Why names matter for women: MINOCA/INOCA (myocardial infarction/ischemia and no obstructive coronary artery disease)

Abstract

The syndromes of myocardial infarction/myocardial ischemia with No Obstructive Coronary Artery Disease (MINOCA/INOCA) are increasingly evident. A majority of these patients have coronary microvascular dysfunction. These patients have elevated risk for a cardiovascular event (including acute coronary syndrome, myocardial infarction, stroke, and repeated cardiovascular procedures) and appear to be at higher risk for development of heart failure with preserved ejection fraction. Terminology such as coronary artery disease or coronary heart disease is often synonymous with obstructive atherosclerosis in the clinician's mind, leaving one at a loss to recognize or explain the phenomenon of MINOCA and INOCA with elevated risk. We review the available literature regarding stable and unstable ischemic heart disease that suggests that use of the ischemic heart disease (IHD) terminology matters for women, and should facilitate recognition of risk to provide potential treatment targets and optimized health.

1. DEFINITION AND TERMINOLOGY

Patients presenting with myocardial infarction with no obstructive coronary artery disease (MINOCA) or symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA) are increasingly recognized within acute coronary syndrome (ACS) and stable ischemic heart disease (SIHD) populations.1, 2 Evidence documents that this is associated with an adverse prognosis, yet no clinical practice management guidelines exist. There is likely overlap between MINOCA and INOCA.3

2. PREVALENCE, COSTS, AND PROGNOSTIC SIGNIFICANCE

2.1. INOCA

The American College of Cardiology–National Cardiovascular Data Registry and the National Heart, Lung and Blood Institute–sponsored Women's Ischemic Syndrome Evaluation (WISE) databases suggest that at least 3 to 4 million women and men with signs/symptoms suggestive of myocardial ischemia have no obstructive coronary artery disease (CAD).4 Such individuals incur healthcare costs and disabilities similar to obstructive CAD, in part due to angina and heart failure (HF) hospitalizations and repeated testing.4, 5 These hospitalizations and repeated angiography are confirmed by a European consecutive‐patient registry.6

Although approximately the same number of women than men die annually from cardiovascular disease (CVD),7 women presenting with INOCA/MINOCA are more likely to have no obstructive CAD on coronary angiography compared with men.8, 9 Such patients are often reassured but offered no specific management, yet have a heightened CVD event risk compared with age‐ and sex‐matched reference subjects.1, 10 An intermediate risk for a major adverse cardiac event (MACE) (death, nonfatal myocardial infarction [MI], nonfatal stroke, and HF hospitalization) rate exceeding 2.5% yearly by 5 years is observed, as well as elevated rates of readmission and repeat angiography triggered by symptom burden.10 At 10 years, CVD death or MI occurred in 6.7% of those with no evident angiographic CAD, and in 12.8% among those with nonobstructive CAD.11 Large, consecutive‐case registry reports have replicated this heightened risk for adverse prognosis and extended the findings to men.1, 2, 12 Table 1 demonstrates a summary of prognosis in INOCA subjects with CMD.13

Table 1.

Natural history studies of patients with coronary microvascular dysfunction13 (Reprinted with permission.)

Author, Year	No.	Population	Method	Outcome Measure	Follow‐up	CMD Outcome Predictor
						Univariate	Multivariate
Britten, 200481	120	Post‐PCI/mild CAD	Intracoronary papaverine or adenosine CFR Doppler flow wire	Cardiac death, ACS, revascularization, stroke	6.5 ± 3 years (14–125 months)	Yes	Yes
Schindler, 200682	72	CAD risk factors without flow‐limiting stenosis	CPT‐MBF increase with 13N‐NH3 PET	CV death, ACS, MI, PCI/CABG, stroke, PTA	66 ± 8 months	Yes	No
Rigo, 200783	86	CAD, LAD 51%–75% stenosis	Vasodilator LAD CFR, Doppler/TTE	Nonfatal MI	30 months, 14 median	Yes	Yes
Nemes, 200884	397	Hospitalized, angina, mostly severe CAD, TEE for AA	Vasodilator LAD CFR, Doppler/TEE	CV death, HF, thrombosis	41 ± 12 months	Yes	Yes
Herzog, 200985	229	Suspect CAD/66% had severe CAD	Vasodilator CFR with 13N‐NH3 PET	CV death, nonfatal MI, hospitalization, PCI/CABG	5.5 ± 2.1 years	Yes	Yes
Tio, 200986	344	Severe CAD, not revascularized, LV systolic dysfunction	Vasodilator CFR with 13N‐NH3 PET	Cardiac death	85 months (1–138 months)	Yes	Yes
Cortigiani, 201087	1660	Chest pain, normal DSE	Vasodilator LAD CFR, Doppler/TTE	Death, MI, revascularization	19 months median	Yes	Yes
Pepine (WISE), 201088	189	Women, angina/ischemia, most with obstructive CAD	Intracoronary Ado‐CFR, Doppler flow wire	Death, nonfatal MI, nonfatal stroke, HF hospitalization	5.4 years (mean)	Yes	Yes
Ziadi, 201134	677	Most had severe CAD	Vasodilator CFR with 82Rb PET	CV death, nonfatal MI	387 days (375–416 days)	Yes	Yes
Balazs (SZEGED study), 201189	45	Women, angina/ischemia, no obstructive CAD	Vasodilator CFR, Doppler/TEE, TTE	Death, CV hospitalization	102 ± 26 months, 113 median	Yes	Yes
Murthy, 201490	1218; 813 women, 405 men	No obstructive CAD (excluded by CTA or PET)	Stress Perfusion, imaging (PET)	CV death, MI, late revascularization (>90 days) or HF hospitalization	3 years	Yes	Yes

Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CAD, coronary artery disease; CFR, coronary flow reserve; CMD, coronary microvascular dysfunction; CPT, cold pressor test; CTA, computed tomography angiography; CV, cardiovascular; DSE, dobutamine stress echo; HF, heart failure; LAD, left anterior descending; LV, left ventricular; MBF, myocardial blood flow; MI, myocardial infarction; PCI, percutaneous coronary intervention; PET, positron emission tomography; PTA, percutaneous transluminal angioplasty; SZEGED, SummariZation of long‐tErm prognostic siGnificance of coronary flow rEserve in special Disorders; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography; WISE, Women's Ischemia Syndrome Evaluation.

2.2. MINOCA

MINOCA represents up to 14% of all acute MIs,14, 15 and is diagnosed more frequently in younger patients and in women than MI in the setting of obstructive CAD.15 African American patients are more frequently diagnosed with MINOCA than those of other ethnicities.16 MINOCA patients may also exhibit a different cardiovascular risk profile than patients with obstructive CAD, as they are less likely to be diagnosed with hyperlipidemia15 and diabetes,17 but have a reported higher prevalence of hypertension.18 MINOCA patients report less angina prior to MI,18 and non–ST‐elevation MI accounts for two‐thirds of cases.15

Although MINOCA prognosis appears more favorable than obstructive CAD MI, it is not benign. The occurrence of recurrent MI and urgent revascularization, as reported by Planer et al., in a propensity‐matched cohort of 197 MINOCA patients was significantly lower than in those with obstructive CAD.19 In a systematic review, analysis of data from 8 studies found that, despite a lower mortality rate than those with obstructive CAD, MINOCA was nonetheless associated with an all‐cause mortality rate of 4.7% at the 12‐month follow‐up.15 Up to 25% of MINOCA patients report persistent angina following MI, and experience similar rates of hospitalization due to angina than their counterparts with obstructive CAD.18 Persistent angina represents an important socioeconomic personal and societal burden, with MINOCA patients reporting worse quality of life due to angina on the Seattle Angina Questionnaire and more dissatisfaction with medical management of their symptoms.18

3. PREDICTORS OF ADVERSE OUTCOMES

3.1. INOCA

Older age, hypertension, diabetes, and smoking have been associated with increased mortality, whereas sex, hyperlipidemia, family history of premature CAD, or pretest CAD likelihood have not.5 Risk‐adjusted analyses found that nonobstructive CAD conferred increased mortality risk vs that of patients with no evident CAD.5

Chest pain persisting at the 1‐year follow‐up predicted MACE among those with INOCA in the WISE study.20 Measures of nonobstructive CAD extent and severity (eg, WISE CAD severity score, number of vessels involved) also appear important in prognosis, but these measures are not well developed.1, 2, 11 A large cohort undergoing coronary computed tomographic angiography propensity matched for age, CAD risk factors, and angina typicality observed elevated death/MI rates in those with nonobstructive CAD vs normal angiograms.21

