Left Atrial Inexcitability in Children With Congenital Lupus-Induced Complete Atrioventricular Block.
ABSTRACT: Congenital atrioventricular block is a well-established immunologic complication of maternal systemic lupus erythematosus. We sought to further characterize the electrophysiological manifestations of maternal systemic lupus erythematosus on neonatal atria.Cases of isolated congenital atrioventricular block treated at our center over the past 41 years were identified. Data were extracted from clinical charts, pacemaker interrogations, ECGs, echocardiograms, and histopathological reports, when available. Of 31 patients with isolated congenital atrioventricular block, 18 were negative for maternal antibodies and had normal epicardial atrial sensing and pacing thresholds. In contrast, 12 of 13 patients with positive maternal antibodies had epicardial pacemakers, 5 (42%) of whom had left atrial (LA) inexcitability and/or atrial conduction delay. In 3 patients, the LA could not be captured despite high-output pacing. The fourth patient had acutely successful LA appendage and left ventricular lead placement. At early follow-up, an increased delay between the surface P-wave and intracardiac atrial depolarization was observed, indicative of atrial conduction delay. The fifth patient exhibited LA lead dysfunction, with atrial under-sensing and an increased capture threshold, 2 weeks after implantation. Biopsies of LA appendages performed in 2 patients showed no evidence of atrial fibrosis or loss of atrial myocytes.Herein, we report previously undescribed yet prevalent electrophysiological ramifications of maternal systemic lupus erythematosus, which extend beyond congenital atrioventricular block to encompass alterations in LA conduction, including LA inexcitability. These manifestations can complicate epicardial pacemaker implantation in newborns. In the absence of histological evidence of extensive atrial fibrosis, immune-mediated functional impairment of electrical activity is suspected.
Project description:Atrial septal defect (ASD) is one of the most common types of congenital heart diseases (CHDs). Most ASDs occur sporadically, but some are inherited and associated with cardiac conduction defects such as atrioventricular block (AVB) or bundle branch block. Mutations in genes encoding transcription factor gene TBX5 and NKX2-5, were found in Holt-Oram syndrome (HOS) and ASD with atrioventricular (AV) conduction defects, respectively. HOS is characterized by upper limb anomaly in addition to ASD and AVB (heart-hand syndrome). ASD associated with NKX2-5 is rare but is reported to cause sudden cardiac death (SCD) or cardiomyopathy. We provide a review of these two diseases.
Project description:Autoimmune congenital heart block (CHB) is an immune-mediated acquired disease that is associated with the placental transference of maternal antibodies specific for Ro and La autoantigens. The disease develops in a fetal heart without anatomical abnormalities that could otherwise explain the block, and which is usually diagnosed in utero, but also at birth or within the neonatal period. Autoantibody-mediated damage of fetal conduction tissues causes inflammation and fibrosis and leads to blockage of signal conduction at the atrioventricular (AV) node. Irreversible complete AV block is the principal cardiac manifestation of CHB, although some babies might develop other severe cardiac complications, such as endocardial fibroelastosis or valvular insufficiency, even in the absence of cardiac block. In this Review, we discuss the epidemiology, classification and management of women whose pregnancies are affected by autoimmune CHB, with a particular focus on the autoantibodies associated with autoimmune CHB and how we should test for these antibodies and diagnose this disease. Without confirmed effective preventive or therapeutic strategies and further research on the aetiopathogenic mechanisms, autoimmune CHB will remain a severe life-threatening disorder.
Project description:Complex cyanotic congenital heart diseases with left isomerism are sometimes associated with atrioventricular nodal conduction disturbances that may need permanent pacing. Surgical palliation in such anatomy connecting the superior vena cava to the pulmonary artery precludes a transvenous access for an endocardial pacing lead to the ventricles. Epicardial leads in these patients fail if the pacing thresholds are very high. We report transhepatic permanent ventricular lead implantation for a young boy with heterotaxy complicated by complete heart block.
Project description:The predisposition of atrial extrasystoles (AES) to trigger cardiac tachyarrhythmia may arise from intramural conduction disorders causing endo-epicardial asynchrony (EEA). This study aimed to determine whether spontaneous AES disturb endo-epicardial conduction. Simultaneous endo-epicardial mapping of the right atrium was performed in patients during cardiac surgery with two 128-electrode arrays. Sixty spontaneous AES were observed in 23 patients and were analyzed for incidence of conduction delay, conduction block and amount of EEA compared to the previous sinus rhythm beat. Both conduction delay and block occurred more often in AES compared to sinus rhythm. The difference in lines of conduction block between the epicardium and endocardium increased in AES causing a greater imbalance of conduction disorders between the layers. The incidence of EEA with differences ?10 ms increased significantly in AES. AES caused delays between the epicardium and endocardium up to 130 ms and EEA to increase for up to half (47%) of the mapping area. Conduction disturbances between the epicardial and endocardial layer giving rise to EEA increase during AES. Asynchronous activation of the atrial layers increases during AES which may be a mechanism for triggering cardiac tachyarrhythmia under the right conditions but EEA cannot be recognized by current mapping tools.
