INTRODUCTION — Cardiovascular disease (CVD) accounts for approximately 40 percent of deaths in patients with end-stage kidney disease (ESKD) [1]. Of these, approximately 8 percent can be attributed to coronary artery disease (CAD) [1]. Patients with advanced stages of chronic kidney disease (CKD), but who are not yet dialysis dependent, also have a markedly increased risk of morbidity and mortality from CVD, including CAD. (See "Patient survival and maintenance dialysis" and "Chronic kidney disease and coronary heart disease".)
This topic reviews the clinical manifestations, screening, and diagnosis of CAD in patients on dialysis. CAD in the general population is discussed elsewhere. (See "Coronary artery disease and myocardial infarction in young people" and "Screening for coronary heart disease".)
Other aspects of CAD in patients on dialysis are presented elsewhere. (See "Secondary prevention of cardiovascular disease in end-stage kidney disease (dialysis)" and "Risk factors and epidemiology of coronary heart disease in end-stage kidney disease (dialysis)".)
CLINICAL MANIFESTATIONS
Stable angina — Patients on dialysis who have obstructive CAD may present with exercise-induced chest discomfort that is similar to that in patients with normal kidney function. However, patients on dialysis often have comorbidities, such as peripheral arterial disease and poor conditioning, that limit their ability to exercise, which may delay their presentation or mask the presence of obstructive CAD.
Angina can be provoked by dialysis. This is because acute fluid and electrolyte shifts and episodes of hypotension during dialysis may precipitate symptomatic ischemia.
Patients on dialysis may also present with exertional dyspnea, intradialytic or interdialytic hypotension, sudden cardiac arrest or death, and arrhythmias [2]. Silent myocardial ischemia is also common in patients on dialysis. (See "Angina pectoris: Chest pain caused by fixed epicardial coronary artery obstruction" and "Acute complications during hemodialysis" and "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)
Acute coronary syndrome — Patients with ESKD who have an acute coronary syndrome (ACS; acute myocardial infarction [AMI] or unstable angina) generally present with the same symptoms as patients without ESKD, including chest pain associated with dyspnea, nausea, vomiting, and diaphoresis [3]. However, compared with the general population, patients with ESKD are more likely to have only atypical symptoms, such as isolated dyspnea, weakness, syncope, palpitations, or cardiac arrest, which may lead to underdiagnosis. In addition, typical symptoms of ischemia (eg, dyspnea) may be attributed to causes other than myocardial ischemia (eg, interdialytic volume overload) [3-7].
Among patients with ESKD, electrocardiogram (ECG) manifestations of ACS are similar to those in the general population. However, baseline abnormalities on the ECG, such as left ventricular hypertrophy and ST-T changes in the absence of ischemia, may mask characteristic changes of ischemia [8]. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Clinical presentation'.)
EVALUATION AND DIAGNOSIS
Evaluation at dialysis initiation — We generally evaluate all patients for CAD and other cardiovascular conditions when they start dialysis. The approach to screening depends upon whether or not the patient is a kidney transplant candidate.
Kidney transplant candidates — Among patients who are potential kidney transplant recipients, the cardiac evaluation is often initiated by the transplant center as part of the pretransplant evaluation. The evaluation of such patients is discussed elsewhere. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient", section on 'Cardiovascular disease'.)
Patients who are not transplant candidates — All patients who are initiating dialysis should undergo a history and physical examination to assess for symptoms and signs of cardiovascular disease (CVD) and an electrocardiogram (ECG). Some centers also routinely obtain a transthoracic echocardiogram once the patient is at dry weight, typically during the first one to three months of initiating dialysis. The ECG and echocardiogram provide a baseline for comparison in the event of future evaluations and may identify signs of remote myocardial infarction (MI) or other cardiac disorders. This approach is based upon expert opinion and is consistent with clinical practice guidelines [9]. (See "Overview of screening and diagnosis of heart disease in patients on dialysis".)
Based upon this initial evaluation, our subsequent approach is as follows:
●Patients who are asymptomatic and have no ECG or echocardiogram abnormalities on initial testing generally do not require further screening for CAD.
●Patients who are symptomatic should be evaluated for CAD as described elsewhere in this topic. (See 'New or worsening symptoms of CAD' below.)
