Effects of SGLT2 inhibitors on cardiac autonomic activity and ventricular remodeling in patients with acute myocardial infarction: study protocol for a clinical trial

Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors exhibit significant cardiovascular protective effects in patients with acute myocardial infarction (AMI) complicated with type 2 diabetes mellitus (T2DM), mainly through enhancing cardiac function and reducing malignant arrhythmias. However, evidence supporting their efficacy in non-diabetic AMI patients is limited. Moreover, the relationship between these benefits and improvements in cardiac autonomic function and left ventricular remodeling remains contentious, complicating the understanding of their mechanisms of action. This study aims to fill this knowledge gap regarding dapagliflozin's effects on cardiac autonomic activity and ventricular remodeling in AMI patients. Methods: This study is a prospective, randomized, open-label, assessor-blinded, single-center trial in AMI patients in China. A total of 110 participants will be randomly allocated in a 1:1 ratio to either receive standardized treatment alone or receive standardized treatment along with10 mg of dapagliflozin taken once daily. The primary endpoint is the change from the baseline to 24 weeks in heart rate variability (HRV) and deceleration capacity (DC) measured by 24-h ambulatory Holter monitoring. Secondary endpoints include changes in the left ventricular remodeling index (a relative change of LV end-diastolic volume, LVRI), left ventricular end-diastolic volume (LVEDV), left ventricular end-diastolic volume (LVESV), and left ventricular ejection fraction (LVEF) from baseline. Changes in various variables from the baseline will also be analyzed, encompassing glucose and lipid levels, blood pressure, body weight, and biomarkers linked to diagnostic and functional parameters of AMI, such as creatine kinase, troponin I (TnI) level, and N terminal pro B type natriuretic peptide (NT-proBNP) level. Discussion: This trial will be the first trial to investigate the effects of dapagliflozin on cardiac autonomic function and ventricular remodeling in AMI patients. Our study aims to enhance understanding of the mechanisms by which dapagliflozin provides cardioprotection, potentially informing future therapeutic strategies for improving outcomes in this population. Trial registration: Clinical trial ID: ChiCTR2400084050. Registration date: May 9, 2024