";g. and Determinants of Risk. or 1,000 Patients, ery: Perioperative Mortality. Reoperations for Valve S

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1 Reoperations for Valve S and Determinants of Risk ";g ery: Perioperative Mortality or, Patients, Bruce W. Lytle, M.D., Delos M. Cosgrove, M.D., Paul C. Taylor, M.D., Carl C. Gill, M.D., Marlene Goormastic, M.P.H., Leonard R. Golding, M.D., Robert W. Stewart, M.D., and Floyd D. Loop, M.D. ABSTRACT One thousand consecutive cardiac reoperations for valve surgery in 89 patients were reviewed to determine in-hospital mortality and indicators of risk. Subgroups based on the number of previous cardiac procedures and the valve or valves replaced or repaired at reoperation (aortic valve, mitral valve, tricuspid valve, or multiple valves and mortality [deathshumber of procedures (% mortality)]) for those subgroups are as follows: Aortic Mihal Tricuspid Multiple Valve Valve Valve Valves Total Reoperation 6/9 (%) 4H8 (%) y (%) M (4%) 98 %) Reoperation /4 (%) 9/ (%) /4 () \ (%) 9/8(%) Reoperations- /6 (%) / (%) Oil () / (6%) 9/ (4%) Predictors of increased risk for a first aortic valve reoperation were advanced age (p =.), endocarditis (p =.8), female sex (p =.4), impaired left ventricular function (p =.9), and number of coronary vessels obstructed by % or more (p =.). For a first mitral valve reoperation, the predictors were advanced age (p <.), preoperative shock or cardiac arrest (p =.ON, previous aortic or tricuspid valve operations (p =.), type of mitral valve procedure (risk for repair of periprosthetic leak was greater than mitral valve replacement which was greater than mitral valve-conserving operation [p =.l), and impaired left ventricular function (p =.9). For a first multiple valve reoperation, the predictors were diabetes (p =.4) and ascites (p =.), whereas patients undergoing mitral valve replacement and tricuspid valve operations were at decreased risk (p =.). Comparison of second reoperations with first reoperations indicates risk increases for multiple operations (p =.) but not for aortic or mitral valve procedures. Rereplacement of a prosthesis (p =.), coronary bypass grafting at reoperation (p =.6), and advanced age (p =.6) increased the risk for second reoperations. Age is the most consistent predictor of risk for patients undergoing valve reoperations. From the Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, OH. Presented at the Twenty-second Annual Meeting of The Society of Thoracic Surgeons, Washington, DC, Jan -9, 986. Address reprint requests to Dr. Lytle, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, 9 Euclid Ave, Cleveland, OH 446. Patients who undergo valve reoperations are seen with a complex array of problems. Because of the low perioperative risk for most primary cardiac surgical procedures, the gradually increasing number of cardiac operations being performed, and favorable late survival of postoperative patients, many patients survive to become potential candidates for reoperations to repair or replace valves. Deterioration of valves following conservative procedures and late complications of valvular prostheses can necessitate valve reoperation, and most studies of valve reoperation have examined subsets of patients undergoing rereplacement of a prosthesis or replacement of native valves previously treated with conservative procedures [l-6. However, the problem is more extensive, as the coexistence of valvular and coronary pathology and dysfunction of multiple valves create a variegated spectrum of patients who have undergone previous cardiac operations but need reoperation for valve procedures. To examine the perioperative risks and identify determinants of survival, the first, cardiac reoperations for valve procedures at the Cleveland Clinic Foundation were reviewed. Material and Methods With the aid of a computerized cardiovascular information registry, we identified the first,ooo cardiac reoperations that included a valve procedure. Eight hundred ninety-seven patients underwent the, reoperations. Patients undergoing a reoperation for a complex congenital heart procedure were excluded, but patients who underwent an initial congenital operation and subsequent reoperation for a valve procedure were included. Patients were considered to be undergoing reoperation if any previous intrapericardial operation (designated as "initial procedure") had been performed, a definition that includes all intracardiac operations, coronary bypass grafting, resection of ascending aortic aneurysm, closed mitral commissurotomy, mammary artery implantation (Vineberg operation), pericardiectomy, and epicardial poudrage. Previous extrapericardial vascular operations, including ligation of patent ductus arteriosus, resection of aortic coarctation, and carotid endarterectomy, were not considered an initial procedure. After designating the study group, we and trained assistants reviewed the records of the patients selected. Information was coded into a research data base for retrieval and analysis. The variables examined for their relationship with inhospital deaths are listed in Table. "Immediate pre- 6 Ann Thorac Surg 4:6-64, Dec 986

2 6 Lytle, Cosgrove, Taylor, et al: Reoperations for Valve Surgery Table. Variables Tested for Association with In-Hospital Deaths Preoperative clinical variables Age Sex New York Heart Association (NYHA) Functional Class Immediate preoperative condition (stable, shock, cardiac arrest) History of cardiac arrest Rhythm (sinus, atrial fibrillation, paced) Conduction (normal, complete heart block, other conduction defects) Preoperative blood urea nitrogen ( mg/ ml) Preoperative bilintbin (> mg/ ml) Peripheral edema Ascites History of hepatic failure Diabetes History of endocarditis Preoperative angiographic variables Left ventricular function (global) Segmental left ventricular impairment Number of coronary vessels stenotic (%) Left main coronary stenosis (%) Valve status (stenosis, insufficiency, normal) Previous operation-related variables Type of operation Bypass (yesho) Date of previous operation Incision Previous operation at Cleveland Clinic Foundation (yeslno) Reoperation-related variables Date of reoperation Emergency operation Type of valve procedure Coronary bypass grafting Cardioplegia Incision Valve pathology Native valve pathology Endocarditis (active) Prosthetic valve failure Periprosthetic leak operative condition" refers to the patient's state on arriving in the operating room. Left ventricular angiograms were analyzed subjectively for diffuse contraction abnormalities and segmental impairment. Definitions used for the other preoperative clinical and angiographic variables have been reported [, 8. Data regarding the pathological state of the valve were obtained from operative and pathology reports. Major pathology groups and criteria for classification were as follows: Endocarditis: This category refers to active endocarditis and included patients with organisms or inflammation documented on the valve specimen, or who did not fulfill those criteria but who underwent operation while still under prolonged antibiotic treatment for clinical endocarditis. Patients with a history of endocarditis who underwent operation for valve dysfunction that was remote from prolonged antibiotic treatment and whose valves showed neither organisms nor active inflammation were considered to have "healed endocarditis" and were placed in other