Showing papers in "Current Cardiology Reports in 2013"

How do elevated triglycerides and low HDL-cholesterol affect inflammation and atherothrombosis?

Abstract: This review article summarizes recent research into the mechanisms as to how elevated levels of triglyceride (TG) and low levels of high- density- lipoprotein cholesterol (HDL-C) contribute to inflammation and atherosclerosis. Evidence supports the role of TG-rich lipoproteins in signaling mechanisms via apolipoproteins C-III and free fatty acids leading to activation of NFKβ, VCAM-1 and other inflammatory mediators which lead to fatty streak formation and advanced atherosclerosis. Moreover, the cholesterol content in TG-rich lipoproteins has been shown to predict CAD risk better than LDL-C. In addition to reverse cholesterol transport, HDL has many other cardioprotective effects which include regulating immune function. The “functionality” of HDL appears more important than the level of HDL-C. Insulin resistance and central obesity underlie the pathophysiology of elevated TG and low HDL-C in metabolic syndrome and type 2 diabetes. Lifestyle recommendations including exercise and weight loss remain first line therapy in ameliorating insulin resistance and the adverse signaling processes from elevated levels of TG-rich lipoproteins and low HDL-C.

Chronic kidney disease as a coronary artery disease risk equivalent

Abstract: Chronic kidney disease (CKD) is associated with accelerated cardiovascular disease (CVD) risk and a higher CVD event rate. Substantial data from prospective cohort studies support the concept that dialysis patients as well as those with advanced stage (stages 3–5) CKD are associated with an increased risk for all-cause and cardiovascular mortality. The risk for coronary artery disease (CAD) increases exponentially with declining kidney function, i.e., stage 3 or higher CKD. Indeed, CVD accounts for more than 50 % of deaths in patients with CKD. CKD patients are more likely to die of CVD than to progress to end stage kidney disease. This increase in CV risk is commonly attributed to co-existence of numerous traditional and nontraditional risk factors for the development of CVD that frequently accompany reduced kidney function. Therefore, CKD itself is now considered an independent CVD risk factor and a coronary artery disease (CAD) equivalent for all-cause mortality. All patients at risk for CAD should be evaluated for kidney disease. Treatments used for management of established CAD might have similar benefits for patients with concomitant CKD.

18F-FDG PET/CT for the assessment of myocardial sarcoidosis

Abstract: Cardiac involvement portends a poor prognosis in patients with sarcoidosis. However, due to the nonspecific clinical manifestations of the disease, patchy myocardial involvement, and the limited diagnostic yield of diagnostic tests, early diagnosis of cardiac sarcoidosis has been exceedingly difficult. As a result, there is no standardized approach for the early diagnosis of cardiac sarcoidosis. Imaging modalities that can both identify disease and predict response to therapy are paramount to improve management of cardiac sarcoidosis. 18F-FDG PET has many practical advantages in assessing disease activity and monitoring treatment response in patients with cardiac sarcoidosis. Accumulating data support the growing role of 18F-fluorodeoxyglucose (18F-FDG) PET in the diagnosis and risk stratification of patients with cardiac sarcoidosis.

Targeted PET/CT Imaging of Vulnerable Atherosclerotic Plaques: Microcalcification with Sodium Fluoride and Inflammation with Fluorodeoxyglucose

Abstract: A significant majority of atherosclerotic plaque ruptures occur in coronary arteries exhibiting none or only modest luminal narrowing on coronary angiography. Emerging data suggest the biological composition of an atherosclerotic plaque (vulnerability to rupture) rather than its degree of stenosis or size is the major determinants for acute clinical events. Thus, the pursuit for noninvasive molecular imaging probes that target plaque composition, such as inflammation and/or microcalcification is a creditable goal. 18 F-fluorodioxyglucose (18 F-FDG) is a metabolic probe that can be imaged using positron emission tomography (PET)/computer tomography (CT) technology to target plaque macrophage glucose utilization and inflammation. Vascular plaque 18 F-FDG uptake has been linked to cardiovascular events such as myocardial infarction and stroke. More recently, another molecular probe 18 F-sodium fluoride (18 F-NaF) was introduced for PET imaging, which targets active microcalcifications in atherosclerotic plaques. Little is known regarding the role of early microcalcification in the initiation and progression of plaque, partly because of lack of a noninvasive imaging modality targeting molecular calcification. 18 F-NaF PET/CT imaging could provide new insights into the complex interaction of plaque, and facilitate understanding the mechanism of plaque calcification. Moreover, when these 2 molecular probes, 18 F-FDG and 18 F-NaF, that target distinct biological processes in an atherosclerotic plaque are used in combination, they may further elucidate the link between local inflammation, microcalcification, progression to plaque rupture, and cardiovascular event.

Echocardiographic Screening for Subclinical Rheumatic Heart Disease Remains a Research Tool Pending Studies of Impact on Prognosis

Abstract: The application of portable echocardiography to the screening of asymptomatic children and young adults for rheumatic heart disease (RHD) in developing countries indicates that the disease may affect 62 million to 78 million individuals worldwide, which could potentially result in 1.4 million deaths per year from RHD and its complications. The World Heart Federation has developed a guideline for the echocardiographic diagnosis of RHD in asymptomatic individuals without a history of acute rheumatic fever (ARF) in order to ensure the reliability, comparability, and reproducibility of findings of the echocardiographic screening studies. Early studies suggest that a third of individuals with asymptomatic subclinical RHD revert to normal echocardiographic findings on repeat testing after 6–12 months, suggesting that repeat echocardiography may be necessary to confirm the findings prior to consideration of interventions such as antibiotic prophylaxis. It is not known, however, whether echocardiographic screening for asymptomatic subclinical RHD or the introduction of antibiotic prophylaxis for affected individuals improves the prognosis of RHD. Furthermore, the cost-effectiveness of this screening method has not been established in the vast majority of affected countries. Therefore, echocardiographic screening for asymptomatic subclinical RHD remains a research tool until studies of impact on prognosis and cost-effectiveness are conducted.

Cardiac Toxicity of Anticancer Agents

Abstract: Modern cancer therapies are highly effective in the treatment of various malignancies, but their use is limited by the potential for cardiotoxicity. The most frequent and typical clinical manifestation of cardiotoxicity is left ventricular dysfunction, induced not only by cytotoxic conventional cancer therapy like anthracyclines, but also by new antitumor targeted therapy such as trastuzumab. The current standard for monitoring cardiac function, based on periodic assessment of left ventricular ejection fraction detects cardiotoxicity only when a functional impairment has already occurred, precluding any chance of preventing its development. A novel approach, based on the use of cardiac biomarkers has emerged in the last decade, resulting in a cost-effective diagnostic tool for early, real-time identification, assessment and monitoring of cardiotoxicity. In particular, prophylactic treatment with enalapril in patients with an early increase in troponin after chemotherapy has been shown to be very effective in preventing left ventricular dysfunction and associated cardiac events. In patients developing cancer treatment induced-cardiomyopathy, complete left ventricular ejection fraction recovery and a reduction of cardiac events may be achieved only when left ventricular dysfunction is detected early after the end of cancer treatment and treatment with angiotensin-converting enzyme inhibitors, possibly in combination with beta-blockers, is promptly initiated.

Genetics of Coronary Artery Disease and Myocardial Infarction - 2013

Abstract: Coronary artery disease is a complex disease influenced by modifiable risk factors as well as genetic susceptibility. The genetics of coronary artery disease and myocardial infarction have long been enigmatic. Recent advances in molecular genetics and biology, bioinformatics, and statistics have allowed us to study the interaction of exogenous and endogenous factors. Recent genome-wide association studies and their meta-analyses have included thousands of patients and healthy individuals and provided the statistical power to identify genetic variants, each associated with a rather small increase in risk. Thus far, more than 45 risk loci have been identified. Nevertheless, the search for genetics-based improvements in therapy and prevention has just begun. Hitherto unrecognized mechanisms may provide promising drug targets and early interventional strategies. Furthermore, the sum of risk alleles may facilitate risk assessment as they provide complementary information to traditional risk scores.

Coffee consumption and cardiovascular health: getting to the heart of the matter.