Project description:Background?:Percutaneous closure of patent foramen ovale (PFO) is recommended for patients presenting with PFO-related stroke. Acute high-grade conduction disturbances occurring during PFO closure procedure have not been previously reported. Case summary?:We describe for the first time a case of reversible complete atrioventricular block which occurred during closure of a PFO. Discussion?:We hypothesized that the block was the result of atrioventricular node compression-likely caused by the right-atrial disc of the 35-mm PFO closure device. We suggest implanting smaller devices in order to prevent atrioventricular conduction disturbances.
Project description:BACKGROUND:Impaired myocardial conduction is the underlying mechanism for re-entrant arrhythmias. Carbon nanotube fibers (CNTfs) combine the mechanical properties of suture materials with the conductive properties of metals and may form a restorative solution to impaired myocardial conduction. METHODS:Acute open chest electrophysiology studies were performed in sheep (n=3). Radiofrequency ablation was used to create epicardial conduction delay after which CNTf and then silk suture controls were applied. CNTfs were surgically sewn across the right atrioventricular junction in rodents, and acute (n=3) and chronic (4-week, n=6) electrophysiology studies were performed. Rodent toxicity studies (n=10) were performed. Electrical analysis of the CNTf-myocardial interface was performed. RESULTS:In all cases, the large animal studies demonstrated improvement in conduction velocity using CNTf. The acute rodent model demonstrated ventricular preexcitation during sinus rhythm. All chronic cases demonstrated resumption of atrioventricular conduction, but these required atrial pacing. There was no gross or histopathologic evidence of toxicity. Ex vivo studies demonstrated contact impedance significantly lower than platinum iridium. CONCLUSIONS:Here, we show that in sheep, CNTfs sewn across epicardial scar acutely improve conduction. In addition, CNTf maintain conduction for 1 month after atrioventricular nodal ablation in the absence of inflammatory or toxic responses in rats but only in the paced condition. The CNTf/myocardial interface has such low impedance that CNTf can facilitate local, downstream myocardial activation. CNTf are conductive, biocompatible materials that restore electrical conduction in diseased myocardium, offering potential long-term restorative solutions in pathologies interrupting efficient electrical transduction in electrically excitable tissues.
Project description:The influence of underlying heart disease or presence of atrial fibrillation (AF) on atrial excitation during sinus rhythm (SR) is unknown. We investigated atrial activation patterns and total activation times of the entire atrial epicardial surface during SR in patients with ischemic and/or valvular heart disease with or without AF.Intraoperative epicardial mapping (N=128/192 electrodes, interelectrode distances: 2 mm) of the right atrium, Bachmann's bundle (BB), left atrioventricular groove, and pulmonary vein area was performed during SR in 253 patients (186 male [74%], age 66±11 years) with ischemic heart disease (N=132, 52%) or ischemic valvular heart disease (N=121, 48%). As expected, SR origin was located at the superior intercaval region of the right atrium in 232 patients (92%). BB activation occurred via 1 wavefront from right-to-left (N=163, 64%), from the central part (N=18, 7%), or via multiple wavefronts (N=72, 28%). Left atrioventricular groove activation occurred via (1) BB: N=108, 43%; (2) pulmonary vein area: N=9, 3%; or (3) BB and pulmonary vein area: N=136, 54%; depending on which route had the shortest interatrial conduction time (P<0.001). Ischemic valvular heart disease patients more often had central BB activation and left atrioventricular groove activation via pulmonary vein area compared with ischemic heart disease patients (N=16 [13%] versus N=2 [2%]; P=0.009 and N=86 [71%] versus N=59 [45%]; P<0.001, respectively). Total activation times were longer in patients with AF (AF: 136±20 [92-186] ms; no AF: 114±17 [74-156] ms; P<0.001), because of prolongation of right atrium (P=0.018) and BB conduction times (P<0.001).Atrial excitation during SR is affected by underlying heart disease and AF, resulting in alternative routes for BB and left atrioventricular groove activation and prolongation of total activation times. Knowledge of atrial excitation patterns during SR and its electropathological variations, as demonstrated in this study, is essential to further unravel the pathogenesis of AF.
