Insulin Resistance Is Associated With Heart Failure With Recovered Ejection Fraction in Patients Without Diabetes

BACKGROUND: Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. METHODS AND RESULTS: A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow‐up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2‐IR). The median HOMA2‐IR level was 1.05 (interquartile range [IQR], 0.67–1.63) in our cohort of patients with HF who were nondiabetic. During follow‐up, 121 (odds ratio [OR], 46.2% [95% CI 40.2–52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2‐IR levels (0.92 [IQR, 0.61–1.37] versus 1.14 [IQR, 0.75–1.78], P=0.007), especially in nonischemic HF. Log(2)‐transformed HOMA2‐IR was inversely correlated to improvements in EF (Pearson's r=−0.25, P<0.001). After multivariable adjustment, a doubling of HOMA2‐IR was associated with a 42.8% decreased likelihood of HFrecEF (OR, 0.572 [95% CI, 0.385–0.827]). CONCLUSIONS: This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.