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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
SPECIAL ARTICLE  
Year : 2020  |  Volume : 31  |  Issue : 3  |  Page : 655-675
Consensus guidelines of cardiovascular risk assessment in kidney transplantation in Saudi Arabia: Review of current practice, evidence, and recommendations


1 Adult Transplant Nephrology, Department of Organ Transplant Center, King Abdulaziz Medical City; King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
2 Department of Transplant Anesthesia, King Abdulaziz Medical City, Riyadh, Saudi Arabia
3 Department of Nephrology, Taif University, Taif, Saudi Arabia
4 Department of Cardiology, King Abdulaziz Medical City, Riyadh, Saudi Arabia
5 Organ Transplant Center, King Abdulaziz Medical City, Riyadh, Saudi Arabia
6 Department of Cardiology, Prince Sultan Military Hospital, Riyadh, Saudi Arabia
7 Department of Renal Transplant, King Faisal Specialty Hospital, Riyadh, Saudi Arabia
8 Department of Renal Transplant, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia
9 Department of Cardiology, King Fahad King Specialist Hospital, Dammam, Saudi Arabia
10 Department of Nephrology and Renal Transplant, King Fahad King Specialist Hospital, Dammam, Saudi Arabia

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Date of Submission13-Apr-2019
Date of Acceptance12-Jun-2019
Date of Web Publication10-Jul-2020
 

   Abstract 


Screening for cardiovascular (CV) disease before transplant is common. However, the clinical utility of screening asymptomatic transplant candidates remains unclear. There is a large degree of variation among the practices of the different transplant centers in the Kingdom of Saudi Arabia (KSA) and among the international guidelines. Opinions are mostly based on mixed observational data with a great potential for bias. When compared to the Western countries, renal-transplant candidates in the KSA are likely to have longer dialysis vintage, higher prevalence of catheter use, higher rate of uncontrolled hyperparathyroidism, and high prevalence of diabetes. These factors are likely to expose renal-transplant candidates to a higher CV risk than those in Western countries. In the absence of any published guideline for CV risk assessment of the renal-transplant candidate in the KSA, we present these guidelines as the first published guidelines in the KSA. These guidelines review the pertinent aspects from the most recent American College of Cardiology/American Heart Association guidelines for cardiac disease evaluation and management among kidney-transplant candidates and reflect on the local practices in the KSA. These guidelines overview many of the daily- encountered challenges in renal transplantation such as the indications for stress testing, screening coronary angiogram and prophylactic revascularization, screening and management of pulmonary hypertension, cardiac surveillance while on the waiting list and duration of dual-antiplatelet therapy before renal transplant. These guidelines were reviewed by a team of consultant nephrologists, cardiologists, anesthesiologists, and transplant surgeons from six major transplant centers in the KSA. The guidelines aim to standardize the practices of CV risk assessment in kidney transplantation in the KSA, according to the most up-to-date available evidence. The expected impact of these guidelines on the current practices is also reviewed here.

How to cite this article:
Arabi Z, Theaby A, Sibai A, Bukhari MA, Al Chaghouri M S, Al-Mallah M, Ohali W, Abdullah K, Kheirallah H, Eid H, Rojolah H, Qaseer M, Hamawi K, Halim M. Consensus guidelines of cardiovascular risk assessment in kidney transplantation in Saudi Arabia: Review of current practice, evidence, and recommendations. Saudi J Kidney Dis Transpl 2020;31:655-75

How to cite this URL:
Arabi Z, Theaby A, Sibai A, Bukhari MA, Al Chaghouri M S, Al-Mallah M, Ohali W, Abdullah K, Kheirallah H, Eid H, Rojolah H, Qaseer M, Hamawi K, Halim M. Consensus guidelines of cardiovascular risk assessment in kidney transplantation in Saudi Arabia: Review of current practice, evidence, and recommendations. Saudi J Kidney Dis Transpl [serial online] 2020 [cited 2020 Aug 4];31:655-75. Available from: http://www.sjkdt.org/text.asp?2020/31/3/655/289452



   Disclaimer Top


This document was designed to aid the qualified healthcare team in making clinical decisions about patient’s care, but it should not be construed as dictating exclusive courses of treatment and/or procedures. No healthcare team member should view these documents and their bibliographic references as a final authority on patient care. These guidelines present the personal opinions of the authors and not necessarily to be formally endorsed by their institutions. Variations from these guidelines may be warranted in actual practice based on individual patient characteristics and clinical judgment in unique care circumstances.


