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Case Report
Fibromuscular Dysplasia and Acute Myocardial Infarction: Evidence for a Unique Clinical and Angiographic Pattern
February 2006
Myocardial infarction (MI) typically occurs in the setting of atherosclerotic coronary artery disease (CAD). However, there are other causes of MI unrelated to atherosclerosis that include spontaneous dissection of the coronary arteries, anomalous origin of coronary arteries, vasculitis, toxins such as carbon monoxide, medications (5-fluorouracil, sumatriptan, ergotamine) and hypercoagulable states.1–7 Fibromuscular dysplasia (FMD) is a condition typically involving small and medium-sized vessels. It has been rarely described in coronary arteries at autopsy8–13 in association with sudden cardiac death.9,14–17 However, MI as the initial manifestation of FMD has not been well recognized.
Case Reports
Case #1. A 50-year-old female without significant risk factors for CAD presented to the emergency room complaining of pressure-like chest discomfort, radiating to her neck and jaw, while walking. On arrival, ECG demonstrated ST-segment elevation in leads II, III, aVF and V3–V5, with reciprocal changes in leads I and aVL. A few minutes later, she developed intermittent ventricular bigeminy and accelerated junctional rhythm. Echocardiography confirmed localized apical and inferior-posterior wall hypokinesis with an estimated left ventricular ejection fraction of 50–60%. Coronary angiography revealed a distal diffuse 75% left anterior descending (LAD) stenosis, progressing to 95% at the apex with TIMI 3 flow (Figure 1A). None of the other coronary arteries had significant disease. The patient’s troponin I level reached a peak of 18.08 ng/mL and inflammatory and vasculitic markers were negative. A “string of beads” pattern (Figure 2A) was recognized in the right femoral angiogram obtained for deployment of a closure device, and a subsequent computed tomography renal angiogram confirmed the diagnosis of FMD (Figure 2B).
Case #2. A 43-year-old female with hypertension diagnosed at age 28 presented with retrosternal pressure-like chest discomfort of sudden onset that radiated to her jaw, throat and both arms. She suffered ventricular tachycardia/fibrillation arrest in the emergency department and was promptly defibrillated. The ECG demonstrated ST-segment elevation in leads V2–V4. Cardiac catheterization showed normal coronary arteries except for a severe diffuse 70% narrowing in the mid- and distal LAD artery with TIMI 3 flow that was not amenable to angioplasty (Figure 1B). There was a small area of anterior-apical hypokinesis, but overall LV systolic function was only mildly impared. Troponin I level reached a peak of 5.9 ng/mL. Due to uncontrolled hypertension, a captopril renal scan was obtained and was consistent with renovascular disease. A subsequent renal angiogram revealed a bilateral “string of beads” (Figure 2C) diagnostic of FMD, with a significant stenosis gradient (130 mmHg). Sequential balloon angioplasty of the right renal artery was then performed, resulting in subsequent improvement in her blood pressure.
Case #3. 54 year-old postmenopausal female nurse with history of asthma, who complained of sudden onset of pressure-like substernal chest discomfort, radiating to her arms and neck, associated with nausea and diaphoresis. An electrocardiogram revealed accelerated junctional rhythm, Q-waves in V2–V3, poor R wave progression and ST-segment elevation in V2–V5. Cardiac catheterization demonstrated normal coronary arteries except for a 90% long diffuse lesion in the mid-LAD with TIMI 3 flow (Figure 1C). Three stents (AVE 24, 12 and 9 mm) were deployed with a 0% residual stenosis. The patient’s troponin concentration peaked at 28.1 ng/mL. Echocardiography revealed severe hypokinesis of the distal interventricular septum and apex with an estimated ejection fraction of 45%. Ventricular function completely recovered on repeat echocardiography 2 months later. During follow up visits, her blood pressure was poorly controlled despite triple drug combination therapy. A noninvasive renal duplex ultrasound suggested significant renal artery stenosis. Subsequent renal angiography demonstrated the characteristic “string of beads” sign diagnostic of FMD in both renal arteries, with a significant mean pressure gradient of 15 mmHg in the distal right main artery. There was no significant gradient in the left renal artery, and she therefore underwent a single right renal angioplasty.
All 3 patients survived their myocardial infarctions and have not had any further cardiac events with 1 to 2 years of follow up.
