Translating cardioprotection for patient benefit: position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology

Abstract

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 pre-clinical 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.

MRI Investigation of New Approach to Improve the Recovery of Myocardial Ischemia Reperfusion Injury by Treatment with Intralipid<sup>®</sup>

“…Patients who survive the initial event could suffer significant morbidity and mortality due to adverse ventricular remodeling resulting in the long-term heart failure. Acute myocardial IRI is the major cause of the adverse effects of CHD on the myocardium [2]. Our results demonstrate that Intralipid ® indeed can protect the resulting injury in hearts due to IRI as shown by our in-vivo non-invasive multi-parameter CMRI in a rat model of acute myocardial infaction.…”

“…Despite of the advancement of revascularization therapy and pharmacological thrombolysis, the long-term outcome of patients after acute myocardial infarction (MI) could be poor [1], due to myocardial ischemia-reperfusion injury (IRI) with resultant cardiomyocyte death and adverse long-term consequences [2] [3]. The abrupt restoration of circulation in the infarct-related artery not only brings in the much needed oxygen and nutrients, but also triggers inflammation and oxidative stress, which may cause greater damage to the tissue, and the subsequent adverse myocardial remodeling.…”

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

“…In contrast to our and previous observations,6 Małek et al did not report any difference in LVEF. The importance of measuring area at risk in addition to infarct size has previously been emphasized given that area at risk has an impact on infarct size 30. Given that infarct size, myocardial salvage index, LVEF, LVH, and MVO are associated with adverse outcome in STEMI patients,20, 22, 31, 32, 33 findings in the present study indicate that the impaired prognosis in patients with acute MI and LVH may directly be attributed to more‐extensive myocardial damage and smaller salvage.…”

Adverse Effects on β‐Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long‐Term Cardiac Function

“…However, the results from longitudinal human studies have not provided a uniform picture of the efficacy and safety of IPoC 8. In 2013 a single‐center study by Freixa et al showed rather a significant deterioration in the myocardial salvage and the myocardial salvage index along with reduced pump function 6 months after myocardial ischemia 9.…”