Current Cardiology Reviews - Volume 5, Issue 3, 2009
Volume 5, Issue 3, 2009
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Thiazolidinediones and Cardiovascular Risk — A Question of Balance
Authors: Erland Erdmann, Bernard Charbonnel and Robert WilcoxBackground: Several recent meta-analyses of adverse event data from randomized controlled trials with rosiglitazone reveal a possible association between this thiazolidinedione and an increased risk of ischemic myocardial events. This has led to debate on the overall clinical benefit of glitazone therapy for type 2 diabetes. Pioglitazone, on the other hand, has the most extensive cardiovascular outcomes database of all current glucose-lowering therapies, including a large prospective randomized controlled trial designed specifically to assess cardiovascular outcomes (PROactive). The available data suggest that pioglitazone is associated with a reduction in macrovascular risk. Aims: In this review, we highlight some of the key factors that need to be considered when assessing the net clinical benefit of thiazolidinediones, focussing on both class effects and those specific to either rosiglitazone or pioglitazone. Results: For pioglitazone there appears to be no increase in the risk of overall macrovascular events and no adverse clinical consequences of developing signs of heart failure. Furthermore, there is good evidence of significant benefit regarding the composite of death, MI or stroke. Conclusion: The benefits seen with pioglitazone appear to outweigh the risks.
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Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance
More LessSevere and occasionally fatal arrhythmias, commonly presenting as Torsade de Pointes [TdP] have been reported with Class III-antiarrhythmics, but also with non-antiarrhythmic drugs. Most cases result from an action on K+ channels encoded by the HERG gene responsible for the IKr repolarizing current, leading to a long QT and repolarization abnormalities. The hydrophobic central cavity of the HERG-K+ channels, allows a large number of structurally unrelated drugs to bind and cause direct channel inhibition. Some examples are dofetilide, quinidine, sotalol, erythromycin, grepafloxacin, cisapride, dolasetron, thioridazine, haloperidol, droperidol and pimozide. Other drugs achieve channel inhibition indirectly by impairing channel traffic from the endoplasmic reticulum to the cell membrane, decreasing channel membrane density (pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol). Whereas, ketoconazole, fluoxetine and norfluoxetine induce both direct channel inhibition and impaired channel trafficking. Congenital long QT syndrome, subclinical ion-channel mutations, subjects and relatives of subjects with previous history of drug-induced long QT or TdP, dual drug effects on cardiac repolarization [long QT plus increased QT dispersion], increased transmural dispersion of repolarization and T wave abnormalities, use of high doses, metabolism inhibitors and/or combinations of QT prolonging drugs, hypokalemia, structural cardiac disease, sympathomimetics, bradycardia, women and older age, have been shown to increase the risk for developing drug-induced TdP. Because most of these reactions are preventable, careful evaluation of risk factors and increased knowledge of drugs use associated with repolarization abnormalities is strongly recommended. Future genetic testing and development of practical and simple provocation tests are in route to prevent iatrogenic TdP.
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Coronary Risk Assessment and Management Options in Chronic Kidney Disease Patients Prior to Kidney Transplantation
Authors: Vanji Karthikeyan and Karthik AnanthasubramaniamCardiovascular disease remains the most important cause of morbidity and mortality among kidney transplant recipients. Nearly half the deaths in transplanted patients are attributed to cardiac causes and almost 5% of these deaths occur within the first year after transplantation. The ideal strategies to screen for coronary artery disease (CAD) in chronic kidney disease patients who are evaluated for kidney transplantation (KT) remain controversial. The American Society of Transplantation recommends that patients with diabetes, prior history of ischemic heart disease or an abnormal ECG, or age ≥50 years should be considered as high-risk for CAD and referred for a cardiac stress test and only those with a positive stress test, for coronary angiography. Despite these recommendations, vast variations exist in the way these patients are screened for CAD at different transplant centers. The sensitivity and specificity of noninvasive cardiac tests in CKD patients is much lower than that in the general population. This has prompted the use of direct diagnostic cardiac catheterization in high-risk patients in several transplant centers despite the risks associated with this invasive procedure. No large randomized controlled trials exist to date that address these issues. In this article, we review the existing literature with regards to the available data on cardiovascular risk screening and management options in CKD patients presenting for kidney transplantation and outline a strategy for approach to these patients.
