Clinical trial NCT00453622: RISK Stratification Using a Combination of Cardiac Troponin T and Brain Natriuretic Peptide in Patients Receiving CRT-D
Official title: RISK Stratification Using a Combination of Cardiac Troponin T and Brain Natriuretic Peptide in Patients Receiving CRT-D
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Keywords: Heart Failure
Cardiac Resynchronization Therapy
Risk stratification
Prediction
Proteomics
Chemokine
cardiac enzymes
Brain Natriuretic Peptide
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
Collaborators: name: VA Pittsburgh Healthcare System
First posted: 2007-03-29
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: heart failure patients indicated for the CRT-D therapy

Brief 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%

Eligibility criteria: 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™

Primary outcomes:
measure: All Cause Death
timeFrame: 1 year follow up
measure: First Heart Failure Hospitalization
timeFrame: 1 year follow up
Secondary outcomes:
measure: • Cause of death and ejection fraction
timeFrame: 1 year follow up
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Veterans' Adminstration Pittsburgh Healthcare System
state: Pennsylvania
Study officials:
affiliation: Veteran's Administration, Pittsburgh Healthcare System
name: Aala Shalaby, MD, FACC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shalaby AA, Abraham WT, Fonarow GC, Bersohn MM, Gorcsan J 3rd, Lee LY, Halilovic J, Saba S, Maisel A, Singh JP, Sonel A, Kadish A. Association of BNP and Troponin Levels with Outcome among Cardiac Resynchronization Therapy Recipients. Pacing Clin Electrophysiol. 2015 May;38(5):581-90. doi: 10.1111/pace.12610. Epub 2015 Mar 30.