Torsion Optimization to Reduce Symptoms and Improve Outcomes in Non-responders (TORSION)

Torsion Optimization to Reduce Symptoms and Improve Outcomes in Non-responders (TORSION). A Randomized Comparison of Torsion-imaging Guided Optimization vs. Usual Settings.

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure, Congestive
• Intervention / Treatment: Other: Torsion optimized; Other: Usual Care

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • University of Calgary

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:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Torsion-guided VV optimization plus AV optimization.	Other: Torsion optimized; Torsion optimized VV timing plus AV optimization (VTI)
Active Comparator: 2; AV optimization only.	Other: Usual Care; AV optimization (VTI) only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improved functional class (≥ 1 class) & remodeling (either ≥ 10% relative reduction in LV ESV or a ≥ 5% absolute increase in LV EF).	Follow up (3-6 months) versus baseline.

Secondary Outcome Measures

Outcome Measure	Time Frame
dyssynchrony and torsion	Follow-up (3-6 months) vs. baseline
mitral regurgitation	Follow-up (3-6 months) vs. baseline
N-terminal BNP level	Follow-up (3-6 months) vs. baseline
quality of life	Follow-up (3-6 months) vs. baseline

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Heart and Stroke Foundation of Canada

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): January 1, 2017

Study Registration Dates

• First Submitted: March 20, 2009
• First Submitted That Met QC Criteria: March 23, 2009
• First Posted (Estimate): March 24, 2009

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: CRT, resynchronization,
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 7345220000