**1. Introduction**

Aortic stenosis is the most frequent valve disease leading to intervention in developed countries, either surgery or catheter, and its incidence increases due to the aging population [1].

The management of aortic stenosis has improved and evolved to a reduction in surgical aggression. Nowadays, the patients with intermediate risk are in the frontier of transcatheter aortic valve implantation (TAVI) and aortic valve replacement (AVR) and more than ever, the heart team has to be more accurate to choose between the different treatment options available, making the decision pathway more complex than a few year before. Our goal is to update the treatment of severe aortic stenosis in those patients where risk assessment scales indicate an intermediate risk. Here, we analyze the current treatment options and their results.

#### **2. Etiology and natural history**

Nowadays, degenerative calcific AS is the most common cause of AS in adults at older ages and represents the leading cause for aortic valve intervention [2–4]. In the other hand, bicuspid aortic valve affects 2% of the population and represents the most common indication for intervention at younger patients [5].

The development of symptoms identifies a paramount point in the natural history of AS, and the interval from the onset of symptoms 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 [6].

### **3. Evaluation and severity classification of aortic stenosis**

Careful exploration for the presence of symptoms (shortness of breath on exertion, angina, dizziness, or syncope) is very important for right patient management. The characteristic systolic murmur draws attention and guides further diagnostic work in the right direction.

**Echocardiography** is the key diagnostic tool [7]. It discriminates the degree of valve calcification, LV function, and wall thickness; helps to identify other associated valve diseases or aortic pathology; and provides prognostic information. The severity of the stenotic lesion can be defined with Doppler echocardiographic measurements. Transoesophageal echocardiography (TOE) provides additional evaluation of concomitant mitral valve abnormalities, and become useful when transthoracic visualization is poor [8]. TOE has gained importance in the assessment and intraprocedure guidance and after TAVI or surgical interventions.

Three-dimensional TOE offers a more detailed examination of valve anatomy than two-dimensional echocardiography and is useful for the assessment and planning of complex valve problems [8]. AS severity could be graded on the basis of a variety of hemodynamic and natural history data as shown in **Table 1**.

Multislice computed tomography (MSCT) and cardiac magnetic resonance (CMR) give additional data on the assessment of the ascending aorta when it is enlarged or to quantifying the valve area, coronary calcification, size and shape of the aortic valve annulus, and its distance to the coronary ostia, which aids in evaluation and prognosis. It is essential to evaluate the feasibility of the various access routes for TAVI, as this provides information on minimal luminal diameters, atherosclerotic plaque burden, the presence of aneurysms or thrombi, etc. [8]. MSCT plays an important role in the diagnostic work-up before transcatheter aortic valve implantation. The risk of radiation exposure—and of renal failure due to contrast injection—should, however, be taken into consideration.


*Based on the recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the European Association of Cardiovascular Imaging and the American Society of Echocardiography [9].*

#### **Table 1.**

*Severe aortic stenosis measurement by echocardiography. The definitions apply only in the presence of normal flow conditions.*

**33**

(EVOLVED-AS) [16].

*Current Management of Severe Aortic Stenosis in Intermediate Risk Patients*

In patients with inadequate echocardiographic quality or discrepant results, CMR should be used to assess the severity of valvular lesions and to assess ventricu-

In physically active patients, an **exercise testing** could be recommended for unmasking symptoms and for risk stratification of asymptomatic patients [10]. Also, exercise stress echocardiography may give prognostic information in asymptomatic severe aortic stenosis [10, 11]. In some patients, it may be necessary to proceed with cardiac catheterization and coronary angiography at the time of initial

**Biomarkers**. Several studies [12–15] report that biomarkers such as B-type natriuretic peptide (BNP) have been shown to be related to functional class and prognosis, particularly in AS and MR. 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 discriminate those patients who can benefit from an early intervention [13–15]. In fact, in the last ESC/EACTS guidelines for the management of valvular heart disease, natriuretic peptides may be of value for risk stratification and timing of intervention, particularly in asymptomatic patients ("markedly elevated BNP levels (>threefold age- and sex-corrected normal range) confirmed by repeated measurements without other explanations") [8].

