Clinical aspects of ischemia with no obstructive coronary artery disease (INOCA).

Ischemia with no obstructive coronary arteries (INOCA) is defined as patients with evidence of myocardial ischemia without obstructive coronary artery disease. About 3-4 million people in the United States have INOCA, more commonly affecting women, and carries adverse morbidity, mortality, and relatively high healthcare costs. The pathophysiology of INOCA appears to be multi-factorial with a variety of contributing mechanisms. Diagnosis of INOCA is suggested by non-invasive or invasive testing consistent with myocardial ischemia. Due to the high prevalence of coronary risk factors and atherosclerosis in the INOCA population, current treatment strategies target angina, coronary atherosclerosis, and atherosclerotic risk factors, as well as burgeoning treatment of coronary microvascular dysfunction (CMD). Ongoing clinical trials are assessing different options.

Contemporary Diagnosis and Management of Patients with MINOCA.

PURPOSE OF REVIEW: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is defined as acute myocardial infarction (MI) with angiographically no obstructive coronary artery disease or stenosis ≤ 50%. MINOCA is diagnostically challenging and complex, making it difficult to manage effectively. This condition accounts for 6-8% of all MI and poses an increased risk of morbidity and mortality after diagnosis. Prompt recognition and targeted management are essential to improve outcomes and our understanding of this condition, but this process is not yet standardized. This article offers a comprehensive review of MINOCA, delving deep into its unique clinical profile, invasive and noninvasive diagnostic strategies for evaluating MINOCA in light of the lack of widespread availability for comprehensive testing, and current evidence surrounding targeted therapies for patients with MINOCA. RECENT FINDINGS: MINOCA is not uncommon and requires comprehensive assessment using various imaging modalities to evaluate it further. MINOCA is a heterogenous working diagnosis that requires thoughtful approach to diagnose the underlying disease responsible for MINOCA further.

Can allostatic load in pregnancy explain the association between race and subsequent cardiovascular disease risk: A cohort study.

OBJECTIVE: To assess the relationship between allostatic load, a measure of cumulative chronic stress in early pregnancy and cardiovascular disease risk, 2-7 years postpartum, and pathways contributing to racial disparities in cardiovascular disease risk. DESIGN: Secondary analysis of a prospective cohort study. SETTING MULTICENTER POPULATION: Pregnant women. METHODS: Our primary exposure was high allostatic load in the first trimester, defined as at least 4 of 12 biomarkers (systolic blood pressure, diastolic blood pressure, body mass index, cholesterol, low-density lipoprotein, high-density lipoprotein, high-sensitivity C-reactive protein, triglycerides, insulin, glucose, creatinine and albumin) in the unfavourable quartile. Logistic regression was used to test the association between high allostatic load and main outcome adjusted for confounders: time from index pregnancy and follow up, age, education, smoking, gravidity, bleeding in the first trimester, index adverse pregnancy outcomes, and health insurance. Each main outcome component and allostatic load were analysed secondarily. Mediation and moderation analyses assessed the role of high allostatic load in racial disparities of cardiovascular disease risk. MAIN OUTCOME MEASURE: Incident cardiovascular disease risk: hypertension, or metabolic disorders. RESULTS: Cardiovascular disease risk was identified in 1462/4022 individuals (hypertension: 36.6%, metabolic disorder: 15.4%). After adjustment, allostatic load was associated with cardiovascular disease risk (adjusted odds ratio [aOR] 2.0, 95% CI 1.8-2.3), hypertension (aOR 2.1, 95% CI 1.8-2.4) and metabolic disorder (aOR 1.7, 95% CI 1.5-2.1). Allostatic load was a partial mediator between race and cardiovascular disease risk. Race did not significantly moderate this relationship. CONCLUSIONS: High allostatic load during pregnancy is associated with cardiovascular disease risk. The relationships between stress, subsequent cardiovascular risk and race warrant further study.

Factors associated with duration of breastfeeding in women giving birth for the first time.

