Surgical Treatment Of Hypertrophic Cardiomyopathy And Rare Disease-causing Genes

Background:Surgery is gold standard treatment for hypertrophic obstructive cardiomyopathy,while large-volume study in China is lacked.This study aims to we report the early-medium outcome and subclinical changes after septal myectomy of our cohort of hypertrophic obstructive cardiomyopathy.Methods:We firstly studied 277 patients with hypertrophic obstructive cardiomyopathy who underwent surgical myectomy and analyzed the follow-up results.Then,we assessed the subclinical change of 182 postoperative patients with NT-proBNP.Results:Median age of the surgical cohort was 47 years(interquartile range,35-54 years),and 168[60.65%]were male.A total of 127 patients(45.85%)underwent concomitant procedures,and 2 patients(0.72%)died in the early perioperative days.The left ventricular outflow gradient decreased from 78 mm Hg(interquartile range,61-100 mm Hg)to 11 mm Hg(interquartile range,8-15 mm Hg)when discharged(P<.001).Of the 228 patients with well-documented anatomic description,more than 80%had various intraventricular anomalies.The cumulative survival was 99.28%(95%confidence interval,97.15-99.82)at 1 year and 96.98%(95%confidence interval,92.56-98.79)at 5 years.Of the surviving 272 patients,268(98.53%)were categorized with functional class I and II of the New York Heart Association classification at the latest evaluation.The NT-proBNP cohort had a median age of 46.2[IQR:36.5-53.1]years,and 106(58.2%)patients were male.NT-proBNP decreased to 816.5[IQR:400.3-1661.8]pg/mL from preoperative 1732.4[IQR:819-3296.5]pg/mL(p<0.001).Baseline NT-proBNP was correlated with gender(p<0.001),maximum septal thickness(p<0.001),and resting pressure gradient(p=0.006).The extent of NT-proBNP decrease was positively correlated with age(p<0.001),baseline NT-proBNP(p<0.001),follow-up time(p = 0.020),and enlargement of the ascending aorta(p = 0.019).NT-proBNP exhibited a persistent decrease after myectomy.Conclusions:Surgical septal myectomy for hypertrophic obstructive cardiomyopathy was safe and effective.Early and medium outcomes were satisfactory.Myectomy also promoted postoperative reverse remodeling of myocardium,which was influenced by age and other factors.Background:Rare variants with uncertain significance beyond MYBPC3and MYH7 are often detected in genetic examination of hypertrophic cardiomyopathy.These rare variants have very low prevalence in patients with hypertrophic cardiomyopathy,and it is hard to determine their clinical significance.Methods:Firstly,we studied the impact of FLNC mutation on clinical outcomes of patients with hypertrophic cardiomyopathy by follow-up investigation.Then,by pedigree analysis we investigated the penetrance of MYL2 R58Q mutation.Lastly,we validated the study results of molecular mechanism of LEOPARD syndrome from tansgenetic mouses with human samples.Results:We found that 7.2%of patients carried FLNC mutations,with a similar frequency to that of controls(4.2%,p = 0.101).The baseline characteristics between HCM patients,with and without mutations,were comparable.FLNC mutations did not increase the risk for either,all-cause mortality(HR 0.746,95%CI 0.222-2.295,p = 0.575)nor cardiac mortality(HR 0.615,95%CI 0.153-1.947,p = 0.354)in HCM patients during a follow-up of 4.7 ± 3.2 years.There was no significant difference in survival,free from sudden cardiac arrest(HR 0.721,95%CI 0.128-3.667,p = 0.660)and heart failure(HR 0.757,95%CI 0.318-1.642,p = 0.447),between HCM patients,with and without FLNC mutations.Pedigree analysis was performed in three families.In the largest family,R58Q had complete cosegregation with HCM phenotype in all investigated adult members.In other two families,R58Q had incomplete penetrance.We examined mTOR activity using myocardial samples from LEOPARD syndrome patients with PTPN11 Y279C or T468M mutation.mTOR activity were not enhanced as presented in mouse models.And conversely,S6 downstream were significantly hypophosphorylated as sarcomere mutated patients.Conclusions:We found low pathogenetic rate and incomplete penetrance of rare gene variants in follow-up study and pedigree analysis.Functional study based on animal models also showed bias with real-world.In the genetic research,environmental impact and individual differences should not be ignored.