BackgroundMyocardial infarction results in a large‐scale cardiomyocyte loss and heart failure due to subsequent pathological remodeling. Whereas zebrafish and neonatal mice have evident cardiomyocyte expansion following injury, adult mammalian cardiomyocytes are principally nonproliferative. Despite historical presumptions of stem cell–mediated cardiac regeneration, numerous recent studies using advanced lineage‐tracing methods demonstrated that the only source of cardiomyocyte renewal originates from the extant myocardium; thus, the augmented proliferation of preexisting adult cardiomyocytes remains a leading therapeutic approach toward cardiac regeneration. In the present study we investigate the significance of suppressing cell cycle inhibitors Rb1 and Meis2 to promote adult cardiomyocyte reentry to the cell cycle.Methods and ResultsIn vitro experiments with small interfering RNA–mediated simultaneous knockdown of Rb1 and Meis2 in both adult rat cardiomyocytes, isolated from 12‐week‐old Fischer rats, and human induced pluripotent stem cell–derived cardiomyocytes showed a significant increase in cell number, a decrease in cell size, and an increase in mononucleated cardiomyocytes. In vivo, a hydrogel‐based delivery method for small interfering RNA–mediated silencing of Rb1 and Meis2 is utilized following myocardial infarction. Immunofluorescent imaging analysis revealed a significant increase in proliferation markers 5‐ethynyl‐2′‐deoxyuridine, PH3, KI67, and Aurora B in adult cardiomyocytes as well as improved cell survivability with the additional benefit of enhanced peri‐infarct angiogenesis. Together, this intervention resulted in a reduced infarct size and improved cardiac function post–myocardial infarction.ConclusionsSilencing of senescence‐inducing pathways in adult cardiomyocytes via inhibition of Rb1 and Meis2 results in marked cardiomyocyte proliferation and increased protection of cardiac function in the setting of ischemic injury.

Introduction:A 56-hole porous tip radiofrequency catheter was developed to provide more uniform cooling with less fluid delivery than a prior 6-hole irrigated design. This study aimed to evaluate the impact of contact force (CF) ablation with the porous tip on complications (congestive heart failure [CHF] and non-CHF related), healthcare resource utilization, and procedural efficiency in patients undergoing de novo paroxysmal atrial fibrillation (PAF) ablations in a real-world setting.Methods: Consecutive de novo PAF ablations were performed between February 2014 and March 2019 by six operators at a single US academic center. The 6-hole design was used through December 2016 with the 56-hole porous tip adopted in October 2016. The outcomes of interest included symptomatic CHF presentation and CHF-related complications.Results: Of 174 patients who were included, mean age was 61.1 ± 10.8 years, 67.8% were male, and 25.3% had a history of CHF. Ablation with the porous tip catheter significantly decreased fluid delivery (1177 vs. 1912 mL with the 6-hole design; p < .0001). CHF-related complications within 7 days, particularly fluid overload, were substantially reduced with the porous tip (15.2% vs. 5.3% of patients; p = .0281) and the proportion of patients with symptomatic CHF presentation within 30 days postablation was significantly lower (14.7% vs. 32.5%; p = .0058). Conclusion:The 56-hole porous tip led to significantly reduced CHF-related complications and healthcare utilization in PAF patients undergoing CF catheter ablation when compared to the prior 6-hole design. This reduction likely results from the significant decrease in fluid delivery during the procedure.