Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3–E334K

Yang, Qianli; Zuo, Li; Ma, Zhiling; Zhu, Xiaoli; Wang, Xuan-Ying; Wang, Bo; Zhao, Xueqin; Zhang, Juan; Wang, Yue; Zhang, Yanmin; Liu, Liwen

doi:10.1007/s00380-021-01834-x

Cited by 3 publications

(3 citation statements)

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“…The age difference may be explained by either later clinical manifestation or delayed diagnosis of HOCM in women. The first explanation is supported by studies that observed a later disease penetrance in women compared with men with the same causing genotype 5 6 27. In addition, Schuldt et al observed that cardiac tissue samples from women undergoing SM had higher levels of heat shock proteins and that sex hormone-associated transcription factors lead to variations in protein expression contributing to the delayed disease onset 28.…”

Section: Discussionmentioning

confidence: 95%

“…Although some sex-related differences were also observed in hypertrophic cardiomyopathy (HCM) studies,5 6 this did not have any influence on current guidelines 1. For instance, disease penetrance, symptom onset and severity of symptoms differ between women and men 5 6. Moreover, women were diagnosed later, had more severe symptoms, more often LVOT obstruction and arrhythmic events 7–15.…”

Section: Introductionmentioning

confidence: 99%

“…Gender has been shown to exert influence on the incidence and outcome of various cardiac diseases 4. Although some sex-related differences were also observed in hypertrophic cardiomyopathy (HCM) studies,5 6 this did not have any influence on current guidelines 1. For instance, disease penetrance, symptom onset and severity of symptoms differ between women and men 5 6.…”

Section: Introductionmentioning

confidence: 99%

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Gender disparities in alcohol septal ablation for hypertrophic obstructive cardiomyopathy

Lawin

Lawrenz

Marx

et al. 2022

Heart

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ObjectiveAlcohol septal ablation (ASA) improves symptoms in hypertrophic obstructive cardiomyopathy (HOCM). We conducted a large retrospective analysis investigating gender effects on outcome after ASA.Methods and results1367 ASAs between 2002 and 2020 were analysed. Women (47.2%) were older (66.0 years (IQR 55.0–74.0) vs 54.0 years (IQR 45.0–62.0); p<0.0001) with more severe symptoms. The interventricular septal diameter (IVSD) was higher in men (21.0 mm (IQR 19.0–24.0) vs 20.0 mm (IQR 18.0–23.0); p<0.0001) but the IVSD indexed to body surface area was higher in women (10.9 mm/m2 (IQR 9.7–12.7) vs 10.2 mm/m2 (IQR 9.0–11.7); p<0.0001). Women had lower exercise-induced left ventricular outflow tract gradients (LVOTG) 1–4 days after ASA (55.0 mm Hg (IQR 30.0–109.0) vs 71.0 mm Hg (IQR 37.0–115.0); p=0.0006). There was a trend for lower resting LVOTG 1–4 days after ASA (20.0 mm Hg (IQR 12.0–37.5) vs 22.0 mm Hg (IQR 13.0–40.0); p=0.0062) and lower exercise-induced LVOTG after 6 months in women (34.0 mm Hg (IQR 21.0–70.0) vs 43.5 mm Hg (IQR 25.0–74.8); p=0.0072), but this was not statistically significant after Bonferroni correction. More women developed atrioventricular (AV) block (20.3% vs 13.3%; p=0.0005) and required a pacemaker (17.4% vs 10.4%; p=0.0002) but not a cardioverter defibrillator (9.0% vs 11.6% in men; p=n .s.). However, in multivariable regression models, there was no evidence that sex independently influenced LVOTG and the occurrence of AV block.ConclusionFemale patients with HOCM were older and had more advanced disease at the time of ASA. Women had superior short-term haemodynamic response to ASA but more often developed AV block after ASA. These results are important to consider for sex-specific counselling before ASA.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gender disparities in alcohol septal ablation for hypertrophic obstructive cardiomyopathy

Lawin

Lawrenz

Marx

et al. 2022

Heart

View full text Add to dashboard Cite

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Hypertrophic cardiomyopathy in MYBPC3 carriers in aging

Ananthamohan,

Stelzer,

Sadayappan

2024

J Cardiovasc Aging

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Hypertrophic cardiomyopathy (HCM) is characterized by abnormal thickening of the myocardium, leading to arrhythmias, heart failure, and elevated risk of sudden cardiac death, particularly among the young. This inherited disease is predominantly caused by mutations in sarcomeric genes, among which those in the cardiac myosin binding protein-C3 (MYBPC3 ) gene are major contributors. HCM associated with MYBPC3 mutations usually presents in the elderly and ranges from asymptomatic to symptomatic forms, affecting numerous cardiac functions and presenting significant health risks with a spectrum of clinical manifestations. Regulation of MYBPC3 expression involves various transcriptional and translational mechanisms, yet the destiny of mutant MYBPC3 mRNA and protein in late-onset HCM remains unclear. Pathogenesis related to MYBPC3 mutations includes nonsense-mediated decay, alternative splicing, and ubiquitin-proteasome system events, leading to allelic imbalance and haploinsufficiency. Aging further exacerbates the severity of HCM in carriers of MYBPC3 mutations. Advancements in high-throughput omics techniques have identified crucial molecular events and regulatory disruptions in cardiomyocytes expressing MYBPC3 variants. This review assesses the pathogenic mechanisms that promote late-onset HCM through the lens of transcriptional, post-transcriptional, and post-translational modulation of MYBPC3 , underscoring its significance in HCM across carriers. The review also evaluates the influence of aging on these processes and MYBPC3 levels during HCM pathogenesis in the elderly. While pinpointing targets for novel medical interventions to conserve cardiac function remains challenging, the emergence of personalized omics offers promising avenues for future HCM treatments, particularly for late-onset cases.

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