Aims: Left bundle branch pacing (LBBP) recently emerges as a novel pacing modality. We aimed to evaluate the feasibility and cardiac synchrony of permanent LBBP in bradycardia patients. Methods and results: Left bundle branch pacing was successfully performed in 56 pacemaker-indicated patients with normal cardiac function. Left bundle branch pacing was achieved by penetrating the interventricular septum (IVS) into the left side sub-endocardium with the pacing lead. His-bundle pacing (HBP) was successfully performed in another 29 patients, 19 of whom had right ventricular septal pacing (RVSP) for backup pacing. The QRS duration, left ventricular (LV) activation time (LVAT), and mechanical synchrony using phase analysis of gated SPECT myocardial perfusion imaging were evaluated. Paced QRS duration in LBBP group was significantly shorter than that in RVSP group (117.8 ± 11.0 ms vs. 158.1 ± 11.1 ms, P < 0.0001) and wider than that in HBP group (99.7 ± 15.6 ms, P < 0.0001). Left bundle branch potential was recorded during procedure in 37 patients (67.3%). Left bundle branch pacing patients with potential had shorter LVAT than those without potential (73.1 ± 11.3 ms vs. 83.2 ± 16.8 ms, P = 0.03). Left bundle branch pacing patients with potential had similar LV mechanical synchrony to those in HBP group. R-wave amplitude and capture threshold of LBBP were 17.0 ± 6.7 mV and 0.5 ± 0.1 V, respectively at implant and remained stable during a mean follow-up of 4.5 months without lead-related complications. Conclusion: Permanent LBBP through IVS is safe and feasible in bradycardia patients. Left bundle branch pacing could achieve favourable cardiac electrical and LV mechanical synchrony.

Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing (LBBAP). This study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). Consecutive patients with reduced left ventricular ejection fraction (LVEF<50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite endpoint was all-cause mortality or heart failure hospitalization (HFH). Secondary endpoints included all-cause mortality, HFH, and echocardiographic measures of reverse remodeling. A total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were followed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary endpoint by 78% compared to both BiVP [7.4% vs. 41.2%; adjusted hazard ratio (aHR) 0.22 (0.08, 0.57), p=0.002] and LVSP [7.4% vs. 47.4%; aHR 0.22 (0.08, 0.63), p=0.004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than BiVP [31.6% vs. 7.2%, aHR 3.19 (1.38, 7.39); p=0.007] but comparable between LBBP and BiVP [2.9% vs. 7.2%, aHR 0.33 (0.07, 1.52), p=0.155]. Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs. 36.2% vs. 16.1%; p<0.001) than BiVP or LVSP. LBBP yielded superior long-term clinical outcomes to BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated due to its high mortality risk.

Brain and muscle arnt-like protein 1 (Bmal1) is a crucial transcription factor, regulating circadian rhythm and involved in multiple heart diseases. However, it is unknown whether Bmal1 promotes diabetic cardiomyopathy (DCM) pathogenesis. The objective of this investigation was to ascertain the vital role of Bmal1 in the progression of DCM. Mice with T2D and H9c2 cardiomyoblasts exposed to high glucose and palmitic acid (HGHP) were used. Cardiomyocyte-specific knockout mouse of Bmal1 (CKB) was also generated, and cardiac Bmal1 was overexpressed in type 2 diabetes (T2D) mice using an adeno-associated virus. Bmal1 gene recombinant adenovirus was used to either knockdown or overexpress in H9c2 cardiomyoblasts. Bmal1 expression was significantly altered in diabetic mice hearts. Bmal1 downregulation in CKB and T2D mice heart accelerated cardiac hypertrophy and diastolic dysfunction, while Bmal1 overexpression ameliorated these pathological changes in DCM mice. Furthermore, DCM mice had significant mitochondrial ultrastructural defects, reactive oxygen species accumulation, and apoptosis, which could be alleviated by overexpressing Bmal1. In H9c2 cardiomyoblasts, genetic downregulation of Bmal1 or HGHP markedly decreased the binding of Bcl2 to IP3R, thus increasing Ca²⁺ release to mitochondria through mitochondria-associated endoplasmic reticulum membranes. Importantly, chromatin immunoprecipitation revealed Bmal1 could bind directly to the Bcl2 gene promoter region. Bmal1 overexpression augmented the Bmal1/Bcl2 binding, enhancing the inhibition of Bcl2 on IP3R activity, thus alleviating mitochondrial Ca²⁺ overload and subsequent cell apoptosis. These results show that Bmal1 is involved in the DCM development through Bcl2/IP3R-mediated mitochondria Ca²⁺ overload. Therapy targeting the circadian clock (Bmal1) can treat DCM.

This study aimed to assess the acute effect of selective His bundle pacing (S-HBP), non-selective His bundle pacing (NS-HBP), and right ventricular septum pacing (RVSP) on electrical synchrony and left ventricular (LV) mechanical synchrony using electrocardiogram and phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Totally 39 patients eligible for pacemaker were enrolled. Thirty-seven patients underwent successful His bundle pacing (HBP) including S-HBP in 23 and NS-HBP in 14 patients, respectively. Thirty-one patients simultaneously underwent backup RVSP. Twenty-three patients received SPECT MPI scans under different pacing modes, including S-HBP low- and high-output, NS-HBP low- and high-output, and RVSP mode. The paced QRS duration (QRSd) in the S-HBP low- and high-output mode and in the NS-HBP high-output mode were similarly compared with the baseline intrinsic QRSd. QRS duration in the NS-HBP low-output mode was slightly longer than the baseline. QRS duration was the longest in the RVSP group. Left ventricular mechanical synchrony parameters in both the S-HBP and the NS-HBP groups were remarkably better than those in the RVSP group. Moreover, LV mechanical synchrony parameters were much better in the S-HBP groups and NS-HBP high-output group. Selective His bundle pacing and high-output NS-HBP could restore normal electrical and LV mechanical synchrony.