, Oudkerk M, Hofman A Oei HH, van Dijck W, van Rooij FJ, Witteman JC. Coronary calcification improves cardiovascular risk prediction in the elderly. Cir‐

[102] Achenbach S. Can CT detect the vulnerable coronary plaque? Int J Cardiovasc Imag‐

[103] Kolodgie FD, Burke AP, Farb A, Gold HK, Yuan J, Narula J, Finn AV, Virmani R. The thin-cap fibroatheroma: A type of vulnerable plaque: The major precursor lesion to

[104] Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Fin‐ kelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circula‐

[105] van der Giessen AG, Toepker MH, Donelly PM, Bamberg F, Schlett CL, Raffle C, Irl‐ beck T, Lee H, van Walsum T, Maurovich-Horvat P, Gijsen FJ, Wentzel JJ, Hoffmann U. Reproducibility, accuracy, and predictors of accuracy for the detection of coronary atherosclerotic plaque composition by computed tomography: An ex vivo compari‐ son to intravascular ultrasound. Invest Radiol. 2010;45:693-701. DOI: 10.1097/RLI.

[106] Schulman-Marcus J, Danad I, Truong QA: State-of-the-Art Updates on Cardiac Com‐ puted Tomographic Angiography for Assessing Coronary Artery Disease. Curr Treat

[107] Wentzel JJ, Janssen E, Vos J, Schuurbiers JC, Krams R, Serruys PW, de Feyter PJ, Slag‐ er CJ. Extension of increased atherosclerotic wall thickness into high shear stress re‐

Options Cardiovasc Med. 2015;17:398. DOI: 10.1007/s11936-015-0398-6.

culation. 2005;112:572-527. DOI: 10.1161/CIRCULATIONAHA.104.488916.

uals. JAMA. 2004;291:210-215. DOI: 10.1001/jama.291.2.210.

ing. 2008;24:311-312. DOI: 10.1007/s10554-007-9281-1.

acute coronary syndromes. Curr Opin Cardiol. 2011;16:285-292.

tion. 2011;123:933-944. DOI: 10.1161/ CIR.0b013e31820a55f5.


tional Cardiovascular Data Registry. J Am Coll Cardiol. 2012;60:2337-2339. DOI: 10.1016/j.jacc.2012.08.990.


(Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). J Am Coll Cardiol. 2014;63:1145-1155. DOI:10.1016/j.jacc.2013.11.043.

[125] Abbara S, Arbab-Zadeh A, Callister TQ, Desai MY, Mamuya W, Thomson L, Wei‐ gold WG. SCCT guidelines for performance of coronary computed tomographic an‐ giography: A report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2009;3:190-204. DOI:10.1016/ j.jcct.2009.03. 004.

tional Cardiovascular Data Registry. J Am Coll Cardiol. 2012;60:2337-2339. DOI:

[117] Pijls NH, van Schaardenburgh P, Manoharan G, Boersma E, Bech JW, et al. Percuta‐ neous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. J Am Coll Cardiol. 2007;49:2105-2111. DOI:10.1016/j.jacc.

[118] Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS. Optimal medical therapy with or without PCI for stable coronary

[119] Lotfi A, Jeremias A, Fearon WF, Feldman MD, Mehran R, Messenger JC, Grines CL, Dean LS, Kern MJ, Klein LW. Expert Consensus Statement on the Use of Fractional Flow Reserve, Intravascular Ultrasound, and Optical Coherence Tomography: A Consensus Statement of the Society of Cardiovascular Angiography and Interven‐

disease. N Engl J Med. 2007;356:1503-1516. DOI: 10.1056/NEJMoa070829.

tions. Catheter Cardiovasc Interv. 2014;83:509-518. DOI: 10.1002/ccd.25222.

2011;58:1211-1218. DOI: 10.1016/j.jacc.2011.06.020.

10.1001/2012.jama.11274.

[120] Nam CW, Mangiacapra F, Entjes R, Chung IS, Sels JW, Tonino PA, De Bruyne B, Pijls NH, Fearon WF; FAME Study Investigators. Functional SYNTAX Score for risk as‐ sessment in multivessel coronary artery disease. J Am Coll Cardiol.

[121] Koo BK, Erglis A, Doh JH, Daniels DV, Jegere S, Kim HS, Dunning A, DeFrance T, Lansky A, Leipsic J, Min JK. Diagnosis of ischemia-causing coronary stenoses by noninvasive fractional flow reserve computed from coronary computed tomographic angiograms. Results from the prospective multicenter DISCOVER-FLOW (Diagnosis of Ischemia-Causing Stenoses Obtained Via Noninvasive Fractional Flow Reserve)

study. J Am Coll Cardiol. 2011;58:1989-1997. DOI: 10.1016/j.jacc. 2011.06.066.

[122] Taylor CA, Fonte TA, Min JK. Computational fluid dynamics applied to cardiac com‐ puted tomography for noninvasive quantification of fractional flow reserve: Scientif‐

ic basis. J Am Coll Cardiol. 2013;61:2233-2241. DOI: 10.1016/j.jacc.2012.11.083.

[123] Min JK, Leipsic J, Pencina MJ, Berman DS, Koo BK, van Mieghem C, Erglis A, Lin FY, Dunning AM, Apruzzese P, Budoff MJ, Cole JH, Jaffer FA, Leon MB, Malpeso J, Mancini GB, Park SJ, Schwartz RS, Shaw LJ, Mauri L. Diagnostic accuracy of fraction‐ al flow reserve from anatomic CT angiography. JAMA. 2012;308:1237-1245. DOI:

[124] Nørgaard BL, Leipsic J, Gaur S, Seneviratne S, Ko BS, Ito H, Jensen JM, Mauri L, De Bruyne B, Bezerra H, Osawa K, Marwan M, Naber C, Erglis A, Park SJ, Christiansen EH, Kaltoft A, Lassen JF, Bøtker HE, Achenbach S; NXT Trial Study Group. Diagnos‐ tic performance of noninvasive fractional flow reserve derived from coronary com‐ puted tomography angiography in suspected coronary artery disease: the NXT trial

10.1016/j.jacc.2012.08.990.

142 Coronary Artery Disease - Assessment, Surgery, Prevention

2007.01.087.


**Surgical Treatment of Coronary Lesions**

[131] Nakanishi K, Fukuda S, Shimada K, Ehara S, Inanami H, Matsumoto K, Taguchi H, Muro T, Yoshikawa J, Yoshiyama M. Non-obstructive low attenuation coronary pla‐ que predicts three-year acute coronary syndrome events in patients with hyperten‐ sion: multidetector computed tomographic study. J Cardiol. 2012;59:167-175. DOI:

[132] Utsunomiya M, Hara H, Moroi M, Sugi K, Nakamura M. Relationship between tissue characterization with 40 MHz intravascular ultrasound imaging and 64-slice comput‐

[133] Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ, JUPITER Study Group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195-2207. DOI:

[134] Fayad ZA, Fuster V, Nikolaou K, Becker C. Computed tomography and magnetic resonance imaging for noninvasive coronary angiography and plaque imaging: Cur‐ rent and potential future concepts. Circulation. 2002;106:2026-2034. DOI:

ed tomography. J Cardiol 2011;57:297-302. DOI: 10.1016/j.jjcc.2011.01.016.

10.1016/j.jjcc. 2011.11.010.

144 Coronary Artery Disease - Assessment, Surgery, Prevention

10.1056/NEJMoa0807646.

10.1161/01.CIR.0000034392.34211.FC.

#### **Chapter 6**

## **Coronary Artery Bypass Surgery**

Kaan Kırali and Hakan Saçlı

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61404

#### **Abstract**

Surgical treatment of coronary artery disease should increase regional coronary flow re‐ serve and not increase any early or late morbidity and mortality more than the other treatment modalities. In the past 50 years, surgical treatment of coronary artery disease has been adapted rapidly worldwide and several techniques have been developed to de‐ crease total surgical risks and to improve early and late results with the highest level of quality of life. In spite of the last guidelines that offer stents for single or multiple vessels disease, the fact is that surgical revascularization has better outcomes in all groups of cor‐ onary artery patients. In the past two decades, the main target has been to limit or elimi‐ nate side effects of extracorporeal circulation and cardioplegia (off-pump), and general anesthesia (awake coronary bypass). The prime goal of surgical revascularization is to ob‐ tain complete revascularization by bypassing all severe stenotic coronary arteries having a diameter larger than 1 mm. Surgical revascularization with cardiopulmonary bypass through a full sternotomy remains the most widely used surgical technique. With the de‐ velopment of stabilization devices, off-pump procedures can be safely performed in most patients with single or multivessel disease. Minimal invasive and/or robotic surgery is an attractive procedure to catch invasive cardiology. The gold standard strategy involves single graft to single target vessel bypass, especially the left internal mammary artery to the left anterior descending artery. The early cumulative mortality rate is below 3%, but lower than 1% in lower-risk patients. There are some variables most predictive of early mortality: older age, female, reoperation, non-elective surgery, left ventricular dysfunc‐ tion, accelerated atherosclerosis. The survival rate is higher than 65% for 15 years. Late mortality is dependent not only on non-use of internal mammarian artery, closure of grafts, progression of native arterial disease but also on comorbidities. Satisfactory quali‐ ty of life after surgery depends on the long-term duration of the freedom from angina, heart failure, rehospitalization and reintervention, and improvement of the exercise ca‐ pacity. Return of angina during the first 6 months depends on incomplete revasculariza‐ tion or graft failure, whereas progression of native-vessel disease and grafts are serious risk factors for the late recurrence of angina. Venous graft occlusion is the most common reason for reintervention, and native vessel disease is the second.

**Keywords:** Coronary artery bypass, arterial graft, revascularization, off-pump, awake

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **1. Introduction**

Coronary artery disease (CAD) is the most common pathology which prepossesses cardiolo‐ gists and cardiac surgeons in the past century. It was the most common (38.8%) cause of death in Turkey in 2013 [1]. Ischemic heart disease was also the most common reason of mortality in the world as reported by the World Health Organization in 2012 [2]. Coronary artery disease is caused by an atherosclerotic plaque which narrows the internal lumen of the coronary artery. This lesion decreases coronary arterial blood flow and oxygen supply to the myocardium, and causes several symptoms such as chest pain, dyspnea, syncope, sometimes pulmonary edema. The low blood flow through the coronary artery territory cannot increase and support the increasing daily-life effort capacity, and the increased demand of oxygenated blood supply starts angina pectoris. There are several examinations such as exercise test, myocardial perfusion scintigraphy and computed tomography, but biplane coronary angiography is the gold standard for diagnosis. An improved understanding of the pathophysiology of CAD has forwarded efforts to increase myocardial blood supply. According to the result of angiography, patients should be treated either medically or with invasive treatment modalities. Because myocardial revascularization prolongs survival, relieves angina, and improves quality of life, percutaneous coronary intervention and coronary artery bypass surgery (CABG) can be the only treatment strategies to perform this revascularization. The general condition of patients is the decisive factor to select the best acceptable revascularization strategy. The most adequate surgical technique will be selected according to the degree and number of the affected coronary artery lesions, lesion type, and lesion location. The potential aim of the minimally invasive techniques is to reduce postoperative patient discomfort, to decrease bleeding and wound infection, and to shorten recovery times.

#### **2. History**

The first method to establish blood supply to the ischemic myocardium is to place the pedicled pectoralis muscle flap on the pericardium performed by Beck in 1935 [3]. The following 10 years passed with the developments such as chemical pericarditis and revascularization through the coronary sinus. Beck I operation (abrasion of the pericardium and epicardium + application of an inflammatory agent + partial occlusion of the coronary sinus) was described in 1945 and Beck II operation (total or partial ligation of the coronary sinus + brachial artery bypass between the descending aorta and the coronary sinus) was introduced in 1947. Vineberg described the direct implantation of internal mammarian artery (IMA) into the myocardium in 1950 [4]. A modification of the Vineberg procedure (anastomosis of a long saphenous vein between the aorta and the apex of the heart) was performed by Smith in 1955. The first successful coronary endarterectomy was performed by Bailey in 1956 [5]. Goetz performed the first successful planned CABG operation in 1960 [6]. The first patch graft technique to enlarge the obstructed left main coronary artery was performed by Effler in 1962 [7]. The first usage of a saphenous vein as an aorta–coronary artery bypass conduit was described by Sabiston in 1962 [8]. Favalaro placed a saphenous vein between the ascending aorta (side-to-end) and the right coronary artery (RCA) (end-to-end) in 1960s. [9] The official start of CABG surgery happened at the end of 1960s and saphenous vein grafts were used in all major branches with the same technique as we use nowadays [10]. Kolessov performed the first successful left internal mammary artery (LIMA) to the left anterior descending (LAD) coronary artery anastomosis on the beating heart through a left thoracotomy in 1964 [11]. Internal mammary artery grafts have been the first choice and gold standard for LAD revas‐ cularization after their superior long-term patency became known [12].

**1. Introduction**

148 Coronary Artery Disease - Assessment, Surgery, Prevention

infection, and to shorten recovery times.

**2. History**

Coronary artery disease (CAD) is the most common pathology which prepossesses cardiolo‐ gists and cardiac surgeons in the past century. It was the most common (38.8%) cause of death in Turkey in 2013 [1]. Ischemic heart disease was also the most common reason of mortality in the world as reported by the World Health Organization in 2012 [2]. Coronary artery disease is caused by an atherosclerotic plaque which narrows the internal lumen of the coronary artery. This lesion decreases coronary arterial blood flow and oxygen supply to the myocardium, and causes several symptoms such as chest pain, dyspnea, syncope, sometimes pulmonary edema. The low blood flow through the coronary artery territory cannot increase and support the increasing daily-life effort capacity, and the increased demand of oxygenated blood supply starts angina pectoris. There are several examinations such as exercise test, myocardial perfusion scintigraphy and computed tomography, but biplane coronary angiography is the gold standard for diagnosis. An improved understanding of the pathophysiology of CAD has forwarded efforts to increase myocardial blood supply. According to the result of angiography, patients should be treated either medically or with invasive treatment modalities. Because myocardial revascularization prolongs survival, relieves angina, and improves quality of life, percutaneous coronary intervention and coronary artery bypass surgery (CABG) can be the only treatment strategies to perform this revascularization. The general condition of patients is the decisive factor to select the best acceptable revascularization strategy. The most adequate surgical technique will be selected according to the degree and number of the affected coronary artery lesions, lesion type, and lesion location. The potential aim of the minimally invasive techniques is to reduce postoperative patient discomfort, to decrease bleeding and wound

The first method to establish blood supply to the ischemic myocardium is to place the pedicled pectoralis muscle flap on the pericardium performed by Beck in 1935 [3]. The following 10 years passed with the developments such as chemical pericarditis and revascularization through the coronary sinus. Beck I operation (abrasion of the pericardium and epicardium + application of an inflammatory agent + partial occlusion of the coronary sinus) was described in 1945 and Beck II operation (total or partial ligation of the coronary sinus + brachial artery bypass between the descending aorta and the coronary sinus) was introduced in 1947. Vineberg described the direct implantation of internal mammarian artery (IMA) into the myocardium in 1950 [4]. A modification of the Vineberg procedure (anastomosis of a long saphenous vein between the aorta and the apex of the heart) was performed by Smith in 1955. The first successful coronary endarterectomy was performed by Bailey in 1956 [5]. Goetz performed the first successful planned CABG operation in 1960 [6]. The first patch graft technique to enlarge the obstructed left main coronary artery was performed by Effler in 1962 [7]. The first usage of a saphenous vein as an aorta–coronary artery bypass conduit was described by Sabiston in 1962 [8]. Favalaro placed a saphenous vein between the ascending

After all of the developments in cardiac surgery, the cornerstone is the development of the cardiopulmonary bypass machine. This staged development has brought CABG surgery as a standard treatment modality after 1960s. The first stage was the discovery of heparin in 1915, which opened the door for open heart surgery. The second stage was the development of a heart–lung machine. The first successful open heart procedures on a human utilizing the heart– lung machine were total left-sided heart bypass procedures, where the patient's own lungs were used to oxygenate the blood. The right-sided heart bypass procedure was performed by Dodrill and colleagues in 1952 [13]. The first successful total cardiopulmonary bypass (CPB) procedure using a heart–lung machine was performed by Gibbon to close an atrial septal defect in 1953 [14]. The third stage was the development of membrane oxygenators in the 1960s. The first successful usage of a membrane oxygenator for extracorporeal circulation was performed by Hill and colleagues in 1972 [15]. The fourth stage was using a potassium-based cardioplegia solution to protect myocardium during open heart surgery. Melrose and colleagues presented the first experimental study with blood cardioplegia in 1955, but toxicity of this solution prevented usage of this cardioplegia for several years [16]. Several types of crystalloid cardioplegia solution with different elements were tried to protect myocardium after a significant protection of myocardium during potassium-induced cardiac arrest was demon‐ strated in 1973 [17]. Follette and colleagues reintroduced the technique of blood cardioplegia in 1978 [18].

After all of the developments in the conventional CABG surgery, the next step has been to minimize the standard surgical revascularization procedure using different techniques. Coronary bypass surgery is performed without opening a cardiac chamber and it is not necessary to use extracorporeal circulation. Continuing ventilation of the lungs eliminates the use of any oxygenator and keeping a beating heart eliminates any pump. Even though the first CABG procedures were performed with off-pump technique, cardiac arrest during on-pump technique has pressurized beating heart surgery. Ankeney tried to increase the interest of the off-pump revascularization in 1972, but it took only 10 years to be able to perform off-pump CABG routinely [19]. Benetti [20] and Buffolo [21] popularized this strategy in 1980s. The first cases were revascularization of anteriorly located coronary arteries. Three limiting factors have inhibited ideal myocardial revascularization: adequate exposure, blood flow, and motion. The technical advances regarding exposure and stabilization have facilitated complete revascula‐ rization. Several new strategies have been developed for off-pump CABG. First strategy was to stabilize the beating heart with different devices [22]. Second strategy was to position the beating heart for the adequate exposure of all epicardial coronary arteries [23]. Third strategy was to minimize surgical intervention with different minimal invasive approaches [24]. Last

step was to avoid general anesthesia to minimize respiratory side effects [25], whereas Kırali and colleagues [26] performed off-pump complete arterial revascularization with using bilateral IMAs for in awake patients. Harvesting IMAs was the other issue for off-pump surgery. Endoscopic IMA harvesting was used, but it did not widespread [27]. Today, we are facing fully endoscopic off-pump myocardial revascularization-assisted robotic surgery. Loulmet [28] was the first to report a successfully completed robotic CABG, but conversion was very common in early series. Stepwise progression of robotic technology and development of specific procedures will result in simpler robotic CABG in the near future [29].

#### **3. General information**

Coronary artery disease varies enormously from patient to patient; therefore, recommenda‐ tions to patients on the basis of predictions and comparisons of outcomes between CABG and the other treatment options are of little value. Surgical treatment of CAD should increase the regional coronary flow reserve and not increase any early or late morbidity and mortality more than the other treatment modalities. Patient-specific features, risks, and predictions are required to offer patients the surgical treatment. Because anginal symptoms are very subjective for both patients and surgeons and there is a weak correlation between the severity of symptoms and the involvement of coronary arteries, the gold standard biplane coronary angiography is the only option to decide which surgical revascularization strategy to use. Perfusion imaging and echocardiography examinations can diagnose associated cardiac pathologies, which require surgical intervention at the same time. Computed tomographic angiography is a new option, but not a suitable alternative, and gives more detailed informa‐ tion about distal vascular bed or ostial lesions. Intravascular ultrasound and fractional flow reserve can clarify the severity of intermediate lesions.

