Coronary Artery Stenosis Following Aortic Valve Replacement and Intermittent Intracoronary Cardioplegia

Coronary Artery Stenosis Following Aortic Valve Replacement and Intermittent Intracoronary Cardioplegia D. Glenn Pennington, M.D., Bulent Dincer, M.D., Hind Bashiti, M.D., Hendrick B. Barner, M.D., George C. Kaiser, M.D., Denis H. Tyras, M.D., John E. Codd, M.D., and Vallee L. Willman, M.D. ABSTRACT From July, 1977, to July, 1980, intermittent cold blood potassium cardioplegia was used in 208 patients undergoing aortic valve replacement. Aortic root injection of the cardioplegic solution at 10 C was followed every 20 to 30 minutes by infusions of the solution through Silastic cannulas sutured in the coronary orifices or reinserted with each injection. Symptoms of myocardial ischemia developed in 6 patients 3 to 30 months postoperatively. Coronary angiography confirmed new stenoses of the left orifice (3 patients), left main trunk (1 patient), left anterior descending coronary artery (2 patients), circumflex coronary artery (1 patient), and right orifice (3 patients). Four patients underwent saphenous vein grafting procedures, with 2 deaths; 2 patients refused reoperation. A seventh patient with 80% stenosis of the circumflex coronary artery and a posterolateral myocardial infarction died 2 months after double-valve replacement. Intermittent cold blood potassium cardioplegia instead of continuous perfusion did not prevent coronary arterial injury. Injuries occurred in the distal coronary arteries as well as the orifices and were not prevented by withdrawal of the cannulas between injections. Tight-fitting cannulas and high-pressure injection should be avoided. A careful search for coronary arterial injury should be made in all symptomatic patients following aortic valve replacement. Stenosis of the coronary ostia following continuous coronary perfusion during aortic valve replacement has been well documented [l-121. From the Departments of Surgery, Cardiology, and Pathology, St. Louis University Hospitals, St. Louis, MO. Presented at the Twenty-eighth Annual Meeting of the Southern Thoracic Surgical Association, Palm Beach, FL, NOV 5-7, 1981. Address reprint requests to Dr. Pennington, Department of Surgery, St. Louis University Medical Center, 1325 S Grand Blvd, St. Louis, MO 63104. The presence of perfusion catheters in the coronary arteries during the entire period of valve replacement was thought to produce local pressure necrosis and subsequent intimal proliferation leading to obstruction of the coronary ostia. In 1980, Force and co-workers [13] reported the cases of 2 patients with coronary ostial stenosis following aortic valve replacement in whom intermittent coronary cannulation was employed for the injection of a cardioplegic solution for myocardial protection. The coronary lesions and clinical courses of these patients were similar to those of patients reported earlier who had continuous coronary perfusion. Since July, 1977, we have used intermittent intracoronary infusions of potassium in cold blood for myocardial protection during aortic valve replacement and have encountered 7 patients with coronary arterial stenoses postoperatively. Material and Method During the period July, 1977 (the time cold blood potassium cardioplegia was first employed at St. Louis University), to July, 1980, 208 patients underwent aortic valve replacement alone or as part of multiple cardiac procedures. Coronary arteriography was performed in all patients prior to aortic valve replacement. Postoperatively, only patients with symptoms of angina pectoris or heart failure underwent coronary arteriography. Patients with Bjork- Shiley valves received Coumadin (sodium warfarin) in doses sufficient to maintain the prothrombin activity at 18 to 20%. Patients with porcine heterograft valves received aspirin and dipyridamole or aspirin alone during the first several months after operation. Coronary lnfusion Technique The method of inducing and maintaining cardioplegia with cold blood and potassium has 576 0003-4975/82/060576-09$01.25 @ 1982 by The Society of Thoracic Surgeons

577 Pennington et al: Coronary Stenosis after AVR been described previously [14, 151. In brief, it is as follows: systemic hypothermia to 25" f 1 C (more recently, 18" to 20 C); aortic crossclamping at the onset of ventricular fibrillation; aortic root perfusion with 300 to 400 ml of blood at 10 C containing potassium chloride at a final concentration of 31 k 2 meq per liter by hand syringe in 50 ml increments; repeat perfusion every 20 to 30 minutes using 200 to 300 ml of blood at 10 C with the same concentration of potassium; and the topical application of crushed ice, made from lactated Ringer's solution, to the heart. For aortic valve replacement, the technique is modified by the placement of soft Spencer-Mallette Silastic cannulas* into the coronary ostia. The cannulas are secured by one of several techniques: a superficial suture near the coronary orifice, a tourniquet suture through the aortic wall at a site remote from the coronary ostia, or holding the cannulas in place by hand with removal and reinsertion for each injection. The amount of cold blood and potassium injected into each coronary artery varied depending on the coronary arterial anatomy, but the left coronary artery usually received more blood than the right. In cases of small, nondominant right coronary arteries, only left coronary infusions were made. Results Of 208 patients undergoing aortic valve replacement, 22 died during the initial hospitalization. One hundred eighty patients were followed for 1 to 39 months (mean, 7.4 months) after operation, and 6 patients were lost to follow-up. New symptoms suggestive of angina pectoris developed in 5 patients 3 to 8 months after operation, and symptoms of heart failure without angina developed in 2. The diagnoses, operative procedures, and status of the coronary arteries in these 7 patients before and after aortic valve replacement are shown in Table 1. Aortic valve replacement was uncomplicated in Patients 1, 2, and 7. Patients 3, 4, and 5 had excessive bleeding requiring extensive suturing for control, and Patient 5 required a gusset to enlarge the annulus. Patient 6 had a heavily calcified, small aortic annulus and poor *DOW Coming Corporation, Midland, MI. ventricular function requiring intraaortic balloon pump support. The specific techniques of coronary cannulation and infusion for each of the 7 patients are shown in Table 2. In all patients the infusions of cold blood and potassium were intermittent at approximately 20- to 30-minute intervals. In 4 patients both right and left coronary cannulas were sutured in place and maintained during the entire period of aortic occlusion; in 1 patient the left coronary cannula was sutured in place and the right was removed and reinserted with each injection; and in 2 patients both cannulas were removed and reinserted with each injection. Although the immediate postoperative course was complicated by poor left ventricular function in Patients 4,5, and 6, all patients were discharged from the hospital in stable condition with no symptoms suggestive of angina pectoris. In Patients 2, 3, 4, and 5 typical severe angina pectoris developed at 5, 8, 3, and 4 months, respectively. In Patient 3, angina was accompanied by slow atrial fibrillation necessitating placement of a temporary transvenous pacemaker. Patient 1 experienced right upper quadrant pain 3 months after aortic valve replacement and a saphenous vein graft to the left anterior descending coronary artery. Subsequently it was determined that this pain was due to cholecystitis. Cardiac catheterization performed prior to cholecystectomy revealed mild aortic insufficiency and 90% stenosis of the previous normal right coronary ostium. The patient refused saphenous vein grafting of the right coronary artery. She tolerated cholecystectomy without difficulty and has subsequently had no pain suggestive of angina pectoris. Patient 6 had severe cardiac cachexia and poor left ventricular function preoperatively, which contributed to a difficult postoperative course. Although he was able to be discharged seventeen days after operation, he returned a week later with poor nutrition and progressive heart failure, culminating in death 2 months after operation. Cardiac catheterization data obtained seven weeks postoperatively revealed severe, diffuse impairment of left ventricular function and 80% stenosis of the circumflex

578 The Annals of Thoracic Surgery Vol 33 No 6 June 1982 Table 1. Data on Patients with Symptoms Postoperatively Patient Preoperative Postoperative No., Age Preoperative Cardiac Initial Onset of Coronary Second (yr), Sex Diagnosis Catheterization Operation Symptoms Arteries Operation 1. 74, F 2.64, M 3. 55, F 4. 53, M 5. 72, M 6. 42, M 7. 56, M Calcific aortic stenosis, 70% stenosis of LAD Calcific aortic stenosis, ascending aortic aneurysm Aortic stenosis Aortic stenosis, mitral stenosis, aortic regurgitation Aortic stenosis Calcific aortic stenosis, calcific mitral stenosis Aortic insufficiency 70% stenosis of LAD, normal RCA Normal coronary arteries?6o% stenosis of LAD origin Normal coronary arteries 60% stenosis of mid-rca, 20% stenosis of LAD, 20% stenosis of circumflex Normal coronary arteries 20-30% stenosis of RCA AVR (No. 19 Bjork- Shiley), SVG to LAD AVR (No. 23 Bjork- Shiley), wrapped aneurysm AVR (No. 21 Bjork- Shiley) AVR (No. 23 Bjork- Shiley), MVR (No. 27 Bjork-Shiley) AVR (No. 21 Bjork- Shiley), enlarged aortic annulus with gusset AVR (No. 19 Bjork- Shiley), MVR (No. 23 Bjork-Shiley) AVR (No. 27 Angell- Shiley porcine xenograft) - 3 mo 5 mo 8 mo 3 mo 4 mo Never fully recovered; no angina 2.5 yr 70% stenosis of LAD with patent SVG, 90% stenosis of RCA orifice 90% stenosis of LAD 95% stenosis of left coronaiy orifice 80% stenosis of left main, 80% stenosis of right orifice 9!j% stenosis of left orifice, 95% stenosis of right orifice, diffuse changes in distal coronary arteries 80% stenosis of mid-circumflex 80% stenosis of left orifice None SVG to LAD SVG to LAD SVG to LAD, SVG to RCA SVG to RCA, sequential SVG to LAD and obtuse marginal LAD = left anterior descending coronary artery; RCA = right coronary artery; AVR = aortic valve replacement; SVG = saphenous vein graft. Table 2. Perfusion Techniques Aortic Root Coronary Time of Injection Volume per Aortic Patient Volume Injection Technique for Occlusion Site of Coronary No. (mu (mu Cannulation (min) Artery Injury 1 200 Left, 100 Not sutured; rein- Right, 100 serted for each injection 2 None Left, 150 Both cannulas su- Right, 50 tured at orifices 3?300 Left, 200 Left-sutured at Right, 200 orifice; rightreinserted for each injection 4 300 Left, 150 Both cannulas su- Right, 50 tured at orifices 5 300 Left, 100 Both cannulas su- Right, 50 tured at orifices 6 None Left, 150 Both cannulas su- Right, 50 tured at orifices 7 None Left, 200 Not sutured; rein- Right, 200 serted for each injection 106 84 123 133 130 90 148 80 Right orifice None None Proximal left anterior descending coronary artery Left orifice Right orifice, left main trunk Right orifice, left orifice, proximal left anterior descending and proximal circumflex coronary arteries Middle of circumflex coronary artery Left orifice

579 Pennington et al: Coronary Stenosis after AVR coronary artery distal to the origin of the first obtuse marginal branch. Postmortem examination of the heart revealed a posterolateral infarction within the distribution of the stenotic circumflex coronary artery Patient 7 began to experience dyspnea with mild exertion more than two years after aortic valve replacement. Postoperative cardiac catheterization revealed normal ventricular function, but there was 80% stenosis of the previously normal left coronary orifice. In spite of continuing symptoms of dyspnea with exertion, he has had no angina and has refused coronary bypass grafting. Patients 2, 3, 4, and 5 underwent saphenous vein grafting procedures to the involved coronary arteries. Patients 2 and 3 had uneventful courses after placement of a graft to the left anterior descending coronary artery, and both have subsequently done well. Patients 4 and 5 had involvement of both the right and left coronary arteries requiring multiple grafts, and both of them had complicated operative and postoperative courses. Three weeks after saphenous vein grafting, Patient 4 died of diffuse subendocardial infarctions of the left ventricle and restrictive fibrous pericarditis. Patient 5 required saphenous vein grafts to the right coronary artery, the left anterior descending coronary artery, and the obtuse marginal branch. The operative course was complicated by severe left ventricular failure and failure to wean from cardiopulmonary bypass in spite of inotropic drugs and intraaortic balloon pump support. Eventually, the patient was separated from cardiopulmonary bypass by use of a Medtronic left ventricular assist device, but he died of extensive bleeding and multiorgan failure during the first postoperative day. The location and nature of the coronary arterial injuries were defined by postoperative coronary angiography in the 7 patients as well as by postmortem examination in Patients 4 and 5. Patient 6 also underwent postmortem examination, but