Multimodal Imaging in MI with Non-obstructive Coronary Arteries: Unraveling Pathophysiology and Guiding Management

Abstract

MI with non-obstructive coronary arteries (MINOCA) represents a complex, heterogeneous syndrome with variable underlying mechanisms and substantial morbidity. The role of multimodality cardiovascular imaging in clarifying etiology and guiding therapy continues to evolve. Multimodality imaging offers insights into the pathophysiology of MINOCA. Coronary angiography remains the first-line diagnostic tool to exclude obstructive coronary disease, while adjunctive functional testing can identify epicardial or microvascular vasospasm. Echocardiography evaluates ventricular function, wall motion abnormalities, and embolic sources, whereas cardiac MRI differentiates ischemic from non-ischemic injury, detects myocardial edema, and assesses scar burden. Intravascular imaging can detect plaque rupture, erosion, or thrombus. Nuclear imaging modalities provide a quantitative assessment of microvascular perfusion and coronary flow reserve. Coronary CT angiography may further characterize non-obstructive plaque or coronary anomalies. This review summarizes the comprehensive evaluation of MINOCA. Integrating modalities can improve diagnostic accuracy, identify the underlying etiology, guide targeted therapy, and inform prognosis, underscoring the importance of a multimodal imaging approach.

MI with non-obstructive coronary arteries (MINOCA) is a complex, heterogeneous clinical entity associated with substantial morbidity and an incompletely defined prognosis. Although the term MINOCA was introduced in the 2010s,1 the syndrome itself was first described nearly 80 years earlier, when patients presenting with clinical features of acute MI (AMI) were observed to have angiographically normal or near-normal coronary arteries.2 Persistent diagnostic uncertainty, misclassification, and the absence of standardized evaluation pathways have contributed to limited evidence-based treatment strategies. Figure 1 shows a timeline of significant events in the history of MINOCA.

Figure 1: Timeline of MI with Non-obstructive Coronary Arteries.

MINOCA = MI with non-obstructive coronary arteries. Created in BioRender. Diaz, G. (2026) https://BioRender.com/jjn1d2w

MINOCA is defined as an AMI occurring in the setting of non-obstructive coronary artery disease (CAD), typically defined as <50% stenosis in major epicardial coronary vessels, without an alternative clinically overt cause for the acute presentation. In 2019, the American Heart Association specified three essential diagnostic criteria.3,4 First, patients must meet criteria for AMI according to the Fourth Universal Definition of MI, including cardiac troponin >99th percentile with a characteristic rise or fall on serial assessment, in conjunction with at least one of the following: symptoms of MI; new ischemic EKG changes; development of pathological Q waves; imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with ischemia; or identification of a coronary thrombus by angiography or autopsy.3,4 Second, coronary angiography must demonstrate non-obstructive coronary arteries, defined as the absence of lesions ≥50% in any major epicardial vessel.

Third, other clinically overt causes of myocardial injury must be excluded, including pulmonary embolism, sepsis, myocarditis, and takotsubo syndrome.

MINOCA is most commonly conceptualized as a predominantly vascular disorder. Proposed etiologies include plaque rupture or erosion, coronary vasospasm, spontaneous coronary artery dissection (SCAD), in situ coronary thrombosis, and coronary thromboembolism.5 Coronary microvascular dysfunction (CMD) probably contributes to the pathophysiology of many MINOCA presentations; however, current evidence is insufficient to define it as an independent etiology.5,6 Earlier frameworks included supply–demand mismatch (type 2 MI) related to conditions such as anemia, hypotension or hypertension, respiratory failure, and tachyarrhythmias or bradyarrhythmias.7 However, more recent definitions have increasingly excluded type 2 MI, narrowing MINOCA to ischemic mechanisms arising from coronary vascular pathology.5 Importantly, MINOCA mimickers, including non-ischemic cardiomyopathies, myocarditis, and takotsubo cardiomyopathy, must be systematically excluded before the diagnosis is established.7

