Paradoxical Normal-Flow Aortic Stenosis Despite Reduced Left Ventricular Ejection Fraction: Insights From the Randomized COMPARE-TAVI 1 Trial.

BACKGROUND

The hemodynamic profile and remodeling patterns of paradoxical low-flow, low-gradient aortic stenosis are well understood. However, some patients with severe aortic stenosis exhibit eccentric remodeling with enlarged left ventricular cavities, enabling a normal flow, low ejection fraction (NF-LEF) phenotype. We assessed the prevalence, hemodynamic characteristics, and post-transcatheter aortic valve implantation outcomes of NF-LEF.

METHODS

In this substudy of the COMPARE-TAVI 1 trial, 979 patients undergoing transfemoral transcatheter aortic valve implantation were stratified by left ventricular ejection fraction (LVEF) (< or ≥50%) and stroke volume index (< or ≥35 mL/m2) into 4 groups: normal flow, normal LVEF, NF-LEF, low flow, normal ejection fraction, and low flow, low ejection fraction.

RESULTS

NF-LEF was observed in 10.7% of patients. Reduced LVEF was associated with previous myocardial infarction, pacemakers, New York Heart Association class >2, atrial fibrillation, moderate or worse mitral regurgitation, and larger left ventricular cavities (P<0.001) with eccentric hypertrophy (P=0.004). Compared with low-flow, low-ejection fraction, patients with NF-LEF more frequently had moderate or worse aortic regurgitation (P=0.007), whereas low flow, low ejection fraction showed poorer diastolic indices, suggesting diastolic dysfunction with high left ventricular filling pressures. Patients with low flow, normal ejection fraction were the most symptomatic and showed less improvement in 6-minute walk distance at 1 year compared with normal flow, normal ejection fraction. During follow-up, both low-flow groups demonstrated significant increases in stroke volume index (P<0.001), whereas LVEF also improved among patients with reduced LVEF (P<0.001).

CONCLUSIONS

NF-LEF is a prevalent aortic stenosis phenotype characterized by preserved flow despite reduced LVEF, likely driven by eccentric remodeling with moderate or worse aortic regurgitation and more favorable diastolic properties, with similar survival and time-to-event outcomes across phenotypes after transcatheter aortic valve implantation at long-term follow-up. Despite higher comorbidity burdens, patients with NF-LEF showed functional and clinical improvements comparable with normal flow, normal ejection fraction, indicating a severe aortic stenosis phenotype.