Diagnostic and Prognostic Role of Myocardial Perfusion Scintigraphy in Kidney Transplant Candidates: Narrative Review

Abstract

Purpose

Cardiac screening in adult kidney transplant candidates with myocardial perfusion scintigraphy (MPS) can reveal findings associated with increased risk for coronary heart disease events, but the exact value of this screening test is still undetermined.

Methods

Narrative review based on the available literature and guidelines on the yield, benefits, and harms of MPS screening in kidney transplant candidates.

Results

Although coronary angiography carries low risk in general population, it is not without risk particularly in patients with complex comorbid disease and the use of intravenous contrast media may precipitate a need for hospitalization and death. We could avoid invasive coronary angiography in patients with chronic kidney disease, although with high coronary calcium score, but good left ventricle function and normal perfusion, evaluated by Gated single-photon emission computed tomographic (SPECT) MPS. In fact, although Gated SPECT MPS has not a high sensitivity, it provides some variables that are closely related to sudden death: post-stress and rest-ejection fraction and left ventricular volumes, left ventricle muscle mass, extent of ischemia and scar.

Conclusions

Gated SPECT MPS is a valid noninvasive cardiac screening test. It can be used as alternative to stress echocardiography in kidney transplant candidates with high cardiovascular risk and a positive or inconclusive exercise tolerance ECG test.

Patients with abnormal perfusion and cardiac dysfunction should undergo invasive coronary artery imaging and endovascular treatment, while angiography could be avoided in patients with normal MPI, having good long-term prognosis.

Keywords

Coronary artery disease Kidney transplant Myocardial scintigraphy

Introduction

Patients with chronic kidney disease (CKD) have a high risk of cardiovascular (CV) events, but the majority of deaths are due to sudden cardiac death, arrhythmia, congestive heart failure, with relatively few caused by vascular events such as myocardial infarction (1). In addition, symptoms of coronary artery disease (CAD) may be atypical due to neuropathy, over-hydration, or low functional capacity. No prospective study has yet demonstrated the benefit of cardiac risk stratification before kidney transplantation. In selected high-risk patients, early referral to cardiac catheterization and coronary revascularization may improve outcomes (2). However, acute deterioration of renal function following diagnostic coronary angiography occurs in approximately 10% of patients (3) and in up to 30% of patients after percutaneous coronary intervention (4). Contrast medium-induced renal dysfunction after coronary procedures carries poor prognosis, especially if dialysis becomes necessary (4, 5). Even in patients already undergoing dialysis, loss of residual renal function is associated with worse outcomes. In addition, coronary revascularization procedures in patients with renal impairment are associated with markedly higher risks of both fatal and nonfatal adverse outcomes (6, 7). Even after transplantation, patients remain at high risk of long-term CV complications. Consequently, careful selection of high-risk patients for referral to coronary angiography and revascularization is of paramount importance. In this review article we address the role of myocardial perfusion scintigraphy as a cardiac screening tool in kidney transplant candidates.

Current status of cardiac evaluation for kidney transplant candidates

To ensure that graft survival is not limited by premature CV death, several regulatory agencies and scientific societies (Tab. I) recommend noninvasive CV assessment of those transplant candidates with multiple risk factors or diabetes, although there is no clear guidance on which imaging method to use (8-9-10-11-12-13). Overall, the current suggestion is to adopt an imaging protocol for CV stratification according to “best local expertise”.

