AMEND-CRT: Mechanical Dyssynchrony as Selection Criterion for CRT

Universitaire Ziekenhuizen KU Leuven

Status: Enrolling

Conditions: Cardiomyopathy, Dilated; Left Ventricular Dyssynchrony; Heart Failure; Cardiac Remodeling, Ventricular

Treatments: Device: Cardiac resynchronization therapy ON; Device: Cardiac resynchronization therapy OFF

Study type: Interventional

Funder types: Other

Identifiers

NCT04225520

S64188_v4.0

Details and patient eligibility

About

Previous experience with cardiac resynchronization therapy (CRT) candidates suggests that selection of these patients can be improved. Current clinical guideline approaches are mainly too unspecific and lead to a high non-responder rate of 30-40%, which causes a burden on health care systems and puts patients at risk of an unnecessary treatment who might benefit more from a conservative approach. Previous work indicated that using the assessment of mechanical dyssynchrony on echocardiography can lower the non-responder rate at least by 50% without compromising sensitivity for detecting amendable patients. The current prospective, randomized, multi-center trial was therefore designed to prove that the characterization of the mechanical properties of the left ventricle can improve patient selection for CRT. Patients will be randomized into one of two study arms: a control study arm with treatment recommendation based on clinical guidelines criteria, or an experimental study arm with treatment recommendation based on the presence of mechanical dyssynchrony. All patients will receive a CRT implantation. In the control study arm, bi-ventricular pacing will be turned on. In the experimental study arm, bi-ventricular pacing will be turned on or off, depending on the presence or absence of mechanical dyssynchrony, respectively. The primary endpoint will be non-inferiority in outcome of a treatment recommendation based on mechanical dyssynchrony, achieved with a lower number of CRT devices implanted, effectively leading to a lower number needed to treat. Outcome measures are the average relative change in continuously measured LVESV per arm and the percentage 'worsened' according to the Packer Clinical Composite Score per arm after 1 year follow-up.

Enrollment: 700 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

(- - - - - - - - - Inclusion Criteria - - - - - - - - -)

The proposed inclusion criteria represent the minimum recommendations for CRT implantation in heart failure patients according to the ESC 2021 guidelines. In addition:

• Patient has a LVEF ≤ 35%
• Patient has a LVEDD ≥ 2.7cm/m² or LVEDD ≥ 50mm (m) and ≥45mm (f)
• Patient has been in a stable medical condition for ≥ 1 month prior inclusion
• Patient underwent complete revascularization in case of ischemia
• Patients is able to understand and willing to provide a written informed consent
• Patient is 18 years or older

(- - - - - - - - - Exclusion Criteria - - - - - - - - -)

Patients with the following conditions will be excluded:

• unreliable left ventricular volume measurements
• severe MR or more than moderate other valvular disease
• pulmonary hypertension, other than secondary to left heart disease
• patient on hemodialysis
• life expectancy < 1 year
• pregnant or breastfeeding

Patients with prior right ventricular pacing between 20% to 80% will be excluded.

Patients with prior right ventricular pacing ≤ 20% or no pacemaker / ICD will be excluded if they have any of the following criteria:

• PR duration > 250ms
• second / third degree atrioventricular block
• intrinsic QRS duration < 130ms
• atrial fibrillation with resting HR < 50/min or > 80/min

Patients with prior right ventricular pacing ≥ 80% will be excluded if they have any of the following criteria:

• sensed AV delay > 250ms
• paced AV delay > 280ms

Patients with a prior pacemaker / ICD scheduled for LBBaP will be excluded regardless of pacing percentage

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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700 participants in 2 patient groups

Treatment recommendation based on guidelines

Active Comparator group

Description:

Treatment of the patient assigned to this arm will be based on the current guidelines for CRT implantation, as issued by the European Society of Cardiology. All patients will receive CRT implantation, with bi-ventricular pacing ON.

Treatment:

Device: Cardiac resynchronization therapy ON

Treatment recommendation based on mechanical dyssynchrony

Experimental group

Description:

Treatment of the patients assigned to this arm will be based on the presence of mechanical dyssynchrony. All patients will receive CRT implantation. Bi-ventricular pacing will be either turned ON or OFF, based on respectively the presence or absence of mechanical dyssynchrony.

Treatment:

Device: Cardiac resynchronization therapy ON

Device: Cardiac resynchronization therapy OFF