Pathology of the sinus node in d-transposition following the Mustard operation

Pathology of the sinus node in d-transposition following the Mustard operation In a pathological study of 32 necropsy specimens from patients with d-transposition who had undergone the Mustard operation, lesions were commonly present in the sinus nodal artery, the sinus node, and the paranodal tissues. These had resulted from surgical injury during placement of the atrial baffle and/or closure of the atriotomy incision. Our findings confirm the pathological findings of others. The pathological observations correlate well with reported electrophysiological studies that show frequent occurrence of postoperative supraventricular arrhythmias due to sinus nodal dysfunction. Twenty-six of the patients died in the early postoperative period, and the sinus nodal artery had been compressed by sutures in 46 percent of these cases. The sinus node either showed acute necrosis or compression by sutures in 77 percent of cases, and the paranodal areas were involved by acute hemorrhage and/or necrosis in 100 percent of cases. Six patients died in the late postoperative period. The sinus nodal artery was replaced by fibrous tissue in three and was compressed or thrombosed in two additional instances. The sinus node was extensively fibrosed in each of the six cases. In every instance, the paranodal areas were involved by fibrosis and disruption by sutures.

William D. Edwards, M.D., and Jesse E. Edwards, M.D., St. Paul and Minneapolis, Minn.

Patients with complete (d)-transposition of the great arteries who have undergone the Mustard operation and who have survived the immediate postoperative period may die as a result of several late complications. Pulmonary venous and systemic venous obstruction are widely recognized late hemodynamic complications. 1 Clinicians also are becoming increasingly aware of the relatively high incidence of postoperative arrhythmias and of sudden unexpected death in such cases.v" Recent electrophysiological investigations in patients having undergone the Mustard operation have established that postoperative supraventricular arrhythmias classically result from sinus nodal dysfunction rather than from interruption of the internodal tracts." to The sinus nodal dysfunction is thought to be a manifestation of trauma to the area of the node caused during the operative procedure. to From the Departments of Pathology, United Hospitals-Miller Division, SI. Paul, Minn., and the University of Minnesota, Minneapolis, Minn. This study was supported by Public Health Service Research Grant 5 ROI HL05694 and Research Trairring Grant 5 Tal HL05570 from the National Heart, Lung and Blood Institute, and by the Saint Paul Foundation, St. Paul, Minn. Received for publication July 22, 1977. Accepted for publication Sept. 30, 1977. Address for reprints: Jesse E. Edwards, M.D., Department of Pathology, United Hospitals-Miller Division, 125 West College Avenue, SI. Paul, Minn. 55102.

0022-5223/78/0275-0213$00.60/0 © 1978 The C. V. Mosby Co.

With this background, the present study was undertaken to study the pathological condition of the sinus node in patients with d-transposition of the great arteries who had undergone the Mustard operation. Observations

In the Cardiovascular Registry of the United Hospitals-Miller Division, there are 32 autopsy specimens from patients with d-transposition of the great arteries that had been subjected to the Mustard operation. Of these 32 specimens, 17 were obtained from the University of Minnesota Hospitals, seven from the Kansas University Medical Center, three from the Minneapolis Children's Medical Center, and the remaining five from other hospitals. From each specimen, step-sections were obtained from the anticipated site of the sinus node. Duplicate sections were stained with hematoxylin and eosin and by the elastic-van Gieson method. It is significant that the sections taken in the anticipated location of the sinus node corresponded to the position of the atriotomy and the placement of the upper aspect of the atrial baffle. (Figs. 1 and 2). Postoperative survival time. The 32 cases were divided into two groups on the basis of the postoperative survival time. Group I comprised those patients who had died within 1 month following the Mustard operation, and Group II comprised those who had died later than the first postoperative month. 213

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Fig. 1. Diagram of heart in right lateral view demonstrating the location of sinus node (SN) and sinus nodal artery (SNA). The node lies in the groove of the sulcus tenninalis (ST) near the junction of the superior vena cava (SVC) and right atrium (RA), adjacent to the base of the right atrial appendage (RAA). The sinus nodal artery usually arises from the proximal portion of the right coronary artery (RC), but it may arise from the circumflex branch. The nodal artery usually passes anteriorly to the superior vena cava, less commonly posteriorly to the superior vena cava (inset). Ao, Aorta. RV, Right ventricle. IVC, Inferior vena cava.

Fig. 2. Specimen of heart viewed from the right from a patient with d-transposition of the great arteries who died immediately after the Mustard operation. The anticipatedsite of the sinus node (SN) is encircled by dots. The atriotomy incision (A) extends to the region of the sinus node. The sinus node artery (SNA) originates from the right coronary artery (RC) . Ao , Aorta. Cir, Circumflex coronary artery. lVC , Inferior vena cava. PT, Pulmonary trunk. RA, Right atrium. RAA, Right atrial appendage. RPA , Right pulmonary artery. RPV, Right pulmonary veins. RV, Right ventricle. SVC, Superior vena cava.

Group I contained 26 patients, ranging in age from 4 months to 19 years (mean age, 4 years) . There were 18 boys and eight girls in this group. Six of these patients died during the operation; 11 died during the first postoperative day; and the remaining nine patients died between 2 days and 4 weeks after the operation. Group II consisted of six patients, ranging in age from 2lh to 8 years (mean age, 4 years). Five boys and one girl composed this group. Postoperative survival time ranged from 5 months to 6 years. Postoperative arrhythmias. Within Group I, postoperative arrhythmias were present in 50 percent (13/26). These included complete heart block, nodal rhythm, various tachyarrhythmias and bradyarrhythmias , transient loss of P waves, and ventricular fibrillation. However, the cause of death was directly related to arrhythmias in only 15 percent (4/26). In the aggregate, the causes of death were numerous and included pulmonary congestion and edema, pneumonia, hypox-

emia, renal failure, acidosis, hyperkalemia, coagulopathy, heart failure, and mechanical complications of the cardiac operative repair, either alone or in combination . Within Group II, postoperative arrhythmias were present in four of the six patients (67 percent). Complete heart block developed in two patients; occasional premature ventricular contractions were present in one; and one patient exhibited arrhythmias only terminally. Sudden unexpected death occurred in four patients, two of whom had had no evidence of postoperative arrhythmias . One of the two patients without identified postoperative arrhythmias had experienced a syncopal episode about 2 years postoperatively and I month prior to sudden death. One of the patients with postoperative arrhythmias had an episode of apnea and cyanosis 5 months postoperatively and several days prior to sudden death. Of the two patients who did not suffer sudden unexpected death, one died during a sec-

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Fig. 3. Group I. Injury to the sinus nodal artery in the early postoperative period. a, Compression of sinus node artery (SNA) and surrounding tissues by sutures (S) closing the atriotomy (a). (Elastic-van Gieson stain, x36.) b, Surgical division of the sinus nodal artery (SNA) by the atriotomy (A).

Segments of the divided artery are present at each side of the atriotomy. Additionally, compression of arterial segments by suture material (S). (Elastic-van Gieson stain, X 18.) c, Organizing occlusive thrombus. (Hematoxylin and eosin, x 36.)

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Fig. 4. Group I. Injury to the sinus node in the early postoperative period. a, Suture (S) within periphery of the sinus node (SN) , resulting in disruption of nodal tissue and mild compression of sinus nodal artery (SNA). (Elastic-van Gieson stain, x90.) b, Compression of sinus nodal artery (SNA) and acute necrosis of sinus node (SN) due to sutures (S) closing atriotomy (A). (Elastic-van Gieson stain, x 12.) c, Acute necrosis of sinus node (SN) and compression of sinus nodal artery (SNA) at atriotomy site (A) due to snaring of the node by sutures (S). (Elastic-van Gieson stain, X36.)

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Fig. 5. Group I. Injury to the sinus paranodal tissues in the early postoperative period. a , Acute hemorrhage surrounding a parasympathetic (vagal) ganglion (G). (Hematoxylin and eosin, X90.) b, Perineural hemorrhage and calcification of necrotic vagal ganglion cells (G). (Hematoxylin and eosin, x90.) c. Acute hemorrhage adjacent to autonomic nerve (N) and sinus nodal artery (SNA) . (Elastic-van Gieson stain, x 90.) d, Acute interstitial hemorrhage associated with acute necrosis (left) and subsequent calcification (right) of atrial myocardial fibers. (Elastic-van Gieson stain, x 90.) ond Mustard operation for pulmonary venous obstruction . The other one was the patient who had had arrhythmias only terminally. Six years postoperatively, he collapsed during exercise, was resuscitated, experienced a variety of arrhythmias, and died the same day. The arrhythmias in this patient, in order of appearance, included asystole , ventricular fibrillation, electrical conversion to sinus rhythm, and finally intermittent nodal rhythm and premature atrial and ventricular contractions. One week prior to death, this patient had had two episodes of dizziness . Pathological findings. Lesions of the sinus nodal artery, the sinus node , and the paranodal tissues were commonly observed in both Groups I and II . Group I. Among the 26 case s in Group I, the sinus nodal artery was normal in 14 (54 percent) and was

involved pathologically in 12 instance s (46 percent) . The most common basis for involvement, seen in nine instances, was simple compression by sutures (Fig. 3, a and b) . Less common lesions observed in three cases were characterized by direct invol vement of the artery. These, noted once per lesion, were intimal fibrous pads , medial elastosis, and an organizing, partially occlusive thrombus (Fig . 3, c). Lesions involving the sinus node were observed in 20 of the 26 cases (77 percent). The lesions of the sinus node , all of which were acute, were represented either by evident necrosis or by compression by sutures (Fig. 4). In some instances, necrosis appeared to take the form of infarction, generally in specimens with identified suture compression of the sinus nodal artery. Among the nine cases in which the sinus nodal artery

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. Fig. 6. Group II. Injury to the region of the sinus node, associatedwith late postoperative death. a, Compressed sinus nodal artery (SNA) with nearby suture material (S) and fibrous obliteration of anticipated site of the sinus node, 9 months postoperatively, (Elastic-van Gieson stain, x36.) b, Fibrous obliteration of anticipated site of sinus node associatedwith suture material(S). Sinus nodal artery (SNA) is patent at this level but was compressed at other levels, 2 years postoperatively, (Elastic-van Gieson stain, X36,) c, Organized thrombus of the sinus nodal artery, 9 monthspostoperatively. (Elastic-van Gieson stain, x 180.) d, Compression of sinus nodal artery by adjacent suture (S), 6 years postoperatively. (Elastic-van Gieson stain, x90.)

was found to be compressed, there was acute infarction of the node in seven. Acute paranodal lesions were present in each of the 26 specimens from Group I. The lesions included interstitial hemorrhage among the myocardial fibers and nerve fibers and necrosis of myocardial fibers (Fig. 5). Calcification of necrotic paranodal muscle fibers or vagal ganglion cells was seen in an occasional case (Fig. 5, b and d). Group Il . Group II specimens commonly showed healed lesions that corresponded to the acute lesions noted in Group I. The sinus node was extensively involved by fibrous tissue in each case. In three the fibrosis obscured any remnant of nodal tissue (Fig. 6, a

and b), whereas in the remammg three some nodal tissue was identifiable. Remnants of the nodal artery were not apparent in three of the cases, as this vessel was lost in the fibrous tissue replacing the node. In the remaining three specimens from this group, the artery was identifiable and in each showed lesions. One per case, there were focal intimal fibrosis, intimal and medial thickening with focal compression, and organized occlusive thrombus with focal compression (Fig. 6, C and d). In all cases, the paranodal areas were involved by fibrosis and were disrupted by old suture material, either from the atriotomy or from placement of the atrial baffle (Fig. 6, a and b) . Acute microfocal paranodal hemorrhages were also present in three of the

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six specimens. No acute lesions were present within the sinus node. Comment

