Matteo Beltrami, Elisa Fedele, Carlo Fumagalli, Francesco Mazzarotto, Francesca Girolami, Cecilia Ferrantini, Raffaele Coppini, Lorenzo Tofani, Bruno Bertaccini, Corrado Poggesi, Iacopo Olivotto
{"title":"Long-Term Prevalence of Systolic Dysfunction in MYBPC3 Versus MYH7-Related Hypertrophic Cardiomyopathy.","authors":"Matteo Beltrami, Elisa Fedele, Carlo Fumagalli, Francesco Mazzarotto, Francesca Girolami, Cecilia Ferrantini, Raffaele Coppini, Lorenzo Tofani, Bruno Bertaccini, Corrado Poggesi, Iacopo Olivotto","doi":"10.1161/CIRCGEN.122.003832","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>At presentation, MYBPC3 patients were less frequently obstructive (15% versus 26%; <i>P</i>=0.005) and had lower LV ejection fraction compared with MYH7 (66±8% versus 68±8%, respectively; <i>P</i>=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; <i>P</i>=0.013). Prevalence of grade II/III diastolic dysfunction at final evaluation was comparable between MYBPC3 and MYH7 patients (<i>P</i>=0.509). In a Cox multivariable analysis, MYBPC3-positive status (hazard ratio, 2.53 [95% CI, 1.09-5.82]; <i>P</i>=0.029), age (hazard ratio, 1.03 [95% CI, 1.00-1.06]; <i>P</i>=0.027), and atrial fibrillation (hazard ratio, 2.39 [95% CI, 1.14-5.05]; <i>P</i>=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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10326,"journal":{"name":"Circulation: Genomic and Precision Medicine","volume":null,"pages":null},"PeriodicalIF":6.0000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation: Genomic and Precision Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCGEN.122.003832","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 1
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.
期刊介绍:
Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations.
Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.