Coarctation of the aorta in adults ROBERT S. FRASER, MD, FRCP[CJ; JANET STOBEY,* B Sc; RICHARD E. ROSSALL, MD, FRCP(C]; J. DVORKIN, MD, FRCP[C]; RUSSELL F. TAYLOR, MD, FRCP[C]
Thirty-six patients, 19 men and 17 women, presented at age 18 or older between 1952 and 1974 with coarctation of the aorta. Of the 14 (390/o) who had associated cardiovascular disease, 12 had aortic stenosis or insufficiency or both. Three patients had infections - two, endocarditis (aortic valve) and one, endarteritis. Three of the seven patients who did not undergo an operation are alive, two at more than 50 years of age. Five patients had myocardial infarctions, two at 35 years of age. Twenty-nine (800/c) had operations; in eight instances the patient was over age 40. All 18 patients undergoing repair of isolated coarctation survived, while only 7 of the 11 patients with associated cardiovascular lesions who underwent repair recovered. Aortic valvular disease and myocardial infarction are serious complicating factors in coarctation of the aorta. Entre 1952 et 1974, 36 patients, 19 hommes et 17 femmes iges de 18 ans ou pius, ont presente une coarctation de l'aorte. Des 14 (390/c) qui avaient une maladie cardiovasculaire associ6e, 12 souffraient d.une st6nose ou d'une insuffisance aortique, ou des deux a Ia fois. Des infections ont et6 constat6es chez trois patients - une endocardite (touchant Ia valvule aortique) chez deux sujets et une endarterite chez un. Trois den sept patients qui n.ont pas eu d'intervention chirurgicale sont vivants, deux ayant depass6 i'ige de 50 ans. Cinq patients ont subit un infarctus du myocarde, dont deux a l'ige de 35 ans. Vingt-neuf sujets (800/c) ont ete oper6s; dans huit cas le patient avait plus de 40 ans. Les 18 patients, chez qui on a procede a Ia refection chirurgicale d'une coarctation isol6e, ont tous surv6cu, alors que seulement 7 des 11 patients qui avaient des l6sions cardiovasculaires associees et qui ont subit Ia m6me intervention ont gueri. L'atteinte de Ia valvule aortique et i'infarctus du myocarde sont de serieuses complications de Ia coarctation de l'aorte. From the division of cardiology, department of medicine, University of Alberta, Edmonton *Summer research student Reprint requests to: Dr. R.S. Fraser, Department of medicine, Clinical Sciences Building, University of Alberta, Edmonton, AB T6G 2G3
Coarctation of the aorta is more frequently recognized and corrected in the child than in the adult patient. It should, nevertheless, be considered as a possible cause of high blood pressure in adults. The experience of physicians whose patients are largely adults is limited by the comparative rarity of coarctation of the aorta.1 For this reason we reviewed the clinical data on all patients with coarctation of the aorta who were first seen in our division of cardiology at age 18 or older between 1952 and 1974.
Patient groups Those with isolated coarctation of the aorta Data for the 22 patients with apparently isolated coarctation of the aorta are summarized in Table I. Eighteen had corrective operations and there were no operative deaths. Patient 10 required a second thoracotomy 2 weeks after operation to control delayed hemorrhage from the site of anastomosis. Patient 5 had ischemic symptoms in his left arm 19 years after his coarctation was bypassed with the left subclavian artery; an operation relieved his symptoms. A 31-year-old patient (no. 12), who was thought at operation to have an uncomplicated coarctation, died 7 months later. At necropsy the aortic valve was found to be bicuspid but not stenotic. Death resulted from hemopericardium due to rupture of a thin-walled atherosclerotic aneurysm of the ascending aorta. Blood pressures recorded within 1 month after operation were compared with preoperative pressures; mean values were 140/88 and 184/100 mm Hg, respectively. Late postoperative pressures, recorded 6 months to 19 years after operation, demonstrated maintenance of the improved values after operation; the mean value was 138/82 mm Hg. Four patients with isolated coarctation did not have an operation. Patient 19 continued to have no symptoms and her blood pressure has remained the same for 14 years. Despite severe hypertension complicated by myocardial infarction and atrial fibrillation, patient 20, who was 51 years old when first seen, lived another 9 years before dying of heart failure. Patient 21 was first recognized as having coarctation when hospitalized for dermatitis at age 40. He refused an operation because he
was asymptomatic. He was continuing to work as a farmer 10 years later and his blood pressure was little changed. Patient 22 recovered from a ruptured berry aneurysm at age 22 and was well and working until she died suddenly from a second intracranial hemorrhage at age 45. Her blood pressure had gradually increased from an initial normal value to one of moderate systolic hypertension. Those with associated congenital cardiovascular lesions Data for these 14 patients are summarized in Table II. Eleven had operations and seven survived. One of the survivors (no. 31) died 4 years later at age 38. He had suffered hemiparesis, attributed to a period of hypotension during operation, but necropsy disclosed three areas of healed myocardial infarct of undetermined age and a recent cerebral embolus in the unaffected hemisphere. Patient 32 had a patent ductus arteriosus ligated at age 17; because of technical difficulties attributed to this operation, a subclavian-aortic bypass was created when the coarctation was treated at age 32. Three patients in this group had no operation. One man, no. 34, who refused operation because of religious beliefs, was in early left ventricular failure at age 49. Patient 35 had aortic insufficiency and endocarditis caused by a nonhemolytic streptococci at age 27. He died 8 years later with gross cardiomegaly and heart failure, and necropsy showed a large, healed myocardial infarct. Patient 36, who was found to have a hypoplastic aorta distal to the coarctation at attempted repair when he was 20 years old, had bacteremia due to Hemophilus influenzae at age 28. Because he had no signs of valvular disease and because the organisms were grown only from blood obtained from the femoral artery, it was thought he had endarteritis. He died of a myocardial infarction at age 35.
