Cardiovascular disease is common in individuals with end-stage renal disease (ESRD) and accounts for between 40 and 45% of all deaths in these patients (
1 , ). At the time of initiation of chronic dialysis treatment in 1999, approximately 25% of patients have a history of ischemic heart disease and about 10% have had myocardial infarction (MI) ( 2 2 , ). Although the rate of death from cardiac disease in ESRD patients in the United States fell in the 8-yr period between 1991 and 1998, the incident rate of MI rose in the second and third years of treatment by 15.7% and 6.8%, respectively ( 3 ). In addition, the short-term and long-term prognosis after acute MI in ESRD patients is poor, with 40% of patients dying of cardiac causes at 1 yr and almost 60% by 3 yr ( 4 ). 5
The high rates of serious and fatal coronary artery disease in ESRD patients underscores the need for a systematic approach to the cardiac assessment of individuals being considered for kidney and kidney-pancreas transplantation. Clinical practice guidelines (
6 , ) and reviews ( 7 8 , ) have recommended that noninvasive screening tests or coronary angiography be performed based on the individual’s estimated risk of CAD. There is agreement that many young patients, including some with diabetes, are at low risk and do not need special investigations ( 9 10 – ), whereas those with angina or history of MI should undergo cardiac catheterization ( 12 8 , ). However, for the older asymptomatic patient with either diabetes or other coronary risk factors, myocardial perfusion studies (MPS) such as thallium scintigraphy or DSE have been recommended ( 9 6 , 8 , ). 9
The diagnostic test characteristics of MPS have been studied, and a wide range of sensitivities for the detection of significant coronary artery disease have been reported (as reviewed in references
and 6 ). However, less is known about whether patients with abnormal MPS are at higher risk for future MI or CD. Although a large number of studies using MPS or DSE have been reported, the prognostic accuracy of many of the individual reports has been limited by small sample sizes (range, 33 to 189), low event rates (range, 3 to 28 events), and the lack of multivariate analysis. Accordingly, to assess the prognostic utility of MPS, we performed a meta-analysis of 12 studies that reported the rate of MI and cardiac death in ESRD patients assessed for kidney or kidney-pancreas transplantation. 7 Materials and Methods
We searched for references included in the National Library of Medicine’s MEDLINE database using OVID between 1977 and October 2000. Primary studies were identified using combinations of MeSH headings and textwords for coronary artery disease, transplantation, prognosis, end-stage renal disease (ESRD), stress nuclear scintigraphy, and dobutamine stress echocardiography. Independently, two researchers (CGR and DJT) reviewed the citation list and identified possibly relevant articles. We obtained all articles judged potentially relevant by either reviewer for further evaluation. A manual search of the reference lists of all review and primary articles identified other possibly relevant studies, which we retrieved for further evaluation. We hand-searched published abstracts, for the years 1995 to 2000, from the proceedings of the American Society of Nephrology, the American College of Cardiology, and the American Heart Association and identified other potentially relevant studies.
We used the following criteria to select articles. First, the study population had to include adult patients with chronic renal insufficiency or ESRD assessed for kidney or kidney-pancreas transplantation. Second, myocardial perfusion testing (exposure) had to include either nuclear scintigraphy (thallium or sestamibi) or DSE. The study had to report the outcomes of cardiac death (CD) and/or MI in the cohort of patients according to the MPS result. The minimum sample size was five patients. Disagreements were resolved by discussion and consensus.
The methodologic quality of individual articles is an important consideration for assessing whether the results of a study are biased. In duplicate and independently, two of us (CGR and DJT) used the following criteria (
) to judge the quality of the original articles. 13 Population.
Studies reporting on all patients assessed for transplantation (inception cohort) were classified as consecutive. Studies that excluded some patients from the cohort or the analysis for any reason were considered nonconsecutive. Studies with unclear methods of cohort assembly were classified as unknown.
Observers unaware of the clinical status of the patient interpreted the test results (yes/no/uncertain).
Clinical outcomes were adjudicated by people unaware of both the test result and the clinical status of the patient (yes/no/unknown). We used the individual studies’ definition of CD and MI.
