Timing Intervention in Symptomatic Normal-Flow, Low-Gradient AS

Study Questions:

What is the long-term mortality of early aortic valve replacement (AVR) versus a strategy of watchful observation among symptomatic patients with normal-flow, low-gradient severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF)?


From 2000 to 2011, 284 consecutive symptomatic patients (136 men, aged 68 ± 10 years) with normal-flow, low-gradient severe AS and preserved LVEF who were potential candidates for early AVR were prospectively evaluated. Normal-flow, low-gradient severe AS was defined as indexed AV area <0.6 cm2/m2 with mean gradient <40 mm Hg and stroke volume index ≥35 ml/m2. Early AVR was performed in 98 patients, while a strategy of watchful observation was selected for 186 patients. Patients in the watchful observation group were referred for AVR if mean gradient was ≥40 mm Hg during follow-up.


There were no significant differences between the early AVR and the watchful observation groups for the risk of overall mortality (hazard ratio [HR], 0.94 for the early AVR; 95% confidence interval [CI], 0.51-1.73) or for the estimated actuarial 8-year mortality rates (17 ± 5% vs. 27 ± 5%, p = 0.84) in the overall cohort. Society of Thoracic Surgeons score, comorbidity index, age, coronary artery disease, etiology of AS, and performance of AVR were associated with overall survival. For 83 propensity-score–matched pairs, the risk of overall death was not significantly different between the two groups (HR, 1.13 for the early AVR; 95% CI, 0.55-2.35; p = 0.74).


Early AVR and a strategy of watchful observation were associated with similar survival among symptomatic patients with normal-flow, low-gradient severe AS and preserved LVEF. The authors concluded that watchful observation with timely performance of AVR if mean gradient increases should be considered a therapeutic option.


This is a provocative study. There are increasing data (and guideline recommendations) to support intervention among symptomatic patients with low-flow, low-gradient severe AS and normal LVEF. However, the prognosis of patients with normal-flow, low-gradient severe AS might be better than the prognosis of those with low-flow, low-gradient AS or normal-flow, high-gradient AS. Although this study supports a conservative approach among symptomatic patients with normal-flow, low-gradient severe AS, two caveats should be considered. First, patients with more advanced symptoms (functional class III or IV dyspnea or angina, or syncope) were excluded, leaving only mildly symptomatic patients for study. Second, this was a prospective registry, and treatment decisions were not prospectively randomized; as such, lower concern about the true severity of AS, or about the true association between AS and symptoms, might have led to different compositions between groups, and account for the favorable outcomes in the delayed intervention group.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Valvular Heart Disease, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and VHD, Interventions and Coronary Artery Disease, Interventions and Structural Heart Disease

Keywords: Aortic Valve, Aortic Valve Stenosis, Cardiac Surgical Procedures, Heart Valve Diseases, Comorbidity, Coronary Artery Disease, Propensity Score, Prospective Studies, Registries, Risk, Stroke Volume, Ventricular Function, Left

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