Transapical Beating-heart Septal Myectomy in Patient With Hypertrophic Obstructive Cardiomyopathy

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the feasibility, the safety and the efficacy of the transapical beating-heart septal myectomy for the treatment of hypertrophic obstructive cardiomyopathy. This is a prospective, single-arm, single-center, first-in-man study.

Detailed Description
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Surgical septal myectomy remains the gold standard for the treatment of hypertrophic obstructive cardiomyopathy. However, conventional septal myectomy is hindered by the demanding expertise that is needed to sufficient relieve the obstruction of the left ventricle outflow tract while guarantee safety. To increase the visualization and minimize the surgical injury of conventional septal myectomy, we have invented a novel beating-heart myectomy device. Through a mini-thoractomy, septal myectomy could be accomplished via a transapical access in the beating heart using the beating-heart myectomy device. The whole process of resection is monitored, navigated, and evaluated by real-time transesophageal and transthoracic echocardiography. Left ventricle outflow tract gradient and the grade of mitral regurgitation are evaluated each time after resection. Multiple resections are performed to tailor sufficient relief of left ventricle outflow tract obstruction and mitral regurgitation, while preventing iatrogenic injuries. After transapical beating-heart septal myectomy, patients is scheduled to be seen for follow-up visits at discharge (about 7 days post operation) and 3 months.

Official Title
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Minimally Invasive Transapical Septal Myectomy in the Beating Hearts for the Treatment of Hypertrophic Obstructive Cardiomyopathy: Safety and Efficacy Results of a Phase I First-in-man Clinical Trial

Conditions
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Hypertrophic Obstructive Cardiomyopathy

Intervention / Treatment
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* Procedure: Transapical beating-heart septal myectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients whose resting or provoked left ventricular outflow tract gradient > 50 mmHg, and maximal ventricular septal wall thickness ≥ 15 mm. Patients with heart function of New York Heart Association ≥ class II. Patients with drug-refractory symptoms or intolerable to pharmaceutical therapies. Patients who was informed the nature of the clinical trial, consented to participate in all of the activities of the clinical trial, and signed the informed consent form. Exclusion Criteria: Patients who were pregnant. Patients who had concomitant diseases such as intrinsic valvular disease or coronary artery disease that needed open-heart surgery. Patients who had severe heart failure with left ventricle ejection fraction < 40%. Patients whose estimated life expectancy < 12 m. Patient who were non-compliant. Patients under circumstances which were considered not suitable or prohibitive for participating the clinical trial at the discretion of the attending medical team and the researchers.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Beating-heart myectomy device
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypertrophic Obstructive Cardiomyopathy<br>Transapical beating-heart septal myectomy for the patient with hypertrophic obstructive cardiomyopathy. | Procedure: Transapical beating-heart septal myectomy<br>* We have invented a beating-heart myectomy device.Through a minimally invasive intercostal incision, septal myectomy could be accomplished via a transapical access in the beating heart using the device. The whole process of resection is monitored, navigated, and evaluated by real-time transesophageal and transthoracic echocardiography. Left ventricle outlet tract gradient and the grade of mitral regurgitation are evaluated each time after resection. Multiple resections are performed to tailor the muscular resection for sufficient relief of left ventricle outlet tract obstruction and mitral regurgitation, while preventing iatrogenic injuries.<br>* Other names: Minimally invasive transapical septal myectomy in the beating hearts;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Death from any cause during the observation period. | 3 months | 
| Procedural success | Resting left ventricle outflow tract gradients < 30 mmHg, provoked left ventricle outflow tract gradients < 50 mmHg, and mitral regurgitation (MR) ≤ grade 1+. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success | Successful accession, delivery, and retrieval of the resection device, successful resection of the septal myocardium, resting left ventricle outflow tract gradient less than 50 mmHg and mitral regurgitation (MR) ≤ grade 2+ during operation after resection, and free from conversion to midline thoracotomy during operation. | 1 day | 
| Septal thickness | Basal and mid septal thickness as measured by echocardiography. | 7 days and 3 months | 
| Left ventricle mass | Left ventricle mass index (the ratio of left ventricle mass to body weight) as measured by cardiac magnetic resonance. | 3 months | 
| Left ventricle volume | Left ventricle end-diastolic volume as measured by echocardiography. | 7 days and 3 months | 
| Cardiac diastolic function | The ratio between early mitral inflow velocity and mitral annular early diastolic velocity ( E/e') as measured by echocardiography. | 7 days and 3 months | 
| Left atria volume | The left atria volume as measured by echocardiography. | 7 days and 3 months | 
| Major adverse cardiovascular and cerebral events | In-hospital mortality, atrioventricular block that need permanent pacemaker implantation, sternotomy conversion, iatrogenic ventricular septal perforation, iatrogenic valvular injury, imaging examination-validated cerebral complications. | 3 months | 
| New York Heart Association class | New York Heart Association class, including grade I, grade II, grade III, grade IV. A higher grade means worse heart function. | 7 days and 3 months | 
| 6-minute walking test | 6-minute walking test. A longer distance means better heart function. | 3 months | 
| Heart function-associated quality of life | Score of the Kansas City Cardiomyopathy Questionnaire. A higher score means better heart function. | 7 days and 3 months | 
| Left ventricular outflow tract gradient | Left ventricular outflow tract gradient as measured by echocardiography. | 7 days and 3 months | 
| Evaluation of the mitral valve | Grade of mitral regurgitation and systolic anterior motion as measured by echocardiography. | 7 days and 3 months | 
| Left ventricular outflow tract diameter | Left ventricular outflow tract diameter as measured by echocardiography. | 7 days and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertrophic Obstructive Cardiomyopathy, Septal Myectomy, Systolic Anterior Motion, Left Ventricle Outflow Tract Obstruction, Mitral Regurgitation, Transapical, Off-pump, Minimally invasive