dissection of the circumflex coronary artery was not performed. Figure 1 illustrates the sites of the coronary arterial injuries in the 7 patients. The three right coronary arterial injuries occurred at the ostia, while the eight left Fig 1. Sites of coronary arterial injury in 7 patients. Each number represents one of the patients. (Ant. Desc. = anterior descending; Ob. Marg. = obtuse marginal; Cx. = circumflex.) coronary arterial injuries occurred at the ostia in three instances, the left main trunk in one, the proximal left anterior descending coronary artery in two, the proximal circumflex coronary artery in one, and the middle of the circumflex in one instance. In Patient 1, the surgeon was concerned that the valve might be partially obstructing the right coronary orifice. However, this could not be demonstrated angiographically. Postoperative coronary angiograms performed in Patient 2 (Fig 2) clearly demonstrated severe stenosis of a previously normal left anterior descending coronary artery. Stenosis of the right coronary ostium in Patient 1 was demonstrated by coronary angiography (Fig 3) as well as by a precipitous drop in pressure as the catheter entered the right coronary orifice. However, ostial stenosis was not demonstrated by angiography in Patient 5. There was 80 to 95% stenosis of the previously normal proximal anterior descending coronary artery and progression of the lesions in the first diagonal and first obtuse marginal branches. At postmortem examination, the left and right coronary orifices were subtotally occluded by irregular soft intima1 masses of white tissue (Fig 4). Microscopic

580 The Annals of Thoracic Surgery Vol 33 No 6 June 1982 A B Fig 2. (Patient 2.) Left coronary arteriograms (A)before and ( B ) 5 months after aortic valve replacement. There is severe stenosis of the previously normal proximal left anterior descending coronary artery. A Fig 3. (Patient 1.) Right coronary arteriograms (A)before and ( B ) 3 months after aortic valve replacement and placement of a saphenous vein graft to the left anterior descending coronary artery. There is severe stenosis of the right ostium, which was confirmed b y a sharp decrease in pressure beyond the orifice. B

581 Pennington et al: Coronary Stenosis after AVR A B Fig 4. (Patient 5.) Specimens of the (A) left and (B) right coronary ostia taken at postmortem examination. There is almost complete obstruction of both ostia by soft intima1 masses of tissue. examination demonstrated that the masses were composed of proliferating intima in a loose stroma (Fig 5). The intimal proliferation was eccentric, producing marked narrowing and irregularity of the lumen. During the period July, 1977, to July, 1980, 7 other survivors of aortic valve replacement underwent coronary angiography 1 to 36 months after the operation. None of them had any evidence of coronary arterial abnormalities that had not been present before aortic valve replacement. If the 22 patients who died and the 6 patients who were lost to follow-up are excluded, the incidence of recognized coronary arterial perfusion injury was 7 out of 180, or 3.9%. Comment The development of coronary arterial injuries in patients following aortic valve replacement can probably be ascribed to several different etiologies. Roberts and Morrow [16] proposed that coronary ostial obstruction results from intimal proliferation in the aortic root due to turbulent flow patterns occurring with ball-valve prostheses. From subsequent reports, it is clear that their theory does not explain the occurrence of postperfusion injury in patients in whom the lesion occurs distal to the coronary orifice [12], patients without substantial intimal thickening of the aortic root [l], patients with disc-type prostheses [4, 7, 101, and patients with porcine heterografts [12, 131. Intimal proliferation in the aortic root probably was not a factor in our patients since 6 had Bjork-Shiley valves and 1 had a porcine heterograft, the site of left coronary injury was distal to the orifice in 4 patients, and there was no marked intimal proliferation in the aortic root of the 3 patients in whom postmortem examinations were performed. Intimal thickening of the base of the aorta involving the coronary ostia has also been reported by Yates and associates [71 and may be the primary etiological factor in some patients. There is at least one reported instance of right coronary ostial stenosis following aortic valve replacement in which a cannula was not placed into the coronary artery [7]. Trimble and co-workers [l] suggested that high coronary perfusion pressures were largely responsible for the coronary lesions observed in 3 of their patients after aortic valve replacement. Constant monitoring of the pressure in the coronary perfusion line was recommended, with maintenance of pressure at less than 90 to 100 mm Hg. However, in other subsequent se-

582 The Annals of Thoracic Surgery Vol 33 No 6 June 1982 A B Fig 5 (Patient 5 ) (A) Photomicrograph of the left coronary orifice demonstrating extensive proliferation of the intima and irregularity of the lumen (B) Photomicrograph of the right coronary orifice demonstrating intima1 proliferation and irregularity of the lumen

583 Pennington et a]: Coronary Stenosis after AVR ries, postperfusion coronary injury developed in 10 patients in spite of strict maintenance of perfusion pressure at 100 to 120 mm Hg [ll, 121 and 100 to 150 mm Hg [lo]. In our patients the manual pressure used for intermittent injections was not measured and could have exceeded a critical level, resulting in localized injury. Since the cannulas were not distensible, the point of maximal pressure would be at the tip of the cannula rather than at the coronary orifice. Excessive tip perfusion pressure could have been the mechanism of injury in 4 of our patients who had left coronary injuries distal to the orifice. It is unlikely that the perfusion catheter was inserted as far as the middle of the circumflex coronary artery, the site of stenosis in Patient 6. In this instance, the injury may have occurred from a jet effect resulting from high-pressure infusion. It is also possible that intimal injury occurred due to local pressure necrosis at the cannulation site. With the Spencer-Mallette Silastic cannulas employed in our patients, this would be most likely to happen at the point where the Silastic bulb contacted the coronary arterial intima. In 4 of our patients, the cannulas were sutured in place and left in the coronary artery during the entire period of aortic clamping. Obviously, in regard to local pressure injury, the intermittent perfusion technique offered no advantage over the continuous perfusion technique in these 4 patients. However, in 2 of our patients and in 2 reported by Force and colleagues [131, the cannulas were left in place only for the 2 to 3 minutes required for injection of the solution and then were withdrawn. It seems unlikely that these brief periods of local occlusion of the vasa vasorum would lead to significant ischemia and pressure necrosis of the intima. A more likely explanation of injury in these patients is that withdrawal and repeated cannulations caused intimal disruption or avulsion. Such an injury would be most likely to occur if a large cannula was forced or wedged into the coronary lumen. The advantage of a snug fit for the coronary cannulas in our infusion technique is that it prevents leakage around the cannulas and assures that the entire injected volume is delivered to the coronary vascular bed. This might be accomplished just as well with a flanged cannula, the small tip of which could be inserted into the coronary lumen and the flange pressed gently against the orifice to prevent leakage. Coronary arterial injuries occurred distal to the coronary orifices in 4 of our patients, a finding which is strikingly different from previous reports of such injuries. Sethi and associates [12] indicated that coronary arterial injury occurred in the left main coronary artery several millimeters beyond the coronary orifice in 1 patient. However, in our patients, injuries were noted in the proximal left anterior descending coronary artery, the proximal circumflex coronary artery, and even in the middle of the circumflex artery. Since these lesions were not present on coronary angiograms prior to aortic valve replacement, the conclusion that they were in some way related to intraoperative events seems inescapable. Whether such distal coronary arterial injuries are truly unique to our series of patients or whether they have simply been overlooked in other series is conjectural. The importance of these distal coronary injuries relates primarily to the mechanism of injury, since factors leading to stenosis of the coronary orifice would not necessarily account for more distal coronary lesions. It is possible that the