Background: The 2 sarcomere genes most commonly associated with hypertrophic cardiomyopathy (HCM), MYBPC3 (myosin-binding protein C3) and MYH7 (β-myosin heavy chain), are indistinguishable at presentation, and genotype-phenotype correlations have been elusive. Based on molecular and pathophysiological differences, however, it is plausible to hypothesize a different behavior in myocardial performance, impacting lifetime changes in left ventricular (LV) function. Methods: We reviewed the initial and final echocardiograms of 402 consecutive HCM patients with pathogenic or likely pathogenic MYBPC3 (n=251) or MYH7 (n=151) mutations, followed over 9±8 years. Results: At presentation, MYBPC3 patients were less frequently obstructive (15% versus 26%; P=0.005) and had lower LV ejection fraction compared with MYH7 (66±8% versus 68±8%, respectively; P=0.03). Both HCM patients harboring MYBPC3 and MYH7 mutations exhibited a small but significant decline in LV systolic function during follow-up; however, new onset of severe LV systolic dysfunction (LV ejection fraction, <50%) was greater among MYBPC3 patients (15% versus 5% among MYH7; P=0.013). Prevalence of grade II/III diastolic dysfunction at final evaluation was comparable between MYBPC3 and MYH7 patients (P=0.509). In a Cox multivariable analysis, MYBPC3-positive status (hazard ratio, 2.53 [95% CI, 1.09-5.82]; P=0.029), age (hazard ratio, 1.03 [95% CI, 1.00-1.06]; P=0.027), and atrial fibrillation (hazard ratio, 2.39 [95% CI, 1.14-5.05]; P=0.020) were independent predictors of severe systolic dysfunction. No statistically significant differences occurred with regard to incidence of atrial fibrillation, heart failure, appropriate implanted cardioverter defibrillator shock, or cardiovascular death. Conclusions: MYBPC3-related HCM showed increased long-term prevalence of systolic dysfunction compared with MYH7, in spite of similar outcome. Such observations suggest different pathophysiology of clinical progression in the 2 subsets and may prove relevant for understanding of genotype-phenotype correlations in HCM.

Long-Term Prevalence of Systolic Dysfunction in MYBPC3 Versus MYH7-Related Hypertrophic Cardiomyopathy / Beltrami, Matteo; Fedele, Elisa; Fumagalli, Carlo; Mazzarotto, Francesco; Girolami, Francesca; Ferrantini, Cecilia; Coppini, Raffaele; Tofani, Lorenzo; Bertaccini, Bruno; Poggesi, Corrado; Olivotto, Iacopo. - In: CIRCULATION. - ISSN 2574-8300. - ELETTRONICO. - (2023), pp. 1-9. [10.1161/CIRCGEN.122.003832]

Long-Term Prevalence of Systolic Dysfunction in MYBPC3 Versus MYH7-Related Hypertrophic Cardiomyopathy

Beltrami, Matteo;Fumagalli, Carlo;Mazzarotto, Francesco;Girolami, Francesca;Ferrantini, Cecilia;Coppini, Raffaele;Tofani, Lorenzo;Bertaccini, Bruno;Poggesi, Corrado;Olivotto, Iacopo
2023

Abstract

Background: The 2 sarcomere genes most commonly associated with hypertrophic cardiomyopathy (HCM), MYBPC3 (myosin-binding protein C3) and MYH7 (β-myosin heavy chain), are indistinguishable at presentation, and genotype-phenotype correlations have been elusive. Based on molecular and pathophysiological differences, however, it is plausible to hypothesize a different behavior in myocardial performance, impacting lifetime changes in left ventricular (LV) function. Methods: We reviewed the initial and final echocardiograms of 402 consecutive HCM patients with pathogenic or likely pathogenic MYBPC3 (n=251) or MYH7 (n=151) mutations, followed over 9±8 years. Results: At presentation, MYBPC3 patients were less frequently obstructive (15% versus 26%; P=0.005) and had lower LV ejection fraction compared with MYH7 (66±8% versus 68±8%, respectively; P=0.03). Both HCM patients harboring MYBPC3 and MYH7 mutations exhibited a small but significant decline in LV systolic function during follow-up; however, new onset of severe LV systolic dysfunction (LV ejection fraction, <50%) was greater among MYBPC3 patients (15% versus 5% among MYH7; P=0.013). Prevalence of grade II/III diastolic dysfunction at final evaluation was comparable between MYBPC3 and MYH7 patients (P=0.509). In a Cox multivariable analysis, MYBPC3-positive status (hazard ratio, 2.53 [95% CI, 1.09-5.82]; P=0.029), age (hazard ratio, 1.03 [95% CI, 1.00-1.06]; P=0.027), and atrial fibrillation (hazard ratio, 2.39 [95% CI, 1.14-5.05]; P=0.020) were independent predictors of severe systolic dysfunction. No statistically significant differences occurred with regard to incidence of atrial fibrillation, heart failure, appropriate implanted cardioverter defibrillator shock, or cardiovascular death. Conclusions: MYBPC3-related HCM showed increased long-term prevalence of systolic dysfunction compared with MYH7, in spite of similar outcome. Such observations suggest different pathophysiology of clinical progression in the 2 subsets and may prove relevant for understanding of genotype-phenotype correlations in HCM.
2023
1
9
Goal 3: Good health and well-being
Beltrami, Matteo; Fedele, Elisa; Fumagalli, Carlo; Mazzarotto, Francesco; Girolami, Francesca; Ferrantini, Cecilia; Coppini, Raffaele; Tofani, Lorenzo; Bertaccini, Bruno; Poggesi, Corrado; Olivotto, Iacopo
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1320312
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