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Background: The ability to increase heart rate during exercise and other stressors is a key homeostatic feature of the sinoatrial node (SAN). When the physiological heart rate response is blunted, chronotropic incompetence limits exercise capacity, a common problem in patients with heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, the mechanisms of chronotropic incompetence remain unknown., Methods: Dahl salt-sensitive rats fed a high-salt diet and C57Bl6 mice fed a high-fat diet and an inhibitor of constitutive nitric oxide synthase (Nω-nitro-L-arginine methyl ester [L-NAME]; 2-hit) were used as models of HFpEF. Myocardial infarction was created to induce HF with reduced ejection fraction. Rats and mice fed with a normal diet or those that had a sham surgery served as respective controls. A comprehensive characterization of SAN function and chronotropic response was conducted by in vivo, ex vivo, and single-cell electrophysiologic studies. RNA sequencing of SAN was performed to identify transcriptomic changes. Computational modeling of biophysically-detailed human HFpEF SAN was created., Results: Rats with phenotypically-verified HFpEF exhibited limited chronotropic response associated with intrinsic SAN dysfunction, including impaired β-adrenergic responsiveness and an alternating leading pacemaker within the SAN. Prolonged SAN recovery time and reduced SAN sensitivity to isoproterenol were confirmed in the 2-hit mouse model. Adenosine challenge unmasked conduction blocks within the SAN, which were associated with structural remodeling. Chronotropic incompetence and SAN dysfunction were also found in rats with HF with reduced ejection fraction. Single-cell studies and transcriptomic profiling revealed HFpEF-related alterations in both the "membrane clock" (ion channels) and the "Ca 2+ clock" (spontaneous Ca 2+ release events). The physiologic impairments were reproduced in silico by empirically-constrained quantitative modeling of human SAN function., Conclusions: Chronotropic incompetence and SAN dysfunction were seen in both models of HF. We identified that intrinsic abnormalities of SAN structure and function underlie the chronotropic response in HFpEF.

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)-characterized by electrical remodeling-is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conduction abnormalities and increased right atrial refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

Background: Pseudoaneurysm of thoracic aorta as a complication of blunt trauma to the chest, can present with a variety of symptoms due to mass compression effect. Here we report the first pseudoaneurysm of thoracic aorta presenting with chronic cough and inappropriate sinus tachycardia. The purpose of this case report is to highlight pseudoaneurysm of thoracic aorta as a rare differential diagnosis for inappropriate sinus tachycardia., Case Presentation: Here we report a case of 29-year-old white woman, a nurse, with history of a motor vehicle accident. She initially presented to medical attention with inappropriate sinus tachycardia 2 years following the motor vehicle accident during her pregnancy. Six years later she underwent sinoatrial node modification after failing a number of medications. Days prior to the ablation she developed a mild cough which became constant within a week following ablation. A computed tomography scan of her chest performed as part of a workup revealed an outpouching of the inferomedial aspect of the aortic arch, which was compressing her left main bronchus. She underwent arch repair surgery and recovered without complications. Four years later she presented with significant symptomatic sinus bradycardia requiring pacemaker placement., Conclusions: This is the first reported case of thoracic pseudoaneurysm of aorta presenting with inappropriate sinus tachycardia due to compression of the vagal nerve and cough as a result of the left main bronchus compressive effect; it highlights the importance of considering structural abnormalities in a differential diagnosis of inappropriate sinus tachycardia before any interventions.

