Congenital coronary artery anomalies inNoonan's syndrome

396

February 1990 American Heart Journal

Brief Communications

with a sudden drop afterwards to a 60% patency rate at 11 years. 4 F r o m their studies on pigs and from clinical studies, F u s t e r and Chesebro 5 described four phases of aortocoronary bypass vein graft disease and indicated the role of platelets in its pathogenesis. Early occlusion, t h a t is within the first month, usually results from platelet deposition at sites of er~dothelial damage, resulting in the formation of an occluding thrombus. Thereafter, an intermediate phase of intimal hyperplasia occurs t h a t is brought about by a proliferation of smooth muscle cells caused by platelet-derived factors. By the end of the first year, graft occlusion results from a rapid progression of such intimal hyperplasia on which superimposed platelet-thrombi may occur. Finally, a phase of atherosclerotic disease occurs in which proliferation of smooth muscle cell connective tissue continues with incorporation of lipid into the lesions. Considering our case, in regard to this sequence of events we note first t h a t the occurrence of such a massive thrombus in the presence of a mild atherosclerotic lesion is unusual. Using their model, F u s t e r and Chesebro 5 postulated t h a t antiplatelet t h e r a p y could be of particular benefit to prevent early occlusion as well as some late occlusions, when thrombus formation is most likely to occur. Antiplatelet t h e r a p y started before the operation and continuing thereafter gave improved graft patency in the early postoperative phase, with a 2 % rate of vein graft occlusion i n the t r e a t e d group compared with 10% in the placebo group. T h e beneficial effect of this t h e r a p y was less evident after 1 year, with a 9 % occlusion rate in the treated group compared with 14% in the placebo group. 5 T h e benefit of a n t i p l a t e l e t t h e r a p y even late after coronary artery bypass graft (CABG) surgery is suggested when one looks at the events t h a t occurred in this case. Indeed, 1 month prior to the advent of symptoms, a stress test showed no evidence of ongoing ischemia, b u t 4 weeks after cessation of antiplatelet t h e r a p y symptoms of myocardial ischemia had developed, and the presence of thrombi was documented within the lumen of a coronary bypass graft. Spontaneous recanalization of infarct-related coronary vessels is known to occur in 40 % of cases within the first 24 hours following a t r a n s m u r a l myocardial infarction, 6 and evidence of a thrombotic process in unstable angina is also well documented. However, we know of no case in the literature with angiographic documentation of spontaneous thrombolysis occurring in a vein graft. If an extensive thrombus can be found with only mild disease of the vein graft and if spontaneous thrombolysis is possible, a more aggressive approach may be warranted with thrombolytic t h e r a p y for acute coronary events occurring "late" after CABG surgery. Saphenous vein grafts could perhaps be salvaged more often t h a n expected. However, the pathophysiologic importance of t h r o m b i after CABG surgery in acute ischemic events has not been adequately evaluated nor has possible thrombolytic t h e r a p y been properly assessed. In summary, this case report suggests t h a t the role of t h r o m b i m a y be i m p o r t a n t in the occlusion of vein grafts even late after surgery. T h e occurrence of such thrombusrelated occlusion may be underestimated. A beneficial role of prolonged a n t i p l a t e l e t t h e r a p y is likely, b u t futher

studies are required. Spontaneous thrombolysis does occur in saphenous vein grafts despite intensive thrombus formation and nonoptimal flow. Thrombolytic therapy should be considered in "late" acute ischemic events following bypass surgery. We gratefully acknowledge the expert assistance of Michel C6t~, MD, and Dennis Chapcot, MD, in reviewing this manuscript and the efficient work of Johanne Leblanc in editing the manuscript. REFERENCES

