Authors: Matthias Thielmann, Vikram Sharma, Nawwar Al-Attar, Heerajnarain Bulluck, Gianluigi Bisleri, Jeroen JH Bunge, Martin Czerny, Péter Ferdinandy, Ulrich H. Frey, Gerd Heusch, Johannes Holfeld, Petra Kleinbongard, Gudrun Kunst, Irene Lang, Salvatore Lentini, Rosalinda Madonna, Patrick Meybohm, Claudio Muneretto, Jean-Francois Obadia, Cinzia Perrino, Fabrice Prunier, Joost P.G. Sluijter, Linda W. Van Laake, Miguel Sousa-Uva, Derek J. Hausenloy
Eur Heart J ehx383; doi: 10.1093/eurheartj/ehx383; Published: 25 July 2017
Introduction: Coronary artery disease (CAD) is one of the leading causes of death and disability in Europe and worldwide. For patients with multi-vessel CAD, coronary artery bypass graft (CABG) surgery is a common approach for coronary revascularization and is of proven symptomatic and prognostic benefit. Due to an ageing population, higher prevalence of comorbidities (such as diabetes mellitus, heart failure, hypertension, and renal failure), and a growing requirement for concomitant surgical procedures (such as valve and aortic surgery), higher risk patients are undergoing surgery. This has resulted in an increased risk of perioperative myocardial injury (PMI) and Type 5 myocardial infarction (MI), both of which are associated with worsened clinical outcomes following CABG surgery. The aetiology and determinants of PMI and Type 5 MI are multi-factorial (see Tables 1 and 2 for a summary). Although diagnostic criteria have been proposed for Type 5 MI (based on an elevation in cardiac biomarkers in the 48-h postoperative period and electrocardiogram/angiography/imaging evidence of MI), there is currently no clear definition for prognostically significant PMI, in terms of the level of postoperative cardiac biomarker elevation, which is associated with worsened clinical outcomes following CABG surgery.
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Authors: Cinzia Perrino, Albert-Laszló Barabási, Gianluigi Condorelli, Sean Michael Davidson, Leon De Windt, Stefanie Dimmeler, Felix Benedikt Engel, Derek John Hausenloy, Joseph Addison Hill, Linda Wilhelmina Van Laake, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Manuel Mayr, Fabrice Prunier, Joost Petrus Geradus Sluijter, Rainer Schulz, Thomas Thum, Kirsti Ytrehus, Péter Ferdinandy
Cardiovasc Research (2017) 113 (7): 725-736; DOI: 10.1093/cvr/cvx070; Published: 29 April 2017
Authors: Rosalinda Madonna, Linda W. Van Laake, Sean M. Davidson, Felix B. Engel, Derek J. Hausenloy, Sandrine Lecour, Jonathan Leor, Cinzia Perrino, Rainer Schulz, Kirsti YtrehusUlf Landmesser, Christine L. Mummery, Stefan Janssens, James Willerson, Thomas Eschenhagen, Péter Ferdinandy, Joost P.G. Sluijter
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First published online: 7 April 2016
Abstract: Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel formation and/or muscle regeneration. Here, we discuss the use of cells in the context of heart repair, and the most relevant results and current limitations from clinical trials using cell-based therapies to treat IHD and HF. We identify and discuss promising potential new therapeutic strategies that include ex vivo cell-mediated gene therapy, the use of biomaterials and cell-free therapies aimed at increasing the success rates of therapy for IHD and HF. The overall aim of this Position Paper of the ESC Working Group Cellular Biology of the Heart is to provide recommendations on how to improve the therapeutic application of cell-based therapies for cardiac regeneration and repair.
