Topic
Recommendation
Evidence grading
Clinical assessment for active cardiac conditions
• A thorough history and physical examination are recommended to identify active cardiac conditions before kidney transplantation
Class I, Level of Evidence C
• Clinical assessment should occur during the initial evaluation and be repeated immediately before anticipated transplantation
Preoperative noninvasive stress testing in the evaluation of kidney transplantation candidates without active cardiac conditions
• Noninvasive imaging stress testing may be considered in kidney transplant candidates with no active cardiac conditions based on the presence of multiple CAD risk factors regardless of functional status
Class IIb, Level of Evidence C
• Relevant risk factors among transplant candidates include diabetes, prior cardiovascular disease, >1 year on dialysis, left ventricular hypertrophy, age >60 years, smoking, hypertension, and dyslipidemia
• The specific number of risk factors that should be used to prompt testing remains to be determined, but ≥3 is considered reasonable
Noninvasive stress testing for cardiac surveillance after listing for kidney transplantation
• Currently the usefulness of periodically screening asymptomatic kidney transplant candidates for myocardial ischemia while on the transplant waiting list to improve the risk of major adverse cardiac events is uncertain
Class IIb, Level of Evidence C
Preoperative 12-lead ECG at evaluation
• Preoperative resting 12-lead ECG is recommended for potential kidney transplant candidates with known coronary heart disease, known peripheral arterial disease, or any cardiovascular symptoms
Class I, Level of Evidence C
Preoperative 12-lead ECG at evaluation
• Preoperative resting 12-lead ECG is reasonable in potential kidney transplant candidates without known cardiovascular disease
Class IIa, Level of Evidence C
12-lead ECG for cardiac surveillance after listing
• Annual performance of 12-lead ECG after listing for kidney transplantation may be reasonable
Class IIb, Level of Evidence C
Preoperative echocardiography at evaluation
• It is reasonable to perform preoperative assessment of left ventricular function by echocardiography in potential kidney transplantation candidates
Class IIa, Level of Evidence B
Echocardiography for cardiac surveillance after listing
• There is no evidence for or against surveillance by repeated left ventricular function tests after listing for kidney transplantation
Preoperative cardiac CT at evaluation
• The usefulness of noncontrast CT coronary artery calcium scoring and cardiac CT angiography is uncertain for the assessment of pretransplant cardiovascular risk
Class IIb, Level of Evidence B
Preoperative measurement of cardiac biomarkers at evaluation
• Measurement of a cTnT level at the time of evaluation for kidney transplant may be considered as an additional prognostic marker
Class IIb, Level of Evidence B
Recommendations for referral to a cardiologist
• Kidney transplantation candidates who have an LVEF less than 50 %, evidence of ischemic left ventricular dilation, exercise-induced hypotension, angina, or demonstrable ischemia in the distribution of multiple coronary arteries should be referred to a cardiologist for evaluation and long-term management according to ACC/AHA guidelines for the general population
Class I, Level of Evidence B
Recommendations for referral to a cardiologist
• Coordination of care: It may be reasonable for each program to identify a primary cardiology consultant for questions related to potential kidney transplantation candidates
Class IIb, Level of Evidence C
Revascularization before transplantation surgery
• Coronary revascularization before transplantation surgery should be considered in patients who meet the criteria outlined in the “2011 ACCF/AHA Guidelines for Coronary Artery Bypass Graft Surgery”
Class I, Level of Evidence B
Revascularization before transplantation surgery
• It is recognized that in some asymptomatic transplantation candidates, the risk of coronary revascularization may outweigh the risk of transplantation and these risks must be weighed by the multidisciplinary transplantation team on a case-by-case basis until further studies are performed in this population
Revascularization before transplantation surgery
• CABG is probably recommended in preference to PCI to improve survival in patients with multivessel CAD and diabetes mellitus
Class IIa, Level of Evidence B
Revascularization before transplantation surgery
• CABG to improve survival and/or to relieve angina despite optimal medical therapy may be reasonable for patients with ESRD with significant (>50 %) left main stenosis or significant (>70 %) stenoses in 3 major vessels or in the proximal left anterior descending artery plus 1 other major vessel, regardless of left ventricular systolic function
Class IIb, Level of Evidence B
