P1665Identifying metabolic treatment strategies for heart failure - A meta-analytic approach

Abstract

Abstract Background Current expert consensus suggests modulation of cardiac glucose oxidation (GO) or fatty acid oxidation (FAO) as a therapeutic approach for heart failure (HF). However, inconsistency exists and there is no systematic evidence supporting this concept. Objective We conducted a systematic review of preclinical studies to assess the role of metabolic treatment in HF. We aimed to identify, via meta-analytic techniques, specific metabolic strategies that potentially improve cardiac function. Methods We searched PubMed, Web of Science and reference lists of identified primary studies from inception to 31 December 2018. We included all interventional studies that assessed changes in cardiac function together with those in cardiac GO and/or FAO in established animal models of HF. Two investigators extracted study characteristics and data independently. We encompassed all available measures of cardiac function in the analysis instead of selecting one single outcome. Effect sizes were calculated as Hedges' g. We used I2 to estimate heterogeneity, metaregression to explore sources of heterogeneity and contour-enhanced funnel plot to assess publication bias. Results Our search returned 64 reports that fulfilled the inclusion criteria (n=1532 animals). The overall effect of treatments associated with metabolic changes was 0.78±0.16 g, p<0.001. There was a high heterogeneity (I2 = 86.7%) and no signs of publication bias. Metaregression revealed that treatments associated with an increase in GO (1.09±0.13 g, p<0.001) markedly enhance cardiac function. In contrast, those associated with decreased GO may worsen outcome. Although most experts suggest inhibiting FAO to improve cardiac function in HF, we found a beneficial result with a large total effect size for approaches that boost FAO (1.69±0.65 g, p<0.01). Conclusions Our data highlight the role of cardiac metabolism in treating HF. Specifically, increasing GO or FAO may considerably improve cardiac function. Furthermore, the findings challenge the common notion that inhibiting cardiac FAO is protective.