Association Of Genotype With Surgery And Clinical Prognosis In Hypertrophic Obstructive Cardiomyopathy

Section 1:Genotype-Positive Status Is Associated with Poor Prognoses in Patients with Hypertrophic Cardiomyopathy Undergoing Septal MyectomyBackground and ObjectiveHypertrophic cardiomyopathy(HCM)is the most prevalent inherited heart disease,caused mainly by mutations in genes encoding sarcomere proteins.Two-thirds of the patients were obstructive hypertrophic cardiomyopathy(OHCM).Septal reduction therapy(SRT)is an important treatment for obstructive hypertrophic cardiomyopathy patients with drug-refractory.Although most patients after septal myectomy have satisfactory surgical results,few patients still have adverse events during the follow-up.Previous studies have found that some preoperative clinical risk factors can optimize the risk stratification and management of patients.This study was conducted to investigate the prognostic value of sarcomere(SARC)mutation in patients with OHCM who underwent septal myectomy.MethodsPatients with OHCM who underwent septal myectomy,and genetic testing were recruited.The 8 SARC genes were screened by whole exome sequencing or gene panel sequencing,and identified variants were validated by Sanger sequencing.Mutations were classified into 5 categories(pathogenic,likely pathogenic,variants of uncertain significance,likely benign and benign)according to the American College of Medical Genetics.Pathogenic mutations were those mutations identified as pathogenic,likely pathogenic,or variants of uncertain significance.Patients carried pathogenic mutation were divided into group of SARC+,otherwise into group of SARC-.The clinical baseline and surgical characteristics of the two groups were studied.Patients were followed 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 stroke.Kaplan-Meier survival curves were generated to show the survival free from the composite end-point events between two groups.Cox regression analysis included age,gender and other indicators into the survival analysis to analyze the factors that affect the long-term efficacy of OHCM patients after surgical treatment.ResultsAccording to the entry criteria,365(60.8%males)patients were included in this study.The average age at operation was(44.3± 13.5)years.Pathogenic mutations were identified in 57.3%(209/365)of the study patients.Patients in the SARC+group were younger(38.8± 12.1 years vs.51.1± 12.6 years,P<0.001)at surgery or diagnosis(36.4±11.9 years vs.48.1±12.5 years,P<0.001)and had a greater interventricular septal thickness(20.1 ±4.2mm vs.18.8±3.8mm,P=0.006).At(36.8±21.1)months follow-up,patients in the SARC+group showed a higher risk of adverse events than those in the SARC-group(P=0.001).Multivariable analysis revealed that SARC mutation(hazard ratio=6.912,95%confidence intervals=2.254 to 21.200,P=0.001)was an independent risk factor for adverse events.Female gender(hazard ratio=2.291,95%confidence intervals=1.034 to 5.007,P=0.041)and preoperative left atrial diameter ≥45 mm(hazard ratio=3.545,95%confidence intervals=1.316 to 9.551,P=0.012)were also found to be independent predictors of the adverse events.ConclusionThe presence of SARC gene mutation is a potential risk factor for poor long-term quality-of-life in OHCM patients undergoing septal myectomy and may be appropriate to consider as an important factor in the risk stratification.Section 2:The Relation between Mitral Valve Abnormalities and Clinical Prognosis in Patients with Obstructive Hypertrophic Cardiomyopathy1.Long Term Outcomes after Septal Myectomy and Concomitant Mitral Valve Surgery in Patients with Obstructive Hypertrophic CardiomyopathyBackground and ObjectiveIn patients with obstructive hypertrophic cardiomyopathy(OHCM)undergoing septal myectomy,some patients need concomitant mitral valve surgery.Concomitant mitral valve surgery mostly due to the unsatisfactory surgical results of the relief of left ventricular outflow tract obstruction or intrinsic mitral valve abnormalities.There are few studies on the effect of different mitral valve surgical procedures on the long-term prognosis of OHCM patients.This study included OHCM patients who underwent septal myectomy and concomitant mitral valve surgery and explore the related factors that affect the survival of patients,in order to improve the comprehensive management of OHCM patients after surgical treatment.MethodsWe screened OHCM patients admitted to the center for septal myectomy concomitant mitral valve surgery from 2013 to 2019.According to different mitral valve surgical procedures,patients are divided into group of mitral repair and group of mitral valve replacement.The clinical baseline and surgical characteristics of the two groups were studied.Patients were followed regularly after surgery to record their survival status and adverse events.The study endpoint was a composite endpoint composed of multiple adverse events,including cardiovascular death,rehospitalization