groups. Periprosthetic leak: In this category were patients with periprosthetic leak and a normally functioning prosthesis, including those with healed endocarditis; patients with active endocarditis were excluded. Prosthetic valve failure: This category excludes patients with active prosthetic valve endocarditis and refers to all other causes of prosthetic valve dysfunction including valve thrombosis, tissue ingrowth, mechanical dysfunction, and calcification and leaflet tears for bioprostheses. No patient underwent operation because of anticipated valve failure. Native valve pathology: This category includes all patients with native valve pathology except those with active native valve endocarditis. Statistical Methods Univariate testing was carried out with chi-square analyses or Fisher's exact test. Variables with at least marginal (p <.) association with mortality in univariate testing were included in multivariate stepwise logistic regression models [9]. Because of the urgency of many of the operations, preoperative catheterization was not carried out in all patients. Therefore, risks for some subgroups were tested using more than one multivariate statistical model. Results Study Group Eight hundred ninety-seven patients underwent,ooo reoperations in a series extending from 98 to 984. There were 8 first reoperations, 8 second reoperations, 6 third reoperations, fourth reoperations, and fifth reoperations. Mortality for first, second, third, fourth, and fifth reoperations was % (9/8), % (9/ 8), 44% (/6), (/), and % (/), respectively. There were 69 aortic valve reoperations including 9 first reoperations (6 deaths [%]), 4 second reoperations ( deaths [%]), and 6 third, fourth, or fifth reoperations ( deaths [%]). For mitral valve procedures there were 48 first reoperations (4 deaths [lo%]), second reoperations (9 deaths [%]), and third, fourth, or fifth reoperations ( deaths [%]). Multiple valve procedures were done as a first reoperation in 4 patients ( deaths [4%]), as a second reoperation in patients ( deaths [%]), and as a third reoperation in patients ( deaths [6%]). More than reoperations increased the risk for mitral procedures (p <.), and more than reoperation increased mortality for multiple valve procedures (p =.Ol), but mortality for aortic reoperations was not significantly influenced by the number of previous procedures. Two hundred seventy-seven of

3 64 The Annals of Thoracic Surgery Vol 4 No 6 December 986 the, reoperations were done for rereplacement of a prosthesis. When patients were grouped according to the date of operation, overall numbers of procedures and risks were: pre-9, 8 procedures and 8 deaths (%); 9-9, 46 procedures and deaths (%); 98-98, 9 procedures and 8 deaths (%); and , 4 procedures and deaths (%). Detailed examinations of risks were carried out for subgroups based on the number of previous cardiac operations and the valve operated on-aortic, mitral, tricuspid, or multiple. First Aortic Valve Reoperation Two hundred thirty-nine patients underwent a first aortic valve reoperation with 6 in-hospital deaths (%) (Table ). The causes of death were: intraoperative myocardial failure, patients (%); postoperative myocardial failure, 4 (%); documented myocardial infarction, (%); renal failure and sepsis, each (8%); and bleeding, respiratory failure, splenic rupture, and multifactors, l each (4%). In total, 8 deaths (69%) were attributed to myocardial dysfunction. Both the age and the prevalence of coronary artery disease have increased recently for patients undergoing a first aortic valve reoperation. In the period, (%) of 9 patients were documented to have stenosis of % or more in at least one coronary vessel, and the mean age was years. Comparable figures for the 8 patients operated on prior to 98 were 8 (9%) with coronary artery disease and a mean age of 49 years. In (%) of the 9 patients, sternal reentry caused catastrophic hemorrhage. Two of these patients died. Twenty-nine patients (%) underwent reoperation for bleeding in the perioperative period, 4 (4%) of whom Table. First Aortic Valve Reoperation: Type of Procedure No. of No. of % Procedure Patients Deaths Mortality AVR AVR + CABG Repair AV periprosthetic leak Repair AV periprosthetic leak + CABG AV conduit AV conduit + CABG AV plasty AV plasty + subaortic resection AV plasty + CABG AV thrombectomy AV thrombectomy + CABG Total 9 6 AVR = aortic valve replacement; CABG = coronary artery bypass grafting; AV = aortic valve died. Blood utilization, while at high levels overall, has decreased in more recent surgical periods. Data on blood usage was available for 6 patients. Mean usage of blood or blood products (fresh frozen plasma or platelets) for patients up to 9 was? ( standard deviation), units whereas for 9 patients from 98 to 984 it was units (p =.6). Overall use decreased because the number of patients who received no blood products increased. Before 98, only patient received no blood products, but from 98 to 984, patients (%) received no blood products (p =.). Patients who did receive transfusion in the more recent surgcal period were given a mean of 9 units. Nine patients (4%) had new postoperative Q waves, of whom died. Seventy patients had postoperative serum glutamic oxaloaortic transaminase (SGOT) elevations greater than units (nomial = 4 units/ ml), and 9 (%) of them died, whereas 4 (%) of the patients with postoperative SGOT levels less than units died (p =,). Postoperative SGOT levels were not available for 9 patients. Preoperative variables (see Table ) with univariate influence (p <.lo) on operative mortality are shown in Table. The type of procedure at reoperation (see Table ) was not significantly associated with mortality. Of the 8 patients with coronary artery disease (stenoses %), 4 underwent bypass grafting at reoperation with 6 (4%) deaths compared with 8 deaths (%) among the 4 who did not receive grafts (p = not significant [NS]). Five patients underwent bypass grafting to treat stenoses of less than %. No initial procedure increased the risk of a first aortic valve reoperation. Major categories of initial procedure and subsequent mortality at reoperation were: aortic valve replacement (/,% [deathhumber of procedures, percent mortality]), aortic valve replacement and coronary bypass grafting (/4, %), mitral valve replacement (/4, 4%), and isolated bypass grafting (4/46, 9%). Combining the groups of patients who had undergone isolated bypass grafting and bypass grafting associated with valve operations at the initial procedure showed that there were 69 patients, 8 (%) of whom died at reoperation. Aortic valve pathology did influence early mortality. Patients with endocarditis were at higher risk; (%) of 9 died (p <.). All deaths occurred in the group of patients undergoing operation for prosthetic valve endocarditis. Thirty-two patients had prosthetic valve failure (8 with bioprostheses, 4 with mechanical prostheses), and (%) death occurred in a patient with failure of a bioprosthesis. Specific pathological findings for the patients with mechanical valve failure were: thrombosis, 9; mechanical dysfunction, ; cloth wear, ; and tissue ingrowth,. Of 8 patients with periprosthetic leak, 8 (%) died; 6 (4%) of 4 for whom the prosthesis was replaced died versus (%) of 8 in whom the leak was repaired (p = NS). The pathology and risk associated with rereplacement of aortic valve prostheses as a first reoperation are shown in Figure.

