Diabetic microvascular complications predicts non‐heart failure with reduced ejection fraction in type 2 diabetes

AIMS: The relationship between diabetic microvascular complications and the incidence of two types of heart failure—heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] < 40%) and non‐HFrEF (LVEF ≥ 40%)—in patients without prior heart failure has not been clarified. We herein examined the association between diabetic microvascular complications and HFrEF or non‐HFrEF in patients with type 2 diabetes mellitus (T2DM) without prior heart failure. METHODS AND RESULTS: In this retrospective cohort study, we assessed the relationship between the presence of diabetic microvascular complications or severity of diabetic retinopathy (no apparent, non‐proliferative and proliferative retinopathy) and nephropathy (normoalbuminuria, microalbuminuria, and macroalbuminuria) at baseline, with the primary outcome of first heart failure hospitalization classified as HFrEF or non‐HFrEF in patients with type 2 diabetes mellitus without prior heart failure. Among 568 patients (69.2% males, mean age 66.2 ± 9.6 years), 70 experienced heart failure hospitalization (HFrEF: 24 and non‐HFrEF: 46). Non‐HFrEF hospitalization but not HFrEF hospitalization was significantly associated with the presence of diabetic microvascular complications. The incidence of non‐HFrEF hospitalization was significantly higher in the proliferative retinopathy group than that in the no apparent retinopathy group (adjusted hazard ratio [HR] 2.96, 95% confidence interval [CI]: 1.09–6.83, P = 0.035) and in those with macroalbuminuria than in those with normoalbuminuria (adjusted HR 4.23, 95% CI: 2.24–7.85, P < 0.001) even after adjustment for age and sex. When non‐HFrEF was classified into heart failure with mildly reduced ejection fraction (HFmrEF) (40% ≤ LVEF < 50%) and heart failure with preserved ejection fraction (HFpEF) (50% ≤ LVEF), HFmrEF and HFpEF hospitalizations were also found to be associated with the progression of retinopathy and nephropathy. CONCLUSIONS: In patients with T2DM without prior heart failure, non‐HFrEF hospitalization was more closely associated with the progression of diabetic microangiopathy than HFrEF. The development of non‐HFrEF may be mediated through a mechanism similar to that of microvascular complications in these patients.