Discussion
Fibromuscular dysplasia (FMD) is a noninflammatory, nonatherosclerotic disease of small- to medium-sized arteries. It affects primarily young females between the ages of 15 to 50 years, and its prevalence has been estimated from 1– 4.4%.18,19 FMD has been demonstrated in almost any vascular bed.8,19,20 Two vascular beds are involved in as many as 28% of cases. The most frequently involved arteries are the renal (60–75%), the extracranial carotid and vertebral (25–30%), the visceral (9%), and the arteries to the extremities (5%).8
FMD initially presents with hypertension, renal infarction, transient ischemic attack and/or stroke. Spontaneous dissection of the carotid, renal and other visceral arteries has been well described.8,13,19–24 FMD has been classified into 3 types according to the dominant arterial wall layer involved: intimal fibroplasia (8,19
Cardiac manifestations of FMD. FMD involving the coronary arteries has been described in case reports and postmortem series, mostly manifested by sudden cardiac death.9,10,14–17,25,26 Less frequently, angina11,27 and MI10,22,23,25,26 have been associated with FMD in adults, but they have also been documented in infants.9,25,26
A retrospective postmortem study reviewing a 30-year experience in a single pathology laboratory found 9 cases of essential hypertension with FMD of small coronary arteries in 1,000 cases of sudden cardiac death.10 All 9 cases had focal FMD involving small arteries, either the atrioventricular nodal artery or the sinoatrial artery. Focal FMD in these arteries was typically less than a few millimeters in length and was not likely to be visible on angiography. Three of these patients died of acute MI, and no details of other coronary involvement are reported. Similarly, in a cohort of 58 patients with FMD affecting the internal carotid artery, there were 4 cases of acute coronary syndrome reported during follow up.24 However, no details of the MI were described. Recently, involvement in major epicardial coronary arteries was reported in a series of 7 patients with FMD.28Coronary anigiographic pattern of FMD. A previous series of patients with FMD presenting with an AMI found LAD involvement in 6 of 7 patients.28 We also found a significant mid-to-distal diffuse LAD stenosis in all 3 patients (Figure 1). Unfortunately, 2 patients were not amenable to angioplasty due to the location and diffuse nature of the stenosis. There have been two reports of spontaneous coronary artery dissection associated with FMD. The first case involved the right coronary artery22 and the second case involved the left main coronary artery, the LAD extending into a second diagonal artery and the left circumflex artery.23 All 3 of our patients were identified retrospectively, 1 of whom was diagnosed and treated at a remote facility. Remarkably, all 3 patients had nearly identical anterior ST-elevation MIs, despite the fact that none of the lesions were totally occlusive at the time of cardiac catheterization. Coronary intravascular ultrasound was not performed since the lesions were long, diffuse and dissection was not suspected. It is possible that these lesions were spontaneous dissections without an intimal flap, and could have been diagnosed if intravascular ultrasound had been performed.29 FMD is well known to cause dissection of the carotid, visceral and renal arteries, probably due to changes in the underlying structure of the arteries. It therefore seems likely that coronary dissection, despite the absence of angiographic evidence, is most likely the pathophysiologic mechanism underlying the acute MI.
Diagnosis of FMD. Imaging studies of the renal arteries, including angiogram, computed tomography angiography and gadolinium 3-D magnetic resonance are used for the diagnosis of FMD in the absence of any other inflammatory/vasculitic processes.8,20,21 However, angiography is considered the gold standard for the diagnosis of FMD. The typical angiographic finding consists of “string of beads” (Figure 2). However, definitive diagnosis requires pathologic analysis of the affected vascular bed8,19 which is only feasible in postmortem cases.
The differential diagnosis of FMD includes atherosclerotic disease, Ehlers-Danlos Type IV (associated with medial fibroplasia) and vasculitis. Ehlers-Danlos Type IV should only be suspected in patients with multiple aneurysms in different vasculatures. Vasculitis is easier to exclude since it is an inflammatory process and is associated with anemia, thrombocytopenia and elevated acute phase reactants.8,19,20
Conclusions
FMD involving the coronary arteries has only rarely been described. There are very few reports of angina, ACS and/or sudden cardiac death associated with FMD. However, the disease should be suspected among those young patients presenting with AMI who have no risk factors for CAD, evidence for vasculitis or other known associated pathologies.
We believe that the prevalence of FMD may be underestimated due to the lack of recognition of coronary involvement in this entity. It is possible that many cardiovascular specialists are unaware of the potential involvement of the coronary arteries by FMD, particularly as its initial manifestation. We believe that all young patients (
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