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Pheochromocytoma: Catecholamine-mediated electrocardiographic changes mimicking ischemia
Volume Number
116 6. Part
Brief
1
Pheochromocytoma: Catecholamine-mediated electrocardiographic changes ischemia
Communications
1363
mimicking
Garrie J. Haas, MD, Manuel Tzagournis, MD, and Harisios Boudoulas, MD. Columbus, Ohio
Electrocardiographic (ECG) abnormalities are common in patients with pheochromocytoma. They are usually nonspecific changes and are of limited diagnostic value, often resulting in diagnostic and therapeutic problems. The following case illustrates a situation in which diverse ECG changes occurring in a patient with pheochromocytoma led to a significant modification of the preoperative evaluation and management. A 74-year-old previously healthy white woman was admitted to the Ohio State University Hospitals for evaluation of syncope. Over the preceding 12 months she had experienced episodes of nausea, lightheadedness, and diaphoresis that were typically precipitated by standing. These symptoms increased in frequency and severity over a several-month period, culminating in frank syncope. The initial physical examination revealed an elderly thin white woman in no distress. The blood pressure was X10/70 mm Hg supine and 90/70 mm Hg sitting; the pulse was 85 beats/min supine and 110 beats/min sitting; respirations and temperature were normal. The lungs were clear. Cardiovascular examination showed a normal jugular venous pressure, a mildly enlarged apical impulse, and normal first and second heart sounds. A midsystolic click and late systolic murmur were present at the apex. Peripheral pulses were normal and there was no cyanosis or edema. The remainder of the physical examination was unremarkable. The chest x-ray film revealed normal cardiac size. The initial ECG on August 26, 1987, showed sinus rhythm with a rate of 83 beats/min, inverted T waves, a prolonged QT interval, and mild ST segment depression laterally. The PR interval was borderline short at 120 msec (Fig. 1, A). During the hospitalization, marked supine blood pressure fluctuations were recorded (230160 to 95/74 mm Hg). Because pheochromocytoma was suspected, plasma levels of epinephrine (E) and norepinephrine (NE) were drawn and were found to be markedly elevated (1148 pg/ml and 2858 pg/ml, respectively; normal values, E = 0 to 140 pg/ml and NE = 200 to 1700 pg/ml). In addition, computed tomography of the abdomen revealed a 3 x 5 cm left adrenal mass. These findings strongly supported the
From
the Division
Supported in part Heart Association. Association.
of Cardiology,
The
Ohio
State
University
Hospitals
by the Central Ohio Heart Chapter of the American Dr. Haas is a Research Fellow of the American Heart
Reprint requests: Harisios Boudoulas, MD, The Hospitals, Division of Cardiology, 1654 Upham Columbus, OH 43210.
Ohio Dr.,
State University 647 Means Hall,
Fig. 1. Characteristic catecholamine-induced ECG prolongation, lateral ST segchanges. In A, QT-interval ment depression, and inverted anterior T waves are evident. The PR interval is borderline short at 120 msec. In B, there is ectopic atria1 tachycardia with diffuse ST segment elevation and upright T waves.
diagnosis of pheochromocytoma. A repeat ECG on September 4, 1987, showed ectopic atria1 tachycardia with diffuse ST segment elevation (Fig. 1, R). The patient had no chest pain or other symptoms suggestive of myocardial ischemia. In preparation for surgery, treatment with phenoxybenzamine, an alpha,-adrenergic blocking agent, was started at 20 mg per day and was increased to 60 mg daily over 1 week. There were no hypertensive or hypotensive episodes during this therapy. Approximately 1 week after initiating treatment with phenoxybenzamine, the patient experienced an episode of substernal chest pain. A subsequent ECG on September 15, 1987, demonstrated sinus tachycardia with diffuse T wave inversion consistent with global subendocardial ischemia (Fig. 2, A). The ECG abnormalities persisted without further clinical evidence of myocardial ischemia. There was no sign of cerebrovascular accident or extreme blood pressure fluctuation during this interval. Serum electrolyte values were normal. Therapy with atenolol, 50 mg daily, was initiated and the patient was transferred to the coronary care unit for monitoring and further cardiac evaluation. Serial determinations of creatine kinase (CK) with MB isoenzymes and a technetium pyrophosphate scan did not support the diagnosis of acute myocardial infarction. Because of the persistent ECG abnormalities, cardiac
1364
Brief
Communications
Fig. 2. Tracing A followed an episode of chest pain and demonstrates sinus tachycardia with symmetric giant T wave inversion and QT interval prolongation. Tracing B was obtained 4 months after tumor removal and shows near complete resolution of these changes.
