Assessment of Vascular Dysfunction in Patients Without Obstructive Coronary Artery Disease: Why, How, and When.

Ischemic heart disease secondary to coronary vascular dysfunction causes angina and impairs quality of life and prognosis. About one-half of patients with symptoms and signs of ischemia turn out not to have obstructive coronary artery disease, and coronary vascular dysfunction may be relevant. Adjunctive tests of coronary vasomotion include guidewire-based techniques with adenosine and reactivity testing, typically by intracoronary infusion of acetylcholine. The CorMicA (Coronary Microvascular Angina) trial provided evidence that routine management guided by an interventional diagnostic procedure and stratified therapy improves angina and quality of life in patients with angina but no obstructive coronary artery disease. In this paper, the COVADIS study group provide a comprehensive review of why, how, and when coronary vascular dysfunction should be assessed invasively. They discuss the rationale through a shared understanding of vascular pathophysiology and clinical evidence. They propose a consensus approach to how an interventional diagnostic procedure is performed with focus on practical aspects. Finally, the authors discuss the clinical scenarios in patients with stable and acute coronary syndromes in which measurement of coronary vascular function may be helpful for patient care.

Mechanisms and diagnostic evaluation of persistent or recurrent angina following percutaneous coronary revascularization.

Persistence or recurrence of angina after a percutaneous coronary intervention (PCI) may affect about 20-40% of patients during short-medium-term follow-up. This appears to be true even when PCI is 'optimized' using physiology-guided approaches and drug-eluting stents. Importantly, persistent or recurrent angina post-PCI is associated with a significant economic burden. Healthcare costs may be almost two-fold higher among patients with persistent or recurrent angina post-PCI vs. those who become symptom-free. However, practice guideline recommendations regarding the management of patients with angina post-PCI are unclear. Gaps in evidence into the mechanisms of post-PCI angina are relevant, and more research seems warranted. The purpose of this document is to review potential mechanisms for the persistence or recurrence of angina post-PCI, propose a practical diagnostic algorithm, and summarize current knowledge gaps.

Individualized cardiovascular risk assessment by cardiovascular magnetic resonance.

Cardiovascular magnetic resonance (CMR) is gaining clinical importance in preventive medicine. Evidence on diagnostic accuracy and prognostic value, in addition to the development of faster imaging, increased availability of equipment and imaging expertise have led to a wide-spread use of CMR in a growing number of clinical indications. The first part of this review summarizes the role of CMR biomarkers for risk assessment focusing on the patients groups that benefit from the use of CMR. In the second part, the future directions for CMR are discussed and their role in prevention of cardiovascular disease.

Noninvasive assessment of endothelial function in clinical practice.

In the fight against cardiovascular diseases, preventive strategies are becoming the focus of attention. One of these strategies proposes to identify individuals who are at a high risk of developing cardiovascular disease. Endothelial dysfunction could improve patient risk stratification and the implementation of preventive strategies. In this review we focus on noninvasive techniques that have recently become available to assess endothelial function: flow-mediated vasodilation as measured by ultrasound of the brachial artery, pulse wave analysis, and finger plethysmography during postischemic hyperemia. We describe the basic principles, the main protocols to perform these techniques, and their clinical value based on the scientific evidence.

Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery.

