http://cardiologia.publicacionmedica.com/contenido/images/stemi_aha_2013.pdf

2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(12)60195-0.pdf

Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial

Context Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. Objective To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. Design, Setting, and Patients A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. Intervention Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. Main Outcome Measures Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO 2 , Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. Results Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO 2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P  Conclusions In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. Trial Registration clinicaltrials.gov Identifier: NCT01087996

https://jamanetwork.com/journals/jama/articlepdf/1388970/jpc120011_2369_2379.pdf

Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: The POSEIDON randomized trial

Myocardial infarction triggers an intense inflammatory response that is essential for cardiac repair, but which is also implicated in the pathogenesis of postinfarction remodelling and heart failure. Signals in the infarcted myocardium activate toll-like receptor signalling, while complement activation and generation of reactive oxygen species induce cytokine and chemokine upregulation. Leukocytes recruited to the infarcted area, remove dead cells and matrix debris by phagocytosis, while preparing the area for scar formation. Timely repression of the inflammatory response is critical for effective healing, and is followed by activation of myofibroblasts that secrete matrix proteins in the infarcted area. Members of the transforming growth factor β family are critically involved in suppression of inflammation and activation of a profibrotic programme. Translation of these concepts to the clinic requires an understanding of the pathophysiological complexity and heterogeneity of postinfarction remodelling in patients with myocardial infarction. Individuals with an overactive and prolonged postinfarction inflammatory response might exhibit left ventricular dilatation and systolic dysfunction and might benefit from targeted anti-IL-1 or anti-chemokine therapies, whereas patients with an exaggerated fibrogenic reaction can develop heart failure with preserved ejection fraction and might require inhibition of the Smad3 (mothers against decapentaplegic homolog 3) cascade. Biomarker-based approaches are needed to identify patients with distinct pathophysiologic responses and to rationally implement inflammation-modulating strategies.

/pdf/the-inflammatory-response-in-myocardial-injury-repair-and-2vph4g25n1.pdf

The inflammatory response in myocardial injury, repair, and remodelling.

In mammals, enlargement of the heart during embryonic development is primarily dependent on the increase in cardiomyocyte numbers. Shortly after birth, however, cardiomyocytes stop proliferating and further growth of the myocardium occurs through hypertrophic enlargement of the existing myocytes. As a consequence of the minimal renewal of cardiomyocytes during adult life, repair of cardiac damage through myocardial regeneration is very limited. Here we show that the exogenous administration of selected microRNAs (miRNAs) markedly stimulates cardiomyocyte proliferation and promotes cardiac repair. We performed a high-content microscopy, high-throughput functional screening for human miRNAs that promoted neonatal cardiomyocyte proliferation using a whole-genome miRNA library. Forty miRNAs strongly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. Two of these miRNAs (hsa-miR-590 and hsa-miR-199a) were further selected for testing and were shown to promote cell cycle re-entry of adult cardiomyocytes ex vivo and to promote cardiomyocyte proliferation in both neonatal and adult animals. After myocardial infarction in mice, these miRNAs stimulated marked cardiac regeneration and almost complete recovery of cardiac functional parameters. The miRNAs identified hold great promise for the treatment of cardiac pathologies consequent to cardiomyocyte loss.

Functional screening identifies miRNAs inducing cardiac regeneration

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)61590-0.pdf

Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial.

Patients are avoiding hospitals for fear of contracting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). We are witnessing a re-emergence of rare complications of myocardial infarctions (MI) due to delayed revascularization. Herein, we describe a case of hemorrhagic pericarditis from thrombolytics administered to a patient with late presenting MI. (Level of Difficulty: Beginner.).

Complication of Late Presenting STEMI Due to Avoidance of Medical Care During the COVID-19 Pandemic

The heart contains c-kit+, lineage- cardiac stem cells (CSCs). Although CSCs improve postinfarction LV dysfunction in animals, their efficacy in humans is unknown. In February 2009, we began SCIPIO...

Abstract 15571: Effect of Cardiac Stem Cells in Patients with Ischemic Cardiomyopathy: Interim Results of the SCIPIO Trial

The left atrial appendage (LAA) in the setting of non-valvular atrial fibrillation (NVAF) is the predominant location for intracardiac thrombus formation. An absent LAA is a very rare congenital cardiac anomaly. We present a case of a 79-year-old female with NVAF, high CHADS2VASC2 score, and high bleeding risk who presented for elective Watchman™ left atrial appendage closure device implant. A pre-procedural transesophageal echocardiography showed an absent LAA. This finding was confirmed with cardiac computed tomography and a left atrial angiogram. The patient was discharged on medical therapy with close outpatient follow-up.

Naresh K Solankhi

Papers

Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial.

Complication of Late Presenting STEMI Due to Avoidance of Medical Care During the COVID-19 Pandemic

Abstract 15571: Effect of Cardiac Stem Cells in Patients with Ischemic Cardiomyopathy: Interim Results of the SCIPIO Trial

A curious case of an absent left atrial appendage.

Meta-analysis of randomized sham controlled trials assessing the role of renal denervation in hypertension