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Eur J Cardiothorac Surg 1999;15:691-696
© 1999 Elsevier Science NL

Early and long term results of coronary artery bypass grafts in patients with dialysis dependant renal failure

Department of Cardiovascular Surgery, Bordeaux Heart University Hospital, Avenue de Magellan, F. 33604 Bordeaux-Pessac, France

Received 21 September 1998; received in revised form 26 February 1999; accepted 10 March 1999.

Corresponding author. Tel.: +33-5-56556437; fax: +33-5-56073665

	Abstract

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

 
Objective: Coronary artery disease is the main cause of mortality and morbidity in patients on renal therapy replacement. The aim of this study was to define peri-operative risk and long term results of coronary artery bypass grafts (CABG) in dialysis patients. Methods: this retrospective study included 82 patients in chronic dialysis who underwent CABG between 1978 and 1997. The mean age was 61±10 years (range 28–81 years), 84% of the patients were male and the average duration of dialysis was 57 months (range 1–148 months). Combined procedures were carotid endarterectomy in one case, left ventricular aneurysm resection in one and valvular replacement in 10 (nine aortic and one mitral replacements). The operation was elective in 42 patients (51%) and urgent in the others. Previous myocardial infarction was found in 37 patients (45%) and left ventricular ejection fraction (LVEF) at less than 45% in 15 patients (18%); 23 patients (28%) were in NYHA class III or IV and regarding angina functional status, 77% in CCS class 3 or 4. Follow-up was complete. Statistical analysis included 30 and pre and peri-operative data. Statistical analysis used Chi-square analysis or Fisher's exact test, and the Mann–Whitney test when appropriate. The estimated probability of survival, including postoperative mortality, was calculated by the method of Kaplan–Meyer, and the Log-Rank test used to compare the results. Results: the hospital mortality was 14.6 % (n=12). Ischemic time and ECC time were significantly lengthened in dead patients (P=0.01). Moreover, use of internal mammary artery was directly related to lower hospital mortality (P=0.02). For previous myocardial infarction, LVEF at less than 45%, diabetes and combined procedure, a P-value of 0.1 was calculated. The follow-up ranged from 1 to 140 months (mean 36 months). There were 39 late deaths. The survival rates (included hospital mortality) were 71±5%, 56±6% and 39±6% at 1, 3 and 5 years, respectively. All surviving patients improved their functional status and had symptomatic relief. Statistical analysis showed significant difference in favor of long term survival for patients younger than 60 years, LVEF >45% and NYHA class I or II. Conclusion: these data confirm that CABG in patients with renal replacement therapy is associated with an high operative and long term mortality. However it allows an improvement of functional status, and so, let possible duration of dialysis. It may be expected that more active prevention and detection of coronary disease might improve these results.

Key Words: End-stage renal failure • Dialysis • Coronary artery bypass graft • Coronary artery disease • Cardiac surgery

	1. Introduction

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

 
Cardiovascular diseases are the main cause of death among patients on renal replacement therapy (RRT) [1]. Data from the Registry of the European Dialysis and Transplant Association [2] have shown a 16- to 19-fold increased risk of myocardial ischemia and infarction when compared with similar populations without renal failure. With the growing number of olders patients under RRT, the number of those who might be suitable for revascularization is likely to increase [2]. Moreover, percutaneous transluminal coronary angioplasty (PTCA) in this group of patients is known to be marked by a high rate of acute complications and poor long term prognosis [3–4]. Concerning coronary artery bypass grafts (CABG), chronic dialysis patients have been recognized for a long time to have a major surgical risk [5], and even if more and more groups consider that these patients must not be rejected [6–15], some points, especially about life expectancy and risk factors for this surgery still remain dubious.

Our experience with this group of patients was reviewed to determine the risk factors for early and late death, to improve the management of these factors and to achieve a better selection of these patients.

	2. Materials and methods

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

 
This retrospective study included 82 consecutive patients in end stage of renal disease who underwent CABG in Haut-Lévèque Hospital, from January 1978 to December 1997. Patients were included for analysis only if they had received some form of renal replacement therapy for at least 1 month prior to coronary bypass. Data were collected from patients’ medical records. Demographic and clinical characteristics of operated patients are summarized in Table 1.

