Hypertrophic Cardiomyopathy : Present and Future,With Translation Into Contemporary Cardiovascular Medicine

Hypertrophic cardiomyopathy (HCM) is a common inherited heart disease with diverse phenotypic and genetic expression, clinical presentation, and natural history. HCM has been recognized for 55 years, but recently substantial advances in diagnosis and treatment options have evolved, as well as increased recognition of the disease in clinical practice. Nevertheless, most genetically and clinically affected individuals probably remain undiagnosed, largely free from disease-related complications, although HCM may progress along 1 or more of its major disease pathways (i.e., arrhythmic sudden death risk; progressive heart failure [HF] due to dynamic left ventricular [LV] outflow obstruction or due to systolic dysfunction in the absence of obstruction; or atrial fibrillation with risk of stroke). Effective treatments are available for each adverse HCM complication, including implantable cardioverter-defibrillators (ICDs) for sudden death prevention, heart transplantation for end-stage failure, surgical myectomy (or selectively, alcohol septal ablation) to alleviate HF symptoms by abolishing outflow obstruction, and catheter-based procedures to control atrial fibrillation. These and other strategies have now resulted in a low disease-related mortality rate of <1%/year. Therefore, HCM has emerged from an era of misunderstanding, stigma, and pessimism, experiencing vast changes in its clinical profile, and acquiring an effective and diverse management armamentarium. These advances have changed its natural history, with prevention of sudden death and reversal of HF, thereby restoring quality of life with extended (if not normal) longevity for most patients, and transforming HCM into a contemporary treatable cardiovascular disease.     

The provision of a time-critical elective surgical service during the COVID-19 Crisis: a UK experience

IntroductionWith the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic.Materials and methodsA protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 ‘clean’ site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff.ResultsA total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive.ConclusionThis study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.     

Evidence for an alcohol-stress link among normal weight adolescents reporting purging behavior

A survey of 1728 tenth grade students was conducted to assess the prevalence of purging behavior, alcohol and drug use, and reported physical and psychological distress. Thirteen percent reported purging behavior. Female purgers outnumbered males 2 to 1. Male purgers were significantly heavier than male nonpurgers. The prevalence of drunkenness and daytime drinking among female purgers was significantly higher than for female nonpurgers. Female purgers were more likely to report using alcohol to reduce stress than nonpurging female peers. Female purgers reported a higher level of psychological distress when perceived situational control is low than female nonpurgers. Significant differences were not found between male purgers and male nonpurgers on variables assessing alcohol use and psychological distress. Educational programs aimed at prevention of eating disorders may need to be developed.     

Activity in the paracingulate and cingulate sulci during word generation: an fMRI study of functional anatomy.

The supracallosal medial frontal cortex can be divided into three functional domains: a ventral region with connections to the limbic system, an anterior dorsal region with connections to lateral prefrontal systems, and a posterior dorsal region with connections to lateral motor systems. Lesion and functional imaging studies implicate this medial frontal cortex in speech and language generation. The current functional magnetic resonance imaging (fMRI) study of word generation was designed to determine which of these three functional domains was substantially involved by mapping individual subjects' functional activity onto structural images of their left medial frontal cortex. Of 28 neurologically normal right-handed participants, 21 demonstrated a prominent paracingu- late sulcus (PCS), which lies in the anterior dorsal region with connections to lateral prefrontal systems. Activity increases for word generation centered in the PCS in 18 of these 21 cases. The posterior dorsal region also demonstrated significant activity in a majority of participants (16/28 cases). Activity rarely extended into the cingulate sulcus (CS) (3/21 cases) when there was a prominent PCS. If there was no prominent PCS, however, activity did extend into the CS (6/7 cases). In no case was activity present on the crest of the cingulate gyrus, which is heavily connected to the limbic system. Thus, current findings suggest that medial frontal activity during word generation reflects cognitive and motor rather than limbic system participation. The current study demonstrates that suitably designed fMRI studies can be used to determine the functional significance of anatomic variants in human cortex.     