OBJECTIVE: To examine maternal, psychosocial, and pregnancy factors associated with breastfeeding for at least 6 months in those giving birth for the first time. METHODS: We performed a planned secondary analysis of an observational cohort study of 5249 women giving birth for the first time. Women were contacted at least 6 months after delivery and provided information regarding breastfeeding initiation, duration, and exclusivity. Maternal demographics, psychosocial measures, and delivery methods were compared by breastfeeding groups. RESULTS: 4712 (89.8%) of the women breastfed at some point, with 2739 (58.2%) breastfeeding for at least 6 months. Of those who breastfed, 1161 (24.7% of the entire cohort), breastfed exclusively for at least 6 months. In the multivariable model among those who ever breastfed, not smoking in the month prior to delivery (adjusted odds ratio [aOR] 2.04, 95%CI 1.19-3.45), having a Master's degree of higher (aOR 1.89, 95%CI 1.51-2.36), having a planned pregnancy (aOR 1.48, 95%CI 1.27-1.73), older age (aOR 1.02, 95% CI, 1.01-1.04), lower BMI (aOR 0.96 95% CI 0.95-0.97), and having less anxiety measured during pregnancy (aOR 0.990, 95%CI 0.983-0.998) were associated with breastfeeding for at least 6 months. Compared to non-Hispanic White women, Hispanic women, while being more likely to breastfeed initially (aOR 1.40, 95%CI 1.02-1.92), were less likely to breastfeed for 6 months (aOR 0.72, 95%CI 0.59-0.88). While non-Hispanic Black women were less likely than non-Hispanic White women to initiate breastfeeding (aOR 0.68, 95%CI 0.51-0.90), the odds of non-Hispanic Black women of continuing to breastfeed for at least 6 months was similar to non-Hispanic White women (aOR 0.92, 95%CI 0.71-1.19). CONCLUSIONS: In this cohort of women giving birth for the first time, duration of breastfeeding was associated with several characteristics which highlight groups at greater risk of not breastfeeding as long as currently recommended. TRIAL REGISTRATION: NCT01322529 (nuMoM2b) and NCT02231398 (nuMoM2b-Heart Health).

Subclinical cardiovascular disease and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) impacts approximately 6%-10% of women worldwide, with hallmark features of hyperandrogenism, irregular menses, infertility, and polycystic appearing ovaries on ultrasound. In addition, PCOS is associated with several endocrine and metabolic disorders, including obesity, insulin resistance and diabetes mellitus, hypertension, dyslipidemia and metabolic syndrome, which all increase the risk for subclinical cardiovascular disease (CVD), the presence of altered vascular endothelium without overt CVD. In this review, we summarize the most recent literature regarding subclinical CVD in women with PCOS, including markers such as flow-mediated dilation, arterial stiffness, coronary artery calcium scores, carotid intima-media thickness and visceral and epicardial fat.

Skin sympathetic nerve activity in patients with chronic orthostatic intolerance.

BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by the development of tachycardia and other symptoms when assuming an upright body position. OBJECTIVE: The purpose of this study was to test the hypothesis that skin sympathetic nerve activity (SKNA) bursts are specific symptomatic biomarkers in patients with chronic OI. METHODS: We used an electrocardiogram monitor with a built-in triaxial accelerometer to simultaneously record SKNA and posture in ambulatory participants. Study 1 compared chronic OI (14 women and 2 men; mean age 35 ± 10 years) with reference control participants (14 women; mean age 31 ± 6 years). Study 2 included 17 participants with chronic OI (15 women and 2 men; mean age 39 ± 12 years) not yet treated with ivabradine, pyridostigmine, or ß-blockers. RESULTS: In study 1, there were 124 episodes (8 ± 4 per participant) of postural changes, with 11 episodes (8.9%) associated with symptoms. In comparison, 0 of 104 postural changes (7 ± 3 per participant) in controls were symptomatic (P = .0011). In participants with chronic OI, the SKNA bursts associated with symptoms had higher burst frequencies, longer burst durations, and larger mean burst areas than did bursts during asymptomatic periods. However, SKNA bursts and tachycardia were asymptomatic in controls. We analyzed 110 symptomatic episodes in study 2 (6 ± 5 per participant). Among them, 98 (89.1%) followed at least 1 SKNA burst. In comparison, only 41 (37.3%) had heart rate exceed 100 beats/min 1 minute before symptom onset (P < .0001). CONCLUSION: SKNA bursts are a highly specific, albeit insensitive, symptomatic biomarker for chronic OI.

Childbearing Among Women Cardiologists: The Interface of Experience, Impact, and the Law.

BACKGROUND: Maternity leave is highly variable in the United States given the lack of a federal workforce mandate. OBJECTIVES: The purpose of this study was to describe the experiences and impact of childbearing on women cardiologists and their careers, within a legal framework. METHODS: A survey was sent to women cardiologists, asking about their experiences while pregnant and on maternity leave. The incidence of complications and career impacts on the cardiologists was assessed. RESULTS: Of 323 respondents who had been pregnant as a practicing cardiologist, extra service or call before maternity leave was required in 37.2%. Of those who performed extra service or call, 17.5% were placed on bedrest before delivery, compared with 7.4% who did not perform extra service or call (P = 0.005). During the year of pregnancy, 41.2% experienced a salary decrease; only 7.4% had their relative value units prorated for time on maternity leave; 23.2% had no paid maternity leave. Self-reported pregnancy complications occurred in 36.5%, those with complications had a 60% greater chance of reporting that pregnancy adversely affected their career, compared with those without complications. Nearly three-fourths (237 respondents) reported experiencing at least one of several troubling practices that are illegal in many circumstances. CONCLUSIONS: Women cardiologists report wide variances in maternity leave in the United States, with many experiencing likely violations of the Family and Medical Leave Act or other statues. Childbearing issues in cardiologists should be addressed to improve the professional and personal lives of women cardiologists and the attractiveness of cardiology to potential trainees.

Association between aspirin use during pregnancy and cardiovascular risk factors 2-7 years after delivery: The nuMoM2b Heart Health Study.

OBJECTIVES: To evaluate the association between aspirin use during first pregnancy and later maternal cardiovascular risk. STUDY DESIGN: In this secondary analysis of a prospective cohort, we included participants who carried their first pregnancy to 20 + weeks, had data regarding aspirin use, and attended a study visit 2-7 years following delivery. The exposure was aspirin use during the first pregnancy. We calculated aspirin use propensity scores from logistic regression models including baseline variables associated with aspirin use in pregnancy and cardiovascular risk. Outcomes of interest were incident cardiovascular-related diagnoses 2-7 years following delivery. Robust Poisson regression calculated the risk of outcomes by aspirin exposure, adjusting for the aspirin use propensity score. MAIN OUTCOME MEASURES: The primary outcome was a composite of incident cardiovascular diagnoses at the time of the study visit: cardiovascular events, chronic hypertension, metabolic syndrome, prediabetes or type 2 diabetes, dyslipidemia, and chronic kidney disease. RESULTS: Of 4,480 women included, 84 (1.9%) reported taking aspirin during their first pregnancy. 52.6% of participants in the aspirin-exposed group and 43.0% in the unexposed group had the primary outcome. After adjusting for the aspirin use propensity scores, aspirin use during the first pregnancy was not associated with any of the outcomes. CONCLUSION: We did not detect an association between aspirin use during the first pregnancy and cardiovascular-related diagnoses 2-7 years later. Our study was only powered to detect a large difference in relative risk, so we cannot rule out a smaller difference that may be clinically meaningful.

Coronary Optical Coherence Tomography and Cardiac Magnetic Resonance Imaging to Determine Underlying Causes of Myocardial Infarction With Nonobstructive Coronary Arteries in Women.

BACKGROUND: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6% to 15% of myocardial infarctions (MIs) and disproportionately affects women. Scientific statements recommend multimodality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) imaging to assess mechanisms of MINOCA. METHODS: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of myocardial infarction. If invasive coronary angiography revealed <50% stenosis in all major arteries, multivessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and nonischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible. RESULTS: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intraplaque cavity, or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% (62/116) of participants undergoing CMR. A nonischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome, or nonischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% (98/116) of the women with multimodality imaging, higher than with OCT alone (P<0.001) or CMR alone (P=0.001). An ischemic cause was identified in 63.8% of women with MINOCA (74/116), a nonischemic cause was identified in 20.7% (24/116) of the women, and no mechanism was identified in 15.5% (18/116). CONCLUSIONS: Multimodality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, 75.5% of which were ischemic and 24.5% of which were nonischemic, alternate diagnoses to myocardial infarction. Identification of the cause of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02905357.

Sex and gender: modifiers of health, disease, and medicine.

Clinicians can encounter sex and gender disparities in diagnostic and therapeutic responses. These disparities are noted in epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment. This Review discusses the fundamental influences of sex and gender as modifiers of the major causes of death and morbidity. We articulate how the genetic, epigenetic, and hormonal influences of biological sex influence physiology and disease, and how the social constructs of gender affect the behaviour of the community, clinicians, and patients in the health-care system and interact with pathobiology. We aim to guide clinicians and researchers to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.

Left ventricular mass and myocardial scarring in women with hypertensive disorders of pregnancy.

AIMS: Hypertensive disorders of pregnancy (HDP) predict future cardiovascular events. We aim to investigate relations between HDP history and subsequent hypertension (HTN), myocardial structure and function, and late gadolinium enhancement (LGE) scar. METHODS AND RESULTS: We evaluated a prospective cohort of women with suspected ischaemia with no obstructive coronary artery disease (INOCA) who underwent stress/rest cardiac magnetic resonance imaging (cMRI) with LGE in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction study. Self-reported history of pregnancy and HDP (gestational HTN, pre-eclampsia, toxaemia and eclampsia) were collected at enrollment. In our cohort of 346, 20% of women report a history of HDP. HDP history was associated with 3.2-fold increased odds of HTN. Women with a history of both HDP and HTN had higher cMRI measured left ventricular (LV) mass compared with women with HDP only (99.4±2.6 g vs 87.7±3.2 g, p=0.02). While we found a similar frequency of LGE scar, we observed a trend towards increased LGE scar size (5.1±3.4 g vs 8.0±3.4 g, p=0.09) among the women with HDP history compared to women without. CONCLUSION: In a high-risk cohort of women with suspected INOCA, 20% had a history of HDP. Women with HDP history were more likely to develop HTN. Our study demonstrates higher LV mass in women with HDP and concomitant HTN. Although the presence of LGE scar was not different in women with and without HDP history, we observed a trend towards larger scar size in women with HDP. Future studies are needed to better assess the relationship of HDP and cardiac morphology and LGE scarring in a larger cohort of women.

Psychological stress, cardiac symptoms, and cardiovascular risk in women with suspected ischaemia but no obstructive coronary disease.

This paper evaluated cross-sectional relationships between psychological stress and coronary artery disease (CAD) risk among women with suspected ischaemia and no obstructive coronary artery disease (INOCA). Between 1996 and 2000, 551 women with INOCA were enrolled in the Women's Ischemia Syndrome Evaluation (WISE) cohort from four U.S. institutions. Between 2009 and 2012, 376 women with INOCA were recruited from two U.S. institutions for an independent cohort study titled WISE-Coronary Vascular Dysfunction (WISE-CVD). Participants underwent coronary angiography and testing for CAD symptoms and risk factors at baseline. Psychological stress was assessed in the form of home/work stress in WISE and home/work stress and financial stress in WISE-CVD. Results showed that home/work stress predicted greater depression, functional impairment, CAD symptoms, and lower self-rated health in WISE but was inconsistent as a predictor in WISE-CVD. In contrast, >60% of WISE-CVD women reported moderate or severe financial stress. Financial stress levels predicted more CAD risk factors and cardiac symptoms, poorer self-rated health, and greater depression and functional impairment. Among women with INOCA, psychological stress was associated with CAD symptoms and CAD risk factors. The prevalence and predictive value of psychological stress in this population supports the inclusion of stress measures in future CAD research.

