DANISH-CRT - Does Electric Targeted LV Lead Positioning Improve Outcome in Patients With Heart Failure and Prolonged QRS

DANISH-CRT - Does Electric Targeted LV Lead Positioning Improve Outcome in Patients With Heart Failure and Prolonged QRS

Does Targeted LV Lead Positioning Towards Latest Local Electric Activation at CRT Implantation Reduce Incidence of the Combined Endpoint "Death or Non-planned Hospitalisation for Heart Failure (HF)" in Patients With HF and Prolonged QRS

Aalborg University Hospital, Odense University Hospital, Rigshospitalet, Denmark, Gentofte University Hospital

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.

Double-blind randomised controlled trial. Patients are included and randomised 1:1 into two groups for implantation of either a CRT-D/P device with the LV lead positioned according to the latest electrical activation in the CS (intervention group) or a CRT-D/P device with the LV lead positioned preferentially in a posterolateral, non-apical position (control group)

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.

Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator with the LV lead positioned preferentially in a posterolateral, non-apical position

Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator with the LV lead positioned according to the latest electrical activation in the CS

Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator

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)

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

Measured by actual device battery longevity + estimated remaining device battery longevity as reported by the device at last study follow-up

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 the baseline ECG parameter QRS complex width on clinical outcome measures in the entire cohort and between the two treatment groups

Predictive value of the baseline ECG parameter QRS complex morphology on clinical outcome measures in the entire cohort and between the two treatment groups

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 cardiac chamber function measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups

Changes in cardiac chamber function measured by echocardiography and cardiac CT during follow-up in the entire cohort and between the two treatment groups

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