Here, we have to take notice of the patient's status in order to choose the type of intervention and the correct timing of it. **Early valve intervention should be strongly recommended in all symptomatic patients with severe AS, because it is the only effective treatment.** "As long as the mean gradient remains >40 mmHg, there is virtually no lower ejection fraction limit for intervention, whether surgery

However, patients with severe comorbidities indicating a survival of <1 year and patients in whom is unlikely that the intervention will improve quality of life or

**Asymptomatic patients**. There is some disagreement about the optimal timing of surgery in asymptomatic patients, and the decision to operate on this kind of

*The available studies do not provide convincing data to support the general recommendation of early SAVR, even in patients with asymptomatic and very severe aortic stenosis, and TAVI is not recommended in asymptomatic patients* [7, 8]. However, subclinical adverse remodeling can precede the development of symptoms and LV dysfunction [16]. Musa et al. performed cardiac magnetic resonance (CMR) in 674 patients who had severe AS and were scheduled for surgical or transcatheter AVR. Myocardial fibrosis (scar) demonstrated by late gadolinium enhancement (LGE) on CMR was common (51%). In a median followup of 3.6 years (interquartile range, 2.6–5.9 years), 21.5% of patients had died. In multivariable analysis, scar (LGE positivity) was independently associated with all-cause and cardiovascular mortality (hazard ratios, 2.39 and 3.14, respectively). The elevated mortality was independent of whether the patients underwent surgical or transcatheter AVR and was similar in patients with infarct and noninfarct scar patterns. These findings raise the possibility that adverse remodeling has irreversible effects before symptoms develop: We may be waiting too long to treat these patients. The authors suggest that physicians might use scar burden to optimize the timing of intervention, a hypothesis currently being evaluated in a randomized trial

survival should be excluded from further interventions.

patient requires careful weighing of the benefits against the risks.

*DOI: http://dx.doi.org/10.5772/intechopen.83422*

lar volumes and systolic function [8].

**4. Indications for intervention**

evaluation [7].

or TAVI" [8].

*Current Management of Severe Aortic Stenosis in Intermediate Risk Patients DOI: http://dx.doi.org/10.5772/intechopen.83422*

In patients with inadequate echocardiographic quality or discrepant results, CMR should be used to assess the severity of valvular lesions and to assess ventricular volumes and systolic function [8].

In physically active patients, an **exercise testing** could be recommended for unmasking symptoms and for risk stratification of asymptomatic patients [10]. Also, exercise stress echocardiography may give prognostic information in asymptomatic severe aortic stenosis [10, 11]. In some patients, it may be necessary to proceed with cardiac catheterization and coronary angiography at the time of initial evaluation [7].

**Biomarkers**. Several studies [12–15] report that biomarkers such as B-type natriuretic peptide (BNP) have been shown to be related to functional class and prognosis, particularly in AS and MR. 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 discriminate those patients who can benefit from an early intervention [13–15]. In fact, in the last ESC/EACTS guidelines for the management of valvular heart disease, natriuretic peptides may be of value for risk stratification and timing of intervention, particularly in asymptomatic patients ("markedly elevated BNP levels (>threefold age- and sex-corrected normal range) confirmed by repeated measurements without other explanations") [8].

#### **4. Indications for intervention**

*Aortic Stenosis - Current Perspectives*

**2. Etiology and natural history**

diagnostic work in the right direction.

