RISK Stratification Using a Combination of Cardiac Troponin T and Brain Natriuretic Peptide in Patients Receiving CRT-D
Condition: Heart Failure
MeSH terms: Heart Failure
Study type: Observational

Summary: 
      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: 
      Primary Endpoint

      The primary endpoint is the occurrence of either death or first HF hospitalization. HF
      hospitalizations must satisfy both of the following criteria:

        1. 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

        2. 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

        1. A positive response to CRT is defined by the following: Improvement in NYHA functional
           class by at least one grade

        2. Improvement in echocardiographic LVEF & left ventricular end diastolic index (LVEDI)

        3. Improvement in patient global clinical assessment

        4. Improvement in 6-minute hall walk by 10%
    

Intervention name(s): Cardiac Resynchronization Therapy-Defibrillator
Intervention type(s): Device
Intervention description(s): Implantation of a CRT-D device
Other intervention name(s): CRT-D device
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        heart failure patients indicated for the CRT-D therapy
      
Biospecimen description: 
      Blood samples will be collected
    
Keywords: Heart Failure; Cardiac Resynchronization Therapy; Risk stratification; Prediction; Proteomics; Chemokine; cardiac enzymes; Brain Natriuretic Peptide