Abstract
ObjectivesTo evaluate clinical outcomes in patients with diabetes, treated by cardiac resynchronization therapy with a defibrillator (CRT-d), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) in addition to conventional hypoglycemic therapy vs. CRTd patients under conventional hypoglycemic drugs.BackgroundPatients with diabetes treated by CRTd experienced an amelioration of functional New York Association Heart class, reduction of hospital admissions, and mortality, in a percentage about 60%. However, about 40% of CRTd patients with diabetes experience a worse prognosis.Materials and methodsWe investigated the 12-months prognosis of CRTd patients with diabetes, previously treated with hypoglycemic drugs therapy (n 271) vs. a matched cohort of CRTd patients with diabetes treated with GLP-1 RA in addition to conventional hypoglycemic therapy (n 288).ResultsAt follow up CRTd patients with diabetes treated by GLP-1 RA therapy vs. CRTd patients with diabetes that did not receive GLP-1 RA therapy, experienced a significant reduction of NYHA class (p value < 0.05), associated to higher values of 6 min walking test (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). GLP-1 RA patients vs. controls at follow up end experienced lower AF events (p value < 0.05), lower VT events (p value < 0.05), lower rate of hospitalization for heart failure worsening (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). To date, GLP-1 RA therapy may predict a reduction of AF events (HR 0.603, CI [0.411–0.884]), VT events (HR 0.964, CI [0.963–0.992]), and hospitalization for heart failure worsening (HR 0.119, CI [0.028–0.508]), and a higher CRT responders rate (HR 3.707, CI [1.226–14.570]).ConclusionsGLP-1 RA drugs in addition to conventional hypoglycemic therapy may significantly reduce systemic inflammation and circulating BNP levels in CRTd patients with diabetes, leading to a significant improvement of LVEF and of the 6 min walking test, and to a reduction of the arrhythmic burden. Consequently, GLP-1 RA drugs in addition to conventional hypoglycemic therapy may reduce hospital admissions for heart failure worsening, by increasing CRTd responders rate.Trial registration NCT03282136. Registered 9 December 2017 “retrospectively registered”
Highlights
Type 2 diabetes mellitus (T2DM) is a frequent co-morbidity, and a negative prognostic risk factor in patients with heart failure and reduced left ventricle ejection fraction (HFrEF), [1]
In this study T2DM patients affected by HFrEF after cardiac resynchronization therapy with a defibrillator (CRT-d) implant were divided randomly in patients receiving GLP1 glucagon-like peptide receptor agonists (RA) therapy plus conventional hypoglycemic therapy vs. patients under conventional hypoglycemic therapy. In these patients we aimed to investigate at 12 months follow up all cause of deaths, cardiac deaths, hospitalizations for HF worsening, CRT-d responders rate, and the arrhythmic burden: atrial fibrillation (AF) events, ventricular tachycardia (VT) events, ventricular fibrillation (VF) events, internal cardioverter defibrillator (ICD) shocks, and strokes events
glucagonlike peptide 1 (GLP-1) RA therapy in addition to standard hypoglycemic drugs vs. standard hypoglycemic drugs may significantly reduce inflammation, and B type natriuretic peptide (BNP) values in failing heart patients with diabetes treated by CRTd
Summary
Type 2 diabetes mellitus (T2DM) is a frequent co-morbidity, and a negative prognostic risk factor in patients with heart failure and reduced left ventricle ejection fraction (HFrEF), [1]. T2DM induces a pro-oxidative/inflammatory status, that altering molecular, metabolic, electrical, and mechanical cardiac functions, may lead to HFrEF [1, 2] In this setting, recently the CHARM trial reported in patients with diabetes a cumulative incidence rate of cardiovascular death or hospitalization for heart failure approximately of 40% over 3 years, with a risk for first hospital admission for heart failure of 155.4 per 1000 patient-years [3]. In this population of HFrEF patients with diabetes the cardiac resynchronization therapy with a defibrillator (CRT-d) is an effective treatment, to improve cardiac performance and functional New York Association Heart (NYHA) class, and to reduce hospital admissions and mortality [4] To date, these clinical effects are observed in about 60% of all treated patients, named as “CRTd responders” [4]. About 40% of CRTd patients with diabetes experience a worse prognosis
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