Disability and operative features One patient with isolated coarctation of the aorta presented with class HI disability, according to the New York Heart Association classification, * two .C1ass II: slight limitation of activity; comfortable at rest or with mild exertion. Class 111: great limitation of activity; comfortable only at rest. Class IV: any physical activity causes discomfort; confined to bed or chair.
CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115 415
had class II disability and the remaining 19 had no symptoms. A number of patients had been told that they had rheumatic valvular heart disease and had been advised to restrict their sports activities as students. Patients with lesions in addition to coarctation more often had symptoms. At presentation two had class IV disability, three, class III, and four, class II, while five had no symptoms. The coarctation was postductal in every case and varied only in severity and length of obstruction. The coarcted segment was resected in all but three patients who had operations; those three had bypass operations. There were no operative or perioperative deaths among the patients with isolated coarctation. Of the four operative or perioperative deaths in patients with associated lesions, one might have been prevented if current techniques of cardiopulmonary bypass had been available. Complications Ischemic heart disease Despite the good results reported for surgical treatment of apparently isolated coarctation of the aorta,2.'5 Maron and colleagues6 found that half of their patients who underwent operation after age 18 later had angina or myocardial infarctions. Premature degenerative and proliferative changes in the coronary arteries have been described in children and young adults with coarctation.7 In our series of 36 patients, 5 had myocardial infarctions and in 3 the infarction occurred before age 40. It is impossible to argue that these events were accelerated or premature, but they were serious or fatal complications in 14% of the patients. Associated disease of the aortic valve Eleven patients (30%) had a significant abnormality of the aortic valve and in six instances the valve was found at operation or autopsy to be bicuspid. These observations are more in keeping with Edwards's report of a frequent association of bicuspid aortic valve and coarctation of the aorta8 than with the reports describing the association of aortic valve disease and coarctation in only 1,2 21. and 22%' of patients. Neither the need for operative repair of the aortic valve nor later death from aortic valvular disease has elicited much comment in other reports.3"'10 Nevertheless, the association of a bicuspid aortic valve with coarctation in 46% of an autopsy series11 seems to be reflected in our series of adults, in whom abnormal aortic valves (although not all confirmed as bicuspid) were found in 30%. In three series surgical treatment of
coarctation of the aorta in patients over 40 years old carried double the risk it did for younger patients,4'1'12 and in one series almost twice as many of the older patients had an associated valvular deformity (21% v. 12%). Disease of the aortic valve rather than age was associated with unsuccessful operation in our series, and all
operative deaths occurred in patients with combined disease. All patients with isolated coarctation of the aorta, including five who were over 40 years of age, survived their operations. Other associated congenital abnormalities The combination of subaortic steno-
Table I-Patients with apparently isolated coarctation of the aorta Blood pressure (mm Hg) Age at Patient operation 1-4 weeks Later8 no. Sex (yr) Preop postop (yr) Complications and course 1
F
42
85
2
M
44
100
3
M
24
4
M
44
198 104 226 108
5
M
25
80
6
F
19
220 110
7
F
19
100
8
F
34
100
9
F
45
10
F
11
130
150 (9)
150
150
Asymptomatic, diabetic
(0.5) Asymptomatic 154 150 90 150 150 140 180
130 -. (4) Asymptomatic 120 (8) Asymptomatic 120 (19) Subclavian-aortic bypas 5; carotidsubclavian graft at a. .e 44 154 (5) Asymptomatic 125 (3) Asymptomatic 120 (3) Asymptomatic 170 -. (2) Asymptomatic 120 intrathoracic b leeding -. (8) weeks pestop, asym ptomatic 120 (8) Asymptomatic
23
90 178 84
144
M
29
160 -.
154
12
M
31
170
120
13
F
22
240 120
130
170
14
M
20
145 -.
15
F
26
16
F
22
17
M
43
180 105
18
F
34
210 84
19
F
37
150 80
(no op)
140 -. (1.5) Well until accidental death 2 years postop 130 -. (0.5) Asymptomatic 145 -. (16) Asymptomatic 150 Myocardial infarction at age 41; . (15) angina at age 49; obese1 diabetic 130 Dacron bypass of coarctation; (9) asymptomatic 150 .-. (14) Asymptomatic
20
F
51
280 110
(no op)
21
M
40
202 68
(no op)
22
F
31
12S 84
(no op)
8After operation or first visit.
416 CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115
120 94 100
118 -. 124 -. 132 -. 156
- (0.6)
Died 7 months pestop of ruptured atherosclerotic aneurysm of ascending aorta; bicuspid aortic valve
- (9)
Congestive heart failure for 15 years; died at age 60 190 -. (10) Asymptomatic Ruptured berry aneurysm at age 22; 160 recovered and working; died at -. (14) age 45 from intracranial bleeding
sis and coarctation of the aorta is infrequently encountered. In both our case and the reported case of a child with this combination,'3 surgical treatment was successful. The diagnosis of berry aneurysm was made only in the patients who bled intracranially, one at age 22 and the other at age 26. The coarctation was resected in one patient and both patients recovered. One died 23 years later from intracranial bleeding, and
although an autopsy was not done it was assumed that an aneurysm was again responsible. Blood pressure after operation Optimistic reports"5'9'14'15 on the decrease in blood pressure after alleviation of coarctation of the aorta were disputed by Maron and colleagues, who found the blood pressure unchanged or increased in 50% of 59 patients whom they were able to re-
Table Il-Patients with coarctatlon of the aorta and associated congenital cardiovascular lesions Blood pressure (mm Hg) Age at Patient operation 1-4 weeks Later* no. Sex (yr) Preop postop (yr) Complications and course 23
F
50
24
F
43
102 -.
124 =..O
- (0)
Bicuspid aortic stenosis; aortlc valvotomy; dIed 4 weeks postop of infection, tampenade
25
M
35
120
-
- (0)
Aortic stenosis; coarctation resected; operative death
26
F
20
160 85
140 80
. (4) 70
-.
-.
-. (18) Aortic insufficiency, asymptomatic
28
M
30
150
-
-.
o
110
(0)
130
-.
-.
-.(6)
Bicuspid
aortic
stenosis;
aortic
valvotomy; died 1 day postop of tamponade, cerebral embolism
Aortic insufficiency, mild effort dyspnea
Aortic
insufficiency,
bicuspid
art oic valve, mitral stenosis; CVA 5years postop, atrial fibrillation; died of multiple sclerosis 6 years postop
29
M
31
190
150 -.
240 -. (6)
Aortic insufficiency; thrombosed - aortic bypass at age subclavian ruptured berry aneurysm age resected at at age 26; 31; coarctation epilepsy, alcoholism
30
M
58
180
-
- (0)
Bicuspid aortic stenosis and insufficiency due to endocarditis; ruptured sinus of Valsalva to left ventricle; aortlc valve replaced, sinus repaired; severe atherosclerosis of left coronary artery; myocardial infarction; operative death
31
M
34
145 .
110 -.
110 (3) -.
32
F
32
164 -.
148 .)TO
no (12) Patent ductus ligated at age 17; -. subclavian-aortic bypass at age 32
33
M
27
-.
-.
-. (14) Subaortic stenosis resected; coarctation resected 2 months later
34
M
48
150
(no op)
- (1)
Aortic stenosis, mitral insufficiency; early failure at age 49
35
M
32
190 60
(no op)
-
Bicuspid aortlc valve with insufficiency; endocarditis at age 27; died age 35of myocardial infarction at
36
H
20
178 -.
(no op)
160 Hypeplastic distal aorta; endarte1. (15) ntis at age 28; died of myocardial infarction at age 35
*After operation or first visit.
155
108
Bicuspid aortic stenosis, patent ductus arteriosus; ductus ligated, coarctation resected; hemiparesis postop; died 4 years pestop of cerebral embolism and myocardlal Infarction
140
evaluate 1 to 25 years after operation. Sellors and Hobsley,' using blood pressure measurements corrected for age, showed that residual hypertension was proportional to the degree of preoperative elevation of pressure. There appeared to be no worsening of residual hypertension over the years of followup, and 6 years after operation the mean systolic and diastolic values were 60 and 80%, respectively, of the corrected preoperative values. March, Hultgren and Gerbode" described an increase in systolic pressure with age but no change in diastolic pressure, and found the average preand postoperative pressures to be 168/96 and 143/86 mm Hg, respectively. These values are close to the average preoperative and late postoperative blood pressures in our patients with isolated coarctation of the aorta - 184/100 and 132/82 mm Hg, respectively. There was a persistent reduction in blood pressure after operation in 17 of the 25 surviving patients, including 3 of the 5 patients undergoing operation when over 40 years old. It appears to be true, as Kirklin and Wallace'7 stated, that "some relief of hypertension can be accomplished even in the sixth decade of life", although the added risk of operation due to degenerative arterial disease, coronary artery disease and aortic valvular disease must be balanced against the advantage of reducing the elevated blood pressure. We thank the surgeons, Drs. J.C. Callaghan, C.M. Couves, C.A. Ross and L.P. Sterns, and the many family physicians who helped in assembling the data in this report.
References I. CAMPBELL M: Incidence of cardiac malformations at birth and later, and neonatal mortality. Br Heart J 35: 189, 1973 2. SCHUSTER SR. Gsoss RE: Surgery for cosretation of the aorta: review of 500 cases. I Thorac Cardiovasc Surg 43: 54, 1962 3. BROM AG: Narrowing of the aortic isthmus and enlargement of the mind. I Thorac Cardiovasc Surg 50: 166. 1965 4. DELAYE J, BERTHOU JD, MILoN H, et al: La st6nose de l.isthme de l'aorte apr.s 30 ans. Evolution compar6e chez des malades op6r6s et non op.res. Coeur Med Interne 12: 3, 1973 5. BRAIMBRIDGE MV, YEN A: Coarctation in the elderly. Circulation 31: 209, 1965 6. MARON BJ, HuMrHRIas JO, ROWE RD. et al: Prognosis of surgically corrected coarctation of the aorta. A 20-year postoperative appraisal. CirculatIon 47: 119, 1973 7. VLOOAVER Z, NEUFELD HN: The coronary arteries in coarctation of the aorta. Circuladon 37: 449, 1968 8. EDWARDS JE: The congenital bicuspid aortic valve. Circulation 23: 485, 1961 9. OSTERMILLER WE JR. SOMERNDIKE JM, HUNTER JA, et al: Coarctation of the aorta in adult patients. I Thorac Cardiovasc Surg 61: 125, 1971 10. SELLoRs TH, HOB5LEY M: Coarctation of the aorta. Effect of operation on blood pressure. Lance: 1: 1387, 1963 11. BECKER AE, BEcluut MJ, EDWARDS JE: Anomalies associated with coarctstion of the aorta; particular reference to infancy. Circulation 41: 1067, 1970 12. COOLEY DA, HALLMAN GL, HAMMAM AS: Congenital cardiovascular anomalies in adults. Results of surgical treatment in 167 patients over age 35. Am I Cardlol 17: 303, 1966
continued on page 434
CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115 417
radioautography (Fig. 2), confirming the presence of thorium dioxide. Thorium dioxide was also demonstrated in the liver biopsy within reticuloendothelial cells lining hepatic sinusoids and within macrophages in the portal triads. Lymph nodes sampled at laparotomy showed changes attributable to lymphangiography and there were small amounts of thorium dioxide in sinusoidal reticuloendothelial cells. An iliac crest biopsy also showed small amounts of thorium dioxide in a few reticuloendothelial cells. Review of the initial cervical lymph node biopsy that showed Hodgkin's disease revealed minute amounts of thorium dioxide, which had not been recognized as such initially, within the macrophages in both uninvolved and involved portions of the lymph node. Discussion A strong association between thorium dioxide administration and subsequent development of malignant tumours, notably of the liver and kidney, is well established.2 In addition, an increased incidence of neoplastic hematologic disorders, especially acute myelogenous leukemia, has been reported after thorium dioxide administration.24 In contrast, few malignant lymphomas have shown this association. Verner and Smith2 reported a well documented case of Hodgkin's disease occurring 12 years after hepatosplenography. Da Silva Horta and colleagues8 listed one case of Hodgkin's disease in their analysis of the Portuguese experience with thorium dioxide, but this case was neither illustrated nor discussed. Da Silva Horta7 also reported a case of reticulum cell sarcoma that appeared 28 years after thorium dioxide administration, and Gardner and Ogilvie8 reported a case of giant follicular lymphoma developing 15 years after cerebral angiography with thorium dioxide. Thus, on the basis of published 1%
