Cardiac disease is well known to be the leading cause

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1 Coronary Artery Bypass Grafting in Who Require Long-Term Dialysis Leena Khaitan, MD, Francis P. Sutter, DO, and Scott M. Goldman, MD Main Line Cardiothoracic Surgeons, Lankenau Hospital, Jefferson Health System, Wynnewood, Pennsylvania Background. Should coronary artery bypass grafting (CABG) be performed in patients on long-term dialysis? This subject has been debated for several years. We retrospectively reviewed the charts of all patients who had CABG from August 1989 to October Methods. We identified 70 patients who were on longterm dialysis and had CABG during that time period. were evaluated by chart review and telephone survey. Forty-nine patients (70%) had unstable angina and 37 patients (52%) had triple vessel disease. Patient risk factors included 60 patients with hypertension (85%), 40 patients with diabetes mellitus (57%), 35 patients who had congestive heart failure (50%), 35 patients who had a previous myocardial infarction (50%), and 31 smokers (44%). Operative procedures included 49 patients who had CABG only and 21 patients who had concomitant CABG with valve replacement or repair. During the postoperative period, complications developed in 50% of patients. Results. Review of these complications showed that 25% of patients required prolonged mechanical ventilation, and 10% of patients had septicemia. Operative mortality was high, with 10 patient deaths (14.3%) within 30 days of the procedure. Six (60%) of these deaths occurred in patients who had CABG and valve repair or replacement. Long-term follow up at 50.3 months showed no improvement in survival in patients who had CABG compared with the known mortality rate of 22% per year in dialysis patients regardless of comorbid conditions. Quality of life subjectively improved in only 41% of patients in follow-up telephone survey. Conclusions. requiring long-term dialysis with coexistent severe cardiac disease should be thoroughly evaluated preoperatively. One must weigh the high morbidity and mortality risk against the limited long-term resolution of angina and ultimate survival. (Ann Thorac Surg 2000;69:1135 9) 2000 by The Society of Thoracic Surgeons Cardiac disease is well known to be the leading cause of death in dialysis patients; it accounts for 47% of deaths in the dialysis-dependent patient population according to the latest renal database [1]. In this patient population cardiac death is higher because of the presence of hypertension, hyperlipidemia, and abnormal carbohydrate metabolism leading to accelerated atherosclerosis [2 4]. Coronary artery bypass grafting (CABG) has become the standard of care for dialysis patients with cardiac disease that is uncontrollable with medical therapy. This becomes increasingly important as more patients go on dialysis, and the dialysis population becomes older. There is a direct correlation between cardiac death and age in the dialysis population. In patients aged 20 to 64 years, cardiac disease accounts for a death rate of 85.3 per 1,000 patient years. In patients aged more than 65 years, cardiac disease accounts for a death rate of per 1,000 years [1]. The first CABG performed in a patient with chronic renal failure was in 1974 by Menzoin and associates [5]. Since then many case reports and retrospective reviews in small groups of patients have been published regarding the benefit and feasibility of CABG in this patient Accepted for publication Oct 2, Address reprint requests to Dr Sutter, Lankenau Hospital, Main Line Cardiothoracic Surgeons, Medical Science Building, Suite 280, 100 Lancaster Ave, Wynnewood, PA 19066; mlcts2220@aol.com. population. Some groups have shown improved survival and improved quality of life [6 9]. Other studies have shown the opposite [10 12]. And yet other studies have shown an improved quality of life but no improvement in survival [13 15]. Because most publications are in groups of 30 patients or fewer, one can make observations but no steadfast conclusions. Therefore CABG in the dialysis patient remains a debated issue. We reviewed our experience in 70 patients who are on long-term dialysis and had cardiac surgery. We studied subgroups that are at higher risk to determine whether CABG is efficacious in this patient population in terms of quality of life and patient survival. and Methods We retrospectively reviewed our ongoing Society of Thoracic Surgery database at The Lankenau Medical Center to identify patients who are on chronic dialysis and who had CABG between August 1, 1989, and October 31, Only patients who were already on dialysis at the time of surgery and dependent on dialysis were included. All patients who became dialysis dependent after CABG This article has been selected for the open discussion forum on the STS Web site: by The Society of Thoracic Surgeons /00/$20.00 Published by Elsevier Science Inc PII S (99)