for heart failure,reoperation for mitral valve,and new-onset postoperative stroke.Kaplan-Meier survival curves were generated to show the survival free from the composite end-point events between two groups.Cox regression analysis included age,gender,preoperative atrial fibrillation,cardiac function and other indicators into the survival analysis to analyze the factors that affect the long-term efficacy of OHCM patients after surgical treatment.ResultsAccording to the entry criteria,a total of 213(125 males)patients were included in this study.The average age at operation was(49.7±11.8)years.According to the procedure of mitral valve surgical,the patients were divided into two groups.There were 183 patients who had mitral valve repair and 30 patients who had mitral valve replacement.The age at operation was mainly between 35 and 65 years old.The age at operation in the group of mitral valve replacement was significantly greater than that of the group of mitral valve repair(53.1±14.0 years vs.49.2±11.5 years,P=0.035),and the proportion of patients with cardiac function Ⅲ/Ⅳ is higher(70%vs.47.5%,P=0.023).In the group of mitral valve repair,the most common surgical operations were mitral valve valvuloplasty and treatment of abnormal chordae.In the mitral valve replacement group,the proportion of mechanical valve replacement is high.After an average follow-up of 35.4±23.9 months,Kaplan-Meier survival curves showed that the incidence of composite endpoint events in the group of mitral valve replacement was significantly higher than that in group of the mitral valve repair(P=0.005).Multivariate Cox analysis showed that mitral valve replacement(hazard ratio=3.551,95%confidence interval=1.172-10.757,P=0.025)and preoperative pulmonary hypertension(hazard ratio=5.219,95%confidence interval=1.682-16.194,P=0.004)were independent predictors of the composite endpoint.ConclusionIn addition to septal myectomy,mitral valve surgery is also an effective method for treating of OHCM,which can effectively alleviate severe mitral valve regurgitation in patients.Compared with patients undergoing mitral valve replacement,patients undergoing mitral valve repair have a better long-term quality of life.For OHCM patients undergoing septal myectomy,it is necessary to consider the influence of the mitral valve and subvalvular tissues on hemodynamics.Operators should conduct a comprehensive evaluation of the patient,and select a reasonable surgical method to improve the survival rate of the patient and improve the prognosis.Section 2:The Relation between Mitral Valve Abnormalities and Clinical Prognosis in Patients with Obstructive Hypertrophic Cardiomyopathy2.Mitral Leaflet Elongation Predicts Nonsustained Ventricular Tachycardia in Patients with Obstructive Hypertrophic CardiomyopathyBackground and ObjectiveMitral valve abnormalities represent a primary phenotypic expression of hypertrophic cardiomyopathy,which is associated with left ventricular outflow tract obstruction.There are limited studies on the morphology of mitral valve leaflets and hypertrophic cardiomyopathy.The impact of mitral valve abnormality on the occurrence of non-sustained ventricular tachycardia(NSVT)in patients with hypertrophic cardiomyopathy(HCM)has not been well determined.We sought to demonstrate the association of mitral valve abnormalities with non-sustained ventricular tachycardia in patients with obstructive HCM.MethodsFrom 2014 to 2019,Patients with obstructive hypertrophic cardiomyopathy were recruited in our hospital who were performed on at least 1 Holter electrocardiographic monitoring and cardiac magnetic resonance(CMR).Patients were divided into two groups according to the presence of NSVT.The patient’s clinical materials were collected.CMR images and Holter electrocardiography were analyzed in all patients.The length of the anterior mitral leaflet and posterior mitral leaflet was measured through CMR imaging data.The two group baseline patient characteristics were compared.Receiver-operating characteristic(ROC)curves were performed to evaluate the prediction performance of the length of the anterior mitral leaflet for NSVT.Univariate analysis was used to identify risk factors.Then variables with P<0.1 at univariable analysis were included in a multivariable logistic regression model to identify the predictor for NSVT.ResultsAccording to entry criteria,a total of 316 patients with OHCM were enrolled in the present study with a mean age of(46.1±14.2)years and 189(60.0%)were females.NSVT occurred in 50 patients(16%).Compared with those without NSVT,the length of anterior mitral leaflet(AML),and posterior mitral leaflet(PML)was significantly increased in patients with NSVT(AML 32.0 ± 5.0mm vs.26.1 ±4.8mm,p<0.001;PML 17.7±3.7mm vs.15.2±2.7mm,p<0.001,respectively).Compared with patients without NSVT,the ratio of late gadolinium enhancement(LGE)and the size of left atrial diameter,maximal left ventricular wall thickness was higher in patients with NSVT.In