Reverse takotsubo cardiomyopathy with use of male enhancers Carlos E. Rodriguez-Castro, MD, Fatima Saifuddin, MD, Mateo Porres-Aguilar, MD, Sarmad Said, MD, David Gough, MD, Tariq Siddiqui, MD, Debabrata Mukherjee, MD, and Aamer Abbas, MD
Reverse takotsubo cardiomyopathy is a rare heart failure condition characterized by systolic dysfunction of the basal segments of the left ventricle in the absence of obstructive coronary artery disease. We present a case of a 54-year-old man with an overdose of Extenze (a male enhancer pill containing yohimbine) who was hospitalized with heart failure due to reverse takotsubo cardiomyopathy.
T
he pathogenesis of reverse takotsubo cardiomyopathy is not well understood, but physical or mental stress is frequently an associated trigger. Less commonly reported, sympathomimeti c states have been linked to this disease entity. Reverse takotsubo cardiomyopathy has been reported in cases of hyperadrenergic states secondary to pheochromocytomas, catecholamine-secreting tumors, administration of beta-receptor agonists, such as dobutamine, and consumption of caffeine and energy drinks. In this report, we describe a case of reverse takotsubo cardiomyopathy relating to an overdose of Extenze, a male enhancer pill containing yohimbine. CASE PRESENTATION A 54-year-old man was admitted to the intensive care unit after ingesting multiple pills of Tylenol and Extenze, a product that contains yohimbine. He complained of abdominal discomfort and mild dyspnea. He was anxious and had a heart rate of 110 beats/minute. The electrocardiogram showed sinus tachycardia, right bundle branch block, and ST segment depression in lead V3 (Figure 1). A radiograph showed pulmonary congestion (Figure 2). His initial troponin I level was 0.94 ng/L; 7 hours later, it was 13 ng/L. Three hours after admission, he became disoriented, hypotensive, and hypoxic and was intubated for respiratory distress due to heart failure. An echocardiogram showed left ventricular systolic dysfunction with basal hypokinesis but normal mid/distal anterior, inferior, and apical contraction (Figure 3). Coronary angiography was normal without any anatomical or functional abnormalities such as coronary spasm, myocardial bridging, or coronary artery disease (Figure 4). Since the patient had an echocardiogram showing reverse takotsubo cardiomyopathy with severely depressed LV systolic function on the same day prior to cardiac catheterization, no ventriculogram was performed. The patient was treated with 78
vasopressors, diuretics, and invasive ventilatory support. After 72 hours, the patient was extubated and transferred to a regular floor. He recovered fully and was discharged after 1 week of hospitalization. Unfortunately, the patient did not follow up in the cardiology clinic; thus, no follow-up echocardiogram was performed. DISCUSSION Takotsubo cardiomyopathy is an increasingly reported syndrome characterized by transient systolic dysfunction of the apical and or mid segments of the left ventricle without the presence of coronary artery disease (1, 2). In contrast, reverse takotsubo cardiomyopathy is a condition with transient systolic dysfunction of the basal segments of the left ventricle. Although transient, reverse, or inverted takotsubo cardiomyopathy was recognized as a different clinical entity >20 years ago, a definite comprehensive pathophysiologic theory for this condition is still lacking (3). Seemingly, reverse takotsubo, which is more common in young female patients with a mean age of 36 years, is thought to be triggered by physical or emotional stress rather than catecholaminergic states. The presence of adrenoreceptors, which are at their apex in older patients, makes the occurrence of the apical variant of takotsubo cardiomyopathy more common among the older population, in contrast to the younger population, where the abundance of adrenoreceptors is within the base of the heart, which may lead to the reverse variant of takotsubo cardiomyopathy (4). There have been documented reports of reverse takotsubo in association with pheochromocytomas, intravenous administration of beta-receptor agonists (dobutamine) or catecholamines, as well as with the use of energy drinks containing caffeine and 1,3-dimethylamylamine (5). The pathophysiology behind this condition relies on two primary theories: vascular dysfunction and catecholamineinduced toxicity. Multifocal vasospasm has been demonstrated From the Department of Internal Medicine (Rodriguez-Castro, Porres-Aguilar, Said), Division of Cardiovascular Diseases (Gough, Siddiqui, Mukherjee, Abbas), Texas Tech University Health Sciences Center, El Paso, Texas; and Jinnah Postgraduate Medical Center, Karachi, Pakistan (Saifuddin). Corresponding author: Carlos E. Rodríguez-Castro, MD, Department of Internal Medicine, Texas Tech University Health Science Center, 4800 Alberta Avenue, El Paso, TX 79905 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2015;28(1):78–80
Figure 1. Supraventricular tachycardia with incomplete right bundle branch block and nonspecific ST wave abnormalities.
in some patients undergoing angiography (6). Molecular studies have revealed that high doses of epinephrine are directly toxic to the cells, causing a rise in adenosine 3’,5’-cyclic monophosphate and calcium levels that then trigger the formation of free oxygen radicals, the initiation of expression of stress response genes, and induction of apoptosis (7). The yohimbine contained in the male enhancement formula Extenze is a competitive antagonist that is selective for alpha-2 receptors located in the central nervous system, where it acts to increase blood pressure and heart rate. It has been well acknowledged that with relatively low doses it can produce side effects such as tachycardia, chest pain, hypertension, lacrimation,
Figure 2. Chest x-ray showing pulmonary vascular congestion. January 2015
tremors, and diaphoresis (8, 9). In addition, yohimbine-containing products have been implicated in cases of hypertension emergencies, severe Raynaud’s phenomenon, angina pectoris, refractory priapism, and even death (10–14). Currently, the association of reverse takotsubo cardiomyopathy and yohimbine is not known. Nonetheless, we think that, given the mechanism of action of yohimbine as a sympathomimetic drug acting on
Figure 3. An apical four-chamber view showing severe hypokinesis of the basal/ mid inferoseptal segment and anterolateral segment of the left ventricle. The apical segment of the left ventricle has normal contractility.
Reverse takotsubo cardiomyopathy with use of male enhancers
79
a
b
Figure 4. Anteroposterior cranial views of the (a) right coronary artery and (b) left coronary arteries show no evidence of any significant coronary artery disease.
the alpha-2 adrenergic receptors, overdose potentially influenced the development of reverse takotsubo cardiomyopathy similar to cases related to pheochromocytomas and administration of dobutamine. 1.
2.
80
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):408–417. Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation 2008;118(25):2754–2762.
3. Angelini P. Reverse, or inverted, transient takotsubo cardiomyopathy: terms and status of an open discussion. Tex Heart Inst J 2013;40(1): 60–63. 4. Ramaraj R, Movahed MR. Reverse or inverted takotsubo cardiomyopathy (reverse left ventricular apical ballooning syndrome) presents at a younger age compared with the mid or apical variant and is always associated with triggering stress. Congest Heart Fail 2010;16(6):284–286. 5. Kaoukis A, Panagopoulou V, Mojibian HR, Jacoby D. Reverse takotsubo cardiomyopathy associated with the consumption of an energy drink. Circulation 2012;125(12):1584–1585. 6. Nojima Y, Kotani J. Global coronary artery spasm caused takotsubo cardiomyopathy. J Am Coll Cardiol 2010;55(9):e17. 7. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5(1):22–29. 8. Westfall TC, Westfall DP. Chapter 10. Adrenergic agonists and antagonists. In Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill, 2006:271. 9. Chu J. Chapter 28. Genitourinary principles. In Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank’s Toxicologic Emergencies, 8th ed. New York: McGraw Hill, 2006:445– 446. 10. Ruck B, Shih RD, Marcus SM. Hypertensive crisis from herbal treatment of impotence. Am J Emerg Med 1999;17(3):317–318. 11. Myers A, Barrueto F Jr. Refractory priapism associated with ingestion of yohimbe extract. J Med Toxicol 2009;5(4):223–225. 12. Epelde Gonzalo F. Yohimbine-induced angina pectoris. An Med Interna 1998;15(12):676. 13. Johnson S, Iazzetta J, Dewar C. Severe Raynaud’s phenomenon with yohimbine therapy for erectile dysfunction. J Rheumatol 2003;30(11):2503– 2505. 14. Anderson C, Anderson D, Harre N, Wade N. Case study: two fatal case reports of acute yohimbine intoxication. J Anal Toxicol 2013;37(8): 611–614.
