Abnormal Coronary Reactivity Research Articles

The role of coronary reactivity testing in women with no obstructive coronary artery disease.

Two-thirds of women with signs and symptoms of ischemia and no obstructive coronary artery disease (INOCA) have abnormal coronary reactivity. These women are challenging to assess, diagnose and manage because of a lack of evidence-based guidelines. Furthermore, they are considered to be at 'low risk' by most physicians, often receive no specific therapy and tend to be dismissed from subspecialty care. Coronary reactivity testing (CRT) is considered the reference-standard for evaluation of epicardial and microvascular coronary function in response to various vasoactive agents. It provides a comprehensive vascular function assessment for diagnosis, a guide for management, and has prognostic benefit that outweighs the risk of the procedure. We recently demonstrated the prognostic value of assessing coronary vascular reactivity in women with signs and symptoms of ischemia, especially those with no obstructive coronary artery disease. Invasive CRT is a feasible, useful method to identify coronary microvascular dysfunction (CMD) and risk stratify women with INOCA. It has a comparable safety record with other invasive procedures. Future research is directed at optimizing patient selection, streamlining of invasive CRT methods using user-friendly catheters to enhance feasibility in the routine clinical setting, and optimizing treatment protocols, with clinical trials designed to evaluate outcomes.

Coronary Artery Spasm, Coronary Reactivity, and Their Psychological Context.

Symptomatic individuals suspected of having myocardial ischemia often have no obstructive atherosclerotic narrowing of epicardial coronary arteries. Abnormal coronary vascular reactivity and, in particular, coronary artery vasospasm (CAS) may be an explanation in a subset of these patients. Psychological factors play an important role in ischemic heart disease, but their role in CAS is not clear; autonomic dysfunction and increased inflammation are two prevailing pathophysiological mechanisms implicated in abnormal coronary reactivity resulting from mental health conditions. Interrelationships between psychological factors, abnormal coronary reactivity, and sex/gender differences are poorly defined in the etiology of CAS. In this issue of Psychosomatic Medicine (2019;81:237-245), Hung et al. report a frequency of less than 0.1% of new-onset CAS in the Taiwanese population, with higher occurrence in women and younger individuals. Patients with CAS had a higher prevalence of previous anxiety and depression compared with those with coronary artery disease and controls, with no sex differences. In this editorial comment, we discuss the potential reasons for underreporting of CAS and the challenges regarding the use of administrative health records for psychosomatic research. In this editorial, a model is presented to explain the association between emotional stressors and mental health factors with CAS, including the role of sympathetic nervous system activation, inflammation, oxidative stress, endothelial dysfunction, and smooth muscle cell dysregulation.

Impact of Abnormal Coronary Reactivity on Long-Term Clinical Outcomes in Women

BackgroundCurrently as many as one-half of women with suspected myocardial ischemia have no obstructive coronary artery disease (CAD), and abnormal coronary reactivity (CR) is commonly found. ObjectivesThe authors prospectively investigated CR and longer-term adverse cardiovascular outcomes in women with and with no obstructive CAD in the National Heart, Lung, and Blood Institute–sponsored WISE (Women’s Ischemia Syndrome Evaluation) study. MethodsWomen (n = 224) with signs and symptoms of ischemia underwent CR testing. Coronary flow reserve and coronary blood flow were obtained to test microvascular function, whereas epicardial CR was tested by coronary dilation response to intracoronary (IC) acetylcholine and IC nitroglycerin. All-cause mortality, major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, stroke, and heart failure), and angina hospitalizations served as clinical outcomes over a median follow-up of 9.7 years. ResultsThe authors identified 129 events during the follow-up period. Low coronary flow reserve was a predictor of increased MACE rate (hazard ratio [HR]: 1.06; 95% confidence interval [CI]: 1.01 to 1.12; p = 0.021), whereas low coronary blood flow was associated with increased risk of mortality (HR: 1.12; 95% CI: 1.01 to 1.24; p = 0.038) and MACE (HR: 1.11; 95% CI: 1.03 to 1.20; p = 0.006) after adjusting for cardiovascular risk factors. In addition, a decrease in cross-sectional area in response to IC acetylcholine was associated with higher hazard of angina hospitalization (HR: 1.05; 95% CI: 1.02 to 1.07; p < 0.0001). There was no association between epicardial IC-nitroglycerin dilation and outcomes. ConclusionsOn longer-term follow-up, impaired microvascular function predicts adverse cardiovascular outcomes in women with signs and symptoms of ischemia. Evaluation of CR abnormality can identify those at higher risk of adverse outcomes in the absence of significant CAD. (Women's Ischemia Syndrome Evaluation [WISE]; NCT00000554)