Epidemiology and Clinical Significance

MINOCA occurs in approximately 6–8% of patients with spontaneous MI undergoing coronary angiography.8–10 MINOCA exhibits substantial demographic variability and is disproportionately represented in specific patient subgroups. Women account for approximately 40–60% of MINOCA cases, compared with roughly 25% of MI with obstructive CAD, and are more than twice as likely as men to present with MINOCA at the time of acute MI.8,10 The condition is also more prevalent among younger patients, with estimates of 10–20% in younger MI cohorts and 8–11% among patients younger than 55 years.8,11 MINOCA occurs more frequently in patients presenting with non-ST-elevation MI (NSTEMI) than STEMI and has been reported at higher rates among Black, Pacific Islanders, and Hispanic patients.10

Compared with patients with obstructive CAD, individuals with MINOCA tend to be younger (mean age approximately 58 versus 61 years) and have fewer traditional cardiovascular risk factors, particularly dyslipidemia; however, approximately 75% have at least one established risk factor, including hypertension, diabetes, smoking, hyperlipidemia, or a family history of CAD.8,10,11 Clinical presentations are often characterized by less prominent ST-segment deviation on EKG and smaller cardiac troponin elevations.10

Although prognosis is more favorable than that of MI with obstructive CAD, MINOCA is associated with significant morbidity and mortality. Major adverse cardiovascular events (MACE) occur in approximately 24% of patients over 4 years, recurrent MI in approximately 7%, and nearly half of patients demonstrate progression to obstructive CAD at the time of a subsequent MI.12,13 Persistent angina affects approximately 25% of patients at 12 months, and 1-year mortality approaches 4.7%, underscoring the need for improved diagnostic and management strategies.14,15

Pathophysiological Mechanisms

The etiologies of MINOCA include atherosclerotic plaque disruption, coronary vasospasm, SCAD, and coronary embolism, which may be broadly categorized as atheroembolic or non-atheroembolic mechanisms (Figure 2).

Figure 2: Etiologies of MI with Non-obstructive Coronary Arteries.

Created in BioRender. Diaz G (2026) https://BioRender.com/kkfq0jo.

Atherosclerotic plaque is characterized by a lipid-rich necrotic core covered by a fibrous cap.16 Plaque disruption, including rupture or erosion, can precipitate platelet activation and thrombin generation, resulting in occlusive or non-occlusive coronary thrombus formation that may embolize distally or undergo spontaneous lysis, leading to myocardial ischemia.7 Plaque erosion, in contrast to rupture, is characterized by thrombosis along an intact fibrous cap and occurs more frequently in younger patients and women. Plaque rupture is defined as the presence of a cavity within the plaque, communicating with the arterial lumen and having an overlying residual fibrous cap fragment.17 Intravascular imaging studies using intravascular ultrasound (IVUS) have demonstrated features of plaque disruption in approximately one-third of patients with MINOCA, supporting an atheroembolic mechanism in a substantial proportion of cases.18,19

Coronary vasospasm results from hyperreactivity of vascular smooth muscle, leading to transient focal or diffuse vasoconstriction that reduces coronary blood flow and precipitates MI. Vasospasm represents a common mechanism of MINOCA, with provocative testing identifying epicardial coronary spasm in up to 46% of patients in one study.20

SCAD occurs when an intimal tear or intramural hematoma within the coronary vessel wall creates a false lumen, resulting in compression of the true lumen and impaired myocardial perfusion. Although an infrequent cause of MINOCA overall, SCAD disproportionately affects younger women, and sex-related hormonal factors are thought to play an important pathogenic role.21

Transient or partial thrombosis at the site of a non-obstructive atherosclerotic plaque may undergo spontaneous fibrinolysis or result in distal coronary embolization, leading to myocardial necrosis that is not readily apparent on coronary angiography because of thrombus size, rapid resolution, or distal location.7

Rationale for Imaging-guided Approach

Application of a structured diagnostic framework for MINOCA may improve diagnostic certainty and enable etiology-specific management, given that therapeutic strategies vary substantially according to the underlying mechanism (Figure 3). Therefore, current guidelines advocate for a multimodality imaging approach to establish the cause of MINOCA.

Figure 3: Diagnostic Algorithm of MI with Non-obstructive Coronary Arteries.

