Current Cardiology Reviews - Volume 4, Issue 3, 2008

Recent increase in human lifespan has shifted the spectrum of aging-related disorders to an unprecedented upsurge in cardiovascular diseases, especially calcific aortic valve stenosis, which has an 80% risk of progression to heart failure and death. A current therapeutic option for calcified valves is surgical replacement, which provides only temporary relief. Recent progress in cardiovascular research has suggested that arterial and valve calcification are the result of an active process of osteogenic differentiation, induced by a pro-atherogenic inflammatory response. At molecular level, the calcification process is regulated by a network of signaling pathways, including Notch, Wnt and TGFbeta/BMP pathways, which control the master regulator of osteogenesis Cbfa1/Runx2. Genetic and in vitro studies have implicated Notch signaling in the regulation of macrophage activation and cardiovascular calcification. Individuals with inactivating Notch1 mutations have a high rate of cardiovascular disorders, including valve stenosis and calcification. This article reviews recent progress in the mechanism of cardiovascular calcification and discusses potential molecular mechanisms involved, focusing on Notch receptors. We propose a calcification model where extreme increases in vascular wall cell density due to inflammation-induced cell proliferation can trigger an osteogenic differentiation program mediated by Notch receptors.

Left ventricular assist devices (LVAD) are currently used to either “bridge” patients with terminal congestive heart failure (CHF) until cardiac transplantation is possible or optionally for patients with contraindications for transplantation (“destination therapy”). Mechanical support is associated with a marked decrease of cardiac dilation and hypertrophy as well as numerous cellular and molecular changes (“reverse cardiac remodeling”), which can be accompanied by improved cardiac function (“bridge to recovery”) in a relatively small subset of patients with heart transplantation no longer necessary even after removal of the device (“weaning”). In the recent past, novel pharmacological strategies have been developed and are combined with mechanical support, which has increased the percentage of patients with improved clinical status and cardiac performance. Gene expression profiles have demonstrated that individuals who recover after LVAD show different gene expression compared to individuals who do not respond to unloading. This methodology holds promise for the future to develop read out frames to identify individuals who can recover after support. Aside from describing the morphological changes associated with “reverse cardiac remodeling”, this review will focus on signal transduction, transcriptional regulation, apoptosis, cell stress proteins, matrix remodeling, inflammatory mediators and aspects of neurohormonal activation in the failing human heart before and after ventricular unloading.

The clinical outcome of cardiovascular diseases as myocardial infarction and stroke are generally caused by rupture of an atherosclerotic plaque. However, the actual cause of a plaque to rupture is not yet established. Interestingly, pathology studies have shown an increased presence of the mast cell, an important inflammatory effector cell in allergy and host defense, in (peri)vascular tissue during plaque progression, which may point towards a causal role for mast cells. Very recent data in mouse models show that mast cells and derived mediators indeed can profoundly impact plaque progression, plaque stability and acute cardiovascular syndromes such as vascular aneurysm or myocardial infarction. In this review, we discuss recent evidence on the role of mast cells in the progression of cardiovascular disorders and give insight in the therapeutic potential of modulation of mast cell function in these processes to improve the resilience of a plaque to rupture.

Interleukin-6 (IL-6) is a well-established, independent indicator of multiple distinct types of cardiovascular disease and all-cause mortality. In this review, we present current understanding of the multiple roles that IL-6 and its signaling pathways through glycoprotein 130 (gp130) play in cardiovascular homeostasis. IL-6 is highly inducible in vascular tissues through the actions of the angiotensin II (Ang II) peptide, where it acts in a paracrine manner to signal through two distinct mechanisms, the first being a classic membrane receptor initiated pathway and the second, a trans-signaling pathway, being able to induce responses even in tissues lacking the IL-6 receptor. Recent advances and new concepts in how its intracellular signaling pathways operate via the Janus kinase (JAK)-Signal Transducer and Activator of Transcription (STAT) are described. IL-6 has diverse actions in multiple cell types of cardiovascular importance, including endothelial cells, monocytes, platelets, hepatocytes and adipocytes. We discuss central roles of IL-6 in endothelial dysfunction, cellular inflammation by affecting monocyte activation/differentiation, cellular cytoprotective functions from reactive oxygen species (ROS) stress, modulation of pro-coagulant state, myocardial growth control, and its implications in metabolic control and insulin resistance. These multiple actions indicate that IL-6 is not merely a passive biomarker, but actively modulates adaptive and pathological responses to cardiovascular stress. Summary: IL-6 is a multifunctional cytokine whose presence in the circulation is linked with diverse types of cardiovascular disease and is an independent risk factor for atherosclerosis. In this review, we examine the mechanisms by which IL-6 signals and its myriad effects in cardiovascular tissues that modulate the manifestations of vascular inflammation.

