Phenotypes of heart failure with preserved ejection fraction and effect of spironolactone treatment

• Published in: ESC Heart Failure Vol. 9; no. 4; pp. 2567 - 2575
• Main Authors: Choy, Manting, Liang, Weihao, He, Jiangui, Fu, Michael, Dong, Yugang, He, Xin, Liu, Chen
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-08-2022; John Wiley and Sons Inc; Wiley
• Subjects: Alcohol use; Algorithms; Anemia; Blood pressure; Body mass index; Cardiac and Cardiovascular Systems; Cardiac arrhythmia; Cardiomyopathy; Cardiovascular disease; Chronic obstructive pulmonary disease; Datasets; Diabetes; Ejection fraction; Feature selection; Genotype & phenotype; Heart Failure; Heart failure with preserved ejection fraction; Hospitalization; Humans; Hypothyroidism; Kardiologi; Kidney diseases; Latent class analysis; Mineralocorticoid Receptor Antagonists; Original; Pacemakers; Patients; pharmacology; Phenotype; Quality of life; Questionnaires; Software; Spironolactone; Stroke Volume; therapeutic use; Variable selection; Variables; Kansas City Missouri; Georgia; United States > US; Russia; Heart failure with preserved ejection fraction; Phenotype; Spironolactone; Latent class analysis; Variable selection
• ISSN: 2055-5822; 2055-5822
• DOI: 10.1002/ehf2.13969

Aims
The aims of this study were to explore phenotypes of heart failure with preserved ejection fraction (HFpEF) and evaluate differential effects of spironolactone treatment.
Methods and results
A swap‐stepwise algorithm was used for variable selection. Latent class analysis based on 10 selected variables was employed in a derivative set of 1540 patients from the TOPCAT trial. Cox proportional hazard models were used to evaluate the prognoses and effects of spironolactone treatment. Three phenotypes of HFpEF were identified. Phenotype 1 was the youngest with low burden of co‐morbidities. Phenotype 2 was the oldest with high prevalence of atrial fibrillation, pacemaker implantation, and hypothyroidism. Phenotype 3 was mostly obese and diabetic with high burden of other co‐morbidities. Compared with phenotype 1, phenotypes 2 (hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.14–1.89; P = 0.003) and 3 (HR: 2.35; 95% CI: 1.80–3.07; P < 0.001) were associated with higher risks of the primary composite outcome. Spironolactone treatment was associated with a reduced risk of the primary outcome only in phenotype 1 (HR: 0.63; 95% CI: 0.40–0.98; P = 0.042).
Conclusions
Three distinct HFpEF phenotypes were identified. Spironolactone treatment could improve clinical outcome in a phenotype of relatively young patients with low burden of co‐morbidities.