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European Journal of Echocardiography 2005 6(5):313-316; doi:10.1016/j.euje.2005.06.009
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Copyright © 2005, The European Society of Cardiology

Ischemic heart disease in renal transplant candidates: Towards non-invasive approaches for preoperative risk stratification

H.H.H. Feringaa, J.J. Baxb, O. Schoutenc and D. Poldermansd,*

aDepartment of Anesthesiology, Erasmus MC, Rotterdam, The Netherlands
bDepartment of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
cDepartment of Vascular Surgery, Erasmus MC, Rotterdam, The Netherlands
dDepartment of Cardiology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands

Received 30 May 2005; .

d.poldermans{at}erasmusmc.nl

* Corresponding author. Tel.: +31 10 4634613; fax: +31 10 4634957.


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This editorial refers to the paper of R. Sharma et al. entitled "Dobutamine stress echocardiography and cardiac troponin T for the detection of significant coronary artery disease and predicting outcome in renal transplant candidates".

The editorial discusses different strategies for cardiac risk assessment in patients with end-stage renal disease undergoing renal transplantation.

Keywords: Dobutamine stress echocardiography; Troponins; End-stage renal disease; Ischemic heart disease; Prognosis

Please see the article by Sharma et al. (doi: 10.1016/j.euje.2005.04.011) to which this editorial pertains.

In patients with end-stage renal failure, coronary artery disease is the leading cause of morbidity and mortality. It has been shown in a prospective randomized study that prophylactic coronary artery revascularization in renal transplant candidates with diabetes and without symptoms of coronary artery disease reduces the incidence of cardiac events.1 The detection of coronary artery disease prior to renal transplantation has therefore been an important goal in transplant programs. The American Society of Transplantation reported guidelines for the pre-transplant evaluation of renal transplant candidates.2 They included the use of non-invasive cardiac stress testing, however, it remained unclear which test to use due to the lack of firm support for a single test.

In this issue of the European Journal of Echocardiography, Sharma et al. evaluated the diagnostic accuracy and prognostic value of dobutamine stress echocardiography (DSE) and elevated baseline plasma cardiac troponin T levels in a study population of 118 consecutive patients with end-stage renal disease. They used coronary angiography for stress test validation and found DSE to be an accurate technique for detecting coronary artery disease (sensitivity of 88%, specificity of 94%). Elevated troponin T levels in addition to an abnormal stress test could not improve the sensitivity of the test, however, it was an important marker for the prognosis in renal transplant candidates (cardiac troponin T level >0.08ng/mL for predicting mortality: sensitivity 75%, specificity of 76%).

Previously published studies evaluating the diagnostic accuracy of DSE for detecting coronary artery disease reported sensitivities of 52–95% and specificities of 71–86%.3,4 In addition, the result of the DSE has been shown to be an independent predictor of prognosis in patients with end-stage renal disease.5–7 The accuracy of these studies may have been limited by small sample sizes, low event rates and the lack of adjustment for clinical risk factors, but a meta-analysis of 12 studies assessed the prognostic utility of DSE and thallium scintigraphy in patients with end-stage renal disease and confirmed that abnormal test results were associated with a higher risk for cardiac events.8 Inducible ischemia was associated with a sixfold increased risk of myocardial infarction and an almost fourfold increased risk of cardiac death. Fixed defects (rest wall motion abnormalities) were also significantly associated with an increased risk of cardiac death.

Cardiac isoforms of troponin I and troponin T, sensitive and specific markers of myocardial injury, have been accepted as standard biomarkers for the diagnosis of acute myocardial infarction and unstable angina pectoris, and identify patients at increased risk for subsequent cardiac events. Elevated troponin levels in asymptomatic patients with renal disease have been well-documented9 and there is substantial evidence that cardiac troponins predict cardiac complications in patients with end-stage renal disease.10–12 Dierkes et al. studied 102 patients with end-stage renal disease on haemodialysis without clinical evidence of acute coronary artery disease and they found a strong association between elevated troponin T levels and all-cause mortality (cardiac troponin T level>0.10ng/mL: sensitivity 83%).10 In a large study cohort of 244 haemodialysis patients, Ooi et al. found that higher plasma cardiac troponin T levels and increasing cardiac troponin T concentrations over time predicted all-cause mortality.11 The association between increases in cardiac troponin T concentrations and mortality was confirmed in a large study cohort of 733 patients with end-stage renal disease, conducted by Apple et al.12

Although the underlying pathophysiological mechanism is still not clearly elucidated, elevated troponin levels may be a marker of subclinical myocyte damage secondary to clinically silent myocardial necrosis.13 The sensitivity of troponin T to predict angiographic artery disease has been demonstrated in patients with a normal renal function; however, future studies are still needed to confirm this in patients with end-stage renal failure.14 It may be difficult to detect elevated plasma cardiac troponin T levels in asymptomatic patients with coronary artery disease, not only because of the transient release of cardiac troponin T during transient myocardial ischemia, but also because cardiac troponins are susceptible to various biochemical modifications, including phosphorylation, oxidation and proteolysis.13 In addition, dialysis may affect serum levels of cardiac troponins.15 Serial troponin measurements may enhance the detection rate of plasma cardiac troponin levels and the value of cardiac troponins to predict coronary artery disease.

