Branch Block, Bundle, Heart Failure
Conditions
Keywords
Heart Failure, Branch Block, Cardiac Resynchronization Therapy
Brief summary
Heart failure is a leading cause of morbidity and mortality. Cardiac resynchronization therapy (CRT) is a well-established treatment for patients with symptomatic heart failure in spite of optimised medical treatment (OMT), reduced left ventricular pump function with left ventricular ejection fraction (LVEF) ≤ 35% and prolonged activation of the ventricles (bundle branch block: BBB). CRT is established by implanting an advanced pacemaker system with three leads in the right atrium, right ventricle, and in the coronary sinus (CS) for pacing the left ventricle (LV), and often is combined with an implantable defibrillator (ICD) function. On average, CRT treatment improves longevity, quality of life and functional class, and reduces heart failure symptoms. Thus, at present, CRT is indicated for heart failure patients on OMT with BBB or chronic right ventricular (RV) pacing. It is, however, a significant problem that 30-40% of CRT patients do not benefit measurably - showing symptomatic improvement or improved cardiac pump function - from this therapy (socalled non-responders). LV lead placement is one of the major determinants of beneficial effect from CRT. Observational studies and three randomised trials with small sample sizes indicate that targeted placement of the LV lead towards a late activated segment of the LV may be associated with improved outcome. Based on this literature, some physicians already search for late activation when positioning the LV lead. However, such a strategy was never tested in a controlled trial with a sample size sufficient to investigate important clinical outcomes. Detailed mapping for a late activation may increase operating times and infection risk, result in use of more electrodes and wires, thereby increasing costs, and increase radiation exposure for patient and staff. Placement of the LV lead in late activated areas close to myocardial scar may even result in higher risk of arrhythmia and death. At present, it is completely unsettled whether targeted positioning of the LV lead to the latest electrically activated area of LV is superior to contemporary standard CRT with regard to improving prognosis for patients with heart failure and BBB. The present study aims to test whether targeting the placement of the LV lead towards the latest electrically activated segment in the coronary sinus branches improves outcome as compared with standard LV lead implant in a patient population with heart failure and CRT indication.
Interventions
DEVICEImplantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator
Implantation of CRT-P/-D device
Sponsors
Aarhus University Hospital
Aalborg University Hospital
Odense University Hospital
Rigshospitalet, Denmark
Gentofte University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients are unaware of treatment arm. All patients undergo the same pre-implant program and follow-up. Healthcare personel performing follow-up are blinded for treatment arm. Outcome events are evaluated by a committee blinded for treatment arm.
Intervention model description
Double-blind randomised controlled trial. Patients are included and randomised 1:1 into two groups for implantation of either 1. a CRT-D/P device with the LV lead positioned according to the latest electrical activation in the CS (intervention group) or 2. a CRT-D/P device with the LV lead positioned preferentially in a posterolateral, non-apical position (control group)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Heart Failure, NYHA II, III, outpatient IV * LVEF ≤35% measured by echocardiography * Optimal medical treatment for heart failure * Bundle Branch Block * Indication for primary CRT-D or CRT-P implantation or upgrade from RV pacing (pacemaker or ICD) to CRT-D or CRT-P * Ischemic heart disease (IHD) or non-IHD * Sinus rhythm or atrial fibrillation * Life expectancy \>2 years * Signed informed consent
Exclusion criteria
* NYHA class I * Acute mycardial infarction (AMI) within the latest 3 months * Coronary artery bypass graft (CABG) within the latest 3 months * Life expectancy \<2 years * Participation in another clinical trial of experimental treatment * Contraindication for establishing implantable device treatment * Previously implanted CRT system * Does not wish to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death or first non-planned hospitalisation for heart failure | All patients will be followed until the last included patient has been followed for two years | Time to death or first non-planned hospitalisation for heart failure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death | All patients will be followed until the last included patient has been followed for two years | Time to death |
| Non-planned hospitalisation for heart failure | All patients will be followed until the last included patient has been followed for two years | Time to first non-planned hospitalisation for heart failure |
| Sudden death | All patients will be followed until the last included patient has been followed for two years | Time to sudden death |
| Cardiac death | All patients will be followed until the last included patient has been followed for two years | Time to cardiac death |
| Clinical response | Follow-up at 3, 6, 12, 24 and 48 months | Increase in New York Heart Association (NYHA) class (≥1 class from baseline) or improved walking distance by six-minute walk test (6MWT) (≥10% from baseline) |
| Quality of Life (QoL) | Follow-up at 6, 12, 24 and 48 months | Changes in score from baseline to follow-up |
| Patient Reported Outcomes (PROs) | Follow-up at 6, 12, 24 and 48 months | Changes in score from baseline to follow-up |
| Echocardiographic measures of LV function | Follow-up at 6, 12, 24 and 48 months | Changes from baseline to follow-up in left ventricular ejection fraction (%) |
| Time to first appropriate ICD Therapy | All patients will be followed until the last included patient has been followed for two years | Time to first appropriate ICD therapy (antitachycardia pacing (ATP) or shock therapy) |
| Time to first inappropriate ICD Therapy | All patients will be followed until the last included patient has been followed for two years | Time to first inappropriate ICD therapy (antitachycardia pacing (ATP) or shock therapy) |
| Numbers of appropriate ICD Therapies | All patients will be followed until the last included patient has been followed for two years | Numbers of appropriate ICD therapies (antitachycardia pacing (ATP) or shock therapy) |
| Numbers of inappropriate ICD Therapies | All patients will be followed until the last included patient has been followed for two years | Numbers of inappropriate ICD therapies (antitachycardia pacing (ATP) or shock therapy) |
| Ventricular tachycardia (VT)/ventricular fibrillation (VF) | All patients will be followed until the last included patient has been followed for two years | Time to first episode of VT/VF |
| Persistent atrial fibrillation | All patients will be followed until the last included patient has been followed for two years | Recorded by the implanted device |
| Any atrial fibrillation | All patients will be followed until the last included patient has been followed for two years | \>30 seconds recorded by the implanted device |
| Implantation time | 0-6 hours, assessed at completion of implantation procedure | Procedure time at implantation |
| Fluoroscopy time | 0-120 minutes, assessed at completion of implantation procedure | Fluoroscopy time at implantation in minutes |
| Fluoroscopy dose | Assessed <24 hours after implantation initiation | Fluoroscopy dose at implantation in mGy |
| Equipment used at implantation | Assessed <24 hours after implantation initiation | Number of LV leads (0-5) used at implantation |
| Device-related outcomes | All patients will be followed until the last included patient has been followed for two years | Periprocedural: lead re-operation, pneumothorax, hemothorax, pericardial bleeding/tamponade and later (30 days post implantation): LV lead re-operation, device replacement due to battery depletion, and infection requiring extraction |
| Battery replacements | All patients will be followed until the last included patient has been followed for two years | Number of device replacements during the study period due to battery depletion |
| Battery longevity estimate | All patients will be followed until the last included patient has been followed for two years | Measured by actual device battery longevity + estimated remaining device battery longevity as reported by the device at last study follow-up |
| QRS complex width | All patients will be followed until the last included patient has been followed for two years | Changes in the ECG parameter QRS complex width during follow-up |
| QRS complex morphology | All patients will be followed until the last included patient has been followed for two years | Changes in the ECG parameter QRS complex morphology during follow-up |
| Predictive value of P-wave | All patients will be followed until the last included patient has been followed for two years | Predictive value of the baseline ECG parameter P-wave on clinical outcome measures in the entire cohort and between the two treatment groups |
| Predictive value of QRS complex width | All patients will be followed until the last included patient has been followed for two years | Predictive value of the baseline ECG parameter QRS complex width on clinical outcome measures in the entire cohort and between the two treatment groups |
| Predictive value of QRS complex morphology | All patients will be followed until the last included patient has been followed for two years | Predictive value of the baseline ECG parameter QRS complex morphology on clinical outcome measures in the entire cohort and between the two treatment groups |
| Changes in cardiac chamber dimensions | All patients will be followed until the last included patient has been followed for two years | Volumes of cardiac chambers (left ventricle, left atrium, right ventricle, right atrium) measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups |
| Changes in left ventricular ejection fraction LVEF | All patients will be followed until the last included patient has been followed for two years | Changes in cardiac chamber function measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups |
| Changes in right ventricular ejection fraction RVEF | All patients will be followed until the last included patient has been followed for two years | Changes in cardiac chamber function measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups |
Countries
Denmark
Contacts
PRINCIPAL_INVESTIGATORJens C Nielsen
Aarhus University Hospital
Outcome results
None listed