Impact of Myocardial Fibrosis on Cardiovascular Structure, Function and Functional Status in Heart Failure with Preserved Ejection Fraction

Figures

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  Fig. 1. Mediation analysis method. Mediation analysis as described by Baron and Kenny [15]. To proceed onto mediation analysis, the independent variable must have a significant effect on both the mediator variable and the outcome variable (direct effect). If either relationship is non-significant, this indicates non-mediation. If significant, the outcome variable is regressed onto both the independent and mediator variables; if the independent variable no longer effects the outcome variable, this indicates full mediation; if the independent variable still predicts the outcome variable but with a smaller size, this indicates partial mediation

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  Fig. 2. Associations with change in extracellular volume (ECV) from baseline to week 52. Correlations between change in ECV and A change in left ventricular end-diastolic volume (LVEDV) index, B change in 6-min walk test (6MWT) and C change in Kansas City cardiomyopathy questionnaire Clinical Summary Score (KCCQ-CSS)

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  Fig. 3. Mediation model. Illustration of the mediation model. Pirfenidone (treatment intervention) has a direct effect on left ventricular (LV) ejection fraction (outcome variable) and a direct effect on extracellular volume (ECV) (mediator variable). Pirfenidone also has an indirect effect on LV ejection fraction via the effect on ECV. Mediation analysis determines whether the change in the mediator variable (ECV) causes the change in the outcome variable (LV ejection fraction), by calculating the proportion of the total effect of treatment on the outcome variable that is due to the indirect effect of treatment on the outcome variable acting via the mediator (ECV), i.e. the proportion of the total treatment effect that is mediated via the mediation variable (ECV). As per Table 4, the proportion of the total effect of pirfenidone on LV ejection fraction that was mediated by ECV was 6.1%, which was not significant (p = 0.608)