A reference equation for maximal aerobic power for treadmill and cycle ergometer exercise testing: Analysis from the FRIEND registry.

Background Maximal oxygen uptake (VOmax) is a powerful predictor of health outcomes. Valid and portable reference values are integral to interpreting measured VOmax; however, available reference standards lack validation and are specific to exercise mode. This study was undertaken to develop and validate a single equation for normal standards for VOmax for the treadmill or cycle ergometer in men and women.

Mindfulness Among Genetic Counselors Is Associated with Increased Empathy and Work Engagement and Decreased Burnout and Compassion Fatigue.

Genetic counselors experience high rates of compassion fatigue and an elevated risk for burnout, both of which can negatively impact patient care and retention in the profession. In other healthcare professions, mindfulness training has been successfully used to address similar negative psychological sequelae and to bolster empathy, which is the foundation of our counseling work. We aimed to assess associations between mindfulness and key professional variables, including burnout, compassion fatigue, work engagement, and empathy.

Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel.

PurposeIntegrating genomic sequencing in clinical care requires standardization of variant interpretation practices. The Clinical Genome Resource has established expert panels to adapt the American College of Medical Genetics and Genomics/Association for Molecular Pathology classification framework for specific genes and diseases. The Cardiomyopathy Expert Panel selected MYH7, a key contributor to inherited cardiomyopathies, as a pilot gene to develop a broadly applicable approach.

Clinically impactful differences in variant interpretation between clinicians and testing laboratories: a single-center experience.

PurposeTo describe the frequency and nature of differences in variant classifications between clinicians and genetic testing laboratories.MethodsRetrospective review of variants identified through genetic testing ordered in routine clinical care by clinicians in the Stanford Center for Inherited Cardiovascular Disease. We compared classifications made by clinicians, the testing laboratory, and other laboratories in ClinVar.

Clinical Cardiovascular Genetic Counselors Take a Leading Role in Team-based Variant Classification.

We sought to delineate the genetic test review and interpretation practices of clinical cardiovascular genetic counselors. A one-time anonymous online survey was taken by 46 clinical cardiovascular genetic counselors recruited through the National Society of Genetic Counselors Cardiovascular Special Interest Group. Nearly all (95.

Care in Specialized Centers and Data Sharing Increase Agreement in Hypertrophic Cardiomyopathy Genetic Test Interpretation.

Background: Clinically impactful differences in the interpretation of genetic test results occur between laboratories and clinicians. To improve the classification of variants, a better understanding of why discrepancies occur and how they can be reduced is needed.

Methods And Results: We examined the frequency, causes, and resolution of discordant variant classifications in the Sarcomeric Human Cardiomyopathy Registry (SHaRe), a consortium of international centers with expertise in the clinical management and genetic architecture of hypertrophic cardiomyopathy.

A method for determining exercise oscillatory ventilation in heart failure: Prognostic value and practical implications.

Background: Exercise oscillatory ventilation (EOV) has been shown to be a powerful prognostic marker in chronic heart failure (CHF). However, EOV is poorly defined, its measurement lacks standardization and it is underutilized in clinical practice. The purpose of this pilot study was to investigate the prognostic value of a modified definition of EOV in patients with CHF.

Role of Genetic Testing in Inherited Cardiovascular Disease: A Review.

Importance: Genetic testing is a valuable tool for managing inherited cardiovascular disease in patients and families, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies and inherited arrhythmias. By identifying the molecular etiology of disease, genetic testing can improve diagnostic accuracy and refine family management. However, unique features associated with genetic testing affect the interpretation and application of results and differentiate it from traditional laboratory-based diagnostics.

Contractile reserve and cardiopulmonary exercise parameters in patients with dilated cardiomyopathy, the two dimensions of exercise testing.

Background: Left ventricular (LV) contractile reserve assessed using imaging and cardiopulmonary exercise testing (CPX) has been shown to predict outcome in patients with dilated cardiomyopathy (DCM). Few clinical studies have, however, analyzed the relationship between them.

Methods: A cohort of 75 ambulatory patients with DCM underwent stress treadmill echocardiography with CPX.

Long-read genome sequencing identifies causal structural variation in a Mendelian disease.

PurposeCurrent clinical genomics assays primarily utilize short-read sequencing (SRS), but SRS has limited ability to evaluate repetitive regions and structural variants. Long-read sequencing (LRS) has complementary strengths, and we aimed to determine whether LRS could offer a means to identify overlooked genetic variation in patients undiagnosed by SRS.MethodsWe performed low-coverage genome LRS to identify structural variants in a patient who presented with multiple neoplasia and cardiac myxomata, in whom the results of targeted clinical testing and genome SRS were negative.

