Effect of Targeting Left Ventricular Lead Position on the Rate of Response to Cardiac Resynchronization Therapy.

Condition(s) targeted: Heart Failure, Congestive; Cardiac Pacing, Artificial; Defibrillators

Intervention: A (Procedure); B (Procedure)

Phase: Phase 2/Phase 3

Status: Active, not recruiting

Sponsored by: University of Calgary

Official(s) and/or principal investigator(s):
Derek V Exner, MD, MPH, Principal Investigator, Affiliation: Libin Cardiovascular Institute of Alberta, University of Calgary

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.

Official title: Investigating Non-Response to Cardiac Resynchronization: Evaluation of Methods to Eliminate Non-Response & Target Appropriate Lead Location (INCREMENTAL).

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study

Primary outcome: Response to cardiac resynchronization therapy (reduction in end systolic volume and reduction in symptoms).

Secondary outcome:

Minnesota Living with Heart Failure score.

Short form thirty six score.

Specific Activity Scale score.

New York Heart Association class.

Six minute walk distance.

Augmentation in regional LV systolic function with dobutamine.

LV volumes.

N-terminal pro-B-type natriuretic peptide.

Microvolt alternans voltage.

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Foothills Hospital, Calgary, Alberta T2N4N1, Canada

Quebec Heart Institute, Ste-Foy, Quebec G1V4G5, Canada

Starting date: January 2005
Ending date: November 2010
Last updated: March 11, 2008