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

Not Applicable
Recruiting
Conditions
Heart Failure
Branch Block, Bundle
Interventions
Device: Implantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter Defibrillator
Registration Number
NCT03280862
Lead Sponsor
Aarhus University Hospital
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1000
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
InterventionImplantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter DefibrillatorImplantation 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
ControlImplantation of a Cardiac Resynchronisation Therapy (CRT) pacing device with or without Implanted Cardioverter DefibrillatorImplantation 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
Primary Outcome Measures
NameTimeMethod
Death or first non-planned hospitalisation for heart failureAll 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 Outcome Measures
NameTimeMethod
Clinical responseFollow-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)

Patient Reported Outcomes (PROs)Follow-up at 6, 12, 24 and 48 months

Changes in score from baseline to follow-up

Sudden deathAll patients will be followed until the last included patient has been followed for two years

Time to sudden death

Persistent atrial fibrillationAll patients will be followed until the last included patient has been followed for two years

Recorded by the implanted device

Fluoroscopy time0-120 minutes, assessed at completion of implantation procedure

Fluoroscopy time at implantation in minutes

Equipment used at implantationAssessed <24 hours after implantation initiation

Number of LV leads (0-5) used at implantation

Non-planned hospitalisation for heart failureAll patients will be followed until the last included patient has been followed for two years

Time to first non-planned hospitalisation for heart failure

Cardiac deathAll patients will be followed until the last included patient has been followed for two years

Time to cardiac death

DeathAll patients will be followed until the last included patient has been followed for two years

Time to death

Time to first appropriate ICD TherapyAll 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)

Battery longevity estimateAll 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

Predictive value of P-waveAll 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 widthAll 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

Changes in cardiac chamber dimensionsAll 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 LVEFAll 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

Quality of Life (QoL)Follow-up at 6, 12, 24 and 48 months

Changes in score from baseline to follow-up

Echocardiographic measures of LV functionFollow-up at 6, 12, 24 and 48 months

Changes from baseline to follow-up in left ventricular ejection fraction (%)

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

Fluoroscopy doseAssessed <24 hours after implantation initiation

Fluoroscopy dose at implantation in mGy

Time to first inappropriate ICD TherapyAll 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 TherapiesAll 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 TherapiesAll 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)

Any atrial fibrillationAll patients will be followed until the last included patient has been followed for two years

\>30 seconds recorded by the implanted device

Implantation time0-6 hours, assessed at completion of implantation procedure

Procedure time at implantation

Device-related outcomesAll 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 replacementsAll 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

QRS complex widthAll 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 morphologyAll 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 QRS complex morphologyAll 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 right ventricular ejection fraction RVEFAll 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

Trial Locations

Locations (5)

Aarhus University Hospital

🇩🇰

Aarhus, Denmark

Gentofte University Hospital

🇩🇰

Gentofte, Denmark

Aalborg University Hospital

🇩🇰

Aalborg, Denmark

Rigshospitalet

🇩🇰

Copenhagen, Denmark

Odense University Hospital

🇩🇰

Odense, Denmark

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