Myocardial revascularization represents an effective treatment strategy shown to prolong survival. In the past 50 years, surgical treatment of CAD has been adapted rapidly worldwide because CABG provides excellent short- and mid-term results in the management of ischemic heart disease with the highest level of quality of life. But long-term results of surgical revas‐ cularization are affected by failure of conduits, and late patency of conduits is affected by grafttype, coronary runoff, and severity of distal native vessel atherosclerosis. Several techniques have been developed to decrease total surgical risks and to improve early and late outcomes, but CABG surgery with or without CPB through median sternotomy remains the standard surgical intervention despite an increasing risk profile and diffusing coronary artery involve‐ ment. The aim of CABG is to increase the blood supply in coronary arteries by obtaining complete revascularization of all severe stenotic epicardial coronary arteries with a diameter larger than 1 mm. However, optimal patency rates can be obtained in saphenous vein grafts with a distal lumen of ≥ 2 mm. Most patients undergoing CABG have extensive three-system disease, often with important stenoses in more than three coronary branches. The standard strategy involves usage of LIMA to the LAD and saphenous veins to the remaining coronary arteries, whereas full arterial revascularization is preferred in young population. "Single graft to single target vessel bypass" is the gold standard for myocardial revascularization, but in some situations sequential bypass or complex configuration of conduits can be used for complete revascularization in the presence of inadequate venous grafts. The condition of the distal coronary vasculature is important for the outcome of bypass conduits, and the rate of CAD progression appears to be three to six times higher in grafted native coronary arteries than that in no grafted native vessels. If coronary arteries are diffusely diseased (> 10 mm) or occluded, several surgical techniques can be chosen to complete surgical revascularization as explained in the next chapter.

Indication for surgical revascularization depends on the need of improvement in the quality and/or duration of life. Despite the increase of CAD, nowadays, the indications for CABG have changed a little, but became more limited. Aggressive percutaneous coronary interventions (PCI) suppress surgery and minimal invasive surgical procedures force surgery. The last guidelines offer stents for single or multiple vessels disease, but the fact that surgical revas‐ cularization has better outcomes in all groups of CAD patients and stents is best used if there are no anatomic indications for CABG. The decision to perform myocardial revascularization with stent or CABG depends mainly on coronary anatomy, left ventricular function, and other medical or non-medical comorbidities that may affect the patient's risk. Patients with more extensive and severe coronary atherosclerosis could have more increasing benefit from surgery over stent therapy.

#### **4. Indications**

step was to avoid general anesthesia to minimize respiratory side effects [25], whereas Kırali and colleagues [26] performed off-pump complete arterial revascularization with using bilateral IMAs for in awake patients. Harvesting IMAs was the other issue for off-pump surgery. Endoscopic IMA harvesting was used, but it did not widespread [27]. Today, we are facing fully endoscopic off-pump myocardial revascularization-assisted robotic surgery. Loulmet [28] was the first to report a successfully completed robotic CABG, but conversion was very common in early series. Stepwise progression of robotic technology and development

Coronary artery disease varies enormously from patient to patient; therefore, recommenda‐ tions to patients on the basis of predictions and comparisons of outcomes between CABG and the other treatment options are of little value. Surgical treatment of CAD should increase the regional coronary flow reserve and not increase any early or late morbidity and mortality more than the other treatment modalities. Patient-specific features, risks, and predictions are required to offer patients the surgical treatment. Because anginal symptoms are very subjective for both patients and surgeons and there is a weak correlation between the severity of symptoms and the involvement of coronary arteries, the gold standard biplane coronary angiography is the only option to decide which surgical revascularization strategy to use. Perfusion imaging and echocardiography examinations can diagnose associated cardiac pathologies, which require surgical intervention at the same time. Computed tomographic angiography is a new option, but not a suitable alternative, and gives more detailed informa‐ tion about distal vascular bed or ostial lesions. Intravascular ultrasound and fractional flow

Myocardial revascularization represents an effective treatment strategy shown to prolong survival. In the past 50 years, surgical treatment of CAD has been adapted rapidly worldwide because CABG provides excellent short- and mid-term results in the management of ischemic heart disease with the highest level of quality of life. But long-term results of surgical revas‐ cularization are affected by failure of conduits, and late patency of conduits is affected by grafttype, coronary runoff, and severity of distal native vessel atherosclerosis. Several techniques have been developed to decrease total surgical risks and to improve early and late outcomes, but CABG surgery with or without CPB through median sternotomy remains the standard surgical intervention despite an increasing risk profile and diffusing coronary artery involve‐ ment. The aim of CABG is to increase the blood supply in coronary arteries by obtaining complete revascularization of all severe stenotic epicardial coronary arteries with a diameter larger than 1 mm. However, optimal patency rates can be obtained in saphenous vein grafts with a distal lumen of ≥ 2 mm. Most patients undergoing CABG have extensive three-system disease, often with important stenoses in more than three coronary branches. The standard strategy involves usage of LIMA to the LAD and saphenous veins to the remaining coronary arteries, whereas full arterial revascularization is preferred in young population. "Single graft to single target vessel bypass" is the gold standard for myocardial revascularization, but in

of specific procedures will result in simpler robotic CABG in the near future [29].

**3. General information**

150 Coronary Artery Disease - Assessment, Surgery, Prevention

reserve can clarify the severity of intermediate lesions.

The only base for the indication of surgical myocardial revascularization is the positive benefits of CABG against no treatment, medical treatment, or treatment by PCI. Regardless of symp‐ toms, indication for CABG is determined by the clinical status of the patient and patientspecific predictors. The main purpose is to improve the quality of life and to prolong the life expectancy. The number of the affected vessels, the degree and the localization of lesions are important to make this decision. 2011 ACCF/AHA Guideline for CABG supports surgical revascularization for patients with extensive and severe multivessel CAD, especially associ‐ ated with left ventricular dysfunction (LVD), renal insufficiency, and/or diabetes mellitus (Table 1) [30]. In the real world, patients with proximal LAD lesion must be sent to surgical revascularization regardless of the number of affected coronary arteries, but cardiologists like to revascularize these patients with stent regardless of the superiority of LIMA-LAD anasto‐ mosis (Figure 1). Although patients with LVD would benefit from CABG more, the real data suggest that poor left ventricular function increases early mortality after surgery. Patients with good left ventricular function can have better prognosis than patients with LVD. Risks and benefits of CABG become more uncertain when resting left ventricular ejection fraction (LVEF) is less than 30%, particularly when it is less than 20%. The only exception is myocardial hibernation which causes severe reduction in resting LVEF. Stable angina requires elective myocardial revascularization, but unstable angina or non-ST-segment elevation acute coro‐ nary syndrome or non-Q-wave myocardial infarction requires priority CABG to prevent patients from transmural myocardial infarction. In the early period (< 4 h) after acute trans‐ mural myocardial infarction, emergency CABG can be a lifesaving procedure, but some patients cannot be salvaged. Myocardial re-revascularization can be necessary when myocar‐ dial ischemia returns after CABG, and stent implantation is the first choice for restenosis of grafted coronary arteries or vein grafts.


Figure 1. The reality of myocardial revascularization strategies in patients with isolated coronary artery disease. CABG = coronary artery bypass grafting; DES = drug eliting stent; DM = diabetes mellitus; LAD = left anterior descending artery; LMC = left main coronary artery disease; LVD = left ventricular dysfunction. CABG = coronary artery bypass grafting; DES = drug eliting stent; DM = diabetes mellitus; LAD = left anterior descend‐ ing artery; LMC = left main coronary artery disease; LVD = left ventricular dysfunction. \*Y = yes; N = no; C = controversial

**Figure 1.** The reality of myocardial revascularization strategies in patients with isolated coronary artery disease.


2. LMCE disease

3. Three-vessel disease

4. Two-vessel disease with proximal LAD stenosis and LVEF < 50% or demonstrable ischemia

5. One- or two-vessel disease without proximal LAD stenosis but with a large territory at risk and high-

risk criteria on noninvasive testing

6. Disabling angına refractory to medical therapy

#### **Class IIa**

patients cannot be salvaged. Myocardial re-revascularization can be necessary when myocar‐ dial ischemia returns after CABG, and stent implantation is the first choice for restenosis of

**No‐risk DM LVD No‐risk DM LVD**

**Revascularization CABG DES**

**‐vessel N N N Y Y Y Proximal LAD Y Y Y N N N ‐vessel without LAD N N N Y Y Y ‐vessel with LAD Y Y Y Y Y Y ‐vessel + proximal LAD Y Y Y N N N ‐vessel Y Y Y C C C ‐vessel + proximal LAD Y Y Y N N N LMC ± other lesions Y Y Y N N N**

Figure 1. The reality of myocardial revascularization strategies in patients with isolated coronary artery disease. CABG = coronary artery bypass grafting; DES = drug eliting stent; DM = diabetes mellitus; LAD = left anterior descending

**Figure 1.** The reality of myocardial revascularization strategies in patients with isolated coronary artery disease.

CABG = coronary artery bypass grafting; DES = drug eliting stent; DM = diabetes mellitus; LAD = left anterior descend‐

(if a large territory at risk on noninvasive studies or LVEF < 50%, IIa and IIb become class I indications)

artery; LMC = left main coronary artery disease; LVD = left ventricular dysfunction.

ing artery; LMC = left main coronary artery disease; LVD = left ventricular dysfunction.

grafted coronary arteries or vein grafts.

152 Coronary Artery Disease - Assessment, Surgery, Prevention

\*Y = yes; N = no; C = controversial

1. LMC stenosis 2. LMCE disease 3. Three-vessel disease

1. LMC stenosis

1. Proximal LAD (one- or two-vessel)

1. One- or two-vessel disease not involving proximal LAD

**Asymptomatic CAD**

**Class I**

**Class IIa**

**Class IIb**

**Stable Angina**

**Class I**

1. Proximal LAD stenosis with one-vessel disease

2. One- or two-vessel disease without proximal Lad stenosis, but with a moderate territory at risk and demonstrable ischemia

**Unstable Angina / Non-ST-Segment Elevation MI (NSTEMI)**

#### **Class I**

1. LMC stenosis

2. LMCE disease

3. Ongoing ischemia not responsive to maximal nonsurgical therapy

#### **Class IIa**

1. Proximal LAD stenosis with one- or two-vessel disease

#### **Class IIb**

1. One- or two-vessel disease without proximal LAD stenosis when PCI not possible (becomes class I if high-risk criteria on noninvasive testing)

#### **ST-Segment Elevation (Q wave) MI**

#### **Class I**

1. Failed PCI with persistent pain or shock and anatomically feasible

2. Persistent or recurrent ischemia refractory to medical treatment with acceptable anatomy who have a significant territory at risk and not a candidate for PCI

3. Requires surgical repair of post-infarct VSD or MR

4. Cardiogenic shock in patients < 75 years of age who have ST elevation, LBBB, or a posterior MI within 18 hours onset

5. Life-threatening ventricular arrhythmias in the presence of ≥ 50% LMC stenosis or three-vessel disease

#### **Class IIa**

1. Primary reperfusion in patients who have failed fibrinolytics or PCI and are in the early stages (6-12 h) of an evolving STEMI

2. Mortality with CABG is elevated the first 3-7 days after STEMI/NSTEMI. After 7 days, criteria for CABG in previous section apply.

#### **Poor LV Function**


Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness or efficacy of a procedure

Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy

Class IIb: Usefulness/efficacy is less well established by evidence/opinion

Class III: Conditions for which there is evidence and/or general agreement that the procedure/treatment is not useful/ effective and in some cases may be harmful

ACC = American College of Cardiology; AHA = American Heart Association; CABG = coronary artery bypass grafting; CAD = coronary artery disease; LAD = left anterior descending artery; LBBB = left bundle branch block, LMC = left main coronary artery; LMCE = left main coronary equivalent; LVEF = left ventricular ejection fraction; MI = myocardial infarction; MR = mitral regurgitation; NSTEMI = non-ST elevation myocardial infarction; PCI = percutaneous transluminal coronary angioplasty; STEMI = ST elevation myocardial infarction; VSD = ventricular septal defect

**Table 1.** AHA/ACC guidlines for CABG

**Class I**

**Class IIa**

**Class I**

**Class IIa**

**Failed PCI Class I**

**Class IIa**

**Class IIb**

**Class I**

**Class IIa**

and effective

**Previous CABG**

1. LMC 2. LMCE

1. LMC

tachycardia

2. Shock

**Life-Threatening ventricular Arrhythmias**

154 Coronary Artery Disease - Assessment, Surgery, Prevention

2. Three-vessel disease

1. Bypassable one- or two-vessel disease

1. Foreign body in critical position

1. Large territory at risk

2. Proximal LAD disease and one- or two-vessel disease

1. Ongoing ischemia with significant territory at risk

2. Shock with coagulopathy and no previous sternotomy

1. Shock with coagulopathy and previous sternotomy

1. Disabling angina refractory to medical therapy

2. Nonpatent previous bypass grafts, but with class I indications for native CAD

Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful

2. Vein grafts supplying LAD or large territory are "/> 50% stenosed

These become class I indications if arrhythmia is resuscitated cardiac death or sustained ventricular

3. Proximal LAD stenosis and two- to three-vessel disease

1. Significant viable territory and noncontractile myocardium

Myocardial revascularization in special circumstances is another important issue (Table 2). The common denominator of these distressed conditions is the accelerated risk of surgery. Intraoperative mortality and morbidity increase after CABG due to the multi-organ dysfunc‐ tion. Prolonged intubation, requiring ultrafiltration or hemodialysis, mechanical hemody‐ namic support, and/or infection risk can be very harmful despite full multisystem treatment. Nowadays, an aggressive strategy is favored to early myocardial revascularization in acute coronary syndrome, and surgical indication can be extended for these patients, but stent implantation is the first choice in the majority of this population. Surgical treatment has the advantage to bypass all occluded and/or stenotic coronary arteries at the same time, which suppresses early adverse outcomes. Left main or left main equivalent disease should be treated surgically, and this pathology is not a contraindication to use arterial grafts in any situation, especially for LIMA to LAD anastomosis. Severe LVD is not considered as an indication for surgery, but patients with hibernating or stunned myocardium can benefit from CABG. The only surgical indication for patients with severe LVD is the possibility of full revascularization during CABG. Otherwise, stent implantation should be the preferred approach. Total occlu‐ sion is not a contraindication for stent; but if it cannot be applied, surgery will be the alternative treatment. The important point is the diffuse involvement of atherosclerosis, which needs endarterectomy or long-segment anastomosis, and the choice of the acceptable revasculariza‐ tion procedure, which will be particularly influenced by the presence of comorbidities, especially in the elderly patients; but they cannot prevent usual surgery. In general, women have a higher risk for perioperative complications, but this adverse outcome can be explained by the presentation of female population at older ages with more extensive CAD, associated risk factors, LVD, and smaller body size. Diabetes is characterized by an inflammatory, proliferative, and prothrombotic state with more diffuse atherosclerosis, which may have a role in the increased risk of restenosis and occlusion. The first option is the complete revascu‐ larization, which is more often performed surgically than percutaneously. Coronary artery disease is a common reason of mortality among patients with end-stage renal failure and CABG is the option for myocardial revascularization. The main problem is the excessive atheroscle‐ rosis with severe calcification on the aortic wall and in the coronary arteries, which make surgery difficult. Recurrent ischemia after CABG or stent implantation is an indication of rerevascularization. Severe stenosis must be treated with stent after previous CABG, but CABG is the first option for re-revascularization after previous PCIs.


**Table 2.** Special circumstances for myocardial revascularization

#### **5. Bypass conduits**

Conduits for CABG are the base of surgical myocardial revascularization, because they are critical to the success of the procedure. Easy harvesting, simple implantation, long-term patency, and possible side effects must be taken into consideration during the preference of usable conduits for each patient to avoid an uneventful postoperative outcome and to achieve better long-term survival. Arterial grafts are favorable because of their long-term patency and resistance against atherosclerosis, which is related to the differences in biological characteris‐ tics between veins and arteries. Early vein graft failure (stenosis or occlusion) is the most important drawback of venous conduits; nevertheless, using venous grafts is still an integral part of coronary surgery. There are some differences between venous and arterial conduits, which may affect the long-term patency rate (Table 3).

1. Veins are more susceptible to vasoactive substances than arteries.

2. The venous wall is supplied by the vaso vasorum whereas the arterial wall may be supplied through the lumen in addition to the vaso vasorum.

3. The arterial endothelium may secrete more endothelium-derived relaxing factor and nitric oxide.

4. The structure of veins is more suited to low pressure whereas the artery to high pressure.

**Table 3.** Differences between venous and arterial grafts

#### **5.1. Arterial grafts**

Arterial grafts are not similar in anatomy or function, and there are differences regarding to contractility and endothelial function. Commonly harvested arterial conduits relate to different groups of arteries in the body (Table 4). The most important variation is the structural histology of arteries, whereas some arteries (Type II and III) contain more smooth muscle cells in their wall, thus are less elastic, or some arteries (Type I) contain more elastic laminae, thus are more elastic. Arterial grafts can develop spasm during surgical harvesting and handling, but the IMA shows the lowest vasospasm rate. Internal mammary artery releases more nitric oxide and endothelium-derived relaxing factor than the other arterial conduits. The reactivity of the arterial conduits changes along the length of arteries and the main mid-portion of them is less reactive than distal or proximal portions. This is the reason why the small and highly vasospastic distal part of the arterial grafts is trimmed before anastomosis. This part of conduits contains relatively smoother muscle cells and has a smaller diameter. The incidence of atherosclerotic changes in arterial conduits is rare and lower than in coronary arteries. Based on the superior long-term patency of the IMA, orientation to the other arteries has been popularized. The radial artery (RA) and the gastroepiploic artery (GEA) have been used for complete revascularization. Their usage has decreased in the past decade due to their lower patency rate, where the early occlusion of both grafts depends on higher response to vaso‐ constructive situations like the inotropic support, the low cardiac output syndrome (LCOS), and usage of different spasmogens.


**Table 4.** Arterial grafts

revascularization. Severe stenosis must be treated with stent after previous CABG, but CABG

Conduits for CABG are the base of surgical myocardial revascularization, because they are critical to the success of the procedure. Easy harvesting, simple implantation, long-term patency, and possible side effects must be taken into consideration during the preference of usable conduits for each patient to avoid an uneventful postoperative outcome and to achieve better long-term survival. Arterial grafts are favorable because of their long-term patency and resistance against atherosclerosis, which is related to the differences in biological characteris‐ tics between veins and arteries. Early vein graft failure (stenosis or occlusion) is the most important drawback of venous conduits; nevertheless, using venous grafts is still an integral part of coronary surgery. There are some differences between venous and arterial conduits,

2. The venous wall is supplied by the vaso vasorum whereas the arterial wall may be supplied through the lumen in

Arterial grafts are not similar in anatomy or function, and there are differences regarding to contractility and endothelial function. Commonly harvested arterial conduits relate to different groups of arteries in the body (Table 4). The most important variation is the structural histology of arteries, whereas some arteries (Type II and III) contain more smooth muscle cells

3. The arterial endothelium may secrete more endothelium-derived relaxing factor and nitric oxide. 4. The structure of veins is more suited to low pressure whereas the artery to high pressure.

is the first option for re-revascularization after previous PCIs.

2. Left main or left main equivalent (proximal LAD and Cx) disease

156 Coronary Artery Disease - Assessment, Surgery, Prevention

9. Previous myocardial revascularization (CABG or stent)

**Table 2.** Special circumstances for myocardial revascularization

which may affect the long-term patency rate (Table 3).

1. Veins are more susceptible to vasoactive substances than arteries.

**Table 3.** Differences between venous and arterial grafts

1. Acute coronary syndrome

**5. Bypass conduits**

addition to the vaso vasorum.

**5.1. Arterial grafts**

4. Total occlusions 5. The elderly population 6. The female population 7. Diabetes mellitus 8. End-stage renal disease

3. Severe left ventricular dysfunction

#### *5.1.1. Internal mammary artery*

The IMAs lie vertically and slightly laterally at a short distance from both margins of the sternum. The length of in situ left IMA is slightly longer than the right and ranges from 15 to 25 cm (mean 20 ± 2 cm). The IMA bifurcates into its terminal branches (musculophrenic and superior epigastric arteries) at the level of the sixth rib, and the in situ IMA should be cut before this distal bifurcation to get the acceptable intraluminal diameter for IMA–coronary artery anastomosis. Excessive traction, stretching, clamping, or misplaced metal clips during harvesting should be avoided to get a nontraumatized IMA without any injury (hematoma, dissection, rupture). We prefer to harvest the IMA using semi-skeletonized technique, which allows an increasing luminal diameter, providing a longer graft, allowing more distal anasto‐ mosis and sequential grafting. The full length of this IMA prevents any tension on the conduit, but some associated maneuvers can be needed to avoid stress on the IMA [31]. Making a window on the pericardium at the left side of the pulmonary artery, where the LIMA is lied down into the pericardium, prevents also the stretch of the LIMA [32]. The full length of the right IMA (RIMA) allows anterior (on the front of the heart) or lateral (through the transverse sinus) wall revascularization with optimal long-term patency, but the RCA revascularization is more difficult due to the distance of the distal segments [33].

