No abstract

Heart failure is one of the major public health challenges facing the Western world. Its prevalence is increasing as the population ages and modern techniques are implemented to manage cardiac disease. In response, there has been a sustained effort to develop novel strategies to address the high levels of associated morbidity and mortality. Indeed, agents that target the renin-angiotensin-aldosterone system (RAAS) have transformed the way in which we manage heart failure. Despite this, mortality in heart failure is poorer than in many malignancies and a large burden of morbidity and recurrent hospitalisation remains. Here, we review the role of RAAS modulation within the field of systolic heart failure. In particular, we provide practical guidance on using current RAAS blockade agents and focus on the recent emergence of new agents that promise additional substantial benefit to those living with left ventricular systolic dysfunction.

Severe mental illnesses, such as schizophrenia and bipolar affective disorder, are associated with excess cardiovascular morbidity and mortality. Cardiovascular risk in psychiatric disorders is partly related to antipsychotic therapy, especially second-generation or atypical antipsychotics. Some antipsychotic medications are associated with proatherogenic conditions including insulin resistance and dyslipidemia. In particular, olanzapine and clozapine have been consistently demonstrated to promote insulin resistance and dyslipidemia. Ziprasidone and amisulpiride may be associated with more favorable metabolic effects. Many of the published data relating to metabolic effects of anti-psychotics originate from retrospective studies. However, prospective randomized-controlled data are emerging, and the latest evidence is described here.

DM is an independent risk factor for the development of HF and its presence confers an adverse prognosis for those already diagnosed with HF.TZDs are potent insulin-sensitisers associated with a number of beneficial cardiovascular effects. However,TZDs increase renal sodium and water reabsorption, leading to fluid retention and overt signs of HF in patients with diabetes. Rosiglitazone has also been associated with an increased risk of myocardial infarction and cardiovascular mortality. However, pioglitazone may have macrovascular benefits. The majority of data on the cardiovascular safety of TZDs are based on non-cardovascular outcome trials and meta-analyses. Concerns regarding the risk of HF and cardiovascular safety of TZDs have led to restrictions on their use in patients with HF. This review addresses the latest evidence for HF with each of the TZD drugs currently available and reflects on the current guidelines regarding their prescription in at-risk patients.

Chronic heart failure (CHF) involves derangements in multiple neurohormonal axes leading to a procatabolic state and wasting syndrome associated with significant mortality. Catabolic abnormalities include excess catecholamines and glucocorticoids. Anabolic defects include deficiencies of sex steroids, insulin resistance, and growth hormone (GH) resistance. These abnormalities are also correlated with increased morbidity and mortality in CHF. Anabolic axes have been augmented in pilot studies in CHF with testosterone, GH, insulin‐like growth factor‐1, and GH secretagogues. Results have been varied although some treatments have been associated with improved surrogate endpoints. This review article explores the current understanding of metabolic derangements in CHF and highlights potential neuroendocrine treatment strategies.

We conclude that ezetimibe is both efficacious and tolerable in cardiac transplant recipients taking cyclosporin. It can be safely considered as add on therapy in patients taking statins (or as monotherapy) to further reduce low-density lipoprotein levels, which may in turn reduce the risk of cardiac allograft vasculopathy.

SUMMARYBackground: Digoxin is the oldest known treatment for heart failure (HF) and has been demonstrated to reduce admissions for worsening heart failure in a large randomized trial recruiting patients in sinus rhythm with heart failure and ejection fraction <45%. This study forms the basis for current international guidelines recommending that digoxin should be considered in patients with symptomatic HF despite optimal doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, b-blockers, and mineralocorticoid receptor antagonists in addition to device therapy, if indicated. However, digoxin predates mortality reducing HF therapies, and this article reviews the historical and recent data. Methods: Multiple PubMed searches were performed including, but not limited to, the search terms "digoxin," "heart failure," "efficacy," "treatment," "side-effects," "morbidity," "mortality," and "arrythmia." Articles were excluded if not relevant, not in English or without abstract. Reference lists of relevant articles were manually searched for further references. Due to the large number of articles retrieved, a selection was reviewed based on the authors' best judgement. Results: Three randomized controlled trials and three large contemporary observational reports of digoxin therapy in heart failure and sinus rhythm were retrieved. Other studies were noted that included patients with heart failure and atrial fibrillation, which were also reviewed. Conclusion: Definitive randomized evidence of digoxin efficacy as add-on therapy in HF is lacking because most landmark trials of modern HF disease modifying agents postdate the randomized studies of digoxin. Furthermore, questions remain regarding the optimum dose of digoxin and there are signals that digoxin may be harmful in some patients with HF. All contemporary data for digoxin in HF are derived from observational studies and the findings are conflicting. Despite two centuries of experience using cardiac glycosides to treat HF, fundamental questions regarding the efficacy and safety of digoxin in HF remain unanswered.

Mechanical circulatory support (MCS) is instituted in patients with advanced heart failure, some of who may experience sufficient recovery in cardiac function to allow withdrawal of mechanical support. The incidence of left ventricular recovery with MCS is unclear as reported series in the literature demonstrate widely divergent rates. A number of clinical parameters (including echocardiographic, haemodynamic and physiological) are used to indicate likely left ventricular recovery during pump speed reduction but no internationally agreed definition exists. Withdrawal of MCS is not without risk and so robust clinical and biochemical definitions are important to minimize patient morbidity and mortality. Here we review our current understanding of left ventricular recovery with MCS.