Ann Thorac Surg 2005;79:1610-1614
© 2005 The Society of Thoracic Surgeons
Original articles: Cardiovascular
Outcomes of Coronary Artery Bypass Grafting in Patients With Connective Tissue Diseases
Thomas J. Birdas, MDa,*,
Jeffrey T. Landis, BSb,
David Haybron, MDb,
Debbie Evers, BSNb,
Pavlos K. Papasavas, MDb,
Philip F. Caushaj, MDb
a Department of Cardiothoracic Surgery, Allegheny General Hospital, Pittsburgh, Pennsylvania
b Department of Surgery, The Western Pennsylvania Hospital, Temple University School of Medicine Western Clinical Campus, Pittsburgh, Pennsylvania
Accepted for publication October 28, 2004.
* Address reprint requests to Dr Birdas, Dept of Cardiothoracic Surgery, Allegheny General Hospital, 320 E N Ave, South Tower, 14th Fl, Pittsburgh, PA 15212 (E-mail: tbirdas1{at}aol.com).
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Abstract
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BACKGROUND: Coronary artery disease represents a significant cause of morbidity and mortality in patients with connective tissue disease. Few reports exist on the results of surgical management of coronary artery disease in these patients.
METHODS: The medical records of patients with connective tissue diseases who underwent coronary artery bypass grafting at our institution between 1995 and 2002 were reviewed for demographic data, perioperative variables, and postoperative complications. The results were compared with data from The Society of Thoracic Surgeons database.
RESULTS: Forty-four patients were identified from a total of 5,496 cases during the study period (0.8%). There were 35 patients with rheumatoid arthritis, 8 with systemic lupus erythematosus, and 1 with scleroderma. Patients with connective tissue diseases were more likely to be women and use immunomodulating agents. They also had a higher incidence of Canadian Cardiovascular Society class IV angina, need for inotropic agents, need for intraaortic balloon pulsation, use of blood transfusions, and leg wound infections. The use of steroids or other immunomodulating agents was associated with increased postoperative complications. Mean follow-up was 35 months. The overall survival and freedom from reintervention at 3 years were 89% and 75%, respectively.
CONCLUSIONS: Coronary artery bypass grafting is a safe treatment modality in patients with connective tissue diseases, with acceptable early results. Wound complications may be a problem in this patient population. Midterm results are less favorable, and reinterventions are frequently required.
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Introduction
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Connective tissue diseases (CTDs) represent a wide spectrum of pathologic processes with the common characteristics of tissue inflammation, frequently of an autoimmune nature [1]. Clinical manifestations depend on the individual organ system involvement. Cardiovascular manifestations are frequent, with various forms of vasculitis being the primary insult [1, 2]. Coronary artery disease (CAD), once thought uncommon in these patients, is now being increasingly recognized as a significant component of the CTD complex [3]. It is the most common cause of death in this group [3], frequently presenting in an accelerated form [4]. Despite that, little is known of the efficacy of contemporary surgical approaches in the management of CAD in these patients. We report our institutional experience for a period of 7 years.
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Patients and Methods
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After obtaining permission from the Institutional Review Board, we reviewed the medical records of all patients who underwent coronary artery bypass grafting (CABG) at our center (Western Pennsylvania Hospital) between July 1, 1995, and June 30, 2002, and were carrying one of the following diagnoses: rheumatoid arthritis (RA), systemic lupus erythematosus, scleroderma, Sjögren's syndrome, ankylosing spondylitis, vasculitis, other CTD. Demographic data, perioperative variables, and postoperative outcomes were collected. Data from The Society of Thoracic Surgeons (STS) database were used for comparison [5]. We obtained follow-up information using medical records from subsequent admissions, office charts, and the Social Security Death Index. Follow-up information was obtained at the completion of our study (August 5, 2002). Freedom from reintervention was defined as freedom from repeat catheterization, percutaneous interventions, or CABG. Statistical comparisons were made with the use of the 
2 test for dichotomous and Student's t test for continuous variables. Kaplan-Meier time-to-event analysis was performed for calculation of overall survival and freedom from reinterventions. Different groups were compared with the log-rank test. A p value of less than 0.05 was considered significant. All calculations were performed with the use of StatView for Windows (v 5.0.1; SAS Institute, Inc, Cary, NC).
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Results
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During the study period, 5,496 isolated CABG operations were performed in our institution. Forty-four patients (0.8%) with a coexistent CTD were identified. There were 35 patients with RA, 8 with systemic lupus erythematosus, and 1 with scleroderma. The demographic characteristics of the study population are seen in Table 1. Mean age was 68.5 years (median, 70 years). Patients with RA were significantly older than the rest (mean, 70.3 versus 61.6 years; p < 0.01); no other features were different between the RA and non-RA groups. Female sex, age more than 65 years, and use of steroids or other immunomodulating medications were significantly more common in our population compared with the cumulative STS data. In this last category, there were 15 patients receiving steroids, 5 patients receiving methotrexate, 4 patients receiving both, and 1 patient receiving azathioprine.
Table 2 shows the perioperative variables. Patients with CTD had a significantly higher incidence of Canadian Cardiovascular Society class IV angina, need for inotropic support, and intraaortic balloon counterpulsation on completion of the operation as well as blood transfusions. The mean number of grafts performed was 3.5 ± 1.3 grafts per patient. The left internal thoracic artery was used in 37 patients (84%), the right internal thoracic artery in 1 patient who had a prior CABG with use of the left internal thoracic artery (2.2%), and 1 patient received a radial artery graft along with a left internal thoracic artery (2.2%). All procedures except for one were performed with the use of cardiopulmonary bypass.
There were two postoperative deaths (operative mortality 4.5%). This compared favorably with our institutional mortality for isolated CABG during the same period (2.6%), as well as the mortality (2.7%) reported in the STS database (not significant in both cases). The postoperative complications are seen in Table 3. Overall, 21 patients (47.7%) experienced postoperative complications (STS, 36.2%; not significant). Leg wound infections were significantly more frequent in our study population (p < 0.001). The use of steroids or other immunomodulating medications was the only factor associated with an increased risk for occurrence of complications in a univariate analysis (odds ratio, 4.9; 95% confidence interval, 1.3 to 18.4). However, when looking at the infectious complications alone, only the presence of diabetes was associated with increased risk (odds ratio, 6.4; 95% confidence interval, 1.01 to 41.1). Owing to the small number of events, no multivariate analysis was performed. The mean length of stay was 7.2 days (range, 0 to 23 days; median, 6 days). Patients who experienced complications had a longer hospital stay (9.0 versus 5.6 days; p < 0.02).
Mean follow-up was 35 months with a median of 28.5 months. There were four late deaths. In addition, 8 patients required subsequent reintervention, defined as coronary catheterization and either percutaneous coronary angioplasty or changes in the medical management. No patient required coronary reoperation. The overall survival and freedom from reinterventions are seen in Figure 1. It should be noted that freedom from reintervention is not reintervention-free survival; deaths were not considered as events in the calculation of the second curve. The overall survival at 3 years was 89% (95% confidence interval, 78% to 99%). The freedom from reintervention at 3 years was 75% (95% confidence interval, 58% to 92%). Using the log-rank test, patients with preoperative use of steroids or other immunomodulating agents were found to be less likely to require subsequent reintervention (p < 0.02; Fig 2). No other factors had a significant effect on either survival or need for reinterventions.
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Fig 2. Freedom from reinterventions: with (solid line) and without (dotted line) use of steroids and immunomodulating agents.
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Comment
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Connective tissue diseases comprise a complex of disorders with unknown cause, although an immune-mediated injury is generally regarded as the primary mechanism [1]. The manifestations vary widely and can involve a number of organ systems. The cardiovascular system is frequently afflicted, primarily in the form of inflammatory involvement of vessels of different caliber (vasculitides). The heart can suffer from primary myocardial or valvular damage, or as a result of coronary arteriosclerosis. This, in turn, is viewed as either a direct manifestation of the disease process (resulting in coronary vasculitis or generalized arteriosclerosis) or a secondary injury, after pharmacologic treatment of the disease (steroids) [1–3, 6, 7].
The exact prevalence of CAD in patients with CTD is not well defined. It has been shown that patients with RA have increased mortality compared with the general population, most of which is attributable to arteriosclerosis-related complications [3, 7]. There is also significant variation among the different disease entities; patients with systemic lupus erythematosus are known to have a tendency for accelerated early coronary arteriosclerosis [4, 8]. Also, there has been increased interest in the past few years in the detection of subclinical atherosclerotic disease in these patients. With the use of carotid ultrasound, patients with RA were found to have increased intima-media thickness, a factor strongly associated with adverse cardiovascular events [3]. Additionally, the outcomes of traditional surgical approaches to the management of CAD in this population have not been extensively studied [9–13]. The few existing reports describe very small case series, primarily of patients with systemic lupus erythematosus. This is an issue with clinical importance, as these patients can potentially be at a higher risk for postoperative complications given their frequently immunocompromised state.