Project description:Due to advances in corrective surgery, congenital heart disease has an ever growing patient population. Atrial arrhythmias are frequently observed pre- and post-surgical correction. Pharmaceutical antiarrhythmic therapy is not always effective, therefore many symptomatic patients undergo catheter ablation therapy. In patients with atrioventricular septal defects (AVSD), ablation therapy itself has mixed success; arrhythmogenic recurrences are common, and because of the anatomical displacement of the atrioventricular node, 3-degree heart block post-ablation is a real concern. In order to develop optimal and safe ablation strategies, the field of congenital cardiac electrophysiology must combine knowledge from clinical electrophysiology with a thorough understanding of the anatomical substrates for arrhythmias. Using image-based analysis and multi-cellular mathematical modeling of electrical activation, we show how the anatomical alterations characteristic of an AVSD serve as arrhythmogenic substrates. Using ex-vivo contrast enhanced micro-computed tomography we imaged post-mortem the heart of a 5 month old male with AVSD at an isometric spatial resolution of 38 ?m. Morphological analysis revealed the 3D disposition of the cardiac conduction system for the first time in an intact heart with this human congenital malformation. We observed displacement of the compact atrioventricular node inferiorly to the ostium of the coronary sinus. Myocyte orientation analysis revealed that the normal arrangement of the major atrial muscle bundles was preserved but was modified in the septal region. Models of electrical activation suggest the disposition of the myocytes within the atrial muscle bundles associated with the "fast pathway," together with the displaced atrioventricular node, serve as potential substrates for re-entry and possibly atrial fibrillation. This study used archived human hearts, showing them to be a valuable resource for the mathematical modeling community, and opening new possibilities for the investigations of arrhythmogenesis and ablation strategies in the congenitally malformed heart.
Project description:Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys, and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased urinary BPA concentrations and cardiovascular disease, yet the direct effects of BPA on the heart are unknown.The goal of our study was to measure the effect of BPA (0.1-100 ?M) on cardiac impulse propagation ex vivo using excised whole hearts from adult female rats.We measured atrial and ventricular activation times during sinus and paced rhythms using epicardial electrodes and optical mapping of transmembrane potential in excised rat hearts exposed to BPA via perfusate media. Atrioventricular activation intervals and epicardial conduction velocities were computed using recorded activation times.Cardiac BPA exposure resulted in prolonged PR segment and decreased epicardial conduction velocity (0.1-100 ?M BPA), prolonged action potential duration (1-100 ?M BPA), and delayed atrioventricular conduction (10-100 ?M BPA). These effects were observed after acute exposure (? 15 min), underscoring the potential detrimental effects of continuous BPA exposure. The highest BPA concentration used (100 ?M) resulted in prolonged QRS intervals and dropped ventricular beats, and eventually resulted in complete heart block.Our results show that acute BPA exposure slowed electrical conduction in excised hearts from female rats. These findings emphasize the importance of examining BPA's effect on heart electrophysiology and determining whether chronic in vivo exposure can cause or exacerbate conduction abnormalities in patients with preexisting heart conditions and in other high-risk populations.
Project description:BACKGROUND:Mitral isthmus (MI) ablation was limited due to technical challenges in the index ablation for long-standing persistent atrial fibrillation (LPeAF). The role of adjunctive MI ablation was controversial. HYPOTHESIS:MI block could be achieved in most patients undergoing repeat LPeAF ablation and was associated with favorable clinical outcomes. METHODS:Of 87 consecutively patients undergoing reablation for recurrent atrial tachyarrhythmias (ATa), 41 patients with residual MI conduction but without pulmonary vein reconnection or left atrial roof conduction were enrolled to treat recurrent atrial flutter (AFL) (n = 20) and AF (n = 21). After AFL ablation and AF cardioversion, MI conduction gaps (CGs) were mapped and closed. RESULTS:MI line was successfully blocked in 37 (90.2%) of 41 patients after closing 1.4?±?0.5 CGs (31 endocardial CGs and 16 epicardial ones) in the initial MI lines. CGs were more often located at the endocardial sites close to the lateral ridge between left atrial appendage and left-sided PVs, midportion of MI and at the epicardial breakthroughs within coronary sinus. At the end of 16.0?±?1.9 months' follow-up, 31 (83.8%) of 37 patients with MI block and 1 of 4 patients without MI block were free of further recurrence of ATa off anti-arrhythmic drugs. MI block was positively associated with ATa-free survival by Cox's regression analysis (hazard ratio [HR]: 0.012, 95% confidence interval [CI]: 0.000-0.456, P = .02). CONCLUSIONS:MI block could be achieved in the majority of patients during repeat ablation for LPeAF. MI block was associated with favorable clinical outcomes after LPeAF reablation.