Author + information
- Received November 1, 2017
- Revision received February 9, 2018
- Accepted February 15, 2018
- Published online August 5, 2019.
- Zachary I. Whinnett, BMBS, PhDa,
- S.M. Afzal Sohaib, MBBS, PhDa,
- Mark Mason, MBBSb,
- Edward Duncan, PhDc,
- Mark Tanner, MBBS, MDd,
- David Lefroy, MBBChira,
- Mohamed Al-Obaidi, MBChB, MDe,
- Sue Ellery, MBBS, BScf,
- Francisco Leyva-Leon, MDg,
- Tim Betts, MDh,
- Mark Dayer, PhDi,
- Paul Foley, MBChB, MDj,
- Jon Swinburn, MD, MBBSk,
- Martin Thomas, MDl,
- Raj Khiani, BSc(Hons), MBBSm,
- Tom Wong, MBChB MDb,
- Zaheer Yousef, MDn,
- Dominic Rogers, MDo,
- Paul R. Kalra, MDp,
- Vignesh Dhileepan, BSca,
- Katherine March, BSca,
- James Howard, MAa,
- Andreas Kyriacou, MBChB, PhDq,
- Jamil Mayet, MDa,
- Prapa Kanagaratnam, PhDa,
- Michael Frenneaux, MDr,
- Alun D. Hughes, MBBS, PhDs and
- Darrel P. Francis, MDa,∗ ()
- aDepartment of Cardiology, International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom
- bDepartment of Cardiology, Royal Brompton & Harefield NHS Trust, Middlesex, United Kingdom
- cDepartment of Cardiology, Bristol Heart Institute, Bristol, United Kingdom
- dDepartment of Cardiology, Western Sussex Hospitals NHS Foundation Trust, West Sussex, United Kingdom
- eDepartment of Cardiology, Frimley Health, Wexham Park Hospital, Slough, United Kingdom
- fDepartment of Cardiology, Brighton & Sussex University Hospitals NHS Trust, Brighton, United Kingdom
- gDepartment of Cardiology, University Hospitals Birmingham NHS Trust, Birmingham, United Kingdom
- hDepartment of Cardiology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
- iDepartment of Cardiology, Taunton & Somerset NHS Foundation Trust, United Kingdom
- jDepartment of Cardiology, Great Western Hospitals NHS Foundation Trust, Swindon, United Kingdom
- kDepartment of Cardiology, Royal Berkshire Hospitals NHS Trust, Reading, United Kingdom
- lDepartment of Cardiology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
- mDepartment of Cardiology, Milton Keynes Hospital NHS Trust, Milton Keynes, United Kingdom
- nDepartment of Cardiology, University Hospital of Wales, Cardiff, United Kingdom
- oDepartment of Cardiology, Royal Free Hospital NHS Trust, London, United Kingdom
- pDepartment of Cardiology, Portsmouth Hospitals NHS Trust, Portsmouth, United Kingdom
- qDepartment of Cardiology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
- rDepartment of Cardiology, Institute of Medical Sciences, University of Aberdeen Foresterhill, Aberdeen, United Kingdom
- sDepartment of Cardiology, Institute of Cardiovascular Sciences, University College London, London, United Kingdom
- ↵∗Address for correspondence:
Dr. Darrel Francis, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, B Block, 2nd Floor, NHLI - Cardiovascular Science, Du Cane Road, London W12 0NN, United Kingdom.
Objectives BRAVO (British Randomized Controlled Trial of AV and VV Optimization) is a multicenter, randomized, crossover, noninferiority trial comparing echocardiographic optimization of atrioventricular (AV) and interventricular delay with a noninvasive blood pressure method.
Background Cardiac resynchronization therapy including AV delay optimization confers clinical benefit, but the optimization requires time and expertise to perform.
Methods This study randomized patients to echocardiographic optimization or hemodynamic optimization using multiple-replicate beat-by-beat noninvasive blood pressure at baseline; after 6 months, participants were crossed over to the other optimization arm of the trial. The primary outcome was exercise capacity, quantified as peak exercise oxygen uptake. Secondary outcome measures were echocardiographic left ventricular (LV) remodeling, quality-of-life scores, and N-terminal pro–B-type natriuretic peptide.
Results A total of 401 patients were enrolled, the median age was 69 years, 78% of patients were men, and the New York Heart Association functional class was II in 84% and III in 16%. The primary endpoint, peak oxygen uptake, met the criterion for noninferiority (pnoninferiority = 0.0001), with no significant difference between the hemodynamically optimized arm and echocardiographically optimized arm of the trial (mean difference 0.1 ml/kg/min). Secondary endpoints for noninferiority were also met for symptoms (mean difference in Minnesota score 1; pnoninferiority = 0.002) and hormonal changes (mean change in N-terminal pro–B-type natriuretic peptide -10 pg/ml; pnoninferiority = 0.002). There was no significant difference in LV size (mean change in LV systolic dimension 1 mm; pnoninferiority < 0.001; LV diastolic dimension 0 mm; pnoninferiority <0.001). In 30% of patients the AV delay identified as optimal was more than 20 ms from the nominal setting of 120 ms.
Conclusions Optimization of cardiac resynchronization therapy devices by using noninvasive blood pressure is noninferior to echocardiographic optimization. Therefore, noninvasive hemodynamic optimization is an acceptable alternative that has the potential to be automated and thus more easily implemented. (British Randomized Controlled Trial of AV and VV Optimization [BRAVO]; NCT01258829)
- biventricular pacing
- cardiac resynchronization therapy
- echocardiographic optimization
- heart failure
- hemodynamic optimization
Funding was provided by the United Kingdom’s cardiovascular charity, the British Heart Foundation (SP/10/002/28189, FS/10/038, FS/11/92/29122, FS/13/44/30291) and the National Institute for Health Research Imperial Biomedical Research Centre. Imperial College London innovations have filed a patient for a hemodynamic optimization method for cardiac resynchronization therapy, and Drs. Whinnett and Francis are named as inventors on this patent. Dr. Mason is on the advisory board of Medtronic; and has received conference support from Boston Scientific and St. Jude Medical. Dr. Leyva-Leon is a consultant for and has received research support from Medtronic, St. Jude Medical, Boston Scientific, and LivaNova. Dr. Dayer has received lecturing fees from Biotronik. Dr. Yousef has received unrestricted education grants from Abbott; and speaker fees and consultancies from Bristol-Myers Squibb, Pfizer, AstraZeneca, and Servier Novartis. Dr. Kalra has received research grants from Alere, Medtronic, Pharmacosmos, and Servier; has received speaker fees from Alere, Amgen, Bristol-Myers Squibb, Novartis, Pfizer, Pharmacosmos, and Servier; and has served on the advisory boards of Abbott, Nova-Nordisk, Novartis, Pharmacosmos, Servier, and Vifor. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 1, 2017.
- Revision received February 9, 2018.
- Accepted February 15, 2018.
- 2019 The Authors