100.65 Abnormal Coronary Reactivity is Associated With Atrial Fibrillation Development: Is Atrial Fibrillation a Vascular Disease?

Coronary artery disease (CAD) risk factors are associated with atrial fibrillation (AF) and impaired endothelial function. We hypothesized that an abnormal coronary reactivity test (Abn-CRT) is associated with AF in patients with non-obstructive CAD. Three hundred patients with chest pain, non-

Gender and microvascular angina.

There are gender differences in the presentation, diagnosis, and treatment of chest pain. When compared to men, women may have more atypical presentations of chest pain. In addition, current diagnostic tools are often not definitive regarding cardiac etiology for chest pain in women. The current diagnostic model of chest pain focuses on significant obstructions within the large coronary arteries as the cause for angina. Microvascular angina (MVA) represents an under-recognized pathophysiologic mechanism that may explain the apparent disparities and elucidate an etiology for the common finding in women of chest pain, ischemia on stress testing, and no obstructive coronary artery disease (CAD) on angiography in the presence of abnormal coronary reactivity testing. Endothelial dysfunction, estrogen deficiency, and abnormal nociception play a role in the pathophysiology of MVA. Treatments are targeted toward these underlying mechanisms. Recognizing the role gender and other pathophysiologic models of chest pain can play in the work-up and treatment of angina may identify a treatable cardiac condition, that would otherwise be discounted as non-cardiac in origin.

Lipoprotein-associated phospholipase A2, a marker of vascular inflammation and systemic vulnerability

As interventional cardiologists, we are sometimes prone to believe that plaque quantity, more than plaque biology, is a determinant of patients' prognosis. This concept is unfortunately challenged in daily practice, as accelerated progression of atherosclerosis, rupture of a plaque that was not critical at angiography, and/or dynamic phenomena such as spasm contribute to determine the patient's prognosis. That the extent and severity of coronary artery disease at angiography is a strong prognostic index for the risk of subsequent (cardio)vascular events is not under discussion. However, our understanding of plaque progression and instability remains far from complete. In line with this concept, Lavi et al. recently reported that the presence of an abnormal coronary reactivity to an endothelium-dependent stimulus identifies areas occupied by plaques with a larger necrotic core, i.e. at higher risk for rupture.1 In addition, a number of studies and anecdotal evidence have shown that endothelial dysfunction and/or oxidative stress, systemic or local, may predict disease progression/instability and overall patient prognosis.2 Although it needs to be acknowledged that the best therapeutic strategy for plaques that are histologically vulnerable but cause no severe stenosis at angiography remains unexplored, the search for new markers and techniques that help in detecting vulnerable plaques and vulnerable patients should be considered a priority of modern cardiology. An effort in this direction is presented by Herrmann et al. 3 who describe the important role of lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and activity, as measured at the level of carotid plaques, in predicting future cardiovascular events. This concept provides further support for the idea that atherosclerosis is a systemic disease, and that plaque activation in a given vascular district is associated with a global increased cardio- or cerebrovascular risk. PLA2s belong to a superfamily that contains 15 separate groups and … *Corresponding author. Tel: +49 6131 17 7250, Fax: +49 6131 17 6615, Email: tmuenzel{at}uni-mainz.de