Asian Cardiovasc Thorac Ann 2001;9:176-181
© 2001 Asia Publishing EXchange Pte Ltd
Myocardial Revascularization in Chronic Renal Failure: 10-year Experience
Edvin Prifti, MD,
Massimo Bonacchi, MD1,
Marzia Leacche, MD,
Giacomo Frati, MD1,
Gabriele Giunti, MD1,
Piero Proietti, MD1,
Antonio Massimo Cricco, MD,
Gianluca Brancaccio, MD,
Barbara Furci, MD,
Arben Baboci, MD,
Michele Toscano, MD1
Institute of Cardiovascular Surgery University of La Sapienza Rome, Italy
1 Institute of Thoracic and Cardiovascular Surgery University of Siena Siena, Italy
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For reprint information contact: Edvin Prifti, MD Tel: 39 05 8549 3522 Fax: 39 05 8549 3616 email: edvinprifti{at}hotmail.com Institute of Cardiac Surgery and Great Vessels, University of La Sapienza, Policlinico Umberto I, Viale del Policlinico 155, Rome 00161, Italy.
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Abstract
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From January 1989 to June 1999, 244 patients with chronic renal failure underwent myocardial revascularization, of whom 56 were undergoing hemodialysis (group 1) and 188 (group 2) did not require hemodialysis. Mean age was 63.4 ± 6.5 years in group 1 and 65.4 ± 7 years in group 2. Hospital mortality was 7% overall; 6 (10.7%) patients died in group 1 versus 11 (5.9%) in group 2 (p > 0.05). Post-operative complications were significantly higher in group 1 versus group 2. Multivariate analysis revealed cerebrovascular disease, myocardial infarction, left ventricular ejection fraction < 35%, and duration of renal failure as strong predictors of poor survival in non-dialysis patients. Left ventricular ejection fraction < 35% and duration of hemodialysis were predictors of late mortality in group 1. The 1-, 3-, and 5-year survival rates were 90%, 76%, and 68% in group 1, and 95.5%, 86%, and 80.7% in group 2 (p < 0.004), respectively. Myocardial revascularization can be carried out in patients with chronic renal failure with acceptable early and late mortality and morbidity, but those undergoing hemodialysis are at substantial risk of major morbid events and poor long-term survival.
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Introduction
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Coronary artery disease is the leading cause of death in patients with chronic renal failure (CRF), and numerous reports have indicated an acceptable outcome of cardiac surgery in hemodialysis (HD) and non-HD cases.1–14 Coronary artery bypass grafting (CABG) in such patients is considered necessary to improve their quality of life and life expectancy.1–5 Operative risk was noted to be significantly higher in HD patients compared to the general cardiac patient population, and long-term survival has been relatively poor.2,5,6 These findings were attributed to the multitude of coexisting noncardiac disorders, pathologic consequences of renal disease and dialysisrelated infective endocarditis, advanced cardiac disease, and older age.1,3,7 Cardiopulmonary bypass (CPB) in CRF patients poses a special problem because of the enormous fluid shifts in various body compartments. In addition, anemia and bleeding diathesis can complicate the peri-operative and postoperative courses. Although recent studies demonstrated a significant improvement in immediate and long-term survival in relatively small series of highly selected HD patients, CABG in HD patients remains controversial.1,5,8,9 The aims of this study were to evaluate the early and late outcome of CABG in HD and non-HD CRF patients, the comorbid features in both groups, and preoperative predictors of poor survival.
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Patients and Methods
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Between January 1989 and June 1999, 244 consecutive CRF patients (study group) underwent CABG in our institutions. They were compared with a control group of 244 patients with normal renal function who were matched for left ventricular ejection fraction (LVEF), type of operation, and age, but not sex (Table 1
). The study group patients were divided into group 1 (56 patients receiving HD for at least 1 month preoperatively) and group 2 (188 non-HD patients with serum creatinine > 16 mg•L–1 for more than 6 months preoperatively). The characteristics of groups 1 and 2 are listed in Table 2. Renal failure in group 1 was attributed to polycystic disease of the kidney (8), systemic lupus erythematosus (6), chronic glomerulonephritis (7), renal vascular disease (6), toxic agents (3), chronic parenchymatous nephritis (7), diabetic nephropathy (8), lithiasis (4), nephrosclerosis (1), and unknown causes (6); 2 patients had undergone renal transplantation with subsequent failure of the donor kidney. All patients underwent coronary angiography before the surgical procedure (Table 2). The calcification score was the sum of all involved coronary artery segments, according to the American Heart Association classification, confirmed by fluoroscopy.
All cardiovascular procedures were performed while the patients were on maintenance hemofiltration. The mean duration of preoperative dialysis in group 1 varied widely (6 months to 9.8 years), preoperative blood urea nitrogen was 1.23 ± 7.8 g•L–1, and creatinine levels were elevated to 75 ± 7 mg•L–1. The perioperative dialysis program consisted of dialysis the evening before surgery, hemo-filtration during CPB, and resumption of dialysis on the 1st or 2nd postoperative day. CABG in all cases was carried out using CPB and moderate systemic hypother-mia. Standard ascending aortic and right atrial cannulation was performed in 233 patients; 11 underwent femoral-axillary artery cannulation because of porcelain aorta. Intermittent cold antegrade and retrograde blood cardio-plegia was used in all cases. In group 1, 4 patients had concomitant mitral valve repair because of mitral re-gurgitation. Arterial grafts comprised 178 left internal mammary arteries, 41 right internal mammary arteries, and 11 radial arteries. The mean aortic crossclamp time was 83 minutes, and the mean CPB time was 115 minutes.
Follow-up data were collected from patients' medical records, questionnaires sent to physicians, and telephone interviews. Actuarial survival was calculated at 1, 3, and 5 years after CABG. Hospital mortality was defined as death for any reason occurring within 30 days after the operation. Perioperative acute myocardial infarction (AMI) was defined as the appearance of new Q waves or signi-ficant loss of R-wave forces, and peak creatine kinase-MB fraction > 10% of total serum creatine kinase. Low cardiac output syndrome was defined as cardiac index < 2 L•min–1•m–2 requiring pharmacological support and/or an intraaortic balloon pump. A neurological complication was defined as any transient or permanent neurological deficit that developed after surgery. Gastrointestinal complications included confirmed diagnosis of upper or lower gastrointestinal hemorrhage, intestinal ischemia, acute cholecystitis, and pancreatitis. Postoperative bleeding was defined as repeat thoracotomy for hemorrhage. Group statistics were expressed as mean ± 1 standard deviation. The Mann-Whitney U test was used for continuous variables. Wilcoxon's signed rank test was used for comparing preoperative and postoperative variables within the same group of patients. Fisher's exact test was used for nonparametric variables. Long-term survival rates were calculated by the Kaplan-Meier method, and statistical significance was calculated by the log rank test. Stepwise logistic regression analysis was carried out to identify independent predictors of survival. Significance between data was accepted when p < 0.05.
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Results
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Most preoperative cardiac and noncardiac factors were significantly higher in the study group than the control group (Table 1
). Within the study group, group 1 had a significantly higher incidence of most preoperative cardiac and noncardiac clinical features compared to group 2 (Table 2). Hospital mortality was 7% overall; 6 (10.7%) patients died in group 1 versus 11 (5.9%) in group 2 (p > 0.05). Causes of death were cardiac (9), infectious (4), intestinal infarction (2), respiratory (1), and technical (1).
Postoperative morbidity was significantly higher (p = 0.032) in group 1 versus group 2 (Table 3). In the 244 study patients, cardiac complications comprised arrhythmias (44), cardiac arrest (3), low cardiac output syndrome (15), cardiac tamponade (7), and aortic rupture (1). Neurological complications included cerebrovascular accident (13), encephalopathy (4), and motor dysfunction (3). Pulmonary complications were respiratory failure (8), pulmonary embolus (3), pleural effusion requiring tube thoracostomy drainage (22), hemoptysis (7), aspiration pneumonia (2), respiratory arrest (4), and atelectasis requiring bron-choscopy (3). Infectious complications included sepsis syndrome (7), urinary infection (14), pneumonia (18), aspergillosis (2), Candida esophagitis (1), sternal or leg wound infection (5), and sinusitis requiring specialist management (2). Gastrointestinal complications comprised acute pancreatitis (3), hemorrhage (12; 8 upper and 4 lower), cholecystitis requiring surgical intervention (4), intestinal infarction (1), and peritonitis (3). Reoperation for mediastinal bleeding was necessary in 7 patients.