Abstract: As coffee-consumption is a widespread tradition, its possible impact on health has been of considerable interest. This review examines the effects of coffee on cardiovascular risk, outlines underlying biological mechanisms, and discusses implications for public health. In the past, coffee was often viewed as a cardiovascular risk-factor. However, in meta-analyses of recent well-controlled prospective epidemiologic studies, coffee-consumption was not associated with risk of coronary heart disease and weakly associated with a lower risk of stroke and heart failure. Also, available evidence largely suggests that coffee-consumption is not associated with a higher risk of fatal cardiovascular events. In randomized trials coffee-consumption resulted in small increases in blood pressure. Unfiltered coffee increased circulating LDL cholesterol and triglycerides concentrations, but filtered coffee had no substantial effects on blood lipids. In summary, for most healthy people, moderate coffee consumption is unlikely to adversely affect cardiovascular health. Future work should prioritize understanding the effects of coffee in at-risk populations.

Mechanisms of Calcification in Aortic Valve Disease: Role of Mechanokinetics and Mechanodynamics

Abstract: The aortic valve is highly responsive to cyclical and continuous mechanical forces, at the macroscopic and cellular levels. In this report, we delineate mechanokinetics (effects of mechanical inputs on the cells) and mechanodynamics (effects of cells and pathologic processes on the mechanics) of the aortic valve, with a particular focus on how mechanical inputs synergize with the inflammatory cytokine and other biomolecular signaling to contribute to the process of aortic valve calcification.

The Growing Problem of Stroke among Young Adults

Abstract: Although overall stroke incidence has been declining in developed countries, there is evidence that stroke in the young is increasing. Increasing incidence may be particularly pronounced among minorities in whom historically a higher burden of stroke has been reported. Compared with older adults, time spent with disability is longer for those affected at younger ages, and new data suggests that among 30-day young adult stroke survivors, increased mortality persists for as long as 20 years. Stroke in young adults is often missed by less experienced clinicians due to its unexpectedness, leading to lost opportunities for intervention. The causes and risk factors for stroke in the young are often rare or undetermined, but young adults with stroke also have a high burden of traditional cardiovascular risk factors, including hypertension, diabetes, obesity, and substance abuse. Disseminating awareness and promoting research on young adult stroke are steps towards reducing the burden of stroke.

Impediments to Adherence to Post Myocardial Infarction Medications

Abstract: Non-adherence to evidence-based medications is a major public health problem. Less than 50 % of patients with coronary artery disease adhere to their prescribed therapies and this has important implications for morbidity, mortality, and health care spending. Like most complex behaviors, medication non-adherence is not solely the result of poor patient choices. Rather, there are myriad potential contributors attributable to patients, health care providers, and, more broadly, the health care system. Interventions including patient education and behavioral modification, improving patient-physician communication, and eliminating copayments for preventive pharmacotherapy have all been studied. Clinicians play a critical role in helping improve adherence and assessment of adherence must become a standard component of each clinical encounter. Ultimately, given the various etiologies that contribute to non-adherence, achieving meaningful gains will undoubtedly require payors, providers, and policymakers to develop, rigorously evaluate, and systematically deploy strategies that address key patient, clinician, and health system factors.

Home Blood Pressure Monitoring Is Better Predictor of Cardiovascular Disease and Target Organ Damage than Office Blood Pressure: A Systematic Review and Meta-Analysis

Abstract: The available, albeit rare, evidence indicates the superiority of home- over office blood pressure monitoring (HBPM vs OBP) to predict cardiovascular (CV) outcomes We performed a systematic review to update the efficacy of HBPM vs OBP as predictors of all-cause mortality, CV death, and target organ damage Two reviewers independently performed the literature search in various databases A meta-analysis with a fixed-effect model was conducted, and the heterogeneity and inconsistency indices were assessed The search identified 291 articles, of which 10 were eligible for inclusion in the study, and five articles published in 2012 were included in the meta-analysis A previous meta-analysis showed the superiority of HBPM over OBP to predict all-cause mortality, CV mortality, and CV events The meta-analysis of articles published in 2012 identified that HBPM was also a better predictor of proteinuria than OBP In conclusion, the results of our systematic review and meta-analysis confirm that HBPM is a better predictor of CV outcomes and target organ damage than OBP

Genetic evaluation of dilated cardiomyopathy.

Abstract: Recent advances have expanded our ability to conduct a comprehensive genetic evaluation for dilated cardiomyopathy (DCM). By evaluating recent literature, this review aims to bring the reader up-to-date on the genetic evaluation of DCM. Updated guidelines have been published. Mutations in BAG3, including a large deletion, were identified in 2 % of DCM. Truncating mutations in TTN were reported in 25 % of DCM. Two new genes have been reported with autosomal recessive DCM. These studies illustrate the role of improved technologies while raising the possibility of a complex genetic model for DCM. The inclusion of TTN has led to an increased genetic testing detection rate of 40 %. While our ability to identify disease-causing variants has increased, so has the identification of variants of unknown significance. A genetic evaluation for DCM must therefore address this complexity.

