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

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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure, Congestive; Cardiac Pacing, Artificial; Defibrillators
• Intervention / Treatment: Procedure: A; Procedure: B

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.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N4N1
      • Foothills Hospital
  • Ontario
    • London, Ontario, Canada
      • London Health Sciences
  • Quebec
    • Ste-Foy, Quebec, Canada, G1V4G5
      • Quebec Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Targeted LV lead placement	Procedure: A; LV lead placement in region of latest mechanical velocity (tissue doppler)
Active Comparator: B; Usual LV lead placement	Procedure: B; LV lead placement in standard (lateral / posterolateral) position.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in end systolic volume plus reduction in symptoms	over 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Minnesota Living with Heart Failure score.	Change over 12 months
Short form thirty six score.	Change over 12 months
Specific Activity Scale score.	Change over 12 months
New York Heart Association class.	Change over 12 months
Six minute walk distance.	Change over 12 months
LV volumes.	Change over 12 months
N-terminal pro-B-type natriuretic peptide.	Change over 12 months
Mortality	Study duration
Hospitalization	Study duration

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Canadian Institutes of Health Research (CIHR); Hoffmann-La Roche; Medtronic; Cambridge Heart Inc.
• Investigators: Principal Investigator: Derek V Exner, MD, MPH, Libin Cardiovascular Institute of Alberta, University of Calgary

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: November 13, 2006
• First Submitted That Met QC Criteria: November 13, 2006
• First Posted (Estimate): November 15, 2006

Study Record Updates

• Last Update Posted (Estimate): November 24, 2015
• Last Update Submitted That Met QC Criteria: November 20, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Cardiac resynchronization therapy; Mechanical dyssynchrony; Biventricular pacing
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CAH 70-3402