4 6 Lytle, Cosgrove, Taylor, et al: Reoperations for Valve Surgery Table. First Aortic Valve Reoperation: Univariate Testing of Preoperative Variables Variable Sex Male 9 Female 44 Age (yr) c NYHA Functional Class I IV Edema No Yes BUN mg/ ml > mg/ ml Diabetes No Yes Emergency operation No Yes No. of coronary vessels % None One Two Three LV function Normal Mild Moderate Severe Segmental LV function 4 No. of No. of % P Patients Deaths Mortality Value <..... <...6. NYHA = New York Heart Association; BUN = blood urea nitrogen, LV = left ventricular. One hundred five patients underwent operation for native valve pathology; 9 (9%) died. These patients had operation for other pathological reasons: who died during reoperation for iatrogenic valve damage which occurred during an initial mitral valve replacement done to treat a sarcoma, who had aortic dissection after aortic valve replacement, and who had an ascending aortic aneurysm. MULTIVARIATE TESTING. The multivariate model, which included the entire group of patients undergoing a first aortic valve reoperation, tested the variables in Table, type of valve procedure at reoperation, coronary artery bypass at reoperation or at initial operation, prosthesis rereplacement, immediate preoperative condition, use of cardioplegia, and initial procedure involving a different valve. Angiographic variables were excluded. Age (p =.), sex (increased risk for women) (p =.4), and valve pathology (patients with endocarditis at highest risk and those with prosthetic valve failure at lowest risk) (p =.8) were significant. In the second model, only the 9 patients with complete angiographic data were included, and age, valve pathology, and sex were tested along with preoperative overall left ventricular function, segmental left ventricular function, left main stenosis of % or more, and the number of coronary vessels with stenosis of % or more. Age (p =.), sex (p =.4), and overall left ventricular function (p =.9) were significantly associated with risk; number of vessels stenotic (p =.) and valve pathology (p =.66) were marginally so. Variables independently associated with increased or decreased risk of death were combined to define subgroups at highest and lowest risks. Of 4 patients who were male, were less than 6 years old, had normal left ventricular function, and were without coronary artery disease or endocarditis, only (.%) died. Six of these patients were operated on for prosthetic valve failure with no deaths. At high risk were women older than 6 years with coronary artery disease and abnormal left ventricular function. Of 9 such patients, 4 (44%) died. Mitral Valve Reopera tion Four hundred fifty-eight patients underwent a first mitral valve reoperation (Table 4) with 4 (%) in-hospital deaths. Five patients (% of deaths) died intraoperatively of myocardial failure, (%) died postoperatively of new myocardial infarction, and 8 (8%) died of postoperative myocardial failure without documented new infarction. Other primary causes of death considered cardiac were: ventricular arrhythmias, (ll%), and posterior ventricular rupture, sudden unexplained death, acute valve failure, and tamponade, (%) each. The primary noncardiac causes of death were: sepsis, 6 (%); respiratory failure, (%); stroke, (4%); pulmonary embolus, (4%); and bleeding, (%). There were 6 patients (%) with multisystem failure in whom a primary cause of death could not be discerned. Cardiac causes accounted for 6% of deaths. The reoperative incision was a median sternotomy in 44 patients (44 deaths [lo%]), a left thoracotomy in (no death), and a right thoracotomy in patients ( death [4%]). Catastrophic hemorrhage during repeat sternotomy occurred in patients (%), of whom 4 (%) died. A transseptal intracardiac approach was used to expose the mitral valve in patients (4 deaths). Thirty-eight patients (8%) underwent reoperation for bleeding, of whom (%) died. Data on blood usage were unavailable for 4 patients. Blood product use decreased from a mean of ll ll units per patient for patients through 9 to t units per patient for

5 66 The Annals of Thoracic Surgery Vol 4 No 6 December 986 AORTIC VALVE ENDOCARDITIS PROSTHESIS PERIPROSTHETIC AORTIC 6/6 (8%) FAILURE x LEAK DISSECTION /9 (.So/o) A BP - MP - BP - MP /8 / I9 / BP A MP /9 MITRAL VALVE ENDOCARDITIS PROSTHESIS FAILURE PERIPROSTHETIC LEAK 6/6 (%) BP A MP A - / / - BP - MP 4/ / - Bi - / Fig. First reoperations. Single valve procedures for rereplacement of a prosthesis: prosthesis type, pathology, and mortality, shozun as deathslnurnber of patients (percent mortality). (BP = bioprosthesis; MP = mechanical prosthesis.) patients from 98 to 984 (p =.). Forty-five patients (%) in the more recent surgical period received no blood products compared with (.%) from 98 through 9 (p =.). New Q waves were noted in patients (%), of whom 4 (4%) died. Elevation of postoperative SCOT levels to greater than units was noted in patients (%), (%) of whom died compared with 8 (%) of patients with maximum SCOT levels of less than units. Postoperative SCOT values were not available for 4 patients. The type of procedure at reoperation (see Table 4) correlated with mortality. When subgroups with and without bypass grafting were combined, conservative procedures involving the mitral valve had less risk (6, %) Table 4. First Mitral Valve Reoperation: Type of Procedure Procedure MVR MVR + CABG MV commissurotomy MV commissurotomy + CABG MV plasty Repair MV periprosthetic leak Repair MV periprosthetic leak + CABG MVR + subaortic resection Total No. of No. of % Patients Deaths Mortality MVR = mitral valve replacement; CABG = coronary artery bypass grafting; MV = mihal valve. than did mitral valve replacement (8/, %) or repair of a periprosthetic leak (6, %) (p <.). Preoperative variables univariately associated with inhospital death include those shown in Table. In addition, (8%) of 8 patients with a history of cardiac arrest died (p =.8). Sixteen operations done as an emergency resulted in deaths (%)(p =.). Five of these patients were in shock, of whom died, and of the in cardiac arrest at the initiation of the operation, died. Valve pathology was not significantly associated with operative risk. Eleven patients had endocarditis, and died; all patients operated on for prosthetic valve endocarditis survived. Sixty patients had prosthetic valve failure, and 6 (%) died (4 of [%] with bioprostheses and of [6%] with mechanical prostheses). Specific pathological conditions for the patients with mechanical valve failure were: valve thrombosis, ( death); tissue ingrowth and valve stenosis, ( death); and mechanical dysfunction, 6. Forty-seven patients had periprosthetic leak with 8 deaths (%); 6 (%) of these deaths occurred among the patients whose periprosthetic leaks were repaired and (%) occurred among the patients whose valves were rereplaced. Mortality and pathology for patients undergoing rereplacement of a prosthetic mitral valve are shown in Figure. Of patients with native mitral valve pathology, 9 (9%) died. The type of initial procedure was related to risk at reoperation. Of patients whose initial procedure involved an operation on either the aortic or tricuspid valve, 8 (6%) died at mitral reoperation. This group was at greater risk than patients in the other major categories of initial procedure, including mitral valve replacement (9/94, % [deathshumber of procedures, percent mortality]), open mitral commissurotomy (/9, 9%), closed mitral commissurotomy (/6, %), and isolated coronary bypass grafting (/6, 6%). For 9 patients, the initial operation involved bypass grafting with or without valve procedures. There was a trend toward increased mortality for this subgroup (/9, %)