In the retrospective review of a busy open-heart surgery practice, we identified 44 patients during a period of 7 years who carried a CTD diagnosis and underwent isolated CABG. This represented an incidence of 0.8% of the total CABG volume at our institution during the study period. Six additional patients were excluded from analysis, as they underwent a combined CABG and valve operation. We used information from the STS database to perform a comparison with regard to patient characteristics and outcomes. These data were publicly available through the CTSNet Web site at the time of the study and referred to the 1997 calendar year [5].
In our study, patients with CTD were more frequently of the female sex, older, and had a higher Canadian Cardiovascular Society score at the time of operation, compared with the STS database population. The age difference can probably be explained by the predominance of patients with RA in our group, who usually tend to be diagnosed at a later age and have a somewhat more indolent course [1]. Patients in the smaller group of systemic lupus erythematosus were indeed younger than their RA counterparts. The predominance of women, not entirely surprising given the predilection of CTD for the female sex, can also explain the presentation at a later age and a more symptomatic stage. This has been quoted as one of the pitfalls of diagnosing CAD in RA patients, as anginal symptoms are frequently attributed to the musculoskeletal system [3].
The difference in transfusion requirements, although striking, should be viewed with caution. Although many patients, primarily with RA, receive nonsteroidal antiinflammatory medications, documentation of their potent antiplatelet effects is not common, as quantitative platelet function tests are done very selectively. In addition, no differences in fresh-frozen plasma or platelet transfusions were seen. It is possible that the higher number of women in the study could also account for this difference. Female patients with smaller body size would be more likely to experience hemodilution while on cardiopulmonary bypass and meet the criteria for transfusion. It is also possible that the observed transfusion rates represent an institutional bias; lack of data for the entire cardiac surgical population during the study period limits our ability to draw definitive conclusions.
Almost half (47.7%) of the patients experienced a postoperative complication. The use of steroid or immunosuppressant medications was a negative prognostic factor for overall occurrence of any complication. Not surprisingly, patients who experienced complications had a longer hospital stay. The only complication that was seen with greater frequency compared with the STS data were wound infections at the vein harvest sites (9.1%). As mentioned earlier, this is one of the main concerns in this population, as these patients are prone to infectious complications, as a result of either the primary disease process or its treatment with immunomodulating agents. Indeed, a significant number of patients in the CTD group (56.8%) were receiving one or more such agent at the time of the surgery. Only the presence of diabetes, however, correlated with the risk for development of an infectious complication. It is possible that the small number of overall events (n = 6) did not allow for further delineation of additional risk factors.
The midterm follow-up data suggest that this group may have inferior results. With a mean follow-up time of 35 months, the 3-year survival and freedom from reintervention, defined as freedom from repeat catheterization, percutaneous interventions, or CABG, were 89% and 75%, respectively. These results, and particularly the need for repeated interventions, do not compare favorably with those reported in the literature [14], in which freedom from cardiologic or surgical reinterventions exceeds 95% at 5 years. Could sex be a confounding factor with regard to outcomes? There has been a tremendous interest on the differences between men and women in all aspects of cardiac surgery, and in particular in CABG surgery [15–17], with factors such as delayed presentation, multiple comorbidities, and poor target vessels used to explain the inferior results seen in some studies. A definitive disadvantage for women, after risk adjustment, has not yet been proven, although this will most likely remain a consideration. In our analysis, sex did not appear to be a significant prognostic factor. A possible explanation for the observed suboptimal midterm results may be the unfavorable effect of the underlying inflammatory process on graft patency and on progression of disease in the native coronary system. Another argument for that hypothesis is that the use of immunomodulating medications had a significant protective effect against reinterventions. Although this may be related to selection bias (patients on such medications were considered high-risk and not referred for further interventions), this observation is certainly interesting. The potential benefit of using immunomodulators to reduce intimal hyperplasia and restenosis has been applied in the development of drug-eluting stents [18]. Less is known on the role of steroids in the same setting, although a benefit has been suggested in some studies [19, 20]. Another study has demonstrated that methotrexate, one of the most commonly used second-line agents in RA, increased the incidence of adverse cardiovascular events, although a more recent study found a decreased risk of death as a result of cardiovascular causes [3]. Further studies are required to clarify whether the underlying CTD activity, as dictated by its natural history and modifications with pharmacologic therapy, affects long-term results after CABG.
The main limitations of the present study are its retrospective nature and the small study group size, which limits the ability to perform more detailed statistical analysis; only examination of a large database can overcome this factor. The diagnosis of a CTD has not been included in the major databases to date. Unfortunately, the lack of a prospectively constructed database in our institution limited our ability to compare our study population directly with the remainder of the cardiac surgical population operated on in our hospital, except for the perioperative mortality data; such a comparison would certainly eliminate institution-related confounding factors. For that reason, we chose to compare our study population with the STS database with regard to demographic and perioperative variables, fully understanding that the results of such a comparison can only be viewed as suggestions for future studies.
