Childhood-onset hypertrophic cardiomyopathy caused by thin-filament sarcomeric variants.

Up to 20% of children with sarcomeric hypertrophic cardiomyopathy (HCM) have disease-causing variants in genes coding for thin-filament proteins. However, data on genotype-phenotype correlations for thin-filament disease are limited. This study describes the natural history and outcomes of children with thin-filament-associated HCM and compares it to thick-filament-associated disease.Longitudinal data were collected from 40 children under 18 years with a disease-causing variant in a thin-filament protein from a single quaternary referral centre. Twenty-one (female n=6, 35.5%) were diagnosed with HCM at a median age of 13.0 years (IQR 8.3-14.0). Over a median follow-up of 5.0 years (IQR 4.0-8.5), three (14.3%) experienced one or more major adverse cardiac events (MACE) (two patients had an out-of-hospital arrest and eight appropriate implantable cardiac defibrillator (ICD) therapies in three patients). One gene carrier died suddenly at age 9 years. Compared with those with thick-filament disease, children with thin-filament variants more commonly experienced non-sustained ventricular tachycardia [NSVT; n=6 (28.6%) vs n=14 (10.8%), p=0.024] or underwent ICD insertion (thin, n=13 (61.9%) vs thick, n=50 (38.5%), p=0.040). However, there was no difference in the incidence of MACE (thin 2.47/100 pt years (95% CI 0.80 to 7.66) vs thick 3.63/100 pt years (95% CI 2.25 to 5.84)) or an arrhythmic event (thin 1.65/100 pt years (95% CI 0.41 to 6.58) vs thick 2.55/100 pt years (95% CI 1.45 to 4.48), p value 0.43).This study suggests that adverse events in thin-filament disease are predominantly arrhythmic and may occur in the absence of hypertrophy, but overall short-term outcomes do not differ significantly from thick-filament disease.

Middle aortic syndrome in children and adolescents.

Middle aortic syndrome is a rare form of renovascular disease that may present with severe hypertension during childhood. Narrowing of the abdominal aorta is often associated with narrowing of the renal and/or other visceral arteries and may be secondary to specific genetic syndromes. Following the optimization of blood pressure control, significant aortic narrowing often requires invasive management, including endovascular and surgical intervention. In younger children, endovascular therapy may be attempted in the first instance to acutely reduce the pressure gradient across the narrowing; however, a sustained benefit is rare. Once the child has grown to accommodate a graft of an adequate size, surgical therapy is indicated for patients in whom medical and/or endovascular management has not resulted in adequate blood pressure control. It is critical that individuals with middle aortic syndrome be managed by an experienced multidisciplinary team that includes medical, endovascular, and surgical expertise that can provide long-term care to monitor for recurrent hypertension and evidence of end-organ damage.

Role of cardiac magnetic resonance strain analysis in patients with hypoplastic left heart syndrome in evaluating right ventricular (dys)function: a systematic review.

OBJECTIVES: Right ventricular dysfunction predicts death in patients with hypoplastic left heart syndrome (HLHS), but differences in morphology and loading conditions make calculation of the ejection fraction (EF), a challenging measure of its function. Our goal was to evaluate how strain measurements with cardiac magnetic resonance feature tracking could be used to evaluate right ventricular function in patients with HLHS. METHODS: A systematic search of the literature was performed by 2 independent researchers using the terms 'population', 'intervention', 'comparison', 'outcome' and 'time criteria'. PubMed and the Ovid database were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Our review included 8 studies with 608 participants with ventricular strain values obtained using cardiac magnetic resonance feature tracking. After stage I palliation, global strain was reduced in patients after a hybrid procedure and a right ventricle-to-pulmonary artery conduit compared with a modified Blalock-Taussig shunt despite similar EFs. Global longitudinal strain did not differ between stage II and stage III (Fontan) palliation. Fontan patients had significantly impaired global longitudinal and circumferential strain compared to the left ventricular strain of the controls. Studies of Fontan patients that included patients with HLHS who were part of a cohort with a single right ventricle showed impaired global circumferential strain compared with the cohort with a single left ventricle, with controls, and over time. In this group, impaired global circumferential strain was associated with major adverse cardiac events. CONCLUSIONS: Cardiac magnetic resonance feature tracking can be used in patients with HLHS to evaluate RV strain and demonstrate differences between surgical strategies, over time and compared with controls. It could be used alongside clinical symptoms and EF values to detect ventricular dysfunction.

How do surgeons decide? Conduit choice in coronary artery bypass graft surgery in the UK†.