A comparison of methods for determining the ventilatory threshold: implications for surgical risk stratification.

Purpose: The ventilatory threshold (VT) is an objective physiological marker of the capacity of aerobic endurance that has good prognostic applications in preoperative settings. Nevertheless, determining the VT can be challenging due to physiological and methodological issues, especially in evaluating surgical risk. The purpose of the current study was to compare different methods of determining VT and to highlight the implications for assessing perioperative risk.

A Reference Equation for Normal Standards for VO Max: Analysis from the Fitness Registry and the Importance of Exercise National Database (FRIEND Registry).

Existing normal standards for maximal oxygen uptake (VO max) are problematic because they tend to be population specific, lack normal distribution and portability, and are poorly represented by women. The objective of the current study was to apply the Fitness Registry and the Importance of Exercise: A National Data Base (FRIEND) Registry to improve upon previous regression formulas for normal standards for VO max using treadmill testing. Maximal treadmill tests were performed in 7783 healthy men and women (20-79years; maximal RER >1.

High-Intensity Interval Training in Patients With Heart Failure With Reduced Ejection Fraction.

Background: Small studies have suggested that high-intensity interval training (HIIT) is superior to moderate continuous training (MCT) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction. The present multicenter trial compared 12 weeks of supervised interventions of HIIT, MCT, or a recommendation of regular exercise (RRE).

Methods: Two hundred sixty-one patients with left ventricular ejection fraction ≤35% and New York Heart Association class II to III were randomly assigned to HIIT at 90% to 95% of maximal heart rate, MCT at 60% to 70% of maximal heart rate, or RRE.

Exercise restrictions trigger psychological difficulty in active and athletic adults with hypertrophic cardiomyopathy.

Objective: We examined the extent and nature of the psychological difficulty experienced by athletic adults with hypertrophic cardiomyopathy (HCM), correlates of that difficulty and coping mechanisms.

Methods: A survey assessed athletic history and psychological impact of exercise restrictions. LASSO penalised linear regression identified factors associated with psychological difficulty.

Early somatic mosaicism is a rare cause of long-QT syndrome.

Somatic mosaicism, the occurrence and propagation of genetic variation in cell lineages after fertilization, is increasingly recognized to play a causal role in a variety of human diseases. We investigated the case of life-threatening arrhythmia in a 10-day-old infant with long QT syndrome (LQTS). Rapid genome sequencing suggested a variant in the sodium channel Na1.

Taming the genome: towards better genetic test interpretation.

Advances in sequencing technology have taught us much about the human genome, including how difficult it is to interpret rare variation. Improvements in genetic test interpretation are likely to come through data sharing, international collaborative efforts to develop disease-gene specific guidelines, and computational analyses using big data.

Interdisciplinary psychosocial care for families with inherited cardiovascular diseases.

Inherited cardiovascular diseases pose unique and complex psychosocial challenges for families, including coming to terms with life-long cardiac disease, risk of sudden death, grief related to the sudden death of a loved one, activity restrictions, and inheritance risk to other family members. Psychosocial factors impact not only mental health but also physical health and cooperation with clinical recommendations. We describe an interdisciplinary approach to the care of families with inherited cardiovascular disease, in which psychological care provided by specialized cardiac genetic counselors, nurses, and psychologists is embedded within the cardiovascular care team.

Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation.

Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood.

Effect of lossy compression of quality scores on variant calling.

Recent advancements in sequencing technology have led to a drastic reduction in genome sequencing costs. This development has generated an unprecedented amount of data that must be stored, processed, and communicated. To facilitate this effort, compression of genomic files has been proposed.

Medical implications of technical accuracy in genome sequencing.

Background: As whole exome sequencing (WES) and whole genome sequencing (WGS) transition from research tools to clinical diagnostic tests, it is increasingly critical for sequencing methods and analysis pipelines to be technically accurate. The Genome in a Bottle Consortium has recently published a set of benchmark SNV, indel, and homozygous reference genotypes for the pilot whole genome NIST Reference Material based on the NA12878 genome.

Methods: We examine the relationship between human genome complexity and genes/variants reported to be associated with human disease.

Sequence to Medical Phenotypes: A Framework for Interpretation of Human Whole Genome DNA Sequence Data.

High throughput sequencing has facilitated a precipitous drop in the cost of genomic sequencing, prompting predictions of a revolution in medicine via genetic personalization of diagnostic and therapeutic strategies. There are significant barriers to realizing this goal that are related to the difficult task of interpreting personal genetic variation. A comprehensive, widely accessible application for interpretation of whole genome sequence data is needed.

Lean body mass and risk of incident atrial fibrillation in post-menopausal women.

Aims: High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF.

Methods And Results: The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998.