Metabolic support for the heart: complementary therapy for heart failure?

The failing heart has an increased metabolic demand and at the same time suffers from impaired energy efficiency, which is a detrimental combination. Therefore, therapies targeting the energy‐deprived failing heart and rewiring cardiac metabolism are of great potential, but are lacking in daily clinical practice. Metabolic impairment in heart failure patients has been well characterized for patients with reduced ejection fraction, and is coming of age in patients with ‘preserved’ ejection fraction. Targeting cardiomyocyte metabolism in heart failure could complement current heart failure treatments that do improve cardiovascular haemodynamics, but not the energetic status of the heart. In this review, we discuss the hallmarks of normal cardiac metabolism, typical metabolic disturbances in heart failure, and past and present therapeutic targets that impact on cardiac metabolism.     

Stem cells for the heart

See related article,pages 101-107.Cardiovascular disease is one of the major health con-cerns of modern societies.In the United States in the year2001 alone,an estimated 64 million people had had one ormore forms of cardiovascular disease,claiming almost onemillion lives,38.5 percent of all deaths(American HeartAssociation).     

A reliable recipe for heart cells?

Deepak Srivastava’s group at the Gladstone Institute of Cardiovascular Disease, University of California San Francisco, reported in the August 6 issue of the journal Cell that to make heart muscle cells, all you need are three factors and some fibroblasts. But is it really that easy?     

Adult zebrafish heart as a model for human heart? An electrophysiological study

The zebrafish has recently emerged as an excellent model for studies of heart development and regeneration. The physiology of the zebrafish heart has been suggested to resemble that of the human heart in many aspects, whereas, in contrast to mammals, the zebrafish has a remarkable ability to regenerate after heart injury. Thus, zebrafish have been proposed as a cost-effective model for genetic and pharmacological screens of factors affecting heart function and repair. However, realizing the full potential of the zebrafish heart as a model will require a better understanding of the electrophysiology of the adult zebrafish myocardium. Here, we characterize action potentials (APs) from intact adult atria and ventricles and find that the overall shape of zebrafish APs is similar to that of humans. We show that zebrafish, like most mammals, display functional acetylcholine-activated K⁺ channels in the atrium, but not in the ventricle. Furthermore, the zebrafish AP upstroke is dominated by Na⁺ channels, L-type Ca²⁺ channels contribute to the plateau phase and I_Kr channels are involved in repolarization. However, despite these similarities between zebrafish and mammalian electrophysiology, we also identified important differences. In particular, zebrafish display a robust T-type Ca²⁺ current in both atrial and ventricular cardiomyocytes. Interestingly, in most mammals T-type Ca²⁺ channels are only expressed in the developing heart or under pathophysiological conditions, indicating that adult zebrafish cardiomyocytes display a more immature phenotype.     

A heart failure specialist’s perspective on cardiac surgery for heart failure

Aside from cardiac transplantation, ventricular assist devices, and the total artificial heart, cardiac surgery now also plays a major role in the overall management of the heart failure patient. For patients with heart failure, cardiac surgery has steadily moved from being a predominant rescue procedure (eg, aneursymectomy, rupture repair, transplantation) to surgical interventions that can prevent or delay the progression of cardiac dysfunction and failure; these operations now include coronary artery bypass surgery, ventricular restoration, and valvular repair/replacement. This article discusses the role and impact of these specific surgical interventions in the setting of ventricular dysfunction and heart failure.     

BNP or echocardiography for monitoring heart failure?

This editorial refers to "Comparison of echocardiography andplasma B-type natriuretic peptide for monitoring the responseto treatment in acute heart failure" by A. Gackowski et al.on page 1788 No-one would question the value of echocardiography for theinitial assessment of patients with heart failure and it isnow a mandatory investigation. Not only can the cause be frequentlycorrectly identified, but important prognostic information canalso be gleaned. In particular, the restrictive filling patternseen with the Doppler mitral inflow velocities is recognizedto be associated with a poor prognosis, especially if it doesnot normalize with initial treatment.¹ The restrictive fillingpattern is also associated with higher atrial natriuretic peptide(ANP) and brain natriuretic peptide levels (BNP) and both peptidescorrelate inversely     

Levosimendan: a new era for inodilator therapy for heart failure?

Levosimendan is a new inotropic and vasodilator agent. The inotropic effect is mediated by calcium concentration-dependent conformational changes in troponin C during systole leading to sensitization of the contractile apparatus to calcium ions. The vasodilator effect is mediated by opening potassium channels on vascular smooth muscle. It has a complex pharmacokinetic profile, with a long-acting metabolite that has hemodynamic effects persisting for approximately 1 week. Although it is absorbed orally, it has been developed only for intravenous use thus far. The hemodynamic effects are not reduced and may be enhanced in the presence of beta-blockers, possibly an important attribute when dealing with exacerbation of heart failure caused by or in the presence of beta-blockers. More patients with heart failure have participated in randomized controlled trials of levosimendan than of any other intravenous inotropic agent. Experience with its use after cardiac surgery is limited. Preliminary observations suggest that hemodynamic changes are associated with symptomatic benefit and a reduction in morbidity and mortality in patients with severe heart failure caused by left ventricular systolic dysfunction, compared with placebo in one study and dobutamine in another. Levosimendan may be the first inotropic agent that it is both safe and effective in altering clinical outcomes relevant for patients. Part of this benefit may be achieved because levosimendan allows other inotropic agents that may have adverse effects on patient outcome to be avoided. Further research is required to confirm whether levosimendan reduces mortality and morbidity compared with a placebo and when administered repetitively. If it does, it may become routine therapy for the treatment of severe heart failure.     

Socks for the dilated heart. Does passive cardiomyoplasty have a role in long-term care for heart failure patients?

Dynamic cardiomyoplasty has been performed in over 1000 patients worldwide but due to limited success the procedure was never been adopted as an alternative approach for the surgical therapy of heart failure. However, observations in these patients showed that the nonstimulated or fibrotic transformed latissimus dorsi by itself led to an improvement of heart failure symptoms. These findings stimulated animal experiments with so-called passive cardiomyoplasty devices. In several animal models, the progression of heart failure could be stopped, and even reversed remodeling could be demonstrated. Several different devices have been developed and tested in animal models. The Acorn CorCap has already passed a successful clinical feasibility study. However, the final evaluation of two multicenter trials has to be awaited to assess the future role of this device in the treatment of heart failure.