After more than ten years of human research in the field of cardiac regenerative medicine, application of stem cells in different phases of ischemic heart disease has come to age. Randomized clinical trials have demonstrated that stem cell therapy can improve cardiac recovery after the acute phase of myocardial ischemia and in patients with chronic ischemic heart disease, and several efficacy phase III trials with clinical endpoints are on their way. Nevertheless, a complete knowledge on the mechanisms of action of stem cells still remains elusive. Of the three main mechanisms by which stem cells could exert their benefit, paracrine signaling from the administered cells and stimulation of endogenous repair are nowadays the most plausible ones. However, in this review we will define and discuss the concept of stem cell potency and differentiation, will examine the evidence available, and will depict future directions of research.

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Over the last years, stem cell therapy has emerged as an inspiring alternative to restore cardiac function after myocardial infarction. A large body of evidence has been obtained in this field but there is no conclusive data on the efficacy of these treatments. Preclinical studies and early reports in humans have been encouraging and have fostered a rapid clinical translation, but positive results have not been uniformly observed and when present, they have been modest. Several types of stem cells, manufacturing methods and delivery routes have been tested in different clinical settings but direct comparison between them is challenging and hinders further research. Despite enormous achievements, major barriers have been found and many fundamental issues remain to be resolved. A better knowledge of the molecular mechanisms implicated in cardiac development and myocardial regeneration is critically needed to overcome some of these hurdles. Genetic and pharmacological priming together with the discovery of new sources of cells have led to a "second generation" of cell products that holds an encouraging promise in cardiovascular regenerative medicine. In this report, we review recent advances in this field focusing on the new types of stem cells that are currently being tested in human beings and on the novel strategies employed to boost cell performance in order to improve cardiac function and outcomes after myocardial infarction.

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Introduction Several case series of ACS have been reported in COVID 19 patients. We aim to study its incidence, characteristics, and three-month prognosis. To put this incidence in perspective we compared it with the incidence of in-hospital ACS during the same period of 2019. Methods Observational multicenter cohort study of 3.108 COVID-19 patients admitted to two hospitals in Madrid between March 1st and May 15th, 2020. Ten patients suffered an ACS while being hospitalized for COVID 19 and were followed for three months. The ACS incidence in hospitalized patients during the same period of 2019 was also studied. Results The incidence of ACS in COVID-19 patients was 3.31‰, significantly higher than in the 2019 period, 1.01‰ (p = 0.013). COVID-19 patients that suffered and ACS frequently had a severe infection, presented with STEMI (80%), and had multivessel disease (67%). Mortality rate (30%) and hospital readmissions at three months (20%) were very high. Conclusions Severe COVID-19 patients develop ACS more frequently than expected. Although the overall incidence was low, it carried a poor immediate and three-month prognosis.

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