1. Rentrop P, Blanke H, Karsch KR, Kostering H, Oster H, Leitz H. Recanalization of an acutely occluded aortocoronary bypass by intragraft fibrinolysis. Circulation 1980;62:1123-6. 2. F~umin H, Goldberg M J, Ruberfire M, Levlne FH. Late thrombolysis of an occluded aortocoronary saphenous vein graft. AM HEART J 1983;'106:40!-3. 3. Vetrovec GW, Leinbach RC, Gold HK, Cowley MJ. Intracoronary thrombolysis in syndromes of unstable ischemia: angiographic and clinical results. AM HEART J 1982;104:946-52. 4. Bourassa MG, Fisher LD, Campeau L, Gillespie M J, McConney M, Lesperance J. Long-term fate of bypass graft: the Coronary Artery Surgery Study and Montreal Heart Institute experiences. Circulation 1985;72(suppl V):71-8. 5. Fuster V, Chesebro JJ. Aortocoronary artery vein graft disease: experimental and clinical approach for the understanding of the role of platelets and platelet inhibitors. Circulation 1985;72(suppl V):65-70. 6. DeWood MA, Spores J, Notske R, Mouser LT~ Burroughs R, Golden MS, Lang HT. Prevalence of total coronary occlusion during the early hours ~f transmural myocardial infarction. N Engl J Med 1980;303.:897-902.

Congenital coronary artery anomalies in Noonan's syndrome Cheuk-Kit T o n g , MB, M R C P ( U K ) , Chun-Ho Cheng, MB, M R C P ( U K ) , C h u - P a k Lau, MD, M R C P ( U K ) , and Wing-Hung Leung, MB, M R C P ( U K ) . Hong Kong

T h e characteristic cardiac lesion in Noonan's syndrome is pulmonary stenosis. Left-sided cardiac anomalies including hypertrophic cardiomyopathy, aortic stenosis, and coarctation have also been d e s c r i b e d J 3 However, only one case of congenital coronary anomaly as a coronary fistula was r e p o r t e d J We describe two more cases of rare congenital coronary anomalies t h a t accompanied this syndrome. Details on the management of the first case have been reportedJ Case No. 1. A 23-year-old m a n was seen with exertional dyspnea. Physical examination revealed a regular pulse, radial-femoral delay, and a displaced apex with a biven-

From the Department of Medicine,University of Hong Kong,Queen Mary Hospital, Hong Kong. Reprint requests: Dr C. K. Tong, Department of Medicine,University of Hong Koag, Queen Mary Hospital, Pokfulam Rd., Hong Kong. 4/4/17526

Volume 119 Number 2, Part 1

Brief Communications

397

Fig. 1. A, Right coronary angiogram with the use of an 8F right Judkins catheter showing a right proximal coronary artery aneurysm that measures 4 cm in length and 2.5 cm in transverse diameter; B, photograph of patient described in case 1 with features of Noonan's syndrome.

tricular cardiac impulse. The pulmonary second sound was loud, and a grade 3/6 continuous murmur was noted at the left sternal border. The electrocardiogram showed evidence of biventricular hypertrophy. By means of cardiac catheterizationi the condition was diagnosed as aortic coarctation of moderate severity, moderate aortic valve stenosis, and patent ductus arteriosus with a large left-toright shunt that caused pulmonary hypertension (Table I). A large right coronary artery aneurysm was found on an

otherwise normal coronary angiogram (Fig. 1, A). A conservative procedure of closed heart surgery, including the ligation of the ductus and correction of coarctation, resulted in a decrease of symptoms. A follow-up study 8 years later showed no progression of the coronary aneurysm. The patient had somatic features compatible with Noonan's syndrome, which includes short stature, hypertelorism, a shield chest, kyphoscoliosis, and mild cubitus valgus (Fig, 1, B). He had a normal karyotype. His intelligence was

398

Brief Communications

February 1990 American Heart Journal

;iiii!i~ii

iiiii~i!ii~iU

Fig. 2. A, Late phase of left ventricular angiogram in the left anterior oblique view. The contrast has been ejected from the left ventricle into the aorta. The single coronary artery is shown to arise from the left coronary sinus and to bifurcate shortly after its origin into two big branches. The right branch crosses back to the right side and runs the usual course of the right coronary artery, B, photograph of patient described in case 2 with features of Noonan's syndrome. normal, and his family history was negative for Noonan's syndrome. Case No. 2. A 10-year-old girl was referred for investigation of a heart murmur. She had a regular, jerky pulse, a

double apical impulse, and a systolic murmur over the left sternal border. An electrocardiogram showed sinus rhythm, left axis deviation, Q waves over inferior leads, and anterior chest leads. A two-dimensional echocardiogram showed