Functional impairment in peripheral artery disease and how to improve it in 2013.

Abstract: Lower extremity peripheral artery disease (PAD) affects 8 million men and women in the United States and will be increasingly common as the U.S. population lives longer with chronic disease. People with PAD have poorer walking endurance, slower walking velocity, and poorer balance, compared with individuals without PAD. People with PAD may reduce their walking activity to avoid leg symptoms. Thus, clinicians should not equate stabilization or improvement in exertional leg symptoms with stabilization or improvement in walking performance in PAD. In addition, even asymptomatic PAD patients have greater functional impairment and faster functional decline than individuals without PAD. Of the 2 FDA-approved medications for treating claudication symptoms, pentoxifylline may not be more efficacious than placebo, whereas cilostazol confers a modest improvement in treadmill walking performance. Supervised treadmill walking exercise is associated with substantial improvement in walking endurance, but many PAD patients do not have access to supervised exercise programs. Unsupervised walking exercise programs may be beneficial in PAD, but data are mixed.

Monitoring of Lipids, Enzymes, and Creatine Kinase in Patients on Lipid-Lowering Drug Therapy

Abstract: A number of plasma lipid parameters have been used to estimate cardiovascular risk and to be targets for treatment to reduce risk. Most risk algorithms are based on total cholesterol (T-C) or low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and most intervention trials have targeted the LDL-C levels. Emerging measures, which in some cases may be better for risk calculation and as alternative treatment targets, are apolipoprotein B and non-HDL-C. Other lipid measures that may contribute in risk analysis are triglycerides (TG), lipoprotein(a), and lipoprotein-associated phospholipase A2. The primary treatment target in cardiovascular prevention is LDL-C, and potential alternative targets are apoB and non-HDL-C. In selected individuals at high cardiovascular (CV) risk, TG should be targeted, but HDL-C, Lp(a), and ratios such as LDL-C/HDL-C or apoB/apoAI are not recommended as treatment targets. Lipids should be monitored during titration to targets. Thereafter, lipids should be checked at least once a year or more frequently to improve treatment adherence if indicated. Monitoring of muscle and liver enzymes should be done before the start of treatment. In stable conditions during treatment, the focus should be on clinical symptoms that may alert muscle or liver complications. Routine measurement of CK or ALT is not necessary during treatment with statins.

Quality of life in adult congenital heart disease: what do we already know and what do we still need to know?

Abstract: Quality of life (QOL) is a key outcome in patients with congenital heart disease (CHD) because CHD has become a chronic condition accompanied by lifelong impairments. Recently, published studies on QOL in adults with CHD have reported inconsistent findings. Patients’ QOL seems to depend on multiple factors and is not solely determined by their heart defect and various medical or demographic characteristics. For instance, evidence suggests that a strong sense of coherence might be an important pathway to improve QOL. However, studies on QOL and its determinants are characterized by important methodological differences and limitations, making it impossible to draw firm conclusions. To fill the gaps in the current evidence base, longitudinal and international research is needed. Furthermore, the research field on QOL in CHD should move on from observational studies to interventional research to guide health professionals in improving QOL.

Chronic total occlusions: patient selection and overview of advanced techniques.

Abstract: Percutaneous treatment of coronary chronic total occlusions (CTOs) remains challenging, mainly due to difficulty in crossing the lesion. However tremendous progress has been achieved recently with expanded use of the retrograde approach and advanced dissection re-entry techniques. The development of the “hybrid” approach from North American operators has provided practical recommendations on how to select initial and subsequent CTO crossing strategies. Moreover, additional information has emerged on the frequency of CTOs among patients undergoing cardiac catheterization and on the adverse prognostic impact of CTOs on clinical outcomes of patients with ischemic cardiomyopathy who have implantable cardioverter defibrillators. Overall, CTO interventions remain a dynamic area with multiple novel technical and clinical developments.

The use of biomarkers in the patient with heart failure.