At the present time, the Mustard operation is by far the most commonly employed corrective procedure for d-transposition of the great arteries. However, this procedure has been associated with various late complications, including pulmonary venous obstruction and superior or inferior vena caval obstruction. 1 Numerous arrhythmias have also been reported following this operation.v" Sudden unexpected death is now recognized as being relatively common in the late postoperative period and supraventricular arrhythmias are thought to be among its causes. 3 In the past, such arrhythmias were considered to have resulted from interruption of atrial nodal tracts." However, recent intra-atrial electrophysiological studies in patients after the Mustard operation have shown that the origin of postoperative supraventricular arrhythmias is in the region of the sinus node.?: 10 Our pathological studies in 32 cases showed common sites of injury to include the sinus node, the paranodal areas, and the sinus nodal artery. These observations confirm the comparable pathological studies in five cases by El-Said and associates.P The common pathological findings of injury to the sinus node and related tissues correlates with electrophysiological studies that indicate faulty function of the sinus node following the Mustard procedure. Injuries like those described have been attributed to one or more of three surgical procedures: (1) cannulation of the superior vena cava, (2) placement of the atrial baffle, or (3) closure of the atriotomy wound. 12-15 Our common findings of suture material at or close to the sinus node suggest that either or both of the latter two possibilities are the more likely causes of injury to the region of the sinus node. The mechanisms by which tissues are injured include compression of the nodal artery with secondary infarction or strangulation of tissues other than vessels by the process of suturing. The fibrotic lesions observed in Group II (late postoperative deaths) are interpreted as healed stages of acute lesions like those noted in Group I. This study was not concerned with atrioventricular conduction disturbances; however, we recognize that such arrhythmias may contribute to disability and even death in some cases. Our studies dealing with the sinus node area reveal disturbances in structure following the Mustard procedure. These disturbances probably underlie supraventricular arrhythmias that commonly occur.

Thoracic and Cardiovascular Surgery

REFERENCES Mair DD, Danielson GK, Wallace RB, McGoon DC: Long-term follow-up of Mustard operation survivors. Circulation 49, 50:Suppl 2:46, 1974 2 Clarkson PM, Barratt-Boyes BG, Neutze 1M: Late dysrhythmias and disturbances of conduction following Mustard operation for complete transposition of the great arteries. Circulation 53:519, 1976 3 Scott LP, Saalouke MG, Shapiro SR, Rios rc, Perry LW: Sudden unexpected death following Mustard's procedure for d-transposition of the great vessels (abstr). Circulation 53, 54:Suppl 2:89, 1976 4 Champsaur GL, Sokol DM, Trusler GA, Mustard WT: Repair of transposition of the great arteries in 123 pediatric patients. Early and long-term results. Circulation 47: 1032, 1973 5 Rodriguez-Fernandez HL, Kelly DT, Collado A, Haller A Jr, Krovetz LJ, Rowe RD: Hemodynamic data and angiographic findings after Mustard repair for complete transposition of the great arteries. Circulation 46:799, 1972 6 Miller BL, Morgan lR, Daicoff GA: Cardiac rhythm after repair of transposition of the great arteries (abstr). Circulation 45, 46:Suppl 2:192, 1972 7 Zuberbuhler lR, Bauersfeld SR: Unusual arrhythmias after corrective surgery for transposition of the great vessels. Am Heart 1 73:752, 1967 8 Khoury GH, Shaher RM, Fowler RS, Keith lD: Preoperative and postoperative electrocardiogram in complete transposition of the great vessels. Am Heart 1 72: 199, 1966 9 Gillette PC, Duff D, Mullins CE, McNamara DG: Sinus node function vs internodal conduction as the mechanism of post Mustard dysrhythmias (abstr). Circulation 53, 54:Suppl 2:184, 1976 10 Gillette PC, El-Said GM, Sivarajan N, Mullins CE, Williams RL, McNamara DG: Electrophysiological abnormalities after Mustard's operation for transposition of the great arteries. Br Heart 1 36: 186, 1974 11 Isaacson R, Titus lL, Merideth 1, Feldt RH, McGoon DC: Apparent interruption of atrial conduction pathways after surgical repair of transposition of great arteries. Am 1 Cardiol 30:533, 1972 12 El-Said G, Rosenberg HS, Mullins CE, Hallman GL, Cooley DA, McNamara DG: Dysrhythmias after Mustard's operation for transposition of the great arteries. Am 1 Cardiol 30:526, 1972 13 Tung KSK, lames TN, Effler DB, McCormack LJ: Injury of the sinus node in open-heart operations. 1 THORAC CARDIOVASC SURG 53:814, 1967 14 EI-Said GM, Gillette PC, Cooley DA, Mullins CE, , McNamara DG: Protection of the sinus node in Mustard's operation. Circulation 53:788, 1976 15 Breckenridge 1M, Stark 1, Bonham-Carter RE, Oelert H, Graham 'GR, Waterston Dl: Mustard's operation for transposition of the great arteries. Review of 200 cases. Lancet 1:1140, 1972