Result of the Physiologic Pacing Registry, an international multicenter prospective observational study of conduction system pacing.

BACKGROUND: Conduction system pacing (CSP), including both left bundle branch area pacing (LBBAP) and His-bundle pacing (HBP) has been proposed as an alternative therapy option for patients with indication for cardiac pacing to treat bradycardia or heart failure. OBJECTIVE: The purpose of this study was to evaluate implant success, safety, and electrical performances of HBP and LBBAP in the multinational Physiological Pacing Registry. METHODS: The international prospective observational registry included 44 sites from 16 countries globally between November 2018 and May 2021. RESULTS: Of 870 subjects enrolled, CSP lead implantation was attempted in 849 patients. Subjects with successful CSP lead implantation were followed for 6 months (5 ± 2 months). CSP lead implantation was successful in 768 patients (90.4%). Implant success was 95.2% (239/251) for LBBAP and 88.5% (529/598) for HBP (P = .002). Procedural duration and fluoroscopy duration were comparable between LBBAP and HBP (P = .537). Capture threshold at implant was 0.69 ± 0.39 V at 0.46 ± 0.15 ms in LBBAP and 1.44 ± 1.03 V at 0.71 ± 0.33 ms in HBP (P <.001). Capture threshold at 6 months was 0.79 ± 0.33 V at 0.44 ± 0.13 ms in LBBAP and 1.59 ± 0.97 V at 0.67 ± 0.31 ms in HBP (P <.001). Pacing threshold rise ≥1 V was observed at 6 months in 3 of 208 (1.4%) of LBBAP and 55 of 418 (13.2%) of HBP (P <.001). Serious adverse events related to implant procedure or CSP lead occurred in 5 of 251 (2.0%) with LBBAP and 25 of 598 (4.2%) with HBP (P = .115). CONCLUSION: This large prospective multicenter study demonstrates that CSP is technically feasible in most patients with relatively higher implant success and suggests that, with current technology, LBBAP may have better pacing parameters than HBP.

Non-continuous mobile electrocardiogram monitoring for post-transcatheter aortic valve replacement delayed conduction disorders put to the test.

AIMS: Permanent pacemaker implantation (PPM-I) remains nowadays the most important drawback of transcatheter aortic valve replacement (TAVR) procedure and the optimal strategy of delayed conduction disturbances (CDs) in these patients is unclear. The study aimed to validate an ambulatory electrocardiogram (ECG) monitoring through a 30 s spot ambulatory digital mobile ECG (AeECG), by using KardiaMobile-6L device in a 30-day period after TAVR procedure. METHODS AND RESULTS: Between March 2021 and February 2022, we consecutively enrolled all patients undergoing TAVR procedure, except pacemaker (PM) carriers. At discharge, all patients were provided of a KardiaMobile-6L device and a spot digital ECG (eECG) recording 1 month schedule. Clinical and follow-up data were collected, and eECG schedule compliance and recording quality were explored. Among 151 patients without pre-existing PM, 23 were excluded for pre-discharge PPM-I, 18 failed the KardiaMobile-6L training phase, and 10 refused the device. Delayed CDs with a Class I/IIa indication for PPM-I occurred in eight patients (median 6 days). Delayed PPM-I vs. non-delayed PPM-I patients were more likely to have longer PR and QRS intervals at discharge. PR interval at discharge was the only independent predictor for delayed PPM-I at multivariate analysis. The overall eECG schedule compliance was 96.5%. None clinical adverse events CDs related were documented using this new AeECG monitoring modality. CONCLUSION: A strategy of 30 s spot AeECG is safe and efficacious in delayed CDs monitoring after TAVR procedure with a very high eECG schedule level of compliance.

The Conjunction Conundrum in Transcatheter Aortic Valve Implantation.

A continuous discussion regarding the predictors for permanent pacemaker implantation (PPI) following transcatheter aortic valve implantation (TAVI) is ongoing, especially in the era of low and medium risk patients. The aim of this article is to review the data so far regarding the pathophysiology, risk factors, and the indications for permanent pacemaker implantation after TAVI. The factors that contribute to rhythm abnormalities post TAVI can be divided into pre-existing conduction abnormalities, patient-related anatomical factors, and peri-procedural technical factors. The latter components are potentially modifiable, and this is where attention should be directed, particularly now that in an era of TAVI expansion towards lower-risk patients.

Monitoring conduction disturbances following TAVR: Feasibility study of early discharge using a novel telemetry patch.