First, we report a sudden fetal death at 33(+3)weeks due to sino-atrial node dualism. The female stillborn was delivered by induced labor. The postmortem examination of the cardiac conduction system revealed a dualism of the sino-atrial node, associated with fragmentation of the atrio-ventricular node and His bundle. These abnormalities of the cardiac conduction system represent the morphological substrate for the development of malignant arrhythmias. In particular, the dualism of the sino-atrial node can cause the dissociation of the longitudinal nodal impulse into two distinct ways of different pulse generation, resulting in supraventricular tachyarrhythmias. This observation suggests new avenues of research on the pathogenesis of the sudden unexpected fetal death. Moreover, our findings confirm the need for an accurate postmortem examination, including serial sectioning of the cardiac conduction system, in every case of unexplained fetal death, following standardized autoptic protocols., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Sinus node dysfunction is frequently observed in patients with congenital heart disease (CHD). Variants in the Vascular Endothelial Growth Factor-A (VEGF) pathway are associated with CHD. In Vegf(120/120) mice, over-expressing VEGF120, a reduced sinoatrial node (SAN) volume was suggested. Aim of the study is to assess the effect of VEGF over-expression on SAN development and function., Methods: Heart rate was measured in Vegf(120/120) and wildtype (WT) embryos during high frequency ultrasound studies at embryonic day (E)12.5, 14.5 and 17.5 and by optical mapping at E12.5. Morphology was studied with several antibodies. SAN volume estimations were performed, and qualitative-PCR was used to quantify expression of genes in SAN tissues of WT and Vegf(120/120) embryos., Results: Heart rate was reduced in Vegf(120/120) compared with WT embryos during embryonic echocardiography (52 ± 17 versus 125 ± 31 beats per minute (bpm) at E12.5, p<0.001; 123 ± 37 vs 160 ± 29 bmp at E14.5, p=0.024; and 177 ± 30 vs 217 ± 34 bmp, at E17.5 p=0.017) and optical mapping (81 ± 5 vs 116 ± 8 bpm at E12.5; p=0.003). The SAN of mutant embryos was smaller and more vascularized, and showed increased expression of the fast conducting gap junction protein, Connexin43., Conclusions: Over-expression of VEGF120 results in reduced heart rate and a smaller, less compact and hypervascularized SAN with increased expression of Connexin43. This indicates that VEGF is necessary for normal SAN development and function., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Rationale: The Slit-Roundabout (Robo) signaling pathway has pleiotropic functions during Drosophila heart development. However, its role in mammalian heart development is largely unknown., Objective: To analyze the role of Slit-Robo signaling in the formation of the pericardium and the systemic venous return in the murine heart., Methods and Results: Expression of genes encoding Robo1 and Robo2 receptors and their ligands Slit2 and Slit3 was found in or around the systemic venous return and pericardium during development. Analysis of embryos lacking Robo1 revealed partial absence of the pericardium, whereas Robo1/2 double mutants additionally showed severely reduced sinus horn myocardium, hypoplastic caval veins, and a persistent left inferior caval vein. Mice lacking Slit3 recapitulated the defects in the myocardialization, alignment, and morphology of the caval veins. Ligand binding assays confirmed Slit3 as the preferred ligand for the Robo1 receptor, whereas Slit2 showed preference for Robo2. Sinus node development was mostly unaffected in all mutants. In addition, we show absence of cross-regulation with previously identified regulators Tbx18 and Wt1. We provide evidence that pericardial defects are created by abnormal localization of the caval veins combined with ectopic pericardial cavity formation. Local increase in neural crest cell death and impaired neural crest adhesive and migratory properties underlie the ectopic pericardium formation., Conclusions: A novel Slit-Robo signaling pathway is involved in the development of the pericardium, the sinus horn myocardium, and the alignment of the caval veins. Reduced Slit3 binding in the absence of Robo1, causing impaired cardiac neural crest survival, adhesion, and migration, underlies the pericardial defects.

The presented case and discussion illustrate the use of CT coronary angiography to depict coronary artery fistulae. A 41-year-old man presented with an acute myocardial infarction. Invasive angiography revealed an incidental coronary artery fistula but was unable to depict its course. CT coronary angiography was undertaken to define the course and termination of the fistula. This confirmed a fistulous connection between the left circumflex artery and the superior vena cava that followed the typical course of an S-shaped sinoatrial nodal artery. Even in such an unusual anomaly this case highlights the ability of CT coronary angiography to accurately depict the coronary artery anatomy.

Noncompaction of the ventricular myocardium (NVM) is a rare unclassified cardiomyopathy which is characterized by multiple prominent trabeculations and deep intertrabecular recesses. This cardiomyopathy can be isolated or in combination with other congenital cardiac disorders, including coronary artery abnormalities. A 56-year-old female patient presented to the cardiology department with complaints of exertional dyspnoea and chest pain. Transthoracic echocardiography revealed left ventricular dilatation with diffuse hypokinesis. Multiple prominent trabeculations with deep inter-trabecular recesses were observed at the left ventricular apex. Also, coronary angiography demonstrated a sinoatrial node artery originating from the posterolateral branch of the right coronary artery.

In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome (SSNS) ADRA2B and eNOS genes polymorphisms. We have established predominance of homozygote genotype of more rare DD allele in patients with SSNS (28%) compared with subjects of control group (8.99%). We have found predominance of heterozygote genotype 4a/4b in patients with SSNS compared with subjects of control group (41.8 and 25.39%, respectively). The data obtained allow to suggest that eNOS gene polymorphism might be associated with SSNS.

In this work we have demonstrated for the first time on the clinico-genetic material association between hereditary sick sinus node syndrome and connexin 40 gene polymorphism. We have revealed that heterozygous variant of connexin 40 gene variant is more frequent among patients with sick sinus node syndrome and their healthy relatives than in persons of control group.

Duplication or absence of parts of the specialized cardiac conduction system in patients with heterotaxy syndrome causes significant clinical disease, but the mechanistic basis by which embryonic disruption of left-right patterning alters conduction system patterning in these patients is not well understood. We sought to determine whether a mouse model of X-linked human heterotaxy recapitulates conduction system abnormalities identified in patients with heterotaxy. Cardiac structure and conduction system patterning were evaluated in Zic3 null embryos from e9.5 to e16.5 using genetic and molecular methods. Severe structural abnormalities involving atrial, ventricular, and conotruncal development were associated with a spectrum of disorganized and ambiguous arrangements throughout the conduction system, including the appearance of duplicated structures. The severity and location of conduction system abnormalities correlated with the severity and location of associated structural heart disease and were identifiable at the earliest stages examined. The Zic3 mouse model provides a novel tool to dissect the mechanistic underpinnings of conduction system patterning and dysfunction and its relationship to cardiovascular malformations, making it a promising model to improve understanding and risk assessment in the clinical arena.

Cardiac rhythm abnormalities, including ventricular arrhythmia, atrial fibrillation and atrioventricular block, have been observed during the acute stage of dengue haemorrhagic fever. Atrioventricular or complete heart block can be fatal and may require a temporary pacemaker. We report a ten-year-old girl who presented with dengue haemorrhagic fever with sinoatrial block and atrioventricular dissociation that had a spontaneous resolution.

Sinus node artery originates from the proximal segment of the right coronary artery, left circumflex artery, or from both. We present a 55-year-old man who underwent coronary angiography for exercise-induced chest pain localized in the epigastric region that resolved within several minutes of resting. He had an anomalous sinus node artery originating from the left anterior descending artery and right coronary artery agenesis. To our knowledge, this is the first reported case of coexistence of these two rare coronary anomalies.

We investigated the role of podoplanin in development of the sinus venosus myocardium comprising the sinoatrial node, dorsal atrial wall, and primary atrial septum as well as the myocardium of the cardinal and pulmonary veins. We analyzed podoplanin wild-type and knockout mouse embryos between embryonic day 9.5-15.5 using immunohistochemical marker podoplanin; sinoatrial-node marker HCN4; myocardial markers MLC-2a, Nkx2.5, as well as Cx43; coelomic marker WT-1; and epithelial-to-mesenchymal transformation markers E-cadherin and RhoA. Three-dimensional reconstructions were made and myocardial morphometry was performed. Podoplanin mutants showed hypoplasia of the sinoatrial node, primary atrial septum, and dorsal atrial wall. Myocardium lining the wall of the cardinal and pulmonary veins was thin and perforated. Impaired myocardial formation is correlated with abnormal epithelial-to-mesenchymal transformation of the coelomic epithelium due to up-regulated E-cadherin and down-regulated RhoA, which are controlled by podoplanin. Our results demonstrate an important role for podoplanin in development of sinus venosus myocardium., (Copyright (c) 2008 Wiley-Liss, Inc.)