catheterization was performed to define the coronary anatomy prior to surgery. Coronary angiography showed plaque disease without evidence of significant obstruction. The left ventricular ejection fraction was 49% (mildly depressed) without segmental contraction abnormalities. The procedure was tolerated well without significant hemodynamic changes. Therapy with alpha- and betaadrenergic blockade was continued and the patient underwent surgery for excision of the left adrenal mass. There were no intraoperative or postoperative complications. Histopathology confirmed the diagnosis of pheochromocytoma. Since hospital discharge on September 26, 1987, the patient has done well without recurrence of hypertension, nausea, dizziness, syncope, or chest pain. Her latest ECG (January 26, 1988) demonstrated marked improvement, with upright T waves in all leads except V, to V3 (Fig. 2, B). E and NE levels were 59 pg/ml and 864 pg/ml, respectively. At the same time, left ventricular function and size by two-dimensional echocardiography were normal. The ~iwrccs lwc changes frequently observed in patients with pheochromocytoma result from enhanced alphaand beta-adrenergic receptor stimulation.1-3 Although several abnormalities have been described, T
wave flattening or inversion is one of the most common and clinically relevant findings. The mechanisms for these T wave changes are multiple.” E, through its beta, effect, has been shown to reduce serum potassium levels4 This may be reflected by the typical ECG changes of hypokalemia including T wave inversion and prominent U waves. Furthermore, catecholamines may produce ischemic ECG changes by inducing myocardial injury. It has been shown5 that beta receptor stimulation increases myocyte calcium concentration. Calcium overload could lead to cellular ischemia or necrosis. In addition, continuous alpha-adrenergic receptor stimulation producing arterial vasoconstriction may produce subendocardial injury. Indeed, recent studies6 have demonstrated that NE infusion in an animal model results in myocardial damage that may be secondary to an alpha-adrenergic receptor-mediated reduction in coronary blood flow. Concurrent increases in chronotropy, inotropy, and afterload resulting from enhanced beta, and alpha, activity would act to increase myocardial ischemia further. Chronic ST segment and T wave changes may be secondary to ventricular hypertrophy resulting from prolonged elevation of serum catecholamines and long-standing arterial hypertension; moreover, the hypertrophic myocardium may further compromise subendocardial blood flow. In the absence of underlying cardiac disease, the ECG changes in patients with pheochromocytoma often revert to normal after tumor removal or alpha-adrenergic blockade.‘,2*1 Evidence that these changes reflect catecholamine-induced reversible myocardial injury has been shown by several investigators. Cheng and Bashour reported resolution of ischemic ECG changes after removal of a pheochromocytoma in a 51-year-old woman. A dramatic improvement in cardiac function and ECG abnormalities were shown in a child with dilated cardiomyopathy and pheochromocytoma after prolonged treatment with phenoxybenzamine and the tyrosine hydroxylase inhibitor, alpha methyl-para-tyrosine.8 Simons and Downing6 have shown that the typical histologic changes of focal myocardial necrosis and perivascular inflammation induced by NE infusion in the rabbit are prevented by alpha-receptor blockade with prazosin. Our case describes a patient who manifested a broad spectrum of catecholamine-induced ECG abnormalities. According to previous reports? 