**8. Treatment of hemodynamically significant disease**

Currently, the ACC/ AHA defines a significant stenosis as "Greater than or equal to 70% luminal diameter narrowing, by visual assessment, of an epicardial stenosis measured in the "worst view" angiographic projection [68]." The exception is the left main artery in which a significant stenosis is defined as " greater or equal to 50% luminal diameter narrowing [68]." A challenge in the interpretation of the data surrounding comparisons of PCI versus CABG the variability in definitions of "significant disease." Interestingly, many of the landmark trials comparing PCI versus CABG actually defined a significant stenosis as greater or equal to 50% [27, 45, 51].

**Figure 7.** A schematic depiction of the concept of fractional flow reserve. On the right is the graphical correlation be‐ tween Flow Q and perfusion pressure P under conditions of maximal hyperemia. The maximal blood flow in the sten‐ otic vessel QS (Red Lines) is directly proportional to the perfusion pressure distal to the lesion. The maximal blood flow in the same vessel hypothetically without the stenosis QN (Blue Lines) is proportional to the perfusion pressure proxi‐ mal to the stenosis Pa which is the same as aortic pressure. QS/QN is therefore equal to Pd/Pa. Reproduced with per‐

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The use of FFR will be come increasingly more relevant in the assessment of patients with multivessel disease. The **Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME)** was a study randomizing 1005 patients to either angiographically guided PCI or PCI guided by fractional flow reserve in patients with multivessel disease of at least moderate severity (greater or equal to 50%) [73]. Patients in the angiographic group were revascularized if PCI was indicated based on visual assessment of angiographic data and clinical data; patients in the FFR group only had PCI if the FFR was < 0.80 [73]. The combined outcome of death, myocardial infarction and repeat revascularization was significantly less in those treated with FFR guided PCI (18.3%) than the angiographically guided PCI (13.2%) [Figure 8] [73]. Death and myocardial infarction, although not a pre-specified outcome, was also significantly less in the FFR group (11.1%) versus the angiographic group (7.3%) [73]. This

Although FFR is early in its development, certainly it has the potential to play a role in classifying the severity of disease for decision-making in MVD. Consider a patient with 3VD with a 50 percent lesion at the proximal LAD. If the proximal LAD lesion is FFR is greater than 0.80, this patient may in fact be classified as two vessel disease with no hemodynamic in‐ volvement of the proximal LAD and hence should receive PCI. While there is limited research exploring the use of FFR in determining the mode of revascularization, this is certainly an area worthy of further study. Currently the ACC advocates the use of FFR guiding revascularization decisions in stable ischemic heart disease with moderate lesions with 50-70% stenosis (**IIa**

mission from Pijls NHJ et al. JACC 2012. 59: 1045-57.

difference persisted to the two-year follow-up [74].

**recommendation, level A evidence**) [14].

Even in the presence of a significant stenosis, myocardial blood flow can be maintained by compensatory mechanisms at rest [69]. Consequently, hemodynamically significant disease has been defined by those lesions, which produce a reduction in coronary flow reserve under conditions of maximal hyperemia [69, 70]. Reduction of coronary flow reserve is generally observed in lesions with as little as 50 percent stenosis but progressively wor‐ sens with the degree of narrowing [70]. There are two implications of this clinically. First, there is a significant interobserver and intraobserver variability in the degree of angiograph‐ ic stenosis [69]. Second, the hemodynamic significance of a given lesion is dependent on the severity of the stenosis, the length of the lesion as well as the presence of collateral blood flow [71].