Objective: The purpose of this study was to use 64-MDCT to investigate the anatomic characteristics of the S-shaped variant of the sinoatrial node (SAN) artery and to describe the clinical implications of the findings in ablative procedures involving the left atrium., Materials and Methods: Coronary CT angiograms of 250 patients (152 men, 98 women; mean age, 60 +/- 12 [SD] years) were retrospectively analyzed for identification of the origin, number, anatomic course, mode of termination, and S-shaped variant of the SAN artery., Results: At least one SAN artery was detected in 244 patients. The S-shaped variant was seen in 35 (14.3%) of these patients. Thirty-four of the variants (30.6% of all left SAN arteries) arose from the proximal to middle portion of the left circumflex artery (mean distance between the ostium of the left circumflex artery and the origin of S-shaped variant, 28.7 +/- 13.1 mm). The other variant (0.7% of all right SAN arteries) originated from the distal right coronary artery. The S-shaped variant was the only artery supplying the SAN in 28 (11.4%) of the patients. In patients with two arteries supplying the SAN, the right SAN artery and the S-shaped variant of the left SAN artery were seen together in seven patients. The S-shaped SAN artery (mean distance from atrial wall, 2.43 +/- 0.992 mm) had a predictable proximal course, lying in the posterior aspect in a groove between the orifices of the left superior pulmonary vein and the left atrial appendage close to the left atrial wall. The terminal segment of the artery approached the nodal tissue posterior to the superior vena cava in 22 patients, anterior to the vena cava in 10 patients, and through branches surrounding the vena cava in two patients., Conclusion: The S-shaped variation of the SAN artery is common and has a characteristic anatomic course. MDCT can be used to plan surgical and catheter-based left atrial interventions in which this artery is at risk of injury.

Introduction: Atrial fibrillation (AF) is a heritable disorder with male predilection, suggesting a sex chromosome defect in certain patients. Loss-of-function truncation mutations in EMD, encoding the nuclear membrane protein emerin, cause X-linked Emery-Dreifuss muscular dystrophy (EDMD) characterized by localized contractures and skeletal myopathy in adolescence, sinus node dysfunction (SND) in early adulthood, and atrial fibrillation as a variably associated trait. This study sought to identify the genetic basis for male-restricted, nonsyndromic sinus node dysfunction and AF in a multigenerational family., Methods and Results: Genealogical and medical records, and DNA samples, were obtained. Progressive SND and AF occurred in four males related through maternal lineages, consistent with X-linked inheritance. Skeletal myopathy was absent, even at advanced ages. Targeted X chromosome genotyping mapped the disease locus to Xq28, implicating EMD as a positional candidate gene. DNA sequencing revealed hemizygosity for an in-frame 3-bp deletion in EMD (Lys37del) in affected males, disrupting a residue within the LEM binding domain critical for nuclear assembly but leaving the remainder of the protein intact. Buccal epithelial cell staining with emerin antibody demonstrated near-total functional loss of emerin. Female relatives underwent prospective electrocardiographic and genetic testing. Those heterozygous for Lys37del had approximately 50-70% emerin-positive nuclei and variable degrees of paroxysmal supraventricular arrhythmia., Conclusions: Mutation of EMD can underlie X-linked familial AF. Lys37del is associated with epithelial cell emerin deficiency, as in EDMD, yet it causes electrical atriomyopathy in the absence of skeletal muscle disease. Targeted genetic testing of EMD should be considered in patients with SND-associated AF and/or family history suggesting X-linked inheritance.

The coxsackievirus and adenovirus receptor (CAR), which mediates infection by the viruses most commonly associated with myocarditis, is a transmembrane component of specialized intercellular junctions, including the myocardial intercalated disc; it is known to mediate cell-cell recognition, but its natural function is poorly understood. We used conditional gene targeting to investigate the possible functions of CAR during embryonic development, generating mice with both germline and tissue-specific defects in CAR expression. Homozygous germline deletion of CAR exon 2 or cardiomyocyte-specific gene deletion at embryonic day 10 (E10) mediated by Cre recombinase expressed under the control of the cardiac troponin T promoter resulted in death by E12.5; embryos showed marked cardiac abnormalities by E10.5, with hyperplasia of the left ventricular myocardium, distention of the cardinal veins, and abnormalities of sinuatrial valves. Within the hyperplastic left ventricle, increased numbers of proliferating cells were evident; persistent expression of N-myc in the hyperplastic myocardium and attenuated expression of the trabecular markers atrial natriuretic factor and bone morphogenic protein 10 indicated that proliferating cardiomyocytes had failed to differentiate and form normal trabeculae. In electron micrographs, individual CAR-deficient cardiomyocytes within the left ventricle appeared normal, but intercellular junctions were ill-formed or absent, consistent with the known function of CAR as a junctional molecule; myofibrils were also poorly organized. When cardiomyocyte-specific deletion occurred somewhat later (by E11, mediated by Cre under control of the alpha-myosin heavy chain promoter), animals survived to adulthood and did not have evident cardiac abnormalities. These results indicate that during a specific temporal window, CAR expression on cardiomyocytes is essential for normal cardiac development. In addition, the results suggest that CAR-mediated intercellular contacts may regulate proliferation and differentiation of cardiomyocytes within the embryonic left ventricular wall.

