Clinical trial NCT00867984: Torsion Optimization to Reduce Symptoms and Improve Outcomes in Non-responders
Official title: Torsion Optimization to Reduce Symptoms and Improve Outcomes in Non-responders (TORSION). A Randomized Comparison of Torsion-imaging Guided Optimization vs. Usual Settings.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Failure, Congestive
Keywords: CRT, resynchronization,
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Canada
First posted: 2009-03-24
Enrollment: 60
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: Approximately 40% of resynchronization therapy recipients do not appear to clearly benefit. These patients are termed 'non-responders'. This study will assess whether a heart ultrasound (echo) technique called 'torsion imaging' can be used to increase the likelihood of benefit from resynchronization therapy.

Detailed description: Background: Despite advances in pharmacotherapy, patients with heart failure (HF) are at high risk for death and hospitalization. Over 25% of patients with systolic HF have dyssynchronous ventricular contraction that impairs left ventricular (LV) function and results in HF progression. Cardiac resynchronization therapy (CRT) is designed to synchronize ventricular mechanical activity, improving cardiac output and reducing HF symptoms. As shown in our pilot data, at least 40% of patients do not respond to CRT despite pre-screening for the presence of longitudinal (long axis) mechanical (velocity) dyssynchrony and targeting LV lead placement to the latest site of latest velocity. Methods to improve the rates of response to CRT are required. Torsion imaging guided optimization of CRT timing is a promising approach and will be tested in this study.

Primary hypothesis: Optimization of inter-ventricular (VV) timing, guided by torsion imaging, will increase functional capacity and reduce LV end systolic volume \[ESV\] in CRT in patients who have not responded after ≥ 6 months. CRT response will be defined by a ≥ 1 functional class improvement and either a ≥ 10% reduction in LV ESV or a ≥ 5% increase in EF at follow-up versus baseline.

Secondary aims: To compare the following in torsion-guided vs usual care patients: a) echo parameters (intra-LV and VV dyssynchrony and torsion, and mitral regurgitation), b) N-terminal BNP levels, and c) generic / disease-specific quality of life.

Methods: Randomized study of patients who have not responded to CRT after ≥ 6 months.

Eligibility criteria: Inclusion Criteria:

* non-response to CRT as indicated,
* stable doses of ACE I / ARB and beta-blocker for ≥ 2 months, \&
* controlled heart rate if in atrial fibrillation.

Exclusion Criteria:

* inadequate images to assess torsion
* no significant augmentation in torsion with optimization
* unable or unwilling to provide informed consent,
* medical condition other than HF likely to cause death within 6 months,
* cardiac transplant planned,
* myocardial infarction or revascularization since CRT implant.

Primary outcomes:
measure: Improved functional class (≥ 1 class) & remodeling (either ≥ 10% relative reduction in LV ESV or a ≥ 5% absolute increase in LV EF).
timeFrame: Follow up (3-6 months) versus baseline.
Secondary outcomes:
measure: dyssynchrony and torsion
timeFrame: Follow-up (3-6 months) vs. baseline
measure: mitral regurgitation
timeFrame: Follow-up (3-6 months) vs. baseline
measure: N-terminal BNP level
timeFrame: Follow-up (3-6 months) vs. baseline
measure: quality of life
timeFrame: Follow-up (3-6 months) vs. baseline
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
Study officials:
affiliation: University of Calgary
name: Derek V Exner, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: