Myocardial infarction or ischemia with no obstructive coronary atherosclerosis

INTRODUCTION AND DEFINITIONS — Most cases of ischemia or acute myocardial infarction (MI) are caused by a stable or unstable atherosclerotic plaque [1]. This includes a supply-demand mismatch in the presence or absence of a significant stenoses. (See "Approach to the patient with suspected angina pectoris", section on 'Pathophysiology' and "Mechanisms of acute coronary syndromes related to atherosclerosis".)

This topic will discuss the potential causes of ischemia and MI that occur in the absence of obstructive atherosclerosis.

The following are useful definitions to refer to for this topic:

●MI – This is defined as a clinical (or pathologic) event in the setting of myocardial ischemia with additional evidence of myocardial injury [2,3]. The diagnosis is secured when there is a dynamic increase in the cardiac enzyme troponin and supportive evidence in the form of typical clinical data (eg, suggestive electrocardiographic changes, imaging evidence of new loss of viable myocardium, new regional wall motion abnormality). The definition of MI (including subtypes of MI) is discussed in detail separately. (See "Diagnosis of acute myocardial infarction", section on 'Definitions'.)

●MI with no obstructive coronary atherosclerosis (MINOCA) – This is a distinct clinical syndrome characterized by evidence of MI with normal or near normal coronary arteries on angiography (stenosis severity ≤50 percent) in the absence of obvious noncoronary causes of MI such as severe hemorrhage or severe respiratory failure [4]. There are several well-defined causes/pathophysiologic mechanisms for MINOCA; the prognosis and management differ for each of these causes.

●Ischemia with no obstructive coronary arteries (INOCA) – This refers to several conditions which cause ischemia (but not necessarily myocardial infarction). Ischemia is caused by a lack of blood flow to the myocardium which causes a supply demand mismatch. The diagnosis of INOCA is made once atherosclerotic coronary artery disease (CAD) as a cause of angina symptoms is excluded.

MINOCA

Epidemiology of MINOCA — In a systematic review of studies, the prevalence of MINOCA among patients with acute MI is between 1 and 15 percent [5], with a mean of 6 percent [6].

●Prevalence – In a meta-analysis of 23 studies, the prevalence of MINOCA was estimated at 8.1 percent among 806,851 consecutive acute MI patients [7]. MINOCA has a worldwide incidence ranging from 2.9 to 10.2 percent [5].

●Patient characteristics – MINOCA disproportionately affects females and may account for up to 50 percent of all MIs in younger women <55 years of age [6,7]. Compared with MI with obstructive coronary artery disease (CAD), MINOCA patients were younger (median age 61 years), and MINOCA was more common in Black and Hispanic patients compared with White patients. Furthermore, MINOCA patients were less likely to present with traditional cardiovascular risk factors including hypertension, dyslipidemia, diabetes, and current smoking history [7].

Causes of MINOCA — MINOCA is a syndrome with many causes [4]. They may involve the epicardial vessels and/or the coronary microcirculation. We recognize that the subdivision into epicardial and microvascular causes may be somewhat arbitrary.

Epicardial

Coronary artery spasm — Coronary artery spasm, as seen in “variant angina,” usually occurs at a localized segment of an epicardial artery, but sometimes involves two or more segments of the same (multifocal spasm) or of different (multivessel spasm) coronary arteries. It may also diffusely involve one or multiple coronary branches [8]. Coronary artery spasm often occurs in patients with CAD. The diagnosis and treatment of coronary artery spasm are discussed in detail separately. (See "Vasospastic angina".)

Among studies in patients with MINOCA, the reported prevalence of coronary spasm is extremely variable (3 to 95 percent). This has been attributed to the different stimuli/provocative tests used to diagnose spasm and different definitions of spasm.

Myocardial bridging refers to the muscle overlying the intramyocardial segment of an epicardial coronary artery (most often the left anterior descending artery). Myocardial bridging is unlikely to cause MINOCA. However, it can predispose the affected artery to spasm. MINOCA patients with bridging seen on coronary angiography should be considered for provocative testing. (See "Myocardial bridging of the coronary arteries", section on 'Diagnosis'.)