The athlete's heart: remodeling, electrocardiogram and preparticipation screening

Highly trained athletes show morphologic cardiac changes (ie, athlete's heart) that are the consequence of several determinants, including type of sport, gender, and, possibly, inherited genetic factors. The extent of physiologic cardiac remodeling may occasionally be substantial in highly trained athletes and may raise a differential diagnosis with structural cardiac disease, such as cardiomyopathies. In addition, athletes demonstrate a spectrum of alterations in the 12-lead electrocardiogram (ECG) pattern, including marked increase in precordial R-wave or S-wave voltages, ST segment or T-wave changes, and deep Q waves suggestive of left ventricular hypertrophy, that may raise the possibility of pathologic heart condition, but have also been viewed as a consequence of the cardiac morphologic remodeling induced by athletic conditioning. To evaluate the clinical significance of these abnormal ECGs, the authors compared ECG patterns to cardiac morphology and function (assessed by two-dimensional echocardiography in individual athlete) in a large population of 1005 elite athletes engaged in a variety of sporting disciplines. Forty percent of the athletes had abnormal ECGs, and a subgroup of about 15% showed distinctly abnormal and often bizarre patterns highly suggestive of cardiomyopathies, such as hypertrophic cardiomyopathy, in the absence of pathologic cardiac changes. Such alterations are likely the consequence of athletic conditioning itself and represent another potential component of athlete's heart syndrome. However, such false-positive ECGs represent a potential limitation to the efficacy of routine ECG testing in the preparticipation cardiovascular screening of large athletic populations.     

Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects

Summary Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for normal subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm³, while that for males was 16.3 cm³ and that for females was 18.0 cm³. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.

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Evaluation du volume des ventricules cérébraux à partir des images obtenues en résonance magnétique nucléaire chez 38 sujets humains

Résumé La détermination exacte du volume des ventricules cérébraux est importante en clinique comme par exemple dans la démence présénile d'Alzheimer, la schizophrénie et l'hypertension intracrânienne bénigne. Des études antérieures ont étudié la fiabilité de la résonance magnétique nucléaire en pratique clinique pour évaluer le volume des ventricules cérébraux. Toutefois une évaluation correcte dans les conditions pathologiques implique une bonne connaissance des données morphométriques du sujet normal. Pour établir ces données sur « le sujet normal », nous avons étudié les coupes obtenues en IRM chez 38 sujets apparemment indemnes de toute pathologie; nous avons calculé le volume ventriculaire dans chaque cas en utilisant des méthodes mises au point auparavant dans notre laboratoire. Les résultats ont été ensuite comparés avec ceux obtenus par d'autres études utilisant soit des moules ventriculaires, soit des coupes tomographiques computérisées. Le volume ventriculaire total moyen chez 38 sujets est de 17,4 cm³, mais il est chez les sujets masculins de 16,3 cm³ et chez les sujets de sexe féminin de 18 cm³. Une corrélation faible mais significative a été trouvée entre l'âge du sujet et le volume ventriculaire, étant entendu que la taille du ventricule augmente avec l'âge.

     

Intracytoplasmic Junctions in Cardiac Muscle Cells

Junctional structures formed by two parts of the plasma membrane of the same cardiac muscle cell were observed in ventricular myocardium of: a) patients with neoplasms, aortic valvular disease or idiopathic hypertrophic subaortic stenosis and b) dogs subjected to prolonged normothermic anoxic cardiac arrest. Most of these structures had features of desmosomes; other, more complex structures had components with features of desmosomes, fasciae adherentes and nexuses, and, therefore, resembled intercalated discs. These intracytoplasmic junctions were localized to: a) the peripheral cytoplasm at the sides or ends of cells, b) narrow invaginations of plasma membranes, c) narrow zones of deep, broad plasmalemmal invaginations and d) narrow branches of T tubules. In patients with idiopathic hypertrophic subaortic stenosis or aortic valvular disease and in the dogs subjected to anoxic cardiac arrest, intracytoplasmic junctions were observed in hypertrophied or degenerated muscle cells which were located in areas of fibrosis and which showed loss of contact with adjacent cells. In patients with neoplasms, intracyto-plasmic junctions were found in degenerated cells which were located in areas of interstitial edema and which also showed loss of contact with adjacent cells. Our observations suggest that remodeling of cell surfaces following loss of intercellular contact is the most likely mechanism of formation of intracytoplasmic junctions.