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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Heart Failure, Congestive

Intervention / Treatment
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* Other: Torsion optimized
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CRT, resynchronization,