CD and MI were categorized by the MPS result. When data on either or both of these endpoints were not reported, data were requested from the authors. We defined a positive test as either: (
1) fixed: any baseline abnormality suggestive of noninducible ischemia (fixed defect on nuclear scintigraphy or resting wall motion abnormality on DSE), or ( 2) reversible: imaging changes suggestive of inducible ischemia (reversible perfusion defects on nuclear scintigraphy or new wall motion abnormalities on DSE). Studies were excluded if ( 1) stress ECG abnormalities or inability to achieve target heart rate were considered in their definition of an abnormal test, ( 2) the cardiac events could not be classified according to the stress imaging results. In addition, low-risk patients who did not have stress imaging performed were also excluded from the analysis. Statistical Analyses
We expressed inter-observer agreement for study selection and individual components of the methodologic quality review as kappa. We calculated the relative risk (RR) and 95% confidence interval (95% CI) for each event using the random effects model (
) using EasyMA 2000 software package ( 14 ). To avoid sparse cells and biased estimates when calculating the pooled RR, we used a constant of 0.25 to represent the number of events for studies in which no cardiac events occurred. Annualized event rates are expressed as the number of patients having MI or CD as a proportion of the number of patients at risk divided by the number of patient-years follow-up. One study ( 15 ) that did not provide data about duration of follow-up was excluded from these calculations. The events during follow-up were classified according to the baseline MPS result. Comparisons of risk of MI and CD were made between negative test results 16 versus positive test results (fixed and reversible combined), negative tests versus fixed defects, negative tests versus reversible defects, and fixed defects versus reversible defects. Sensitivity, specificity, and positive and negative predictive values were calculated using standard methods. We tested for homogeneity using the method of Cochran Q ( ). 17
We planned a prespecified subgroup analysis of diabetic and nondiabetic patients. Five studies were restricted to diabetic patients (
16 , 18 – ), five studies contained a mixed population of diabetic and nondiabetic patients ( 21 11 , 22 – ), whereas the remaining two studies provided sufficient information to distinguish MPS results and cardiac events for diabetic and nondiabetic patients ( 25 12 , ). Therefore, we report the primary endpoints according to MPS result in a combined analysis of all studies, and in two sub-groups of patients: ( 26 1) diabetic patients and ( 2) mixed population of diabetic and nondiabetic patients. Results
One hundred sixty-six studies were identified using our search strategy, 11 of which were published in English and met all inclusion criteria (
11 , 12 , 16 , 18 – ). One additional study was identified from references of the primary studies and review articles ( 25 ). Of the 12 studies included for analysis, four used DSE, and the other eight studies used myocardial scintigraphy. Of the myocardial scintigraphy studies, four used dipyridamole as a pharmacologic stress agent, and four used exercise. 26
Six other studies were identified as potentially relevant, but they were excluded for a variety of methodologic reasons. Two studies did not meet the criterion of independent reporting of MI and cardiac death and were excluded (
27 , ). One abstract was potentially relevant, but it contained insufficient data to classify MI and cardiac death by MPS result ( 28 ). The three remaining studies evaluated diabetic transplant candidates using stress-induced ECG abnormalities and/or failure to attain target heart rate in their definition of a positive test ( 29 30 – ) and were excluded. 32 Table 1 summarizes the characteristics and methodology of the 12 individual studies. The interobserver agreement for consecutive cohort assembly, definition of positive test result, blinding of interpreter of test to clinical status of the patient, and completeness of follow-up were reflected in the following κ values of 0.68, 0.93, 0.77, 0.96, respectively. Follow-up of patients was over 98% complete in each study. Table 1: Methodologic review of included primary studies a Combined Analysis
The results of the combined analysis are based on nine studies involving 670 patients reporting on MI (
11 , 16 , 18 – 21 , 23 – ) and 12 studies involving 913 patients reporting on CD ( 25 11 , 12 , 16 , 18 – ). 26 Risk of Myocardial Infarction
Nine of 388 patients with negative MPS had an MI, whereas 21 of 282 with a positive MPS had an MI, representing an annualized event rate of 1.6% and 4.3% for negative and positive MPS, respectively (
Tables 2 and 3). Figure 1A shows the individual study and pooled relative risk (RR) for MI. The RR of MI following a positive test was 2.73 (95% CI, 1.25 to 5.97; P = 0.01) when compared with patients with a negative test. No significant heterogeneity existed among individual study results ( P = 0.71). Figure 1.:
Myocardial infarction. (A) Positive
versus negative tests; (B) Reversible defects versus negative tests; (C) Fixed defects versus negative tests; (D) Reversible versus fixed defects. Table 2: Cardiac events classified by population type and characteristics of myocardial perfusion abnormality Table 3: Cardiac events and patient follow-up a
When considering the nature of the positive test result (fixed or reversible), the RR of MI was increased in individuals with reversible perfusion defects. In the comparison of reversible defects to normal perfusion images, the RR of MI was 6.19 (95% CI, 1.69 to 22.7;
P < 0.01; Figure 1B). Similarly, the RR of MI was 7.07 (95% CI, 0.93 to 53.5; P = 0.058) when comparing reversible defects to fixed defects ( Figure 1D). The RR of MI was not increased in individuals with fixed defects compared with normal perfusion images (RR 1.12 [95% CI, 0.1 to 12.2]; Figure 1C). Risk of Cardiac Death
Sixteen of 505 patients with negative MPS had a CD
versus 63 of 408 patients with a positive test, representing an annualized event rate of 1.8% and 6.9% for negative and positive MPS, respectively ( Tables 2 and 3). Figure 2A shows the individual study and pooled RR of cardiac death. The RR of a CD among patients with a positive test was 2.92 (95% CI, 1.66 to 5.12; P < 0.001) compared with patients with a negative test. No significant heterogeneity existed among individual study results ( P = 0.79) Figure 2.:
Cardiac death. (A) Positive
versus negative tests; (B) Reversible defects versus negative tests; (C) Fixed defects versus negative tests; (D) Reversible versus fixed defects.
The presence of both reversible and fixed perfusion abnormalities was associated with an increased risk of CD when compared with normal test results. Patients with reversible defects also had a RR of CD 3.82 (95% CI, 1.83 to 7.94;
P < 0.001; Figure 2B) compared with patients with normal images. Similarly, the RR of CD was 4.74 (95% CI, 2.26 to 9.92; P < 0.001) when patients with fixed defects were compared with those with normal test results ( Figure 2C). The RR of CD was not increased in patients with reversible defects compared with those with fixed perfusion defects (RR 0.78 [95% CI, 0.48 to 1.25]; P = 0.29; Figure 2D).
If future MI or CD is considered the gold standard against which MPS results are to be applied, the sensitivity of MPS is 0.80 for CD and 0.70 for MI. The specificity is 0.59 for both MI and CD. The overall incidence of MI was 4.5% and of CD was 8.7%, representing average annualized event rates of 2.8% for MI and 4.3% for CD. The positive predictive value for MI is 7.4% and for CD is 15.4%. The negative predictive value of normal MPS in the combined analysis was 97.7% for MI and 96.9% for CD.
In the diabetic subgroup, data for MI was available in five studies (
16 , 18 – ) involving 338 patients and for CD in seven studies ( 21 12 , 16 , 18 – 21 , ) involving 423 patients. 26
Five of 213 diabetic patients with a negative MPS had an MI
versus 11 of 125 diabetic patients with a positive MPS, representing an annualized event rate of 2.4% and 8.4% for negative and positive MPS, respectively. A positive test result was associated with a RR of MI (2.68 [95% CI, 0.95 to 7.57]; P = 0.06) of borderline statistical significance when compared with patients with negative test results ( Figure 1A, “Diabetics”). However, when studies were analyzed according to the type of the perfusion defect, patients with diabetes assessed for transplantation who had reversible perfusion defects had an RR of MI of 9.29 (95% CI, 1.77 to 48.8) compared with diabetics with normal perfusion images ( P < 0.01; Figure 1B). Comparisons of the other perfusion defects in the diabetic subgroups (fixed defects versus normal tests; reversible versus fixed defects) were not statistically significant ( Figures 1, C and D).