8 one would expect resolution of these changes following treatment with an alphaadrenergic blocking agent. To the contrary, our patient developed profound ischemic changes following treatment with phenoxybenzamine. We believe this reflects enhanced beta-adrenergic stimulation and underscores the importance of achieving total pharmacologic blockade in these patients. Unopposed beta-adrenergic activity may have resulted in cardiac ischemia by increasing myocardial oxygen demand (increased contractility and heart rate) or by increasing intracellular calcium content. Failure of these changes to reverse following beta-receptor blockade with atenolol may indicate inadequate drug concentration, excess beta,-adrenergic effect, or myocardial necro-
Volume Number
116 5, Part 1
sis. It is doubtful that inadequate alpha-receptor blockade was a significant factor, since the blood pressure was well controlled with phenoxybenzamine. Although T wave changes may occur in patients with mitral valve prolapse9 (a condition suggested by this patient’s initial physical examination), it seems unlikely that this would explain the close association between ECG changes and specific interventions (i.e., drug therapy, tumor excision). Failure of the ECG to make a complete return to normal 4 months postoperatively suggests that minor irreversible subendocardial necrosis may have occurred, but these ECG changes may also be related to mitral valve prolapse.g In conclusion, this case demonstrates that diverse ECG abnormalities of rhythm, conduction, and repolarization may occur in patients with pheochromocytoma. The paroxysmal nature and different degree of catecholamine secretion from this tumor probably accounts for the variability of these changes. Importantly, the ECG abnormalities may persist or worsen following adequate alphaadrenergic blockade. This may occur in the absence of obstructive coronary artery disease or other clinically detectable cardiac pathology. Although the mechanism for these changes is unclear, unopposed beta-adrenergic receptor stimulation may be a major factor. The nonspecificity and acute nature of the ECG changes associated with pheochromocytoma will often warrant coronary angiography prior to surgery. Although alpha-adrenergic blockade and blood pressure control are essential before any invasive procedure, complete alpha- and beta-receptor blockade may be important for further myocardial protection, especially when ECG abnormalities are present initially.
REFERENCES
1. Huang SK, Rosenberg NJ, Denes P. Short PR interval and narrow QRS complex associated with pheochromocytoma: electrophysiologic observations. d Am Co11 Cardiol 1984; 3:872. 2. Sayer WJ, Moser M, Mattingly TW. Pheochromocytoma and the abnormal electrocardiogram. AM HEART J 1953;48:42. 3. Lepeschkin E, Marchet H, Schroeder G, et al. Effect of epinephrine and norepinephrine on the electrocardiogram in 100 normal subjects. Am J Cardiol 1960;5:594. 1. Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta?-receptor stimulation by circulating epinephrine. N Engl J Med 1983;309:143 4. ,-I. Bloom S, Davis UL. Calcium as mediator of isoproterenolinduced myocardial necrosis. Am J Path01 1972;69:459. 6. Simons M. Downina SE. Coronarv vasoconstriction and catecholamine cardiomyopathy. AM HEART J 1985;109:297. 7. Cheng TO, Bashour TT. Striking electrocardiographic changes associated with pheochromocytoma masquerading as ischemic heart disease. Chest 1976,70:397. 8. Imperato-McGinley J, Gautier T, Ehlers K, et al. Reversibility of catecholamine-induced dilated cardiomyopathy in a child with pheochromocytoma. N Engl J Med 1987;316:793. 9. Boudoulas H, Wooley CF. Mitral valve prolapse: clinical presentation and diagnostic evaluation. In: Boudoulas H, Wooley CF, editors. Mitral valve prolapse and the mitral valve prolapse syndrome. New York: Futura Publishing Company, Inc, 1988:302.
