Twin atrioventricular nodes, arrhythmias, and survival in pediatric and adult patients with heterotaxy syndrome.

BACKGROUND: Heterotaxy syndrome is likely to involve arrhythmias from associated conduction system abnormalities, which are distinct in different subtypes of isomerism and may change further after interventions and remodeling. OBJECTIVE: The purpose of this study was to understand the risk of arrhythmias and its relation to isomerism subtypes. METHODS: Patients diagnosed between 1980 and 2019 as having heterotaxy syndrome were enrolled and grouped as right atrial isomerism (RAI), left atrial isomerism (LAI), or indeterminate isomerism. RESULTS: Of the 366 patients enrolled, 326 (89.1%) had RAI, 35 (9.6%) LAI, and 5 (1.4%) indeterminate isomerism; 71 (19.4%) patients were adults. Arrhythmias occurred in 37.2% of patients (109 supraventricular tachycardia [SVT], 8 atrial fibrillation/flutter, 12 ventricular tachycardia, and 14 paced bradycardia). Freedom from arrhythmias by the age of 1, 5, 10, 20, and 40 years was 0.849, 0.680, 0.550, 0.413, and 0.053, respectively. Twin atrioventricular nodes were identified in 51.5% of patients with RAI, 8.7% of patients with LAI, and 40.0% of patients with indeterminate isomerism and were the key predictors of SVT. Indeterminate isomerism was also a risk factor for SVT. Other forms of tachycardia appeared relatively late. Sinus bradycardia with junctional rhythm was common in LAI (48.7%) and less in indeterminate isomerism (20.0%), with none occurring in RAI. Only in patients with RAI who showed the poorest survival, ventricular tachycardia worsened the long-term survival. CONCLUSION: RAI was the predominant subtype of heterotaxy in this cohort. Collectively, the median RAI/LAI ratio was 0.731 and 5.450 in Western and East Asian studies, respectively. Arrhythmias, tachycardia, or paced bradycardia were common, but the spectrum was distinct among subtypes.

Unusual variants of pre-excitation: From anatomy to ablation: Part I-Understanding the anatomy of the variants of ventricular pre-excitation.

The famous quotation of Winston Churchill, made in his radio broadcast of 1939 regarding Russia's next move, specifically "A riddle wrapped up in a mystery, inside an enigma," perfectly fits the current understanding of unusual accessory atrioventricular pathways, including the variants producing ventricular pre-excitation. It was many decades after their original descriptions that we came better to begin to understand most of their structure-function relationships. Their mysterious pathophysiology was sometimes unveiled after invasive treatments, such as surgical ablation of the atrioventricular conduction axis instead of the accessory pathway itself. Speculations made on this basis have largely been validated by subsequent clinical experience. Most of the names suggested for description of the pathways have stood well the test of time. For some of them, however, this is not the case, with the initial names becoming confusing. In a series of reviews, we re-visit those accessory pathways producing ventricular pre-excitation other than classical Wolff-Parkinson-White syndrome. To set the scene, in this initial review, we describe the development and anatomy of the normal atrioventricular conduction axis, along with the insulating tissues of the atrioventricular junctions. We have sought to illustrate our explanations by using virtual dissection of computerized tomographic datasets, since they retain the intact heart within the setting of the body. These images illustrate well the value of attitudinally appropriate terminology. Thereafter, we discuss the electrophysiological manifestations of the abnormal anatomical pathways which provide the potential for both accessory atrioventricular and intraventricular conduction.

Overexpression of KCNN3 results in sudden cardiac death.

BACKGROUND: A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias. METHODS AND RESULTS: We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3(T/T)) and heterozygote (SK3(+/T)) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3(T/T) mice (7 of 19 SK3(T/T) mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3(T/T) mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3(T/T) mice have slower ventricular conduction compared with WT controls (SK3(T/T) vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3(T/T) mice demonstrated inducible atrial arrhythmias (50% of SK3(T/T) vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3(T/T) vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3(T/T) mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3(T/T) vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06). CONCLUSION: Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction.

Tachycardia associated with twin atrioventricular nodes in an infant with heterotaxy and interruption of inferior vena cava.

We report a 12-month-old boy with heterotaxy and interruption of inferior vena cava who showed sustained tachycardia associated with twin atrioventricular nodes (AVNs). Atrioventricular reciprocating tachycardia with antegrade conduction through the posterior AVN and retrograde conduction through the anterior AVN were successfully ablated using an upper approach from the left internal jugular vein.