Visceral heterotaxy syndromes have been associated with complex congenital heart disease and several attempts have been made to classify these lesions. One area of controversy that remains is the existence of atrial isomerism. In this case report we provide definite anatomic evidence of the existence of left atrial isomerism, wherein both the atria have smooth walls, finger-like appendages, and absence of the pectinate muscles and sinus node., (Copyright 2003 Wiley-Liss, Inc.)

The outcome of surgical repair of sinus venosus atrial septal defect was reviewed retrospectively. The operation was performed on 44 children aged 8 to 163 months, between April 1985 and November 1998. Median cardiopulmonary bypass and aortic crossclamp times were 58 minutes (range, 29 to 141 minutes) and 29 minutes (range, 4 to 67 minutes), respectively. Use of blood products decreased from 4.5 units per patient in the first period (1985 to 1989) to 0.6 units in the last period (1995 to 1998). Median intensive care and hospital stays were 2 days (range, 1 to 12 days) and 6 days (range, 4 to 16 days), respectively. There was 1 early death (2.3%). Complications included reexploration for bleeding in 2 patients (4.5%) and for superior vena cava obstruction in 1 (2.3%), and arrhythmias in 3 (6.8%), which required a pacemaker in one. During follow-up of 15 to 176 months, 83.8% of patients were in sinus rhythm. One required angioplasty for superior vena cava stenosis, hemodynamically insignificant residual shunt was found in 3, and mild superior vena cava stenosis in 3. Repair of sinus venosus atrial septal defect carries a low mortality and morbidity, but long-term follow-up is needed to monitor potential sinus node dysfunction and superior vena cava stenosis.

This long-term study sought to determine the clinical implication of defective sinus node and AV conduction tissue in patients with left atrial isomerism (LAI). From 1984 to 1998, a total of 22 patients were identified as LAI. Patient age at the last follow-up ranged from 2 to 276 months (90+/-70 months). Associated cardiac anomalies were interruption of the inferior vena cava (n = 18, 82%), common atrium (n = 9, 41%), AV canal (n = 14, 64%), double-outlet right ventricle (n = 8, 36%), and pulmonary stenosis (n = 15, 68%). Palliative interventions were performed in 16 patients (Fontan-type operation in 4 patients, shunt followed by Fontan-type operation in 2, repair of septal defect in 4, and extracardiac intervention in 6). During the follow-up, over half of the patients (n = 14, 64%) developed bradyarrhythmia (onset age: from 1 to 264 months; median 78 months): junctional rhythm (n = 11), sinus bradycardia (n = 8) (5 patients also had junctional rhythm), and AV block (n = 2, both also had junctional rhythm). The probability free from bradyarrhythmia was 80% and 46% at the age of 2 and 6 years, respectively. None of the bradyarrhythmias were directly related to open-heart surgery. Besides, junctional ectopic tachycardia occurred after Fontan-type operation in three of six patients. In two patients, a Mahaim-like pathway was identified during the electrophysiological study. The patients with LAI had a high probability of developing bradyarrhythmias due to abnormal sinus node function. Varied AV conduction abnormalities may include compromised AV conduction, junctional ectopic tachycardia after Fontan-type operation, and an association of Mahaim-like pathway.

