Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)

Study Overview
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Brief Summary
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The EchoCRT trial evaluates the effects of Cardiac Resynchronization Therapy (CRT) on mortality and morbidity of subjects with heart failure due to left ventricular systolic dysfunction, already receiving optimized HF medication, with a narrow QRS width (< 130 ms) and echocardiographic evidence of ventricular dyssynchrony.

Official Title
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Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT)

Conditions
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Heart Failure, Ventricular Dyssynchrony

Intervention / Treatment
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* Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women 18 years of age or older. Understand the nature of the procedure. Give written informed consent. Willing and able to complete all testing required by the clinical protocol. Indication for an implantable cardioverter defibrillator (ICD). NYHA class III-IV within the last three months prior to enrollment and at baseline (at baseline only: also Stage C according to ACC/AHA guidelines). Stable optimal pharmacologic therapy for HF. An ejection fraction ≤ 35% within one year prior to enrollment and confirmed on the baseline echocardiogram. Increased left ventricular dimension, defined as LVEDD ≥ 55 mm. Resting QRS duration < 130 ms evidenced by a historical 12-lead ECG prior to enrollment and at baseline. Ventricular dyssynchrony assessed by echocardiography locally and confirmed by the echo core lab. One of the two following criteria has to be present to include the subject in the study: Intra-left ventricular dyssynchrony measured by color Tissue Doppler Imaging (TDI) with an opposing wall delay of ≥ 80 ms in the 4-chamber or apical long-axis view. Speckle-tracking radial strain septal-posterior wall delay ≥ 130 ms. Exclusion Criteria: Implanted pacemaker or defibrillator with >10% ventricular pacing, as demonstrated by device statistics averaged over at least the last three months prior to enrollment. Women who are pregnant, lactating, or planning to become pregnant during the course of the trial. Bradycardia pacing indication. Surgically correctable primary valvular heart disease, i.e. aortic stenosis, torn cordae, or flail segment. Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within the past 3 months prior to enrollment. Enzyme-positive myocardial infarction within the past 3 months prior to enrollment. Angiographic evidence of coronary disease, candidates for coronary revascularization likely to undergo coronary artery bypass graft surgery or percutaneous coronary intervention in the next 3 months. Irreversible brain damage from preexisting cerebral disease. Reversible non-ischemic cardiomyopathy such as acute viral myocarditis. Permanent second or third degree heart block. Chagas disease. Persistent or paroxysmal atrial fibrillation within one month prior to enrollment. Expected to receive heart transplantation within six months. Current inotropic therapy. Acutely decompensated heart failure. Contrast dye allergy and unable or unwilling to undergo pretreatment with steroids and/or diphenhydramine. Life expectancy of less than six months. Presence of any disease, other than the subject's cardiac disease associated with a reduced likelihood of survival for the duration of the trial, (e.g. cancer). Significant renal insufficiency defined as a serum creatinine > 2.5 mg/dL (> 221 µmol/L) within the last four weeks prior to enrollment.. Liver failure, defined as three times the upper limit of normal for aminotransferases. Participation in any other clinical trial. Unable to return for follow-up visits due to distance from the clinic. Do not anticipate being a resident of the area for the scheduled duration of the trial.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CRT=ON<br>Cardiac Resynchronization Therapy activated. | Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D)<br>* All patients will receive a commercially available BIOTRONIK Lumax HF-T CRT-D system with ICD back-up enabled. Patients will be randomized to CRT=ON or CRT=OFF.<br>* Other names: Lumax HF-T CRT-D system;|
