Sex-dependent QRS guidelines for Cardiac Resynchronization Therapy using Computer Model Predictions

Angela Wing Chung Lee; Declan P. O'Regan; Justin Simon Gould; Baldeep Singh Sidhu; Benjamin Sieniewicz; Gernot Plank; David R Warriner; Pablo Lamata; Christopher Aldo Rinaldi; Steven Alexander Niederer

doi:10.1016/j.bpj.2019.08.025

Sex-dependent QRS guidelines for Cardiac Resynchronization Therapy using Computer Model Predictions

Angela Wing Chung Lee, Declan P. O'Regan, Justin Simon Gould, Baldeep Singh Sidhu, Benjamin Sieniewicz, Gernot Plank, David R Warriner, Pablo Lamata, Christopher Aldo Rinaldi, Steven Alexander Niederer

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

96 Downloads (Pure)

Abstract

Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50–100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9–13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9–13 ms lower QRSd thresholds for female CRT guidelines.

Original language	English
Pages (from-to)	2375-2381
Journal	Biophysical Journal
Volume	117
Issue number	12
Early online date	28 Aug 2019
DOIs	https://doi.org/10.1016/j.bpj.2019.08.025
Publication status	Published - 17 Dec 2019

Access to Document

10.1016/j.bpj.2019.08.025Licence: CC BY

Sex-dependent QRS guidelines_LEE_Accepted12August2019_ePublished28August2019_GOLD VoR (CC BY)Final published version, 793 KBLicence: CC BY

Cite this

@article{54ed8a6b3cc94ac0b2b7a6045470f1d0,

title = "Sex-dependent QRS guidelines for Cardiac Resynchronization Therapy using Computer Model Predictions",

abstract = "Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50–100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9–13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9–13 ms lower QRSd thresholds for female CRT guidelines.",

author = "Lee, {Angela Wing Chung} and O'Regan, {Declan P.} and Gould, {Justin Simon} and Sidhu, {Baldeep Singh} and Benjamin Sieniewicz and Gernot Plank and Warriner, {David R} and Pablo Lamata and Rinaldi, {Christopher Aldo} and Niederer, {Steven Alexander}",

year = "2019",

month = dec,

day = "17",

doi = "10.1016/j.bpj.2019.08.025",

language = "English",

volume = "117",

pages = "2375--2381",

journal = "Biophysical Journal",

issn = "0006-3495",

publisher = "Elsevier BV",

number = "12",

}

TY - JOUR

T1 - Sex-dependent QRS guidelines for Cardiac Resynchronization Therapy using Computer Model Predictions

AU - Lee, Angela Wing Chung

AU - O'Regan, Declan P.

AU - Gould, Justin Simon

AU - Sidhu, Baldeep Singh

AU - Sieniewicz, Benjamin

AU - Plank, Gernot

AU - Warriner, David R

AU - Lamata, Pablo

AU - Rinaldi, Christopher Aldo

AU - Niederer, Steven Alexander

PY - 2019/12/17

Y1 - 2019/12/17

N2 - Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50–100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9–13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9–13 ms lower QRSd thresholds for female CRT guidelines.

AB - Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50–100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9–13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9–13 ms lower QRSd thresholds for female CRT guidelines.

U2 - 10.1016/j.bpj.2019.08.025

DO - 10.1016/j.bpj.2019.08.025

M3 - Article

SN - 0006-3495

VL - 117

SP - 2375

EP - 2381

JO - Biophysical Journal

JF - Biophysical Journal

IS - 12

ER -

Sex-dependent QRS guidelines for Cardiac Resynchronization Therapy using Computer Model Predictions

Abstract

Access to Document

Fingerprint

Cite this