INTRODUCTION: Despite the technological advances and increasing operator experience, the rate of permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) has not decreased over time. With a continuous downward trend in post-TAVR length of stay, prolonged home-monitoring may have a key role in detecting potentially serious conduction abnormalities after TAVR discharge. METHODS: In this study, the ZioPatch-AT monitor was used to detect conduction abnormalities after TAVR discharge. The cardiac monitoring device was systematically provided to all patients having pre-existing right bundle branch block or developing intra-/peri-procedural conduction disturbances, in the absence of guideline indication for PPI at discharge. RESULTS: From a total of 75 patients at high-risk of conduction disturbances, 8 (11%) of them underwent PPI and most of them (6/8) were detected before symptoms' occurrence. Paired analysis between baseline and discharge electrocardiograms detected a significant widening of the QRS in all patients; on the contrary, PR length was significantly increased only in the group experiencing HAVB after discharge (p < 0.01). CONCLUSIONS: In an early post-TAVR discharge era, 30-day outpatient cardiac rhythm monitoring is potentially a safe solution to allow timely recognition of new conduction disturbances requiring PPI.

Incidence of carditis and predictors of pacemaker implantation in patients hospitalized with Lyme disease.

BACKGROUND: Lyme carditis, defined as direct infection of cardiac tissue by Borrelia bacteria, affects up to 10% of patients with Lyme disease. The most frequently reported clinical manifestation of Lyme carditis is cardiac conduction system disease. The goal of this study was to identify the incidence and predictors of permanent pacemaker implantation in patients hospitalized with Lyme disease. METHODS: A retrospective cohort analysis of the Nationwide Inpatient sample was performed to identify patients hospitalized with Lyme disease in the US between 2003 and 2014. Patients with Lyme carditis were defined as those hospitalized with Lyme disease who also had cardiac conduction disease, acute myocarditis, or acute pericarditis. Patients who already had pacemaker implants at the time of hospitalization (N = 310) were excluded from the Lyme carditis subgroup. The primary study outcome was permanent pacemaker implantation. Secondary outcomes included temporary cardiac pacing, permanent pacemaker implant, and in-hospital mortality. RESULTS: Of the 96,140 patients hospitalized with Lyme disease during the study period, 10,465 (11%) presented with Lyme carditis. Cardiac conduction system disease was present in 9,729 (93%) of patients with Lyme carditis. Permanent pacemaker implantation was performed in 1,033 patients (1% of all Lyme hospitalizations and 11% of patients with Lyme carditis-associated conduction system disease). Predictors of permanent pacemaker implantation included older age (OR: 1.06 per 1 year; 95% CI:1.05-1.07; P<0.001), complete heart block (OR: 21.5; 95% CI: 12.9-35.7; P<0.001), and sinoatrial node dysfunction (OR: 16.8; 95% CI: 8.7-32.6; P<0.001). In-hospital mortality rate was higher in patients with Lyme carditis (1.5%) than in patients without Lyme carditis (0.5%). CONCLUSIONS: Approximately 11% of patients hospitalized with Lyme disease present with carditis, primarily in the form of cardiac conduction system disease. In this 12-year study, 1% of all hospitalized patients and 11% of those with Lyme-associated cardiac conduction system disease underwent permanent pacemaker implantation.

Premature atrial contractions with multiple patterns of aberrant conduction followed by torsade de pointes in a patient with polymyalgia rheumatica: A case report.

RATIONALE: Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited. PATIENT CONCERNS: An 85-year-old Japanese woman with active PMR developed first syncope. DIAGNOSIS: Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP. INTERVENTIONS: Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective. OUTCOMES: Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia. LESSONS: IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.

Nonalcoholic Fatty Liver Disease: An Emerging Driver of Cardiac Arrhythmia.

Cardiac arrhythmias and the resulting sudden cardiac death are significant cardiovascular complications that continue to impose a heavy burden on patients and society. An emerging body of evidence indicates that nonalcoholic fatty liver disease (NAFLD) is closely associated with the risk of cardiac arrhythmias, independent of other conventional cardiometabolic comorbidities. Although most studies focus on the relationship between NAFLD and atrial fibrillation, associations with ventricular arrhythmias and cardiac conduction defects have also been reported. Mechanistic investigations suggest that a number of NAFLD-related pathophysiological alterations may potentially elicit structural, electrical, and autonomic remodeling in the heart, contributing to arrhythmogenic substrates in the heart. NAFLD is now the most common liver and metabolic disease in the world. However, the upsurge in the prevalence of NAFLD as an emerging risk factor for cardiac arrhythmias has received little attention. In this review, we summarize the clinical evidence and putative pathophysiological mechanisms for the emerging roles of NAFLD in cardiac arrhythmias, with the purpose of highlighting the notion that NAFLD may serve as an independent risk factor and a potential driving force in the development and progression of cardiac arrhythmias.

