Aims This multicentre observational study aimed to prospectively assess the efficacy of left bundle branch area pacing (LBBAP) in heart failure patients with left bundle branch block (LBBB) and compare the 6‐month outcomes between LBBAP and biventricular pacing (BVP). Methods and results Consecutive patients with LBBB and left ventricular ejection fraction (LVEF) ≤ 35% were prospectively recruited if they had undergone LBBAP as a primary or rescue strategy from three separate centres from March to December 2018. Patients who received BVP in 2018 were retrospectively selected by using 2 to 1 propensity score matching to minimize bias. Implant characteristics and echocardiographic parameters were assessed during the 6‐month follow‐up. LBBAP procedure succeeded in 81.1% (30/37) of patients, with selective LBBAP in 10 patients, and 3 of 20 patients combined non‐selective LBBAP and LV lead pacing for further QRS narrowing. LBBAP resulted in significant QRS narrowing (from 178.2 ± 18.8 to 121.8 ± 10.8 ms, P < 0.001, paced QRS duration ≤ 130 ms in 27 patients) and improved LVEF (from 28.8 ± 4.5% to 44.3 ± 8.7%, P < 0.001) during the 6‐month follow‐up. The comparison between 27 patients with LBBAP alone and 54 of 130 matching patients with BVP showed that LBBAP delivered a greater reduction in the QRSd (58.0 vs. 12.5 ms, P < 0.001), a greater increase in LVEF (15.6% vs. 7.0%, P < 0.001), and greater echocardiographic (88.9% vs. 66.7%, P = 0.035) and super response (44.4% vs. 16.7%, P = 0.007) to cardiac resynchronization therapy. Conclusions LBBAP could deliver cardiac resynchronization therapy in most patients with heart failure and LBBB, and might be a promising alternative resynchronization approach to BVP.

Background: Drug-coated balloons (DCB), alone or in combination with drug-eluting stents (DES), may be used to treat diffuse coronary lesions. We aimed to explore the efficacy and safety of DCB in patients with diffuse coronary lesions.Methods: Consecutive patients with diffuse coronary lesions (lesion length > 25 mm) who underwent DCB and/or DES between January 2015 and December 2019 were included in this prospective, observational, multicenter study. The DCB group included 355 patients (360 lesions), of which 142 patients (143 lesions, 39.7%) received the DCB-only strategy and 213 patients (217 lesions, 60.3%) received the hybrid strategy (DCB combined with DES). The DES group included 672 patients (831 lesions) treated with DES alone. Target lesion revascularization (TLR) during 3-year follow-up was the primary outcome of interest. The secondary outcome was major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and target vessel revascularization.Results: The two groups had comparable baseline clinical and lesion characteristics. Lesion length was similar (43.52 ± 16.46 mm vs. 44.87 ± 15.80 mm, P = 0.181), but the stent length in the DCB group was significantly shorter (24.02 ± 23.62 mm vs. 51.89 ± 15.81 mm, P < 0.001). Ten lesions (2.8%) in the DCB group received bailout stents. Over 3 years of follow-up, no significant difference in TLR incidence between the groups (7.3 vs. 8.3%, log-rank P = 0.636) was observed. Incidence of MACE also did not differ significantly (11.3 vs. 13.7%, log-rank P = 0.324). No thrombosis events occurred in the DCB group, while four patients (0.6%) in the DES group experienced stent thrombosis (log-rank P = 0.193). Moreover, similar TLR and MACE rates were observed between DCB-only and hybrid strategies (TLR: 6.4 vs. 8.0%, log-rank P = 0.651; MACE: 11.4 vs. 11.2%, log-rank P = 0.884).Conclusion: Long-term outcomes show that the efficacy and safety of the DCB strategy (DCB alone or combined with DES) are similar to those of DES alone in diffuse coronary lesions. These findings suggest that this strategy is a promising alternative for select patients with diffuse coronary lesions.