●Patients who are asymptomatic but whose screening ECG or echocardiogram shows abnormalities suggestive of CAD (ie, new Q waves, reduced left ventricular ejection fraction (LVEF) of <40 percent, or focal wall motion abnormalities) require further evaluation for CAD. For most patients, we prefer noninvasive imaging with a pharmacologic stress rather than coronary angiography or an exercise stress test as the initial diagnostic test. We typically prefer dobutamine stress echocardiography (DSE), which has a slightly higher diagnostic accuracy than myocardial perfusion scintigraphy (MPS) in patients with ESKD. However, some cardiologists proceed directly to coronary angiography without prior noninvasive testing in patients who are at medium or high risk for CAD (eg, patients who smoke, patients with diabetes) and in whom preservation of residual kidney function is not a major concern.
Patients who have abnormal noninvasive imaging for CAD are then evaluated with coronary angiography on a case-by-case basis depending upon the severity of ischemia or infarction identified by stress testing. By avoiding angiography in selected patients, this approach may help preserve residual kidney function in patients who are just starting dialysis. Patients who have a normal noninvasive test for CAD require no further testing unless they develop symptoms concerning for CAD. (See 'New or worsening symptoms of CAD' below.)
Evidence for the diagnostic accuracy of noninvasive stress testing in asymptomatic patients on dialysis is limited and largely extrapolated from studies that included kidney transplant candidates or a heterogeneous group of patients with and without symptoms of CAD. A Cochrane meta-analysis of randomized trials and observational studies comparing the diagnostic accuracy of noninvasive screening tests in potential kidney transplant candidates reported a pooled sensitivity and specificity of 0.79 and 0.89, respectively, for DSE and 0.74 and 0.70, respectively, for MPS [10,11]. However, this difference was no longer statistically significant when the analysis was limited to studies that defined CAD with a reference threshold of ≥70 percent stenosis (figure 1).
Other tests that are used to screen for CAD in the general population, such as electron beam computed tomography (EBCT) and noninvasive coronary computed tomographic angiography (CCTA), are less well studied in the ESKD population:
●EBCT has a sensitivity of 0.64 and specificity of 0.65, which are too low for the high-risk ESKD population [10] (figure 2).
●CCTA requires peripheral intravenous (IV) access and a moderate volume of IV contrast and may be nondiagnostic in the presence of coronary calcium, which is common in patients with ESKD. We agree with the Kidney Disease Outcomes Quality Initiative guidelines, which state that further study is required prior to recommending the use of CCTA to screen for CAD in patients on dialysis [12]. In one study of kidney transplant candidates who underwent CCTA and coronary angiography, CCTA had a sensitivity of 93 percent and a specificity of 63 percent for a coronary artery stenosis ≥50 percent [13].
●Exercise ECG testing in this population is typically limited by the inability of patients to achieve a target heart rate. Studies of the accuracy of exercise ECG have small sample size; the reported sensitivity is 36 percent and specificity is 91 percent [10].
Evaluation of symptomatic patients
Suspected acute coronary syndrome — The approach to the patient on dialysis suspected of having an acute coronary syndrome (ACS) is generally the same as that for patients without kidney disease. It is based upon the clinical presentation, ECG, and relevant laboratory tests, including a time-appropriate rise and fall in cardiac biomarkers. A detailed discussion of the diagnosis and treatment of acute myocardial infarction (AMI) in patients without kidney disease is presented elsewhere. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department" and "Diagnosis of acute myocardial infarction" and "Cardiac troponins in patients with kidney disease".)
New or worsening symptoms of CAD — All patients on dialysis who develop new or worsening symptoms of coronary artery disease (CAD) should be evaluated for CAD [14,15] (see 'Clinical manifestations' above). This diagnostic evaluation should be performed in collaboration with a cardiologist, whose role is to assist with the selection and interpretation of tests and to formulate a plan for antianginal therapy.
Choice of initial testing — For patients on dialysis who have symptoms suspicious for CAD, our approach to the choice of initial diagnostic testing is as follows (algorithm 1):
●For most patients, we obtain noninvasive stress testing with a dobutamine stress echocardiogram (DSE). While there are few high-quality studies to support this approach in this population, our rationale for initial testing with a DSE is based upon our experience and the following general principles:
•Stress imaging can diagnose or exclude the presence of obstructive CAD in patients with chronic kidney disease (CKD) without the need for an invasive procedure or exposure to iodinated contrast. Avoiding the risk of contrast-induced nephropathy may be particularly important for patients in whom preservation of residual kidney function is a goal of care. (See "Patient survival and maintenance dialysis", section on 'Residual kidney function'.)
