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

NCT03450252 | Completed DMC

• 1 other identifier: V11_27 10 20
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiomyopathy, Hypertrophic

Keywords

HCM; Mid-cavity; Pacing

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Symptomatic assessment via SF36 questionnaire

  Pre-implant, 4 months, and 8 months

• Symptomatic assessment via Kansas City Cardiomyopathy questionnaire

  Pre-implant, 4 months, and 8 months

• Symptomatic assessment via calculation of New York Heart Association (NYHA) functional class

  Pre-implant, 4 months, and 8 months

• Exercise performance assessed by 6 minute walk test (6MWT)

  Pre-implant, 4 months, and 8 months

• Exercise performance assessed by Cardiopulmonary exercise testing (CPET) stress echocardiography.

  Pre-implant, 4 months, and 8 months

Study Arms (2)

Active pacing

EXPERIMENTAL

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

Back-up pacing

SHAM COMPARATOR

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

Interventions

Active pacing DEVICE

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.

Active pacing

Back-up pacing DEVICE

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.

Back-up pacing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, \>18 years.
• Referred for PPM +/- ICD implantation for either primary prevention of sudden cardiac death or other indications such as heart block or obstructive physiology.
• 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.
• All patients should be taking maximum tolerated doses of beta blockers or verapamil with or without disopyramide.
• Symptoms refractory to optimum medical therapy as above, for example breathlessness, chest pain, dizziness, or syncope.

You may not qualify if:

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

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

Barts Heart Centre

London, Thames, EC1A 7BE, United Kingdom

Location

Related Publications (1)

• Malcolmson JW, Hughes RK, Husselbury T, Khan K, Learoyd AE, Lees M, Wicks EC, Smith J, Simms AD, Moon JC, Lopes LR, O'Mahony C, Sekhri N, Elliott PM, Petersen SE, Dhinoja MB, Mohiddin SA. Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing. Circ Arrhythm Electrophysiol. 2024 Jul;17(7):e012570. doi: 10.1161/CIRCEP.123.012570. Epub 2024 Jun 19.

  PMID: 39012930 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Study Officials

• Saidi A Mohiddin, BSc, MBChB, FRCP, MD

  Barts Health NHS Trust and Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Taking part in this study will involve recording the information at a pre-implant visit, a visit for cardiac pacemaker implantation and follow-up visits four and eight months later. At the pre-implant visit, participants will undergo assessment of symptoms, physical performance and blood test for a protein, Brain natriuretic peptide (BNP). During the pacemaker implantation, the investigators will record the pressures within the heart using a catheter during both active pacing and back-up pacing settings. The day after the pacemaker implant participants will undergo double-blind randomisation into either the treatment or non-treatment arm (active or back-up pacing respectively). At four months, cross-over takes place with assessment as above, before device reprogramming into either the treatment or non-treatment arm depending on which was completed first. At the end of the second four month period, participants will undergo repeat assessment as above. That will conclude the study.

Study Record Dates

• First Submitted: January 17, 2018
• First Posted: March 1, 2018
• Study Start: February 9, 2018
• Primary Completion: January 20, 2023
• Study Completion: January 20, 2023
• Last Updated: February 1, 2023

Record last verified: 2023-02

Locations

GB (1)