2 1136 KHAITAN ET AL Ann Thorac Surg CABG IN DIALYSIS PATIENTS 2000;69: Table 1. Survey Questions 1. How did the surgery affect your quality of life in terms of your living situation? 11% of patients who were living independently now live in assisted living 5% of patients who were living independently now live in a nursing home 76% of patients living situation stayed the same 2. How long did it take you to recover from the operation? In all patients surveyed, it took approximately 2.2 months to recover, on average 3. Did your presenting symptoms improve after your heart surgery? 65% of patients said yes, the symptoms improved 24% of patients said no, the symptoms did not improve 11% of patients said they could not remember 4. Is your overall health the same/better/worse since surgery? And in what way? 14.8% of patients said their overall health status is the same 41% of patients said their overall health status is better 33% of patients said their health status is worse 5. How has the surgery affected your lifestyle? 13% of patients who were hospitalized infrequently before their cardiac surgery are now hospitalized frequently 26% of patients report fewer hospitalizations after their cardiac surgery 55% of patients report the frequency of hospitalizations to be unchanged 6. Have you had angina or shortness of breath since the surgery? If yes, how long after your procedure? 31% of patients reported cardiac symptoms after the procedure 68% had no recurrent cardiac symptoms after the procedure 7. Have you been admitted to the hospital since your CABG for cardiac disease? If yes, how long after your procedure? Have you been admitted more than once? Have you had any cardiac interventions since your CABG? 35% were admitted to the hospital since their operation for cardiac reasons 5% of patients have required a cardiac intervention since CABG were excluded from this study as were patients with chronic renal failure who were not on dialysis and patients with chronic renal insufficiency. Information was also obtained from patient chart review and by telephone survey. Telephone survey was conducted by two people. The patient or the closest living relative was interviewed. All were asked a standardized set of questions in an objective format. Telephone interview focused on questions regarding the patients quality of life with regards to their living situation (independent versus assisted), their overall health status since the operation, frequency of hospitalizations, and cardiac symptoms since CABG (Table 1). Data were analyzed using a 2 analysis, Fischer exact test, Wilcoxon analysis, Kaplan-Meier estimates, and a multivariable model. A series of univariable Cox proportional hazards models was used to identify significant predictors of survival. Kaplan-Meier survival curves were computed to compare patient groups and account for variable follow-up times. From August 1989 to October 1997, 7,200 patients had cardiac procedures at the Lankenau Hospital. Seventy patients were identified who fit inclusion criteria. There were 44 men and 26 women. Mean age was 62.5 years with a range of 37 to 83 years. At the time of CABG, 58 patients were on hemodialysis, and 12 patients were on peritoneal dialysis. All patients were followed by renal consultants throughout their hospitalization. Most patients had renal failure secondary to diabetes or hypertension. A high number of risk factors were noted in the population. Forty-nine patients (70%) had unstable angina, 40 patients (57%) had diabetes mellitus, 35 patients (50%) had congestive heart failure (CHF), and 35 patients (50%) had preoperative myocardial infarction (Table 2). All patients had CABG, but with 50 patients had CABG only and 20 patients had CABG with valve replacement or repair. Presenting symptoms included angina, shortness of breath, myocardial infarction, and syncope. The indication for the procedure in 67 patients was failure of medical therapy to treat cardiac disease. The other 3 patients had the procedure after they were noted to have significant cardiac disease during examination for renal transplantation. Another 5 patients who later had renal transplant were placed on the transplant list after their cardiac operation. Criteria for renal transplantation are based on the Patient Care and Education Committee of the American Society of Transplant Physicians [16]. Table 2. Patient Risk Factors Risk Factor Number of %of Hypertension Diabetes mellitus Congestive heart failure Smoker Peripheral vascular disease a Hypercholesterolemia Cerebrovascular disease Chronic obstructive pulmonary disease Preoperative myocardial infarction Triple vessel disease Unstable angina New York Heart Association class I II III IV Left main artery 50% a Peripheral vascular disease is defined as patients who have claudication or had a peripheral bypass procedure.