SCAD = spontaneous coronary artery dissection. Created in BioRender. Diaz, G. (2026) https://BioRender.com/82wddmd

One proposed stepwise approach begins with confirmation of MINOCA at the time of coronary angiography, ideally supplemented by left ventriculography. Subsequent evaluation includes exclusion of alternative diagnoses through careful angiographic review and transthoracic echocardiography (TTE). Early cardiac MRI (CMR) is then recommended to differentiate ischemic from non-ischemic myocardial injury and identify infarction patterns. Intravascular imaging with optical coherence tomography (OCT) or IVUS may further elucidate plaque disruption, SCAD, or other occult coronary abnormalities. When an etiologic diagnosis remains uncertain, adjunctive testing, including coronary functional assessment, coronary CT angiography (CCTA), or nuclear imaging, may provide additional diagnostic insight.5,7,19 This framework is the focus of this paper, but other approaches exist. A recent study of patients with chest pain and elevated troponin who underwent an imaging protocol of CCTA, iodine-enhanced CT, and CMR imaging found that the CT-based protocol accurately distinguished between ischemic and inflammatory myocardial injury in patients presenting with MINOCA. One of the notable aspects of this framework is the possibility to bypass invasive coronary angiography; however, current guidelines continue to require coronary angiography as the initial diagnostic step.22 See Table 1 for a summary of MINOCA imaging modalities.

Table 1: Summary of MI with Non-obstructive Coronary Arteries Imaging Modalities.

Imaging Modality	Advantages	Disadvantages	Applicability
Invasive coronary angiography	Rule out obstructive coronary artery disease If performed with provocation testing, may identify vasospasm	Invasive Inability to show wall or intravascular pathologies Low resolution Limited to epicardial vasculature Requires contrast	Initial test
Optical coherence tomography/intravascular ultrasound	Identify spontaneous coronary artery dissection, recent plaque rupture, plaque density	Invasive Technician-dependent Not widely available	Increased diagnostic specificity, especially with cardiac MRI
Transthoracic echocardiography	Non-invasive Inexpensive May identify features of MI with non-obstructive coronary arteries mimickers	Technician-dependent	Can occur before or after coronary angiography
Cardiac MRI	Can identify underlying cause of MI with non-obstructive coronary arteries or mimickers Can identify infarct and myocardial edema Prognostic value	Higher cost Limited availability Time-consuming	Early use can identify transient causes
Coronary CT angiography	Non-invasive Anatomic assessment	Radiation exposure Requires iodinated contrast	Adjunct, can reduce further invasive testing
PET/single photon emission CT	Non-invasive Assesses myocardial blood flow, coronary flow reserve	Higher cost Lower spatial resolution Requires specialized infrastructure	Adjunct, can reduce further invasive testing

Coronary Angiography

In suspected MINOCA, coronary angiography serves to exclude obstructive CAD and other angiographically apparent causes of MI. Careful, systematic review of angiographic findings is essential to identify potential mechanisms of injury. Subtle luminal irregularities may indicate plaque rupture or erosion, while radiolucent flaps, diffuse narrowing, or angiographic haziness can raise suspicion for SCAD.23,24 Left ventricular wall motion abnormalities assessed by ventriculography may suggest takotsubo cardiomyopathy.23

Although not routinely performed during the initial angiographic evaluation, coronary functional testing represents a valuable adjunct in selected patients. Intracoronary acetylcholine or adenosine provocation can identify coronary vasomotor disorders, including epicardial and microvascular spasm.25 Epicardial spasm is visualized angiographically as reversible focal or diffuse vessel narrowing, whereas microvascular spasm is diagnosed when ischemic symptoms and EKG changes occur following acetylcholine administration in the absence of epicardial vasoconstriction.26

Several limitations of coronary angiography complicate the diagnostic evaluation of MINOCA. Angiography provides limited assessment of the vessel wall and intravascular pathology, has relatively low spatial resolution, and may inadequately visualize distal or microvascular abnormalities. In cases of SCAD, angiographic findings may be subtle or non-obstructive, leading to under-recognition of the condition.27,28 In addition, the requirement for iodinated contrast restricts its use in patients with advanced kidney disease.29 Invasive coronary functional testing also incurs additional cost and procedural time due to the need for specialized guidewires and extended cath lab resources.12

Echocardiography

TTE should be performed early in the evaluation of patients with suspected MINOCA to assess left ventricular function and regional wall motion. As a non-invasive modality, TTE can help triage patients for further evaluation with CMR or invasive testing and is typically feasible shortly before or after coronary angiography in clinically stable patients. Specific findings may suggest distinct diagnoses, including apical ballooning in takotsubo cardiomyopathy, global left ventricular dysfunction in viral myocarditis, and pericardial effusion in pericarditis.30–32 TTE also provides pressure estimates, visualization of intracardiac shunts, and ventricular function, which can aid in identifying alternative cardiomyopathies and deprioritizing MINOCA in the differential diagnosis. TTE can also evaluate potential embolic causes of MINOCA, including patent foramen ovale via bubble study, intracardiac thrombus in the left atrium or left ventricle, and valvular vegetations.5 When thromboembolism is strongly suspected, transesophageal echocardiography – the gold standard for left atrial and left atrial appendage thrombus – should be considered.33

Cardiac MRI

Early CMR with late gadolinium enhancement (LGE), T1/T2 mapping, and extracellular volume (ECV) assessment can differentiate ischemic from non-ischemic myocardial injury and identify alternative diagnoses. For example, MINOCA typically demonstrates an ischemic pattern, whereas takotsubo cardiomyopathy and myocarditis show characteristic non-ischemic patterns.34 Ischemic patterns include subendocardial or transmural LGE in coronary artery territories, whereas myocarditis typically demonstrates midwall/subepicardial LGE in non-coronary distributions, and takotsubo typically shows extensive edema without significant LGE.35

The Lake Louise Criteria provide diagnostic criteria for non-ischemic myocardial inflammation. The criteria are comprised of at least one T2-based marker for myocardial edema and at least one T1-based marker for associated myocardial injury, with supporting criteria of evidence of pericarditis or systolic dysfunction.36 Myocardial edema is evidenced by regional high T2 signal intensity (T2SI) or a global T2SI >2.0 on T2-weighted images.37 T1 and T2 mapping increase diagnostic sensitivity and specificity of CMR, as demonstrated by a study which showed that patients undergoing CMR for cardiomyopathy had improved diagnostic sensitivity for myocarditis when a T1 and T2 mapping protocol was used (69% versus 89%, p = 0.008).37,38 Additionally, ECV measurements can enhance evaluation of myocardial fibrosis and edema compared to LGE alone. In a study of patients suspected to have subacute, severe myocarditis, ECV quantification combined with LGE in CMR significantly improved the diagnostic accuracy compared to using Lake Louise Criteria.39

CMR is a central tool in the evaluation of MINOCA and is recommended by both the European Society of Cardiology and the American College of Cardiology/American Heart Association.40,41 In a meta-analysis of patients with MINOCA who underwent CMR within 10 days of the acute event, a definitive diagnosis was established in 63% of cases. Among these, only 22% were confirmed as MINOCA, while 68% were reclassified, most commonly as myocarditis (31%).34 When myocardial edema is incorporated into the diagnostic criteria for MINOCA, CMR confirms the diagnosis in approximately 50–80% of patients.5,19,42 Vasodilator stress CMR with quantitative perfusion mapping is particularly useful in the detection of CMD, a possible contributor to multiple MINOCA etiologies. Stress CMR can compare measurements of absolute myocardial blood flow (MBF) at rest and with stress, allowing for a calculation of myocardial perfusion reserve. Stress myocardial blood flow ≤2.19 ml/g/min or myocardial perfusion reserve ≤2.06 indicates CMD. This diagnostic method has been validated with the gold standard index of microcirculatory resistance which is obtained during coronary angiography.43 Limitations of CMR include timing- and technique-dependent diagnostic yield, the potential to miss small infarcts or transient abnormalities, cost, and the need for specialized equipment and expertise.

The diagnostic yield of CMR varies with timing, ranging from 57% when performed after 2 weeks to 84% when performed within 2 weeks of the acute event. This variability may reflect normalization of imaging findings in takotsubo cardiomyopathy, acute myocarditis, myocardial stunning, or very small infarcts.37 Early CMR combined with high peak troponin (≥211 ng/l) provides the highest diagnostic yield, with a positive predictive value of 94% and negative predictive value of 34%. Even when performed after 14 days or in patients with low troponin, diagnostic yield remains high at 72%.37 Other factors that improve CMR utility include older age, male sex, and ST-segment elevation on EKG.37 However, only 44% of MINOCA patients demonstrate a characteristic ischemic pattern on CMR, even when plaque disruption is visualized on OCT, highlighting the role of advanced techniques such as T1/T2 mapping and ECV assessment.44

Optical Coherence Tomography and Intravascular Ultrasound

Invasive imaging of the coronary arteries using intravascular modalities such as IVUS or OCT can aid in establishing a definitive etiology in MINOCA by identifying plaque disruption, SCAD, or coronary thrombosis.7,19 OCT and IVUS are the only modalities that can definitively identify plaque disruption and are recommended in MINOCA patients who have non-obstructive CAD on coronary angiography. OCT is the only modality sufficient to identify plaque erosion, which may be an underdiagnosed etiology of MINOCA.45 In a meta-analysis of 17,539 patients with MINOCA who underwent coronary angiography, OCT, and/or coronary vasomotor testing, OCT found an acute diagnosis in 62% of patients and coronary vasomotor tests were positive in 49%, proving their diagnostic capabilities in this population.46

OCT employs near-infrared light to generate high-resolution images of the vessel, allowing visualization ofthe fibrous cap, thrombus, calcification, and the distinct layers of the vessel wall, including the intima, media, and adventitia.47 OCT is the only modality sufficient to diagnose plaque erosion in vivo. In women with MINOCA, OCT studies have identified recent plaque rupture and intraplaque hemorrhage as the etiology.48 In SCAD, OCT can assist in measuring the length of intramural hematomas, degree of luminal compromise, and thickness of the dissected intimal tear.49 Limitations of OCT include its inability to assess vasospasm, potential risk of propagating the false lumen in SCAD, and contraindication in patients with significant renal impairment due to contrast use.29

IVUS uses ultrasonic waves to image the vessel wall and classify plaque composition as soft, fibrous, calcified, or mixed. IVUS has identified culprit lesions in up to 38% of MINOCA cases but is unable to detect plaque erosion due to its resolution capabilities.17 While intravascular imaging is not routinely performed during initial coronary angiography and is limited by institutional availability, these modalities provide important diagnostic insight in MINOCA.

Nuclear Imaging

Nuclear imaging can be a valuable tool in the evaluation of MINOCA, particularly for assessing myocardial perfusion and identifying ischemia in the absence of obstructive coronary disease. PET provides high-resolution, quantitative assessment of myocardial blood flow and myocardial flow reserve, allowing detection of impaired perfusion even at the microvascular level. PET has demonstrated superior sensitivity and specificity compared with single photon emission CT (SPECT) for identifying CMD; however, newer cadmium-zinc-telluride SPECT (CZT-SPECT) systems have been validated to quantify myocardial flow reserve, and one study comparing CZT-SPECT to PET found higher sensitivity and accuracy of CZT-SPECT for detecting CAD.50,51 Compared to SPECT, the use of CZT-SPECT systems may also decrease study times.52

CMD contributes to myocardial ischemia in MINOCA but is generally not considered a standalone etiology. The pathophysiology is impaired regulation of blood flow in the microcirculation due to endothelial dysfunction, smooth muscle hyperreactivity, or structural remodeling, leading to inadequate perfusion during stress or spontaneous microvascular spasm.5 Identification of CMD can explain persistent symptoms, inform prognosis, and guide medical therapy, although current consensus statements do not classify CMD as a primary MINOCA etiology.5,7

In combination with PET or SPECT imaging, 18F-fluorodeoxyglucose (FDG) uptake can be useful in assessing myocardial inflammation and identifying MINOCA mimickers such as myocarditis or sarcoidosis. Focal FDG uptake with a corresponding perfusion defect is characteristic of myocarditis; however, other inflammatory states including myocardial ischemia can present similarly. FDG uptake scans can be helpful complements to CMR tissue characterization or as an alternative to CMR if combined with CT.53

CT Coronary Angiography

CCTA is not a first-line diagnostic tool for MINOCA, as acute evaluation typically relies on invasive coronary angiography, which allows immediate assessment of coronary anatomy, adjunctive testing, and potential intervention.5,20 CCTA is most useful when invasive angiography is inconclusive, not feasible, or for follow-up evaluation to further characterize coronary plaque or detect anomalies. In NSTEMI acute coronary syndrome, the VERDICT trial demonstrated that CCTA can effectively rule out obstructive disease, with a negative predictive value of 91% and sensitivity of 97%; however, the RAPID-CTCA trial found that early use of CCTA did not reduce death or subsequent MI.54,55