•Stress imaging can be used to identify areas of myocardium that may correspond to stenotic vessels identified by coronary angiography. Thus, stress imaging can inform the approach to percutaneous coronary intervention at the time of coronary angiography.
•Pharmacologic stress with dobutamine is more likely to achieve the myocardial workload required for a diagnostic study than an exercise stress [10].
•DSE may have higher diagnostic accuracy than myocardial perfusion imaging [10]. In addition, echocardiography may identify other cardiac abnormalities (eg, pericardial effusion, valve disease) that other methods cannot identify. A discussion of the diagnostic accuracy of DSE and other noninvasive tests is presented elsewhere in this topic. (See 'Patients who are not transplant candidates' above.)
●If DSE cannot be performed or is not available, we typically perform MPS. If MPS cannot be performed and preservation of residual kidney function is not a concern, CCTA or invasive coronary angiography are alternative options. Exercise ECG testing is only appropriate when other tests are not available; it has a low sensitivity and specificity in patients with CKD [10]. (See "Clinical use of coronary computed tomographic angiography" and "Clinical use of coronary computed tomographic angiography", section on 'As an alternative to functional stress testing'.)
Evidence for the diagnostic accuracy of these tests is presented elsewhere in this topic. (See 'Patients who are not transplant candidates' above.)
Coronary angiography for selected patients — Coronary angiography is the gold standard for the diagnosis of CAD in patients with or without advanced kidney disease. In symptomatic patients who have undergone initial noninvasive testing, the need for coronary angiography is based upon the severity of the patient's symptoms and the findings from noninvasive testing (algorithm 1) (see 'Choice of initial testing' above). As previously mentioned, clinical decisions should be made in close collaboration with a cardiologist.
●For patients who have persistent moderate to severe symptoms, moderate to severe ischemia on stress testing (eg, suspicious for left anterior descending [LAD] or multivessel disease) or evidence of high-risk coronary anatomy on CCTA (eg, LAD, left main, or multivessel CAD), or an LVEF of <40 percent, we refer for coronary angiography. The goal of coronary angiography in these patients is to confirm the extent of CAD and offer the possibility of revascularization to relieve symptoms. If preservation of residual kidney function is a goal, we typically use methods to prevent contrast-induced nephropathy in preparation for coronary angiography. (See "Prevention of contrast-associated acute kidney injury related to angiography".)
●For patients who have mild symptoms and either mild ischemia on stress testing or CAD without high-risk coronary anatomy on CCTA, medical management without angiography may be appropriate. If the patient's symptoms cannot be controlled with medical therapy alone, we refer for coronary angiography. This approach is similar to that for patients without kidney disease who have mild ischemia. (See "Chronic coronary syndrome: Indications for revascularization", section on 'Uncertain efficacy of revascularization'.)
●For patients who have mild symptoms and either a nondiagnostic or negative stress test, we refer for coronary angiography rather than obtain a different type of stress study. This approach is based upon the relatively high pretest probability of CAD in patients on dialysis and the need to establish the presence and extent of CAD. In our experience, additional noninvasive studies lead to delayed diagnosis.
The benefit of early coronary angiography versus optimal medical therapy was examined in the ISCHEMIA-CKD trial, which randomly assigned 777 patients with advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73 m2 or on dialysis) who had moderate to severe ischemia on a stress imaging study to an invasive strategy (coronary angiography and, if appropriate, coronary revascularization plus optimal medical therapy) or a conservative strategy (optimal medical therapy alone) [16]. At a median of 2.2 years, rates of the primary composite outcome of death or nonfatal MI were similar between the two groups (36.4 versus 36.7 percent) for the entire study cohort and for the subset of patients on dialysis. There was also no significant benefit to angina-related health status with the invasive strategy [17]. A posthoc analysis of a subset of 194 patients waitlisted for kidney transplant (25 percent of the total trial participants) yielded similar findings [18].
While these results do not support routine angiography and revascularization in patients with CKD and a positive stress test, we feel that there is still a role for angiography in patients who have high-risk features as described above. In addition, several features and findings from the trial should be considered when interpreting the results:
●The initial stress tests were not obtained to diagnose symptoms in many patients, which likely diminishes the effect of the mandatory angiography specified by the trial protocol.
●Approximately 25 percent of patients with a positive stress test had no CAD at angiography, which suggests a relatively high rate of false positive stress tests. Notably, the severity of ischemia on stress testing was determined at individual clinical sites rather than at a central lab.
●Fifteen percent of patients in the early intervention group did not have coronary angiography within three years of enrollment, while 31 percent of patients assigned to the conservative strategy underwent coronary angiography within three years. The reasons for these crossovers were neither protocol driven nor due to a clinical event.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)
SUMMARY AND RECOMMENDATIONS
●Clinical manifestations – Coronary artery disease (CAD) is common among patients with end-stage kidney disease (ESKD).
•Stable angina – Patients may present with exercise-induced chest discomfort that is similar to that in patients with normal kidney function. However, patients on dialysis often have comorbidities that limit their ability to exercise, which may delay their presentation or mask the presence of obstructive CAD. They may also present with exertional dyspnea, intradialytic or interdialytic hypotension, sudden cardiac arrest or death, and arrhythmias. Silent myocardial ischemia is also common. (See 'Stable angina' above.)
•Acute coronary syndrome (ACS) – Patients with ESKD who have an ACS (acute myocardial infarction [AMI] or unstable angina) generally present with the same symptoms as patients without ESKD. However, compared with the general population, patients with ESKD are more likely to have only atypical symptoms, which may lead to underdiagnosis. (See 'Acute coronary syndrome' above.)
●Evaluation at dialysis initiation – We generally evaluate all patients for CAD and other cardiovascular conditions when they start dialysis:
•Among patients who are potential kidney transplant recipients, the cardiac evaluation is often initiated by the transplant center as part of the pretransplant evaluation, as discussed elsewhere. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient", section on 'Cardiovascular disease'.)
•Patients who are not kidney transplant candidates should undergo a history and physical, electrocardiogram (ECG), and a transthoracic echocardiogram once the patient is at dry weight. Patients who are asymptomatic but whose screening ECG or echocardiogram shows abnormalities suggestive of CAD (ie, new Q waves, reduced left ventricular ejection fraction (LVEF) of <40 percent, or focal wall motion abnormalities) require further evaluation for CAD. For most patients, we obtain noninvasive stress imaging with dobutamine stress echocardiography (DSE). Patients with abnormal stress imaging are then evaluated with coronary angiography on a case-by-case basis depending upon the severity of ischemia or infarction identified by stress testing. (See 'Patients who are not transplant candidates' above.)
●Evaluation of symptomatic patients
•Suspected ACS – The approach to the patient on dialysis suspected of having an ACS is generally the same as that for patients without kidney disease, as discussed in detail elsewhere. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
•New or worsening symptoms of CAD – For most patients on dialysis who have new or worsening symptoms suspicious for CAD, we obtain noninvasive stress testing with a DSE (algorithm 1). If a DSE cannot be performed or is not available, we typically perform MPS. If MPS cannot be performed and preservation of residual kidney function is not a concern, coronary computed tomographic angiography (CCTA) or invasive coronary angiography are alternative options. Exercise ECG testing is only appropriate when other tests are not available. (See 'Choice of initial testing' above.)
In symptomatic patients who have undergone initial noninvasive testing, the need for coronary angiography is based upon the severity of the patient's symptoms and the findings from noninvasive testing (see 'Coronary angiography for selected patients' above):
-For patients who have persistent moderate to severe symptoms, moderate to severe ischemia on stress testing or evidence of high-risk coronary anatomy on CCTA, or an LVFH of <40 percent, we refer for coronary angiography.
-For patients who have mild symptoms and either mild ischemia on stress testing or CAD without high-risk coronary anatomy on CCTA, medical management without angiography may be appropriate. If the patient's symptoms cannot be controlled with medical therapy alone, we refer for coronary angiography.
-For patients who have mild symptoms and either a nondiagnostic or negative stress test, we refer for coronary angiography rather than obtain a different type of stress study. (See 'Coronary angiography for selected patients' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges William L Henrich, MD, MACP, who contributed to earlier versions of this topic review.