#### *5.1.2. Radial artery*

The radial artery with higher patency rate according to saphenous vein can be a second alternative bypass conduit instead of vein grafts. The RA can have more atherosclerotic changes at the time of harvest than the IMA. The RA is very vasoreactive, and therefore is very sensitive to competitive flow. In the past two decades, using the RA as a pedicled arterial graft has been the preferred conduit as the second bypass graft, but the mid- and long-term patency rates are controversial. The failure of the RA grafts depends on three general ways: complete occlusion, string sign, or focal stenosis. The graft failure rate is the highest at the right system and equal to the saphenous vein graft [34]. The mid-term patency on the left coronary system is higher if the proximal anastomosis is performed on the ascending aorta [35]. Because the IMAs have higher long-term patency rates than the RA and the acceptable approach is using both IMAs for the left coronary system, usage of the RA has not increased and the saphenous vein is a more practicable conduit with a comparable patency rate than the RA for the right system [36]. The patient's nondominant arm is chosen for harvest, but the extremity must have adequate ulnar collateral circulation and the recurrent radial branch should be left intact [37]. The harvest of the left RA can be performed easily and simultaneously with the LIMA. Transient paresthesia, numbness, and thumb weakness could be seen, but the symptoms resolve with time [38].

#### *5.1.3. Gastroepiploic artery*

The gastroepiploic artery has been used as an alternative conduit or as part of an all-arterial revascularization strategy. The widespread use of the GEA has not been adopted due to the increased harvesting time, the potential abdominal complications, and inadequate early- and long-term patency rates. Opening the abdomen is a serious intervention and the GEA may be used only in patients who require any abdominal aortic surgery [39]. This arterial conduit has been used usually for the RCA revascularization because the in situ right GEA can reach only to the distal branches of the RCA.

#### *5.1.4. Other arteries*

Bilateral IMAs and the RA are often adequate to get full arterial complete myocardial revas‐ cularization. These grafts can be used in situ or in combined fashion, and distal anastomoses can be made single or sequential. Revascularization with the other arterial conduits has been left as an anecdotal use in the literature. Maybe, they can be used during redo or tredo CABG operations if there is no another conduits left. The studies on these arterial grafts have been left as academic researches [40].

#### **5.2. Venous grafts**

dissection, rupture). We prefer to harvest the IMA using semi-skeletonized technique, which allows an increasing luminal diameter, providing a longer graft, allowing more distal anasto‐ mosis and sequential grafting. The full length of this IMA prevents any tension on the conduit, but some associated maneuvers can be needed to avoid stress on the IMA [31]. Making a window on the pericardium at the left side of the pulmonary artery, where the LIMA is lied down into the pericardium, prevents also the stretch of the LIMA [32]. The full length of the right IMA (RIMA) allows anterior (on the front of the heart) or lateral (through the transverse sinus) wall revascularization with optimal long-term patency, but the RCA revascularization

The radial artery with higher patency rate according to saphenous vein can be a second alternative bypass conduit instead of vein grafts. The RA can have more atherosclerotic changes at the time of harvest than the IMA. The RA is very vasoreactive, and therefore is very sensitive to competitive flow. In the past two decades, using the RA as a pedicled arterial graft has been the preferred conduit as the second bypass graft, but the mid- and long-term patency rates are controversial. The failure of the RA grafts depends on three general ways: complete occlusion, string sign, or focal stenosis. The graft failure rate is the highest at the right system and equal to the saphenous vein graft [34]. The mid-term patency on the left coronary system is higher if the proximal anastomosis is performed on the ascending aorta [35]. Because the IMAs have higher long-term patency rates than the RA and the acceptable approach is using both IMAs for the left coronary system, usage of the RA has not increased and the saphenous vein is a more practicable conduit with a comparable patency rate than the RA for the right system [36]. The patient's nondominant arm is chosen for harvest, but the extremity must have adequate ulnar collateral circulation and the recurrent radial branch should be left intact [37]. The harvest of the left RA can be performed easily and simultaneously with the LIMA. Transient paresthesia, numbness, and thumb weakness could be seen, but the symptoms

The gastroepiploic artery has been used as an alternative conduit or as part of an all-arterial revascularization strategy. The widespread use of the GEA has not been adopted due to the increased harvesting time, the potential abdominal complications, and inadequate early- and long-term patency rates. Opening the abdomen is a serious intervention and the GEA may be used only in patients who require any abdominal aortic surgery [39]. This arterial conduit has been used usually for the RCA revascularization because the in situ right GEA can reach only

Bilateral IMAs and the RA are often adequate to get full arterial complete myocardial revas‐ cularization. These grafts can be used in situ or in combined fashion, and distal anastomoses can be made single or sequential. Revascularization with the other arterial conduits has been

is more difficult due to the distance of the distal segments [33].

158 Coronary Artery Disease - Assessment, Surgery, Prevention

*5.1.2. Radial artery*

resolve with time [38].

*5.1.3. Gastroepiploic artery*

to the distal branches of the RCA.

*5.1.4. Other arteries*

#### *5.2.1. Greater saphenous vein*

The saphenous vein is one of the most commonly used conduits in CABG. The early- and longterm patency of vein grafts is worse than that of arterial grafts, and one third of the vein grafts shows an important reduction in flow compared with the early postoperative period. Second disadvantage is easy kinking or torsion after anastomosis, which can cause fatal myocardial ischemia. However, its easiness to harvest, availability, usability, resistance to spasm, and acceptable long-term patency rate make vein grafts the second choice for revascularization conduits. There are no detrimental effects of harvest technique on vein morphology, endothe‐ lial structure or function, or graft patency. Saphenous vein can be harvested with an open (conventional = standard) or endoscopic technique. Endoscopic or minimal invasive harvest techniques could be more harmless. Open harvesting can be achieved with a complete or bridged approach. In reality, no-touch technique during open-vein harvest, in which the vein is removed with a pedicle of surrounding tissue, prevents vein injury and prolongs long-term durability. Specifically, vein grafts must not be grasped with forceps, stretched, or overdis‐ tended to avoid any endothelial damage. All venous tributaries should be ligated or clipped away from the vein itself and the lumen of the graft should not be injured, narrowed, or left with a blind sac on the side branches.

#### *5.2.2. Other veins*

Alternative venous grafts such as the lesser saphenous and cephalic veins are seldom secon‐ dary choice for vein graft. The lesser saphenous vein could be harvested with the same technique performed during standard vein harvest. Arm veins have significantly lower patency rate than saphenous veins, and for that reason, they are not used as a venous conduit.

#### **6. Surgical procedures**

Coronary bypass surgery can be performed with different techniques. The most common approach for CABG is on-pump revascularization via median sternotomy and under general anesthesia. Patients' characteristics and risk factors forward surgeons to prefer the appropriate approach for each individual case. Different techniques, variant approaches, new technologies, surgeon experience, and associated cardiovascular or organ pathologies restrict or direct cardiac surgeons to specific CABG procedures (Table 5). The benefits of off-pump techniques can be more evident for patients with high risk, especially for complications associated with cardiopulmonary bypass (CPB) and aortic manipulation. Myocardial protection prevents perioperative infarction and/or postischemic ventricular dysfunction (Table 6). Although considerable progress has been made in this field, the ideal technique has not yet to be discovered due to complex nature of ischemia–reperfusion cascade during surgical revascu‐ larization.


2. Systemic hypothermia and elective fibrillatory arrest

**Table 6.** Myocardial protection

#### **6.1. On-Pump CABG**

considerable progress has been made in this field, the ideal technique has not yet to be discovered due to complex nature of ischemia–reperfusion cascade during surgical revascu‐

larization.

**A. Arrested heart surgery with CPB B. Fibrillating heart surgery with CPB**

4. IABP support **D. Beating heart surgery without CPB**

**C. Beating heart surgery with circulatory support (central or peripheral)**

1. Standard off-pump through the median sternotomy (OPCAB)

1. Veno-arterial support (CPB, ECMO) 2. Atrio-arterial support (LHB devices) 3. Veno-venous support (RHB devices)

160 Coronary Artery Disease - Assessment, Surgery, Prevention

2. Minimal invasive off-pump (MIDCAB) 3. Endoscobic off-pump (OP-TECAB)

4. Robotically assisted off pump (BHTECAB)

1. Crystalloid cardioplegia (hypothermic) 2. Blood cardioplegia (cold – warm – tepid)

b) Retrograde (continuous)

1. Intermittent aortic cross-clamping with fibrillation 2. Systemic hypothermia and elective fibrillatory arrest

c) Combined

**B. Beating heart surgery**

1. off-pump CABG 2. on-pump CABG **C. Fibrillating heart surgery**

**Table 6.** Myocardial protection

a) Antegrade (intermittent, continuous)

i. Antegrade (arrest) – retrograde (continuous)

ii. antegrade (arrest and intermittent) – conduits (intermittent)

iii. antegrade (arrest) – retrograde (continuous) – conduits (intermittent)

5. Awake off-pump (ACAB)

**Table 5.** Surgical revascularization techniques

**A. Arrested heart (cardioplegic) surgery**

On-pump CABG surgery is the standard conventional technique for myocardial revasculari‐ zation which is performed via CPB. Despite the fact that off-pump CABG was the first performed technique, on-pump CABG has been used widespread around the world and became the first choice for surgery. An empty, nonbeating heart, a bloodless surgical field, and an easy exposure are essential reasons to prefer on-pump CABG for success of the revascula‐ rization procedure. Cardiopulmonary bypass technique includes several stages: cannulation, extracorporeal circulation, myocardial protection, distal with/without proximal anastomoses, and weaning from CPB.

Arterial cannulation for inflow and venous cannulation for outflow are necessary to establish extracorporeal circulation. Arterial cannulation is performed mostly on the ascending aorta, but in case of a contraindication, alternative arteries (femoral or axillary artery) can be preferred. The right atrium is the first choice for venous cannulation; but if there is a contra‐ indication, femoral vein can be used. After inserting the cannulas and finishing harvest of grafts, cardiopulmonary bypass machine starts to work. Blood comes out from the right atrium to the venous blood reservoir, then passes through the oxygenator and is sent to the aorta with a pump. A roller or centrifugal pump is used to continue body perfusion with an acceptable arterial pressure.

Extracorporeal circulation for support during cardiac surgery is uniform, because blood contacting to foreign, nonendothelial surfaces is collected in the reservoir and continuously recirculated throughout the body after oxygenated in the oxygenator. The heart and lung machine has some side effects on the body, which increases early and late morbidity and mortality. There are several adverse effects which cause organ dysfunctions (Table 7). The inflammatory reaction to CPB starts a powerful thrombotic stimulus and the production, release, and circulation of vasoactive and cytotoxic substances that influence the whole body. The inflammatory response produces the cytotoxic compounds and activates neutrophils and monocytes that will destroy organ and tissue cells. On the other hand, the body is able to resist and repair the most part of the cellular damage, although some abnormalities may appear later. The body temperature is lowered according to surgical procedures, but usually mild hypothermic (32–34°C) body perfusion is preferred for isolated CABG procedures to avoid cold or warm body temperature.


**Table 7.** Adverse effects of cardiopulmonary bypass

After cross-clamping the ascending aorta, cardiac arrest is achieved with a cardioplegic solution. Cardioplegic solutions containing a variety of chemical agents are used to arrest the heart rapidly in diastole, create a bloodless anastomotic field, and prevent myocardium against ischemia-reperfusion injury. Blood cardioplegia is chosen for myocardial protection of the arrested heart. Both cold (4–10°C) and warm (37°C) blood cardioplegic solutions have temperature-related advantages and disadvantages. But, tepid (29–32°C) blood cardioplegic solution is the other effective alternative to reduce anaerobic lactic acid released during the arrest period. The best and easiest way to prepare blood cardioplegic solution is to get isothermic (= body perfusion temperature; 32–34°C) blood directly from the pump. The most common cause of postoperative LCOS is inadequate myocardial preservation. There are many different ways of administering the cardioplegic solution: intermittent antegrade ± antegrade via grafts, continuous retrograde, or combined. Continuous retrograde cardioplegia is preferred for severe LMC lesions or diffuse multivessel disease; intermittent antegrade cardioplegia can preserve the myocardium in the other cases effectively. Noncardioplegic surgery is used very seldom, and elective fibrillatory arrest with systemic hypothermia is particularly applicable in case of severely calcified "porcelain aorta", where clamping the ascending aorta may be associated with increased risk of stroke and aortic dissection.

On-pump coronary artery bypass gives an advantage to the surgeon to make the distal anastomoses safely and confidently. Arteriotomy sites should be chosen as accurate as possible to reach the largest-sized coronary target, but distal enough to keep away from obstruction or significant atherosclerotic stenosis. If any target coronary artery has an intramyocardial course, this coronary artery must be opened at the epicardial indentation (for the LAD) or the myocardium on the reflection of the coronary artery can be divided with tight sharp dissection until the coronary artery is reached (for the Cx). The coronary arteriotomy must be performed at least 1.5 times the luminal diameter of the distal coronary artery to get acceptable blood flow, and the distal end of the conduit should be cut vertically at least the luminal diameter of the coronary artery to avoid any anastomotic kinking. Longer incision is not necessary and cannot increase blood supply; but if the graft has a wide diameter, the coronary arteriotomy should be kept open as long as to perform a successful anastomosis. The aim of the anastomosis is to connect the graft and the target coronary artery with fully endothelial approximation affording minimal resistance to flow. Sequential grafting permits efficient use of grafts and the distal anastomosis must be performed on the largest target vessel. The most important drawback of sequential grafting is the source of two or more distal targets on a single graft, where the flow could not be enough for this large myocardial area. For that reason, sequential anastomoses must be performed only on the branches of the same coronary artery. The LAD artery should be revascularized alone or sequential on itself. With the same reason, the IMA should be anastomosed on the LAD alone. Any composite grafting on the IMA (T- or Ygrafting) can increase the risk of inadequate perfusion of the LAD. Coronary arteriotomy and anastomotic technique in diffuse diseased coronary arteries are discussed in the next chapter. Proximal anastomoses are performed after the distal anastomoses under the same cross-clamp or after releasing the cross-clamp under the side-clamp during the rewarming. If the ascending aorta is severely calcific, proximal anastomoses can be performed on the in situ IMAs or brachiocephalic artery, or on the prosthetic tubular graft after the replacement of the ascending aorta.

On completion of all distal with/without proximal anastomoses, the aortic cross-clamp is removed and the heart begins to beat. The patient is prepared for conversion from mechanic circulation to native circulation, and during this period the bypass grafts are checked for kinks, twists, or tension and for presence of hemostasis. Persistency or regional wall motion abnor‐ malities may require bypass graft revision or replacement of additional bypass graft.

#### **6.2. Off-Pump CABG**

After cross-clamping the ascending aorta, cardiac arrest is achieved with a cardioplegic solution. Cardioplegic solutions containing a variety of chemical agents are used to arrest the heart rapidly in diastole, create a bloodless anastomotic field, and prevent myocardium against ischemia-reperfusion injury. Blood cardioplegia is chosen for myocardial protection of the arrested heart. Both cold (4–10°C) and warm (37°C) blood cardioplegic solutions have temperature-related advantages and disadvantages. But, tepid (29–32°C) blood cardioplegic solution is the other effective alternative to reduce anaerobic lactic acid released during the arrest period. The best and easiest way to prepare blood cardioplegic solution is to get isothermic (= body perfusion temperature; 32–34°C) blood directly from the pump. The most common cause of postoperative LCOS is inadequate myocardial preservation. There are many different ways of administering the cardioplegic solution: intermittent antegrade ± antegrade via grafts, continuous retrograde, or combined. Continuous retrograde cardioplegia is preferred for severe LMC lesions or diffuse multivessel disease; intermittent antegrade cardioplegia can preserve the myocardium in the other cases effectively. Noncardioplegic surgery is used very seldom, and elective fibrillatory arrest with systemic hypothermia is particularly applicable in case of severely calcified "porcelain aorta", where clamping the

162 Coronary Artery Disease - Assessment, Surgery, Prevention

ascending aorta may be associated with increased risk of stroke and aortic dissection.

On-pump coronary artery bypass gives an advantage to the surgeon to make the distal anastomoses safely and confidently. Arteriotomy sites should be chosen as accurate as possible to reach the largest-sized coronary target, but distal enough to keep away from obstruction or significant atherosclerotic stenosis. If any target coronary artery has an intramyocardial course, this coronary artery must be opened at the epicardial indentation (for the LAD) or the myocardium on the reflection of the coronary artery can be divided with tight sharp dissection until the coronary artery is reached (for the Cx). The coronary arteriotomy must be performed at least 1.5 times the luminal diameter of the distal coronary artery to get acceptable blood flow, and the distal end of the conduit should be cut vertically at least the luminal diameter of the coronary artery to avoid any anastomotic kinking. Longer incision is not necessary and cannot increase blood supply; but if the graft has a wide diameter, the coronary arteriotomy should be kept open as long as to perform a successful anastomosis. The aim of the anastomosis is to connect the graft and the target coronary artery with fully endothelial approximation affording minimal resistance to flow. Sequential grafting permits efficient use of grafts and the distal anastomosis must be performed on the largest target vessel. The most important drawback of sequential grafting is the source of two or more distal targets on a single graft, where the flow could not be enough for this large myocardial area. For that reason, sequential anastomoses must be performed only on the branches of the same coronary artery. The LAD artery should be revascularized alone or sequential on itself. With the same reason, the IMA should be anastomosed on the LAD alone. Any composite grafting on the IMA (T- or Ygrafting) can increase the risk of inadequate perfusion of the LAD. Coronary arteriotomy and anastomotic technique in diffuse diseased coronary arteries are discussed in the next chapter. Proximal anastomoses are performed after the distal anastomoses under the same cross-clamp or after releasing the cross-clamp under the side-clamp during the rewarming. If the ascending aorta is severely calcific, proximal anastomoses can be performed on the in situ IMAs or

The conventional on-pump CABG can be harmful for patients because of the side effects of the heart–lung machine causing fatal complications like stroke, renal, or respiratory failure. Although off-pump revascularization procedures have gained popularity because of the avoidance of the heart–lung machine during surgery in the past two decades, offpump CABG appears to have reached a plateau, and currently approximately 20% of all CABG procedures are performed on the beating heart without CPB. The main refuse is to success uncomplicated distal anastomoses on the beating heart, which needs bloodless and immobile anastomotic area. Coronary collateral circulation is not necessary until 15 min; but if the anastomotic duration will be longer, an intracoronary shunt may be used to prevent intraoperative ischemia [41].

#### **6.3. OPCAB**

Ideal candidates for off-pump coronary artery bypass (OPCAB) include those undergoing primary CABG with good target anatomy and preserved ventricular function. The benefit may be small in low-risk patients, but it is also not so much in high-risk patients. High-risk patients with diffuse multivessel disease and/or LVD cannot tolerate longer ischemia during distal anastomosis, cardiac manipulation, and/or displacement, which cause ventricular arrhythmia or hemodynamic deterioration. Standard OPCAB is performed through the median sternoto‐ my, and cardiac positioners and stabilizers increase the ability of the manipulation of heart with minimal hemodynamic compromise during lateral and/or inferior wall revascularization. A suction-based positioner is placed at the apex to pull the heart in the appropriate direction. The heart is not compressed, anatomo-functional geometry is keeped, and cardiac positioning is usually well tolerated. Then, a stabilizer is established with minimal tension on the epicar‐ dium to get a motionless anastomotic area. Some maneuvers may be used to get better exposure such as Trendelenburg position, turning the table toward any side, deep traction stitches; but usually they are not necessary. Medical support can be necessary to stabilize the arterial blood pressure and pulse rate. Anesthesia management is important not to make a per-operative myocardial infarction and life-threatening arrhythmia during distal anastomoses. Heparini‐ zation dose is lower than that in the standard on-pump CABG surgery. A soft silastic retractor tape is placed around the proximal segment of the lesion for transient occlusion of coronary blood flow, whereas a second tape could be placed around the distal segment in the presence of strong coronary backflow. The field is kept free of blood with a humidified CO2 or O2 blower. Careful attention must be paid to the sequence of grafting because regional myocardial perfusion is temporarily interrupted in the beating heart (Table 8). As a general rule, the collateralized vessel is grafted first and the collateralizing vessel grafted last. Additional option is a "proximal first" approach. But in our experience, the priority for grafting belongs to the in situ LIMA conduit and LIMA-LAD anastomosis is performed first. There is no doubt to manipulate the heart after this anastomosis, which is the main safety valve of the off-pump revascularization.

**First**, to revascularize the LAD with in situ LIMA to get fully LAD perfusion immediately after finishing the anastomosis.

**Second**, to anastomose the other in situ conduits to the target vessels (first IMA-LAD, then IMA-Cx, then RGEA-RCPD)

**Third**, to perform distal anastomoses of completely occluded or collateralized coronary arteries first, and then to perform proximal anastomoses.

to perform proximal anastomoses first, and then to perform distal anastomoses.

**Fourth**, to use an intracoronary shunt when beware of a large, dominant RCA with moderated proximal stenosis.

**Fifth**, to pass small or intramyocardial vessels on the lateral wall with an appropriate lesion for stent.

**Sixth,** to avoid any sequential grafting and to apply one-to-one bypass grafting.

**Seventh**, to keep away from endarterectomy if not total occluded coronary artery is present.

**Eight**, to convert on-pump beating heart surgery if moderate MR is present in patients with Cx and/or distal RCA lesions.

**Table 8.** Sequence of grafting in OPCAB

#### **6.4. MIDCAB**

Minimally invasive direct coronary artery bypass (MIDCAB) procedures have evolved to minimize surgical trauma caused by CPB and aortic manipulation, to avoid wound compli‐ cations developed by full median sternotomy and open harvesting techniques for bypass conduits, and to prevent respiratory troubles caused by prolonged mechanical ventilation. Only contraindication is emergent revascularization, and severe chronic obstructive pulmo‐ nary disease may also not be ideally suited to minithoracotomies. This surgical strategy is a very attractive procedure for coronary patients due to excellent cosmetic and an early and quick recovery. This approach has begun with the single LAD revascularization, but then it has been generalized to multivessel CABG. Another situation for MIDCAB is hybrid proce‐ dures, where all coronary arteries that required revascularization (except the LAD) are stented. There are several procedures to perform MIDCAB for single or multiple coronary artery revascularization (Table 9). The main difference of some MIDCAB techniques is the selective right lung ventilation and fast-track approach for extubation.

A. Incisional (avoid from sternotomy)

#### 1. Mini-thoracotomy (MIDCAB)

2. Mini-sternotomy

a) Reversed-J-inferior partial sternotomy

b) T-sternotomy

3. Rib cage lifting technique

4. Subxiphoidal approach

B. Instrumental

Careful attention must be paid to the sequence of grafting because regional myocardial perfusion is temporarily interrupted in the beating heart (Table 8). As a general rule, the collateralized vessel is grafted first and the collateralizing vessel grafted last. Additional option is a "proximal first" approach. But in our experience, the priority for grafting belongs to the in situ LIMA conduit and LIMA-LAD anastomosis is performed first. There is no doubt to manipulate the heart after this anastomosis, which is the main safety valve of the off-pump

**First**, to revascularize the LAD with in situ LIMA to get fully LAD perfusion immediately after finishing the

**Second**, to anastomose the other in situ conduits to the target vessels (first IMA-LAD, then IMA-Cx, then RGEA-

**Third**, to perform distal anastomoses of completely occluded or collateralized coronary arteries first, and then to

**Fourth**, to use an intracoronary shunt when beware of a large, dominant RCA with moderated proximal stenosis.

**Eight**, to convert on-pump beating heart surgery if moderate MR is present in patients with Cx and/or distal RCA

Minimally invasive direct coronary artery bypass (MIDCAB) procedures have evolved to minimize surgical trauma caused by CPB and aortic manipulation, to avoid wound compli‐ cations developed by full median sternotomy and open harvesting techniques for bypass conduits, and to prevent respiratory troubles caused by prolonged mechanical ventilation. Only contraindication is emergent revascularization, and severe chronic obstructive pulmo‐ nary disease may also not be ideally suited to minithoracotomies. This surgical strategy is a very attractive procedure for coronary patients due to excellent cosmetic and an early and quick recovery. This approach has begun with the single LAD revascularization, but then it has been generalized to multivessel CABG. Another situation for MIDCAB is hybrid proce‐ dures, where all coronary arteries that required revascularization (except the LAD) are stented. There are several procedures to perform MIDCAB for single or multiple coronary artery revascularization (Table 9). The main difference of some MIDCAB techniques is the selective

**Fifth**, to pass small or intramyocardial vessels on the lateral wall with an appropriate lesion for stent.

**Seventh**, to keep away from endarterectomy if not total occluded coronary artery is present.

to perform proximal anastomoses first, and then to perform distal anastomoses.

**Sixth,** to avoid any sequential grafting and to apply one-to-one bypass grafting.

right lung ventilation and fast-track approach for extubation.

revascularization.

164 Coronary Artery Disease - Assessment, Surgery, Prevention

perform proximal anastomoses.

**Table 8.** Sequence of grafting in OPCAB

anastomosis.

RCPD)

lesions.

**6.4. MIDCAB**

1. Conventional

2. Endoscopic

3. Robotic assisted fully endoscopic (TECAB)

C. Respiratuar (avoid from extended mechanical ventilation)

1. Limited mechanic ventilation (fast track anesthesia = intraoperative extubation)

2. Spontaneous ventilation with high thoracic epidural anesthesia (ACAB)

D. Circulatuar (avoid from cardiopulmonary bypass)


**Table 9.** Minimal invasive surgical techniques

#### *6.4.1. Minithoracotomy*

Standard MIDCAB is usually performed through a left anterior minithoracotomy. The skin incision is made 5–6 cm long in the fourth intercostal space, but removal of a rib is not necessary in any case. This approach is used for single vessel bypass (LIMA-LAD), and the anastomosis is performed with/without any stabilizator. Rib dislocation or fracture is very seldom. After the completion of the anastomosis, the rest of the operation is standard and the patient can be extubated in the operating room or in a couple of hours in the intensive care unit. The patient can be discharged on the 3rd or 4th postoperative day. Because this approach is a highly demanding technical procedure and must be performed by experienced surgeons, this singlevessel CABG procedure will remain an alternative revascularization strategy to stent for patients with complex proximal LAD lesion, chronic occlusions, and in-stent restenosis.

#### *6.4.2. Ministernotomy*

This approach is preferred mostly by unexperienced surgeons because of similar technical manipulations of the full median sternotomy procedure. The sternotomy is performed partially and divided from xiphoid to the second intercostal space in a down to up direction. Then, the sternum is transected obliquely to the left side (reverse-J-inferior ministernotomy) for single-vessel CABG or the sternum is cut bilaterally (T-sternotomy) for multivessel CABG. These both partial lower median sternotomy techniques leave the manubrium intact to preserve the continuity and stability of the superior thoracal aperture for early and late postoperative recovery. Furthermore, conversion to full sternotomy is more practical than the other small thoracotomy techniques. Only reverse-J-inferior ministernotomy can obstruct proximal anastomosis on the ascending aorta if any free graft is used for bypass surgery [42]. The rest of the surgical revascularization is similar to the conventional CABG procedures. Reverse-J-inferior sternotomy approach preserves respiratory function postoperatively and accelerates the early postoperative recovery, especially in ACAB [43]. T-ministernotomy causes less chest tube drainage, and shorter recovery with early discharge [44].

#### **6.5. TECAB**

Robotically assisted totally endoscopic coronary bypass surgery (TECAB) is the most advanced form of less invasive surgical coronary revascularization, which can be an elegant surgical component to hybrid revascularization. However, procedural complexity and a steep learning curve have limited its penetrance in the surgical community. The procedure can be applied on on-pump or off-pump. There are several instruments for anastomoses, but on-pump is more acceptable. Peripheral cannulation is the main disadvantage in some patients, who are not candidates for TECAB.

#### **6.6. ACAB**

Awake coronary artery bypass (ACAB) surgery has been offered as a new and unique technique to decrease the adverse effects of general anesthesia. This new modality of CABG combines the minimal invasive nature of MIDCAB with the avoidance of endotracheal intubation and mechanical ventilation. Due to its nature, ACAB offers several advantages over general anesthesia, including better analgesia, decreased myocardial ischemia, improved pulmonary function, reduced stress response, and discharge in couple days of surgery. Cardiac sympatholysis achieves bradycardia, coronary and arterial grafts' vasodilatation and prevents arrhythmia. The aim of this technique is to provide somatosensory and motor block at the T1 and T8 levels and motor block of the intercostal muscles while preserving diaphragmatic respiration. Thoracic sympatholysis allows complete arterial revascularization with bilateral IMAs with/without RA [45]. A perfect understanding and cooperation between patient and anesthesiologist is necessary for ACAB, while an excellent collaboration between cardiac surgeon and anesthesiologist provides a flawless procedure. Combining advanced anesthetic and high-level surgical merit, this alternative CABG procedure makes surgical treatment feasible and suitable for patients who are not candidates for conventional general anesthesia with endotracheal intubation.

#### **7. Special circumstances**

extubated in the operating room or in a couple of hours in the intensive care unit. The patient can be discharged on the 3rd or 4th postoperative day. Because this approach is a highly demanding technical procedure and must be performed by experienced surgeons, this singlevessel CABG procedure will remain an alternative revascularization strategy to stent for patients with complex proximal LAD lesion, chronic occlusions, and in-stent restenosis.

This approach is preferred mostly by unexperienced surgeons because of similar technical manipulations of the full median sternotomy procedure. The sternotomy is performed partially and divided from xiphoid to the second intercostal space in a down to up direction. Then, the sternum is transected obliquely to the left side (reverse-J-inferior ministernotomy) for single-vessel CABG or the sternum is cut bilaterally (T-sternotomy) for multivessel CABG. These both partial lower median sternotomy techniques leave the manubrium intact to preserve the continuity and stability of the superior thoracal aperture for early and late postoperative recovery. Furthermore, conversion to full sternotomy is more practical than the other small thoracotomy techniques. Only reverse-J-inferior ministernotomy can obstruct proximal anastomosis on the ascending aorta if any free graft is used for bypass surgery [42]. The rest of the surgical revascularization is similar to the conventional CABG procedures. Reverse-J-inferior sternotomy approach preserves respiratory function postoperatively and accelerates the early postoperative recovery, especially in ACAB [43]. T-ministernotomy

causes less chest tube drainage, and shorter recovery with early discharge [44].

Robotically assisted totally endoscopic coronary bypass surgery (TECAB) is the most advanced form of less invasive surgical coronary revascularization, which can be an elegant surgical component to hybrid revascularization. However, procedural complexity and a steep learning curve have limited its penetrance in the surgical community. The procedure can be applied on on-pump or off-pump. There are several instruments for anastomoses, but on-pump is more acceptable. Peripheral cannulation is the main disadvantage in some patients, who are not

Awake coronary artery bypass (ACAB) surgery has been offered as a new and unique technique to decrease the adverse effects of general anesthesia. This new modality of CABG combines the minimal invasive nature of MIDCAB with the avoidance of endotracheal intubation and mechanical ventilation. Due to its nature, ACAB offers several advantages over general anesthesia, including better analgesia, decreased myocardial ischemia, improved pulmonary function, reduced stress response, and discharge in couple days of surgery. Cardiac sympatholysis achieves bradycardia, coronary and arterial grafts' vasodilatation and prevents arrhythmia. The aim of this technique is to provide somatosensory and motor block at the T1 and T8 levels and motor block of the intercostal muscles while preserving diaphragmatic respiration. Thoracic sympatholysis allows complete arterial revascularization with bilateral

*6.4.2. Ministernotomy*

166 Coronary Artery Disease - Assessment, Surgery, Prevention

**6.5. TECAB**

**6.6. ACAB**

candidates for TECAB.

Coronary artery surgery is not unique because of other tissue and/or organ pathologies (Table 10). Coronary revascularization can be performed isolated in patients with single- or multi‐ vessel disease or combined with other coronary artery interventions and/or cardiac proce‐ dures. Associated non-coronary arterial pathologies can make CABG procedures more complex. Surgical strategies for diffuse CAD are discussed in the next chapter.


**Table 10.** Special situations

#### *Ascending Aorta Pathologies*

Ascending aortic pathologies can be treated with different methods. Ascending aortic athero‐ sclerosis can be a very important risk factor for distal embolization, especially for stroke. Epiaortic ultrasound is the only method to identify the extent of atherosclerosis of the ascend‐ ing aorta. Severe atherosclerosis of the ascending aorta forwards surgeons to the right axillary or femoral artery cannulation. Coronary bypass is performed with "no-touch technique" using only pedicled arterial conduits or composite grafts (T- or Y-graft). If aortic valve replacement is required, the ascending aorta replacement will be performed. Ascending aortic aneurysm and/or dissection required a composite graft replacement during CABG; proximal anastomo‐ ses can be performed easily on the tubular graft or composite conduits can be used.

#### *Left Ventricular Dysfunction*

Nowadays, most patients with multivessel disease are candidates for surgical revasculariza‐ tion, but the depressed left ventricular function could be a serious contraindication for surgery or risk factor for early adverse outcomes. Resting regional perfusion defects and LV systolic function are improved after CABG in at least 65% of patients with LVD. However, preopera‐ tively depressed resting global left ventricular systolic function cannot change less than 2 weeks after surgery. If this improvement fails to occur, incomplete revascularization or early graft failure is usually found. When preoperative global LVD is severe (LVEF < 30%), myo‐ cardial scarring is usually greater and limits recovery of left ventricular function. Complete revascularization is more effective than CABG strategy for myocardial recovery, and there is no reason to prefer OPCAB with incomplete revascularization [46].

#### *Ischemic Mitral Regurgitation*

Ischemic LVD represents the first leading cause for mitral regurgitation (MR), which can alter the spatial relationship between the papillary muscles and chordae tendineae and thereby results in functional MR. Some degree of functional MR is found approximately 30% of patients undergoing CABG. In most cases, MR develops from tethering of the posterior leaflet because of regional LVD. The incidence and severity of MR vary inversely with the LVEF and directly with the left ventricular end-diastolic pressure. Correction of reversible ischemia changes the left ventricular geometry and functional MR can decrease or it can be corrected intraopera‐ tively using a ring. The new designed 3D mitral rings are useful, but MR can worsen with time if the left ventricular remodeling continues.

#### *Valvular Pathologies*

Nonischemic mitral valve diseases are not common with CAD, but they are not contraindica‐ tions for coronary surgery. Mitral stenosis is rare, but mitral valve resection with subvalvular apparatus does not decrease left ventricular function. Degenerative mitral valve regurgitation can be associated with LVD; in this situation, subvalvular apparatus should be preserved to prevent the limited left ventricular function. Tricuspid regurgitation is a rare pathology and seen mostly secondary to the left-side valvular diseases, and can be a sign of pulmonary hypertension.

Degenerative aortic stenosis is the most common associated cardiac pathology because of advanced age of CAD patients. Aortic stenosis can be moderate or severe, but asymptomatic. The decision for aortic stenosis may be mixed. If CABG is the decisive indication, the indication for moderate aortic stenosis is more flexible and aortic valve replacement should be performed to prevent patients from reoperation. Aortic valve stenosis with moderate signs (mean gradient > 30 mmHg; aortic valve area 1–1.5 cm2 ), pathologic bicuspid aortic valve, or severe annulo‐ valvular calcification can indicate for associated aortic valve replacement. Stentless biological valves must be the first choice if the aorticoventricular continuity is not disturbed [47].

#### *Acute Coronary Syndrome*

*Ascending Aorta Pathologies*

168 Coronary Artery Disease - Assessment, Surgery, Prevention

*Left Ventricular Dysfunction*

*Ischemic Mitral Regurgitation*

*Valvular Pathologies*

hypertension.

if the left ventricular remodeling continues.

Ascending aortic pathologies can be treated with different methods. Ascending aortic athero‐ sclerosis can be a very important risk factor for distal embolization, especially for stroke. Epiaortic ultrasound is the only method to identify the extent of atherosclerosis of the ascend‐ ing aorta. Severe atherosclerosis of the ascending aorta forwards surgeons to the right axillary or femoral artery cannulation. Coronary bypass is performed with "no-touch technique" using only pedicled arterial conduits or composite grafts (T- or Y-graft). If aortic valve replacement is required, the ascending aorta replacement will be performed. Ascending aortic aneurysm and/or dissection required a composite graft replacement during CABG; proximal anastomo‐

ses can be performed easily on the tubular graft or composite conduits can be used.

no reason to prefer OPCAB with incomplete revascularization [46].

Nowadays, most patients with multivessel disease are candidates for surgical revasculariza‐ tion, but the depressed left ventricular function could be a serious contraindication for surgery or risk factor for early adverse outcomes. Resting regional perfusion defects and LV systolic function are improved after CABG in at least 65% of patients with LVD. However, preopera‐ tively depressed resting global left ventricular systolic function cannot change less than 2 weeks after surgery. If this improvement fails to occur, incomplete revascularization or early graft failure is usually found. When preoperative global LVD is severe (LVEF < 30%), myo‐ cardial scarring is usually greater and limits recovery of left ventricular function. Complete revascularization is more effective than CABG strategy for myocardial recovery, and there is

Ischemic LVD represents the first leading cause for mitral regurgitation (MR), which can alter the spatial relationship between the papillary muscles and chordae tendineae and thereby results in functional MR. Some degree of functional MR is found approximately 30% of patients undergoing CABG. In most cases, MR develops from tethering of the posterior leaflet because of regional LVD. The incidence and severity of MR vary inversely with the LVEF and directly with the left ventricular end-diastolic pressure. Correction of reversible ischemia changes the left ventricular geometry and functional MR can decrease or it can be corrected intraopera‐ tively using a ring. The new designed 3D mitral rings are useful, but MR can worsen with time

Nonischemic mitral valve diseases are not common with CAD, but they are not contraindica‐ tions for coronary surgery. Mitral stenosis is rare, but mitral valve resection with subvalvular apparatus does not decrease left ventricular function. Degenerative mitral valve regurgitation can be associated with LVD; in this situation, subvalvular apparatus should be preserved to prevent the limited left ventricular function. Tricuspid regurgitation is a rare pathology and seen mostly secondary to the left-side valvular diseases, and can be a sign of pulmonary

Acute coronary syndromes cover a wide spectrum of CAD, while non-ST-segment elevation is the best and risk-free indication for early CABG, if stent implantation is ineffective. Isolated and limited elevation of troponin is not a contraindication for early surgical treatment. Surgical revascularization can be postponed in patients with transmural myocardial infarction without life-threatening complications. But, acute hemodynamic deterioration is a serious and often fatal complication of ongoing myocardial infarction, and delay of CABG can be disadvanta‐ geous.

#### *Carotid Artery Disease*

Carotid artery disease is an important risk factor of stroke after CABG, especially in the older age group, and the prevalence is higher than 30%. Routine carotid sonographic evaluation is the most widely used preoperative screening test to detect important asymptomatic carotid artery stenosis. If the preoperative carotid Doppler study demonstrates significant stenosis (>80%), it must be verified by arteriography. Combined surgical revascularization has been used in most centers with two different approaches: concomitant or staged. In both approaches, carotid endarterectomy is performed primarily to prevent stroke. When a concomitant procedure is performed, carotid endarterectomy can be performed during hypothermic CPB before CABG, which provides additional brain protection [48]. Neither strategy has not been proved to be superior to another, and an individualized approach is most appropriate. Preoperative stenting is a more suitable alternative approach to combine carotid endarterec‐ tomy and CABG.

