4178Insulin treatment is associated with increased risk of device-treated ventricular tachyarrhythmia in patients with diabetes and heart failure

Abstract

Abstract Background It is debated whether insulin use is associated with a pro-arrhythmic effect. There is paucity of studies investigating this aspect in patients with heart failure (HF), where use of insulin is associated with an increased mortality risk. Purpose We aimed to investigate whether patients receiving insulin had higher risk of device-treated ventricular tachyarrhythmia (VTA) in a population of HF patients with medically treated diabetes and primary prevention implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy with defibrillator (CRT-D). Methods Information on ICD/CRT-D implantation and therapy, comorbidities, diabetes, diabetes-related complications and medication were obtained through Danish nationwide registers. From 2007 through 2016 we identified all primary prevention ICD/CRT-D implantations in HF patients with diabetes, defined as treatment with antidiabetic medication within one year prior to implantation. Patients were divided into two groups; Insulin treated vs. non-insulin treated patients. Endpoints of interest were VTA, defined as appropriate ICD therapy, and all-cause mortality. Cumulative incidence curves and adjusted Cox proportional Hazards regression analyses were used to assess risk of outcomes. Adjustment variables included age, gender, ischemic heart disease (IHD), left ventricular ejection fraction (LVEF), ICD vs. CRT-D, diuretic use (as a proxy for severity of HF), prior VTA and diabetes-related complications, identified from diagnosis codes for diabetic nephro-, retino-, and neuropathy, multiple diabetic complications and unspecified diabetic complications. Results We identified 1240 patients with HF and diabetes with a primary prevention ICD/CRT-D. The majority of patients had type 2 diabetes (94%). Of these 479 patients (39%) were treated with insulin and 761 (61%) were not. Patients were primarily male (85%) with mean age of 66.9±8.3 years, mean LVEF of 25.6±7.5%, 42% had CRT-D and 58% ICD, without differences between the groups. The insulin-treated group had a higher occurrence of diabetes-related complications (81% vs. 42%, p<0.01) and IHD (95% vs. 90%, p<0.01). During a mean follow-up of 3.1±2.1 years, 74 insulin treated patients (16%) and 86 non-insulin treated patients (11%) experienced VTA (p=0.034), with higher 5-year cumulative incidence of VTA in the insulin group. Insulin treatment was associated with significantly increased risk of VTA (HR = 1.45; 95% CI [1.04–2.03], p=0.031) and all-cause mortality (HR=1.27; 95% CI [1.03–1.58], p=0.027), as compared with non-insulin treated patients. Figure 1 Conclusion In HF patients with diabetes implanted with a primary prevention ICD/CRT-D, treatment with insulin was associated with a significant 45% increased risk of device-treated ventricular tachyarrhythmias and 27% increased risk of all-cause mortality. These findings support further clinical trials to evaluate the safety of insulin in patients with HF and type 2 diabetes.