cases it appears that thorium dioxide has a stronger association with leukemia than with lymphoma. External irradiation is also more strongly associated with leukemia than with lymphoma, as illustrated by results of follow-up studies on American radiologists,9 survivors of Hiroshima and Nagasaki'0'1' and patients treated for ankylosing spondylitis." Anderson and associates'3 speculated that lymphomas develop in patients who receive high doses of radiation that alter the body's immune system, whereas leukemias develop in patients exposed to smaller doses of radiation that induce bone marrow hypoplasia. After injection, most of the thorium dioxide is rapidly phagocytosed by reticuloendothelial cells throughout the body; the site of predominant deposition appears to vary considerably from one individual to another. The half-life of thorium is long, 1.4 x 1010 years, and it has been stated that 500 to 540 rad may be delivered to the spleen and 1200 to 1400 rad to the liver within 20 years after the injection of 20 ml of thorium dioxide suspension.' Most of the radiation consists of a-particles but /3- and y-particles are also important. Muth and colleagues'4 gave an excellent discussion of the radiation dose in different organs due to thorium. Reliable data for lymph nodes is not available, but it has been suggested that nodal absorption may be high,' and it is not unreasonable to speculate that a lymphoma might develop after prolonged local irradiation. In the initial biopsy from our patient thorium dioxide deposits were scanty and were overlooked. Thus, it is possible that an association between thorium dioxide and Hodgkin's disease or other types of lymphoma may be more frequent than is currently appreciated. References 1. CARBONE PP, KAPLAN HS, MUSSHOFF K, et al: Report of the committee on Hodgkin's disease staging classification. Cancer Res 31: 1860, 1971 2. GRAMPA G: Radiation injury with particular reference to Thorotrast, in Pathology Annual 1971, vol 6, SOMMERS SC (ed), New York, Appleton, 1971, pp 147-69 3. ABBArF JD: Leukemia and other fatal blood dyscrasias in thorium dioxide patients. Ann NY Acad Sd 145: 767, 1967 4. FABER M, JOHANSEN C: Leukemia and other hematological diseases after Thorotrast. Ibid. p 755 5. VERNER JV JR, SMiTh AG: Hodgkin's disease following administration of Thorotrast. South Med / 56: 524, 1963 6. DA SILVA HORTA J, AssArr JD, CAVOLLA DA
MarrA L, et al: Malignancy and other late effects following administration of Thorotrast. Lancet 2: 201, 1965
FIG. 2-Alpha tracks and thorium dioxide pigment In section of spleen, demonstrated by antoradiography (H-E; xlOOO).
7. DA SILVA HORTA J: Late effects of Thorotrast on the liver and spleen, and their efferent lymph nodes. Ann NY Acad Sd 145: 676, 1967 8. GARDNER DL, OGILVIE RF: The late results of injection of Thorotrast: two cases of neoplastic disease following contrast angiography. I Pathol Bacteriol 78: 133, 1959
434 CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115
9. Lewis EB: Leukemia, multiple mycloma, and aplastic anemia in American radiologists. Science 142: 1492, 1963 10. ANDERSON RE: Malignant lymphoma. Hum Pathol 2: 515, 1971 II. Idem: Leukemia and related disorders. Ibid, p 505 12. COURT BROWN WM, DOLL R: Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis. Br Med J 2: 1327, 1965 13. ANDERSON RE, NIsHlYAMA H, II Y, et al: Pathogenesis of radiation-related leukaemia and lymphoma. Speculations based primarily on experience of Hiroshima and Nagasaki. Lance: 1: 1060, 1972 14. Mum H, EDELMANN L, GILLMAIER L, et al: Radiation dose in different organs of Thorotrast patients, in Assessment of Radioactive
Contamination in Man, Vienna, International Atomic Energy Agency, 1972, pp 457-67
COARCTA TION continued from page 417 13. AWAD JA, MANNIX EP .sR: Congenital valvular and subvalvular aortic stenosis with associated coarctation of the aorta and patent ductus arteriosus. Report of a case with successful surgical correction. I Thorac Cardtovasc Surg 43: 203, 1962 14. WRIGHT JL, BURCHELL HB, Wooo EH: Hemodynamic and clinical appraisal of coarctation 4 to 7 years after resection and end-to-end anastomosis of aorta. Circulation 24: 806,
1956 15. RATHI L, KEITH 3D: Post-operative blood pressure in coarctation of the aorta. Br Heart 1 26: 671, 1964 16. MARCH HW, HULTGREN HN, GERBODE F: Im-
mediate and remote effects of resection on the hypertension in coarctation of the aorta. Br Heart 1 22: 361, 1960
17. KIRKLIN 3W, WALLACE RB: The Heart, 2nd
ed, HURST JW, LOGAN RB (eds), New York,
McGraw. 1970, p 722
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Thirty-six patients, 19 men and 17 women, presented at age 18 or older between 1952 and 1974 with coarctation of the aorta. Of the 14 (390/o) who had associated cardiovascular disease, 12 had aortic stenosis or insufficiency or both. Three patients had infections - two, endocarditis (aortic valve) and one, endarteritis. Three of the seven patients who did not undergo an operation are alive, two at more than 50 years of age. Five patients had myocardial infarctions, two at 35 years of age. Twenty-nine (800/c) had operations; in eight instances the patient was over age 40. All 18 patients undergoing repair of isolated coarctation survived, while only 7 of the 11 patients with associated cardiovascular lesions who underwent repair recovered. Aortic valvular disease and myocardial infarction are serious complicating factors in coarctation of the aorta. Entre 1952 et 1974, 36 patients, 19 hommes et 17 femmes iges de 18 ans ou pius, ont presente une coarctation de l'aorte. Des 14 (390/c) qui avaient une maladie cardiovasculaire associ6e, 12 souffraient d.une st6nose ou d'une insuffisance aortique, ou des deux a Ia fois. Des infections ont et6 constat6es chez trois patients - une endocardite (touchant Ia valvule aortique) chez deux sujets et une endarterite chez un. Trois den sept patients qui n.ont pas eu d'intervention chirurgicale sont vivants, deux ayant depass6 i'ige de 50 ans. Cinq patients ont subit un infarctus du myocarde, dont deux a l'ige de 35 ans. Vingt-neuf sujets (800/c) ont ete oper6s; dans huit cas le patient avait plus de 40 ans. Les 18 patients, chez qui on a procede a Ia refection chirurgicale d'une coarctation isol6e, ont tous surv6cu, alors que seulement 7 des 11 patients qui avaient des l6sions cardiovasculaires associees et qui ont subit Ia m6me intervention ont gueri. L'atteinte de Ia valvule aortique et i'infarctus du myocarde sont de serieuses complications de Ia coarctation de l'aorte. From the division of cardiology, department of medicine, University of Alberta, Edmonton *Summer research student Reprint requests to: Dr. R.S. Fraser, Department of medicine, Clinical Sciences Building, University of Alberta, Edmonton, AB T6G 2G3
Coarctation of the aorta is more frequently recognized and corrected in the child than in the adult patient. It should, nevertheless, be considered as a possible cause of high blood pressure in adults. The experience of physicians whose patients are largely adults is limited by the comparative rarity of coarctation of the aorta.1 For this reason we reviewed the clinical data on all patients with coarctation of the aorta who were first seen in our division of cardiology at age 18 or older between 1952 and 1974.
Patient groups Those with isolated coarctation of the aorta Data for the 22 patients with apparently isolated coarctation of the aorta are summarized in Table I. Eighteen had corrective operations and there were no operative deaths. Patient 10 required a second thoracotomy 2 weeks after operation to control delayed hemorrhage from the site of anastomosis. Patient 5 had ischemic symptoms in his left arm 19 years after his coarctation was bypassed with the left subclavian artery; an operation relieved his symptoms. A 31-year-old patient (no. 12), who was thought at operation to have an uncomplicated coarctation, died 7 months later. At necropsy the aortic valve was found to be bicuspid but not stenotic. Death resulted from hemopericardium due to rupture of a thin-walled atherosclerotic aneurysm of the ascending aorta. Blood pressures recorded within 1 month after operation were compared with preoperative pressures; mean values were 140/88 and 184/100 mm Hg, respectively. Late postoperative pressures, recorded 6 months to 19 years after operation, demonstrated maintenance of the improved values after operation; the mean value was 138/82 mm Hg. Four patients with isolated coarctation did not have an operation. Patient 19 continued to have no symptoms and her blood pressure has remained the same for 14 years. Despite severe hypertension complicated by myocardial infarction and atrial fibrillation, patient 20, who was 51 years old when first seen, lived another 9 years before dying of heart failure. Patient 21 was first recognized as having coarctation when hospitalized for dermatitis at age 40. He refused an operation because he
was asymptomatic. He was continuing to work as a farmer 10 years later and his blood pressure was little changed. Patient 22 recovered from a ruptured berry aneurysm at age 22 and was well and working until she died suddenly from a second intracranial hemorrhage at age 45. Her blood pressure had gradually increased from an initial normal value to one of moderate systolic hypertension. Those with associated congenital cardiovascular lesions Data for these 14 patients are summarized in Table II. Eleven had operations and seven survived. One of the survivors (no. 31) died 4 years later at age 38. He had suffered hemiparesis, attributed to a period of hypotension during operation, but necropsy disclosed three areas of healed myocardial infarct of undetermined age and a recent cerebral embolus in the unaffected hemisphere. Patient 32 had a patent ductus arteriosus ligated at age 17; because of technical difficulties attributed to this operation, a subclavian-aortic bypass was created when the coarctation was treated at age 32. Three patients in this group had no operation. One man, no. 34, who refused operation because of religious beliefs, was in early left ventricular failure at age 49. Patient 35 had aortic insufficiency and endocarditis caused by a nonhemolytic streptococci at age 27. He died 8 years later with gross cardiomegaly and heart failure, and necropsy showed a large, healed myocardial infarct. Patient 36, who was found to have a hypoplastic aorta distal to the coarctation at attempted repair when he was 20 years old, had bacteremia due to Hemophilus influenzae at age 28. Because he had no signs of valvular disease and because the organisms were grown only from blood obtained from the femoral artery, it was thought he had endarteritis. He died of a myocardial infarction at age 35.
Disability and operative features One patient with isolated coarctation of the aorta presented with class HI disability, according to the New York Heart Association classification, * two .C1ass II: slight limitation of activity; comfortable at rest or with mild exertion. Class 111: great limitation of activity; comfortable only at rest. Class IV: any physical activity causes discomfort; confined to bed or chair.
CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115 415
had class II disability and the remaining 19 had no symptoms. A number of patients had been told that they had rheumatic valvular heart disease and had been advised to restrict their sports activities as students. Patients with lesions in addition to coarctation more often had symptoms. At presentation two had class IV disability, three, class III, and four, class II, while five had no symptoms. The coarctation was postductal in every case and varied only in severity and length of obstruction. The coarcted segment was resected in all but three patients who had operations; those three had bypass operations. There were no operative or perioperative deaths among the patients with isolated coarctation. Of the four operative or perioperative deaths in patients with associated lesions, one might have been prevented if current techniques of cardiopulmonary bypass had been available. Complications Ischemic heart disease Despite the good results reported for surgical treatment of apparently isolated coarctation of the aorta,2.'5 Maron and colleagues6 found that half of their patients who underwent operation after age 18 later had angina or myocardial infarctions. Premature degenerative and proliferative changes in the coronary arteries have been described in children and young adults with coarctation.7 In our series of 36 patients, 5 had myocardial infarctions and in 3 the infarction occurred before age 40. It is impossible to argue that these events were accelerated or premature, but they were serious or fatal complications in 14% of the patients. Associated disease of the aortic valve Eleven patients (30%) had a significant abnormality of the aortic valve and in six instances the valve was found at operation or autopsy to be bicuspid. These observations are more in keeping with Edwards's report of a frequent association of bicuspid aortic valve and coarctation of the aorta8 than with the reports describing the association of aortic valve disease and coarctation in only 1,2 21. and 22%' of patients. Neither the need for operative repair of the aortic valve nor later death from aortic valvular disease has elicited much comment in other reports.3"'10 Nevertheless, the association of a bicuspid aortic valve with coarctation in 46% of an autopsy series11 seems to be reflected in our series of adults, in whom abnormal aortic valves (although not all confirmed as bicuspid) were found in 30%. In three series surgical treatment of
coarctation of the aorta in patients over 40 years old carried double the risk it did for younger patients,4'1'12 and in one series almost twice as many of the older patients had an associated valvular deformity (21% v. 12%). Disease of the aortic valve rather than age was associated with unsuccessful operation in our series, and all
operative deaths occurred in patients with combined disease. All patients with isolated coarctation of the aorta, including five who were over 40 years of age, survived their operations. Other associated congenital abnormalities The combination of subaortic steno-
Table I-Patients with apparently isolated coarctation of the aorta Blood pressure (mm Hg) Age at Patient operation 1-4 weeks Later8 no. Sex (yr) Preop postop (yr) Complications and course 1
F
42
85
2
M
44
100
3
M
24
4
M
44
198 104 226 108
5
M
25
80
6
F
19
220 110
7
F
19
100
8
F
34
100
9
F
45
10
F
11
130
150 (9)
150
150
Asymptomatic, diabetic
(0.5) Asymptomatic 154 150 90 150 150 140 180
130 -. (4) Asymptomatic 120 (8) Asymptomatic 120 (19) Subclavian-aortic bypas 5; carotidsubclavian graft at a. .e 44 154 (5) Asymptomatic 125 (3) Asymptomatic 120 (3) Asymptomatic 170 -. (2) Asymptomatic 120 intrathoracic b leeding -. (8) weeks pestop, asym ptomatic 120 (8) Asymptomatic
23
90 178 84
144
M
29
160 -.
154
12
M
31
170
120
13
F
22
240 120
130
170
14
M
20
145 -.
15
F
26
16
F
22
17
M
43
180 105
18
F
34
210 84
19
F
37
150 80
(no op)
140 -. (1.5) Well until accidental death 2 years postop 130 -. (0.5) Asymptomatic 145 -. (16) Asymptomatic 150 Myocardial infarction at age 41; . (15) angina at age 49; obese1 diabetic 130 Dacron bypass of coarctation; (9) asymptomatic 150 .-. (14) Asymptomatic
20
F
51
280 110
(no op)
21
M
40
202 68
(no op)
22
F
31
12S 84
(no op)
8After operation or first visit.
416 CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115
120 94 100
118 -. 124 -. 132 -. 156
- (0.6)
Died 7 months pestop of ruptured atherosclerotic aneurysm of ascending aorta; bicuspid aortic valve
- (9)
Congestive heart failure for 15 years; died at age 60 190 -. (10) Asymptomatic Ruptured berry aneurysm at age 22; 160 recovered and working; died at -. (14) age 45 from intracranial bleeding
sis and coarctation of the aorta is infrequently encountered. In both our case and the reported case of a child with this combination,'3 surgical treatment was successful. The diagnosis of berry aneurysm was made only in the patients who bled intracranially, one at age 22 and the other at age 26. The coarctation was resected in one patient and both patients recovered. One died 23 years later from intracranial bleeding, and
although an autopsy was not done it was assumed that an aneurysm was again responsible. Blood pressure after operation Optimistic reports"5'9'14'15 on the decrease in blood pressure after alleviation of coarctation of the aorta were disputed by Maron and colleagues, who found the blood pressure unchanged or increased in 50% of 59 patients whom they were able to re-
Table Il-Patients with coarctatlon of the aorta and associated congenital cardiovascular lesions Blood pressure (mm Hg) Age at Patient operation 1-4 weeks Later* no. Sex (yr) Preop postop (yr) Complications and course 23
F
50
24
F
43
102 -.
124 =..O
- (0)
Bicuspid aortic stenosis; aortlc valvotomy; dIed 4 weeks postop of infection, tampenade
25
M
35
120
-
- (0)
Aortic stenosis; coarctation resected; operative death
26
F
20
160 85
140 80
. (4) 70
-.
-.
-. (18) Aortic insufficiency, asymptomatic
28
M
30
150
-
-.
o
110
(0)
130
-.
-.
-.(6)
Bicuspid
aortic
stenosis;
aortic
valvotomy; died 1 day postop of tamponade, cerebral embolism
Aortic insufficiency, mild effort dyspnea
Aortic
insufficiency,
bicuspid
art oic valve, mitral stenosis; CVA 5years postop, atrial fibrillation; died of multiple sclerosis 6 years postop
29
M
31
190
150 -.