Sex differences in crude mortality rates and predictive value of intensive care unit-based scores when applied to the cardiac intensive care unit.

BACKGROUND: Limited data exists regarding sex differences in outcome and predictive accuracy of intensive care unit-based scoring systems when applied to cardiac intensive care unit patients. METHODS: We reviewed medical records of patients admitted to cardiac intensive care unit from 1 January 2011-31 December 2016. Sex differences in mortality rates and the performance of intensive care unit-based scoring systems in predicting in-hospital mortality were analyzed. Calibration was assessed by the Hosmer-Lemeshow test and locally weighted scatterplot smoothing curves. Discrimination was assessed using the c statistic and receiver-operating characteristic curve. RESULTS: Among 6963 patients, 2713 (39%) were women. Overall in-hospital and cardiac intensive care unit mortality rates were similar in women and men (9.1% vs 9.4%, p=0.67 and 5.9% vs 6%, p=0.88, respectively) and in age and major diagnosis subgroups. Of the scoring systems, Acute Physiology and Chronic Health Evaluation III and Sequential Organ Failure Assessment had poor calibration (Hosmer-Lemeshow p value <0.001), while Simplified Acute Physiology Score II performed better (Hosmer-Lemeshow p value 0.09), in both women and men. All scores had good discrimination (C statistics >0.8). In the subgroups of acute myocardial infarction and heart failure patients, all scores had good calibration (Hosmer-Lemeshow p>0.001) and discrimination (C statistic >0.8) while in diagnosis subgroups with highest mortality, the calibration varied among scores and by sex, and discrimination was poor. CONCLUSIONS: No sex differences in mortality were seen in cardiac intensive care unit patients. The mortality predictive value of intensive care unit-based scores is limited in both sexes and variable among different subgroups of diagnoses.

Adverse Pregnancy Outcomes Are Associated with Reduced Coronary Flow Reserve in Women With Signs and Symptoms of Ischemia Without Obstructive Coronary Artery Disease: A Report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Study.

Background: We assessed history of adverse pregnancy outcomes (APOs) and coronary microvascular dysfunction (CMD) in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) cohort of women with signs and symptoms of ischemia without obstructive coronary artery disease (CAD). We hypothesized that women with CMD with symptoms and signs of ischemia, without obstructive CAD, are more likely to have a history of APO. Materials and Methods: WISE-CVD recruited women with suspected ischemia found to have no obstructive CAD (n = 324). A subset of these women underwent coronary reactivity testing, including coronary flow reserve (CFR) (n = 185). Relationship between history of any APO and CMD was assessed by multivariable linear regression analyses. APOs included any of the following: hypertension during pregnancy, preeclampsia, eclampsia, gestational diabetes, or intrauterine growth restriction (low-birth-weight child). Results: Overall, 79/324 (24%) women reported at least one APO. Women with APOs were younger (52 vs. 56 years, p = 0.001), were more likely obese (body mass index 32 vs. 29 kg/m2, p = 0.004), and had a history of hypertension (56% vs 36%, p = 0.002), but otherwise had no additional differences in cardiac risk variables versus women without APOs. Among the subgroup who underwent invasive CFR testing (n = 185), those with an APO had lower CFR (2.53 vs. 2.76, p = 0.016) versus those without APO. Conclusions: History of APOs in women with signs and symptoms of ischemia without obstructive CAD is associated with lower CFR indicative of CMD. Whether common pathways involving diffuse microvascular dysfunction may account for this suggested association remains unclear. Further investigation is needed to expand on these exploratory findings.

