Meteorin-like/Meteorin-β (Metrnl/Metrnβ) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrnβ in cardiac disease is completely unknown. Here, we show that Metrnβ-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus–mediated specific overexpression of Metrnβ in the heart prevents the development of cardiac remodeling. Furthermore, Metrnβ inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrnβ in cardiomyocyte cell cultures indicated an autocrine action of Metrnβ on the heart, in addition to an endocrine action. Moreover, Metrnβ is highly produced in the heart, and analysis of circulating Metrnβ concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value.

Background: Short-term variability of repolarization derived from the QT-interval (STV-QT) has previously been demonstrated to increase prior to arrhythmias in both humans and animals. To continuously monitor the arrhythmic risk by a cardiovascular implantable electronic device (CIED), a fully automatic method to determine STV on intracardiac electrograms (STV-EGM auto ) has been developed. This method demonstrated high effectiveness in monitoring and predicting Torsade de Pointes arrhythmias in the CAVB dog model. However, this technique has not been evaluated in arrhythmias related to ischemia yet. Purpose: To assess the novel automatic method of arrhythmic risk monitoring by CIEDs through STV-EGM auto measurements in a porcine model of ischemia-induced ventricular fibrillation (VF). Methods: Myocardial infarction was induced in 8 anesthetized pigs by balloon occlusion of the left anterior descending coronary artery for 75 minutes, followed by reperfusion. Monitoring included a 12-lead ECG and a duodecapolar EGM catheter in the right ventricle. STV-EGM auto and STV-QT, our gold standard calculated by the method of fiducial segment averaging, were assessed at baseline, occlusion, one minute before VF and just before VF. The STV values and the percentual changes from baseline to the successive three timepoints were compared between STV-EGM auto and STV-QT. Results: VF occurred 21±8.8 minutes after occlusion. Both STV-EGM auto and STV-QT increased significantly from baseline to VF (1.1±0.8 ms vs 2.4±1.5 ms, p<0.05; 1.0±0.5 ms vs 2.2±0.9 ms, p<0.05, respectively). The percentual change in STV-EGM auto from baseline to occlusion, one minute before VF and VF showed an excellent correlation with the changes in STV-QT from baseline to the successive timepoints (r 2 = 0.94; p<0.001). Bland-Altman analysis of the values showed a small bias of 0.26 ms and 95% limits of agreement between -1.1 and 1.6 ms. Conclusion: The STV values derived from the fully-automatic method for continuous STV measurements on intracardiac EGM signals (STV-EGM auto ) show values and trends similar to the clinically validated STV-QT in a porcine model of ischemia-related VF. Future integration of this technique in CIEDs can furnish continuous monitoring of arrhythmic risk.