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

Abstract

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.

Keywords: coronary vessels; magnetic resonance imaging; myocardial infarction; tomography, optical coherence; women.

Figures

Figure 1.. Study flow.

Sites were instructed to enter all consecutive women with MI who were referred for cardiac catheterization into the screening log. A total of 512 site-months of screening logs were submitted between September 2016 and March 2020. Reasons for ineligibility for preangiography consent are shown. One site screened exclusively after angiography and enrolled patients who had OCT conducted for clinical indications. History of coronary artery disease typically included history of percutaneous coronary intervention or coronary artery bypass grafting. OCT was aborted in 1 participant with MINOCA as a result of coronary spasm before images were acquired. Other reasons OCT was not completed in patients with MINOCA were: interventional cardiologist’s assessment that risk of OCT was elevated because of small arteries or excessive tortuosity (n=4), risk of additional contrast (eg, high-contrast load, allergy, or volume overload; n=5), or angiographic evidence of coronary spasm (n=1); cath laboratory scheduling concerns (n=4); ventricular septal defect (n=1); and unexpected technical difficulties (n=1). An additional 3 patients with nonobstructive CAD were determined by the interventional cardiologist to have an alternate explanation for troponin elevation and OCT was not performed (eg, hemodynamically significant aortic stenosis). CMR in the 2 patients with uninterpretable OCT showed infarction in both cases. Reasons that CMR was not available included: participant refused CMR after initial consent (n=16), claustrophobia in scanner (n=3), scheduling issues (n=4), pacemaker (n=1), and CMR performed but not interpretable (n=5; 3%). *Includes 10 pilot patients recruited at New York University, during a time when screening logs were not maintained. CAD indicates coronary artery disease; cath, cardiac catheterization; CMR, cardiac magnetic resonance; eGFR, estimated glomerular filtration rate; MI, myocardial infarction; MI-CAD, myocardial infarction with ≥stenosis in a major epicardial vessel; MINOCA, myocardial infarction with nonobstructive coronary arteries (

Figure 2.. Findings of OCT and CMR in women with MINOCA.

Findings of each core laboratory and the final diagnosis are shown. Note that calcified nodule was not observed. Some patients did not undergo CMR despite eligibility after angiography and OCT (see Figure 1 for reasons CMR was not performed). CMR indicates cardiac magnetic resonance; MINOCA, myocardial infarction with nonobstructive coronary arteries (

Figure 3.. Representative OCT images demonstrating the various types of culprit lesions in women with MINOCA.

In all OCT figures (Figure 3 and Figures II through V in the Data Supplement), the most proximal frame of OCT is shown in the right panel, the middle frame of OCT is shown in the center panel, and the most distal frame of OCT is shown in the left panel. A, Plaque rupture. In the proximal frame, there is discontinuity of a thin fibrous cap (>), indicating a plaque rupture, although it includes motion artifact. There is red thrombus superimposed on the rupture site in the mid frame (>>). In the distal frame, there are focal low-intensity regions indicating injected contrast within the ruptured cavity (→). The underlying plaque is a lipidic plaque (*). B, Intraplaque cavity. Intraplaque cavity: in the proximal, mid, and distal frames, there are low-intensity regions with limited attenuation indicating organized thrombus and/or injected contrast in the ruptured cavity (→) overlaying a high-backscattered fibrous cap (>). The fibrous cap (>) in the proximal frame looks thin, but there was no discontinuity of the fibrous cap, implying previous rupture with sealing. C, Layered plaque. There is a heterogeneous layer (→) overlaying a lipidic plaque (*) indicating healing of a recent plaque rupture event. In the mid frame, there is a focal low-intensity region (>) at the edge of the luminal interface of the layered plaque, indicating a potential site of previous rupture of the fibrous cap. D, Mural thrombus without plaque rupture. There is a homogeneous region with irregular surface indicating platelet-rich mural thrombus (>). Within the underlying lipidic plaque, no clear rupture was observed. E, Intimal bumping consistent with coronary artery spasm. Intimal bumping: there is diffuse intimal wrinkling (←—→) along with thickening of the arterial media (→) indicating spasm. F, Spontaneous coronary artery dissection. There is a dissection plane causing hematoma (←→) exterior to the arterial media, within the adventitia. There is an intimal tear (>, proximal frame) along with contrast flow into the false lumen (*). MINOCA indicates myocardial infarction with nonobstructive coronary arteries (<50% stenosis in all major epicardial vessels); and OCT, optical coherence tomography.

Figure 4.. Representative CMR images in women with MINOCA.

A through F, Myocardial infarction. A through C, T2-weighted images. D through F, Late gadolinium enhanced images, arranged from basal (left) to apical (right). There is subendocardial-to-transmural late gadolinium enhancement of the basal anterior and anteroseptal, mid anterior, and the apical anterolateral wall (>). T2-weighted imaging demonstrates increased signal within and extending beyond the area of late gadolinium enhancement (—→), affecting the LAD territory, including all apical segments. G through I, Regional edema without late gadolinium enhancement. The anterior and anteroseptal walls were hypokinetic (C, systolic frame). This wall motion abnormality was matched by evidence of T2 signal enhancement in the matching regions (D). There was no evidence of infarction on late gadolinium-enhanced imaging (E). J and K, Myocarditis. Multiple foci of late gadolinium enhancement of the anterolateral wall (F), which is matched by T2 hyperintensity in the matching anterolateral wall and anterior wall (G). On cine imaging, there was diffuse hypokinesis of the left ventricle. L and M, takotsubo syndrome. H, Systolic frame demonstrates hypokinesis of the anterior wall, apex, and apical-to-mid inferior wall with preserved contraction at the base. I, T2-weighted imaging with hyperintensity in the anterior wall, apex, and apical-to-mid inferior wall. N, Absence of late gadolinium enhancement. CMR indicates cardiac magnetic resonance; LAD, left anterior descending; and MINOCA, myocardial infarction with nonobstructive coronary arteries (<50% stenosis in all major epicardial vessels).

Figure 5.. OCT and CMR findings in women with MINOCA (n=116).

Specific OCT culprit lesions were related to CMR findings as follows (number of cases with CMR completed, findings): plaque rupture n=7 (2 infarct-pattern LGE, 5 normal); thrombus without plaque rupture n=5 (2 infarct-pattern LGE, 3 regional injury without LGE); intraplaque cavity n=21 (6 infarct-pattern LGE, 10 regional injury without LGE, 2 normal, 3 myocarditis); layered plaque n=15 (5 infarct-pattern LGE, 5 regional injury without LGE, 5 normal); intimal bumping n=2 (1 regional injury without LGE, 1 myocarditis); spontaneous coronary artery dissection n=1 (1 infarct-pattern LGE). CMR indicates cardiac magnetic resonance; LGE, late gadolinium enhancement; MINOCA, myocardial infarction with nonobstructive coronary arteries (

Figure 6.. Representative cases of plaque disruption causing MINOCA.

Top, Representative case of plaque rupture with red thrombus in a wraparound LAD coronary artery with associated apical inferior wall infarction. A 44-year-old woman with no coronary artery disease risk factors who presented with chest pain persisting after transfusion in the context of heavy menstrual bleeding, hemoglobin 7 mg/dL. Peak troponin I was 3.25 ng/mL. A, Angiography of the LAD coronary artery demonstrated a lucency in the proximal LAD with <50% angiographic stenosis. Note that the LAD terminates well past the apex at the inferior wall of the left ventricle. B, OCT image showed a protruding mass with irregular surface indicating mural red thrombus (→). Proximally, there is a low intensity region (* in B1) with clear demarcation indicating cavity in the lipidic plaque. Adjacent thin cap fibroatheroma was observed (▻). C and D, CMR late gadolinium enhanced images, short (C) and long axis (D). There is a small, transmural infarction in the mid-to-apical inferior wall, corresponding with the terminus of the LAD. Bottom, Representative case of layered plaque in LAD coronary artery with associated anterior wall infarction. A 41-year-old woman with hypertension and history of cerebral sinus venous thrombosis who presented with 4.5 hours of midsternal chest pain at rest. The presenting ECG showed equivocal ST elevation in the anterior precordial leads, and cardiac troponin I was 5.1 ng/mL. She was taken urgently for cardiac catheterization showing mild-moderate LAD stenosis after intracoronary nitroglycerin; no intervention was performed. Four days later, because of nonsustained ventricular tachycardia, the patient was referred for repeat coronary angiography (E), showing 20% to 30% LAD stenosis. F1 through F3, OCT images corresponding with proximal mild stenosis showed a layered plaque (white triangles) underlying lipidic plaque (*); images are arranged from distal to proximal, left to right. G through M, The myocardial extent of infarction (H, I, L, and M) was matched by regional wall motion abnormality and evidence of edema on the postcontrast cine SSFP (T2/T1-weighted) imaging (G, J, and K). CMR indicates cardiac magnetic resonance; LAD, left anterior descending; MINOCA, myocardial infarction with nonobstructive coronary arteries (<50% stenosis in all major epicardial vessels); OCT, optical coherence tomography; and SSFP, steady-state free precession.

Figure 7.. Case with myocarditis on CMR affecting the lateral wall and intimal bumping in left circumflex coronary artery on OCT.

A 29-year-old woman with no cardiac risk factors, history of anxiety, who presented with 2 days of midsternal chest pain and normal ECG; there was no fever. An echocardiogram reportedly demonstrated normal left ventricular wall motion. Troponin peaked at 4.57 ng/mL. A, Coronary angiography showed normal coronary arteries. B1 through B3, Left circumflex artery OCT showed intimal bumping (→) consistent with recent coronary artery spasm (panels are arranged from distal in B1 to proximal in B3). C through E, Postcontrast cine SSFP images (T2/T1-weighted) showed enhancement in the apical lateral wall in short- (C) and long-axis (D) views. Epicardial LGE in the same area of the distal lateral wall (E). The final diagnosis was determined to be myocarditis on the basis of consensus review. CMR indicates cardiac magnetic resonance; LGE, late gadolinium enhancement; and OCT, optical coherence tomography.