6 ~ 6 Lytle, Cosgrove, Taylor, et al: Reoperations for Valve Surgery Table. First Mitral Valve Reoperation: Univariate Testing of Preoperative Variables Variable No. of No. of % P Patients Deaths Mortality Value Age (Yr) <. < > 9 4 NYHA Functional Class I 4 8 IV 89 BUN. mg/ ml 4 > mg/ ml 6 Bilirubin. mg/ ml >. mg/ ml NYHA = New York Heart Association; BUN = blood urea nitrogen... versus patients without revascularization at the initial operation (4/49, 9%), but not a significant difference (p =.). The type of incision employed at the initial procedure was also not significant; mortality at reoperation following initial procedures using a median sternotomy was 4 of (%); left thoracotomy, of 4 (8%); right thoracotomy, of (9%); and bilateral thoracotomy, of (%). MULTIVARIATE ANALYSIS. The multivariate model, which included all patients undergoing a first mitral valve reoperation, tested the same variables examined in regard to first aortic valve operations. Increasing age (p <.), previous operation on the aortic or tricuspid valve (p =.), and preoperative shock or cardiac arrest (p =.) increased mortality. The type of procedure was significant (p =.); repair of a periprosthetic leak was associated with highest risk, conservative mitral valve operations with lowest risk, and mitral valve replacements were intermediate. A second multivariate model, which included angiographic variables for the 4 patients for whom complete angiographic data were available, identified age ( p <.), previous aortic valve or tricuspid valve operation ( p =.), and left ventricular function (p =.) as independent predictors of risk. Of the 94 patients less than 6 years old without a previous aortic or tricuspid valve operation and with normal left ventricular function who were not in cardiac arrest or in shock, (4%) died. There were patients more than 6 years old with abnormal left ventricular function and with operations on the aortic or tricuspid valve at the initial procedure; 4 (8%) died at reoperation. Multiple Valve Operations Of the 4 patients who underwent a first reoperation involving multiple valves (Table 6), (4%) died in the. Table 6. First Reoperation for Multiple Valve Procedures Procedure AVR + MVR AVR + MV repair AVR + TVop AVR + MVR + TVop AVR + MV repair + TV OP MVR+TVop MVR + AV repair MVR + AV repair + TV OP AV repair + MV repair MV repair + TV repair AV repair + TV repair Multiple valve reoperation with bypass Total No. of No. of % Patients Deaths Mortality AVR = aortic valve replacement; MVR = mitral valve replacement; MV = mitral valve; repair = conservative native valve operation or repair of periprosthetic leak; TV op = tricuspid valve replacement or repair. hospital. Seven (%) died of intraoperative myocardial failure, (%) of postoperative myocardial failure, (%) of documented perioperative myocardial infarction, (%) of multiple causes, and (%) each of bleeding, sepsis, renal failure, and pulmonary embolism. Twelve deaths (6% of deaths) were due to cardiac causes. All first multiple valve reoperations were done through a median sternotomy. In patients (%), catastrophic hemorrhage occurred, and 4 (%) of these patients died. Twenty-two patients (%) required reoperation for bleeding, 4 of whom (8%) died. Prior to 98, * units of blood products per patient were used and (%) of 9 patients received no blood compared with a mean of f 6 units per patient (p = NS) from 98 to 984 and of 8 patients (8%) who received no blood (p =.). Postoperative SGOT levels were available for 8 patients. Two patients had new Q waves (both died), and of the 44 patients (4%) who had maximum postoperative SGOT levels greater than units, 6 (4%) died. The reoperative procedures are shown in Table 6. There were 6 operations on valves with deaths (%) versus deaths (%) among the 9 patients undergoing double valve reoperation (p =.). Patients undergoing mitral valve replacement and a tricuspid valve operation (either replacement of repair) were at decreased risk with death (%) among patients (p =.6). The type of initial procedure was not associated with mortality; only patients had undergone previous bypass grafting. The preoperative variables univariately associated with risk are shown in Table. Small numbers of pa- 4

7 68 The Annals of Thoracic Surgery Vol 4 No 6 December 986 Table. First Multiple Valve Reoperation: Univariate Testing of Preoperative Variables No. of No. of % P Variable Patients Deaths Mortality Value Ascites Yes No Diabetes No Yes LV function Normal Mild Moderate Severe LV = left ventricular Table 8. Second Valve Reoperation No. of No. of % Procedure Patients Deaths Mortality Aortic valve AVR AVR + CABG Valved conduit Periprosthetic leak Mitral valve. MVR. MVR + CABG Thrombectomy Repair periprosthetic leaks 6 Open mitral commissu- tients in some subgroups precluded testing of the entire range of some variables. For example, only patients years of age or older underwent operation ( death) and of patients who were in shock or who had arrest at operation, died. In the multiple valve group, the pathological causes of valve dysfunction were often disparate, which made each subgroup extremely small. Three patients had endocarditis of at least valve (no deaths), and patients underwent reoperation because of prosthesis failure with 4 (%) deaths; all the deaths occurred in the group of 6 patients undergoing reoperation for mechanical valve failure, whereas none of the patients undergoing operation for failure of a bioprosthesis died. Thirty patients had prosthetic valve rereplaced ( deaths, %), and had prostheses replaced ( death, %). Multivariate testing of the same variables examined in regard to first aortic and mitral reoperations along with the type of multiple valve procedure indicated that diabetes (p =.4) and ascites (p =.) had independent influence increasing risk and that patients undergoing mitral valve replacement and a tricuspid operation were at less risk (p =.). Testing the patients for whom angiograpahic data were available did not identify any angiographic descriptors as significant, although there was a trend associating mortality and abnormal left ventricular function with univariate comparisons. Tricuspid Valve Operation Ten patients underwent a first reoperation for tricuspid valve procedures including replacements ( deaths), tricuspid repairs, and valve exploration. Catastrophic hemorrhage