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

Not Applicable

Completed

• Conditions: Cardiomyopathy, Hypertrophic
• Interventions: Device: Active pacing; Device: Back-up pacing

• Registration Number: NCT03450252
• Lead Sponsor: Barts & The London NHS Trust

Brief Summary

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.

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 Timeline

• Study First Submitted: 2018-01-17
• Study Start: 2018-02-09
• Study First Submitted QC: 2018-02-27
• Study First Posted: 2018-03-01
• Primary Completion: 2023-01-20
• Study Completion: 2023-01-20
• Last Update Submitted: 2023-01-31
• Status Verified: 2023-02
• Last Update Posted: 2023-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 17

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Active pacing	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.
Back-up pacing	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Barts Heart Centre; 🇬🇧 London, Thames, United Kingdom