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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Device: Cardiac Resynchronization Therapy-Defibrillator

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%

• Study Type: Observational
• Enrollment (Actual): 222

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • Veterans' Adminstration Pittsburgh Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

heart failure patients indicated for the CRT-D therapy

Description

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™

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Abbott Medical Devices
• Collaborators: VA Pittsburgh Healthcare System
• Investigators: Principal Investigator: Aala Shalaby, MD, FACC, Veteran's Administration, Pittsburgh Healthcare System

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: March 27, 2007
• First Submitted That Met QC Criteria: March 28, 2007
• First Posted (Estimate): March 29, 2007

Study Record Updates

• Last Update Posted (Actual): February 4, 2019
• Last Update Submitted That Met QC Criteria: February 1, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Heart Failure; Risk stratification; Proteomics; Cardiac Resynchronization Therapy; Prediction; cardiac enzymes; Chemokine; Brain Natriuretic Peptide
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CRD303