Spencer-Mallette perfusion catheter could be forced into the proximal left anterior descending or even into the origin of the circumflex coronary artery. However, it is extremely unlikely that that cannula could be forced distally as far as the middle portion of the circumflex coronary artery. It seems more reasonable to assume that these distal injuries occurred as the result of intimal disruption produced by a jet effect resulting from high pressure localized at the tip of the catheter. The true incidence of coronary arterial perfusion injury following aortic valve replacement is not known in our own patients or in those of previous reports. Since in our study only symptomatic patients underwent coronary angiography postoperatively, some coronary lesions may have gone undetected. It seems that severe coronary ostial lesions would produce symptoms, but 2 of our patients (Patients 1 and 7) never had angina pectoris. In another patient (Patient 6) with no angina pectoris, postopera-

584 The Annals of Thoracic Surgery Vol 33 No 6 June 1982 tive cardiac catheterization was performed because of heart failure. Stenosis of the middle of the circumflex coronary artery was an unexpected finding. The discovery of a posterolatera1 infarction at postmortem examination suggested that the coronary lesion contributed to the patient s death. While it currently does not seem warranted to recommend routine postoperative coronary angiography in all patients undergoing aortic valve replacement, there must be a high index of suspicion for such lesions. It is clear that the use of intermittent coronary perfusion instead of continuous perfusion has not prevented the occurrence of postperfusion coronary arterial injury. These injuries occurred whether the cannulas were left in place or were withdrawn and reinserted for each infusion. Further efforts must be made to develop a technique of coronary perfusion that will allow for adequate myocardial protection without the risk of coronary arterial injury. References Trimble AS, Bigelow WG, Wigle ED, Silver MD: Coronary ostial stenosis: a late complication of coronary perfusion in open-heart surgery. J Thorac Cardiovasc Surg 57:792-795, 1969 Le Sage CH, Vogel JHK, Blount SG: Iatrogenic coronary occlusion disease in patients with prosthetic heart valves. Am J Cardiol26:123-129, 1970 Najafi H, Escamilla HA, Clark JG: Acute coronary insufficiency and life-threatening cardiac arrhythmias eight months after triple heart valve replacement. Surg Clin North Am 50:1119-1127, 1970 Nukhjavan FK, Mavanho V, Goldberg H: Iatrogenic stenosis of the proximal portion of the coronary arteries: report of three cases treated with aortocoronary anastomosis. Am Heart J 83:318-321, 1972 5. Reed GE, Spencer FC, Boyd AD, et al: Late complications of intraoperative coronary artery perfusion. Circulation 47,48:Suppl3:80-84, 1973 6. Black LL, McComb RJ, Silver MD: Vascular injury following heart valve replacement. Ann Thorac Surg 15:19-29, 1973 7. Yates JD, Kirsh MM, Sodeman TM, et al: Coronary ostial stenosis: a complication of aortic valve replacement. Circulation 49:530-534, 1974 8. Hazan E, Rioux C, Dequirot A, Mathey J: Postperfusion stenosis of common left coronary artery. J Thorac Cardiovasc Surg 69:703-707, 1975 9. Bjork VO, Henze A, Szamosi A: Coronary ostial stenosis: a complication of aortic valve replacement or coronary perfusion? Scand J Thorac Cardiovasc Surg 1O:l-6, 1976 10. Midell AI, DeBoer A, Bermudez G: Postperfusion coronary ostial stenosis: incidence and significance. J Thorac Cardiovasc Surg 72:80-85, 1976 11. Chawla SK, Najafi H, Javid H, Serry C: Coronary obstruction secondary to direct cannulation. Ann Thorac Surg 23:135-138, 1977 12. Sethi GI, Scott SM, Takaro T: Iatrogenic coronary artery stenosis following aortic valve replacement. J Thorac Cardiovasc Surg 77:760-767,1979 13. Force TL, Raabe DS, Coffin L, DeMentes JD: Coronary ostial stenosis following aortic valve replacement without continuous coronary perfusion. J Thorac Cardiovasc Surg 80:637-641, 1980 14. Laks H, Bamer HB, Kaiser G: Cold blood cardioplegia. J Thorac Cardiovasc Surg 77:319-322, 1979 15. Barner HB, Kaiser GC, Codd JE, et al: Clinical experience with cold blood as the vehicle for hypothermic potassium cardioplegia. Ann Thorac Surg 29:224-227, 1980 16. Roberts WC, Morrow HG: Late postoperative pathological findings after cardiac valve replacement. Circulation 35,36:Suppl 1:48-62, 1967