**3. Evaluation and grading the degree of stenosis**

Patient history and physical examination remain essential. Careful exploration for the pres‐ ence of symptoms (shortness of breath on exertion, angina, dizziness, or syncope) is critical for proper patient management. It is important to be aware that patients may not notice symptoms but they significantly reduce their activities. The characteristic systolic murmur draws attention and guides further diagnostic work in the right direction. However, on oc‐ casion the murmur may, be faint and the primary presentation may be heart failure of un‐ known cause. The disappearance of the second aortic sound is specific to severe AS, however, it is not a sensitive sign.

Several studies [6-9] reports that biomarkers such as B-type natriuretic peptide (BNP) has been shown to be related to functional class and prognosis, particularly in AS and MR. In fact, Lancellotti et al. [9] reports in their study that a left atrial area index of > or = 12.4 cm2/m2, systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events (death, symptoms, or surgery). They found, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters. However, Natriuretic peptides have been shown to predict symptom free survival and outcome in normal- and low-flow severe AS and may be useful in asymptomatic patients, helping to discriminates those pa‐ tients who can benefits from an early intervention [7-9]. Nevertheless, evidence regarding its incremental value in risk stratification remains limited so far.

Echocardiography is indicated when there is a systolic murmur of grade III/VI or higher, a single S2, or symptoms that might be due to AS [10]. A 2-dimensional (2D) echocardiogram is valuable for assessing valve anatomy and function and determining the LV response to pressure overload. In nearly all patients, the severity of the stenotic lesion can be defined with Doppler echocardiographic measurements. Echocardiography is also used to assess LV size and function, degree of hypertrophy, and presence of other associated valvular disease. Transoesophageal echocardiography (TOE) is rarely helpful for the quantification of AS, as valve area planimetry becomes difficult in calcified valves [11] however, it is useful when transthoracic visualization is poor and leaflets only moderately calcified [12]. TOE may, however, provide additional evaluation of mitral valve abnormalities and has gained impor‐ tance in assessing annulus diameter before TAVI and in guiding the procedure. Intraproce‐ dural TOE enables us to monitor the results of percutaneous procedures [11]. Threedimensional TOE offers a more detailed examination of valve anatomy than twodimensional echocardiography and is useful for the assessment of complex valve problems or for monitoring surgery and percutaneous intervention [11]. Three-dimensional echocar‐ diography (3DE) is useful for assessing anatomical features which may have an impact on the type of intervention chosen, if it is needed. AS severity could be graded on the basis of a variety of hemodynamic and natural history data, using definitions of aortic jet velocity, mean pressure gradient, valve area and velocity ratio as shown in Table 1.


**Table 1.** Classification of the Severity of Aortic Valve Disease in Adults

of elderly people: 25% of people aged 65 to 74, and 48% of people older than 84 years [3,4]. This calcific disease progresses from the base of the cusps to the leaflets, eventually causing a reduction in leaflet motion and effective valve area without commissural fusion. Calcific AS is an active disease process characterized by lipid accumulation, inflammation, and calci‐ fication, with many similarities to atherosclerosis. In approximately half of cases there is a bicuspid aortic valve basis. Bicuspid aortic valve valvulopathy affects 2% of the population, making it the most frequent congenital anomaly, representing the more common cause

Patient history and physical examination remain essential. Careful exploration for the pres‐ ence of symptoms (shortness of breath on exertion, angina, dizziness, or syncope) is critical for proper patient management. It is important to be aware that patients may not notice symptoms but they significantly reduce their activities. The characteristic systolic murmur draws attention and guides further diagnostic work in the right direction. However, on oc‐ casion the murmur may, be faint and the primary presentation may be heart failure of un‐ known cause. The disappearance of the second aortic sound is specific to severe AS,

