February 2016 at a Glance. Focus Issue on Cardiac Regeneration, Medical Treatment and Cardiac Devices

Five articles deal with cardiac regeneration. An overview presents the Committee for Advanced Therapies of the European Medicines Agency viewpoint on cell-based therapies for cardiac repair.1 Different therapies and endpoints to be used in experimental models and for patients with acute myocardial infarction and heart failure (HF) are thoroughly discussed.1 A second review discusses an alternative approach, compared with the traditional ones, based on cell delivery, in situ reprogramming of endogenous cardiac fibroblasts into functional cardiomyocytes.2 This has been achieved in experimental models using critical transcription factors, microRNA mimics, and small molecules able to cause fibroblast reprogramming to cells with cardiomyocyte-like morphology, gene expression, and spontaneous contraction. These new cells are able to improve cardiac function in post-infarction models. The results and future perspectives are nicely reviewed in this issue of the journal.2 Finally, the design of a randomized controlled trial of cardiopoietic regenerative therapy in patients with HF (CHART-1) is presented.3 Patients are randomized to a sham procedure or the injection of cardiopoietic stem cells. These cells are obtained through the expansion and conditioning of non-regenerative patient-derived stem cells towards the cardiac lineage using a cardiogenic conditioning medium administered through a new retention-enhanced intramyocardial injection catheter.4 The primary efficacy endpoint is a hierarchical composite one including mortality, worsening HF, quality of life, 6 minute walk test and left ventricular volumes and function at 9 months.3 With regard to medical treatment, an analysis from the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan trial (EVEREST) shows an attenuation of the osmolality changes induce by tolvaptan administration with their disappearance at week 56, consistently with its lack of effects on outcomes. The Authors hypothesize that counter-regulatory up-regulation of vasopressin may have attenuated tolvaptan-induced osmolality changes as well as its effects on symptoms and diuretic needs.5 A meta-analysis of 11 randomized controlled trials of implantable telemonitoring devices in patients with HF shows a 44% reduction in the total number of visits and planned visits with a slight increase in unplanned visits and no difference in hospitalization and mortality rates. Costs of treatment were reduced because of the reduction in planned visits.6 New studies continue to add data to the large database regarding predictive factors of the response to cardiac resynchronization therapy.7, 8 In this issue of the journal, Stolfo et al. show that an early improvement in right ventricular dysfunction, in those patients in whom it is impaired at baseline, can be a further independent predictor of a favorable outcome after cardiac resynchronization therapy in HF patients.9 Enjoy this issue more focused on translational medicine and devices.

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