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Current Management of Traumatic Rupture of the Descending Thoracic Aorta
Authors: Riyad Karmy-Jones, Nichole Jackson, William Long and Alan SimeoneTraumatic rupture of the descending thoracic aorta remains a leading cause of death following major blunt trauma. Management has evolved from uniformly performing emergent open repair with clamp and sew technique to include open repair with mechanical circulatory support, medical management and most recently, endovascular repair. This latter approach appears, in the short term, to be associated with perhaps better outcome, but long term data is still accruing. While an attractive option, there are specific anatomic and physiologic factors to be considered in each individual case.
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Toll-Like Receptors and Myocardial Ischemia/Reperfusion, Inflammation, and Injury
Authors: David J. Kaczorowski, Atsunori Nakao, Kenneth R. McCurry and Timothy R. BilliarCardiac ischemia/reperfusion (I/R) injury occurs in several important clinical contexts including percutaneous coronary interventions for acute myocardial ischemia, cardiac surgery in the setting of cardiopulmonary bypass, and cardiac transplantation. While the pathogenesis of I/R injury in these settings is multifactorial, it is clear that activation of the innate immune system and the resultant inflammatory response are important components of I/R injury. Toll-like receptor 4 (TLR4), originally identified as the sensor for bacterial lipopolysaccharide (LPS), has also been shown to serve as a sensor for endogenous molecules released from damaged or ischemic tissues. Accordingly, recent findings have demonstrated that TLR4 not only plays a central role as a mediator of cardiac dysfunction in sepsis, but also serves as a key mediator of myocardial injury and inflammation in the setting of I/R. Furthermore, TLR4 may play a role in the development of atherosclerotic lesions. Other studies have implicated TLR4 in the adverse remodeling that may occur after ischemic myocardial injury. This emerging body of literature, which is reviewed here, has provided new insight into the early molecular events that mediate myocardial injury and dysfunction in the setting of I/R injury.
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The GH/IGF-1 Axis and Heart Failure
Authors: Graziella Castellano, Flora Affuso, Pasquale Di Conza and Serafino FazioThe growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis regulates cardiac growth, stimulates myocardial contractility and influences the vascular system. The GH/IGF-1 axis controls intrinsic cardiac contractility by enhancing the intracellular calcium availability and regulating expression of contractile proteins; stimulates cardiac growth, by increasing protein synthesis; modifies systemic vascular resistance, by activating the nitric oxide system and regulating non-endothelial-dependent actions. The relationship between the GH/IGF-1 axis and the cardiovascular system has been extensively demonstrated in numerous experimental studies and confirmed by the cardiac derangements secondary to both GH excess and deficiency. Several years ago, a clinical non-blinded study showed, in seven patients with idiopathic dilated cardiomyopathy and chronic heart failure (CHF), a significant improvement in cardiac function and structure after three months of treatment with recombinant GH plus standard therapy for heart failure. More recent studies, including a small double-blind placebo-controlled study on GH effects on exercise tolerance and cardiopulmonary performance, have shown that GH benefits patients with CHF secondary to both ischemic and idiopathic dilated cardiomyopathy. However, conflicting results emerge from other placebo-controlled trials. These discordant findings may be explained by the degree of CHF-associated GH resistance. In conclusion, we believe that more clinical and experimental studies are necessary to exactly understand the mechanisms that determine the variable sensitivity to GH and its positive effects in the failing heart.
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Triglycerides and Cardiovascular Risk
Authors: K. E.L. Harchaoui, M. E. Visser, J. J.P. Kastelein, E. S. Stroes and G. M. Dallinga-ThieIn 1996 a meta-analysis was published showing that an increase in plasma triglyceride (TG) levels was associated with an increase in CHD risk, even after adjustment for high density lipoprotein cholesterol (HDL-C) levels. Very recently, two studies were published that further extent the early observation and showed the importance of nonfasting plasma triglyceride (TG) levels in the prediction of risk on coronary heart disease (CHD). In the current review we have summarized all available evidence obtained in clinical studies showing that treatment guidelines should reconsider to include nonfasting TG in their risk assessments as nonfasting TG levels may better predict CVD risk.
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Diminished Renal Function and the Incidence of Heart Failure
By Johan ArnlovHeart failure is one of the most common, costly, disabling and deadly diseases. During the last decade, several different indices reflecting renal function such as creatinine-based glomerular filtration rate, circulating levels of cystatin C and low-grade albuminuria have been demonstrated to be independent risk factors for heart failure. This review summarizes our current knowledge of the relationship between diminished renal function and the incidence of heart failure in the community, and also in individuals with increased risk of heart failure such as patients with overt cardiovascular disease, hypertension or diabetes. This review will also put forward important areas of future research in this field.
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Cardiac Amyloidosis Responding to Bortezomib: Case Report and Review of Literature
Authors: Edriss Charaf, Said B. Iskandar, Ashley Blevins, Bernard Abi-Saleh and Stephen FahrigWe report a case of a 53-year old patient with symptoms of congestive heart failure in whom a restrictive cardiomyopathy and a kappa-chain monoclonal gammopahty were diagnosed. Treatment with eight cycles of Bortezomib, a proteasome inhibitor, resulted in a significant regression of myocardial amyloid deposition and a notable clinical and hemodynamic improvement. Over the last few years, the management of cardiac amyloidosis has taken advantage of many of the advances of the chemotherapeutic regimens, as well as the wider availability of stem cell transplantation. The management of cardiac amyloidosis is also expected to evolve and improve with the better understanding of the specific mechanisms of amyloidogenesis and myocardial deposition. This will probably make certain molecules targeting specific sites in this process, as potentially effective and minimally toxic compared therapy with the currently used ones. In this article, we describe one of the first reported cases of cardiac amyloidosis, successfully treated with Bortezomib. We describe and discuss the mechanisms of action of Bortezomib and provide a detailed review of cardiac amyloidosis, from pathophysiology to diagnosis and treatment.
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Clinical Applications for Cardiovascular Magnetic Resonance Imaging at 3 Tesla
Authors: Allison G. Hays, Michael Schar and Sebastian KelleCardiovascular magnetic resonance (CMR) imaging has evolved rapidly and is now accepted as a powerful diagnostic tool with significant clinical and research applications. Clinical 3 Tesla (3 T) scanners are increasingly available and offer improved diagnostic capabilities compared to 1.5 T scanners for perfusion, viability, and coronary imaging. Although technical challenges remain for cardiac imaging at higher field strengths such as balanced steady state free precession (bSSFP) cine imaging, the majority of cardiac applications are feasible at 3 T with comparable or superior image quality to that of 1.5 T. This review will focus on the benefits and limitations of 3 T CMR for common clinical applications and examine areas in development for potential clinical use.
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Myocardial Energetics in Left Ventricular Hypertrophy
Authors: Mohammad N. Jameel and Jianyi ZhangThe heart carries out its pumping function by converting the chemical energy stored in fatty acids and glucose into the mechanical energy of actin-myosin interaction of myofibrils. Development of congestive heart failure is usually preceded by a period of compensated left ventricular hypertrophy (LVH) and alterations in myocardial bioenergetics have been considered to play an important role in this transition. Myocardial energetic state that is reflected by the ratio of Phosphocreatine to Adenosine Triphosphate (PCr/ATP) is significantly decreased in hearts with LVH. The severity of this abnormality is linearly related to the severity of cardiac hypertrophy as well as left ventricular (LV) dysfunction, and is independent of a persistent myocardial ischemia. The decrease in PCr/ATP is accompanied by a decrease in creatine kinase flux and alterations in substrate utilization in LVH hearts. Moreover, there is a profound heterogeneity in alterations in myocardial energy metabolism in hearts with post-infarction hypertrophy with the most severe abnormality present in the inner layers of the periscar border zone (BZ). This review will discuss various aspects of myocardial energetics in animal models of three different types of LVH (pressure-overload, volume overload and post-infarction) with a brief description of myocardial energetics in humans with LVH.
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Volumes & issues
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Volume 21 (2025)
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Volume 20 (2024)
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Volume 19 (2023)
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Volume 18 (2022)
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Volume 17 (2021)
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Volume 16 (2020)
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Volume 15 (2019)
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Volume 14 (2018)
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Volume 13 (2017)
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Volume 12 (2016)
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Volume 11 (2015)
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Volume 10 (2014)
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Volume 9 (2013)
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Volume 8 (2012)
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Volume 7 (2011)
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Volume 6 (2010)
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Volume 5 (2009)
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Volume 4 (2008)
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Volume 3 (2007)
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Volume 2 (2006)
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Volume 1 (2005)
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