Table I

Recommendations of different guidelines on noninvasive stress testing

Association	Guideline
American Heart Association and American College of Cardiology Foundation (8)	Noninvasive stress testing may be considered in kidney transplantation candidates with no active cardiac conditions based on the presence of multiple CAD risk factors regardless of functional status.
UK Renal Association (9)	There is no compelling evidence that pre-transplantation screening for CAD with subsequent coronary intervention is effective in patients with established renal failure in preventing future cardiac events or reducing mortality after transplantation.
European Renal Association/European Dialysis and Transplantation Association (10)	We recommend performing noninvasive stress imaging (myocardial perfusion or dobutamine stress echocardiography) in kidney transplant candidates with high risk and a positive or inconclusive exercise tolerance test.
British Columbia (Canada) Transplant agency (11)	Patients with prolonged duration of dialysis (>5 years), family history of CAD in first degree relative, history of smoking, dyslipidemia, BMI greater than 30, history of hypertension, and above all diabetes mellitus, should undergo noninvasive screening test.
	Useful tests include: myocardial perfusion imaging scan, exercise dobutamine echocardiography.
KHA-CARI Guideline, Australia (12)	Kidney transplant candidates with a moderate or high clinical risk of cardiovascular disease should undergo cardiac stress testing: MPS or stress echo prior to transplantation.
European Association of Urology (13)	An extensive cardiac work-up is recommended for patients with a history of CAD, severe peripheral artery disease, or a history of stroke or severe occlusive cerebrovascular disease and a long history of renal insufficiency/dialysis, as well as for elderly and/or diabetic patients. The work-up includes: echocardiography, exercise electrocardiogram and/or exercise thallium scintigraphy or stress echocardiography in patients with a low exercise capacity, coronary angiography in every suspicious case, especially in dialysis patients who are elderly and/or diabetic, or in patients with a long history of renal disease.

The UK Renal Association suggests that there is no compelling evidence that pre-transplantation screening for coronary artery disease with subsequent coronary intervention is effective in patients with established renal failure in preventing future cardiac events or reducing mortality after transplantation. However, the UK Renal Association also indicates that screening tests may be used to identify high-risk patients for exclusion from the transplant waiting list (9).

Accordingly, many transplant centers continue to use stress/rest myocardial perfusion single-photon emission computed tomographic (SPECT) imaging because of long-standing data supporting its prognostic utility in end-stage renal disease (ESRD) (14-15-16-17).

Technical aspects of myocardial perfusion scintigraphy

The most used tracers for MPS are the isonitrile compounds labeled with technetium-99m (^99mTc): sestamibi and tetrofosmin. These tracers distribute in the myocardium proportionally to regional blood flow and, after entering the myocardial cells, have an extremely low washout, allowing the acquisition of perfusion images up to two hours from the injection. It is therefore necessary to perform a double injection in order to compare the myocardial perfusion after stress and at rest. The two studies are carried out preferably on different days. An average activity of 740 MBq is used for each study. The estimated effective radiation dose to the patients is 10 mSv for a two-day protocol, compared to 15-20 mSv of a coronary computed tomography angiography (18).

The tomographic acquisition (SPECT) is currently performed with dual headed gamma cameras, with variable geometry. The tomographic sections obtained allow a good visualization of the left ventricle, whose walls have a greater thickness than those of the others chambers of the heart. The acquisition with gated technique allows to evaluate ejection fraction, left ventricular volumes, and regional myocardial motility with no additional time and dose. MPI provides functional significance of any coronary stenosis, while coronary angiography provides morphological information of coronary tree.

In normal subjects, there is a homogeneous tracer uptake inside the left ventricle walls (Fig. 1A).

Fig. 1

(A) Myocardial perfusion scintigraphy with ^99mTc-tetrofosmin. Subject with no regions of reduced or absent perfusion. (B) Myocardial perfusion scintigraphy with ^99mTc-tetrofosmin. Photopenic antero-septal area extended to the apex typical of left anterior descending (LAD) artery occlusion.

The presence of fixed defects in both stress and rest images is usually expression of myocardial infarction, or very severe ischemia, while the presence of reversible defects is expression of transient ischemic changes (Fig. 1B).

