Early Left Ventricular Unloading or Conventional Approach After Venoarterial Extracorporeal Membrane Oxygenation: The EARLY-UNLOAD Randomized Clinical Trial.

BACKGROUND: Although venoarterial extracorporeal membrane oxygenation (VA-ECMO) is beneficial for the treatment of profound cardiogenic shock, peripheral VA-ECMO cannulation can increase left ventricular afterload, thus compromising myocardial recovery. We investigated whether early routine left ventricular unloading can reduce 30-day mortality compared with the conventional approach in patients with cardiogenic shock undergoing VA-ECMO. METHODS: This randomized clinical trial involved 116 patients with cardiogenic shock undergoing VA-ECMO from March 2021 to September 2022 at Chonnam National University Hospital, Gwangju, South Korea. The patients were randomly assigned to undergo either early routine left ventricular unloading with transseptal left atrial cannulation within 12 hours after randomization (n=58) or the conventional approach, which permitted rescue transseptal left atrial cannulation in case of an increased left ventricular afterload (n=58). The primary outcome was all-cause mortality within 30 days. RESULTS: All 116 randomized patients (mean age, 67.6±13.5 years; 34 [29.3%] women) completed the trial. At 30 days, all-cause death had occurred in 27 (46.6%) patients in the early group and 26 (44.8%) patients in the conventional group (hazard ratio, 1.02 [95% CI, 0.59-1.74]; P=0.942). Crossover to rescue transseptal left atrial cannulation occurred in 29 patients (50%) in the conventional group according to a clear indication. Time to rescue transseptal cannulation in the conventional group was a median of 21.8 (interquartile range, 12.4-52.2) hours after randomization. There were no significant differences in other secondary outcomes between the 2 groups except for a shorter time to disappearance of pulmonary congestion in the early group (median, 3 [interquartile range, 2-6] versus 5 [interquartile range, 3-7] days; P=0.027). CONCLUSIONS: Among patients with cardiogenic shock undergoing VA-ECMO, early routine left ventricular unloading with transseptal left atrial cannulation did not reduce 30-day mortality compared with the conventional strategy, which permitted rescue transseptal left atrial cannulation. These findings should be cautiously interpreted until the results of multicenter trials using other unloading modalities become available. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04775472.

Early left ventricular unloading after extracorporeal membrane oxygenation: rationale and design of EARLY-UNLOAD trial.

AIMS: The clinical benefits of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for profound cardiogenic shock are well known. However, peripheral VA-ECMO increases the left ventricular afterload, thus compromising myocardial recovery. Recent studies have revealed the benefit of left ventricular unloading using various methods applied at different times. The EARLY-UNLOAD trial compares the clinical outcomes of early left ventricular unloading and conventional approach after VA-ECMO. METHODS AND RESULTS: The EARLY-UNLOAD trial is a single-centre, open-label, randomized trial that recruited 116 patients with cardiogenic shock undergoing VA-ECMO. Patients meeting the inclusion criteria were randomized in a 1:1 ratio to two groups: routine left ventricular unloading via intracardiac echocardiography-guided transseptal left atrial cannulation within 12 h of VA-ECMO initiation or conventional approach that indicates rescue left ventricular unloading if clinical signs of an increased left ventricular afterload are present. The primary endpoint is the cumulative incidence of all-cause death within 30 days, and patients will be followed-up for 12 months. A key secondary endpoint is a composite measure of all-cause death and rescue transseptal left atrial cannulation in the conventional group (suggestive of VA-ECMO treatment failure) within 30 days. The enrolment of patients was finished in September 2022. CONCLUSIONS: The EARLY-UNLOAD trial is the first randomized controlled trial to compare early left ventricular unloading and conventional approach after VA-ECMO using the same unloading modality. The results could impact clinical practice to overcome the haemodynamic issues associated with VA-ECMO.

A Conductive and Adhesive Hydrogel Composed of MXene Nanoflakes as a Paintable Cardiac Patch for Infarcted Heart Repair.

Myocardial infarction (MI) is a major cause of death worldwide. After the occurrence of MI, the heart frequently undergoes serious pathological remodeling, leading to excessive dilation, electrical disconnection between cardiac cells, and fatal functional damage. Hence, extensive efforts have been made to suppress pathological remodeling and promote the repair of the infarcted heart. In this study, we developed a hydrogel cardiac patch that can provide mechanical support, electrical conduction, and tissue adhesiveness to aid in the recovery of an infarcted heart function. Specifically, we developed a conductive and adhesive hydrogel (CAH) by combining the two-dimensional titanium carbide (Ti3C2Tx) MXene with natural biocompatible polymers [i.e., gelatin and dextran aldehyde (dex-ald)]. The CAH was formed within 250 s of mixing the precursor solution and could be painted. The hydrogel containing 3.0 mg/mL MXene, 10% gelatin, and 5% dex-ald exhibited appropriate material characteristics for cardiac patch applications, including a uniform distribution of MXene, a high electrical conductivity (18.3 mS/cm), cardiac tissue-like elasticity (30.4 kPa), strong tissue adhesion (6.8 kPa), and resistance to various mechanical deformations. The CAH was cytocompatible and induced cardiomyocyte (CM) maturation in vitro, as indicated by the upregulation of connexin 43 expression and a faster beating rate. Furthermore, CAH could be painted onto the heart tissue and remained stably adhered to the beating epicardium. In vivo animal studies revealed that CAH cardiac patch treatment significantly improved cardiac function and alleviated the pathological remodeling of an infarcted heart. Thus, we believe that our MXene-based CAH can potentially serve as a promising platform for the effective repair of various electroactive tissues including the heart, muscle, and nerve tissues.