Background: Host autoimmune activity in myocarditis has been proposed to play a role in development of cardiac disease, but evidence of autoimmunity and relationship to outcomes have not been evaluated in pediatric myocarditis.
Methods: We performed a multi-institutional study of children with clinical myocarditis. Newly diagnosed patients were followed for up to 12 months and previously diagnosed patients at a single follow-up for serum levels of autoantibodies to human cardiac myosin, beta-adrenergic receptors 1 and 2, muscarinic-2 receptors, and antibody-mediated protein kinase A (PKA) activation in heart cells in culture. Results were compared with those of healthy control children.
Results: Both previously diagnosed patient at follow-up (P = .0061) and newly diagnosed patients at presentation (P = .0127) had elevated cardiac myosin antibodies compared with control subjects. Antibody levels were not associated with recovery status at follow-up in either group. PKA activation was higher at presentation in the newly diagnosed patients who did not recovery normal function (P = .042).
Conclusions: Children with myocarditis have evidence of autoantibodies against human cardiac myosin at diagnosis and follow-up compared with control subjects. Differences in antibody-mediated cell signaling may contribute to differences in patient outcomes, as suggested by elevated antibody-mediated PKA activation in heart cells by the serum from nonrecovered patients.
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http://dx.doi.org/10.1016/j.cardfail.2016.02.009 | DOI Listing |
CPT Pharmacometrics Syst Pharmacol
January 2025
Huashan Hospital, Fudan University, Shanghai, China.
Mavacamten is a cardiac myosin inhibitor for adults with obstructive hypertrophic cardiomyopathy (HCM). Dose optimization is performed 4 weeks after starting mavacamten, guided by periodic echo measurements of Valsalva left ventricular outflow tract gradient (VLVOTg) and left ventricular ejection fraction (LVEF). Previously, a population pharmacokinetic (PPK) model was developed and exposure-response (E-R) of VLVOTg (efficacy) and LVEF (safety) was used to identify the mavacamten titration regimen with the optimal benefit/risk ratio, now included in the US prescribing information.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
PhysioLab, University of Florence, 50019 Sesto Fiorentino, Italy.
In maximally Ca-activated demembranated fibres from the mammalian skeletal muscle, the depression of the force by lowering the temperature below the physiological level (~35 °C) is explained by the reduction of force in the myosin motor. Instead, cooling is reported to not affect the force per motor in Ca-activated cardiac trabeculae from the rat ventricle. Here, the mechanism of the cardiac performance depression by cooling is reinvestigated with fast sarcomere-level mechanics.
View Article and Find Full Text PDFGenes (Basel)
January 2025
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua Medical School, 35128 Padova, Italy.
Since its first pathological description over 65 years ago, hypertrophic cardiomyopathy (HCM), with a worldwide prevalence of 1:500, has emerged as the most common genetically determined cardiac disease. Diagnostic work-up has dramatically improved over the last decades, from clinical suspicion and abnormal electrocardiographic findings to hemodynamic studies, echocardiography, contrast-enhanced cardiac magnetic resonance, and genetic testing. The implementation of screening programs and the use of implantable cardioverter defibrillators (ICDs) for high-risk individuals have notably reduced arrhythmic sudden deaths, altering the disease's mortality profile.
View Article and Find Full Text PDFAm J Cardiol
January 2025
Department of Cardiovascular Medicine, Baystate Medical Center and Division of Cardiovascular Medicine, University of Massachusetts-Baystate, Springfield, Massachusetts, USA. Electronic address: https://twitter.com/AGoldsweig.
Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by myocardial hypertrophy, which can obstruct left ventricular outflow. Cardiac myosin inhibitors (CMIs) have emerged as a novel therapeutic agent targeting cardiac muscle hypercontractility.
Objective: To compare the efficacy and safety of CMIs mavacamten and aficamten vs.
Gene
January 2025
Laboratory of Molecular Biology, Department of Biochemistry, School of Basic Medical Sciences, Anhui Medical University, Hefei, China. Electronic address:
Hyperlipidemia and myocardial apoptosis caused by myocardial ischemia are the main causes of high mortality rates in cardiovascular diseases. Previous studies have indicated that Krüppel-like factor 4 (KLF4) is involved in the induction of cardiac myocyte apoptosis under various stress conditions. In current study, we discovered that KLF4 also participates in palmitic acid (PA)-induced cardiac myocyte apoptosis.
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