Combining Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in CRT Treatment

Study Overview
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Brief Summary
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For patients with advanced heart failure, Cardiac Resynchronization Therapy (CRT) has been a major improvement. The treatment improves symptoms and prolongs life in selected patients with heart failure. However, with the current selection criteria and methods for implanting the pacemaker, only 60-70% of the patients derive significant benefit from the treatment. New imaging techniques, including advanced ultrasound and computed tomography, in combination with new versatile multi-pole electrodes, have made an individually tailored therapy possible. Using these techniques in combination, the study will investigate the effect of individually based optimal placement of the pacemaker electrodes vs. standard care. The optimal LV electrode position is defined as pacing a viable segment with the latest mechanical delay, targeting a specific segment of the coronary sinus as visualised on cardiac CT. The hypothesis is that this will increase the number of positive responders from 65% to 85%.

Official Title
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Individually Tailored Cardiac Resynchronization Therapy - Combing Myocardial Strain and Cardiac CT to Optimize Left Ventricular Lead Placement in Cardiac Resynchronization Therapy

Conditions
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Heart Failure

Intervention / Treatment
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* Other: Imaging guided LV lead positioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic heart failure (New York Heart Association functional class II - IV) despite stabile optimal medical therapy. Wide QRS ≥ 120 milliseconds on standard ECG. LV systolic dysfunction (EF ≤ 35%). Written informed consent. Accepted for CRT-P or CRT-D treatment Exclusion Criteria: Life expectancy < 12 months. Recent myocardial infarction (< 3 months). Significant valve disease Chronic atrial fibrillation Pregnancy Severely impaired renal function (estimated glomerular filtration rate (eGFR) < 30 ml/min) Unable to give written informed consent.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Imaging guided LV lead positioning<br> | Other: Imaging guided LV lead positioning<br>* LV lead positioning guided by echocardiography (mechanical strain evaluation by speckle tracking) in combination with cardiac CT. A viable segment with the latest mechanical activation is targeted, and an appropriate optimal cardiac vein segment is then chosen using the CT images.<br>|
| No Intervention: Standard LV lead positioning<br>The LV lead position is decided at the discretion of the treating physician. Cardiac CT images are available for viewing, but no echocardiography data regarding segmental myocardial strain are available. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive response to CRT treatment | The primary efficacy endpoint will evaluate the effect of echocardiography and cardiac CT guided placement of the left ventricular lead vs standard care (i.e. position of the left ventricular lead at the discretion of the treating physician). Number of patients with positive response to CRT (YES or NO). A positive response is defined as survival in combination with either a reduction in end systolic left ventricular volume ≥ 15% by echocardiography (volume responder) and / or improvement ≥ 1 NYHA class and ≥10% improvement in 6 minute hall walk test (clinical responder). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to CRT (on-treatment analysis) | Evaluate the effect of optimal LV placement (post hoc analysis of both groups) versus non-optimal LV lead placement. Optimal lead placement is defined as pacing from a viable segment with the latest mechanical activation (by myocardial strain measurement). Outcome measure is the same as in the primary outcome measure. | 6 months | 
| Heart failure morbidity | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to hospitalisation for worsening of heart failure | 6 months 2 years and 5 years | 
| Morbidity and mortality | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to a composite endpoint of all cause mortality and hospitalisation for worsening of heart failure (2 years and 5 years). | 6 months 2 years and 5 years | 
| Mortality | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to all cause mortality | 6 months, 2 years and 5 years | 
| Left ventricular dyssynchrony | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to echocardiography measured changes in LV dyssynchrony | 6 months | 
| Ventricular tachycardia | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to number of treated ventricular tachycardia episodes | 6 months 2 years and 5 years | 
| Quality of life | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in the Minnesota Living with heart failure Quality of Life questionnaire | 6 months 2 years 5 years | 
| Myocardial viability | Evaluate the concordance in viability assessment using myocardial strain evaluation (echocardiography) compared to cardiac MRI. | Peroperative | 
| Biochemical markers of heart failure | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in blood natriuretic peptide (BNP) levels | 6 months | 
| Left ventricular systolic function | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in LV ejection fraction | 6 months | 
| Myocardial viability | Evaluate the concordance between echocardiography (strain evaluation with speckle tracking) and cardiac MRI viability images (late gadolinium enhancement). | 6 months | 
| MRI left ventricular dyssynchrony | Evaluate if MRI dyssynchroni evaluation has incremental value over echocardiography alone for predicting the effect of cardiac resynchronization therapy. | 6 months | 
| Left ventricular diastolic dimension | Evaluate the effect of echocardiography guided LV lead placement compared to standard care in relation to the change in left ventricular diastolic dimension | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac resynchronization therapy, Echocardiography, Cardiac computed tomography