Prevalence of Cardiac Arrhythmias and Distal Conduction Disorders in Patients With Chronic Chagas' Disease and Elevated Autoantibodies Against M2 Muscarinic Acetylcholine Receptors.

Chagas' disease (ChD) is a parasitic disease endemic to regions of Latin America and with an increasingly global reach. Up to 30% of patients with ChD develop severe dilated cardiomyopathy, ventricular arrhythmias, conduction disorders and/or sudden cardiac death. Autoantibodies against M2 muscarinic acetylcholine receptors (M2 mAChR) have been implicated in the pathogenesis of ChD. We sought to understand whether there was an association between anti-M2 mAChR autoantibody titers in patients with chronic ChD and the presence of distal cardiac conduction disorders or cardiac arrhythmias. We conducted a cross-sectional study in 79 patients from Argentina and Bolivia with chronic ChD without evident structural heart disease. Autoantibody titers were measured using indirect enzyme-linked immunosorbent assay. Elevated anti-M2 mAChR autoantibody titers were associated with the presence of distal conduction disease but not with cardiac arrhythmias. High anti-M2 mAChR autoantibody levels could assist with identifying early structural heart disease in patients with chronic ChD.

Predictors of high-degree conduction disturbances and pacemaker implantation after transcatheter aortic valve replacement: Prognostic role of the electrophysiological study.

BACKGROUND: Predictors of high-degree atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) are recognized, but the electrophysiological study's (EPS) role is still a subject to debate. The objective of our study was to determine factors associated with PPM implantation including the potential role of EPS before and/or after TAVR. METHODS AND RESULTS: Seventy four consecutive patients (pts) were included and 21 pts (28.4%) received a PPM during the immediate postoperative follow-ups (until Day 5): HAVB in 15 pts (71.4%), prophylactic implantation due to a documented increased HV interval ≥ 95-100 ms plus LBBB in 2 pts (9.5%), a high-degree HV block evidenced at the EPS plus LBBB in 3 pts (14.3%) and one additional patient was implanted for AV-block in presence of AFib (4.8%). In the multivariate model 1 including parameters before TAVR, both prosthesis diameter and PR lengthening remained significantly associated with PPM as well RBBB. In the multivariate model 2 including parameters after TAVR, only HV remained significantly associated with the risk of PPM (OR = 1.15 (1.05-1.26), p = .004). When all the significant variables in models 1 and 2 were analyzed together in model 3, only HV after TAVR remained significantly associated with an increased risk of PPM. CONCLUSIONS: In this prospective observational study, it was revealed that a Day 4-5 EPS is likely to more precisely stratify the risk of PPM implantation regarding its ability to discover asymptomatic severe infra-hisian conduction disturbances particularly in presence of LBBB. Multivariate analysis confirmed the prognostic value of HV alteration.

Fibrosis and Conduction Abnormalities as Basis for Overlap of Brugada Syndrome and Early Repolarization Syndrome.

Brugada syndrome and early repolarization syndrome are both classified as J-wave syndromes, with a similar mechanism of arrhythmogenesis and with the same basis for genesis of the characteristic electrocardiographic features. The Brugada syndrome is now considered a conduction disorder based on subtle structural abnormalities in the right ventricular outflow tract. Recent evidence suggests structural substrate in patients with the early repolarization syndrome as well. We propose a unifying mechanism based on these structural abnormalities explaining both arrhythmogenesis and the electrocardiographic changes. In addition, we speculate that, with increasing technical advances in imaging techniques and their spatial resolution, these syndromes will be reclassified as structural heart diseases or cardiomyopathies.

Prognosis and Natural History of Conduction System Disease in Patients Undergoing Coronary Angiography.

BACKGROUND: Infranodal conduction abnormalities, including right or left bundle branch block bifascicular block, and nonspecific intraventricular conduction block are common electrocardiogram (ECG) abnormalities with uncertain persistence and prognostic significance. We evaluated their trajectory and prognostic significance in patients undergoing coronary angiography. METHODS: We linked an institutional ECG repository with the provincial coronary angiography registry and administrative databases. We included patients without severe left ventricular dysfunction who had an ECG within 180 days of angiography. Multivariable Cox models were used to assess associations between conduction abnormalities and a composite outcome, including all-cause mortality, heart failure hospitalizations, placement of a permanent pacemaker, and placement of an implantable cardiac defibrillator or cardiac resynchronization therapy defibrillator. Serial ECGs were used to model conduction disease as a time-dependent repeated measure. RESULTS: We included 10,786 patients (mean age, 62.3 ± 12.4 years; 70.3% were male), of whom 2530 (23.4%) had baseline conduction abnormality. During a median follow-up of 3.5 years, conduction normalized in 885 patients (34.9%) and the composite outcome occurred in 1541 patients (14.3%). After multivariable adjustment, intraventricular conduction block (adjusted hazard ratio, 1.42; P = 0.001) and bifascicular block (adjusted hazard ratio, 1.59; P = 0.003) were associated with increased risk of the composite outcome. Left bundle branch block was not associated with the composite outcome. CONCLUSIONS: Regression of conduction abnormalities was frequent among patients undergoing coronary angiography, primarily for suspected acute coronary syndrome. After adjustment for important confounders including extent of coronary artery disease, infranodal conduction abnormalities were associated with a modest increase in cardiovascular risk.

