Association between phenotypic clusters and treatment response in heart failure with preserved ejection fraction

Presented at the ESC HF 2021 by Alicia Uijl (Utrecht, The Netherlands)

Introduction and methods

All major HFpEF trials have demonstrated neutral findings. The reason of these failed HFpEF trials is unknown; were the wrong patients included, was the wrong treatment examined or the wrong outcome assessed? These questions have resulted in a one size fits all vs. targeted approach debate with regard to therapy for HFpEF patients. A targeted approach may consider phenotypical clusters based on patients characteristics.

This study investigated the association of renin-angiotensin system (RAS)-inhibitors and beta-blockers with all-cause mortality and HF hospitalization in HFpEF clusters.

Five HFpEF phenotypic clusters were identified in a subset of 6909 HFpEF patients in the SwedeHF registry by a latent class analysis with 10 characteristics: a young low comorbidity cluster, a AF- hypertension cluster, an elderly-AF cluster, an obese-diabetes cluster, and a cardiorenal cluster. These clusters were applied to the total HFpEF population in the SwedeHF registry (21.000 patients) and treatment effects of RAS-inhibitors and beta-blockers were studied.

Results

• There was no interaction for the treatment effect of RAS-inhibitors on all-cause mortality across HFpEF clusters (overall HR 0.83, 95%CI:0.79-0.87, P<0.0001).
• There was an interaction for the treatment effect of beta-blockers on all-cause mortality across HFpEF clusters, with a significant reduction in the young cluster (HR 0.65, 95%CI:0.50-0.84) and the AF-hypertension cluster (HR 0.85, 95%CI: 0.76-0.94), and not for the other clusters (overall HR 0.90, 95%CI: 0.85-0.95, P<0.0001).
• There was no reduction in HF hospitalization with use of RAS-inhibitors or beta-blockers and no interactions were observed for clusters of HFpEF.

Conclusion

The association between use of beta-blockers and all-mortality was heterogenous across clusters, with a significant reduction in the young cluster and the AF-hypertension cluster. These findings are relevant for future trial design in HFpEF and could lead to more precision-medicine for these patients.

– Our coverage of ESC HF 2021 is based on the information provided during the congress –

Find the article on phenotypic clusters in HFpEF online at Eur J Heart Fail