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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertrophic Obstructive Cardiomyopathy
• Intervention / Treatment: Procedure: Transapical beating-heart septal myectomy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xiang Wei, M.D.; Phone Number: +8613995525956; Email: xiangwei@tjh.tjmu.edu.cn
• Study Contact Backup: Name: Jing Fang, M.D.; Phone Number: +8613296640596; Email: jingfang@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Xiang Wei, M.D.; Phone Number: +8613995525956; Email: xiangwei@tjh.tjmu.edu.cn
      • Contact: Jing Fang, M.D.; Phone Number: +8613296640596; Email: jingfang@hust.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients whose resting or provoked left ventricular outflow tract gradient > 50 mmHg, and maximal ventricular septal wall thickness ≥ 15 mm.
2. Patients with heart function of New York Heart Association ≥ class II.
3. Patients with drug-refractory symptoms or intolerable to pharmaceutical therapies.
4. 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:

1. Patients who were pregnant.
2. Patients who had concomitant diseases such as intrinsic valvular disease or coronary artery disease that needed open-heart surgery.
3. Patients who had severe heart failure with left ventricle ejection fraction < 40%.
4. Patients whose estimated life expectancy < 12 m.
5. Patient who were non-compliant.
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypertrophic Obstructive Cardiomyopathy; Transapical beating-heart septal myectomy for the patient with hypertrophic obstructive cardiomyopathy.

Procedure: Transapical beating-heart septal myectomy; 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.; Other Names: Minimally invasive transapical septal myectomy in the beating hearts

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xiang Wei
• Investigators: Study Chair: Xiang Wei, M.D., Tongji Hospital

Publications and helpful links

General Publications

• Fang J, Wang R, Liu H, Su Y, Chen J, Han X, Wei Y, Chen Y, Cheng L, Wei X. Transapical septal myectomy in the beating heart via a minimally invasive approach: a feasibility study in swine. Interact Cardiovasc Thorac Surg. 2020 Feb 1;30(2):303-311. doi: 10.1093/icvts/ivz249.

Helpful Links

• Transapical septal myectomy in the beating heart via a minimally invasive approach: a feasibility study in swine

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2022
• Primary Completion (Anticipated): April 15, 2023
• Study Completion (Anticipated): July 15, 2023

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Estimate): December 7, 2022
• Last Update Submitted That Met QC Criteria: December 4, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Mitral Regurgitation; Transapical; Off-pump; Hypertrophic Obstructive Cardiomyopathy; Septal Myectomy; Systolic Anterior Motion; Left Ventricle Outflow Tract Obstruction; Minimally invasive
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: 2022-S013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All of the conclusive participant data, after removing the individual information of privacy, will be uploaded as supporting information when publishing the current study.
• IPD Sharing Time Frame: After the current study is published.
• IPD Sharing Access Criteria: All readers who were interested in the current study.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No