Abstract: Heart failure is a major burden to the health care system in terms of not only cost, but also morbidity and mortality. Appropriate use of biomarkers is critically important to allow rapid identification and optimal risk stratification and management of patients with both acute and chronic heart failure. This review will discuss the biomarkers that have the most diagnostic, prognostic, and therapeutic value in patients with heart failure. We will discuss established biomarkers such as natriuretic peptides as well as emerging biomarkers reflective of myocyte stress, myocyte injury, extracellular matrix injury, and both neurohormonal and cardio-renal physiology.

Percutaneous Mitral and Aortic Paravalvular Leak Repair: Indications, Current Application, and Future Directions

Abstract: Paravalvular regurgitation (PVR) is a symptomatic or asymptomatic complication after surgical valve replacement. It may be related to calcification, infection or tissue friability and occurs in 5 % to 17 % of surgical implanted heart valves. Reoperation is associated with a higher morbidity and mortality than the index procedure. Percutaneous closure of PVR can be an effective and lower risk alternative to reoperation. However, feasibility for percutaneous closure has to be assessed by defining the shape, size and location of the defect. Echocardiography with three-dimensional defect reconstruction is a cornerstone for guiding percutaneous PVR closure. Access for aortic PVR is usually retrograde via the femoral artery and access to mitral PVR either retrograde from the aorta, transvenous-transseptal or transapical. Meticulous planning and prudent procedural execution by experienced operators ensuring no impingement of the prosthetic leaflets leads to a high success rate of percutaneous PVR repair.

Acute hypertensive response management in patients with acute stroke.

Abstract: Acute elevation in blood pressure (acute hypertensive response) is commonly observed in the early period of both ischemic and hemorrhagic stroke. The management of acute hypertensive response depends upon the underlying intracranial pathology. Management of acute hypertensive response has been the focus of many trials and studies such as the SCAST trial, CHHIPS trial, COSSACS trial, INTERACT, and ATACH trial, which are discussed here. However, there were many limitations to these trials including time of presentation, different pathophysiology of ischemic strokes versus hemorrhagic strokes, and patient related factors. Ongoing clinical trials which take these limitations into account include ENCHANTED trial, ATACH II trial, INTERACT 2 trial, and ENOS trial. The results of these trials are expected to modify current guidelines of acute stroke, both ischemic and hemorrhagic, and potentially improve clinical outcomes and quality of life.

Coronary Calcium: New Insights, Recent Data, and Clinical Role

Abstract: Calcium artery calcium (CAC) scoring has become an integral part in the era of preventive cardiology, it has been extensively studied and been validated as a powerful tool for cardiovascular risk assessment in conjunction with other traditional well established scoring systems such as Framingham risk score. In addition, CAC testing has found its way into emergency department algorithms assessing low to intermediate risk patients presenting with chest pain, this strategy was recently adopted by the UK NICE guidelines, confidently ruling out cardiac origin of chest pain. Several studies have demonstrated that risk assessment using CAC was motivational to patients leading to better adherence to their preventive practices as well as to medications. Accordingly, this test has several recommendations for use by national and international guidelines.

Cerebral Microbleeds and Macrobleeds: Should They Influence Our Recommendations for Antithrombotic Therapies?

Abstract: Intracerebral hemorrhage (ICH, or macrobleeds) and cerebral microbleeds-smaller foci of hemosiderin deposits commonly detected by magnetic resonance imaging of older adults with or without ICH-are both associated with an increased risk of future ICH. These hemorrhagic pathologies also share risk factors with ischemic thromboembolic conditions that may require antithrombotic therapy, requiring specialists in cardiology, internal medicine, and neurology to weigh the benefits vs hemorrhagic risks of antithrombotics in individual patients. This paper will review recent advances in our understanding of hemorrhage prone cerebrovascular pathologies with a particular emphasis on use of these markers in decision making for antithrombotic use.

