Incidence and Implications of J waves Observed During Coronary Angiography.

J waves may be observed during coronary angiography (CAG), but they have not been fully studied. We investigated the characteristics of J waves in 100 consecutive patients during CAG. The patients and their family members had no history of cardiac arrest. Approximately 60% of patients had ischemic heart disease, previous myocardial infarction, or angina pectoris, but at the time of this study, the right coronary artery was shown to be normal or patent after stenting. Electrocardiogram was serially recorded to monitor J waves and alteration of the QRS complex during CAG. In 12 patients (12%), J waves (0.249 ± 0.074 mV) newly appeared during right CAG, and in another 13 patients (13%), preexisting J waves increased from 0.155 ± 0.060 mV to 0.233 ± 0.133 mV during CAG. Left CAG induced no J waves or augmentation of J waves. Distinct alterations were observed in the QRS complex during CAG of both coronary arteries. Mechanistically, myocardial ischemia induced by contrast medium was considered to result in a local conduction delay, and when it occurred in the inferior wall, the site of the late activation of the ventricle, the conduction delay was manifested as J waves. In conclusion, J waves were confirmed to emerge or increase during angiography of the right but not the left coronary artery. Myocardial ischemia induced by contrast medium caused a local conduction delay that was manifested as J waves in the inferior wall, the site of the late activation of the ventricle.

Modulation of Cardiac Arrhythmogenesis by Epicardial Adipose Tissue: JACC State-of-the-Art Review.

Obesity is a significant risk factor for arrhythmic cardiovascular death. Interactions between epicardial adipose tissue (EAT) and myocytes are thought to play a key role in the development of arrhythmias. In this review, the authors investigate the influence of EAT on arrhythmogenesis. First, they summarize electrocardiographic evidence showing the association between increased EAT volume and atrial and ventricular conduction delay. Second, they detail the structural cross talk between EAT and the heart and its arrhythmogenicity. Adipose tissue infiltration within the myocardium constitutes an anatomical obstacle to cardiac excitation. It causes activation delay and increases the risk of arrhythmias. Intercellular electrical coupling between cardiomyocytes and EAT can further slow conduction and increase the risk of block, favoring re-entry and arrhythmias. Finally, EAT secretes multiple substances that influence cardiomyocyte electrophysiology either by modulating ion currents and electrical coupling or by stimulating fibrosis. Thus, structural and paracrine cross talk between EAT and cardiomyocytes facilitates arrhythmias.

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.

Impact of conduction disturbances on left ventricular mass regression and geometry change following transcatheter aortic valve replacement.

Our study aimed to compare the difference of LV mass regression and remodeling in regard of conduction disturbances (CD) following transcatheter aortic valve replacement (TAVR). A prospective analysis of 152 consecutive TAVR patients was performed. 53 patients (34.9%) had CD following TAVR, including 30 (19.7%) permanent pacemaker implantation and 23 (15.2%) new left bundle branch block. In 123 patients with 1-year follow-up, significant improvement of LV ejection fraction (LVEF) (baseline vs 12-month: 65.1 ± 13.2 vs 68.7 ± 9.1, P = 0.017) and reduced LV end-systolic volume (LVESV) (39.8 ± 25.8 vs 34.3 ± 17.1, P = 0.011) was found in non-CD group (N = 85), but not in CD group (N = 38). Both groups had significant decrease in LV mass index (baseline vs 12-month: 148.6 ± 36.9 vs. 136.4 ± 34.7 in CD group, p = 0.023; 153.0 ± 50.5 vs. 125.6 ± 35.1 in non-CD group, p < 0.0001). In 46 patients with 3-year follow-up, only non-CD patients (N = 28) had statistically significant decrease in LV mass index (Baseline vs 36-month: 180.8 ± 58.8 vs 129.8 ± 39.1, p = 0.0001). Our study showed the improvement of LV systolic function, reduced LVESV and LV mass regression at 1 year could be observed in patients without CD after TAVR. Sustained LV mass regression within 3-year was found only in patients without CD.

Analysis of the shape of the T-wave in congenital long-QT syndrome type 3 by geometric morphometrics.

