Citations

BACKGROUND: Catheter ablation of ventricular arrhythmias, one of the most rapidly growing procedures in cardiac electrophysiology, is associated with magnetic resonance imaging–detected brain lesions in more than half of cases. Although a retrograde aortic approach is conventional, modern tools enable entry through a transseptal approach that may avoid embolization of debris from the arterial system. We sought to test the hypothesis that a transseptal puncture would mitigate brain injury compared with a retrograde aortic approach. METHODS: The TRAVERSE trial (Transseptal Versus Retrograde Aortic Ventricular Entry to Reduce Systemic Emboli) was a multicenter randomized controlled comparative effectiveness trial. Patients with left ventricular arrhythmias undergoing catheter ablation procedures were randomly assigned to a transseptal puncture approach compared (1:1) with a retrograde aortic approach. The primary outcome was the presence of an acute brain lesion detected by magnetic resonance imaging. Secondary outcomes included clinically manifest complications, procedural efficacy, and 6-month neurocognitive assessments. RESULTS: Among the 62 patients randomly assigned to a retrograde aortic approach with postoperative brain magnetic resonance imaging, 28 (45%) exhibited an acute brain lesion compared with 19 of the 69 (28%) of those randomized to a transseptal puncture ( P =0.036). No differences in clinically manifest complications or procedural efficacy were observed. More patients in the retrograde aortic arm were categorized as having a high likelihood of cognitive impairment at 6 months (33% compared with 19% of those in the transseptal arm), but substantial loss to follow-up was present. CONCLUSIONS: Among patients undergoing left ventricular catheter ablation procedures, a transseptal approach reduced the risk of acute brain lesions by nearly half compared with a retrograde aortic approach without sacrificing safety or efficacy. Given a likely embolic pathogenesis, the brain magnetic resonance imaging findings may reflect a propensity to other organ damage; these findings may extend to other procedures requiring left ventricular entry. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03946072.

BACKGROUND: Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). METHODS: A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. RESULTS: The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β–mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. CONCLUSIONS: Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.