OBJECTIVE: To determine the effectiveness and cost effectiveness of using information from circulating biomarkers to inform the prioritisation process of patients with stable angina awaiting coronary artery bypass graft surgery. DESIGN: Decision analytical model comparing four prioritisation strategies without biomarkers (no formal prioritisation, two urgency scores, and a risk score) and three strategies based on a risk score using biomarkers: a routinely assessed biomarker (estimated glomerular filtration rate), a novel biomarker (C reactive protein), or both. The order in which to perform coronary artery bypass grafting in a cohort of patients was determined by each prioritisation strategy, and mean lifetime costs and quality adjusted life years (QALYs) were compared. DATA SOURCES: Swedish Coronary Angiography and Angioplasty Registry (9935 patients with stable angina awaiting coronary artery bypass grafting and then followed up for cardiovascular events after the procedure for 3.8 years), and meta-analyses of prognostic effects (relative risks) of biomarkers. RESULTS: The observed risk of cardiovascular events while on the waiting list for coronary artery bypass grafting was 3 per 10,000 patients per day within the first 90 days (184 events in 9935 patients). Using a cost effectiveness threshold of pound20,000- pound30,000 (euro22,000-euro33,000; $32,000-$48,000) per additional QALY, a prioritisation strategy using a risk score with estimated glomerular filtration rate was the most cost effective strategy (cost per additional QALY was < pound410 compared with the Ontario urgency score). The impact on population health of implementing this strategy was 800 QALYs per 100,000 patients at an additional cost of pound 245,000 to the National Health Service. The prioritisation strategy using a risk score with C reactive protein was associated with lower QALYs and higher costs compared with a risk score using estimated glomerular filtration rate. CONCLUSION: Evaluating the cost effectiveness of prognostic biomarkers is important even when effects at an individual level are small. Formal prioritisation of patients awaiting coronary artery bypass grafting using a routinely assessed biomarker (estimated glomerular filtration rate) along with simple, routinely collected clinical information was cost effective. Prioritisation strategies based on the prognostic information conferred by C reactive protein, which is not currently measured in this context, or a combination of C reactive protein and estimated glomerular filtration rate, is unlikely to be cost effective. The widespread practice of using only implicit or informal means of clinically ordering the waiting list may be harmful and should be replaced with formal prioritisation approaches.

Neopterin for risk assessment in angina pectoris.

Inflammation plays a major pathogenic role in atherosclerosis and its complications. Among the inflammatory cells that take part in this process, activated macrophages contribute significantly to atherosclerotic plaque progression, fibrous cap disruption and intracoronary thrombus formation. Neopterin, a pteridine derivative and a byproduct of the guanosine triphosphate-biopterin pathway, is mainly produced by activated macrophages. This article reviews the existing evidence suggesting an important role for neopterin as a marker for cardiovascular risk and also as a possible pathogenic factor in atherosclerosis.

A review of methods for assessment of coronary microvascular disease in both clinical and experimental settings.

Obstructive disease of the large coronary arteries is the prominent cause for angina pectoris. However, angina may also occur in the absence of significant coronary atherosclerosis or coronary artery spasm, especially in women. Myocardial ischaemia in these patients is often associated with abnormalities of the coronary microcirculation and may thus represent a manifestation of coronary microvascular disease (CMD). Elucidation of the role of the microvasculature in the genesis of myocardial ischaemia and cardiac damage-in the presence or absence of obstructive coronary atherosclerosis-will certainly result in more rational diagnostic and therapeutic interventions for patients with ischaemic heart disease. Specifically targeted research based on improved assessment modalities is needed to improve the diagnosis of CMD and to translate current molecular, cellular, and physiological knowledge into new therapeutic options.

A comparative study of markers of inflammation for the assessment of cardiovascular risk in patients presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome.

BACKGROUND: The role of inflammation in the pathogenesis of acute coronary syndrome (ACS) is established. Little is known however, regarding the use of inflammatory markers as predictors of future cardiovascular events in patients presenting to the emergency department (ED) with suspected ACS. HYPOTHESIS: To assess whether biomarkers that predict cardiovascular risk in apparently healthy individuals and coronary artery disease patients are useful predictors of future cardiovascular events in patients presenting to the ED with chest pain suggestive of ACS. METHODS: We compared the abilities of serum C-reactive protein (hs-CRP), albumin and leukocyte count to identify subjects with ACS and those who are at high risk of developing events during a 30-day follow-up. RESULTS: 144 patients (mean age 62+/-13 years, 45 female) presenting to the ED <3 h after the onset of symptoms suggestive of ACS were evaluated. Final hospital diagnoses were non-ischemic chest pain in 43 (30%) and ACS in 101 (70%) patients. Patients with ACS had significantly higher leukocyte count (p<0.0001) and hs-CRP levels (p<0.02) and lower albumin concentrations, compared to patients with NICP (p<0.0001). Lower albumin concentrations (p=0.03) and hs-CRP (p=0.049) were predictors of recurrent events at 30 days. On multivariate analysis, however, only leukocyte count was a predictor of ACS (OR 20.9; 95% CI: 3.7-19.5; p=0.01) and high hs-CRP levels were a predictor of clinical outcome (OR 2.8; 95% CI: 1.5-5.2; p=0.001). CONCLUSIONS: Leukocyte count is an independent predictor of ACS in patients presenting to the ED with chest pain suggestive of ACS and high hs-CRP levels are an independent predictor of clinical outcome in ACS patients.