Performance of myocardial perfusion scintigraphy

The diagnostic accuracy of a noninvasive test like myocardial perfusion scintigraphy is low. Wang et al (19) performed a systematic review of the diagnostic test accuracy of MPS compared with angiography in detecting significant CAD in potential kidney transplant recipients. Seven studies (317 participants) evaluated MPS (20-21-22-23-24-25-26). The sensitivity of MPS varied from 29%-92%, and specificity, from 50%-88%. Pooled sensitivity was 0.69 (95% CI, 0.48-0.85), and specificity was 0.77 (95% CI, 0.59-0.89). Removing from the analysis the only one study (24) which used a reference threshold of ≥50% stenosis instead of ≥70% stenosis, the pooled sensitivity was 0.68 (95% CI, 0.43-0.85), and specificity improved to 0.80 (95% CI, 0.60-0.91). Patients with end-stage kidney disease often have hypertension, left ventricular hypertrophy, and decreased coronary flow reserve, all of which may account for the decreased specificity of MPS in transplant candidates, due to the higher incidence of false-positive uptake defects (27). The reason for the low sensitivity of MPS in transplant recipients compared with the general population is less clear. One possible explanation is that any discrepancy between MPI and coronary angiography can depend on the fact that the coronary angiography provides morphological information of coronary tree, while the MPI provides the functional significance of any coronary stenosis. Another explanation may be cardiac parasympathetic denervation, particularly in diabetic patients who have CKD, which would decrease the relative efficacy of dipyridamole (routinely used in MPS as stress test) compared with dobutamine (routinely used in stress echocardiography) (28, 29). In fact, three studies of the Cochrane review (22-23-24) included only diabetic patients. Moreover, MPS is not able to detect subclinical atherosclerosis, potentially predisposing the patient in the longer term to subsequent obstructive CV events.

Alternative methods for cardiac risk evaluation in kidney transplant candidates

Hybrid SPECT/CT imaging offers the opportunity to combine anatomic evaluation of coronary stenosis alongside a functional assessment of myocardial ischemia. The coronary artery calcium score (CACS), as assessed by using non-enhanced CT, provides an absolute measure of coronary calcification, adds prognostic information, and correlates moderately with obstructive CAD (30, 31). Coronary computed tomography angiography (CTA) has been shown in several multicenter studies to have a high sensitivity (30, 32). However, its specificity is not optimal due to false-positive results in patients with extensive coronary calcifications or high/irregular heart rates. Winther et al (33) compared the accuracy of diagnosing obstructive CAD by using CACS, coronary CTA and SPECT (with invasive coronary angiography as the reference) in 138 patients referred for pre-transplant cardiac evaluation: 43% treated with dialysis. In a patient-level model, the sensitivity and specificity, respectively, for diagnosing obstructive CAD were: CACS (threshold of 400), 67% and 77%; coronary CTA, 93% and 63%; SPECT MPS, 53% and 82%; hybrid (CACS/SPECT), 33% and 97%; and hybrid (coronary CTA/SPECT), 67% and 86%. The authors concluded that coronary CTA is a reliable test with high sensitivity and a high negative predictive value for diagnosing obstructive CAD before kidney transplantation. A noninvasive approach using either coronary CTA or a combination of coronary CTA and SPECT to rule out obstructive CAD seems recommendable. The reduced diagnostic performance of MPS SPECT in advanced CKD patients may be due to false-negative results in patients with severe CAD and balanced ischemia, in addition to an impaired response to myocardial stress agents. Noninvasive imaging methods are insensitive for detecting the presence of diffuse mild atherosclerosis and its impact on coronary epicardial and microcirculatory function and myocardial ischemia. Several investigations have suggested that renal disease is associated with abnormal coronary vasodilator function (34), which may result from multiple mechanisms (35), including decreased capillary density (36), leading to microvascular dysfunction as well as vascular remodeling in epicardial arteries (37). Noninvasive measure of coronary vasodilator reserve by positron emission tomography (PET) perfusion agents, integrates the hemodynamic effects of local epicardial coronary stenosis, the fluid dynamic effects of diffuse atherosclerosis, and the presence of coronary microvascular dysfunction (29, 38).

Prognostic value of myocardial perfusion scintigraphy

MPS has been validated as a powerful prognostic tool for predicting adverse cardiovascular outcomes in patients with known or suspected CAD. Wong et al (39) showed that a positive ^99mTc myocardial perfusion scanning, defined by the presence of a reversible defect, was associated with three times the risk of post-transplantation cardiac events and nearly twice the risk of death compared with normal test results. Aalten et al (40), demonstrated that after the introduction of the standardized cardiac assessment program, the incidence of significant cardiac ischemia assessed by noninvasive cardiac stress testing in high-risk renal transplant patients was low (6.6%) and was followed by revascularization in 67% of positive tests (4.4% of the tested population). A non-significant decrease in kidney transplant perioperative cardiac events (3.8% vs. 7.6% of historic controls) was observed.

