Skeletal Muscle Involvement in Patients With Truncations of Titin and Familial Dilated Cardiomyopathy.

Background: Genetic variants in titin (TTN) are associated with dilated cardiomyopathy (DCM) and skeletal myopathy. However, the skeletal muscle phenotype in individuals carrying heterozygous truncating TTN variants (TTNtv), the leading cause of DCM, is understudied.

Objectives: This study aimed to assess the skeletal muscle phenotype associated with TTNtv.

Angiotensin receptor blockers in patients with hypertrophic cardiomyopathy: A comparison of VANISH and INHERIT randomized trials.

Purpose: To identify the cause of discrepancy between the INHERIT trial and VANISH trial in regards to disease modification of angiotensin receptor II blockers in hypertrophic cardiomyopathy (HCM).

Methods: We replicated the data analysis used in VANISH, converting individual change in each component of the composite endpoint into a z-score and applying this z-score to the INHERIT results.

Results: No significant improvement was identified in the composite z-score between the 2 groups at 12-month follow-up (P = .

Cardiac Remodeling in Subclinical Hypertrophic Cardiomyopathy: The VANISH Randomized Clinical Trial.

Importance: Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression.

Objective: To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM.

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

Background: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children.

Methods: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed.

Genome-wide meta-analysis identifies 93 risk loci and enables risk prediction equivalent to monogenic forms of venous thromboembolism.

We report a genome-wide association study of venous thromboembolism (VTE) incorporating 81,190 cases and 1,419,671 controls sampled from six cohorts. We identify 93 risk loci, of which 62 are previously unreported. Many of the identified risk loci are at genes encoding proteins with functions converging on the coagulation cascade or platelet function.

Family Screening in Dilated Cardiomyopathy: Prevalence, Incidence, and Potential for Limiting Follow-Up.

Background: According to patterns of inheritance and incomplete penetrance, fewer than half of relatives to dilated cardiomyopathy probands will develop disease.

Objectives: The purpose of this study was to investigate the prevalence and incidence, and to identify predictors of developing familial dilated cardiomyopathy (FDC) in relatives participating in family screening.

Methods: The study was a retrospective, longitudinal cohort study of families screened and followed from 2006 to 2020 at a regional assembly of clinics for inherited cardiomyopathies.

Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside in the gene, which encodes the PKP2 protein (plakophilin-2).

Methods: We describe a comprehensive characterization of the ARVC molecular landscape as determined by high-resolution mass spectrometry, RNA sequencing, and transmission electron microscopy of right ventricular biopsy samples obtained from patients with ARVC with mutations and left ventricular ejection fraction >45%.

Hemodynamic Effects of Cyclic Guanosine Monophosphate-Dependent Signaling Through β3 Adrenoceptor Stimulation in Patients With Advanced Heart Failure: A Randomized Invasive Clinical Trial.

Background: β3-AR (β3-adrenergic receptor) stimulation improved systolic function in a sheep model of systolic heart failure (heart failure with reduced ejection fraction [HFrEF]). Exploratory findings in patients with New York Heart Association functional class II HFrEF treated with the β3-AR-agonist mirabegron supported this observation. Here, we measured the hemodynamic response to mirabegron in patients with severe HFrEF.

Electrocardiographic Findings, Arrhythmias, and Left Ventricular Involvement in Familial ST-Depression Syndrome.

Background: Familial ST-depression syndrome is an inherited disease characterized by persistent, nonischemic ST-deviations, and risk of arrhythmias and heart failure. We aimed at further characterizing the ECG, arrhythmias, and structural characteristics associated with this novel syndrome.

Methods: Retrospective analysis of data from consecutive families with familial ST-depression Syndrome in Denmark.

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

Background: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both.

Objective: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures.

Dilated cardiomyopathy caused by truncating titin variants: long-term outcomes, arrhythmias, response to treatment and sex differences.

Background: Truncating variants in titin (TTNtv) are the most common cause of dilated cardiomyopathy (DCM). We evaluated the genotype-phenotype correlation in TTNtv-DCM, with a special focus on long-term outcomes, arrhythmias, response to treatment and sex-related presentation.

Methods: Data on patient characteristics and outcomes were collected retrospectively from electronic health records of patients genotyped at two Danish heart transplantation centres.

Results of an open label feasibility study of sodium valproate in people with McArdle disease.