CCTA provides high-resolution imaging of the coronary tree and enables visualization of plaque beyond the lumen. Artificial intelligence-based plaque analysis can quantify total plaque burden and characterize morphology, including calcified, noncalcified, and low-attenuation plaques.56,57 In MINOCA, CCTA can detect potential mechanisms of ischemia such as plaque rupture or erosion, identify high-risk plaque features, quantify pericoronary fat, and detect SCAD.56,58

The pericoronary fat attenuation index (pFAI) can be assessed using CCTA and is an indicator of coronary artery inflammation, which is associated with vulnerable, high-risk plaques that could be implicated in MINOCA.59 Studies have also found pFAI to be a predictor of cardiac mortality, and in a study of patients with MINOCA and takotsubo syndrome, the mean pFAI was significantly higher compared to controls (-68.37 ± 8.29 versus -78.03 ± 6.20, p<0.0001).60,61 CCTA also plays a role in follow-up evaluation, particularly in patients with SCAD identified on initial imaging, as it can reduce the need for repeat invasive angiography, which may precipitate further dissection. Overall, while CCTA is not the first-line tool in acute MINOCA, it provides complementary non-invasive information that can refine diagnosis, risk stratification, and longitudinal management.

Imaging-guided Management

Patients with atherothrombotic disease would benefit from long-term antiplatelet and statin therapy. In contrast, patients with coronary vasospasm would benefit from long-acting nitrates or calcium-channel blockers. Patients with SCAD may benefit from β-blockers and screening for fibromuscular dysplasia. Finally, patients with MI from supply–demand mismatch may only require treatment for their underlying concurrent illness.

The goal of imaging in MINOCA is to identify the underlying mechanism, as treatment strategies vary accordingly. In most cases, conventional secondary prevention therapies for AMI are indicated, including antiplatelet therapy, statins, β-blockers, and, in patients with left ventricular dysfunction, guideline-directed medical therapy.7

In MINOCA due to plaque disruption identified by OCT or IVUS, treatment aligns with AMI guidelines, including aspirin and aggressive risk factor modification. Although the SWEDEHEART study did not stratify outcomes by plaque etiology, there is evidence supporting dual antiplatelet therapy in cases of plaque rupture or erosion.7

First-line therapy for coronary vasospasm, including vasospastic angina associated with MINOCA and identified with provocative intracoronary testing, is calcium channel blockers, which reduce smooth muscle contractility and prevent spasm.62

When MINOCA is secondary to coronary embolism or thrombosis, often associated with hypercoagulable states, treatment should target the underlying disorder, including antiplatelet or anticoagulant therapy and hematology consultation.5,7

For SCAD, acute revascularization is generally avoided because lesions often heal spontaneously, and intervention may propagate dissection or intramural hematomas. Medical therapy typically includes β-blockers and aspirin, with careful avoidance of high-intensity or strenuous exercise. Pregnancy and the postpartum period require individualized risk assessment and multidisciplinary care, as SCAD is a leading cause of acute coronary syndrome in these populations.49,63,64 Long-term follow-up includes surveillance for recurrent SCAD, management of cardiovascular risk factors, and evaluation for underlying arteriopathies, such as fibromuscular dysplasia or connective tissue disorders. Short-term dual antiplatelet therapy may be considered if percutaneous coronary intervention is performed, but aspirin monotherapy is typically sufficient in conservatively managed patients.7,63,64

Prognostic Value

Given the availability of multimodality imaging in MINOCA, imaging phenotypes may help predict prognosis. CMR findings are particularly informative. Patients with a normal CMR have excellent outcomes at 10 years.65,66 In contrast, the presence of myocardial injury is associated with worse outcomes. In an observational study of 198 MINOCA patients followed for a mean of 33.7 months, those with LGE and myocardial edema had a 20.7% incidence of MACE, compared with 6.7% in patients without LGE and with myocardial edema, and 2.7% in patients with normal CMR (p=0.006).42 Patients with regional edema had worse outcomes than those with normal imaging, and infarcted myocardium portended the poorest prognosis. Similarly, a meta-analysis demonstrated that MINOCA confirmed by CMR was associated with increased MACE (OR 2.4; 95% CI [1.6–3.59]).34,42 Specific CMR features correlating with MACE included higher LGE burden, larger area at risk, microvascular obstruction, and elevated T2 and T1 values.42

