Objectives: Cardiovascular disease is the major cause of morbidity and mortality in patients on renal replacement therapy and in kidney transplant recipients. There are no specific recommendations for preoperative cardiac risk assessment before renal transplant. The aim of our study was to analyze preoperative cardiac test frequencies, test results, patient characteristics, and relations between cardiac stress test results and severe coronary artery disease.
Materials and Methods: We retrospectively examined patients who underwent renal transplant between December 2011 and December 2016 in our hospital (Ankara, Turkey). Our study group included 216 patients. All patients had preoperative echocar-diography. We recorded results of exercise stress tests, myocardial perfusion scintigraphy, and coronary angiography. For all patients, preoperative complete blood cell count, creatinine, high-density lipoprotein, triglycerides, low-density lipoprotein, and red cell distribution width values were obtained and recorded.
Results: We classified patient groups according to presence or absence of severe coronary artery disease. Fourteen of 66 patients had severe coronary artery disease. In univariate analyses, age, having a history of familial coronary artery disease, diabetes mellitus, presence of coronary artery disease, and triglyceride levels were risk factors for severe coronary artery disease. In multivariate analysis, diabetes mellitus, presence of coronary artery disease, and having a history of familial coronary artery disease were statistically significant.
Conclusions: Renal transplant recipients are a special patient population, and there must be specific suggestions for this population. If patients present with more than 1 risk factor, a stress test should be performed to evaluate cardiovascular risk. In some patients, especially those whose risk factors include prior cardiovascular disease or diabetes mellitus, stress tests should be skipped and patients should directly undergo coronary angiography to look for severe coronary artery disease.
Key words : Coronary artery disease, Kidney transplantation, Stress test
Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients on renal replacement therapy and in kidney transplant recipients.1 Cardiovascular mortality is defined as death as a result of arrhythmias, cardiomyopathy, cardiac arrest, myocardial infarction, atherosclerotic heart disease, and pulmonary edema. Presently, 50% to 60% of deaths can be directly attributed to CVD, with an incidence of ischemic heart disease being approximately 1 per 100 person-years at risk.2 It should be mentioned that kidney transplant recipients also have a higher risk of fatal and nonfatal cardiovascular events than the general population but have a lower risk than dialysis patients on wait lists.3,4 The 2007 US Renal Data System report revealed that the 5-year survival was only 35% among general dialysis patients.5 There are actually no specific recommendations for preoperative cardiac risk assessment before renal transplant. The 2014 European Society of Cardiology guidelines on cardiovascular risk assessment and care before noncardiac surgery stated that renal transplant is a moderate risk procedure, with no specific recommendations for the care of these patients.6 Therefore, the purpose of preoperative cardiac risk evaluations in patients with end-stage renal disease is to reduce cardiovascular short- and long-term mortality and morbidity.
The aim of our study was to analyze preoperative cardiac test frequencies, test results, patient characteristics, and the relation between cardiac stress test results and severe coronary artery disease.
Materials and Methods
We retrospectively examined patients who under-went renal transplant between December 2011 and December 2016 in our hospital in Ankara, Turkey. During this period, renal transplant procedures were performed on 280 patients (62 were pediatric patients and 2 were excluded from the study due to data loss for various reasons). As a result, 216 patients were retrospectively screened.
All patients had preoperative echocardiography. We recorded results of exercise stress tests, myocardial perfusion scintigraphy, and coronary angiography. For exercise stress test results, we used the following definitions: maximally normal (if a patient achieved more than 95% of age-adjusted heart rate), submaximally normal (if a patient achieved between 85% and 95% of age-adjusted heart rate), nondiagnostic (if a patient achieved less than 85% of age-adjusted heart rate), and positive (positive ischemic symptoms or at least 2-mm horizontal or downsloping ST depression in 2 consecutive leads). Myocardial perfusion scinti-graphy results were divided into 2 groups: ischemia-positive and ischemia-negative. In patients who underwent coronary angiography, we separated angiography results into 5 groups: normal coronary arteries, minimal coronary artery disease, severe coronary artery disease (at least 1 lesion over 70% in 1 epicardial coronary artery or its branch) requiring percutaneous coronary intervention, severe coronary artery disease (as above) requiring coronary artery bypass surgery, severe coronary artery disease (as above) not amenable to intervention and assigned to medical therapy.
For all patients, preoperative complete blood cell count, creatinine level, high-density lipoprotein, triglyceride levels, low-density lipoprotein, and red blood cell distribution width values were obtained and recorded.
This study was approved by the Baskent University Institutional Review Board (Project No. KA17/127).