Several studies [6-9] reports that biomarkers such as B-type natriuretic peptide (BNP) has been shown to be related to functional class and prognosis, particularly in AS and MR. In fact, Lancellotti et al. [9] reports in their study that a left atrial area index of > or = 12.4 cm2/m2, systolic annular velocity of < or = 4.5 cm/s, E/Ea ratio >13.8, late diastolic annular velocity of < or = 9 cm/s, and BNP of > or = 61 pg/ml were identified as the best cutoff values to predict events (death, symptoms, or surgery). They found, in asymptomatic AS, tissue Doppler imaging and BNP measurements provide prognostic information beyond that from clinical and conventional echocardiographic parameters. However, Natriuretic peptides have been shown to predict symptom free survival and outcome in normal- and low-flow severe AS and may be useful in asymptomatic patients, helping to discriminates those pa‐ tients who can benefits from an early intervention [7-9]. Nevertheless, evidence regarding its

Echocardiography is indicated when there is a systolic murmur of grade III/VI or higher, a single S2, or symptoms that might be due to AS [10]. A 2-dimensional (2D) echocardiogram is valuable for assessing valve anatomy and function and determining the LV response to pressure overload. In nearly all patients, the severity of the stenotic lesion can be defined with Doppler echocardiographic measurements. Echocardiography is also used to assess LV size and function, degree of hypertrophy, and presence of other associated valvular disease. Transoesophageal echocardiography (TOE) is rarely helpful for the quantification of AS, as valve area planimetry becomes difficult in calcified valves [11] however, it is useful when transthoracic visualization is poor and leaflets only moderately calcified [12]. TOE may, however, provide additional evaluation of mitral valve abnormalities and has gained impor‐

among young adults [5].

452 Calcific Aortic Valve Disease

however, it is not a sensitive sign.

**3. Evaluation and grading the degree of stenosis**

incremental value in risk stratification remains limited so far.

Based on the European Society of Cardiology (ESC) Guidelines on the management of valv‐ ular heart disease [12], American College of Cardiology/American Heart Association (ACC/ AHA) Guidelines for the Management of Patients With valvular heart disease [10] and ASE/EAE Recommendations for Quantitation of Stenosis Severity, [13] ACC/AHA guide‐ lines use lower mean gradient cutoffs as indicated in parentheses. The ESC definitions apply only in the presence of normal flow conditions. The velocity ratio is included in the ASE/EAE guidelines only.

Multi-slice computed tomography (MSCT) and cardiac magnetic resonance (CMR) provide additional information on the assessment of the ascending aorta when it is enlarged. MSCT may be useful in quantifying the valve area and coronary calcification, which aids in assess‐ ing prognosis. MSCT may contribute to the evaluation of the severity of valve disease, par‐ ticularly in AS, either indirectly by quantifying valvular calcification, or directly through the measurement of valve planimetry. Also, MSCT has become an important diagnostic tool for evaluation of the aortic root, the distribution of calcium, the number of leaflets, the ascend‐ ing aorta, and peripheral artery pathology and dimensions before undertaking TAVI [11]. In patients with inadequate echocardiographic quality or discrepant results, CMR should be used to assess the severity of valvular lesions—particularly regurgitant lesions—and to as‐ sess ventricular volumes and systolic function, as CMR assesses these parameters with high‐ er reproducibility than echocardiography [11]. In practice, the routine use of CMR is limited because of its limited availability, compared with echocardiography. Due to its high nega‐ tive predictive value, MSCT may be useful in excluding CAD in patients who are at low risk of atherosclerosis [11]. MSCT plays an important role in the work-up of high-risk patients with AS considered for TAVI. The risk of radiation exposure—and of renal failure due to contrast injection—should, however, be taken into consideration.

patients with severe AS based on the ESC Guidelines on the management of valvular heart disease [12] and ACC/ AHA Guidelines for the Management of Patients with valvular heart

Although there are no prospective randomized trials, data from retrospective analysis indi‐ cates that patients with moderate AS (mean gradient in the presence of normal flow 30–50

coronary surgery. However, individual judgement must be recommended [12], based on the evolution of the echocardiography severity parameters and the patient's clinical evaluation.

Based on the ESC Guidelines on the management of valvular heart disease [12] and ACC/ AHA Guidelines for the Management of Patients with valvular heart diseaseb [10].

