Current Cardiology Reviews - Volume 4, Issue 2, 2008

Despite of vast improvements in treatment, myocardial infarction often leads to heart failure (HF) which remains the leading cause of death in developed countries. Other than heart transplantation, therapeutic options have a limited role in improving out comes in patients with severe HF. It is therefore no surprise that cardiac cell therapy has raised many hopes as a novel therapeutic approach aimed at cardiac myocyte replacement/regeneration termed “cellular cardiomyoplasty”. However, the ideal source, cell type, critical cell number, and mode of application for optimal therapeutic effect have not been defined thus far. Recent observations of the beneficial effect of cell transplantation in animal experiments have generated tremendous excitement and stimulated clinical studies suggesting that this approach is feasible, safe, and potentially effective in humans. Cell-based myocardial regeneration is currently being explored for a wide range of cardiac disease states, including acute and chronic ischemic myocardial damage, cardiomyopathy and as biological heart pacemakers. The main purpose of this article is to review recent literature on the use of various cells for the examination of their in vitro cardiogenic potential and their in vivo capacity to engraft and improve the functional properties of the infarcted heart.

We herein reported 2 successful neonates with Ebstein's anomaly and small pulmonary arteries undergoing Starnes operation preserving the patent ductus arteriosus. Subsequent Blalock-Taussig shunt was carried out 1 or 2 months after the first surgery. One case had already undergone a successful Fontan operation, and the other had a successful bidirectional Glenn shunt so far. This staged Starnes strategy might be a safe and simple choice for neonates with Ebstein's anomaly and small pulmonary arteries.

For over one decade Glycoproteins IIb/IIIa inhibitors (GPI) have been administered to prevent coronary artery thrombosis. Initially these agents were used for acute coronary syndromes and subsequently as adjunctive pharmacotherapy for percutaneous coronary interventions (PCIs). Most benefit of GPI emerged from reduction of ischemic events: mostly non-q-wave myocardial infarctions (NQWMIs) during PCI. However, individual randomized clinical trials could not demonstrate that any of these agents could significantly reduce mortality in any clinical subset of patients. Studies of employing prolonged oral GPI administration resulted in excessive death. The non-homogenous statistically-significant reduction of ischemic endpoints was accompanied by an excess of bleeding, vascular complications, and thrombocytopenia. The clinical and ecomomic burden of major bleeding and thrombocytopenia is substantial. The ACUITY trial has initiate a new debate regarding the efficacy and safety of GPI. Selective “patient-tailored” use of GPI limited to moderate-high risk PCI patients with low bleeding propensity is suggested. Research of new algorithms emphasizing abbreviated GPI administration, careful access site and bleeding surveillance, in conjunction with lower doses of unfractionated heparin or new and safer anti-thrombins may further enhance patient safety.

Heart failure represents a major source of morbidity and mortality in industrialized nations. As the leading hospital discharge diagnosis in the United States in patients over the age of 65, it is also associated with substantial economic costs. While the acute symptoms of volume overload frequently precipitate inpatient admission, it is the symptoms of chronic heart failure, including fatigue, exercise intolerance and exertional dyspnea, that impact quality of life. Over the last two decades, research into the enzymatic, histologic and neurohumoral alterations seen with heart failure have revealed that hemodynamic derangements do not necessarily correlate with symptoms. This “hemodynamic paradox” is explained by alterations in the skeletal musculature that occur in response to hemodynamic derangements. Importantly, gender specific effects appear to modify both disease pathophysiology and response to therapy. The following review will discuss our current understanding of the systemic effects of heart failure before examining how exercise training and cardiac resynchronization therapy may impact disease course.

Ankle brachial index (ABI) has been utilized in the management of peripheral arterial disease (PAD).ABI is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. Even so, this critical test is underutilized. The purpose of this review is to summarize available evidence associated with ABI methodology variances, ABI usage in the treatment of PAD, and ABI efficacy in predicting cardiovascular disease. This review further evaluates how ABI is used in the prognosis and follow-up of lower extremity arterial disease.We reviewed the most current American College of Cardiology guidelines for the management of PAD, the Trans Atlantic Intersociety Consensus (TASC) working group recommendations, and searched the Medline for the following words: ankle brachial index, ABI sensitivity and specificity, and peripheral arterial disease. The ABI is a simple, noninvasive clinical test that should not only be applied to diagnose PAD, but also to provide important prognostic information about future cardiovascular events. Although the ABI has been employed in clinical practice for some time, our review of various studies reveals a lack of standardization regarding both the method of measuring ABI and the cutoff point for abnormal ABI. It is extremely important that we understand all aspects of this crucial test, as it is now being recommended as part of a patient's routine health risk assessment.

