Factors Relating to Late Sudden Death in Patients Having Aortic Valve Replacement John T. Santinga, M.D., Marvin M. Kirsh, M.D., Jairus D. Flora, Jr., Ph.D., and James F. Brymer, M.D. ABSTRACT The preoperative and postoperative characteristics of a group of 16 patients who died unexpectedly and a control group of 52 late survivors with aortic protheses are reviewed. There were no preoperative differences between the groups for duration of congestive heart failure, electrocardiographic findings, cardiothoracic ratio, or hemodynamic findings. However, on the standard electrocardiogram postoperatively, there were more ventricular arrhythmias in the patients who died suddenly (7 of 16 or 44%) compared with the survivors (5 of 49 or 10%) (p < 0.05). There were more patients with congestive failure in the study group (10 of 16 or 62%) compared with the controls (4 of 52 or 8%) (p < 0.05). Patients exhibiting these findings are at risk of sudden death. Arrhythmia monitoring prior to discharge may also be helpful in selecting patients for antiarrhythmia treatment. One of the important unresolved problems following aortic valve replacement is late sudden death. Its incidence in reported series ranges between 7 and 38% [l-31. The present investigation was undertaken to determine whether there are any preoperative or postoperative findings that can be used to predict which patients are predisposed to sudden death following aortic valve replacement. Material and Methods The study population for sudden death was composed of patients who underwent Starr- Edwards aortic valve replacement at the Uni- From the Department of Internal Medicine, Division of Cardiology, Department of Thoracic Surgery, and Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, MI. Accepted for publication Feb 22, 1979. Address reprint requests to Dr. Santinga, Department of Internal Medicine, Division of Cardiology, University of Michigan Medical Center, 1405 E Ann St, Ann Arbor, MI 48109. versity of Michigan Medical Center from 1967 to 1977. Patients with associated cardiac defects or clinically significant disease of other cardiac valves were excluded as were patients who died of cerebral embolism or hemorrhage. Unexpected death was defined as a nonhospitalized patient who had an acute event with loss of consciousness and was either dead or in ventricular fibrillation on arrival at a medical facility. Sixteen patients, 3 women and 13 men, fulfilled these criteria. They ranged from 27 to 67 years old (mean age, 52 years). A group of 52 patients who were long-term survivors of isolated Starr-Edwards aortic replacement served as the control group. There were 13 female and 39 male patients ranging from 17 to 74 years old (mean age, 52 years). They had been operated on during the same period as the study group, and all had the Starr-Edwards 1260 aortic prosthesis. These patients had survived at least 2 years and had a mean follow-up of forty-six months. Preoperatively, the types of valve lesion in the 16 patients who died suddenly were as follows: aortic stenosis, 6 patients (38%); mixed lesions, 3 patients (19%); and aortic insufficiency, 7 patients (44%). Of 48 survivors, 21 (44%) had aortic stenosis; 12 (25%) had mixed lesions; and 15 (31 YO) had aortic insufficiency. In addition, 4 patients had replacement of a defective prosthetic valve. The preoperative New York Heart Association (NYHA) Functional Classification for the two groups was as follows: Class I, none in the study group and 2 (4%) in the control group; Class 11, 8 (50%) in the study group and 27 (52%) in the control group; Class 111, 7 (44%) in the study group and 22 (42%) in the controls; and Class IV, 1(6%) in the study group and 1 (2%) in the controls. The preoperative electrocardiograms were reviewed for ventricular arrhythmias, left ventricular hypertrophy, and conduction abnormalities (Table). There were no differences 249 0003-49751801030249-05$01.25 @ 1978 by John T. Santinga
250 The Annals of Thoracic Surgery Vol 29 No 3 March 1980 between the two groups in the preoperative tracings. Ventricular arrhythmias were recorded when there were three or more premature ventricular beats on the mounted 12-lead electrocardiogram taken with a single-channel machine. The tracings averaged from 15 to 25 complexes. Left ventricular hypertrophy was read when the voltage exceeded the normals given in the Minnesota code [41. Conduction abnormalities were read when the QRS interval exceeded the normals in this code and were classed as complete right and left bundle-branch block. Infarction was also read when the Q wave exceeded the criteria given in the Minnesota code. The mean duration of congestive heart failure prior to operation was 1.9 years for the study group and 3 years for the control group. The cardiothoracic ratio was taken from a preoperative posteroanterior chest roentgenogram. For 13 patients in the study group for whom roentgenograms were available, the preoperative cardiothoracic ratio was 0.58; it was 0.56 for the 37 patients in the control group for whom roentgenograms were available. Preoperative cardiac catheterization was carried out in all patients. Hemodynamic data for the study and control groups were available for some patients in each group. Average left ventricular end-diastolic pressure was 22 mm Hg for 13 patients in the sudden death group and 24 mm Hg for 49 of the survivors. Average pulmonary artery systolic pressure was 48 mm Hg for 12 patients in the sudden death group and 41 mm Hg for 45 survivors. The aortic gradient was 68 mm Hg for 10 patients in the study group and 75 mm Hg for 36 patients in the control group. The left ventricular ejection fraction was calculated from the right anterior oblique view using standard angiography of the left ventricle. Average left ventricular ejection fraction was 61% for 10 patients in the study group and 63% for 40 of the survivors. The coronary arteriograms were graded by the scoring system of Friesinger and co-workers [5]: no disease = 0; < 50% = 1; 50-90% = 2; multiple 50-90% = 3; 90-99% = 4; and total occlusion = 5. The individual scores for the left anterior descending, lateral circumflex, and right coronary arteries were added together to give the total score. Seven patients in the study group had normal coronary arteriography, with all the scores in the range of 0 to 3. Twentyeight patients in the control group had normal coronary arteriograms; 1 had a score of 2 to 5 and 1, a score of greater than 6. A uniform perfusion technique was used throughout with a bubble oxygenator at a flow rate of 2.5 liters per minute per square meter of body surface. In 75% of the patients, coronary perfusion at a temperature of 28 C was employed during aortic valve replacement. An attempt was made to maintain the heart in normal sinus rhythm during the time of aortic cross-clamping. In 25% of the patients, hypothemic ischemic arrest (28 C) was employed. Results Several methods of myocardial protection were used. For 6 patients in the study group, mean coronary perfusion time with the heart beating was 84 minutes (range, 60 to 120 minutes). For 22 patients in the control group, it was 86 minutes (range, 52 to 136 minutes). Mean coronary perfusion time with the heart in ventricular fibrillation was 77 minutes (range, 60 to 113 minutes) for 6 patients in the study group; for 18 patients in the control group, it was 85 minutes (range, 53 to 132 minutes). The time of hypothermic arrest averaged 57 minutes (range, 47 to 67 minutes) for 4 patients in the study group; it was 61 minutes (range, 51 to 87 minutes) for 13 patients in the control group. There were no significant differences between the two groups regarding the method of myocardial preservation or duration of cross-clamping. Postoperatively, NYHA Functional Classification was as follows: Class I, 3 patients (19'/0) in the study group and 34 (65%) in the control group; Class 11, 9 (56%) in the study group and 18 (35%) in the control group; Class 111, 4 (25%) in the study group. There were no patients in Class IV. Fewer patients in the sudden death group were in Class I compared with the control group (p < 0.05). The frequency and severity of postoperative congestive failure for both groups also show a significant increase in congestive failure in the
251 Santinga et al: Late Sudden Death after AVR Electrocardiographic Findings in the Sudden Death Patients (Group A) Compared with a Control Group of Survivors (Group B)a Finding LVH Conduction defect Pacing Infarction Ventricular arrhythmias Preoperative Percentages Postoperative Percentages Group A Group B (N = 16) (N = 49) Group A Group B "In parentheses are the numbers.of patients with the electrocardiographic abnormality. < 0.05 by the chi-square method. LVH = left ventricular hypertrophy. sudden death group compared with the control group (p < 0.05). Of the 16 patients in the study group, 5 (31%) had severe congestive failure; 5 (31%) had moderate failure; and 6 (38%) had no congestive failure. Of the 52 survivors, only 2 (4%) had severe congestive failure; only 2 (4%) had moderate failure; and 48 (92%) had no failure. Onset of congestive failure occurred within 2 years of operation in 8 of the 10 patients in the study group. Digitalis and diuretics were used by 11 of the 16 patients in the study group and 20 of the 52 patients in the control group. The cardiothoracic ratio for the postoperative period remained at 0.58 for the group experiencing sudden death and decreased in the survivors to 0.52. The interval from operation to death for the survivors is as follows: 6 patients died within the first year; 6 patients in the second year; and 1 patient each year for the third, fourth, fifth, and tenth years. The postoperative electrocardiographic findings for the two groups are listed in the Table. The most striking finding is the significantly higher incidence of ventricular arrhythmias in the sudden death group in comparison to the survivors, 44% and 10940, respectively (p < 0.05). Comment As a result of improvements in intraoperative and postoperative management, aortic valve replacement can now be accomplished with an operative risk of 5% or less. Long-term survival following aortic valve replacement is influenced by the severity of the preexisting heart disease, intraoperative injury to the myocardium, and prosthetic-valve related complications [6, 71. The cardiac causes of death include congestive heart failure and myocardial infarction. Some are sudden and unexplained. The exact incidence of sudden unexplained deaths is difficult to determine since sudden deaths are usually classified with the myocardial causes of late deaths in most reported series. Isom and colleagues 181 in 1977 reported that of 47 late deaths from myocardial factors, 14 were sudden and unexplained (30% incidence). The results of the present study demonstrate that none of the preoperative indices could predict which patients would die suddenly following aortic valve replacement. There was no statistically significant difference between the long-term survivors and those who died suddenly with respect to Functional Class, type of valve lesion, cardiothoracic ratio, duration of congestive heart failure, incidence of ventricular arrhythmias, and electrocardiographic findings of myocardial infarction, intraventricular conduction abnormalities, left ventricular hypertrophy, left ventricular end-diastolic pressure, or left ventricular ejection fraction. However, patients who died suddenly did exhibit postoperative characteristics that were different from those of long-term survivors. In those patients who died suddenly, there was an increased postoperative incidence of congestive heart failure and a greater frequency of ven-
252 The Annals of Thoracic Surgery Vol 29 No 3 March 1980 tricular arrhythmias. The postoperative cardiothoracic ratios in the study group did not decrease following operation while those in the survivors did (p < 0.05). The increased frequency of postoperative congestive heart failure in the group dying suddenly cannot be explained on the basis of a greater impairment of function preoperatively since the preoperative duration of congestive heart failure, cardiothoracic ratio, left ventricular end-diastolic pressure, and ejection fraction were similar in the two groups of patients. Eleven of the 16 patients with sudden death were on a regimen of digitalis and diuretics. Therefore digitalis toxicity is a possibility. However, 20 of the longterm survivors also were on a regimen of these medications. This reduces the likelihood that digitalis toxicity is a major cause of sudden death. That the major cause of death following aortic valve replacement in our institution and in other reported series is myocardial failure and that most deaths in this and other series occur within 2 to 3 years of operation suggest that the most probable cause of death is operative injury, since in our patients the preexisting myocardial function was the same for both groups. Subendocardial necrosis is the most common cause of death following technically successful cardiac operations [9-111. The hearts of as many as 90% of the patients who died after openheart operation have left ventricular subendocardial necrosis. It can occur without anatomical obstruction of the coronary arteries and is thought to be caused by a discrepancy between subendocardial oxygen supply and demand during the operative period. In our patients who died late, infarctions, if present, were likely subendocardial in nature; only 1 of