Current Cardiology Reviews - Volume 1, Issue 3, 2005

Atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the development of acute coronary syndromes. Plaques with a large extracellular lipid-rich core, thin fibrous cap due to reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells, appear to be vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses, resulting from biomechanical and hemodynamic forces acting on plaques, are concentrated. Reduced matrix synthesis as well as increased matrix degradation predisposes vulnerable plaques to rupture in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization. The broad concept of plaque stabilization, although attractive, has not yet been rigorously validated in humans. This article reviews the mechanism of atherosclerosis development and the pathophysiology of acute coronary syndromes in order to provide a molecular and cellular basis for understanding how plaque passivation might be accomplished in clinical medicine.

Cardiovascular magnetic resonance (CMR) imaging is one of the newest and most versatile imaging modalities in cardiovascular medicine, specifically in the evaluation of ischemic heart disease. Due to its excellent blood-pool-tomyocardium contrast and to its three-dimensional coverage, CMR has emerged as the "gold standard" in the assessment of resting left ventricular (LV) and right ventricular (RV) size and function. CMR can also be applied for stress testing, using vasodilator stress for perfusion analysis or dobutamine stress for functional analysis. Lately, CMR has become an invaluable tool in the assessment of myocardial viability. A recently introduced, novel inversion recovery gradient echo sequence for infarct imaging is the first in-vivo technique to assess the transmural extent of myocardial infarction. The predictive value of late contrast enhancement for functional recovery after revascularization has been validated both in acute and chronic human myocardial infarction. Contractile reserve during low-dose dobutamine infusion may have incremental predictive value in nontransmural infarction. Coronary magnetic resonance angiography (CMRA) can be used for the evaluation of anomalous coronary arteries and bypass grafts. CMRA of the native coronary arteries will need further development before routine clinical application. CMR also plays an important role in the evaluation of arrhythmogenic right ventricular cardiomyopathy, pericardial disease, cardiac masses, congenital heart disease, and pulmonary venous anatomy. Its potential applications continue to expand as more cardiovascular imagers are trained in these techniques.

The introduction of drug eluting stents (DES) has the potential to revolutionize interventional cardiology. Despite the dramatic improvements demonstrated in randomised trials of the currently available DES restenosis still occurs in complex lesions. An effective DES requires the combination of a stent, a drug delivery system such as a polymer and pharmaceutical agent. This article will summarize some of the recent developments in the rapidly evolving field of drug delivery platforms.

In patients with acute myocardial infarction, prompt restoration of blood flow is essential for myocardial salvage. However, the means by which reperfusion is initiated may play a crucial role in determining cardiomyocyte survival and, ultimately, clinical outcome. The newly described phenomenon of 'postconditioning' represents a modification of early reperfusion, whereby the first few moments of reflow are 'stuttered'. This simple alteration of reflow hemodynamics has recently been shown to significantly reduce infarct size in experimental models. Our aims in this mini-review are to: (1) highlight the emerging insights into the characteristics and cellular mechanisms of postconditioning-induced cardioprotection; and (2) discuss the potential clinical applications, such as controlled reperfusion during cardiac catheterization, of postconditioning.

Aspirin, the most widely used antiplatelet agent, irreversibly acetylates the enzyme cyclooxygenase 1 (COX-1), thereby inhibiting platelet thromboxane synthesis and subsequent platelet aggregation. Although aspirin has been demonstrated to reduce the odds of serious atherothrombotic events and death in high-risk patients by 25%, subsets of patients fail to respond to therapy and continue to suffer atherothrombotic events. This aspirin treatment failure may be due to sub-optimal bioavailability (e.g. because of non-compliance or under-dosing) or may be a consequence of the as yet poorly understood phenomenon of aspirin resistance. In this review, we summarize the current laboratory methods used to identify aspirin-resistant patients, outline the cellular mechanisms that may contribute to aspirin resistance, and discuss the clinical implications of this important issue.

With advancing age the large arteries of the body become more stiff and less compliant, which causes an increase in systolic blood pressure and pulse pressure as well as a decrease in diastolic blood pressure. A perusal of the literature reveals that in the last few years there is ample evidence and multiple publications claiming that a wide pulse pressure, reflecting large artery stiffness, is a significant and at times independent risk factor for cardiovascular disease particularly in the elderly. This article presents a review and a summary of the salient studies and trials conducted in different institutions and countries correlating the increase in pulse pressure with cardiovascular outcomes primarily cardiovascular mortality, coronary artery disease, myocardial infarction, congestive heart failure and stroke. The information available, although mainly consistent, is insufficient to determine if the encountered relationship of wide pulse pressure and cardiovascular events is causal or whether wide pulse pressure is just a marker of an underlying disease. There has been no trial to test the benefit of treating wide pulse pressure. In order to decide if pulse pressure will become clinically useful for the definition and management of hypertension and for cardiovascular risk stratification we will need more research and randomized clinical trials to explore if reversal in coronary risk and cardiovascular complications is obtained with drugs that decrease pulse pressure and if pulse pressure monitoring will be useful for coronary risk stratification.

Dual chamber pacemaker therapy was considered to be the optimal treatment for most patients with symptomatic bradycardias. During the last decade, the percentage of dual chamber pacing increased to more than 60% in the United States and Western Europe. Yet, recent multicenter trials (CTOPP, MOST, UKPACE) on dual chamber pacemaker therapy failed to demonstrate a clear prognostic advantage compared to single chamber ventricular pacing. Moreover, clinical benefits of dual chamber pacing like a lower incidence of atrial arrhythmias, a reduction of hospitalization for heart failure or quality of life improvements were lower than expected or even absent. This article discusses the above mentioned studies and their limitations, reviews the increasing evidence for avoiding right (apical) ventricular stimulation and presents current approaches to differential pacemaker therapy.

Calcific aortic stenosis (AS) is the most prevalent heart disease requiring valve replacement in the elderly. Mild to moderate stenosis is usually asymptomatic, however, when becomes severe it is associated with significant morbidity and mortality including left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction, congestive heart failure, angina, arrhythmias, and syncope. Aortic sclerosis, described as focal areas of increased echogenecity and thickening of aortic valve leaflets without restricted motility, is also associated with increased risk of death from cardiovascular causes. Regular follow-up is important to monitor hemodynamic progression of the aortic valve disease and the development of symptoms. Progression of AS shares many histological and immunochemical similarities with the process of atherosclerosis. They both are based on a chronic inflammatory process with infiltration and activation of leukocytes and a rise in systemic inflammatory markers. Epidemiological studies identified several risk factors for calcific aortic valve disease such as male sex, hypertension, smoking, and raised serum creatinin, cholesterol and calcium concentrations. Many of these are also the risk factors for atherosclerosis. Thus, AS is not just an age related degenerative process; its development is highly complex and shares a number of risk factors common for atherosclerosis. Lipids play an important role in the development and progression of AS, and there is growing evidence that cholesterol lowering may retard or prevent its progression. New research suggests that medical therapies may retard the progression of AS and reduce the need for surgery. This article will review the molecular and cellular basis of calcific AS, and mainly will focus on the potential for medical treatment alternatives.

While coarctation of the aorta may be a simple obstruction to flow from ascending to descending aorta, its repair has been varied and complex. Historically, many of the surgical options tried for this lesion have met with initial enthusiasm until long-term data on recurrence rate and complications were accrued. This review will present the complexity of historical therapeutic options with particular focus on long-term outcomes. Before any surgical or transcatheter technique for coarctation therapy can be considered a standard, awareness of the twenty-year outcome is warranted.

The endothelium exerts a paracrine function by releasing a number of mediators that control vascular tone and smooth muscle cell proliferation, platelet aggregation, monocyte and leukocyte adhesion, and thrombosis. Coronary microvascular endothelium is involved not only in the control of blood flow to myocardial tissue, but also in the regulation of myocyte metabolism and contractile function. Thus, coronary microcirculation might be the initial site of pathological events leading to development and progression of cardiac dysfunction and failure. Although this pathophysiological mechanism has been hypothesized on the basis of very solid clinical and experimental evidence, yet it has not been sufficiently considered and explored by the scientific community. The present review highlights the studies that have principally contributed to define the critical role played by coronary microvascular endothelium in the regulation of cardiac function, and to elaborate the intriguing hypothesis that coronary microcirculatory dysfunction is a major pathogenetic factor involved in the genesis of heart failure.