The use of inotropic agents was significantly greater in the study group compared to the control group (92/244, 38% versus 64/244, 26%; p = 0.027). In the study group (Table 4), intensive care unit stay was significantly longer in group 1 versus group 2 (p < 0.001). Postoperative creatinine levels in group 2 were significantly higher than preoperative levels (36 ± 13 versus 25 ± 11 mg•L–1; p < 0.001), and the use of ultrafiltration postoperatively was higher in group 2 than the control group (29% versus 5.5%; p < 0.001); 18/64 (28%) CRF patients who had postoperative HD became dialysis-dependent (Table 4).
Univariate analysis of all preoperative and perioperative variables revealed several predictors of in-hospital mortality in CRF non-HD patients (Table 5). Predictors of late mortality were age (p = 0.04), cerebrovascular disease (p = 0.01), LVEF < 35% (p = 0.007), and duration of CRF (p = 0.002). Multivariate analysis identified cerebrovascular disease (p < 0.022), preoperative AMI (p < 0.011), LVEF < 35% (p < 0.007), and CRF duration (p < 0.0l) as independent predictors of survival. Univariate analysis in HD patients (Table 6) showed cerebrovascular disease (p < 0.04), LVEF < 35% (p < 0.001), and HD duration (p < 0.0017) to be strong predictors of in-hospital mortality. LVEF < 35% (p < 0.0l) and HD duration (p < 0.007) were identified as predictors of late mortality. Multivariate analysis was not employed due to the small number of deaths.
Mean follow-up of the 227 survivors was 37 months (range, 5 to 93 months). Actuarial survival rates at 1, 3, and 5 years were 90%, 76%, and 68%, respectively, in group 1, and 95.5%, 86%, and 80.7% in group 2 (Figure 1). Overall survival was significantly higher in group 2 versus group 1 (p < 0.004). Mortality was 22 patients in group 1 and 34 patients in group 2. In group 1, 3 of the late deaths were in patients who had undergone completely arterial myocardial revascularization versus 19 in patients who had saphenous vein and left internal mammary artery grafts (p = 0.011). Cardiac disease was the cause of late mortality in 13 patients in group 1 and 22 in group 2. Three patients in group 1 and 8 in group 2 required reoperation after 1.4 ± 0.5 years; 3 patients (group 1) underwent successful renal transplantation 2.2 ± 0.4 years after CABG. Of the 34 surviving patients in group 1, 31 were free from anginal pain, 2 had stable angina, and 1 had unstable angina at follow-up.
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Figure 1. Overall actuarial survival after coronary artery bypass grafting in patients with chronic renal failure who required hemodialysis (group 1) and those who did not require hemodialysis preoperatively (group 2).
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Discussion
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Approximately 40% to 50% of deaths in HD patients have been attributed to coronary artery disease.4,15 It remains unclear whether the progress of coronary artery disease is accelerated in dialysis-dependent patients compared to the general population.5,8,9 Other reports proposed that cardiac disorders might be aggravated by renal failure or comorbidity associated with endstage renal disease.16 Calcification of valves, coronary arteries, and the conduction system may be accelerated in HD patients, and septic events such as endocarditis may be regarded as typical complications of long-term HD.3,5,11 Despite the many published series of cardiac intervention in such cases, long-term results are scarce.1–6,8,11,12,17–21 Recently, a few studies in small numbers of HD patients reported acceptable medium and long-term outcomes in this subgroup.22,23 However, it is difficult to compare results because the inclusion criteria varied.
