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Objective In MADIT-CRT, patients with non-LBBB (right bundle branch block or nonspecific ventricular conduction delay) and a prolonged PR-interval derived significant clinical benefit from cardiac resynchronization therapy with defibrillator (CRT-D) compared to an implantable cardioverter defibrillator (ICD)-only. We aimed to study the long-term outcome of non-LBBB patients by baseline PR-interval with CRT-D versus ICD-only. Methods Non-LBBB patients ( n  = 534) were dichotomized based on baseline PR-interval: normal PR (PR < 230 ms), and markedly prolonged PR (PR ≥ 230 ms). The primary end point was heart failure (HF) or death. Secondary end points were HF only and all-cause death. Results In patients with a prolonged PR-interval, CRT-D treatment related to a 67 % significant reduction in the risk of HF/death (HR = 0.33, 95 % CI 0.16–0.69, p  = 0.003), 69 % decrease in HF (HR = 0.31, 95 % CI 0.14–0.68, p  = 0.003), and 76 % reduction in the risk of death (HR = 0.24, 95 % CI 0.07–0.80, p  = 0.020) compared to ICD-only (median follow-up 5.8 years). In normal PR-interval patients, CRT-D therapy was associated with a trend towards increased risk of HF/death (HR = 1.49, 95 % CI 0.98–2.25, p  = 0.061), and significantly increased mortality (HR = 2.27, 95 % CI 1.16–4.44, p  = 0.014). Significant statistical interaction with the PR-interval was demonstrated for all end points. Results were consistent for QRS 130–150 ms and QRS > 150 ms. Conclusion In MADIT-CRT, non-LBBB patients with a prolonged PR-interval derive sustained long-term clinical benefit with reductions in heart failure or death from CRT-D implantation, compared to an ICD-only. Our findings support implantation of CRT-D in non-LBBB patients with prolonged PR-interval irrespective of baseline QRS duration.

Right ventricular (RV) pacing has been linked with lead-induced tricuspid regurgitation (TR), left ventricular (LV) dysfunction, and dyssynchrony, but the effect of pacing on RV function is unclear. We sought to investigate the effect of pacing on RV synchrony, RV function, and TR, and their association with LV function. In this substudy of the PROTECT-PACE (Protection of left ventricular function during right ventricular pacing) study of the effects of RV pacing in patients with preserved ejection fraction, 145 patients (76 RV apex and 69 non-RV apex pacing) had measurable RV parameters. We assessed tricuspid annular plane systolic excursion (TAPSE), time difference between peak TAPSE and peak mitral annular plane systolic excursion (TM-APSE-dif), global LV longitudinal strain, E/e’, TR vena contracta, and TR peak gradient. Echocardiography was performed just after implantation and at 2 years. TR parameters significantly worsened after 2 years, but pacing site was not associated with changes in RV and TR parameters. No temporal change in TAPSE and TM-APSE-dif was observed overall, but worsening of TM-APSE-dif was associated with worsening TAPSE. Global longitudinal strain and E/e’ both deteriorated over 2 years; these changes were significantly associated. In a multivariate regression, worsening global longitudinal strain and worsening TM-APSE-dif were significantly associated with deterioration of TAPSE. Furthermore, increased E/e’ and its deterioration were associated with worsening TR vena contracta and TR peak gradient, respectively. Decreased TAPSE was also associated with deterioration of TR vena contracta. In conclusion, RV pacing appears to worsen TR, an effect which might be caused by elevated LV filling pressure due to LV dysfunction. In this study, RV pacing did not affect RV function during 2-year follow-up, but such an effect might occur if RV dyssynchrony or LV dysfunction occurred after pacing. The effect of RV pacing site on RV and TR mechanics was minor.

