Asian Cardiovasc Thorac Ann 2000;8:150-154
© 2000 Asia Publishing EXchange Pte Ltd
Role of Pretransplant Arteriography in Diabetic End-Stage Renal Disease
Naveen Garg, DM,
Aditya Kapoor, MD, DM,
Chirammal Valappil Umesan, MD,
Raj Kumar Sharma, MD1,,
Nakul Sinha, MD, DM
Department of Cardiology
1 Department of Nephrology
Sanjay Gandhi Post-Graduate Institute of Medical Sciences
Lucknow, India
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For reprint information contact: Nakul Sinha, MD, DM Tel: 91 522 44 0700 Ext. 2223 Fax: 91 522 44 0973 email: nsinha{at}sgpgi.ac.in Department of Cardiology, Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India.
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Abstract
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Diabetic renal transplant candidates have a high prevalence of obstructive coronary artery disease that is a major cause of morbidity and mortality. This study sought to stratify the risk for renal transplantation by correlating noninvasive tests with arteriographic findings. Fifty-two diabetics (46 males, 6 females) with end-stage renal disease were evaluated noninvasively and by coronary arteriography. The mean age was 46 ± 6 years. Twenty-five patients (48%) had noninvasive evidence of coronary artery disease (angina in 10, old myocardial infarction on electrocardiogram in 6, ST-T changes in 8, regional wall motion abnormality on echocardiography in 8, positive dobutamine echocardiogram in 4, and positive dipyridamole thallium tests in 13). Obstructive coronary artery disease was demonstrated by arteriography in 27 (51.9%). Concordance between noninvasive findings and arteriography was 65.3%. Obstructive coronary disease was present in 66.7% of those with 2 noninvasive indications, in all with more than 2 indications, and in all cases of regional wall motion abnormality. Thus, more than 2 positive noninvasive parameters or wall motion abnormality on an echocardiogram were highly predictive of coronary disease.
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Introduction
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Diabetic renal transplant candidates have a high incidence of significant obstructive coronary artery disease (CAD), which increases with age.1,2 Manske and colleagues3 reported a prevalence as high as 88% in patients over 45 years of age. CAD and cardiovascular complications are major determinants of survival in patients with end-stage renal disease (ESRD). Nearly half of the deaths among dialyzed diabetics and 30% to 50% of deaths before and after renal transplantation are from cardiac causes.4 Pretransplant revascularization of coronary vessels with greater than 75% diameter loss decreases the short-term cardiac morbidity and mortality of diabetic transplant candidates.5 Thus, there is a need to identify renal trans-plant candidates at high risk of cardiac death, to allow more effective use of donor kidneys. Diagnosis of obstruc-tive CAD by clinical symptoms or an exercise electro-cardiogram (ECG) is unreliable in these patients. Both exercise thallium and dipyridamole thallium tests have unacceptably low sensitivity in diabetic patients with ESRD.6,7 Many centers now recommend pretransplant coronary arteriography for most diabetic transplant candidates.3,8 However, this is an invasive procedure with a definite, albeit low, risk. Therefore, noninvasive pre-transplantation risk stratification is highly desirable. This study was undertaken to determine the correlation between angiographically determined obstructive CAD and various clinical and noninvasive parameters in diabetic ESRD patients who were candidates for transplantation.
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Patients and Methods
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Fifty-two prospective renal transplant candidates were enrolled in the risk stratification algorithm. Inclusion criteria were age over 40 years, non-insulin-dependent diabetes mellitus, and creatinine clearance less than 10 mL•min–1. All patients underwent detailed clinical evaluation regarding history of angina, previous myo-cardial infarction (MI), smoking habits, hypertension, family history of CAD, age at onset of diabetes, and dialysis history. A detailed cardiovascular examination was performed with special emphasis on cardiac size, murmur, gallop sounds, evidence of cardiac failure, and peripheral bruits. Blood pressure was measured from the arm that did not have a fistula. Family history of CAD was defined as MI or sudden cardiac death in first-degree male relatives before 55 years of age or first-degree female relatives before 65 years. Onset of hypertension was defined as the start of antihypertensive therapy. Congestive heart failure was suspected if one of the following was present: history of orthopneic or paroxysmal nocturnal dyspnea; hospitalization for shortness of breath; cardio-megaly and gallop sounds; evidence of interstitial edema on chest radiograph.