at repeat median sternotomy occurred in patient, who survived. Because of the small numbers of patients, detailed analysis of indicators of risk was not possible. All First Valve Reoperations Multivariate testing with a statistical model that examined all patients undergoing a first valve reoperation rotomy Tricuspid valve TVR Valvoplasty Multiple valves AVR + MVR AVR + MVR + CABG AVR + mitral valve commissurotomy AVR + MVR + TVR MVR + TV op Repair aortic and mitral valve periprosthetic leaks Repair mitral valve periprosthetic leaks + TVR AVR = aortic valve replacement; CABG = coronary artery bypass grafting; MVR = mitral valve replacement; TVR = hicuspid valve replacement; TV op = hicuspid valve replacement or repair. identified age (p <.), preoperative shock or cardiac arrest (p =.Owl), endocarditis (p <.), and triple valve operations (p =.OM) as independent variables increasing risk. Cardioplegia was associated (p =.) with decreased risk. The likelihood of postoperative SGOT elevation had no association with the use of cardioplegia for any first reoperation subgroup. Second Valve Reoperations One hundred twenty-eight patients underwent a second valve reoperation with 9 (%) deaths (Table 8). The number of operations and deaths for valve subgroups were: aortic valve, 4 operations and deaths (%); mitral valve, and 9 (%); tricuspid valve, 4 and ; and multiple valve, and (%). When compared with first reoperations, risk was higher for patients undergoing a second reoperation for a multiple valve procedure (p =.) but not for those having single valve reoperations. The causes of death were: intraoperative myocardial failure, 4 patients; postoperative myocardial failure, 4; stroke, ; documented acute myocardial infarction, ; respiratory failure, ; and hemorrhage, ventricular arrhythmia, tamponade, and multiple causes, each. When examined according to valve subgroups (aortic, mitral, and multiple), the type of proce-

8 69 Lytle, Cosgrove, Taylor, et al: Reoperations for Valve Surgery dure (see Table 8) was not associated with risk. However, when all valve groups were examined together, there were patients who underwent bypass grafting at the second reoperation with (%) deaths compared with 4 deaths (%) among 8 patients not receiving grafts (p =.). Fifty-two patients underwent rereplacement of a prosthesis with (%) deaths versus 6 (9%) deaths among 6 patients who did not undergo prosthesis rereplacement (p =.8). Univariate examination of the preoperative variables listed in Table according to valve subgroups (aortic, mitral, and multiple) did not identify any with a significant (p <.) influence on mortality. There were trends toward increasing mortality with increasing age and NYHA Functional Class. Aortic valve pathology groups and mortality were: endocarditis (all prosthetic valve), 6 and death; native valve pathology, 4 and death; prosthetic valve failure, and death; and periprosthetic leak, 8 and no deaths. Mitral valve groups were: endocarditis (all prosthetic valve), 4 and no deaths; native valve pathology, 4 and death; prosthetic valve failure, 8 with 6 deaths ( of with biological prostheses and of with mechanical valves); and periprosthetic leak, and deaths. Pathology and outcome for patients undergoing a second reoperation that was a single valve operation for aortic or mitral prosthetic valve rereplacement are shown in Figure. Median sternotomy was used at the second reoperation in all instances except for patients who underwent mitral procedures through a right thoracotomy. In patients (4%) catastrophic hemorrhage occurred at reoperative median stemotomy, with no deaths. Reoperation for bleeding was needed in (%) of 4 patients having aortic valve operation ( death), (4%) of patients having mitral valve operation (no deaths), and 4 Fig. Second reoperations. Single valve procedure for rereplacement ofa prosthesis: prosthesis type, pathology, and mortality, shown as deathslnumber of patients (percent mortality). (BP = bioprosthesis; MP = mechanical prosthesis.) (%) of patients having multiple valve operation ( deaths). The mean use of blood products per patient from 98 to 984 for second reoperations was 6 units for aortic valve procedures, 8 8 units for mitral valve procedures, and 4 units for multiple valve procedures. Three of 8 aortic valve patients, of 8 mitral valve patients, and of 6 multiple valve patients received no blood products. None of these figures represent an improvement over the 98 to 9 period. MULTIVARIATE ANALYSIS. For the entire group of patients undergoing a second valve reoperation, multivariate analysis of variables including age, sex, NYHA Functional Class, bypass at reoperation, number of valves reoperated on (aortic versus mitral versus multiple), rereplacement of a prosthesis, endocarditis, and cardioplegia identified prosthesis rereplacement (p =.), bypass at reoperation (p =.6), and age (p =.6) as independent indicators of increased perioperative mortality. Third, Fourth, and Fifth Valve Reoperations The mean age of patients undergoing or more reoperations was 49 years (range, to 6 years), and only patients were older than 6 years. Ten patients had NYHA Functional Class symptoms ( deaths), and had Class IV symptoms (6 deaths). Of 6 patients who underwent a third valve reoperation, (44%) died. Four patients underwent aortic valve replacement, for periprosthetic leak ( of whom died of ventricular arrhythmias), for endocarditis, and for calcific stenosis of the native aortic valve. Eight patients had a third reoperation for mitral valve disease, and 4 died. Two patients were operated on for thrombosed mechanical mitral prostheses (both died, following thrombectomy and the other, a valve replacement), and patient underwent operation for mechanical valve dysfunction. Three patients had periprosthetic leaks, of whom died following valve replacement, of sepsis and the other of renal failure. Mitral valves were replaced in patients because of rheumatic native valve disease; AORTIC VALVE ENDOCARDITIS PROSTHESIS FAILURE PERIPROSTHETIC LEAK /6 / / A - BP MP BP A MP n - - BP - UP / / / m ENDOCARDITIS MITRAL VALVE PROSTHESIS FAILURE 6/ A - BP MP / j/. A MP PERIPROSTHETIC LEAK /6 - BP _. /