Brief
Communications
1365
Successful treatment of anaina oectoris . with liver transplantation and bilateral internal mammary bypass graft surgery in familial hypercholesterolemia John E. Brush, Jr., MD, Martin B. Leon, MD, Thomas E. Starzl, MD, Carl Gill, MD, and Jeffrey M. Hoeg, MD. Bethesda, Md., Pittsburgh, and Cleveland, Ohio
Pa.,
Familial hypercholesterolemia (FH) is a disease characterized by elevated plasma cholesterol levels, tendon xanthomas, xanthelasmas, and widespread atherosclerosis resulting in premature acute myocardial infarction and sudden cardiac death.’ The severity of atherosclerosis is directly related to the plasma low-density lipoprotein (LDL) cholesterol level. Previous attempts to treat coronary artery disease in homozygous patients have been unrewarding. With a persistent elevation in plasma cholesterol concentration, the atherosclerotic process continues unabated. Surgical management of angina in these patients has been similarly unrewarding; saphenous vein bypass grafting carries the risk of dislodging and embolizing atherosclerotic plaques from the ascending aorta at the time of operation, since the atherosclerosis is particularly severe in the ascending aorta at the site of graft anastomosis.2 Moreover, a persistent elevation in plasma cholesterol is associated with a high rate of saphenous vein graft occlusion. Percutaneous transluminal coronary angioplasty has also been disappointing in patients with homozygous FH due to a high frequency of early restenosis (unpublished observations). We report a patient with severe FH who has had successful alleviation of angina pectoris and who has maintained graft patency 1 year following liver transplantation and bilateral internal mammary artery (IMA) bypass grafting. This is the first report of combined liver transplantation and IMA implantation as a radical treatment approach for this form of advanced coronary artery disease. VP is a 13-year-old young man who had xanthomas detected at age 18 months that led to the diagnosis of homozygous FH. He was treated with a low-fat, lowcholesterol diet until age 5, when cholestyramine was started; at age 9. nicotinic acid was added. When the patient was referred to the National Institutes of Health (NIH) at age 11, he complained of exertional angina. He had widespread yellow xanthomas, a 316 systolic ejectiontype murmur at the upper sternal border, and bruits over both carotid arteries and both femoral arteries. He was
From the C‘arditk!gy Branch and Molecular Disease Branch, National Heart. Lung. and Blood Institute, National’s Institutes of Health; The i’nirersir ot’ Pittshurgh School of Medicine: and the Cleveland Clinic. Reprint requests: .John E. Brush, Jr., MD, Cardiology Branch, National Institutes of Health. Building 10, Room 7B-15, Bethesda, MD 20892.
116 6. Part
Brief
1
Pheochromocytoma: Catecholamine-mediated electrocardiographic changes ischemia
Communications
1363
mimicking
Garrie J. Haas, MD, Manuel Tzagournis, MD, and Harisios Boudoulas, MD. Columbus, Ohio
Electrocardiographic (ECG) abnormalities are common in patients with pheochromocytoma. They are usually nonspecific changes and are of limited diagnostic value, often resulting in diagnostic and therapeutic problems. The following case illustrates a situation in which diverse ECG changes occurring in a patient with pheochromocytoma led to a significant modification of the preoperative evaluation and management. A 74-year-old previously healthy white woman was admitted to the Ohio State University Hospitals for evaluation of syncope. Over the preceding 12 months she had experienced episodes of nausea, lightheadedness, and diaphoresis that were typically precipitated by standing. These symptoms increased in frequency and severity over a several-month period, culminating in frank syncope. The initial physical examination revealed an elderly thin white woman in no distress. The blood pressure was X10/70 mm Hg supine and 90/70 mm Hg sitting; the pulse was 85 beats/min supine and 110 beats/min sitting; respirations and temperature were normal. The lungs were clear. Cardiovascular examination showed a normal jugular venous pressure, a mildly enlarged apical impulse, and normal first and second heart sounds. A midsystolic click and late systolic murmur were present at the apex. Peripheral pulses were normal and there was no cyanosis or edema. The remainder of the physical examination was unremarkable. The chest x-ray film revealed normal cardiac size. The initial ECG on August 26, 1987, showed sinus rhythm with a rate of 83 beats/min, inverted T waves, a prolonged QT interval, and mild ST segment depression laterally. The PR interval was borderline short at 120 msec (Fig. 1, A). During the hospitalization, marked supine blood pressure fluctuations were recorded (230160 to 95/74 mm Hg). Because pheochromocytoma was suspected, plasma levels of epinephrine (E) and norepinephrine (NE) were drawn and were found to be markedly elevated (1148 pg/ml and 2858 pg/ml, respectively; normal values, E = 0 to 140 pg/ml and NE = 200 to 1700 pg/ml). In addition, computed tomography of the abdomen revealed a 3 x 5 cm left adrenal mass. These findings strongly supported the
From
the Division
Supported in part Heart Association. Association.
