Current Cardiology Reviews (v.13, #2)

Meet Our Editorial Board Member by Irving H. Zucker (85-85).

Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease by John D. Bowman, Salim Surani, Michael A. Horseman (86-93).
Background: Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or contributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmental microbes that are in part modulated through a series of receptors known as toll-like receptors. Endotoxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure.

Objective: The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogenesis of atherosclerotic heart disease.

Conclusion: Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in atherosclerotic disease prevention and treatment.


Cardiovascular disease continues to be the leading cause of death in industrialised societies. The idea that the arterial smooth muscle cell (ASMC) plays a key role in regulating many vascular pathologies has been gaining importance, as has the realisation that not enough is known about the pathological cellular mechanisms regulating ASMC function in vascular remodelling. In the past decade endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been recognised as a stress response underlying many physiological and pathological processes in various vascular cell types. Here we summarise what is known about how ER stress signalling regulates phenotypic switching, trans/dedifferentiation and apoptosis of ASMCs and contributes to atherosclerosis, hypertension, aneurysms and vascular calcification.

Right Heart Catheterization Through Persistent Left Superior Vena Cava, an Extremely Rare Procedure and Review of Current Literature by Nattapong Sricharoen, Mohammad Chamsi-Pasha, Ahmed Sami Abuzaid, Abdel Rahman Al Emam (106-109).
Persistent left superior vena cava (PLSVC) is encountered occasionally during angiographic procedures. It usually coexists with right superior vena cava and drains to the right atrium through the coronary sinus, but multiple variations are described. Although PLSVC is extensively reported in the literature, there are very few articles addressing right heart catheterization in patients with isolated PLSVC. We present a patient with absent right superior vena cava and PLSVC draining to a dilated coronary sinus diagnosed during right heart catheterization in the setting of pulmonary hypertension. We were able to safely complete the procedure through the right internal jugular vein. Transthoracic echocardiography and chest CT scan were consistent with this finding. Although clinically silent most of the time, undiagnosed PLSVC can lead to catastrophic consequences when the patient undergoes invasive procedures. If PLSVC is suspected, the anatomy of the thoracic venous system must be identified before invasive cardiac procedures.

Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque by Paolo Golino, Plinio Cirillo, Raffaele De Palma, Saverio D';Elia, Alberto Morello, Francesco S. Loffredo, Giovanni Cimmino (110-117).
In the last twenty years, our comprehension of the molecular mechanisms involved in the formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its complications, such as rupture or ulceration. According to the new terminology, “vulnerable plaque” identifies an inflamed atherosclerotic lesion that is particularly prone to rupture. Once disrupted, prothrombotic material is exposed to the flowing blood, thus activating coagulation cascade and platelet aggregation, ultimately leading to acute thrombus formation within the coronary vessel. To date this is the key event underlying the clinical manifestations of acute coronary syndromes (ACS).

The degree of vessel occlusion (complete vs. incomplete) and the time of blood flow cessation will define the severity of clinical picture. This phenomenon seems to be the final effect of a complex interaction between different local and systemic factors, involving the degree of inflammation, type of cells infiltration and the rheological characteristics of blood flow at the site of plaque rupture, thrombogenic substrates within the atherosclerotic lesion and different soluble mediators, already present or acutely released in the circulating blood. This article will review currently available data on the pathophysiology of ACS, emphasizing the immunological and inflammatory aspects of vulnerable plaque. We may postulate that intraplaque antigens and local microenvironment will define the immune-inflammatory response and cells phenotype, thus determining the severity of clinical manifestations.


Strain Imaging Echocardiography: What Imaging Cardiologists Should Know by Angel Lopez-Candales, Dagmar F. Hernandez-Suarez (118-129).
Despite recent advances in clinical imaging, echocardiography remains as the most accessible and reliable noninvasive. Since knowledge of left ventricular systolic function remains so critically important in determining prognosis; every effort should be made to prevent subjective estimations. The advent of strain imaging echocardiography now offers a readily available and portable imaging tool that not only offers an objective characterization of myocardial dynamics; but also allows for early detection of subclinical left ventricular dysfunction. This review outlines the basic concepts of strain imaging to better understand the mechanism of myocardial function as well their applicability in the least common cardiac diagnosis among current clinical practice.

Colchicine is a well-established drug approved by the Food and Drug Administration (FDA) for the prevention and treatment of gout. It possesses unique anti-inflammatory properties. Interests in the usage of colchicine in cardiovascular medicine have been rekindled recently with several large trials been carried out to investigate its efficacy in treatment of various cardiac conditions including pericarditis, postpericardiotomy syndrome, atrial fibrillation and coronary artery disease. In this review, the basic pharmacological properties of colchicine will be discussed, and the evidences of its benefits for different applications in cardiovascular medicine will be reviewed.

Current State of Bioabsorbable Polymer-Coated Drug-Eluting Stents by Dongming Hou, Barbara Huibregtse, Keith Dawkins, Joseph Donnelly, Kristine Roy, Jack P. Chen, Abhilash Akinapelli (139-154).
Drug-eluting stents (DES) have been shown to significantly reduce clinical and angiographic restenosis compared to bare metal stents (BMS). The polymer coatings on DES elute antiproliferative drugs to inhibit intimal proliferation and prevent restenosis after stent implantation. Permanent polymers which do not degrade in vivo may increase the likelihood of stent-related delayed arterial healing or polymer hypersensitivity. In turn, these limitations may contribute to an increased risk of late clinical events. Intuitively, a polymer which degrades after completion of drug release, leaving an inert metal scaffold in place, may improve arterial healing by removing a chronic source of inflammation, neoatherosclerosis, and/or late thrombosis. In this way, a biodegradable polymer may reduce late ischemic events. Additionally, improved healing after stent implantation could reduce the requirement for long-term dual antiplatelet therapy and the associated risk of bleeding and cost. This review will focus on bioabsorbable polymer-coated DES currently being evaluated in clinical trials.

Adherence to Secondary Prophylaxis for Acute Rheumatic Fever an d Rheumatic Heart Disease: A Systematic Review by Ronny Gunnarsson, Alan R. Ruben, Benjamin M. Reeves, Priya M. Kevat (155-166).
Background: Optimal delivery of regular benzathine penicillin G (BPG) injections prescribed as secondary prophylaxis for acute rheumatic fever (ARF) and rheumatic heart disease (RHD) is vital to preventing disease morbidity and cardiac sequelae in affected pediatric and young adult populations. However, poor uptake of secondary prophylaxis remains a significant challenge to ARF/RHD control programs.

Objective: In order to facilitate better understanding of this challenge and thereby identify means to improve service delivery, this systematic literature review explored rates of adherence and factors associated with adherence to secondary prophylaxis for ARF and RHD worldwide.

Methods: MEDLINE was searched for relevant primary studies published in the English language from 1994-2014, and a search of reference lists of eligible articles was performed. The methodological quality of included studies was evaluated using a modified assessment tool.

Results: Twenty studies were included in the review. There was a range of adherence to varying regimens of secondary prophylaxis reported globally, and a number of patient demographic, clinical, socio-cultural and health care service delivery factors associated with adherence to secondary prophylaxis were identified.

Conclusion: Insights into factors associated with lower and higher adherence to secondary prophylaxis may be utilized to facilitate improved delivery of secondary prophylaxis for ARF and RHD. Strategies may include ensuring an effective active recall system, providing holistic care, involving community health workers and delivering ARF/RHD health education.