Cardiac development demystified by use of the HDBR atlas.

Much has been learned over the last half century regarding the molecular and genetic changes that take place during cardiac development. As yet, however, these advances have not been translated into knowledge regarding the marked changes that take place in the anatomical arrangements of the different cardiac components. As such, therefore, many aspects of cardiac development are still described on the basis of speculation rather than evidence. In this review, we show how controversial aspects of development can readily be arbitrated by the interested spectator by taking advantage of the material now gathered together in the Human Developmental Biology Resource; HDBR. We use the material to demonstrate the changes taking place during the formation of the ventricular loop, the expansion of the atrioventricular canal, the incorporation of the systemic venous sinus, the formation of the pulmonary vein, the process of atrial septation, the remodelling of the pharyngeal arches, the major changes occurring during formation of the outflow tract, the closure of the embryonic interventricular communication, and the formation of the ventricular walls. We suggest that access to the resource makes it possible for the interested observer to arbitrate, for themselves, the ongoing controversies that continue to plague the understanding of cardiac development.

Outpatient care of adults with congenital heart disease in the UK: a qualitative appraisal of the clinician perspective.

OBJECTIVE: This study aimed to explore clinicians' perspectives of ambulatory care in adult congenital heart disease (ACHD). METHODS: Semistructured interviews were carried out remotely (Zoom) with a range of physicians providing ambulatory care to patients with ACHD across the UK. The chronic care model, thrive and candidacy frameworks were used to design prompt guides and subsequently develop themes. A framework approach was used to code and analyse transcripts, which were managed in NVivo. RESULTS: 21 clinicians (43% females, 38% specialists) from 10/12 ACHD networks in the UK participated. Shared themes included the purpose of the clinic appointment, problems in the 'hub-and-spoke' care system, role of the general practitioner and ACHD specialist nurse, communication with patients, burden of ambulatory care and patient self-management. Reflecting on these themes, participants identified resources, what care and how and by it is delivered alongside the role of the patient as key areas for future research. CONCLUSIONS: The present structure of ACHD ambulatory care is neither patient-centred nor equitable. The concerned clinicians raise the question whether increasing resource alone without changing structure will lead to better outcomes for patients.

eNOS plays essential roles in the developing heart and aorta linked to disruption of Notch signalling.

eNOS (NOS3) is the enzyme that generates nitric oxide, a signalling molecule and regulator of vascular tone. Loss of eNOS function is associated with increased susceptibility to atherosclerosis, hypertension, thrombosis and stroke. Aortopathy and cardiac hypertrophy have also been found in eNOS null mice, but their aetiology is unclear. We evaluated eNOS nulls before and around birth for cardiac defects, revealing severe abnormalities in the ventricular myocardium and pharyngeal arch arteries. Moreover, in the aortic arch, there were fewer baroreceptors, which sense changes in blood pressure. Adult eNOS null survivors showed evidence of cardiac hypertrophy, aortopathy and cartilaginous metaplasia in the periductal region of the aortic arch. Notch1 and neuregulin were dysregulated in the forming pharyngeal arch arteries and ventricles, suggesting that these pathways may be relevant to the defects observed. Dysregulation of eNOS leads to embryonic and perinatal death, suggesting mutations in eNOS are candidates for causing congenital heart defects in humans. Surviving eNOS mutants have a deficiency of baroreceptors that likely contributes to high blood pressure and may have relevance to human patients who suffer from hypertension associated with aortic arch abnormalities.

A case report of complex congenital heart disease co-existing with hypertrophic cardiomyopathy.

Background: Myocardial abnormalities are sometimes overlooked in congenital heart disease (CHD). The co-existence of hypertrophic cardiomyopathy is so uncommon that it is assumed to be a coincidence rather than an association. Case summary: A 24-year-old gentleman, who was previously clinically well following a staged Fontan palliation for single-ventricle CHD, was transferred to our centre following an out-of-hospital cardiac arrest. He had return of spontaneous circulation after a period of cardiopulmonary resuscitation. Initial electrocardiogram showed sinus bradycardia. Computed tomography pulmonary angiography ruled out pulmonary embolism. Transthoracic echocardiography and cardiac magnetic resonance (CMR) demonstrated marked ventricular hypertrophy with no left ventricular outflow tract obstruction. Punctate areas of late gadolinium enhancement were noted in the basal septum, and T1 values were consistent with fibrosis. Cardiac catheterization demonstrated low Fontan pressures and normal coronaries. Ventricular tachycardia rapidly degenerating into ventricular fibrillation was induced during electrophysiological studies. Genetic testing demonstrated a pathogenic cardiac myosin-binding protein C variant consistent with co-existent hypertrophic cardiomyopathy. Bisoprolol was initiated and a subcutaneous implantable cardiac defibrillator implanted 4 weeks after his initial presentation. Two years on, he remains well with no therapies from his defibrillator. As well as Fontan surveillance, cascade testing, exercise prescription, and pre-conception counselling were addressed during follow-up. Discussion: In CHD, ventricular hypertrophy may relate to congenital or acquired systemic outflow tract obstruction. Contemporary CMR techniques combined with genetic testing can be useful in differentiating between hypertrophy caused by congenital anomaly vs. concurrent cardiomyopathies. Multidisciplinary expertise is critical for accurate diagnosis and optimal care.