Pacing techniques in the management of supraventricular tachycardias. Part 2. An implanted atrial synchronous pacemaker with a short atrioventricular delay for the prevention of paroxysmal supraventricular tachycardias.

An implanted atrial synchronous pacemaker with an atrioventricular delay of 30 msec is described. This pacemaker was implanted into a patient with paroxysmal supraventricular tachycardia due to an intra AV nodal reciprocal mechanism. The pacemaker was able to trigger from atrial potentials following atrial premature beats down to a coupling time of 300 msec. Following each triggering atrial potential, a ventricular stimulus was applied 30 msec later thereby producing a ventricular premature beat in response to each sinus beat or each atrial premature beat. Retrograde conduction from this atrial premature beat blocked the re-entry mechanism within the AV node and prevented the initiation of tachycardia. A detailed discussion on all parameters of function of this pacemaker is presented.     

Heart rate turbulence after ventricular and atrial premature beats in subjects without structural heart disease

INTRODUCTION: Studies assessing heart rate (HR) behavior after premature beats have focused on HR responses to ventricular premature beats (VBPs), but there is less information of HR behavior after atrial premature beats (APBs). METHODS AND RESULTS: HR turbulence after VPBs and APBs was first measured in response to ambient APBs and VPBs occurring during 24-hour ambulatory ECG recordings in 29 subjects without structural heart disease, and in response to programmed atrial (AE) and ventricular extrastimuli (VE) in 6 subjects undergoing electrophysiologic (EP) examination. Turbulence onset (TO) was more negative (-2.3 +/- 3.2% vs -0.9 +/- 2.8%, P < 0.01) and turbulence slope (TS) was steeper (11 +/- 11 vs 5.1 +/- 4.1 msec/R-R interval, P < 0.05) after VPBs than APBs. Compared to VPBs, the acceleration of HR after APBs was delayed by one beat, and APBs were associated with a short R-R interval preceding the APB, resulting in a blunted TO. Studies of patients undergoing an EP test confirmed the one-beat delay of HR acceleration and the blunted TO after programmed AE compared to VE (P < 0.05). TO and TS after VPBs were related to baroreflex sensitivity. TO also was related to 24-hour standard deviation of N-N intervals (SDNN). However, the TO or TS following APBs was not related to either SDNN or baroreflex sensitivity. CONCLUSION: HR behavior is different in response to APBs and VBPs among subjects without structural heart disease. Different definitions and calculation formulas should be used in the analysis of HR turbulence after APBs and VPBs.     

Ventricular Echo Beats and Retrograde Atrioventricular Nodal Exits in the Dog Heart: Multiplicity in Their Electrophysiologic and Anatomic Characteristics

INTRODUCTION: A single ventricular echo beat frequently is induced in the dog heart by ventricular pacing, but it has not been investigated using a concomitant ablative technique. We studied the effects of ablating the anterior atrial input to the AV node on ventricular echo beats induced in the dog heart to evaluate their electrophysiologic characteristics, the anatomic reentrant circuit, and the retrograde AV nodal exits. METHODS AND RESULTS: In 20 dogs, an epicardial radiofrequency current was applied to the right anterior septum in an attempt to ablate the anterior input to the AV node. Ventricular programmed stimulation was performed to evaluate the ventricular echo beat and the retrograde AV nodal exit before and after ablation. The AV junction was examined with light microscopy. Seventeen dogs in which the PR interval was prolonged significantly from 108+/-17 msec to 153+/-19 msec (P < 0.001) were selected for ventricular echo evaluation; 3 dogs in which persistent second- or third-degree AV block was induced by ablation were excluded. Ventricular echo beats, which were induced in 13 of 17 dogs, were classified into the anterior type (n = 6) or posterior type (n = 7) according to the earliest atrial activation site during the echo beat. The retrograde AV nodal exit site showed anterior-exit only (n = 10), posterior-exit only (n = 2), and dual-exit (n = 5) patterns. After ablation, the anterior-type ventricular echo beat was noninducible in all 6 dogs, whereas the posterior-type ventricular echo beat was noninducible in only 3 of 7 dogs. In 17 dogs, VA conduction was not demonstrated after ablation in 3 dogs, all of which showed the anterior-exit only pattern. CONCLUSION: The effect of ablation on the ventricular echo beats and retrograde AV nodal exit site suggests multiplicity in their electrophysiologic and anatomic characteristics in the dog heart.     

