OBJECTIVES:This study was designed to evaluate the evidence base for the 2014 American Heart Association/American College of Cardiology (AHA/ACC) guidelines for severe aortic stenosis (SAS) and preserved left ventricular ejection fraction by comparing the natural history of the disease in subgroups of low-gradient (LG) aortic stenosis patients with high-gradient (HG) patients. BACKGROUND:The 2014 AHA/ACC valvular disease guidelines recommend estimation of stroke volume index by echocardiography in patients with suspected LG SAS and preserved left ventricular ejection fraction. METHODS:PubMed, Embase, and Scopus databases were searched for all studies that have compared the natural history of SAS with preserved ejection fraction in flow-gradient patterns. We studied the following 3 subgroups: HG, low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). The random effects model was used to pool individual study results. The end-point was long-term all-cause mortality. RESULTS:A total of 9 studies with 3,065 patients fulfilled the criteria. Compared to HG SAS, both LFLG and NFLG patients had a higher burden of comorbidities such as coronary artery disease and hypertension. Atrial fibrillation was more prevalent in LFLG patients. Moreover, end-diastolic volume index was smaller for LFLG patients and indexed aortic valve area was larger for NFLG patients. All-cause mortality was similar between HG and LFLG subgroups (relative risk: 1.07; 95% confidence interval: 0.83 to 1.38; p = 0.60), whereas patients with NFLG had a significantly lower all-cause mortality compared to the HG subgroup (relative risk: 0.64; 95% confidence interval: 0.47 to 0.86; p = 0.004). CONCLUSIONS:Patients with LFLG SAS have similar outcomes compared to HG SAS but worse compared to NFLG SAS. These findings support estimating stroke volume index in patients with suspected LG SAS. All analyses revealed high heterogeneity and further high-quality studies are necessary.

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