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Published on: August 8, 2022
Restrictive cardiomyopathy: from genetics and clinical overview to animal modeling
Michelle Chintanaphol1, Buyan-Ochir Orgil2,3, Neely R Alberson2,3
1College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Insights
Restrictive cardiomyopathy (RCM) is a rare heart muscle disease causing stiff ventricles. Research into its genetic causes and cellular mechanisms is crucial for developing new treatments.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Restrictive cardiomyopathy (RCM) is a rare, severe heart muscle disorder.
- It causes diastolic dysfunction, characterized by abnormal relaxation and stiff ventricles.
- RCM accounts for 2-5% of pediatric cardiomyopathy cases with notable survival rates.
Purpose of the Study:
- To summarize the characteristics, causes, and known genetic links of RCM.
- To highlight current understanding of RCM pathogenesis.
- To emphasize the need for further research into RCM mechanisms for therapeutic development.
Main Methods:
- Literature review of RCM characteristics, prevalence, and survival rates.
- Analysis of genetic associations and etiological factors.
- Summary of revealed pathogenetic mechanisms from cell and animal models.
Main Results:
- RCM presents with diastolic dysfunction, atrial enlargement, and preserved ventricular size/systolic function.
- Familial RCM comprises 30% of cases, linked to genes like cTnT, cTnI, and MYH7.
- Pathogenesis involves increased Ca2+ sensitivity, sarcomere disruption, and protein aggregates.
Conclusions:
- Understanding RCM's genetic basis and pathogenesis is vital.
- Further research is necessary to develop novel therapeutic strategies for RCM.
- Targeting underlying mechanisms may reverse restrictive cardiomyopathic phenotypes.
Abstract:
Restrictive cardiomyopathy (RCM), a potentially devastating heart muscle disorder, is characterized by diastolic dysfunction due to abnormal muscle relaxation and myocardial stiffness resulting in restrictive filling of the ventricles. Diastolic dysfunction is often accompanied by left atrial or bi-atrial enlargement and normal ventricular size and systolic function. RCM is the rarest form of cardiomyopathy, accounting for 2-5% of pediatric cardiomyopathy cases, however, survival rates have been reported to be 82%, 80%, and 68% at 1-, 2-, and 5-years after diagnosis, respectively. RCM can be idiopathic, familial, or secondary to a systemic disorder, such as amyloidosis, sarcoidosis, and hereditary hemochromatosis. Approximately 30% of cases are familial RCM, and the genes that have been linked to RCM are cTnT, cTnI, MyBP-C, MYH7, MYL2, MYL3, DES, MYPN, TTN, BAG3, DCBLD2, LNMA, and FLNC. Increased Ca2+ sensitivity, sarcomere disruption, and protein aggregates are some of the few mechanisms of pathogenesis that have been revealed by studies utilizing cell lines and animal models. Additional exploration into the pathogenesis of RCM is necessary to create novel therapeutic strategies to reverse restrictive cardiomyopathic phenotypes.
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