9 64 The Annals of Thoracic Surgery Vol 4 No 6 December 986 neither died. Three multiple valve operations were done. One patient underwent aortic and mitral valve replacement for dysfunction of mechanical prostheses, and another received mitral and tricuspid prostheses for periprosthetic leak; both died. One patient undergoing repair of an aortic periprosthetic leak and replacement of a mitral prosthesis for healed endocarditis survived. One patient had rereplacement of a thrombosed mechanical tricuspid prosthesis without difficulty. In of the 6 patients, major vascular structures were entered during repeat median sternotomy; none of these patients survived. Two patients had fourth reoperations for valve replacement because of periprosthetic leaks ( aortic, mitral), and survived. Two fifth reoperations ( aortic, l mitral) were performed, both for periprosthetic leak. Neither patient survived. Complications of Reoperative Sternotomy In a total of 6 patients, catastrophic hemorrhage occurred during sternal reentry. The structures entered and the number of eventual deaths were: right atrium, and 4 deaths; right ventricle, 6 and 4 deaths; innominate vein, 4 and deaths; aorta, and death; saphenous vein graft, 4; internal mammary artery graft, ; pulmonary artery, and death; inferior vena cava, ; and right coronary artery, and death. Of the deaths, occurred intraoperatively. Comment The mortality associated with reoperations for valvular heart disease is higher than that for primary valve procedures. Studies [lo, of valve procedures that examine risk with multivariate statistical methods have disagreed as to whether or not previous cardiac operation is an independent variable increasing mortality. Although we did not examine data for primary valve operations in this study, perioperative mortality for these reoperations clearly exceeds that for patients undergoing primary valve procedures at our institution when compared by univariate analysis [, 8. For patients undergoing single valve procedures, second reoperations were not more risky than first reoperations, but by the third reoperation, risks were high for all subgroups. Patients undergoing reoperative valve operations are a very heterogeneous group, and one of the goals of this study was to define more precisely high-risk and low-risk subgroups. Age had a major impact on mortality. It is not surprising that age was an indicator of risk, since it has been shown to influence to some degree the mortality associated with primary valve procedures, coronary bypass grafting, and combinations of these procedures. However, advanced age increased mortality much more dramatically for this series than it has for primary procedures. Patients undergoing first single-valve reoperation had a mortality of % if they were years or older, % if they were between 6 and years, and only 4% if they were less than 6 years old. Women were at increased risk for aortic valve reoperations but not for mitral procedures. We [, 8 had also found women to be at increased risk when undergoing aortic valve replacement combined with bypass grafting but not when mitral valve replacement is combined with revascularization. Preoperative functional class had only minor influence. When classed according to NYHA criteria, univariate analysis showed that patients undergoing a first mitral valve reoperation with Class IV symptoms were at increased risk, but this was not significant in the multivariate model. Only the small group of patients whose hemodynamic derangement was so profound that they were in cardiac arrest or shock at the time of operation were identified as a high-risk group in the mutivariate setting. The risk of operation for asymptomatic patients could not be assessed because none were included in this series. Because many severely ill patients did not undergo catheterization prior to operation, the predictive value of angiographic variables was more difficult to define. Nevertheless, abnormal left ventricular function adversely influenced risk for both aortic valve and mitral valve procedures. The presence of coronary artery disease slightly increased risk for patients undergoing first aortic valve reoperations and second reoperations but did not influence the outcome for patients undergoing first mitral valve reoperations. Severe coronary artery atherosclerosis was not present in enough patients undergoing multiple valve procedures to evaluate its effect. When the subset of patients undergoing first aortic valve reoperations who had coronary artery disease was considered, those patients who underwent bypass grafting had slightly lower risk compared with those whose coronary disease was left untreated, but the difference was not statistically significant. There was a discernible trend toward higher risk the more valves that were abnormal. Patients undergoing first mitral reoperations who had had aortic or tricuspid procedures during their initial operation were at increased risk. First reoperations on multiple valves carried a slight but insignificant increase in risk over single valve procedures and when all first reoperations were tested together, triple valve operations were associated with a higher mortality. For patients undergoing a second reoperation, multiple valve procedures were associated with significantly increased mortality. For first reoperations, the type of initial procedure did not appear to influence the mortality of reoperation except for those patients whose initial procedure was carried out on a valve different from the valve reoperated on. The risk of first reoperations following conservative mitral procedures and mitral valve replacement was equivalent, and isolated coronary revascularization as an initial procedure did not significantly increase mortality for any subgroup of valve reoperations. Reoperations for late prosthesis-related complications deserve careful analysis because opinions concerning strategies for primary valve replacement may be based

10 64 Lytle, Cosgrove, Taylor, et al: Reoperations for Valve Surgery in part not only on the likelihood of reoperation but also on the risk of those reoperative procedures. Patients undergoing first reoperations for replacement of a prosthesis were not at increased risk when compared with other first reoperations but when second reoperations were considered, patients having prosthesis replacement had significantly higher mortality. In our series, no patient underwent a repeat procedure because of predicted failure of a well-functioning prosthetic valve or because of recurrent embolism in the absence of other symptoms. Previous studies (, 6, have demonstrated that reoperation for those indications is associated with low risk. Reoperations for endocarditis, on the other hand, have been associated with high risk [-. In our series that was true for patients undergoing first aortic valve reoperations for prosthetic valve endocarditis ( patients and deaths), but patients with active endocarditis of prosthetic mitral valves had no deaths in reoperations (including prosthetic mitral rereplacements that were part of multiple valve procedures. Contrary to some previous reports [4, 6-8], we did not find that reoperation for dysfunctional mechanical prostheses was associated with high mortality. First reoperation to rereplace bioprostheses that had failed had a risk ( of, %) similar to that reported by Bortolotti and co-workers [9]. However, second reoperations for failed bioprostheses were not as benign, as 4 of 9 patients died. Periprosthetic leak as an indication for either first or second single valve reoperations was associated with a mortality of approximately %. For aortic reoperations, there was a trend toward a decreased risk when the leak could be repaired. However, repair of mitral periprosthetic leaks was not as successful, with a risk of more than twice that of a mitral