Timing of transplant surgery in relation to PCI
• In patients in whom coronary revascularization with PCI is appropriate for mitigation of cardiac symptoms and who need transplantation surgery in the subsequent 12 months, a strategy of balloon angioplasty or BMS placement followed by 4–12 weeks of dual antiplatelet therapy is probably indicated
Class IIa, Level of Evidence B
Timing of transplant surgery in relation to PCI
• Transplantation surgery is not recommended within 4 weeks of coronary revascularization with balloon angioplasty
Class III, Level of Evidence B
Timing of transplant surgery in relation to PCI
• Transplantation surgery within 3 months of BMS placement and within 12 months of DES placement is not recommended, particularly if the anticipated time of post-stent dual antiplatelet therapy will be shortened
Class III, Level of Evidence B
Antiplatelet therapy in relation to recent PCI
• In patients who have received DES and who must undergo urgent surgical procedures that mandate the discontinuation of thienopyridine therapy, it is reasonable to continue aspirin if at all possible and to restart the thienopyridine as soon as possible
Class IIa, Level of Evidence C
Antiplatelet therapy in relation to recent PCI
• In cases when urgent surgery must be performed in patients taking aspirin and thienopyridines after coronary stent placement and who are at high risk for bleeding complications, a strategy of stopping the thienopyridine 5 days before surgery and continuing aspirin perioperatively may be reasonable. The thienopyridine should be restarted as soon as possible postoperatively
Class IIb, Level of Evidence B
Antiplatelet therapy in relation to recent PCI
• It may be reasonable to perform kidney transplantation surgery without interruption of clopidogrel therapy if the risk of bleeding is low
Class IIb, Level of Evidence C
Noninvasive Testing for Coronary Artery Disease in Asymptomatic Kidney Transplant Candidates: Modalities and Testing Accuracy
Several consensus-based recommendations for cardiac risk assessment among kidney transplant candidates have been offered in the past decade (Table 10.2). The 2001 American Society of Transplantation “Guidelines for the Evaluation of Renal Transplant Candidates” advanced recommendations that (1) “high-risk patients,” defined as those with diabetes, prior ischemic heart disease, or ≥2 traditional cardiovascular risk factors, should have a cardiac stress test; (2) patients with positive stress tests should be studied by invasive coronary angiography; and (3) patients with critical coronary lesions should undergo revascularization prior to transplantation [15]. In 2005, the National Kidney Foundation/Kidney Disease Outcomes Quality Initiative (NKF/KDOQI) “Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients” recommended that patients on the kidney transplant waitlist with a history of diabetes mellitus or known coronary artery disease (CAD) undergo noninvasive cardiac stress testing at baseline and then subsequently every 12 months until transplantation [16]. NKF/DOQI also recommended a similar evaluation strategy for transplantation candidates deemed at high risk per Framingham criteria (≥2 traditional risk factors, left ventricular ejection fraction (LVEF) ≤40 %, or peripheral arterial disease) [16].
Table 10.2
Published recommendations for noninvasive testing in asymptomatic kidney transplant candidates
Reference | Recommendations |
---|---|
2012 AHA/ACCF Scientific Statement [14] | • Noninvasive stress testing may be considered in kidney transplantation candidates with no active cardiac conditions on the basis of the presence of multiple CAD risk factors regardless of functional status (Class IIb, Level of Evidence C) |
• Relevant risk factors among transplantation candidates include diabetes mellitus, prior cardiovascular disease, >1 year on dialysis, LV hypertrophy, age >60 years, smoking, hypertension, and dyslipidemia; the specific number of risk factors that should be used to prompt testing remains to be determined, but the committee considers ≥3 to be reasonable | |
2007 ACC/AHA Perioperative Guidelines for Noncardiac Surgery [17] | • No testing recommended if functional status ≥4 METS |
• If functional status <4 METS or unknown, then consideration of noninvasive stress testing is recommended based on the following clinical risk factors: | |
– Ischemic heart disease | |
– Compensated or prior heart failure | |
– Diabetes | |
– Renal insufficiency | |
– Cerebrovascular disease | |
• Recommendations for testing are stronger if ≥3 clinical risk factors are present but may be considered in those with 1–2 risk factors | |
2007 Lisbon Conference [59] | Acknowledges that there are no data establishing that screening of asymptomatic patients in itself prevents cardiac events. Testing should be considered in highest-risk patients with the following conditions: |