   Table of Contents Top


Review of the Evidence of Current Practice of Cardiovascular Risk Assessment in Kidney Transplantation in the Kingdom of Saudi Arabia

1.1 The need to establish guidelines of cardiovascular risk assessment in kidney transplantation in the Kingdom of Saudi Arabia (KSA)

1.2 The high prevalence of asymptomatic CAD among renal-transplant candidates in the KSA

1.3 The sensitivity and specificity of testing for CAD of noninvasive testing

1.4 The prognostic value of stress testing in renal-transplant candidates in relation to future clinical outcomes

1.5 The prognostic value of screening cardiac angiography in renal-transplant candidates in relation to future clinical outcomes

1.6 The prognostic value of cardiac intervention (angioplasty) in asymptomatic renal-transplant candidates in relation to future clinical outcomes

1.7 The prognostic value of stress testing, coronary angiography or even intervention in the CKD population in the preoperative setting?

1.8 The prognostic value of stress testing, coronary angiography or even intervention in the general population?

1.8. (A) The value of stress testing in asymptomatic diabetic patients

1.8. (B) The value of stress testing before major vascular surgery

1.8. (C) The value of revascularization in asymptomatic high-risk patients from the general population in the perioperative setting

1.8. (D) Revascularization versus medical therapy for CAD in nonperioperative setting

1.8. (E) Myocardial ischemic burden and interventions.

Guidelines of Cardiovascular Risk Assessment in Kidney Transplantation

2.1 Outlines from the AHA Guidelines

2.2 Definitions for the Class of Recommendation (I–III) and Evidence Level (A–C)

2.3 Major AHA recommendations and their review by committee

2.3.1 Determining whether the transplantation candidate has an active cardiac condition

2.3.2 Recommendations for referral to a cardiologist

2.3.3 Indications for noninvasive stress testing in kidney transplantation candidates without active cardiac conditions

2.3.4 Echocardiography in kidney-transplantation candidates

2.3.5 Screening and management of pulmonary hypertension

2.3.6 Recommendations for coronary revascularization and related care before kidney transplantation

2.3.7 Routine prophylactic coronary revascularization

2.3.8 Cardiac surveillance after listing for transplantation

2.3.9 Noncontrast CT calcium scoring and cardiac CT angiography in kidney transplantation candidates

2.3.10 Duration of dual-antiplatelet therapy after PCI?

2.3.11 Waiting time after acute coronary syndrome or cerebrovascular accident

2.3.12 Evaluation and management of renal-transplant candidates with uremic cardiomyopathy and congestive heart failure

2.3.13 Estimating of perioperative risk of renal-transplant surgery

2.3.14 Cardiac clearance pathway of renal-transplant candidates.

Evaluation of patients while on the waiting list and the expected results of the implementation of the new guidelines at the local centers and the national level

Conclusion

References


   Review of the Current Practice of Cardiovascular Risk Assessment in Kidney Transplantation in the Kingdom of Saudi Arabia Top


1.1 The need to establish guidelines of cardiovascular risk assessment in kidney transplantation in the Kingdom of Saudi Arabia

There is a large degree of variation among the practices of the renal-transplant centers in the KSA regarding cardiovascular (CV) risk assessment of renal-transplant candidates. Some centers may prefer to perform stress testing on all renal-transplant candidates (including those with low risk). Other centers may require cardiac catheterization as the first-line screening test before transplant for most patients.

This issue is not unique to the KSA but reflects that providers and centers in the KSA tend to use different international guidelines. In 2011, Friedman et al[1] reported that if four different screening guidelines were applied to the same patient population, the range of proportion screened ranged between 20% and 100%.

In the KSA, providers who follow the European Renal Best Practice Guidelines may obtain a screening stress test for any renal-transplant candidate with any single risk factor (including age >50 years), and exercise stress test will be the first screening modality, and only if abnormal dobutamine stress test or nuclear imaging stress test can be performed.[2] Providers who follow the American College of Cardiology/American Heart Association (ACC/ AHA) guidelines will obtain nuclear testing for renal candidates with three or more risk factors, including age >60 years.[3],[4],[5],[6] On the other hand, many providers will start with screening cardiac catheterization, and they may view the pretransplant period as a golden window for cardiac intervention due to the fear of affecting the precious and newly implanted graft by contrast-associated nephropathy if cardiac catheterization were needed post-transplantation.