Gated SPECT MPS, which allows a simultaneous evaluation of myocardial perfusion and function, increments the prognostic power of MPS (41-42-43-44-45). Hakeem et al (17) assessed the prognostic utility of Gated SPECT MPS in patients with varying degrees of renal dysfunction and the impact of CKD on cardiac death prediction. The study population was predominantly composed of patients with stage III CKD. Presence of ischemia was independently predictive of cardiac death, all-cause mortality, and nonfatal myocardial infarction. Patients with normal MPS and CKD had higher cardiac death event rates than those with no CKD and normal MPS (2.7% vs. 0.8%, p = 0.001). Multivariate Cox analysis revealed that both perfusion defects (hazard ratio [HR]: 1.90, 95% CI 1.47 to 2.46) and CKD (HR 1.96, 95% CI 1.29 to 2.95) were independent predictors of cardiac death after accounting for risk factors, left ventricular dysfunction, pharmacological stress, and symptoms. The results are in agreement with those of the meta-analysis by Rabbat et al (15), which evaluated the prognostic utility of thallium MPS for predicting myocardial infarction (MI) and cardiac death (CD) in patients with ESRD (stage V) assessed for kidney and kidney-pancreas transplantation. Patients with inducible ischemia had a 6-fold increased risk of MI and a 4-fold increased risk of CD, whereas fixed defects (scars) were only predictive of CD (relative risk 4.7) and not of MI. The increased rate of CD relative to baseline in the group of CKD and normal MPS (2.7% vs. 0.8%), is very close to the 3% reference value defined as high risk by the American College of Cardiology/American Heart Association, and may be due to mechanisms other than myocardial ischemia. There is growing evidence that patients with CKD have unrecognized left-ventricle dysfunction, both systolic and diastolic. The addition of ejection fraction to the Cox analysis greatly increased the X² index, indicating the importance of left-ventricle systolic dysfunction (ejection fraction <40%) as a predictor of CD in patients with CKD. Similar results were obtained by Venkataraman et al (14) which examined the prognostic power of MPI in 150 patients with ESRD candidates for renal transplantation with known coronary anatomy using angiography, followed for 3.4 years. In a multivariate model, abnormal MPS results (left-ventricle ejection fraction ≤40% or abnormal perfusion) was the strongest independent predictor of all-cause mortality (adjusted OR 2.5, 95% CI 1.2 to 5.3, p = 0.012). Diabetes mellitus was also an independent predictor, with an adjusted OR of 2.2, whereas the number of narrowed arteries using coronary angiography was not. Gated SPECT MPS provides some variables that might be related to sudden death: post-stress and rest-ejection fraction and left-ventricular volumes, left-ventricle muscle mass, extent of ischemia and scar. This may explain the superiority of MPS over coronary angiography in predicting death. In a recently published study, Moody et al (46) evaluated the prognostic utility of calcium scoring as an adjunct to MPS in ESRD obtained by hybrid technology SPECT/CT. Coronary artery calcium score (CACS) is in fact a surrogate marker of atherosclerotic burden and a strong predictor of adverse cardiovascular events in subjects at intermediate risk from the general population (47). In the multivariate model, abnormal perfusion on SPECT (HR 4.18, 95% CI 1.43 to 12.27, p = 0.009), but not moderate-to-severe CACS (HR 2.4, 95% CI 0.76 to 8.20; p = 0.13), independently predicted all-cause death or MI. The risk of CD and MI increased significantly with the presence and extent of SPECT abnormality. Therefore, MPS continues to be a useful method to identify those subjects with ESRD at high cardiovascular risk. In a study of 1126 largely asymptomatic patients with no ESRD, after a much longer duration of follow-up (median 6.9 years), Chang et al (48) demonstrated that CACS offered incremental risk prediction in subjects with a normal perfusion result. The relative increase in all-cause death/MI was limited to those with high CACS (>400 U) and survival curves only began separating after 3 years. The follow-up duration of only a median of 18 months in the study of Moody et al (46) could be an explanation for the failure of CACS to provide incremental risk predictive value over SPECT. A second possible explanation relates to the particular pathophysiology of arterial calcification in ESRD (1), that is not limited to the intima as in atherosclerosis, causing obstructive coronary disease, but also affects the media (arteriosclerosis), which is associated with pressure overload and heart failure. Moreover, the prevalence of moderate and severe CACS in these patients may be a consequence of other factors including abnormal calcium-phosphate handling, rather than reflecting atherosclerosis alone. The high rates of left ventricle hypertrophy, dilatation, and fibrosis in CKD and their robust association with an adverse cardiovascular prognosis offer alternative targets for intervention (49-50-51).