ECG, chest radiography, detailed lipid profile, and two-dimensional echocardiogram with color-flow imaging were performed in all patients. Dipyridamole thallium imaging and dobutamine stress echocardiography were carried out in some patients. The ECG was evaluated for evidence of MI, abnormal ST-T changes, and left ventricular hypertrophy. Evidence of MI was regarded as positive if significant Q waves were present in more than one lead. ST-T segment abnormality was noted as present if either of the following were detected in the absence of bundle branch block and left ventricular hypertrophy: ST-segment depression or elevation of at least 1 mm; inverted T wave in any lead where the QRS complex had a net positive deflection. Left ventricular hypertrophy was coded as present or absent according to Romhilt and Estes' criteria.9 Chest radiographs were evaluated for cardiac size and evidence of pulmonary venous hypertension. Two-dimensional color-flow echocardiography determined cardiac size, left ventricular hypertrophy, ejection fraction, and regional wall motion abnormality. Dobutamine stress echocardiography was carried out according to standard protocols in standard transthoracic views.10 Dipyridamole thallium scans were undertaken after giving 400 mg of oral dipyridamole and injecting 1.5 mCi of Tl-201 one hour later. Stress views were acquired in anterior, left anterior oblique-45°, and left anterior oblique-70° pro-jections, redistribution images were obtained after 3 hours. Studies were interpreted both qualitatively and quanti-tatively using a computer analysis system. Planar thallium was performed in all cases. The test was considered normal if the patient had no chest pain, no significant ST de-pression in the ECG during stress, and no significant perfusion defect. The test was considered positive if it revealed a significant defect that was either fixed or reversible on delayed imaging, based on circumferential count profile analysis.
Coronary arteriography was carried out in all patients as part of the routine pretransplant screening. Informed consent was obtained in all cases. Patients were dialyzed the day before and after arteriography. Coronary arterio-graphy was performed via a femoral approach, using the standard Judkins technique in standard views, with Urografin 76% (Schering AG, Berlin, Germany).11 Each angiogram was independently reviewed by two ex-perienced cardiologists who were blinded to the clinical data and uninvolved in patient management. Obstructive CAD was defined as the presence of one or more epicardial coronary arteries with greater than 50% diameter stenosis.
Continuous variables were calculated as mean ± standard deviation and compared by unpaired Student's t test. Categorical variables were expressed as percentages and analyzed by Z test. Differences were considered statistically significant if the value of p was < 0.05.
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Results
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The mean age of the 52 patients was 46 ± 6 years (range, 41 to 52 years). The majority (28) were between 40 and 45 years, 15 were in the 45 to 50 years age group, and 9 were above 50 years. There were 46 males and 6 females. All patients had hypertension. Noninvasive evidence of CAD was present in 25 patients (48%) in the form of angina pectoris in 10, ECG evidence of old MI in 6, ST-T changes on the ECG in 8, regional wall motion abnormality on echocardiography in 8, positive dipy-ridamole thallium scan in 13, and positive dobutamine stress echocardiography in 4 patients. One, 2, or 3 positive noninvasive indications of CAD were present in 7, 12, and 6 patients, respectively.
Coronary arteriography revealed obstructive CAD in 27 (51.9%) patients (Table 1
). One patient with right coronary artery disease had spontaneous dissection of the right coronary artery. One patient with left anterior descending coronary artery disease had an anomalous left anterior descending artery arising from the right coronary sinus and passing in front of the right ventricular outflow tract. No complications were noticed except in one patient who developed acute pulmonary edema in the post-procedure period, which was treated successfully by urgent hemo-dialysis with ultrafiltration. There were no groin compli-cations.
As depicted in Table 2, there were no statistically significant differences in the various clinical predictors among patients with and without obstructive CAD, except ECG evidence of old MI for which the p value reached near statistical significance. The correlation between noninvasive indicators of CAD and arteriography findings are shown in Table 3. Dipyridamole thallium scans were performed in 19 patients, the correlation with arteriography is shown in Table 4. Among the different noninvasive indicators of CAD, regional wall motion abnormality observed on echocardiography had the highest predictive value of 100%. The predictive values of the other indicators are given in Table 5. When multiple noninvasive para-meters were positive, the likelihood of obstructive CAD on arteriography increased. With 1, 2, and 3 noninvasive indicators in a patient, the likelihood of obstructive CAD on arteriography was 42.8%, 66.7%, and 100%, respectively.
Successful live related-donor renal transplantation was performed in 36 (69.2%) patients. Of the remaining 16 patients, 7 (13.5%) died before transplantation (3 because of a coronary event, 2 from septicemia, 2 from unknown causes), while 9 (17.3%) patients did not undergo transplantation because of unacceptably high coronary risk. In the 27 patients with obstructive CAD, successful renal transplantation was carried out in 12 (44.5%), 6 (22.2%) died before transplantation (3 from coronary events, 2 from septicemia, 1 from an unknown cause), while transplantation was not undertaken in 9 (33.3%) because of unacceptably high operative risk; there were non-reconstructible coronary lesions in 5 and the other 4 patients refused a coronary revascularization procedure.