Acute thrombosis at the site of nonobstructive eccentric plaque thrombosis — Many atherosclerotic plaques expand outward rather than encroaching on the arterial lumen. These "positively remodeled" plaques are often lipid rich and have a thin fibrous cap; they are vulnerable to rupture into the lumen [1,9,10]. MINOCA in this setting may be caused by:

●Transient and partial thrombosis at the site of a nonobstructive plaque with subsequent spontaneous fibrinolysis and distal embolization

●Coronary erosion with loss of surface endothelium, possibly due to hyaluronan and neutrophil accumulation [1,11]. (See "Mechanisms of acute coronary syndromes related to atherosclerosis".)

The reason for these cases to be labeled as MINOCA is that angiography is of limited utility for the purpose of elucidating plaque-related thrombosis as a cause of thrombosis due to its low resolution and the fact that it does not interrogate the lumen of the vessel. (See "Intravascular ultrasound, optical coherence tomography, and angioscopy of coronary circulation" and 'Nonobstructive eccentric CAD' below.)

As MINOCA is associated with a risk of recurrent cardiovascular events over time, comparable to that of patients with acute coronary syndromes (ACS) and obstructive atherosclerosis [6,12,13], patients with acute thrombosis at the site of nonobstructive coronary arteries require dual antiplatelet treatment for 12 months and statins. In particular, long-term lipid-lowering therapy with statins after MI is associated with a significant increase of the fibrous-cap thickness, paralleling the reduction of the lipid content of the plaque [14]. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)

Spontaneous coronary artery dissection — Spontaneous coronary artery dissection (SCAD) is more common among young women, and sex-related hormones play an important pathogenetic role. SCAD is frequently associated with fibromuscular dysplasia in other vascular beds.

In the majority of patients, SCAD is obstructive and can be diagnosed on coronary angiography; in other, less obvious cases, intravascular imaging is necessary for an accurate diagnosis. The diagnosis and treatment of SCAD are discussed in detail separately. (See "Spontaneous coronary artery dissection".)

Microvascular

Takotsubo cardiomyopathy — Takotsubo or stress cardiomyopathy is characterized by apical ballooning of the left ventricle in the absence of obstructive CAD. The prevalence of Takotsubo cardiomyopathy is reported to range between 1.2 and 2.2 percent of all ACS cases, and females in the postmenopausal age are affected most frequently [15,16]. The diagnosis and treatment of Takotsubo cardiomyopathy are discussed in detail separately. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy".)

Coronary microvascular dysfunction — Coronary microvascular dysfunction is characterized by transient myocardial ischemia-associated ST-segment changes and angina that is either spontaneous or induced by intracoronary administration of acetylcholine and not due to obstructive CAD or epicardial spasm [17]. About 25 percent of patients with ACS and no obstructive CAD have evidence of coronary microvascular dysfunction, although an increase of troponin is infrequent [18]. The diagnosis and treatment of coronary microvascular dysfunction are discussed in detail separately. (See "Microvascular angina: Angina pectoris with normal coronary arteries".)

Viral myocarditis — One-third of cases of MINOCA are attributed to viral myocarditis. Adenoviruses, parvovirus B19 (PVB19), human herpesvirus 6, and Coxsackie virus are considered the most common causes of viral myocarditis. The diagnosis and treatment of viral myocarditis are discussed in detail separately. (See "Myocarditis: Causes and pathogenesis" and "Clinical manifestations and diagnosis of myocarditis in adults".)

