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 Coady; Katherine 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

doi:10.1093/europace/euw136

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 journal › Article › peer-review

45 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 language	English
Pages (from-to)	1178-1186
Number of pages	9
Journal	Europace
Volume	19
Issue number	7
DOIs	https://doi.org/10.1093/europace/euw136
Publication status	Published - 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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10.1093/europace/euw136

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Jones, S., Lumens, J., Sohaib, S. M. A., Finegold, J. A., Kanagaratnam, P., Tanner, M., Duncan, E., Moore, P., Leyva, F., Frenneaux, M., Mason, M., Hughes, A. D., Francis, D. P., Whinnett, Z. I., Chaturvedi, N., Davies, W., Lim, B., Lefroy, D., Peters, N. S., ... Dayer, M. (2017). Cardiac resynchronization therapy: Mechanisms of action and scope for further improvement in cardiac function. Europace, 19(7), 1178-1186. https://doi.org/10.1093/europace/euw136

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, DP, Whinnett, ZI, Chaturvedi, N, Davies, W, Lim, B, Lefroy, D, Peters, NS, Coady, E, March, K, Williams, S, Manoharan, K, Do Couto Francisco, N, Carvalho, VM, Kyriacou, A, Rudd, A, Sivaswamy, N, Singh, S, Thomas, M, Swinburn, J, Foley, P, Betts, T, Webster, D, Rogers, D, Wong, T, Sharma, R, Ellery, S, Yousef, Z, Anderson, L, Al-Obaidi, M, Margerison, N, Barrett, S, Kalra, P, Khiani, R & Dayer, M 2017, 'Cardiac resynchronization therapy: Mechanisms of action and scope for further improvement in cardiac function', Europace, vol. 19, no. 7, pp. 1178-1186. https://doi.org/10.1093/europace/euw136

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title = "Cardiac resynchronization therapy: Mechanisms of action and scope for further improvement in cardiac function",

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.",

keywords = "AV delay, Cardiac resynchronization therapy, CRT, CRT mechanisms, Resynchronization",

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

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: {\textcopyright} 2016 The Author.",

year = "2017",

month = jul,

day = "1",

doi = "10.1093/europace/euw136",

language = "English",

volume = "19",

pages = "1178--1186",

journal = "Europace",

issn = "1099-5129",

publisher = "Oxford University Press",

number = "7",

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TY - JOUR

T1 - Cardiac resynchronization therapy

T2 - Mechanisms of action and scope for further improvement in cardiac function

AU - Jones, Siana

AU - Lumens, Joost

AU - Sohaib, S. M.Afzal

AU - Finegold, Judith A.

AU - Kanagaratnam, Prapa

AU - Tanner, Mark

AU - Duncan, Edward

AU - Moore, Philip

AU - Leyva, Francisco

AU - Frenneaux, Mike

AU - Mason, Mark

AU - Hughes, Alun D.

AU - Francis, Darrel P.

AU - Whinnett, Zachary I.

AU - Chaturvedi, Nishi

AU - Davies, Wyn

AU - Lim, Boon

AU - Lefroy, David

AU - Peters, Nicholas S.

AU - Coady, Emma

AU - March, Katherine

AU - Williams, Suzanne

AU - Manoharan, Karikaran

AU - Do Couto Francisco, Nadia

AU - Carvalho, Vasco Miranda

AU - Kyriacou, Andreas

AU - Rudd, Amelia

AU - Sivaswamy, Nadiya

AU - Singh, Satnam

AU - Thomas, Martin

AU - Swinburn, Jon

AU - Foley, Paul

AU - Betts, Tim

AU - Webster, David

AU - Rogers, Dominic

AU - Wong, Tom

AU - Sharma, Rakesh

AU - Ellery, Susan

AU - Yousef, Zaheer

AU - Anderson, Lisa

AU - Al-Obaidi, Mohamed

AU - Margerison, Nicky

AU - Barrett, Stephanie

AU - Kalra, Paul

AU - Khiani, Raj

AU - Dayer, Mark

N1 - 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.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - AV delay

KW - Cardiac resynchronization therapy

KW - CRT

KW - CRT mechanisms

KW - Resynchronization

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DO - 10.1093/europace/euw136

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AN - SCOPUS:85026349936

SN - 1099-5129

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EP - 1186

JO - Europace

JF - Europace

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ER -

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

Abstract

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Keywords

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