Myocardial revascularization was performed in 8 (15.4%) patients; before transplantation in 7 and afterwards in the other case. Successful uncomplicated percutaneous trans-luminal coronary angioplasty was achieved in 5 patients before transplantation. One patient who had associated severe rheumatic mitral stenosis in addition to severe right coronary artery disease, underwent successful balloon mitral valvotomy and right coronary angioplasty. Two patients had successful uncomplicated coronary artery bypass graft surgery before transplantation (including the patient with left main disease). The patient who underwent coronary artery bypass grafting after renal transplantation, died in the postoperative period from septicemia.
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Discussion
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Evaluation of the extent of CAD in these patients is important in deciding suitability for renal transplantation as prior myocardial revascularization was required in 13.5% and another 17.3% were not transplanted because of high coronary risk. The finding that obstructive CAD was present in 51.9% of these patients agrees with earlier studies where the incidence varied from 25% to 55%, depending on the definition of significant obstructive CAD and the group studied (age group, dialysis dependent, or not requiring dialysis).1,2 Analysis of demographic factors including age, sex, duration of diabetes, and duration of pretransplant dialysis failed to identify any significant difference between patients with or without obstructive CAD. Similarly, history of angina, hyperten-sion, cardiomegaly and left ventricular dysfunction, lipid levels, and abnormal ST-T changes in ECG failed to identify patients with CAD. Only ECG evidence of old MI reached near statistical significance for prediction of obstructive CAD. Lorber and colleagues12 in an angio-graphic study of 77 consecutive diabetic pre-renal-transplant patients reported that previous MI was the only significant difference among patients with or without CAD. Braun and colleagues1 found that angina, cardio-megaly, and previous MI were predictive factors for CAD but they correctly identified it in only 64.1% of cardiac patients. In our study, noninvasive evaluation correctly identified 65.3% of patients with CAD.
The poor predictive value of angina can be partly explained by silent ischemia. On the other hand, patients with ESRD may have angina in the absence of CAD because of increased myocardial oxygen demand due to left ventricular hypertrophy and hypertension, and decreased oxygen supply because of coexistent anemia. ECG is unreliable in these patients because of electrolyte imbalance, medication, and anemia. The value of exercise ECG is often limited by poor exercise tolerance and inability to perform exercise or achieve the target heart rate.
Dipyridamole thallium has been proposed by many investigators as the noninvasive modality of choice for detection of CAD.13,14 Data from thallium scintigraphy are limited in diabetic patients with ESRD and sensitivity varying from 29% to 86% has been reported.6,15 In this study, dipyridamole thallium appropriately classified patients as with or without CAD in only 68.3% of cases, which is unacceptable for a screening test. Several mechanisms have been proposed for the poor sensitivity of dipyridamole thallium imaging in these patients. Dipyridamole is a coronary vasodilator that produces regional hyperemia in proportion to the flow reserve of each coronary vessel.16 The presence of collaterals, known to be increased in hypertrophied heart and in ESRD, may prevent establishment of a zone of disparate flow and thereby produce apparent homogenous perfusion even in the presence of significant obstructive disease. Perhaps more interesting are data regarding adenosine levels in ESRD and the altered vascular reactivity of adenosine in diabetic patients. The vasodilator effect of dipyridamole is mediated via adenosine that is increased in ESRD, leading to reduced vascular responsiveness to dipy-ridamole, thus accounting for the high number of false-negative results.17 Diminished coronary artery sensitivity to adenosine has been demonstrated in diabetic dogs and sheep.18,19 Given the conflicting clinical results of dipy-ridamole thallium imaging, the lack of information on these scans in diabetics, and the theoretical considerations potentially limiting efficacy, it falls short of being an adequate screening test in diabetic ESRD patients.
It was concluded that diabetic ESRD patients above 40 years of age have a high incidence of obstructive CAD that is difficult to predict from clinical indictors and noninvasive diagnostic tools. However, when echocardio-graphy showed regional wall motion abnormality or the patient had 3 or more positive noninvasive indicators, CAD was confirmed by arteriography and this may help in risk stratification for subsequent coronary events before or after renal transplantation.
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References
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Braun WE, Phillips DF, Vidt DG, Novick AC, Nakamoto S, Popowniak KL, et al. Coronary artery disease in 100 diabetics with end-stage renal failure. Transplant Proc 1984;16:603–7.[Medline]
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Abstract
Introduction
