Sex-Specific Response to Cardiac Resynchronization Therapy

Varma, Niraj; Lappé, Jason M.; He, Junyu; Niebauer, Mark; Manne, Mahesh; Tchou, Patrick

doi:10.1016/j.jacep.2017.02.021

Cited by 50 publications

(53 citation statements)

References 25 publications

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“…These interactions are important because any given value of QRSd, the determinant of any individual's candidacy for CRT, represents a composite result of delayed myocardial conduction (ie, the substrate for CRT) but also increased LV size (mass/volume), which may degrade CRT benefit 5. The ratio of QRSd/LV size was shown recently to be a better predictor of CRT effect than QRSd alone in patients with LBBB, and it differed between sexes and among individuals 3, 6…”

Section: Discussionmentioning

confidence: 99%

“…Then, enrolled patients were dichotomized by median LVEDV value (LVEDV Median ). Because LV size generally is larger in male CRT recipients,3, 6 and men were the driver for worse outcomes with CRT in the whole EchoCRT trial cohort,8 we compared CRT effect according to LV size in each sex. We then assessed the quotient QRSd/LVEDV to test the hypothesis that patients with larger QRSd/LVEDV ratios benefited from CRT.…”

Section: Methodsmentioning

confidence: 99%

“…The ratio of QRSd/LV size may better index CRT substrate. When applied, this was superior to the unadjusted QRSd in predicting successful CRT measured by short‐term hemodynamic effects or long‐term remodeling among patients with left bundle branch block (LBBB) 3, 6. Patients with a high index score (relatively large QRSd and small LV size) had higher probability of CRT response compared with those with a low index score (smaller QRS and large LV size) who could worsen with treatment.…”

mentioning

confidence: 98%

“…However, there is increasing recognition that QRSd may be prolonged not only by reduced myocardial conduction velocity (His‐Purkinje lesions) but also by increased left ventricular (LV) dimension acting to extend the “travel distance” of the propagating wavefront 2. The distinction is important because the former is the target for CRT, but the latter (itself influenced by heart failure [HF] remodeling, sex, and body size/height3, 4) limits CRT response 5. Hence, any given QRSd reflects the sum effect of factors with opposite implications for CRT success, and this balance may differ among individuals with identical QRSd values.…”

mentioning

confidence: 99%

“…In addition, because among conventionally selected patients undergoing CRT (LBBB and LV ejection fraction [LVEF] <35%), men have greater LV dilation,3, 6 and numerically a higher all‐cause mortality was reported in male patients randomized to CRT‐ON in the EchoCRT trial,8 we assessed interactions of sex with LV size and CRT effect.…”

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confidence: 99%

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Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial

Varma

Søgaard

Bax

et al. 2018

JAHA

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BackgroundLonger QRS duration (QRSd) improves, but increased left ventricular (LV) end‐diastolic volume (LVEDV) reduces, efficacy of cardiac resynchronization therapy (CRT). QRSd/LVEDV ratios differ between sexes. We hypothesized that in the EchoCRT (Echocardiography Guided Cardiac Resynchronization Therapy) trial enrolling patients with heart failure with QRSd <130 ms, those with larger LVEDV would deteriorate but those with the highest QRSd/LVEDV would improve with CRT.Methods and ResultsPrimary outcome in patients (n=787, 72% men, 93% New York Heart Association class III, QRSd <130 ms, LV ejection fraction ≤35%, LV dilation and dyssynchrony) randomized to CRT‐ON or CRT‐OFF and followed up for 19 months was compared according to LVEDV (height indexed) or QRSd/LVEDV ratio, in multivariable analysis. Structural remodeling was assessed echocardiographically 6 months after implantation. Patients with baseline LVEDV higher than or equal to median worsened with CRT (death/heart failure hospitalization: CRT‐ON versus CRT‐OFF, 35.2% versus 24.5% [hazard ratio, 1.64; 95% confidence interval, 1.11–2.42; P=0.012]), but those with LVEDV lower than median remained unaffected. Patients with the highest QRSd/LVEDV ratio improved with CRT (death/heart failure hospitalization in top quartile: 20.9% in CRT‐ON [n=91] versus 28.3% in CRT‐OFF [n=106] [hazard ratio, 0.64; 95% confidence interval, 0.34–1.24; P=0.188], versus the remaining quartiles: 31.7% in CRT‐ON [n=300] versus 24.8% in CRT‐OFF [n=290] [hazard ratio, 1.47; 95% confidence interval, 1.07–2.02; P=0.016], test for interaction P=0.046). QRSd and dyssynchrony were similar between groups. The 3‐way test for interaction indicated no sex‐specific effects. However, numerically, men with LVEDV higher than or equal to median accounted for worse outcomes of CRT‐ON. Women, with the highest QRSd/LVEDV ratio exhibited significant reverse remodeling.Conclusion CRT has opposite effects among patients with heart failure with QRSd <130 ms according to LV size: worsening outcomes in patients with larger LV, but inducing beneficial effects in those with smaller LV.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT00683696.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial

Varma

Søgaard

Bax

et al. 2018

JAHA

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Interaction of left ventricular size with the outcome of cardiac resynchronization therapy in Japanese patients

Ito,

Kondo,

Nakano

et al. 2024

Clinical Cardiology

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BackgroundWe analyzed the influence of the QRS duration (QRSd) to LV end‐diastolic volume (LVEDV) ratio on cardiac resynchronization therapy (CRT) outcomes in heart failure patients classified as III/IV per the New York Heart Association (NYHA) and with small body size.HypothesisWe proposed the hypothesis that the QRSd/LV size ratio is a better index of the CRT substrate.MethodsWe enrolled 114 patients with advanced heart failure (NYHA class III/IV, and LV ejection fraction >35%) who received a CRT device, including those with left bundle branch block (LBBB) and QRSd ≥120 milliseconds (n = 60), non‐LBBB and QRSd ≥150 milliseconds (n = 30) and non‐LBBB and QRSd of 120−149 milliseconds (n = 24).ResultsOver a mean follow‐up period of 65 ± 58 months, the incidence of the primary endpoint, a composite of all‐cause death and hospitalization for heart failure, showed no significant intergroup difference (43.3% vs. 50.0% vs. 37.5%, respectively, p = .72). Similarly, among 104 patients with QRSd/LVEDV ≥ 0.67 (n = 54) and QRSd/LVEDV < 0.67 (n = 52), no significant differences were observed in the incidence of the primary endpoint (35.1% vs. 51.9%, p = .49). Nevertheless, patients with QRSd/LVEDV ≥ 0.67 showed better survival than those with QRSd/LVEDV < 0.67 (14.8% vs. 34.6%, p = .0024).ConclusionAdvanced HF patients with a higher QRSd/LVEDV ratio showed better survival in this small‐body–size population. Thus, the risk is concentrated among those with a larger QRSd, and patients with a relatively smaller left ventricular size appeared to benefit from CRT.

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Differences in clinical characteristics and reported quality of life of men and women undergoing cardiac resynchronization therapy

et al. 2020

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Aims Response to cardiac resynchronization therapy (CRT) is known to be associated with a number of clinical characteristics, including QRS duration and morphology, gender, height, and the aetiology of heart failure (HF). We assessed the relation of gender and baseline characteristics with QRS duration and Kansas City Cardiomyopathy Questionnaire. Methods and results AdaptResponse is a global randomized trial. The trial enrolled CRT-indicated patients with New York Heart Association classes II-IV HF, left bundle branch block (QRS ≥ 140 ms in men, ≥130 ms in women), and baseline PR interval ≤200 ms. In total, 3620 patients were randomized, including 1569 women (43.3%) approaching the actual proportion of women in the HF population. Women were older and more often New York Heart Association class III or IV than men (55.6% vs. 48.7%), had less frequent ischaemic cardiomyopathy (21.2% vs. 39.5%), and had a 5.1 ms shorter QRS duration than men. Women were more often depressed (18.5% vs. 9.7%), had a significantly lower Kansas City Cardiomyopathy Questionnaire score, and had differences in medication prescriptions. Conclusions AdaptResponse is the largest randomized CRT trial and enrolled more women than any other landmark CRT trial. Women differed from men with regard to baseline characteristics and quality of life. Whether these differences translate into clinical outcome differences will be examined further in the AdaptResponse trial.

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Sex-Specific Response to Cardiac Resynchronization Therapy

Abstract: Sex differences in the QRSd-response relationship among CRT patients with LBBB were unexplained by application of strict LBBB criteria or by BSA, but resolved by QRSd normalization for heart size using LV mass or volume.

Cited by 50 publications

References 25 publications

Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial

Interaction of Left Ventricular Size and Sex on Outcome of Cardiac Resynchronization Therapy Among Patients With a Narrow QRS Duration in the EchoCRT Trial

Interaction of left ventricular size with the outcome of cardiac resynchronization therapy in Japanese patients

Differences in clinical characteristics and reported quality of life of men and women undergoing cardiac resynchronization therapy

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