McArdle disease results from a lack of muscle glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy.

Hydroxylated Long-Chain Acylcarnitines are Biomarkers of Mitochondrial Myopathy.

Context: Plasma acylcarnitines are biomarkers of β-oxidation and are useful in diagnosing several inborn errors of metabolism but have never been investigated systematically in patients with mitochondrial myopathy.

Objective: We hypothesized that acylcarnitines can also be biomarkers of mitochondrial myopathy and sought to investigate the prevalence and pattern of elevated acylcarnitines.

Design: This was a prospective cohort study of patients with confirmed mitochondrial myopathy followed at Copenhagen Neuromuscular Center, Rigshospitalet, Copenhagen, Denmark.

Moderate-intensity aerobic exercise improves physical fitness in bethlem myopathy.

Introduction: Bethlem myopathy is caused by dysfunctional collagen VI assembly, leading to varying degrees of hyperlaxity, contractures and muscle weakness. Previous studies demonstrate that cardiovascular training is safe and beneficial in patients with myopathies. However, exercise exacerbates the dystrophic phenotype in collagen VI-knockout mice.

Adaptations in Mitochondrial Enzymatic Activity Occurs Independent of Genomic Dosage in Response to Aerobic Exercise Training and Deconditioning in Human Skeletal Muscle.

Mitochondrial DNA (mtDNA) replication is thought to be an integral part of exercise-training-induced mitochondrial adaptations. Thus, mtDNA level is often used as an index of mitochondrial adaptations in training studies. We investigated the hypothesis that endurance exercise training-induced mitochondrial enzymatic changes are independent of genomic dosage by studying mtDNA content in skeletal muscle in response to six weeks of knee-extensor exercise training followed by four weeks of deconditioning in one leg, comparing results to the contralateral untrained leg, in 10 healthy, untrained male volunteers.

[Precision cardiology].

Cardiology relies on a huge amount of data derived from clinical observations, case-specific considerations and randomised controlled trials. At best, medical intervention relieves symptoms and reduces disease consequences or complications. Rarely, it redirects the cause.

Progressive fat replacement of muscle contributes to the disease mechanism of patients with single, large-scale deletions of mitochondrial DNA.

Muscle dysfunction in mitochondrial myopathy is predominantly caused by insufficient generation of energy. We hypothesise that structural changes in muscles could also contribute to their pathophysiology. The aims of this study were to determine fat fractions and strength in selected muscles in patients with chronic progressive external ophthalmoplegia (CPEO), and compare progression of muscle fat fraction with age in individuals with CPEO vs.

Impaired glycogen breakdown and synthesis in phosphoglucomutase 1 deficiency.

Objective: We investigated metabolism and physiological responses to exercise in an 18-year-old woman with multiple congenital abnormalities and exertional muscle fatigue, tightness, and rhabdomyolysis.

Methods: We studied biochemistry in muscle and fibroblasts, performed mutation analysis, assessed physiological responses to forearm and cycle-ergometer exercise combined with stable-isotope techniques and indirect calorimetry, and evaluated the effect of IV glucose infusion and oral sucrose ingestion on the exercise response.

Results: Phosphoglucomutase type 1 (PGM1) activity in muscle and fibroblasts was severely deficient and PGM1 in muscle was undetectable by Western blot.

Skeletal muscle metabolism during prolonged exercise in Pompe disease.

Objective: Pompe disease (glycogenosis type II) is caused by lysosomal alpha-glucosidase deficiency, which leads to a block in intra-lysosomal glycogen breakdown. In spite of enzyme replacement therapy, Pompe disease continues to be a progressive metabolic myopathy. Considering the health benefits of exercise, it is important in Pompe disease to acquire more information about muscle substrate use during exercise.

MRI as outcome measure in facioscapulohumeral muscular dystrophy: 1-year follow-up of 45 patients.

There is no effective treatment available for facioscapulohumeral muscular dystrophy type 1 (FSHD1), but emerging therapies are under way that call for a better understanding of natural history in this condition. In this prospective, longitudinal study, we used quantitative MRI to assess yearly disease progression in patients with FSHD1. Ambulatory patients with confirmed diagnosis of FSHD1 (25/20 men/women, age 20-75 years, FSHD score: 0-12) were tested with 359-560-day interval between tests.