#### *Abdominal Aortic Disease*

When an abdominal aortic pathology is elective, it should be postponed after CABG. The combination of an abdominal aortic aneurysm and CAD can be seen more common in elderly patients. A combined procedure can be necessary in patients with unstable CAD and abdomi‐ nal aortic aneurysm. Combined surgical treatment using CBP is a safe and effective strategy. Because conventional surgery can increase complications postoperatively, any minimal invasive combined approach can improve early postoperative outcomes.

#### *Peripheral Vascular Disease*

Patients with CAD and peripheral atherosclerosis are older and have more widespread vascular disease with/without end-organ damage. Coronary atherosclerosis is usually diffuse and requires more complicated surgical revascularization. Left subclavian artery stenosis is a major contraindication for harvesting LIMA, but left subclavian artery bypass or stent implantation can increase LIMA flow. In this situation, RIMA can be used as a pedicled graft to LAD, or LIMA can be used as a free graft. Iliac artery stenosis with LIMA collateral circulation is another contraindication for LIMA-LAD anastomosis, but peripheral artery revascularization can solve this problem. Except severe peripheral stenosis, staged surgical approach should be preferred (CABG first).

#### *Chronic Renal Failure*

One of the main reasons of death in 40 to 50% of patients on hemodialysis is coronary athero‐ sclerosis. It is well known that cardiac pathologies have more serious outcomes if the establish‐ ed renal failure is concomitant, especially the progression of the CAD is more accelerated in hemodialysis patients. Calcification of the coronary territory is a serious complication of longterm hemodialysis and complicates surgical revascularization. Cerebral and/or visceral vascular complications related to accelerated atherosclerosis and particle embolization after CABG are seen more often in patients with end-stage renal failure than in other patients. Hemodialysis-dependent patients are at high risk of CPB-related complications such as bleeding, volume overload, and cerebrovascular events during conventional CABG, whereas OPCAB surgery can be the optimum revascularization strategy to prevent these complica‐ tions [49].

#### *Malignancy*

Recently, cardiac disease and malignancy are seen together more frequently in patients undergoing surgical revascularization. Cancer therapy should be applied as soon as possible after diagnosis; however, patients with high risk of a major cardiac event should take cardiac surgery as a priority. Conventional open cardiac surgery causes a transient immunosuppres‐ sion due to increasing immunoregulatory factors. Although these biochemical changes are short term and not likely to induce carcinogenesis, they may lead to cancer surveillance with the spread and growth potential of coexisting cancer cells. Overall mortality increases after open heart surgery, and a shorter time interval (especially < 2 years) between the cancer diagnosis and subsequent cardiac surgical intervention can aggravate cancer-specific deaths. Results of a multicenter research show that on-pump CABG surgery with CPB increases significantly the relative risk of skin melanoma, cancer of the lung and bronchus, and overall cancer incidence when compared with those patients who underwent OPCAB [50]. Off-pump myocardial revascularization must be preferred over the use of CPB in combined surgery to prevent the adverse effects of the extracorporeal circulation, especially during lung surgery [51]. Further researches may obtain optimal strategies for management of cancer patients with cardiovascular comorbidities.

#### *Chronic Obstructive Pulmonary Disease*

Chronic obstructive pulmonary disease (COPD) is often considered as a risk factor for postoperative outcomes after CABG, but the presence and worsening of COPD do not show any increase in mortality following surgical revascularization in patients with COPD com‐ pared with normal patients. However, severe COPD patients have more frequent pulmonary infections, atrial fibrillation, and a longer hospital stay when they are compared with mild to moderate COPD patients and patients with normal spirometry. Cardiopulmonary bypass has adverse effects on the alveolar stability by activation of the complement cascade, sequestration of the neutrophil in the pulmonary vascular territory, release of the oxygen-derived free radicals, and change of the composition of alveolar surfactant. Atelectasis is the most observed complication after CPB and mechanical ventilation, especially in the first two days after the operation. Because patients with COPD are affected negatively from adverse effects of both CPB and full median sternotomy in the mean of postoperative pulmonary complications, it seems more advantageous that this patient group will be operated on using OPCAB, especially with minimal invasive techniques [52].

#### **8. Outcomes**

major contraindication for harvesting LIMA, but left subclavian artery bypass or stent implantation can increase LIMA flow. In this situation, RIMA can be used as a pedicled graft to LAD, or LIMA can be used as a free graft. Iliac artery stenosis with LIMA collateral circulation is another contraindication for LIMA-LAD anastomosis, but peripheral artery revascularization can solve this problem. Except severe peripheral stenosis, staged surgical

One of the main reasons of death in 40 to 50% of patients on hemodialysis is coronary athero‐ sclerosis. It is well known that cardiac pathologies have more serious outcomes if the establish‐ ed renal failure is concomitant, especially the progression of the CAD is more accelerated in hemodialysis patients. Calcification of the coronary territory is a serious complication of longterm hemodialysis and complicates surgical revascularization. Cerebral and/or visceral vascular complications related to accelerated atherosclerosis and particle embolization after CABG are seen more often in patients with end-stage renal failure than in other patients. Hemodialysis-dependent patients are at high risk of CPB-related complications such as bleeding, volume overload, and cerebrovascular events during conventional CABG, whereas OPCAB surgery can be the optimum revascularization strategy to prevent these complica‐

Recently, cardiac disease and malignancy are seen together more frequently in patients undergoing surgical revascularization. Cancer therapy should be applied as soon as possible after diagnosis; however, patients with high risk of a major cardiac event should take cardiac surgery as a priority. Conventional open cardiac surgery causes a transient immunosuppres‐ sion due to increasing immunoregulatory factors. Although these biochemical changes are short term and not likely to induce carcinogenesis, they may lead to cancer surveillance with the spread and growth potential of coexisting cancer cells. Overall mortality increases after open heart surgery, and a shorter time interval (especially < 2 years) between the cancer diagnosis and subsequent cardiac surgical intervention can aggravate cancer-specific deaths. Results of a multicenter research show that on-pump CABG surgery with CPB increases significantly the relative risk of skin melanoma, cancer of the lung and bronchus, and overall cancer incidence when compared with those patients who underwent OPCAB [50]. Off-pump myocardial revascularization must be preferred over the use of CPB in combined surgery to prevent the adverse effects of the extracorporeal circulation, especially during lung surgery [51]. Further researches may obtain optimal strategies for management of cancer patients with

Chronic obstructive pulmonary disease (COPD) is often considered as a risk factor for postoperative outcomes after CABG, but the presence and worsening of COPD do not show any increase in mortality following surgical revascularization in patients with COPD com‐ pared with normal patients. However, severe COPD patients have more frequent pulmonary infections, atrial fibrillation, and a longer hospital stay when they are compared with mild to

approach should be preferred (CABG first).

170 Coronary Artery Disease - Assessment, Surgery, Prevention

*Chronic Renal Failure*

tions [49].

*Malignancy*

cardiovascular comorbidities.

*Chronic Obstructive Pulmonary Disease*

Because CABG is probably the most performed procedure in cardiac surgery, an enormous amount of information is available about morbidity and mortality, and also long-term survival. Comparison with stent can never give us the real world results, because every patient has his/ her specific risk analysis. The early mortality and morbidity rates for isolated CABG are stabilized (Table 11) [53].



**Table 11.** STS-database for isolated CABG (July 2011 – March 2013; N = 197.672)

#### *Operative Mortality*

The risk profile of patients with isolated CAD has changed in the past decade and they have more complicated comorbidities: older age, LVD, accelerated coronary atherosclerosis, a higher burden of non-coronary atherosclerotic disease, re-operation, emergency operation, multi-stent application, multi-organ pathologies. However, early outcomes after CABG continue to improve and the early cumulative mortality rate is below 2%, lower than 1% in lower-risk patients. The most common reasons for death are heart failure (65%), neurologic events (7.5%), hemorrhage (7%), respiratory failure (5.5%), and dysrhythmia (5.5%).

*Long-Term Survival*

The survival rate after isolated CABG is higher than 98% for the first month and 97% for first year, 92% for 5 years, 80% for 10 years, 65% for 15 years, and 51% for 20 years. Late mortality depends on non-use of ITA, closure of grafts, progression of native coronary atherosclerosis, and also comorbidities. Procedure-related factors that influence long-term survival include complete revascularization, selection of bypass grafts, and intraoperative myocardial protec‐ tion. Mortality rate is the highest in the first month, but it is parallel to that of general population after the first postoperative year. Time-related prevalence of sudden death is low after CABG (at least, 95% for the first 10 years) and the most significant risk factor for sudden death is LVD.

#### *Quality of Life*

**Operative Characteristics** Elective 42.2% OPCAB 16.6%

Full median sternotomy 98.5%

IMA use 100% LIMA 94% BIMA 5.1%

Cardiopulmonary bypass 91 (71 – 115)

Any blood products used 31.4%

Operative mortality 1.5% Mortality or morbidity 11.8% Permanent stroke 1.2% Re-exploration 2.2%

Renal failure required dialysis 1.8% Prolonged ventilation 8.2% Mediastinitis 0.3% Surgical site infection 1.2%

**Table 11.** STS-database for isolated CABG (July 2011 – March 2013; N = 197.672)

*Operative Mortality*

*Long-Term Survival*

Sepsis 0.7%

The risk profile of patients with isolated CAD has changed in the past decade and they have more complicated comorbidities: older age, LVD, accelerated coronary atherosclerosis, a higher burden of non-coronary atherosclerotic disease, re-operation, emergency operation, multi-stent application, multi-organ pathologies. However, early outcomes after CABG continue to improve and the early cumulative mortality rate is below 2%, lower than 1% in lower-risk patients. The most common reasons for death are heart failure (65%), neurologic

events (7.5%), hemorrhage (7%), respiratory failure (5.5%), and dysrhythmia (5.5%).

Skin-to-skin 225 (183 – 275) Operating room 301 (253 – 359)

RBC 2 units **Early Outcomes**

IMA harvesting technique (standard direct vision) 98.9%

Operation durations (minutes)

172 Coronary Artery Disease - Assessment, Surgery, Prevention

Satisfactory quality of life after CABG is the most important and favorable outcome for all patients who quantify that according to freedom from angina, heart failure, re-hospitalization or re-intervention, and to improvement of a reasonable exercise capacity. Maximal exercise capacity is generally improved at least for 3 to 10 years after CABG, whereas degree of recovery and ultimate exercise capacity reached depend on preoperative LV function, completeness of revascularization, and long-term graft patency. When preoperative global LV dysfunction is severe (EF < 30%), myocardial scarring usually affects a wide area and limits improvement of LV function. But, incomplete revascularization of viable myocardium is the primary cause of the failure of postoperative recovery. Global LV function during exercise begins to increase noticeably 2 weeks after CABG in most patients; however, when it still does not improve in 3 months after CABG, one or more bypass grafts are usually occluded or stenosed.

#### *Recurring Myocardial Ischemia*

Return of angina is the most common post-CABG ischemic event. Freedom from angina is approximately 95% at 1 year, 80% at 5 years, 60% at 10 years, 40% at 15 years, and 20% at 20 years. Return of angina during the first 6 months depends on incomplete revascularization or graft failure, whereas progression of native-vessel disease and grafts are serious risk factors for the late recurrence of angina. Including perioperative myocardial infarction, the overall freedom from new myocardial infarction after first surgical complete revascularization is 95% at least 5 years, 85% at 10 years, 75% at 15 years, 55% at 20 years. The overall freedom from any re-intervention (stent or re-CABG) is about 97% at 5 years, 90% at 10 years, 70% at 15 years, and 50% at 20 years. Venous graft occlusion (incidence: 15% at the first year, and 60% at 10 years) is the most common reason for re-intervention, and progression of atherosclerosis in the native coronary arteries (incidence: 50% at 10 years) is the second. Using IMA(s) reduces the frequency of reoperation, but not the frequency of stent implantation. Requirement of reoperation begins to rise noticeably after 5 years and it is usually preferred when the left main or LAD disease is life threatening. Because the operative risk is double in the second CABG than those in the primary, stent implantation with the assistance of embolic protection devices for stenotic vein grafts or native vessels is used more often in symptomatic patients with patent IMA-LAD anastomosis.

#### *Early Postoperative Complications*

**1.** Perioperative myocardial infarction is defined by appearance of new Q waves or signifi‐ cant elevation of myocardial biomarkers. It relates with early or late death and also with

postoperative ischemic cardiomyopathy. It depends on inadequate myocardial preserva‐ tion, incomplete revascularization or graft failure. Prevalence of perioperative myocardial infarction is between 2.5 and 5%. Early renewing or completing revascularization of the target vessels can be lifesaving.


#### **Author details**

Kaan Kırali\* and Hakan Saçlı

\*Address all correspondence to: kaankirali@sakarya.edu.tr

Department of Cardiovascular Surgery, Faculty of Medicine, Sakarya University, Turkey

#### **References**

.

postoperative ischemic cardiomyopathy. It depends on inadequate myocardial preserva‐ tion, incomplete revascularization or graft failure. Prevalence of perioperative myocardial infarction is between 2.5 and 5%. Early renewing or completing revascularization of the

**2.** Low cardiac output syndrome varies between 4 and 9% and develops during or after the operation and increases operative mortality 10- to 15-fold. Inotropic supports with/ without intra-aortic balloon pump support or mechanical circulation support must be used to maintain a systolic blood pressure > 90 mmHg or a cardiac index > 2.2 L/min/m2

**3.** Adverse neurologic events after surgery can be major or minor. Type 1 deficits (stupor, coma) are more fatal, but the incidence is lower than 1.5%. Severe atherosclerosis of the ascending aorta and/or severe stenosis with/without any calcification in the carotid arteries are the most common risk factors for the type 1 neurologic events. Type 2 deficits are characterized by deterioration of intellectual function and memory, but it is more difficult to characterize. The risk factors are CPB, aortic manipulation, or air embolization. Off-pump is not superior to on-pump, but avoidance of proximal anastomoses on the

**4.** Renal failure can develop after cardiac surgery and the incidence of renal dysfunction not requiring dialysis rises to 6.5%, but requiring hemodialysis is below 1.5%. Operative mortality rate is directly related to patients' renal functions: proximately 1% with good renal function, 20% with renal dysfunction, 60% with renal dysfunction and dialysis. Older age (< 70 years), LVD, diabetes mellitus with silent renal dysfunction, preoperative renal dysfunction (creatinine > 2 mg/dL), and LCOS are the major risk factors for postop‐ erative renal failure. Off-pump CABG can be a more appropriate alternative for complete revascularization in patients with chronic renal failure or patients with estimated

**5.** Deep sternal wound infection carries a mortality rate of 25%. Obesity and diabetes are strong independent risk factors for mediastinitis, whereas reoperation, re-exploration for bleeding, and blood transfusions are other variables. The use of bilateral IMAs does not increase mediastinitis risk, especially with skeletonization technique. However, bilateral IMA harvest must be avoided in obese diabetic women or patients with severe COPD. In spite of all the recent advances in open cardiac surgery, mediastinitis still is an important

risk factor for early mortality, but it does not affect the graft patency [54].

Department of Cardiovascular Surgery, Faculty of Medicine, Sakarya University, Turkey

ascending aorta can prevent type 2 neurologic deficits.

target vessels can be lifesaving.

174 Coronary Artery Disease - Assessment, Surgery, Prevention

postoperative renal dysfunction.

and Hakan Saçlı

\*Address all correspondence to: kaankirali@sakarya.edu.tr

**Author details**

Kaan Kırali\*


[31] Mansuroğlu D, Şişmanoğlu M, Ömeroğlu SN, Kırali K, İpek G, Yakut C. A simple method to prevent internal thoracic artery tension: Single pericardio-thoracic suture technique. J Card Surg 2004;19(3):264–6.

[17] Gay WA Jr, Ebert PA. Functional, metabolic, and morphologic effects of potassium-

[18] Follette DM, Mulder DG, Maloney JV, Buckberg GD. Advantages of blood cardiople‐ gia over continuous coronary perfusion or intermittent ischemia. Experimental and

[19] Ankeney JL. To use or not use the pump oxygenator in coronary bypass operations

[20] Benetti FJ. Direct coronary surgery with saphenous vein bypass without either cardi‐ opulmonary bypass or cardiac arrest. J Cardiovasc Surg (Torino) 1985;26(3):217–22.

[21] Buffolo E, Andrade JCS, Succi JE, et al. Direct revascularization of the myocardium without extracorporeal circulation. Description of the technic and preliminary re‐

[22] Ömeroğlu SN, Kırali K, Güler M, et al. Midterm angiographic assessment of coro‐ nary artery bypass grafting without cardiopulmonary bypass. Ann Thorac Surg

[23] Eleveli G, Mataracı İ, Büyükbayrak F, Erkin A, Şişmanoğlu M, Kırali K. Complete re‐ vascularization with or without cardiopulmonary bypass using arterial grafts: the six-month angiographic results. Turkish J Thorac Cardiovasc Surg 2011;19(1):1–6.

[24] Işık Ö, Dağlar B, Kırali K, et al. Coronary bypass surgery via minithoracotomy on the

[25] Karagöz H, Sönmez B, Bakkaloğlu B, et al. Coronary artery bypass grafting in the conscious patient without endotracheal general anesthesia. Ann Thorac Surg

[26] Kırali K, Koçak T, Güzelmeriç F, et al. Off-pump awake coronary revascularization using bilateral internal thoracic arteries. Ann Thorac Surg 2004;78(5):1598–603.

[27] Kırali K, Güler M, Dağlar B, et al. Videothoracoscopic internal mammary artery har‐ vest for coronary artery bypass. Asian Cardiovasc Thorac Ann 1999;7(4):259–62.

[28] Loulmet D, Carpentier A, d'Attellis N, et al. Endoscopic coronary artery bypass grafting with the aid of robotic assisted instruments. J Thorac Cardiovasc Surg

[29] Lehr EJ, Chitwood W Jr, Bonatti J. Technique of totally endoscopic robot-assisted offpump coronary artery bypass grafting. In: Raja SG and Amrani M. (Eds.) Off-Pump Coronary Artery Bypass Grafting. New York, NY: Nova Science Publishers, Inc.

[30] 2011 ACCF/AHA Guideline for coronary artery bypass surgery: executive summary.

induced cardioplegia. Surgery 1973;74(2):284–90.

176 Coronary Artery Disease - Assessment, Surgery, Prevention

[editorial]. Ann Thorac Surg 1975;19(1):108–9.

sults. Arq Bras Cardiol 1982;38(5):365–73.

2000;70(3):844–9.

2000;70(1):91–6.

1999;118(1):4–10.

2012, pp.123–143.

Circulation 2011;124(23):2610–42.

clinical study. J Thorac Cardiovasc Surg 1978;76(5):604–19.

beating heart. Ann Thorac Surg 1997;63(Suppl1):S57–60.