Medication Adherence in Patients with Diabetes and Dyslipidemia: Associated Factors and Strategies for Improvement

Abstract: Dyslipidemia and diabetes mellitus are commonly coincident, and together contribute to the development of atherosclerotic disease. Medication therapy is the mainstay of treatment for dyslipidemia. Optimal medication therapy for dyslipidemia in patients with diabetes reduces cardiovascular events but necessitates patients take multiple medications. As a result, sub-optimal adherence to medication therapy is common. Factors contributing to medication non-adherence in patients taking multiple medications are complex and can be grouped into patient-, social and economic-, medication therapy-, and health provider and health system-related factors. Strategies aimed at improving medication adherence may target the patient, health care providers, or health systems. Recent data suggest medication non-adherence contributes to racial health disparities. In addition, health literacy, cost-related medication non-adherence, and patient beliefs regarding medication therapy have all been recently described as factors affecting medication adherence. Data from within the last year support an important role for regular contact between patients and health care providers to effectively address these factors. Cost-related barriers to medication adherence have recently been addressed through examination of health system approaches to decreasing cost-related non-adherence.

PCSK9 Inhibitors: Potential in Cardiovascular Therapeutics

Abstract: Despite the efficacy of statin therapy, patients treated with these agents face substantial residual risk that is associated with achieved levels of LDL cholesterol (LDL-C). These observations suggest a potential benefit of additional strategies to promote further LDL-C reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an attractive target in this regard. Abrogation of PCSK9 function prevents PCSK9-mediated catabolism of LDL receptors, increases cell surface LDL receptor density, and promotes clearance of LDL and other atherogenic lipoproteins from the circulation. Thus far, the most advanced approaches to block PCSK9 action are monoclonal antibodies and anti-sense oligonucleotides. Among statin-treated patients, these agents may produce additional LDL-C lowering exceeding 50 %. In rare genetic experiments of nature, individuals with dominant negative or dual loss of function mutations of PCSK9 appear to have no adverse health effects resulting from lifelong, very low levels of LDL-C. In short-term trials, PCSK9 antibodies have been generally well-tolerated. However, evidence to support long-term safety and efficacy of PCSK9 therapy to reduce cardiovascular risk awaits the results of large cardiovascular outcome trials.

The treatment of hypertension during pregnancy: when should blood pressure medications be started?

Abstract: Hypertensive pregnancy disorders (HPD) are important causes of maternal and fetal morbidity and mortality worldwide. In addition, a history of HPD has been associated with an increased risk for maternal cardiovascular disease later in life, possibly because of irreversible vascular and metabolic changes that persist beyond the affected pregnancies. Therefore, treatment of HPD may not only improve immediate pregnancy outcomes, but also maternal long-term cardiovascular health. Unlike the recommendations for hypertension treatment in the general population, treatment recommendations for HPD have not changed substantially for more than 2 decades. This is particularly true for mild to moderate hypertension in pregnancy, defined as a blood pressure of 140–159/90–109 mm Hg. This review focuses on the goals of therapy, treatment strategies, and new developments in the field of HPD that should be taken into account when considering blood pressure targets and pharmacologic options for treatment of hypertension in pregnant women.

Is cardiac resynchronization therapy an antiarrhythmic therapy for atrial fibrillation? A systematic review and meta-analysis.

Abstract: The impact of cardiac resynchronization therapy (CRT) on atrial fibrillation (AF) burden is poorly characterized. To assess the influence of CRT on AF, we performed a systematic literature search in MEDLINE using the MeSH headings “cardiac resynchronization therapy” or “cardiac pacing, artificial” and “atrial fibrillation.” Selected studies were peer-reviewed and written in English. Most studies enrolled patients meeting traditional CRT criteria. Ten observational studies and two secondary analyses of clinical trials were identified. Although ten studies suggest that CRT favorably impacts AF, one secondary analysis of a clinical trial showed no effect of CRT on new-onset AF. In a meta-analysis of three studies examining the effect of CRT on persistent or permanent AF, the combined rate of conversion from persistent or permanent AF to sinus rhythm was 0.107 (95 % confidence interval 0.069-0.163). Prospective studies, particularly among patients not meeting traditional CRT criteria, are needed.

