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A case of unusual acute coronary syndrome
American Journal of Emergency Medicine 31 (2013) 758.e1–758.e2
Contents lists available at SciVerse ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A case of unusual acute coronary syndrome Abstract Pheochromocytoma is a rare tumor that usually develops ahead of the neuroectodermal chromaffin cells of the adrenal medulla, but it may arise anywhere within plexus of sympathetic adrenergic nerves. Headache, palpitations, tremor, excessive sweating, abdominal pain, and hypertensive paroxysm are the common clinical presentations of the tumor, but it has also been reported several cardiac symptoms. Takotsubo cardiomyopathy is a widely accepted syndrome generally characterized by transient systolic dysfunction of the apical or, more rarely, of the mid left ventricular segments (inverted takotsubo). A case of pheochromocytoma presenting as inverted takotsubo is described in this article. A 28-year-old man, 20 cigarettes/day smoker, without other cardiovascular risk factors, was admitted to our emergency department because of onset of dizziness, diaphoresis, stomachache, and vomiting at awakening and persisting during the day. Physical examination was unremarkable, and blood pressure was normal. The rest electrocardiogram (ECG) showed a sinus tachycardia of 105 beats per minute, tall upright T waves with ST-segment depression in V4 to V6 leads and increased troponin (Roche Troponin T, 0.07 ng/mL). In the coronary care unit, serial ECG showed a gradual resolution of ST-segment depression with persistent tall upright T waves. A transthoracic echocardiogram revealed a severe ventricular dysfunction (ejection fraction, 30%) with akinesis of the basal and midventricular segments sparing the apex. An acute coronary syndrome (ACS) was suspected, so the patient was treated with aspirin, clopidogrel, fondaparinux, and β-blockers and underwent coronary angiography that revealed normal coronary arteries. To exclude a vasospasm, an intracoronary ergonovine test was performed showing an unspecific diffuse vasoconstriction. The left ventricular angiogram revealed a recovery of the left ventricular function with ejection fraction of 65%. Cardiac magnetic resonance confirmed the full recovery of the left ventricular contractility without segmental wall motional abnormalities and showed a left ventricular hypertrophy with interventricular septal thickness of 15 mm without delayed enhancement. At light of these findings, a Takotsubo syndrome, with an inverted contractility pattern, was supposed. The day after, at awakening, the patient experimented a new episode of dizziness, diaphoresis, stomachache, and vomiting. The ECG was unchanged, and no increased troponin was detected. As abdominal pain persisted, an abdominal echography was required revealing the presence of 76 × 68 mm mass in the right hepatorenal space with dishomogeneous echogenicity and fluid areas. Computed tomography (CT) and magnetic resonance imaging (MRI) (Figure) confirmed the presence of an abdominal mass, which could be related to cystic pheochromocytoma. The urinary and blood tests showed elevated levels of catecholamines and chromogranin A consistent with diagnosis of pheochromocytoma. 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
Pheochromocytoma is a rare catecholamine-secreting tumor typically located in the adrenal medulla or along the sympathetic ganglia. It exerts distant effects by secretion of catecholamines and usually manifests with headache, sweating, tachycardia, pallor, hypertension, and abdominal pain but also with cardiac symptoms simulating an ACS like angina, dyspnea, syncope [1], ST-segments and T-waves abnormality, elevated cardiac biomarkers, and temporary impairment of the left ventricular function. Liao et al [1] reported cardiovascular manifestations in patients discharged with diagnosis of pheochromocytoma; of note, angina was a frequent initial presentation, often associated with abnormal ECG. Approximately 15% of patients with non-ST-elevation ACS have normal coronary arteries. The pathophysiology is heterogeneous, and possible mechanisms include coronary artery spasm, embolism, acute thrombosis followed by recanalization, congenital abnormalities, and other causes such as myocarditis and takotsubo syndrome [2]. Takotsubo cardiomyopathy is a widely accepted syndrome generally characterized by transient systolic dysfunction of the apical (apical ballooning syndrome) or, more rarely, of the mid left ventricular segments (inverted takotsubo). Pheochromocytoma has been associated with inverted pattern [3]. In our case, an inverted takotsubo was suspected because of transient severe cardiac dysfunction with typical motion abnormalities. Nonetheless, diagnostic criteria for takotsubo syndrome [4] recommend to rule out the diagnosis of pheochromocytoma to confirm the diagnosis [5,4]. Pheochromocytoma