Pacemaker Therapy for Drug-refractory Symptoms in Mid-cavity Hypertrophic Cardiomyopathy

Distal Ventricular Pacing and Intraventricular Gradient Reduction for Symptomatic Relief in Drug Refractory Hypertrophic Cardiomyopathy Patients With Mid-cavity Obstruction

The main aim of this study is to assess the acute effects of a pacemaker on reducing abnormally high intracavity pressures in the hearts of patients with mid-cavity obstructive hypertrophic cardiomyopathy (HCM). During a 12-month period of double-blinded follow-up, descriptive data will be collected on patients symptomatic and physical performance during dichotomous pacemaker settings for 6-months each (active and back-up). The statistical information collected will be used to design a much larger research trial of patient benefit.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiomyopathy, Hypertrophic
• Intervention / Treatment: Device: Active pacing; Device: Back-up pacing

Detailed Description

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, affecting 1 in 500 of the general population. It is characterised by abnormal thickening of the heart muscle. The various patterns of thickening of the muscle in the main pumping chamber, or left ventricle (LV), can result in obstruction to blood flow within the heart, raising the pressures in the heart and placing extra strain on the heart muscle.

The obstruction can cause patients to suffer from symptoms such as shortness of breath and chest pain, along with poor exercise tolerance, and dizzy spells. In very symptomatic patients with the commonest type of obstruction, invasive procedures performed either via an open-heart or keyhole operation can reduce the increased basal septal muscle mass at the point of obstruction. However, in around 1 in 10 HCM patients, the obstruction is deep within the LV where a ring of thick muscle blocks blood flow when it contracts. These patients provide a challenge for doctors, as this type of obstruction is much less suitable for open heart or keyhole operation.

An alternative is to use a cardiac pacemaker to alter the timing of the contraction in the ring of thick muscle such that different parts of the ring contract at different times and thereby reduce obstruction to blood flow. The investigators' early experience with this new treatment shows that carefully placing the pacemaker wires can reduce the obstruction and improve patient symptoms.

Key questions of this research include:

• How much can optimal ventricular pacing reduce the obstruction by?
• How important is choosing which part of the heart the pacemaker activates first?
• Does reducing obstruction in this way make patients better in the short and long term?

• Study Type: Interventional
• Enrollment (Anticipated): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Thames
    • London, Thames, United Kingdom, EC1A 7BE
      • Barts Heart Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, >18 years.
2. Referred for PPM +/- ICD implantation for either primary prevention of sudden cardiac death or other indications such as heart block or obstructive physiology.
3. HCM patients with evidence of mid-cavity gradient demonstrated by echocardiography and gradient ≥30 mmHg confirmed by cardiac catheterisation at rest or with isoprenaline provocation.
4. All patients should be taking maximum tolerated doses of beta blockers or verapamil with or without disopyramide.
5. Symptoms refractory to optimum medical therapy as above, for example breathlessness, chest pain, dizziness, or syncope.

Exclusion Criteria:

1. Patients with multi-level obstruction, i.e. across the mid-cavity and outflow tract.
2. Patients with moderate or severe valvular stenosis or regurgitation.
3. Patients with a history of myocardial infarction or acute coronary syndrome.
4. Patients unable to provide informed consent.
5. Patients in atrial fibrillation.
6. Pregnancy.
7. Renal failure.
8. If considered unsuitable by clinician.
9. Patients already participating in trials involving invasive procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active pacing; Active ventricular pacing. The pacemaker is set-up with a short atrio-ventricular delay to allow for appropriate pacing capture of the ventricle.	Device: Active pacing; Ventricular pacing via the invasive haemodynamic study-defined optimal pacing site in order to relieve pressure gradient across the mid-cavity obstruction in mid-cavity obstructive variant hypertrophic cardiomyopathy.
Sham Comparator: Back-up pacing; Back-up pacing. The pacemaker is set-up to sense and pace only in the right atrium (AAI) without any pacing capacity in the ventricle.	Device: Back-up pacing; Back-up pacing. The pacemaker is set-up to sense and pace only in the right atrium (AAI) without any pacing capacity in the ventricle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive gradient (mmHg)	Acute invasively defined gradient change in mmHg across the mid-cavity with optimal ventricular pacing setting	Measured during pacemaker implant. Pressure gradients will be measured at different pacing sites during the implant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic assessment via SF36 questionnaire	Generalised health related questionnaire	Pre-implant, 4 months, and 8 months
Symptomatic assessment via Kansas City Cardiomyopathy questionnaire	Cardiomyopathy health related questionnaire	Pre-implant, 4 months, and 8 months
Symptomatic assessment via calculation of New York Heart Association (NYHA) functional class	Classification of extent of heart failure	Pre-implant, 4 months, and 8 months
Exercise performance assessed by 6 minute walk test (6MWT)	Sub-maximal exercise test	Pre-implant, 4 months, and 8 months
Exercise performance assessed by Cardiopulmonary exercise testing (CPET) stress echocardiography.	Maximal exercise test with simultaneous echocardiography	Pre-implant, 4 months, and 8 months
Levels of Brain Natriuretic Peptide	Protein associated with heart failure	Pre-implant, 4 months, and 8 months

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Investigators: Principal Investigator: Saidi A Mohiddin, BSc, MBChB, FRCP, MD, Barts Health NHS Trust and Queen Mary University of London

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2018
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: January 17, 2018
• First Submitted That Met QC Criteria: February 27, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 30, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: HCM; Pacing; Mid-cavity
• 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: V11_27 10 20

Drug and device information, study documents

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