Parminder S Chaggar

Neuroendocrine Effects on the Heart and Targets for Therapeutic Manipulation in Heart Failure

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.

Review article: Thiazolidinediones and heart failure

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.

Effect of antipsychotic medications on glucose and lipid levels

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 antipsychotics originate from retrospective studies. However, prospective randomized‐controlled data are emerging, and the latest evidence is described here.

The efficacy and tolerability of ezetimibe in cardiac transplant recipients taking cyclosporin.

Background. Despite statin treatment, hyperlipidemia remains problematic after cardiac transplantation and is associated with the development of cardiac allograft vasculopathy. The cholesterol absorption inhibitor ezetimibe may offer a viable option for add on therapy; however, questions have been raised regarding the safety of this during concomitant cyclosporin treatment. Methods. This is the first placebo controlled, randomized double blinded trial assessing the efficacy and tolerability of ezetimibe in cardiac transplant recipients receiving cyclosporin. Sixty-eight cardiac transplant patients were randomized to receive ezetimibe (10 mg) or matching placebo for 6 months in addition to usual treatments. Fasting blood tests were performed at regular time intervals during the study. Results. Fifty-nine patients completed the study. At 6 months, ezetimibe had reduced total cholesterol by 18% (5.4±1.1 to 4.4±0.7 mmol/L, P<0.001), low-density lipoprotein cholesterol by 26% (3.0±1.0 to 2.1±0.7 mmol/L, P<0.001), and triglycerides by 13.5% (2.3±1.3 to 1.8±0.9 mmol/L, P=0.02). Tolerability was excellent with no patients experiencing predefined safety endpoints. An equal number of patients withdrew consent from each arm of the study because of perceived side effects. Specific analysis confirmed ezetimibe had no significant effect on cyclosporin levels. Conclusion. 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.

Myocardial recovery with mechanical circulatory support

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.

The renin-angiotensin-aldosterone system in heart failure for the non-specialist: the past, the present and the future

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.

The transfemoral approach for cardiac resynchronization therapy

Cardiac resynchronization (CRT) is a well-established treatment for heart failure and standard superior implantation has a high success rate with acceptable risk profile. When the superior approach is not feasible, surgical epicardial leads are considered. We present a case of transfemoral CRT as a viable alternative to surgical systems and discuss implant factors including lead choice and deep vein thrombosis.

Prolonged asystole in a patient with an isolated left ventricular assist device

Left ventricular assist devices (LVADs) are well established in the management of end-stage heart failure as either destination therapy, a bridge prior to cardiac transplantation or during myocardial recovery. Despite LVADs requiring adequate left ventricular preload to effectively augment systemic circulation, there have been rare cases of patients with LVADs surviving sustained, normally fatal arrhythmias, such as ventricular fibrillation and asystole. Whilst current reports describe an LVAD patient surviving 15 days with such an arrhythmia, we describe the case of a patient with an LVAD surviving 104 days of asystole via a Fontan mechanism of circulation, which we believe is the longest known survival of a sustained fatal arrhythmia. This case highlights the physiology of circulations supported by LVADs and the unique challenges that may arise in managing ambulant LVAD patients, such as predicting prognosis. Given the increasing use of LVADs to treat end-stage heart failure, these issues are likely to become more frequently encountered in the future.

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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.

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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.