All patients underwent standard cardiopulmonary bypass at moderate hypothermia (30–32°C), with pump flow rates of 1.8–2.2 l/min per m² and arterial pressure maintain greater than 50 mmHg by fluid filling or use of vasoconstrictive drugs when appropriate. The extra corporeal circuit was routinely primed with isotonic cristalloid solution or with fresh plasma and fresh blood added to maintain hematocrit higher than 25%. Since 1986, per-operative hemofiltration was used if necessary. Myocardial protection was achieved, in all patients except one, by critalloid solution and topical cooling. To avoid hemodilution and hyperkaliemia, cardioplegic solution was aspirated via the right atrium (double caval cannulation and tapes placed around the cannula). Proximal anastomosis were performed before or during aortic cross-clamping as surgeons are accustomed to. Follow-up was completed 100% in all patients.

Operation was performed on an emergency basis in 40 patients. Left internal mammary artery has been used in 52 patients (63%). The patients received a mean of 2.3 grafts (range 1–4). Associated procedures included mechanical valve replacement (aortic: n=9; mitral: n=1), carotid endarterectomy (n=1) and left ventricular aneurysm resection (n=1). None of the patients who underwent aortic valvular replacement had a transvalvular aortic gradient more than 55 mmHg, and in all cases except one, symptoms were mainly attributed to coronary disease. Mean extra-corporal-circulation (ECC) time and cross clamping time were 82±3 min (range 20–156 min) and 50±3 min (range 11–118 min), respectively.

For all patients, 30 pre-, peri- and postoperative data (Appendix A) were analyzed for their association with operative mortality and long term survival. Mean values are expressed as the mean±SD. Statistical analysis used chi-square analysis or Fisher's exact test, and the Mann–Whitney test where appropriate. The estimated probability of survival, including postoperative mortality, was calculated by the method of Kaplan–Meyer, and the Log-Rank test used to compare the results. For Log-Rank test, analysis of age was achieved by steps of 5 years, and for ejection fraction by steps of 5%. All procedures were performed using the statistical softward package SPSS (SPSS Inc., Chicago, IL).

	3. Results

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

 
Hospital mortality, defined as 30 days mortality, was 14.6% (12 cases). Death was due to an acute myocardial infarction (n=4), to a cardiac arrest following hypotension and low cardiac output during hemodialysis (n=3), to tamponade (n=2), and to multi-organ-failure in two cases. The last death was due to technical failure of the dialysis. Hospital mortality decreased along years, from eight deaths between the years 1978 and 1990 (n=42 patients), to four deaths for the last 40 patients. There were no deaths among 19 patients (P=0.06) since 1995. Hospital morbidity was summarized in Table 2, and was referred to non specific postoperative complications with a slightly elevated rate of reoperation for bleeding and for sternal infection than in usual coronary-bypass population.

View this table: [in this window] [in a new window]   Table 2. Hospital morbidity (30 days).

Statistical analysis of hospital mortality were not significant for sex, age, duration of dialysis, emergency procedure and preoperative functional status. Statistical difference was found for ECC (P=0.01), cross clamp time (P=0.01) and in favor of use of the mammary artery (P=0.02). For previous myocardial infarction, left ventricular ejection fraction (LVEF) at less than 45%, diabetes and combined procedure, a P-value of 0.1 was calculated.

Regarding long term survival, the estimated survival rate at 1, 3 and 5 years, including hospital mortality was 71±5%, 56±6% and 39±6%, respectively (Fig. 1) . Statistical analysis of studied data has indicated that LVEF at less than 45%, pre-operative NYHA class III or IV and patients older than 60 years were at higher risk of late death (Figs.2,3and4) .

View larger version (15K): [in this window] [in a new window]   Fig. 1. Longterm survival, including hospital mortality, for the 82 chronic dialysis patients operated on (calculated with the Kaplan–Meyer method).

View larger version (19K): [in this window] [in a new window]   Fig. 2. Comparison of longterm survival (hospital mortality included) for patients with LVEF >45% vs. LVEF <45% (P<0.05 for statistical analysis with Log-Rank test).

View larger version (19K): [in this window] [in a new window]   Fig. 3. Comparison of longterm survival (hospital mortality included) for patients in classes I or II of the NHYA vs. classes III or IV (P<0.05 for statistical analysis with Log-Rank test).

View larger version (20K): [in this window] [in a new window]   Fig. 4. Comparison of longterm survival (hospital mortality included) for patients older than 60 years old or not (P<0.05 for statistical analysis with Log-Rank test).