Cardiac death occurred in 3 of 252 diabetic patients with a negative MPS
versus 20 of 171 diabetic patients with a positive MPS, representing an annualized event rate of 0.9% and 6.8% for negative and positive MPS, respectively. The RR of CD was (3.95 [95% CI, 1.48 to 10.5]; P = 0.006; Figure 2A) in diabetic patients with a positive test when compared with diabetic patients with a negative test. The analysis based on the nature of the perfusion defect revealed that, when compared with those with normal perfusion images, those with reversible perfusion defects had an RR of CD of 3.97 (95% CI, 1.17 to 13.5; P = 0.03; Figure 2B), and those with fixed perfusion defects had an RR of CD of 4.70 (95% CI, 1.31 to 16.9; P = 0.02; Figure 2C). No increase in risk was observed when comparing fixed versus reversible defects in patients with diabetes. Mixed Population.
In the mixed population group, data for MI was available in four studies (
11 , 23 – ) involving 332 patients and for CD in 7 studies involving 490 patients ( 25 11 , 12 , 22 – ). 26
Cardiac death occurred in 13 of 253 patients with negative MPS
versus 43 of 237 patients with positive MPS, representing an annualized event rate of 2.2% and 7.0% for negative and positive MPS, respectively. A positive test result was associated with an increased RR of CD (2.52 [95% CI, 1.25 to 5.08]; P = 0.01; Figure 2A, “Mixed”) when compared with those with a negative test. The RR of CD was also significantly increased in patients with reversible (RR, 3.77 [95% CI, 1.40 to 10.2]; P < 0.01; Figure 2B) or fixed (RR, 4.76 [95% CI, 1.93 to 11.8]; P < 0.001; Figure 2C) perfusion defects when compared with those with normal perfusion images. In these studies, the risk of future MI was not significantly associated with MPS results.
Table 3 summarizes the event rates in the combined population and in subgroups of diabetic patients and the mixed group of patients. In patients with negative MPS result, 8 of 277 patients followed for 6107.5 patient-months had an MI (average event rate, 1.6%/yr). Cardiac deaths occurred in 16 of 394 patients followed for 10945.5 patient-months (average event rate, 1.8%/yr). Discussion
The results of this meta-analysis confirm that individuals with abnormal MPS before kidney or kidney-pancreas transplantation are at higher future risk for cardiac events than those individuals with normal tests. Compared with patients with normal tests, those with evidence of inducible ischemia (reversible defects, new wall motion abnormality) have a sixfold increase in the risk of MI and an almost fourfold risk of cardiac death. In addition, patients with noninducible ischemia (fixed defects, resting wall motion abnormality) also have a significantly higher risk of cardiac death (RR, 4.7) but not MI (RR, 1.1). Diabetic patients have a similar pattern of risk, with reversible defects alone strongly associated with MI (RR, 9.3) and both fixed and reversible defects associated with cardiac death (RR, 4.0 to 4.7).
The results of our meta-analysis may be limited by several potential biases. In many studies we included, positive test results led to coronary angiography and may have introduced a verification bias. Verification bias occurs when the screening test result leads to a confirmatory or gold standard test such as a coronary angiogram (
). If the results of coronary angiography led to coronary revascularization, the rate of MI and cardiac death may change and could alter the predictive accuracy of the noninvasive cardiac tests. For example, the results of a randomized controlled trial of surgical revascularization 33 versus medical therapy by Manske et al. ( ) suggest diabetic patients with asymptomatic CAD benefit from pretransplant coronary revascularization. In this study, 26 patients with type I diabetes mellitus, left ventricular ejection fraction >35%, and asymptomatic coronary artery lesions judged to be hemodynamically significant were randomized to medical therapy, consisting of ASA and a calcium channel blocker or revascularization. Nine of thirteen patients in the medical group 34 versus 2 of 13 in the revascularization group experienced fatal or nonfatal myocardial infarctions. This study suggests that coronary revascularization in patients with type I diabetes reduces the risk of subsequent cardiac events, and this could result in an underestimate of the risk associated with a positive MPS. The effect of this potential bias on our results cannot be estimated because the numbers of patients treated with revascularization have not been reported in the studies we reviewed.