The characteristic shape of the T-wave in congenital long-QT syndrome type 3 (LQTS3) is considered a late-onset T-wave. We analyzed the difference in the shapes of the T-waves of V5 in the electrocardiograms (ECGs) of LQTS3 cases and normal subjects using generalized Procrustes analysis. The J and Q points of LQTS3 cases are shifted to the upper left compared to those of normal subjects. SdFmax is the point on the ECG where the second derivative is first maximized. SdFmax is the point where the change in the slope of the ascending limb of the T-wave is maximized. SdFmax in LQTS3 cases is shifted to the lower right compared to normal subjects. The interval from J to SdFmax in LQTS3 cases is expanded compared with that of normal subjects. From principal component analysis of the Procrustes mean shape of the T-wave landmarks, the second principal component shows a shift of SdFmax to the lower right. These results can quantitatively explain why the T-wave of LQTS3 cases looks like a late-onset T-wave. After being fitted to a multivariate logistic regression model, LQTS3 cases and normal subjects can be distinguished by the second independent component.

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.

Variant Intronic Enhancer Controls SCN10A-short Expression and Heart Conduction.

BACKGROUND: Genetic variants in SCN10A, encoding the neuronal voltage-gated sodium channel NaV1.8, are strongly associated with atrial fibrillation, Brugada syndrome, cardiac conduction velocities, and heart rate. The cardiac function of SCN10A has not been resolved, however, and diverging mechanisms have been proposed. Here, we investigated the cardiac expression of SCN10A and the function of a variant-sensitive intronic enhancer previously linked to the regulation of SCN5A, encoding the major essential cardiac sodium channel NaV1.5. METHODS: The expression of SCN10A was investigated in mouse and human hearts. With the use of CRISPR/Cas9 genome editing, the mouse intronic enhancer was disrupted, and mutant mice were characterized by transcriptomic and electrophysiological analyses. The association of genetic variants at SCN5A-SCN10A enhancer regions and gene expression were evaluated by genome-wide association studies single-nucleotide polymorphism mapping and expression quantitative trait loci analysis. RESULTS: We found that cardiomyocytes of the atria, sinoatrial node, and ventricular conduction system express a short transcript comprising the last 7 exons of the gene (Scn10a-short). Transcription occurs from an intronic enhancer-promoter complex, whereas full-length Scn10a transcript was undetectable in the human and mouse heart. Expression quantitative trait loci analysis revealed that the genetic variants in linkage disequilibrium with genetic variant rs6801957 in the intronic enhancer associate with SCN10A transcript levels in the heart. Genetic modification of the enhancer in the mouse genome led to reduced cardiac Scn10a-short expression in atria and ventricles, reduced cardiac sodium current in atrial cardiomyocytes, atrial conduction slowing and arrhythmia, whereas the expression of Scn5a, the presumed enhancer target gene, remained unaffected. In patch-clamp transfection experiments, expression of Scn10a-short-encoded NaV1.8-short increased NaV1.5-mediated sodium current. We propose that noncoding genetic variation modulates transcriptional regulation of Scn10a-short in cardiomyocytes that impacts NaV1.5-mediated sodium current and heart rhythm. CONCLUSIONS: Genetic variants in and around SCN10A modulate enhancer function and expression of a cardiac-specific SCN10A-short transcript. We propose that noncoding genetic variation modulates transcriptional regulation of a functional C-terminal portion of NaV1.8 in cardiomyocytes that impacts on NaV1.5 function, cardiac conduction velocities, and arrhythmia susceptibility.

Electrophysiological Study-Guided Permanent Pacemaker Implantation in Patients With Conduction Disturbances Following Transcatheter Aortic Valve Implantation.

Conduction disturbances remain common following transcatheter aortic valve implantation (TAVI). Aside from high-degree atrioventricular block (HAVB), their optimal management remains elusive. Invasive electrophysiological studies (EPS) may help stratify patients at low or high risk of HAVB allowing for an early discharge or permanent pacemaker (PPM) implantation among patients with conduction disturbances. We evaluated the safety and diagnostic performances of an EPS-guided PPM implantation strategy among TAVI recipients with conduction disturbances not representing absolute indications for PPM. All patients who underwent TAVI at a single expert center from June 2017 to July 2020 who underwent an EPS during the index hospitalization were included in the present study. False negative outcomes were defined as patients discharged without PPM implantation who required PPM for HAVB within 6 months of the initial EPS. False positive outcomes were defined as patients discharged with a PPM with a ventricular pacing percentage <1% at follow-up. A total of 78 patients were included (median age 83.5, 39% female), among whom 35 patients (45%) received a PPM following EPS. The sensitivity, specificity, positive and negative predictive values of the EPS-guided PPM implantation strategy were 100%, 89.6%, 81.5%, and 100%, respectively. Six patients suffered a mechanical HAVB during EPS and received a PPM. These 6 patients showed PPM dependency at follow-up. In conclusion, an EPS-guided PPM implantation strategy for managing post-TAVI conduction disturbances appears effective to identify patients who can be safely discharged without PPM implantation.