Feasibility of Patient-Centric Remote Dried Blood Sampling: The Prediction, Risk, and Evaluation of Major Adverse Cardiac Events (PRE-MACE) Study.

Background: Remote patient monitoring can shift important data collection opportunities to low-cost settings. Here, we evaluate whether the quality of blood-samples taken by patients at home differs from samples taken from the same patients by clinical staff. We examine the effects of socio-demographic and patient reported outcomes (PRO) survey data on remote blood sampling compliance and quality. Methods: Samples were collected both in-clinic by study-staff and remotely by subjects at home. During cataloging the samples were graded for quality. We used chi-squared tests and logistic regressions to examine differences in quality and compliance between samples taken in-clinic versus samples taken by subjects at-home. Results: 64.6% of in-clinic samples and 69.7% of samples collected remotely at home received a Good (compared to Not Good) quality grade (chi2 = 4.91; p =.03). Regression analysis found remote samples had roughly 1.5 times higher odds of being Good quality compared to samples taken in-clinic (p <.001; 95% CI 1.18-2.03). Increased anxiety reduced odds of contributing a Good sample (p =.04; 95% CI.95-1.0). Response rates were significantly higher for in-clinic sampling (95.8% vs 89.8%; p <.001). Conclusion: Blood-samples taken by patients at home using a microsampling device yielded higher quality samples than those taken in-clinic.

Premature atherosclerosis in premenopausal women: Does cytokine balance play a role?

Contributory risk factors to premature coronary artery disease (CAD) in premenopausal women are poorly understood and data on this subset of women is lacking. There is growing evidence that the process of inflammation is a part of the atherosclerotic process. Mechanistic insights from animal work suggest that the profile of circulating cytokines reflects both endothelial integrity and the presence of immune and progenitor cells. Significant differences in pro- and anti-inflammatory cytokine concentrations between patients with and without CAD exist. Young women with obstructive CAD may experience differences in pro-inflammatory cytokines and the recruitment of reparative cells that secrete T-Helper (Th2 cytokines compared to women without CAD. Thus, cytokine balance may play a role in obstructive CAD in young women. In this pilot study we set out to identify an array of circulating inflammatory marker profiles which could be useful for the development of risk assessment and preventive strategies. We tested the hypothesis that an increase in serologic Th1 cytokines relative to Th2)/hematopoietic regulatory (HR) cytokines is related to premature coronary atherosclerosis in premenopausal women.

Role of Stress Cardiac Magnetic Resonance Imaging in Women with Suspected Ischemia but No Obstructive Coronary Artery Disease.

OBJECTIVE: Signs and symptoms of ischemia but no obstructive coronary artery disease (CAD) is often a diagnostic dilemma in women. The use of stress cardiac magnetic resonance imaging (CMRI) for advanced diagnostic assessment in these patients is a non-ionizing radiation option, but the diagnostic utility in this population is unknown. We examined the diagnostic role of stress CMRI in our patient population of these women. METHODS: We analyzed 113 consecutive female patients from 2/2006-11/2007 who had prior cardiac evaluations for signs and symptoms of ischemia but no obstructive CAD who underwent stress CMRI, which included anatomic, functional, adenosine stress perfusion and delayed enhancement imaging. RESULTS: The population demographics of 113 women included a mean age of 55±12.2 years with an average body mass index (BMI) of 25 ± 4.5. Overall, 43% had hypertension, 4% had diabetes and 3% were smokers. Overall, 80/113 (70%) demonstrated abnormal stress CMRI results. The majority of patients demonstrated findings consistent with subendocardial perfusion abnormalities suggestive of coronary microvascular dysfunction (CMD). Of note, 3 patients (4%) were diagnosed with congenital coronary anomalies or cardiomyopathy not detected in prior cardiac evaluations. CONCLUSION: Among women with signs and symptoms of ischemia but no obstructive CAD, stress CMRI is frequently abnormal and is valuable in diagnosis of CMD. Stress CMRI appears useful for advanced diagnostic assessment in these diagnostically challenged patients.