More than 800 renal transplants are performed yearly in the KSA,[7] but there are yet no published data about the CV risk and assessment of the renal-transplant candidate in KSA. Moreover, end-stage renal disease (ESRD) patients in the KSA are generally younger than those in Western countries (30% of ESRD patients in the KSA are less 40 versus 15% in USA)[8],[9] [Table 1] and [Table 2]. These patients are remaining dialysis-dependent unless they undergo kidney transplantation. In addition, diabetes is also very prevalent in KSA and starts at a younger age leading to higher rates of diabetic micro and macrovascular complications,[10],[11],[12],[13] Moreover, the use of hemodialysis catheter (versus fistula) is much higher in the KSA.[13],[14],[15],[16],[17] There is also a higher rate of uncontrolled hyperparathyroidism in the KSA. These factors are likely to expose renal-transplant candidates in the KSA to a higher CV risk than those in Western countries.
Table 1: Transplant data from King Abdulaziz Medical City 2018 as an example of renal transplant candidates profile in the KSA.

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Table 2: The cardiovascular risk factors of kidney-transplant candidates in the KSA compared to USA.

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On the other side,

  1. Most of kidney transplantations are from living-related donors, which reduce the CV risk by providing better and faster kidney function [Table 1]
  2. The time gap between workup initiation and living donor transplantation is much shorter in comparison to deceased donor kidney transplantation, which reduces the risk while waiting for transplantation and the need to re-test [Table 1]
  3. Donors in the KSA are much younger (around 27 compared to 46 in the west [Table 1]
  4. Recipients in the KSA are much younger than the western patients (around 46 vs. 57 years), which makes the prevalence of cardiac disease much less [Table 1]
  5. The rate of preemptive kidney transplant is about 10% of the patients (as compared to 2.5% in the USA).[8],[9],[18],[19]


[Table 1] depicts transplant data from KAMC 2018 as an example of the profile of the renal-transplant candidates in the KSA.

[Table 2] depicts the CV risk factors of kidney-transplant candidates in the KSA compared to the USA.

In the view of the lack of enough data in the KSA, the authors’ committee (6 transplant nephrologists, 5 cardiologists, 1 anesthesiologist, and 2 transplant surgeons from 6 major transplant centers in the KSA, which perform collectively >85% of renal transplants in the KSA)[20] reviewed a set of CV recommendations tailored to our local ESRD population in view of the most recent ACC/AHA guidelines 2012 for cardiac disease evaluation and management among kidney-transplant candidates.



1.2 The prevalence of asymptomatic coronary artery disease among renal-transplant candidates

The prevalence of asymptomatic coronary artery disease (CAD) among renal-transplant candidates is high at 50%.[21] The risk of myocardial infarction (MI) is also highest in the first three months posttransplant, especially in deceased donor kidney transplants.[22]

There are no published data on the prevalence of asymptomatic CAD among renal-transplant candidates in KSA. However, the overall mortality rate of ESRD in the KSA is 8 deaths/year. The leading cause of death is CV (51%) followed by unknown/sudden death (27%).[8]

Many renal-transplant candidates in the KSA start dialysis at an early age due to unknown primary kidney disease (likely glomerulonephritis). These patients are likely to have a lower CV risk. On the other hand, those with diabetes, older patients, or those who stay on dialysis for prolonged duration are at much higher CV risk. The incidence of asymptomatic CAD among these patients is expected to be very high.



1.3 Sensitivity and specificity of noninvasive stress tests myocardial perfusion study

In a meta-analysis, the overall pooled sensitivity of PET for the detection of obstructive CAD was 90% [95% confidence interval (CI), 0.88–0.92], with a specificity of 88% (95% CI, 0.85–0.91) and area under the curve (AUC) of 0.95. On the other hand, Tc-99m single-photon emission computerized tomography (SPECT) has sensitivity and specificity of 85% (95% CI, 0.82–0.87) and 85% (95% CI, 0.82–0.87), respectively, with an AUC of 0.90.[23]

In patients with renal failure, adding calcium score may help in risk prediction and disease detection. In a study of 138 patients referred for pretransplant cardiac evaluation, they underwent coronary artery calcium score, coronary computed tomography angiography, SPECT, and invasive coronary angiography. Using coronary angiography as the gold standard, the positive predictive value of SPECT increased from 44% to 77% when combined with coronary calcium scoring with no significant change in specificity (84%).[24]

In the view of lack of data in the KSA, we extrapolate the sensitivity and specificity of PET and SPECT in the KSA from the international studies.[25]

[Table 3] shows the sensitivity and specificity of each modality of stress testing in renal-transplant candidates.
Table 3: Stress testing in renal-transplant candidates

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1.4 The prognostic value of positive stress test concerning the risk of major adverse cardiac events in asymptomatic kidney-transplant candidates

The available observational data are inconclusive.

