Current Cardiology Reviews - Volume 8, Issue 3, 2012

Atherosclerosis is a systemic vascular pathology that is preceded by endothelial dysfunction. Vascular inflammation "fuels" atherosclerosis and creates the milieu for episodes of intravascular thromboses. Thrombotic events in the coronary vasculature may lead to asymptomatic progression of atherosclerosis or could manifest as acute coronary syndromes or even sudden cardiac death. Thrombus encountered in the setting of acute coronary syndromes has been correlated with acute complications during percutaneous coronary interventions such as no-reflow, acute coronary occlusion and long term complications such as stent thrombus. This article reviews the pathophysiology of coronary thrombogenesis and explores the complications associated with thrombus during coronary interventions.

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion method in patients with STelevation myocardial infarction (STEMI), when performed in a timely manner and by skilled operators. However, this strategy has shown to be limited in environments with lack of PCI facilities and delay in the first medical contact-toballoon time for logistic reasons. Pretreatment with fibrinolysis and/or glycoprotein IIb/IIIa inhibitors before PCI has the potential to provide early pharmacologic reperfusion before definitive PCI in STEMI patients. However, current data suggest that facilitated PCI does not offer any advantage over primary PCI. Conversely, a role for pharmacoinvasive recanalization, defined as pharmacological reperfusion followed by rapid transfer for routine delayed coronary angiography and PCI may still be considered in centers without on-site PCI capability.

Managing coronary thrombus is a challenging task and requires adequate knowledge of the various antithrombotic agents available. In this article, we will briefly analyze the risk-benefit profile of antithrombotic agents, with critical analysis of the scientific evidence available to support their use. Since thrombus consists of platelets and coagulation cofactors, an effective antithrombotic strategy involves using one anticoagulant with two or more antiplatelet agents. Unfractionated heparin traditionally has been the most commonly used anticoagulant but is fast being replaced by relatively newer agents like LMWH, direct thrombin inhibitors, and Factor Xa inhibitors. In recent years, the antiplatelet landscape has changed significantly with the availability of more potent and rapidly acting agents, like prasugrel and ticagrelor. These agents have demonstrated a sizeable reduction in ischemic outcomes in patients with ACS, who are treated invasively or otherwise, with some concern for an increased bleeding risk. Glycoprotein IIb/IIIa inhibitors have an established role in high risk NSTE ACS patients pretreated with dual antiplatelets, but its role in STEMI patients, treated with invasive approach and dual antiplatelets, has not been supported consistently across the studies. Additionally, in recent years, its place as a directly injected therapy into coronaries has been looked into with mixed results. In conclusion, a well-tailored antithrombotic strategy requires taking into account each patient's individual risk factors and clinical presentation, with an effort to strike balance between not only preventing ischemic outcomes but also reducing bleeding complications.

The clinical benefit of percutaneous intervention (PCI) depends on both angiographic success at the site of intervention as well as the restoration of adequate microvascular perfusion. Saphenous vein graft intervention is commonly associated with evidence of distal plaque embolization, which is correlated with worse clinical outcomes. Despite successful epicardial intervention in the acute MI patient treated with primary PCI, distal tissue perfusion may still be absent in up to 25% of cases [1-3]. Multiple devices and pharmacologic regimens have been developed and refined in an attempt to protect the microvascular circulation during both saphenous vein graft intervention and primary PCI in the acute MI setting. We will review the evidence for various techniques for embolic protection of the distal myocardium during saphenous vein graft PCI and primary PCI in the native vessel.

Primary percutaneous coronary intervention, (pPCI), of native coronaries and saphenous vein grafts (SVGs), is the recommended reperfusion strategy for STEMI, and an early invasive approach is recommended for high risk patients with UA/NSTEMI. Although PCI effectively restores flow in the infarct related artery/culprit vessel in both situations, myocardial perfusion often remains suboptimal due to microvascular obstruction, partly attributed to distal embolization of thrombus. Hence, thrombectomy (manual or mechanical), prior to stenting may further reduce hard clinical end points in patients with ACS. This article discusses accumulated evidence regarding the safety and effectiveness of thrombectomy in culprit native coronaries and SVGs in such patients, as well as possible strategies for maximizing its benefits relative to the size of the thrombotic burden.

The no reflow phenomenon can happen during elective or primary percutaneous coronary intervention. This phenomenon is thought to be a complex process involving multiple factors that eventually lead to microvascular obstruction and endothelial disruption. Key pathogenic components include distal atherothrombotic embolization, ischemic injury, reperfusion injury, and susceptibility of coronary microcirculation to injury. Thus, pharmacologic and mechanical strategies to prevent and treat no reflow target these mechanisms. Specifically, pharmacologic therapy consisting of vasodilators and antiplatelet agents have shown benefit in the treatment of no-reflow and mechanical therapies such as distal protection and aspiration thrombectomy have also shown benefit.

Photoplethysmography is one of the optical techniques has been developed for experimental use in vascular disease. It has several advantages over other traditional experimental approaches. Because of its non-invasive, safe, costeffective and easy-to-use properties, it is considered as a useful diagnostic tool. The further developments in the Photoplethysmograph may replace it among other tools used in the assessment of vascular diseases such as blood test and ultrasound. This overview discusses the different terminologies used for the photoplethysmograph and reveals the research discontinuity among different disciplines. Moreover, it suggests standard terminologies as a resolution for a confusion persisted for more than 50 years.

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.

The concept of dominant frequency (DF) has been used as a way to express local atrial activation rate during atrial fibrillation (AF). The rotor theory explaining the pathophysiology of AF is widely based upon spatial distribution of DF in the atria. Using frequency domain analysis to represent the rate of atrial activation by DF can avoid some of the limitations of time domain analysis of signals during AF. Understanding the concept of DF is of utmost importance to the proper use and interpretation of frequency domain analysis in AF. The current review focuses on the basic principles and methodology of frequency domain analysis using the Fourier transform during different types of AF. It also provides an update of the published experimental and clinical data on frequency domain analysis in light of the rotor theory for AF maintenance.

Antiplatelet and antithrombotic agents significantly alter the clinical course of patients with acute coronary syndrome (ACS) and hence form the bedrock of the management pathway of this closely related continuum of coronary pathologies. The contemporary therapeutic armamentarium for the treatment of ACS now reflects the many technical and pharmacological advances that took place over the last two decades. In the original 1996 American College of Cardiology/ American Heart Association (ACC/AHA) guidelines for the management of acute myocardial infarction, only one antiplatelet agent (Aspirin) and one anticoagulant (unfractionated heparin) were recommended as class I therapies. Since then many newer agents have been developed and approved for routine clinical use in ACS patients. Recent research has focussed on improving efficacy on one hand and reducing bleeding complications on the other. This review focuses on the mechanism, efficacy, safety profile and clinical trial evidence of P2 Y12 receptor antagonist antiplatelet agents, glycoprotein IIb/IIIa receptor inhibitors (GPI), protease-activated receptor-1 (PAR-1) inhibitors, thrombin inhibitor bivalirudin and Factor Xa inhibitors fondaparinaux and rivaroxaban.