An unmet need: arrhythmia detection by implantable loop recorder in the systemic right ventricle.

AIMS: Patients with systemic right ventricles are at high risk of sudden cardiac death. Arrhythmia is a significant risk factor. Routine Holter monitoring is opportunistic with poor adherence. The aim of this study was to determine if continuous rhythm monitoring with an implantable loop recorder (ILR) could allow early detection of clinically important arrhythmias. METHODS AND RESULTS: Implantable loop recorder implantation was offered to patients with atrial switch repair for transposition of the great arteries. Recordings were made with symptoms or, automatically for pauses, significant bradycardia or tachycardia and reviewed by the multi-disciplinary team. Twenty-four out of 36 eligible patients underwent ILR implantation with no complication. Forty-two per cent had preserved ventricular function, 75% were NYHA functional class I, 88% had low sudden cardiac death risk, 33% had previous intra-atrial re-entrant tachycardia (IART), and none had known conduction disease. Eighteen out of 24 (75%) patients made 52 recordings (52% automated) over 39.5 months (1.6-72.5). Thirty-two out of 52 (62%) recordings in 15/24 (63%) of the cohort were clinically significant and included sinus node disease (two patients), atrioventricular block (two patients), IART (seven patients), and IART with sinus node disease or atrioventricular block (four patients). Implantable loop recorder recordings prompted medication change in 11 patients [beta-blockers (n = 9), anti-coagulation (n = 5), and stopping anti-coagulation (n = 1)] and device therapy recommendation in seven patients [five pacemakers (three: atrioventricular block) and two defibrillators]. Two patients declined intervention; one suffered an arrhythmic death. Intra-atrial re-entrant tachycardia and clinically relevant conduction disease were detected in patients irrespective of sudden cardiac death risk. CONCLUSION: Continuous monitoring with an ILR in patients with systemic right ventricle following atrial switch detects clinically relevant arrhythmias that impact decision-making. In this cohort, clinically relevant arrhythmias did not correlate with sudden cardiac death risk.

Risk Stratification for Sudden Cardiac Death in Repaired Tetralogy of Fallot.

There has been significant progress in the prevention of sudden cardiac death in repaired tetralogy of Fallot. Contemporary cohorts report greater survival attributable to improved surgical techniques, heart failure management, and proactive strategies for risk stratification and management of ventricular arrhythmias including defibrillator implantation and ablation technology. Over the last 25 years, our understanding of predictive risk factors has also improved from invasive and more limited measures to individualized risk prediction scores based on extensive demographic, imaging, electrophysiological, and functional data. Although each of these contemporary scoring systems improves prediction, there are important differences between the study cohorts, included risk factors, and imaging modalities that can significantly affect interpretation and implementation for the individual patient. In addition, accurate phenotyping of disease complexity and anatomic repair substantially modulates this risk and the mechanism of sudden death. Routine implementation of risk stratification within repaired tetralogy of Fallot management is important and directly informs primary prevention defibrillator implantation as well as consideration for proactive invasive strategies including ventricular tachycardia ablation and pulmonary valve replacement. Assessment and risk stratification by a multidisciplinary team of experts in adult congenital heart disease are crucial and critical. Although we have increased understanding, reconciliation of these complex factors for the individual patient remains challenging and often requires careful consideration and discussion with multidisciplinary teams, patients, and their families.

De grands progrès ont été réalisés pour prévenir la mort subite d'origine cardiaque chez les patients ayant une tétralogie de Fallot réparée (TFr). Dans les cohortes contemporaines, l'amélioration du taux de survie peut être attribuée à l'évolution des techniques chirurgicales, à la prise en charge de l'insuffisance cardiaque et à la mise en place de stratégies proactives pour la stratification du risque d'arythmies ventriculaires et pour leur prise en charge, notamment par l'implantation de défibrillateurs et l'ablation. Au cours de 25 dernières années, les moyens utilisés pour caractériser les facteurs de risque à valeur prédictive sont passés de mesures limitées et invasives à l'établissement de scores individualisés basés sur de grands corpus de données démographiques, électrophysiologiques, fonctionnelles et d'autres issues de l'imagerie. Bien que chacun de ces systèmes contemporains d'évaluation du risque permette de raffiner notre capacité prédictive, des différences importantes entre les cohortes à l'étude, les facteurs de risque considérés et les modalités d'imagerie peuvent influencer l'interprétation des scores et les soins prodigués à un patient en particulier. De plus, la description phénotypique exacte de la complexité de la maladie et de la réparation anatomique permet de moduler la stratification du risque de mort subite d'origine cardiaque et son mécanisme possible. Il importe que la stratification du risque fasse partie intégrante de la prise en charge de la TFr puisqu'elle oriente directement le choix de mettre ou non en place un défibrillateur en prévention primaire, et qu'elle fasse partie de l'équation lorsque des stratégies invasives proactives, comme l'ablation de la tachycardie ventriculaire ou le remplacement de la valve pulmonaire, sont envisagées. La mesure et la stratification du risque par une équipe multidisciplinaire d'experts en cardiopathies congénitales sont donc des étapes cruciales. Même si les connaissances se sont affinées au fil du temps, il peut être difficile de faire la synthèse de ces facteurs complexes dans le cas d'un patient en particulier. C'est pourquoi il faut bien souvent se tourner vers l'équipe multidisciplinaire, le patient et ses proches pour évaluer rigoureusement les options.

A retrospective evaluation of catheter ablation in atrial flutter post cardiac transplantation.