Cathelicidin-related antimicrobial peptide (CRAMP), antimicrobial peptide, was reported to protect against myocardial ischemia/reperfusion injury. In the pathology of diabetic cardiomyopathy, endothelial-to-mesenchymal transition (EndMT) results from hyperglycemia-induced endothelial injury, leading to cardiac fibrosis. This study aims to evaluate the effect of CRAMP on EndMT and cardiac fibrosis on diabetic mice heart. Mice were subjected to streptozotocin to induce diabetes. CRAMP was administered by intraperitoneal injection (1 or 8 mg/kg/d) for 4 weeks from 12 weeks till 16 weeks after final streptozotocin injection. Cardiac dysfunction was observed in diabetic mice. Only 8 mg/kg/d CRAMP treatment proved cardiac function. Increased EndMT and fibrosis level were also observed in diabetic mice heart. 8mg/kg CRAMP inhibited EndMT and fibrosis level in diabetic mice. Mouse heart endothelial cells (MHECs) were treated with CRAMP and exposed to high glucose. Hyperglycemia-induced EndMT in MHECs was also attenuated by CRAMP treatment. Activation of TGFβ/Smad signalling was increased in diabetic mice heart tissue and hyperglycemia stimulated MHECs, which was prevented following CRAMP treatment. Activation of AMPKa1/mTOR showed similar changes. AMPKa1 siRNA abrogated the effects of CRAMP in MHECs. TGFβ/Smad inhibitor LY2109761 and AMPKa agonist AIRCA mimic the effect of CRAMP. In summary, CRAMP can inhibit EndMT, cardiac fibrosis and protect against diabetic cardiomyopathy by regulating AMPKa1/TGFβ signalling.

Previous studies demonstrated that Bailcalin (BAI) prevented cardiac injuries under different disease models. Whether BAI protected against type 2 diabetes mellitus- (T2DM-) associated cardiomyopathy was investigated in this study. T2DM was established by the combination of streptozotocin injection and high-fat diet in mice. BAI was administered daily for 6 months. After evaluating cardiac functions, mice hearts were removed and processed for morphological, biochemical, and molecular mechanism analyses. Neonatal rat cardiomyocytes (NRCM) were isolated and treated with high glucose and palmitate (HG/Pal) for in vitro investigation. BAI significantly ameliorated T2DM-induced cardiomyocyte hypertrophy, interstitial fibrosis, and lipid accumulation accompanied by markedly improved cardiac functions in diabetic mice. Mechanically, BAI restored decreased phosphorylation of AMPK and enhanced expression and nuclei translocation of Nrf2. In in vitro experiments, BAI also prevented NRCM from HG/Pal-induced apoptosis and oxidative stress injuries by increasing p-AMPK and Nrf2 accumulation. The means by which BAI restored p-AMPK seemed to be related to the antioxidative effects of Nrf2 after silencing AMPK or Nrf2 in NRCM. Furthermore, BAI regulated Nrf2 by inhibiting Nrf2 ubiquitination and consequent degradation mediated by Keap1. This study showed that BAI alleviated diabetes-associated cardiac dysfunction and cardiomyocyte injuries in vivo and in vitro via Keap1/Nrf2/AMPK-mediated antioxidation and lipid-lowering effects. BAI might be a potential adjuvant drug for diabetes cardiomyopathy treatment.

Aims: An increasing body of evidence suggests that drug-coated balloon (DCB) angioplasty represents a valuable option for revascularization in selected patients with coronary bifurcation disease. However, there remains a paucity of real-world observational evidence on the efficacy of DCB in left main (LM) true bifurcation lesion. We compared clinical and angiographic outcomes of hybrid [DCB + drug-eluting stent (DES)] versus DES-only strategy (provisional stenting or two-stent strategies) in de novo LM true bifurcated lesions.Methods: The primary endpoint was the 2-year composite rate of target lesion failure (TLF): cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (CD-TLR). A routine 1-year angiographic follow-up was scheduled. Propensity-score matching was utilized to assemble a cohort of patients with similar baseline characteristics.Results: Among 1077 eligible patients, 199 who received DCB treatment and 398 who were assigned to DES therapy had similar propensity scores and were included in the analysis. TLF within 2 years occurred in 13 patients (7.56%) assigned to DCB group, and 52 patients (14.36%) assigned to DES group (odds ratio: 0.487; 95% confidence interval: 0.258–0.922; P = 0.025; Log-rank P = 0.024). Compared with the DES group, the DCB group resulted in a lower rate of CD-TLR (2.91% vs. 9.42%; P = 0.007). Cardiac death, TVMI, all-cause mortality, and stent thrombosis were comparable between both groups. Patients treated with DES-only were associated with a higher late lumen loss (0.42 ± 0.62 mm vs. 0.13 ± 0.42 mm, P < 0.001) compared with the DCB group at 1 year. In sensitivity analysis, the DCB group also presented a lower incidence of TLF, CD-TLR and stent thrombosis both compared to the two-stent strategy and compared to provisional stenting (Ps < 0.05).Conclusion: The 2-year results of PCI utilizing DCB for LM true bifurcation lesions are superior to employing DES alone in terms of safety and effectiveness.