In nondiabetic patients with ESRD, the effect of verification bias on the predictive accuracy of noninvasive cardiac testing is more difficult to assess. No randomized controlled trial comparing medical therapy
versus revascularization exists, so optimal treatment strategies are unknown. If verification bias in nondiabetic patients led to angioplasty or bypass procedures, the noninvasive cardiac tests would overestimate the risk of MI and cardiac death if revascularization increased perioperative risk and/or did not improve the long-term prognosis. There is evidence to support this pattern of morbidity and mortality in ESRD patients who are treated with coronary revascularization. In a large observational study of 14,306 diabetic and nondiabetic ESRD patients who had coronary revascularization, in-hospital mortality rate ranged from 5.4 to 12.5%; by 2 yr, 30 to 40% of patients had either died of heart disease or had nonfatal MI ( ). These findings suggest that a verification bias could overestimate the accuracy of positive MPS. 35
Four of the twelve studies included in this meta-analysis used exercise instead of pharmacologic stress, which may introduce bias in two ways. First, patients unable to exercise to achieve a target heart rate may have falsely negative MPS. If these patients had a future risk of cardiac events similar to the risk of patients with positive MPS, their inclusion in the normal test group would tend to decrease the relative risk of future cardiac events associated with a positive test, thereby underestimating the true risk associated with a positive MPS. Second, it is unclear whether patients with ESRD selected for pharmacologic stress have exercise capacity that is more limited than patients selected for exercise testing. In the general population, exercise capacity is a powerful independent prognostic factor in men referred for exercise testing (
). Therefore, it is possible that underlying comorbidity, as reflected in ability to exercise, may influence the choice of either pharmacologic or exercise testing, which could result in misleading risk estimates when the results of the two strategies are combined. However, the lack of heterogeneity in the pooled analysis suggests that the results are probably generalizable to both groups’ patients. 36
Several methodologic features of the studies we reviewed limit our understanding of the prognostic accuracy of MPS. First, because we were unable to determine from the primary studies when patients had cardiac events, the usual statistical analysis applied to survival data could not be performed. As a consequence, the findings in
Table 3 are limited to a description of the proportions of patients with and without cardiac events according to their MPS test result, and the average event rate per 100 patient-years of follow up. Second, the results of our meta-analysis are based on univariate analyses and are not adjusted for other important prognostic factors such as age, diabetes, and known coronary artery disease. It is therefore important to ask whether the noninvasive test results are still valid when these other prognostic variables are considered. Older age, diabetes, and left ventricular dysfunction and hypertrophy are strongly associated with MI and cardiac death in ESRD patients ( 5 , 37 , ). However, only 1 of the 12 studies included in this meta-analysis used multivariate analysis to confirm the independent prognostic value of noninvasive tests in predicting cardiac outcomes. Bates and colleagues reported that in 53 patients that a new wall motion abnormality was associated with future cardiac events (odds ratio 12.7) ( 38 ). Brown 21 et al. ( ) found that both reversible defects on thallium scintigraphy and left ventricular dysfunction were independently associated with the combined outcome of future MI or CD. Recently, we have confirmed the findings of these investigators. In a study of 441 consecutive patients being assessed for kidney transplantation, we used a Cox regression analysis to confirm that abnormal thallium/sestamibi test results were still predictive of MI and CD (RR, 2.5) when adjusted for both age and diabetes ( 27 ). Similar results were found in a meta-analysis of 15 published reports on preoperative pharmacologic stress risk stratification of patients without kidney disease undergoing vascular surgery ( 39 ). Taken together, these findings provide preliminary support that MPS accurately stratify risk in ESRD patients who have multiple risk factors for heart disease. 40
What are the implications of our findings for the clinician assessing patients for kidney and kidney-pancreas transplantation? First, the combined analysis of any MPS abnormality has adequate sensitivity for future MI or CD (0.70 and 0.80, respectively). Thus, when the average annualized incidence is between 3 to 5%, the negative predictive value exceeds 96%. These values are comparable to MPS test properties in detecting angiographically significant CAD (
). Second, our results also show that evidence of inducible ischemia on MPS is strongly associated with MI and cardiac death in both diabetic and nondiabetic patients, supporting the recommendation that such patients be evaluated with coronary angiography ( 24 5 – ). Third, we found that patients with non-inducible ischemia were at significantly higher risk for future cardiac death but not MI. However, we could not establish if the higher risk of cardiac death in these patients was related to ongoing ischemia, left ventricular dysfunction, arrhythmias, or a combination of these processes, becuase the studies in our meta-analysis did not control for key prognostic factors. Parfrey 8 et al. ( ) reported that left ventricular hypertrophy and systolic dysfunction are independent risk factors for 41 de novo ischemic heart disease, especially in older patients and those with diabetes. At present, however, it is unknown which demographic and clinical factors are associated with and mediate the higher risk of death from heart disease in patients with non-inducible ischemia. In the absence of other data, and given the higher mortality risk for patients with non-inducible ischemia on MPS, our practice has been to offer cardiac catheterization to these individuals.
