Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease

Abstract

Background: There is no angiographically demonstrable obstructive coronary artery disease (CAD) in a significant minority of patients with myocardial infarction, particularly women. We sought to determine the mechanism(s) of myocardial infarction in this setting using multiple imaging techniques.

Methods and results: Women with myocardial infarction were enrolled prospectively, before angiography, if possible. Women with ≥50% angiographic stenosis or use of vasospastic agents were excluded. Intravascular ultrasound was performed during angiography; cardiac magnetic resonance imaging was performed within 1 week. Fifty women (age, 57±13 years) had median peak troponin of 1.60 ng/mL; 11 had ST-segment elevation. Median diameter stenosis of the worst lesion was 20% by angiography; 15 patients (30%) had normal angiograms. Plaque disruption was observed in 16 of 42 patients (38%) undergoing intravascular ultrasound. There were abnormal myocardial cardiac magnetic resonance imaging findings in 26 of 44 patients (59%) undergoing cardiac magnetic resonance imaging, late gadolinium enhancement (LGE) in 17 patients, and T2 signal hyperintensity indicating edema in 9 additional patients. The most common LGE pattern was ischemic (transmural/subendocardial). Nonischemic LGE patterns (midmyocardial/subepicardial) were also observed. Although LGE was infrequent with plaque disruption, T2 signal hyperintensity was common with plaque disruption.

Conclusions: Plaque rupture and ulceration are common in women with myocardial infarction without angiographically demonstrable obstructive coronary artery disease. In addition, LGE is common in this cohort of women, with an ischemic pattern of injury most evident. Vasospasm and embolism are possible mechanisms of ischemic LGE without plaque disruption. Intravascular ultrasound and cardiac magnetic resonance imaging provide complementary mechanistic insights into female myocardial infarction patients without obstructive coronary artery disease and may be useful in identifying potential causes and therapies. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00798122.

Figure 1

Patient flow and proportion with plaque disruption. *All patients initially consented to CMR but then declined. ** includes 5 patients with ST elevation myocardial infarction. CMR=cardiac magnetic resonance imaging; IVUS=intravascular ultrasound

Figure 2

Representative angiographic and intravascular ultrasound (IVUS) images in patients with plaque disruption. The site of plaque rupture or ulceration is marked with an arrow on each angiogram. The artery with the abnormality is indicated for each patient. The right panel for each IVUS image shows the outline of the luminal border (yellow) and external elastic lamina (red) corresponding to each IVUS image directly to its left.

Figure 3

Representative CMR images showing late gadolinium enhancement (LGE) (left) with corresponding end-diastolic cine image (right) Panel A: Small, nearly transmural LGE involving the mid inferior wall (arrow). Panel B: Patchy areas of LGE throughout the left ventricle which are primarily midwall, with some septal areas extending to the right ventricular subendocardium (white arrows) and a nearly transmural area in the apical lateral wall (black arrow). Panel C: Representative images showing a mixed pattern of LGE: multiple separate areas of enhancement demonstrating midwall (white arrow) and transmural (black arrows) involvement.

Figure 4

Co-localization of angiographic, IVUS and CMR images in patients with different constellations of findings. The site of IVUS imaging is marked on each angiogram. A: Plaque rupture with increased T2 signal and absent LGE. Left coronary angiogram (i) with corresponding IVUS showing plaque rupture in the mid LAD (ii-iii). T2 signal hyperintensity is noted to involve the mid anterior and mid and apical anterior septal walls (iv-v). No LGE is noted within the myocardium in 2 planes (vi-vii). Normal LV function (viii-ix). B: Plaque rupture with LGE. Angiogram of the left coronary artery (i) with corresponding IVUS showing plaque rupture in the proximal LAD (ii-iii). The site of the IVUS images is marked with an arrow. Subendocardial to transmural LGE involving the basal anteroseptal wall in shown in 3-chamber and short axis views (iv-v). T2-weighted imaging was not performed in this patient. Normal LV function (vi-vii). C: Ischemic-type LGE without plaque rupture on IVUS. Left coronary angiogram (i). IVUS of the LCX showing mixed-fibrofatty plaque without rupture (ii-iii). The LAD and LCX were imaged with IVUS in this case. T2 signal hyperintensity of the mid inferior, mid inferoseptal and adjacent right ventricular walls near the right ventricular insertion (iv). Transmural LGE involving subsegments of the same region (v). Normal LV function (vi-vii) D: Non-ischemic type LGE with minimal atherosclerosis on IVUS. Left coronary angiogram (i). Normal IVUS of the LCX (ii-iii). T2 signal hyperintensity of the basal inferior/inferolateral wall (iv). Focal area of mid-myocardial LGE involving the same region. (v) Normal LV function (vi-vii).

Figure 5

Angiographic and IVUS images from a patient with tako-tsubo cardiomyopathy and plaque ulceration. Angiogram shown in the top panel with arrow marking the site of the IVUS image shown in the lower panels, with and without contours outlining the intimal border (yellow) and external elastic lamina (red). Note that the LAD is a large vessel which wraps around the LV apex; this was also true of the other case of tako-tsubo cardiomyopathy with plaque ulceration in the left main coronary artery (not shown).