Overview

This trial is active, not recruiting.

Condition chronic heart failure
Treatment cardiac resynchronisation therapy
Sponsor University Hospitals Coventry and Warwickshire NHS Trust
Collaborator Medtronic
Start date November 2013
End date June 2016
Trial size 58 participants
Trial identifier NCT02541773, version 10 20 Jan 2016

Summary

The purpose of this study is to understand the behaviour of certain blood markers in patients with heart failure who undergo a cardiac device implantation procedure called cardiac resynchronization therapy (CRT). CRT is an effective treatment for heart failure, but up to 30% of people do not respond and have poor outcomes (1,2). Despite extensive investigation, identifying these patients continues to be a challenge. The study intends to describe the changes in these blood markers before and after CRT and to examine any potential clinical value.

The idea behind the study is that these blood markers alter in heart failure and change with CRT implantation. Furthermore the pattern of marker expression before implant and after may predict response and outcome.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Observational model cohort
Time perspective prospective
Arm
Undergoing CRT implantation, all will be observed for 6 months and will be defined at the end of the observation period as responder or non-responder
cardiac resynchronisation therapy
Routine implantation of CRT - part of standard of care

Primary Outcomes

Measure
Clinical Response
time frame: 6 months

Secondary Outcomes

Measure
Major Adverse Cardiovascular Outcomes
time frame: 12 months
Echocardiographic Response
time frame: 6 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Age > 18 years 2. Left ventricular ejection fraction ≤35% on echocardiography 3. NYHA Class III/IV symptoms or milder symptoms with: - NYHA I (LVEF <35% and QRS>150msec on resting ECG) - NYHA II (LVEF <35% with either QRS>150msec or QRS 120-149msec with Left Bundle Branch Block on resting ECG) 4. Optimal medical therapy for heart failure that the patient tolerates (ACEi, Beta-Blocker, Mineralocorticoid) for > 3 months 5. QRS duration ≥120-149msec with LBBB on resting ECG or QRS duration >150msec on resting ECG 6. Patient consent to participation in the study Exclusion Criteria: 1. Acute heart failure decompensation < 6/52 before implant 2. Significant cognitive impairment 3. Acute coronary syndrome < 6/52 before implant 4. Chronic kidney disease stage V (requiring dialysis) 5. Terminal illness with likely survival < 1 year after implant Post Procedure Exclusions: 1. Failure of procedure (e.g. coronary sinus anatomy) 2. Complication resulting in poor/ none biventricular pacing (e.g. phrenic nerve stimulation, lead displacement/ damage)

Additional Information

Official title The Characterisation of Vascular Biomarkers Before and After Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure and Their Role in Predicting Response
Principal investigator Faizel Osman, MD FRCP FESC
Description Study Design A prospective, non-randomised, self-control study of unselected heart failure patients undergoing CRT implantation, all recruited within two years All participants having CRT implantation at University Hospital Coventry and Warwickshire will be screened using the eligibility criteria (outlined below). Participants will have three assessments within six months (baseline, 6 weeks and 6 months approximately). All visits coincide with routine clinical visits for CRT implantation and interrogation. Assessments at all three time points will include clinical data (including New York Heart Association functional class), quality of life measurements (Minnesota Living with Heart Failure questionnaire), echocardiography data (left ventricular volumetric assessment, ejection fraction), electrocardiograph, functional capacity (6 minute-walk test) and body composition assessment (air displacement). Peripheral blood samples will be taken to examine novel vascular biomarkers and to examine renal function, full blood count, diabetic control (HBA1c - only diabetics) and Brain Natruetic Peptide. Coronary sinus samples will be taken for novel vascular biomarkers in a small proportion of the cohort. Blood Sampling and Storage Participants are asked to starve for two hours and rest for one hour before blood sampling. Coronary sinus blood sampling occurs at the time of coronary sinus cannulation before contrast is injected. Blood samples (serum/plasma) are taken in citrate and EDTA tubes. The samples stand at room temperature for a minimum of 30 minutes and undergo centrifugation within an hour. Centrifugation (3500rpm for 10 minutes) occurs at room temperature. Samples are then stored in -80 freezer. Laboratory Analysis Samples will undergo final analysis at the University of Warwick and Kings College London. Novel vascular biomarkers of heart failure that exist as proteins in the serum will be analysed using enzyme-linked immunosorbent assay (ELISA) techniques previously outlined in publications (3-6). The specific novel vascular biomarkers represent different aspects of adverse ventricular remodelling; myocardial stress [Growth Differentiation Factor-15] and extracellular remodelling [Matrix Metalloproteinases -2 & -9, Aminoterminal Propeptides of Type I Collagen (PINP), Aminoterminal Propeptides of Type III Collagen (PIIINP), Carboxy-Terminal Telopeptide of Type I Collagen (CITP)] (4-7). These markers will undergo quantification using ELISA techniques that have previously described in the literature (8, 9). Micro Ribonucleic Acids (miRNA) profiling will be undertaken in coronary sinus and peripheral samples and will be compared to those taken after CRT implantation. Responders will be compared to non-responders to determine variation in profile between these two distinct groups. Profiling and quantification will be performed as described in previous publications (10-12). Specific cardiac miRNA will be pre-selected to screen and quantify, especially those have already been proven to have altered expression in heart failure (13-16). Device Implantation CRT devices (pacemaker of defibrillator) are implanted by two independent operators at our single centre in a standard fashion. CRT is implanted traditionally in the left deltopectoral groove. Venous access is via the cephalic>axillary>subclavian veins (all operators can cannulate either vein based on individual patient). Right ventricular lead for the majority of patients will be implanted at the right ventricular apex. Right atrial leads will be planned to be implanted in the right atrial appendage. Patients in permanent Atrial Fibrillation will not have a right atrial lead implanted. Coronary sinus will be cannulated and angiography performed to roadmap anatomy for lead deployment site. The most lateral position will be favoured in a basal/ mid-cavity position. At the point of coronary sinus cannulation blood samples (plasma/serum will be taken). Post procedure patients undergo targeted echocardiography and a chest x-ray film. Post procedure on the day of implant patients will undergo CRT interrogation and optimisation of programming. Echocardiography A focused echocardiographic study assessing the left ventricle will be performed to the recommended international standard (17). The left ventricular systolic and diastolic function will be fully assessed. Volumetric assessment will be performed using Simpson's method (17). Diastolic function will be assessed by performing volumetric assessment of the left atrium, measuring pulse wave inflow of ventricular filling and TDI of the lateral and septal walls [apical 4 chamber]. All scans will be performed on the departmental machines [GE systems, Vivid 7] and by the same operator. Scans will be performed independently and previous scans will not have been reviewed before this scan. Full analysis will be conducted once all scans have been performed. Inter- and Intra-Observer Variability Echocardiography Study An inter- and intra-observer variability study will be performed to ensure standardisation of echocardiographic examinations. Twenty percent of echocardiograms will be randomly selected to have measurements and conclusions reviewed. An independent cardiologist/ cardiac physiologist (accredited by the British Society of Echocardiography) will be blinded to selected echocardiograms and will validate reporting and measurements of these examinations. Body Composition Air-displacement plethysmography (Bodpod) is an easily accessible and safe tool to measure body composition (18). The assessment is reproducible and is comparable to other measures of body composition (18). The major advantage of Bodpod is that it is safe for patients who have had a CRT implanted. The University of Warwick and University Hospital Coventry and Warwickshire (UHCW) has one of the few facilities in their Human Metabolic Unit to perform Bodpod.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by University Hospitals Coventry and Warwickshire NHS Trust.