• Diabetes | |
• Prior cardiovascular disease | |
• Multiple cardiac risk factors, such as diabetes, >1 year on dialysis, LV hypertrophy, age >60 years, smoking, hypertension, and dyslipidemia | |
Does not specify number of risk factors to justify testing | |
2005 NKF/KDOQI Guidelines [16] | Noninvasive stress testing recommended for: |
• All patients with diabetes. Repeat every 12 months | |
• All patients with known CAD: | |
– If not revascularized, repeat every 12 months | |
– If prior PCI, repeat every 12 months | |
– If prior CABG, repeat after first 3 years, then every 12 months | |
• Repeat every 24 months in “high-risk” nondiabetic patients, defined as: | |
– ≥2 traditional risk factors | |
– Known history of CAD | |
– LVEF ≤40 % | |
– Peripheral vascular disease | |
2001 AST Guidelines [122] | • Noninvasive stress testing recommended for patients at “high risk,” defined as renal disease from diabetes, prior history of ischemic heart disease, or ≥2 risk factors |
• Coronary angiography for possible revascularization before transplantation recommended for patients with a positive stress test | |
• Revascularization before transplantation recommended for patients with critical coronary lesions | |
2000 European Best Practice Guidelines [123] | • Thallium scanning recommended for patients with history of myocardial infarction or “high-risk” clinical features |
• Coronary angiography recommended if thallium scanning positive | |
• Revascularization advised if lesions are suitable |
In contrast, the 2007 American College of Cardiology (ACC)/AHA “Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery” promote an algorithm that considers the presence of active cardiac conditions, the type of noncardiac surgery, patient functional capacity, and clinical risk profile [17]. These ACC/AHA guidelines identify four “active” cardiac conditions warranting specific evaluation and treatment before noncardiac surgery, including unstable coronary syndromes (unstable or severe angina or MI within the past 30 days), decompensated heart failure, significant arrhythmia, and severe valvular heart disease. If none of the active cardiac conditions are present, the ACC/AHA algorithm then risk stratifies patients on the basis of functional capacity. If functional status is estimated as at least four metabolic equivalents (METS, where four is equivalent to the ability to climb a flight of stairs) in a patient without an active cardiac condition, then no further testing is recommended. Patients with lower or unknown functional capacity who are scheduled for intermediate-risk surgery (reported cardiac perioperative morbidity rates generally 1–5 %) are also generally recommended to proceed with surgery, regardless of the number of risk markers. However, consideration of noninvasive testing is given a Class IIb/Level of Evidence (LOE) recommendation “if it will change management.” Kidney transplantation is typically considered an intermediate-risk surgery.
A recent single-center study quantified the frequency of recommended testing and the observed results of cardiac testing (primarily dobutamine stress echocardiography (DSE) or myocardial perfusion scintigraphy (MPS)) that would result from application of different clinical practice guidelines among 204 consecutive patients who were determined to be free of active cardiac conditions by a cardiologist at the time of transplant evaluation [18]. Active cardiac conditions were defined according to the ACC/AHA criteria [17]. If followed precisely, 20 % of patients met criteria for cardiac testing by ACC/AHA guidelines for noncardiac surgery, whereas use of the NKF/KDOQI guidelines would have resulted in testing 100 % of the sample. Among the 178 (87 %) patients who underwent stress tests, the prevalence of ischemia was similar among those for whom testing was and was not recommended per the ACC/AHA guidelines, 10.3 % vs. 9.4 %, respectively. The relatively low use of coronary revascularization after pretransplant cardiac evaluation also raises concern for the clinical and cost-effectiveness of pretransplant cardiac evaluation as currently applied. Several registry-based and single-center observational studies have found that only 2.9–9.5 % of patients who receive pretransplant cardiac stress testing or angiography proceeded to percutaneous coronary intervention (PCI) or surgical bypass [13, 19–22].
In formulating current recommendations regarding noninvasive testing for CAD in kidney transplant candidates, the 2012 AHA/ACCF Scientific Statement on “Cardiac Disease Evaluation and Management Among Kidney and Liver Transplantation Candidates” [14] weighed the following considerations:
1.
Noninvasive cardiac stress testing by DSE or MPS has prognostic value for cardiac events and mortality but imperfect sensitivity and specificity for detecting angiographically defined CAD in patients with ESRD.
