British randomised controlled trial of AV and VV optimization ("BRAVO") study: rationale, design, and endpoints

Zachary I Whinnett, S M Afzal Sohaib, Siana Jones, Andreas Kyriacou, Katherine March, Emma Coady, Jamil Mayet, Alun D Hughes, Michael Frenneaux, Darrel P Francis, BRAVO Investigators, Zachary I Whinnett, S M Afzal Sohaib, Siana Jones, Andreas Kyriacou, Katherine March, Emma Coady, Jamil Mayet, Alun D Hughes, Michael Frenneaux, Darrel P Francis, BRAVO Investigators

Abstract

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/design: 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.

Discussion: 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.

Trial registration: Clinicaltrials.gov NCT01258829.

Figures

Figure 1
Figure 1
Flowchart of study design. Patients visit 4 times and undergo 2 AV/VV delay optimizations according to the echocardiographic and finometer protocols.
Figure 2
Figure 2
Calculating the relative change in systolic blood pressure (Sys BPrel (mmHg) between a reference atrio-ventricular delay (AVD) of 120 ms and a tested AVD of 40 ms. Eight beats from the continuous arterial pressure waveform are averaged from each AVD (top picture), this process is repeated to include a minimum of 6 transitions for each AVD tested (middle picture). SBPrel plotted against the AVD (lower picture) is an average of the change in systolic blood pressure (8-beat average).
Figure 3
Figure 3
Echocardiographic optimization of atrio-ventricular delay (AVD) using the iterative method. Abbreviations E wave, A wave.

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