RISK Stratification Using a Combination of Cardiac Troponin T and Brain Natriuretic Peptide in Patients Receiving CRT-D

Study Overview
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Brief Summary
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The purpose of the study is to identify if the combined use of cardiac troponin enzyme (cTnT) and brain natriuretic peptide (BNP) can predict Heart Failure (HF)improvement and all-cause mortality in patients implanted with cardiac pacemaker-defibrillation devices (CRT-D). Novel biochemical markers identifying patients with high risk cardiac mortality detected by plasma protein analysis will also be evaluated. Hypothesis #1: The combined use of cTnT and BNP at just before implant will predict and risk stratify all cause mortality or HF hospitalization up to 12 months. Hypothesis #2: The change in levels of said biomarkers at different points of follow-up can predict response to CRT through 12 months. Hypothesis #3: The levels of a panel of novel inflammatory mediators, namely chemokines, will be correlated with improvement in 6-minute walk testing, quality of life, and left ventricular ejection fraction in CRT patients.

Detailed Description
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Primary Endpoint The primary endpoint is the occurrence of either death or first HF hospitalization. HF hospitalizations must satisfy both of the following criteria: Admission to hospital for >24 hours with at least one of the following HF worsening symptoms: Increased CHF class Orthopnea Paroxysmal nocturnal dyspnea Edema Dyspnea on exertion, or Gastrointestinal (GI) symptoms attributable to HF Placement on the Status I heart transplant list AND One or more of the following intensive treatment(s) for HF within 24 hours of admission: Intravenous (IV) diuresis IV inotropic medications prescribed during the hospitalization, or Increasing frequency of dialysis for patients with chronic renal failure 2.3 Secondary Endpoints Secondary endpoints include: Cause of death Change in NYHA functional class Number of HF related hospitalizations Performance on a standard 6-minute hall walk test Quality of Life as measured by the Minnesota Living with Heart Failure (MLWHFQ) questionnaire Patient global clinical assessment Left ventricular ejection fraction (LVEF) measured by echocardiography LV volume measured by echocardiography LV lead placement position QRS duration at baseline and with CRT Number of AT/AF, VT/VF episodes Frequency of appropriate/inappropriate ICD therapy % Atrial and Ventricular Pacing Antiarrhythmic drug utilization Study related complications 2.3.1 Response to CRT A positive response to CRT is defined by the following: Improvement in NYHA functional class by at least one grade Improvement in echocardiographic LVEF & left ventricular end diastolic index (LVEDI) Improvement in patient global clinical assessment Improvement in 6-minute hall walk by 10%

Official Title
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RISK Stratification Using a Combination of Cardiac Troponin T and Brain Natriuretic Peptide in Patients Receiving CRT-D

Conditions
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Heart Failure

Intervention / Treatment
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* Device: Cardiac Resynchronization Therapy-Defibrillator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Referred for implantation of CRT-D according to currently accepted guidelines. 18 years or older Ability to independently comprehend and complete a QOL questionnaire Ability to provide informed consent for a study and be willing and able to comply with the prescribed follow-up Has stable conventional medications at least one month prior to enrollment Exclusion Criteria: Inability to successfully implant an intravascular lead CRT-D device. (i.e. exclude epicardial leads) Myocardial infarction or unstable angina in the last 3 weeks Chronic atrial fibrillation (continuous AF lasting > 1 Month) within 1 year prior to enrollment or having undergone cardioversion for AF in the past month Status 1 classification for cardiac transplantation Currently participating in a clinical trial that includes an active treatment arm Life expectancy of less than 6 months. Recent (within 24 hours) administration of Nesiritide™

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: Cardiac Resynchronization Therapy-Defibrillator|Implantation of a CRT-D device|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All Cause Death |  | 1 year follow up | 
| First Heart Failure Hospitalization |  | 1 year follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • Cause of death and ejection fraction |  | 1 year follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Cardiac Resynchronization Therapy, Risk stratification, Prediction, Proteomics, Chemokine, cardiac enzymes, Brain Natriuretic Peptide