BACKGROUND: Atrial flutter is the most common arrhythmia post cardiac transplantation. Observational studies in the non-transplant population have shown prognostic benefit with catheter ablation; however, there are no data in the heart transplant population. OBJECTIVES: This study evaluated the experience of catheter ablation in atrial flutter post cardiac transplantation. METHODS: A retrospective review of experience of late onset atrial flutter at the Freeman Hospital, Newcastle-upon-Tyne, UK, between 1985 and January 2020. RESULTS: Sixty eight of the 722 patients who survived 6 months post cardiac transplantation developed late atrial flutter giving an incidence of 9.4%. Thirty-two patients were managed with ablation with treatment largely determined by time of flutter onset. Kaplan Meier estimates for arrhythmia free survival post first ablation for organized atrial arrhythmias was 83.3% at 1 year. Kaplan-Meier estimates for median survival post onset of atrial arrhythmias treated with ablation was 11.34 years (95% CI 8.00-14.57), compared to 5.79 years in patients managed medically (95%CI 2.26-9.32) (P = .026). CONCLUSIONS: Atrial flutter is an important late complication of cardiac transplantation. Patients treated with ablation in the modern era had increased survival compared to a historical cohort.

4D flow MRI assessment of right atrial flow patterns in the normal heart - influence of caval vein arrangement and implications for the patent foramen ovale.

AIM: To investigate atrial flow patterns in the normal adult heart, to explore whether caval vein arrangement and patency of the foramen ovale (PFO) may be associated with flow pattern. MATERIALS AND METHODS: Time-resolved, three-dimensional velocity encoded magnetic resonance imaging (4D flow) was employed to assess atrial flow patterns in thirteen healthy subjects (6 male, 40 years, range 25-50) and thirteen subjects (6 male, 40 years, range 21-50) with cryptogenic stroke and patent foramen ovale (CS-PFO). Right atrial flow was defined as vortical, helico-vortical, helical and multiple vortices. Time-averaged and peak systolic and diastolic flows in the caval and pulmonary veins and their anatomical arrangement were compared. RESULTS: A spectrum of right atrial flow was observed across the four defined categories. The right atrial flow patterns were strongly associated with the relative position of the caval veins. Right atrial flow patterns other than vortical were more common (p = 0.015) and the separation between the superior and inferior vena cava greater (10±5mm versus 3±3mm, p = 0.002) in the CS-PFO group. In the left atrium all subjects except one had counter-clockwise vortical flow. Vortex size varied and was associated with left lower pulmonary vein flow (systolic r = 0.61, p = 0.001, diastolic r = 0.63 p = 0.002). A diastolic vortex was less common and time-averaged left atrial velocity was greater in the CS-PFO group (17±2cm/sec versus 15±1, p = 0.048). One CS-PFO subject demonstrated vortical retrograde flow in the descending aortic arch; all other subjects had laminar descending aortic flow. CONCLUSION: Right atrial flow patterns in the normal heart are heterogeneous and are associated with the relative position of the caval veins. Patterns, other than 'typical' vortical flow, are more prevalent in the right atrium of those with cryptogenic stroke in the context of PFO. Left atrial flow patterns are more homogenous in normal hearts and show a relationship with flow arising from the left pulmonary veins.

Expression of the BMP receptor Alk3 in the second heart field is essential for development of the dorsal mesenchymal protrusion and atrioventricular septation.

RATIONALE: The dorsal mesenchymal protrusion (DMP) is a prong of mesenchyme derived from the second heart field (SHF) located at the venous pole of the developing heart. Recent studies have shown that perturbation of its development is associated with the pathogenesis of atrioventricular (AV) septal defect. Although the importance of the DMP to AV septation is now established, the molecular and cellular mechanisms underlying its development are far from fully understood. Prior studies have demonstrated that bone morphogenetic protein (BMP) signaling is essential for proper formation of the AV endocardial cushions and the cardiac outflow tract. A role for BMP signaling in regulation of DMP development remained to be elucidated. OBJECTIVE: To determine the role of BMP signaling in DMP development. METHODS AND RESULTS: Conditional deletion of the BMP receptor Alk3 from venous pole SHF cells leads to impaired formation of the DMP and a completely penetrant phenotype of ostium primum defect, a hallmark feature of AV septal defects. Analysis of mutants revealed decreased proliferative index of SHF cells and, consequently, reduced number of SHF cells at the cardiac venous pole. In contrast, volume and expression of markers associated with proliferation and active BMP/transforming growth factor ß signaling were not significantly altered in the AV cushions of SHF-Alk3 mutants. CONCLUSIONS: BMP signaling is required for expansion of the SHF-derived DMP progenitor population at the cardiac venous pole. Perturbation of Alk3-mediated BMP signaling from the SHF results in impaired development of the DMP and ostium primum defects.

The pathogenesis of atrial and atrioventricular septal defects with special emphasis on the role of the dorsal mesenchymal protrusion.

Partitioning of the four-chambered heart requires the proper formation, interaction and fusion of several mesenchymal tissues derived from different precursor populations that together form the atrioventricular mesenchymal complex. This includes the major endocardial cushions and the mesenchymal cap of the septum primum, which are of endocardial origin, and the dorsal mesenchymal protrusion (DMP), which is derived from the Second Heart Field. Failure of these structures to develop and/or fully mature results in atrial septal defects (ASDs) and atrioventricular septal defects (AVSD). AVSDs are congenital malformations in which the atria are permitted to communicate due to defective septation between the inferior margin of the septum primum and the atrial surface of the common atrioventricular valve. The clinical presentation of AVSDs is variable and depends on both the size and/or type of defect; less severe defects may be asymptomatic while the most severe defect, if untreated, results in infantile heart failure. For many years, maldevelopment of the endocardial cushions was thought to be the sole etiology of AVSDs. More recent work, however, has demonstrated that perturbation of DMP development also results in AVSD. Here, we discuss in detail the formation of the DMP, its contribution to cardiac septation and describe the morphological features as well as potential etiologies of ASDs and AVSDs.