  • Studies showing positive association


    • In a meta-analysis by Rabbat et al in 2003 (data from 12 studies), myocardial perfusion studies (MPSs), such as thallium scintigraphy and dobutamine stress echocardiography (DSE), showed that positive tests had a significantly increased respiratory rate (RR) of MI [2.73 (95% CI, 1.25–5.97); P = 0.01] and cardiac death [2.92 [(95% CI, 1.66–5.12)]; P <0.001, when compared with negative tests. Subgroup analyses of studies of diabetic patients indicated that positive tests were associated with significantly increased risk of future MI and CD in both diabetic and non-diabetic ESRD patients.[25]
    • In a study by Patel et al, the 42-month cardiac event-free survival rate was 97% in patients with normal myocardial perfusion SPECT and 85% in patients with abnormal SPECT images (RR 5.04, 95% CI 1.4–17.6, P = 0.006).[26]
    • 99mTechnetium sestamibi myocardial perfusion scanning in a study from the UK (the European Best Practice Guideline), the unadjusted hazard ratio of cardiac event with reversible defect on MPS was 3.1 (95% CI, 1.1–18.2) and hazard ratio of death with reversible defect on MPS was 1.92 (95% CI, 1.1–4.4).[27]


  • Studies showing no association


    • De Lima et al, in 2003, have found that neither MPS nor DSE results were independently associated with future major adverse cardiac event (MACE) in moderate-to-high-risk kidney-transplant candidates. However, the probability of event-free survival at 48 months was 94% in patients with <70% stenosis on coronary angiogram and 54% in patients with ≥70% stenosis. Multivariate analysis showed that the sole predictor of cardiac events was critical coronary lesions (P = 0.003). De Lima concluded that coronary angiography may still be necessary for detecting CAD and determining cardiac risk in renal-transplant candidates.[28] o Gill et al in 2005 found that the results of noninvasive cardiac investigations before wait-listing were not predictive of the time to CV event after waitlisting.[29]




1.5 The prognostic value of performing “screening cardiac catheterization” in high-risk transplant candidates? Data are mixed

  • Studies showing positive association


    • De Lima et al, 2003 reported that the finding of CAD on coronary angiography, but not noninvasive screening, was associated with an increased risk of future MACE.[28] o Welsh et al[30] showed, in renal-transplant candidates with diabetes, that myocardial perfusion imaging had poor negative predicted value (with normal imaging in 50.3% of the patients having CAD more than or equal to 50%). Angiographic evidence of CAD ≥70% (odds ratio 1.81, 95% CI, 1.02–3.23) was the only independent predictor of MACEs.


  • Studies showing no association


    • Hage et al in 2007 found that the presence and severity of coronary disease on angiography was not predictive of survival. Coronary revascularization did not impact survival (P = 0.6) except in patients with 3-vessel disease (P = 0.05). The best predictor of death was left ventricular ejection fraction, measured by gated myocardial perfusion imaging.[31]




1.6 The prognostic value of cardiac intervention (angioplasty) in asymptomatic renal-transplant candidates in relation to future clinical outcome.

Kumar et al in 2011 suggested that preemptive coronary revascularization is not only associated with excellent survival rates not only in patients subsequently transplanted but also in those patients waiting on dialysis for a deceased donor transplant.[32] However, despite the excellent survival benefit associated with coronary intervention reported in this trial, the fact that it was a single-center study and that there was no comparable arm of similar patients who did not undergo screening coronary angiography makes it difficult to draw a final conclusion on the study’s question of the value of preemptive coronary angiography and coronary intervention.

In a more recent study,[33] coronary angiography was offered to CKD patients who had CV screening before renal transplant and found to have evidence of high myocardial ischemic burden on DSE. The decision to intervene on the coronary arteries was left to the interventional cardiologist and was mainly based on the angiographic appearance of the coronary stenosis. When deemed appropriate, the stenotic lesions were investigated further using pressure wire studies. The majority of the patients who require coronary intervention underwent percutaneous coronary intervention (PCI) and fewer patients were referred for surgical revascularization. The study overall showed worse event-free survival in patients who had CAD requiring intervention than those who had no intervention. Coronary intervention per se, however, did not appear to affect to alter the prognosis or improve survival.