the correlation analysis,AML length had a positive correlation with left ventricular end-diastolic volume index,maximal left ventricular wall thickness and LGE presence and a negative correlation with age and left ventricular ejection fraction,while PML correlated with left atrial diameter,left ventricular end-diastolic volume index and left ventricular mass.In univariate analysis,AML and PML were identified as risk factors for NSVT.Multivariate logistic regression analysis indicated that elongated AML and PML were significantly independent predictors of NSVT(AML:odds ratio 1.261,95%confidence intervals=1.156-1.375,P<0.001;PML:odds ratio 1.126,95%confidence intervals=1.001-1.265,P=0.047).Furthermore,the area under the receiver operating characteristic curve for AML was 0.812.At a cutoff value of 27.5mm,AML length had a sensitivity of 86%and specificity of 65%.ConclusionElongated mitral leaflets are characteristic cardiac structural changes in patients with hypertrophic cardiomyopathy and also positively associated with arrhythmia.The length of the mitral leaflets is associated with age,left ventricular end-diastolic volume index,and left ventricular ejection fraction.Elongated mitral leaflets independently correlated with NSVT in patients with obstructive HCM.Furthermore,the morphological abnormalities of mitral valve could serve as a useful marker for improving risk stratification of SCD and may play a role in optimizing surgical strategy for patients with obstructive HCM.Section 3:Efficiency for Reoperation in Patients with Obstructive Hypertrophic Cardiomyopathy after Septal Reduction TherapyBackground and ObjectiveSeptal reduction therapy(SRT)is an important treatment for obstructive hypertrophic cardiomyopathy patients with drug-refractory.Operations can be categorized as septal reduction therapy(SRT)and alcohol septal ablation(ASA).After the treatment of SRT,most patients have a good recovery and an improvement of clinical symptoms.But there are still a few patients who need to be treated with a secondary procedure of SM.This study aims to analyze the clinical characteristics and surgical outcomes of patients with OHCM undergoing repeated septal reduction therapy(SRT).MethodsWe retrospectively analyzed the clinical characteristics of OHCM patients who received repeated SRT from January 2014 to December 2019 in Fuwai Hospital.Patients were divided into two groups according to the primary procedure of SRT.The clinical data and surgical results were summarized and analyzed.Patients were followed regularly after operations.The survival status adverse events were recorded.ResultsA total of 31 patients(21 males)were included in the study.The average age was(48.7±12.2)years.There were 7 patients in the SM group and 24 patients in the ASA group.All patients have performed SM during the hospital stay,of which 18 patients(58.1%)undergoing SM surgery alone.The remaining 13 patients were performed on other procedures in the same period,such as mitral valve angioplasty in 6 patients,tricuspid valve procedures in 1 patient,myocardial unroofing in 1 patient,Maze operation in 5 patients.Preoperative electrocardiogram showed that 4 patients in the SM group presented with complete left bundle branch block,and 7 patients in the ASA group presented with complete right bundle branch block.After the operation,4 patients were implanted with permanent pacemakers due to complete atrioventricular block,of which 3 patients were in the ASA group with complete right bundle branch block.During the perioperative period,except for one death caused by electrical storm,the remaining patients had no serious complications.Compared with preoperative data,the post-echocardiography showed a significant reduction in left ventricular outflow tract gradient[(64.0±37.4)mmHg vs.(10.2±8.9)mmHg,P<0.001],and the thickness of interventricular septum[(17.8±3.9)mm vs.(12.7±2.1)mm,P<0.001].The moderate or severe mitral valve regurgitation was significantly reduced after the operation(P<0.001),and the systolic anterior motion disappeared.During the follow-up period of(23.5± 10.9)months,no long-term death or reoperation occurred.The results of follow-up echocardiography showed that,except for 2 patients who had left ventricular outflow tract obstruction again,the left atrial diameter thickness of interventricular septum and left ventricular outflow tract gradient and were significantly lower compared with preoperative echocardiography.ConclusionThe surgery of SM in OHCM patients with a history of previous SRT procedures is a safe and effective treatment.Patients were at the risk of developing atrioventricular block after the procedure of SM and ASA.It is important to identify patients who had intraventricular conduction before surgery to assess the risk of developing complete atrioventricular block requiring permanent pacemaker treatment,especially for patients with the first procedure of ASA,patients were at high risk of developing atrioventricular block.