Coronary artery embolism — Coronary artery embolism is an uncommon cause of MINOCA. It is a form of acute MI that often affects the microcirculation, although angiographically visible embolization of epicardial coronary artery branches may also occur. It should be suspected in patients with MINOCA and one of the following conditions associated with high risk of systemic embolism:

●Prosthetic heart valves

●Atrial fibrillation

●Dilated cardiomyopathy with apical thrombus

●Rheumatic heart disease with mitral stenosis

●Infective endocarditis

●Atrial myxoma

Paradoxical embolism is a rare cause of MINOCA. Importantly, in patients in whom paradoxical embolism is suspected, coronary angiography needs to be carefully analyzed for the identification of amputation (also called “stops”) of distal (peripheral) coronary branches. Transthoracic, transesophageal, and contrast-enhanced echocardiography are used to detect of cardiac sources of embolism as causes of MINOCA. (See "Cardiac tumors" and "Postoperative complications among patients undergoing cardiac surgery", section on 'Myocardial infarction' and "Echocardiography in detection of cardiac and aortic sources of systemic embolism", section on 'Potential sources of emboli'.)

Criteria for the diagnosis of coronary artery embolism have been proposed (table 1).

The prevalence and features of MI from coronary artery embolism were evaluated in a study of 1776 patients with a first MI who underwent diagnostic coronary arteriography and transthoracic echocardiography (TTE) [19]. Criteria for the clinical diagnosis of definite or probable cardiac embolism were established. The following findings were noted:

●The prevalence of cardioembolism was 2.9 percent; of these, about 15 percent had emboli in multiple coronary arteries.

●Atrial fibrillation was the most common underlying cause (73 percent). Other causes included cardiomyopathy and valvular heart disease.

●In a propensity score-matched analysis, patients with coronary embolism had a higher incidence of cardiac death than those in the noncoronary embolism group (hazard ratio 9.29; 95% CI 1.13-76.5).

Distal coronary artery embolism can occur in patients with coronary artery aneurysms, which can be detected by routine coronary angiography. Intravascular ultrasound or optical coherence tomography can provide additional information as to whether the aneurysm(s) is a potential source of thrombus.

Clinical features — The clinical presentation of MINOCA is similar to that of patients with ACS with obstructive CAD [6].

Patient characteristics — Patients with MINOCA versus MI with obstructive CAD often have the following characteristics:

●Age – In one study, the pooled mean age was 55 years [6], and in another the median age was 61 years [5].

●Sex – The Virgo Study showed that among adults presenting with MI and aged 18 to 55 years, women had five times greater odds of having MINOCA than men (14.9 versus 3.5 percent; odds ratio 4.84; 95% CI 3.29-7.13) [20].

●Cardiovascular disease risk factor burden – Patients with MINOCA have a similar burden of most traditional cardiovascular risk factors (eg, diabetes, smoking, hypertension, and family history), with the exception of hyperlipidemia, which occurred less often (21 versus 32 percent) [6].

●Race-ethnicity – MINOCA is more common in Black and Hispanic patients compared with White patients [5]

●Cancer – Patients with MINOCA have a relatively high prevalence of cancer. In a registry of 520 patients with angiographically confirmed MINOCA, the prevalence of cancer was 23 percent [21].

Similarity to atherosclerotic cardiovascular disease — In patients with MINOCA, the results of electrocardiogram and biomarker testing mimic those of patients with atherosclerotic coronary obstruction. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Electrocardiogram assessment' and "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Cardiac biomarkers and other laboratory testing'.)

Diagnosis of MINOCA — Our approach to elucidating the cause of MINOCA uses information in the patient’s history, from their angiogram, and from an imaging assessment of left ventricular (LV) wall motion, preferably with transthoracic echocardiography (TTE) (algorithm 1). If TTE has not been performed before coronary angiography, it can be performed in the catheterization laboratory or left ventriculography can be performed as a substitute.

Coronary angiography — For patients meeting the definition of acute MI (see 'Introduction and definitions' above and "Diagnosis of acute myocardial infarction", section on 'Definitions'), the diagnosis of MINOCA is made based on the finding of no major luminal irregularities at the time of coronary angiography (ie, no lesions obstructing the luminal diameter by more than 50 percent). The diagnosis of MINOCA is nearly always made once coronary angiography confirms there is no obstructive coronary artery atherosclerotic disease.

For patients who meet the diagnostic criteria for MINOCA, we recommend that an attempt be made to establish the specific cause/triggering mechanism, as prognosis and management vary with the cause. (See 'Causes of MINOCA' above.).

For patients who have some evidence of atherosclerotic disease in the coronary circulation, and no other cause for MINOCA has been found, we believe it is reasonable to assume the patient has had an ACS attributable to atherosclerotic disease. The management of these patients is discussed in detail separately. (See "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction", section on 'Summary and recommendations'.)

Spontaneous coronary artery dissection — The diagnosis of SCAD is made at the time of angiography, upon visualization of one or more coronary artery dissections. This is discussed in detail separately. (See "Spontaneous coronary artery dissection", section on 'Diagnosis'.)

Nonobstructive eccentric CAD — If the finding of nonobstructive atherosclerotic CAD is made (ie, stenosis <50 percent.), we evaluate further for evidence of acute thrombosis at the site of nonobstructive eccentric plaque. This is usually done with intravascular ultrasound or optimal coherence tomography. (See 'Acute thrombosis at the site of nonobstructive eccentric plaque thrombosis' above.)

Assessment of left ventricular function — In patients in whom angiography does not reveal a diagnosis, we obtain or refer to prior imaging of LV wall motion (eg, TTE, cardiac magnetic resonance imaging, or left ventriculography). (See "Tests to evaluate left ventricular systolic function".)

The function and structure can provide useful information regarding specific etiology of MINOCA.

Apical ballooning — Left ventriculography or echocardiography showing apical ballooning with akinesis or dyskinesis of the apical one-half to two-thirds of the LV suggests a diagnosis of stress or Takotsubo cardiomyopathy. (See 'Takotsubo cardiomyopathy' above.)

Systolic dysfunction — The finding of systolic dysfunction raises the possibility of viral myocarditis. Specific findings on TTE include LV dilation, changes in LV geometry (eg, development of a more spheroid shape), and wall motion abnormalities. The systolic dysfunction is generally global, but may be regional or segmental. This is discussed in detail separately. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Cardiac imaging' and "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Echocardiography'.)

Cardiac magnetic resonance imaging enables detection of various features of myocarditis, including evidence of inflammatory hyperemia and edema, late gadolinium enhancement suggestive of myocyte necrosis, and scar. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Cardiovascular magnetic resonance'.)

An endomyocardial biopsy can also be helpful in the diagnosis of viral myocarditis in some patients. This is discussed in detail separately. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Endomyocardial biopsy'.)

Normal systolic function — Coronary artery embolism should be considered in patients with prosthetic heart valves, chronic atrial fibrillation, dilated cardiomyopathy with apical thrombus, infective endocarditis, and atrial myxoma. If coronary artery embolism is suspected, testing for markers of thrombophilia (eg, protein C and S deficiency, as well as enhanced Factor VII activity) can also be helpful and if positive, point towards this diagnosis.

Ischemia with nonobstructed coronary arteries as a cause of MI

Cornary artery vasospasm — Patients with a chronic pattern of recurrent episodes of chest pain suggesting episodic angina are more likely to have vasospasm than other diagnoses. (See 'Coronary artery spasm' above.)

Microvascular dysfunction — Microvascular disease is sometimes also associated with regional wall motion abnormalities. (See 'Coronary microvascular dysfunction' above.)

Regional wall motion abnormalities may indicate that an epicardial cause of MINOCA (such as vasospasm or thrombosis, or a nonobstructive atherosclerotic plaque) is likely.

Coronary artery embolism — Aside from coronary angiography and assessment of LV wall motion, the following tests may be useful for elucidating the cause of MINOCA (see 'Coronary artery embolism' above):

●Optical coherence tomography or intravascular ultrasound. (See 'Acute thrombosis at the site of nonobstructive eccentric plaque thrombosis' above and 'Spontaneous coronary artery dissection' above.)