The result of this study was rather similar to the findings of older studies which showed that cardiac event-free survival was worse in patients noted to have significant coronary disease (≥50% stenosis in at least one coronary artery) on coronary angiography[34] and that coronary intervention did not improve overall prognosis.[35]

In the only RCT, Manske et al in 1992 suggested that revascularization, when compared to medical therapy, decreased the frequency of cardiac events in insulin-dependent diabetic kidney-transplant candidates. The study included only 26 patients in total and subjects with >75% stenosis in at least one vessel. In all, two of 13 re-vascularized subjects compared with 10 of 13 medically managed subjects had a CV event with a median follow-up of 8 months, and four medically managed subjects died of MI. However, this study is very small and old. The CV event rate was markedly high. Medical management consisted only of a calcium channel blocker and aspirin, making the results difficult to interpret in the setting of much improved medical management of CVD. No modern large trials have been conducted among kidney-transplant candidates.[36]



1.7 The prognostic value of angioplasty versus medical treatment in general CKD population?

Sedlis et al reviewed, in a post hoc analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, the benefit of revascularization versus medical therapy in asymptomatic CKD patients. CKD was defined as a glomerular filtration rate of <60 mL/min/1.73 m2 (only few patients were with advanced CKD) and no difference was seen in all-cause mortality or nonfatal MI in those who received PCI versus optimal medical management.[37] The lack of difference of clinical outcome between these two treatment modalities noted on the original COURAGE trial persisted on another extended follow-up study when patients were followed up for a maximum of 15 years (median of 6.5 years). The result was similar on subgroup assessment including patients with CKD.



1.8 The prognostic value of stress testing, cardiac catheterization or angioplasty in asymptomatic nonrenal patients from the general population. 1.8. (A) The value of stress testing in asymptomatic diabetic patients

In the detection of ischemia in asymptomatic diabetes (DIAD) trial in 2009, Young et al studied 1123 subjects with type-2 diabetes and no symptoms of CAD who were randomized to MPS versus no screening. The overall rate of coronary revascularization was low in both groups: 31 (5.5%) in the screened group and 44 (7.8%) in the unscreened group [heart rate (HR), 0.71; 95% CI, 0.45–1.1; P = 0.14]; the difference was not statistically different. No difference in cardiac death or nonfatal MI was seen at 4.8 years.[38]



1.8. (B) The value of stress testing before major vascular surgery

In the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocar-diography (DECREASE) trial in 2006, Poldermans et al randomized 770 subjects with intermediate risk (1 or 2 risk factors) to echocardiographic stress testing or no testing before major vascular surgery. All patients were receiving beta-blocker therapy with tight HR control scheduled for major vascular surgery. Those with extensive stress-induced ischemia were considered for revascularization. The primary end-point was cardiac death or MI at 30- day after surgery. Regardless of allocated strategy, patients with a HR <65 bpm had lower risk than the remaining patients. Poldermans et al concluded that cardiac testing could safely be omitted in intermediate-risk patients, provided that beta-stblockers aiming at tight HR control are prescribed.[39],[40] The result of this study supported the findings of another earlier randomized but much smaller study that assessed the efficacy of DSE in risk stratification in 99 patients before vascular surgery. This study revealed that positive DSE offered no positive predictive value for adverse cardiac events up to one year post-operatively.[41] Conversely, older data suggested that positive DSE predicts late cardiac events postoperatively and that the risk increases proportionally to the number of myocardial segments noted to have stress-induced ischemia on DSE.[42],[43]



1.8. (C) The value of revascularization in asymptomatic high-risk patients from the general population in the perioperative setting

In the Coronary Artery Revascularization Prophylaxis study, McFalls et al studied preoperative revascularization in a high-risk group before elective major vascular surgery (a situation very similar to that currently faced by the kidney-transplant community).

