Current Cardiology Reviews - Volume 7, Issue 1, 2011

Cardiovascular disease (CVD) represents the number one and leading cause of death globally, and the majority of CVD is caused by atherosclerosis. Atherosclerosis is a systemic disease that leads to myocardial infarction, stroke and lower limb ischemia. Pathological studies have given insight to development of atherosclerosis and the importance of local plaque vulnerability and cardiovascular events. Due to the burden of cardiovascular disease, identification of the individual patient at risk for cardiovascular events and treatment stratification is needed. Furthermore, efforts at primary prevention for major risk sources and secondary prevention of recurrence are very important. For example, following stroke due to carotid artery stenosis, the likelihood of recurrence is relatively high (up to 10% for early embolic recurrence) but currently we have no options to predict who will and who will not suffer a secondary event. Although large series of patients have been reported in literature, some clinical aspects of the natural course of the disease are still poorly defined, creating doubts how to select the patient that will benefit from revascularization considering perioperative morbidity from the procedure itself. The predictive power of classical risk factors is limited, especially in patients with manifest atherosclerosis. Prediction models are often made by non patient treating authors; making them distant from what it is all about: daily care for the individual patient. Imaging modalities have focused on the characteristics of the vulnerable plaque, and options for non-invasive imaging need to be further explored. Serum biomarkers have also been studied extensively. In line with the important relation between vulnerable plaques and cardiovascular events, plaque biomarker studies have been initiated. These longitudinal studies are based on the concept, that a vulnerable plaque contains predictive information for future (cardiovascular) events. Results look promising and plaque markers can be used to subsequently develop imaging modalities to identify patients at relatively high risk. The objective of this supplement is to present an update on relevant aspects related to clinical manifestations, biological characteristics, implications of biobanking for individual patient risk identification, and imaging developments, in order to contribute to the better understanding of individual patient directed medical care. The most relevant aspects are discussed in the following 5 chapters: 1) “Risk scores for chest pain patients at the emergency room”. Chest pain is a common reason for presentation to the emergency department (ED). The vast majority of patients with chest pain are due to causes other than Acute Coronary Syndrome. The developed HEART score is specifically designed to stratify all chest pain patients and proved to be a strong predictor of event free survival on one hand and potentially life threatening cardiac events on the other hand. 2) Biomarkers derived from histological controlled studies have long time been skye-high…but there seem to be pitfalls, creating some disbalance. We hope you will find out reading the contribution from our Experimental Cardiology Department entitled “Plaque markers predictive for outcome: challenging the definition of the vulnerable plaque?; 3) With increasing life expectancy clinicians are more often confronted with patients of higher age. Octogenarians were often excluded from randomized trials comparing CAS to CEA because they were considered high-risk for revascularization. Conflicting results on the peri-procedural outcome of carotid revascularization in these patients have been reported, and Reichmann et al. summarize and evaluate whether age above 80 years should be an upper limit for indicating carotid revascularization in the manuscript “Octogenarians and carotid plaque: histologically based risk for adverse perioperative outcome?; 4) Future direction for adequate patient selection will be imaging guided treatment checked by the gold standard of histology. This approach will have a high impact for patients, health care systems and society. In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-)invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. and Den Hartog et al. propose a new study protocol entitled “The application of 7Tesla MRI in determining carotid plaque characteristics in patients with high grade carotid artery stenosis”; and 5) Biobanks are an extremely valuable resource that enables us to study the influence of both genetic and environmental factors on the development of multifactorial diseases such as atherosclerosis. The review by Scholtes et al. “Biobanking of vascular tissue: opportunities and pitfalls” will focus on the advantages and pitfalls in atherosclerotic biobanking. Hopefully, all being interested in patient selection improvement and the role of biobanking working in the field of cardiovascular diseases will enjoy the contents of this mini-guest editorial and will find topics of personnal interest or food for thought and spirit for future investigations and research. I would like to acknowledge in particularly Dr Jianyi Zhang, editor-in-Chief of the Current Cardiology Reviews series, for the kind invitation to participate in this editorial.