3 Ann Thorac Surg KHAITAN ET AL 2000;69: CABG IN DIALYSIS PATIENTS 1137 Table 3. Complications Table 4. Causes of Death Complication Number of %of Cause of Death Perioperative Death a Late Death Prolonged mechanical ventilation Atrial fibrillation Gastrointestinal complication a 8 11 Septicemia 7 10 Pneumonia 7 10 Reoperative bleeding 7 10 Transfusion requirement Cerebrovascular accident 6 8 Cardiac 5 11 Pulmonary 3 Sepsis 3 1 Renal failure 4 Malignancy 1 Multisystem organ failure 2 2 Unknown 5 a Death within 30 days of procedure. a Defined as bleeding or ileus postoperatively. Results Short-Term Follow-up Postoperatively, 50% of patients had complications, with an average of three complications per patient. The most severe complications were those of prolonged mechanical ventilation (18 patients, 26%), atrial fibrillation (15 patients, 21%), and gastrointestinal complications (8 patients, 11%). All 70 patients (100%) received perioperative transfusions (Table 2). Average hospital stay was 24 days per patient. There were no complications in the 8 patients who later had kidney transplant. Hospital death, defined as occurring within 30 days of operation, was high at 14.3% (10 patients). Five patients died of cardiac causes, 3 died of sepsis, and 2 patients died secondary to multisystem organ failure (Table 3). A higher mortality rate was also noted in the older patients, with seven of the 10 deaths (70%) occurring in patients older than 65 years. were also subgrouped into those who had CABG alone versus CABG with valve replacement or repair. Six of the hospital deaths occurred in the 20 patients who had concomitant valvular procedures (30%). Long-Term Follow-Up Mean follow-up time was 50.3 months in the total patient population. Only 6 patients were lost to follow-up. Of the remaining 64 patients, 37 are currently deceased. There were 27 late deaths. Twenty-seven patients are currently alive. Mean survival after CABG was 40 months. Mean time to death after CABG was 29 months (Fig 1). In the CABG and valve operation subgroup, mean survival was only 20.7 months. Mean time to death after CABG with valve replacement or repair was 15 months. The causes of late death included 11 patients who died of cardiac causes, 3 of pulmonary causes, and 2 patients of multisystem organ failure (Table 4). Four patients were listed as dying from renal failure. These patients opted to discharge themselves from dialysis secondary to other medical conditions and died of uremia. Eight patients later had renal transplants, and all are currently alive and doing well. Only 1 of the patients who went on to transplant had both CABG and valve repair. Three of these patients had the CABG in preparation for the renal transplant. The other 5 patients were considered to be transplant candidates after having their cardiac procedure. The criteria used for transplant are best defined by the American Society of Transplant Physicians [16]. Statistical analysis was done to identify the subgroup of patients who had worse outcomes after CABG. Risk factors that were considered included age, cardiomegaly, CHF, diabetes, and hypertension. In a univariable and multivariable model, the only risk factors that were noted to be statistically significant were CHF ( p 0.01) and cardiomegaly ( p 0.02) (Table 5). In Figure 1, the expected survival of dialysis patients after CABG is shown. Fifty percent of patients were dead at 38 months follow-up. with cardiomegaly have a risk of Table 5. Relative Risk Factor Comparison Between Alive Versus Dead Risk Factor Alive (n 27) Dead (n 37) p Value Fig 1. Kaplan-Meier Survival Estimates for all. Cardiomegaly Congestive heart failure Chronic obstructive pulmonary disease Subendocardial infarct Female gender Pulmonary hypertension

4 1138 KHAITAN ET AL Ann Thorac Surg CABG IN DIALYSIS PATIENTS 2000;69: mortality that is increased threefold compared with the other patients who had CABG (Fig 2). In patients with CHF, the relative risk was 3.75 (Fig 3). In Figures 2 and 3, it is evident that the patients with these risk factors are likely to die sooner after their CABG. Although the perioperative mortality rate was higher in patients older than 65 years, this was not an independent risk factor for long-term survival. A telephone survey was conducted to assess patient survival and satisfaction with the procedure. The 10 patients who died perioperatively (within 30 days of their procedure) and the 6 patients lost to follow-up were excluded. For the few patients who