can be diagnosed at CT usually showing areas of hemorrhage, necrosis, or cystic changes, in a large mass, calcifications and intense enhancement after contrast medium injection. MRI is superior to CT to screen extra-adrenal tumors and adequately diagnose adrenal pheochromocytomas, especially in case of intra-lesion hemorrhage or cystic changes. In cystic pheochromocytomas, MRI shows a signal intensity as high as cerebrospinal fluid on T2-weigted images, associated with minimal enhancement on immediate postgadolinium images (Fig.). Many cases of pheochromocytoma-induced takotsubo were reported [6,7]. Reported cases could be only a result of the scientific speculation because, to date, there are no data from published trials but only studies about the possible association of pheochromocytomas with takotsubo. However, this association could be due to the increased release of cathecolamines. Wittstein et al reported higher plasma catecholamine levels in patients with left ventricular dysfunction, after emotional stress, than in patients with Killip Class III acute myocardial infarction [8]. Oxidation of catecholamines results in the formation of highly toxic metabolites and free radicals causing intracellular calcium overload and myocardial cell damage. The typical histologic signs of catecholamines toxicity have been described as focal,
758.e2
Case Report / American Journal of Emergency Medicine 31 (2013) 758.e1–758.e2
Fig. Right pheocromocytoma: MRI diagnosis. A large right adrenal mass showing a quite hyperintense signal intensity on T1-weighted in-phase image (A), a strong hyperintensity on T2-weighted axial scan (B), not losing signal intensity on T1-weighted out-of-phase axial image (C) is well documented (arrows). The lesion minimally enhances on immediate postgadolinium image (D, arrow). These signs are consistent with MRI diagnosis of cystic pheochromocytoma.
mononuclear, inflammatory areas of fibrotic response and characteristic contraction bands. On the other hand, catecholamines can induce multivessel epicardial spasm, microvascular spasm, acute and transient coronary microvascular dysfunction by activating β-receptors. These mechanisms are responsible of the myocardial stunning and the wall motional abnormalities [9]. The surgical resection of pheochromocytoma was associated with a regression of the electrocardiographic and echocardiographic abnormalities [10,11]. Our patient underwent surgical resection of the neoplasia. Electrocardiographic abnormalities returned to the basal pattern and symptoms regressed. In patients with unexpected ACS, normal or minimally diseased coronary arteries and inverted takotsubo-like left ventricular dysfunction, a pheochromocytoma may be suspected and should be investigated by imaging to avoid mistakes in treatment. Maria Teresa Cardillo MD Roberta Della Bona MD Annalisa Caroli MD Institute of Cardiology Catholic University of the Sacred Heart, Rome, Italy Anna Lia Valentini MD Institute of Radiology Catholic University of the Sacred Heart, Rome, Italy Luigi M. Biasucci MD Institute of Cardiology Catholic University of the Sacred Heart, Rome, Italy E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2012.11.019
References [1] Liao WB, Liu CF, Chiang CW, et al. Cardiovascular manifestations of pheochromocytoma. Am J Emerg Med 2000;18(5):622-5. [2] Bassand JP, Hamm C. New European guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction—what are the new and key messages. Pol Arch Med Wewn 2007;117(9):391-3. [3] Takizawa M, Kobayakawa N, Uozumi H, et al. A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of catecholamines in stress-induced cardiomyopathy or takotsubo cardiomyopathy. Int J Cardiol 2007;114(1):e15-7. [4] Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 2008;155(3):408-17. [5] Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;141(11):858-65. [6] Kim S, Yu A, Filippone LA, et al. Inverted-Takotsubo pattern cardiomyopathy secondary to pheochromocytoma: a clinical case and literature review. Clin Cardiol 2010;33(4):200-5. [7] Gervais MK, Gagnon A, Henri M, et al. Pheochromocytoma presenting as inverted Takotsubo cardiomyopathy: a case report and review of the literature. J Cardiovasc Med (Hagerstown) 2010. [8] Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352(6):539-48. [9] Sanchez-Recalde A, Costero O, Oliver JM, et al. Images in cardiovascular medicine. Pheochromocytoma-related cardiomyopathy: inverted Takotsubo contractile pattern. Circulation 2006;113(17):e738-9. [10] Kimura S, Mitsuma W, Ito M. Inverted Takotsubo contractile pattern caused by pheochromocytoma with tall upright T-waves, but not typical deep T-wave inversion. Int J Cardiol 2010;139(2):e15-7. [11] Zegdi R, Parisot C, Sleilaty G, Deloche A, Fabiani JN. Pheochromocytomainduced inverted Takotsubo cardiomyopathy: a case of patient resuscitation with extracorporeal life support. J Thorac Cardiovasc Surg 2008;135(2): 434-5.