Chest pain is a common reason for presentation to the emergency department (ED). Absolute criteria for Acute Coronary Syndrome without ST elevation (NSTE-ACS) are lacking. An acute coronary syndrome (ACS) needs to be distinguished from a variety of other cardiac and non-cardiac diseases that may cause chest pain. For patients with confirmed ACS, several scoring methods can be applied in order to distinguish patients in the coronary care unit who may benefit most from therapies. The PURSUIT, TIMI, GRACE and FRISC risk scores are well validated with this respect. However, none of these risk scores has been used in the identification of an ACS in the emergency setting. The vast majority of patients with chest pain due to causes other than ACS were not evaluated in these trials. An evidence- based systematic stratification and policy for these patients does not currently exist. The more recently developed HEART score is specifically designed to stratify all chest pain patients in the ED. The HEART score was validated in a retrospective multicenter study and proved to be a strong predictor of event free survival on one hand and potentially life threatening cardiac events on the other hand. The HEART score facilitates risk stratification of chest pain patients in the ED.

Cardiovascular disease is the leading cause of death in Western countries and current research is still focusing on optimizing therapeutic approaches in the battle against this multifactorial disease. Concepts regarding the pathogenesis of many cardiovascular diseases originate from observations of human atherosclerotic tissue obtained from autopsies or during vascular surgery. These observations have helped us to disentangle the pathophysiology of atherosclerosis. However, identifying vulnerable patients, those prone to developing cardiovascular complications, remains difficult. The search for predictive cardiovascular biomarkers continues and large, well organized biobanks are needed to discover or validate novel biomarkers. Biobanks are an extremely valuable resource that enables us to study the influence of both genetic and environmental factors on the development of multifactorial diseases such as atherosclerosis. This review will focus on the advantages and pitfalls in atherosclerotic biobanking.

Background and purpose: Carotid Angioplasty and Stenting (CAS) has emerged as an alternative to Carotid Endarterectomy (CEA) in treatment of carotid stenotic disease. With increasing life expectancy clinicians are more often confronted with patients of higher age. Octogenarians were often excluded from randomized trials comparing CAS to CEA because they were considered high-risk for revascularization. Conflicting results on the peri-procedural outcome of carotid revascularization in these patients have been reported. In order to objectively evaluate whether age above 80 years should be an upper limit for indicating carotid revascularization we systematically reviewed the currently available literature. Methods: Literature was systematically reviewed between January 2000 and June 2010 using Pubmed and Embase, to identify all relevant studies concerning CAS and CEA in octogenarians. Inclusion criteria were 1) reporting outcome on either CEA or CAS; and 2) data subanalysis on treatment outcome by age. The 30-day Major Adverse Event (MAE) rate (disabling stroke, myocardial infarction or death) was extracted as well as demographic features of included patients. Results: After exclusion of 23 articles, 46 studies were included in this review, 18 involving CAS and 28 involving CEA. A total of 2.963 CAS patients and 14.365 CEA patients with an age >80 years were reviewed. The MAE rate was 6.9% (range 1.6 - 24.0%) following CAS and 4.2% (range 0 - 8.8%) following CEA. A separate analysis in this review included the results of one major registry 140.376 patients) analyzing CEA in octogenarians only reporting on 30-day mortality and not on neurological or cardiac adverse events. When these data were included the MAE following CEA is 2.4% (range 0 - 8.8%) Conclusions: MAE rates after CEA in octogenarians are comparable with the results of large randomized trials in younger patients. Higher complication rates are described for CAS in octogenarians. In general, age > 80 years is not an absolute cut off point to exclude patients from carotid surgery. In our opinion, CEA should remain the golden standard in the treatment of significant carotid artery stenoses, even in the very elderly.

Cardiovascular disease (CVD) is the number one cause of death globally, and the majority of CVD is caused by atherosclerosis. Atherosclerosis is a systemic inflammatory disease that leads to myocardial infarction, stroke and lower limb ischemia. Pathological studies have given insight to development of atherosclerosis and the importance of local plaque vulnerability, leading to thrombus formation and cardiovascular events. Due to the burden of cardiovascular disease, identification of patients at risk for cardiovascular events and treatment stratification is needed. The predictive power of classical risk factors is limited, especially in patients with manifest atherosclerosis. Imaging modalities have focused on the characteristics of the vulnerable plaque. However, it has become evident that not all so-called vulnerable plaques lead to rupture and subsequent thrombosis. The latter obviously limits the positive predictive value for imaging assessment of plaques and patients at risk. Serum biomarkers have also been studied extensively, but have very limited application in a clinical setting for risk stratification. In line with the important relation between vulnerable plaques and cardiovascular events, plaque biomarker studies have been initiated. These longitudinal studies are based on the concept, that a vulnerable plaque contains predictive information for future cardiovascular events, also in other territories of the vascular tree. Results look promising and plaque markers can be used to develop imaging modalities to identify patients at risk, or to monitor treatment effect. Plaque biomarker studies do not challenge the definition of the vulnerable plaque, but use its concept in favor of prediction improvement for vascular patients.