Objectives: To clarify the prevalence and mechanism of supraventricular tachycardia in patients with right atrial isomerism., Background: Paired SA and dual atrioventricular (AV) nodes have been described in patients with right atrial isomerism. However, the clinical significance remains unclear., Methods: From 1987 to 1996, a total of 101 patients (61 male, 40 female) and four fetuses were identified with right atrial isomerism. The diagnosis of supraventricular tachycardia exclude the tachycardia with prolonged QRS duration or AV dissociation, and primary atrial tachycardia., Results: The median follow-up duration was 38 months (range 0.2-270 months). Supraventricular tachycardia was documented in 25 patients (24.8%) and one fetus (25%) (onset age ranged from prenatal to 14 years old; median 4 years old). Actuarial Kaplan-Meier analysis revealed that the probability of being free from tachycardia was 67% and 50% at 6 and 10 years of age, respectively. These tachycardias could be converted by vagal maneuvers in one, verapamil in seven, propranolol in four, digoxin in two, procainamide in one, and rapid pacing in five. Spontaneous conversion was noted in six (including the fetus). Seven cases had received electrophysiological studies. Reciprocating AV tachycardia could be induced in five and echo beats in one. The tachycardia in three patients was documented as incorporating a posterior AV node (antegrade) and an anterior or a lateral AV node (retrograde). Two of them received radiofrequency ablation. Successful ablation in both was obtained by delivering energy during tachycardia, aimed at the earliest retrograde atrial activity and accompanied by junctional ectopic rhythm. The patient with echo beats developed tachycardia soon after operation., Conclusions: Supraventricular tachycardia is common in patients with right atrial isomerism and can occur during the prenatal stage. Drugs to slow conduction through the AV node may help to terminate the tachycardia. Radiofrequency ablation is a safe and effective treatment alternative to eliminate tachycardia.

The sinus node artery (SNA) arises from the right coronary artery in near 60% of the cases and from the left circumflex artery in the remaining ones. We described the case of a patient in whom the SNA took off from the proximal part of the left main trunk. A 59 year-old male underwent coronary arteriography because of unstable angina. Soon after the incannulation of the left coronary ostium with a 7F catheter critical bradycardia ensued without ECG changes of ischemia. The arrhythmia spontaneously reverted by removing the catheter. Further contrast injections were carried out with a smaller diagnostic catheter (5F); the left main trunk was normal with the SNA arising from the very proximal part of it. It is likely that the heart rate slowing was elicited by a temporary occlusion (and related ischemia) of the anomalous SNA by the diagnostic catheter. This anomaly may therefore provoked heart arrhythmias during diagnostic or interventional procedures.

An unusual case of left isomerism in a 52-year-old woman with early-onset atrial fibrillation was presented. Magnetic resonance imaging clearly delineated the morphology of both atrial appendages, the vascular anatomy and all other associated anomalies, obviating further invasive studies. The discovery of left isomerism at advanced age indicates that abnormal atrial situs itself is of less clinical importance, and despite the associated sinus node dysfunction may predispose the heart to atrial fibrillation.

The histological study of the conduction system has been done in a case of "straddling tricuspid valve". The main anomalies observed were an AV node located more anteriorly but at the left of the posterior interventricular septum and an hypertrophic bifasicular right bundle branch with an unusual anterior radiation. These morphological features allow to discuss the embryology of the conduction system and of the interventricular septum in that congenital cardiopathy.

A case of fetal and neonatal persistent atrial tachycardia is described in a child with complete transposition of the great arteries. At autopsy, serial sections of the conducting tissue showed that the sinus node was hypoplastic and markedly fibrotic. The sinus node consisted of a small area of cells clustered around the nodal artery. Although the underlying mechanism of neonatal persistent tachycardia is unclear, it is possible that the hypoplasia and fibrosis of the sinus node was the substrate in the present case. This mechanism should be considered in any newborn infant in whom sinus rhythm cannot be established.