Tolerance of CPB is conceivably reduced by impaired renal function. Multiple comorbid disorders including platelet dysfunction and susceptibility to infection predispose CRF patients to increased operative mortality and morbidity.3,4,10 Some surgeons recommend HD more than 24 hours before CPB; others advocate intraoperative HD.24 We preferred intraoperative hemofiltration which affords acceptable control of water and electrolyte (mainly K+) balance until maintenance HD can be resumed. The hematocrit was raised if necessary to 30% by blood transfusion before surgery. In HD patients with depressed left ventricular function, peritoneal dialysis was instituted after the surgical procedure to avoid hemodynamic instability. Hospital mortality in HD patients was higher but not significantly, compared to CRF non-HD patients. Other studies have demonstrated higher postoperative mortality in HD patients, ranging from 3% to 31% (mean, 12%).5,7,8,10,11,13,20–23
Complications after CABG were significantly higher in HD patients compared to CRF non-HD patients. Susceptibility to infection in HD patients is attributed to decreased leukocyte chemotaxis and leukopenia.25 Accelerated atherosclerosis and diffuse cholesterol embolization syndrome are manifested by cerebrovascular or visceral vessel complications.7 The higher incidence of preoperative AMI, triple-vessel disease, and heavily calcified coronary lesions supports the concept of accelerated atherosclerosis in HD patients. The need for inotropic agents postoperatively demonstrated that CRF patients in general and HD patients specifically are at substantial risk of major cardiac complications. The status of CRF non-HD patients worsened significantly postoperatively as reflected in their increased creatinine levels; HD was required in 64 cases. There was a higher incidence of preoperative noncardiac comorbidity in CRF patients compared to those with normal renal function, and in HD versus CRF non-HD patients. Pepper and colleagues14 suggested that morbidity and late mortality in HD patients were heavily influenced by noncardiac comorbid diseases. Rostand and colleagues15 found advanced age to be the major factor affecting mortality, and Samuels and colleagues8 concluded that age > 70 years was the most important predictor of mortality. Other studies revealed that New York Heart Association functional class IV and cerebrovascular disease were strong predictors of poor survival, and that mortality was related to the duration of HD.4–6,21 Nakayama and colleagues13 found a higher coronary calcification score in HD patients. Incomplete revascularization due to heavily calcified coronary arteries and poor vessel quality in HD patients was addressed by Koyanagi and colleagues.9 In a series of 70 HD patients undergoing CABG, Khaitan and colleagues20 found congestive heart failure, cardio-megaly, and concomitant valve surgery to be predictors of poor survival. Recently, Hosoda and colleagues23 reported a very poor outcome in patients with diabetic nephropathy undergoing CABG. In our series, strong predictors of poor overall survival in CRF non-HD patients were cerebrovascular disease, AMI, LVEF < 35%, and CRF duration. Cerebrovascular disease, LVEF < 35% and HD duration were strong predictors of poor survival in HD patients. Durations of CRF and HD seem to be important factors in early and late outcome, probably due to associated comorbidity.
Studies of long-term survival of HD patients and CRF non-HD patients undergoing CABG are limited. Samuels and colleagues8 found 5% mortality at 30 months in CRF non-HD patients. In HD patients, Nakayama and colleagues13 reported 71% survival at 5 years, whereas Khaitan and colleagues20 noted only 40% survival at 3.5 years. In our study, 68% of HD patients and 80.7% of CRF non-HD patients were still alive 5 years after surgery. Some have argued that CABG does not alter the long-term survival of HD patients.17 Others found mortality > 8% per year and an actuarial mortality of almost 50% after 5 years in HD patients who did not undergo CABG.22 The similar long-term survival rates in patients who underwent surgery and the general CRF population indicates that a therapeutic benefit exists, as the CABG patients had proven coronary artery disease at the time of operation, and conceivably a lower life expectancy. According to these data, CABG certainly improved the long-term survival in HD patients. Survival was significantly better in CRF non-HD patients than HD patients, demonstrating that HD patients are at a substantial risk of late mortality due to noncardiac (accelerated atherosclerosis, HD-related infection, diabetes, cerebrovascular disease, hypertension) and cardiac comorbidity (poor quality of coronary arteries inducing high incidence of AMI with consequent left ventricular dysfunction, important calcification of the conduction system with potential for malignant arrhythmias). Long-term survival was better in HD patients undergoing CABG with arterial rather than saphenous vein grafts. However, CABG does affect the aggressive nature of atherosclerosis in HD patients, implying that long-term graft patency would be lower than in non-HD patients. Total arterial myocardial revascularization offered better long-term survival because of the superior patency of arterial conduits over saphenous vein.
It was concluded from these findings that CRF patients may undergo CABG with acceptable postoperative mortality and morbidity. Cerebrovascular disease, preoperative AMI, LVEF < 35%, or a long history of CRF carry an increased risk of poor outcome. HD patients have a higher mortality rate and substantial risk of major morbid events, while LVEF < 35% and long HD duration increase the mortality rate. Careful selection of HD patients, precise information on the quality of the coronary arteries, well-defined indications for surgical procedures, and meticulous technique are prerequisites for successful myocardial revascularization in this subgroup. CABG improves long-term survival in HD patients, especially when only arterial conduits are employed.
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Acknowledgments
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This study was supported by IRCCS NEUROMED, Via Atinense N.18, 86077 (Isernia), Pozzilli, Italy.
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References
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Abstract
Introduction
