Heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a major cause of cardiovascular morbidity and mortality. Contrary to initial beliefs, HFpEF is now known to be as common as heart failure with reduced ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a prevalence that has been steadily rising over the past two decades, it is very likely that HFpEF will represent the dominant heart failure phenotype over the coming few years. The scarcity of trials in this semi-discrete form of heart failure and lack of unified enrolment criteria in the studies conducted to date might have contributed to the current absence of specific therapies. Understanding the epidemiological, pathophysiological and molecular differences (and similarities) between these two forms of heart failure is cornerstone to the development of targeted therapies. Carefully designed studies that adhere to unified diagnostic criteria with the recruitment of appropriate controls and adoption of practical end-points are urgently needed to help identify effective treatment strategies

The role of endothelin-1 in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH

CADUCEUS, SCIPIO, ALCADIA: Cell therapy trials using cardiac-derived cells for patients with post myocardial infarction LV dysfunction, still evolving.

The early results of the CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction study were recently published in the Lancet [1]. This study is a phase 1 prospective randomised study, performed at two centres. The study was designed to test the hypothesis that intracoronary infusion of autologous cardiac-derived cells following myocardial infarction can reduce the size of the infarct and increase the amount of viable myocardium. The eligible patients were randomised in a 2:1 ratio to receive CDCs or standard care. In all, 17 patients were randomised to cell therapy and 8 to standard care. The cell therapy consisted of an infusion of 25 million cells into the infarct related artery, 1.5–3 months after successful primary angioplasty in patients who developed LV dysfunction (EF less than 37 per cent). The cells were derived from RV endomyocardial biopsies performed within the previous 37 days. The number of cells was determined from previous experimental studies of the maximum number of cells which can be injected without inducing infarction. The study was not blinded because of ethical considerations regarding performing right ventricular biopsy on the controls. The exclusion criteria included patients who had evidence of right ventricular infarction, or could not have an MRI examination because of claustrophobia or prior insertion of devices. There was no death, myocardial infarction or serious arrhythmia reported in either group during the period of follow up, which was between 6-12 months. Serious adverse events were observed in 24 percent of the intervention group versus 12 per cent in the controls (p not significant)

The Burundi Heart Centre: From concept to design.

Burundi is one of the worlds poorest nations, which is also reflected in its relative lack of cardiac facilities, particularly those catering to young children and adults. The authors discuss current efforts to build The Burundi Heart Centre to help address this challenge. In particular, they highlight how the project can act as a case study for a sustainable architecture that involves local people and uses locally available materials in a contemporary and innovative way

Utility of mass spectrometry for the diagnosis of the unstable coronary plaque.

Mass spectrometry is a powerful technique that is used to identify unknown compounds, to quantify known materials, and to elucidate the structure and chemical properties of molecules. Recent advances in the accuracy and speed of the technology have allowed data acquisition for the global analysis of lipids from complex samples such as blood plasma or serum. Here, mass spectrometry as a tool is described, its limitations explained and its application to biomarker discovery in coronary artery disease is considered. In particular an application of mass spectrometry for the discovery of lipid biomarkers that may indicate plaque morphology that could lead to myocardial infarction is elucidated

NaNog: A pluripotency homeobox (master) molecule.

One of the most intriguing aspects of cell biology is the state of pluripotency, where the cell is capable of self-renewal for as many times as deemed necessary , then at a specified time can differentiate into any type of cell. This fundamental process is required during organogenesis in foetal life and importantly during tissue repair in health and disease. Pluripotency is very tightly regulated, as any dysregulation can result in congenital defects, inability to repair damage, or cancer. Fuelled by the relatively recent interest in stem cell biology and tissue regeneration, the molecules implicated in regulating pluripotency have been the subject of extensive research. One of the important molecules involved in pluripotency, is NaNog, the subject of this article

Tissue plasminogen activator-based clot busting: Controlled delivery approaches.

Cardiovascular diseases are the leading cause of death worldwide. Thrombosis, the formation of blood clot (thrombus) in the circulatory system obstructing the blood flow, is one of the main causes behind various ischemic arterial syndromes such as ischemic stroke and myocardial infarction, as well as vein syndromes such as deep vein thrombosis, and consequently, pulmonary emboli. Several thrombolytic agents have been developed for treating thrombosis, the most common being tissue plasminogen activator (tPA), administrated systemically or locally via IV infusion directly proximal to the thrombus, with the aim of restoring and improving the blood flow. TPA triggers the dissolution of thrombi by inducing the conversion of plasminogen to protease plasmin followed by fibrin digestion that eventually leads to clot lysis. Although tPA provides powerful thrombolytic activity, it has many shortcomings, including poor pharmacokinetic profiles, impairment of the reestablishment of normal coronary flow, and impairment of hemostasis, leading to life-threatening bleeding consequences. The bleeding consequence is ascribed to the ability of tPA to circulate throughout the body and therefore can lysis all blood clots in the circulation system, even the good ones that prevent the bleeding and promote injury repair. This review provides an overview of the different delivery approaches for tPA including: liposomes, ultrasound-triggered thrombolysis, anti-fibrin antibody-targeted tPA, camouflaged-tPA, tpA-loaded microcarriers, and nano-modulated delivery approaches

A global perspective of arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited heart disease characterized by ventricular arrhythmias and sudden cardiac death especially in the young. ARVC has been traditionally associated with the Mediterranean basin, as many seminal studies on the disease have originated from research groups of this region. Today, however, numerous ARVC registries from all over the world emphasize that the disease does not have a specific racial or geographical predilection. This work provides a review on the global perspective of ARVC