Summary of findings'. 'Summary of results.

Summary of results: Results of studies on cardiac testing in kidney transplant candidates
Review question: Comparison of non‐invasive cardiac screening tests with coronary angiography for the detection of significant CAD in potential kidney transplant recipients Patient population: Kidney transplant candidates undergoing pre‐transplant cardiac evaluation Setting: Investigations performed in hospital or in an outpatient setting Geographical location: Studies were conducted in USA (12 studies), Brazil (4 studies), India, (3 studies) the UK (3 studies), Australia (1 study), Canada (1 study), and Spain (1 study) Index test : Any non‐ or minimally invasive test used to assess risk of CAD. Reference standard: Coronary angiography Included studies: DSE (13 studies; 745 participants), MPS (9 studies; 582 participants), EST (2 studies; 129 participants), EBCT (1 study; 97 participants), DSF (1 study; 86 participants), exercise ventriculography (1 study; 35 participants), CIMT (1 study; 105 participants), resting wall motion abnormality on echocardiography (2 studies; 265 participants), left ventricular dysfunction on echocardiography (1 study; 52 participants), mitral annular calcification on echocardiography (1 study; 125 participants), resting ECG (3 studies; 263 participants).
Limitations
Only DSE and MPS were evaluated in detail, although these also had only a limited number of included comparisons with small sample sizes. No studies were found investigating cardiopulmonary exercise testing, CT coronary angiography, magnetic resonance angiography or cardiac magnetic resonance imaging. Fewer than five studies were found for each of EBCT, resting ECG, conventional echocardiography, exercise ventriculography, DSF and CIMT. Sparse directly comparative data also resulted in low power to detect important differences in accuracy between tests. Significant heterogeneity was present among studies investigating the same screening test. Although differences in study population characteristics (e.g. prevalence of chest pain) and test application (diagnostic test threshold, criteria for positive test, choice of stress agent and stress protocol, and operator variability) likely contributed to heterogeneity, we were hindered from estimating their contributions because of relatively sparse data, which resulted in low power. Partial verification, where not all patients who received screening tests also received coronary angiography, occurred in 5/25 comparisons. This may have affected estimates of sensitivity and specificity. Two different reference standard thresholds (≥ 70% stenosis or ≥ 50% stenosis) were used in the included studies, with most studies only using one reference standard threshold or the other. An overall analysis pooling the results of all studies regardless of threshold may introduce additional heterogeneity due to a threshold effect.
Results
Test	DSE	MPS
Number of studies [all studies]	13	9
Number of participants [all studies]	745	582
Pooled sensitivity (95% CI) [all studies]	0.79 (0.67 to 0.88)	0.74 (0.54 to 0.87)
Pooled specificity (95% CI) [all studies]	0.89 (0.81 to 0.94)	0.70 (0.51 to 0.84)
Number of studies [≥ 70% stenosis]	9	7
Number of participants [≥ 70% stenosis]	668	517
Pooled sensitivity (95% CI) [≥ 70% stenosis]	0.76 (0.60 to 0.87)	0.67 (0.48 to 0.82)
Pooled specificity (95% CI) [≥ 70% stenosis]	0.88 (0.78 to 0.94)	0.77 (0.61 to 0.88)
Number of false diagnoses of ≤ 70% coronary artery stenosis in a standard population of 100 patients (false negative rate)	24 (13 to 40) per 100	33 (18 to 52) per 100
Number of false diagnoses of ≥ 70% coronary artery stenosis in a standard population of 1000 patients (false positive rate)	12 (6 to 22) per 100	23 (12 to 39) per 100
Positive likelihood ratio [≥ 70% stenosis] (95% CI)	6.44 (3.03 to 13.70)	2.89 (1.39 to 5.99)
Negative likelihood ratio [≥ 70% stenosis] (95% CI)	0.26 (0.13 to 0.50)	0.43 (0.23 to 0.80)
Post test probability after positive screening test result for a patient with low risk (10% to 29% pre test probability) disease	42% to 72%	24% to 54%
Post test probability after positive screening test result for a patient with intermediate risk (30% to 59% pre test probability) disease	73% to 90%	55% to 81%
Post test probability after positive screening test result for a patient with high risk (60% to 90% pre test probability) disease	91% to 98%	81% to 96%
Post test probability after negative screening test result for a patient with low risk (10% to 29% pre test probability) disease	3% to 10%	5% to 15%
Post test probability after negative screening test result for a patient with intermediate risk (30% to 59% pre test probability) disease	10% to 27%	16% to 38%
Post test probability after negative screening test result for a patient with high risk (60% to 90% pre test probability) disease	28% to 70%	39% to 79%
Conclusions and comments
Both tests, especially DSE, have a role as triage tests for intermediate risk transplant candidates, with negative results precluding the need for further evaluation with coronary angiography, thereby avoiding unnecessary risk to patients and potentially reducing healthcare costs. Given the wide heterogeneity in the estimates for both DSE and MPS, there is still considerable uncertainty in the true post‐test probabilities of each test. Current evidence suggests that, where feasible, DSE should be used as the screening investigation of choice over MPS.
Applicability of tests in clinical practice
Both DSE and MPS have a role as triage tests for the intermediate risk transplant candidates, with negative results reducing the need for further evaluation with coronary angiography. In high risk patients, a positive non‐invasive DSE or MPS confirms the high risk of severe CAD, but a negative result does not conclusively rule out severe CAD. In these patients, one may consider proceeding immediately to coronary angiography and avoid using functional tests. The relatively low sensitivity and specificity of both DSE and MPS however means that they are not perfect triage tests and a significant number of patients will either have their significant CAD missed (false negatives) or be referred in vain for coronary angiography (false positive). Despite the shortcomings of the non‐invasive tests in their role as triage tests, the very select nature of the population and the unique challenges facing cardiac investigation in this population (particularly, the need to avoid complications arising from an invasive gold standard) and the lack of an alternate better performing test means that we are forced to accept an imperfect triage test. Functional testing may provide additional prognostic information, although an investigation into this was not included under the scope of this review.
Costs
None of the studies included a cost‐effectiveness evaluation. MPS is known to be more expensive than DSE, although both are less expensive than the reference standard, coronary angiography.

CAD ‐ coronary artery disease; CI: confidence interval; CIMT: carotid intimal medial thickness; DSE: Dobutamine stress echocardiography; MPS: Myocardial perfusion scintigraphy