Clinical trial NCT00399594: Effect of Targeting Left Ventricular Lead Position on the Rate of Response to Cardiac Resynchronization Therapy.
Official title: Investigating Non-response to Cardiac Resynchronization: Evaluation of Methods to Eliminate Non-response & Target Appropriate Lead Location (INCREMENTAL).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heart Failure, Congestive
Cardiac Pacing, Artificial
Defibrillators
Keywords: Mechanical dyssynchrony
Biventricular pacing
Cardiac resynchronization therapy
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Medtronic
name: Hoffmann-La Roche
name: Cambridge Heart Inc.
First posted: 2006-11-15
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Identifying \& optimizing strategies to reduce the burden of heart failure is vital. Despite advances in pharmacotherapy, patients with heart failure are at high risk for death \& hospitalization. Cardiac resynchronization therapy (CRT) synchronizes ventricular mechanical activity, improves cardiac output \& reduces HF symptoms. However, \~50% of patients do not clearly respond to CRT. Sub-optimal placement of the LV pacing lead appears to be an important reason for non-response.

This study will assess whether targeted LV lead placement will result in an increased probability of CRT response at 52 weeks vs. usual (lateral wall) lead placement.

Detailed description: Background. Identifying \& optimizing strategies to reduce the burden of heart failure (HF) is vital. Despite advances in pharmacotherapy, patients with HF are at high risk for death \& hospitalization. Over 25% of patients with systolic HF have dyssynchronous ventricular contraction that results in paradoxical septal motion, further impairing left ventricular (LV) function \& HF progression. Cardiac resynchronization therapy (CRT) synchronizes ventricular mechanical activity, improves cardiac output \& reduces HF symptoms. However, \~50% of patients do not clearly respond to CRT. Sub-optimal placement of the LV pacing lead appears to be an important reason for non-response.

Screening. Mechanical synchrony is vitally important in optimizing CRT response. Patients will be pre-screened with echocardiograms (echo) \& CRT provided to only those with dyssynchrony. The predicted rate of CRT response in patients pre-screened for dyssynchrony is estimated at 65%.

CRT response. The combined use of a valid \& simple measure of functional capacity with a reproducible measure of LV volume is optimal in identifying CRT responders. These outcomes will be assessed using the Specific Activity Scale \& radionuclide angiography (RNA), respectively.

Primary hypothesis. Targeted LV lead placement will result in an increased probability of CRT response at 52 weeks vs. usual (lateral wall) lead placement. CRT response will be defined as ≥ 10% relative reduction in LV end systolic volume \& ≥ 1 Specific Activity Scale class improvement.

Eligibility criteria: Inclusion Criteria:

* LV EF ≤ 0.40 measured within 3 months of enrollment,
* SAS class 3 or 4 symptoms indicative of moderate to severe functional capacity limitation due to heart failure within 1 month of enrollment.
* Confirmed dyssynchrony on screening echo (1.1.9), \&
* On stable doses of ACE inhibitor or angiotensin II blocker \& a beta-blocker for ≥ 2 months unless medically contra-indicated.
* Controlled heart rate if in permanent AF (resting \<70 \& maximal \<120).

Exclusion Criteria:

* Unable or unwilling to provide informed consent,
* Medical condition other than heart failure likely to cause death \< 1 year,
* Cardiac transplant planned within 6 months,
* Known contra-indication to transvenous CRT device implant (e.g., active sepsis, artificial tricuspid valve, known vascular occlusion that will prevent delivery of leads transvenously),
* Clinically significant myocardial infarction within last 2 months, or
* Coronary bypass graft surgery ≤ 2 months or coronary angioplasty ≤ 1 month

Primary outcomes:
measure: Change in end systolic volume plus reduction in symptoms
timeFrame: over 12 months
Secondary outcomes:
measure: Minnesota Living with Heart Failure score.
timeFrame: Change over 12 months
measure: Short form thirty six score.
timeFrame: Change over 12 months
measure: Specific Activity Scale score.
timeFrame: Change over 12 months
measure: New York Heart Association class.
timeFrame: Change over 12 months
measure: Six minute walk distance.
timeFrame: Change over 12 months
measure: LV volumes.
timeFrame: Change over 12 months
measure: N-terminal pro-B-type natriuretic peptide.
timeFrame: Change over 12 months
measure: Mortality
timeFrame: Study duration
measure: Hospitalization
timeFrame: Study duration
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences
state: Ontario
city: Ste-Foy
country: Canada
facility: Quebec Heart Institute
state: Quebec
Study officials:
affiliation: Libin Cardiovascular Institute of Alberta, University of Calgary
name: Derek V Exner, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: