Observations on Myocardial Function During Chronic Catecholamine Oversecretion

Q interval during normal intraventricular conduction is also not unusual. l6 , 1 8 It is conceivable that the prolonged H-Q interval in our patient during normal QRS

morphology suggests a ·diffuse disease of the conduction system. In that case it is possible that subclinical dysfunction of right bundle branch and left posterior fascicle became unmasked in the form of right bundle branch block and left posterior hemiblock as a result of the diminished blood supply during anginal episodes.

REFERENCES 1 Proudfit WL, Hodgman JR: Physical signs during angina pectoris. Progr Cardiovasc Dis 10:283-286, 1968 2 Prinzmetal M, Kennamer R, Merliss R, et al: Angina pectoris I. A variant form of angina pectoris. Am J Med 27 :375-388, 1959 3 Botti RE: A variant form of angina pectoris with recurrent transient complete heart block. Am J Cardiol 17:443446, 1966 4 Gillilan RE, Hawley RR, Warbasse JR: Second degree heart block occurring in a patient with Prinzmetal variant angina. Am Heart J 77 :380-382, 1969 5 Scherlag RJ, Lau SH, Helfant RH, et al: Catheter technique for recording His bundle activity in man. Circulation 29:13-18,1969 6 Bauer GE: Transient bundle branch block. Circulation 29:730-738, 1964 7 Bauer CE, Julian DC, Valentine PA: Bundle branch block in acute myocardial infarction. Br Heart J 27:724730,1965 8 Godman MJ, Alpert BA, Julian DG: Bilateral bundle branch block complicating acute myocardial infarction. Lancet 2:345-347, 1971 9 Gooch AS, McDonnell D: Analysis of transient arrhythmias and conduction disturbances occurring during submaximal treadmill exercise testing. Progr Cardiovasc Dis 13:293-307, 1970 10 Julian DC, Vallani CW, Godman MJ, et al: Prolongation of QRS duration in acute myocardial infarction. Progr Cardiovasc Dis 13:56-71, 1970 11 Norris RM, Croxson MS: Bundle branch block in acute myocardial infarction. Am Heart J 27 :728-733, 1970 12 Roos JC, Dunning AJ: Right bundle branch block and left axis deviation in acute myocardial infarction. Br Heart J 32:847-851, 1970 13 Col JJ, Weinberg SL: Incidence and mortality of intraventricular conduction defects in acute myocardial infarction. Am J Cardiol29:344-350, 1972 14 Lichstein E, Gupta PK, Chadda K, et al: Findings of prognostic value in patients with incomplete bilateral bundle branch block complicating acute myocardial infarction. Am J Cardiol32:913-918, 1973 15 Rosenbaum MB, Elizari MF, Lazzari JO: The Hemiblocks. Tampa, Tampa Tracings, 1970 16 Narula OS, Samet P: Right bundle branch block with normal left or right axis deviation. Analysis by His bundle recordings. Am J Med 51:432-455, 1971 . 17 Haft JI, Weinstock M, De Guia R, et al: Assessment of atrio-ventricular conduction in right and left bundle branch block using His bundle electrograms and atrial pacing. Am J Cardiol27:474-480, 1971 18 Gupta PK, Chadda K, Lichstein E, et al: Intraventricular conduction time in patients with bundle branch block. J Electrocardiol6: 181-192, 1973 19 Rosen KM, Rahimtoola SH, Chuquimia R, et al: Electrophysiological significance of first degree atrioventricular block with intraventricular conduction disturbance. Circulation 43:491-502, 1971

CHEST, 66: 5, NOVEMBER, 1974

Observations on Myocardial Function During Chronic Catecholamine Oversecretion A young patient with pheochromocytoma"

Nicholas A. Yankopoulos, M.D.,·· Alfredo C. Montero, M.D.,t William G. Curd, t-; M.D., Michel E. Kahil, M.D., and Roberl E. Condon, M.D.

Observations on myocardial function were made ill a young patient ill whom a pheochromocytoma was secreting large amounts of c:atecbolamines, primarily nor-

epillephrine. Without history of Iougstanding or severe hypertension, the patient showed evidence of left ventricnlar failDre. When the heart size bad returned to DOrmai as a resnIt of preoperative treatment, there was stiU a loud atrial gallop and hemodynamic evidence of loss of myocardial reserve.

T

here are only a few patients in the literature with evidence of myocardial injury due to catecholamines from functioning pheochromocytoma.v" This patient is particularly appropriate to report because of his young age and, therefore, expected good myocardial reserve.

CASE REPoRT A 27-year-old carpenter entered the Houston VA Hospital because of progressive fatigue of five-six months duration. He had experienced excessive perspiration and tachycardia for four-five years. Fatigue and nonproductive cough had begun five-six months prior to admission and became progressive and disabling. Moderate exertional dyspnea was present. There was no orthopnea, paroxysmal nocturnal dyspnea or leg swelling. One month prior to admission, he began coughing up small amounts of white sputum which was occasionally blood-tinged after a severe bout of coughing. Blood pressure and roentgenogram of the chest two years prior to admission were normal. There was no history of headaches, excessive alcoholic intake or poor dietary habits. On admission, he weighed 162 lb, was afebrile, but appeared moderately ill. He had a regular heart rate of 144 beats per minute and regular respirations of 22 per minute. The blood pressure with the patient in a recumbent position was 135/115 nun Hg, decreasing to 125/95 in the sitting position. The neck veins were not distended. On auscultation, a few rales were heard over the lung bases p>steriorly. Cardiac size could not be determined by palpation of the chest. The heart sounds were heard clearly and a prominent atrial gallop was present at the lower left sternal border and at the apex. The liver and spleen were not palpable. There was no peripheral edema. Funduscopic examination was normal. All peripheral pulses were normal. His admission white blood cell count was 10,300 cells/nunS with a normal differential and a hematocrit of 46 ·From the Cardiac Evaluation Laboratory and the Departments of Medicine and Surgery, Veterans Administration Hospital, and Baylor University College of Medicine, Houston, Texas; Department of Medicine, V. A. Hospital, Sepulveda, California and University of California at Los Angeles. ••Associate Professor of Medicine in Residence, UCLA. tAssistant Professor of Medicine, Baylor College of Medicine. Reprint requests: Dr. Yankopoulos, VA Hospital, Sepulveda,

California 91343

MYOCARDIAL FUNCTION DURING CHRONIC CATECHOLAMINE OVERSECRETION 585

8 18 66

72 9 66

FIGURE 1. Chest roentgenogram (PA view): A (left). On admission-showing cardiomegaly and increased bronchovascular markings. B (right). Twenty days later-after therapy with bed rest, diuretics and digitalis.

+

percent. The urinalysis revealed a specific gravity of 1.017, albumin and no sugar, cells or casts. The serum creatinine was 1.7 mg/l00 ml. A two-hour post prandial blood sugar was 226 mg/l00 ml, The serum Na- was 142 mEq/liter and serum K+ 4.9 mEq/liter. The arm-to-tongue circulation time was 90 seconds. Chest roentgenogram on admission showed moderate, generalized cardiomegaly (Fig lA) with increase in bronchovascular markings, especially near the hilum suggesting pulmonary infiltrates. The electrocardiogram showed sinus tachycardia of 145 beats/min and suggested biatrial enlargement and left ventricular hypertrophy -the P waves were prominent and diphasic in lead VI; the QRS voltage was borderline high and the T waves low in lead 2, inverted in leads 1, aVL, V4 -6. Treatment by bed rest, digitalization and one injection of meralluride (Mercuhydrin) resulted in an 11-pound weightloss, by the fifth hospital day complete disappearance of cough and considerable decrease of the cardiac silhouette roentgenographically. Antibiotics were not given. Thereafter, his weight remained stable. Roentgenogram of the chest on the 19th hospital day showed the heart to be normal in size (Fig IB). Although the heart size had returned to normal, the blood pressure continued to be elevated and to exhibit a fall in the sitting or standing position. Repeated measurements of blood pressure on the ward during the next two months disclosed a range between 140 and 150 nun Hg systolic, 90 and 110 nun Hg diastolic in the recumbent position. The patient continued to have a sinus tachycardia of 100-120 beats/min, easily audible, sharp heart sounds and prominent atrial gallop by auscultation and phonocardiogram which diminished in the sitting position. The electrocardiogram remained abnormal and on three occasions showed paroxysmal atrial tachycardia of 120 beatsimin-P wave inverted in lead 2 and PR interval 0.14 second. The urinary vanillyl mandelic acid (VMA) content was 18, 14, and 22 mg respectively in three 24-hour specimens (normal 0.5-7.0); the urinary norepinephrine content was 4,450 micrograms (normal less than 75) and epinephrine content was 26 micrograms (normal less than 21) in a 24-hour specimen. A nephrotomogram during intravenous radiocontrast infusion raised the possibility of a right suprarenal mass. Renal arteriograms were performed to further elucidate the patient's disease. During renal arterio-

586 YANKOPOUlOS ET At

grams via the brachial artery, cardiac evaluation was also

carried out.