Benefits and limits of single chamber atrial pacing with adaptive rate

Twelve patients with isolated symptomatic sinus node dysfunction or bradycardia-tachycardia syndrome with atrial chronotropic incompetence during exercise testing were managed by single chamber rate responsive atrial pacing (AAIR) when AV conduction was normal, or by a dual chamber DDDR pacemaker programmed in the AAIR mode when AV conduction was abnormal, and followed up for 12.5 +/- 9.8 months. The patients were assessed clinically, by 3 monthly ECG and Holter recordings and comparative exercise tests in AAI and AAIR modes at the 6th month. One patient with an AAIR system was excluded at M21 because of symptomatic AV block requiring reimplantation of a DDD pacemaker. Ten of the 11 remaining patients are asymptomatic and have an excellent quality of life; one patient had invalidating symptoms on exercise attributed to the "AAIR pacemaker syndrome" which were corrected by reprogramming the pacemaker and modifying the medical therapy. The comparative exercise stress tests showed a significantly higher heart rate in the AAIR mode compared to AAI pacing at the initial and intermediate exercise levels (30 to 70 W); on the other hand, the heart rates were not significantly different at the highest exercise levels although in the AAI mode, the terminal acceleration sometimes occurred in junctional rhythm whereas it was usually an atrial paced rhythm in the AAIR mode. The total duration of exercise was longer in the AAIR mode (+22%; p less than 0.01) when the 8/11 patients with chronotropic incompetence during the baseline study were considered. The spike-R interval adapted normally to exercise in only one case: in the other patients, the interval remained constant or, in the worst of cases (N = 4), it increased paradoxically, to result in the "AAIR pacemaker syndrome": this phenomenon is observed mainly in patients treated by antiarrhythmics and/or betablockers. The AAIR mode would therefore seem to be a simple, effective and reliable method of treating patients with sinus node dysfunction and chronotropic incompetence; however, the failure of adaptation of the PR interval is a real limitation to its use and may constitute an argument in favour of the choice of a DDR pacemaker in these patients.     

Disposition of the atrioventricular conduction tissues in the heart with isomerism of the atrial appendages: its relation to congenital complete heart block.

OBJECTIVES. Our goal was to compare histologically the mechanisms producing congenital complete heart block in normally structured hearts and in hearts with isomerism of the atrial appendages. BACKGROUND. It is known that several different histologic patterns can underscore the existence of congenital complete heart block in the normally structured heart, and that block is particularly frequent in the setting of isomerism of the atrial appendages. The histologic findings in the latter setting were compared and contrasted with those found in the normally structured heart. METHODS. Serial section techniques were used to study 14 hearts with isomerism of the atrial appendage (12 with left isomerism and 2 with right isomerism) and 7 normally structured hearts. RESULTS. Discontinuity between the atrioventricular (AV) node and the ventricular conduction tissues was found in 10 of the 12 hearts with left isomerism; the other 2 hearts had a normally formed conduction axis and heart block was not present in these cases. In both hearts with right isomerism, "slings" of ventricular conduction tissue connected dual AV nodes; congenital complete heart block was not present in either case. In six of the seven cases with a normally structured heart, anti-Ro antibodies had been found in the maternal serum. All six of these hearts had discontinuity between the atrial tissues and the ventricular conduction axis. Intraventricular discontinuity was found in the seventh case, in which anti-Ro antibodies were not found in the mother. CONCLUSIONS. The pattern of congenital complete heart block in cases with left isomerism is discontinuity between the AV node and the conduction axis, in contrast to the pattern of atrial-axis discontinuity produced in the normally structured heart when anti-Ro antibodies are found in the maternal serum.     

Determinants of the ventricular rate during atrial fibrillation

Determinants of the ventricular cycle length during atrial fibrillation were examined in 52 patients. Thirty-three patients had structural heart disease and none had an accessory atrioventricular (AV) connection. The AV node effective and functional refractory periods, the shortest atrial pacing cycle length associated with 1:1 conduction, the AV node conduction time and indexes of concealed conduction in the AV node were measured in the baseline state (36 patients) and after modification of sympathetic tone by infusion of isoproterenol or propranolol (8 patients each). Atrial fibrillation was then induced with rapid atrial pacing, and the mean, shortest and longest ventricular cycle lengths were measured. Variables that correlated most strongly with the mean RR interval during atrial fibrillation were the AV node effective refractory period (r = 0.93; p less than 0.001), AV node functional refractory period (r = 0.87; p less than 0.001) and shortest atrial pacing cycle length associated with 1:1 conduction (r = 0.91; p less than 0.001). The AH interval during sinus rhythm (r = 0.74; p less than 0.001) and during atrial pacing at the shortest cycle length with 1:1 conduction (r = 0.52; p less than 0.001) had weaker correlations. Measures of concealed conduction did not improve the prediction of the mean or longest ventricular cycle length during atrial fibrillation. In conclusion, the refractory periods and conductivity of the AV node are the best indicators of the potential of the node to transmit atrial impulses to the ventricles during atrial fibrillation. The degree of concealed conduction in the AV node is a less important determinant of the mean ventricular rate during atrial fibrillation.     