  • 510 subjects with risk factors or positive noninvasive stress test and >70% stenosis in one or more major coronary vessel on cardiac cath were studied
  • Patients were randomized to either revascularization or medical management
  • No difference was seen in mortality at a median of 2.7 years, or in the 30-day postoperative MI
  • McFalls et al concluded that coronary artery revascularization before elective vascular surgery does not significantly alter the long-term outcome. On the basis of these data, a strategy of coronary artery revascularization before elective vascular surgery among patients with stable cardiac symptoms cannot be recommended.[44]




1.8. (D) Revascularization versus medical therapy for coronary artery disease in nonperioperative setting

In the COURAGE trial, Boden et al, 2007 randomized 2287 patients (a nonperioperative setting) with objective evidence of myocardial ischemia and significant CAD on angiography to medical management versus percutaneous coronary intervention. No difference in all-cause mortality or non-fatal MI was found (follow-up of 4.6 years). Boden et al concluded that in patients with stable CAD, PCI did not reduce the risk of death, MI, or other major CV events when added to optimal medical therapy.[45] It is worth noting, however, that the use of drug-eluting stents in COURAGE trial was low not exceeding 3% of all PCI cases.

Furthermore, the selection criteria in COURAGE trial arguably did not target high-risk patients. Around 60% of the patients who were enrolled in the trial based on positive nuclear stress scan had less than moderate myocardial ischemia. Hence, the result of the trial could have diluted with the number of patients who were unlikely to benefit from coronary revascularization.

Similar pattern was noted in another landmark trial BARI-2D,[46] which showed no difference in all-cause mortality in patients with stable ischemic heart disease who had either PCI or CABG in addition to optimal medical therapy versus those who were managed by optimal medical therapy alone after 5.3 years of follow-up. Du-ring an extended follow-up of up to 15 years of the COURAGE Clinical Trial, Sedlis et al did not find a difference in survival between an initial strategy of PCI plus medical therapy and medical therapy alone in patients with stable ischemic heart disease.[47]



1.8. (E) Myocardial ischemic burden and interventions

Myocardial ischemic burden has been suggested to be another basis of selection of patients with stable ischemic heart disease who would prognostically benefit from coronary revascularization. In one large single-center observational study, more than 10,000 patients were referred for stress perfusion testing.[48] At two-year follow-up, 150 deaths and nearly 500 acute coronary syndrome cases were identified. The study revealed that patients who had >10% myocardial ischemic burden, which is considered to be moderate ischemia or more by nuclear imaging studies, and managed by revascularization, had a better outcome than those managed by medical treatment alone. Conversely, medical treatment alone appeared to be associated with a better outcome that revascularization in those with <10% ischemic burden. Although this 10% ischemic burden mark was adopted in certain clinical practice, the results need to be interpreted with caution given that this study was conducted in a single center that was an advanced imaging center, and the CIs of the results variables were relatively wide. In addition, only around 40% of patients with more than 10% ischemic burden actually underwent coronary revascularization, suggesting that the criteria for selecting these patients to revascularization was based on other clinical variables and not only on this ischemic burden cutoff, suggesting a potential selection bias.

Another observational study assessed the burden of myocardial ischemia by stress echocardiography again showed that better outcome is associated with revascularization in patients who were found to have severe ischemia compromising at least eight ischemic segments on the wall motion score index.[49] However, the amount of ischemia associated with worse outcome in this study was much higher than that noted in the nuclear imaging study. Moreover, the same potential selection bias might exist in this study. Overall, coronary revascularization appears to be effective in improving symptoms and reducing myocardial ischemia, especially in patients who have large baseline myocardial ischemic burden. However, there are no data from controlled randomized trials that can suggest that revascularization improve the prognosis in patients with stable CAD.

Although demand-mediated ischemia from obstructive plaques contributes to perioperative cardiac events, rupture of nonobstructive plaques has long been understood to be a significant contributor in both non-operative[10] and perioperative settings.[51]






   The Guidelines of Cardiovascular Risk Assessment in Kidney Transplantation in the Kingdom of Saudi Arabia Top


In the view of the limited international data and the lack of similar studies in the KSA, the reviewing committee has adopted the ACC/ AHA guidelines on cardiac disease evaluation and management in renal-transplant candidates 2012 with modifications as below.

2.1 Outlines from the American Heart Association guidelines

The authors have adopted the following recommendations from the summary of the ACC/AHA guidelines about cardiac disease evaluation and management in renal-transplant candidates 2012 [Table 4].
Table 4: Outlines from the American Heart Association guidelines.

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2.2 Definitions for the class of recommend- dation (I–III) and evidence level (A–C)

[Table 5] shows the definitions for the Class of Recommendation (I–III) and Evidence Level (A–C).
Table 5: Definitions for the Class of Recommendation (I–III) and Evidence Level (A–C).

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2.3 Major recommendations

2.3.1 Determining whether the transplantation candidate has an active cardiac condition

A thorough history and physical examination are recommended to identify active cardiac conditions before renal transplantation (Class I; Level of Evidence C) as per the AHA guidelines.

