Po-628-06 effect of angiotensin receptor neprilysin inhibitor and empagliflozine on ischemic ventricular tachycardia substrate: a high-density mapping and mri study

Angiotensin receptor neprilysin inhibitor (ARNI) and empagliflozine reduce cardiovascular death in heart failure, but mechanistic data on this effect are scarce. To assess the effect of ARNI and empagliflozine on scar remodeling and ventricular tachycardia (VT) inducibility in a swine model of chronic myocardial infarction (MI). Left anterior descending artery MI was induced in 40 Landrace Large X White pigs. Thirty-one animals (78%) survived the MI induction procedure and were randomized to receive treatment with beta-blocker (BB) only (group 1, n=7), empagliflozine+BB (group 2, n=8), ARNI + BB (group 3, n=8) or empagliflozine + ARNI + BB (group 4, n=8). Contrast-enhanced (ce)-MRI were performed at 2-day (baseline) and 1-month post-MI and were post-processed with ADAS 3D; ventricular scar subtypes and borderzone (BZ) corridors volume were measured. EP study with endo-epicardial high-density mapping was performed 1-month post-MI. VT was inducible in 21/31 subjects (68%). Treatment with ARNI (groups 3 and 4) showed a significant reduction of VT inducibility (OR 0.15 [0.026-0.91], p=0.03) compared to non-ARNI groups (100%, 75%, 50% and 50% for groups 1, 2, 3 and 4, respectively), representing a 30% relative risk reduction. Treatment with empagliflozine (group 2) did not reduce VT inducibility (p=0.704). Baseline ceMRI data showed a mean core and BZ scar mass of 5.4±3.1 and 6.1±3.1 grams, respectively, without significant differences in the percentage of core scar. The mean number of corridors was 2.1±1.2 with a mean mass of 1.3±1.0, without significant differences across groups. Treatment with ARNI and empagliflozine significantly reduced the number (+1.0, -1.1, -1.2 and -1.7 corridors for groups 1, 2, 3 and 4, respectively; p=0.021) and mass of corridors (+0.3, -1.6, -0.8 and -0.4 grams for groups 1, 2, 3 and 4, respectively; p=0.012) at the follow-up ceMRI. ARNI and empagliflozine groups tended to reduce overall BZ mass compared to the control group (reduction of the BZ percentage -1.2±4, -4.9±2, -5.6±2, -3.8±4; p=0.102). Treatment with ARNI reduced VT inducibility by 30% after MI, likely driven by a significant reduction of the number and mass of BZ corridors. Empagliflozine reduced the number and mass of BZ corridors, without impact on VT inducibility.View Large Image Figure ViewerDownload Hi-res image Download (PPT)