Spontaneous resolution of sinoatrial exit block and atrioventricular dissociation in a child with dengue fever.

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.

PDK1 regulates vascular remodeling and promotes epithelial-mesenchymal transition in cardiac development.

One essential downstream signaling pathway of receptor tyrosine kinases (RTKs), such as vascular endothelial growth factor receptor (VEGFR) and the Tie2 receptor, is the phosphoinositide-3 kinase (PI3K)-phosphoinositide-dependent protein kinase 1 (PDK1)-Akt/protein kinase B (PKB) cascade that plays a critical role in development and tumorigenesis. However, the role of PDK1 in cardiovascular development remains unknown. Here, we deleted PDK1 specifically in endothelial cells in mice. These mice displayed hemorrhage and hydropericardium and died at approximately embryonic day 11.5 (E11.5). Histological analysis revealed defective vascular remodeling and development and disrupted integrity between the endothelium and trabeculae/myocardium in the heart. The atrioventricular canal (AVC) cushion and valves failed to form, indicating a defect in epithelial-mesenchymal transition (EMT), together with increased endothelial apoptosis. Consistently, ex vivo AVC explant culture showed impeded mesenchymal outgrowth. Snail protein was reduced and was absent from the nucleus in AVC cells. Delivery of the Snail S6A mutant to the AVC explant effectively rescued EMT defects. Furthermore, adenoviral Akt delivery rescued EMT defects in AVC explant culture, and deletion of PTEN delayed embryonic lethality of PDK1 endothelial deletion mice by 1 day and rendered normal development of the AVC cushion in the PDK1-deficient heart. Taken together, these results have revealed an essential role of PDK1 in cardiovascular development through activation of Akt and Snail.

Nodoventricular pathway associated with twin AV nodes: complexity of ablation in single ventricle physiology.

We report the case of a patient with heterotaxy syndrome including complex single ventricular morphology and interrupted IVC in association with twin conduction systems and a nodoventricular accessory pathway connection. The presence of 3 distinct QRS morphologies was inadvertently discovered during a hemodynamic catheterization study and prompted formal EP testing prior to hepatic venous inclusion into the Fontan circuit and loss of access to the atrial chamber for testing and therapy. This patient underscores the importance of close surveillance and high index of suspicion of arrhythmia mechanisms in patients with heterotaxy syndrome in conjunction with single ventricle morphology.

Selective slow pathway ablation using transseptal approach in a patient with surgically corrected partial atrioventricular canal defect and atrioventricular nodal reentrant tachycardia of the common type.

A 26-year-old woman with partial atrioventricular (AV) canal defect surgically closed with pericardial patch in a mode that the triangle of Koch had become part of the left atrium underwent successful slow pathway ablation for slow-fast AV nodal reentrant tachycardia. Transseptal approach was used because of the atypical post-operative anatomy. Transseptal catheter ablation of the slow pathway can be a reasonable and safe alternative in patients subjected to this type of operation.

Accessory pathway reciprocating tachycardia involving twin AV nodes in a patient with atrioventricular discordance and mitral atresia.

The atrioventricular (AV) conduction system in AV discordance remains unclear, especially in cases with complex cardiac anomaly. We report a case of accessory pathway reciprocating tachycardia in atrioventricular discordance (AVD) and mitral atresia with twin AV nodes. In this case, the anterior AV node was located along the atretic mitral valve. The anterior AV node was involved in tachycardia and the posterior AV node acted as a bystander during tachycardia. The anterior AV node in AVD can be located along the atretic mitral valve, and one of twin AV nodes might act as a bystander during AV reciprocating tachycardia.

Echocardiographic characteristics of the criss-cross heart.