Nowadays, degenerative calcific AS is the most common cause of AS in adults at older ages and represents the leading cause for aortic valve intervention [2–4]. In the other hand, bicuspid aortic valve affects 2% of the population and represents

The development of symptoms identifies a paramount point in the natural history of AS, and the interval from the onset of symptoms to the time of death is approximately 2 years in patients with heart failure, 3 years in those with syncope,

Careful exploration for the presence of symptoms (shortness of breath on exertion, angina, dizziness, or syncope) is very important for right patient management. The characteristic systolic murmur draws attention and guides further

**Echocardiography** is the key diagnostic tool [7]. It discriminates the degree of valve calcification, LV function, and wall thickness; helps to identify other associated valve diseases or aortic pathology; and provides prognostic information. The severity of the stenotic lesion can be defined with Doppler echocardiographic measurements. Transoesophageal echocardiography (TOE) provides additional evaluation of concomitant mitral valve abnormalities, and become useful when transthoracic visualization is poor [8]. TOE has gained importance in the assessment and intraprocedure guidance and after TAVI or surgical interventions.

Three-dimensional TOE offers a more detailed examination of valve anatomy than two-dimensional echocardiography and is useful for the assessment and planning of complex valve problems [8]. AS severity could be graded on the basis of a

Multislice computed tomography (MSCT) and cardiac magnetic resonance (CMR) give additional data on the assessment of the ascending aorta when it is enlarged or to quantifying the valve area, coronary calcification, size and shape of the aortic valve annulus, and its distance to the coronary ostia, which aids in evaluation and prognosis. It is essential to evaluate the feasibility of the various access routes for TAVI, as this provides information on minimal luminal diameters, atherosclerotic plaque burden, the presence of aneurysms or thrombi, etc. [8]. MSCT plays an important role in the diagnostic work-up before transcatheter aortic valve implantation. The risk of radiation exposure—and of renal failure due to contrast

) <0.6

*Based on the recommendations on the echocardiographic assessment of aortic valve stenosis: a focused update from the* 

*Severe aortic stenosis measurement by echocardiography. The definitions apply only in the presence of normal* 

) <1 Velocity ratio <0.25

*European Association of Cardiovascular Imaging and the American Society of Echocardiography [9].*

variety of hemodynamic and natural history data as shown in **Table 1**.

injection—should, however, be taken into consideration.

Peak velocity (m/s) ≥4 Mean gradient (mmHg) ≥40

the most common indication for intervention at younger patients [5].

and 5 years in those with angina, with a high risk of sudden death [6].

**3. Evaluation and severity classification of aortic stenosis**

**32**

**Table 1.**

*flow conditions.*

Indexed AVA (cm2

AVA (cm2

/m2

Here, we have to take notice of the patient's status in order to choose the type of intervention and the correct timing of it. **Early valve intervention should be strongly recommended in all symptomatic patients with severe AS, because it is the only effective treatment.** "As long as the mean gradient remains >40 mmHg, there is virtually no lower ejection fraction limit for intervention, whether surgery or TAVI" [8].

However, patients with severe comorbidities indicating a survival of <1 year and patients in whom is unlikely that the intervention will improve quality of life or survival should be excluded from further interventions.

**Asymptomatic patients**. 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.

*The available studies do not provide convincing data to support the general recommendation of early SAVR, even in patients with asymptomatic and very severe aortic stenosis, and TAVI is not recommended in asymptomatic patients* [7, 8]. However, subclinical adverse remodeling can precede the development of symptoms and LV dysfunction [16]. Musa et al. performed cardiac magnetic resonance (CMR) in 674 patients who had severe AS and were scheduled for surgical or transcatheter AVR. Myocardial fibrosis (scar) demonstrated by late gadolinium enhancement (LGE) on CMR was common (51%). In a median followup of 3.6 years (interquartile range, 2.6–5.9 years), 21.5% of patients had died. In multivariable analysis, scar (LGE positivity) was independently associated with all-cause and cardiovascular mortality (hazard ratios, 2.39 and 3.14, respectively). The elevated mortality was independent of whether the patients underwent surgical or transcatheter AVR and was similar in patients with infarct and noninfarct scar patterns. These findings raise the possibility that adverse remodeling has irreversible effects before symptoms develop: We may be waiting too long to treat these patients. The authors suggest that physicians might use scar burden to optimize the timing of intervention, a hypothesis currently being evaluated in a randomized trial (EVOLVED-AS) [16].