periprosthetic leak corrected by valve replacement. Operation-related variables could not be demonstrated to have had a major impact. Cardioplegia had a marginal association with decreased risk in the multivariate model examining all first reoperations, but not in other statistical models. It may be that the changes in the patient population (older patients with more coronary disease) have masked a beneficial influence of enhanced myocardial protection. Reoperations for conservative mitral valve procedures (commissurotomy or valvoplasty) were camed out at extremely low risk, which supports the continued use of these operations when the valvular pathology is appropriate. Twenty-five patients underwent mitral reoperations through a right thoracotomy with only death, an observation to be considered when a median sternotomy is not needed for aortic exposure. Most perioperative deaths were cardiac related. Catastrophic hemorrhage during reoperative median sternotomy occurred in 6 patients and greatly influenced the outcome of that subset, as of the patients died. However, the technical problems associated with a reoperative median sternotomy did not have a dramatic impact on overal mortality. Myocardial function did have a strong influence. Perioperative transmural myo- cardial infarction (as manifested by new Q waves) was not common but when it occurred, it was associated with a high subsequent mortality. Despite relative nonspecificity, SGOT levels were used as an indicator of postoperative cardiac enzyme elevation because this measurement was the only value consistently available throughout the study period. Postoperative elevation of SGOT was common, occumng in 9% of first reoperations. Patients whose highest postoperative SGOT levels were less than units had a % risk of subsequent death, whereas of the first reoperations where enzyme levels were elevated, 8% resulted in perioperative death. Perioperative myocardial protection has not been ideal, despite the use of cold crystalline potassium cardioplegia and systemic hypothermia, and the inability to completely protect the myocardium contributed in a major way to mortality. The common thread meandering through the analyses of the multiple subgroups of this study is that previous operation is a factor that magnifies the negative influence of other variables. By itself, previous operation did not create high risk, particularly when patients undergoing a first reoperation were considered. In the absence of specific high-risk characteristics, first reoperations were quite safe. However, the addition of highrisk characteristics elevated mortality more dramatically than has been the case when primary operations have been considered. For example, when we studied patients undergoing primary aortic valve replacement combined with bypass grafting, we found advanced age to have a slight negative influence on in-hospital risk, but it did not have nearly as strong an impact as it did on patients more than years of age undergoing a first aortic valve reoperation for whom mortality was 44%. Further, age, coronary artery disease, the number of valves involved, and the number of previous operations are factors that have a more profound impact when combined than they do individually. First reoperations for single valve procedures were relatively safe except when performed in older patients. There was a trend toward increasing risk when coronary artery disease was added to the pathological condition, a trend that became striking when second reoperations were examined. Second reoperations for single valve procedures did not carry a high mortality, but multiple valve operations as second operations camed higher risk compared with first multiple valve reoperations. Few patients, particularly those with high-risk indicators, undergo valve reoperations that, over the long term, are truly elective. The timing of repeat valve operation can sometimes be manipulated, but effective alternative therapy for the patient with severe valve dysfunction is not apparent. It is tempting to adjust strategies of primary valve surgery (such as routine placement of mechanical prostheses) in ways designed to decrease the need for reoperation. However, the majority of patients in our study who underwent operation for valve prosthesis-related complications had mechanical prostheses, and other reviews of the long-term results of

11 64 The Annals of Thoracic Surgery Vol 4 No 6 December 986 primary valve replacement have noted similar proportions of patients with mechanical valves and bioprostheses undergoing reoperation, although for different indications [4]. These observations combined with the apparently enhanced survival for some subsets of patients receiving bioprostheses (, 8, or undergoing conservative valve procedures indicate to us that routine use of mechanical prostheses is not an optimal solution to the problem of valve reoperations. Finally, the fact that only 8% of the patients in this series underwent reoperation because of a need for replacement of a prosthesis makes it obvious that the problems of valve reoperation will continue to present themselves even in the unlikely event a permanent valve prosthesis emerges. We are indebted to Maura Schnauffer for data collection, project management, and assistance with data analysis. References Rossiter SJ, Miller DC, Stinson EB, et al: Aortic and mitral prosthetic valve reoperations. Arch Surg 4:9, 99 Sandza JG Jr, Clark RE, Ferguson TB, et al: Replacement of prosthetic heart valves: fifteen-year experience. J Thorac Cardiovasc Surg 4:864, 9 Magdligan DJ Jr, Lam CR, Lewis JW Jr, Davila JC: Mitral valve: the third time around. Circulation 8:Suppl :6, 98 Cohn LH, Koster JK Jr, VandeVanter S, Collins JJ Jr: The inhospital risk of rereplacement of dysfunctional mitral and aortic valves. Circulation 66: Suppl :, 98 Husebye DG, Pluth JR, Piehler JM, et al: Reoperation on prosthetic heart valves: an analysis of risk factors in patients. J Thorac Cardiovasc Surg 864, 98 Wideman FE, Blackstone EH, Kirklin JW, et al: Hospital mortality of re-replacement of the aortic valve: incremental risk factors. J Thorac Cardiovasc Surg 8:69, 98 Lytle BW, Cosgrove DM, Loop FD, et al: Replacement of aortic valve combined with myocardial revascularization: determinants of early and late risk for patients, Circulation 68:49, 98 Lytle BW, Cosgrove DM, Gill CC, et al: Mitral valve replacement combined with myocardial revascularization: early and late results for patients, 9 to 98. Circulation :9, 98 Cox DR: The Analysis of Binary Data. London, Chapman & Hall, 9 Blackstone EH, Kirklin JW: Death and other time-related events after valve replacement. Circulation, 98 Scott WC, Miller DC, Haverich A, et al: Operative risk of mitral valve replacement: discriminant analysis of,9 procedures. Circulation : Suppl8, 98 Reitz BA, Stinson EB, Griepp RB, Shumway NE: Tissue valve replacement of prosthetic heart valves for throm- boembolism. Am J Cardiol 4:, 98 Stewart S, DeWeese JA: The determinants of survival following