Patient selection for AVR for AS is well outlined by ACCF/AHA and ESC guidelines. Prob‐ lems arise when the patients present significant symptoms and significant structural disease, complicated by the presence of significant comorbidity. A number of risk algorithms for car‐ diac surgery have been developed. Experience accrued since the development of the Parson‐

) will generally benefit from valve replacement at the time of

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455

New Therapeutic Approaches to Conventional Surgery for Aortic Stenosis in High-Risk Patients

disease [10] is shown in Figure 2.

mmHg, valve area 1.0–1.5 cm2

**Figure 2.** Management of Severe Aortic Stenosis.

**5. Risk stratification**

ACC/AHA recommendations has been shown in parentheses.

There are contraindications for exercise testing in symptomatic patients with AS, however it is useful for unmasking symptoms and in the risk stratification of asymptomatic patients with severe AS [12]. Stress tests are currently under-used in patients with asymptomatic AS. In some patients, it may be necessary to proceed with cardiac catheterisation and coronary angiography at the time of initial evaluation [10]. This could be appropriate if there is a dis‐ crepancy between clinical and echocardiographic examinations or if symptoms might be due to coronary artery disease (CAD).

#### **4. Indications for surgery**

Early valve replacement should be strongly recommended in all symptomatic patients with severe AS, because it is the only effective treatment. Thus, the development of symptoms identifies a critical point in the natural history of AS. The interval from the onset of symp‐ toms to the time of death is approximately 2 years in patients with heart failure, 3 years in those with syncope, and 5 years in those with angina, with a high risk of sudden death (Figure 1).

**Figure 1. Natural History.** Ross J Jr. & Braunwald E, 1968 [14]

There is some disagreement about the optimal timing of surgery in asymptomatic patients, and the decision to operate on this kind of patient requires careful weighing of the benefits against the risks. Early elective surgery, at the asymptomatic stage, can only be recommend‐ ed in selected patients, with low operative risk [12]. A proposed management strategy for patients with severe AS based on the ESC Guidelines on the management of valvular heart disease [12] and ACC/ AHA Guidelines for the Management of Patients with valvular heart disease [10] is shown in Figure 2.

Although there are no prospective randomized trials, data from retrospective analysis indi‐ cates that patients with moderate AS (mean gradient in the presence of normal flow 30–50 mmHg, valve area 1.0–1.5 cm2 ) will generally benefit from valve replacement at the time of coronary surgery. However, individual judgement must be recommended [12], based on the evolution of the echocardiography severity parameters and the patient's clinical evaluation.

**Figure 2.** Management of Severe Aortic Stenosis.

Based on the ESC Guidelines on the management of valvular heart disease [12] and ACC/ AHA Guidelines for the Management of Patients with valvular heart diseaseb [10]. ACC/AHA recommendations has been shown in parentheses.

### **5. Risk stratification**

of atherosclerosis [11]. MSCT plays an important role in the work-up of high-risk patients with AS considered for TAVI. The risk of radiation exposure—and of renal failure due to

There are contraindications for exercise testing in symptomatic patients with AS, however it is useful for unmasking symptoms and in the risk stratification of asymptomatic patients with severe AS [12]. Stress tests are currently under-used in patients with asymptomatic AS. In some patients, it may be necessary to proceed with cardiac catheterisation and coronary angiography at the time of initial evaluation [10]. This could be appropriate if there is a dis‐ crepancy between clinical and echocardiographic examinations or if symptoms might be

Early valve replacement should be strongly recommended in all symptomatic patients with severe AS, because it is the only effective treatment. Thus, the development of symptoms identifies a critical point in the natural history of AS. The interval from the onset of symp‐ toms to the time of death is approximately 2 years in patients with heart failure, 3 years in those with syncope, and 5 years in those with angina, with a high risk of sudden death

There is some disagreement about the optimal timing of surgery in asymptomatic patients, and the decision to operate on this kind of patient requires careful weighing of the benefits against the risks. Early elective surgery, at the asymptomatic stage, can only be recommend‐ ed in selected patients, with low operative risk [12]. A proposed management strategy for

contrast injection—should, however, be taken into consideration.

due to coronary artery disease (CAD).

