Differential effect of cardiac resynchronization therapy in patients with diabetes mellitus: a long-term retrospective cohort study

Aims: Cardiac resynchronization therapy (CRT) has become an important therapy in patients with heart failure with reduced left ventricular ejection fraction (LVEF). The effect of diabetes on long-term outcome in these patients is controversial. We assessed the effect of diabetes on long-term outcome in CRT patients and investigated the role of diabetes in ischaemic and non-ischaemic cardiomyopathy.

Methods and results: All patients undergoing CRT implantation at our institution between November 2000 and January 2015 were enrolled. The study endpoints were (i) a composite of ventricular assist device (VAD) implantation, heart transplantation, or all-cause mortality; and (ii) reverse remodelling (improvement of LVEF ≥ 10% or reduction of left ventricular end-systolic volume ≥ 15%). Median follow-up of the 418 patients (age 64.6 ± 11.6 years, 22.5% female, 25.1% diabetes) was 4.8 years [inter-quartile range: 2.8;7.4]. Diabetic patients had an increased risk to reach the composite endpoint [adjusted hazard ratio (aHR) 1.48 [95% CI 1.12-2.16], P = 0.041]. Other factors associated with an increased risk to reach the composite endpoint were a lower body mass index or baseline LVEF (aHR 0.95 [0.91; 0.98] and 0.97 [0.95; 0.99], P < 0.01 each), and a higher New York Heart Association functional class or creatinine level (aHR 2.14 [1.38; 3.30] and 1.04 [1.01; 1.05], P < 0.05 each). Early response to CRT, defined as LVEF improvement ≥ 10%, was associated with a lower risk to reach the composite endpoint (aHR 0.60 [0.40; 0.89], P = 0.011). Reverse remodelling did not differ between diabetic and non-diabetic patients with respect to LVEF improvement ≥ 10% (aHR 0.60 [0.32; 1.14], P = 0.118). However, diabetes was associated with decreased reverse remodelling with respect to a reduction of left ventricular end-systolic volume ≥ 15% (aHR 0.45 [0.21; 0.97], P = 0.043). In patients with ischaemic cardiomyopathy, survival rates were not significantly different between diabetic and non-diabetic patients (HR 1.28 [0.83-1.97], P = 0.101), whereas in patients with non-ischaemic cardiomyopathy, diabetic patients had a higher risk of reaching the composite endpoint (HR 1.65 [1.06-2.58], P = 0.027). The latter effect was dependent on other risk factors (aHR 1.47 [0.83-2.61], P = 0.451). The risk of insulin-dependent patients was not significantly higher than in patients under oral antidiabetic drugs (HR 1.55 [95% CI 0.92-2.61], P = 0.102).

Conclusions: Long-term follow-up revealed diabetes mellitus as independent risk factor for all-cause mortality, heart transplantation, or VAD in heart failure patients undergoing CRT. The detrimental effect of diabetes appeared to weigh heavier in patients with non-ischaemic compared with ischaemic cardiomyopathy.