Patients were divided into 2 broad groups on the basis of their angiographic results: those with and those without severe coronary artery disease. Logistic regression analyses were done to find factors predictive of the need for coronary intervention. Data are expressed as means ± standard deviation unless stated otherwise. Categorical data were analyzed with Fisher exact test and the chi-square test. P < .05 was considered statistically significant. All analyses were undertaken using the SPSS statistical program (version 17; SPSS, Chicago, IL, USA).
Our study included 216 adult patients. Patient demographics, clinical characteristics, and laboratory parameters are shown in Table 1.
Echocardiographic parameters are shown in Table 2. All patients with severe coronary artery disease had left ventricular hypertrophy; although it was more prevalent than in those without severe coronary artery disease, it was not statistically significant (P = .056) (Table 3).
Exercise stress tests were conducted in 131 patients (60.6%), with 13 patients (9.9%) having a maximally normal test, 80 patients (61.6%) having a sub-maximally normal test, 37 patients (28.2%) having a nondiagnostic exercise test, and 1 patient (0.8%) having a positive exercise stress test.
Myocardial perfusion scintigraphy was per-formed in 49 patients (22.7%), with ischemia documented in 22 patients (44.9%). Sixty-six patients (30.6%) underwent coronary angiography. Thirty-five patients (53%) had normal coronary arteries and 17 (25.8%) had minimal coronary artery disease. Five patients (7.6%) received coronary stents, 2 patients (3.0%) underwent bypass surgery, and 7 patients (10.6%) were put on medical therapy with a lesion over 70% in at least 1 vessel.
We classified patient groups according to presence of severe coronary artery disease. Fourteen of 66 patients had severe coronary artery disease. Table 3 shows the comparison of risk factors for severe coronary artery disease. In univariate analyses, age, having a history of familial coronary artery disease, diabetes mellitus, presence of coronary artery disease, and triglyceride levels were risk factors for severe coronary artery disease. In multivariate analysis, diabetes mellitus, presence of coronary artery disease, and having a history of familial coronary artery disease were statistically significant.
Cardiovascular disease is endemic in the end-stage renal disease population. In as much as patients with CVD have impaired renal function, patients with chronic kidney disease have CVD as the major predictor of mortality.7 Therefore, it is of importance that potential kidney transplant recipients are carefully evaluated to detect and treat coexisting situations that may affect transplant candidacy, perioperative risk, and survival after transplant.
Several studies have shown that there are traditional and nontraditional risk factors for CVD in posttransplant patients. The traditional risk factors include advanced age, diabetes mellitus, male sex, smoking cigarettes, hypertension, and elevated serum cholesterol levels. The nontraditional risk factors include reduced kidney function after transplant, need for dialysis before transplant, transplant rejection, immunosuppressive drug use, elevated levels of lipoprotein (a) and C-reactive protein, and low physical activity.8-11
According to the European Society of Cardiology guidelines, routine resting echocardiography is not recommended for low- and intermediate-risk surgery (evidence level class III, C). With high-risk surgery, this procedure may be considered (class IIb, C).6 Renal transplant has been identified as an intermediate-risk surgery. However, the situation of potential kidney transplant recipients is much more challenging because we perform all diagnostic tests to assess eligibility for kidney transplant. Because this could be more than an intermediate-risk surgery, great caution should be exercised.
The basic test after electrocardiography is echocardiography. In our renal transplant recipients, all participants had a resting echocardiography test. Previous studies have not mentioned any specific signs of CVD on echocardiography in this population. However, in our study, diastolic dysfunction was associated with coronary artery disease requiring intervention. However, our results may have been influenced by the small number of patients with severe coronary artery disease.
An exercise electrocardiography stress test provides limited information because it is not feasible in end-stage renal disease patients due to poor functional status and high prevalence of left ventricular hypertrophy that limits the specificity of the test.12 In our study, it was the most common stress test used; however, 38 of 131 patients (29%) could not reach the target heart rate, and just 13 patients (9.9%) ended tests at maximal heart rate. One patient who had a positive stress test had a normal coronary angiogram. In contrast, a patient who had a normal exercise test at maximum heart rate needed percutaneous coronary intervention after coronary angiography. These results are in agreement with literature reports and recom-mendations. The exercise stress test is an inexpensive and noninvasive stress test; however, it does not give enough information about CVD risk. Therefore, this test can be omitted for preoperative risk stratification.
Currently, myocardial perfusion imaging (MPI) with single photon emission computed tomography and dobutamine stress echocardiography (DSE) remain mainstays of coronary artery disease surveillance in this population. In our center, we also used MPI for further evaluations after exercise stress tests. Several studies have examined the diagnostic accuracy of these tests. Sensitivity and specificity exhibit a wide range of results between older and newer studies. Gowdak and associates13 studied 219 patients, and MPI was done in 63% of the cohort. The group found that the test’s sensitivity was 62% and specificity was 62%. In another study, Wang and colleagues14 examined the Cochrane Database; both DSE and MPI had moderate sensitivity and specificity in detecting coronary artery stenosis in kidney transplant candidates (for DSE: pooled sensitivity = 0.79, pooled specificity = 0.89, for MPI: pooled sensitivity = 0.74, pooled specificity = 0.70). It appears that DSE is slightly more sensitive and specific; however, when only studies that defined coronary artery stenosis using a reference threshold of ≥ 70% stenosis on coronary angiography were considered, a slight change occurred in these pooled estimates of accuracy (for DSE: pooled sensitivity = 0.76, specificity = 0.88; for MPI: pooled sensitivity = 0.67, pooled specificity = 0.77). As a result, no differences appear to exist between DSE and MPI for coronary artery disease with greater than 70% stenosis. Therefore, it can be suggested that the testing modality chosen largely depends on the center’s experience. In our study, we performed 49 MPIs (22.7%) of which 22 yielded positive results for ischemia. Of these 22 patients, coronary angiography was performed in 17 patients, with 4 patients having severe coronary artery disease and 5 having minimal coronary artery disease.
As mentioned previously, traditional risk factors are also important for patient selection for invasive methods. In our study, univariate analyses revealed that age, diabetes mellitus, history of familial coronary artery disease, history of coronary artery disease, and high triglyceride levels were predictive of severe coronary artery disease. In multivariate analyses, we found that diabetes mellitus, history of familial coronary artery disease, and history of coronary artery disease were independent risk factors of severe coronary artery disease. Several observational studies showed that diabetes mellitus, left ventricular hypertrophia, age over 50 years, more than 1 year on dialysis, tobacco abuse, hypertension, left ventricular ejection fraction < 40%, and dyslipidemia were independent risk predictors of CVD and cardiac mortality in kidney transplant candidates.15-18 The European Society of Cardiology guidelines on noncardiac surgery recommend that imaging stress testing may be considered in patients with 1 or 2 clinical risk factors and poor functional capacity (< 4 metabolic equivalents) before
high-risk and intermediate-risk surgery with a class IIb recommendation and level of evidence C.6 They identified the risk factors of ischemic heart disease (angina pectoris and/or previous myocardial infarction), heart failure, stroke or transient ischemic attack, and renal dysfunction (serum creatinine > 2 mg/dL or a creatinine clearance of < 60 mL/min/1.73 m2) for perioperative cardiac events. Similarly, the 2012 American Heart Association/American College of Cardiology consensus statement recommended imaging stress tests on the evaluation and management of cardiac disease in kidney and liver transplant candidates with no active cardiac conditions on the basis of the presence of multiple coronary artery disease risk factors regardless of functional status (class IIb, with level of evidence C).12 Relevant risk factors among transplant candidates, per the 2012 American Heart Association/American College of Cardiology statement, include diabetes mellitus, prior CVD, > 1 year on dialysis, left ventricular hypertrophy, age > 60 years, smoking, hypertension, and hyperlipidemia.12 The statement indicated that, if there are 3 or more risk factors, a stress test should be considered for preoperative assessment with a class IIb recommendation and a level of evidence of C. Our findings were similar to the literature and to both guidelines’ recommendations. Thus we must be cautious in patients who are over 50 years old, have diabetes mellitus, have a history of familial coronary artery disease, and have had prior CVD and hyperlipidemia. In some special conditions, we may skip stress testing or imaging modalities and visualize coronary arteries directly with coronary angiography. It may prevent wasted time with other tests, and, even more importantly, it can provide more accurate information.
In conclusion, there is no consensus about preoperative assessment of this patient population. However, it is a general agreement that renal transplant recipients are a special patient population, and there must be specific suggestions for this population because transplant is not just an intermediate-risk procedure because the patient population has other specific risk factors. Generally speaking, if a patient has more than 1 risk factor, stress tests should be performed to evaluate cardiovascular risk and the choice of stress test should perhaps depend on the experience of the center. As mentioned previously, DSE and MPI have similar accuracy for estimating perioperative cardiovascular risk. In some patients, especially those who have risk factors such as prior CVD or diabetes mellitus, stress test may be skipped and patients may directly undergo coronary angiography to look for severe coronary artery disease.
DOI : 10.6002/ect.2017.0145
From the 1Cardiology Department, the 2Nephrology Department, and the
Surgery Department, Baskent University Faculty of Medicine, Ankara, Turkey
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Kerem Can Yilmaz, Fevzi Cakmak Avenue, 10th Street No. 45, Cardiology Department, Bahcelievler, Ankara, Turkey
Phone: +90 312 2036868 1376
Table 1. Demographic Characteristics of 216 Study Patients
Table 2. Preoperative Test Results of Renal Transplant Recipients (N = 216)
Table 3. Comparison Of Demographic Characteristics and Laboratory Results in Patients Who Had Coronary Angiography