Volume 119 Number 2, Part 1

evidence of hypertrophic c a r d i o m y o p a t h y with asymmetrical septal hypertrophy. The diagnosis was confirmed by means of cardiac catheterization (Table I). In addition, a left ventricular angiogram in the left anterior oblique view showed opacification of a single coronary artery t h a t originated from the left coronary cusp and bifurcated into two branches; one followed the usual course of the left coronary artery, whereas the other branch crossed back toward the right side to run the usual course of the right coronary artery (Fig. 2, A). This p a t i e n t also h a d the somatic features of Noonan's syndrome with dwarfism, hypertelorism, neck webbing, and m a r k e d cubitus valgus. Her karyotype was normal, and her family history was negative for the syndrome. She remained amenorrheic up to her present age of 15, when a photograph was t a k e n (Fig. 2, B). During the p a s t 5 years, while she was on maintenance regimen of propranolol, she had experienced several episodes of retrosternal pain t h a t required repeated hospitalization. She never had syncope. R e p e a t e d Holter monitoring did not reveal any significant arrythmia. A calcium antagonist was administered, and there, was no improvement. She was advised to have coronary angiography for further delineation of the coronary abnormality, b u t her family refused. Both single coronary artery and coronary artery aneurysms represent distinctly rare congenital coronary anomalies. Their associations with the other congenital cardiac anomalies described here have not been reported. T h e incidence of congenital cardiovascular anomalies in Noonan's syndrome has been estimated at about 50% .5 In addition to cardiac defects in which p u l m o n a r y stenosis is common, various vascular anomalies have been described. The more common ones include aortic coarctation and peripheral p u l m o n a r y a r t e r y stenosis; both account for about 5% of reported cardiovascular lesions. 2 Other vascular anomalies include abnormal brachiocephalic vessels, 3 abnormal systemic and pulmonary venous return, 2, 3 hemangiomas,2 and various lymphatic problems s u c h as intestinal lymphangiectasia and pulmonary lymphangiectasia. 2 Hypertrophic c a r d i o m y o p a t h y with asymmetrical septal hypert r o p h y was recognized only much later in Noonan's syndrome, 3 which had p r e s u m a b l y been underdiagnosed previously because of the inadequate use of left heart catheterizationJ 3 W i t h the advent of echocardiography, a subsequent s t u d y indicated t h a t hypertrophic cardiomyop a t h y was not uncommon in this syndrome. 5 So far, only one case of coronary anomaly occurring as a coronary artery fistula has been described. 1 We have reported two cases of rare coronary anomalies in this syndrome. Since such coronary lesions m a y not produce symptoms, their actual incidence m a y have been underestimated. Because such lesions m a y cause serious complications, a more liberal use of coronary angiography in routine catheterization for Noonan's syndrome should be considered. The m a n a g e m e n t of the first case has been discussed. 4 In brief, acute thrombosis and progressive enlargement t h a t can lead to rupture are the two major complications, both of which are being accelerated by atheroscterosisJ Unlike t h e static course followed over 8 years in case No. 1, acute myocardial infarction secondary to acute thrombosis has

Brief Communications

399

T a b l e I. Cardiac catheterization d a t a

Case I Pressure (ram Hg)

SVC IVC RA RV PA PAW LV Asc AO Des AO Cardiac output Pulmonary flow *LV-AO gradient *RV-PA gradient

Oxygen saturation (%)

Case 2 Pressure (mm Hg)

Oxygen saturation (%)

10/7/8/2 55/0-5 30/13

73 88 77 77 78

160/0-8 118/78

99 99

66 7I 13/8/6/5 65 75/0-10 69 75/50 83 21/6/16/6 210/0-15 95 160/90 95 110/70 95 4.75 L/min

4.34 L/min

10.2 L/rain

4.34 L/min 40 mm Hg (rest) 90 mm Hg (postectopic) 25 mm Hg (rest) 45 mm Hg (postectopic)

SVC, Superior vena cava; IVC, Inferior vena cava; RA, Right atrium; RV, Right ventricle; PA, Pulmonary artery; PAW, Pulmonary artery wedge; LV, Left ventricle; Asc AO, Ascending aorta; Des AO, Descending aorta. *Both gradients occurred at the subvalvular region.

recently been reported in two young patients. One of t h e m eventually required a h e a r t transplant. 6 Surgical resection of the aneurysm might offer the possibility of a cure and should be considered particularly when open heart surgery is required for correction of concomitant anomalies. T h e use of antiplatelet agents and preventive measures for atherosclerosis would be advisable. 4 Atherosclerosis t h a t involves the proximal p a r t of a single coronary artery would also be hazardous. In addition, in cases in which a major branch of the single coronary artery crosses between the aorta and the right ventricular outflow tract, intermittent obstruction in coronary flow m a y occur with exercise and hence m a y cause myocardial ischemia. 7 Kinking of the coronary branch as a result of increased blood flow through the p u l m o n a r y artery and the aorta during exercise has been postulated as the responsible mechanism. 7 Cases of sudden death during exercise have been reported. In this regard, an analogy can be drawn to the anomalous origin of coronary artery in which the artery passes between the aorta and the right ventricular outflow tract. When the left coronary artery is involved, a 30% incidence of sudden death has been quoted, s W h e n the right coronary artery is involved, association with myocardial ischemia or sudden death has also been reported. 9 In our patient, if the branch t h a t supplies the right coronary territory crosses between the a o r t a and the p u l m o n a r y outflow tract, myocardial ischemia m a y occur o n e x e r t i o n and account for her symptoms of angina. It is unfortunate t h a t she refused coronary

400

Brief Communications

angiography, which could also rule out coronary atherosclerosis. In summary, Noonan's syndrome may be associated with a higher incidence of coronary anomalies t h a n previously recognized. The correct delineation of such anomalies in addition to other cardiac defects would help direct the proper m a n a g e m e n t of each case. Coronary angiography should be considered during cardiac catheterization in these patients. REFERENCES

1. Nora JJ, Nora AH, Sinha AK, Spangler RD, Lubs HA. The Urlich-Noonan syndrome (Turner phenotype). Am J Dis Child 1974;127:48-55. 2. Pearl W. Cardiovascular abnomalies in Noonan's syndrome. Chest 1977;71:677-9. 3. Ehlers KH, Engle MA, Levin AR, Deely WJ. Eccentric ventricular hypertrophy in familial and sporadic instances of 46 XX, XY Turner phenotype. Circulation 1972;45:639-52. 4. Wong CK, Cheng CH, Lau CP, Leung WH. Asymptomatic congenital coronary artery aneurysm in adulthood. Eur Heart J 1989 (In press) 5. Nora JJ, Lortscher RH, Spangler RD. EchocardiograPhic studies of left ventricular disease in Urlich-Noonan syndrome. Am J Dis Child 1975;129:1417-20. 6. Lablanche JM, Brimont O, Vileram D, Peltier JM, Fourrier JL, Bertrand ME. Congenital aneurysm of the coronary arteries. Appropos of two cases. Ann Cardiol Angeiol (Paris) 1988;37:83-5. 7. Levin DC, Gardiner GA. Coronary arterigraphy. In: Braunward E, ed. Heart disease: a textbook of cardiovascular medicine. Philadelphia, WB Saunders, 1988:288. 8. Liberthson RR, Dinsmore RE, Fallon JT. Aberrant coronary artery origin from the aorta. Report of 18 patients, review of the literature, and delineation of the natural history and management. Circulation 1979;59:748-54. 9. Roberts WC, SiegelRJ, Zipes DP. Origin ofthe right coronary artery from the left sinus of Valsalva and its functional consequences: analysis of 10 necropsy patients. Am J Cardiol 1982;49:863-8.

Giant inferior wall left ventricular aneurysm Nicholas L. DePace, MD, Steven Dowinsky, MD, William Untereker, MD, Gerald M. LeMole, MD, Pasquale M. Spagna, MD, and Steven G. Meister, MD.

Philadelphia, Pa.

Left ventricular aneurysm is the most common mechanical complication of acute myocardial infarction; its incidence is approximately 15% (range 3% to 38%). Only 9% of all infarct-related aneurysms involve the inferior wall, and they are rarely extensive. We describe an unusual case of "giant" inferior wall aneurysm in a patient presenting with From the Department of Cardiology, Pennsylvania Hospital; and Cardiothoracic Department, Medical Collegeof Pennsylvania. Reprint requests: NicholasDePace, MD, Dept. of Cardiology,MedicalCollegeof Pennsylvania,1417 OregonAve.,2nd Floor,Philadelphia, PA 19145. 4/4/17356

February 1990 American Heart Journal

congestive heart failure. This case is unusual because of t h e very large size of the aneurysm in this location and this communication details how successful resection can be undertaken. A 51-year-old white man sustained an inferior wall myocardial infarction complicated by congestive heart failure and hypotension. T h e p a t i e n t underwent a post-infarction stress test, which disclosed markedly ischemic electrocardiographic changes. Cardiac catheterization revealed threevessel disease. Left ventriculography confirmed depressed left ventricular function, with an ejection fraction of 30 %. There was posterolateral and inferoapical akinesis. T h e p a t i e n t successfully underwent uncomplicated three-vessel coronary artery bypass surgery and did well for 2 years. He then presented with congestive h e a r t failure and symptoms consistent with low cardiac output. A two-dimensional echocardiogram revealed left ventricular and left atrial enlargement. Doppler interrogation disclosed mitral regurgitation. A huge inferior aneurysm was noted (Fig. 1). T h e remainder of the ventricle (nonaneurysmal residual myocardium) was diffusely hypokinetic, b u t was contracting. A radionuclide angiogram revealed a reduced ejection fraction of 22 % (regional ejection fraction index of 53 % ). T h e ventricle was m a r k e d l y enlarged with an end-diastolic volume of 540 ml and an end-systolic volume of 425 ml. T h e patient underwent cardiac catheterization when he failed to improve despite m a x i m u m medical therapy. Catheterization again revealed severe triple-vessel coronary artery disease, mild mitral regurgitation, and p a t e n t grafts to the left anterior descending, right coronary artery, and obtuse marginal branch of the left circumflex coronary artery. Left ventricular end-diastolic pressure was elevated. Left ventriculography performed in the right anterior oblique and left anterior oblique projections showed an extremely large inferoapical aneurysm in size approximating the size of the body of the left ventricular cavity (Fig. 2, A and B). The neck of the aneurysm was wide, suggesting true aneurysmal etiology. Because of refractory congestive heart failure and low cardiac output, the p a t i e n t underwent left ventricular aneurysm incision and repair via a left thoracotomy. The aneurysm measured approximately 18 cm in diameter and was a true aneurysm. Surgery was well tolerated. Postoperatively, the ejection fraction increased to 41% (regional ejection fraction index of 75 % ), with a m a r k e d decrease in left ventricular end-diastolic volume to 375 cc and in end-systolic Volume to 221 cc. There was marked improvement in the anteroapical and inferior wall motion. T h e p a t i e n t is currently doing well without recurrent congestive heart failure. Inferior wall aneurysms are uncommon, presumably because there are four muscle layers in the base but only three in t h e apex. Furthermore, the base and septum have dual blood supplies, whereas the apex usually has only one. Also, the lack of bulbospiral muscle increases the likelihood of left ventricular aneurysm in the apex. 1 Resecting inferior wall aneurysms is more difficult t h a n resecting anterior wall aneurysms because of the care required to avoid disruption of papillary m u s c l e - m i t r a l valve continuity. In our patient, congestive heart failure resulted from he-