## **Surgical Treatment in Diffuse Coronary Artery Disease**

Kaan Kırali and Yücel Özen

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61514

#### **Abstract**

[43] Kırali K, Kayalar N, Özen Y, Sareyyüpoğlu B, Güzelmeriç F, Koçak T, Yakut C. Re‐ versed-J inferior versus full median sternotomy: which is better for awake coronary

[44] Kırali K. (Abstract) Mini-T sternotomy for awake coronary revascularization with bi‐ lateral internal thoracic artery. Interactive Cardiovasc Thorac Surg 2004;3(Suppl

[45] Kırali K. Composite bilateral internal thoracic artery grafts via standard sternotomy for lateral wall revascularization in conscious patients. Heart Surg Forum 2005;8(6):

[46] Kırali K, Rabus MB, Yakut N, et al. Early- and long-term comparison of the on- and off-pump bypass surgery in patients with left ventricular dysfunction. Heart Surg

[47] Kırali K. Stentless bioprostheses for aortic valve replacement. In: Aikawa E (Ed.). Cal‐ cific Aortic Valve Disease. In Tech, Croatia, 2013: pp. 411–449 (ISBN

[48] Ozen Y, Aksoy E, Sarikaya S, Aydin E, Altas O, Rabus MB, Kirali K. Effect of hypo‐ thermia in patients undergoing simultaneous carotid endarterectomy and coronary

[49] Erentuğ V, Akıncı E, Kırali K, et al. Complete off-pump coronary revascularization in patients with dialysis-dependent renal disease. Tex Heart Inst J 2004;31(2):153–6. [50] Pinto CA, Marcella S, August DA, Holland B, Kostis JB, Demissie K. Cardiopulmona‐ ry bypass has a modest association with cancer progression: a retrospective cohort study. http://www.ncbi.nlm.nih.gov/pubmed/24180710 BMC Cancer (web)

[51] Ömeroğlu SN, Erdoğan HB, Kırali K, et al. Combined coronary artery bypass graft‐

[52] Güler M, Kırali K, Toker ME, et al. Different CABG methods in patients with chronic

[53] Harskamp RE, Brennan JM, Xian Y, et al. Practice patterns and clinical outcomes af‐ ter hybrid coronary revascularization in the United States. An analysis from the STS

[54] Mansuroğlu D, Ömeroğlu SN, Kaya E, Kırali K, et al. Does mediastinitis affect the

ing and lung surgery. Asian Cardiovasc Thorac Ann 2004;12(3):260–2.

obstructive pulmonary disease. Ann Thorac Surg 2001;71(1):152–7.

adult cardiac database. Circulation 2014;130(11):872–9.

graft patency? J Card Surg 2005;20(3):208–11.

artery bypass graft surgery. Cardiovasc J Afr 2015;26(1):17–20.

bypass surgery. J Card Surg 2005;20(5):463–8.

1):S64–5.

340–4.

Forum 2002;5(2):177–81.

178 Coronary Artery Disease - Assessment, Surgery, Prevention

978-953-51-1150-4).

2013;13:519.

Diffuse coronary artery atherosclerosis can be defined as "consecutive or longitudinal" and "complete or partial" obstruction in coronary vessels. Most of the patients with dia‐ betes, hyperlipidemia, chronic renal insufficiency, connective tissue disease, and multistented coronary arteries have diffuse atherosclerotic lesions in the coronary territory. Viable large myocardium without necrosis is the only coronary bypass indication in these patients, because it is very difficult to find any healthy area for anastomosis. This type of coronary occlusion frequently stimulates the formation of collateral vessels that protect against extensive myocardial ischemia. The choice of a surgical method also depends on the nature of the coronary artery, and multisegment plaques and healthy-area intervals simplify complete revascularization. On the other hand, a more aggressive treatment mo‐ dality should be preferred when no soft site can be identified for arteriotomy or there is an extensively diseased area that is not amenable to grafting. The less invasive techniques are "don't touch the plaque" techniques (jumping multi-bypass, sequential bypass, hy‐ brid interventions). Sometimes an aggressive diffuse plaque formation needs to be treat‐ ed with "touch the plaque" techniques (long-segment anastomosis, patch-plasty, endarterectomy ± patch-plasty). In simple forms, a limited long-segment anastomosis of conduits eliminates the occlusion of the limited atherosclerotic plaque where the whole lesion is opened and cross-covered by the graft. In the accelerated form of coronary arte‐ riosclerosis, the atherosclerotic plaque appears widespread and the full-length lumen of the coronary artery can get very narrow or occluded totally. The long-segment lesion is usually calcified and it inhibits any kind of stitching; however, the plaque can be separat‐ ed easily from the arterial wall in order to create an appropriate lumen in the total oc‐ cluded coronary artery. Because the aggressive endarterectomy increases the operation risk, the arteriotomy should be extended until the normal lumen with normal intima in the distal segment of the coronary artery. In general, severity and distribution of coronary arteriosclerosis tend to increase with time but the rate of increase is highly variable and difficult to predict. Although diffuse atherosclerosis is severe enough, it is uncommon to render any patient unsuitable for surgery.

**Keywords:** Diffuse atherosclerosis, endarterectomy, patch-plasty, sequential bypass, jumping bypass

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

#### **1. Introduction**

Coronary artery disease usually involves the proximal portion of the larger epicardial coronary arteries, but generally not their intramural branches. In most patients, atherosclerotic lesions in coronary territory are segmental and eccentric, and they affect particularly bifurcations and sharp curvatures, whereas the rest of long segments of coronary arteries are plaque-free. Diffuse coronary artery disease can be defined as the presence of multiple atherosclerotic stenoses or long-segment occlusions in coronary territory. Atheromatous materials spread toward distal and retain a long segment of coronary arteries which can obstruct coronary lumen "consecutive or longitudinal" and "complete or partial".

In general, severity and distribution of coronary arteriosclerosis tend to increase with time but the rate of increase is highly variable and difficult to predict. Diffuse atherosclerosis severe enough to render the patient unsuitable for surgery is uncommon. On the other hand, progression of atherosclerosis in the native coronary arteries after coronary bypass surgery is not rare and accelerated atherosclerosis usually is the main contraindication for reoperation. The early and late results of endarterectomy are inferior to those of routine coronary bypass, but it offers a viable alternative not to leaving a territory ungrafted. Rate of aggressive progression of atherosclerosis cannot as yet be examined directly in multivariable risk factor analyses, but this progression can be slowed by intensive lipid-lowering therapy.

The nature of atherosclerotic coronary artery disease is a chronic inflammation and fibropro‐ liferation of large- and medium-sized epicardial arteries consisting of the progressive depo‐ sition or degenerative accumulation of lipid-containing plaques on the innermost layer of the arterial wall. The basic mechanism of atherosclerosis is endothelial dysfunction which is characterized by the reduction of the endothelium-derived vasodilators, especially nitric oxide, and an increase in endothelium-derived contracting factors. The immune-inflammatory response involving macrophages, T-lymphocytes and intimal smooth muscle cells tries healing and repairing injured endothelium, stabilizing plaques, protecting rupture, and avoiding thrombosis. If the atherosclerotic stimuli persist over long time, the reparative response may accelerate and target to the progressive occlusion of the arterial lumen. Progressive diffuse coronary artery stenosis involves the following processes: local atheroma, lipid accumulation, biologic stimuli of vessel wall, chronic inflammation, cellular necrosis, plaque formation and complications, and calcification. Arterial wall injury is most often related to age, diabetes, smoking, dyslipidemia, hypertension, hyperuremia, and immunosuppressive therapy, which trigger and accelerate the inflammatory response aimed at restoring arterial wall integrity. During the progression of atherosclerosis, endothelial and smooth muscle cells die by apop‐ tosis, and an atheromatous plaque covers the defects of the endothelium. A vulnerable plaque is a nonobstructive, silent coronary lesion, which suddenly becomes obstructive and sympto‐ matic. Plaque rupture with/without thrombotic complications is the main reason for this acute coronary syndrome with/without complications. The lesions responsible for acute episodes are generally less calcified than plaques responsible for chronic stable angina, because calcification is the last part of the healing response to atherosclerosis and it appears to have no direct link to thrombosis. Because diffuse type of coronary disease is time-consuming, slowly developing occlusions frequently stimulate the formation of collateral vessels that protect myocardium against extensive ischemia. Viable large myocardium without necrosis is the only indication for coronary revascularization in these patients (without mechanical complications of myocardial infarction), because it is very difficult to find any healthy area for anastomosis. Consequently, the relative severity and associated risk balance between focal stenosis and diffuse disease cannot be easily compared when making revascularization decisions [1]. The physiological anatomy of coronary arteries must be detailed for myocardial revascularization, but quantifying the anatomic severity of diffuse lesions is difficult. Lower coronary flow reserve associated with severe diffuse disease may neutralize or override any potential benefit from eliminating stenosis by stents. On the other hand, more diffusely expanded coronary atherosclerosis can cause higher mortality rate during coronary bypass artery grafting (CABG) than focal lesions because of association of more complicated vessels, which are not appro‐ priate for suturing or distal perfusion after anastomosis. Patients with diffuse coronary artery disease can also face a twofold increased risk of in-hospital mortality or major morbidities, which is independent of reoperation [2].

#### **2. Etiology**

**1. Introduction**

180 Coronary Artery Disease - Assessment, Surgery, Prevention

Coronary artery disease usually involves the proximal portion of the larger epicardial coronary arteries, but generally not their intramural branches. In most patients, atherosclerotic lesions in coronary territory are segmental and eccentric, and they affect particularly bifurcations and sharp curvatures, whereas the rest of long segments of coronary arteries are plaque-free. Diffuse coronary artery disease can be defined as the presence of multiple atherosclerotic stenoses or long-segment occlusions in coronary territory. Atheromatous materials spread toward distal and retain a long segment of coronary arteries which can obstruct coronary

In general, severity and distribution of coronary arteriosclerosis tend to increase with time but the rate of increase is highly variable and difficult to predict. Diffuse atherosclerosis severe enough to render the patient unsuitable for surgery is uncommon. On the other hand, progression of atherosclerosis in the native coronary arteries after coronary bypass surgery is not rare and accelerated atherosclerosis usually is the main contraindication for reoperation. The early and late results of endarterectomy are inferior to those of routine coronary bypass, but it offers a viable alternative not to leaving a territory ungrafted. Rate of aggressive progression of atherosclerosis cannot as yet be examined directly in multivariable risk factor

The nature of atherosclerotic coronary artery disease is a chronic inflammation and fibropro‐ liferation of large- and medium-sized epicardial arteries consisting of the progressive depo‐ sition or degenerative accumulation of lipid-containing plaques on the innermost layer of the arterial wall. The basic mechanism of atherosclerosis is endothelial dysfunction which is characterized by the reduction of the endothelium-derived vasodilators, especially nitric oxide, and an increase in endothelium-derived contracting factors. The immune-inflammatory response involving macrophages, T-lymphocytes and intimal smooth muscle cells tries healing and repairing injured endothelium, stabilizing plaques, protecting rupture, and avoiding thrombosis. If the atherosclerotic stimuli persist over long time, the reparative response may accelerate and target to the progressive occlusion of the arterial lumen. Progressive diffuse coronary artery stenosis involves the following processes: local atheroma, lipid accumulation, biologic stimuli of vessel wall, chronic inflammation, cellular necrosis, plaque formation and complications, and calcification. Arterial wall injury is most often related to age, diabetes, smoking, dyslipidemia, hypertension, hyperuremia, and immunosuppressive therapy, which trigger and accelerate the inflammatory response aimed at restoring arterial wall integrity. During the progression of atherosclerosis, endothelial and smooth muscle cells die by apop‐ tosis, and an atheromatous plaque covers the defects of the endothelium. A vulnerable plaque is a nonobstructive, silent coronary lesion, which suddenly becomes obstructive and sympto‐ matic. Plaque rupture with/without thrombotic complications is the main reason for this acute coronary syndrome with/without complications. The lesions responsible for acute episodes are generally less calcified than plaques responsible for chronic stable angina, because calcification is the last part of the healing response to atherosclerosis and it appears to have no direct link to thrombosis. Because diffuse type of coronary disease is time-consuming, slowly

analyses, but this progression can be slowed by intensive lipid-lowering therapy.

lumen "consecutive or longitudinal" and "complete or partial".

Most of the patients with diabetes, hyperlipidemia, chronic renal insufficiency, connective tissue disease, heart transplantation, and multi-stented coronary arteries have diffuse athero‐ sclerotic lesions in the coronary territory. All of these diseases affect and accelerate coronary arteriosclerosis differently [3]. Restenosis after first CABG can also be a reason for the diffuse coronary atherosclerosis, but usually these patients have ungraftable diffuse diseased coronary vasculature and none of the specific revascularization methods can be used.

#### **2.1. Diabetes mellitus**

Compared with nondiabetic patients, diabetes mellitus increases the incidence of coronary artery disease two to four times as much and accelerates the nature of the atherosclerosis. The nature of coronary artery disease in diabetic patients is clinically challenging because it causes an extensive and diffuse multivessel involvement. Hyperglycemia is directly related to the atherosclerotic development, progression, and instability due to induced endothelial dysfunc‐ tion (abnormal nitric oxide biology, increased endothelin and angiotensin II, reduced prosta‐ cyclin activity), abnormalities in lipid metabolism (high triglyceride and LDL-cholesterol, low HDL-cholesterol), systemic inflammation (increased oxidative stress, accumulation of advanced glycation and products), and disorders in the proteo-fibrinolytic system and platelet biology (thrombosis). Hyperglycemia can deplete the cellular NADPH pool and induce with high levels of fatty acids to oxidative stress on phospholipids and proteins. Insulin resistance is the main actor to the endothelial dysfunction in type II diabetes, and endothelial dysfunction is closely complicated with microangiopathy and atherosclerosis in diabetic patients. Endo‐ thelial dysfunction decreases the capacity of nitric oxide synthase enzyme and depleted nitric oxide, which effects endothelial cell-dependent vasodilatation. Overexpression of growth factors causes endothelial cells and vascular smooth muscle proliferation. All of these negative changes accelerate atherosclerosis in all arterial territories, and the involvement of coronary arteries can be very extensive and diffuse with either serious jumping stenoses or long-segment narrowing with/without occlusion. The optimal strategy of coronary revascularization is controversial, but CABG has better long-term survival and freedom from re-interventions [4]. Diabetic patients have a higher restenosis rate after stent implantation and also progression of diffuse disease after stent implantation forms new lesions in diabetic patients than non-diabetic patients more often. Clinical outcomes in CABG patients are similar for diabetic and nondiabetic patients, while outcomes after stent could be worse for diabetic patients [5]. In diabetic patients with multivessel coronary artery disease, rates of death and myocardial infarction in 5 years are significantly lower in patients treated with CABG due to more complete revascu‐ larization, which bypasses several lesions and prevents coronary territory against progressive proximal coronary stenosis [6]. On the other hand, the operative risk in patients with diabetes might be a consequence of a preoperatively endothelial dysfunction and an inflammatory response to extracorporeal circulation characterized by an impaired release of interleukin-6 and increased turnover of E-selectin [7]. Simple distal anastomosis for each coronary artery cannot be enough to supply blood along the coronary territory, and most of the diabetic patients with diffuse multivessel coronary artery disease require specific surgical revascula‐ rization modalities, which can increase perioperative myocardial damage and operative mortality.

#### **2.2. Hypercholesterolemia**

Cholesterol is one of the most important risk factors for the development of premature coronary artery disease, which is characterized without any serious intravascular stenosis. Cholesterol levels and coronary artery disease show a strong and linear relationship, whereas cholesterol levels even in the normal range may inhibit endothelium-dependent vasodilatation in all arterial beds. The pathogenesis of atherosclerosis in the obese population can be related to metabolic syndrome associated with insulin intolerance and dyslipidemia, which cause endothelial dysfunction with decreasing nitric oxide production. Lowering of LDL-cholesterol rather than moderate weight loss is more effective to improve endothelial function, because the coronary vasculature is affected by the atherosclerosis process, and the most atherosclerotic lesions are associated with remarkable neovascularization of the vasa vasorum, which can cause intra-plaque rupture and bleeding. Hypercholesterolemia is one of the most important factors to stimulate this process and its role begins in the early atherosclerotic remodeling before plaque formation [8]. Hyperlipidemia-related coronary lesions are very predisposed to spread lengthways coronary territory and cause diffuse stenosis or occlusion, and calcification is usually associated with this type of atherosclerosis.

#### **2.3. End-stage renal disease**

A strong relationship subsists between chronic renal failure and coronary artery disease, and atherosclerosis can be accelerated in patients with end-stage renal disease due to multifactorial reasons [9]. Increased oxidative stress, hyperhomocysteinemia, hyperlipidemia, hyperglyce‐ mia and others are also important comorbidities. The main pathology is the impairment of endothelium-dependent vasodilatation. Dialysis-dependent renal failure patients undergoing CABG can have a greater degree of distal and/or diffuse coronary artery disease burden compared with matched patients with silent renal failure. The diffuseness of coronary atherosclerosis in patients with end-stage renal disease can be severe and the intraluminal lesions are usually calcified. Extensive calcification of all arterial structures in the body can inhibit conventional CABG strategies, which increase surgical outcomes. Impaired distal runoff of the coronary arteries is another strong independent predictor of operative mortality. All kinds of complex anastomotic techniques can be used in these patients, and endarterectomy can be very easy to perform to get adequate distal run-off. Restenosis after CABG is not uncommon in this group of patients, especially if saphenous vein is used.

#### **2.4. Connective tissue disease**

changes accelerate atherosclerosis in all arterial territories, and the involvement of coronary arteries can be very extensive and diffuse with either serious jumping stenoses or long-segment narrowing with/without occlusion. The optimal strategy of coronary revascularization is controversial, but CABG has better long-term survival and freedom from re-interventions [4]. Diabetic patients have a higher restenosis rate after stent implantation and also progression of diffuse disease after stent implantation forms new lesions in diabetic patients than non-diabetic patients more often. Clinical outcomes in CABG patients are similar for diabetic and nondiabetic patients, while outcomes after stent could be worse for diabetic patients [5]. In diabetic patients with multivessel coronary artery disease, rates of death and myocardial infarction in 5 years are significantly lower in patients treated with CABG due to more complete revascu‐ larization, which bypasses several lesions and prevents coronary territory against progressive proximal coronary stenosis [6]. On the other hand, the operative risk in patients with diabetes might be a consequence of a preoperatively endothelial dysfunction and an inflammatory response to extracorporeal circulation characterized by an impaired release of interleukin-6 and increased turnover of E-selectin [7]. Simple distal anastomosis for each coronary artery cannot be enough to supply blood along the coronary territory, and most of the diabetic patients with diffuse multivessel coronary artery disease require specific surgical revascula‐ rization modalities, which can increase perioperative myocardial damage and operative

Cholesterol is one of the most important risk factors for the development of premature coronary artery disease, which is characterized without any serious intravascular stenosis. Cholesterol levels and coronary artery disease show a strong and linear relationship, whereas cholesterol levels even in the normal range may inhibit endothelium-dependent vasodilatation in all arterial beds. The pathogenesis of atherosclerosis in the obese population can be related to metabolic syndrome associated with insulin intolerance and dyslipidemia, which cause endothelial dysfunction with decreasing nitric oxide production. Lowering of LDL-cholesterol rather than moderate weight loss is more effective to improve endothelial function, because the coronary vasculature is affected by the atherosclerosis process, and the most atherosclerotic lesions are associated with remarkable neovascularization of the vasa vasorum, which can cause intra-plaque rupture and bleeding. Hypercholesterolemia is one of the most important factors to stimulate this process and its role begins in the early atherosclerotic remodeling before plaque formation [8]. Hyperlipidemia-related coronary lesions are very predisposed to spread lengthways coronary territory and cause diffuse stenosis or occlusion, and calcification

A strong relationship subsists between chronic renal failure and coronary artery disease, and atherosclerosis can be accelerated in patients with end-stage renal disease due to multifactorial reasons [9]. Increased oxidative stress, hyperhomocysteinemia, hyperlipidemia, hyperglyce‐ mia and others are also important comorbidities. The main pathology is the impairment of

mortality.

**2.2. Hypercholesterolemia**

182 Coronary Artery Disease - Assessment, Surgery, Prevention

**2.3. End-stage renal disease**

is usually associated with this type of atherosclerosis.

Several connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, Takayasu disease) are characterized by vascular dysfunction and excessive fibrosis. The presence of coronary microvascular dysfunction is the common pathologic change in various chronic inflammatory diseases [10]. Cardiac manifestation of these chronic diseases can be estimated lower, because most of them are asymptomatic. Diffuse form of these pathologies has a distressed clinical course with severe organ involvement. First, an endothe‐ lial injury occurs early in the disease process leading to endothelial dysfunction. Myofibro‐ blasts drawn into the arterial wall by cellular growth factors contribute to the thickening of the intimal layer, compromising regional blood flow by narrowing the arterial lumen. In the absence of epicardial coronary stenosis, the abnormal coronary flow is dependent on the structural remodeling of the small coronary arteries and arterioles. Aggressive surgical interventions are usually ineffective, but multi-anastomoses can be applicable. Because diffuse atherosclerosis shows strict adhesions between arterial wall layers, endarterectomy can never satisfy to load out the intra-arterial lumen for appropriate anastomosis.

