British randomised controlled trial of AV and VV optimization ("BRAVO") study: rationale, design, and endpoints.
BACKGROUND
Echocardiographic optimization of pacemaker settings is the current standard of care for patients treated with cardiac resynchronization therapy. However, the process requires considerable time of expert staff. The BRAVO study is a non-inferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular (VV) delay with an alternative method using non-invasive blood pressure monitoring that can be automated to consume less staff resources.


METHODS
BRAVO is a multi-centre, randomized, cross-over, non-inferiority trial of 400 patients with a previously implanted cardiac resynchronization device. Patients are randomly allocated to six months in each arm. In the echocardiographic arm, AV delay is optimized using the iterative method and VV delay by maximizing LVOT VTI. In the haemodynamic arm AV and VV delay are optimized using non-invasive blood pressure measured using finger photoplethysmography. At the end of each six month arm, patients undergo the primary outcome measure of objective exercise capacity, quantified as peak oxygen uptake (VO2) on a cardiopulmonary exercise test. Secondary outcome measures are echocardiographic measurement of left ventricular remodelling, quality of life score and N-terminal pro B-type Natriuretic Peptide (NT-pro BNP). The study is scheduled to complete recruitment in December 2013 and to complete follow up in December 2014.


CONCLUSIONS
If exercise capacity is non-inferior with haemodynamic optimization compared with echocardiographic optimization, it would be proof of concept that haemodynamic optimization is an acceptable alternative which has the potential to be more easily implemented.


BACKGROUND
Clinicaltrials.gov NCT01258829.
International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, 59-61 North Wharf Road, London W2 1LA, UK. z.whinnett@imperial.ac.uk.
Zachary I
ZI
Whinnett
S M Afzal
SM
Sohaib
Siana
S
Jones
Andreas
A
Kyriacou
Katherine
K
March
Emma
E
Coady
Jamil
J
Mayet
Alun D
AD
Hughes
Michael
M
Frenneaux
Darrel P
DP
Francis
D015415:Biomarkers / Q000097:blood; D001795:Blood Pressure Determination / Q000379:methods*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D058409:Cardiac Resynchronization Therapy Devices; D002985:Clinical Protocols; D018592:Cross-Over Studies; D015150:Echocardiography, Doppler; D005080:Exercise Test; D017079:Exercise Tolerance; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006439:Hemodynamics; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D017156:Photoplethysmography; D011237:Predictive Value of Tests; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain