Current Cardiology Reviews - Volume 1, Issue 2, 2005

Two families of peroxisome proliferating-activated receptor (PPAR) ligands are utilized clinically to address abnormalities of blood-borne cardiovascular risk factors. PPAR-α ligands, the fibrates, lower plasma triglycerides and increase high-density lipoprotein (HDL)-cholesterol leading to positive outcomes in clinical trials such as the Veterans Affairs HDL Intervention Trial. PPAR-γ ligands, the recently introduced family of thiazolidinediones, act as insulin sensitizers to alleviate the hyperglycemia of insulin resistant states such as Type 2 diabetes. The primary aim of treating the cardiovascular risk factors is to reduce the burden of cardiovascular disease, mostly atherosclerotic vascular disease. Considerable evidence is emerging that PPAR ligands can exert anti-atherogenic activity. Although the agents acting on their target nuclear receptors are primarily regulators of gene transcription it may be that some actions are independent of gene transcription and represent direct inhibition of atherogenic signalling pathways in the vasculature. The direct actions including inhibition of vascular smooth muscle cell proliferation and inhibition of glycosaminoglycan elongation on proteoglycans, the latter leading to reduced low-density lipoprotein (LDL) binding, provide in vitro examples of antiatherogenic actions. PPAR ligands reduce atherosclerosis in animal models such as the ApoE-null mouse and PPAR-γ attenuate in-stent restenosis in patients with diabetes. The actions of these agents have lead to suggestions that they may be useful in vascular therapy even in the absence of the underlying risk factor abnormality. However, they may also represent tools and provide insights into areas where agents directly targeting atherosclerotic mechanisms may be developed to provide combined therapy with agents targeting traditional risk factors.

Objective - To assess the risk of atrial fibrillation (AF) recurrence requiring hospitalisation or its transition to long-lasting AF in patients with earlier or present AF from the clinical characteristics, the duration of AF-disease, and the signal-averaged P wave duration (SAPWD). Design -We studied 111 consecutive patients (40 women; median age 65 years, range 30-85 years) with earlier or present AF. The SAPWD was measured on inclusion; the follow-up median follow-up time was 184 days (range 171-437). Endpoints were hospitalisation due to recurrent AF or transition to AF lasting longer than two days. Results -During follow-up 5 patients died, 33 patients were hospitalised with AF, and 9 patients developed long-lasting AF. Multiple logistic regression analysis showed three risk factors of interest: history of hypertension, OR=3.67 (95% CI 1.61 to 8.37), duration of AF disease longer than two years, OR=3.22 (95% CI 1.31 to 7.86), and non-significantly prolonged SAPWD above 140 ms, OR=1.87 (95% CI 0.60 to 5.82). The probability of relapse in patients without risk factors was 9%, with one risk factor 16-27%, with two risk factors 37-54%, and with three risk factors 74% (p=0.0005). Conclusions -Hypertension and long history of AF disease were associated with an increased risk of AF-relapse.

Radiocontrast Nephropathy (RCN) is a well-known complication after the intravascular administration of contrast medium occurring in approximately 15% of all cases. RCN can potentially be prevented by identifying subjects with major and minor risk factors and administering preventive strategies. Pharmacologically, volume expansion with intravenous isotonic saline, N-acetylcysteine, and the use of low-osmolar contrast are the most proven prophylactic approaches. However, the weight of evidence is beginning to build for more novel protective measures, such as the use of iso-osmolar contrast, sodium bicarbonate infusion, and periprocedural hemofiltration. This comprehensive review provides the interventional community a practical treatment paradigm for patients at risk for RCN.

Anaemia occurs commonly in chronic heart failure (CHF) and is associated with a poor prognosis. Polycythaemia occurs much less frequently, but two recent large scale studies have also shown it to be associated with a poor prognosis. When defined as haemoglobin less than 12 g/dL for both men and women, as many as 50% of patients hospitalised with CHF are anaemic. The prevalence of anaemia among CHF outpatients is lower (in the region of 15%). Anaemia in heart failure patients is associated with older age, female gender, and greater cardiac dysfunction, renal insufficiency and a history of hypertension. It is likely that anaemia is both a cause and consequence of CHF and a variety of factors may contribute to its development. The most common pattern is that of 'anaemia of chronic disease', although iron deficiency has been reported in up to a fifth of cases. Potential pathophysiological mechanisms include the renal impairment of heart failure, drug side effects, hyporesponsiveness to erythropoietin, haemodilution, and the proinflammatory state of heart failure which causes cytokine-mediated bone marrow suppression. Anaemia is also related to the severity of the heart failure syndrome and has been reported to be an independent risk factor for mortality. Treatment of anaemia with erythropoietin and intravenous iron therapy has been shown to ameliorate the anaemia and to improve symptoms and functional capacity. Anaemia is a potentially reversible risk factor in CHF. Large scale clinical trials are needed to determine whether treatment improves long term survival and what the target haemoglobin should be.

