Effects of SGLT2i therapy on cardiac electrophysiological properties and arrhythmias in diabetic patients with implantable cardiac defibrillator
Celestino Sardu, Maria Consiglia Trotta, Ludovica Vittoria Marfella, Giovambattista D'Amico, C. La Marca, Ciro Mauro, Matteo Santamaria, Valerio Giordano, Fabrizio Turriziani, Concetta Rafaniello, Ferdinando Carlo Sasso, Paolo Calabrò, Carmine Pizzi, Raffaele Marfella, Annalisa Capuano, Giuseppe Paolisso
Abstract
Sodium-glucose-transporter-2-inhibitors (SGLT2i) reduce ventricular-tachycardia (VT) and cardiac deaths in diabetic patients with internal-cardioverter-defibrillators (ICD) and/or cardiac-resynchronization-therapy (CRT). SGLT2i might improve cardiac electrophysiological-properties, reducing inflammation and sympathetic tone. We evaluated SGLT2i effects on lead-parameters, arrhythmias, ICDs' interventions, and heart failure (HF) hospitalizations and cardiac deaths in diabetics at 1 year of follow-up. At 1 year of follow-up, 334 SGLT2i-users vs. 794 non-users patients had lower heart rate, best clinical status, lowest B-type-natriuretic-peptide (BNP) and N-terminal pro-BNP, and inflammatory markers and catecholamines (p < 0.05). SGLT2i-users vs. non-users showed cardiac remodeling and increased cardiac pump (p < 0.05), significant reduction of right-ventricle (RV) and left-ventricle (LV) pacing, increase of RV/LV impedance and sensing at follow-up end (p < 0.05). C-reactive-protein (CRP) inversely linked to RV sensing and linearly to RV pacing. CRP and tumor-necrosis-alpha (TNFa) inversely linked to RV and shock impedance (p < 0.05). At follow-up end, SGLT2i-users vs. non-users showed lower rate of VT (36 (10.8 %) vs. 138 (17.4 %)), inappropriate-shocks (32 (9.6 %) vs. 118 (14.9 %)), HF hospitalizations (50 (15.0 %) vs. 216 (27.2 %)), and cardiac deaths (10 (3.0 %) vs. 53 (6.7 %)), (p < 0.05). BNP (HR 1.101, CI 95 % 1.000-1.305), CRP (HR 1.034, CI 95 % 1.007-1.061), and SGLT2i (HR 0.592, CI 95 % 0.410-0.854) predicted VT; SGLT2i (HR 0.611, CI 95 % 0.413-0.903) predicted inappropriate-shocks; BNP (HR 1.012, CI 95 % 1.001-1.040) predicted appropriate-shocks. CRP (HR 1.102, 1.077-1.127), ischemic cardiomyopathy (HR 1.284, CI 95 % 1.14-1.870), and SGLT2i (HR 0.497, CI 95 % 0.365-0.677) predicted HF-hospitalizations. SGLT2i (HR 0.677, CI 95 % 0.222-0.860) predicted cardiac deaths. SGLT2i improve electrophysiological-properties and reduce arrhythmias in diabetics with ICD/CRT.