The excessive reactive oxygen species (ROS) and hypoxia deteriorate the inflammation‐related diseases such as myocardial infarction (MI), and thereby deter the normal tissue repair and recovery and further lead to severe fibrosis and malfunction of tissues and organs. In particular, the MI has become one of the leading causes of death nowadays. In this study, a novel type of injectable hydrogel with dual functions of ROS scavenging and O2 generating is fabricated for MI treatment in vivo. The hydrogel is formed within 3 s from the synthetic ROS‐cleavable hyperbranched polymers and methacrylate hyaluronic acid (HA‐MA) under UV‐irradiation. Addition of biocompatible and applicable catalase in vivo enables the further transition of H2O2, a major type of ROS, to O2 and H2O. Results of rat MI model demonstrate that this hydrogel can significantly remove excessive ROS, inhibit cell apoptosis, increase M2/M1 macrophage ratio, promote angiogenesis, reduce infarcted area, and improve cardiac functions. With the appropriate degradation rate, simple structure and composition without cell seeding, and very excellent MI therapeutic effect, this ROS scavenging and O2 generating hydrogel has a great promise to be applied clinically.

Background: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with non-ischemic cardiomyopathy (NICM), an increasingly prevalent population referred for advanced therapies globally. Methods: We conducted an international, multi-center, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for implantable cardioverter defibrillator (ICD) implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomized (1:1) to ablation + an ICD versus conventional medical therapy + an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite endpoint of VT recurrence, cardiovascular hospitalization, or death. Results: Randomized patients had a mean age of 55 years old (IQR 46-64) and left ventricular ejection fraction of 40 % (IQR 30-49 %); 81 % were male. The underlying heart disease was ischemic cardiomyopathy (ICM) in 35 %, NICM in 30 %, and arrhythmogenic cardiomyopathy (ARVC) in 35 %. Ablation was performed a median of 2 days prior to ICD implantation (IQR 5 days prior to 14 days after). At 31-months, the primary outcome occurred in 49.3 %of the ablation group and 65.5 % in the control group (HR 0.58, 95 % CI, 0.35-0.96; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (HR 0.51 [95 %CI, 0.29-0.90 ]; P=0.02). A statistically significant reduction in both ICD shocks (10.0 vs 24.6 %; p=0.03) and anti-tachycardia pacing (16.2 % vs 32.8 %; p=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0 % vs. 33.7 %; HR 0.82 [95 % CI, 0.43-1.56 ]; P=0.55) or mortality (8.9% vs 8.8 %, HR 1.40 [95 %CI, 0.38-5.22 ]; P=0.62]) were observed. Ablation-related complications occurred in 8.3 % of patients. Conclusions: Among patients with cardiomyopathy of varied etiologies, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies.

Excessive reactive oxygen species (ROS) generated after myocardial infarction (MI) result in the oxidative injury in myocardium. Implantation of antioxidant biomaterials, without the use of any type of drugs, is very appealing for clinical translation, leading to the great demand of novel biomaterials with high efficiency of ROS elimination. In this study, a segmented polyurethane (PFTU) with a high density of ROS-scavenging backbone units is synthesized by the reaction of poly(thioketal) dithiol (PTK) and poly(propylene fumarate) diol (PPF) (soft segments), thioketal diamine (chain extender), and 1,6-hexamethylene diisocyanate (HDI). Its chemical structure is verified by gel permeation chromatography (GPC), 1 H nuclear magnetic resonance ( 1 H NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The electrospun composite PFTU/gelatin (PFTU/Gt) fibrous patches show good antioxidation capacity and ROS-responsive degradation in vitro. Implantation of the PFTU/gelatin patches on the heart tissue surface in MI rats consistently decreases the ROS level, membrane peroxidation, and cell apoptosis at the earlier stage, which are not observed in the non-ROS-responsive polyurethane patch. Inflammation and fibrosis are also reduced in the PFTU/gelatin-treated hearts, resulting in the reduced left ventricular remodeling and better cardiac functions postimplantation for 28 d.

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