Baylor University Medical Center Proceedings
Volume 28, Number 1
Reverse takotsubo cardiomyopathy is a rare heart failure condition characterized by systolic dysfunction of the basal segments of the left ventricle in the absence of obstructive coronary artery disease. We present a case of a 54-year-old man with an overdose of Extenze (a male enhancer pill containing yohimbine) who was hospitalized with heart failure due to reverse takotsubo cardiomyopathy.
T
he pathogenesis of reverse takotsubo cardiomyopathy is not well understood, but physical or mental stress is frequently an associated trigger. Less commonly reported, sympathomimeti c states have been linked to this disease entity. Reverse takotsubo cardiomyopathy has been reported in cases of hyperadrenergic states secondary to pheochromocytomas, catecholamine-secreting tumors, administration of beta-receptor agonists, such as dobutamine, and consumption of caffeine and energy drinks. In this report, we describe a case of reverse takotsubo cardiomyopathy relating to an overdose of Extenze, a male enhancer pill containing yohimbine. CASE PRESENTATION A 54-year-old man was admitted to the intensive care unit after ingesting multiple pills of Tylenol and Extenze, a product that contains yohimbine. He complained of abdominal discomfort and mild dyspnea. He was anxious and had a heart rate of 110 beats/minute. The electrocardiogram showed sinus tachycardia, right bundle branch block, and ST segment depression in lead V3 (Figure 1). A radiograph showed pulmonary congestion (Figure 2). His initial troponin I level was 0.94 ng/L; 7 hours later, it was 13 ng/L. Three hours after admission, he became disoriented, hypotensive, and hypoxic and was intubated for respiratory distress due to heart failure. An echocardiogram showed left ventricular systolic dysfunction with basal hypokinesis but normal mid/distal anterior, inferior, and apical contraction (Figure 3). Coronary angiography was normal without any anatomical or functional abnormalities such as coronary spasm, myocardial bridging, or coronary artery disease (Figure 4). Since the patient had an echocardiogram showing reverse takotsubo cardiomyopathy with severely depressed LV systolic function on the same day prior to cardiac catheterization, no ventriculogram was performed. The patient was treated with 78
vasopressors, diuretics, and invasive ventilatory support. After 72 hours, the patient was extubated and transferred to a regular floor. He recovered fully and was discharged after 1 week of hospitalization. Unfortunately, the patient did not follow up in the cardiology clinic; thus, no follow-up echocardiogram was performed. DISCUSSION Takotsubo cardiomyopathy is an increasingly reported syndrome characterized by transient systolic dysfunction of the apical and or mid segments of the left ventricle without the presence of coronary artery disease (1, 2). In contrast, reverse takotsubo cardiomyopathy is a condition with transient systolic dysfunction of the basal segments of the left ventricle. Although transient, reverse, or inverted takotsubo cardiomyopathy was recognized as a different clinical entity >20 years ago, a definite comprehensive pathophysiologic theory for this condition is still lacking (3). Seemingly, reverse takotsubo, which is more common in young female patients with a mean age of 36 years, is thought to be triggered by physical or emotional stress rather than catecholaminergic states. The presence of adrenoreceptors, which are at their apex in older patients, makes the occurrence of the apical variant of takotsubo cardiomyopathy more common among the older population, in contrast to the younger population, where the abundance of adrenoreceptors is within the base of the heart, which may lead to the reverse variant of takotsubo cardiomyopathy (4). There have been documented reports of reverse takotsubo in association with pheochromocytomas, intravenous administration of beta-receptor agonists (dobutamine) or catecholamines, as well as with the use of energy drinks containing caffeine and 1,3-dimethylamylamine (5). The pathophysiology behind this condition relies on two primary theories: vascular dysfunction and catecholamineinduced toxicity. Multifocal vasospasm has been demonstrated From the Department of Internal Medicine (Rodriguez-Castro, Porres-Aguilar, Said), Division of Cardiovascular Diseases (Gough, Siddiqui, Mukherjee, Abbas), Texas Tech University Health Sciences Center, El Paso, Texas; and Jinnah Postgraduate Medical Center, Karachi, Pakistan (Saifuddin). Corresponding author: Carlos E. Rodríguez-Castro, MD, Department of Internal Medicine, Texas Tech University Health Science Center, 4800 Alberta Avenue, El Paso, TX 79905 (e-mail: [email protected]). Proc (Bayl Univ Med Cent) 2015;28(1):78–80
Figure 1. Supraventricular tachycardia with incomplete right bundle branch block and nonspecific ST wave abnormalities.
