Geert Kleinnibbelink

RV Strain in Pulmonary Hypertension 6 149 Study quality All studies included in our meta-analysis were assessed for quality using the Quality In Prognosis Studies (QUIPS) checklist for measuring study quality by two authors (H.H. and G.K.). 32 The QUIPS checklist exists of 31 items divided over six domains; study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding and statistical analysis and reporting. For each domain, several items were evaluated after which the domain was scored for the presence of low, moderate or high risk of bias. As recommended, a predefined overall rating was applied. 32 Studies with a high risk of bias score in a single domain or ≥ 3 scores of moderate risk of bias in different domains were rated as high risk of bias and excluded from this review ( Supplementary Table 1 ). Echocardiographic assessment To ensure high quality and consistency of the RVLSmeasurement we only included studies which reported adherence to the ASE guidelines for echocardiographic assessment of the right heart 33 and/or chamber quantification 34 , used a (focused) RV apical 4 chamber view and traced the endocardial border for RVLS determination. Statistical analysis Review Manager 5.3 (Cochrane Community) was used to perform a meta-analysis of the reported multivariate HRs. The reported HRs [95%-CI] were converted to a log (HR) and the complementing standard error (SE) using the formula: The resulting values were inserted in the inverse variance method for calculation of HRs using a random effects analysis to calculate the mean weighted HR [95% CI] for all studies. Separate analysis were performed for 1) a combined endpoint of mortality and PH-related events and 2) all-cause mortality. To provide further insight in the relation between RVLS and the risk for the combined endpoint or all-cause mortality , we calculated the relative reduction of RVLS (in %) for which the HR was determined. For this purpose, we defined the relative reduction of RVLS as: the difference between the mean RVLS of the

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