#### **2.5. Heart transplantation**

The occurrence of coronary artery disease is common in posttransplant patients, and athero‐ sclerotic process is different from normally occurring coronary artery disease. This type of atherosclerosis is specific for heart transplanted patients, and it affects the entire length of the coronary arteries, and diffuse intimal proliferation develops without damage to the internal elastic lamina in contrast to classic atherosclerosis. The intimal proliferation developed by smooth muscle cells and macrophages contains cholesterol crystals and lipid components, but calcification is rare. This lesion affects large epicardial coronary arteries as well as the pene‐ trating intramyocardial branches, and occlusion of these small branches is the first reason for acute coronary syndrome. Coronary endothelial vasodilator dysfunction is a common and early indicator for graft atherosclerosis, which is caused by both immunological and classic risk factors. The immunological response is the first stimulus causing endothelial damage and this injury alters endothelial permeability, with consequent myointimal hyperplasia and extracellular matrix synthesis. Alloimmune injury starts when donor antigens expressed from the donor endothelial cells interact with recipient dendritic cells, and the activated macro‐ phages secrete several factors, which stimulate the proliferation of smooth muscle cells and vascular remodeling [11]. Before microvasculature occlusions, stent or standard CABG can be preferred for the treatment of newly developed epicardial lesions, but endarterectomy may not be usually applicable in most diffuse cases, and retransplantation is the only option under these circumstances.

#### **2.6. Multistented coronary arteries**

The problem of restenosis after stenting represents a special case of arterial hyperplastic disease and the in-stent restenosis is made from myxomatous tissue, whereas accelerated intimal hyperplasia occludes the distal segment of the same coronary vessel after stenting. Availability of access to healthy coronary wall for revascularization is usually feasible in patients receiving a single stent implantation in one or each coronary artery. However, the distal vascular bed of multi-stented coronary artery is often influenced by the accelerated atherosclerosis and diffusely diseased where it is impossible to find any healthy area for distal anastomosis. Sometimes, open endarterectomy with removal of stent(s) can remain the last option for surgical revascularization.

#### **3. Surgical treatment techniques**

Diffuse atherosclerosis has been highly widespread among patients with coronary artery disease in the last two decades, because simple lesions are usually treated with stent inter‐ ventions in the early phase of the coronary pathology. Diffuse coronary lesion and reduced coronary flow reserve can be silent due to several collaterals, but it might result in severe functional limitation, chronic low-level ischemia, and myocardial remodeling. Low-level ischemia can be a potential driver of both first coronary vasomotor and myocardial dysfunc‐ tion, and then remodeling in heart failure with preserved ejection fraction. Diffuse atheroscle‐ rosis and microvascular dysfunction-associated coronary artery disease comorbid conditions may guide new, more effective, aggressive, and therapeutic interventions for global cardio‐ vascular risk reduction due to complete revascularization. There is no difference in event-free survival between CABG or stent implantation in patients with high coronary flow reserve; however, CABG is significantly more effective than stent in patients with low coronary flow reserve [12]. Diffuseness of coronary artery disease is a serious risk factor for early and late adverse events after coronary revascularization, but the acceptable strategy should be complete revascularization. Standard bypass method (finding an appropriate lumen and performing anastomosis) is usually not possible in the diffusely diseased coronary arteries, and such a region, which may be found at most distal, cannot be expected to bring any benefit. For this reason, in such cases, it is required to apply a complex method other than standard bypass method. When the atherosclerotic stenosis is local, it is technically possible and easy to revascularize the distal segment directly, but in diffuse coronary artery disease or in the presence of diffuse stenotic regions, different techniques should be implemented for complete revascularization.

The treatment of the diffused-type coronary artery disease has always been an issue; however, this scenario is challenging for cardiac surgeons because diffuse atheromatous lesions frequently render epicardial coronary vessels unsuitable for conventional distal grafting. However, there are some strategies to perform a complete revascularization with increasing complexity and mortality risk sequentially in these patients. Second, to attenuate or prevent perioperative infarction and/or postischemic ventricular dysfunction caused by inadequate myocardial protection, there are many different administrative ways for cardioplegic solu‐ tions, but the optimal delivery method of cardioplegia also remains controversial. Off-pump bypass can be another option when coronary artery is totally occluded and retrograde flow supplies the myocardium.

The aggressive involvement type of atherosclerosis is the corner stone for coronary revascu‐ larization, and the first choice of the aggressive surgical techniques also depends on this nature (Table 1). A coronary artery with multisegment plaques and healthy-area intervals simplifies complete revascularization, and multiple revascularization of this coronary artery with different methods seems applicable by every cardiac team. On the other hand, a more aggres‐ sive treatment modality should be preferred when no soft site can be identified for arteriotomy or there is an extensively diseased area not amenable to grafting or no other methods except transplantation. The routine application for arteriotomy in patients with local stenosis is to perform the anastomotic incision proximal enough to get the larger-sized coronary target but distal enough from atherosclerotic lesion. Arteriotomy should be more complicated or extended to get appropriate coronary lumen and anastomotic area in patients with diffuse coronary lesions. The main goal of CABG is to finish complete revascularization using different surgical approaches during open-heart surgery. Using a single graft or multi-grafts or a hybrid procedure (stent + bypass) is a reliable option to revascularize all segments of each coronary artery: **don't touch the plaque techniques**. Sometimes an aggressive plaque formation needs to be touched using extended arteriotomy with/without endarterectomy and patch-plasty: **touch the plaque techniques**.

#### **Don't Touch the Plaque Techniques**

#### **1. Jumping bypass technique**

phages secrete several factors, which stimulate the proliferation of smooth muscle cells and vascular remodeling [11]. Before microvasculature occlusions, stent or standard CABG can be preferred for the treatment of newly developed epicardial lesions, but endarterectomy may not be usually applicable in most diffuse cases, and retransplantation is the only option under

The problem of restenosis after stenting represents a special case of arterial hyperplastic disease and the in-stent restenosis is made from myxomatous tissue, whereas accelerated intimal hyperplasia occludes the distal segment of the same coronary vessel after stenting. Availability of access to healthy coronary wall for revascularization is usually feasible in patients receiving a single stent implantation in one or each coronary artery. However, the distal vascular bed of multi-stented coronary artery is often influenced by the accelerated atherosclerosis and diffusely diseased where it is impossible to find any healthy area for distal anastomosis. Sometimes, open endarterectomy with removal of stent(s) can remain the last option for

Diffuse atherosclerosis has been highly widespread among patients with coronary artery disease in the last two decades, because simple lesions are usually treated with stent inter‐ ventions in the early phase of the coronary pathology. Diffuse coronary lesion and reduced coronary flow reserve can be silent due to several collaterals, but it might result in severe functional limitation, chronic low-level ischemia, and myocardial remodeling. Low-level ischemia can be a potential driver of both first coronary vasomotor and myocardial dysfunc‐ tion, and then remodeling in heart failure with preserved ejection fraction. Diffuse atheroscle‐ rosis and microvascular dysfunction-associated coronary artery disease comorbid conditions may guide new, more effective, aggressive, and therapeutic interventions for global cardio‐ vascular risk reduction due to complete revascularization. There is no difference in event-free survival between CABG or stent implantation in patients with high coronary flow reserve; however, CABG is significantly more effective than stent in patients with low coronary flow reserve [12]. Diffuseness of coronary artery disease is a serious risk factor for early and late adverse events after coronary revascularization, but the acceptable strategy should be complete revascularization. Standard bypass method (finding an appropriate lumen and performing anastomosis) is usually not possible in the diffusely diseased coronary arteries, and such a region, which may be found at most distal, cannot be expected to bring any benefit. For this reason, in such cases, it is required to apply a complex method other than standard bypass method. When the atherosclerotic stenosis is local, it is technically possible and easy to revascularize the distal segment directly, but in diffuse coronary artery disease or in the presence of diffuse stenotic regions, different techniques should be implemented for complete

these circumstances.

surgical revascularization.

revascularization.

**3. Surgical treatment techniques**

**2.6. Multistented coronary arteries**

184 Coronary Artery Disease - Assessment, Surgery, Prevention

This technique is used for revascularization of the same coronary artery with more than one anastomosis (Figure 1). Most patients with diffuse coronary artery disease have multiple severe stenoses along coronary arteries or diseased coronary artery may have critically important side branches before the last stenosis that could not be bypassed. Jumping bypass is performed via single or multiple conduits on the same coronary artery and is the only solution to supply blood throughout the diseased coronary artery, especially for the left anterior descending (LAD) artery and the right coronary artery (RCA). The circumflex artery (Cx) may have multiple major branches and each one does not need to be revascularized consecutively with this technique; on the contrary, these branches should be revascularized separately with sequential grafting. The jumping bypass technique has several advantages to avoid unexpected adverse complications intraoperatively (Table 2). It is the simpler technique to perform complete revascularization in diffuse coronary disease patients. This technique can be applied via different approaches.


**Table 1.** Aggressive bypass strategies for diffusely diseased coronary territory

1. To achieve complete revascularization of the same major coronary artery

2. To supply blood to the myocardium via grafting major side branches of the same coronary artery

3. To avoid more aggressive surgical procedures ("touch the plaque" techniques)

4. To shorten ischemic and cardiopulmonary bypass times

5. To salvage myocardium from perioperative myocardial infarction caused by graft failure

**Table 2.** Advantages of the jumping bypass technique

#### **a. Jumping grafting with multiple conduits**

This approach is the easiest approach, and it is usually used for the LAD revascularization, whereas the RCA is seldom preferred. This jumping bypass approach using more than one conduit is usually preferred in emergency situations to salvage myocardium perioperatively, but it can also be used in elective cases. Two arteriotomies are performed on the same coronary

**Figure 1.** Jumping grafting is an alternative to multi-revascularization of the same coronary artery with multi-segment stenoses. **a)** Jumping grafting with multiple conduits. **b)** Jumping grafting with a single conduit. **c)** Jumping grafting with a composite conduit. **d)** Jumping grafting with a bifurcated conduit.

1. To achieve complete revascularization of the same major coronary artery

**Table 1.** Aggressive bypass strategies for diffusely diseased coronary territory

4. To shorten ischemic and cardiopulmonary bypass times

A. No-touch the plaque techniques

1. Jumping bypass (the same coronary artery)

2. Sequential bypass (multiple coronary arteries)

3. Hybrid revascularization (different coronary arteries)

a. with multiple grafts b. with a single graft

186 Coronary Artery Disease - Assessment, Surgery, Prevention

c. with a composite graft d. with a bifurcated graft

a. with a single graft

B. Touch the plaque techniques

2. patch-plasty

a. closed b. open

1. long-segment anastomosis

3. endarterectomy ± patch-plasty

b. with a composite graft c. with a bifurcated graft

**Table 2.** Advantages of the jumping bypass technique

**a. Jumping grafting with multiple conduits**

3. To avoid more aggressive surgical procedures ("touch the plaque" techniques)

2. To supply blood to the myocardium via grafting major side branches of the same coronary artery

This approach is the easiest approach, and it is usually used for the LAD revascularization, whereas the RCA is seldom preferred. This jumping bypass approach using more than one conduit is usually preferred in emergency situations to salvage myocardium perioperatively, but it can also be used in elective cases. Two arteriotomies are performed on the same coronary

5. To salvage myocardium from perioperative myocardial infarction caused by graft failure

artery and both are grafted by different conduits (Figure 1a). Two conduits are anastomosed in an end-to-side fashion, and this approach achieves double suppliers with double sources. This approach is usually preferred for the LAD, and the left internal mammarian artery (LIMA) is often anastomosed between the proximal and distal lesions, because the length of LIMA is usually not enough to reach to the distal segment. The distal segment of the coronary artery is revascularized using a second conduit, especially with a vein graft. In elective and planned surgery, the second graft could be an arterial conduit: the right internal thoracic artery (RIMA) or radial artery (RA). In the emergency salvage re-exploration after perioperative myocardial infarction, the saphenous vein graft (SVG) should be chosen for its precipitous harvesting. This approach can be preventative against early graft failure, whereas the second independent conduit can continue to supply blood. This approach is also lifesaving when perioperative myocardial infarction is developed because of the graft failure, and the second graft is anastomosed at the distal part of the affected coronary artery. This alternative procedure is mostly used to salvage myocardium when the LIMA or the other conduit does not work due to any reason perioperatively.

#### **b. Jumping grafting with a single conduit**

This approach can be used for the LAD or RCA elective and planned revascularization, but it is not feasible for emergency surgery. This approach is similar to sequential bypass technique, but the only difference is to be a single target vessel requiring multiple anastomoses. If harvesting of a second conduit is not possible due to any reason and the target coronary artery has multiple stenosis, the harvested single graft can be anastomosed on the same coronary artery consecutively (Figure 1b). In situ or free conduits can be used for jumping grafting. The double arteriotomies are made in the direction of the long axis at the mid and distal soft segments of the target coronary artery, and a single proximal arteriotomy is made at the conduit. The two proximal incisions are aligned parallel and the proximal anastomosis is performed in a side-to-side fashion and created kissing anastomosis, which is the critical part of this approach, but "aligned perpendicular and created a diamond-shaped anastomosis" is never used for this anastomosis like the routine sequential bypass technique. The distal end of the graft is anastomosed to the distal arteriotomy on the target coronary artery as the standard end-to-side fashion. Using a larger graft for consecutive anastomoses on the same coronary artery can be performed with a lower technical risk than the LIMA because of its borderline diameter, and the best conduits for this approach are the RA and SVG. This approach is often complication free and consecutive grafting of the same target coronary artery permits efficient use of limited conduits, but it is preferred rarely.

#### **c. Jumping grafting with a composite conduit**

This approach can be used for the LAD revascularization. This approach is more timeconsuming than the other approaches and needs more attention. A composite conduit can be built as T- or Y-graft with the in situ LIMA. This second graft is usually prepared from a free arterial graft (a short segment of the RA or RIMA), and both free ends of the second arterial conduit are anastomosed on the same coronary artery, whereas the LIMA is anastomosed at the middle part of the second conduit conduit (T-graft) or the LIMA is anastomosed on the LAD, whereas both free ends of the second arterial conduit are anastomosed on the distal segment of the LAD and at the middle part of the LIMA (Y-graft) (Figure 1c). This application arranges uniform distal anastomoses using the same conduit with the same diameter and prevents stealing coronary blood by any larger conduit. In the absence of the second arterial graft, a short SVG can be also used as the composed part.

#### **d. Jumping grafting with a bifurcated conduit**

This approach can be used for the LAD or RCA revascularization. This approach is easy to apply, but it is very uncommon to find a bifurcated conduit in the body. The two branches of the LIMA have a smaller diameter and are very vasospastic, which are not suitable for grafting. The only option is to harvest the SVG with its first major bifurcated branches (Figure 1d). The advantages are avoiding the second proximal anastomosis on the ascending aorta or on the other conduit, any handicap caused by anastomosis between both grafts, and technical difficulties and risks of kissing anastomosis.

#### **2. Sequential bypass technique**

approach can be preventative against early graft failure, whereas the second independent conduit can continue to supply blood. This approach is also lifesaving when perioperative myocardial infarction is developed because of the graft failure, and the second graft is anastomosed at the distal part of the affected coronary artery. This alternative procedure is mostly used to salvage myocardium when the LIMA or the other conduit does not work due

This approach can be used for the LAD or RCA elective and planned revascularization, but it is not feasible for emergency surgery. This approach is similar to sequential bypass technique, but the only difference is to be a single target vessel requiring multiple anastomoses. If harvesting of a second conduit is not possible due to any reason and the target coronary artery has multiple stenosis, the harvested single graft can be anastomosed on the same coronary artery consecutively (Figure 1b). In situ or free conduits can be used for jumping grafting. The double arteriotomies are made in the direction of the long axis at the mid and distal soft segments of the target coronary artery, and a single proximal arteriotomy is made at the conduit. The two proximal incisions are aligned parallel and the proximal anastomosis is performed in a side-to-side fashion and created kissing anastomosis, which is the critical part of this approach, but "aligned perpendicular and created a diamond-shaped anastomosis" is never used for this anastomosis like the routine sequential bypass technique. The distal end of the graft is anastomosed to the distal arteriotomy on the target coronary artery as the standard end-to-side fashion. Using a larger graft for consecutive anastomoses on the same coronary artery can be performed with a lower technical risk than the LIMA because of its borderline diameter, and the best conduits for this approach are the RA and SVG. This approach is often complication free and consecutive grafting of the same target coronary artery

This approach can be used for the LAD revascularization. This approach is more timeconsuming than the other approaches and needs more attention. A composite conduit can be built as T- or Y-graft with the in situ LIMA. This second graft is usually prepared from a free arterial graft (a short segment of the RA or RIMA), and both free ends of the second arterial conduit are anastomosed on the same coronary artery, whereas the LIMA is anastomosed at the middle part of the second conduit conduit (T-graft) or the LIMA is anastomosed on the LAD, whereas both free ends of the second arterial conduit are anastomosed on the distal segment of the LAD and at the middle part of the LIMA (Y-graft) (Figure 1c). This application arranges uniform distal anastomoses using the same conduit with the same diameter and prevents stealing coronary blood by any larger conduit. In the absence of the second arterial

This approach can be used for the LAD or RCA revascularization. This approach is easy to apply, but it is very uncommon to find a bifurcated conduit in the body. The two branches of

to any reason perioperatively.

**b. Jumping grafting with a single conduit**

188 Coronary Artery Disease - Assessment, Surgery, Prevention

permits efficient use of limited conduits, but it is preferred rarely.

**c. Jumping grafting with a composite conduit**

graft, a short SVG can be also used as the composed part.

**d. Jumping grafting with a bifurcated conduit**

This technique is used for revascularization of more than one target coronary arteries or major branches of the same coronary artery with the same conduit. The number of the sequential bypassed vessels depends on the availability of multi-conduits, which allow one or more sequential bypass at the same time. If harvesting adequate conduits is feasible, the true way is bypassing all diseased coronary artery separately as the "one graft-to-one target coronary artery" rule. The main purpose of this technique is the efficient usage of limited conduits to achieve complete revascularization (Table 3). The most distal anastomosis should be to the furthest target coronary artery with an acceptable diameter, and the conduit is anastomosed at several coronary arteries before its proximal anastomosis. The most possible drawback is more than one distal anastomoses with a single proximal source that can cause an aggravated risk of inadequate myocardial perfusion. It cannot be hazardous, if the equal coronary territory is bypassed with the same conduit sequentially. On the other hand, if the distal coronary artery has a small diameter, it would be hazardous, and this smaller distal anastomosis lies under the risk of total occlusion because of preferential graft flow to the larger proximal coronary arteries. All available conduits can be used for sequential grafting, especially the SVG. The RA is usually used for sequential anastomosis during full arterial revascularization [13]. The LIMA should not be used for sequential bypass grafting, if it supplies the LAD flow, but it can be used as a donor for composite T- or Y-grafting of other arterial conduits, especially with the RIMA, in order to achieve complete arterial revascularization. The distal anastomosis is performed with the standard end-to-side technique and all proximal anastomoses with the side-to-side technique. Both the target coronary artery and the conduit are incised longitudi‐ nally and aligned perpendicular to each other, and all proximal sequential anastomoses must be constructed in a diamond-shaped fashion to prevent any stenosis, kinking, distortion or tension on the anastomoses and conduit. Both the arteriotomy and the incision on the conduit should not exceed the diameter of the conduit. The distal anastomosis is completed first and the other anastomoses are performed towards the proximal consecutively.


2. To perform complete revascularization if conduits are inappropriate

3. To supply blood to the myocardium via grafting major side branches of the same or different coronary arteries

4 To avoid more aggressive surgical procedures ("touch the plaque" techniques)

5. To shorten ischemic and cardiopulmonary bypass times

6. To salvage myocardial revascularization intraoperatively when the conduits are shorter for proximal anastomosis on the ascending aorta.