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.

Stimulation and propagation of activation in conduction tissue: Implications for left bundle branch area pacing.

BACKGROUND: Characterizing wavefront generation and impulse conduction in left bundle (LB) has implications for left bundle branch area pacing (LBBAP). OBJECTIVES: The purpose of this study was to describe the pacing characteristics of LB and to study the role of pacing pulse width (PW) in overcoming left bundle branch block. METHODS: Twenty fresh ovine heart slabs containing well-developed and easily identifiable tissues of the conduction system were used for the study. LB stimulation, activation, and propagation were studied under baseline conditions, simulated conduction slowing, conduction block, and fascicular block. RESULTS: The maximum radius of the LB early activation increased up to 13.4 ± 2.4 mm from the pacing stimulus, and the time from stimulus to evoked potential shortened when pacing PW was increased from 0.13 to 2 ms at baseline. Conduction slowing and block induced by cooling could be resolved by increasing pacing PW from 0.25 to 1.5 ms over a distance of 10 ± 1.5 mm from the pacing stimulus. The LB strength-duration (SD) curve was shifted to the left of the myocardial SD curve. CONCLUSION: Increasing PW resolved conduction slowing and block and bypassed the experimental model of fascicular block in LB. Precise positioning of the LB lead in left ventricular subendocardium is not mandatory in LBBAP, as the SD curve of LB was shifted to the left of the myocardium SD curve and could be captured from a distance by optimizing PW.

Connexin45 (GJC1) loss-of-function mutation contributes to familial atrial fibrillation and conduction disease.

BACKGROUND: Atrial fibrillation (AF) represents the most common clinical cardiac arrhythmia and substantially increases the risk of cerebral stroke, heart failure, and death. Although causative genes for AF have been identified, the genetic determinants for AF remain largely unclear. OBJECTIVE: This study aimed to investigate the molecular basis of AF in a Chinese kindred. METHODS: A 4-generation family with autosomal-dominant AF and other arrhythmias (atrioventricular block, sinus bradycardia, and premature ventricular contractions) was recruited. Genome-wide scan with microsatellite markers and linkage analysis as well as whole-exome sequencing analysis were performed. Electrophysiological characteristics and subcellular localization of the AF-linked mutant were analyzed using dual whole-cell patch clamps and confocal microscopy, respectively. RESULTS: A novel genetic locus for AF was mapped to chromosome 17q21.3, a 3.23-cM interval between markers D17S951 and D17S931, with a maximum 2-point logarithm of odds score of 4.2144 at marker D17S1868. Sequencing analysis revealed a heterozygous mutation in the mapping region, NM_005497.4:c.703A>T;p.(M235L), in the GJC1 gene encoding connexin45 (Cx45). The mutation cosegregated with AF in the family and was absent in 632 control individuals. The mutation decreased the coupling conductance in cell pairs (M235L/M235L, M235L/Cx45, M235L/Cx43, and M235L/Cx40), likely because of impaired subcellular localization. CONCLUSION: This study defines a novel genetic locus for AF on chromosome 17q21.3 and reveals a loss-of-function mutation in GJC1 (Cx45) contributing to AF and other cardiac arrhythmias.

Anatomy of the cardiac conduction system.

The specialized cardiomyocytes that constitute the conduction system in the human heart, initiate the electric impulse and result in rhythmic and synchronized contraction of the atria and ventricles. Although the atrioventricular (AV) conduction axis was described more than a century ago by Sunao Tawara, the anatomic pathway for propagation of impulse from atria to the ventricles has been a topic of debate for years. Over the past 2 decades, there has been a resurgence of conduction system pacing (CSP) by implanting pacing leads in the His bundle region in lieu of chronic right ventricular pacing that is associated with worse clinical outcomes. The inherent limitations of implanting the leads in the His bundle region has led to the emergence of left bundle branch area pacing in the past 3 years as an alternative strategy for CSP. The clinical experience from performing CSP has helped electrophysiologists gain deeper insight into the anatomy and physiology of cardiac conduction system. This review details the anatomy of the cardiac conduction system, and highlights some of the recently published articles that aid in better understanding of the AV conduction axis and its variations, the knowledge of which is critical for CSP. The remarkable evolution in technology has led to visualization of the cardiac conduction system using noninvasive, nondestructive high-resolution contrast-enhanced micro-computed tomography imaging that may aid in future CSP. We also discuss from anatomical perspective, the differences seen clinically with His bundle pacing and left bundle branch area pacing.

