New opportunities in hxfx / transplantation

While in adults major advances in heart failure therapy in patients with dilated cardiomyopathy were documented in the last two decades, research on the mechanism and therapies of heart failure in children with left ventricular dilated cardiomyopathy has lagged behind. Despite the lack of sufficient randomized prospective studies, ACE inhibitors are first line and ß-receptor antagonists are second-line strategies in children. Following the adult guidelines, without having data concerning the pediatric population, mineral corticoids are also accepted in the treatment of pediatric heart failure, while diuretics should only be used to achieve a euvolemic status...

BACKGROUND: The long-term progression of idiopathic dilated cardiomyopathy (DCM) in pediatric patients compared with adult patients has not been previously characterized. In this study, we compared outcome and long-term progression of pediatric and adult DCM populations. METHODS AND RESULTS: Between 1988 and 2014, 927 DCM patients were consecutively enrolled. The pediatric population (aged <18 years at enrollment) included 47 participants (5.1%). At presentation, the pediatric population compared with adult patients had a significantly increased occurrence of familial forms (P=0...

Cardiac stress can induce morphological, structural and functional changes of the heart, referred to as cardiac remodeling. Myocardial infarction or sustained overload as a result of pathological causes such as hypertension or valve insufficiency may result in progressive remodeling and finally lead to heart failure (HF). Whereas pathological and physiological (exercise, pregnancy) overload both stimulate cardiomyocyte growth (hypertrophy), only pathological remodeling is characterized by increased deposition of extracellular matrix proteins, termed fibrosis, and loss of cardiomyocytes by necrosis, apoptosis and/or phagocytosis...

HLA incompatible organ transplant tolerance is the holy grail of transplantation. Stable engraftment of an HLA mismatched allograft and life-long tolerance induction, though feasible in highly selected cohorts with depletional protocols, is not ready for generalized application to the entire transplant recipient pool. It has thus been important to harness biomarkers that can uncover mechanisms and tools for monitoring HLA mismatched recipients that develop a state of operational tolerance, during accidental immunosuppression withdrawal secondary to problems of over-immunosuppression (infection or malignancy) or toxicity (mostly cosmetic or cardiovascular)...

Elevated serum soluble (s) suppressor of tumorigenicity-2 is observed during cardiovascular and inflammatory bowel diseases. To ascertain whether modulated ST2 levels signify heart (HTx) or small bowel transplant (SBTx) rejection, we quantified sST2 in serially obtained pediatric HTx (n = 41) and SBTx recipient (n = 18) sera. At times of biopsy-diagnosed HTx rejection (cellular and/or antibody-mediated), serum sST2 was elevated compared to rejection-free time points (1714 ± 329 vs. 546.5 ± 141.6 pg/mL; p = 0...

PURPOSE OF REVIEW: We describe the general strategies for the management of cardiac amyloidosis with particular focus on the use of cardiac transplantation for amyloid cardiomyopathy. Within this article, we highlight recent data regarding the use of combined heart transplant-chemotherapy, use of cardiac transplant in mutant amyloid disease, and underutilization of cardiac transplantation in sarcoidosis. RECENT FINDINGS: Several center experiences have been recently published, describing management strategies in AL amyloid, with focus on timing of chemotherapy as it relates to transplant, and in mutant amyloid in particular...

Better postoperative management of patients who have undergone single ventricle (SV) Fontan procedure could potentially reduce long-term complications and improve the quality of life for patients. The present study determined the effect of tadalafil on myocardial and endothelial function and exercise performance after modified Fontan operation. Patients who had undergone SV modified Fontan operation were enrolled in this clinical trial. The demographic characteristics of the patients were recorded. Before administration of tadalafil and after the trial, ventricular function (MPI, EF, FS, E/A, VTI), exercise performance, and endothelial function were evaluated for sonographic and biochemical markers (FMD, IMT, ICAM, VCAM, NO) using echocardiography, exercise testing, vascular ultrasonography, and biochemical measurements, respectively...

BACKGROUND: As atrial fibrillation (AF) carries twice the mortality hazard when compared with a similar population without diagnosed AF, the importance of risk stratifying is obvious. Several variables are related to outcome: age, comorbidities, and use of several medications, particularly oral anticoagulants. The CHA2DS2VASc score is an extremely useful tool to predict thromboembolic events and also mortality. The international normalized ratio (INR) variability is a treatment efficacy variable also associated with morbidity in patients receiving warfarin...

Cardiovascular disorders or cardiovascular diseases (CVD) are major illness associated with heart and blood vessels. Reactive oxygen species (ROS), generated during excessive oxidative stress, are responsible for the pathophysiology of various cardiovascular disorders including atherosclerosis, cardiac hypertrophy, cardiomyopathy, heart failure, ventricular remodeling, ischemia/reperfusion injury and myocardial infarction. Cellular "redox homeostasis" generally maintains the healthy physiology in cardiac myocytes and endothelial cells...

Nitrovasodilators have long been used as first-line treatment for hypertensive acute heart failure (AHF). Although effective for BP control and symptom alleviation, this class of agents has never been shown to improve mortality or prevent hospital readmissions. Consequently, there has been tremendous interest in development of newer vasodilators with more beneficial therapeutic profiles. In this review, we focus on three of the most promising agents currently being studied: serelaxin, ularitide, and TRV027...

It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction. Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become chronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead to compromised pump function and patient death...