Hypertrophic Cardiomyopathy

Marian, Ali J.

doi:10.1002/9780470691977.ch3

Cited by 3 publications

(3 citation statements)

References 220 publications

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“…For instance, HCM has strong genetic causal links, making genetic testing information particularly valuable, but because the data have been collected from predominantly White ancestry populations, it is unclear how representative it may for populations of other ancestries. 86 Incorporating VUS into multigene panels, especially when testing diverse ancestral populations, could help clarify their association with disease. In clinics today, even if a pathogenic mutation has not been identified after testing an index patient, non-White European patients diagnosed with cardiomyopathy may still present with (or eventually have) a strong familial pattern and be classified as having idiopathic cardiomyopathy.…”

Section: Potential Considerations To Bridge Disparities In Hereditary...mentioning

confidence: 99%

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives

Huang,

Verma,

Mok

et al. 2024

Glob Med Genet

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Background Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.

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Section: Potential Considerations To Bridge Disparities In Hereditary...mentioning

confidence: 99%

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives

Huang,

Verma,

Mok

et al. 2024

Glob Med Genet

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“…Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder affecting more than 1:500 in the general population [1][2][3] . HCM has always been defined with various myocardial changes and concentrating on disease-causing mutations related to sarcomeric genes [4][5][6] .…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy

Ibrahim

Latif

Roshdy

et al. 2023

Preprint

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Background and aims: Changes in the phenotype and genotype in Hypertrophic Obstructive Cardiomyopathy (HOCM) are thought to involve the myocardium as well as extracardiac tissues. The extent and significance of extra-myocardial changes has not been adequately studied. We here describe the structural and functional changes in the ascending aorta of HOCM patients. Methods: Changes in the aortic wall were studied in a cohort of 102 consecutive HOCM patients undergoing myectomy, and 10 normal controls. Biopsies were examined histologically, immunohistochemically and by electron microscopy. Changes in protein expression were quantified using morphometry and western blotting. Pulse wave velocity (PWV) was measured using Cardiac Magnetic Resonance (CMR), in 86 HCM patients compared to 166 age-matched normal controls. Results: In HCM, the number of medial lamellar units (MLU) was significantly decreased, associated with an increase in the interlamellar distance and a preserved thickness of the aortic wall, as compared to controls. Electron microscopy showed an altered lamellar structure with disorientation of elastin fibers from the circumferential direction. There was an altered composition and orientation of smooth muscle cells. In addition, there was a significant decrease in alpha-smooth muscle actin, smooth muscle myosin, smooth muscle 22 and integrin beta1, and a significant increase in calponin and caspase3. Fibulins 1, 2 and 5, had a reduced expression in HOCM aortic biopsies. Functionally, PWV was significantly higher in HOCM patients compared to healthy controls. Conclusion: In HOCM patients, specific molecular and structural changes in the composition and organisation of the arterial wall have been identified. This was associated with increased stiffness of the arterial wall. Keywords: HCM, Aortic wall, lamellae, ECM, PWV

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“…In contrast, conventional treatment for HCM in patients with phenocopy conditions is not expected to impart significant benefits [50]. The true incidence of phenocopy condition in patients with the clinical diagnosis of HCM is likely to be approximately 10% [47]. …”

Section: Introductionmentioning

confidence: 99%

Experimental Therapies in Hypertrophic Cardiomyopathy

Marian

2009

J. of Cardiovasc. Trans. Res.

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The quintessential clinical diagnostic phenotype of human hypertrophic cardiomyopathy (HCM) is primary cardiac hypertrophy. Cardiac hypertrophy is also a major determinant of mortality and morbidity including the risk of sudden cardiac death (SCD) in patients with HCM. Reversal and attenuation of cardiac hypertrophy and its accompanying fibrosis is expected to improve morbidity as well as decrease the risk of SCD in patients with HCM. The conventionally used pharmacological agents in treatment of patients with HCM have not been shown to reverse or attenuate established cardiac hypertrophy and fibrosis. An effective treatment of HCM has to target the molecular mechanisms that are involved in the pathogenesis of the phenotype. Mechanistic studies suggest that cardiac hypertrophy in HCM is secondary to activation of various hypertrophic signaling molecules and, hence, is potentially reversible. The hypothesis is supported by the results of genetic and pharmacological interventions in animal models. The results have shown potential beneficial effects of angiotensin II receptor blocker losartan, mineralocorticoid receptor blocker spironolactone, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors simvastatin and atorvastatin, and most recently, N-acetylcysteine (NAC) on reversal or prevention of hypertrophy and fibrosis in HCM. The most promising results have been obtained with NAC, which through multiple thiol-responsive mechanisms completely reversed established cardiac hypertrophy and fibrosis in three independent studies. Pilot studies with losartan and statins in humans have established the feasibility of such studies. The results in animal models have firmly established the reversibility of established cardiac hypertrophy and fibrosis in HCM and have set the stage for advancing the findings in the animal models to human patients with HCM through conducting large-scale efficacy studies.

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Hypertrophic Cardiomyopathy

Cited by 3 publications

References 220 publications

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives

Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives

Structural and Functional Characterization of the Aorta in Hypertrophic Obstructive Cardiomyopathy

Experimental Therapies in Hypertrophic Cardiomyopathy

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