| Background Hypertrophic cardiomyopathy(HCM)is a genetically determined heart muscle disease most often caused by mutations in one of several sarcomere genes that encode components of the contractile apparatus.HCM is characterized by left ventricular hypertrophy(LVH)of various morphologies,with a wide rige of clinical manifestations and hemodynamic abnormalities.It is one of the main reasons of sudden cardiac death in young people andathletes.Objective To explore the clinical characteristics and gene mutations of different types in hypertrophic cardiomyopathy,and to analyze the relationship between Two common genotypes of MYBPC3,MYH7 with clinical phenotype.Methods The study population were selected from patients with hypertrophic cardiomyopathy who underwent Whole Exome Sequencing(WES)in Sir Run Run Shawn Hospital affiliated to Zhejiang University between September 1,2017 and December 31,2019.Collected the clinical data including: age,sex,body mass index(BMI),associated with disease(including hypertension,diabetes,coronary artery disease,atrial fibrillation),surgery history(including chemical ablation,radiofrequency ablation,ablation of ventricular tachycardia,ICD,double chamber pacemaker,CRT-p,PCI etc.).medication history,electrocardiogram(ECG),echocardiography(UCG)and cardiac magnetic resonance(CMR).Patients were divided into obstructive hypertrophic cardiomyopathy(HOCM),non-obstructive hypertrophic cardiomyopathy(HNCM)and apical hypertrophic cardiomyopathy(Ap HCM),and the clinical characteristics and gene mutations of different types were compared.According to the gene mutation,the patients were divided into gene positive and negative groups,In patients with gene positive,two genotypes and clinical characteristics were analyzed detailedly.Results A total of 126 probands patients with hypertrophic cardiomyopathy were enrolled,and 123 probands HCM were finally analyzed.The age was 24-85 years old,with an average age of 56.1±15.0.,80(65.0%)males totally.HOCM 35(28.5%),HNCM 63(51.2%),Ap HCM 25(20.3%).The HNCM gene positive mutation rate was higher(61.9% vs 28.0%,P=0.016),with the main mutation of MYBPC3.Ap HCM was more common in male(92.0% vs 48.6%?63.5%,P=0.002),and mutations of MYBPC3 and MYH7 were more common.The 5 years risk score of sudden death in three groups were(H=7.022,P=0.030),and there was statistical significance between HOCM and Ap HCM groups.the incidence of hypertension was the highest(48.6% vs28.6,P=0.048.48.6% vs 0.0%,P < 0.001)in HOCM.CCB drugs were frequently used (54.3% vs 15.9%,8.0%,P < 0.001).The incidence of diabetes was higher in HNCM patients(28.6% vs 0.0%,P=0.001).Among the 123 patients with HCM,63(51.0%)were genotype-positive(G+),60(49.0%)were genotype-negative(G-),the G+ average age was 56.1±15.0,41(33.3%)were male,the G-average age was 54.0±13.3,and 39(31.7%)were male.39.7% had P/LP variants in MYBPC3,26.6% in MYH7,4.8% in TNNT2 and3.2% in TNNI3.patients with G+were more likely to have chest distress(69.8% vs 40.0%,P=0.001),while patients with G-were more likely to have no clinical symptoms(21.7% vs 4.8%,P=0.01),and G-patients were more likely to be complicated with ECG abnormalities(18.3% vs 4.8%,P=0.037).Patients with positive genes were more likely to be associated with FHCM(20.6% vs 3.3%,P= 0.035),FHSCD(23.8% vs8.3%,P= 0.020),NSVT(39.7% vs 6.5%,P= 0.001),had a higher 5-year sudden death score(U=1381.0,p=0.010),were more likely to be in the high-risk group for sudden death(23.8% vs 5.0%,P= 0.004),and had more ICD implantation(14.5% vs 5.0%,P<0.001).A higher prevalence of left ventricular hypertrophy was observed in G-patients(56.7% vs 30.2%,P=0.003).interventricular septum was more severe in patients with G+(21.0±5.27 vs 17.5±5.27,P<0.001),which was easily associated with myocardial scar formation,which was about 1.3 times that of patients with G-.Patients with Gwere more likely to be associated with apex hypertrophy and right atrial enlargement(52.7% vs 22.2%,P=0.002),(16.7% vs 0.0%,P=0.002),and were more likely to have larger diameter of the ascending aorta than those with G+(32.5±4.1 vs 28.7±3.7,P < 0.001).Patients with G-showed higher R wave in V5(2.57±1.23 vs 1.97±1.08,P=0.009),and more T-wave inversion in ECG(38.3% vs 12.7%,P=0.001).Among the patients with genotype-positive,the comparison between the two main genotypes with negative groups,which showed that MYBPC3 mutation had a higher sudden death score than the negative patients(P=0.024).MYBPC3 mutation is more likely to be associated with NSVT than MYH7 and gene negative patients(P=0.009). MYH7 mutations seemed to be more likely to be associated with left ventricular systolic dysfunction(P=0.034)and left atrial enlargement(P=0.014).ICD implantation was more common in MYBPC3 mutations(20.0% vs 5.0%,P=0.045).The gene positive rate seemed to increase with the number of risk factors,and the incidence of G+ with left ventricular apex aneurysm(LVAA)was about 8 times higher than of G-patients(14.3% vs 1.7%,P=0.017),but no specific mutation was found to cause the LVAA.Conclusion1.The genotype-positive of non-obstructive hypertrophic cardiomyopathy was higher than that of obstructive hypertrophic cardiomyopathy and apex hypertrophic cardiomyopathy.The mutations of MYBPC3 and MYH7 were more common in the patients with apical hypertrophic cardiomyopathy similar to hypertrophic cardiomyopathy.2.genotype-positive were associated with family history,family history of sudden cardiac death,non-sustained ventricular tachycardia(NSVT)and left ventricular apex aneurysm(LVAA),which had higher 5-year SCD score and ICD implantation rate.3.The more associated risk factors,the gene positive rate seems to be more higher.MYBPC3 mutation seems to be more likely to combine with NSVT and ICD implantation.while MYH7 mutation is likely to combine with decreaseing left ventricular systolic function and along with left atrium expand.This study suggests that Whole Exome Sequencing for hypertrophic in chinese patients may provide useful clinical information on risk factors for Sudden Cardiac Death in chinese patients,requiring large-scale,prospective,multicenter studies to examine the relationship between SCD,clinical characteristics and genotype. |
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