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      How to Diagnose and Manage Angina Without Obstructive Coronary Artery Disease: Lessons from the British Heart Foundation CorMicA Trial

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          Abstract

          Patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (INOCA) present a diagnostic and therapeutic challenge. Microvascular and/or vasospastic angina are the two most common causes of INOCA; however, invasive coronary angiography lacks the sensitivity to diagnose these functional coronary disorders. In this article, the authors summarise the rationale for invasive testing in the absence of obstructive coronary disease, namely that correct treatment for angina patients starts with the correct diagnosis. They provide insights from the CORonary MICrovascular Angina (CorMicA) study, where an interventional diagnostic procedure was performed with linked medical therapy to improve patient health. Identification of these distinct disorders (microvascular angina, vasospastic angina or non-cardiac chest pain) is key for stratifying INOCA patients, allowing prognostic insights and better patient care with linked therapy based on contemporary guidelines. Finally, they propose a framework to diagnose and manage patients in this common clinical scenario.

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          Most cited references48

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          Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction.

          Coronary endothelial dysfunction is characterized by vasoconstrictive response to the endothelium-dependent vasodilator acetylcholine. Although endothelial dysfunction is considered an early phase of coronary atherosclerosis, there is a paucity of information regarding the outcome of these patients. Thus, this study was designed to evaluate the outcome of patients with mild coronary artery disease on the basis of their endothelial function. Follow-up was obtained in 157 patients with mildly diseased coronary arteries who had undergone coronary vascular reactivity evaluation by graded administration of intracoronary acetylcholine, adenosine, and nitroglycerin and intracoronary ultrasound at the time of diagnostic study. Patients were divided on the basis of their response to acetylcholine into 3 groups: group 1 (n=83), patients with normal endothelial function; group 2 (n=32), patients with mild endothelial dysfunction; and group 3 (n=42), patients with severe endothelial dysfunction. Over an average 28-month follow-up (range, 11 to 52 months), none of the patients from group 1 or 2 had cardiac events. However, 6 (14%) with severe endothelial dysfunction had 10 cardiac events (P<0.05 versus groups 1 and 2). Cardiac events included myocardial infarction, percutaneous or surgical coronary revascularization, and/or cardiac death. Severe endothelial dysfunction in the absence of obstructive coronary artery disease is associated with increased cardiac events. This study supports the concept that coronary endothelial dysfunction may play a role in the progression of coronary atherosclerosis.
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            Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events.

            Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus. We identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD (P< 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27-1.83) for patients with normal coronary arteries and 1.85 (1.51-2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07-1.56) and 1.52 (1.24-1.88), respectively. Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
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              International standardization of diagnostic criteria for microvascular angina.

              Standardization of diagnostic criteria for ischemic symptoms due to coronary microvascular dysfunction (CMD) is needed for further investigation of patients presenting with anginal chest pain consistent with "microvascular angina" (MVA). At the annual Coronary Vasomotion Disorders International Study Group (COVADIS) Summits held in August 2014 and 2015, the following criteria were agreed upon for the investigative diagnosis of microvascular angina: (1) presence of symptoms suggestive of myocardial ischemia; (2) objective documentation of myocardial ischemia, as assessed by currently available techniques; (3) absence of obstructive CAD ( 0.80) (4) confirmation of a reduced coronary blood flow reserve and/or inducible microvascular spasm. These standardized criteria provide an investigative structure for mechanistic, diagnostic, prognostic and clinical trial studies aimed at developing an evidence base needed for guidelines in this growing patient population. Standardized criteria will facilitate microvascular angina registries and recruitment of suitable patients into clinical trials. Mechanistic research will also benefit from the implementation of standardized diagnostic criteria for MVA.
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                Author and article information

                Journal
                Interv Cardiol
                Interv Cardiol
                ICR
                Interventional Cardiology Review
                Radcliffe Cardiology
                1756-1477
                1756-1485
                21 May 2019
                May 2019
                : 14
                : 2
                : 76-82
                Affiliations
                [1. ] West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital UK
                [2. ] British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow UK
                Author notes

                Disclosure: TJF has no conflicts of interest. CB is employed by the University of Glasgow, which holds consultancy and research agreements with companies that have commercial interests in the diagnosis and treatment of angina. These companies include Abbott Vascular, AstraZeneca, Boehringer Ingelheim, GSK, Menarini Pharmaceuticals, Opsens, Philips and Siemens Healthcare. CorMicA study is an investigator-initiated clinical trial that was funded by the British Heart Foundation (PG/17/2532884; RE/13/5/30177; RE/18/634217). Clinicaltrials.gov: NCT03193294.

                Correspondence: Tom J Ford, British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK. E: tom.ford@ 123456glasgow.ac.uk
                Article
                10.15420/icr.2019.04.R1
                6545998
                31178933
                0ea879e2-8df5-42ef-927e-04e92791b716
                Copyright © 2019, Radcliffe Cardiology

                This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

                History
                : 10 February 2019
                : 17 April 2019
                Page count
                Pages: 7
                Categories
                Coronary

                stable angina pectoris,elective coronary angiography,microvascular angina,vasospastic angina,coronary vasoreactivity testing,coronary physiology,ischaemia

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