Cardiac surveillance awaiting kidney transplantation

Cardiac surveillance by MPS while on the waiting list for transplantation is another area of uncertainty. The optimal frequency for repeat noninvasive stress testing for patients awaiting kidney transplantation is unknown. Cardiac surveillance policies among listed candidates differ across transplant centers. Among 68 transplant centers surveyed to determine current practices, 18% did not reevaluate candidates (52). About half of centers relied on the initial cardiac evaluation and cardiac history, with varying criteria used to determine cardiovascular status.

Kidney Disease Outcomes Quality Initiative guidelines (53) indicated an evaluation of coronary artery disease in dialysis patients, dependent on individual patient status, ranging from 12 months (diabetics, high-risk patients) to 36 months (low-risk patients). In patients fulfilling criteria for individual risk, coronary artery disease evaluation should also include exercise or pharmacological stress echocardiographic or nuclear imaging tests (53) especially in symptomatic patients.

In a more recent assessment, it was recommended that the usefulness of periodically screening asymptomatic kidney transplantation candidates for myocardial ischemia while on the transplant waiting list to reduce the risk of major adverse cardiovascular events is uncertain (8).

Conclusion

MPS is a valid noninvasive cardiac screening test. It can be used as an alternative to stress echocardiography in kidney transplant candidates with high cardiovascular risk and a positive or inconclusive exercise tolerance ECG test. Recent suggestions of adding a coronary artery calcium score do not seem to improve sensitivity and specificity of MPS, which are suboptimal. A perfusion defect on MPS associated to abnormal contractile function being an independent predictor of adverse outcome in potential renal transplant candidates, should be evaluated by invasive coronary artery imaging and, if necessary, submitted to endovascular treatment. Otherwise patients with normal MPI, having good long-term prognosis, may not undergo angiography.

Footnotes

Financial support: No grants or funding have been received for this study.

Conflict of interest: None of the authors has financial interest related to this study to disclose.

References

Bashir

Moody

Edwards

Ferro

Townend

Steeds

Coronary artery calcium assessment in CKD: utility in cardiovascular disease risk assessment and treatment?

Am J Kidney Dis 2015;65(6):937–948

Charytan

Wallentin

Lagerqvist

Early angiography in patients with chronic kidney disease: a collaborative systematic review. Clin J Am Soc Nephrol 2009;41032–1043

Shin

Choi

Youn

Comparison of contrast-induced nephrotoxicity of iodixanol and iopromide in patients with renal insufficiency undergoing coronary angiography. Am J Cardiol 2011;108189–194

Rihal

Textor

Grill

Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;1052259–2264

Gruberg

Mintz

Mehran

The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol 2000 361542–1548

Cooper

O'Brien

Thourani

Impact of renal dysfunction on outcomes of coronary artery bypass surgery: results from the Society of Thoracic Surgeons National Adult Cardiac Disease. Circulation 2006;1131063–1070

Naidu

Selzer

Jacobs

Renal insufficiency is an independent predictor of mortality after percutaneous coronary intervention. Am J Cardiol 2003;92160–1164

Lentine

Costa

Weir

Cardiac disease evaluation and management among kidney and liver transplantation candidates: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2012;60434–480

Dudley

Harden

Joint UK renal association and British transplant society clinical practice guidelines: assessment of the potential kidney transplant recipient. Hampshire UK: UK renal association 2010. http://www.renal.org/docs/default-source/guidelines-resources/Assessment_of_the_potential_kidney_transplant_recipient_FIRST_DRAFT_-_19_September_2010.pdf?sfvrsn=0. Accessed October 5, 2016.

10.

Abramowicz

Cochat

Claas

FHJ

European Renal Best Practice Guideline on kidney donor and recipient evaluation and perioperative care. Nephrol Dial Transplant 2015;301790–1797

11.

British Columbia Transplant agency. Clinical guidelines for kidney transplantation. 2015. http://www.transplant.bc.ca/sites/default/files/documents/files/ClinicalGuidelinesforKidneyTransplantation.pdf. Accessed October 5, 2016.

12.

Campbell

Pilmore

Gracey

Mulley

Russell

McTaggart

KHA-CARI guideline: recipient assessment for transplantation. Nephrology 2013;18(6):455–62

13.

Karam

Kälble

Alcaraz

European Association of Urology guidelines on renal transplantation. 2014 http://uroweb.org/wp-content/uploads/27-Renal-Transplant_LRV2-May-13th-2014.pdf. Accessed October 5, 2016.

14.

Venkataraman

Hage

Dorfman

Role of myocardial perfusion imaging in patients with end-stage renal disease undergoing coronary angiography. Am J Cardiol 2008;1021451–1456

15.

Rabbat

Treleaven

Russell

Ludwin

Cook

Prognostic value of myocardial perfusion studies in patients with end-stage renal disease assessed for kidney or kidney-pancreas transplantation: a meta-analysis. J Am Soc Nephrol 2003 14431–439

16.

Bhatti

Hakeem

Dhanalakota

Prognostic value of regadenoson myocardial single-photon emission computed tomography in patients with different degrees of renal dysfunction. Eur Heart J Cardiovasc Imaging 2014;15933–940

17.

Hakeem

Bhatti

Dillie

Predictive value of myocardial perfusion single-photon emission computed tomography and the impact of renal function on cardiac death. Circulation 2008;1182540–2549

18.

Einstein

Moser

Thompson

Cerqueira

Henzlova

Radiation dose to patients from cardiac diagnostic imaging. Circulation 2007;1161290–1305

19.

Wang

Fahim

Hayen

Cardiac testing for coronary artery disease in potential kidney transplant recipients: a systematic review of test accuracy studies. Am J Kidney Dis 2011;57476–487

20.

De Lima

JJG

Sabbaga

Vieira

Coronary angiography is the best predictor of events in renal transplant candidates compared with noninvasive testing. Hypertension 2003;42 263–268

21.

Garcia-Canton

Culebras

Hernandez-Briz

Dobutamine stress echocardiography and stress 99M-technetium methoxyisobutylisonitrile SPECT in the assessment of coronary artery disease in kidney transplant candidates [ASN abstract A3603]. J Am Soc Nephrol 1998;9815

22.

Vandenberg

Rossen

Grover-McKay

Shammas

Burns

Rezai

Evaluation of diabetic patients for renal and pancreas transplantation: noninvasive screening for coronary artery disease using radionuclide methods. Transplantation 1996;621230–1235

23.

Boudreau

Strony

duCret

Perfusion thallium imaging of type I diabetes patients with end stage renal disease: comparison of oral and intravenous dipyridamole administration. Radiology 1990;175103–105

24.

Garg

Kapoor

Umesan

Sharma

Sinha

Role of pretransplant arteriography in diabetic end-stage renal disease. Asian Cardiovasc Thorac Ann 2000;8150–154

25.

Marwick

Steinmuller

Underwood, Ineffectiveness of dipyridamole SPECT thallium imaging as a screening technique for coronary artery disease in patients with end-stage renal failure. Transplantation 1990;49100–103

26.

Worthley

Unger

Mathew

Russ

Horowitz

Usefulness of tachycardic-stress perfusion imaging to predict coronary artery disease in high-risk patients with chronic renal failure. Am J Cardiol 2003;921318–1320

27.

Houghton

Frank

Carr

von Dohlen

Prisant

Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease. J Am Coll Cardiol 1990;1543–51

28.

Ragosta

Samady

Isaacs

Gimple

Sarembock

Powers

Coronary flow reserve abnormalities in patients with diabetes mellitus who have end-stage renal disease and normal epicardial coronary arteries. Am Heart J 2004 1471017–1023

29.