Contents lists available at SciVerse ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A case of unusual acute coronary syndrome Abstract Pheochromocytoma is a rare tumor that usually develops ahead of the neuroectodermal chromaffin cells of the adrenal medulla, but it may arise anywhere within plexus of sympathetic adrenergic nerves. Headache, palpitations, tremor, excessive sweating, abdominal pain, and hypertensive paroxysm are the common clinical presentations of the tumor, but it has also been reported several cardiac symptoms. Takotsubo cardiomyopathy is a widely accepted syndrome generally characterized by transient systolic dysfunction of the apical or, more rarely, of the mid left ventricular segments (inverted takotsubo). A case of pheochromocytoma presenting as inverted takotsubo is described in this article. A 28-year-old man, 20 cigarettes/day smoker, without other cardiovascular risk factors, was admitted to our emergency department because of onset of dizziness, diaphoresis, stomachache, and vomiting at awakening and persisting during the day. Physical examination was unremarkable, and blood pressure was normal. The rest electrocardiogram (ECG) showed a sinus tachycardia of 105 beats per minute, tall upright T waves with ST-segment depression in V4 to V6 leads and increased troponin (Roche Troponin T, 0.07 ng/mL). In the coronary care unit, serial ECG showed a gradual resolution of ST-segment depression with persistent tall upright T waves. A transthoracic echocardiogram revealed a severe ventricular dysfunction (ejection fraction, 30%) with akinesis of the basal and midventricular segments sparing the apex. An acute coronary syndrome (ACS) was suspected, so the patient was treated with aspirin, clopidogrel, fondaparinux, and β-blockers and underwent coronary angiography that revealed normal coronary arteries. To exclude a vasospasm, an intracoronary ergonovine test was performed showing an unspecific diffuse vasoconstriction. The left ventricular angiogram revealed a recovery of the left ventricular function with ejection fraction of 65%. Cardiac magnetic resonance confirmed the full recovery of the left ventricular contractility without segmental wall motional abnormalities and showed a left ventricular hypertrophy with interventricular septal thickness of 15 mm without delayed enhancement. At light of these findings, a Takotsubo syndrome, with an inverted contractility pattern, was supposed. The day after, at awakening, the patient experimented a new episode of dizziness, diaphoresis, stomachache, and vomiting. The ECG was unchanged, and no increased troponin was detected. As abdominal pain persisted, an abdominal echography was required revealing the presence of 76 × 68 mm mass in the right hepatorenal space with dishomogeneous echogenicity and fluid areas. Computed tomography (CT) and magnetic resonance imaging (MRI) (Figure) confirmed the presence of an abdominal mass, which could be related to cystic pheochromocytoma. The urinary and blood tests showed elevated levels of catecholamines and chromogranin A consistent with diagnosis of pheochromocytoma. 0735-6757/$ – see front matter © 2013 Elsevier Inc. All rights reserved.
Pheochromocytoma is a rare catecholamine-secreting tumor typically located in the adrenal medulla or along the sympathetic ganglia. It exerts distant effects by secretion of catecholamines and usually manifests with headache, sweating, tachycardia, pallor, hypertension, and abdominal pain but also with cardiac symptoms simulating an ACS like angina, dyspnea, syncope [1], ST-segments and T-waves abnormality, elevated cardiac biomarkers, and temporary impairment of the left ventricular function. Liao et al [1] reported cardiovascular manifestations in patients discharged with diagnosis of pheochromocytoma; of note, angina was a frequent initial presentation, often associated with abnormal ECG. Approximately 15% of patients with non-ST-elevation ACS have normal coronary arteries. The pathophysiology is heterogeneous, and possible mechanisms include coronary artery spasm, embolism, acute thrombosis followed by recanalization, congenital abnormalities, and other causes such as myocarditis and takotsubo syndrome [2]. Takotsubo cardiomyopathy is a widely accepted syndrome generally characterized by transient systolic dysfunction of the apical (apical ballooning syndrome) or, more rarely, of the mid left ventricular segments (inverted takotsubo). Pheochromocytoma has been associated with inverted pattern [3]. In our case, an inverted takotsubo was suspected because of transient severe cardiac dysfunction with typical motion abnormalities. Nonetheless, diagnostic criteria for takotsubo syndrome [4] recommend to rule out the diagnosis of pheochromocytoma to confirm the diagnosis [5,4]. Pheochromocytoma can be diagnosed at CT usually showing areas of hemorrhage, necrosis, or cystic changes, in a large mass, calcifications and