2.
Associations of coronary stenoses by invasive coronary angiography with subsequent survival in ESRD patients are also inconsistent, likely because plaque instability is more important for major adverse cardiac event (MACE) risk than angiographic stenosis and most plaque disruption events (erosion or rupture) producing acute coronary syndromes are not localized to sites of angiographic stenosis.
3.
Coronary revascularization in asymptomatic patients has failed to show benefit before surgery or among nonsurgical patients, except in a small subset of patients with high-risk anatomic lesions.
Accuracy of Noninvasive Testing for CAD in Kidney Transplantation Candidates
Among studies evaluating associations between cardiac stress testing results and angiographically defined obstructive CAD in cohorts with chronic kidney disease (CKD) stage 5 (glomerular filtration rate (GFR) <15 mL/min/1.73 m2 or dialysis dependence), DSE and MPS have sensitivities varying from 0.44 to 0.89 and 0.29 to 0.92 and specificities ranging from 0.71 to 0.94 and 0.67 to 0.89, respectively, for identifying one or more coronary stenoses ≥70 % [23–31]. In a recent meta-analysis assessing the pooled sensitivity and specificity of DSE and MPS in kidney transplant candidates, both DSE and MPS had moderate sensitivity and specificity in detecting significant coronary artery stenosis on invasive coronary angiography in patients who are kidney transplant candidates (DSE (13 studies), pooled sensitivity 0.79 (95 % CI 0.67 to 0.88) and pooled specificity 0.89 (95 % CI 0.81 to 0.94); MPS (9 studies), pooled sensitivity 0.74 (95 % CI 0.54 to 0.87) and pooled specificity 0.70 (95 % CI 0.51 to 0.84)) [32]. When limited to studies that defined CAD as ≥70 % stenosis on coronary angiography, there was little change in these pooled estimates of accuracy (DSE (nine studies), pooled sensitivity 0.76 (95 % CI 0.60 to 0.87) and specificity 0.88 (95 % CI 0.78 to 0.94); MPS (seven studies), pooled sensitivity 0.67 (95 % CI 0.48 to 0.82) and pooled specificity 0.77 (95 % CI 0.61 to 0.88)) [32]. There was evidence that DSE had improved accuracy over MPS (p = 0.02) when all studies were included in the analysis, but this was not significant when the authors excluded studies which did not verify all results with coronary angiography or use a reference standard threshold of ≥70 % stenosis (p = 0.09) [32].
The operational characteristics of the type of stress imaging may differ in ESRD compared with non-ESRD patients. In one study of coronary flow reserve in 64 patients with normal epicardial arteries, 57 % (12/21) of those with diabetic nephropathy had high resting coronary basal flow with no incremental response to adenosine compared with 18 % (2/11) of diabetic patients without renal failure and 9 % (3/32) of nondiabetic patients [33], suggesting impaired vasodilator reserve in diabetic ESRD patients. Overall, the accuracy of inotropic stress echocardiography for the purpose of screening to identify high-risk coronary anatomy may be somewhat superior to that of vasodilator stress nuclear perfusion imaging; however, patient-specific variables, such as echocardiography imaging quality or prior testing results, may guide providers in the selection of stress imaging modality. Comparative studies using contemporary imaging technology (e.g., attenuation correction in MPS) are needed.
Despite the imperfect accuracy of stress testing for the detection of coronary stenoses, abnormal MPS and DSE test results have shown prognostic value for cardiac events and mortality in the ESRD population [21, 27, 30, 31, 34–39]. In a meta-analysis of 12 studies employing either thallium-201 MPS or DSE, ESRD patients with inducible ischemia had approximately six times the risk of myocardial infarction and four times the risk of cardiac death as patients without inducible defects, and patients with fixed defects had nearly five times the risk of cardiac death [40]. The percentage of ischemic segments by DSE was an independent predictor of mortality among 485 patients with advanced renal failure and offered prognostic information beyond clinical characteristics alone [41]. In a study of 126 ESRD patients who underwent 99 m-technetium MPS as part of their pretransplant assessment, the presence of a reversible defect was associated with three times the risk of posttransplant cardiac events and nearly twice the risk of death compared with normal test results [42].