Introduction: In patients with carotid artery stenosis histological plaque composition is associated with plaque stability and with presenting symptomatology. Preferentially, plaque vulnerability should be taken into account in pre-operative work-up of patients with severe carotid artery stenosis. However, currently no appropriate and conclusive (non-) invasive technique to differentiate between the high and low risk carotid artery plaque in vivo is available. We propose that 7 Tesla human high resolution MRI scanning will visualize carotid plaque characteristics more precisely and will enable correlation of these specific components with cerebral damage. Study objective: The aim of the PlaCD-7T study is 1: to correlate 7T imaging with carotid plaque histology (gold standard); and 2: to correlate plaque characteristics with cerebral damage ((clinically silent) cerebral (micro) infarcts or bleeds) on 7 Tesla high resolution (HR) MRI. Design: We propose a single center prospective study for either symptomatic or asymptomatic patients with haemodynamic significant (70%) stenosis of at least one of the carotid arteries. The Athero-Express (AE) biobank histological analysis will be derived according to standard protocol. Patients included in the AE and our prospective study will undergo a pre-operative 7 Tesla HR-MRI scan of both the head and neck area. Discussion: We hypothesize that the 7 Tesla MRI scanner will allow early identification of high risk carotid plaques being associated with micro infarcted cerebral areas, and will thus be able to identify patients with a high risk of periprocedural stroke, by identification of surrogate measures of increased cardiovascular risk.

The autonomic nervous system interacts in the pathophysiology of heart failure. Dysfunction of the sympathetic nervous system has been identified as an important prognostic marker in patients with chronic heart failure. At present, cardiac sympathetic nerve imaging with 123-iodine metaiodobenzylguanidine [123-I MIBG] has been employed most frequently for the assessment of cardiac sympathetic innervation and activation pattern. The majority of studies have shown that cardiac sympathetic dysfunction as assessed with 123-I MIBG imaging is a powerful predictor for heart failure mortality and morbidity. Additionally, 123-I MIBG imaging can be used for prediction of potentially lethal ventricular tachyarrhythmias in heart failure patients. At present however, the lack of standardization of 123-I MIBG imaging procedures represents an evident issue. Standardized criteria on the use of 123-I MIBG imaging will further strengthen the clinical use of 123-I MIBG imaging in heart failure patients.

Compensation is a self-protective mechanism in diseases, which may lead to a unique form of homeostasis deviates from that in physiological conditions. The kind of compensatory homeostasis can be embodied as various degrees accompanying disease progression (denoted as compensatory degree). Compensatory homeostasis provides a window for the transition from disease to healthy state. The causes of compensatory homeostasis themselves may be identified as targets for effective measures to eliminate compensation. Compensatory homeostasis embodies significantly mostly in the developing process of chronic diseases, which may help to explain in theory why intensive therapeutic strategies led to unexpected outcome in clinical practice. In addition, a large body of clinical evidence has valued traditional Chinese medicine (TCM), which is based on shifting compensatory homeostasis to the overall human body homeostasis, complementary to Western medicine in the management of chronic disease. In this review, we will briefly summarize the concept of compensation and attempt to bridge Western and traditional Chinese medicine through homeostasis and compensatory homeostasis based on an ample of evidence obtained from both disciplines.

Heyde's syndrome is the association between calcific aortic stenosis and gastrointestinal bleeding due to angiodysplasia. Alterations in von Willebrand factor due to turbulence across the diseased aortic valve have been incriminated in the pathophysiology of this syndrome. Replacement of the aortic valve has been reported to stop the bleeding, but this is debatable. Along with a review of the relevant medical literature, we hereby report a 68 year old patient with aortic stenosis and severe recurrent gastrointestinal bleeding that completely subsided following aortic valve replacement.