Background: Fabry disease is a hereditary genetic defect resulting in reduced activity of the enzyme α-galactosidase-A and the accumulation of globotriaosylceramide (Gb3) in body fluids and cells. Gb3 accumulation was especially reported for the vascular endothelium in several organs. Methods: Three Fabry disease patients were screened using a micro-RNA screen. An in vitro approach in human endothelial cells was used to determine miRNA regulation by Gb3. Results: In a micro-RNA screen of three Fabry patients undergoing enzyme replacement therapy, we found that miRNAs let-7a and let-7d were significantly increased after therapy. We demonstrate in vitro in endothelial cells that Gb3 induced activation of NF-κB and activated downstream targets. In addition, NF-κB activity directly reduced let-7a and let-7d miRNA expression as inhibiting NF-kB nuclear entry abolished the Gb3 effects. Conclusion: We suggest that let-7a and let-7d are potential markers for enzyme activity and inflammation in Fabry disease patients.

Percutaneous coronary intervention of chronic total occlusion (CTO PCI) is a challenging procedure with high complication rates and, as not yet fully understood long-term clinical benefits. Ischemic symptom relief in patients with high ischemic burden is to date the only established clinical indication to undergo CTO PCI, supported by randomized controlled trials. In this context, current guidelines suggest attempting CTO PCI only in non-invasively assessed viable CTO correspondent myocardial territories, with large ischemic areas. Hence, besides a comprehensive coronary angiography lesion evaluation, the information derived from non-invasive cardiac imaging techniques is crucial to selecting candidates who may benefit from the revascularization of the occluded vessel. Currently, there are no clear recommendations for a non-invasive myocardial evaluation or choice of imaging modality pre-CTO PCI. Therefore, selecting among available options is left to the physician’s discretion. As CTO PCI is strongly recommended to be carried out explicitly in experienced centers, full access to non-invasive imaging for risk-benefit assessment as well as a systematic institutional evaluation process has to be encouraged. In this framework, we opted to review the current myocardial imaging tools and their use for indicating a CTO PCI. Furthermore, based on our experience, we propose a cost-effective systematic approach for myocardial assessment to help guide clinical decision-making for patients presenting with chronic total occlusions.