Current Cardiology Reviews - Volume 3, Issue 1, 2007

Heart failure carries significant morbidity and mortality burden, with median survival from onset of symptoms been reported as low as 1.7 years among men and 3.2 years among women. It is the only major cardiovascular disease which is increasing in incidence and prevalence. There are several reasons for this including general aging of the population, improved outcomes from acute cardiovascular disease, and worsening risk factor profile in United States including increasing obesity and diabetes trends. Heart failure is also widely prevalent, with a reported prevalence of about 5 million people in the United States. A wide variety of demographic characteristics, life style factors, comorbidites, pharmacologic exposures, biochemical markers, echocardiographic parameters, and genetic markers have been linked to heart failure risk. Several risk factors such as increasing age, male gender, and prior MI are well established with respect to new onset heart failure chances whereas others risk factors such as many of the genetic markers are more recently discovered and need to undergo further evaluation to assess their association. This review article outlines the current state of the literature on risk factors for developing heart failure.

Emerging evidence suggests that cardiac adiposity may play an important role in the development of an unfavorable cardiovascular risk profile. The concept of adiposity of the heart, as new cardiovascular risk factor and marker, is rapidly emerging. Recent papers suggest that epicardial fat, an index of cardiac visceral adiposity could locally modulate the morphology and function of the heart. The close anatomical relationship between epicardial adipose tissue and the adjacent myocardium should readily allow local paracrine interactions between these tissues. Epicardial fat may play a functional and mechanical role in left ventricular hypertrophy, atrial dilatation or diastolic dysfunction. Echocardiography has been recently proposed for the direct assessment of epicardial adipose tissue. Echocardiographic assessment of epicardial fat may be a helpful tool not only for diagnostic purposes, as marker of visceral adiposity and inflammation, but also for therapeutic interventions with weight reduction drugs or pharmaceuticals targeted to adipose tissue. Nevertheless the subject is in its infancy and further studies are needed. In fact it is difficult to determine whether epicardial fat has a direct pathogenic role in the development of cardiac changes. It also remains to be determined whether this location of fat is physiologically or pathologically important and whether it can be used to replace abdominal obesity, or its surrogate marker, waist circumference, as a cardiovascular risk factor. In this article, epicardial adipose tissue's structure, function, method of assessment and reliability as a marker of visceral and cardiac adiposity is briefly reviewed.

Immunoglobulin therapy has been used for the treatment of primary and secondary antibody deficiency for more than 25 years. It is a safe preparation with no long-term side effect. Although the mode of action remains unknown, the drug is thought to have potent immunomodulating and anti-inflammatory actions. Recently we have found that immunoglobulin treatment is beneficial upon myocardial diseases and atherosclerosis. In basic aspects, immunoglobulin therapy for experimental myocarditis has been found to be effective not only by the Fab portion for anti-pathogen effects but by the Fc portion for antiinflammatory effects. Also, the drug was useful for the treatment of experimental atherosclerosis in apolipoprotein E-deficient mice. In clinical aspects, the effect of immunoglobulin administration for fulminant myocarditis and acute dilated cardiomyopathy was investigated. Immunoglobulin administration was very useful for the treatment of such patients. That is, although the study population was small, the drug showed the potential beneficial effects against active myocardial damage with myocardial dysfunction, and the left ventricular ejection fraction of the patients was recovered by the treatment. Accordingly, immunoglobulin treatment for patients with heart failure and atherosclerosis appears to be novel and effective treatment strategies.

Ventricular arrhythmias are common in the setting of acute myocardial infarction (AMI). In today's era of reperfusion therapy, anti-arrhythmic medications, and Implantable Cardioverter Defibrillators (ICDs), an understanding of these arrhythmias and the prognosis of patients with these arrhythmias is essential in determining the proper treatment strategy. In general, ventricular arrhythmias occurring in the first 48 hours (early) following admission for AMI do not predict an increased risk of arrhythmias in follow-up. While early sustained ventricular tachycardia and ventricular fibrillation predict increased in-hospital mortality, the medium and long-term mortality is comparable to control populations in most studies. In contrast, ventricular arrhythmias occurring after 48 hours (late) generally predict an increased risk of arrhythmias and sudden cardiac death. This review focuses on the different ventricular arrhythmias which occur in both the early and late stages following myocardial infarction. Special attention is made to the incidence and prognosis of these arrhythmias, and how this relates to current treatment recommendations.

