**2. Patients selection**

Aortic stenosis is frequently associated with advanced age and numerous cardiovascular non-cardiovascular diseases. Because of that, the treatment choice is based on a careful and 360° patient evaluation.

#### **2.1 General screening: symptoms and prognostic impact**

A typical benign course characterizes aortic valve stenosis during most of its natural history. At the same time, a drastic prognostic worsening occurs after symptoms onset, with an event-free survival of only 30–50% at two years and with an average survival of just 2–3 years without aortic valve replacement [14–17]. For that reason, looking for even vague symptoms and closer follow-up have a central role during the medical visit. Aortic stenosis typically manifests itself with effort angina, dyspnea, progressively evolving to congestive heart failure, pre-syncopal, and syncopal events. However, symptoms may be atypical, like fatigue or tiredness, especially in the elderly who, for concomitant reasons, are not able to perform relevant efforts. Usually, in western countries, the onset of the symptoms occurs between 7th and 9th decade of life as a consequence of progressive calcification of valvular cusps [18]. In elderly/complex patients, a critical effort should be to recognize the most likely cause of symptoms, especially in mild or moderate aortic stenosis, as symptoms normally occur in severe stenosis. Moreover, aortic stenosis shares the same risk factors and symptoms as other cardiac and noncardiac diseases. Dyspnea can be present in asthma, chronic obstructive pulmonary disease (COPD), anemia, renal failure, deconditioning, and coronary artery disease (CAD), which could also be manifest with angina and arrhythmias-related presyncope or syncope. In particular, CAD in aortic valve stenosis patients is highly-prevalent; it was found in 69.7% of patients addressed to TAVR in the PARTNER II trial and in 69.2% of patients assigned to SAVR in the SURTAVI trial [7, 9]. Coronary angiography is recommended in assessing each patient with severe aortic stenosis to identify patients that could benefit from contemporary coronary revascularization [13].

In general, aortic valve stenosis progression is constant, with an average annual reduction in the valvular aortic area of 0.03 ± 0.01 cm2/year and about 2.7 ± 0.1 mmHg in the mean transaortic pressure gradient [19]. To improve proper follow-up and identify the most suitable time to proceed to aortic valve replacement, In 2020, American Heart Association (AHA)/American College of Cardiology (ACC) guidelines classify patients into 4 stages according to the natural history phase of aortic valve stenosis: from those at risk of development aortic stenosis (Stage A), to progressive aortic stenosis with mild or moderate calcifications (Stage B), to asymptomatic severe aortic stenosis with normal or reduced left ventricular ejection fraction (LVEF) (Stage C), and to symptomatic aortic stenosis with normal or reduced LVEF (Stage D). This classification is useful in the management of patients because each stage is associated with a proper diagnostic-therapeutic iter; in particular, aortic valve replacement is recommended in all Stage D patients and in Stage C with reduced LVEF (< 50%) [20]. In fact, despite improving symptoms in the short term, medical therapy is not capable of changing the natural history of severe aortic stenosis; therefore, aortic valve replacement is the only effective therapy.

## **2.2 Risk stratification**

According to 2021 ESC/EACTS guidelines for the management of valvular heart disease, aortic valve replacement is recommended for every symptomatic severe aortic stenosis (IB) and asymptomatic severe aortic stenosis with systolic left ventricular dysfunction (LVEF <50% IB; < 55% IIa B) without another cause, undergoing coronary artery bypass graft (CABG) or surgical intervention on the ascending aorta or another heart valve, demonstrable symptoms or sustained fall in blood pressure (> 20 mmHg)

#### *Transcatheter Treatment of Aortic Valve Disease Clinical and Technical Aspects DOI: http://dx.doi.org/10.5772/intechopen.105860*

on exercise testing (IIa B-C), and/or procedural low-risk plus a risk parameter (very severe aortic stenosis, severe valve calcification and peak aortic valve velocity progression ≥0.3 m/sec/year, markedly elevated brain natriuretic peptide levels) [13].

Once indication to valve replacement is defined, the choice between surgical and transcatheter intervention lies on age, surgical hazard, previous cardiac surgery, a concomitant cardiac condition requiring intervention, technical parameters, comorbidities, and frailty. These parameters should be evaluated by a multidisciplinary heart team, whose role is predominant, especially in moderate-risk patients, in which cases guidelines provide less indications [13]. Aspects favoring SAVR are younger age (typically <75 years), low surgical risk, no previous thoracic surgery, coronary or heart valve disease requiring intervention, and nonrelevant comorbidities, while older age (≥ 75 years), high surgical risk, previous thoracic surgery, and comorbidities favor TAVR. The scores that are commonly used in the definition of the surgical risk are Society of Thoracic Surgeons Mortality (STS) score and EuroSCORE II. Although, these scores were born and developed for stratifying risk in patients undergoing cardiac surgery and not for those who are scheduled for transcatheter therapy. Moreover, they provide just only low correlation with 30-day mortality [21]. In a recent multicenter study performed on patients assigned to TAVI, STS score and EuroSCORE II demonstrated just a moderate correlation and a low accuracy for inhospital adverse events and for 30-day and medium-term mortality, pointing out the necessity of dedicated scores [22].