The right atrial mean pressure was 3 mm Hg (normal 0-8) during a heart rate of 120 beats/minute. The contour of the right atrial pressure tracing showed prominent "a" wave of 5 mm Hg without distinguishable "c" or "v" waves. With only minimal manipulation of the catheter in the right atrium, the patient developed atrial flutter with a 2: 1 ventricular response of 164 beats/min which persisted throughout the procedure. During this rhythm, the left ventricular enddiastolic pressure was 24 mm Hg (normal less than 12), the pulmonary arterial wedge pressure was 25 mm Hg (normal less than 13), the aortic pressure was 150/126 nun Hg, the pulmonary arterial pressure was 31/27 with a mean of 30 nun Hg (normal less than 30 systolic and less than 20 mean), and right atrial mean pressure 6 mm Hg, The cardiac index by dye dilution method was 2.25 liters/min/M2 (normal 2.54.5), the peripheral resistance was 2,440 dyne-sec-em-s (normal less than 1800). The arteriogram was obtained by injecting radiocontrast material in the abdominal aorta at the level of the diaphragm. Four and one-half seconds after the appearance of contrast material in the aorta, a mass was faintly outlined over the upper pole of the right kidney. Blood volume was measured preoperation. By the 131 1 method, the plasma volume was 3,180 ml (expected 2,770), red cell volume 2,120 ml (expected 2,260) and total blood volume 5,300 ml (expected 5,930). At the time of surgical exploration of the abdomen, both kidneys and adjacent structures were carefully examined. A pheochromocytoma of the right adrenal gland was found and excised. It weighed 56 gms and contained 5.12 mg of norepinephrine and 0.24 mg of epinephrine per gram of wet tissue. Postoperation, his heart size remained normal, the blood pressure and heart rate returned to normal and the atrial gallop disappeared. Twenty-four hour urinary VMA's and glucose tolerance test were within normal limits. The electrocardiogram IJ' months after operation had returned towards normal but remained abnormal-P waves no longer suggested biatrial enlargement; however, T waves were flat in 1, slightly inverted in aVL and inverted in V4 -6. One year postoperation, the electrocardiogram showed somewhat high QRS

CHEST, 66: 5, NOVEMBER, 1974

voltage, otherwise within normal limits. The patient was asymptomatic. DISCUSSION

This patient was under the influence of large amounts of catecholamines, primarily norepinephrine. From the history, the secretion seems to have shown no wide lluctuations but to have increased in the course of five or more years. Myocardial damage was suggested by the severity of cardiac failure on admission, in the absence of longstanding or severe hypertension, and later by the abnormal hemodynamic status during moderate tachycardia-the left ventricular pressure was elevated and the cardiac index was slightly lower than expected for comparable heart rate." In animals, there is considerable evidence for myocardial muscle damage following infusion of cateeholamines. I •S - I O In man, most of the evidence for myocardial muscle damage by catecholamines is derived from autopsy studies. The incidence of detection of myocardial muscle necrosis at autopsy appears to depend upon how avidly lesions were looked for. Szakacs and Cannon" found marked association between catecholamines and pathologic myocardial lesions. Their survey of autopsy material yielded 17 cases of pheochromocytoma, myocarditis being found at autopsy in all of them. Van Vliet, Burchell and Titus- found evidence of active carditis microscopically in 15 of 22 patients who were found at autopsy to have functioning pheochromocytoma. In two additional patients, fibrosis was found and thought to represent healed carditis. The incidence of clinically significant myocarditis is probably far less than in the autopsy material. Occasionally, carditis is evident clinically, as exemplified by one of 22 patients of Van Vliet et al,' the one patient of Engelman and Sjoerdsma" with malignant pheochromocytoma and probably the one patient of Engelman et al. 3 Kline· states that two of his seven patients studied at autopsy had clinical evidence of myocarditis. More recently, two patients have been reported presenting with cardiomyopathy without impressive elevation in blood pressure due to oversecretion of epinephrine rather than norepinephrine.s-" The incidence of exertional dyspnea and congestive heart failure in patients with pheochromocytoma also varies. No detailed clinical study is available of the 22 patients of Van Vliet, Burchell and Titus' other than that of the 15 patients with active myocarditis at autopsy; 11 had symptoms and signs of acute left ventricular failure. A clinical report from the same medical oenter-! in which the clinical features of 76 patients were examined (the diagnosis of 69 patients was confirmed at operation) showed that dyspnea was present in 11 patients (14 percent) and cardiomegaly or congestive heart failure or both in 9 patients (12 percent).