Imperfect Correlations of Coronary Stenosis with Subsequent MACEs in ESRD Patients
Angiographic studies from the 1970s have documented a high prevalence of coronary stenoses among patients on long-term dialysis [43–47]. More recently, angiographically significant CAD was found in 53 % of a sample of 30 incident ESRD patients without known cardiac history who consented to screening angiography, including 10 (83 %) of the 12 participants with diabetes, although notably angiographic significance was liberally defined as lesions >50 % [48]. Recent reports of angiography in patients undergoing transplant evaluation identified angiographically significant CAD in 42–81 % of samples, with a higher prevalence in subgroups defined as “high risk” by clinical criteria and with use of more liberal angiographic definitions of CAD [22, 29, 30, 49–53].
Despite the high prevalence of CAD in ESRD patients, reported associations of angiographic coronary stenoses with subsequent clinical events in ESRD patients have varied. In one prospective study of 126 renal transplant candidates clinically classified as moderate (age ≥50 years) or high (diabetes, extracardiac vascular disease, or known CAD) coronary risk, MPS, DSE, and coronary angiography were performed in all participants [29]. Clinical risk stratification and coronary angiography predicted MACE after median follow-up of 46 months, but results of MPS and DSE were not significantly correlated with MACE. Several observational studies reported increased unadjusted risk of all-cause mortality and MACE in patients with angiographic CAD [30, 50], while other studies found correlations of angiography and outcomes only in certain patient subgroups, such as those with proximal CAD [49] or with nondiabetic renal failure [51]. Several recent studies have found no associations of CAD with survival of ESRD patients and kidney transplant candidates [22, 52, 53].
Lack of Evidence that Coronary Revascularization Benefits Asymptomatic Patients Before Surgery or in General, Except for a Small Subset of Patients with High-Risk Anatomic Lesions
There are significant gaps in the literature regarding the outcomes of prophylactic coronary revascularization before kidney transplantation. Only one small randomized trial of revascularization has been performed in this patient population. In 1992, Manske et al. randomly assigned 31 insulin-dependent diabetic transplant candidates with CAD (>75 % stenosis) to revascularization or medical therapy with a calcium channel blocker and aspirin [54]. Ultimately, 10 of 13 medically managed and 2 of 13 revascularized patients reached the primary MACE endpoint including unstable angina, myocardial infarction, or cardiac death. The contemporary relevance of these findings is limited by the small sample size, high event rate among the medically managed group, and subsequent advances that have occurred in medical management of CAD.
While there are no contemporary randomized trials of prophylactic coronary revascularization in kidney transplant candidates, several observational studies have described outcomes after coronary revascularization in selected cohorts of potential kidney transplant candidates. In an observational study of 300 patients who underwent multimodality testing as part of the candidate evaluation at one center, crude survival was not different in patients who underwent revascularization compared with those who underwent angiography without revascularization or no angiography [22]. Among 3,698 patients evaluated for kidney transplant at a single center in 2001–2004, MPS was performed in 60 %, and 7 % of the sample subsequently underwent coronary angiography. The presence and severity of CAD on angiography were not predictive of survival, and coronary revascularization was associated with survival only in patients with 3-vessel CAD [52].
A recent study described one center’s experience (2006–2009) under a protocol in which potential kidney transplant candidates were evaluated by angiography based on the presence of any of the following criteria: age >50 years, diabetes mellitus, any cardiac symptoms, or electrocardiogram (ECG) evidence of ischemia or prior infarction [55]. Among the 657 patients who underwent angiography, significant CAD (defined as >75 % stenosis of one or more coronary arteries, >50 % left main stem stenosis, or an equivocal lesion with flow limitation) was found in 28 %, of whom 55 % were asymptomatic and without prior CAD history. Patients with significant CAD who underwent revascularization followed by transplant (n = 51, 1-year survival 100 %, 3-year survival 97 %) or by continued waiting (n = 177, 1-year survival 95 %, 3-year survival 81 %) had superior survival to the 16 patients who declined revascularization (1-year survival 75 %, 3-year survival 37 %). While this study demonstrates excellent survival in transplant recipients who received preemptive revascularization, the lack of a comparator group of similar patients who did not undergo angiography before transplant prevents inferences regarding the impact of the management approach on outcomes.