●Acetylcholine challenge. (See 'Assessment of vasospasm' below and 'No coronary stenosis or ≤50 percent' below.)

●Cardiac magnetic resonance imaging with contrast material – This test can be helpful if the history or echocardiogram suggest Takotsubo cardiomyopathy or myocarditis; cardiac magnetic resonance imaging may be helpful to confirm the diagnosis. Cardiac magnetic resonance imaging can also aid in the diagnosis of MINOCA [22]. In a meta-analysis of 26 studies of over 3600 patients, a specific cause of MINOCA was identified in only 22 percent of patients. Subsequent cardiac magnetic resonance imaging helped reclassify 68 percent of these patients into a different MINOCA etiology.

●Endomyocardial biopsy – This can be useful in some patients who are suspected of having myocarditis as an etiology of MINOCA. This is discussed in detail separately. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Endomyocardial biopsy'.)

●Contrast-enhanced echocardiography and TTE – If clinical data suggest coronary microembolism, transthoracic or transesophageal echocardiography or contrast-enhanced echocardiography is required to detect a cardiac source of embolism.

MINOCA management and prognosis

●Management – The treatment of MINOCA is specific to the underlying cause. The accurate diagnosis of the underlying cause of MINOCA can be obtained in the vast majority of patients using intravascular imaging, provocative coronary testing, and cardiac magnetic resonance imaging. (See 'Causes of MINOCA' above.)

In an observational study from the SWEDEHEART registry, 9466 consecutive patients with MINOCA were followed for subsequent major adverse cardiac events [23]. During a mean follow-up of 4.1 years, 2183 (23.9 percent) patients experienced a major adverse cardiac event. The hazard ratios (95% CI) for major adverse cardiac events were 0.77 (0.68 to 0.87), 0.82 (0.73 to 0.93), and 0.86 (0.74 to 1.01) in patients on statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta blockers, respectively. For patients on dual antiplatelet therapy followed for one year, the hazard ratio was 0.90 (0.74 to 1.08). The authors showed long-term beneficial effects of treatment with statins and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers on outcome in patients with MINOCA, a trend toward a positive effect of beta blocker treatment, and a neutral effect of dual antiplatelet therapy. Each of the treatments might have a beneficial effect in a specific patient subset with a common cause of MINOCA, while the effect may be diluted in the whole MINOCA population. Thus, the observational nature of this study makes us uncertain of the potential magnitude of the benefit or lack of benefit of these interventions. For the time being, the major effort is to accurately diagnose the underlying cause of MINOCA in the vast majority of patients by using intravascular imaging, provocative coronary testing, and cardiac magnetic resonance imaging. This is the key premise for a personalized form of treatment.

●Prognosis – Given the heterogeneity of causes, studies of the prognosis of patients with MINOCA are of limited value, as prognosis may be influenced by the cause and degree of myocardial damage associated with the MI.

•Mortality – In a meta-analysis of eight studies that reported all-cause mortality in patients with MINOCA, in-hospital mortality was 0.9 percent, and 12-month mortality was 4.7 percent [6]. When restricted to studies directly comparing MINOCA and MI due to obstructive CAD, in-hospital and 12-month mortality were lower in patients with MINOCA (1.1 versus 3.2 percent and 3.5 versus 6.7 percent, respectively).

•Prognostic factors – Of interest, reduced LV ejection fraction, nonobstructive CAD, use of beta blockers during follow-up, and ST-segment depression on the admission electrocardiogram are significant predictors of long-term prognosis [24].

●Race-ethnic disparities – In the WISE study of 580 women with ischemia with nonobstructive coronary arteries (17 percent of whom were Black), Black women had an increased risk of major cardiovascular events (all-cause mortality, nonfatal MI, stroke, and hospitalization for either angina or heart failure) compared with those of other race-ethnicities (52 versus 33 percent; hazard ratio1.57; 95% CI 1.04-2.38) [25]. Black women also had an increased risk of cardiovascular mortality (11 versus 6 percent; age-adjusted hazard ratio 2.46; 95% CI 1.18-5.12). A prior report in the same cohort suggested that atypical symptom presentation may be a barrier to timely diagnosis and treatment; these factors and the higher burden of cardiovascular risk factors may underlie poorer outcomes for Black women [26].