Can the clinician be reassured by the finding of a normal MPS in asymptomatic patients who are at higher risk because of older age or diabetes? The patients included in this meta-analysis, including those with normal tests, all had risk factors for cardiac disease (as the original indication for the MPS). For example,
Table 3 shows that among 102 diabetic patients with normal MPS, the incidence of MI was 2.4% per year. Similarly, among 141 diabetic patients with normal MPS, the incidence of CD was 0.9% per year. Although the specificity of MPS for future cardiac events is low, the negative predictive value is high for both MI and CD. These findings indicate a relatively low event rate among high-risk patients with normal tests; however, when compared with young patients without diabetes or other risk factors for CAD, patients with normal MPS still appear to be at higher risk. In two studies that followed low-risk patients, cardiac death occurred in 1 of 94 patients followed for a mean of 48 mo ( ) and in none of 72 patients followed for a mean of 12.2 mo ( 12 ). These findings suggest that over time, patients who have risk factors and normal MPS still have a higher cardiac risk than previously recognized. 11
In summary, we performed a meta-analysis of 12 observational studies involving 913 patients assessed with MPS as part of their cardiac evaluation before kidney or kidney-pancreas transplantation. We conclude that in patients with ESRD assessed for transplantation and evaluated using nuclear scintigraphy or DSE, a negative test result is associated with a low event rate for each of MI and cardiac death. Conversely, patients with abnormal myocardial perfusion studies are at higher long-term risk for MI or cardiac death. This was observed for both fixed and reversible perfusion defects. The data from these studies should be useful to clinicians when counseling patients about cardiac risk and making decisions about subsequent cardiac investigations before kidney or kidney-pancreas transplantation.
Dr. Rabbat is the recipient of the 1999–2001 Kidney Foundation of Canada Hoffmann-LaRoche Fellowship, Dr. Treleaven is the recipient of a 2001–2003 Kidney Foundation of Canada Fellowship, and Dr. Cook is a Chair of the Canadian Institutes for Health Research.