CDGSH iron-sulfur domain-containing protein 2 (Cisd2) is pivotal to mitochondrial integrity and intracellular Ca2+ homeostasis. In the heart of Cisd2 knockout mice, Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Furthermore, Cisd2 deficiency disrupts Ca2+ homeostasis via dysregulation of sarco/endoplasmic reticulum Ca2+-ATPase (Serca2a) activity, resulting in an increased level of basal cytosolic Ca2+ and mitochondrial Ca2+ overload in cardiomyocytes. Most strikingly, in Cisd2 transgenic mice, a persistently high level of Cisd2 is sufficient to delay cardiac aging and attenuate age-related structural defects and functional decline. In addition, it results in a younger cardiac transcriptome pattern during old age. Our findings indicate that Cisd2 plays an essential role in cardiac aging and in the heart's electromechanical functioning. They highlight Cisd2 as a novel drug target when developing therapies to delay cardiac aging and ameliorate age-related cardiac dysfunction.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Recently, a connection has been observed between the presence of first-degree atrioventricular block (FDAVB) and cardiovascular outcomes, although the pathophysiology of this association remains poorly understood. Considering the period 2000-2023, we retrospectively included HCM patients at sinus rhythm at the first appointment and sought possible interactions of FDAVB (defined as PR interval >200 ms) with different clinical and imaging variables and with the occurrence of cardiovascular events, including atrial fibrillation (AF). A total of 97 patients were included, of whom 57 (58.8%) were men, with a mean age of 51±19 years, and 14 (14.4%) had FDAVB. During a median of 4.29 (percentile 25 1.92, percentile 75 7.67) years of follow-up, 35 cardiovascular events occurred, including 13 de novo diagnoses of AF, 8 hospitalizations due to heart failure, 8 new-onset strokes, 4 myocardial infarctions, and 2 implantations of cardio defibrillators in secondary prevention; no HCM-related death occurred. We did not find any association between outcomes and the presence of FDAVB. The role of FDAVB as a prognostic marker in HCM patients requires further investigation. We found that FDAVB patients were older, more frequently reported dyspnea, had a larger QRS duration, a higher ratio of early mitral inflow velocity to mean early diastolic mitral annular velocity (E/e’), and lower maximal left ventricle wall thickness by magnetic resonce (p<0.05). After multivariable alysis, FDAVB was independently associated with a higher echocardiographic E/e’ ratio (p=0.039) (odds ratio=1.588). This is the first paper to document an independent association between FGAVB and a higher E/e’ ratio in HCM patients.

There are limited data available on the development of arrhythmias in patients at risk of high-degree atrioventricular block (HAVB) or complete heart block (CHB) following transcatheter aortic valve replacement (TAVR). This study aimed to explore the incidence and evolution of arrhythmias by monitoring patients at risk of HAVB or CHB after TAVR using smartwatches. We analyzed 188 consecutive patients in the prospective SMART TAVR (smartwatch-facilitated early discharge in patients undergoing TAVR) trial. Patients were divided into 2 groups according to the risk of HAVB or CHB. Patients were required to trigger a single-lead electrocardiogram (ECG) recording and send it to the Heart Health App via their smartphone. Physicians in the central ECG core lab would then analyze the ECG. The incidence and timing of arrhythmias and pacemaker implantation within a 30-day follow-up were compared. All arrhythmic events were adjudicated in a central ECG core lab. The mean age of the patients was 73.1 (SD 7.3) years, of whom 105 (55.9%) were men. The mean discharge day after TAVR was 2.0 (SD 1.8) days. There were no statistically significant changes in the evolution of atrial fibrillation or atrial flutter, Mobitz I, Mobitz II, and third-degree atrial ventricular block over time in the first month after TAVR. The incidence of the left bundle branch block (LBBB) increased in the first week and decreased in the subsequent 3 weeks significantly (P<.001). Patients at higher risk of HAVB or CHB received more pacemaker implantation after discharge (n=8, 9.6% vs n=2, 1.9%; P=.04). The incidence of LBBB was higher in the group with higher HAVB or CHB risk (n=47, 56.6% vs n=34, 32.4%; P=.001). The independent predictors for pacemaker implantation were age, baseline atrial fibrillation, baseline right bundle branch block, Mobitz II, and third-degree atrioventricular block detected by the smartwatch. Except for LBBB, no change in arrhythmias was observed over time in the first month after TAVR. A higher incidence of pacemaker implantation after discharge was observed in patients at risk of HAVB or CHB. However, Mobitz II and third-degree atrioventricular block detected by the smartwatch during follow-ups were more valuable indicators to predict pacemaker implantation after discharge from the index TAVR. ClinicalTrials.gov NCT04454177; https://clinicaltrials.gov/study/NCT04454177.

Background ICI-associated myocarditis is an uncommon yet potentially fatal condition, particularly when concomitant with atrioventricular block (AVB) necessitating pacing. The role of pacing therapy for ICI-associated AVB remains unknown. Objectives The aim of this study is to investigate the efficacy and safety of pacing therapy for ICI-associated AVB. Methods Patients with ICI-associated myocarditis admitted to Peking Union Medical College Hospital from May 1st 2019 to April 30th 2024 were consecutively screened and the patients with AVB requiring pacing therapy were retrospectively included. Baseline clinical characteristics and initial temporary pacing therapy were evaluated. Follow-up assessments were conducted to evaluate the survival rate and the recovery of atrioventricular conduction. Results A total of 43 patients with ICI-associated myocarditis were screened. Among them, a total of 11 (11/43, 25.6%) patients (mean age 64.5 ± 8.6 years, female 18.2%) were diagnosed with advanced or complete AVB and subsequently underwent pacing therapy. Short-term (within 90-days after procedure) survival rate was 72.7% (8/11). Atrioventricular conduction recovered in 4 (4/11, 36.4%) patients, without AVB recurrence after temporary pacemaker removal. For safety endpoints, right ventricular (RV) pacing parameters including pacing threshold, sensing amplitude and impedance were acceptable and no procedure-related complications occurred except RV temporary active fixation lead dislodgement in 1 patient (1/11, 9.1%). No pacing system related-infection occurred. Conclusions Pacing therapy for ICI-associated AVB demonstrates both safety and efficacy. ICI-associated AVB shows a high rate of recovery. Temporary pacemaker with active fixation lead may be a reasonable option for the initial pacing therapy.

Eosinophilic fasciitis (EF) is a rare connective tissue disorder characterized by the involvement of the dermis, subcutaneous tissue, and fascia. The treatment for EF usually involves long-term use of glucocorticoids and immunosuppressants. Patients with EF are at risk of developing third-degree atrioventricular (AV) block during the course of the disease. The distinctive features of EF, the side effects of its treatment, and the inherent limitations of transvenous pacemakers (TVPs) present significant challenges in the management of patients with EF who also have third-degree AV block. We present the case of a 64-year-old Chinese male diagnosed with EF and concomitant third-degree AV block. Given the patient’s skin tissue characteristics, the increased risk of infection associated with long-term immunosuppressive therapy, and the potential complications related to TVPs we chose to implant a leadless pacemaker(LP) in the apical region of the right ventricle. This case report underscores the importance of identifying potential cardiovascular complications in EF patients treated with corticosteroids and immunosuppressants. It also highlights the clinical benefit of LP implantation in managing patients with EF and third-degree AV block, especially in terms of minimizing device-related complications and infection risks. This study offers a fresh perspective on the treatment of EF patients who have third-degree AV block and advocates for the use of LPs as a preferred option for cardiac pacing in this patient group. Further research is warranted to evaluate the indications and potential benefits of LPs in a wider range of patients. Clinical trial number Not applicable.

