Anne-Marie Koop

90 systematic reviews in animal data form experimental studies. However, we feel that the use of Hedge’s g encompasses a specific point that should be addressed. Since the use of effect sizes implies standardized mean differences, calculations are based on a pooled SD, although unequal variances may be present. This may induce type I errors. However, the small and unequal sample sizes will likely cancel out this effect. An alternative statistic method would be statistics by using Z-scores, but because we aimed to provide an overview of the results of the different studies, by the visualization by figures, this method was not preferred. The interpretation of meta-analysis results were challenged by substantial degrees of heterogeneity, which was partly explored by performing (1) meta-regression analysis for duration and degree of pressure load, and (2) t-tests or OneWay ANOVA of the results of the different models. This resulted in three significant correlations with duration and various differences between models. Only one correlation was found with the degree of RV pressure load, which could be due to the fact included studies encompass significant loading conditions. Systematically test for the effect of used species was impossible due to the fact only one study concerned animal species other than rat. This, however, contributed to large homogeneity at this particular point. Further, we decided to use an almost similar approach for human as for animal studies in order to be able to apply the same methods regarding meta- analysis. Subsequently, a number of clinical studies were excluded from meta- analysis due to aspects regarding study-design. Nevertheless, most of excluded studies described FDG-uptake and supported the in the meta-analyses presented results. Other human studies that were excluded from the meta-analyses described uptake of fatty acids, as has been described above. Considerations regarding future research Due to use of differing designs of the included studies, power of the meta-analysis is limited. In contrast to clinical trials, replication is still scarce in experimental research. Current study emphasizes the need for replication and the use of more standardization in models, methods and outcome variables in studies studying metabolic derangements in RV pressure load. This could achieved in joint publications of between different research groups. Available data describes in certain extend the degree and duration of pressure load. In pursuing actual translation, absolute determination of pressure load will be necessary in both animals and human, aiming on differentiation between the actual component of pressure load and the etiology of disease including potential comorbidities. Performing studies by means of replicationand theuseof standardized models is essential to draw robust conclusions about metabolic derangements in the pressure loaded right ventricle.

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