**Figure 1. Natural History.** Ross J Jr. & Braunwald E, 1968 [14]

**4. Indications for surgery**

(Figure 1).

454 Calcific Aortic Valve Disease

Patient selection for AVR for AS is well outlined by ACCF/AHA and ESC guidelines. Prob‐ lems arise when the patients present significant symptoms and significant structural disease, complicated by the presence of significant comorbidity. A number of risk algorithms for car‐ diac surgery have been developed. Experience accrued since the development of the Parson‐ net scale reveals that this scale assigns too much weight to age. Nowadays the STS score and logistic EuroSCORE are the most commonly used. These provide information concerning short term operative risks, however, they are not able to predict symptom resolution, quali‐ ty-of-life improvement, or return to independent living.

ports that only STS-PROM correlated with mortality rates [17]. Thielmann et al [18] also re‐ port that the logistic EuroSCORE and the Parsonnet score clearly overestimated the risk of mortality, whereas the STS score and the additive EuroSCORE were much more accurate in

New Therapeutic Approaches to Conventional Surgery for Aortic Stenosis in High-Risk Patients

http://dx.doi.org/10.5772/54333

457

Certain authors, such as Rosenhek [19] and others, suggest the need to include other varia‐ bles such as cognitive function and functional capacity in surgical risk stratification, mainly in the elderly group. There are physiological characteristics inherent to elderly patients that make them different in risk estimation; an example of this is the amount of creatinine con‐ sidered in the EuroSCORE scale as a predictor of mortality. This scale assigned a particular score (2 points) to patients with creatinine levels greater than 2.26 mg / dl, which through a logistic regression analysis could estimate risk in percentage terms. However creatinine is not the best parameter to define renal function and its value can be influenced by various factors such as age, race, muscle mass and metabolic state, as has been demonstrated in sev‐ eral studies, hence glomerular filtration rate provides a much more accurate estimation [20]. Obviously in the elderly there is a physiological involution of organs and systems that should be taken into account since surgery represents a stressful situation that can reveal or tip the balance for certain pathologies. However, numerous reports have demonstrated ex‐ cellent results in terms of morbidity and mortality in most patients. Hospital mortality is sig‐ nificantly related to the preoperative presence of depressed left ventricular systolic function, pulmonary hypertension, symptoms of heart failure, kidney failure, long-standing mitral valve disease, and nutritional deficiencies. When these risk factors are absent in the preoper‐ ative period, mortality is similar to that of the youngest patients. It should be emphasized that risk models serve as one aspect of patient selection, but need to be considered alongside

predicting the risk of mortality.

**6.1. Elderly patient**

an aortic valve area (AVA) ≤1.2 cm<sup>2</sup>

critical aortic stenosis (AVA ≤0.8 cm<sup>2</sup>

clinical judgement and other methods of risk assessment.

**6. High risk and elderly patients, are they the same?**

The ageing of the population is an important social and sanitary phenomenon. Consensus about allowing access to health care unconstrained by age limits, together with increased life expectancy and advances in highly specialised medicine have brought us to the point where surgical treatment is indicated in progressively older sectors of the population [21]. The di‐ agnosis and management of valvular heart disease in the elderly has been affected by the dramatic increase in life expectancy that began in the last half of the 20th century. In the United States, for example, the number of persons aged 80 years or older is expected to in‐ crease from 6.9 million in 1990 to approximately 25 million by the year 2050. As a result, de‐ generative valve disease is likely to become an increasing problem. In the Helsinki Ageing Study [22], 501 randomly selected men and women aged 75 to 86 underwent imaging and Doppler echocardiography. The prevalence of at least moderate aortic stenosis, defined as

and velocity ratio ≤0.35, was 5 percent; the prevalence of

, and velocity ratio ≤0.35) increased with age from 1 to 2

As discussed above (see also Evaluation and Grading the Degree of Stenosis), several stud‐ ies have reported the usefulness of BNP in risk stratification of asymptomatic or mildly symptomatic patients, which could help to discriminate which patients would benefit from an early surgical management. However, there is not enough evidence to recommend the routine use of these biomarkers.

