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

Heart Failure With Reduced Ejection Fraction Clinical Trial

— READAPT  

Official title:

CompaRative Study of the Effects of Left ventriculAr and Biventricular Pacing on inDices of cArdiac Function and Clinical Course of Heart Failure PatienTs: Rationale and Design of the READAPT Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04420065
• Other study ID #: READAPT
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2020
• Source: National and Kapodistrian University of Athens
• Contact: Christina Chrysohoou, MD PhD
• Phone: 00306944435168
• Email: chrysohoou[@]usa.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 220
• Est. completion date: December 31, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

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

Locations

Country	Name	City	State
Greece	First University Department of Cardiology, Hippokrateion General Hospital	Athens	Attica

Sponsors (1)

Lead Sponsor	Collaborator
National and Kapodistrian University of Athens

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in patient exercise capacity	Assessed by cardiopulmonary exercise test in terms of maximal oxygen consumption in ml/kg/min	12 months
Secondary	Number of hospitalizations for heart failure	Data retrieved from online patient file will be used to compare number of unplanned hospitalizations for worsening heart failure between groups	12 months
Secondary	Left ventricular function	Assessed by ejection fraction (in %), strain echocardiography - changes in % global longitudinal peak strain and diastolic function indices (E/e')	12 months
Secondary	Right ventricular function	Assessed by strain echocardiography in terms of two-dimensional % global longitudinal peak strain	12 months
Secondary	Ventriculoarterial coupling for both systemic and pulmonary circulation	Assessed by the noninvasive single-beat echocardiographic method in terms of distance from 1 (value associated with maximization of stroke work for a given contractility)	12 months