3.2. MINOCA

Female sex and a younger age (median age = 59 vs 64 years for MINOCA vs obstructive CAD, P < 0.0001) were the only independent clinical predictors of MINOCA in the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) registry of 38 301 non–ST‐elevation myocardial infarction patients.22 In an observational study of 131 patients diagnosed with MINOCA who underwent cardiac magnetic resonance imaging (cMRI), ST‐elevation myocardial infarction at presentation and late gadolinium enhancement (LGE) were associated with an increased risk of developing ventricular tachycardia or ventricular fibrillation during index hospitalization, but not with the occurrence of sudden death at 1 year.23 Repeat hospitalizations for chest pain are associated with increased risk of repeat investigations and procedures.10

4. PATHOPHYSIOLOGY

4.1. MINOCA/INOCA

Mechanisms contributing to INOCA appear multifactorial and may operate alone or in combination.24 Although these may include hypertension, severe aortic stenosis, severe anemia, type II MI, shunts, certain drugs, HF or cardiogenic shock, Prinzmetal variant angina (coronary spasm), myocardial diseases (eg, myocarditis), congenital heart disease, coronary anomalies, myocardial bridging, and other causes, underlying mechanisms and appropriate diagnostic and management strategies in these settings are often evident.

4.1.1. Atherosclerosis

The pathophysiology of atherosclerosis is now clearly related to chronic inflammation with periods of minor plaque rupture, erosion, and distal embolism resulting in MI.25 Evidence linking microvascular and inflammatory responses to risk factors indicates that oxidative stress, reduced nitric oxide (NO) bioavailability, and endothelial activation are common early features of coronary microvascular responses to atherosclerosis risk factors.26 Essentially, all INOCA patients with chronic angina studied by intravascular ultrasound (IVUS) to date have some coronary atherosclerosis.27, 28 A greater burden of risk factors is associated with more atherosclerosis, concealed by compensatory positive remodeling, yielding diffuse nonobstructive CAD.27 Two single‐center reports of nonobstructive CAD presenting with ACS suggest that plaque rupture is observed in the minority: 38% of 42 women29 and 37% of men and women.30 The former study found that plaque ulceration was also frequent, in addition to LGE.29 The latter study found plaque ruptures frequently appeared with larger plaque burden and positive remodeling.30

4.1.2. Coronary Microvascular Dysfunction

One proposed mechanism contributing to MINOCA/INOCA is coronary microvascular dysfunction (CMD),31 defined as epicardial and/or microvascular endothelial and/or nonendothelial dysfunction that limits myocardial perfusion, most often detected as reduced coronary flow reserve (CFR) detected by invasive doppler or noninvasive advanced imaging such as positron emission tomography (PET) or cMRI. CMD may occur in the absence of obstructive CAD and myocardial diseases, in myocardial diseases, in obstructive CAD, or may be iatrogenic.31 Coronary vasomotor dysfunction, even without flow‐limiting stenosis, identifies patients at risk for cardiac death.32, 33, 34 There is limited correlation between anatomic CAD severity and functional impairment, as reflected in the CFR.35 Diabetic patients without obstructive CAD but with impaired CFR experienced cardiac death rates similar to those for nondiabetic patients with CAD.36

To understand CMD mechanistic pathways, WISE investigation has explored genotypic pathways of arterial vasomotion, including bradykinin and related peptides (terminal kinins), which promote vasodilation, endothelial NO production, and vascular permeability. We hypothesized that the kinin system's protective effect on the coronary circulation may be reduced in patients with polymorphic (deficient) alleles of the Bradykinin B1R gene. Evaluation of 141 WISE women who underwent quantitative coronary angiography and genetic analysis for the guanine (G)–cytosine (C) polymorphism at position −699 of the gene demonstrated a lesser CFR to adenosine associated with the B1R gene polymorphism (CG genotype). The mean CFR was 2.05 ± 0.30 (abnormal is <2.32), while wildtype women (GG genotype) had a normal mean CFR of 2.78 ± 0.15 (P = 0.047). This change in flow ratio was due to a decrease in velocity (P = 0.022), rather than to a change in coronary cross‐sectional area (P = 0.78). A significant difference in flow ratio by genotype was also seen in response to nitroglycerin, where women with the polymorphism had a flow ratio of 2.47 ± 0.24 versus 3.36 ± 0.14 for the wildtype genotype (P = 0.029). When acetylcholine (an endothelial mediator) was tested, no difference was seen by genotype (P = 0.55). No difference by genotype was seen for age, severity of angiographic CAD, hypertension, diabetes, dyslipidemia, or smoking. We concluded that in addition to early atherosclerosis, these data suggest that intrinsic genetic factors contribute to coronary smooth muscle reactivity as well.37 Furthermore, in 667 WISE women, diabetics were compared to nondiabetics in terms of survival and NOS3 genetic polymorphism. The median follow‐up was 5.9 years. In nondiabetics the Asp298 variant was associated with poor survival (n = 504, percent survival 1, 3, and 5 years: Glu298Glu = 98%/97%/96%, Glu298Asp = 99%/96%/94%, Asp298Asp = 94%/94%/86%, P = 0.048). This interaction was not seen in diabetics (n = 160, P = 0.92). This survival impact was not evident in subjects with no obstructive CAD at entry (n = 239), as the obstructive CAD subset Asp298 was exclusively associated with poor outcomes (% survival: Glu298Glu = 97%/90%/88%; Glu298Asp = 97%/86%/82%; Asp298Asp = 92%/83%/65%; P = 0.02). As in the larger cohort, the impact of Asp298 in women with obstructive CAD was exclusively in nondiabetics (P = 0.002) and was not evident in subjects with diabetes (P = 0.57). The impact of this allele was eliminated by the presence of diabetes, and this genetic interaction suggests a role of NO imbalance in diabetic vasculopathy.38

5. DIAGNOSIS

5.1. Invasive testing

Assessment of coronary vascular function includes measurements of coronary blood flow (CBF) and epicardial coronary artery diameter with endothelium‐dependent probes: acetylcholine (Ach), bradykinin, substance‐P, L‐NMMA, shear‐stress, and CFR with predominantly endothelium‐independent probes: adenosine or nitroglycerin. Exercise, pacing‐induced tachycardia, cold pressor test (CPT), and mental stress have also been used to elicit abnormalities in CBF. WISE‐CVD project data suggest a strong correlation between Ach and CPT coronary artery diameter changes in women.28 Reports from testing over 1500 ACS and SIHD patients indicate an excellent safety record, with no deaths and <1% procedure‐related adverse experiences like those observed with coronary angiography.39, 40, 41

IVUS can be useful in the proximal portions of epicardial coronary artery vessels in search of potential etiologies of MINOCA, including plaque rupture or ulceration, presence of thrombus, or spontaneous coronary artery dissection.29 IVUS identified plaque disruption in 38% of patients and plaque ulceration in 10% of a cohort of MINOCA patients, and in the hands of experienced operators, is a tool of interest in identifying precise etiologies in this patient population. Optical coherence tomography (OCT) has a 10‐fold higher resolution than IVUS42 and has a 92% sensitivity and 75% specificity for identification of plaques with a large lipid pool and thin fibrous cap.43 These lesions are associated with a similar risk of cardiovascular events at follow‐up as patients with ACS and obstructive CAD. IVUS and OCT have become key imaging modalities during invasive angiography to better define MINOCA.

5.2. Noninvasive testing

PET is a highly accurate, reproducible, and modifiable procedure providing comprehensive evaluation of CBF, including myocardial perfusion, left ventricular (LV) function, and CFR. There is a strong association between impaired CFR and impaired LV myocardial relaxation or elevated filling pressures, strongest among those with cardiac troponin elevations.44 Transthoracic echo Doppler can measure coronary flow velocity (CFV), by pulsed‐wave Doppler of the left anterior descending coronary artery at rest and after dipyridamole, and a prior publication in INOCA patients demonstrated that 26% had and abnormal CFV reserve <2.0.45 Those with low CFV reserve had significantly greater physical limitation and disease perception scores using the Seattle Angina Questionnaire. cMRI can detect failure of subendocardial perfusion to increase appropriately in response to stress in INOCA subjects.46, 47 A semiquantitative approach with measurement of myocardial perfusion reserve index (MPRI) detects CMD in women with INOCA.48 cMRI can also be used to detect and further characterize myocardial edema and scarring in patients diagnosed with MINOCA, providing insight into potential pathophysiological mechanisms. In a study conducted by Reynolds et al., women with MINOCA were prospectively enrolled and underwent cMRI within 1 week of diagnosis. Twenty‐six of the 44 (59%) patients who underwent cMRI had abnormal findings. T2 signal hyperintensity (T2+) indicating edema was found in 9 patients and LGE compatible with myocardial scarring in 17 patients.29 These findings indicate that MINOCA is associated to true myocardial anomalies detectable on cMRI, suggestive of ischemic but also nonischemic etiologies that need to be considered in patient management.