Authors: Sandrine Lecour, Hans E. Bøtker, Gianluigi Condorelli, Sean M. Davidson, David Garcia-Dorado, Felix B. Engel, Peter Ferdinandy, Gerd Heusch, Rosalinda Madonna, Michel Ovize, Marisol Ruiz-Meana, Rainer Schulz, Joost P.G. Sluijter, Linda W. Van Laake, Derek M. Yellon, Derek J. Hausenloy
Reference: Cardiovascular Research Journal .doi:10.1093/cvr/cvu225
First published online: 24 October 2014
Abstract: Ischaemic heart disease (IHD) remains the leading cause of death and disability worldwide. As a result, novel therapies are still needed to protect the heart from the detrimental effects of acute ischaemia–reperfusion injury, in order to improve clinical outcomes in IHD patients. In this regard, although a large number of novel cardioprotective therapies discovered in the research laboratory have been investigated in the clinical setting, only a few of these have been demonstrated to improve clinical outcomes. One potential reason for this lack of success may have been the failure to thoroughly assess the cardioprotective efficacy of these novel therapies in suitably designepre-clinicalal experimental animal models. Therefore, the aim of this Position Paper by the European Society of Cardiology Working Group Cellular Biology of the Heart is to provide recommendations for improving the preclinical assessment of novel cardioprotective therapies discovered in the research laboratory, with the aim of increasing the likelihood of success in translating these new treatments into improved clinical outcomes.
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Authors : Hausenloy DJ, Erik Bøtker H, Condorelli G, Ferdinandy P, Garcia-Dorado D, Heusch G, Lecour S, van Laake LW, Madonna R, Ruiz-Meana M, Schulz R, Sluijter JP, Yellon DM, Ovize M.
Reference: Cardiovasc Research Journal. 2013 Apr 1; 98(1):7-27. doi: 10.1093/cvr/cvt004. Epub 2013
First time published: 19 January 2013
Summary: Coronary heart disease (CHD) is the leading cause of death and disability worldwide. Despite current therapy, the morbidity and mortality for patients with CHD remains significant. The most important manifestations of CHD arise from acute myocardial ischaemia–reperfusion injury (IRI) in terms of cardiomyocyte death and its long-term consequences. As such, new therapeutic interventions are required to protect the heart against the detrimental effects of acute IRI and improve clinical outcomes. Although a large number of cardioprotective therapies discovered in preclinical studies have been investigated in CHD patients, few have been translated into the clinical setting, and a significant number of these have failed to show any benefit in terms of reduced myocardial infarction and improved clinical outcomes. Because of this, there is currently no effective therapy for protecting the heart against the detrimental effects of acute IRI in patients with CHD. One major factor for this lack of success in translating cardioprotective therapies into the clinical setting can be attributed to problems with the clinical study design. Many of these clinical studies have not taken into consideration the important data provided from previously published pre-clinical and clinical studies. The overall aim of this ESC Working Group Cellular Biology of the Heart Position Paper is to provide recommendations for optimizing the design of clinical cardioprotection studies, which should hopefully result in new and effective therapeutic interventions for the future benefit of CHD patients.
Authors: Michel Ovize, Gary F. Baxter, Fabio Di Lisa, Peter Ferdinandy,David Garcia-Dorado, Derek J. Hausenloy, Gerd Heusch, Jakob Vinten-Johansen,Derek M. Yellon, and Rainer Schulz
Reference: Cardiovasc Research Journal (2010) 87 (3): 406-423. doi: 10.1093/cvr/cvq129
First time published: 6 May 2010
Abstract: Ischaemic postconditioning (brief periods of ischaemia alternating with brief periods of reflow applied at the onset of reperfusion following sustained ischaemia) effectively reduces myocardial infarct size in all species tested so far, including humans. Ischaemic postconditioning is a simple and safe manoeuvre, but because reperfusion injury is initiated within minutes of reflow, postconditioning must be applied at the onset of reperfusion. The mechanisms of protection by postconditioning include: formation and release of several autacoids and cytokines; maintained acidosis during early reperfusion; activation of protein kinases; preservation of mitochondrial function, most strikingly the attenuation of opening of the mitochondrial permeability transition pore (MPTP). Exogenous recruitment of some of the identified signalling steps can induce cardioprotection when applied at the time of reperfusion in animal experiments, but more recently cardioprotection was also observed in a proof-of-concept clinical trial. Indeed, studies in patients with an acute myocardial infarction showed a reduction of infarct size and improved left ventricular function when they underwent ischaemic postconditioning or pharmacological inhibition of MPTP opening during interventional reperfusion. Further animal studies and large-scale human studies are needed to determine whether patients with different co-morbidities and co-medications respond equally to protection by postconditioning. Also, our understanding of the underlying mechanisms must be improved to develop new therapeutic strategies to be applied at reperfusion with the ultimate aim of limiting the burden of ischaemic heart disease and potentially providing protection for other organs at risk of reperfusion injury, such as brain and kidney.
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