Pacing in Heart Failure With Preserved LVEF (MAPPLE)

The Effect of Biventricular Pacing in Heart Failure With Preserved Left Ventricular Ejection Fraction: A Pilot Mechanistic Analysis

A random-order cross-over pilot trial of a CE marked device (pacemaker) outside its current intended purposes.

The study will comprise 10 patients. Recruitment of patients will take place from The University Hospital of Wales (Cardiff & Vale University Health Board [CVUHB]). All patients recruited will have septal flattening during exercise demonstrated using contrast stress (exercise) echocardiography.

All 10 patients will be implanted with a CRT-pacemaker device and will be tested on all three of the following settings on separate visits (with a gap of up to 5 days between visits) in random order:

Routine Medical Therapy Routine Medical Therapy + LVP Routine Medical Therapy + BiVP

Study Overview

• Status: Enrolling by invitation
• Conditions: Heart Failure
• Intervention / Treatment: Device: CRT-pacemaker device set to Routine Medical Therapy; Device: CRT-pacemaker device set to Routine Medical Therapy + LVP; Device: CRT-pacemaker device set to Routine Medical Therapy + BiVP

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Cardiff, United Kingdom, CF14 4UJ
    • University Hospital Wales

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Clinical features consistent with heart failure. All patients will have symptoms of moderate to severe heart failure with New York Heart Association (NHYA) classification III or IV symptoms (for at least 3 months).
2. LV Ejection Fraction less or equal to 50%, with no evidence of significant valvular disease, no hypertrophic or restrictive cardiomyopathy, and no evidence of pericardial constriction.
3. Additionally all patients will have demonstrated evidence of septal flattening during exercise using contrast echocardiography.
4. Adults (over 18 years)
5. Negative test for Covid during surgical pre-assessment, and adherence to prescribed self-isolation before implantation.
6. Two weeks or more following final dose of vaccination against coronavirus.

Exclusion Criteria:

1. Inability to provide informed consent.
2. Enrolment in other clinical studies.
3. BMI more than 35
4. Objective evidence of significant lung disease on formal lung function testing
5. Previous (within three months) or scheduled coronary revascularisation or other cardiac surgery
6. Acute coronary syndrome (within the previous three months)
7. History of atrial fibrillation (AF)
8. Renal insufficiency requiring haemodialysis
9. Life expectancy less than 6 months
10. Prosthetic heart valves
11. Blood coagulation disorders
12. Immunocompromised patients (e.g. AIDS, patients on steroids, cytotoxic drugs, and radiation therapy)
13. Currently pregnant, or intending to conceive.
14. Recent positive Covid test (up to 14 days prior to pre-assessment).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Routine Medical Therapy	Device: CRT-pacemaker device set to Routine Medical Therapy; Medtronic Serena™ QUAD CRT-P MRI™ SureScan™ W4TR05 set to Routine Medical Therapy
Experimental: Routine Medical Therapy + LVP	Device: CRT-pacemaker device set to Routine Medical Therapy + LVP; Medtronic Serena™ QUAD CRT-P MRI™ SureScan™ W4TR05 set to Routine Medical Therapy + LVP
Experimental: Routine Medical Therapy + BiVP	Device: CRT-pacemaker device set to Routine Medical Therapy + BiVP; Medtronic Serena™ QUAD CRT-P MRI™ SureScan™ W4TR05 set to Routine Medical Therapy + BiVP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in septal radius of curvature (corrected for LV area) between rest and peak exercise on stress echocardiography across the three pacing states.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in LV area between rest and exercise across the three pacing states	12 weeks
Change in Systolic and Diastolic mechanical Dyssynchrony Assessment on echocardiography across the three pacing states	12 weeks
Change in rest and exercise E/E' on echocardiography across the three pacing states	12 weeks

Collaborators and Investigators

• Sponsor: Cardiff and Vale University Health Board
• Collaborators: Norfolk and Norwich University Hospitals NHS Foundation Trust; Cardiff Metropolitan University
• Investigators: Principal Investigator: Zaheer Yousef, Cardiff and Vale University Health Board

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2023
• Primary Completion (Estimated): March 31, 2024
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: July 10, 2017
• First Posted (Actual): July 12, 2017

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 203878

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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