Mauricio et al. examined whether there was evidence of abnormal perfusion compatible with CMD on cMRI in INOCA patients.49 Forty patients underwent adenosine stress cMRI, with 63% of patients exhibiting abnormal stress perfusion. There was a trend toward higher probability of T2+ among those with stress perfusion abnormalities (P = 0.06), which matched the location of T2+ in all patients who were found to have both. Semiquantitative perfusion analysis was also performed, and a quarter of patients had abnormal MPRI, although this was not associated with LGE or T2+. CMD may represent an underlying pathological substratum predisposing the myocardium to edema and potential necrosis as detected by cMRI, and subsequent MINOCA, in the setting of vasospasm, endothelial dysfunction, or coronary microemboli.29

6. MANAGEMENT

Potential therapies for MINOCA/INOCA with evidence of CMD include therapeutic lifestyle change, management of risk factors, and lifestyle modifications such as weight loss,50 smoking cessation, high‐fiber diet, fruits and vegetables consumption, and regular physical activity.50, 51

Figure 1.

Annualized major adverse cardiac event (MACE) rates by sex and coronary flow reserve (CFR).90 Abbreviations: CAD, coronary artery disease; CMD_PET, coronary microvascular dysfunction positron emission tomography; ds, days; HF, heart failure; MI, myocardial infarction (Reprinted with permission

Prior statin trials using IVUS have documented prevention of progression, or even regression, of atherosclerosis in coronary arteries, as well as coronary endothelial and/or vascular smooth muscle function in subjects with nonobstructive CAD.52 Fluvastatin and the combination of fluvastatin and diltiazem improved CFR.53 Two small pilot studies have shown administration of atorvastatin improved CFR after 2 months54 and 6 months.55 Angiotensin converting enzyme (ACE) inhibitors have been shown to improve exercise tolerance and angina symptoms.56 In a WISE ancillary trial, women who received quinapril had improved CFR and angina symptoms.57 Patients with essential hypertension had marked improved CBF after 12 months of treatment with perindopril, with regression of periarteriolar fibrosis seen on biopsy.58 In patients already on an ACE inhibitor, the addition of an aldosterone blocker did not improve endothelial function,59 although in subjects with diabetes, the addition of spironolactone has been shown to improve coronary microvascular function.60 A statin plus ACE inhibitor (atorvastatin and ramipril) at 6 months improved Seattle Angina Questionnaire scores and exercise duration vs placebo. Mechanistically, the combination produced greater increases in brachial artery flow‐mediated dilation vs placebo and reduced extracellular superoxide dismutase.56

Additional approaches to CMD treatment are listed in Table 2. β‐blockers reduce myocardial oxygen consumption and increase diastolic filling time, reducing the number of angina episodes in patients46 and improving ischemic threshold. Carvedilol has been shown to improve endothelial function.61 One study of intracoronary diltiazem did not improve CFR in CMD patients, but rather had a predominant vasodilatory effect on the epicardial arteries.62 Despite these findings, patients with abnormal vasodilator reserve have improved symptoms, less nitrate usage, and improved exercise tolerance after being treated with verapamil or nifedipine.63 The use of nitrates may improve patient's symptoms, but there are limited data on their effect on endothelial function. Ranolazine is an antianginal that inhibits the late sodium current; however, results on CMD have been conflicting.64, 65, 66 Another drug, ivabradine, which reduces heart rate through its effect on I_f of the sinoatrial node, was found to improve symptoms but had no effect on coronary microvascular function, as reported by Villano et al.66 Aminophylline, a nonselective adenosine‐receptor antagonist, blocks the mediation of nociception, and some improvement in symptoms and exercise capacity were seen with short‐term intravenous67 and oral aminophylline68 in these patients. Fasudil, a ρ kinase inhibitor, has been shown to be effective for vasospastic angina. Two studies have found improvement of CFR with infusion of L‐arginine.69 However Lerman et al. found that after oral supplementation for 6 months, there was no improvement in CFR, only a significant improvement in CBF.70 Imipramine has been shown to reduce frequency of pain.71, 72

Table 2.