Technical aspects will be discussed in a separate section (see Anatomical assessment).

#### **2.3 Futility**

Transcatheter aortic valve implantation was developed to improve prognosis and has revolutionized the treatment of elderly patients affected by severe aortic stenosis. The expansion in indication and the spread among centers determined the increase of its demand. Consequently, adequate patients selection has become fundamental to avoid wasted resources. Currently, TAVI represents a highly expensive intervention and a relevant issue in a health system where economic resources are limited. However, cost/efficacy analysis had demonstrated a non-inferiority of TAVI respective to SAVR in the long run; in particular, Cohen *et al*. [23] demonstrated how, despite a higher procedural cost, TAVI allows significantly reduced follow-up costs, compared to SAVR. According to the 2017 American College of Cardiology (ACC) consensus, avoiding intervention on patients who are not going to benefit in survival or quality of life is appropriate. In particular, futility is defined for patients with a life expectancy inferior to 1 year and for those with expected survival with benefit of <25% at 2 years, as evaluated with NYHA class and/or Canadian Cardiovascular Society (CCS) angina grade improvement [24].

In the recent frailty in older adults undergoing aortic valve replacement (FRAILTY-AVR; NCT01845207) study, 646 TAVI patients have been stratified with several frailty scores. The one that had the major correlation with prognosis was the essential frailty toolset (ETF) score. This score is composed of 4 items: mobility (assessed by the time necessary to get up from a chair), cognitive function, hemoglobin value, and serum albumin value. It is interesting to notice that the highest (i.e. the worst) score (5) was associated with a mortality rate of 63% and a major disability rate of 16%. The persistence of a high ETF score value after interventions focused on its reduction could be a futility marker in this kind of patient [25].

In addition to the futility issue, the TAVI's outcome still has several possibilities of improvement; after implantation, there is a 30-days mortality rate of 7.8% and 2.2%, with old and new devices, respectively [26]. Moreover, considering 5 years of follow-up derived from major trials, the mortality rates exponentially increase. In the Core Valve US pivotal extreme and High-Risk trial (NCT01240902), a prospective, multicenter, and single-arm clinical trial of TAVI enrolling 639 patients with severe aortic stenosis at extreme surgical risk, with a mean age of 82.8 ± 8.4 years, a 5-year mortality rate of 71.6% was observed (with futility of 50.8%) [27]. The same behavior was confirmed in the PARTNER I and II trials, enrolling, respectively, inoperable and surgical intermediate-risk patients randomly assigned to TAVI or SAVR, reporting a 5-year mortality of 71.8% vs. 93.6% (p < 0.0001; PARTNER I) and of 47.9% and 43.4% (p = 0.21; PARTNER II) [6, 7]. It is interesting to notice that a rapid increase in mortality is observed after about 30 days from intervention [28]. Several studies have demonstrated that in patients undergoing TAVI, after an early phase of high cardiovascular risk, this drastically reduces but, in elderly, non-valvular heart failure and noncardiac diseases represent the main causes of death. According to Chen et al. metanalysis, main etiologies are: infections/sepsis (14%), cancer (7%), renal insufficiency (4%), multi-organ failure (3%), and other causes (23%) [29]. This scenario is easily understandable considering that TAVI patients are generally older and have more comorbidities, compared to patients addressed to conventional surgery, and despite valvular disease correction, advanced age and comorbidities still represent a heavy frailty burden [30, 31]. Although, age is not automatically a synonymous of frailty, the latter has demonstrated to significantly affect the outcome of patients undergoing TAVI even in the 90-years-old population [32].

Several factors are associated with increased morbidity and mortality at 1 year after aortic valve replacement among cardiac conditions, atrial fibrillation (AF), left ventricular systolic dysfunction, mitral regurgitation, pre-capillary pulmonary hypertension, and right ventricular dysfunction. Among extracardiac conditions, COPD and restrictive lung diseases, chronic kidney disease, cancer, advanced age, and frailty are the most impacting from a prognostic point of view [33]. In this context, a fundamental question concerns if aortic valve replacement may improve or resolve symptoms and associated conditions affecting prognosis. Indeed, left ventricular systolic dysfunction, when other potential causes are excluded, improves in about two-thirds of the patients from 48 hours to 1-year post aortic valve replacement [34], and mitral regurgitation, especially if functional, may be positively affected after TAVI [35]. Conversely, COPD (with poor exercise tolerance, oxygen-dependency or use of noninvasive ventilation), precapillary pulmonary hypertension (especially with systolic pulmonary artery pressure > 60 mmHg), primary mitral valve regurgitation, active cancer, and cognitive impairment are unlikely to get better after aortic valve replacement and are thus associated with a worse prognosis [36–38].

Considering the multidimensional phenotype and the discordance among the various tests and scores used in clinical practice, quantifying the impact of frailty could be challenging. Its assessment is however essential in patients' selection in order to improve extracardiac diseases and avoid vain invasive procedures.

#### *2.3.1 Balloon aortic valvuloplasty (BAV)*

Widely used in high surgical risk patients since it was first introduced by Cribier *et al*. in 1985, BAV is progressively gaining significance in patients' stratification,