2.3.2 Recommendations for referral to a cardiologist

The authors recommend that all kidney transplantation candidates who have abnormal echo or abnormal stress test will be referred to cardiology.

2.3.3 Indications for noninvasive stress testing in kidney transplantation candidates without active cardiac conditions

AHA guidelines recommend that 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. Relevant risk factors among transplantation can-didates include diabetes mellitus, prior cardiovascular disease (CVD), more than one 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 the committee considers three or more as reasonnable (Class IIb; Level of Evidence C).

We acknowledge that many renal-transplant candidates have multiple risk factors especially those >50 years. In a study by Delville et al, renal-transplant candidates older than 50 years were found to have HTN in 94%, dyslipidemia in 80%, smoking in 45%, diabetes in 23%, and history of CAD in 21%. LVH was present in 50%. Sixty-two percent of the candidates exhibited more than four traditional risk factors in this study.[52] Based on the high prevalence of risk factors among the renal-transplant candidates in the KSA and the high incidence of CAD at lower age, the reviewing committee recommends to start screening for asymptomatic CAD at a lower age (50 years instead of 60) and this is in concordance with the European guidelines.[2]2.3.3.1 The authors recommend scree-ning by stress testing for asymp-tomatic renal-transplant candidates and the indications are given in [Table 6].
Table 6: Indications for stress testing for asymptomatic renal-transplant candidates.

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2.3.4 Echocardiography in kidney transplantation candidates

  • A baseline Echo should be performed for all potential kidney transplantation candidates (Class IIa; Level of Evidence B) as per the AHA guidelines
  • There is no evidence for or against surveillance by repeated left ventricular function tests after listing for kidney transplantation.
  • Renal-transplant candidates with moderate aortic stenosis, “rapid progressors”, warrant a yearly echocardiogram and monitoring for early symptoms (Class IIb; Level of Evidence C) guidelines from the AHA.


2.3.5 Screening and management of pulmonary hypertension (right ventricular systolic pressure)

  1. All the renal-transplant candidates are recommended to have an Echo to evaluate for pulmonary hypertension. Echo should be performed when the patient is close to his/her dry weight. (Class IIa; Level of Evidence C)
  2. Classification of echographic right ventricular systolic pressure is shown in [Table 7]
  3. If right heart catheterization confirms the presence of significant pulmonary arterial hypertension (as defined by mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge ≤15 mm Hg, and pulmonary vascular resistance of >3 Wood units) in the absence of an identified secondary cause (e.g., obstructive sleep apnea, left heart disease), referral to a consultant with expertise in pulmonary arterial hypertension management and advanced vasodilator therapies is reasonable (Class IIa; Level of Evidence C)[53] [Table 8].
Table 7: Classification of right ventricular systolic pressure.

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Table 8: Management of renal-transplant candidates with right ventricular systolic pressure.

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2.3.6 Recommendations for coronary revascularization and related care before kidney transplantation

The authors adopted the AHA recommendation:

  1. 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). It is recognized that in some asymptomatic transplantation candidates, the risk of coronary revascularization may outweigh the risk of transplantation and the multidisciplinary transplantation team must weigh these risks on a case-by-case basis until further studies are performed in this population.
  2. Coronary artery bypass grafting (CABG) is probably recommended in preference to PCI to improve survival in patients with multi-vessel CAD and diabetes mellitus (Class IIa; Level of Evidence B).
  3. 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 three major vessels or in the proximal left anterior descending artery plus one other major vessel, regardless of left ventricular systolic function (Class IIb; Level of Evidence B)
  4. Transplant candidates are placed on hold for six months post-CABG.


2.3.7 Routine prophylactic coronary revascularization

  1. It is not recommended that routine prophylactic coronary revascularization be performed in patients with stable CAD, absent symptomatic or survival indications, before transplantation surgery (Class III; Level of Evidence B) The committee adopted the AHA recommendation.


2.3.8 Cardiac surveillance after listing for transplantation

  1. The usefulness of periodically screening asymptomatic kidney transplantation candidates for myocardial ischemia while on the transplant waiting list to reduce the risk of MACEs is uncertain (Class IIb; Level of Evidence C).


The authors adopted the above AHA recommendation.

