Myocardial fibrosis: biomedical research from bench to bedside

Myocardial fibrosis refers to a variety of quantitative and qualitative changes in the interstitial myocardial collagen network that occur in response to cardiac ischaemic insults, systemic diseases, drugs, or any other harmful stimulus affecting the circulatory system or the heart itself. Myocardial fibrosis alters the architecture of the myocardium, facilitating the development of cardiac dysfunction, also inducing arrhythmias, influencing the clinical course and outcome of heart failure patients. Focusing on myocardial fibrosis may potentially improve patient care through the targeted diagnosis and treatment of emerging fibrotic pathways. The European Commission funded the FIBROTARGETS consortium as a multinational academic and industrial consortium with the primary aim of performing a systematic and collaborative search of targets of myocardial fibrosis, and then translating these mechanisms into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. This review focuses on those methodological and technological aspects considered and developed by the consortium to facilitate the transfer of the new mechanistic knowledge on myocardial fibrosis into potential biomedical applications.     

Reticular telangiectatic erythema associated with an implantable cardioverter defibrillator

Reticular telangiectatic erythema (RTE) is a skin reaction associated with implantable cardiac devices (ie, pacemakers and cardioverter defibrillators). We present a patient who developed an erythematous patch over the implantable cardioverter defibrillator site. We discuss the clinical features, histologic findings, and patch testing of this entity.     

Myocardial Interstitial Fibrosis in Heart Failure: Biological and Translational Perspectives

Myocardial interstitial fibrosis contributes to left ventricular dysfunction leading to the development of heart failure. Basic research has provided abundant evidence for the cellular and molecular mechanisms behind this lesion and the pathways by which it imparts a detrimental impact on cardiac function. Translation of this knowledge, however, to improved diagnostics and therapeutics for patients with heart failure has not been as robust. This is partly related to the paucity of biomarkers to accurately identify myocardial interstitial fibrosis and to the lack of personalized antifibrotic strategies to treat it in an effective manner. This paper summarizes current knowledge of the mechanisms and detrimental consequences of myocardial interstitial fibrosis, discusses the potential of circulating and imaging biomarkers available to recognize different phenotypes of this lesion and track their clinical evolution, and reviews the currently available and potential future therapies that allow its individualized management in heart failure patients.     

Surgery of Cosmetic Sequelae After Breast‐Conserving Therapy

Abstract: Although a considerable number of patients have an unfair cosmetic result after breast‐conserving therapy, which correlates with poor psychosocial functioning, surprisingly, really only very few patients undergo surgical correction. The purpose of this article was to report our experience in the surgical treatment of such patients and analyze a special subgroup which required bilateral reduction mammaplasty because of associated symptomatic macromastia and their desire to reduce their breast size. From July 2000 to November 2008, some 23 patients consulted for unsatisfactory cosmetic outcome after breast‐conserving therapy, fourteen of them accepting the surgical treatment proposed and these were operated upon. We used the following techniques: reduction mammaplasty of the contralateral breast for symmetrization (9), bilateral reduction mammaplasty (4), one mammaplasty and augmentation of contra‐lateral breast and one myocutaneous dorsi flap for surgical correction of ipsilateral breast. One patient had serious complications, having partial necrosis of the areola, fat and breast skin necrosis, and needed reoperation for surgical removal of necrotic tissue. Some factors such as obesity and heavy smoking habits could explain this. We were able to evaluate cosmetic outcome in ten patients; late cosmetic outcome was good in seven patients, fair in two and poor in one. Despite the fact that most patients treated by breast‐conserving therapy are satisfied with the fact that they have retained their breasts and minimized an unfair cosmetic outcome, cosmetic evaluation should be introduced as a matter of routine.     

Searching for new mechanisms of myocardial fibrosis with diagnostic and/or therapeutic potential

Myocardial fibrosis is the result of excessive fibrillar collagen synthesis and deposition without reciprocally balanced degradation. It causes cardiac dysfunction, arrhythmias, and ischaemia, and thereby determines the clinical course and outcome of cardiac patients even when adequately treated. Therefore, further research is needed to identify and better understand the factors that trigger and maintain the myocardial fibrotic response against different injuries in a variety of cardiac diseases. Here, we will focus on the following major areas of research: molecules that stimulate the differentiation of fibroblasts into myofibroblasts and subsequently alter collagen turnover (e.g. cardiotrophin‐1, galectin‐3, NADPH oxidases, and neutrophil gelatinase‐associated lipocalin), microRNA‐induced alterations of collagen gene expression, and matricellular protein‐ and lysyl oxidase‐mediated alterations of collagen cross‐linking and deposition.