of Cardiology,
The
Ohio
State
University
Hospitals
by the Central Ohio Heart Chapter of the American Dr. Haas is a Research Fellow of the American Heart
Reprint requests: Harisios Boudoulas, MD, The Hospitals, Division of Cardiology, 1654 Upham Columbus, OH 43210.
Ohio Dr.,
State University 647 Means Hall,
Fig. 1. Characteristic catecholamine-induced ECG prolongation, lateral ST segchanges. In A, QT-interval ment depression, and inverted anterior T waves are evident. The PR interval is borderline short at 120 msec. In B, there is ectopic atria1 tachycardia with diffuse ST segment elevation and upright T waves.
diagnosis of pheochromocytoma. A repeat ECG on September 4, 1987, showed ectopic atria1 tachycardia with diffuse ST segment elevation (Fig. 1, R). The patient had no chest pain or other symptoms suggestive of myocardial ischemia. In preparation for surgery, treatment with phenoxybenzamine, an alpha,-adrenergic blocking agent, was started at 20 mg per day and was increased to 60 mg daily over 1 week. There were no hypertensive or hypotensive episodes during this therapy. Approximately 1 week after initiating treatment with phenoxybenzamine, the patient experienced an episode of substernal chest pain. A subsequent ECG on September 15, 1987, demonstrated sinus tachycardia with diffuse T wave inversion consistent with global subendocardial ischemia (Fig. 2, A). The ECG abnormalities persisted without further clinical evidence of myocardial ischemia. There was no sign of cerebrovascular accident or extreme blood pressure fluctuation during this interval. Serum electrolyte values were normal. Therapy with atenolol, 50 mg daily, was initiated and the patient was transferred to the coronary care unit for monitoring and further cardiac evaluation. Serial determinations of creatine kinase (CK) with MB isoenzymes and a technetium pyrophosphate scan did not support the diagnosis of acute myocardial infarction. Because of the persistent ECG abnormalities, cardiac
1364
Brief
Communications
Fig. 2. Tracing A followed an episode of chest pain and demonstrates sinus tachycardia with symmetric giant T wave inversion and QT interval prolongation. Tracing B was obtained 4 months after tumor removal and shows near complete resolution of these changes.
catheterization was performed to define the coronary anatomy prior to surgery. Coronary angiography showed plaque disease without evidence of significant obstruction. The left ventricular ejection fraction was 49% (mildly depressed) without segmental contraction abnormalities. The procedure was tolerated well without significant hemodynamic changes. Therapy with alpha- and betaadrenergic blockade was continued and the patient underwent surgery for excision of the left adrenal mass. There were no intraoperative or postoperative complications. Histopathology confirmed the diagnosis of pheochromocytoma. Since hospital discharge on September 26, 1987, the patient has done well without recurrence of hypertension, nausea, dizziness, syncope, or chest pain. Her latest ECG (January 26, 1988) demonstrated marked improvement, with upright T waves in all leads except V, to V3 (Fig. 2, B). E and NE levels were 59 pg/ml and 864 pg/ml, respectively. At the same time, left ventricular function and size by two-dimensional echocardiography were normal. The ~iwrccs lwc changes frequently observed in patients with pheochromocytoma result from enhanced alphaand beta-adrenergic receptor stimulation.1-3 Although several abnormalities have been described, T
wave flattening or inversion is one of the most common and clinically relevant findings. The mechanisms for these T wave changes are multiple.” E, through its beta, effect, has been shown to reduce serum potassium levels4 This may be reflected by the typical ECG changes of hypokalemia including T wave inversion and prominent U waves. Furthermore, catecholamines may produce ischemic ECG changes by inducing myocardial injury. It has been shown5 that beta receptor stimulation increases myocyte calcium concentration. Calcium overload could lead to cellular ischemia or necrosis. In addition, continuous alpha-adrenergic receptor stimulation producing arterial vasoconstriction