reoperation on prosthetic cardiac valves. Ann Thorac Surg :, 98 Miller DC, Oyer PE, Stinson EB, et al: Ten to fifteen year reassessment of the performance characteristics of the Stan-Edwards Model 6 mitral valve prosthesis. J Thorac Cardiovasc Surg 8:, 98. Ivert TSA, Dismukes WE, Cobbs CG, et al: Prosthetic valve endocarditis. Circulation 69, Maronas JM, Rufilanchas JJ, Villagra F, et al: Reoperation for dysfunction of the Bjork-Shiley mitral disc prosthesis: report of eight cases. Am Heart J 9:6, 9. Magilligan DJ, Oyama C, Alan M: Comparison of dysfunction with mechanical and porcine mitral valve prostheses. Circulation : Suppl :9, Karp RB, Cyras RJ, Blackstone EH, et al: The Bjork-Shiley valve: intermediate-term follow-up. J Thorac Cardiovasc Surg 86,98 9. Bortolotti U, Milano A, Mazzucco A, et al: Results of reoperation for primary tissue failure of porcine bioprostheses. J Thorac Cardiovasc Surg 9:64, 98. Cohn LH, Alfred EN, DiSesa VJ, et al: Early and late risk of aortic valve replacement. J Thorac Cardiovasc Surg 88:69, 984 Discussion OR. JAMES K. KIRKLIN (Birmingham, AL): I thank Dr. Lytle for providing me with a copy of his rather extensive manuscript, and I compliment him and his co-authors on a very nice presentation and a superb and extremely detailed study using multivariate logistic techniques of analysis in this rather heterogeneous group of patients. Perhaps some of the underlying truths generated by this study are underscored by a much less extensive analysis carried out at the University of Alabama at Birmingham on rereplacement of aortic valve prostheses for the years 9 to 99 (Wideman FE, Blackstone EH, Kirklin JW, et al: Hospital mortality of re-replacement of the aortic valve; incremental risk factors. J Thorac Cardiovasc Surg 8:69, 98). Of note is that for initial valve replacement and actually for the first rereplacement, the mortality was quite low. But there was a significant and important increase in mortality with more than rereplacement. Similarly, Dr. Lytle has found that with more than operations, there was an increased risk of death for mitral valve replacement and for multiple valve replacements. Interestingly, however, at the Cleveland Clinic, they did not find this same risk for aortic valve replacement. But these operations are clearly more challenging and include a higher-risk subset of patients than those patients undergoing primary valve replacement, and certainly require special consideration in our surgical planning. I ask Dr. Lytle if he would comment on what knowledge he has of the incidence of periprosthetic leak as it relates to the number of operations performed on either the aortic or the mitral valve from his data analysis. Also, has this experience in this rather detailed analysis altered the views of the Cleveland Clinic regarding the choice of prosthesis for primary valve replacement? It is noteworthy in Dr. Lytle s analysis that myocardial dysfunction was associated with a high percentage of the hospital deaths. Specifically, at first reoperation for aortic valve replacement, as many as 69% of the deaths were attributed to myocardial dysfunction and 6% of the deaths after mitral valve rereplacement were attributed to myocardial dysfunction. Similarly at the University of Alabama in the same era, acute and chronic cardiac failure accounted for 6% of the hospital deaths after aortic prosthetic valve rereplacement (Wideman et al). I think this emphasizes the very important problem of myocardial preservation in this subset of patients who frequently have evidence of left ventricular hypertrophy, extensive suben-

12 64 Lytle, Cosgrove, Taylor, et al: Reoperations for Valve Surgery docardial fibrosis, and reduced myocardial reserves. Perhaps the extreme form of decreased myocardial reserves is noted in those patients who are seen in shock, and Dr. Lytle has found this to be an incremental risk factor for those patients undergoing reoperative valve replacement. I wonder if Dr. Lytle would also comment on his current recommendations for myocardial preservation or any alterations that are made at the Cleveland Clinic in this potentially difficult subset of patients. Dr. Lytle has also noted a small but important incidence of acadents at repeat stemotomy. I wonder if he would comment on any changes or evolution in their techniques to prevent this problem. Finally, I have one word about prosthetic valve endocarditis, which has been a very difficult and high-risk situation for patients undergoing rereplacement of valves. Dr. Lytle mentioned that about 4% of patients with aortic prosthetic valve endocarditis died at reoperation, and this was an important risk factor. Likewise, at the University of Alabama there was an important increase in hospital mortality with aortic valve rereplacement for endocarditis (Wideman et al). I think this emphasizes the great importance of making every effort to prevent contamination in the operating room at the initial operation for valve replacement. Again, I congratulate Dr. Lytle and his colleagues on a really very nice study. DR. LYTLE: I thank Dr. Kirklin for his observations. I cannot comment on the incidence of periprosthetic leak following reoperation since we have not completed our long-term followup of these patients. Catastrophic hemorrhage during repeat median stemotomy occurred in 6 of the,ooo reoperations. It occurred in 8 first reoperations (.%), (4%) second reoperations, and (9%) third reoperations. This complication was associated with a high mortality, as of the 6 patients eventually died. When we examined causes of perioperative deaths, we found % were noncardiac and % were classified as technical, a category in which we included catastrophic hemorrhage during median stemotomy and posterior ventricular rupture following mitral valve replacement. Close to 6% of all deaths were cardiac in nature, and most appeared to be related to myocardial dysfunction. We have not discussed myocardial protection in much detail because it did not appear to have a strong influence on mortality. The use of cardioplegia is a relatively recent development and is covariant with many patient-related variables that can increase risk, possibly masking a beneficial influence of cardioplegia. Obviously, however, myocardial protection during these reoperations was not optimal, and we will need to look at this closely. Another question was whether the results of this study have changed our strategies of prosthesis selection for primary operations. Not in a major way. We have a preference for bioprostheses because our studies of combined valve and coronary procedures show improved survival for patients with bioprostheses. Further, the risk of a first reoperation for rereplacement of a prosthesis has not been high except for patients with aortic valve endocarditis. However, second reoperations for rereplacement of a failed bioprostheses, although small in number, were associated with a relatively high risk. The use of mechanical prostheses does not ensure tkeedom from reoperation.