ISCHEMIA WITH NO OBSTRUCTIVE CORONARY DISEASE

Epidemiology of INOCA — One study reported that 50 percent of people undergoing elective angiography for chest pain had no obstructive coronary artery disease (CAD) [27]. Still, the diagnosis of ischemia with no obstructive coronary arteries (INOCA) was not confirmed in these individuals, making it impossible to estimate an exact prevalence of this condition.

Causes of INOCA

Coronary artery spasm — This condition is discussed in detail separately. (See "Vasospastic angina".)

Microvascular disease — This condition and disease associations are discussed in detail separately. (See "Microvascular angina: Angina pectoris with normal coronary arteries".)

Coronary artery anomaly — These are discussed in detail separately. (See "Congenital and pediatric coronary artery abnormalities".)

Clinical features of INOCA — The clinical presentation of INOCA is similar to that of angina from obstructive CAD. (See "Approach to the patient with suspected angina pectoris".)

Evaluation and diagnosis of INOCA — Patients with INOCA are often evaluated with either invasive or noninvasive cardiac testing to determine the cause of their symptoms. Many patients present with angina or anginal equivalent symptoms. Establishing the specific diagnosis with functional testing is important, as it has been shown to influence the healthcare experiences, quality of life, and emotional states of women with INOCA [28].

Invasive versus noninvasive evaluation — Patients may be referred for invasive angiography because of pronounced and/or refractory angina symptoms, for further diagnostic evaluation after noninvasive testing (eg, to guide therapy or due to an equivocal test), or due to a lack of available noninvasive testing for INOCA. The approach to diagnostic testing of patients with angina, including choice of specific testing, is discussed separately. (See "Approach to the patient with suspected angina pectoris", section on 'Patient without known coronary artery disease'.)

We often pursue noninvasive testing in patients in whom previous evaluations (imaging, invasive angiography, or coronary computed tomographic angiography) have ruled out obstructive CAD and those in whom the likelihood of obstructive CAD has been assessed to be low or intermediate.

Patients requiring an invasive evaluation — This testing includes visual assessment of coronary artery lesions and possibly hemodynamic assessment of individual lesions and/or coronary flow reserve testing. (See "Clinical use of coronary artery pressure flow measurements".)

Coronary stenosis ≥50 percent

Fractional flow reserve assessment — Among patients with coronary stenosis ≥50 percent , we assess fractional flow reserve (FFR)

●FFR <0.8 – Ischemia from obstructive CAD is the likely etiology of symptoms. We treat and reassess symptoms in regular follow-up.

●FFR ≥0.8 – CAD is present; however, it is not hemodynamically significant and thus not a likely cause of symptoms. We continue our assessment for vasospasm. (See 'Assessment of vasospasm' below.)

Assessment of vasospasm — Upon intracoronary injection of acetylcholine, we assess for reproduction of chest pain and ischemic electrocardiographic changes, which indicate that vasospasm is present. In these patients, if the vasospasm constricts the coronary artery lumen ≥90 percent upon visual examination, epicardial vasospasm is diagnosed. If not, microvascular vasospasm is diagnosed.

No coronary stenosis or ≤50 percent — For these patients, we assess microvascular disease by testing coronary flow reserve with a Doppler wire. If there is a coronary flow reserve <2 or index of microcirculatory resistance <25, we diagnose microvascular dysfunction. We continue assessment for vasospasm. (See 'Assessment of vasospasm' above.)

Patients requiring noninvasive evaluation — Such patients typically undergo stress test (algorithm 2). (See "Stress testing for the diagnosis of obstructive coronary heart disease" and "Selecting the optimal cardiac stress test".)