could not be located, additional information was obtained by chart review. Twenty-seven patients were contacted by telephone. At the time of telephone survey, 27 patients were deceased, and the closest living relative was interviewed. Most patients said that their living situation remained the same after the cardiac procedure. Sixty-five percent said their cardiac symptoms improved postoperatively, but only 41% said that their overall health status improved. This translates to 59% of patients feeling the same or worse after their procedure (Table 1). Fig 2. Kaplan-Meier Survival Estimates by Cardiomegaly. Fig 3. Kaplan-Meier Survival Estimates by Congestive Heart Failure. Comment In this study we present a large series of dialysisdependent patients who had CABG. It is known that these patients have worse outcomes than the usual patient who undergoes open heart operation, yet these patients continue to appear on the cardiothoracic surgeon s schedule. Many studies have been published reviewing small groups of patients with varying conclusions some report patients with longer survival, others show patients to have higher morbidity and mortality rates. It is difficult to compare all of these studies because the inclusion criteria are inconsistent. We have included only patients who were dialysis dependent and had CABG with or without valve replacement or repair. In the short term, these patients generally fared poorly. The perioperative mortality rate was 14.3% in this study, and these patients had many complications and prolonged hospital stays. In the subgroup that had concomitant valvular and cardiac revascularization, the perioperative mortality rate was 30%. In the nondialysis population at this institution, the perioperative mortality rate is 2% with hospital stays of 7 days or fewer. With the tremendous increase in morbidity, it is difficult to operate on these patients. The obvious next question is, what would happen to these patients in this time period if they were not revascularized. Unfortunately, the answer to this question is not known and it is difficult to obtain. Such a prospective randomized study cannot be done. At long-term follow-up, the mortality rate in this population was similar to that of the general dialysis population. The expected mortality rate for any dialysis patient is 22% per year [1]. In patients who had CABG at this institution, the mortality rate also was 22% per year. If one assumes that these patients would have died sooner without surgical intervention, then perhaps the patient s outcomes were improved by revascularization. Some of the interesting findings in this review include the subgroups identified as being at higher risk of death after CABG. with cardiomegaly and CHF had a mortality risk increased three to four times that of the remainder of the patients in this group. Also, patients with concomitant valve operations had a decreased survival compared with the CABG only patients. In the follow-up telephone survey, we found that 33% of patients thought that their health status deteriorated after the cardiac operation, and 15% of patients thought that their health status did not change. Although the questions are general and subjective, they were asked objectively, and patients responded honestly. When asked more specifically, 65% of patients stated that the symptom that led to their cardiac procedure improved. However, 35% felt their cardiac symptoms did not improve. Should cardiac surgeons continue to perform CABG in this group of patients? This is a difficult question to answer because at least 40% of patients do feel better in

5 Ann Thorac Surg KHAITAN ET AL 2000;69: CABG IN DIALYSIS PATIENTS 1139 the long term. However, the risk of death is high in dialysis-dependent patients who have CABG. The patient should be aware of this. If one assumes that these patients were so ill before their CABG and certainly would have not survived much longer, then CABG in this patient population may be justified. Operating on these patients could improve the final outcome. Again, without a prospective randomized study, this question cannot be answered. The patients who later have kidney transplant benefit greatly from their CABG. These patients comprise a different population. The conditions and performance status that must be met to qualify for transplantation are rigorous [16]. Most would not be able to have a transplant without a cardiac operation. Only 3 patients who had transplants in this series had their cardiac