Quantitative PET/CT measures of myocardial flow reserve and atherosclerosis for cardiac risk assessment and predicting adverse patient outcomes

Abstract: Conventional scintigraphic myocardial perfusion imaging with SPECT/CT or with PET/CT has evolved as an important clinical tool for the diagnostic assessment of flow-limiting epicardial lesions and risk stratification of patients with suspected CAD. By determining the relative distribution of radiotracer-uptake in the left-ventricular (LV) myocardium during stress, the presence of flow-limiting CAD lesions can be identified. While this approach successfully identifies epicardial coronary artery lesions, the presence of subclinical and non-obstructive CAD may go undetected. In this direction, the concurrent ability of PET/CT to assess absolute myocardial blood flow (MBF) in ml/g/min, rather that relative regional distribution of radiotracer-uptake, and myocardial flow reserve (MFR), expands the scope of conventional myocardial perfusion imaging from the identification of more advanced and flow-limiting epicardial lesions to (1) subclinical CAD, (2) an improved characterization of the extent and severity of CAD burden, and (3) the discovery of "balanced" reduction in myocardial blood flow as a consequence of 3 vessel CAD. Concurrent to the PET data, the CT component of the hybrid PET/CT allows the assessment of coronary artery calcification as an indirect surrogate for CAD burden, without contrast, or with contrast angiography to directly denote coronary stenosis and/or plaque morphology with CT. Hybrid PET/CT system, therefore, has the potential to not only identify and characterize flow-limiting epicardial lesions but also subclinical stages of functional and/or structural stages of CAD. Whether the application of PET/CT for an optimal assessment of coronary pathology, its downstream effects on myocardial perfusion, and coronary circulatory function will in effect lead to changes in clinical decision-making process, investiture in preventive health care, and improved long-term outcome, awaits scientific verification.

Update on type 2 diabetes as a cardiovascular disease risk equivalent.

Abstract: Type 2 diabetes increases the risk of cardiovascular disease (CVD) from two- to four-fold. In our large Finnish population-based study published in 1998 subjects with medication for type 2 diabetes had as high a risk of fatal and nonfatal myocardial infarction (MI) during the 7- year follow-up as non-diabetic subjects with a prior MI, suggesting that type 2 diabetes is a CVD equivalent. In another large study, including all 3.3 million residents of Denmark, subjects requiring glucose-lowering therapy exhibited a CVD risk similar to that of non-diabetic subjects with a prior MI. Subsequent studies have not systematically replicated aforementioned results. Some studies have supported the concept that type 2 diabetes is a CVD equivalent only in some subgroups, and many studies have reported negative findings. This is likely to be due to many differences across the studies published, for example ethnicity, gender, age and other demographic factors of the populations involved, study design, validation of diabetes status and CVD events, statistical analyses (adjustments for confounding factors), duration of diabetes, and treatment of hyperglycemia among diabetic participants. Varying results reflect the fact that not all diabetic patients are at a similar risk for CVD. Therefore, CVD risk assessment and the tailoring of preventive measures should be done individually, taking into consideration each patient’s long-term risk of developing cardiovascular events.

T-wave alternans as an arrhythmic risk stratifier: state of the art.

Abstract: Microvolt level T-wave alternans (MTWA), a phenomenon of beat-to-beat variability in the repolarization phase of the ventricles, has been closely associated with an increased risk of ventricular tachyarrhythmic events (VTE) and sudden cardiac death (SCD) during medium- and long-term follow-up. Recent observations also suggest that heightened MTWA magnitude may be closely associated with short-term risk of impending VTE. At the subcellular and cellular level, perturbations in calcium transport processes likely play a primary role in the genesis of alternans, which then secondarily lead to alternans of action potential morphology and duration (APD). As such, MTWA may play a role not only in risk stratification but also more fundamentally in the pathogenesis of VTE. In this paper, we outline recent advances in understanding the pathogenesis of MTWA and also the utility of T-wave alternans testing for clinical risk stratification. We also highlight emerging clinical applications for MTWA.

Stem Cell Therapy for Pediatric Dilated Cardiomyopathy

Abstract: Dilated cardiomyopathy is a serious and life-threatening disorder in children. It is the most common form of pediatric cardiomyopathy. Therapy for this condition has varied little over the last several decades and mortality continues to be high. Currently, children with dilated cardiomyopathy are treated with pharmacological agents and mechanical support, but most require heart transplantation and survival rates are not optimal. The lack of common treatment guidelines and inadequate survival rates after transplantation necessitates more therapeutic clinical trials. Stem cell and cell-based therapies offer an innovative approach to restore cardiac structure and function towards normal, possibly reducing the need for aggressive therapies and cardiac transplantation. Mesenchymal stem cells and cardiac stem cells may be the most promising cell types for treating children with dilated cardiomyopathy. The medical community must begin a systematic investigation of the benefits of current and novel treatments such as stem cell therapies for treating pediatric dilated cardiomyopathy.