Correlation Between Genotype And Myocardial Fibrosis And Clinical Prognosis In Patients With Hypertrophic Cardiomyopath

Background and objectiveHypertrophic cardiomyopathy(HCM)is the most common hereditary cardiomyopathy,accounting for about 1/500 of the normal population.The clinical manifestations showed great heterogeneity,ranging from asymptomatic to heart failure,malignant arrhythmia and sudden cardiac death.Sarcomere gene mutation(SARC)and myocardial fibrosis are both associated with poor clinical outcomes in HCM patients.The aim of this study was to determine the relationship between sarcomere gene mutation and myocardial fibrosis measured by both histopathology and late gadolinium enhancement(LGE)in cardiac magnetic resonance imaging(CMR).MethodsA total of 227 HCM patients who underwent septal myectomy and completed genetic testing and CMR were enrolled in this study.Patients were divided into SARCgroup and SARC+group by the existence of pathogenic/likely pathogenic sarcomere gene mutation.We retrospectively analyzed basic characteristics,sarcomere gene mutation and myocardial fibrosis measured by CMR and histopathology.ResultsIn our study,the mean age was 43 years old,and 152 patients(67.0%)were male.A total of 107 patients(47.1%)carried sarcomere gene mutation.A correlation was found between the histopathological myocardial fibrosis and CMR-LGE(LGE+14.3±7.5%VS LGE-9.0±4.3%;P=0.001;LGE quantification r=0.314;P<0.001).HCM patients with SARC+showed a high probability of fibrosis both in histopathology(myocardial fibrosis ratio 15.3±8,0%VS 12.4±6.5%;P=0.003)and CMR examination(LGE+98.1%VS 84.2%;LGE quantification 8.3%VS 5.8%;both P<0.001).Linear regression analysis showed that sarcomere gene mutation(B=2.661;P=0.005)and left atrial diameter(B=0.240;P=0.001)were independent risk factors for histopathological myocardial fibrosis.Also,the myocardial fibrosis ratio was significantly higher in the MYH7 group(MYH7 18.1±9.6%VS MYBPC3 13.1±5.2%;P=0.019).ConclusionsHCM patients carried with sarcomere gene mutation had a higher myocardial fibrosis extent than patients without mutation,and a significant difference in myocardial fibrosis was also observed between the MYBPC3 and MYH7 groups.In addition,a high consistency was found between CMR-LGE and histopathological myocardial fibrosis in HCM patients.Background and objectiveHypertrophic cardiomyopathy(HCM)patients are often associated with mitral valve abnormalities,mainly manifested in mitral valve elongation.Whether mitral valve elongation is a result of genetics or hemodynamics remains controversial.This study was aimed to explore the correlation between sarcomere gene mutation(SARC)and mitral valve length in patients with hypertrophic cardiomyopathy.MethodsThree hundred and forty-three HCM patients who underwent surgery and performed genetic testing and cardiac magnetic resonance(CMR)were enrolled.We retrospectively analyzed basic characteristics,sarcomere gene mutation and mitral valve length(AML:anterior mitral valve length;PML:posterior mitral valve length)measured in CMR.ResultsMean age was 44 years old,and 212(61.8%)were male.The leaflet lengths of SARC+patients were significantly longer than those of SARC-(AML25.34±4.09 VS 23.64±4.29 mm;PML 12.67±2.55 VS 11.46±2.44 mm;both P<0.001),even after adjusted by body surface area(iAML:14.59±2.90 VS 13.46±2.67 mm/m2;P=0.001;iPML:7.27±1.58 VS 6.52±1.47 mm/m2;P<0.001).After linear regression analysis,age(B=-0.101;P<0.001),interaction between SARC and age(B=0.075;P=0.037),left atrial diameter(B=0.100;P=0.002)and systolic anterior motion(B=2.131;P=0.038)were independent related factors of AML.SARC(B=1.232;P<0.001),interventricular septal thickness(B=0.100;P=0.018),left ventricular end-diastole diameter(B=0.081;P=0.001)and systolic anterior motion(B=1.307;P=0.037)were independent risk factors of PML.ConclusionsSARC gene mutation was an independent risk factor of posterior mitral valve length in hypertrophic cardiomyopathy patients,and can increase risk of anterior mitral valve elongation.Background and objectiveThe clinical manifestations showed great heterogeneity in hypertrophic cardiomyopathy(HCM)patients,ranging from asymptomatic to malignant arrhythmia,sudden death and heart failure.Many studies showed that myocardial fibrosis was associated with poor clinical outcomes in HCM patients.Due to the paucity of myocardium tissue,previous studies generally assessed myocardial fibrosis by cardiac magnetic resonance.The aim of this study was to figure out the relationship between myocardial fibrosis measured by histopathology and clinical prognosis.MethodsA total of 423 HCM patients who underwent septal myectomy were enrolled in this study.Patients were divided into mild,moderate and severe myocardial fibrosis group by the pathological fibrosis extent.Patients were followed up regularly after surgery to record their survival status and adverse events.The primary endpoints were composite adverse events of cardiovascular death,heart failure requiring hospitalization,new-onset atrial fibrillation and new-onset stroke.ResultsIn our study,the mean age was 46 years old,and 270 patients(63.8%)were male.With a median follow-up of 29.43 months(interquartile range:19.67-38.03 months),25 patients(6.4%)had primary endpoint events.4(1.0%)patients died of cardiovascular reason(3 patients suffered sudden cardiac death and 1 patient died of myocardial infarction),14(3.6%)patients were hospitalized due to heart failure,5(1.3%)patients had new-onset atrial fibrillation,and 2(0.5%)patients had new-onset stroke.The 3-year survival rate without the primary endpoint events was 95.0±1.0%.Kaplan-Meier survival analysis showed significant difference among the three groups in the primary endpoint event-free survival rate(Log rank P=0.043).Multivariate Cox regression analysis showed that age(Hazard Ratio=1.078,95%CI:1.030-1.129;P=0.001)and severe myocardial fibrosis(Hazard Ratio=4.133,95%CI:1.063-16.072;P=0.040)were independent risk factors for primary endpoint events in HCM patients.ConclusionsA significant difference was found in the occurrence of primary endpoint events among mild,moderate and severe myocardial fibrosis group.And severe myocardial fibrosis was an independent risk factor for primary endpoint events in HCM patients.