Cardiac magnetic resonance defines mechanisms of sex-based differences in outcomes following cardiac resynchronization therapy

Figures

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  FIGURE 1. Flow diagram of the study design. Patients were enrolled over approximately a 10-year period from 2011 to 2021. Before CRT device implantation, the baseline parameters of the patients were recorded based on findings from MRI, echocardiography, electrocardiograms, exercise testing, and laboratory studies. Additional parameters (such as QLV which indicates late activation of LV pacing cite) were gathered during the CRT procedure. Six months after CRT, patients received follow-up MRI/echocardiograms, laboratory studies, and exercise testing to calculate response measures. Finally, patients were followed for long-term survival with routine interrogations.

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  FIGURE 2. Significant pre-CRT CMR findings and post-CRT response measures stratified only by sex. (A) LVEDVI (p < 0.04), (B) ICM presence (p 0.0001), (C) CURE-SVD (p = 0.04) are highlighted as these parameters were found to be significantly different between males and females. Compared with males, females were more likely to have smaller LVEDVI, less frequency of ICM, and lower CURE-SVD. In (D–F), the response measures stratified by sex only (as opposed to sex and cardiomyopathy type in Figure 4) are shown to be similar by group.

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  FIGURE 3. Differences in dyssynchrony, LV size, RV function, hormonal activity, and CRT response measures among cohort stratified by sex and cardiomyopathy type. (A) CURE-SVD, (B) pre-CRT LVEDVI, (C) RVEF, (D) log(pre-CRT BNP), (E) LVESVI-FC, and (F) log(post-CRT BNP) were compared among the four different groups (females with ICM, males with ICM, females with NICM, and males with NICM) using ANOVA. Significant differences between group means were noted for (A) CURE-SVD (p = 0.003), (D) log(pre-CRT BNP) (p = 0.01), (E) LVESVI-FC (p = 0.0006), and (F) log(post-CRT BNP) (p = 0.05). The Tukey post hoc analysis demonstrated differences for pairwise comparisons with *p < 0.05 with the NICM female group as the reference.

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  FIGURE 4. Kaplan–Meier survival curves. Kaplan–Meier curves for survival are shown with stratification by: (A) males vs. females, (B) males with ICM vs. females with NICM, and (C) males vs. NICM versus females with NICM. Females had better survival than males (A, p = 0.007, HR = 0.45), and females with NICM had better survival than males with NICM (C, p = 0.009, HR = 0.67). There was no significant difference in survival between females with ICM and males with ICM (B, p = 0.17, HR = 0.91).

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  FIGURE 5. Scatter plots of pre-CRT parameters versus post-CRT response measures for stratified cohort. (A) CURE-SVD versus LVESVI-FC for all patients is shown with color and shade based on grouping. Many of the darker points (ICM) appear in the highlighted upper right-hand corner (larger CURE-SVD and positive, unfavorable LVESVI-FC) while many of the lighter points (NICM) appear in the highlighted lower left-hand corner (lower CURE-SVD and negative, favorable LVESVI-FC). Many of the green points (male) appear in the highlighted upper right-hand corner while many of the purple points (female) appear in the highlighted lower left-hand corner. (B) log(pre-CRT BNP) versus log(post-CRT BNP) is shown and exhibits similar trends. The plot in panel (A) demonstrates clustering of LVESVI-FC and CURE-SVD by sex/cardiomyopathy group, while the plot in panel (B) demonstrates differences in BNP by sex/cardiomyopathy group.