In stable general population samples, recent randomized trials have failed to support benefit of revascularization over contemporary medical management, including the CARP and DECREASE-V trials performed among patients awaiting major vascular surgery [56, 57]. Randomized comparison of PCI plus optimal medical therapy among 2,238 patients with stable CAD (≥70 % stenosis in at least one proximal epicardial coronary artery and objective evidence of myocardial ischemia) also found no benefit on the risk of MACE over 4.6 years compared with optimal medical therapy alone [57]. Secondary analysis of 320 participants with CKD defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 found that, while CKD was associated with increased risk of death or nonfatal MI, the incidence of death or MI in CKD patients did not differ by treatment arm [58].
Weighing these data, the 2012 AHA/ACCF writing group acknowledged that there are “no definitive data at this time for or against screening for myocardial ischemia among kidney transplant candidates who are free of active cardiac conditions” [14]. However, until more data are available, the authors recommended consideration of CAD risk factors to target screening of patients with the highest pretest likelihood of prognostically significant CAD. Risk factors for CAD deemed relevant to transplant candidates in a 2007 report from an international collaboration of the NKF and the Transplantation Society called the Lisbon Report include diabetes, prior cardiovascular disease, >1 year on dialysis, left ventricular hypertrophy, age >60, smoking, hypertension, and dyslipidemia [59]. When compared with the ACC/AHA “Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery,” screening transplant candidates with multiple risk factors defined by the Lisbon report appeared to improve sensitivity and specificity for the identification of CAD (sensitivity 94 % vs. 77 %; specificity 33 % vs. 24 %) and reduce the overall frequency of testing in a retrospective analysis of data from one center [18]. The Class IIb/LOE C recommendation of the 2012 AHA/ACCF Scientific Statement on consideration of noninvasive stress testing in kidney transplant candidates with no active cardiac conditions based on the presence of multiple CAD risk factors regardless of functional status is shown in Table 10.1. The Scientific Statement also recommends a randomized trial of the impact of screening for CAD on pre- and posttransplant MACE among potential transplant candidates, such as a randomized comparison of four approaches to the preoperative cardiovascular evaluation: (1) cardiac catheterization for all candidates, including fractional flow reserve measurement in indeterminate lesions, (2) noninvasive imaging stress testing (DSE or MPS) for all patients, (3) noninvasive stress testing based on presence of ≥3 cardiac risk factors, and (4) ACC/AHA cardiac evaluation and care algorithm for noncardiac surgery [14].
Cardiac Surveillance After Listing for Kidney Transplantation
Along with the uncertainty regarding which asymptomatic patients to screen for CAD the optimal frequency for repeat noninvasive testing among kidney transplant candidates on the waiting list is not known. The NKF/KDOQI guidelines recommended repeat stress testing with imaging once a year among subgroups on the transplant list including diabetic patients regardless of symptoms [16]. These guidelines parallel recommendations from the American Society of Transplantation’s 2002 conference on waitlist management [60].
Notably, among patients without organ failure, the cardiac event rate (cardiac death or nonfatal MI) was only 0.6 % over 2–3 years in 7,376 patients after a normal MPS, suggesting that the “warranty” on a normal imaging stress test is at least 2 years in the general population [61] however, only 10 % of participants in this study were diabetic. A large cohort study found low and similar cardiac event rates among diabetic and nondiabetic persons up to 2 years after normal stress MPS, although the diabetic cohort experienced a greater event rate after 2 years [61]. Outcomes after a normal MPS also vary with renal function. In an observational cohort study of the Veterans Affairs database with an average of 2 years of follow-up, annualized cardiac mortality after a normal MPS (defined as no scar or ischemia) rose in a graded manner with declining renal function: eGFR ≥90 mL/min/1.73 m2, 0.4 %; eGFR 60–89 mL/min/1.73 m2, 0.9 %; eGFR 30–59 mL/min/1.73 m2, 2.2 %; and eGFR <30 mL/min/1.73 m2, 4.7 % [62].