Aims to quantify the functional significance of coronary stenosis lead to the development of the concept Fractional Flow Reserve (FFR) [72]. FFR is a hemodynamic construct defined as the maximal blood flow distal to a stenosis compared with the maximal blood flow in the same vessel, hypothetically in the absence of any stenosis, conditions of maximal hyperemia [72]. Flow can be characterized by the following equation: Pressure (P) = Flow (Q) \* Resistance (R) [72]. For a given lesion, the FFR is the maximal flow for the stenotic vessel (Qs)/ maximal flow if the vessel were normal (Qn). Since, under maximal hypere‐ mia, the resistance becomes a constant, Q is only dependent on the pressure and fraction‐ al flow reserve can be defined by a ratio of aortic pressure (Pa)/ pressure distal to the lesion (Pd) [Figure 7] [72]. FFR allows for the functional assessment of ischemia at the time of coronary angiogram [72].

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guidelines recommend that PCI (or emergency CABG) should be performed on patients who candidates for revascularization in the setting of STEMI and severe heart failure or cardiogenic shock *(Class I recommendation, Level B evidence)* [14, 26]. Although the data upon which this recommendation is based does not show a preferential benefit to either mode of revasculari‐ zation, both guidelines favor PCI as the primary mode of revascularization in cardiogenic shock [14, 26]. The ACC guidelines do recognize however, that "select patients with severe

Currently, the ACC/ AHA defines a significant stenosis as "Greater than or equal to 70% luminal diameter narrowing, by visual assessment, of an epicardial stenosis measured in the "worst view" angiographic projection [68]." The exception is the left main artery in which a significant stenosis is defined as " greater or equal to 50% luminal diameter narrowing [68]." A challenge in the interpretation of the data surrounding comparisons of PCI versus CABG the variability in definitions of "significant disease." Interestingly, many of the landmark trials comparing PCI versus CABG actually defined a significant stenosis as greater or equal to 50%

Even in the presence of a significant stenosis, myocardial blood flow can be maintained by compensatory mechanisms at rest [69]. Consequently, hemodynamically significant disease has been defined by those lesions, which produce a reduction in coronary flow reserve under conditions of maximal hyperemia [69, 70]. Reduction of coronary flow reserve is generally observed in lesions with as little as 50 percent stenosis but progressively wor‐ sens with the degree of narrowing [70]. There are two implications of this clinically. First, there is a significant interobserver and intraobserver variability in the degree of angiograph‐ ic stenosis [69]. Second, the hemodynamic significance of a given lesion is dependent on the severity of the stenosis, the length of the lesion as well as the presence of collateral blood

Aims to quantify the functional significance of coronary stenosis lead to the development of the concept Fractional Flow Reserve (FFR) [72]. FFR is a hemodynamic construct defined as the maximal blood flow distal to a stenosis compared with the maximal blood flow in the same vessel, hypothetically in the absence of any stenosis, conditions of maximal hyperemia [72]. Flow can be characterized by the following equation: Pressure (P) = Flow (Q) \* Resistance (R) [72]. For a given lesion, the FFR is the maximal flow for the stenotic vessel (Qs)/ maximal flow if the vessel were normal (Qn). Since, under maximal hypere‐ mia, the resistance becomes a constant, Q is only dependent on the pressure and fraction‐ al flow reserve can be defined by a ratio of aortic pressure (Pa)/ pressure distal to the lesion (Pd) [Figure 7] [72]. FFR allows for the functional assessment of ischemia at the time of

3VD or LM disease can benefit from emergency CABG" [14].

[27, 45, 51].

336 Artery Bypass

flow [71].

coronary angiogram [72].

**8. Treatment of hemodynamically significant disease**

**Figure 7.** A schematic depiction of the concept of fractional flow reserve. On the right is the graphical correlation be‐ tween Flow Q and perfusion pressure P under conditions of maximal hyperemia. The maximal blood flow in the sten‐ otic vessel QS (Red Lines) is directly proportional to the perfusion pressure distal to the lesion. The maximal blood flow in the same vessel hypothetically without the stenosis QN (Blue Lines) is proportional to the perfusion pressure proxi‐ mal to the stenosis Pa which is the same as aortic pressure. QS/QN is therefore equal to Pd/Pa. Reproduced with per‐ mission from Pijls NHJ et al. JACC 2012. 59: 1045-57.

The use of FFR will be come increasingly more relevant in the assessment of patients with multivessel disease. The **Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME)** was a study randomizing 1005 patients to either angiographically guided PCI or PCI guided by fractional flow reserve in patients with multivessel disease of at least moderate severity (greater or equal to 50%) [73]. Patients in the angiographic group were revascularized if PCI was indicated based on visual assessment of angiographic data and clinical data; patients in the FFR group only had PCI if the FFR was < 0.80 [73]. The combined outcome of death, myocardial infarction and repeat revascularization was significantly less in those treated with FFR guided PCI (18.3%) than the angiographically guided PCI (13.2%) [Figure 8] [73]. Death and myocardial infarction, although not a pre-specified outcome, was also significantly less in the FFR group (11.1%) versus the angiographic group (7.3%) [73]. This difference persisted to the two-year follow-up [74].

Although FFR is early in its development, certainly it has the potential to play a role in classifying the severity of disease for decision-making in MVD. Consider a patient with 3VD with a 50 percent lesion at the proximal LAD. If the proximal LAD lesion is FFR is greater than 0.80, this patient may in fact be classified as two vessel disease with no hemodynamic in‐ volvement of the proximal LAD and hence should receive PCI. While there is limited research exploring the use of FFR in determining the mode of revascularization, this is certainly an area worthy of further study. Currently the ACC advocates the use of FFR guiding revascularization decisions in stable ischemic heart disease with moderate lesions with 50-70% stenosis (**IIa recommendation, level A evidence**) [14].

**Figure 8.** Kaplan-Meier Survival Curves according to study group PCI guided by angiography alone versus PCI guided by FFR in addition to angiography. FFR=fractional flow reserve, PCI=percutaneous coronary intervention. Reproduced with permission from Tonino PAL et al. Fractional flow reserve versus angiography or guiding percutanous coronary intervention. NEJM 2009. 360(3):213-224.

ischemic coronary artery disease [Figure 9] [14, 26]. In fact, recent data has demonstrated a rise

**Figure 9.** Variation in Revascularization for Multivessel Disease Across 17 Cardiac Centers in Ontario. Reproduced with permission from Schwalm JD et al. SYNTAX Score and Real World Revascularization Patterns. Canadian Cardiovascular

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SignificantvariabilityinPCI:CABGratiobetweenprovinces/states,betweenhospitalsandeven betweenindividualinterventionalists suggests thatthe trends inrevascularizationpractices are not entirely explained by changes in population or advancements in revascularization techniques [76-80].InOntario,Canada,PCItoCABGratiosvaryconsiderablybetweenhospitals from 1.3 to 6.1 [81]. In multivessel disease, this ratio ranges from 0.24 to 5.0 [figure 9] [82]. The physician performing the diagnostic catheterization (interventional cardiologist versus noninterventional cardiologist), the coronary anatomy (LM, 3VD, 2VD), and the treating hospital

Two possible hypotheses for the presence of such dramatic variability in the management of multi-vessel disease include misinterpretation of the evidence and misclassification of disease complexity at the time of diagnostic angiogram. There are complex interacting variables upon which the final therapeutic decision is based, including: (1) complexity of coronary anatomy, (2) presence or absence of prognostically important factors favoring surgery, (3) degree of active functional ischemia, (4) complex co-morbid state of patient, (5) patient preferences and social factors, (6) local resources and expertise. All of these factors may affect the patient's suitability for CABG and likelihood to benefit prognostically from surgical revascularization. Application of the large body of evidence in this variable clinical milieu is a complex process. The management algorithm is further complicated when considering the patient's role in the decision-making process and the steps required to ensure truly "informed" patient consent.

in PCI with DES in patients with Class I recommendation for surgery [25].

Congress 2011 Vancouver, BC. Abstract Presentation.

were the three strongest determinants of the ultimate therapeutic strategy [58].