OCT also provides prognostic insight. Patients with atherosclerotic culprit lesions on OCT have a higher risk of MACE than those without identified lesions, with plaque rupture associated with worse outcomes than plaque erosion.67,68 A meta-analysis of intravascular diagnostic techniques in MINOCA found an increased 1-year risk of MI in patients with 1–49% coronary stenosis compared with patients with 0% stenosis (RR 1.80; 95% CI [1.26–2.59]).46

Inflammatory plaque rupture, particularly when accompanied by local or systemic inflammation, further increases the risk of atherothrombotic recurrence.44

Regarding general prognosis, studies report variable results. The SWEDEHEART registry of 199,163 first-MI patients found that 24% of MINOCA patients experienced a MACE over a mean follow-up of 4.5 years, with overall mortality of 13%, although true ischemic MINOCA was not confirmed in all cases.12 In the VIRGO study of 2,690 patients <55 years of age who presented with acute MI, 11% ultimately had MINOCA. Those patients had higher short-term survival but similar or worse long-term outcomes compared with MI with obstructive coronary disease.44,69 Systematic reviews indicate that in-hospital and 12-month mortality is lower in MINOCA than in MI-CAD, yet the annual mortality remains higher than in patients with stable chest pain without prior MI.8

Future Directions

Research on MINOCA evaluation and management is expanding as we gain more insight into the implications on morbidity and mortality. Hybrid imaging, particularly combining nuclear imaging (PET or SPECT) with high-resolution imaging (CCTA or CMR) provides information on structure, function, and perfusion to improve diagnostic accuracy and assess the risk of MACE in CAD.70–72 Emerging CT-based strategies for myocardial tissue characterization may serve as an adjunct to CMR or facilitate tissue evaluation when CMR availability is limited or delayed. Late contrast enhancement (LCE) can be likened to LGE in CMR, with similar efficacy in detecting myocardial scar and fibrosis.

In a study of patients presenting with chest pain, stably elevated troponin, and absence of AMI based on clinical evaluation, a CT-based protocol of triple-rule-out CT (ruling out obstructive MI, aortic dissection, and pulmonary embolism) and LCE scan were used. CMR was performed within 1 week and used as a reference standard. In 42 of 84 participants without obstructive CAD, the LCE scan diagnosed myocarditis (52%), takotsubo cardiomyopathy (10%), and additional specific diagnoses (19%), allowing for a formal diagnosis in 90% of the sample compared to 50% prior to LCE. Compared to CMR/LGE there was underestimation of scar, but CT can be rapidly obtained and is more accessible than CMR in some institutions, making CT-based approaches important to continue investigating, possibly as an early study in the MINOCA diagnostic pathway.73

The 2015 PROMISE trial showed CCTA to be an acceptable alternative to functional stress testing in low-to-intermediate risk patients with chest pain. While this is not the phenotype of MINOCA patients and should not be first line, this trial contributed greatly to the body of research on imaging-based approaches to suspected CAD.74

MINOCA is a heterogeneous working diagnosis that requires a multimodal approach to investigation, both during angiography and subsequently with CMR. Identification of the underlying cause is paramount. Approximately two-thirds of cases may be related to plaque disruption that can be difficult to identify without further imaging. Multimodal imaging should be used to unravel the diverse mechanisms underlying MINOCA, including plaque disruption, thrombosis, coronary vasomotor dysfunction, and SCAD. Strategic integration of intracoronary imaging, echocardiography, and CMR, and adjunctive modalities, such as OCT/ IVUS, coronary functional testing CCTA, nuclear imaging, and hybrid imaging, allows for precise etiologic classification, moving MINOCA management beyond a ‘one-size-fits-all’ approach.

Conclusion

Imaging-informed diagnosis facilitates targeted, mechanism-specific therapies that have the potential to improve clinical outcomes, reduce recurrent events, and avoid unnecessary or harmful treatments. Future progress in MINOCA care will depend on the widespread adoption of imaging-centered diagnostic frameworks that foster collaboration among cardiologists, imagers, and subspecialists.