Cardiac Resynchronization Therapy, Heart Failure
Conditions
Keywords
left bundle branch pacing, biventricular pacing, cardiac resynchronization therapy
Brief summary
Conduction system pacing vs biventricular resynchronization therapy in systolic dysfunction and wide QRS: mortality, heart failure hospitalization or cardiac transplant (CONSYST-CRT II trial). Superiority trial that aims to study the composite endpoint consisting of all-cause mortality, cardiac transplant or heart failure hospitalization at 12-month follow-up.
Detailed description
To date, studies have shown that conduction system pacing could get similar clinical and echocardiographic responses to those obtained with biventricular therapy. This study will randomize 320 patients to a strategy of biventricular pacing versus conduction system pacing. CONSYST-CRT II study will analyze a clinical endpoint as primary endpoint and the following parameters in both groups: left ventricular ejection fraction, ventricular volumes, echocardiographic response (\>=15% decrease in left ventricular end-systolic volume), NYHA functional class, heart failure hospitalization, all-cause mortality, cardiac transplant, QRS shortening, echocardiographic dyssynchrony (atrioventricular, interventricular, intraventricular) and global longitudinal strain. As a secondary endpoint, baseline predictors of response to conduction system pacing and biventricular pacing according to cardiac magnetic ressonance and electrocardiographic imaging will be studied. Clinical, electrocardiographic, echocardiographic follow-up will be performed during 12 months.
Interventions
PROCEDUREConduction system pacing
Conduction system pacing implant as a Resynchronization therapy.
PROCEDUREBiventricular pacing
Biventricular pacing implant
Sponsors
Hospital Clinic of Barcelona
Institut d'Investigacions Biomèdiques August Pi i Sunyer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Intervention model description
The first 130 patients have been recruited in the context of the CONSYST I study (ClinicalTrials.gov Identifier: NCT05187611). It is planned to perform an interim analysis (intermediate analysis) for the primary endpoint in all randomized patients who received intervention. The formal limits of stopping the study will be determined by the limits of futility and effectiveness defined by the rules of sequential stopping using the O'Brien-Fleming method. The interim analysis will be performed with a sample recruitment of 50%. Members of the Data Monitoring Committee, but not any trial investigator, will be informed of the results of the interim analysis. A p of 0.0054 (two-sided alpha) will be required for the interim analysis and 0.049 in the final analysis.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must indicate acceptance to participate in the study by signing an informed consent document. * Patient must be ≥ 18 years of age. * Left bundle branch block, QRS ≥130 and LVEF \<=35%. No indication of stimulation for AV block. * Non-left bundle branch block, QRS ≥150 and LVEF \<=35%. * Resynchronization therapy indication for ventricular dysfunction (LVEF \<40%) and indication of cardiac pacing for AV block. * LVEF \<=35% in NYHA class III or IV, atrial fibrillation and intrinsic QRS \>=130 ms, provided a strategy to ensure biventricular capture is in place.
Exclusion criteria
* Myocardial infarction, unstable angina or cardiac revascularization during the previous 3 months. * Pregnancy. * Participating currently in a clinical investigation that includes an active treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite end-point: all-cause mortality, cardiac transplant or heart failure hospitalization. | 1 year | Clinical follow-up at 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in left ventricular ejection fraction. | 6 months; 1 year | Left ventricular ejection fraction measured with Simpson method with echocardiography. |
| Change in left ventricular end-systolic volume. | 6 months; 1 year | Left ventricular volumes measured with echocardiography. Simpson rule from 2- and 4-chamber apical views. |
| Echocardiographic response. | 6 months; 1 year | \>=15% decrease in left ventricular end-systolic volume |
| Change in NYHA functional class. | 6 months; 1 year | NYHA functional class I, II, III, or IV |
| QRS shortening. | Immediately after the intervention | QRS duration (milliseconds). QRS onset measured from fast deflection and from spike. |
| Correction of septal flash. | 15 days; 6 months; 1 year | Fast inward-outward movement of the interventricular septum in early systole. Using M-mode in parasternal short and long-axis views, septal flash was quantified (in millimeters) as the highest amplitude of the early inward motion measured from the resting position prior to the onset of septal contraction. The pair of septal flash measures (baseline and final) was obtained at the axis with the highest baseline SF. |
| Correction of auriculoventricular dyssynchrony. | 15 days; 6 months; 1 year | Left ventricular filling time. The left ventricular filling time was measured from the onset of the E-wave to the end of the A-wave, and the R-R interval was measured to calculate the percentage of filling time relative to the cardiac cycle (LV filling time/RR, %). |
| Correction of interventricular dyssynchrony. | 15 days; 6 months; 1 year | Quantified using pulsed Doppler and calculated as the time difference between QRS onset and the onset of the flow wave in the right and left outflow tracts. |
| Change in global longitudinal strain (GLS). | 15 days; 6 months; 1 year | Strain myocardial deformation of the left ventricle was quantified offline from 2-dimensional echocardiography using speckle tracking (2Dstrain, Echo Pac, version 202.41.0, GE Healthcare Milwaukee, WI). The long-axis cine images (2-, 3-, and 4-chamber views), were used to determine GLS. |
| Description of baseline predictors of response to conduction system pacing and biventricular pacing. Cardiac fibrosis quantification. | Baseline (pre intervention). | Cardiac fibrosis quantification (grams of fibrosis) |
| Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Left ventricular activation time (LVAT), ms. | Baseline (pre intervention). And immediately after the intervention | Left ventricular activation time (LVAT), ms. |
| Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Ventricular electrical uncoupling (VEU). | Baseline (pre intervention). And immediately after the intervention | Ventricular electrical uncoupling (VEU) = mean left ventricular activation time - mean right ventricular activation time, ms |
| Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Left ventricular dyssynchrony index (LVDI). | Baseline (pre intervention). And immediately after the intervention | Left ventricular dyssynchrony index (LVDI): standard deviation of individual activations recorded from the left ventricle. |
| Description of baseline predictors of response to conduction system pacing and biventricular pacing with Electrocardiographic Imaging. Conduction velocity (cm/s). | Baseline (pre intervention). And immediately after the intervention | Conduction velocity (cm/s). |
Countries
Spain
Contacts
CONTACTJose Mª Tolosana, MD, PhD
CONTACTMargarida Pujol López, MD
PRINCIPAL_INVESTIGATORJosé Mª Tolosana, MD, PhD
Hospital Clínic de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer
PRINCIPAL_INVESTIGATORMargarida Pujol López, MD
Hospital Clínic de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer
STUDY_CHAIRLluís Mont, MD, PhD
Hospital Clínic de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer
Outcome results
None listed