the 16 patients had electrocardiographic evidence of a transmural infarction. We would agree with Isom and co-workers [7, 81 that these deaths result from operative infarction, which increases the propensity for sudden fatal arrhythmias. This has been shown for coronary disease but is less well recognized for valvular disease 1121. The increase in ventricular arrhythmias postoperatively in the study group would be in agreement with this mechanism. Operative injury would also ac- count for the related high incidence of recurrent congestive heart failure in those patients who died suddenly. Of interest is the observation that sudden death occurred irrespective of the method of myocardial preservation in our series. It occurred in patients in whom aortic valve replacement was carried out utilizing coronary perfusion while keeping the empty heart beating throughout the period of aortic cross-clamping. This would suggest that an optimum method of preserving the hypertrophied myocardium of patients with aortic disease has not as yet been perfected. The results of this study suggest that left ventricular dysfunction, probably resulting from intraoperative injury, is a major causative factor in those patients who die suddenly and unexpectedly following aortic valve replacement. Those at risk to die suddenly are patients in whom congestive heart failure and ventricular ectopy occur following aortic valve replacement. In addition, the cardiothoracic ratio on chest roentgenogram in these patients fails to decrease in size. Patients with this clinical profile should be carefully evaluated using periodic Holter monitoring and, if complex ventricular arrhythmias are detected, the use of antiarrhythmic drugs should be considered. Future endeavors to prevent this cataclysmic complication should center around improved methods of myocardial preservation during operation. References 1. 2. 3. 4. 5. 6. Barnhorst DA, Oxman HA, Connolly DC, et al: Long-term followup of isolated replacement of the aortic or mitral valve with Starr-Edwards prosthesis. Am J Cardiol35:228, 1975 Braun LO, Kincaid OW, McGoon DC: Prognosis of aortic valve replacement in relation to the preoperative heart size. J Thorac Cardiovasc Surg 65:381, 1973 Buckberg GD, Towers 8, Paglia DE, et al: Subendocardial ischemia after cardiopulmonary bypass. J Thorac Cardiovasc Surg 64:669, 1972 DeBoer A, Midell AI: Isolated aortic valve replacement: analysis of factors influencing survival after replacement with the Starr-Edwards prosthesis. Ann Thorac Surg 17:360, 1974 Friesinger GC, Page EE, Ross RS: Prognostic significance of coronary arteriography. Trans Assoc Am Physicians 83:78, 1970 Hodam R, Starr A, Raible D, et al: Totally cloth-
253 Santinga et al: Late Sudden Death after AVR covered prosthesis: a review of two years clinical experience. Circulation 41,42:Suppl 2:II-33, 1970 7. Isom 0, Dembrow JM, Glassman E, et al: Factors influencing long-term survival after isolated aortic valve replacement. Circulation 49,5O:Suppl 2:II-154, 1974 8. Isom 0, Spencer F, Glassman E, et al: Longterm results in 1,375 patients undergoing valve replacements with the Starr-Edwards clothcovered steel ball prosthesis. Ann Surg 186:310, 1977 9. Najafi H, Henson D, Dye WS, et al: Left ven- tricular hemorrhagic necrosis. Ann Thorac Surg 7:550, 1969 10. Rose GA, Blackburn H: Cardiovascular Survey Methods. Geneva, World Health Organization, 1968, p 138 11. Taber RE, Morales AR, Fine G: Myocardial necrosis and the postoperative low-cardiac-output syndrome. Ann Thorac Surg 4:12, 1967 12. Weaver WD, Lorch GS, Alvarez HA, et al: Angiographic findings and prognostic indicators in patients resuscitated from sudden cardiac death. Circulation 54395, 1976 Notice from the American Board of Thoracic Surgery The American Board of Thoracic Surgery now requires that candidates pass both the written and oral portions of the certifying examination. In 1980 and thereafter, a written examination will be given prior to the oral examination. It will be necessary to pass the written examination before the oral examination can be taken. The closing date for registration for 1981 is August 1,1980. The exact times and places of these examinations will be announced later. A candidate applying for admission to the 1981 certifying examination must fulfill all the requirements for the Board in force at the time the application is received. Please address all communications to the American Board of Thoracic Surgery, 14640 E Seven Mile Road, Detroit, MI 48205.