may produce subendocardial injury. Indeed, recent studies6 have demonstrated that NE infusion in an animal model results in myocardial damage that may be secondary to an alpha-adrenergic receptor-mediated reduction in coronary blood flow. Concurrent increases in chronotropy, inotropy, and afterload resulting from enhanced beta, and alpha, activity would act to increase myocardial ischemia further. Chronic ST segment and T wave changes may be secondary to ventricular hypertrophy resulting from prolonged elevation of serum catecholamines and long-standing arterial hypertension; moreover, the hypertrophic myocardium may further compromise subendocardial blood flow. In the absence of underlying cardiac disease, the ECG changes in patients with pheochromocytoma often revert to normal after tumor removal or alpha-adrenergic blockade.‘,2*1 Evidence that these changes reflect catecholamine-induced reversible myocardial injury has been shown by several investigators. Cheng and Bashour reported resolution of ischemic ECG changes after removal of a pheochromocytoma in a 51-year-old woman. A dramatic improvement in cardiac function and ECG abnormalities were shown in a child with dilated cardiomyopathy and pheochromocytoma after prolonged treatment with phenoxybenzamine and the tyrosine hydroxylase inhibitor, alpha methyl-para-tyrosine.8 Simons and Downing6 have shown that the typical histologic changes of focal myocardial necrosis and perivascular inflammation induced by NE infusion in the rabbit are prevented by alpha-receptor blockade with prazosin. Our case describes a patient who manifested a broad spectrum of catecholamine-induced ECG abnormalities. According to previous reports? 8 one would expect resolution of these changes following treatment with an alphaadrenergic blocking agent. To the contrary, our patient developed profound ischemic changes following treatment with phenoxybenzamine. We believe this reflects enhanced beta-adrenergic stimulation and underscores the importance of achieving total pharmacologic blockade in these patients. Unopposed beta-adrenergic activity may have resulted in cardiac ischemia by increasing myocardial oxygen demand (increased contractility and heart rate) or by increasing intracellular calcium content. Failure of these changes to reverse following beta-receptor blockade with atenolol may indicate inadequate drug concentration, excess beta,-adrenergic effect, or myocardial necro-
Volume Number
116 5, Part 1
sis. It is doubtful that inadequate alpha-receptor blockade was a significant factor, since the blood pressure was well controlled with phenoxybenzamine. Although T wave changes may occur in patients with mitral valve prolapse9 (a condition suggested by this patient’s initial physical examination), it seems unlikely that this would explain the close association between ECG changes and specific interventions (i.e., drug therapy, tumor excision). Failure of the ECG to make a complete return to normal 4 months postoperatively suggests that minor irreversible subendocardial necrosis may have occurred, but these ECG changes may also be related to mitral valve prolapse.g In conclusion, this case demonstrates that diverse ECG abnormalities of rhythm, conduction, and repolarization may occur in patients with pheochromocytoma. The paroxysmal nature and different degree of catecholamine secretion from this tumor probably accounts for the variability of these changes. Importantly, the ECG abnormalities may persist or worsen following adequate alphaadrenergic blockade. This may occur in the absence of obstructive coronary artery disease or other clinically detectable cardiac pathology. Although the mechanism for these changes is unclear, unopposed beta-adrenergic receptor stimulation may be a major factor. The nonspecificity and acute nature of the ECG changes associated with pheochromocytoma will often warrant coronary angiography prior to surgery. Although alpha-adrenergic blockade and blood pressure control are essential before any invasive procedure, complete alpha- and beta-receptor blockade may be important for further myocardial protection, especially when ECG abnormalities are present initially.