Activation of afferent cutaneous or mixed nerves, such as the sural or the sciatic, results in changes in sympathetic activity and arterial blood pressure by excitatory somatosympathetic reflexes (SSR). The underlying causes and modulation of SSR functions in the dorsal medulla are poorly understood. This review focuses our recent findings incorporated with the publications from other investigators implicating that: 1) The gracile nucleus is an integration center for somatic and visceral information flowing into the thalamus, and sensory stimulation of the hindlimb somatic afferent modifies neuronal activities in the nucleus tractus solitarius (NTS); 2) nitric oxide (NO) in the NTS produces decreases in arterial blood pressure and heart rate, but the effects are independent to baroreflexes; 3) L-arginine-derived NO synthesis in the gracile nucleus inhibits the excitatory cardiovascular responses to stimulus-evoked SSR; and 4) Neuronal NO synthase (nNOS) expression is increased in the dorsal medulla, the gracile nucleus and the NTS by electrical stimulation of the sural nerve. These results suggest that stimulation of somato-sensory afferents induces nNOS expression in the dorsal medulla, and L-arginine-derived NO synthesis in the nuclei produces an inhibitory regulation of excitatory SSR, which plays a role in the feedback autonomic control of the circulation.

Vasa vasorum are microscopic vessels that perfuse the walls of macroscopic arteries and veins. Numerous observations over the years underpin the speculation that vasa vasorum play a significant role in arterial disease. For instance, atheromatous plaques tend to form in arteries that normally have vasa vasorum, when there is damage to the outer adventitia or when vasa vasorum are ligated. Although, atheromatous plaques do form in small arteries that do not initially have vasa vasorum - they do so only when the plasma concentrations of lipids are exceptionally high, such as occurs in LDL-/- apoE-/- double knockout mice. Recent developments in micro-CT imaging provide 3D images of intact segments of arteries and therefore can now provide heretofore inaccessible information. Examples are the perfusion territory size and location of individual vasa vasorum “trees” as well as an index of the spatial distribution of solute diffusion into, and washout from, the arterial wall. In addition, several types of genetically modified “knockout” mice that have recently been developed have a propensity for developing atheromatous plaques and vasa vasorum and thereby serve as powerful tools to further examine the biomolecular and genetic aspects of atheroma development and the response to interventions.

It is well known that the renin-angiotensin system (RAS) is a crucial regulator of the cardiovascular system playing an important role in the control of blood pressure and cardiac function. The relevance of the RAS in cardiovascular diseases is illustrated by the efficiency of RAS blockade to improve survival and cardiac function in patients with heart failure. Emerging evidence suggest that, at least, part of the benefits observed with the use of angiotensin-converting enzyme inhibitors (ACEi) and AT1 receptor blockers (ARBs) could be attributed to the increased Ang-(1-7) levels observed during administration of these agents. Moreover, several experimental studies in animal models of cardiomyopathies have demonstrated that Ang-(1-7) can exert its effects through direct effects produced by ligation to its recent identified Gprotein coupled receptor Mas or indirectly through ACE or AT1 receptors-related mechanisms. The identification of the novels components of the RAS, ACE2 and Ang-(1-7) receptor Mas, provided essential elements for considering the existence of a vasodilator arm of the RAS, represented by the ACE2-Ang-(1-7)-Mas axis. This review briefly highlights the Ang-(1-7) effects in the heart, paying special attention to emerging data suggesting its cardioprotective actions in several cardiomyopathies with focus on the possible role of the ACE2-Ang-(1-7)-Mas axis. In addition, we will discuss the relationship between Ang-(1-7), SRA blockers, and the kallikrein-kinin system.