OBJECTIVES: Conduits used in coronary artery bypass grafting may have significant impact on outcomes, but evidence is mixed and there is large variation in practice. This study provides insights into the opinions of the UK surgeons on conduit use and their decision-making processes. METHODS: A questionnaire was created using the Ottawa Decision Support Framework to elicit the importance that surgeons placed on bilateral internal mammary artery grafting, skeletonization, total arterial revascularization and sequential anastomoses on a scale of 1-10. Scores ≥8 were deemed 'important' and ≤3 'not important'. Surgeons were asked to specify changes to practice in frail patients or emergencies. Additional questions included conduit type used, factors affecting decision-making and vein harvesting methods. Questionnaires were administered in person with data analysed centrally. RESULTS: Ninety-seven consultant cardiac surgeons from 25 centres responded. Thirty-two percent surgeons routinely used radial arteries and 36% used right internal mammary artery. High-quality evidence contributed most to decision-making receiving a total of 328/960 points, with consultant experience being the second (255/960 points). There was a bimodal distribution of perceived importance of bilateral internal mammary artery use, with 29 (30%) 'important' and 'not important' scores each. 23% of surgeons found total arterial revascularization important. Most surgeons (64%) preferred pedicled mammary arteries. Twenty-six percent of surgeons considered sequential grafting to be important. CONCLUSIONS: Low uptake of total arterial revascularization and bilateral internal mammary artery among the UK consultants may be due to the lack of high-quality evidence demonstrating a significant benefit. It is also possible that reluctance to use certain conduits may stem from low levels of exposure to conduits or inadequate training, particularly given the importance of consultant experience on decision-making.

Medical student exposure to cardiothoracic surgery in the United Kingdom.

OBJECTIVES: There has been declining interest in cardiothoracic surgery amongst medical graduates. This survey examines the exposure of British medical students to cardiothoracic surgery in various settings and its relationship with students' interest in the speciality. METHODS: A questionnaire composed of 14 quantitative and qualitative items was distributed amongst 162 medical students. The survey included questions on demographics, interest in cardiothoracic surgery, mechanisms of exposure to the speciality and desire to pursue a career in cardiothoracic surgery before and after exposure. RESULTS: Amongst the surveyed students, 71.0% reported exposure to cardiothoracic surgery as part of their medical school curricula and 24.7% reported extracurricular exposure. Of the students, 46.7% reported clinical exposure. Overall, 27.1% of students reported interest in a career in cardiothoracic surgery, which was higher amongst students who had curricular (29.6%), clinical (35.5%) or extracurricular exposure (50.0%). Amongst interested students, 43.2% engaged in extracurricular cardiothoracic activities compared with 16.1% of students not interested in pursuing the speciality. Confidence in career choice after exposure increased more in interested students (20.4%) than not interested students (1.6%). Students rated exposure and mentorship as the most important factor in promoting a career in cardiothoracic surgery. CONCLUSIONS: Medical students with an interest in cardiothoracic surgery are more likely to organize independent attachments in the speciality and attend extracurricular events; however, many students might fail to identify cardiothoracic surgery as an area of interest because of the lack of exposure at medical school.

Piloting the Use of Patient-Specific Cardiac Models as a Novel Tool to Facilitate Communication During Cinical Consultations.

This pilot study aimed to assess the impact of using patient-specific three-dimensional (3D) models of congenital heart disease (CHD) during consultations with adolescent patients. Adolescent CHD patients (n = 20, age 15-18 years, 15 male) were asked to complete two questionnaires during a cardiology transition clinic at a specialist centre. The first questionnaire was completed just before routine consultation with the cardiologist, the second just after the consultation. During the consultation, each patient was presented with a 3D full heart model realised from their medical imaging data. The model was used by the cardiologist to point to main features of the CHD. Outcome measures included rating of health status, confidence in explaining their condition to others, name and features of their CHD (as a surrogate for CHD knowledge), impact of CHD on their lifestyle, satisfaction with previous/current visits, positive/negative features of the 3D model, and open-ended feedback. Significant improvements were registered in confidence in explaining their condition to others (p = 0.008), knowledge of CHD (p < 0.001) and patients' satisfaction (p = 0.005). Descriptions of CHD and impact on lifestyle were more eloquent after seeing a 3D model. The majority of participants reported that models helped their understanding and improved their visit, with a non-negligible 30% of participants indicating that the model made them feel more anxious about their condition. Content analysis of open-ended feedback revealed an overall positive attitude of the participants toward 3D models. Clinical translation of 3D models of CHD for communication purposes warrants further exploration in larger studies.

The low/high BCS permeability class boundary: physicochemical comparison of metoprolol and labetalol.

Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability class boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability class reference drug. Labetalol's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5-7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol-buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitro PAMPA permeability assay. The results of the in vivo perfusion studies in rats lay between the two contradictory in vitro studies; metoprolol was shown to have moderately higher rat intestinal permeability than labetalol. Theoretical distribution of the ionic species of the drugs was in corroboration with the experimental in vitro and the in vivo data. We propose three characteristics that the optimal permeability class reference drug should exhibit: (1) fraction dose absorbed in the range of 90%; (2) the optimal marker drug should be absorbed largely via passive transcellular permeability, with no/negligible carrier-mediated active intestinal transport (influx or efflux); and (3) the optimal marker drug should preferably be nonionizable. The data presented in this paper demonstrate that neither metoprolol nor labetalol can be regarded as optimal low/high-permeability class boundary standard. While metoprolol is too conservative due to its complete absorption, labetalol has been shown to be a substrate for P-gp-mediated efflux transport, and both drugs exhibit significant segmental-dependent permeability along the gastrointestinal tract. Nevertheless, the use of metoprolol as the marker compound does not carry a risk of bioinequivalence: Peff value similar to or higher than metoprolol safely indicates high-permeability classification. On the other hand, a more careful data analysis is needed if labetalol is used as the reference compound.