2.3.9 Noncontrast computed tomography calcium scoring and cardiac computed tomography angiography in kidney transplantation candidates

  1. The committee adopted the AHA recommendation that:


The usefulness of noncontrast CT calcium scoring and cardiac CT angiography is uncertain for the assessment of pre-transplantation CV risk (Class IIb; Level of Evidence B).[54]

2.3.10 Duration of dual-antiplatelet therapy after percutaneous coronary intervention before kidney transplantation

The duration of dual anti-platelet therapy is as per cardiology advice. Important factors to consider in perioperative DAPT management are the type, number, and size of stents versus the risk of delaying renal transplantation in favor of prolonging DAPT to prevent stent thrombosis. A newer generation of DESs with enhanced biocompatibility and reduced thrombogenicity may require only 1–6 months of DAPT depending on the type of stent, but more evidence is needed.[55] [Table 9].
Table 9: The duration of anti-platelet treatment in renal transplant candidates.

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2.3.11 Waiting time after acute coronary syndrome or cerebrovascular accident

Renal-transplant candidates are typically placed on hold for six months following acute coronary syndrome or cerebral vascular event.

2.3.12 Evaluation and management of renal transplant candidates with uremic cardiomyopathy and congestive heart failure

Uremic cardiomyopathy is not uncommonly encountered in dialysis population in the KSA. These patients are typically young patients who just started renal replacement therapy or patients on peritoneal dialysis with insufficient clearance (e.g., lost their residual renal function). These patients had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort.

Correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.[56]

Kidney transplantation in ESRD patients with advanced systolic heart failure results in an increase in LVEF, improves functional status of congestive heart failure (CHF), and increases survival. To abrogate the adverse effects of prolonged dialysis on myocardial function, ESRD patients should be counseled for kidney transplantation as soon as the diagnosis of systolic heart failure is esta- blished[57] [Table 10].
Table 10: Evaluation of renal-transplant candidates with uremic cardiomyopathy.

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[Algorithm 1] shows the pathway of uremic cardiomyopathy kidney transplantation candidates.



2.3.13 Estimating of the risk of renal transplant surgery

Renal transplant is considered as an intermediate risk surgery (peri-operative cardiac risk 1%–5%).[44] Recipient-related risk factors such as CAD or CHF may increase the cardiac risk.[44],[45] It should be kept in mind that even high-risk patients may benefit from transplant over dialysis.

2.3.14 Cardiac CLEARANCE pathway of renal transplant candidates

[Algorithm 2] shows the cardiac clearance pathway for kidney transplantation candidates.




   Evaluation of Patients while on the Waiting List and the Expected Effects of the Implementation of the New Guidelines at the Local and National Levels Top


[Table 11] shows the evaluation of patients while on the waiting list and the expected effects of the implementation of the new guidelines at local and national levels.
Table 11: Evaluation of patients while on the waiting list and the expected effects of the implementation of the new guidelines at the local and national levels.

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   Conclusion Top


These guidelines present the first published guidelines of CV risk assessment in the KSA. These guidelines are reviewed by consultants from six major transplant centers in KSA (including transplant nephrologists, cardiologists, transplant surgeons, and anesthesiologists). These guidelines are designed according to the international guidelines.

In Saudi Arabia, the renal transplantation candidates are presumably having more prevalent risk factors of CVDs than in western countries. There is also a large degree of variation among the practices of the different transplant centers in the KSA and among the international guidelines. Due to the lack of published data about CVD among renal-transplant candidates in the KSA, the international evidence is reviewed here.

In summary, the evidence for screening or intervening in potential renal-transplant recipients is uncertain not only among asymptomatic renal-transplant candidates but also in asymptomatic patients with CKD and general population. It is essential to recognize the prognostic value and the limitation of each stage of screening of asymptomatic renal transplant candidates. Stress testing has sub-optimal sensitivity and specificity in CKD. There is limited or no evidence that screening by stress testing or coronary angiogram improves perioperative MACE. There is also limited or no evidence that preemptive coronary revascularization in asymptomatic potential recipients improves the long-term outcomes after transplantation. This effort is hoped to help to standardize the practices of CV assessment among the renal-transplant centers in the KSA by utilizing the best available evidence in this field. These guidelines are also hoped to serve as a useful educational tool and a ground for future researches in this area.[58]

Conflict of interest: None declared.



 
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Correspondence Address:
Ziad Arabi
Adult Transplant Nephrology, Department of Organ Transplant Center, King Abdulaziz Medical City, Riyadh
Saudi Arabia
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DOI: 10.4103/1319-2442.289452

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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