**Table 3.** Advantages of the sequential bypass technique

#### **a. Sequential grafting with a single conduit**

This approach can be used for all coronary arteries and is the most used approach for complete revascularization. If harvesting of sufficient conduits is not possible due to any reason and there are a large number of target coronary arteries, the harvested single graft can be anasto‐ mosed on the different coronary arteries (RCA-Cx-Diagonal-LAD) or on the several branches of a single coronary artery (Cx 1-3) sequentially (Figure 2a). All free grafts are suitable for this sequential bypass approach. The best conduit for this approach is the SVG or RA. Proximal anastomosis is always performed on the ascending aorta without any concern on the longterm patency [14]. In situ arterial grafts should be used alone to the target coronary artery, especially both IMAs. First, the distal end of the graft is anastomosed to the distal target coronary artery in an end-to-side fashion. The other proximal coronary arteries are bypassed consecutively through the anterior surface of the heart. The small arteriotomies are made in the direction of the long axis of the target coronary artery and small incisions are made at the conduit. The two incisions are aligned perpendicularly creating a diamond-shaped anasto‐ mosis and the sequential anastomosis is performed in a side-to-side fashion, which is the critical part of this approach; however, "aligned parallel and created a kissing anastomosis" is never used for this anastomoses. This approach is often complication free, and sequential grafting of the different target coronary arteries permits efficient use of limited conduits.

#### **b. Sequential grafting with a composite conduit**

This approach can be performed in two different methods. The first method is usually used if the distal SVGs remain shorter for proximal anastomosis on the ascending aorta intraopera‐ tively, especially for revascularization of the Cx-branches. A composite conduit can be built as Y-graft and the second short graft is usually anastomosed on the main conduit, and the most preferred conduits are the SVG and RA (Figure 2b-1). The main graft is anastomosed to the largest target coronary artery first, and the proximal anastomosis of the other shorter graft(s) is performed on this main graft before or after releasing the aortic cross-clamp. The second method is used for complete arterial revascularization of all coronary arteries, but this method is more time-consuming and needs more competency (Figure 2b-2). This composite conduit is prepared for T- or Y-graft and it can reach all surfaces of the heart. The most preferred conduits are the LIMA as a pedicle graft source and the RIMA as a composed part for grafting all target coronary arteries.

#### **c. Sequential grafting with a bifurcated conduit**

This approach can be used for revascularization of the distal RCA- or Cx-branches (Figure 2c). This approach is easy to apply, but it is very uncommon to find a bifurcated conduit in the body. The advantages are avoiding the second proximal anastomosis on the ascending aorta, any handicap caused by anastomosis between both grafts, and technical difficulties and risks of kissing anastomosis.

#### **3. Hybrid revascularization**

The standard hybrid coronary revascularization combines the benefits of the LIMA-to-LAD grafting and stent implantation to the other coronary territory. The hybrid revascularization

**a. Sequential grafting with a single conduit**

190 Coronary Artery Disease - Assessment, Surgery, Prevention

**b. Sequential grafting with a composite conduit**

**c. Sequential grafting with a bifurcated conduit**

coronary arteries.

of kissing anastomosis.

**3. Hybrid revascularization**

This approach can be used for all coronary arteries and is the most used approach for complete revascularization. If harvesting of sufficient conduits is not possible due to any reason and there are a large number of target coronary arteries, the harvested single graft can be anasto‐ mosed on the different coronary arteries (RCA-Cx-Diagonal-LAD) or on the several branches of a single coronary artery (Cx 1-3) sequentially (Figure 2a). All free grafts are suitable for this sequential bypass approach. The best conduit for this approach is the SVG or RA. Proximal anastomosis is always performed on the ascending aorta without any concern on the longterm patency [14]. In situ arterial grafts should be used alone to the target coronary artery, especially both IMAs. First, the distal end of the graft is anastomosed to the distal target coronary artery in an end-to-side fashion. The other proximal coronary arteries are bypassed consecutively through the anterior surface of the heart. The small arteriotomies are made in the direction of the long axis of the target coronary artery and small incisions are made at the conduit. The two incisions are aligned perpendicularly creating a diamond-shaped anasto‐ mosis and the sequential anastomosis is performed in a side-to-side fashion, which is the critical part of this approach; however, "aligned parallel and created a kissing anastomosis" is never used for this anastomoses. This approach is often complication free, and sequential grafting of the different target coronary arteries permits efficient use of limited conduits.

This approach can be performed in two different methods. The first method is usually used if the distal SVGs remain shorter for proximal anastomosis on the ascending aorta intraopera‐ tively, especially for revascularization of the Cx-branches. A composite conduit can be built as Y-graft and the second short graft is usually anastomosed on the main conduit, and the most preferred conduits are the SVG and RA (Figure 2b-1). The main graft is anastomosed to the largest target coronary artery first, and the proximal anastomosis of the other shorter graft(s) is performed on this main graft before or after releasing the aortic cross-clamp. The second method is used for complete arterial revascularization of all coronary arteries, but this method is more time-consuming and needs more competency (Figure 2b-2). This composite conduit is prepared for T- or Y-graft and it can reach all surfaces of the heart. The most preferred conduits are the LIMA as a pedicle graft source and the RIMA as a composed part for grafting all target

This approach can be used for revascularization of the distal RCA- or Cx-branches (Figure 2c). This approach is easy to apply, but it is very uncommon to find a bifurcated conduit in the body. The advantages are avoiding the second proximal anastomosis on the ascending aorta, any handicap caused by anastomosis between both grafts, and technical difficulties and risks

The standard hybrid coronary revascularization combines the benefits of the LIMA-to-LAD grafting and stent implantation to the other coronary territory. The hybrid revascularization

**Figure 2.** Sequential grafting is the best alternative for the multivessel revascularization in the absence of adequate conduits. **a)** Sequential grafting with a single conduit. **b)** Sequential grafting with a composite conduit: **1-** classic ap‐ proach with inadequate saphenous vein grafts; **2-** T- or Y- graft for total arterial revascularization. **c)** Sequential graft‐ ing with a bifurcated conduit.

technique can be chosen with several indications in patients with diffuse coronary artery disease (Table 4). Patients with severe comorbidities or patients with multiple stenoses may be the best candidates for this procedure. If complete multivessel surgical revascularization increases operative adverse outcomes in high-risk patients, stent implantation in one or more coronary arteries, except the LAD, can be a preventative alternative to complete myocardial revascularization (Table 4). Hybrid revascularization can be performed concomitant or staged. Concomitant hybrid revascularization needs a specific operating room, whereas staged hybrid revascularization can be performed in every clinic. Percutaneous coronary intervention is applied before or after CABG. The decision depends on the severity of proximal lesions which may not be revascularized, and the aim is the avoidance of any perioperative myocardial infarction. Especially proximal or ostial left main or LAD serious stenosis should be treated by stent, if single LIMA-to-LAD grafting cannot achieve complete blood supply to the LAD territory. Ungraftable RCA or Cx vessels with severe stenosis should be treated by percuta‐ neous intervention to achieve complete revascularization.


**Table 4.** Indication for hybrid revascularization

#### **Touch the Plaque Techniques**

#### **1. Long-segment (1-3 cm) anastomosis**

This technique is chosen when the plaque with limited length obstructs the coronary blood flow. This simplest form includes a limited long-segment anastomosis of a conduit to eliminate the occlusion of the limited atherosclerotic plaque (Figure 3). This technique is a prolonged version of the standard anastomosis technique to revascularize proximal and distal segments of the coronary artery and makes jumping grafting with/without a second graft unnecessary. The whole diseased coronary artery segment is opened at full length of the atherosclerotic lesion and the arteriotomy is extended bidirectionally until the healthy coronary artery lumen comes out. The aim of this maneuver is to forward graft blood flow directly into the healthy coronary artery lumen bidirectionally. The distal end of the graft is opened longer than coronary arteriotomy to prevent any tension, tightening, stenosis or inadequately anastomotic length of the conduit, and then the graft is anastomosed on the coronary arteriotomy longitu‐ dinally. All attention should be directed to avoid any distal embolization of atherosclerotic debris or to prevent the continuity of the coronary artery.

#### **2. Patch-plasty (> 3 cm) anastomosis**

A diffusely diseased coronary artery cannot be grafted by conventional grafting technique and side branches and/or distal segment would not be revascularized. This technique is preferred mostly for the LAD, but the RCA or the Cx artery can be also bypassed with this technique. The patch-plasty technique is necessary if any kind of endarterectomy cannot be applied and the long-segment lesions should be opened in full length. The main principle is to avoid touching the atherosclerotic plaques during the patch reconstruction. The in situ or free conduit can be used alone (Figure 4a) or it can be anastomosed onto the second graft, which is sewn on the long-segment arteriotomy as a hood (Figure 4b). The arteriotomy can be made as long as the length of the attainable epicardial coronary artery, and then a conduit is used to close this arteriotomy without the occlusion of side branches. The graft should also be opened as long as the arteriotomy and anastomosed with a running single suture. In the standard approach, the bites can be taken at the free ends of the arteriotomy to get the largest lumen

by stent, if single LIMA-to-LAD grafting cannot achieve complete blood supply to the LAD territory. Ungraftable RCA or Cx vessels with severe stenosis should be treated by percuta‐

This technique is chosen when the plaque with limited length obstructs the coronary blood flow. This simplest form includes a limited long-segment anastomosis of a conduit to eliminate the occlusion of the limited atherosclerotic plaque (Figure 3). This technique is a prolonged version of the standard anastomosis technique to revascularize proximal and distal segments of the coronary artery and makes jumping grafting with/without a second graft unnecessary. The whole diseased coronary artery segment is opened at full length of the atherosclerotic lesion and the arteriotomy is extended bidirectionally until the healthy coronary artery lumen comes out. The aim of this maneuver is to forward graft blood flow directly into the healthy coronary artery lumen bidirectionally. The distal end of the graft is opened longer than coronary arteriotomy to prevent any tension, tightening, stenosis or inadequately anastomotic length of the conduit, and then the graft is anastomosed on the coronary arteriotomy longitu‐ dinally. All attention should be directed to avoid any distal embolization of atherosclerotic

A diffusely diseased coronary artery cannot be grafted by conventional grafting technique and side branches and/or distal segment would not be revascularized. This technique is preferred mostly for the LAD, but the RCA or the Cx artery can be also bypassed with this technique. The patch-plasty technique is necessary if any kind of endarterectomy cannot be applied and the long-segment lesions should be opened in full length. The main principle is to avoid touching the atherosclerotic plaques during the patch reconstruction. The in situ or free conduit can be used alone (Figure 4a) or it can be anastomosed onto the second graft, which is sewn on the long-segment arteriotomy as a hood (Figure 4b). The arteriotomy can be made as long as the length of the attainable epicardial coronary artery, and then a conduit is used to close this arteriotomy without the occlusion of side branches. The graft should also be opened as long as the arteriotomy and anastomosed with a running single suture. In the standard approach, the bites can be taken at the free ends of the arteriotomy to get the largest lumen

neous intervention to achieve complete revascularization.

1. Invisible coronary artery during surgery threatening a huge myocardium

debris or to prevent the continuity of the coronary artery.

**2. Patch-plasty (> 3 cm) anastomosis**

3. To shorten cardiopulmonary and ischemic times

192 Coronary Artery Disease - Assessment, Surgery, Prevention

**Table 4.** Indication for hybrid revascularization

**1. Long-segment (1-3 cm) anastomosis**

**Touch the Plaque Techniques**

5. Impaired or diseased conduits

4. Absence of sufficient conduits for complete revascularization

2. Multiple stenosis with a very proximal lesion threatening proximal larger branches

**Figure 3.** Long-segment anastomosis (1-3 cm) is the simplest alternative to eliminate the distal eccentric lesion.

(Figure 5a). If the lateral walls of the coronary arteriotomy are much calcified, the bites can also be taken very closely to the septal branches, however, this approach needs grafting epicardial side branches separately (Figure 5b). This technique is more useful for the diffusely occluded LAD to perfuse septal branches as far as possible or for the distal major branches of the RCA with septal branches. The Cx artery can be grafted with this technique to make the anastomosis safe.

**Figure 4.** Patch-plasty is the best alternative to avoid endarterectomy in the extended long-segment (> 3 cm) diffuse coronary artery disease. **a)** The in situ or free conduit is anastomosed onto the long-segment coronary artery as a patch. **b)** The limited second conduit is anastomosed as a hood and the main conduit is anastomosed onto this conduit.

**Figure 5.** The stitching maneuvers of the patch-plasty technique. **a)** Bites on the free margins of the coronary arterioto‐ my. **b)** Bites close to the septal branches.

#### **3. Endarterectomy with/without patch-plasty**

In the accelerated form of coronary arteriosclerosis, the atherosclerotic plaque appears widespread and the full-length lumen of the coronary artery can be narrowed strictly or occluded totally. Coronary endarterectomy can be applied via off- or on-pump techniques, but the Cx endarterectomy with off-pump technique is used very seldom because it is more difficult and needs more competence [15]. This technique can be often used for every coronary artery, but it is usually preferred for the LAD and RCA [16]. The long-segment lesion is usually calcified and it inhibits any kind of stitching; however, the plaque can be separated easily from the arterial wall. Endarterectomy and graft anastomosis is preferred only to create an appro‐ priate lumen in the total occluded coronary artery due to the removal of the atheromatous material. Long-standing atherosclerosis permits a successful endarterectomy to get adequate distal run-off. All debris and layer until the adventitia should be removed, and then the vessel wall is reconstructed with a conduit. The early occlusion of the endarterected coronary artery is caused by thrombosis or intimal flap formation, but the reason for late occlusion is intimal hyperplasia. The endarterectomy and patch plasty approach has a very satisfactory graft patency compared with the other approaches for the coronary territory [17,18].

#### **a. Closed Endarterectomy**

The closed approach is preferred for the LAD or RCA (Figure 6a). Approximately 2 cm arteriotomy is performed and an endarterectomy plane between the medial layer and the adventitia is developed with the coronary scissors. The circumferential plane is performed and the core is pulled out from the distal arterial wall. Distal plaque removal causes usually a better coronary distal bed, but proximal plaque removal via a limited arteriotomy can cause poor outcomes as the native vessel laceration resulting native coronary artery dissection or a native passage of high blood flow from the aorta to the distal coronary resulting competition, and early thrombosis. To optimize the technique, avoiding proximal endarterectomy by the pullout method and cutting the proximal part without any traction would come along with better results [19]. The core usually is separated cleanly from the distal vessel, but all debris must be cleaned from the septal ostia. If the core branches can be reached, major side branches are endarterectomized separately. The main aim is to get the distal core without any rupture; otherwise the arteriotomy should be extended until the ruptured distal end to continue the closed endarterectomy.

**Figure 6.** Endarterectomy is the most aggressive method for coronary bypass surgery. **a)** Closed endarterectomy. **b)** Open endarterectomy.

#### **b. Open Endarterectomy + Patch-plasty**

**Figure 5.** The stitching maneuvers of the patch-plasty technique. **a)** Bites on the free margins of the coronary arterioto‐

In the accelerated form of coronary arteriosclerosis, the atherosclerotic plaque appears widespread and the full-length lumen of the coronary artery can be narrowed strictly or occluded totally. Coronary endarterectomy can be applied via off- or on-pump techniques, but the Cx endarterectomy with off-pump technique is used very seldom because it is more difficult and needs more competence [15]. This technique can be often used for every coronary artery, but it is usually preferred for the LAD and RCA [16]. The long-segment lesion is usually calcified and it inhibits any kind of stitching; however, the plaque can be separated easily from the arterial wall. Endarterectomy and graft anastomosis is preferred only to create an appro‐ priate lumen in the total occluded coronary artery due to the removal of the atheromatous material. Long-standing atherosclerosis permits a successful endarterectomy to get adequate distal run-off. All debris and layer until the adventitia should be removed, and then the vessel wall is reconstructed with a conduit. The early occlusion of the endarterected coronary artery is caused by thrombosis or intimal flap formation, but the reason for late occlusion is intimal hyperplasia. The endarterectomy and patch plasty approach has a very satisfactory graft

patency compared with the other approaches for the coronary territory [17,18].

The closed approach is preferred for the LAD or RCA (Figure 6a). Approximately 2 cm arteriotomy is performed and an endarterectomy plane between the medial layer and the

my. **b)** Bites close to the septal branches.

194 Coronary Artery Disease - Assessment, Surgery, Prevention

**a. Closed Endarterectomy**

**3. Endarterectomy with/without patch-plasty**

The open approach is a useful procedure for the total occluded LAD (Figure 6b). The open approach prevents any obstruction of septal branches and inadequate endarterectomy of diagonal branches. The arteriotomy is started at the middle segment of the LAD and extended bidirectionally as proximal and distal as possible. If septal branches are easy to be revascular‐ ized with long-segment grafting, anastomosis can be finished without endarterectomy. If the direct anastomosis is impossible because of severe calcified vessel wall or no lumen, a longsegment endarterectomy should be performed to separate the core from the adventitia. The core is removed gently and both ends of the core at the ends of the arteriotomy should be cut without any traction. Because aggressive endarterectomy increases the operation risk, the arteriotomy should be extended until the normal lumen with normal intima in the distal and proximal segments of the coronary artery. All coronary arteries have very small lumen and thin wall at the distal, and the arteriotomy should be stopped 2-3 cm before the last bifurcation. The arteriotomy is reconstructed with a long segment of the conduit or a graft patch into which the in situ conduit is anastomosed.

#### **Author details**

Kaan Kırali\* and Yücel Özen

\*Address all correspondence to: imkbkirali@yahoo.com

Department of Cardiovascular Surgery, Koşuyolu Herat and Research Hospital, Istanbul, Turkey

#### **References**


taneous coronary intervention using drug-eluting stenting in patients with diabetes. Interactive Cardiovasc Thorac Surg 2014;19(6):1002-1007.

ized with long-segment grafting, anastomosis can be finished without endarterectomy. If the direct anastomosis is impossible because of severe calcified vessel wall or no lumen, a longsegment endarterectomy should be performed to separate the core from the adventitia. The core is removed gently and both ends of the core at the ends of the arteriotomy should be cut without any traction. Because aggressive endarterectomy increases the operation risk, the arteriotomy should be extended until the normal lumen with normal intima in the distal and proximal segments of the coronary artery. All coronary arteries have very small lumen and thin wall at the distal, and the arteriotomy should be stopped 2-3 cm before the last bifurcation. The arteriotomy is reconstructed with a long segment of the conduit or a graft patch into which

Department of Cardiovascular Surgery, Koşuyolu Herat and Research Hospital, Istanbul,

[1] Gould KL, Johnson NP. Physiologic severity of diffuse coronary artery disease: Hid‐

[2] McNeil M, Buth K, Brydie A, MacLaren A, Baskett R. The impact of diffuseness of coronary artery disease on the outcomes of patients undergoing primary and reoper‐ ative coronary artery bypass grafting. Eur J Cardiothorac Surg 2007;31(5):827-833.

[3] Hadi HA, Carr CS, Suwaidi JA. Endothelial dysfunction: Cardiovascular risk factors,

[4] Kurlansky P, Herbert M, Prince S, Mack MJ. Improved long-term survival for diabet‐ ic patients with surgical versus interventional revascularization. Ann Thorac Surg

[5] Kappetein AP, Head SJ, Morice MC, et al. Treatment of complex coronary artery dis‐ ease in patients with diabetes: 5-year results comparing outcomes of bypass surgery and percutaneous coronary intervention in the SYNTAX trial. Eur J Cardiothorac

[6] Fanari Z, Weiss SA, Zhang W, Sonnad SS, Weintraub WS. Meta-analysis of three randomized controlled trials comparing coronary artery bypass grafting with percu‐

therapy, and outcome. Vasc Health Risk Manag 2005;1(3):183-198.

the in situ conduit is anastomosed.

196 Coronary Artery Disease - Assessment, Surgery, Prevention

and Yücel Özen

2015;99(4):1298–1305.

Surg 2013;43(5):1006-1013.

\*Address all correspondence to: imkbkirali@yahoo.com

den high risk. (Editorial) Circulation 2015;131(1):4-6.

**Author details**

Kaan Kırali\*

Turkey

**References**

