Paced Dyssynchrony and Myocardial Perfusion IN apiCal Hcm

NCT04231032 | Terminated DMC

• 1 other identifier: V1.2_25 08 21
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. A relatively common subgroup of HCM patients have apical HCM - a type of heart muscle disease that causes abnormal muscle thickening towards the tip (apex) of the heart. This can impair the heart's own blood flow through the thickened heart muscle. We think this is one of the causes for symptoms such as shortness of breath and chest pain. If medications are ineffective at treating symptoms, there are few further options available, limited to invasive heart surgery. This study aims to determine if it is possible to improve the blood flow within by altering the settings of patients' permanent pacemakers, dynamic microvascular obstruction is an important cause of perfusion abnormalities in HCM and whether introducing localized dyssynchrony with ventricular pacing improves this. This phased study will include patients with apical HCM that already have implanted pacemaker devices to remove risks associated with device implantation. The study may provide insights into novel mechanisms for symptoms in HCM and provide new methods for treating a patient group in whom therapeutic options can be extremely limited.

Conditions

Hypertrophic Cardiomyopathy

Keywords

Apical hypertrophic cardiomyopathy; Pacemaker; Perfusion

Outcome Measures

Primary Outcomes (1)

• Myocardial perfusion mapping

  Percentage change in regional myocardial perfusion between baseline and pacing measured using myocardial blood flow (MBF) mapping at Cardiovascular Magnetic Resonance (CMR) imaging.

  Acute changes during the CMR scan on Visit 1 (day 1)

Secondary Outcomes (13)

• Proportion successfully completing the CMR scan with interpretable images.

  After all visit 1 completed (within 6 months)

• Myocardial contractility via CMR

  Acute changes during the CMR scan on Visit 1 (day 1)

• Myocardial contractility via echocardiography

  Acute changes during the echocardiogram scan on Visit 1 (day 1)

• Proportion unwilling to proceed to Phase B.

  After all visit 1 completed (within 6 months).

• Recruitment rate.

  12 months.

Study Arms (2)

Active ventricular pacing

ACTIVE COMPARATOR

Asynchronous dual chamber pacing (DOO mode) at a heart rate just higher than that expected to be achieved with adenosine infusion (same rate in each arm)

Other: Asynchronous dual chamber pacing (DOO) with paced ventricular activation

Back-up ventricular pacing

PLACEBO COMPARATOR

Asynchronous atrial pacing with intrinsic ventricular activation (AOO mode) at a heart rate just higher than that expected to be achieved with adenosine infusion (same rate in each arm)

Other: Asynchronous atrial pacing (AOO) with intrinsic ventricular activation

Interventions

Asynchronous dual chamber pacing (DOO) with paced ventricular activation OTHER

Alteration of the participant's existing pacemaker mode to either paced or intrinsic ventricular activation (in an order based upon randomisation).

Active ventricular pacing

Asynchronous atrial pacing (AOO) with intrinsic ventricular activation OTHER

Alteration of the participant's existing pacemaker mode to either paced or intrinsic ventricular activation (in an order based upon randomisation).

Back-up ventricular 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.
• HCM patients with apical HCM defined as apical hypertrophy with apical LV systolic obliteration and the presence of characteristic ECG changes. Participants with a mixed cardiac phenotype will be considered if they also meet these criteria and do not have resting outflow tract obstruction.
• A programmable intracardiac pacing device with a right atrial lead and an apically / low septal located right ventricular lead.
• Willing and able to provide informed consent.

You may not qualify if:

• Outflow tract obstruction \>50 mmHg at rest due to systolic anterior mitral movement.
• Evidence of high-grade heart block.
• Moderate or severe primary valvular disease.
• Unrevascularised, known, significant coronary disease: the significance of any known coronary disease will be determined after discussion with an independent clinician.
• Atrial fibrillation at the time of randomisation.
• Inability to undergo CMR with adenosine stress and gadolinium contrast imaging.
• Pregnancy.

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

Barts Heart Centre

London, Thames, EC1A 7BE, United Kingdom

Location

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic; Apical Hypertrophic Cardiomyopathy

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Hypertrophy, Left Ventricular; Cardiomegaly

Study Officials

• Saidi A Mohiddin, MBChBFRCPMD

  Barts & The London NHS Trust

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Double-blind, randomised, cross-over design

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 18, 2020
• Study Start: June 2, 2021
• Primary Completion: February 20, 2023
• Study Completion: February 20, 2023
• Last Updated: April 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)