Comparison of echocardiography and device based algorithm for atrio-ventricular delay optimization in heart block patients

AIM: To compare the atrio-ventricular (AV/PV) delay optimization by echocardiography and intra-cardiac electrocardiogram (IEGM) based QuickOpt algorithm in complete heart block (CHB) patients, implanted with a dual chamber pacemaker. METHODS: We prospectively enrolled 20 patients (age 59.45 ± 18.1 years; male: 65%) with CHB, who were implanted with a dual chamber pacemaker. The left ventricular outflow tract velocity time-integral was measured after AV/PV delay optimization by both echocardiography and QuickOpt algorithm method. Bland-Altman analysis was used for agreement between the two techniques. RESULTS: The optimal AV and PV delay determined by echocardiography was 155.5 ± 14.68 ms and 122.5 ± 17.73 ms (P < 0.0001), respectively and by QuickOpt method was 167.5 ± 16.73 and 117.5 ms ± 9.10 ms (P < 0.0001), respectively. A good agreement was observed between optimal AV and PV delay as measured by two methods. However, the correlation of the optimal AV (r = 0.0689, P = 0.77) and PV (r = 0.2689, P = 0.25) intervals measured by the two techniques was poor. The time required for AV/PV optimization was 45.26 ± 1.73 min by echocardiography and 0.44 ± 0.08 min by QuickOpt method (P < 0.0001). CONCLUSION: The programmer based IEGM method is an automated, quick, easier and reliable alternative to echocardiography for the optimization of AV/PV delay in CHB patients, implanted with a dual chamber pacemaker.     

Congenital heart block related to maternal autoantibodies: descriptive analysis of a series of 18 cases from a single center

The objective of this study was to describe the clinical and immunological characteristics of maternal autoimmune-mediated fetal congenital heart block (CHB) in a cohort of pregnant women from an autoimmune disease pregnancy clinic. This is a retrospective observational study of all women presenting with CHB in our autoimmune disease pregnancy clinic from January 1997 to December 2014. In addition, perinatal outcome is also described. Fourteen patients accounting for 18 fetuses with CHB were identified. The median age was 32.5 years (range, 22–40). Seven (50 %) patients had Sjögren’s syndrome, and the remaining seven were asymptomatic carriers of autoantibodies. All patients had anti-Ro/SSA antibodies, and 11/13 (85 %) had anti-La/SSB antibodies. The median gestational age at the time of CHB was 22 weeks (range 18–28). Complete third degree CHB was detected in 12 (67 %). Seven cases of CHB were treated with dexamethasone, two with ritodrine, and one with the association of dexamethasone, ritodrine, and terbutaline. In 9 (50 %) cases that presented with, or developed, very poor prognosis factors, such as a ventricular rate below 50–55 bpm and/or the presence of fetal hydrops, parents opted for the termination of pregnancy, after dedicated counseling. Finally, there were nine newborns (seven males [78 %]) with median age at delivery of 37 weeks (range, 32–39). A definitive epicardial pacemaker was placed in six newborns, four of them within 2 weeks of life. CHB is a severe complication related to maternal anti-Ro/SSA and anti-La/SSB antibodies. Our results confirm previous data showing that therapy is ineffective, and most of the surviving patients will require neonatal pacemaker.     