in some patients undergoing angiography (6). Molecular studies have revealed that high doses of epinephrine are directly toxic to the cells, causing a rise in adenosine 3’,5’-cyclic monophosphate and calcium levels that then trigger the formation of free oxygen radicals, the initiation of expression of stress response genes, and induction of apoptosis (7). The yohimbine contained in the male enhancement formula Extenze is a competitive antagonist that is selective for alpha-2 receptors located in the central nervous system, where it acts to increase blood pressure and heart rate. It has been well acknowledged that with relatively low doses it can produce side effects such as tachycardia, chest pain, hypertension, lacrimation,
Figure 2. Chest x-ray showing pulmonary vascular congestion. January 2015
tremors, and diaphoresis (8, 9). In addition, yohimbine-containing products have been implicated in cases of hypertension emergencies, severe Raynaud’s phenomenon, angina pectoris, refractory priapism, and even death (10–14). Currently, the association of reverse takotsubo cardiomyopathy and yohimbine is not known. Nonetheless, we think that, given the mechanism of action of yohimbine as a sympathomimetic drug acting on
Figure 3. An apical four-chamber view showing severe hypokinesis of the basal/ mid inferoseptal segment and anterolateral segment of the left ventricle. The apical segment of the left ventricle has normal contractility.
Reverse takotsubo cardiomyopathy with use of male enhancers
79
a
b
Figure 4. Anteroposterior cranial views of the (a) right coronary artery and (b) left coronary arteries show no evidence of any significant coronary artery disease.
the alpha-2 adrenergic receptors, overdose potentially influenced the development of reverse takotsubo cardiomyopathy similar to cases related to pheochromocytomas and administration of dobutamine. 1.
2.
80
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):408–417. Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation 2008;118(25):2754–2762.
3. Angelini P. Reverse, or inverted, transient takotsubo cardiomyopathy: terms and status of an open discussion. Tex Heart Inst J 2013;40(1): 60–63. 4. Ramaraj R, Movahed MR. Reverse or inverted takotsubo cardiomyopathy (reverse left ventricular apical ballooning syndrome) presents at a younger age compared with the mid or apical variant and is always associated with triggering stress. Congest Heart Fail 2010;16(6):284–286. 5. Kaoukis A, Panagopoulou V, Mojibian HR, Jacoby D. Reverse takotsubo cardiomyopathy associated with the consumption of an energy drink. Circulation 2012;125(12):1584–1585. 6. Nojima Y, Kotani J. Global coronary artery spasm caused takotsubo cardiomyopathy. J Am Coll Cardiol 2010;55(9):e17. 7. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (takotsubo) cardiomyopathy—a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008;5(1):22–29. 8. Westfall TC, Westfall DP. Chapter 10. Adrenergic agonists and antagonists. In Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill, 2006:271. 9. Chu J. Chapter 28. Genitourinary principles. In Nelson LS, Lewin NA, Howland M, Hoffman RS, Goldfrank LR, Flomenbaum NE, eds. Goldfrank’s Toxicologic Emergencies, 8th ed. New York: McGraw Hill, 2006:445– 446. 10. Ruck B, Shih RD, Marcus SM. Hypertensive crisis from herbal treatment of impotence. Am J Emerg Med 1999;17(3):317–318. 11. Myers A, Barrueto F Jr. Refractory priapism associated with ingestion of yohimbe extract. J Med Toxicol 2009;5(4):223–225. 12. Epelde Gonzalo F. Yohimbine-induced angina pectoris. An Med Interna 1998;15(12):676. 13. Johnson S, Iazzetta J, Dewar C. Severe Raynaud’s phenomenon with yohimbine therapy for erectile dysfunction. J Rheumatol 2003;30(11):2503– 2505. 14. Anderson C, Anderson D, Harre N, Wade N. Case study: two fatal case reports of acute yohimbine intoxication. J Anal Toxicol 2013;37(8): 611–614.
Baylor University Medical Center Proceedings
Volume 28, Number 1
