Hpertrophic Cardiomyopathy Assessment And Its Risk Stratification Using Stress Echocardiography Based On Multi-modality Imaging

Hypertrophic cardiomyopathy(HCM)is a genetic disorder that is primarily inherited in an autosomal dominant manner and is the primary cause of unexpected cardiac arrest among young individuals.While the monogenetic theory has been the primary explanation for its etiology,it fails to account for the diverse anatomical,functional,and clinical manifestations of the disease.Current research on HCM focuses on prognostic indicators and risk factors,yet there exist numerous challenges.For instance,the relationship between HCM’s cardiac electrical activity,myocardial function,and myocardial perfusion remains enigmatic.Additionally,the precise role of myocardial perfusion in the progression of HCM is unclear.Furthermore,the significance of exercise capacity in predicting HCM risk is not fully understood.Lastly,the lack of consensus on risk assessment parameters recommended by guidelines for HCM poses difficulties in clinical risk stratification evaluation.The hypothesis of this research is: the application of the new technology of " Stress Echocardiography Based on Multi-modality Imaging " can systematically and deeply evaluate the characteristics and abnormal changes of HCM exercise stress electrocardiogram(ECG),echocardiographic cardiac function and myocardial perfusion,and it is also helpful for clinical risk stratification of HCM more accurately.The goals of this research are:(1)evaluate the characteristics of electrophysiology,myocardial mechanics,myocardial perfusion,and Metabolic Equivalent of Task(METS)of various HCM subtypes.(2)Explore the pathophysiological correlation between the above characteristic parameters and pathogenic genes,obstruction,anatomic location of hypertrophy and positive events.(3)Finding the new method and parameter for METS assessment without exercise and clarifying its risk assessment value.(4)Reveal the risk factors with strong predictive performance for high-risk HCM.(5)Establish a risk assessment model for diverse HCM subtypes,so as to achieve individualized and accurate risk stratification of HCM and ultimately improve the long-term prognosis.This study is carried out in five parts.Subjects were tested with "stress echocardiography based on multi-modality imaging" based on genetic testing.All HCM patients were followed up for 5 years,and the endpoint was any event of heart failure,ventricular tachycardia,atrial fibrillation,defibrillator implantation,ICD implantation or unexplained syncope.HCM was further divided into different subgroups based on genotype,hemodynamics,anatomical phenotype and end-point events,and the following five parts of research were carry out: the first part was to analyze the exercise ECG characteristics and risk assessment of each subgroup.In the second part,the stress echocardiography characteristics and risk assessment of each subgroup were analyzed.In the third part,the characteristics of stress myocardial enhancement imaging and risk assessment of of each subgroup were performed.The fourth part was to analyze the pathological correlation and risk prediction efficiency of the multimodal ultrasound parameters.The fifth part was to establish and validate the risk stratification model of HCM which based on multi-modality imaging of stress echocardiography.The literature study,case study,descriptive study,quantitative/semi-quantitative analysis,comparative analysis,logistic regression,ROC curve,delong test,bayesian generalized linear model,sample size estimation verification,simulation method,survival time,leave-one-out cross-validation,COX regression and Kaplan-Meier were used in the above research section.The study found that: 1.The depolarization repolarization time(FRI-QTcd)and dispersion FRI-QTcd of HCM resting and peak values were significantly prolonged,and the depolarization repolarization time reserve ΔFRI-QTcd% deteriorated.METS of all types of HCM were generally reduced,and the reduction of METS in pathogenic genome,obstruction group and positive event group was more significant,especially in the positive event group,the average METS was as low as 5.62.METS had excellent predictive power for positive cardiovascular events(AUC: 0.95).2.The overall longitudinal strain and reserve of left ventricle and left atrial strain and reserve of all HCM types were significantly reduced,and the systolic reserve and diastolic reserve of pathogenic genome,obstruction group and positive event group were almost lost.The resting left atrial storage strain predicted METS well(AUC 0.93).Resting left atrial storage strain and METS were equally good predictors of positive events(AUC: 0.93,0.95).3.The resting and peak myocardial perfusion velocity and intensity were decreased,blood flow was decreased,perfusion time was prolonged,and the corresponding reserve was decreased.In particular,the reserve of perfusion velocity was almost deteriorated or even lost in the pathogenic genome,resting obstruction group and positive event group.Resting myocardial perfusion velocity was a good predictor of METS and positive events(AUC: 0.96,0.92).4.METS were moderately associated with resting and peak left atrial storage strain,resting and peak left ventricular global longitudinal strain,and resting and peak myocardial perfusion velocity(r=0.74,0.72,-0.54,-0.59,0.74,0.68).Resting myocardial perfusion velocity was moderately correlated with resting left atrial storage strain and global left ventricular longitudinal strain(r=0.57,-0.52),and peak myocardial perfusion velocity was moderately correlated with peak left atrial storage strain and global left ventricular longitudinal strain(r=0.58,-0.59).Positive events were moderately correlated with METS,resting and peak left atrial stored strain,peak left ventricular longitudinal strain,and pathogenic genes(r=-0.70,-0.67,-0.61,0.58,0.54).Resting myocardial perfusion velocity and resting left atrial storage strain were equally good predictors of METS(AUC: 0.96,0.93),contributing to the "evaluation of METS without exercise." METS,resting left atrial storage strain,resting and peak myocardial perfusion velocity also had equally good predictive power for positive events(AUC: 0.95,0.93,0.92,0.93),which were excellent characteristic risk factors for HCM.5.Through the systematic analysis of "PASS sample size verification estimation,leave-one-out model cross validation,survival time,COX proportional hazard model,Kaplan-Meier curve",it was proved that the current sample size of this study was scientific and reasonable for modeling.On this basis,the HCM risk stratification model constructed by METS,resting left atrial storage strain,resting and peak myocardial perfusion velocity,resting and peak myocardial perfusion segments had the highest elpd＿loo value(-27.54),which suggested that the model had better prediction effect.In summary,the adverse cardiovascular events occurrences in HCM are attributed to various factors,including myocardial perfusion,cardiac function,and pathogenic genes.Notably,myocardial perfusion is influenced by pathogenic genes,pathological structure,obstruction,and cardiac function.Furthermore,it significantly impacts cardiac electrical activity,cardiac function,and METS.The HCM risk stratification model developed through "Stress Echocardiography Based on Multi-modality Imaging" demonstrates excellent predictive efficacy.This model not only enhances and enhances the current risk assessment framework,but also offers a fresh theoretical perspective and clinical diagnostic and treatment support.It can effectively facilitate the clinical implementation of personalized and precise risk stratification of HCM,thereby enhancing long-term prognosis.The model holds significant clinical application value and practical relevance.