Efficacy of Renin-angiotensin-aldosterone-system inhibitors for heart failure with preserved ejection fraction and left ventricular hypertrophy -from the KUNIUMI Registry Acute Cohort-

Background Heterogeneity of heart failure (HF) with preserved ejection fraction (HFpEF) would contribute to the difficulty in identifying effective treatments, and interest in the phenogrouping of HFpEF as a potential means for predicting patients who respond to cardioprotective drugs has been increasing. Methods We studied 468 first-hospitalized HFpEF patients among 1971 acute-hospitalized HF patients from KUNIUMI Registry Acute Cohort. The primary endpoint was defined as HF-rehospitalization and cardiovascular death over a median follow-up period of 508 days. Results In HFpEF patients with left ventricular hypertrophy (LVH), patients prescribed renin-angiotensin-aldosterone-system (RAAS) inhibitors had similar outcomes compared to those without (HR, 0.77; 95% CI 0.51-1.16; p = 0.21), and the outcome was also similar between patients with and without RAAS inhibitors’ prescription in HFpEF patients without LVH. Moreover, in HFpEF patients with LVH and mild-moderate chronic kidney disease (CKD), which was determined as an estimated glomerular filtration rate (eGFR) of 30-60 mL/min/1.73 m2, patients prescribed RAAS inhibitors had significantly favorable outcomes compared to those without (HR 0.39; 95% CI 0.19-0.80; p = 0.01). In HFpEF patients with LVH and severe CKD, which was defined as eGFR <30 mL/min/1.73 m2, the outcome was similar between patients with and without RAAS inhibitor prescription. Multivariable Cox regression analysis showed that the prescription of RAAS inhibitors was the only independent predictor of outcome in HFpEF patients with LVH and mild-moderate CKD (HR 0.49; 95% CI 0.25–0.94; p = 0.03). Conclusions Our findings showed the importance of HFpEF phenogrouping for identifying effective pharmacological treatments.