240 -. (6)
Aortic insufficiency; thrombosed - aortic bypass at age subclavian ruptured berry aneurysm age resected at at age 26; 31; coarctation epilepsy, alcoholism
30
M
58
180
-
- (0)
Bicuspid aortic stenosis and insufficiency due to endocarditis; ruptured sinus of Valsalva to left ventricle; aortlc valve replaced, sinus repaired; severe atherosclerosis of left coronary artery; myocardial infarction; operative death
31
M
34
145 .
110 -.
110 (3) -.
32
F
32
164 -.
148 .)TO
no (12) Patent ductus ligated at age 17; -. subclavian-aortic bypass at age 32
33
M
27
-.
-.
-. (14) Subaortic stenosis resected; coarctation resected 2 months later
34
M
48
150
(no op)
- (1)
Aortic stenosis, mitral insufficiency; early failure at age 49
35
M
32
190 60
(no op)
-
Bicuspid aortlc valve with insufficiency; endocarditis at age 27; died age 35of myocardial infarction at
36
H
20
178 -.
(no op)
160 Hypeplastic distal aorta; endarte1. (15) ntis at age 28; died of myocardial infarction at age 35
*After operation or first visit.
155
108
Bicuspid aortic stenosis, patent ductus arteriosus; ductus ligated, coarctation resected; hemiparesis postop; died 4 years pestop of cerebral embolism and myocardlal Infarction
140
evaluate 1 to 25 years after operation. Sellors and Hobsley,' using blood pressure measurements corrected for age, showed that residual hypertension was proportional to the degree of preoperative elevation of pressure. There appeared to be no worsening of residual hypertension over the years of followup, and 6 years after operation the mean systolic and diastolic values were 60 and 80%, respectively, of the corrected preoperative values. March, Hultgren and Gerbode" described an increase in systolic pressure with age but no change in diastolic pressure, and found the average preand postoperative pressures to be 168/96 and 143/86 mm Hg, respectively. These values are close to the average preoperative and late postoperative blood pressures in our patients with isolated coarctation of the aorta - 184/100 and 132/82 mm Hg, respectively. There was a persistent reduction in blood pressure after operation in 17 of the 25 surviving patients, including 3 of the 5 patients undergoing operation when over 40 years old. It appears to be true, as Kirklin and Wallace'7 stated, that "some relief of hypertension can be accomplished even in the sixth decade of life", although the added risk of operation due to degenerative arterial disease, coronary artery disease and aortic valvular disease must be balanced against the advantage of reducing the elevated blood pressure. We thank the surgeons, Drs. J.C. Callaghan, C.M. Couves, C.A. Ross and L.P. Sterns, and the many family physicians who helped in assembling the data in this report.
References I. CAMPBELL M: Incidence of cardiac malformations at birth and later, and neonatal mortality. Br Heart J 35: 189, 1973 2. SCHUSTER SR. Gsoss RE: Surgery for cosretation of the aorta: review of 500 cases. I Thorac Cardiovasc Surg 43: 54, 1962 3. BROM AG: Narrowing of the aortic isthmus and enlargement of the mind. I Thorac Cardiovasc Surg 50: 166. 1965 4. DELAYE J, BERTHOU JD, MILoN H, et al: La st6nose de l.isthme de l'aorte apr.s 30 ans. Evolution compar6e chez des malades op6r6s et non op.res. Coeur Med Interne 12: 3, 1973 5. BRAIMBRIDGE MV, YEN A: Coarctation in the elderly. Circulation 31: 209, 1965 6. MARON BJ, HuMrHRIas JO, ROWE RD. et al: Prognosis of surgically corrected coarctation of the aorta. A 20-year postoperative appraisal. CirculatIon 47: 119, 1973 7. VLOOAVER Z, NEUFELD HN: The coronary arteries in coarctation of the aorta. Circuladon 37: 449, 1968 8. EDWARDS JE: The congenital bicuspid aortic valve. Circulation 23: 485, 1961 9. OSTERMILLER WE JR. SOMERNDIKE JM, HUNTER JA, et al: Coarctation of the aorta in adult patients. I Thorac Cardiovasc Surg 61: 125, 1971 10. SELLoRs TH, HOB5LEY M: Coarctation of the aorta. Effect of operation on blood pressure. Lance: 1: 1387, 1963 11. BECKER AE, BEcluut MJ, EDWARDS JE: Anomalies associated with coarctstion of the aorta; particular reference to infancy. Circulation 41: 1067, 1970 12. COOLEY DA, HALLMAN GL, HAMMAM AS: Congenital cardiovascular anomalies in adults. Results of surgical treatment in 167 patients over age 35. Am I Cardlol 17: 303, 1966
continued on page 434
CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115 417
radioautography (Fig. 2), confirming the presence of thorium dioxide. Thorium dioxide was also demonstrated in the liver biopsy within reticuloendothelial cells lining hepatic sinusoids and within macrophages in the portal triads. Lymph nodes sampled at laparotomy showed changes attributable to lymphangiography and there were small amounts of thorium dioxide in sinusoidal reticuloendothelial cells. An iliac crest biopsy also showed small amounts of thorium dioxide in a few reticuloendothelial cells. Review of the initial cervical lymph node biopsy that showed Hodgkin's disease revealed minute amounts of thorium dioxide, which had not been recognized as such initially, within the macrophages in both uninvolved and involved portions of the lymph node. Discussion A strong association between thorium dioxide administration and subsequent development of malignant tumours, notably of the liver and kidney, is well established.2 In addition, an increased incidence of neoplastic hematologic disorders, especially acute myelogenous leukemia, has been reported after thorium dioxide administration.24 In contrast, few malignant lymphomas have shown this association. Verner and Smith2 reported a well documented case of Hodgkin's disease occurring 12 years after hepatosplenography. Da Silva Horta and colleagues8 listed one case of Hodgkin's disease in their analysis of the Portuguese experience with thorium dioxide, but this case was neither illustrated nor discussed. Da Silva Horta7 also reported a case of reticulum cell sarcoma that appeared 28 years after thorium dioxide administration, and Gardner and Ogilvie8 reported a case of giant follicular lymphoma developing 15 years after cerebral angiography with thorium dioxide. Thus, on the basis of published 1%
cases it appears that thorium dioxide has a stronger association with leukemia than with lymphoma. External irradiation is also more strongly associated with leukemia than with lymphoma, as illustrated by results of follow-up studies on American radiologists,9 survivors of Hiroshima and Nagasaki'0'1' and patients treated for ankylosing spondylitis." Anderson and associates'3 speculated that lymphomas develop in patients who receive high doses of radiation that alter the body's immune system, whereas leukemias develop in patients exposed to smaller doses of radiation that induce bone marrow hypoplasia. After injection, most of the thorium dioxide is rapidly phagocytosed by reticuloendothelial cells throughout the body; the site of predominant deposition appears to vary considerably from one individual to another. The half-life of thorium is long, 1.4 x 1010 years, and it has been stated that 500 to 540 rad may be delivered to the spleen and 1200 to 1400 rad to the liver within 20 years after the injection of 20 ml of thorium dioxide suspension.' Most of the radiation consists of a-particles but /3- and y-particles are also important. Muth and colleagues'4 gave an excellent discussion of the radiation dose in different organs due to thorium. Reliable data for lymph nodes is not available, but it has been suggested that nodal absorption may be high,' and it is not unreasonable to speculate that a lymphoma might develop after prolonged local irradiation. In the initial biopsy from our patient thorium dioxide deposits were scanty and were overlooked. Thus, it is possible that an association between thorium dioxide and Hodgkin's disease or other types of lymphoma may be more frequent than is currently appreciated. References 1. CARBONE PP, KAPLAN HS, MUSSHOFF K, et al: Report of the committee on Hodgkin's disease staging classification. Cancer Res 31: 1860, 1971 2. GRAMPA G: Radiation injury with particular reference to Thorotrast, in Pathology Annual 1971, vol 6, SOMMERS SC (ed), New York, Appleton, 1971, pp 147-69 3. ABBArF JD: Leukemia and other fatal blood dyscrasias in thorium dioxide patients. Ann NY Acad Sd 145: 767, 1967 4. FABER M, JOHANSEN C: Leukemia and other hematological diseases after Thorotrast. Ibid. p 755 5. VERNER JV JR, SMiTh AG: Hodgkin's disease following administration of Thorotrast. South Med / 56: 524, 1963 6. DA SILVA HORTA J, AssArr JD, CAVOLLA DA
MarrA L, et al: Malignancy and other late effects following administration of Thorotrast. Lancet 2: 201, 1965
FIG. 2-Alpha tracks and thorium dioxide pigment In section of spleen, demonstrated by antoradiography (H-E; xlOOO).
7. DA SILVA HORTA J: Late effects of Thorotrast on the liver and spleen, and their efferent lymph nodes. Ann NY Acad Sd 145: 676, 1967 8. GARDNER DL, OGILVIE RF: The late results of injection of Thorotrast: two cases of neoplastic disease following contrast angiography. I Pathol Bacteriol 78: 133, 1959
434 CMA JOURNAL/SEPTEMBER 4, 1976/VOL. 115
9. Lewis EB: Leukemia, multiple mycloma, and aplastic anemia in American radiologists. Science 142: 1492, 1963 10. ANDERSON RE: Malignant lymphoma. Hum Pathol 2: 515, 1971 II. Idem: Leukemia and related disorders. Ibid, p 505 12. COURT BROWN WM, DOLL R: Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis. Br Med J 2: 1327, 1965 13. ANDERSON RE, NIsHlYAMA H, II Y, et al: Pathogenesis of radiation-related leukaemia and lymphoma. Speculations based primarily on experience of Hiroshima and Nagasaki. Lance: 1: 1060, 1972 14. Mum H, EDELMANN L, GILLMAIER L, et al: Radiation dose in different organs of Thorotrast patients, in Assessment of Radioactive
Contamination in Man, Vienna, International Atomic Energy Agency, 1972, pp 457-67
COARCTA TION continued from page 417 13. AWAD JA, MANNIX EP .sR: Congenital valvular and subvalvular aortic stenosis with associated coarctation of the aorta and patent ductus arteriosus. Report of a case with successful surgical correction. I Thorac Cardtovasc Surg 43: 203, 1962 14. WRIGHT JL, BURCHELL HB, Wooo EH: Hemodynamic and clinical appraisal of coarctation 4 to 7 years after resection and end-to-end anastomosis of aorta. Circulation 24: 806,
1956 15. RATHI L, KEITH 3D: Post-operative blood pressure in coarctation of the aorta. Br Heart 1 26: 671, 1964 16. MARCH HW, HULTGREN HN, GERBODE F: Im-
mediate and remote effects of resection on the hypertension in coarctation of the aorta. Br Heart 1 22: 361, 1960
17. KIRKLIN 3W, WALLACE RB: The Heart, 2nd
ed, HURST JW, LOGAN RB (eds), New York,
McGraw. 1970, p 722
Noludar® Roche. (methyprylon) Rx summary: Indications Insomnia due to mental unrest, excitement, fear, worry or extreme fatigue. Adverse reactions Nausea, headache, drowsiness, vertigo, paradoxical excitation, and skin rash. Precautions As with other hypnotic agents, patients should be advised to abstain from alcohol during treatment with Noludar as the individual response cannot be foreseen. Dosage Adults: 1 capsule at bedtime. Children: over 6 years - 100 mg at bedtime. 2to6years-75 mg at bedtime. 6 months to 2 years -50 mg at bedtime. Supply Capsules, 300 mg; 100, 500. Elixir, 50 mg/tsp. (5 ml); 400 ml. Complete prescribing information available on request. ®Reg. Trade Mark Hoff mann-La Roche Limited