Investigation of the effect of epicardial adipose tissue thickness on cardiac conduction system in children with type 1 diabetes mellitus.

Objectives Investigation of the association between epicardial adipose tissue thickness (EATT) and P-wave dispersion (Pd), QT dispersion (QTd), corrected QT dispersion (QTcd) and Tp-e interval in children with Type 1 Diabetes Mellitus (T1DM) was aimed. Methods Forty-one children with T1DM and 41 age- and gender-matched healthy children were included in the study. Demographical characteristics of all cases were examined. In echocardiography; in addition to conventional echocardiographic measurements, end-systolic EATT was measured from right ventricular free wall. In electrocardiogram; Pd, QTd, QTcd and Tp-e interval durations, as well as Tp-e/QT and Tp-e/QTc ratios were calculated. Correlation values between EATT and electrocardiographic parameters were also noted. Results Mean age of the patient group was determined to be 12.43 ± 3.04 years and that of the control group was determined to be 12.08 ± 2.56 years. There was no significant difference between the groups in regard to age, gender, body weight, height and body mass index. In the patient group; EATT, Pd, QTd, QTcd and Tp-e interval were determined to be significantly higher compared to the control group. In the patient group, no significant correlation was determined between EATT and Pd, QTd, QTcd and Tp-e. However, when both patient and control groups were evaluated together, a statistically significant positive correlation was determined between EATT and Pd, QTd, QTcd and Tp-e. Conclusions In children with T1DM, an increase in epicardial adipose tissue thickness and in risk of cardiac arrhythmias has been demonstrated. To reveal the possible unfavorable effects of EATT on cardiac conduction system in T1DM patients needs further studies.

A distinct molecular mechanism by which phenytoin rescues a novel long QT 3 variant.

BACKGROUND: Genetic variants in SCN5A can result in channelopathies such as the long QT syndrome type 3 (LQT3), but the therapeutic response to Na+ channel blockers can vary. We previously reported a case of an infant with malignant LQT3 and a missense Q1475P SCN5A variant, who was effectively treated with phenytoin, but only partially with mexiletine. Here, we functionally characterized this variant and investigated possible mechanisms for the differential drug actions. METHODS: Wild-type or mutant Nav1.5 cDNAs were examined in transfected HEK293 cells with patch clamping and biochemical assays. We used computational modeling to provide insights into altered channel kinetics and to predict effects on the action potential. RESULTS: The Q1475P variant in Nav1.5 reduced the current density and channel surface expression, characteristic of a trafficking defect. The variant also led to positive shifts in the voltage dependence of steady-state activation and inactivation, faster inactivation and recovery from inactivation, and increased the "late" Na+ current. Simulations of Nav1.5 gating with a 9-state Markov model suggested that transitions from inactivated to closed states were accelerated in Q1475P channels, leading to accumulation of channels in non-inactivated closed states. Simulations with a human ventricular myocyte model predicted action potential prolongation with Q1475P, compared with wild type, channels. Patch clamp data showed that mexiletine and phenytoin similarly rescued some of the gating defects. Chronic incubation with mexiletine, but not phenytoin, rescued the Nav1.5-Q1475P trafficking defect, thus increasing mutant channel expression. CONCLUSIONS: The gain-of-function effects of Nav1.5-Q1475P predominate to cause a malignant long QT phenotype. Phenytoin partially corrects the gating defect without restoring surface expression of the mutant channel, whereas mexiletine restores surface expression of the mutant channel, which may explain the lack of efficacy of mexiletine when compared to phenytoin. Our data makes a case for experimental studies before embarking on a one-for-all therapy of arrhythmias.

Late ventricular standstill following an elective TAVI.