In a cohort study from Brisbane, Australia, including 107 CKD patients with baseline and repeat DSE tests after mean follow-up time of 1.8 years, 19 % of the 73 CKD patients with normal baseline DSE results developed inducible ischemia or new scar on repeat testing [63]. Despite the potential for conversion of normal noninvasive tests to abnormal at a rate of approximately 10 % per year, an argument that “periodic cardiac surveillance testing after waitlist may be unnecessary” is supported by a prospective, observational study of patients on the kidney transplant waitlist in British Columbia in 1998–2001 [64]. Among kidney transplant candidates with normal cardiac stress testing at listing, the reference cardiac surveillance guideline recommended annual testing in those with diabetes, testing every 2 years in those with ischemic heart disease or peripheral vascular disease, and testing every 3 years in others. Surveillance based on ongoing clinical assessment resulted in fewer investigations than suggested by guidelines over a mean follow-up period of 3.7 years. Total cardiovascular event rates after listing did not differ in subsets who received the recommended frequency of cardiac tests compared with those in whom testing was guided by symptoms. Weighing these data, the 2012 AHA/ACCF Scientific Advisory Committee on pretransplant cardiac evaluation concluded that the usefulness of periodically screening asymptomatic kidney transplant candidates for myocardial ischemia while on the transplant waiting list to improve the risk of MACE is currently uncertain (Table 10.1) [14].
Use Other Testing in the Pretransplant Cardiac Evaluation
Resting Electrocardiogram
While there are limited data on the association of preoperative ECG with posttransplant outcomes, data are available on the natural history and prognostic value of baseline ECG abnormalities in dialysis patients. In one study of 12-lead ECG findings among 221 chronic hemodialysis patients compared with patients non-dialysis requiring CKD and patients without kidney disease, the prevalence of ECG abnormalities was 65 %, 41 %, and 5 %, respectively [65]. Significant differences between dialysis patients and normal controls included left ventricular hypertrophy (19 % vs. 0.7 %), evidence of ischemia (7.2 % vs. 0.6 %), premature ventricular contractions (6.8 % vs. 0.3 %), nonspecific ST-T changes (6 % vs. 0.3 %), atrial fibrillation (5.4 % vs. 0 %), left atrial enlargement (2.7 % vs. 0 %), and old MI (1.4 % vs. 0 %). Eighty-seven hemodialysis patients were followed by serial ECG for an average of 7.5 years, during which 39 % maintained normal ECGs, 31 % had abnormal but stable ECGs, 25 % had worsening of their ECG findings, and 5 % had apparent improvement. In another study of 1,738 asymptomatic diabetic patients who were free of known CAD, the presence of pathologic Q waves on ECG was the strongest independent correlate of abnormal “high-risk” MPS results (OR 3.92) [66]. Sixty-one percent of patients with high-risk MPS results were found to have angiographic evidence of left main CAD, 3-vessel CAD, or 1- or 2-vessel with proximal left anterior descending CAD.
Given the low cost and the prognostic implications of ECG abnormalities, the 2012 AHA/ACCF Scientific Statement on pretransplant cardiac evaluation recommends a preoperative resting ECG among all potential transplant candidates but with a stronger evidence class among those with symptoms or known atherosclerotic vascular disease (Table 10.1) [14]. Serial ECG changes in dialysis patients can be expected and thus periodic monitoring of ECGs (e.g., annually) while on the waitlist may be appropriate, although there are no data to support an optimal time interval between repeated ECG tests.
Exercise Treadmill Testing and Exercise Stress Echocardiography
Exercise as the form of cardiovascular stress including exercise treadmill stress testing (ETT) alone or in combination with stress echocardiography or MPS, is the most commonly used method for the performance of stress testing, in ambulatory general population patients in whom there is no evidence of left bundle branch block or significant resting ST segment deviation. Exercise duration and the occurrence and severity of exercise-induced chest discomfort and ECG changes provide important diagnostic and prognostic information. However, there is limited data regarding the diagnostic and prognostic value of regular ETT in pretransplant populations. Based on documented improvements in test accuracy using stress imaging modalities as compared to ETT and the high rate of baseline ST segment abnormalities and left ventricular hypertrophy in pretransplant patients that may limit accuracy of ETT, the use of ETT has not been widely studied in this population [30]. In addition, the majority of studies evaluating stress echocardiography and MPS have used inotropic or vasodilator stress imaging likely as a way to standardize stress imaging protocols among the study populations [32]. Given the increased cost (and risks in the case of dobutamine administration) associated with pharmacologic stress imaging, studies evaluating the accuracy and prognostic value of exercise stress imaging protocols among appropriately selected patients requiring kidney transplantation are needed.
