Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial

Nadeev Wijesuriya; Vishal Mehta; Felicity De Vere; Sandra Howell; Steven A. Niederer; Haran Burri; Johannes Sperzel; Leonardo Calo; Bernard Thibault; Wenjiao Lin; Kwangdeok Lee; Andrea Grammatico; Niraj Varma; Marianne Gwechenberger; Christophe Leclercq; Christopher A. Rinaldi

doi:10.1161/JAHA.123.035279

Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial

Nadeev Wijesuriya, Vishal Mehta, Felicity De Vere, Sandra Howell, Steven A. Niederer, Haran Burri, Johannes Sperzel, Leonardo Calo, Bernard Thibault, Wenjiao Lin, Kwangdeok Lee, Andrea Grammatico, Niraj Varma, Marianne Gwechenberger, Christophe Leclercq, Christopher A. Rinaldi

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

Abstract

BACKGROUND: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. METHODS AND RESULTS: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing) trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. CONCLUSIONS: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

Original language	English
Article number	e035279
Pages (from-to)	e035279
Journal	Journal of the American Heart Association
Volume	13
Issue number	12
DOIs	https://doi.org/10.1161/JAHA.123.035279
Publication status	Published - 18 Jun 2024

Keywords

cardiac resynchronization therapy
heart failure
sex differences

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10.1161/JAHA.123.035279

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Wijesuriya, N., Mehta, V., De Vere, F., Howell, S., Niederer, S. A., Burri, H., Sperzel, J., Calo, L., Thibault, B., Lin, W., Lee, K., Grammatico, A., Varma, N., Gwechenberger, M., Leclercq, C., & Rinaldi, C. A. (2024). Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial. Journal of the American Heart Association, 13(12), e035279. Article e035279. https://doi.org/10.1161/JAHA.123.035279

@article{75105b2915324cef993a729e7b6bd607,

title = "Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial",

abstract = "BACKGROUND: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. METHODS AND RESULTS: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing) trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. CONCLUSIONS: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.",

keywords = "cardiac resynchronization therapy, heart failure, sex differences",

author = "Nadeev Wijesuriya and Vishal Mehta and {De Vere}, Felicity and Sandra Howell and Niederer, {Steven A.} and Haran Burri and Johannes Sperzel and Leonardo Calo and Bernard Thibault and Wenjiao Lin and Kwangdeok Lee and Andrea Grammatico and Niraj Varma and Marianne Gwechenberger and Christophe Leclercq and Rinaldi, {Christopher A.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors and Abbott.",

year = "2024",

month = jun,

day = "18",

doi = "10.1161/JAHA.123.035279",

language = "English",

volume = "13",

pages = "e035279",

journal = "Journal of the American Heart Association",

issn = "2047-9980",

publisher = "American Heart Association, Inc.",

number = "12",

}

Wijesuriya, N , Mehta, V , De Vere, F , Howell, S , Niederer, SA, Burri, H, Sperzel, J, Calo, L, Thibault, B, Lin, W, Lee, K, Grammatico, A, Varma, N, Gwechenberger, M, Leclercq, C & Rinaldi, CA 2024, 'Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial', Journal of the American Heart Association, vol. 13, no. 12, e035279, pp. e035279. https://doi.org/10.1161/JAHA.123.035279

TY - JOUR

T1 - Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy

T2 - A Post Hoc Analysis of the MORE-MPP CRT Trial

AU - Wijesuriya, Nadeev

AU - Mehta, Vishal

AU - De Vere, Felicity

AU - Howell, Sandra

AU - Niederer, Steven A.

AU - Burri, Haran

AU - Sperzel, Johannes

AU - Calo, Leonardo

AU - Thibault, Bernard

AU - Lin, Wenjiao

AU - Lee, Kwangdeok

AU - Grammatico, Andrea

AU - Varma, Niraj

AU - Gwechenberger, Marianne

AU - Leclercq, Christophe

AU - Rinaldi, Christopher A.

PY - 2024/6/18

Y1 - 2024/6/18

N2 - BACKGROUND: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. METHODS AND RESULTS: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing) trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. CONCLUSIONS: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

AB - BACKGROUND: Studies have reported that female sex predicts superior cardiac resynchronization therapy (CRT) response. One theory is that this association is related to smaller female heart size, thus increased relative dyssynchrony at a given QRS duration (QRSd). Our objective was to investigate the mechanisms of sex-specific CRT response relating to heart size, relative dyssynchrony, cardiomyopathy type, QRS morphology, and other patient characteristics. METHODS AND RESULTS: This is a post hoc analysis of the MORE-CRT MPP (More Response on Cardiac Resynchronization Therapy with Multipoint Pacing) trial (n=3739, 28% women), with a subgroup analysis of patients with nonischemic cardiomyopathy and left bundle-branch block (n=1308, 41% women) to control for confounding characteristics. A multivariable analysis examined predictors of response to 6 months of conventional CRT, including sex and relative dyssynchrony, measured by QRSd/left ventricular end-diastolic volume (LVEDV). Women had a higher CRT response rate than men (70.1% versus 56.8%, P<0.0001). In subgroup analysis, regression analysis of the nonischemic cardiomyopathy left bundle-branch block subgroup identified QRSd/LVEDV, but not sex, as a modifier of CRT response (P<0.0039). QRSd/LVEDV was significantly higher in women (0.919) versus men (0.708, P<0.001). CRT response was 78% for female patients with QRSd/LVEDV greater than the median value, compared with 68% with QRSd/LVEDV less than the median value (P=0.012). The association between CRT response and QRSd/LVEDV was strongest at QRSd <150 ms. CONCLUSIONS: In the nonischemic cardiomyopathy left bundle-branch block population, increased relative dyssynchrony in women, who have smaller heart sizes than their male counterparts, is a driver of sex-specific CRT response, particularly at QRSd <150 ms. Women may benefit from CRT at a QRSd <130 ms, opening the debate on whether sex-specific QRSd cutoffs or QRS/LVEDV measurement should be incorporated into clinical guidelines.

KW - cardiac resynchronization therapy

KW - heart failure

KW - sex differences

UR - http://www.scopus.com/inward/record.url?scp=85196581815&partnerID=8YFLogxK

U2 - 10.1161/JAHA.123.035279

DO - 10.1161/JAHA.123.035279

M3 - Article

C2 - 38879456

AN - SCOPUS:85196581815

SN - 2047-9980

VL - 13

SP - e035279

JO - Journal of the American Heart Association

JF - Journal of the American Heart Association

IS - 12

M1 - e035279

ER -

Heart Size Difference Drives Sex-Specific Response to Cardiac Resynchronization Therapy: A Post Hoc Analysis of the MORE-MPP CRT Trial

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