Background Weil’s disease is an infection caused by Leptospira bacteria. Leptospirosis may cause arrhythmias, such as atrial fibrillation and ST-T segment changes. We report a rare case of total atrioventricular block induced by leptospirosis. Early diagnosis and prompt management present particular challenges. Case report A 43-year-old Asian woman was referred from internal medicine to cardiology owing to an electrocardiogram abnormality. She complained of worsening chest discomfort 3 days earlier, accompanied by fever, nausea, and intermittent headaches. The patient appeared lethargic and jaundiced; blood pressure was 81/43 mmHg, heart rate was 41 bpm, respiratory rate was 20 times/minute, and temperature was 38.2 °C. The electrocardiogram showed a total atrioventricular block with a junctional escape rhythm of 45 bpm. Laboratory tests revealed increased renal and liver function, thrombocytopenia (98,000/µL), and positive immunoglobulin G and M anti- Leptospira . The patient was diagnosed with Weil’s disease (Faine’s score 32) and total atrioventricular block. The initial management involved fitting the patient with a transcutaneous pacemaker and giving dopamine 5 mcg/kgBW/minute, titrated to a target systolic blood pressure of > 90 mmHg. The patient was also scheduled to undergo temporary transvenous pacing. However, the patient died of suspected cardiogenic shock due to a deterioration in clinical condition. Conclusion Leptospirosis can cause rare but fatal arrhythmias, as seen in this case of fulminant leptospirosis with total atrioventricular block. Clinicians should be vigilant and consider this potential complication in similar cases.

In this trial, patients with atrioventricular block and systolic dysfunction were randomly assigned to receive biventricular or right ventricular pacing. Clinical outcomes were superior with biventricular pacing. These data may extend the use of this pacing mode. Trials of cardiac-resynchronization therapy (CRT) have included patients with advanced systolic heart failure and prolonged QRS duration. 1 These trials have specifically excluded patients with a moderate-to-high degree of atrioventricular block who require ventricular pacing in order to evaluate the effects of CRT independently of the potentially confounding detrimental effects of right ventricular pacing. Whereas right ventricular pacing achieves the primary goal of restoring an adequate heart rate in patients with atrioventricular block, studies suggest that right ventricular apical pacing may lead to progressive left ventricular dysfunction and heart failure in patients with preexisting left ventricular dysfunction, 2 , 3 presumably owing to . . .

Background Conventional right ventricular pacing (RVP) causes cardiac dyssynchrony, and increases risk of pacing-induced cardiomyopathy (PICM), heart failure hospitalization and mortality. Left bundle branch area pacing (LBBAP) is a promising physiological pacing modality, we compared the effect of LBBAP on cardiac function with RVP in patients with atrioventricular block (AVB). Methods A total of 118 patients with AVB who successfully underwent LBBAP were enrolled between June 2019 and June 2022. Among them, 110 patients with a baseline LVEF ≥ 50% were propensity-matched 1:1 with 49 patients who underwent RVP during the same period. Ultimately, 41 patients with well-matched baseline characteristics in both groups were included in the analysis. Echocardiographic parameters and NYHA classification at 1-year follow-up were compared between the groups. Results Left ventricular ejection fraction (LVEF) remained stable in patients with LVEF ≥ 50% (62.9 ± 2.9 vs. 62.9 ± 3.3, P  = 0.960), and improved significantly in patients with LVEF < 50% (58.0 ± 9.9% vs. 44.2 ± 5.5%, P  < 0.05) at 1-year follow-up in the LBBAP group. Propensity score matching for baseline characteristics yielded 41 matched pairs. Changes in LVEF and left ventricular end-diastolic diameter (LVEDD) in the LBBAP group were significantly different from those in the RVP group: LVEF [-2.8(-5.0, -0.6), P  = 0.015] and LVEDD [1.3(0.1, 2.5), P  = 0.036], respectively. Compared with baseline, NYHA classification improved significantly in the LBBAP group (1.3 ± 0.5 vs. 1.0 ± 0.2, P  < 0.05), while remained changed in the RVP group (1.3 ± 0.4 vs. 1.1 ± 0.3, P  = 0.232). LBBAP showed a tendency to reduce PICM compared with RVP (0% vs. 9.8%), though the difference was not significant ( P  = 0.124). Conclusions LBBAP might be a preferable pacing modality to improve cardiac remodeling and function in patients requiring high ventricular pacing burden compared with conventional RVP.