ArticleThe Journal of clinical investigation2000
An abnormal Ca(2+) response in mutant sarcomere protein-mediated familial hypertrophic cardiomyopathy.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00319982 (Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem), which is not on this map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Treatment of Preclinical Hypertrophic Cardiomyopathy With Diltiazem
Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 229 citations in OpenAlex.
- Phenotypic Spectrum of Subclinical Sarcomere-Related Hypertrophic Cardiomyopathy and Transition to Overt Disease.Circulation. Genomic and precision medicine · 2024Pooled it
- Diltiazem treatment for pre-clinical hypertrophic cardiomyopathy sarcomere mutation carriers: a pilot randomized trial to modify disease expression.JACC. Heart failure · 2015Trial
- Divergent myocardial functional adaptation in hypertrophic cardiomyopathy versus hypertensive left ventricular hypertrophy: insights from longitudinal strain and non-invasive myocardial work.Journal of echocardiography · 2026Article
- Redox Imbalance and Genetic Mutations in Heart Failure: Synergistic Mechanisms and Therapeutic Strategies.Genes · 2026Review
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Contribution of hypoxia-inducible factor 1alpha to pathogenesis of sarcomeric hypertrophic cardiomyopathy.Scientific reports · 2025Article
- Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2024Article
- Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts.bioRxiv : the preprint server for biology · 2024Article
- MYH7 in cardiomyopathy and skeletal muscle myopathy.Molecular and cellular biochemistry · 2024Review
- Cytoskeletal disarray increases arrhythmogenic vulnerability during sympathetic stimulation in a model of hypertrophic cardiomyopathy.Scientific reports · 2023Article
- Article
- Review
- Lumican accumulates with fibrillar collagen in fibrosis in hypertrophic cardiomyopathy.ESC heart failure · 2023Article
- Cardiac Resynchronization Therapy and Hypertrophic Cardiomyopathy: A Comprehensive Review.Biomedicines · 2023Review
- RBPMS2 Is a Myocardial-Enriched Splicing Regulator Required for Cardiac Function.Circulation research · 2022Article
- Cardiovascular effects of immunosuppression agents.Frontiers in cardiovascular medicine · 2022Review
- Mass-Spectrometry-Based Functional Proteomic and Phosphoproteomic Technologies and Their Application for Analyzing Ex Vivo and In Vitro Models of Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2021Review
- Titin M-line insertion sequence 7 is required for proper cardiac function in mice.Journal of cell science · 2021Article
- Preventative therapeutic approaches for hypertrophic cardiomyopathy.The Journal of physiology · 2021Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dominant-negative sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), a disease characterized by left-ventricular hypertrophy, angina, and dyspnea that can result in sudden death. We report here that a murine model of FHC bearing a cardiac myosin heavy-chain gene missense mutation (alphaMHC(403/+)), when treated with calcineurin inhibitors or a K(+)-channel agonist, developed accentuated hypertrophy, worsened histopathology, and was at risk for early death. Despite distinct pharmacologic targets, each agent augmented diastolic Ca(2+) concentrations in wild-type cardiac myocytes; alphaMHC(403/+) myocytes failed to respond. Pretreatment with a Ca(2+)-channel antagonist abrogated diastolic Ca(2+) changes in wild-type myocytes and prevented the exaggerated hypertrophic response of treated alphaMHC(403/+) mice. We conclude that FHC-causing sarcomere protein gene mutations cause abnormal Ca(2+) responses that initiate a hypertrophic response. These data define an important Ca(2+)-dependent step in the pathway by which mutant sarcomere proteins trigger myocyte growth and remodel the heart, provide definitive evidence that environment influences progression of FHC, and suggest a rational therapeutic approach to this prevalent human disease.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.