procedure as a result of findings during the preoperative transplant examination. The other 5 patients were placed on the list only after having their CABG. These transplant patients may be a slightly different patient population, as all have done well in our experience and had no major complications in the perioperative period. Such patients should have CABG if needed. For dialysis-dependent patients not in line for transplant but with medically uncontrollable cardiac disease, the question becomes more difficult. There has been no prospective randomized study to compare how patients with the same disease and no CABG fare. One casecontrolled study in a small group of patients found that the mortality rate is much higher in the dialysis patient compared with a nondialysis patient with the same cardiac profile [11]. That study would be more interesting if the control group was also dialysis dependent but did not have CABG. In our experience, survival is the same regardless of whether a patient on long-term dialysis has CABG. Additionally, patients with CHF and cardiomegaly have a greater risk of dying than even the average dialysis patient who has CABG. Based on these data, one cannot refuse to perform CABG in this patient population. However, the surgeon should inform the patient that less than half of patients feel better after operation and that the risk of complications and perioperative mortality is higher than that for the nondialysisdependent patient. Surgeons may want to avoid operating on patients with cardiomegaly, CHF, or those who also need valvular repair or replacement. In a dialysis-dependent patients with medically uncontrollable cardiac disease, surgeons should be aware of the high morbidity and mortality rates associated with CABG in this population. Only patients who cannot continue their current lifestyle secondary to their cardiac disease should have CABG. These patients should know that their cardiac symptoms improve 60% of the time but that less than half of these patients will report improved health status overall. Additionally, CABG will not improve the patient s long-term survival, and patients with CHF, cardiomegaly, or valve operations will have a worse outcome with an increased risk of death. References 1. United States Renal Data System, Bethesda Maryland: National Institutes of Health, Haire HM, Sherrard DJ, Scardapane D, Curtis FK, Brunzell JD. Smoking, hypertension and mortality in a maintenance dialysis population. Cardiovasc Med 1978;3: Bagdade JD. Uremic lipidemia, an unrecognized abnormality in triglyceride production and removal. Arch Intern Med 1970;126: Hampers CL, Lowrie EG, Soeldner JS, Merrill JP. The effect of uremia on glucose metabolism. Arch Intern Med 1970;126: Menzoin J, Davis RC, Idelson BA, et al. Coronary artery bypass surgery and renal transplantation: a case report. Ann Surg 1974;179: Blum U, Skupin M, Wagner R, Mathies G, et al. Early and long-term results of cardiac surgery in dialysis patients. J Cardiovasc Surg 1994;2: Batiuk TD, Kurtz SB, Oh JK, Orszulak TA. Coronary artery bypass operation in dialysis patients. Mayo Clin Proc 1991; 66: Rinehart AL, Herzog CA, Collins AJ, et al. A comparison for coronary angioplasty and coronary artery bypass grafting outcomes in chronic dialysis patients. Am J Kidney Dis 1995; 25: Francis GS, Sharma B, Collins AL, Helseth HK, et al. Coronary-artery surgery in patients with end-stage renal disease. Ann Intern Med 1980;92: Blakeman BM, Pifarre R, Sullivan HJ, et al. Cardiac surgery for chronic renal dialysis patients. Chest 1989;95: Deutsch E, Bernstein RC, Addonizio P, Kussmaul WG III. Coronary artery bypass surgery in patients on chronic hemodialysis. A case-control study. Ann Intern Med 1989;110: Samuels LE, Sharma S, Morris RJ, et al. Coronary artery bypass grafting in patients with chronic renal failure: a reappraisal. J Cardiac Surg 1996;11: Jahangiri M, Wright J, Edmondson S, Magee P. Coronary artery bypass graft surgery in dialysis patients. Heart 1997; 78: Owen CH, Cummings RG, Sell TL, et al. Coronary artery bypass grafting in patients with dialysis-dependent renal failure. Ann Thorac Surg 1994;58: Salem MM, Mujais S. Coronary revascularization in dialysis patients: the need for vigilance. Intl J Artif Organs 1991;14: Kasiske BL, Ravenscraft M, Ramos EL, et al. The evaluation of renal transplant candidates: clinical practice guidelines. Patient Care and Education Committee of the American Society of Transplant Physicians. J Am Soc Nephrol 1995;6: 1 34.