Effects of Preferential Left Ventricular Pacing on Ventriculoarterial Coupling and Clinical Course of Heart Failure

NCT ID: NCT04420065

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2024-12-31

Brief Summary

Randomized trial of adult patients to study the effects of preferential left ventricular pacing on ventriculoarterial coupling of both systemic and pulmonary circulation, indices of systolic and diastolic function of both ventricles, and clinical course of patients with advances dyssynchronous heart failure.

Detailed Description

Study hypothesis is that preferential left ventricular (LV) pacing, delivered by means of the AdaptivCRT® algorithm and in conjunction with automated V-V delay adjustments, will lead to improvements over standard biventricular pacing (BVP) in the function of all cardiac chambers, reduce arrhythmic burden, improve ventricular-arterial coupling (VAC), and patient functional status. It would be interesting to study what changes in right-side VAC (RVAC) can be appreciated with the activation of the preferential LV pacing algorithm and how they relate to each other, i.e. whether LV is driven towards maximizing output whilst RV shifts to optimizing energy efficiency.

READAPT is a single-center, prospective, randomized trial of heart failure patients eligible for CRT according to current European heart failure guidelines. Informed written consent is required from all study participants.

Adult (aged 18-80 years old), consenting patients with any cardiomyopathy type, diagnosed at least 6 months prior (to exclude recent myocarditis cases that may remit and confound outcomes), on optimal medical therapy for at least 3 months, and an existing I/IIa indication for a cardiac resynchronization therapy - defibrillator (CRT-D) device will be enrolled and randomized into 2 groups, one receiving standard CRT (Group 1 - G1), and one with activation of the preferential LV pacing algorithm (Group 2 - G2). Enrollment date will amount to the baseline assessment date, with device implantation occurring preferably within 48 hours. READAPT will include patients with both new CRT-D implantation and an upgrade from an existing defibrillator or pacemaker with no prior left ventricular lead placement.

Conditions

Heart Failure With Reduced Ejection Fraction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Classical biventricular pacing

Commercially available LV-pacing capable CRT devices and quadripolar leads will be implanted. Right ventricular (RV) and right atrial (RA) leads will be placed according to standard practice. The LV lead will also be placed according to standard practice, targeting to a lateral, posterolateral, or anterolateral branch of the coronary sinus (CS). Interventricular delay programmed will be determined based on stroke volume maximization, and will be used as a criterion for BVP optimization. Atrioventricular delay optimization shall be automatically performed by the device.

Group Type: ACTIVE_COMPARATOR

Biventricular pacing

Intervention Type: DEVICE

Standard biventricular pacing, with V-V delay programmed based on stroke volume maximization, and A-V delay delegated to the device

Preferential left ventricular pacing

In G2 patients, an algorithm for preferential left ventricular pacing will be activated. Following selection of the dipole maximizing stroke volume during simultaneous LV-RV pacing, subsequent V-V delay optimization shall be delegated to the algorithm. Based on previous studies, a subgroup analysis of G2 will be performed, comparing those receiving ≥50% with those receiving \<50% preferential LV pacing evaluated over the total duration of the study (12 months).

Group Type: EXPERIMENTAL

Preferential left ventricular pacing

Intervention Type: DEVICE

Activation of an algorithm attempting to provide preferential left ventricular pacing in an anticipatory manner, thus potentially preventing iatrogenic, pacing-related, right ventricular dysfunction, and improving coupling and outcomes in dyssynchronous heart failure patients

Interventions

Preferential left ventricular pacing

Activation of an algorithm attempting to provide preferential left ventricular pacing in an anticipatory manner, thus potentially preventing iatrogenic, pacing-related, right ventricular dysfunction, and improving coupling and outcomes in dyssynchronous heart failure patients

Intervention Type: DEVICE

Biventricular pacing

Standard biventricular pacing, with V-V delay programmed based on stroke volume maximization, and A-V delay delegated to the device

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

Age 18-80 years old Provided informed consent Any cardiomyopathy type, diagnosed at least 6 months prior (to exclude recent myocarditis cases that may remit and confound outcomes) On optimal medical therapy for at least 3 months, An existing I/IIa indication for a CRT-D device Both new CRT-D implantation and an upgrade from an existing ICD or pacemaker with no prior left ventricular lead placement.

Exclusion Criteria

1. Have an existing Class I recalled lead,

2. Are anticipated to need heart transplantation within the next 9 months,

3. Have undergone cardiac transplantation less than 40 days prior to enrolment,

4. Have had a cerebrovascular accident or transient ischemic attack within 3 months of enrollment,

5. Have had a recent myocardial infarction less than 40 days prior to enrollment, or unstable angina or cardiac revascularization less than 3 months prior to enrolment,

6. Have documented moderate to severe/severe mitral/aortic/tricuspid/pulmonary insufficiency (noninvasive VAC calculation impossible),

7. Exhibit a daily burden of premature ventricular complexes (PVCs) of either ≥10% of total QRSs or ≥10,000 on ambulatory ECG recording21, 22 (to exclude PVC-related, potentially reversible cardiomyopathy),

8. Are currently participating in a clinical investigation that includes an active treatment arm,

9. Have diagnosed pulmonary hypertension other than class II (left heart-related),

10. Have known stage IV-V renal dysfunction (clearance estimated by the Cockcroft-Gault equation),

11. Have permanent atrial fibrillation,

12. Have complete atrioventricular block,

13. Have a prolonged (>200msec) PQ interval on surface ECG (thus invalidating the option for preferential LV pacing),

14. Are pregnant or planning to become pregnant during the duration of the study (in case of unplanned pregnancy the patient will have to be excluded from the study),

15. Have an expected life expectancy of <12 months, or

16. Undergo major adaptations to their pharmacological regimens during follow-up (e.g. initiation of neprilysin inhibitors).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National and Kapodistrian University of Athens

OTHER

Sponsor Role: lead

Responsible Party

Christina Chrysohoou

Cardiology Consultant, Director of Cardiology, Senior Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

First University Department of Cardiology, Hippokrateion General Hospital

Athens, Attica, Greece

Countries

Greece

Central Contacts

Christina Chrysohoou, MD PhD

Role: CONTACT

chrysohoou@usa.net

00306944435168

Christos-Konstantinos Antoniou, MD PhD

Role: CONTACT

ckantoniou@hotmail.gr

00306972708430

Facility Contacts

Manina Anastasopoulou

Role: primary

00302132088027

Other Identifiers

READAPT

Identifier Type: -

Identifier Source: org_study_id