1. US Renal Data System: Appendix H, Mortality and causes of death, In: USRDS 2000 Annual Data Report, Bethesda, MD, National Institutes of Health National Institute of Diabetes, Digestive, Kidney Diseases, 2000, pp 659
2. Foley RN, Parfrey PS, Sarnak MJ: Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol 9: S16–S23, 1998
3. US Renal Data System: Patient characteristics at the beginning of ESRD, In: USRDS 2001 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, Bethesda, MD, National Institutes of Health, National Institute of Diabetes, Digestive, Kidney Diseases, 2001,p 58
4. US Renal Data System: Cardiovascular special studies, In: USRDS 2001 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, MD, National Institutes of Health, National Institute of Diabetes, Digestive, Kidney Diseases, 2001,p 153
5. Herzog CA, Ma JZ, Collins AJ: Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N Engl J Med 339: 799–805, 1998
6. Kasiske BL, Ramos EL, Gaston RS, Bia MJ, Danovitch GM, Bowen PA, Lundin PA, Murphy KJ: 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 6: 1–34, 1995
7. Kasiske BL, Cangro CB, Hariharan S, Hricik DE, Kerman RH, Roth D, Rush DN, Vazquez MA, Weir MR: The evaluation of renal transplantation candidates: Clinical practice guidelines. Am J Transplant 1 [Suppl 2]: 1–95, 2002
8. Herzog CA: Diagnosis and treatment of ischemic heart disease in dialysis patients. Curr Opin Nephrol Hypertens 6: 558–565, 1997
9. de Lemos JA, Hillis LD: Diagnosis and management of coronary artery disease in patients with end-stage renal disease on hemodialysis. J Am Soc Nephrol 7: 2044–2054, 1996
10. Manske CL, Thomas W, Wang Y, Wilson RF: Screening diabetic transplant candidates for coronary artery disease: Identification of a low risk subgroup. Kidney Int 44: 617–621, 1993
11. Lewis MS, Wilson RA, Walker K, Stegeman-Olsen J, Norman DJ, Barry JM, Bennett WM: Factors in cardiac risk stratification of candidates for renal transplant. Journal of Cardiovascular Risk 6: 251–255, 1999
12. Le A, Wilson R, Douek K, Pulliam L, Tolzman D, Norman D, Barry J, Bennett W: Prospective risk stratification in renal transplant candidates for cardiac death. Am J Kidney Dis 24: 65–71, 1994
13. Laupacis A, Wells G, Richardson WS, Tugwell P: Users’ guides to the medical literature. V. How to use an article about prognosis. Evidence-Based Medicine Working Group. JAMA 272: 234–237, 1994
14. Fleiss JL: The statistical basis of meta-analysis. Stat Methods Med Res 2: 121–145, 1993
15. Cucherat M: EasyMA 2000, Lyon, France, 1997
16. Mistry BM, Bastani B, Solomon H, Hoff J, Aridge DL, Lindsey LM, Schmid S, Chaitman BR, Garvin PJ: Prognostic value of dipyridamole thallium-201 screening to minimize perioperative cardiac complications in diabetics undergoing kidney or kidney-pancreas transplantation. Clin Transplant 12: 130–135, 1998
17. Biggerstaff BJ, Tweedie RL: Incorporating variability in estimates of heterogeneity in the random effects model in meta-analysis. Stat Med 16: 753–768, 1997
18. Camp AD, Garvin PJ, Hoff J, Marsh J, Byers SL, Chaitman BR: Prognostic value of intravenous dipyridamole thallium imaging in patients with diabetes mellitus considered for renal transplantation. Am J Cardiol 65: 1459–1463, 1990
19. Iqbal A, Gibbons RJ, McGoon MD, Sterioff S, Frohnert PP, Velosa JA: Noninvasive assessment of cardiac risk in insulin-dependent diabetic patients being evaluated for pancreatic transplantation using thallium-201 myocardial perfusion scintigraphy. Clin Transplant 5: 13–19, 1991
20. Vandenberg BF, Rossen JD, Grover-McKay M, Shammas NW, Burns TL, Rezai K: Evaluation of diabetic patients for renal and pancreas transplantation: Noninvasive screening for coronary artery disease using radionuclide methods. Transplantation 62: 1230–1235, 1996
21. Bates JR, Sawada SG, Segar DS, Spaedy AJ, Petrovic O, Fineberg NS, Feigenbaum H, Ryan T: Evaluation using dobutamine stress echocardiography in patients with insulin-dependent diabetes mellitus before kidney and/or pancreas transplantation. Am J Cardiol 77: 175–179, 1996