OBJECTIVE: To assess the ultrasonic characteristics of the criss-cross heart, and explore the value of echocardiography in the diagnosis of this rare congenital cardiac defect. METHODS: We reviewed the echocardiographic findings in 4 patients having criss-crossed atrioventricular connections at our hospital, and compared the findings with observations at surgery in 3 of the patients. RESULTS: In all 4 patients, there was usual atrial arrangement, right hand ventricular topology, and concordant atrioventricular connections. The inlet components of the ventricular mass, however, crossed such that the apical component of the morphologically right ventricle was situated anteriorly and superiorly, and extended to the left relative to the apex of the morphologically left ventricle. The ventriculo-arterial connections were concordant in 1 patient, double outlet from the morphologically right ventricle in 2, and discordant in the other. In all 4 patients, it proved impossible to obtain the standard 4-chamber view showing simultaneously all four chambers and both atrioventricular valves. A series of apical 4-chamber or subcostal coronal views, obtained by tilting the transducer from posterior to anterior, demonstrate initially the connection of the left-sided left atrium and the right-sided left ventricle through the mitral valve. More anterior angulation of the transducer then showed the right-sided right atrium to be connected to the left-sided right ventricle through the tricuspid valve, confirming the presence of twisted atrioventricular connections. Color Doppler imaging displayed the crossing of the atrioventricular connections without mixing of the streams. Short-axis views across the ventricular mass confirmed that the right ventricle was superior, anterior, and to the left of the left ventricle, and demonstrated the horizontal position of the ventricular septum. When viewed subcostally, the distance between the tricuspid valve and the orifice of the inferior vena cava was significantly increased relative to normal findings. The echocardiographic findings were confirmed during surgical interventions in 3 patients, apart from the failure to diagnose one instance of persistent patency of the left superior vena cava. CONCLUSIONS: The failure to obtain a characteristic 4-chamber view in any cut was diagnostic for recognition of the criss-crossed atrioventricular junctions. Transthoracic echocardiography provides definitive images of this rare arrangement, and accurately defines the associated cardiac abnormalities.

Dual atrioventricular nodal physiology in young child.

Dual atrioventricular nodal physiology has been reported. Atrioventricular nodal reentrant tachycardia is the most common supraventricular tachycardia associated with dual atrioventricular nodal physiology. We present a case of dual atrioventricular nodal physiology in a 12-year-old Italian boy.

Relaciones biométricas del anillo atrioventricular izquierdo y las arterias coronarias en el hombre / Biometric relationships between the left atrioventricular ring and the coronary arteries in man

La relación de las arterias coronarias con los anillos atrioventriculares se torna importante en casos de reemplazo o plastía de la valva correspondiente. La proximidad de la rama circunfleja de la arteria coronaria izquierda al anillo atrioventricular izquierdo, a nivel de la comisura anterior, ha traído complicaciones quirúrgicas, en algunos casos con resultados fatales. Basado en lo anterior, estudiamos las relaciones biométricas entre las arterias coronarias y el anillo atrioventricular izquierdo. Utilizamos 58 corazones de individuos chilenos, 28 fijados en formaldehído al 10 por ciento y 30 frescos de individuos brasileños, de edades comprendidas entre 18 y 84 años, de ambos sexos y sin aparente cirugía cardíaca. Disecamos la región de ambos surcos coronarios, para luego clasificar las piezas según el tipo de dominancia coronaria. Luego, los atrios fueron resecados dejando visibles los anillos atrioventriculares y su relación con las arterias coronarias. Se efectuaron mediciones de la distancia de las arterias coronarias y sus ramas en relación al anillo atrioventricular izquierdo. Se establecieron 5 puntos en la porción posterior del anillo, distribuidos en sentido antihorario. Los puntos 1 y 5 localizados a nivel de las comisuras anterior y posterior, respectivamente. La menor distancia entre las ramas de las arterias coronarias y el anillo atrioventricular izquierdo se presentó en corazones con dominancia coronaria izquierda, y fue de 3,8 mm (corazones fijados) y 3,0 mm (corazones frescos).El tercio proximal de la rama circunfleja, asociado a una mayor proximidad al anillo mitral, constituye el área de mayor predisposición a una lesión iatrogénica durante un reemplazo y/o plastía valvar.

The relationships between the coronary arteries and the atrioventricular rings are important in cases of substitution or plastic of the corresponding valve. The vicinity of the circumflex branch of the left coronary artery to the left atrioventricular ring, at level of the previous corner, it has brought surgical complications, in some cases with fatal results. Due to this, we consider necessary to study the relationships biometric between the coronary arteries and the left atrioventricular ring. We use 58 hearts, 28 fixed hearts of Chilean individuals and 30 fresh hearts of Brazilian individuals, of ages between 18 and 84 years, of both sexes and without apparent heart surgery. The region of both coronary sulcus was dissected and we classified the pieces according to the type of coronary dominance. Later on, the atrium were dried up leaving visible the atrioventricular rings and their relationship with the coronary arteries. Measurement of the distances were made (in mm) of the coronary arteries and their branches, in relation to the left atrioventricular ring. Five points settled down in the later portion of the ring, distributed in having felt anti-timetable. The points 1 and 5 located at level of the previous and later corners, respectively. The smallest distance between the branches of the coronary arteries and the left atrioventricular ring was presented in hearts with left coronary dominance, and it was of 3,8 mm (fixed hearts) and 3,0 mm (fresh hearts).

