Cardiac Remodeling, Ventricular, Cardiomyopathy, Dilated, Heart Failure, Left Ventricular Dyssynchrony
Conditions
Keywords
Cardiac resynchronization therapy, Heart failure, Mechanical dyssynchrony, Echocardiography, Apical rocking, Septal flash, Left ventricle
Brief summary
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.
Interventions
DEVICECardiac resynchronization therapy ON
Implantation of a CRT device. Bi-ventricular pacing will be turned ON.
DEVICECardiac resynchronization therapy OFF
Implantation of a CRT device. Bi-ventricular pacing will be turned OFF.
Sponsors
Universitaire Ziekenhuizen KU Leuven
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Volume response and Packer Clinical Composite Score | 12 months follow-up | 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 left ventricular end-systolic volume and the proportion of patients 'worsened' according to the Packer Clinical Composite Score after 12 months follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect on left ventricular function in both arms | 12 months follow-up | * ≥ 10% difference in relative change in left ventricular ejection fraction and/or * ≥1.5% difference in absolute change in global longitudinal strain and/or * improvement in myocardial work from baseline to month 12 |
| Difference in quality of life as measured by the Minnesota Living with Heart Failure questionnaire score and EuroQol 5D index score in both arms | 12 months follow-up | * ≥ 5 points difference in change on the Minnesota Living with Heart Failure questionnaire score and/or * ≥0.08 points difference in change on the EuroQol 5D index score from baseline to month 12 |
| Difference in 6 minute walk test distance in both arms | 12 months follow-up | ≥ 45 meters difference in change from baseline to month 12 |
| Difference in predictive value for volume response | 12 months follow-up | ≥15% relative reduction in left ventricular end-systolic volume from baseline to month 12 will be considered as a response |
| Difference in predictive value for long-term patient outcome in both arms | 1 year, 3 years and 5 years follow-up | Cox's proportional hazards model: * At 1 year for 'worsened' PCCS * At 3 and 5 years for cardiovascular mortality and heart failure hospitalization |
| Difference in long-term patient outcome in both arms | 3 years and 5 years follow-up | * Kaplan Meier survival analysis for heart failure hospitalization * Kaplan Meier survival analysis for cardiovascular mortality * Kaplan Meier survival analysis for combined heart failure hospitalization and cardiovascular mortality * Kaplan Meier survival analysis for all-cause mortality |
Countries
Belgium, Brazil, France, Germany, Hungary, Latvia, Poland, Portugal, Romania, Spain, Switzerland
Contacts
PRINCIPAL_INVESTIGATORJens-Uwe Voigt, MD, PhD
Universitaire Ziekenhuizen KU Leuven
Outcome results
None listed