Clinical trial NCT04420065: Effects of Preferential Left Ventricular Pacing on Ventriculoarterial Coupling and Clinical Course of Heart Failure
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: Heart failure
Cardiac resynchronization therapy
Preferential left ventricular pacing
Ventriculoarterial coupling
Echocardiography
Cardiopulmonary exercise test
Lead sponsor: National and Kapodistrian University of Athens
Sponsor class: OTHER
First posted: 2020-06-09
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients randomized after enrollment to receive either standard biventricular pacing, or preferential left ventricular pacing (left ventricle will be resynchronized, but right ventricle will be activated through the intrinsic conduction system)
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Changes in patient exercise capacity
timeFrame: 12 months
Secondary outcomes:
measure: Number of hospitalizations for heart failure
timeFrame: 12 months
measure: Left ventricular function
timeFrame: 12 months
measure: Right ventricular function
timeFrame: 12 months
measure: Ventriculoarterial coupling for both systemic and pulmonary circulation
timeFrame: 12 months
Other outcomes:
Locations:
city: Athens
country: Greece
facility: First University Department of Cardiology, Hippokrateion General Hospital
state: Attica
Study officials:
References: