Tara Sedlak (biography and disclosures)
What I did before
Women with myocardial infarction (MI) have a two fold higher rate of no obstructive coronary artery disease (CAD), defined as <50% stenosis in any epicardial coronary artery on angiogram, than men (1). Specifically, amongst ST elevation MI (STEMI) patients, 10.2% of women versus 6.8% of men, respectively, will have no obstructive CAD. Further, amongst non-ST elevation MI (NSTEMI)/unstable angina (UA) patients, 9.1-30.5% of women versus 4.2-13.9% of men will have no significant CAD (1). Despite this, outcomes including death during hospitalization following an MI are higher among women (particularly women <55 years) as compared to men (2).
In the past, the etiology of MI in these women was unclear. As such, it was my practice and that of many other cardiologists to offer re-assurance to women with MI and no obstructive CAD and to then discharge them home on no medications or on calcium channel blockers alone for presumed vasospasm. In a large retrospective cohort study of 1,489,745 patients undergoing angiography in the United States, non-obstructive CAD patients were significantly less likely to receive aspirin (odds ratio = 0.37), statins (odds ratio = 0.45), β-blockers (odds ratio = 0.46), or ACEI/ARBs (odds ratio = 0.83) compared with obstructive CAD patients (3).
What changed my practice
Reynolds et al. published a prospective study in 2011 in Circulation investigating the mechanisms of MI in women without obstructive CAD (4). In women with an MI referred for clinically indicated angiography, but found to have <50% CAD in any epicardial artery, researchers performed intravascular ultrasound (IVUS) in two out of three coronary arteries and cardiac magnetic resonance imaging (CMRI) within 1 week of the MI. Forty-two consecutive patients were studied; 92% presented with chest pain and 22% had ST segment elevation on ECG; mean troponins were 1.6 ng/ml. They found that 16 patients (38%) had plaque disruption on IVUS including 12 patients with plaque rupture and 4 patients with plaque ulceration. Plaque rupture was identified in segments that appeared normal on angiography, though it was not found in patients with completely normal angiograms without any luminal irregularities. Thirty-nine percent had late gadolinium enhancement (LGE) on CMRI, the most common pattern of which was ischemic. Fifty-three percent had T2 signal hyperintensity in at least one area, indicating acute myocardial edema. The latter pattern was more common among patients with plaque disruption on IVUS. Together, IVUS and CMRI identified abnormalities in 70% of patients. The conclusion was that plaque rupture is a common cause of MI with no obstructive CAD among women. Further, in women with CMRI abnormalities but no plaque disruption on IVUS, vasospasm, embolism, or missed spontaneous coronary artery dissection (SCAD) may be potential etiologies.
What I do now
Plaque rupture is a common cause of MI in women without obstructive CAD and may occur in angiographically normal segments. This highlights an important limitation of angiography among women as supported by Khuddus et al. who reported that among women with stable angina but no obstructive CAD, only 30.4% of patients had discernable mild CAD on angiography, though 79% had atherosclerosis when IVUS was used (5). Following the publication of the above study by Reynolds et al., several changes should be considered when managing an MI among women with no obstructive CAD. First, IVUS could be considered at the time of angiography, particularly among patients with localizing features on ECG, so as to direct which artery IVUS should be performed. The choice to do this would be up to the interventionalist at the time of the angiogram however at times, patients are referred back for repeat angiography and IVUS to help with the diagnosis. Second, CMRI could be considered to look for ischemic late gadolinium enhancement or T2 signal hyperintensity and are often still present months after the event. These findings would be particularly helpful if a lesion is seen on angiography and corresponds with localization of abnormalities on CMRI. CMRI can also be helpful to diagnose other conditions that could cause troponin elevation such as Takotsubo cardiomyopathy, which is more common among women, and myocarditis. While this technique is typically only available in tertiary care centers, we routinely order it in the Women’s Heart Health Clinic and can help coordinate it for patients coming from rural communities. Third, I routinely consider statins and aspirin in patients without obstructive CAD, particularly in those with mild luminal irregularities. Plaque rupture is common and often found in angiographically normal segments. Fourth, I strive to determine the etiology of MI in these women as prognosis and management may vary widely. SCAD (spontaneous coronary artery dissection) is often missed on initial review of the angiogram, so I routinely re-review the images with a trained interventionalist. If a patient is located in a rural setting, films can be reviewed through the Women’s Heart Health Clinic at Vancouver General Hospital. If found, SCAD is a contra-indication to pregnancy and has important patient management implications.
Finally, while it can be difficult and frustrating for both the physician and patient to treat and diagnose MI in women without obstructive CAD, referral to the Women’s Heart Health Clinic (phone: 604-875-5487 or fax: 604-875-5504) at Vancouver General Hospital may be helpful. Typical wait times are 4-6 weeks. If patients are located in a rural setting, we also will consult with physicians over the phone and/or arrange specialized testing such as repeat angiograms with IVUS or CMRI at the same time as the clinic visit particularly when patients are travelling from afar.
- Bugiardini R., and Bairey Merz, C.N. Angina with normal coronary arteries: a changing philosophy. JAMA 2005; 293: 477-84. (Request from CPSBC or view with UBC)
- Vaccarino V., Parsons L., Every N.R., et al. Sex-based differences in early mortality after myocardial infarction. NEJM 1999; 341: 217-225. (Request from CPSBC or view with UBC)
- Maddox, T.M., Ho, P.M., Roe, M., et al. Utilization of secondary prevention therapies in patients with non-obstructive coronary artery disease identified during cardiac catheterization: insights from the National Cardiovascular Data Registry Cath-PCI Registry. Circ Cardiovascular Qual Outcomes 2010; 3: 632-41. 9 (View article)
- Reynolds, H.R., Srichai, M.B., Iqbal, S.N., et al. Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease. Circulation 2011; 124: 1414-25. (View article)
- Khuddus, M.A., Pepine, C.J., Handberg, E.M., et al. An intravascular ultrasound analysis in women experiencing chest pain in the absence of obstructive coronary artery disease: a sub-study from the National Heart, Lung, and Blood Institute-Sponsored Women’s Ischemic Syndrome Evaluation (WISE). J Interv Cardiol 2010; 23: 511-9. (View article)