Correlation Between Myocardial Deformation and Coronary Artery Tortuosity in Patients With Hypertrophic Cardiomyopathy

Study Overview
=================
Brief Summary
-----------------
Correlation between Myocardial Deformation and Coronary Tortuosity and Analysis of Genetic Factors Among Hypertrophic Cardiomyopathy Patients

Detailed Description
-----------------
Excessive tortuosity of the coronary arteries (TCA) is a somewhat common finding in patients referred for coronary angiography, reported in 14-40% of patients referred for angiography. The presence of TCA has been associated with chest pain and myocardial perfusion abnormalities during stress in the absence of obstructive coronary artery disease. Fluid dynamic modeling suggests that stress-induced ischemia may be attributable to a reduction in distal coronary artery perfusion pressure from viscous and turbulence energy losses. The physiologic reasons for TCA are unclear. The roles of TCA on prognosis of HCM are also needed to explore. Pre-clinical studies where elastases and collagenases were used to alter arterial morphology together with genetic and pathologic analysis of rare clinical disorders such as arterial tortuosity syndrome have indicated that arterial tortuosity arises from abnormalities in arterial elastin fibers and extracellular matrix. Apart from inherited disorders, some but not all studies have linked TCA with hypertension and female sex, and with increased left ventricular (LV) mass from pressure but not volume overload and smaller heart size. Hypertrophic cardiomyopathy (HCM) is associated with an increased left ventricular (LV) wall thickness. HCM is the most common genetic heart disease, characterized by marked clinical and morphologic heterogeneity. Diagnosis is usually based on the echocardiographic finding of unexplained left ventricular (LV) hypertrophy, defined by increased wall thickness in 1 or more LV segments. LV mass is generally assumed to be increased in patients with phenotypically expressed HCM, based largely on early pathological studies. TCA among HCM patients have not been studied. So, firstly, we choose HCM and non-HCM patients to investigate the relationship between TCA and HCM, and further explore the potential roles of TCA for prognosis in HCM. In HCM patients, disruption of the ordered arrangement of myofibers alters normal cardiac mechanical function, resulting in temporal and spatial heterogeneity in regional myocardial contractility. Although global LV function is generally unaltered, asynchrony and asynergy in regional function lead to delayed diastolic relaxation and impaired diastolic filling. Whilst LV ejection fraction is frequently normal in both, LV strain assessment could differentiate, compared to normal person. Cardiovascular magnetic resonance (CMR), by virtue of its high-resolution volumetric reconstruction of the LV chamber, currently affords a highly accurate and reproducible quantitative assessment of mass . So secondly, we sought to establish if cardiovascular magnetic resonance myocardial feature tracking (CMR-FT), an emerging method allowing accurate assessment of myocardial deformation, differentiates between HCM with or without TCA. Additionally, we want to explore the potential genetic factor on TCA in HCM. This is a single-center, retrospective, case control study that will evaluate the difference of TCA between HCM and non-HCM, and explore the prognostic roles of TCA in the first part. In the second part, we will use CMR-FT to compare the myocardial strain between HCM with or without TCA and analyze the relationship of strain and TCA. In the third part, we choose HCM patients and non-HCM to investigate potential genetic factors for TCA in HCM.

Official Title
-----------------
Correlation Between Myocardial Deformation and Coronary Artery Morphology in Patients With Hypertrophic Cardiomyopathy and Analysis of Genetic Factors：A Prospective, Single-center, Case-control Study

Conditions
-----------------
Myocardial Deformation, Coronary Artery Anomaly, Hypertrophic Cardiomyopathy, Genetic Mutation, Prognosis

Intervention / Treatment
-----------------
* Other: no intervention


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must meet all the following inclusion criteria to be eligible for participation in this study 18<age≤85； Patients with hypertrophic cardiomyopathy and without hypertrophic cardiomyopathy undergoing coronary angiography and echocardiography; Willing to sign informed consent. Exclusion Criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study All coronary arteries can not be shown clearly in coronary angiography Prior coronary artery bypass surgery, valve prosthesis Connective tissue disease Cardiac dilatation(left ventricular end diastolic diameter, ≥55mm male，≥50mm female ) Congenital heart failure, LVEF<35% Coronary total occlusion, changes in coronary morphology, such as long stents implantation（≥12mm）

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| hypertrophic cardiomyopathy<br>patients with hypertrophic cardiomyopathy | Other: no intervention<br>* there is no intervention, we just chose patients diagnosed with hypertrophic cardiomyopathy and underwent CAG, and patients without hypertrophic cardiomyopathy as control ,the two groups are matched with age, gender and hypertension.<br>|
| control without hypertrophic cardiomyopathy<br>controls without hypertrophic cardiomyopathy | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| coronary artery tortuosity and tortuosity score in hypertrophic cardiomyopathy patients | Severe tortuosity was defined as ≥2 consecutive curvatures of ≥180° in a major epicardial coronary artery ≥2 mm in diameter . Mild tortuosity was defined as either ≥3 consecutive curvatures of 45° to 90° in a major epicardial coronary artery, or ≥3 consecutive curvatures of 90° to 180° in an artery <2 mm in diameter. The tortuosity score was calculated as a sum of scores for each major epicardial coronary artery (left anterior descending, left circumflex, right coronary artery) with 0=no tortuosity, 1=mild tortuosity,2=tortuosity, 3=severe tortuosity. We will evaluate if the patients have coronary artery tortuosity and assess the number of tortuosity score for every coronary artery and add the score up for every patients. | six months | 
| prognostic roles of coronary artery tortuosity in hypertrophic cardiomyopathy | retrospectively included HCM patients with echocardiography and coronary angiography (CAG), in Fuwai Central China Cardiovascular Hospital from 1st Dec 2017 to 10th Jun 2021. All patients were followed up until the censoring day of 1st July 2022. The primary outcomes were composite of all-cause death, maglinant arrhythmia, ischemic stroke. Death was documented according to medical records, death certificates, or follow-up questionnaires by family members. Arrhythmia included ventricular fibrillation, sustained ventricular tachycardia, second-degree type II and third-degree atrioventricular block. | 2017/12/01-2022/07/01 | 
| prognostic roles of coronary artery tortuosity in hypertrophic cardiomyopathy | etrospectively included HCM patients with echocardiography and coronary angiography (CAG), in Fuwai Central China Cardiovascular Hospital from 1st Dec 2017 to 10th Jun 2021. All patients were followed up until the censoring day of 1st July 2022. The secondary outcomes were composite of primary outcomes and rehospitalization. | 2017/12/01-2022/07/01 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myocardial strain and strain rate in hypertrophic cardiomyopathy patients with coronary artery tortuosity | observe the difference of myocardial strain between hypertrophic cardiomyopathy with and without coronary artery tortuosity, Global longitudinal strain (GLS), global longitudinal strain rate (GLSR), global circumferential strain (GCS), global circumferential strain rate (GCSR), global radial strain (GRS), and global radial strain rate (GRSR) of the LV and RV will be calculated and segmental strain and strain rate will also be assessed respectively | six months | 
| genetic factors(such as genetic mutation site for HCM(MYBPC3,MYH7,ACTC1,TNNI3)) for hypertrophic cardiomyopathy patients with coronary artery tortuosity | do genetic testing, observe the difference for genetic factors such as gene mutation for hypertrophic cardiomyopathy with and without coronary artery tortuosity, all the 40 genes which has been found to be implicated in HCM will be tested, such as MYBPC3, MYH7, TPM1,TNNT2 and TNNI3. | two months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hypertrophic cardiomyopathy, tortuosity of coronary arteries, myocardial strain, prognosis, genetic mutation