We investigated the clinical features, surface ECG findings, associated with congenital heart disease (CHD), and status at follow-up in 103 children who underwent intracardiac electrophysiologic evaluation of supraventricular tachycardia (SVT). Age at catheterization ranged from 2 days to 17 years (mean 4.2 years). Diagnosis of the mechanism was based upon standard electrophysiologic techniques. Of the 103 patients, 37 had reentry without a bypass tract (10 sinoatrial node, two atrial muscle, and 25 atrioventricular node); 51 had reentry with a bypass tract (28 manifest Wolff-Parkinson-White [WPW], 18 unidirectional retrograde accessory pathway [URAP], an five Lown-Ganong-Levine); and 15 had an ectopic focus (11 atrial, four junctional). Distinguishing features among the common types are depicted in Table III. We conclude that in children the various mechanisms of SVT (1) are likely to be found in different clinical situations, (2) have a different potential for surgical cure, and (3) have a different prognosis for long-term treatment. Since curative surgery was theoretically possible in 57% of our patients (WPW, concealed WPW, atrial, and junctional ectopic), we recommend electrophysiologic study in any patient who has had frequent recurrences of SVT for longer than 1 year and who requires drugs in addition to digoxin for treatment.

This is a serial section examination of the conduction system of five hearts of various types of dextrocardia. In one case of dextroversion the conduction system was found to be normal. In one case of mirror-image dextrocardia the conduction system was normal but in the opposite spatial position. In one heart of mixed (discordant) dextrocardia, the sinoatrial node was in correct morphologic position. There were two atrioventricular nodes - a posterior node close to the coronary sinus and an anterior node in the roof of the morphologic right atrium. They formed two separate bundles which joined in the left ventricle to form a "sling". In two cases of presumptive mirror-image dextrocardia, with a common atrium in situs inversus according to the morphology of the atrial appendages, with common atrioventricular orifice (CAVO), the sinoatrial node was situated in wrong positions. Two atrioventricular nodes and bundles again formed a sling. There are various types of slings in discordant dextrocardia.

Histologic examination of serial sections of the conduction system of the hearts of three young persons who died suddenly while engaged in active sports was performed. In no case were electrocardiogram tracings available. One patient, an 11-year-old girl, had micro-Ebstein's anomaly of the tricuspid valve associated with a septoseptal Kent fascicle through a wide gap of the central fibrous annulus and upper Mahaim fibers. Another patient, a 24-year-old football player, had a focal, 75 per cent obstructing atherosclerotic plaque in the proximal descending coronary artery, with scattered band necrosis and patchy myocardial fibrosis; upper and lower Mahaim fibers joined the atrioventricular node and the left bundle branch with the crest of the interventricular septum. The third patient, a 26-year-old cycling champion, had a conspicuous atrial fascicle of ordinary and transitional myocardium bypassing the atrioventricular node to anastomose with the His bundle (James accessory atrioventricular pathway). These findings indicate that atrioventricular conduction system abnormalities may play a fatal arrhythmogenic role in sudden death and raise questions regarding the prevention of electrical instability in young people engaged in active sports.

The incidence of electrical instability of the heart is high in patients with absence of the right and persistence of the left superior caval vein when the latter connects to the coronary sinus. It has been suggested that a large coronary sinus may influence the susceptibility to arrhythmias. we studied the conduction tissues of 8 hearts from the cardiopathological collection of Children's Hospital of Pittsburgh. Six of these specimens had a persistent left superior caval vein connecting to the coronary sinus. There were 4 with absence of the right superior caval vein, 3 of which were in the group with persistent left veins. We evaluated the sinus node and the specialized atrioventricular junctional area, comparing them with known normals. The coronary sinus varied in size from through it. The size did not alter the histology of the adjacent conduction tissue. In contrast, the sinus node was abnormal in 3 of the 4 hearts with absent right superior caval vein. This may be the key factor in the development of arrhythmias when the right superior caval vein is absent or abnormal.

We have recently studied a case of complete heart block in which there was considerable difficulty in deciding whether it was of congenital or acquired origin. This was because the heart block was first discovered at the age of 2 years in the course of acute diphtheria. Though diphtheritic infections are known to affect the cardiac conduction system, authenticated cases of post-diphtheritic block persisting after the infection are rare, and, furthermore, histopathological study in this case revealed discontinuity between the atrial tissues and the more peripheral parts of the atrioventricular conduction tissues. This has been more commonly observed in congenital cases of complete heart block and it has been postulated on theoretical grounds that this could be thebasis for congenital heart block; on the other hand, it has been noted in a single casethought to be of acquired origin. Review of the evidence available failed to allow accurate classification of the case into either congenital or acquired categories. Thenormal, segmental development of the atrioventricular node, each segment being of different embryological origin, is discussed and the case presented is understandable in thelight of this.