| Active Comparator: CRT=OFF<br>Cardiac Resynchronization Therapy deactivated. | Device: Implantable Cardioverter Defibrillator with Cardiac Resynchronization Therapy (BIOTRONIK Lumax HF-T CRT-D)<br>* All patients will receive a commercially available BIOTRONIK Lumax HF-T CRT-D system with ICD back-up enabled. Patients will be randomized to CRT=ON or CRT=OFF.<br>* Other names: Lumax HF-T CRT-D system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Primary Endpoint: Number of Subjects With First Hospitalization for Worsening Heart Failure or Death | The primary efficacy endpoint will evaluate the effect of CRT=ON versus CRT=OFF in time to event of a combined endpoint of all-cause mortality or first hospitalization for worsening heart failure. | From date of randomization until date of death from any cause or date of first hospitalization for worsening heart failure, whichever came first, assessed up to date of study exit, with a mean treatment duration of 1.6 years | 
| Number of Subjects That Underwent Implant Attempt Without System- or Implant-Related Complications (Complication-Free) | The primary safety endpoint will evaluate the complication-free rate of the Lumax HF-T CRT-D devices in the narrow QRS subject population. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Hospitalizations for Worsening Heart Failure (Hospitalizations Per Subject-year) | Evaluate the effects of CRT=ON compared to CRT=OFF on the rate of hospitalization for worsening heart failure (WHF). | Study duration from randomization to study exit | 
| New York Heart Association (NYHA) Classification Change | Evaluate the effects of CRT=ON compared to CRT=OFF in relation to the change in NYHA classification. NYHA classes: Class I - Subjects with cardiac disease, but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation,dyspnea, or anginal pain. Class II - Subjects with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III - Subjects with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV - Subjects with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. | 6 months | 
| Change in Quality of Life (QOL) Scores From Baseline to 6-Month Follow-up | Quality of Life was evaluated using the Minnesota Living with Heart Failure (MLHF) Quality of Life (QOL) Questionnaire.The questionnaire consists of 21 questions to measure the subjects' perception of how their HF and its treatment affected their ability to live as they wanted during the last month. The questions describe different ways in which some people are affected (i.e. physical, socioeconomic, and psychological impairments). If a question does not apply to a subject or is not related to their HF, then they can answer with a 0. If it does apply to them, then they can rate (from 1 to 5) how much it has affected them. From the 21 questions, the lowest possible total score is 0, and the highest possible total score is 105. A lower score is desirable. Therefore, a negative change in QOL score from baseline to 6 months represents an improvement in quality of life, while a positive change in QOL score from baseline to 6 months represents a worsening in quality of life. | Changes between baseline and 6 months | 
| Composite Score of Death, Hospitalization for Worsening Heart Failure and Change in Quality of Life (QOL) | Evaluate the effects of CRT=ON compared to CRT=OFF in relation to a composite endpoint of all-cause mortality, hospitalization for worsening heart failure and change in the MLHF Quality of Life Questionnaire. This composite endpoint used a weighted scoring scale based on the African-American Heart Failure Trial (A-HeFT) study Endpoint Score. (Taylor, AL, Ziesche, S, Yancy, C, et al. Combination of Isosorbide Dinitrate and Hydralazine in Blacks with Heart Failure. N Engl J Med 2004; 351:2049-57.) Composite Endpoint Scoring: Vital Status: Death (-3), Survival to end of trial (0), Hospitalization: 1st hospitalization for HF (-1), No hospitalization (0), QOL score:* Improvement by ≥ 10 units (+2), Improvement by 5-9 units (+1), Change by < 5 units (0), Worsening by 5-9 units (-1), Worsening by ≥ 10 (-2). Possible total score -6 to +2. *QOL score details are provided in Secondary Outcome Measure 5. | Composite of death, worsening heart failure hospitalization (up to 24 months), and change in QOL (at 6 months) | 
| Number of Subjects With All-cause Mortality | Evaluate the all-cause mortality rate between the CRT=ON compared to CRT=OFF group. | From date of randomization up to date of study exit, with a mean treatment duration of 1.6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac Resynchronization Therapy, Heart Failure, Ventricular Dyssynchrony, Mechanical Dyssynchrony, Intraventricular Dyssynchrony, Echocardiography, Normal QRS, Heart Disease, EchoCRT