22. Marwick TH, Steinmuller DR, Underwood DA, Hobbs RE, Go RT, Swift C, Braun WE: Ineffectiveness of dipyridamole SPECT thallium imaging as a screening technique for coronary artery disease in patients with end-stage renal failure. Transplantation 49: 100–103, 1990
23. Brennan DC, Vedala G, Miller SB, Anstey ME, Singer GG, Kovacs A, Barzilai B, Lowell JA, Shenoy S, Howard TK, Davila-Roman VG: Pretransplant dobutamine stress echocardiography is useful and cost-effective in renal transplant candidates. Transplant Proc 29: 233–234, 1997
24. Herzog CA, Marwick TH, Pheley AM, White CW, Rao VK, Dick CD: Dobutamine stress echocardiography for the detection of significant coronary artery disease in renal transplant candidates. Am J Kid Dis 33: 1080–1090, 1999
25. Marwick TH, Lauer MS, Lobo A, Nally J, Braun W: Use of dobutamine echocardiography for cardiac risk stratification of patients with chronic renal failure. J Intern Med 244: 155–161, 1998
26. Brown JH, Vites NP, Testa HJ, Prescott MC, Hunt LP, Gokal R, Mallick NP: Value of thallium myocardial imaging in the prediction of future cardiovascular events in patients with end-stage renal failure. Nephrol Dial Transplant 8: 433–437, 1993
27. Brown KA, Rimmer J, Haisch C: Noninvasive cardiac risk stratification of diabetic and nondiabetic uremic renal allograft candidates using dipyridamole-thallium-201 imaging and radionuclide ventriculography. Am J Cardiol 64: 1017–1021, 1989
28. Reis G, Marcovitz PA, Leichtman AB, Merion RM, Fay WP, Werns SW, Armstrong WF: Usefulness of dobutamine stress echocardiography in detecting coronary artery disease in end-stage renal disease. Am J Cardiol 75: 707–710, 1995
29. Welsh RC, Cockfield S, Halloran PF, Campbell P, Taylor D: Nonivasive cardiac assessment of diabetic nephropathy renal transplant candidates [abstract]. J Am Coll Cardiol 33: 335A, 1999
30. Philipson JD, Carpenter BJ, Itzkoff J, Hakala TR, Rosenthal JT, Taylor RJ, Puschett JB: Evaluation of cardiovascular risk for renal transplantation in diabetic patients. Am J Med 81: 630–634, 1986
31. Holley JL, Fenton RA, Arthur RS: Thallium stress testing does not predict cardiovascular risk in diabetic patients with end-stage renal disease undergoing cadaveric renal transplantation. Am J Med 90: 563–570, 1991
32. Morrow CE, Schwartz JS, Sutherland DE, Simmons RL, Ferguson RM, Kjellstrand CM, Najarian JS: Predictive value of thallium stress testing for coronary and cardiovascular events in uremic diabetic patients before renal transplantation. Am J Surg 146: 331–335, 1983
33. Jaeschke R, Guyatt G, Sackett DL: Users’ guides to the medical literature. III. How to use an article about a diagnostic test. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 271: 389–391, 1994
34. Manske CL, Wang Y, Rector T, Wilson RF, White CW: Coronary revascularisation in insulin-dependent diabetic patients with chronic renal failure. Lancet 340: 998–1002, 1992
35. Herzog CA, Ma JZ, Collins AJ: Long-term outcome of dialysis patients in the United States with coronary revascularization procedures. Kidney Int 56: 324–332, 1999
36. Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE: Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 346: 793–801, 2002
37. Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE: The prognostic importance of left ventricular geometry in uremic cardiomyopathy. J Am Soc Nephrol 5: 2024–2031, 1995
38. Foley RN, Parfrey PS, Harnett JD, Kent GM, Martin CJ, Murray DC, Barre PE: Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. Kidney Int 47: 186–192, 1995
39. Rabbat CG, Lambert K, Stanton EB, Churchill DN, Russell JD: Long term prognostic significance of clinical risk stratification and myocardial perfusion studies in patients assessed for renal transplantation [Abstract]. Am J Transplant 1: 378, 2001
40. Shaw LJ, Eagle KA, Gersh BJ, Miller DD: Meta-analysis of intravenous dipyridamole-thallium-201 imaging (1985 to 1994) and dobutamine echocardiography (1991 to 1994) for risk stratification before vascular surgery. J Am Coll Cardiol 27: 787–798, 1996
41. Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray D, Barre PE: Outcome and risk factors of ischemic heart disease in chronic uremia. Kidney Int 49: 1428–1434, 1996