Conduction Disorders: The Value of Surface ECG.

PURPOSE OF REVIEW: The purpose of the current mini-review is to describe the importance of surface ECG for the diagnosis of conduction disorder. METHODS: The MEDLINE/PubMed database was used, with the keywords "ECG" and "conduction disorders"; over the past 10 years. Other documents were included because of their relevance. MAIN FINDINGS: Data on the anatomy and function of the cardiac electrical system have been described. Conduction disorders including sinus node dysfunction, atrioventricular blocks, intraventricular conduction disorders are exposed as to their epidemiology, etiology, presentation, anatomical site of impaired conduction of the electrical stimulus. The importance of ECG in patients with a cardiac implantable electronic device was also discussed, in addition to future perspectives. CONCLUSION: Surface ECG allows the diagnosis of atrioventricular and intraventricular conduction disorder and its anatomical block site most of the time, without the need for invasive tests such as electrophysiological study. Dysfunctions of cardiac implantable electronic devices can be diagnosed by ECG, as well as the prediction of response to cardiac resynchronization therapy.

Clinical outcomes of His-Purkinje conduction system pacing.

His-Purkinje conduction system pacing (HPCSP) in the form of His bundle pacing (HBP) and left bundle branch pacing (LBBP) allows normal left ventricular activation, thereby preventing the adverse consequences of right ventricular pacing. HBP has been established for several years with centers from China, Europe, and North America reporting their experience. There is international guidance as to how to implant such systems with the differing patterns of His bundle capture clearly described. LBBP is a more recent innovation with potential advantages including improved pacing parameters. HPCSP has been extensively studied in a variety of indications including cardiac resynchronization therapy, atrioventricular node ablation, and bradycardia pacing. This review will focus on the clinical outcomes of HPCSP including mortality and morbidity of heart failure hospitalization and symptoms.

His bundle pacing: Tips and tricks.

His bundle (HB) pacing is an established modality for achieving physiological pacing with a low risk of long-term lead-related complications. The development of specially designed lead and delivery tools has improved the feasibility and safety of HB pacing (HBP). Knowledge of the anatomy of HB region and the variations is essential for successful implantation. Newer delivery systems have further improved procedural outcomes. Challenging implant cases can be successfully performed by reshaping the current sheaths, using "sheath in sheath" technique or "two-lead implantation technique." Special attention to the lead parameters at implant, programming, and follow-up is necessary for successful long-term outcomes with HBP. Widespread use of HBP by electrophysiologists and further advances in dedicated delivery systems and leads are essential to further improve the effectiveness of the implantation.

Long-term outcome of intraventricular conduction delays in the general population.

BACKGROUND: Previous population studies have presented conflicting results regarding the prognostic impact of intraventricular conduction delays (IVCD). METHODS: We studied long-term prognostic impact and the association with comorbidities of eight IVCDs in a random sample of 6,299 Finnish subjects (2,857 men and 3,442 women, mean age 52.8, SD 14.9 years) aged 30 or over who participated in the health examination including 12-lead ECG. For left bundle branch block (LBBB) and non-specific IVCD (NSIVCD), two different definitions were used. RESULTS: During 16.5 years' follow-up, 1,309 of the 6,299 subjects (20.8%) died and of these 655 (10.4%) were cardiovascular (CV) deaths. After controlling for known clinical risk factors, the hazard ratio for CV death, compared with individuals without IVCD, was 1.55 for the Minnesota definition of LBBB (95% confidence interval 1.04-2.31, p = .032) and 1.27 (95% confidence interval 0.80-2.02, p = .308) for the Strauss' definition of LBBB. Subjects with NSIVCD were associated with twofold to threefold increase in CV mortality depending on the definition. While right bundle branch block, left anterior fascicular block and incomplete bundle branch blocks were associated with seemingly higher mortality, this was no longer the case after adjustment for age and sex. The presence of R-R' pattern was not associated with any adverse outcome. CONCLUSIONS: In a population study with long-term follow-up, NSIVCD and Minnesota definition of LBBB were independently associated with CV mortality. Other IVCDs had no significant impact on prognosis. The prognostic impact of LBBB and NSIVCD was affected by the definition of the conduction disorder.