Cardiomyocyte transplantation into the failing heart-new therapeutic approach for heart failure?

Heart failure, frequently the consequence of irreversible myocardial damage with subsequent formation of akinetic scar tissue, is a highly prevalent disease, and in its advanced stages associated with high mortality. The transplantation of exogenous cells with the inherent ability to contract has been put forward as one potential treatment strategy to increase contractility and cardiac performance. Besides skeletal myoblasts or stem cells from various sources, immature cardiomyocytes, such as fetal or neonatal cardiomyocytes, have been transplanted into normal, cryoinjured, infarcted myocardium, as well as into models of global heart failure. Survival of transplanted immature cardiomyocytes has been demonstrated up to 6–7 months, accompanied by vascularization of the grafted tissue. Transplants developed sarcomeric structures and other morphological features of differentiation. The principal possibility of cell-to-cell coupling between graft and host cells was demonstrated after cardiomyocyte transplantation into normal hearts and in some studies in damaged myocardium. But most long-term follow-up investigations in models of myocardial infarction reported that optimal integration of the engrafted cells appeared to be hindered by scar tissue, separating the transplant from the host. Nonetheless, in several studies, improved parameters of cardiac performance were demonstrated ex-vivo and in vivo. Potential mechanisms might involve beneficial effects on the remodeling process. In this review, we critically evaluate the potential value of cardiomyocyte transplantation as a new approach in the treatment of the syndrome of heart failure.     

Statins for heart failure: at the crossroads between cholesterol reduction and pleiotropism?

Statins are being hailed as the new aspirin--but are they beneficial for patients with heart failure?     

What is the optimal medical management of ischemic heart failure?

Ischemic heart disease is an important and common contributor to the development of heart failure. Theoretically, all patients with heart failure may benefit from treatment designed to retard progressive ventricular dysfunction and arrhythmias. Patients with ischemic heart disease may also theoretically benefit from the relief of ischemia, the prevention of coronary occlusion, and revascularization. However, there is little evidence to show that the presence or absence of coronary disease modifies the benefits of effective treatments such as angiotensin-converting enzyme inhibitors and beta-blockers. Moreover, there is no evidence that treatment directed specifically at myocardial ischemia or coronary disease alters outcome in patients with heart failure. Treatments aimed at relieving painless myocardial ischemia have not been shown to alter prognosis. Lipid-lowering therapy is theoretically attractive for patients with heart failure and coronary disease; however, theoretical concerns also exist about the safety of such agents, and patients with heart failure have been excluded from large outcome studies very effectively. Some agents, such as aspirin, designed to reduce the risk of coronary occlusion seem ineffective or harmful in patients with heart failure, although warfarin may be safe and possibly effective. There is no evidence yet that revascularization improves prognosis in patients with heart failure, even in patients who are shown to have extensive myocardial hibernation. On current evidence, revascularization should be reserved for the relief of angina. Large-scale, randomized controlled trials are currently underway that are investigating the role of specific treatments targeted at coronary syndromes. The Carvedilol Hibernation Reversible Ischemia Trial: Marker of Success study is investigating the effects of carvedilol in a large cohort of patients with and without hibernating myocardium. The Warfarin and Antiplatelet Therapy in Chronic Heart Failure study is comparing the efficacy of aspirin, clopidogrel, and warfarin. The Heart Revascularization Trial-United Kingdom study is assessing the effect of revascularization on mortality in patients with heart failure and myocardial hibernation. Smaller scale studies are assessing the safety and efficacy of statin therapy in patients with heart failure. Only once the outcomes to these and other planned trials are known can the medical community know how best to treat their patients.     

What is the role of beta-adrenergic signaling in heart failure?

This review addresses open questions about the role of beta-adrenergic receptors in cardiac function and failure. Cardiomyocytes express all three beta-adrenergic receptor subtypes-beta1, beta2, and, at least in some species, beta3. The beta1 subtype is the most prominent one and is mainly responsible for positive chronotropic and inotropic effects of catecholamines. The beta2 subtype also increases cardiac function, but its ability to activate nonclassical signaling pathways suggests a function distinct from the beta1 subtype. In heart failure, the sympathetic system is activated, cardiac beta-receptor number and function are decreased, and downstream mechanisms are altered. However, in spite of a wealth of data, we still do not know whether and to what extent these alterations are adaptive/protective or detrimental, or both. Clinically, beta-adrenergic antagonists represent the most important advance in heart failure therapy, but it is still debated whether they act by blocking or by resensitizing the beta-adrenergic receptor system. Newer experimental therapeutic strategies aim at the receptor desensitization machinery and at downstream signaling steps.     

Xanthine oxidase inhibition for chronic heart failure: is allopurinol the next therapeutic advance in heart failure?

A substantial body of evidence has accumulated to suggest a role for the xanthine oxidase metabolic pathway in the pathophysiology of chronic heart failure and other cardiovascular diseases.     

Exploring the relationship between β-adrenergic receptor kinase-1 and physical symptoms in heart failure

Background

The relationship between physical heart failure (HF) symptoms and pathophysiological mechanisms is unclear.