Aging is one of the important risk factors for cardiovascular disease. Cardiovascular structure and function are continually under the remodeling process as we age. Two forms of vascular remodeling are associated with physiological and pathological processes: (1) angiogenesis, a process of developing new capillaries from pre-existing capillaries, and (2) arteriogenesis, a process of forming functional collateral conduit arteries from the existing small arteries or arterioles in the matured individual. Current research suggests that aging may attenuate the both angiogenesis and arteriogenesis by producing less angiogenic stimulating cytokines, or by increasing expression of anti-angiogenic factors. Yet, aged individuals remain responsive to physical (e.g. exercise training) and/or biochemical stimuli (e.g. exogenous angiogenic growth factors) to improve the angiogenic and arteriogenic capacity. At present our knowledge of the biological mechanisms of aging and angiogenesis/arteriogenesis interactions is limited. NO-donors, single (FGF-2, VEGF, PDGFs) or combined angiogenic growth factors (VEGF, Ang-1) demonstrated efficacy in promoting collateral function in the ischemic tissues of aged animals. Future studies should aim at the basis of aging-impaired angiogenic capacity at molecular level, and search for more effective strategies for therapeutic angiogenesis to treat ischemic cardiovascular diseases.

Pulmonary artery banding is a suitable approach for complex heart defects suitable to later bi-ventricular repair, functionally uni-ventricular hearts, and left ventricular retraining. Despite the existence of a very large spectrum of congenital heart defects and clinical situations with potential indication for pulmonary artery banding, the availability of only the conventional surgical technique is still limiting the application of this approach. A solution to the clinical need for an adjustable pulmonary artery banding has been found with a telemetrically controlled adjustable pulmonary artery banding, FloWatch® (EndoArt, Lausanne, Switzerland). This new implantable, wireless, bat-tery free, device (FloWatch®), demonstrated the feasibility of repeated progressive occlusions and re-openings of the de-vice at the wanted percentage of occlusion through a remote control, with long-term experimental evaluation in animals, followed by successful introduction in clinical practice in different institutions. The availability of a reliable adjustable pulmonary artery banding, avoiding any re-operation and the need for pulmonary artery reconstruction at the moment of de-banding, has substantially modified the clinical management of infants with congenital heart defects with increased pulmonary artery blood flow and pressures. New therapeutic strategies can now be considered to expand the applicability of this device.

Once regarded as “noise”, the Doppler shift recorded from moving myocardium provides a great deal of information about cardiac function and forms the basis of tissue Doppler imaging (TDI). TDI is rapidly becoming a routine part of echocardiographic evaluation of the heart. Given the large amplitude signal obtained with TDI, recordings of myocardial velocities are technically easy to acquire and they provide reproducible, quantitative measurements even when 2- dimensional images are suboptimal. Although TDI has broad potential utility in cardiac functional assessment, its most rigorously validated applications include: 1) estimation of left ventricular filling pressures; 2) assessment of systolic and diastolic function; 3) quantification of ventricular dyssynchrony and evaluation for cardiac resynchronization therapy; and 4) detection of myocardial ischemia or segmental contractile dysfunction. Here we highlight some of the fascinating discoveries that led to the development of TDI and discuss its clinical application in each of these areas. Because TDI is such a powerful means of noninvasively assessing cardiac physiology and pathophysiology, its application in clinical practice will undoubtedly continue to increase as it is becomes more widely understood.

Despite advances in the techniques of ‘off-pump’ Cardiac surgery, the vast majority of cardiac operations still involve using cardiopulmonary bypass (CPB) along with some form of myocardial protection. The extracorporeal circuits used in the modern bypass-machine have developed considerably in the last few decades. However contact activation of blood leading to a systemic inflammatory response is to some degree inevitable. Although often remaining sub-clinical and resolving promptly at the end of CPB, in its most extreme form this inflammatory response may be associated with the development of the systemic inflammatory response syndrome (SIRS) that can often lead to major organ dysfunction syndrome (MODs) and death. Here we review the pathophysiology behind the development of this “whole body” inflammatory response and consider the mechanical and pharmacological methods that are currently used to minimise it.