Cardiac resynchronization therapy: Mechanisms of action and scope for further improvement in cardiac function

Siana Jones, Joost Lumens, S. M.Afzal Sohaib, Judith A. Finegold, Prapa Kanagaratnam, Mark Tanner, Edward Duncan, Philip Moore, Francisco Leyva, Mike Frenneaux, Mark Mason, Alun D. Hughes, Darrel P. Francis*, Zachary I. Whinnett, Nishi Chaturvedi, Wyn Davies, Boon Lim, David Lefroy, Nicholas S. Peters, Emma CoadyKatherine March, Suzanne Williams, Karikaran Manoharan, Nadia Do Couto Francisco, Vasco Miranda Carvalho, Andreas Kyriacou, Amelia Rudd, Nadiya Sivaswamy, Satnam Singh, Martin Thomas, Jon Swinburn, Paul Foley, Tim Betts, David Webster, Dominic Rogers, Tom Wong, Rakesh Sharma, Susan Ellery, Zaheer Yousef, Lisa Anderson, Mohamed Al-Obaidi, Nicky Margerison, Stephanie Barrett, Paul Kalra, Raj Khiani, Mark Dayer

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Aims Cardiac resynchronization therapy (CRT) may exert its beneficial haemodynamic effect by improving ventricular synchrony and improving atrioventricular (AV) timing. The aim of this study was to establish the relative importance of the mechanisms through which CRT improves cardiac function and explore the potential for additional improvements with improved ventricular resynchronization. Methods and Results 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. The simulations suggest that 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 201 ms and LV activation time is reduced by 25 ms (typical for current CRT methods), then AV delay optimization is responsible for 69% of overall improvement. Reducing LV activation time by an additional 25 ms produced an additional 2.6 mmHg increase in blood pressure (30% of effect size observed with current CRT). In the clinical population, ventricular fusion significantly shortened QRS duration ("-27 ± 23 ms, P < 0.001) and improved systolic blood pressure (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 resynchronization can be developed. Clinical Trial Registration Our clinical data were obtained from a subpopulation of the British Randomised Controlled Trial of AV and VV Optimisation (BRAVO), which is a registered clinical trial with unique identifier: NCT01258829, https://clinicaltrials.gov.

Original languageEnglish
Pages (from-to)1178-1186
Number of pages9
JournalEuropace
Volume19
Issue number7
DOIs
Publication statusPublished - 1 Jul 2017

Bibliographical note

Funding Information:
This work was supported by the UKs cardiovascular charity, the British Heart Foundation (BHF) (SP/10/002/28189) and the National Institute for Health Research. Z.W. (FS/13/44/30291), D.F. (FS/10/038), and A.S. (FS/11/92/29122) receive funding from the BHF. J.L. receives funding from the Dr E. Dekker program of the Dutch Heart Foundation (2012T010). Funding to pay the Open Access publication charges for this article was provided by British Heart Foundation.

Publisher Copyright:
© 2016 The Author.

Keywords

  • AV delay
  • Cardiac resynchronization therapy
  • CRT
  • CRT mechanisms
  • Resynchronization

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