Although both are accurate in low-risk patients, accuracy is reduced in higher-risk subsets [15]. The logistic EuroSCORE is based on 12 covariates derived from 14,799 patients under‐ going all types of cardiac operations in 8 European countries in 1995. On the other hand, the STS risk predictor is based on 24 covariates derived from 67,292 patients undergoing isolat‐ ed AVR only in the United States between 2002 and 2006. Both use an algorithm based on the presence of coexisting illnesses in order to estimate 30-day operative mortality. There is a much simpler variation of the EuroSCORE logistic model, which can be calculated at the patient's bedside, adding points manually. This model is called the additive EuroSCORE. It assigns a specific value to each risk factor, and the points are simply added to obtain the es‐ timated operative mortality rate.

With improved outcomes after cardiac surgery in more recent years, EuroSCORE has be‐ come less well calibrated. EuroSCORE II has been developed using data from 22.381 pa‐ tients who underwent cardiac surgery during 2010, and represents a necessary and timely update of the original EuroSCORE models. EuroSCORE II improves on the original logistic EuroSCORE, though mainly for combined AVR and CABG cases. However, concerns still exist, about its use for isolated AVR procedures, aortic surgery and miscellaneous proce‐ dures. There is still room for improvement in risk modelling and several studies are current‐ ly being carried out to validate EuroScore II. Nevertheless, Grant et al [16] report that EuroSCORE II performs well overall in contemporary UK adult cardiac surgery, with good discrimination for all kinds of cardiac surgery; in fact, they report that the logistic Euro‐ SCORE is now obsolete and their study demonstrates that it is appropriate to use Euro‐ SCORE II as a generic risk model for contemporary UK cardiac surgery.

There is growing debate about the definition of high-risk patients and the validity of risk as‐ sessment using different risk-scoring systems for prediction of mortality (see also **High-Risk Patient**). Current models do not include some risk factors that may be particularly important in the prediction of outcomes for high- or very high-risk populations including frailty, pulmonary hypertension (PH), porcelain aorta, and the presence of hepatic dysfunc‐ tion, although all these have been included in EuroSCORE II.

Nevertheless, the sample of elderly patients considered for the design of these scales repre‐ sents a small proportion of the population, resulting in less accurate risk assessment, and in‐ terpretation should be made with caution. In this regard, a recent study which included 1245 elderly patients (mean age 77.2 years) who underwent AVR with or without CABG re‐ ports that only STS-PROM correlated with mortality rates [17]. Thielmann et al [18] also re‐ port that the logistic EuroSCORE and the Parsonnet score clearly overestimated the risk of mortality, whereas the STS score and the additive EuroSCORE were much more accurate in predicting the risk of mortality.

Certain authors, such as Rosenhek [19] and others, suggest the need to include other varia‐ bles such as cognitive function and functional capacity in surgical risk stratification, mainly in the elderly group. There are physiological characteristics inherent to elderly patients that make them different in risk estimation; an example of this is the amount of creatinine con‐ sidered in the EuroSCORE scale as a predictor of mortality. This scale assigned a particular score (2 points) to patients with creatinine levels greater than 2.26 mg / dl, which through a logistic regression analysis could estimate risk in percentage terms. However creatinine is not the best parameter to define renal function and its value can be influenced by various factors such as age, race, muscle mass and metabolic state, as has been demonstrated in sev‐ eral studies, hence glomerular filtration rate provides a much more accurate estimation [20]. Obviously in the elderly there is a physiological involution of organs and systems that should be taken into account since surgery represents a stressful situation that can reveal or tip the balance for certain pathologies. However, numerous reports have demonstrated ex‐ cellent results in terms of morbidity and mortality in most patients. Hospital mortality is sig‐ nificantly related to the preoperative presence of depressed left ventricular systolic function, pulmonary hypertension, symptoms of heart failure, kidney failure, long-standing mitral valve disease, and nutritional deficiencies. When these risk factors are absent in the preoper‐ ative period, mortality is similar to that of the youngest patients. It should be emphasized that risk models serve as one aspect of patient selection, but need to be considered alongside clinical judgement and other methods of risk assessment.