A further criticism may be the relatively short follow-up. Although this is true, the study primarily focuses on perioperative outcomes; in addition, the reported midterm results are already inferior to those expected, therefore longer follow-up would logically reinforce our findings.
In summary, patients with CTDs and CADs can safely undergo CABG, with acceptable early outcomes. Wound infections at the vein harvest sites can be a potential problem. Preoperative treatment with steroids or other immunomodulating agents is associated with increased risk for complications. The midterm results appear somewhat inferior to those seen in the general population, and reinterventions may frequently be required.
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References
|
|---|
- Disorders of immune-mediated injury. In: Braunwald F, Kasper D, Hauser S, Longo D, Jameson L, eds. Harrison's principles of internal medicine. New York: McGraw-Hill, 2001:1947–2029..
- Davidson A, Diamond B. Autoimmune diseases N Engl J Med 2001;345:340-350.[Free Full Text]
- del Rincon I, Escalante A. Atherosclerotic cardiovascular disease in rheumatoid arthritis Curr Rheumatol Rep 2003;5:278-286.[Medline]
- Asanuma Y, Oeser A, Shintani AK, et al. Premature coronary-artery atherosclerosis in systemic lupus erythematosus N Engl J Med 2003;349:2407-2415.[Abstract/Free Full Text]
- 1999 Data Analyses of the STS National Cardiac Surgery Database, http://www.ctsnet.org/doc/2986. August 5, 2002..
- Meyer O. Atherosclerosis and connective tissue diseases Joint Bone Spine 2001;68:564-575.[Medline]
- Goodson N. Coronary artery disease and rheumatoid arthritis Curr Opin Rheumatol 2002;14:115-120.[Medline]
- D Agate DJ, Kokolis S, Belilos E, et al. Premature coronary artery disease in systemic lupus erythematosus with extensive reocclusion following coronary artery bypass surgery J Invasive Cardiol 2003;15:157-163.[Medline]
- Bossert T, Falk V, Gummert JF, Rahmel A, Mohr FW. Coronary artery bypass grafting in patients with systemic lupus erythematosus Z Kardiol 2003;92:219-221.[Medline]
- Ura M, Sakata R, Nakayama Y, Ohtsuka Y, Saito T. Coronary artery bypass grafting in patients with systemic lupus erythematosus Eur J Cardiothorac Surg 1999;15:697-701.[Abstract/Free Full Text]
- Moro H, Hayashi J, Ohzeki H, et al. Surgical management of cardiovascular lesions caused by systemic inflammatory diseases Thorac Cardiovasc Surg 1999;47:106-110.[Medline]
- Rinaldi RG, Carballido J, Betancourt B, Sartori M, Almodovar EA. Coronary artery bypass grafting in patients with systemic lupus erythematosusReport of 2 cases. Tex Heart Inst J 1995;22:185-188.[Medline]
- Nishinaka T, Koyanagi H, Endo M, Nishida H. Coronary artery bypass in systemic lupus erythematosus using total autogenous arterial bypass J Card Surg 1994;9:440-442.[Medline]
- Sergeant P, Blackstone E, Meyns B, Stockman B, Jashari R. First cardiological or cardiosurgical reintervention for ischemic heart disease after primary coronary artery bypass grafting Eur J Cardiothorac Surg 1998;14:480-487.
- Guru V, Fremes S, Tu J. Time-related mortality for women after coronary artery bypass graft surgery: a population-based study J Thorac Cardiovasc Surg 2004;127:1158-1165.[Abstract/Free Full Text]
- Vaccarino V, Koch C. Long-term benefits of coronary bypass surgery: are the gains for women less than for men? J Thorac Cardiovasc Surg 2003;126:1707-1711.[Free Full Text]
- Koch C, Khandwala F, Nussmeier N, Blackstone E. Gender and outcomes after coronary artery bypass grafting: a propensity-matched comparison J Thorac Cardiovasc Surg 2003;126:2032-2043.[Abstract/Free Full Text]
- Babapulle MN, Eisenberg MJ. Coated stents for the prevention of restenosis: part II Circulation 2002;106:2859-2866.[Free Full Text]
- Kakio T, Matsumori A, Ohashi N, et al. The effect of hydrocortisone on reducing rates of restenosis and target lesion revascularization after coronary stenting less than 3 mm in stent diameter Intern Med 2003;42:1084-1089.[Medline]
- Hoepp LM, DeWeese JA, Elbadawi A. Effect of steroids and immunosuppression on anastomotic intimal hyperplasia in femoral arterial bypass grafts Surg Forum 1976;27:215-216.[Medline]
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Abstract
Introduction