Resting Echocardiography
Multiple studies have consistently demonstrated the diagnostic and prognostic value of resting echocardiography among dialysis patients [30, 67, 68]. The “NKF/KDOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients” recommend that a resting echocardiogram be performed in all patients at the initiation of dialysis, once the patient has achieved dry weight (ideally within 1–3 months of dialysis initiation) [16]. Two reports from one large center using stress MPS in potential candidates meeting AST criteria for pretransplant ischemia evaluation found left ventricular systolic dysfunction, defined as LVEF less than 40–45 %, in 16–18 % of patients [69, 70]. The majority (61–63 %) of these patients did not have evidence of ischemia by perfusion imaging. Median survival in patients with LVEF <40 % was 49 months compared with 72 months in patients with higher LVEF; after adjustment for ischemia and other risk factors, the relative risk of mortality increased by 2.5 % for each percent decline in LVEF [70]. Further, the 2007 ACC/AHA guidelines on preoperative evaluation in patients undergoing noncardiac surgery recommend the performance of testing to assess left ventricular function among patients with unexplained dyspnea or with known heart failure and a change in functional status [17]. As described in the 2012 AHA/ACCF Scientific Statement, it is reasonable to perform preoperative echocardiography in potential kidney transplantation candidates (Table 10.1) [14].
Other Imaging: Cardiac CT
In addition to MPS and DSE, noninvasive image-based testing for CAD is available using cardiac computed tomography (CT) (Table 10.3). Noncontrast CT for detection and quantification of coronary artery calcification (CAC scoring) has been shown to significantly improve cardiovascular risk prediction as compared to the Framingham score and highly sensitive C-reactive protein in asymptomatic patients without kidney disease [71–73]. Elevated CAC scores (median Agatston score 595, interquartile range 76–1,600) were identified in a sample of 205 adult maintenance hemodialysis patients [74], and similar studies have reported markedly greater coronary calcification in ESRD compared with non-ESRD patients, with greatest disparities according to ESRD status in young cohorts [75–77]. Although one study reported Agatston CAC scores to be an independent predictor of death in chronic hemodialysis patients [78], the role of calcium scoring as a prognostic marker in the ESRD population is uncertain [79]. Other studies report poor correlation between CAC scores and the likelihood of angiographic CAD in patients with advanced kidney disease [80–82], a finding that may reflect the high burden of medial vascular calcification in ESRD compared to the intimal atherosclerotic plaque calcification seen in the non-ESRD population [83]. Modern (64–320-slice and dual-source) coronary computed tomography angiography (CTA) is a highly accurate and prognostically informative noninvasive tool for the diagnosis of CAD when used to evaluate symptomatic patients with low-to-intermediate pretest probability of obstructive coronary stenosis [84–86]. However, coronary CTA has not been adequately studied in patients with significant kidney disease, and its accuracy may be limited in this population due to a high burden of calcified coronary atherosclerosis. Further, the safety of CTA in patients with advanced kidney disease is a concern related to the attendant exposure to iodinated contrast. The “ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 Appropriate Use Criteria for Cardiac Computed Tomography” consider coronary CTA as an option among patients undergoing cardiac surgery for noncoronary indications (e.g., valve replacement) when the pretest CAD risk is either intermediate (appropriate) or low (uncertain) but deem that there are currently no appropriate indications for coronary CTA as part of the preoperative evaluation for noncardiac surgery [87]. Currently, the usefulness of noncontrast CT for CAC scoring and coronary CT angiography is uncertain for the assessment of pretransplant cardiovascular risk (Table 10.1) [14].
Table 10.3
![](https://freepngimg.com/download/social_media/63059-media-icons-telegram-twitter-blog-computer-social.png)
Advantages and disadvantages of available methods for detecting coronary artery disease
![](https://freepngimg.com/download/social_media/63059-media-icons-telegram-twitter-blog-computer-social.png)
Stay updated, free articles. Join our Telegram channel
![](https://clinicalpub.com/wp-content/uploads/2023/09/256.png)
Full access? Get Clinical Tree
![](https://videdental.com/wp-content/uploads/2023/09/appstore.png)
![](https://videdental.com/wp-content/uploads/2023/09/google-play.png)
![](https://clinicalpub.com/wp-content/uploads/2023/09/banner1.png)