Case Reports
Metastatic Carcinoid Disease Inducing Coronary Vasospasm
Danny J. Eapen, MD Stephen Clements, Jr., MD Peter Block, MD Laurence Sperling, MD
Herein, we report a case of progressive coronary vasospasm in a 70-year-old man who had a long-standing history of metastatic gastrointestinal carcinoid tumor. Despite octreotide, nitrate, and calcium channel-blocker therapy, the patient’s urinary 5-hydroxy-indole acetic acid level increased, coinciding with an increased frequency of flushing episodes with chest discomfort. In the cardiac catheterization laboratory, we captured an episode that was associated with diffuse right coronary artery spasm, ST-segment elevation, and intense symptoms. We attribute the patient’s coronary vasospasm to his metastatic carcinoid disease. (Tex Heart Inst J 2012;39(1):76-8)
C
arcinoid-related heart disease has been well documented, but little is known about carcinoid-related variant angina pectoris. Few case reports in the medical literature describe this phenomenon.1-3 In animal and human models, serotonin has been shown to induce vasoconstriction in atherosclerotic coronary arteries, whereas it elicits vasodilation in normal coronary arteries.4 Current controversy exists as to which serotonin receptor subtype elicits this response. Carcinoid tumors have also been known to produce other polypeptides and amines (including histamine) that theoretically could augment the coronary vasospastic response.5 Herein, we report a case of coronary vasospasm in a man who had nonobstructive coronary artery disease and a history of metastatic carcinoid tumor.
Case Report Key words: Angina pectoris, variant/drug therapy; coronary disease/physiopathology; coronary vasospasm/diagnosis/etiology/ physiopathology; flushing/ etiology; malignant carcinoid syndrome/complications; octreotide/administration & dosage; treatment outcome From: Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia 30322 Address for reprints: Danny J. Eapen, MD, 1364 Clifton Rd., Suite D415, Atlanta, GA 30322 E-mail:
[email protected] © 2011 by the Texas Heart ® Institute, Houston
76
In May 2008, a 70-year-old man with a long-standing history of gastrointestinal carcinoid disease and nonobstructive coronary artery disease was admitted after multiple episodes of severe chest discomfort. These episodes occurred at rest, were associated with intense facial flushing and occasional diarrhea, were induced by alcohol intake, and were relieved with sublingual nitroglycerin. After having experienced similar episodes of chest discomfort 5 years earlier, the patient had been diagnosed with hepatic metastasis of the carcinoid tumor. Octreotide therapy was then initiated, and the patient reported symptomatic relief during the next 5 years. His 5-hydroxy-indole acetic acid (5-HIAA) levels were consistently in the low 20-mg/d range (normal, 0–15 mg/d). Upon this hospital admission, however, the 5-HIAA level was 31 mg/d, and an electrocardiogram (ECG) showed sinus bradycardia with T-wave inversions in the inferior leads. No elevation in cardiac enzyme levels was noted. During coronary catheterization, the patient had another episode of severe chest discomfort with facial flushing. Visualization of his right coronary artery (RCA) (Fig. 1) revealed mid-territory spasm (Fig. 2), and an ECG showed 5-mm ST-segment elevation in the inferior leads (Fig. 3). After the patient’s symptoms abated, repeat injection of the RCA showed resolution of the spasm. The patient at first was treated medically for his symptoms with use of oral nitrates, a calcium-channel blocker, and an increased dose of octreotide therapy. However, his symptoms did not abate. He presented at the hospital approximately 2 weeks later with similar symptoms and inferior ST-segment elevations, and RCA vasospasm again was seen during cardiac catheterization (Fig. 4). It was decided to place 2 adjacent stents at the site of RCA vasospasm (Fig. 5). The patient reported no further episodes of chest discomfort at his 1-, 2-, and 3-year follow-up appointments.
Metastatic Carcinoid Disease and Coronary Vasospasm
Volume 39, Number 1, 2012
Fig. 1 Coronary angiogram shows the right coronary artery at baseline.
Fig. 4 Coronary angiogram during catheterization before intervention shows the right coronary artery during vasospasm, with the flow wire in place.
Fig. 2 Coronary angiogram during diagnostic catheterization shows the right coronary artery during vasospasm.
Fig. 5 Coronary angiogram shows the right coronary artery after stent placement.
Discussion
Fig. 3 Lead III of electrocardiogram during vasospasm.
Texas Heart Institute Journal
Coronary vasospasm has classically been described as cardiac chest pain that occurs mainly at rest and in association with ST-segment elevation.6 This process occurs primarily in patients with mild atherosclerosis and is secondary to endothelial dysfunction adjacent to or in the atherosclerotic area.7 Ergonovine, acetylcholine, and serotonin are agents well known to precipitate spasm in predisposed coronary arteries. Serotonin has been shown to have a biphaMetastatic Carcinoid Disease and Coronary Vasospasm
77
sic, dose-dependent response,4 dilating normal coronary arteries and constricting atherosclerotic arteries. In addition to calcium-channel blockers and nitrates, other therapies include octreotide (a long-acting synthetic somatostatin) and serotonin antagonists such as methiothepin8 and cyproheptadine.9 We used coronary stenting in our patient, given the confinement of vaso spasm to a focal arterial segment and the recurrence of potentially life-threatening episodes despite medical therapy. The documented vasospasm, elevated 5-HIAA levels, classically associated symptoms of flushing and diarrhea, and alcohol use as a precipitant all suggested a strong relationship between metastatic carcinoid disease and coronary vasospasm in our patient.
References 1. Topol EJ, Fortuin NJ. Coronary artery spasm and cardiac arrest in carcinoid heart disease. Am J Med 1984;77(5):950-2. 2. Muszkat M, Shalit M, Lotan C, Ben-Yehuda A. Coronary vasospasm associated with uncontrolled carcinoid tumour. J Intern Med 2000;247(2):295-8.
78
Metastatic Carcinoid Disease and Coronary Vasospasm
3. Petersen KG, Seemann WR, Plagwitz R, Kerp L. Evidence for coronary spasm during flushing in the carcinoid syndrome. Clin Cardiol 1984;7(8):445-8. 4. Sheridan FM. The vasoactive effect of serotonin on canine coronary arteries after ischemia and reperfusion. Coron Artery Dis 1994;5(6):481-6. 5. Granerus G, Lindell SE, Waldenstrom J, Westling H, White T. Histamine metabolism in carcinoidosis. Lancet 1966;1 (7449):1267-8. 6. Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina pectoris. I. A variant form of angina pectoris; preliminary report. Am J Med 1959;27:375-88. 7. Vanhoutte PM. Platelet-derived serotonin, the endothelium, and cardiovascular disease. J Cardiovasc Pharmacol 1991;17 Suppl 5:S6-12. 8. Chester AH, Martin GR, Bodelsson M, Arneklo-Nobin B, Tadjkarimi S, Tornebrandt K, Yacoub MH. 5-Hydroxytryptamine receptor profile in healthy and diseased human epicardial coronary arteries. Cardiovasc Res 1990;24(11):932-7. 9. Schecter AD, Chesebro JH, Fuster V. Refractory Prinzmetal angina treated with cyproheptadine. Ann Intern Med 1994; 121(2):113-4.
Volume 39, Number 1, 2012