Since its original description in 1994, alcohol septal ablation (ASA) has emerged as a minimally invasive modality for treatment of hypertrophic obstructive cardiomyopathy compared to surgical myomectomy. This catheter-based intervention relies on the injection of absolute alcohol into the septal perforator to induce a controlled infarction of the hypertrophied septum and consequently abolish the dynamic outflow obstruction. This gradient reduction has been correlated with a significant clinical improvement in the patient's symptomatology and with left ventricular remodeling. The procedure has been refined throughout the years, especially with the introduction of myocardial contrast echocardiography for localization of the area at risk of infarction and the reduction in the amount of alcohol used. Major complications of ASA are uncommon in large referral centers but conduction system disturbances has been the most commonly reported complications of ASA with 10% of patients necessitating permanent pacemaker implantation for complete heart block. ASA has not been compared to the gold standard surgical myomectomy in a randomized prospective study. We review the clinical aspects of this procedure and provide some historical background.

It has been established that patients with chronic kidney disease (CKD) suffer from frequent cardiovascular events. On the other hand, recent studies suggest that renal damage tends to worsen in patients with cardiovascular diseases (CVD). Although the mechanisms for the cardiorenal association are unclear, the presence of arteriosclerotic risk factors common to both CVD and CKD is important. In arteriosclerosis, vascular derangement progresses not only in the heart but also in the kidney. In addition, heart failure, cardiac catheterization and hesitation of medical treatments due to renal dysfunction may explain the progression of renal damage. Therefore, the goal of treatments is a total control of arteriosclerotic risk factors. Medication should be selected among agents with protective effects on both heart and kidney. It is important to always consider the presence of CKD for the treatment of the cardiovascular disease and strictly control the risk factors.

Over 30 million people are currently living with human immunodeficiency virus (HIV) infection, and over 2 million new infections occur per year. HIV has been found to directly affect vascular biology resulting in an increased risk of cardiovascular disease compared to uninfected persons. Although HIV infection can now be treated effectively with combination antiretroviral medications, significant toxicities such as hyperlipidemia, diabetes, and excess cardiovascular co-morbidity; as well as the potential for significant drug-drug interactions between HIV and cardiovascular medications, present new challenges for the management of persons infected with HIV. We first review basic principles of HIV pathogenesis and treatment and then discuss relevant clinical management strategies that will be useful for cardiologists who might be involved in the care of HIV infected patients.

Several autoantibodies directed against cardiac cellular proteins including G-protein-linked receptors, contractile proteins and mitochondrial proteins, have been identified in patients with dilated cardiomyopathy (DCM). Among these autoantibodies, anti-β1-adrenoreceptor (AR) antibodies have long been discussed in terms of their pathogenetic role in DCM. Anti-β1-AR antibody-positive patients with DCM showed significant deterioration of NYHA functional class as well as reduced cardiac function compared to those in autoantibody-negative patients. Various studies with a limited number of patients indicate that the use of immunoadsorption to eliminate immunoglobulin G (IgG) significantly improves cardiac performance and clinical status in heart failure patients. Since removal of autoantibodies of the IgG3 subclass induces hemodynamic improvement and an increase in the left ventricular ejection fraction, antibodies belonging to IgG3 such as anti-β1-AR antibodies might play an important role in reducing cardiac function in patients with DCM. According to a recent report, however, the effect of hemodynamic improvement by immunoadsorption threapy was similar among patients who were positive and negative for anti-β1-AR antibodies, indicating that the beneficial effects of immunoadsorption might be not directly associated with the selective elimination of the β1-AR autoantibodies. Immunoadsorption therapy is a new therapeutic option for patients with DCM and heart failure, but further investigations are required to elucidate the specific antigens of cardiac autoantibodies responsible for the hemodynamic effects.

In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.

Cardiac MDCT is here to stay. And, it is more than just imaging coronary arteries. Understanding the differences in and the benefits of one CT scanner from another will help you to optimize the capabilities of the scanner, but requires a basic understanding of the MDCT imaging physics. This review provides key information needed to understand the differences in the types of MDCT scanners, from 64 - 320 detectors, flat panels, single and dual source configurations, step and shoot prospective and retrospective gating, and how each factor influences radiation dose, spatial and temporal resolution, and image noise.