Cardiac Resynchronisation Therapy: mechanisms of action and scope for further improvement in cardiac function

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Title: Cardiac Resynchronisation Therapy: mechanisms of action and scope for further improvement in cardiac function
Authors: Jones, S
Lumens, J
Sohaib, SMA
Finegold, JA
Kanagaratnam, P
Tanner, M
Duncan, E
Moore, P
Leyva, F
Frenneaux, M
Mason, M
Hughes, AD
Francis, D
Whinnett, ZI
The BRAVO Investigators, on behalf of the BRAVO Investigators
Item Type: Journal Article
Abstract: Background Cardiac resynchronisation therapy(CRT) may exert its beneficial hemodynamic effect by improving ventricular synchrony and improving atrioventricular(AV) timing. Aims To establish the relative importance of the mechanisms through which CRT improves cardiac function and explore the potential for additional improvements with improved ventricular resynchronisation. Methods We performed simulations using the CircAdapt haemodynamic model and performed haemodynamic measurements while adjusting AV delay, at low and high heart rates, in 87 patients with CRT devices. We assessed QRS duration, presence of fusion and haemodynamic response. Results The simulations suggest intrinsic PR interval and the magnitude of reduction in ventricular activation determine the relative importance of the mechanisms of benefit. For example, if PR interval is 201ms and LV activation time is reduced by 25ms (typical for current CRT methods) then AV delay optimisation is responsible for 69% of overall improvement. Reducing LV activation time by an additional 25ms produced an additional 2.6mmHg increase in BP (30% of effect size observed with current CRT). In the clinical population, ventricular fusion significantly shortened QRS duration (∆-27±23ms, P <0.001), and, improved SBP (mean 2.5 mmHg increase). Ventricular Fusion was present in 69% of patients, yet in 40% of patients with fusion, shortening AV delay (to a delay where fusion was not present) produced the optimal haemodynamic response. Conclusions Improving LV preloading by shortening AV delay is an important mechanism through which cardiac function is improved with CRT. There is substantial scope for further improvement if methods for delivering more efficient ventricular resynchronisation can be developed.
Issue Date: 13-Jul-2016
Date of Acceptance: 20-Apr-2016
ISSN: 1532-2092
Publisher: Oxford University Press (OUP)
Start Page: 1178
End Page: 1186
Journal / Book Title: Europace
Volume: 19
Issue: 7
Copyright Statement: © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
British Heart Foundation
Funder's Grant Number: SP/10/002/28189
Keywords: Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
Cardiac resynchronization therapy
AV delay
CRT mechanisms
BRAVO Investigators
cardiac resynchronisation therapy
1103 Clinical Sciences
Cardiovascular System & Hematology
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine

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