Biomarkers Correspond with Echocardiographic Phenotypes in Heart Failure with Preserved Ejection Fraction: A Secondary Analysis of the RELAX Trial

BackgroundLittle is known about the relationship between structural phenotypes in in heart failure with preserved ejection fraction (HFpEF) and cardiac biomarkers. We used cluster analysis to identify cardiac structural phenotypes and their relationships to biomarkers in HFpEF. Methods and resultsLatent class analysis (LCA) was applied to echocardiographic data including left atrial enlargement (LAE), diastolic dysfunction (DD), E/e, EF[≤]55%, and right ventricular dysfunction from 216 patients enrolled in the RELAX trial. Three structural phenotypes were identified. Phenotype A had the most grade II DD. Phenotype B had the most grade III DD, worst LAE, elevated E/e and right ventricular dysfunction. Phenotype C had the least DD and moderate LAE. Phenotypes B and C had prevalent atrial fibrillation (AF). Phenotype B patients had increased carboxy-terminal telopeptide of collagen type I (CITP), cystatin-c (CYSTC), endothelin-1 (ET1), NT-proBNP, and high-sensitivity troponin I (TNI). Type A had the next highest CITP and CYSTC levels while Type C had next highest NT-proBNP. ConclusionsStructural HFpEF phenotypes demonstrated different characteristics including cardiac biomarkers. These findings may help explain phenotype-specific differences in natural history and prognosis, and they may represent phenotype-specific pathophysiology that could be amenable to targeted therapy.