Left ventricular function, congestion, and effect of empagliflozin on heart failure risk after myocardial infarction

Background Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). Objective To evaluate the association between left ventricular ejection fraction (LVEF), congestion, or both on outcomes and the impact of empagliflozin in reducing HF risk post-MI. Methods In the EMPACT-MI trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both to empagliflozin 10 mg daily or placebo and followed for a median of 17.9 months. Results Among 6522 patients, the mean baseline LVEF was 41%+9%; 2648 patients (40.6%) presented with LVEF<45% alone, 1483 (22.7%) presented with congestion alone, and 2181 (33.4%) presented with both. Among patients in the placebo arm, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (hazard ratio [HR] 1.49; 95%CI, 1.31-1.69; P<0.0001), first HF hospitalization (HR, 1.64; 95%CI, 1.37-1.96; P<0.0001), and total HF hospitalizations (rate ratio [RR], 1.89; 95%CI, 1.51-2.36; P<0.0001). Presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR 1.52, 1.94, and RR 2.03, respectively). Empagliflozin reduced the risk for first (HR 0.77, 95%CI 0.60-0.98) and total (RR 0.67, 95%CI 0.50-0.89) HF hospitalization, irrespective of LVEF or congestion or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. Conclusions In patients with AMI, severity of LV dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion

Effect of empagliflozin on heart failure outcomes after acute myocardial infarction: insights from the EMPACT-MI trial

Background: Empagliflozin reduces the risk of heart failure events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, and in those with prevalent heart failure irrespective of ejection fraction. While EMPACT-MI showed empagliflozin does not reduce the risk of the composite of hospitalization of heart failure and all-cause mortality, the impact of empagliflozin on first and recurrent heart failure events in patients after myocardial infarction is unknown. Methods: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for heart failure based on newly developed left ventricular ejection fraction of <45% and/or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for heart failure outcomes. Results: Over a median of follow-up of 17.9 months, the risk for first heart failure hospitalization and total heart failure hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 (3.6%) vs. 153 (4.7%) patients with events, HR 0.77 [95% CI 0.60, 0.98], P=0.031 for first heart failure hospitalization and 148 vs. 207 events, RR 0.67 [95% CI 0.51, 0.89], P=0.006 for total heart failure hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total heart failure hospitalizations. Post-discharge need for new use of diuretics, renin-angiotensin modulators, and mineralocorticoid receptor antagonists were less in patients randomized to empagliflozin than placebo (all p<0.05). Conclusions: In patients after acute myocardial infarction with left ventricular dysfunction or congestion, empagliflozin reduced the risk of heart failure

Mild Paravalvular Leak May Pose an Increased Thrombogenic Risk in Transcatheter Aortic Valve Replacement (TAVR) Patients-Insights from Patient Specific In Vitro and In Silico Studies

In recent years, the treatment of aortic stenosis with TAVR has rapidly expanded to younger and lower-risk patients. However, persistent thrombotic events such as stroke and valve thrombosis expose recipients to severe clinical complications that hamper TAVR’s rapid advance. We presented a novel methodology for establishing a link between commonly acceptable mild paravalvular leak (PVL) levels through the device and increased thrombogenic risk. It utilizes in vitro patient-specific TAVR 3D-printed replicas evaluated for hydrodynamic performance. High-resolution µCT scans are used to reconstruct in silico FSI models of these replicas, in which multiple platelet trajectories are studied through the PVL channels to quantify thrombogenicity, showing that those are highly dependent on patient-specific flow conditions within the PVL channels. It demonstrates that platelets have the potential to enter the PVL channels multiple times over successive cardiac cycles, increasing the thrombogenic risk. This cannot be reliably approximated by standard hemodynamic parameters. It highlights the shortcomings of subjectively ranked PVL commonly used in clinical practice by indicating an increased thrombogenic risk in patient cases otherwise classified as mild PVL. It reiterates the need for more rigorous clinical evaluation for properly diagnosing thrombogenic risk in TAVR patients

Predictors and risk-adjusted outcomes of new-onset postoperative atrial fibrillation in repeat surgical and valve-in-valve transcatheter aortic valve replacement

Aim: New-onset postoperative atrial fibrillation/flutter (POAF/AFL) complications have not been well studied for repeat aortic valve replacements (r-AVR); this study identified risk factors predisposing to POAF/AFL and POAF/AFL’s effect upon risk-adjusted outcomes.Methods: Using New York State’s Statewide Planning and Research Cooperative System records (2005-2018), multivariable forward selection models identified risks predictive of POAF/AFL. To identify POAF/AFL’s impact upon risk-adjusted mortality/morbidity (MM) and 30-day readmission (READMIT), forward selection logistic regression models applied Firth bias correction to address data sparsity.Results: Of the 242 r-AVR patients, 147 underwent repeat surgical aortic valve replacements (r-SAVR) and 95 underwent valve-in-valve transcatheter aortic valve replacements (ViV-TAVR); 39.46% of r-SAVR and 43.16% of ViV-TAVR patients had POAF/AFL. R-SAVR patients with POAF/AFL were older (69.7 ± 11.1 vs. 56.7 ± 13.2 years, P < 0.01) compared to R-SAVR patients without POAF/AFL. Multivariable models identified an enhanced POAF/AFL risk for elderly (OR: 1.05, 95%CI: 1.03-1.07, P < 0.01) and cerebral vascular disease (OR: 2.18, 95%CI: 1.05-4.55, P = 0.04) patients. Bivariately, POAF/AFL was associated with READMIT, but not MM. Correspondingly, multivariable models found POAF/AFL increased READMIT (OR: 3.12, 95%CI: 1.46-6.65, P < 0.01), but not MM. However, black race (OR: 4.97, 95%CI: 1.61-15.37, P < 0.01) and Elixhauser score (OR: 1.05, 95%CI: 1.02-1.08, P < 0.01) increased risk for MM.Conclusion: More common in older and cerebrovascular disease patients, 41% of r-AVR patients with POAF/AFL had increased READMIT risk; thus, future investigations should focus on improving POAF/AF r-AVR patients’ post-discharge continuity of care