REFERENas 1 Van Vliet PO, Burchell HG, Titus JL: Focal myocarditis associated with pheochromocytoma. N Eng! J Med 274: 1102-1108, 1966 2 Engelman K, Sjoerdsma A: Chronic medical therapy for pheochromocytoma. Ann Intern Med 61:229-241, 1964

CHEST, 66: 5, NOVEMBER, 1974

3 Engelman K, Watts RwE, Klinenberg JR, et al: Clinical, physiological and biochemical studies of a patient with xanthinuria and pheochromocytoma. Am J Med 37:839861, 1964 4 Kline IK: Myocardial alterations associated with pheochromocytomas. Am J Pathol38:539-547, 1961 5 Garcia R, Jennings JM: Pheochromocytoma masquerading as cardiomyopathy. Am J CardioI29:568-571, 1972 6 Baker G, Zeller NH, Weitzner S, et al: Pheochromocytoma without hypertension presenting as cardiomyopathy. Am Heart J 83:688-693, 1972 7 Ross J Jr, Linhart JW, Braunwald E: Effects of changing heart rate in man by electrical stimulation of the right atrium. Studies at rest, during exercise, and with isoproterenol. Circulation 32:549-558, 1965 8 Szakacs JE, Cannon A: I-Norepinephrine myocarditis. Am J Clin Pathol30:425-434, 1958 9 Szakacs JE, Mehlman B: Pathologic changes induced by I-Norepinephrine. Am J CardioI5:619-627, 1960 10 Chappel Cl, Rona G, Balazs T, et al: Comparison of cardiotoxic actions of certain sympathomimetic amines. Can J Biochem Physiol 37 :35-42, 1959 11 Gifford RW Ir, Kvale WF, Maher Fr, et al: Clinical features, diagnosis and treatment of pheochromocytoma: a review of 76 cases. Mayo Clin Proc 39:281-302, 1964

Paradoxic Coronary Embolism in a Patient with Mid-Systolic Click Syndrome* John W. Schatz, Mai, MC, and James A. Fischer, Mai, MC EmboUc coronary artery disease is an uncommon C8Ulle of death. A paradoxic thromboembolism to the left coronary artery was the reason for death In a 53-year-old man who presented with a mld-systoUc click syndrome and chest pain. His clinical course and postmortem findings are presented. Pandoxic coronary artery embolism is reviewed. An unusual etiology of systoUc click syndromes is suggested. Tbougbts about therapy are ~ sented. Coronary embolism is an unusual form of coronary artery disease. Most cases are associated with bacterial endocarditis. I However, intracardiac thrombus, luetic aortitis, atherosclerotic disease of the aorta, proximal coronary artery thrombus, pulmonary vein thrombus, calcified valves, parasites, cardiac bypass, tumor, coronary angiography, air and paradoxic venous thrombus have been reported as etiologic agents of embolic coronary disease. We recently participated in the management of a man with paradoxic coronary embolism and the unusual association of a mid-systolic click. His case is presented below.

CASEREroRT A 53-year-old Caucasian man was well until November 11, ·From the Department of Cardiology, Silas B. Hays Army Hospital, Fort Ord, California. The contents herein do not represent the views of the Department of ~e Armyof the United States. Reprint requests: Dr. Schatz, Silas Hays Army Hospltal, Fort

Ord, Callfomia 93941

PARADOXIC CORONARY EMBOLISM 587