Severe Mitral Regurgitation in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis

BACKGROUND: Patients with paradoxical low-flow, low-gradient severe aortic stenosis exhibit low transvalvular flow rate (Q), while maintaining preserved left ventricular ejection fraction. Severe mitral regurgitation (MR) also causes a low-flow state, adding complexity to diagnosis and management. This study aimed to examine the impact of severe MR on outcomes in paradoxical low-flow, low-gradient severe aortic stenosis. METHODS: Data from an institutional echo database identified 1189 patients with adjudicated severe aortic stenosis (aortic valve area ≤1.0 cm²), low transaortic gradients (mean gradient <40 mm Hg), preserved left ventricular ejection fraction (≥50%), and low-flow rate (Q ≤210 mL/s) to confirm paradoxical low-flow, low-gradient severe aortic stenosis. Subgroups were based on MR severity (severe and non-severe). Clinical outcomes included all-cause mortality, aortic valve replacement, heart failure hospitalizations, and a composite outcome. RESULTS: In the severe MR group (n=80), patients had lower flow rates, increased left ventricular dimensions, and a more eccentric hypertrophy pattern compared with non-severe MR (n=1109). Over a follow-up of up to 5 years, severe MR correlated with higher all-cause mortality (P=0.02) and aortic valve replacement rates (P=0.012). After multivariable adjustment, severe MR was independently associated with increased all-cause mortality risk (hazard ratio=1.43; P=0.011) and composite outcome (hazard ratio=1.64; P<0.001). Aortic valve replacement significantly reduced mortality at every MR degree, with the most substantial impact in severe MR (hazard ratio=0.18; P<0.001). Propensity-adjusted models demonstrated a stronger aortic valve replacement impact with increasing MR degree (P_interaction=0.044). CONCLUSIONS: Severe MR in paradoxical low-flow, low-gradient severe aortic stenosis is associated with adverse outcomes and distinctive left ventricular remodeling. Aortic valve replacement improves survival across all MR grades, with greater impact in severe MR.