NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Early Feasibility Study

Background:

Some people have a condition in which the wall (septum) that separates the two main pumping chambers of the heart is too thick. This thick septum causes a condition called "left ventricular outflow tract obstruction" (LVOTO), which reduces blood flow out of the heart. LVOTO can cause serious heart disease; symptoms may include shortness of breath, chest pain, heart failure, or death. Researchers want to find better ways to treat LVOTO.

Objective:

To test a new procedure where excess tissue is sliced away from the septum in people with LVOTO. This procedure is called "septal scoring along midline endocardium" (SESAME).

Eligibility:

Adults aged 21 years with LVOTO.

Design:

Participants will have baseline tests. They will have imaging scans and tests of their heart structure and function. They will take a walking test and answer questions about how their heart condition affects their life.

Participants will stay in the hospital 2 to 6 days for the SESAME procedure.

They will be completely or partially asleep for the procedure. A tube will be inserted into the mouth and down the throat to take pictures of the heart. Pictures may also be taken with a tube inserted inside the heart.

Next, tubes will be inserted into the groin and guided through the blood vessels up to the heart. Guidewires will be inserted into the heart. Doctors will watch the path the wires take with x-rays and ultrasound. When the wire is in the correct place, it will be electrified to slice excess tissue away from the septum.

Participants will have 3 follow-up visits within 1 year.

Study Overview

• Status: Not yet recruiting
• Conditions: Aortic Valve Stenosis; Hypertrophic Cardiomyopathy; Mitral Valve Disease; Left Ventricular Septal Hypertrophy
• Intervention / Treatment: Device: Septal Scoring Along Midline Endocardium

Detailed Description

Cardiac interventricular septal reduction therapies - to relieve left ventricular outflow tract obstruction from transcatheter valve replacement or hypertrophic cardiomyopathy - have inherent limitations including dependence on coronary anatomy, high pacemaker implantation rate, and surgical morbidity. We developed a novel transcatheter ventricular myotomy called SEptal Scoring Along the Midline Endocardium (SESAME) that relies on intramyocardial guidewire navigation and transcatheter electrosurgery. SESAME has been performed on a small number of patients using off label devices.

This study systematically characterizes the safety and early feasibility of SESAME at 1 enrolling site. SESAME is performed as septal reduction therapy in a heterogeneous group of subjects, including symptomatic hypertrophic cardiomyopathy and resting or provoked left ventricular outflow obstruction (LVOTO); and severe symptomatic mitral and/or aortic valve disease at high risk of standard heart surgical therapy and requiring later transcatheter heart valve implantation combined with manifest or potential LVOTO.

A key goal of this study is to attempt to capture generalizable knowledge from as many patients as possible, and to add a limited number of research procedures to characterize the safety and provisional effectiveness of SESAME. Absent realistic non-clinical models of HCM or LVH combined with aortomitral disease, we believe little more information can be gleaned without clinical investigation.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Annette Stine, R.N.; Phone Number: (301) 402-5558; Email: stinea@nhlbi.nih.gov
• Study Contact Backup: Name: Robert J Lederman, M.D.; Phone Number: (301) 402-6769; Email: lederman@nih.gov

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
      • Contact: Robert Lederman, M.D.; Phone Number: 301-402-6769; Email: lederman@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

In order to be eligible to participate in the study, candidates must meet all of the following criteria:

• Adults age >= 21 years

• Requires debulking of left ventricular septum for one of three phenotypes

  • 1: Hypertrophic cardiomyopathy; OR
  • 2: Left ventricular septal hypertrophy, mitral valve disease and/or aortic valve stenosis warranting/following transcatheter heart valve implantation, WITH intracameral gradient >= (30mmHg peak while resting; 50mmHg peak when provoked); OR
  • 3: Left ventricular septal hypertrophy, mitral valve disease warranting transcatheter heart valve implantation, and risk of iatrogenic left ventricular outflow tract obstruction (LVOTO), Neo-LVOT <= 200 mm^2, WITHOUT intracameral gradient >= (30mmHg peak while resting; 50mmHg peak when provoked)

• Septal diastolic thickness on CT:

  • Total >=12 mm, and
  • Predicted residual septal thickness >= 6 mm, and
  • Predicted laceration depth >= 6 mm

• Severely symptomatic, any of

  • NYHA Class III or greater
  • Canadian Angina Class CCS III or greater
• Explicitly chooses investigational SESAME over conventional treatment approaches including (1) cardiac myosin inhibitor therapy, if eligible (HCM only); (2) transcoronary alcohol septal ablation, if eligible; or (3) surgical left ventricular myotomy and/or myectomy, if eligible
• Concurrence of the multidisciplinary institutional heart team that the candidate is at high risk for surgical myectomy
• Concurrence of the study Central Clinical Eligibility Committee
• Willing to return for all scheduled follow-up activities, and eligible or able to undergo required protocol and testing

Additional selection criteria for Hypertrophic Cardiomyopathy

- High risk of surgical myotomy/myectomy according to the multidisciplinary heart team

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

• Does not consent to participate, or unable to consent to participate
• Requires antegrade SESAME access (because of mechanical aortic valve)
• Prior completed transcoronary alcohol septal ablation, or prior surgical myectomy
• Pregnant
• Hemodynamic instability or emergency procedure
• eGFR < 30 mL/min/1.73m^2
• Survival despite successful procedure expected < 12months

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: SESAME Arm	Device: Septal Scoring Along Midline Endocardium; Transcatheter ventricular myotomy called SEptal Scoring Along the Midline Endocardium (SESAME) that relies on intramyocardial guidewire navigation and transcatheter electrosurgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical success	The primary feasibility endpoint is Technical success (measured at exit from the catheterization laboratory). All of the following must be present:-Alive-Procedure success including-Successful myocardial entry, navigation, and snaring of guidewire traversal system; and -Successful laceration of septal myocardium	1 day
Safety	Safety is measured as freedom from all of the following:-All-cause mortality-All stroke (disabling and non-disabling)-Major cardiac structural complication requiring intervention (such as iatrogenic ventricular septal defect, iatrogenic aortic valve regurgitation, iatrogenic mitral regurgitation, or pericardial tamponade) related to SESAME	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete heart block requiring permanent pacemaker	Complete heart block requiring permanent pacemaker	Discharge

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Robert J Lederman, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: February 17, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: February 12, 2024

More Information

Terms related to this study

• Keywords: transcatheter electrosurgery; transcatheter ventricular myotomy; Cardiac interventricular septal reduction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Hypertrophy; Cardiomyopathies; Cardiomyopathy, Hypertrophic
• Other Study ID Numbers: 10001640; 001640-H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

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