Severe aortic stenosis is defined as an aortic valve peak velocity exceeding 4 m/s, mean pressure over 40 mm Hg, or a valve area less than 1 cm² (indexed ≤0.6 cm²/m²). Current consensus guidelines recommend close monitoring of patients with severe aortic stenosis, particularly to detect symptoms or left ventricular systolic dysfunction, which is defined when the ejection fraction falls below 50%. However, recent years have seen a shift from expectant management in asymptomatic severe aortic stenosis due to the poor prognosis associated with sudden complications, including sudden death. Consequently, various international groups are advocating early aortic valve replacement (AVR) before symptom onset to potentially reduce left ventricular dysfunction and mortality. Studies have identified predictors of poor prognosis, highlighting the long-term survival benefit of early AVR in asymptomatic patients. 

The present study analyzes the advantages of early AVR in asymptomatic patients with a mean follow-up of 8.5 years. It is a retrospective analysis based on data from 2002 to 2020, collected from routine follow-ups or cardiology visits and supplemented with mortality data. Survivors were assessed through one-year echocardiographic and survival tracking, with comparisons made by age and sex in a cohort format. Pre-AVR echocardiographic data were obtained preoperatively and included parameters such as left ventricular mass index, left atrial diameter, right ventricular systolic pressure, mean E/E’ ratio, and E/A ratio, as per current echocardiographic guidelines. Post-discharge follow-up echocardiograms were recorded, with a total of 594 studies in 201 patients. The mean echocardiographic follow-up duration was 6.2 ± 0.2 years, with 25% followed for over 2 years, 75% for more than 7 years, and 10% for more than 13 years. Adverse effects analyzed included persistent or progressive left ventricular hypertrophy and diastolic dysfunction post-AVR. Mortality from all causes was analyzed according to the STS Adult Cardiac Database specifications, and survival was evaluated with Kaplan-Meier analysis, comparing age- and sex-matched survival with the U.S. general population. 

In total, 272 consecutive patients with a mean age of 66.5 years, 41% of whom were female, were included. The average STS risk score was 1.94%, and 23 patients (8.5%) underwent concomitant aortic surgery. The preoperative aortic valve gradient was 45.4 mm Hg, the mean left ventricular mass index was 101 g/m², the average E/E’ ratio was 14.5, and the median left ventricular ejection fraction was 60% (IQR 55-65%). There was no operative mortality, and complications in 49 patients included atrial fibrillation and acute renal failure. The median hospital stay was 6 days (IQR 5-7 days). Symptom-free survival rates were 100%, 88%, 72%, and 52% at 1, 5, 10, and 15 years, respectively. The long-term evaluation of left ventricular remodeling and diastolic dysfunction was reliable at 15 years. Severe left ventricular hypertrophy was present in 21% of patients, and 46% had diastolic dysfunction, both of which were present preoperatively. Male sex and higher preoperative left ventricular mass index correlated with an E/E’ ratio >14. In the follow-up period, 44 deaths occurred, and Cox univariate analysis identified an elevated E/E’ ratio and moderate or severe preoperative left ventricular hypertrophy as risk factors for reduced survival. 

In conclusion, this study proposes early AVR in patients with asymptomatic severe aortic stenosis, though further studies with larger populations and extended follow-up are needed. 

COMMENTARY: 

Current clinical guidelines, with a IIa recommendation, identify two circumstances favoring early intervention: ventricular dysfunction associated with an ejection fraction less than 50% and severe aortic stenosis with a post-valve velocity over 5 m/s or an indexed aortic valve area (AVA) of ≤0.6 cm²/m². 

The primary findings of this study were that: 1) asymptomatic patients with severe aortic stenosis exhibit greater left ventricular hypertrophy and advanced diastolic dysfunction; 2) AVR improved left ventricular hypertrophy, but diastolic dysfunction did not improve, especially in patients with a preoperative E/E’ >14; 3) AVR in asymptomatic patients with preserved left ventricular systolic function demonstrated excellent outcomes with no postoperative mortality; and 4) moderate to severe left ventricular hypertrophy predicts long-term diastolic dysfunction and reduces long-term survival. 

Study limitations include: 1) observational and single-center design; 2) no serum proBNP-NT measurement in a relatively young (mean age 66 years) and possibly active population; 3) non-standardized data collection in echocardiograms; the E/E’ ratio, a reliable diastolic dysfunction predictor, is recommended to be supplemented by the E/A ratio, tricuspid regurgitation velocity, and indexed left atrial volume. 

In essence, this study evaluates the long-term outcomes of AVR in asymptomatic patients with severe aortic stenosis and preserved left ventricular function, essential for determining the appropriate timing of aortic valve replacement. Understanding the prognostic implications of severe asymptomatic aortic stenosis is crucial, as these patients may experience sudden acute events or sudden death before symptom onset, guiding a more proactive treatment approach. Severe aortic stenosis also interacts with other cardiovascular and metabolic diseases that impact long-term prognosis, as do delays in healthcare access, especially in resource-limited settings. Thus, early intervention in this pathology is compelling, while acknowledging that not all patients are clear surgical candidates, as reflected by the low-risk profile of the cohort in this study. 

Current evidence advises caution in patient selection, avoiding any expectation of mandatory treatment; evidence of significant improvement in adverse prognostic indicators remains insufficient. 

REFERENCE: 

Javadikasgari H, McGurk S, Newell PC, Awtry JA, Sabe AA, Kaneko T. Evolving concept of aortic valve replacement in asymptomatic patients with severe aortic stenosis. Ann Thorac Surg 2024;117:796-803. doi: 10.1016/j.athoracsur.2023.08.015.