REFERENCES
1. Huang SK, Rosenberg NJ, Denes P. Short PR interval and narrow QRS complex associated with pheochromocytoma: electrophysiologic observations. d Am Co11 Cardiol 1984; 3:872. 2. Sayer WJ, Moser M, Mattingly TW. Pheochromocytoma and the abnormal electrocardiogram. AM HEART J 1953;48:42. 3. Lepeschkin E, Marchet H, Schroeder G, et al. Effect of epinephrine and norepinephrine on the electrocardiogram in 100 normal subjects. Am J Cardiol 1960;5:594. 1. Brown MJ, Brown DC, Murphy MB. Hypokalemia from beta?-receptor stimulation by circulating epinephrine. N Engl J Med 1983;309:143 4. ,-I. Bloom S, Davis UL. Calcium as mediator of isoproterenolinduced myocardial necrosis. Am J Path01 1972;69:459. 6. Simons M. Downina SE. Coronarv vasoconstriction and catecholamine cardiomyopathy. AM HEART J 1985;109:297. 7. Cheng TO, Bashour TT. Striking electrocardiographic changes associated with pheochromocytoma masquerading as ischemic heart disease. Chest 1976,70:397. 8. Imperato-McGinley J, Gautier T, Ehlers K, et al. Reversibility of catecholamine-induced dilated cardiomyopathy in a child with pheochromocytoma. N Engl J Med 1987;316:793. 9. Boudoulas H, Wooley CF. Mitral valve prolapse: clinical presentation and diagnostic evaluation. In: Boudoulas H, Wooley CF, editors. Mitral valve prolapse and the mitral valve prolapse syndrome. New York: Futura Publishing Company, Inc, 1988:302.
Brief
Communications
1365
Successful treatment of anaina oectoris . with liver transplantation and bilateral internal mammary bypass graft surgery in familial hypercholesterolemia John E. Brush, Jr., MD, Martin B. Leon, MD, Thomas E. Starzl, MD, Carl Gill, MD, and Jeffrey M. Hoeg, MD. Bethesda, Md., Pittsburgh, and Cleveland, Ohio
Pa.,
Familial hypercholesterolemia (FH) is a disease characterized by elevated plasma cholesterol levels, tendon xanthomas, xanthelasmas, and widespread atherosclerosis resulting in premature acute myocardial infarction and sudden cardiac death.’ The severity of atherosclerosis is directly related to the plasma low-density lipoprotein (LDL) cholesterol level. Previous attempts to treat coronary artery disease in homozygous patients have been unrewarding. With a persistent elevation in plasma cholesterol concentration, the atherosclerotic process continues unabated. Surgical management of angina in these patients has been similarly unrewarding; saphenous vein bypass grafting carries the risk of dislodging and embolizing atherosclerotic plaques from the ascending aorta at the time of operation, since the atherosclerosis is particularly severe in the ascending aorta at the site of graft anastomosis.2 Moreover, a persistent elevation in plasma cholesterol is associated with a high rate of saphenous vein graft occlusion. Percutaneous transluminal coronary angioplasty has also been disappointing in patients with homozygous FH due to a high frequency of early restenosis (unpublished observations). We report a patient with severe FH who has had successful alleviation of angina pectoris and who has maintained graft patency 1 year following liver transplantation and bilateral internal mammary artery (IMA) bypass grafting. This is the first report of combined liver transplantation and IMA implantation as a radical treatment approach for this form of advanced coronary artery disease. VP is a 13-year-old young man who had xanthomas detected at age 18 months that led to the diagnosis of homozygous FH. He was treated with a low-fat, lowcholesterol diet until age 5, when cholestyramine was started; at age 9. nicotinic acid was added. When the patient was referred to the National Institutes of Health (NIH) at age 11, he complained of exertional angina. He had widespread yellow xanthomas, a 316 systolic ejectiontype murmur at the upper sternal border, and bruits over both carotid arteries and both femoral arteries. He was
From the C‘arditk!gy Branch and Molecular Disease Branch, National Heart. Lung. and Blood Institute, National’s Institutes of Health; The i’nirersir ot’ Pittshurgh School of Medicine: and the Cleveland Clinic. Reprint requests: .John E. Brush, Jr., MD, Cardiology Branch, National Institutes of Health. Building 10, Room 7B-15, Bethesda, MD 20892.