Left cardiac isomerism in the Sonic hedgehog null mouse.

Sonic hedgehog (Shh) is a secreted morphogen necessary for the production of sidedness in the developing embryo. In this study, we describe the morphology of the atrial chambers and atrioventricular junctions of the Shh null mouse heart. We demonstrate that the essential phenotypic feature is isomerism of the left atrial appendages, in combination with an atrioventricular septal defect and a common atrioventricular junction. These malformations are known to be frequent in humans with left isomerism. To confirm the presence of left isomerism, we show that Pitx2c, a recognized determinant of morphological leftness, is expressed in the Shh null mutants on both the right and left sides of the inflow region, and on both sides of the solitary arterial trunk exiting from the heart. It has been established that derivatives of the second heart field expressing Isl1 are asymmetrically distributed in the developing normal heart. We now show that this population is reduced in the hearts from the Shh null mutants, likely contributing to the defects. To distinguish the consequences of reduced contributions from the second heart field from those of left-right patterning disturbance, we disrupted the movement of second heart field cells into the heart by expressing dominant-negative Rho kinase in the population of cells expressing Isl1. This resulted in absence of the vestibular spine, and presence of atrioventricular septal defects closely resembling those seen in the hearts from the Shh null mutants. The primary atrial septum, however, was well formed, and there was no evidence of isomerism of the atrial appendages, suggesting that these features do not relate to disruption of the contributions made by the second heart field. We demonstrate, therefore, that the Shh null mouse is a model of isomerism of the left atrial appendages, and show that the recognized associated malformations found at the venous pole of the heart in the setting of left isomerism are likely to arise from the loss of the effects of Shh in the establishment of laterality, combined with a reduced contribution made by cells derived from the second heart field.

Left main coronary thrombosis: unusual complication after radiofrequency ablation of left accessory atrioventricular pathway.

Radiofrequency ablation (RFA) has established itself as a first-line therapy for the curative treatment of many patients with supraventricular or atrioventricular tachycardias and has exhibited a generally low incidence of serious sequelae (N Engl J Med. 1991;324:1612; Lancet. 1991;337:1557). Coronary artery injury is a rare complication. We present a patient with an acute thrombotic total occlusion of the left main coronary artery immediately after the end of RFA who was successfully treated with emergency percutaneous transluminal coronary angioplasty. This case illustrates an unusual coronary complication of RFA and serves as an exceptional example of survival with a good short-term prognosis after this unusual etiology of myocardial infarction.

Long-term outcome of twin atrioventricular node and supraventricular tachycardia in patients with right isomerism of the atrial appendage.

BACKGROUND: Twin AV nodes and resulting supraventricular tachycardia (SVT) have been described in right atrial isomerism (RAI). OBJECTIVE: We sought to analyze the long-term outcome of patients with RAI with a focus on rhythm disturbances. METHODS: Retrospective study of 257 patients (152 male and 105 female, 1,171 patient-years) with RAI diagnosed between 1980 and 2005. RESULTS: SVT in 68 patients (26%) occurred at various ages from the prenatal period to 15 years and was only significantly associated with balanced ventricles (P = .009). Cardioversion was achieved in by verapamil in 6 of 6 cases (100%), adenosine in 18 of 21 cases (88%) and propranolol in 10 of 12 cases (83%). Electrocardiographic evidence of twin AV nodes, as shown by 2 discrete non-pre-excited QRS complexes, was found in 28 of 44 (64%) patients with more than 2 electrocardiograms, and was more frequent in those with balanced ventricles rather than a dominant ventricle and would increase risk of SVT. Recurrence of SVT was documented in 27 (40%) patients 1 day to 4.5 years after the first episode. However, the occurrence or recurrence of SVT was not associated with increased all-cause or surgical mortality or sudden death. Successful catheter ablation of ventriculoatrial pathways with junctional ectopic tachycardia at radiofrequency energy delivery was obtained in 5 of 6 patients. CONCLUSION: This study showed that twin AV nodes in RAI patients could be disclosed by serial electrocardiograms and that SVT, most likely a twin node tachycardia, was common and tended to recur but could be managed by ablation or medication.