The remarkable progresses in stem cell research and cell biological technology over the past decade have assured an exciting future for myocardial regeneration in the treatment of heart failure. In theory, we can regenerate damaged myocardium using in vivo, ex vivo, and in vitro approaches. The in vivo approach accelerates endogenous regeneration, which can be achieved by regulating cardiomyocytes to enter the cell cycle, activating cardiac stem cells, or mobilizing bone marrow stem cells, to repair the injured heart. The ex vivo approach delivers ex vivo treated autologous cells for myocardial regeneration, and includes the implantation of ex vivo expanded autologous skeletal myoblasts, bone marrow stem cells, cardiomyocytes, fibroblasts, or other tissue stem cells. Finally, the in vitro approach can also help to repair the damaged heart by implanting fetal cardiomyocytes or embryo stem cell-derived cardiomyocytes. We give an overview of the experimental studies and clinical applications of myocardial regeneration, and discuss the feasibility and problems associated with the various approaches and plans for myocardial regeneration in the treatment of heart failure.

Apoptosis is a genetically controlled, cell autonomous pathway for cellular demise with distinct ligands, signaling pathways and characteristic morphologic alterations. It may determine the evolution, progression and biologic behavior of atherosclerotic lesions. Prior to the appearance of atherosclerotic lesions, endothelial cell apoptosis may be the basis of endothelial dysfunction that often precedes the formation of macroscopic lesions. In early lesions, it is plausible that a biphasic pattern of cellular turnover involving apoptosis may modulate cellular growth and senescence in early years of postnatal life. The progression of fatty streaks may depend on cellular content and extent of oxidization of LDL that may influence the rate of foam cell apoptosis and removal of cellular debris. In established atherosclerotic lesions apoptosis of different cell types may contribute to plaque erosion (endothelial cells), plaque progression (macrophages and T cells) and plaque thinning and rupture (VSMCs and macrophages). The exact role of apoptosis in acute ischemic events, however, remains unresolved. Visualization of apoptotic macrophages at sites of plaque rupture suggests a role in precipitating acute events. On the other hand, it appears that some strategies that limit atherosclerosis tend to increase macrophage and VSMC apoptosis. Macrophage apoptosis, by removing a potent source of inflammatory cytokines from the lesion, can favorably influence disease progression. Modulation of apoptosis as a therapeutic tool in atherosclerosis requires further studies to elucidate the molecular pathways and cellular signaling involved in apoptotic cell death.

Exercise Testing still holds firm ground as a simple non-invasive investigative tool for the diagnosis of Coronary Artery Disease. It is a commonly used technique for evaluating patients with cardiac symptoms. Exercise Testing requires appropriate patient preparation and selection. Proper history and physical examination is imperative in order to identify possible contraindications to testing and to determine pretest probability. Manual blood pressure measurements are required to assess a patient's condition during the test for safety. The test should be stopped if ominous signs and/or symptoms occur. Although there are several protocols in use, ramp testing is the preferred technique. Exercise capacity has the greatest prognostic value of all responses in all patient subgroups. There is a 2-10% decrease in mortality and a 5% decrease in health care costs per MET. The Duke Treadmill Score, the drop of heart rate in recovery and the “simple angiographic predictive scores” should to be part of every exercise test report.

Pericarditis is a rare manifestation of tuberculous disease. The appropriate diagnostic workup and optimal therapeutic management are not well defined. The etiology of constrictive pericarditis is often obscure, but is frequently associated with viral infection and tuberculosis, especially in the developing countries. The disease has decreased in industrialized countries but continues to be important in immunosuppressed patients including those with HIV/AIDS. The literature suggests that the optimal management includes an open pericardial window with pericardial biopsy, both for diagnosis and to prevent fluid reaccumulation. Corticosteroids may offer some benefit. The objectives of this review are to review the pathogenesis and clinical manifestations of tuberculous pericarditis, highlight the diagnostic difficulties, and discuss optimal case management including surgery, and the potential role of corticosteroids.