	4. Discussion

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

Until recently, literature relative to patients under RRT who have underwent CABG was limited to groups of patients under 40 [6–12]. Moreover, the follow-up of these studies was limited to a few years. So, with 82 patients and a mean follow-up of 36 months (ranging from 1 to 140 months), and with 26 patients followed for more than 48 months, this study is the largest ever published. Nevertheless, the retrospective feature of the study and its length (20 years) might affect the validity of some conclusions. Especially, the emergency basis of the procedure, and the quality of operative and intensive cares’ management have notably changed among the years.

Patients data in this study were similar to those previously published [6–15], in particular those concerning age, previous myocardial infarction, emergency basis of the procedure and functional status of patients. On the contrary, the average duration of dialysis before surgery was a lot longer (57 months vs. 20–31 months). This high figure is only found by Deleuze et al. [12]. This could indicate a more serious severity of coronary artery disease [7,12], responsible in part for a higher risk of mortality or morbidity.

Hospital mortality was 14.6% among 12 patients. These figures were superior to those reported by Ko et al. [8] (mean: 9%, range: 2.6–20%) in an English literature review encompassing 296 patients. However, one of the deaths occurred in a patient operated in the early phase of an acute large anterior infarction, and another was directly linked to a technical problem during dialysis. Moreover, mortality rate has recently dropped with no deaths recorded among the last 19 patients (P=0.06) (January 1995 to December 1997). This reduction in mortality rate could be partially explained by recently frequent use of mammary artery. In fact, this graft began to be applied in 1985, but as of 1992, it became routine procedure. Univariate analysis showed that lack of use of IMA was directly related to high hospital mortality. This result corresponds to that of Koyanagi et al. [15], who reported no deaths among 23 patients with intensive use of arterial grafts. Note that as reported earlier [6], we did not observe significant increment of morbidity when internal thoracic artery was used. These superior results with mammary artery might be explained by a lower thrombosis susceptibility during postoperative hypotension. In fact, in chronic dialysis patients, arterial baroreflex function is thought to be impaired and so contributes to the lack of the baroreflex control of heart rate, which might explain poor blood pressure regulation [17], associated with hypotension and low cardiac output occurring during and after hemodialysis [18]. For few years, a better knowledge of this phenomenon drove us to especially monitor patients's filling and postoperative preloads (via a catheter placed in the left atrium, for a pressure usually maintained between 13 and 15 mmHg). This specific management is also partly responsible for the recent improvement in our results.

According to other authors [10,12,14,19], the perioperative program consisted of hemodialysis the day before the procedure in order to avoid hemodynamic instability that might arise immediately after dialysis. The dialysis was restarted as soon as it was necessary, usually the day after. We have no experience of postoperative peritoneal dialysis which is advocated by Ko et al. [8] and others [11,15,21]. For them, its advantages would be to start immediately after surgery, not to require a specialized team, to avoid bleeding due to anticoagulation, to control electrolytic disorders, to lessen the risk of infective endocarditis and especially to avoid hemodynamic instability [8]. However, this technique needs an intra-peritoneal catheter in those patients prone to infection [22], and to postoperative gastrointestinal complications [8,23], and is known to have disadvantages as protein loss, respiratory disturbances, and pericardial or pleural effusion due to diaphragmatic leakage [15]. Moreover, in the event of postoperative bleeding, hemodialysis can be achieved with low-molecular-weight-heparin or even without heparin [24]. In regards to electrolytic disorders, the systematical use of double caval cannula which allows collection of the infused cardioplegia, avoided major hyperkaliemia in all patients.

ECC time and cross-clamping time were also significant in the statistical analysis of early mortality. This had to be referred to technical difficulties in these patients. According to other reports [10,12,26], coronary arteries were much more calcified than in normal patients. However, we were always able to graft mainly diseased vessels with no use of coronary endarterectomy.

Some authors have reported that age [20], preoperative NYHA class IV [8,10,12], emergency procedure [8], associated procedure [8,9,12] and pulmonary hypertension [12] were important predictors of hospital mortality. Our results did not confirm these results, as they did not shown significant difference for LVEF 45%. For previous myocardial infarction and diabetic patients, our results are not significant (P0.1), but as for other data, a larger series of patients would be necessary to have more conclusive results.

