Abstract
Patients with paradoxical low-flow, low-gradient severe aortic stenosis (LFLGAS) exhibit low transvalvular flow rate (Q), while maintaining preserved left ventricular ejection fraction (LVEF). Concomitant severe mitral regurgitation (MR) contributes to the low flow state, adding complexity to diagnosis and management. This study aimed to examine the impact of severe MR on outcomes in paradoxical LFLGAS. Data from an institutional echo database identified 1,189 patients with adjudicated severe aortic stenosis (AVA≤1.0 cm 2 ), low transaortic gradients (mean gradient<40 mmHg), preserved LVEF (≥50%), and low flow rate (Q≤210 ml/sec), to confirm paradoxical LFLGAS. Subgroups were based on MR severity (severe and non-severe). Clinical outcomes included all-cause mortality, aortic valve replacement (AVR), heart failure hospitalizations, and a composite outcome. In the severe MR group (n=80), patients had lower flow rates, increased LV dimensions and a more eccentric hypertrophy pattern compared to non-severe MR (n=1,109). Over a median 5-year follow-up, severe MR correlated with higher all-cause mortality (p=0.02) and AVR rates (p=0.012). After adjustment, severe MR was independently associated with increased all-cause mortality risk (HR=1.43, p=0.011) and composite outcome (HR=1.64, p<0.001). AVR significantly reduced mortality at every MR degree, with the most substantial impact in severe MR (HR=0.18, p<0.001). Propensity-adjusted models demonstrated a stronger AVR impact with increasing MR degree (p-for-interaction=0.044). Severe MR in paradoxical LFLGAS is associated with adverse outcomes and distinctive LV remodeling. Aortic valve replacement improves survival across all MR grades, with greater impact in severe MR.
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