Murthy

Naya

Foster

Coronary vascular dysfunction and prognosis in patients with chronic kidney disease. JACC Cardiovasc Imaging 2012;5(10):1025–1034

30.

Budoff

Dowe

Jollis

Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (assessment by coronary computed tomographic angiography of individuals undergoing invasive coronary angiography) trial. J Am Coll Cardiol 2008;521724–1732

31.

Raff

Abidov

Achenbach

SCCT guidelines for the interpretation and reporting of coronary computed tomographic angiography. J Cardiovasc Comput Tomogr 2009;3 122–136

32.

Miller

Rochitte

Dewey

Diagnostic performance of coronary angiography by 64-row CT. N Engl J Med 2008;3592324–2336

33.

Winther

Svensson

Jorgensen

Diagnostic performance of coronary CT angiography and myocardial perfusion imaging in kidney transplantation candidates. JACC Cardiovasc Imaging 2015;8553–562

34.

Chade

Brosh

Higano

Lennon

Lerman

Mild renal insufficiency is associated with reduced coronary flow in patients with non-obstructive coronary artery disease. Kidney Int 2006;69(2):266–271

35.

Amann

Ritz

Microvascular disease - the Cinderella of uraemic heart disease. Nephrol Dial Transplant 2000;15(10):1493–1503

36.

Amann

Breitbach

Ritz

Mall

Myocyte/capillary mismatch in the heart of uremic patients. J Am Soc Nephrol 1998;9(6):1018–1022

37.

Schwarz

Buzello

Ritz

Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrol Dial Transplant 2000;15(2):218–223

38.

Joki

Hase

Nakamura

Yamaguchi

Onset of coronary artery disease prior to initiation of haemodialysis in patients with end-stage renal disease. Nephrol Dial Transplant 1997;12(4):718–723

39.

Wong

Little

Vinjamuri

Technetium myocardial perfusion scanning in prerenal transplant evaluation in the United Kingdom. Transplant Proc 2008;401324–1328

40.

Aalten

Peeters

van der Vlugt

Hoitsma

Is standardized cardiac assessment of asymptomatic high-risk renal transplant candidates beneficial?

Nephrol Dial Transplant 2011;26(9):3006–3012

41.

Hachamovitch

Hayes

Friedman

Cohen

Berman

Stress myocardial perfusion single-photon emission computed tomography is clinically effective and cost effective in risk stratification of patients with a high likelihood of coronary artery disease (CAD) but no known CAD. J Am Coll Cardiol 2004;43200–208

42.

Hachamovitch

Berman

Kiat

Exercise myocardial perfusion SPECT in patients without known coronary artery disease: incremental prognostic value and use in risk stratification. Circulation 1996;93905–914

43.

Hachamovitch

Berman

Shaw

Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation 1998;97535–543

44.

Valeti

Miller

Hodge

Gibbons

Exercise single-photon emission computed tomography provides effective risk stratification of elderly men and elderly women. Circulation 2005;1111771–1776

45.

Shaw

Hendel

Cerquiera

Ethnic differences in the prognostic value of stress technetium-99m tetrofosmin gated single-photon emission computed tomography myocardial perfusion imaging. J Am Coll Cardiol 2005;451494–1504

46.

Moody

Lin

Stoodley

Prognostic utility of calcium scoring as an adjunct to stress myocardial perfusion scintigraphy in end-stage renal disease. Am J Cardiol 2016;1179 1387–1396

47.

Alpert

Thygesen

Antman

Bassand

Myocardial infarction redefined–a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36959–969

48.

Chang

Nabi

The coronary artery calcium score and stress myocardial perfusion imaging provide independent and complementary prediction of cardiac risk. J Am Coll Cardiol 2009;541872–1882

49.

Schiffrin

Lipman

Mann

Chronic kidney disease: effects on the cardiovascular system. Circulation 2007;11685–97

50.

Mahmoodi

Matsushita

Woodward

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis. Lancet 2012;3801649–1661

51.

Fox

Matsushita

Woodward

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet 2012;3801662–1673

52.

Zarifian

O'Rourke

Managing the kidney waiting list. Prog Transplant 2006;16242–246

53.

K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis 2005; 45(Suppl):S1–153