Signs of first-degree heart block occur in one-third of fetuses of pregnant women with anti-SSA/Ro 52-kd antibodies

OBJECTIVE: To prospectively investigate the development of fetal heart block in anti-SSA/Ro 52-kd-positive women, and to evaluate the usefulness of serial Doppler echocardiography in detecting early signs of congenital heart block. METHODS: Twenty-four women with anti-SSA/Ro 52-kd antibodies and consequently increased risk for fetal heart block were followed up weekly, between 18 and 24 weeks of gestation, with two Doppler echocardiographic methods designed to estimate the time delay between hemodynamic events caused by atrial and ventricular depolarizations. Two hundred eighty-four women with normal pregnancies served as controls. Anti-Ro 52-kd, anti-Ro 60-kd, and anti-La antibodies were investigated by immunoblotting and enzyme-linked immunosorbent assay using recombinant proteins. RESULTS: In anti-Ro 52-kd-positive women, fetal atrioventricular (AV) time intervals were longer and heart rates were slightly lower compared with those in controls. Eight of 24 fetuses had signs of first-degree block. One of these fetuses had progression to complete block, and another showed recovery from second-degree block to first-degree block with betamethasone treatment. In the remaining 6 fetuses, spontaneous normalization occurred before or shortly after birth. Fetuses with normal AV time intervals at 18-24 weeks had normal electrocardiographic results at birth. CONCLUSION: Anti-Ro 52-kd-positive pregnant women frequently carry fetuses with Doppler echocardiographic signs of first-degree AV block. These blocks revert spontaneously in the majority of fetuses, but progression to a more severe degree of block may occur in some. Serial Doppler echocardiographic measurement of AV time intervals is suggested as a useful method for surveillance of these high-risk pregnancies.     

Ventricular echo beats during ventricular pacing or junctional bradycardia: studies in the normal canine heart

In 15 adult dogs ventricular echoes were elicited during sinus rhythm by incremental ventricular pacing and during atrioventricular (AV) junctional rhythm by depressing simultaneously AV junctional automaticity and retrograde AV nodal conduction. Concomitant slowing of AV junctional automaticity and conduction was achieved by selective intranodal administration of verapamil. In three dogs incremental pacing from either ventricle failed to retrogradely activate the atria, and in each case the site of block was found to be in the AV node. In two dogs with retrograde atrial capture there was little or no rate-dependency of retrograde ventriculoatrial (VA) conduction. During incremental ventricular pacing a single ventricular echo beat was observed in 10 of the 12 dogs that had atrial capture, and the atrium appears to be an essential link in the production of each ventricular echo. Ventricular echo occurred when the time allotted for retrograde VA conduction amounted to 70 +/- 4% of the duration of the ventricular pacing cycle length. During AV junctional rhythm, a single ventricular echo was elicited in half of the dogs and in each of those cases intranodal verapamil produced a profound depression of retrograde VA conduction. These experiments suggest that retrograde AV nodal longitudinal dissociation occurs in the slow current-dependent cells of the AV node.     

Tachycardia-induced cardiomyopathy: atrial fibrillation and congestive heart failure

Tachycardia-induced cardiomyopathy occurs as a result of prolonged, excessive heart rates. Ventricular function may improve significantly upon control of the heart rate. We present a case of a patient with atrial fibrillation with rapid ventricular response who showed a dramatic improvement in left ventricular function following AV nodal ablation and insertion of a pacemaker. We also review the history and pathophysiology of tachycardia-induced cardiomyopathy.     

Transient entrainment and interruption of atrioventricular node tachycardia

The possibility of transiently entraining and interrupting the common type of atrioventricular (AV) node tachycardia (anterograde slow, retrograde fast AV node pathway) was studied using atrial and ventricular pacing in 18 patients with paroxysmal AV node tachycardia. Transient entrainment occurred in all patients. During atrial pacing, localized block in the AV node for one beat followed by anterograde conduction over the fast pathway was observed in three patients. During ventricular pacing, localized block for one beat followed by retrograde conduction over the slow pathway was not observed in any patient. Neither atrial nor ventricular fusion beats were observed during entrainment. These observations indicate in a way not previously shown that reentry involving two functionally dissociated pathways in the AV node is the underlying mechanism of paroxysmal AV node tachycardia. The inability to demonstrate atrial or ventricular fusion beats during entrainment suggests a true intranodal location of the reentrant circuit. Finally, the ability to transiently entrain intranodal tachycardia demonstrates that this electrophysiologic phenomenon is not exclusively limited to macroreentrant circuits.     

Functional basis of sinus bradycardia in congenital heart block

Congenital heart block (CHB) is a conduction abnormality characterized by complete atrioventricular (AV) block. CHB affects fetuses and/or newborn of mothers with autoantibodies reactive with ribonucleoproteins 48-kDa SSB/La, 52-kDa SSA/Ro, and 60-kDa SSA/Ro. We recently established animal models of CHB and reported, for the first time, significant sinus bradycardia preceding AV block. This unexpected observation implies that the spectrum of conduction abnormalities extends beyond the AV node to also affect the SA node. To test this hypothesis, we investigated the functional basis of this sinus bradycardia by characterizing the effects of antibodies from mothers with CHB children (positive IgG) on ionic currents that are known to significantly contribute to spontaneous pacing in SA node cells. We recorded L- (I(Ca.L)) and T- (I(Ca.T)) type Ca2+, delayed rectifier K+ (I(K)), hyperpolarization-activated (I(f)) currents, and action potentials (APs) from young rabbit SA node cells. We demonstrated that positive IgG significantly inhibited both I(Ca.T) and I(Ca.L) and induced sinus bradycardia but did not affect I(f) and I(K). Normal IgG from mothers with healthy children did not affect all the currents studied and APs. These results establish that IgG from mothers with CHB children causes substantial inhibition of I(Ca.T) and I(Ca.L), two important pacemaker currents in rabbit SA node cells and point to both I(Ca.T) and I(Ca.L) as major players in the ionic mechanism by which maternal antibodies induce sinus bradycardia in CHB. These novel findings have important clinical significance and suggest that sinus bradycardia may be a potential marker in the detection and prevention of CHB. The full text of this article is available online at http://circres.ahajournals.org     

Electrophysiological characteristics of fetal atrioventricular block.

OBJECTIVES: The purpose of our work was to define the complex electrophysiological characteristics seen in second- (2 degrees) and third-degree (3 degrees) atrioventricular block (AVB) and to longitudinally follow the development of atrial and ventricular heart rate and rhythm patterns with a goal of identifying heart rate and rhythm patterns associated with urgent delivery or neonatal pacing. BACKGROUND: The electrophysiological characteristics of congenital AVB before birth have not been extensively studied, yet the mortality from this disease is substantial. Along with advances in fetal therapies and interventions, a comprehensive natural history specific to the etiology of AVB, as well as the electrophysiological factors influencing outcome, are needed to best select treatment options. METHODS: Twenty-eight fetuses with AVB were evaluated by fetal magnetocardiography; 21 fetuses were evaluated serially. RESULTS: Fetuses with 2 degrees AVB and isolated 3 degrees AVB showed: 1) diverse atrial rhythms and mechanisms of atrioventricular conduction during 2 degrees AVB; 2) junctional ectopic tachycardia and ventricular tachycardia during 3 degrees AVB; 3) reactive ventricular and atrial fetal heart rate (FHR) tracings at ventricular rates >56 beats/min; and 4) flat ventricular FHR tracings at ventricular rates <56 beats/min despite reactive atrial FHR tracings. In contrast, fetuses with 3 degrees AVB associated with structural cardiac disease exhibited predominantly nonreactive heart rate tracings and simpler rhythms. CONCLUSIONS: Second-degree AVB, isolated 3 degrees AVB, and 3 degrees AVB associated with structural cardiac disease manifest distinctly different electrophysiological characteristics and outcome. Fetuses with 2 degrees AVB or isolated 3 degrees AVB commonly exhibited complex, changing heart rate and rhythm patterns; all 19 delivered fetuses are alive and healthy. Fetuses with structural cardiac disease and 3 degrees AVB exhibited largely monotonous heart rate and rhythm patterns and poor prognosis. Junctional ectopic tachycardia and/or ventricular tachycardia may be characteristic of an acute stage of heart block.     

Use of terbutaline in the treatment of complete heart block in the fetus

Between 1989 and 2000, 21 fetuses were diagnosed with complete atrioventricular block. Seven women with fetal ventricular rates of less than 60 were given oral terbutaline, and 6 of these had an initial increase in the fetal ventricular rate. Four fetuses (57%) maintained an increased average rate of 60 beats per minute and survived. Two fetuses returned to rates below 55 and died. The final fetus, with hypertrophic cardiomyopathy, was unresponsive. Terbutaline, therefore, is initially effective in raising the fetal ventricular rate, but this effect may be transient.     

Predictors of complete heart block after alcohol septal ablation for hypertrophic cardiomyopathy and the timing of pacemaker implantation

Catheter-based alcohol septal ablation has recently been introduced for the treatment of left ventricular outflow tract obstruction in hypertrophic obstructive cardiomyopathy. It is associated with various conduction disturbances and may lead to transient or persistent complete heart block (CHB). Electrocardiographic (ECG) changes and predictors of developing CHB and the timing of permanent pacemaker implantation have been variable among the different studies. Among 50 patients studied, we found that a new right bundle branch pattern was the most common new ECG change after septal ablation and that baseline left bundle branch block was strongly associated with the development of CHB (P = 0.004); 9 patients (18%) required permanent pacemaker implantation of whom 7 (78%) remained pacemaker dependent at 14 days with no delayed recovery of atrioventricular conduction. This favors an early pacemaker implantation strategy.     

Unidirectional complete heart block.

Forty-two patients with complete heart block were subjected to electrophysiological studies wherein apart from localization of the site of the conduction defect, ventricular pacing was done to assess ventriculo-atrial (VA) conduction and concealed ventriculo-nodal (VN) conduction. There was evidence of retrograde conduction in the presence of orthograde CHB in 22 patients (52.4 per cent). Fifteen patients (35.7 per cent) had VA conduction and seven (16.6 per cent) had concealed VN conduction. In patients with supra-Hisian CHB, three of the nine patients had VA conduction while of the 11 patients with intra-Hisian CHB, six had retrograde conduction (four with VA and two with concealed VN conduction). In the infra-Hisian CHB group, of the 22 patients, eight had VA conduction and five had concealed conduction. Incremental ventricular pacing induced VA Wenckebach periods at VPR from 110 to 133/minute with a VA interval of 110 to 130 msec. In view of the induction of Wenckebach VA periods, the recording of retrograde H potentials in some cases, and relatively long VA conduction time, it is surmised that retrograde conduction in the presence of orthograde CHB takes place through the AV conduction system.     

Pseudosimultaneous fast and slow pathway conduction: a common electrophysiologic finding in patients with dual atrioventricular nodal pathways

Two ventricular responses following termination of rapid atrial pacing were noted in 24 of 87 patients with dual atrioventricular (AV) nodal pathways and supraventricular tachycardia. In all 24 patients, the AH intervals of the first and second ventricular responses were comparable with those of the fast and slow pathways, respectively. Careful analysis of the whole pacing sequence revealed that, in 21 patients, this phenomenon resulted from sustained slow pathway conduction with long AH intervals. In these patients, as the AH interval of each paced beat was progressively lengthened during pacing, the corresponding His bundle and ventricular responses were pushed one cycle behind the current atrial paced beat, so that the last paced beat was followed by two His bundle and ventricular responses. In only three patients did double ventricular responses result from simultaneous fast and slow pathway conduction. One of these three patients also showed two ventricular responses resulting from sustained slow pathway conduction. Several factors predispose to the occurrence of this phenomenon in patients with dual AV nodal pathways. These include an ability to sustain slow pathway conduction, a longer slow pathway AH interval, a shorter sinus AH interval (fast pathway) and a shorter atrial paced cycle length that sustains slow pathway conduction. In conclusion, sustained slow pathway conduction with resultant long AH intervals is the mechanism of two ventricular responses following termination of atrial pacing in most patients with dual AV nodal pathways. This phenomenon should be distinguished from the rare occurrence of double ventricular responses to an atrial impulse due to simultaneous fast and slow pathway conduction.     

Molecular and ionic basis of congenital complete heart block.

Congenital heart block (CHB), detected at or before birth in a structurally normal heart, is strongly associated with autoantibodies reactive with the intracellular soluble ribonucleoproteins 48kD SSB/La, 52kD SSA/Ro, and 60kD SSA/Ro. CHB is presumed to be due to the transplacental passage of autoantibodies from the mother into the fetal circulation. Varying degrees of heart block have been reported. Although second degree block has, on rare occasion, reverted to normal sinus rhythm, complete atrio-ventricular (AV) block is irreversible. CHB carries substantial mortality and morbidity, with > 60% of affected children requiring lifelong pacemakers. The recurrence rate exceeds, by at least twofold, that of the first birth and is likely to influence the decision to have more children. Curiously, the mother's heart is almost never affected (with complete heart block) despite exposure to identical circulating autoantibodies. As part of our continuing effort to understand the complex factors contributing to the pathogenesis of CHB, we have established an animal model of CHB by immunizing female mice with recombinant proteins/antigens, reproduced the human complete AV block in an isolated Langendorff perfused fetal heart, and correlated these findings with L-type Ca channel inhibition by maternal antibodies from mothers of children with CHB. In addition, we established a passive animal model by directly injecting maternal antibodies into pregnant mice and reported significant sinus bradycardia, indicating that the spectrum of conduction abnormalities may extend beyond the AV node. All together, the data provided strong evidence supporting an etiologic role of antibody/Ca channel involvement in the pathogenesis of CHB. However, other yet unknown factors seem necessary to explain the full expression of CHB.