Treatment of subjects with angina, evidence of myocardial ischemia, and no obstructive coronary artery disease91 (Reprinted with permission.)

Microvascular Coronary Dysfunction

Abnormal endothelial function

Angiotensin converting enzyme inhibitors

HMG CoA reductase inhibitors (statins)

L‐arginine supplementation

Aerobic exercise

Enhanced external counterpulsation

Abnormal nonendothelial function

β‐blockers/α‐ and β‐blockers

Nitrates

Antianginal

Ranolazine

Ivabradine

Xanthine derivatives

Abnormal smooth muscle function (Prinzmetal's angina)

Calcium channel blockers

Nitrates

Abnormal cardiac nociception

Low dose tricyclic medication

Spinal cord stimulation

Cognitive behavioral therapy

Abbreviations: HMG CoA, 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A.

Spinal cord stimulation has been shown to normalize abnormal pain perception73 and improve angina symptoms and increase exercise tolerance.74 Enhanced external counterpulsation uses pneumatic cuffs applied to the patient's legs. Sequential inflation and deflation synchronized to the cardiac cycle improves hemodynamics.75 It has been shown to improve angina in a small case series.76 Cognitive behavioral therapy can reduce symptom severity and frequency.77 Cardiac rehabilitation can be helpful as it improves blood pressure, BMI, and exercise capacity.78

Patients with MINOCA are less likely to be treated and discharged on guideline‐recommended therapies than those with obstructive CAD, including β‐blockers, statins, ACE inhibitors/angiotensin receptor blockers (ARB), and dual antiplatelet therapy.17 Although no randomized controlled trials regarding the use of these therapies in the context of MINOCA exist, Lindahl et al. recently conducted an observational study of medical therapy for secondary prevention in 9466 MINOCA patients.79 MACEs, including all‐cause mortality, hospitalization for MI, ischemic stroke, and heart failure were lower in all patients who were discharged on statins (hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.68‐0.87) and ACE inhibitor/ARB (HR: 0.82, 95% CI: 0.73‐0.93), and this was also true for both women and men. β‐blockers were not associated with lower MACE overall, but with lower incidence of MI (HR: 0.74, 95% CI: 0.56‐0.97), and patients discharged with dual antiplatelet therapy seemed to have a similar rate of MACEs than those without such therapy.79 The association of statins and ACE inhibitors/ARB to lower rates of adverse outcomes may be in part explained by the efficient treatment of underlying atherosclerosis and endothelial dysfunction with these agents in a proportion of these patients, which prevents disease progression, plaque rupture, and further cardiovascular events, and has been shown to improve outcomes in those with CMD as described above. Prospective studies are needed to confirm these associations and improve management of MINOCA patients.

7. CONCLUSIONS

The prevalence of no obstructive CAD among clinically ordered coronary angiograms conducted for myocardial infarction or evidence of suspected myocardial ischemia (MINOCA/INOCA) is increasing.1, 2, 8, 80 A majority of these patients have CMD, an elevated risk for a cardiovascular event (including ACS, MI, HF, and anginal hospitalization and repeated cardiovascular procedures). At present, there is no uniform, comprehensive diagnostic strategy or algorithm for risk stratification for these patients; however, invasive and noninvasive coronary flow reserve testing can be useful. Although small trials have suggested benefit from ACE inhibitors and statins, there is a lack of appropriately designed clinical outcome trials to inform evidence‐based therapeutic strategies. The next steps needed to address knowledge gaps include evidence‐based approaches to the definition, diagnostic evaluation, risk stratification, and management of MINOCA/INOCA patients, including large outcome clinical trials.

Conflicts of interest

The authors declare no potential conflicts of interest.

Pacheco Claudio C, Quesada O, Pepine CJ, Noel Bairey Merz C. Why names matter for women: MINOCA/INOCA (myocardial infarction/ischemia and no obstructive coronary artery disease). Clin Cardiol. 2018;41:185–193. 10.1002/clc.22894