Do asymptomatic people with severe valvular aortic stenosis and normal left ventricular function benefit from valve replacement?
At the outset it may be mentioned that this discussion pertains only to patients who are candidates for surgical aortic valve replacement (SAVR), as transcatheter aortic valve implantation (TAVI) is not recommended in asymptomatic patients.
There are currently no convincing data that all patients with severe valvular aortic stenosis (AS) who have normal left ventricular function and are asymptomatic by history and during exercise testing may benefit from early valve replacement and current guidelines, therefore, recommend watchful waiting for these patients.
However, recently some parameters have been found, the presence of which may warrant early surgery in such patients.
A new recommendation added in recent guidelines is that SAVR should be considered in patients presenting with severe pulmonary hypertension when surgical risk is low. The negative impact of pulmonary hypertension on long-term outcome was reported in a study including more than 1000 patients with severe AS supporting the guidelines.
In this study, 1019 with severe AS and LV ejection fraction ≥50% were divided into three groups according to the level of their peak tricuspid regurgitation velocity (TRV) at the time of enrolment: Group 1 (n = 695, 68%) when TRV was ≤2.8 m/s; Group 2 (n = 212, 21%) when TRV was between 2.9 m/s and 3.4 m/s and Group 3 (n = 112, 11%) when TRV was > 3.4 m/s. Median overall follow-up was 31 [6–182] months.
Dividing the whole population into two groups with a 3.4 m/s TRV threshold, multivariate analysis, after covariate adjustment, including surgery showed that Group 3 exhibited major excess mortality (adjusted HR 1.46 [1.10–1.95], P = 0.009).
Although current guidelines do no longer include the recommendation that surgery may be considered in asymptomatic patients with an increase in mean gradient >20 mmHg on exercise, exercise testing may be performed to objectively assess symptom status, exercise workload, blood pressure response and ST changes. An increase in pulmonary artery systolic pressure (PASP) to >60 mm Hg and a lack of an increase in ejection fraction (EF) are indicators of a poor prognosis. Although global longitudinal strain (GLS) is a better marker of LV dysfunction, cut-off values for exercise-induced changes in GLS have not been established to aid in clinical decision making.
An exercise test may be considered abnormal in the presence of (1) angina, syncope or presyncope; (2) dyspnoea or maximal exhaustion to functional capacity (5 Metabolic equivalents (METS) in patients aged <70 years or 4 METS in patients aged >70 years); (3) decrease in systolic blood pressure of >20 mm Hg; (4) ST-segment depression of >2 mm; or (5) more than three consecutive ventricular premature beats or ventricular tachycardia during exercise or recovery.
Recently, Nakatsuma et al showed in a large multicentre cohort of 387 patients from the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry, that high B-type natriuretic peptide (BNP) levels were associated with a higher risk for AS-related adverse events in asymptomatic severe AS with normal left ventricular ejection fraction. Patients with BNP <100 pg/mL had a low event rate for ‘aortic valve-related death or heart failure hospitalization (2% at 1 year), and those with BNP <300 pg/mL had a low rate of sudden death (1% at 1 year) and aortic valve-related death (2% at 1 year). Although this was a retrospective study and firmer evidence from a randomized study is warranted, the study results suggest that asymptomatic patients with BNP levels of <100 pg/mL might be safely followed with watchful waiting strategy.
Valve calcification and rate of increase of peak aortic jet velocity:
Rosenhek R et all studied the natural history of 128 consecutive patients with asymptomatic, severe aortic stenosis from 1994, prospectively followed until 1998. Of the patients with moderately or severely calcified aortic valves whose aortic-jet velocity increased by 0.3 m per second or more within one year, 79 percent underwent surgery or died within two years of the observed increase.
Other predictive factors: Older age, presence of atherosclerotic risk factors, excessive LV hypertrophy, and abnormal longitudinal LV function
Untreated severe AS causes on the long-term progressive damage to other heart structures. Genereux et al. accordingly classified five stages of disease: no extra-valvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or TV damage (Stage 3), and right ventricular damage (Stage 4). One-year mortality increased continuously from 4.4% (Stage 0) to 24.5% (Stage 4). The extent of cardiac damage was independently associated with increased mortality after aortic valve replacement (AVR). These data emphasize once more the importance of timely intervention.
Thus, there are several pointers to indicate that early surgery rather than waiting may be advantageous for asymptomatic patients with severe aortic stenosis with normal LV systolic function. The chief ones are pulmonary hypertensions, exercise parameters, biomarkers and annual increase in peak jet velocity in calcified valves.
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