Coronary angiography is an effective method for detecting CAD and is essential for the performance of percutaneous transluminal coronary angiography and revascularization surgery, however, it is invasive, expensive and potentially nephrotoxic. Dissimilarities in sensitivity and specificity for DSE and myocardial scintigraphy to detect anatomic evidence of coronary artery disease have been reported in patients with end-stage renal failure, and the use of invasive coronary angiography might still be necessary to rule out significant coronary artery disease.16 Coronary angiography in comparison to non-invasive stress testing might have stronger prognostic value in patients with end-stage renal disease.16 However, the good negative predictive value of non-invasive stress testing suggests that patients with no stress-induced myocardial ischemia do not need further coronary angiography. In addition, the risk of contrast-associated nephropathy is an important concern in these patients. Coronary angiography should only be performed in patients with end-stage renal disease, when coronary artery revascularization is considered a reasonable option.

Recently, interest has focused on coronary CT scanning as non-invasive method for diagnosing coronary artery disease. Coronary calcification detected by coronary CT scanning has been shown to be associated with silent myocardial ischemia as assessed with myocardial perfusion studies and to detect coronary artery disease in symptomatic patients.17 Coronary calcification is frequently observed in patients with end-stage renal failure and coronary CT may be a promising tool to improve cardiac risk stratification in these population.

Traditionally, coronary artery disease in patients with end-stage renal disease has been treated conservatively, but these patients may gain from an aggressive treatment strategy, including mechanical coronary revascularization for clinically significant coronary artery disease. Manske et al. randomly assigned 26 asymptomatic diabetic renal transplant candidates to medical treatment or coronary revascularization and demonstrated that revascularization significantly decreased the frequency of cardiac events during follow-up.1 Retrospective studies also suggest that mechanical coronary revascularization is associated with improved outcomes, compared to medical therapy alone in patients with end-stage renal disease.18 Prophylactic mechanical coronary artery revascularization before surgery may only be recommended in patients with advanced left main coronary artery disease or unstable cardiac symptoms. However, many physicians are reluctant to perform mechanical coronary revascularization procedures in patients with end-stage renal disease because of the poor outcomes compared to patients with normal renal function. The Coronary Artery Revascularization Prophylaxis trial showed that long-term outcome after elective major vascular surgery was not significantly altered by coronary artery revascularization before surgery in 510 patients with stable coronary artery disease randomly assigned to either revascularization or no revascularization.19 Large, prospective, randomized, controlled trials are needed to prove a survival benefit of preoperative coronary artery revascularization in renal transplant candidates with stable coronary artery disease. Besides surgical strategies, attention should also be focused on medical treatment strategies for cardiovascular disease, which may be under-utilized in patients with severe chronic kidney disease.

Appropriate preoperative evaluation of renal transplant candidates is not only mandated to identify those at increased cardiac risk, but also because the number of available organs is limited and early death of a recipient can be prevented by pre-transplant coronary intervention. Dobutamine stress echocardiography is widely recognized as an accurate diagnostic method for use in the general population and several studies have proved its diagnostic and prognostic value in patients with end-stage renal disease. Dobutamine stress testing has substituted exercise stress testing, because a substantial number of patients do not reach 85% of their maximum heart rate during exercise stress testing. It furthermore avoids the potentially nephrotoxic influence of contrast material as observed during nuclear imaging techniques. The ideal algorithm, incorporating risk factors, laboratory results, non-invasive stress testing, coronary angiography and preoperative coronary revascularization for the work-up of renal transplant patients still has to be validated.


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 Abstract
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Related articles in Eur J Echocardiogr:

Dobutamine stress echocardiography and cardiac troponin T for the detection of significant coronary artery disease and predicting outcome in renal transplant candidates
R. Sharma, D. Pellerin, D.C. Gaze, J.S. Shah, C.P. Streather, P.O. Collinson, and S.J. Brecker
Eur J Echocardiogr 2005 6: 327-335. [Abstract] [FREE Full Text]  




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