The myocardium is mainly composed of long-lived postmitotic cells with, if there is any at all, a very low rate of replacement through the division and differentiation of stem cells. As a consequence, cardiac myocytes gradually undergo pronounced age-related alterations which, furthermore, occur at a rate that inversely correlates with the longevity of species. Basically, these alterations represent the accumulation of structures that have been damaged by oxidation and that are useless and often harmful. These structures (so-called ‘waste’ materials), include defective mitochondria, aberrant cytosolic proteins, often in aggregated form, and lipofuscin, which is an intralysosomal undegradable polymeric substance. The accumulation of ‘waste’ reflects the insufficient capacity for autophagy of the lysosomal compartment, as well as the less than perfect functioning of proteasomes, calpains and other cellular digestive systems. Senescent mitochondria are usually enlarged, show reduced potential over their inner membrane, are deficient in ATP production, and often produce increased amounts of reactive oxygen species. The turnover of damaged cellular structures is hindered by an increased lipofuscin loading of the lysosomal compartment. This particularly restricts the autophagic turnover of enlarged, defective mitochondria, by diverting the flow of lysosomal hydrolases from autophagic vacuoles to lipofuscin-loaded lysosomes where the enzymes are lost, since lipofuscin is not degradable by lysosomal hydrolases. As a consequence, aged lipofuscin- rich cardiac myocytes become overloaded with damaged mitochondria, leading to increased oxidative stress, apoptotic cell death, and the gradual development of heart failure. Defective lysosomal function also underlies myocardial degeneration in various lysosomal storage diseases, while other forms of cardiomyopathies develop due to mitochondrial DNA mutations, resulting in an accumulation of abnormal mitochondria that are not properly eliminated by autophagy. The degradation of iron-saturated ferritin in lysosomes mediates myocardial injury in hemochromatosis, an acquired or hereditary disease associated with iron overload. Lysosomes then become sensitized to oxidative stress by the overload of low mass, redox-active iron that accumulates when iron-saturated ferritin is degraded following autophagy. Lysosomal destabilization is of importance in the induction and/or execution of programmed cell death (either classical apoptotic or autophagic), which is a common manifestation of myocardial aging and a variety of cardiac pathologies.

Atherosclerosis is a chronic inflammatory disorder characterized by immune cell activation, inflammation driven plaque formation and subsequent destabilization. In other disorders of an inflammatory nature, the chronic inflammatory state per se has been linked to acceleration of the atherosclerotic process which is underlined by an increased incidence of cardiovascular disease (CVD) in disorders such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and antiphopholipid (Hughes) syndrome (APS). SLE is an autoimmune disease that may affect any organ. Premature coronary heart disease has emerged as a major cause of morbidity and mortality in SLE. In addition to mortality, cardiovascular morbidity is also markedly increased in these patients, compared with the general population. The increased cardiovascular risk can be explained only partially by an increased prevalence of classical risk factors for cardiovascular disease; it also appears to be related to inflammation. Inflammation is increasingly being considered central to the pathogenesis of atherosclerosis and an important risk factor for vascular disease. Recent epidemiologic and pathogenesis studies have suggested a great deal in common between the pathogenesis of prototypic autoimmune disease such as SLE and that of atherosclerosis. We will review traditional risk factors for CVD in SLE. We will also discuss the role of inflammation in atherosclerosis, as well as possible treatment strategies in these patients.

Neurologic injury in patients with congenital heart disease remains an important source of morbidity and mortality. Advances in surgical repair and perioperative management have resulted in longer life expectancies for these patients. Current practice and research must focus on identifying treatable risk factors for neurocognitive dysfunction, advancing methods for perioperative neuromonitoring, and refining treatment and care of the congenital heart patient with potential neurologic injury. Techniques for neuromonitoring and future directions will be discussed.

Septal necrosis + peripheral left blocks. Because of an extensive septal necrosis, the manifestation of the initial ventricular activation forces decreases in the precordial leads. With left bifascicular block (LASB + LPSB), the first ventricular activation forces become more evident and the electrical signs of septal necrosis can be concealed. In the presence of a trifascicular block, manifestation of the first ventricular electromotive forces diminishes again and the electrical signs of septal necrosis become evident once more. Small Q waves are present in leads V1 to V4. Extensive anterior necrosis + peripheral blocks. This necrosis is manifested by QS complexes from V2 to V6. An associated left bifascicular block reduces the electrical manifestation of dead tissue: QS complexes persist only in V3 and V4. In turn, a coexisting trifascicular block causes the presence of QS complexes from V2 to V5. Posteroinferior necrosis + peripheral blocks. Electromotive forces of the ventricular activation shift upward, due to a posteroinferior necrosis and QS or QR complexes are recorded in leads aVF, II and III. An associated left bifascicular block displaces the main electromotive forces downward, posteriorly and to the left, due to a delay of the posteroinferior activation fronts. The ventricular complexes become positive and wider in all leads, reflecting the potential variations of the inferior portions of the left ventricle: aVF, II, III, sometimes V5 and V6. Consequently, the electrical signs of necrosis are reduced or abolished. Due to a trifascicular block, wide and slurred QS complexes are recorded in aVF, II, III and sometimes in V5 and V6.