Regarding hospital morbidity, the incidence of postoperative bleeding requiring reoperation and sternal infection appeared, in our series, to be slightly more elevated (3.6%) than in our general coronary bypass graft population. These results might be explained by homeostasis disturbances and anticoagulation during dialysis, and by susceptibility to infection known in chronic dialysis patients [22]. Previous studies have also shown a high perioperative mortality in these patients due to endocarditis [7,11]; no such case was reported in this series.

Long term survival of these patients (hospital mortality included: 71±5% at one year, 56±6% at 3 years, and 39±6% at 5 years) was comparable to that cited in others reports [7–10,12,13]. For patients alive at 30 days after the procedure, mortality was in general similar to the dialysis population [25], even though 77% of our patients had unstable angina or angina during dialysis which would have made the duration of dialysis impossible in the near future. However, it was clearly diminished compared to the usual coronary bypass population [27]. Moreover, our results were better than those in dialysis patients with symptomatic coronary disease who were treated medically [28]. Finally, more than half of the known late deaths were related to cardiac causes, as was previously noted [8–12].

According to Kaul et al. [10] longterm survival in our patients is longer in patients under 60 years of age and in those without congestive heart failure. The effect of these variables appeared early during the survival function. No significant difference was found in longterm survival rate when duration of maintenance dialysis was studied. This point had been point out previously by Batiuk et al. [7] and Kaul et al. [10]. Longterm results with mammary artery were not significantly better in our series probably because of the small numbers of patients surviving more than 7 years. Finally, excellent longterm functional status of surviving patients (more than 80% of the patients in CCS and NYHA class 1 or 2) has been found by us, as by all others authors [6–15]. Four of these patients underwent successful kidney transplantation during the follow-up. Myocardial revascularisation could improve longterm results of these patients, especially those with insulin-dependent diabetes [29], and could allow us to screen patients awaiting kidney transplantation for silent coronary artery disease.

In conclusion, patients with chronic renal failure, following renal replacement therapy, can undergo coronary artery bypass with an acceptable operative risk. Use of mammary artery appeared to be safe and favorable for early outcome. Special interest on fluid filling during intensive-care management might improve the early results by avoiding hemodynamic instability occurring during dialysis. Early and longterm results, even in patients with poor LVEF or with functional signs of congestive heart failure, are to be compared with the short spontaneous survival rate of these patients, and in our opinion justify the extent of indications of myocardial revascularisation in chronic dialysis patients.

	Footnotes

 
Presented at the 12th Annual Meeting of the European Association for Cardio-thoracic Surgery, Brussels, Belgium, September 20–23, 1998.

	Appendix A. Variables studied

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

 
Preoperative variables studied

Age

Sex

Etiology of renal disease

Duration of dialysis

Type of dialysis

Previous kidney transplantation

Emergency Procedure

Hypertension

Insulin-dependent diabetes

Non-insulin-dependent diabetes

Smoking history

Dyslipemia

History of myocardial infarction

Stroke

Obesity

Chronic obstructive lung disease

Peripheral vascular disease

NYHA class I to IV

CCS class 1 to 4

Associated valvular procedure

Left ventricular ejection fraction (<35%, <40%, <45%, <50%)

Extent of coronary disease (single-, double-, or triple-vessel disease)

Left main coronary artery disease

Left anterior descending coronary artery disease

Intraoperative variables studied

Aortic cross-clamp time

Cardiopulmonary bypass time

Use of internal mammary artery

Year of operation

Postoperative variables studied

Sternal infection

Tamponnade

	Appendix B. Conference discussion

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

 
Dr Dion (Brussels, Belgium): We are also interested in the outcome of coronary surgery in patients on dialysis. We were impressed also by the positive influence of the use of the left and of the right mammary artery grafts. Also, some of these patients are able to be transplanted after CABG, and these patients certainly benefit the most from the procedure. You didn't mention whether any patient reached kidney transplantation thanks to CABG. Do you mean that these patients should not be transplanted? What is the percentage of patients being transplanted and what is the outcome?

Dr Labrousse: In our series, only four patients were transplanted during the follow-up, and only a few of them, about 25 or 26, were on a waiting list of kidney transplantation before surgery.

	References

Top Abstract 1. Introduction 2. Materials and methods... 3. Results 4. Discussion Appendix A. Variables studied... Appendix B. Conference... References

 

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