Optimal patient selection by the Heart Team is essential for a successful TAVI program.

First of all, patient’s operative risk should be assessed according not only to age and severity of heart disease but also to systemic comorbidities (e.g., respiratory failure, kidney and liver disease, prior cerebrovascular accident, neurological deficit, peripheral vascular disease, previous or current cancer, connective tissue and autoimmune diseases, etc.).

Risk assessment depends on the combination of multiple evaluations:

The guidelines state that selected patients should be expected to gain improvement in their quality of life and to have a life expectancy of 1 year after consideration of their comorbidities. It should be noted that some patients’ risk is even too high also for TAVI and that significant comorbidities (e.g., severe chronic obstructive pulmonary disease) may lead to persistent impaired quality of life and high mortality despite TAVI.

Different algorithms are described in literature to estimate the risk of mortality and perioperative morbidity, which were built on the basis of large cardiac surgery series. The scores most widely used in clinical practice to predict operative mortality in cardiac surgery are:

Although many other risk scores are available (Ambler, Initial Parsonnet, Cleveland Clinic, French, Pons, and Ontario Province Risk score among the others), most of them take into account a limited number of variables with poor predictive value. In the current practice, a patient is considered to be at high surgical risk when the estimated 30-day mortality is >10 % with STS score and >20 % with EuroSCORE II. However, if used for TAVI risk stratification, they showed a weak predictive power [12], since they were developed from and for unselected surgical patients and they do not take into account clinical and anatomical variables (radiation heart disease, heavily calcified or porcelain ascending aorta, the intrinsic fragility of the patient (“frailty”), and liver disease) that could have a role in TAVI prognosis. However, a TAVI-oriented risk stratification score is still missing.

The frailty is defined by slowness, weakness, exhaustion, wasting and malnutrition, poor endurance and inactivity, and loss of independence which reflect the poor physical and cognitive performance of the patient. The frailty is often estimated subjectively on the basis of a so-called eyeball test but can be objectified with some simple tests such as analysis of physical performance by measuring gait speed and grip strength. These continuous measures are reproducible and can be reassessed at various time points; in addition, they don’t require language translation. Evaluation of physical performance should always be accompanied by assessment of mental abilities, underweight (BMI <20 kg/m² and/or weight loss 5 kg/year), activity level, and independence in activities of daily living. The most utilized is the Katz Activities of Daily Living Index, which evaluates independence in feeding, bathing, dressing, transferring, toileting, and urinary continence and independence in ambulation (no walking aid or assist required or 5 m walk in <6 s) [13, 14].

Laboratory findings (e.g., serum albumin <3.5 g/dL, elevated inflammatory markers, anemia) may further reflect the health state and physiological reserve of the frail patient.

One essential part of the initial risk stratification is represented by the evaluation of the presence of preprocedural cognitive dysfunction with degrees varying from mild cognitive impairment to dementia, particularly in populations of elderly patients, in order to weigh carefully the risk, the benefit, and the cost-effectiveness of invasive procedures. Furthermore, preexisting cognitive impairment can worsen during hospitalization, and careful differential diagnosis with new cerebrovascular complications could be challenging.

Different neurocognitive tests are available (e.g., Mini-Mental State Examination, Clinical Dementia Rating Scale), and a cognitive assessment should be considered systematically in Heart Team evaluations, eventually carried out by neuropsychological experts.

Numerous comorbidities are not included in the commonly used risk score, but they should be considered in risk stratification for TAVI (Table 1.1).

First of all, heart function at transthoracic echocardiography must be taken into account: patients with low ejection fraction (<40 %) could present as low-flow, low-gradient severe AS that should be distinguished by pseudostenosis by means of low-dose dobutamine stress echo: in true severe AS with recovery of function, the ejection fraction increases with parallel increase of mean aortic gradient, whereas in pseudostenosis the mean aortic gradient does not increase at the increase of ejection fraction. Patients with low-flow, low-gradient severe AS have been associated with high mortality after AVR, up to 35 % in those without contractile reserve [15] and with a resting mean gradient <20 mmHg [16]. TAVI is a feasible approach in this subset of patients [17]: despite a high short-term mortality, the surviving patients showed symptomatic benefit and significant improvement of myocardial function and exercise capacity along with significant improvement in quality of life. Patients with paradoxically low-flow, low-gradient severe AS (i.e., with preserved ejection fraction and low stroke volume index (<35 ml/m²)) have increased mortality after TAVI, independently of ejection fraction [18]. Nevertheless, feasibility and safety of TAVI have been demonstrated in low-flow, low-gradient, severe AS and preserved ejection fraction [19].

Risk assessment should include coronary artery disease evaluation. Appropriate revascularization strategies in the setting of AS should be considered in the Heart Team and should be individualized based on comorbidities and bleeding risk factors. When needed, percutaneous coronary intervention can be safely performed in patients eligible to TAVI, without an increased risk of short-term adverse outcomes [20].

The presence of severe of pulmonary hypertension is an independent predictor for mortality after surgical AVR, as may reflect more advanced state of disease [21]. Advanced disease of other organs, including severe obstructive lung disease, is independently associated with increased mortality in patients undergoing TAVI [22].

Many major organ systems may be compromised in elderly population affected by severe AS, thus increasing surgical risk beyond common used risk scores. Therefore, a systematic approach should be used to analyze multiple comorbidities. In Table 1.2 a schematic method of evaluation of patient eligible to TAVI is reported, utilized in Padua University for Heart Team discussion.