Transcatheter aortic valve implantations (TAVIs) may be complicated by a need for permanent pacemaker implantation post procedure, usually due to local trauma or compression on the conduction system. There are some features that might help predict that a patient is high risk for developing conduction disease following TAVI, for example, underlying right bundle branch block or use of certain types of TAVI. It might also become apparent during the procedure, or before temporary wire removal post procedure. Higher risk patients may undergo rhythm monitoring for longer periods post TAVI. We present a case where a patient required an unexpected emergency pacemaker following a TAVI, despite low risk clinical features, a low risk baseline ECG, and the use of a low risk TAVI valve. In addition, this very significant conduction disease only became apparent over 72 hours following implantation, despite normal resting ECGs and telemetry up to that point.

Early sarcomere and metabolic defects in a zebrafish pitx2c cardiac arrhythmia model.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. The major AF susceptibility locus 4q25 establishes long-range interactions with the promoter of PITX2, a transcription factor gene with critical functions during cardiac development. While many AF-linked loci have been identified in genome-wide association studies, mechanistic understanding into how genetic variants, including those at the 4q25 locus, increase vulnerability to AF is mostly lacking. Here, we show that loss of pitx2c in zebrafish leads to adult cardiac phenotypes with substantial similarities to pathologies observed in AF patients, including arrhythmia, atrial conduction defects, sarcomere disassembly, and altered cardiac metabolism. These phenotypes are also observed in a subset of pitx2c+/- fish, mimicking the situation in humans. Most notably, the onset of these phenotypes occurs at an early developmental stage. Detailed analyses of pitx2c loss- and gain-of-function embryonic hearts reveal changes in sarcomeric and metabolic gene expression and function that precede the onset of cardiac arrhythmia first observed at larval stages. We further find that antioxidant treatment of pitx2c-/- larvae significantly reduces the incidence and severity of cardiac arrhythmia, suggesting that metabolic dysfunction is an important driver of conduction defects. We propose that these early sarcomere and metabolic defects alter cardiac function and contribute to the electrical instability and structural remodeling observed in adult fish. Overall, these data provide insight into the mechanisms underlying the development and pathophysiology of some cardiac arrhythmias and importantly, increase our understanding of how developmental perturbations can predispose to functional defects in the adult heart.

Clinical and genetic characteristics of childhood-onset myotonic dystrophy.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is caused by a CTG (cytosine-thymine-guanine) trinucleotide repeat expansion. Congenital DM (CDM) presents in the first month of life, whereas individuals with infantile and juvenile DM1 have later onset of symptoms. METHODS: We performed a retrospective chart review of patients with childhood-onset DM1 seen at one of three locations in Dallas, Texas between 1990 and 2018. Symptoms, disease course, cognitive features, and family history were reviewed. RESULTS: Seventy-four patients were included; CDM was diagnosed in 52 patients. There was maternal inheritance in 74% of patients. CTG repeat number ranged from 143 to 2300. Neuropsychiatric and cognitive deficits were common. Over half of the patients had GI disturbances, and orthopedic complications were common. DISCUSSION: Myotonic dystrophy type 1 in children requires a multidisciplinary approach to management. Presenting symptoms vary, and repeat expansion size does not necessarily directly relate to severity of symptoms. A consensus for outcome measures is required.

One-Year Follow-Up of Conduction Abnormalities After Transcatheter Aortic Valve Implantation With the SAPIEN 3 Valve.

Long-term evolution of new-onset conduction abnormalities and need of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) have not been extensively evaluated. We describe the incidence and time course of new conduction abnormalities and the rate of PPI with the new-generation transcatheter aortic valve prosthesis Edwards SAPIEN 3 (S3). In total, 266 patients with severe aortic stenosis who underwent TAVI were retrospectively analyzed. Twelve-lead electrocardiograms at baseline, after TAVI, at discharge, at 1-, 6-, and 12-month follow-up were evaluated to identify conduction abnormalities and PPI requirements to investigate the correlates of PPI. After TAVI, a significant increase in PR interval duration and in QRS complex width was observed. New-onset left bundle branch block was observed in 65 patients (24%) after TAVI. The number of patients with left bundle branch block was maximum at hospital discharge and decreased at 12-month follow-up (39% and 32%, respectively). Thirty-five patients (13%) required PPI during the follow-up. However, paced rhythm was only observed in 7% of the patients with a complete 12-month follow-up. Patients who underwent PPI had a higher prevalence of first-degree atrioventricular block, complete right bundle branch block, and wider QRS complex at baseline. Baseline right bundle branch block and QRS width immediately after TAVI were the only variables independently associated with PPI. In conclusion, conduction disorders have a temporary nature after TAVI and showed a trend toward stabilization during the following months. With this new-generation device, the incidence of new conduction abnormalities requiring PPI is relatively low.