intense enhancement after contrast medium injection. MRI is superior to CT to screen extra-adrenal tumors and adequately diagnose adrenal pheochromocytomas, especially in case of intra-lesion hemorrhage or cystic changes. In cystic pheochromocytomas, MRI shows a signal intensity as high as cerebrospinal fluid on T2-weigted images, associated with minimal enhancement on immediate postgadolinium images (Fig.). Many cases of pheochromocytoma-induced takotsubo were reported [6,7]. Reported cases could be only a result of the scientific speculation because, to date, there are no data from published trials but only studies about the possible association of pheochromocytomas with takotsubo. However, this association could be due to the increased release of cathecolamines. Wittstein et al reported higher plasma catecholamine levels in patients with left ventricular dysfunction, after emotional stress, than in patients with Killip Class III acute myocardial infarction [8]. Oxidation of catecholamines results in the formation of highly toxic metabolites and free radicals causing intracellular calcium overload and myocardial cell damage. The typical histologic signs of catecholamines toxicity have been described as focal,
758.e2
Case Report / American Journal of Emergency Medicine 31 (2013) 758.e1–758.e2
Fig. Right pheocromocytoma: MRI diagnosis. A large right adrenal mass showing a quite hyperintense signal intensity on T1-weighted in-phase image (A), a strong hyperintensity on T2-weighted axial scan (B), not losing signal intensity on T1-weighted out-of-phase axial image (C) is well documented (arrows). The lesion minimally enhances on immediate postgadolinium image (D, arrow). These signs are consistent with MRI diagnosis of cystic pheochromocytoma.
mononuclear, inflammatory areas of fibrotic response and characteristic contraction bands. On the other hand, catecholamines can induce multivessel epicardial spasm, microvascular spasm, acute and transient coronary microvascular dysfunction by activating β-receptors. These mechanisms are responsible of the myocardial stunning and the wall motional abnormalities [9]. The surgical resection of pheochromocytoma was associated with a regression of the electrocardiographic and echocardiographic abnormalities [10,11]. Our patient underwent surgical resection of the neoplasia. Electrocardiographic abnormalities returned to the basal pattern and symptoms regressed. In patients with unexpected ACS, normal or minimally diseased coronary arteries and inverted takotsubo-like left ventricular dysfunction, a pheochromocytoma may be suspected and should be investigated by imaging to avoid mistakes in treatment. Maria Teresa Cardillo MD Roberta Della Bona MD Annalisa Caroli MD Institute of Cardiology Catholic University of the Sacred Heart, Rome, Italy Anna Lia Valentini MD Institute of Radiology Catholic University of the Sacred Heart, Rome, Italy Luigi M. Biasucci MD Institute of Cardiology Catholic University of the Sacred Heart, Rome, Italy E-mail address: [email protected]
http://dx.doi.org/10.1016/j.ajem.2012.11.019
References [1] Liao WB, Liu CF, Chiang CW, et al. Cardiovascular manifestations of pheochromocytoma. Am J Emerg Med 2000;18(5):622-5. [2] Bassand JP, Hamm C. New European guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction—what are the new and key messages. Pol Arch Med Wewn 2007;117(9):391-3. [3] Takizawa M, Kobayakawa N, Uozumi H, et al. A case of transient left ventricular ballooning with pheochromocytoma, supporting pathogenetic role of catecholamines in stress-induced cardiomyopathy or takotsubo cardiomyopathy. Int J Cardiol 2007;114(1):e15-7. [4] Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (Tako-Tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J 2008;155(3):408-17. [5] Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004;141(11):858-65. [6] Kim S, Yu A, Filippone LA, et al. Inverted-Takotsubo pattern cardiomyopathy secondary to pheochromocytoma: a clinical case and literature review. Clin Cardiol 2010;33(4):200-5. [7] Gervais MK, Gagnon A, Henri M, et al. Pheochromocytoma presenting as inverted Takotsubo cardiomyopathy: a case report and review of the literature. J Cardiovasc Med (Hagerstown) 2010. [8] Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352(6):539-48. [9] Sanchez-Recalde A, Costero O, Oliver JM, et al. Images in cardiovascular medicine. Pheochromocytoma-related cardiomyopathy: inverted Takotsubo contractile pattern. Circulation 2006;113(17):e738-9. [10] Kimura S, Mitsuma W, Ito M. Inverted Takotsubo contractile pattern caused by pheochromocytoma with tall upright T-waves, but not typical deep T-wave inversion. Int J Cardiol 2010;139(2):e15-7. [11] Zegdi R, Parisot C, Sleilaty G, Deloche A, Fabiani JN. Pheochromocytomainduced inverted Takotsubo cardiomyopathy: a case of patient resuscitation with extracorporeal life support. J Thorac Cardiovasc Surg 2008;135(2): 434-5.