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A novel rabbit model of variably compensated complete heart block.

Complete heart block (CHB) provides a useful substrate for study of bradycardia-dependent ventricular arrhythmias and cardiac function. Existing CHB animal models are limited by surgical recovery time and reliance on intrinsic escape rhythms. We describe a novel closed-chest rabbit model of CHB involving transcatheter radiofrequency (RF) atrioventricular (AV) node ablation and ventricular rate control with chronic transvenous pacing. Permanent CHB was achieved in 34 of 38 attempts overall. Procedural mortality due to cardiac tamponade (n = 2), airway complications (n = 2), and unknown causes (n = 5) occurred in nine animals. Survivors with CHB (n = 28) were maintained for < or = 22 days, during which there were three late deaths related to infection (n = 1) or respiratory distress (n = 2). None of the survivors with CHB showed recovery of AV conduction or pacemaker capture loss during chronic ventricular pacing at about one-half normal sinus rates, and 25 animals surviving to death showed no overt signs of hemodynamic compromise such as lethargy, poor feeding, or respiratory distress. This approach provides a reproducible nonsurgical CHB model with adjustable ventricular rate control.

Animals↗

Congenital complete heart block.

Congenital complete heart block in utero has become diagnosed more frequently with the clinical use of fetal echocardiography. The fetus with complete heart block may remain asymptomatic or may develop congestive heart failure. Congenital complete heart block is more frequently seen in infants of mothers with systemic lupus erythematosus, both clinically manifested and subclinical systemic lupus erythematosus with positive antibodies (SS-A and SS-B antibodies). At birth, the neonate with complete heart block may remain asymptomatic and may not require a pacemaker to increase the heart rate. The indications for a pacemaker in neonates with complete heart block have been discussed. Both in-utero and neonatal management of congenital complete heart block are discussed to manage congestive heart failure in a fetus. Four patients with congenital complete heart block are presented covering a broad spectrum of clinical presentation, diagnosis, and management both in the fetal and neonatal period.

Adult↗

Complete heart block.

Complete heart block (CHB) occurs when atrial impulses are not conducted to the ventricles. It occurs in association with many conditions, including acute myocardial infarction. In the setting of acute myocardial infarction (MI), certain characteristic conduction disturbances tend to precede development of CHB. Knowledge of these disturbances provides rational indications for emergency temporary pacing of acute MI patients.

Bundle-Branch Block↗

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

Action Potentials↗

Congenital complete heart block in structurally normal heart--a study of 44 cases.

Data of 44 patients with congenital complete heart block and structurally normal heart have been analysed. Thirty one patients were asymptomatic (group I) and 13 patients had symptoms of low cerebral perfusion like syncope, near syncope or convulsions (group II). A ventricular rate on surface ECG was found to be significantly lower in the symptomatic group (56.7 +/- 13.2 beats per minute, bpm, in group I and 46.5 +/- 6.0 bpm in group II). Similarly wide QRS escape rhythm of greater than 0.10 seconds was more often seen in group II (2/13) as compared to group I (2/31) though the difference did not reach statistical significance. Presence of pauses of more than 3.0 seconds on ambulatory ECG monitoring were infrequent in both the groups (group I 1/7, group II 2/7), however more often seen in group II. Electrophysiological studies carried out in 11 patients were not helpful in differentiating the two groups and all the patients including two with a wide QRS escape rhythm on surface ECG showed suprahisian level of block. The corrected junctional recovery time in two groups did not show any statistical difference. A persistently slow ventricular rate of less than 50 bpm during waking hours, wide QRS escape rhythm and pauses of greater than 3 seconds on ambulatory monitoring are suggestive of high risk to the patient and may justify implantation of permanent pacemaker even in asymptomatic patients.

Adolescent↗

Late recovery of atrioventricular conduction after pacemaker implantation for complete heart block associated with surgery for congenital heart disease.

