Viability and Cardiac Resynchronization Therapy

Study Overview
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Brief Summary
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30% of heart failure patients that receive a device for cardiac resynchronization therapy fail to show clinical improvement. The reason for lack of response is still unclear but factors such as scar tissue in the heart musculature, inadequate lead placement, device-settings and the degree of dyssynchrony before implant seems to be important. In this study, these factors are further investigated.

Detailed Description
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Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure, depressed left ventricular function and a wide QRS-complex. Large clinical trials have demonstrated unequivocal improvements in functional status, morbidity and mortality. However, 30 % of heart failure patients treated with a CRT-device do not benefit clinically. Several factors have been suggested to be important for the response to CRT such as mechanical dyssynchrony, presence of scar tissue in the myocardium, and device-optimization (among others). It is the purpose of this study to investigate the importance of these factors. 100 patients with ischemic cardiomyopathy, eligible to CRT according to current guidelines, will be included. Patients are randomised to two arms. One group will have atrioventricular (AV)-optimization after implantation, the other AV -and interventricular (VV)-optimization. After 4 months patients are crossed-over to the other arm. Preimplantation patients are MR-scanned and low-dose dobutamine stress-echocardiography is performed. Furthermore patients will be examined by echocardiography and evaluation of clinical status Mechanical dyssynchrony can predict response to CRT. b. Measures of mechanical dyssynchrony is related to myocardial viability and conduction. Individual optimization based on conduction times will increase benefit to CRT. b. The effect of adding VV-optimization is related to myocardial viability. > 30 % of non-viable tissue globally in the myocardium is predictive of lack of CRT- response. b. Non-viable tissue located in the area of the left ventricular lead is predictive of non-response.

Official Title
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The Importance of Viability for Response to Cardiac Resynchronization Therapy

Conditions
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Heart Failure, Ischemic Cardiomyopathy

Intervention / Treatment
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* Device: AV-optimization followed by AV- and VV-optimization
* Device: AV- and VV-optimization followed by AV-optimization only.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LVEF</= 35%, QRS-duration>/= 120 ms, NYHA-class II- IV. Ischemic heart disease (> 50% stenosis in 1 or more major epicardial coronary artery or prior PCI or CABG.) Optimal treatment ( beta-blocker, ACE-1 or ARB and spironolactone) Exclusion Criteria: Pregnancy Unstable angina pectoris Chronical atrial fibrillation Severe valvular disease Dementia or mental retardation Severe claustrophobia Acute myocardial infarction < 3 months Severe health condition threatening short-term survival Severe kidney insufficiency, GFR < 35 ml/min/1.73 m2 Metal implants contraindicative of magnetic resonance scan

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CRT group 1<br> | Device: AV-optimization followed by AV- and VV-optimization<br>* Patients are AV-optimized the first 4 months,then AV- and VV-optimized the next 4 months.<br>|
| Active Comparator: CRT group 2<br> | Device: AV- and VV-optimization followed by AV-optimization only.<br>* Patients are AV- and VV-optimized the first 4 months,then AV-optimized the next 4 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responders:Echocardiographic:>/= 10% increase in Left ventricular ejection fraction (LVEF) or >/= 15 % reduction in left ventricular end-systolic volume (LVESV) |  | 4 and 8 months, ( follow up- 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| LVESV, LVEDV, Cardiac output (CO), Minnesota Living with Heart Failure Questionnaire (MLHFQ) ProBNP Others: t-wave modulation all-cause mortality, cardiac death, hospitalization |  | 4 and 8 months (follow-up after 2 years) | 
| Clinical: >/= 25% increase in 6-min walk test or >/= 1 reduction in NYHA-class |  | 4 and 8 months (follow-up 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Cardiac resynchronization therapy, Optimization, Viability, Mechanical dyssynchrony