Cardiac resynchronization therapy with a defibrillator (CRTd) in failing heart patients with type 2 diabetes mellitus and treated by glucagon-like peptide 1 receptor agonists (GLP-1 RA) therapy vs. conventional hypoglycemic drugs: arrhythmic burden, hospitalizations for heart failure, and CRTd responders rate

Abstract

Objectives: To 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.

Background: Patients 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 methods: We 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).

Results: At 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]).

Conclusions: GLP-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".

Fig. 1

Kaplan survival curve free for all cause deaths (upper part), and cardiac deaths (lower part) event in GLP-1 agonist users (blu color), and non GLP-1 agonist users (green color). p value > 0.05

Fig. 2

Kaplan survival curve free for hospital admission (upper part), and cardiac resynchronization with a defibrillator (CRTd) response (lower part) event in GLP-1 agonist users (blu color), and non GLP-1 agonist users (green color). *p value < 0.05 for both images

Fig. 3

Kaplan survival curve free for stroke events (upper part), and ventricular tachycardia (VT) events (lower part) event in GLP-1 agonist users (blu color), and non GLP-1 agonist users (green color). *p value < 0.05 for VT events

Fig. 4

In the upper part of figure the Kaplan survival curve free from atrial fibrillation (AF) events. In lower part the study endpoints events at 12th month of follow up in overall population, patients with diabetes GLP-1 agonist users vs. never GLP-1 agonist users. *p value < 0.05 for both images. AF: atrial fibrillation; CRTd: cardiac resynchronization with a defibrillator; VT: ventricular tachycardia