OBJECTIVES: Pacemaker implantation is a standard recommendation for patients with persistent complete heart block following surgery for congenital heart disease. This study was performed to determine the incidence and clinical significance of late recovery of atrioventricular conduction following pacemaker implantation. METHODS: Between 1990 and 2001, 5662 open cardiac procedures for congenital heart defects were performed at our institution. The postoperative course of all patients with complete heart block in whom a permanent pacemaker was implanted was followed on a monthly basis, by either clinical or transtelephonic follow-up. RESULTS: A total of 72 patients with persistent postoperative complete heart block underwent pacemaker implantation. After insertion of the pacemaker, recovery of atrioventricular conduction was recognized in 7 of 72 patients (9.6%) at a median of 41 days (18-113 days) after the initial cardiac operation. These included 3 patients with ventricular septal defect, 2 with ventricular inversion or single ventricle, and 1 each with left ventricular outflow tract obstruction and atrioventricular septal defect. During a mean follow-up of 4.4 +/- 2.6 years, there was no late recurrence of heart block. Three patients had residual right bundle branch block and 1 had first-degree atrioventricular block. CONCLUSIONS: Atrioventricular conduction may return in a small but significant percentage of patients following pacemaker implantation for complete heart block associated with congenital heart surgery. When recovery of atrioventricular conduction occurs within the first months after surgery it appears reliable, which suggests that lifelong cardiac pacing may not be necessary in these individuals.

Atrioventricular Node↗

Autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor in children with congenital heart block.

Isolated congenital heart block may be associated with autoimmune disorder such as Sjögren Syndrome and systemic lupus erythematosus. In this work we demonstrate circulating autoantibodies against neonatal heart M1 muscarinic acetylcholine receptor (mAChR) in the sera of children with congenital heart block. This antibody were able to react with the second extracellular loop of the human M1 mAChR as demonstrated using a synthetic peptide in enzyme immune assay and binding assay. Affinity purified anti-peptide IgG as well as total IgG from children with congenital heart block, interfered with the specific radioligand occupancy from neonatal heart M1 mAChR, interacting irreversibly. The antipeptide antibodies also displayed an 'agonist-like' activity, i.e. decreased contractility, activated nitric oxide synthase activity and increased production of cyclic GMP. All of these effects were selectively blunted by pirenzepine and neutralized by the synthetic M1 peptide. Both binding and biological effects were obtained using neonatal rat heart instead adult heart and were independent of Ro/SS-A and La/SS-B antibodies and were also absent in the sera of normal children. A clinical relevance of these findings is demonstrated by a strong association between the existence of circulating M1 mAChR antipeptide antibodies and the presence of isolated congenital heart block, making these antibodies a proper marker of this disease.

Amino Acid Sequence↗

Complete heart block complicating retrograde left-heart catheterization of patients with cardiac allografts.

The development of complete heart block during left-sided cardiac catheterization is an uncommon event. We describe three cases of complete heart block complicating left-sided cardiac catheterization of patients with cardiac allografts. Review of the cases performed at our institution suggests that complete heart block during left-sided catheterization may be more common in patients with cardiac allografts.

Aged↗

Successful in utero therapy of fetal heart block.

OBJECTIVE: Congenital complete heart block is associated with maternal autoantibodies to Ro and La proteins, which injure the fetal cardiac conduction system. We administered dexamethasone to the mothers of five fetuses with heart block caused by maternal antibodies. STUDY DESIGN: We diagnosed five cases of fetal heart block at 20 to 23 weeks and treated all mothers with dexamethasone 4 mg orally each day for the remainder of the pregnancy. All patients were positive for anti-SS-A (anti-Ro) and/or anti-SS-B (anti-La) antibodies. RESULTS: Four patients had complete heart block, and one had second-degree block. In two patients (one with complete heart block, one with second-degree heart block) the degree of block lessened with treatment. Hydrops in three complete heart block patients resolved after treatment. Maternal antibody levels did not change. Matched maternal and cord samples at delivery showed similar antibody levels. CONCLUSIONS: Complete heart block can respond to transplacental glucocorticoid therapy with improved cardiac conduction. Because there may be a concurrent myocarditis, treatment in utero may also improve cardiac contractility, leading to the observed rapid resolution of hydrops. Treatment with steroids that cross the placenta should be considered for newly diagnosed cases of complete heart block with positive antibody screens.

Adolescent↗