Ischemia on stress test — If the stress test shows ischemia, the next step is to evaluate myocardial blood flow to aid in diagnosis as follows:

●Reduced myocardial blood flow – In these patients, we diagnose microvascular disease with ischemia.

●Normal myocardial blood flow – In these patients, microvascular disease is not present; however, INOCA likely is present. We therefore assess for vasospasm and other causes of INOCA. (See 'Assessment of vasospasm' above and "Clinical use of coronary artery pressure flow measurements".)

No ischemia on stress test — Our next step is to assess myocardial blood flow to aid in diagnosis as follows:

●Reduced myocardial blood flow – In these patients, we diagnose microvascular disease without ischemia.

●Normal myocardial blood flow – A diagnosis of INOCA is unlikely, and thus we search for alternative diagnoses. (See "Evaluation of the adult with chest pain in the emergency department" and "Outpatient evaluation of the adult with chest pain".)

Management — The treatment of INOCA is specific to the underlying cause. Thus, accurate diagnosis of the underlying cause of INOCA can be obtained in the vast majority of patients using intravascular imaging, provocative coronary testing, and cardiac magnetic resonance imaging. (See 'Causes of INOCA' above.)

RECOMMENDATIONS OF OTHERS — A European Society of Cardiology working group has published a position paper on myocardial infarction with nonobstructive coronary arteries [29]. The content of that paper is similar to the content of this topic review.

SUMMARY

●Introduction and definitions – Myocardial infarction with no obstructive coronary atherosclerosis (MINOCA) is a syndrome with multiple potential causes. Ischemia with no obstructive coronaries (INOCA) refers to several potential diagnoses that cause ischemia not caused by obstructive coronary disease. (See 'Introduction and definitions' above.)

●MINOCA

•Epidemiology – In a systematic review of studies, the prevalence of MINOCA among patients with acute MI is between 1 and 15 percent. (See 'Epidemiology of MINOCA' above.)

•Causes – The causes of MINOCA can be categorized as epicardial, microvascular, and embolic. (See 'Causes of MINOCA' above.)

•Diagnosis – Our approach to elucidating the cause of MINOCA uses information in the patient’s history, from their angiogram, and from an imaging assessment of left ventricular (LV) wall motion, preferably with transthoracic echocardiography (TTE) (algorithm 1). If TTE has not been performed before coronary angiography, it can be performed in the catheterization laboratory or left ventriculography can be performed as a substitute.

•Management and prognosis – The treatment of MINOCA is specific to the underlying cause. Thus, accurate diagnosis of the underlying cause of MINOCA can be obtained in the vast majority of patients using intravascular imaging, provocative coronary testing, and cardiac magnetic resonance imaging. (See 'Causes of MINOCA' above.)

Given the heterogeneity of causes, studies of the prognosis of patients with MINOCA are of limited value, as prognosis may be influenced by the cause and the degree of myocardial damage associated with the MI.

●INOCA

•Epidemiology – The exact prevalence of INOCA is uncertain. (See 'Epidemiology of INOCA' above.)

•Causes – Potential causes of INOCA include coronary artery spasm, microvascular disease, and coronary artery anomaly. (See 'Causes of INOCA' above.)

•Clinical features – The clinical presentation of INOCA is similar to that of angina from obstructive coronary artery disease (CAD). (See "Approach to the patient with suspected angina pectoris".)

•Diagnosis – Patients with INOCA are often evaluated with either invasive or noninvasive cardiac testing to determine the cause of their symptoms. Many patients present with angina or anginal equivalent symptoms. Patients may be referred for invasive angiography because of pronounced and/or refractory angina symptoms, for further diagnostic evaluation after noninvasive testing (eg, to guide therapy or due to an equivocal test), or due to a lack of available noninvasive testing for INOCA. (See 'Evaluation and diagnosis of INOCA' above.)

•Management – The treatment of INOCA is specific to the underlying cause. (See 'Management' above.)