INTRODUCTION — Cardiovascular disease (CVD) accounts for almost half the deaths of patients with end-stage kidney disease (ESKD) [1-4]. Of these, approximately 20 percent can be attributed to coronary artery disease (CAD), also referred to as coronary heart disease (CHD). Patients with varying 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 CHD. (See "Patient survival and maintenance dialysis" and "Chronic kidney disease and coronary heart disease".)

This topic reviews screening, clinical manifestations, and diagnosis of stable CHD and acute coronary syndrome in ESKD patients. CHD in the general population is discussed elsewhere. (See "Coronary heart disease and myocardial infarction in young men and women" and "Screening for coronary heart disease".)

Other aspects of CHD in dialysis patients 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)".)

STABLE CORONARY HEART DISEASE — Many of the issues concerning the presentation and evaluation of the stable ESKD patient suspected of having CHD are the same in those in the general population. (See "Screening for coronary heart disease" and "Coronary heart disease and myocardial infarction in young men and women", section on 'Clinical presentation' and "Clinical features and diagnosis of coronary heart disease in women", section on 'Clinical presentation'.)

The following sections will specifically address issues unique to dialysis patients. However, as noted in the following sections, very few randomized trials have been performed in these individuals.

Clinical manifestations — Angina may be provoked by hemodialysis. This is because fluid shifts and episodes of hypotension during dialysis commonly precipitate symptomatic ischemia.

Dialysis patients often have significant exercise limitations due to comorbidities such as peripheral arterial disease and poor conditioning, which prevent typical exercise-induced chest discomfort when they are off dialysis. However, some dialysis patients with angina have a fairly typical history of exercise-induced chest discomfort that is similar to those with normal kidney function.

Patients may also present with exertional dyspnea, intradialytic or interdialytic hypotension, sudden cardiac arrest or death, and arrhythmias [5]. (See "Angina pectoris: Chest pain caused by fixed epicardial coronary artery obstruction" and "Acute complications during hemodialysis".)

Silent myocardial ischemia is also common in dialysis patients [6]. (See "Silent myocardial ischemia: Epidemiology, diagnosis, treatment, and prognosis".)

Screening and evaluation — We generally screen all patients for CHD and other cardiovascular conditions when they start dialysis and whenever there is a change in clinical symptoms or marked change in hemodynamic stability during hemodialysis. The specific evaluation depends on patient comorbidities. Among transplant candidates, the cardiac evaluation is often initiated by the transplant center. The evaluation of such patients is discussed elsewhere. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)

The evaluation of patients who are not transplant candidates is discussed in this topic review. The evaluation of transplant candidates is discussed elsewhere. (See "Kidney transplantation in adults: Evaluation of the potential kidney transplant recipient".)

Screening at dialysis initiation — All new dialysis patients undergo a complete history and physical examination and baseline electrocardiography (ECG) at the initiation of maintenance dialysis, although it is not clear whether screening with ECG eventually leads to improved outcomes.

The ECG provides a baseline for comparison in the event of future evaluations (such as among patients who develop chest pain during hemodialysis). In addition, the ECG may reveal undiagnosed atrial fibrillation, which is common among patients with advanced chronic kidney disease (CKD). (See "Epidemiology of and risk factors for atrial fibrillation", section on 'Chronic kidney disease' and "Atrial fibrillation in adults: Use of oral anticoagulants".)

Among dialysis patients, ECG abnormalities, including left ventricular hypertrophy and the absence of sinus rhythm, have been shown to be associated with increased risk of cardiovascular events and death [7].

We obtain a transthoracic echocardiogram within one to three months of initiation of maintenance dialysis. We do not obtain screening echocardiogram at the very start of dialysis, because patients are often mildly to moderately volume overloaded. Volume-dependent changes that are observed on echocardiograms that are obtained at the beginning of dialysis (such as elevated left ventricular end-diastolic pressure, increased estimated pulmonary artery systolic pressure, or reduced left ventricular ejection fraction) may become normal once dry weight has been attained through more rigorous fluid management on dialysis.

Patients who have a persistent reduction in ejection fraction of <40 percent at one to three months after dialysis initiation and do not have a previously established diagnosis of CHD generally require further evaluation for CHD including noninvasive stress imaging and/or coronary angiography if patients are considered candidates for revascularization. CHD is a common cause of reduced ejection fraction [8]. This approach is consistent with recommendations from the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline for the management of heart failure [9] and with the Kidney Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines [10].

The approach to the evaluation of such patients may vary among cardiologists. For many patients, particularly patients who are considered less likely to have CHD (such as younger patients without diabetes), the authors of this topic review perform stress testing with dobutamine echocardiography first. Patients who have abnormal stress imaging are evaluated with angiography. By avoiding angiography in selected patients, this approach may help to preserve residual kidney function in patients who are just starting dialysis. Better residual kidney function has been associated with increased survival among dialysis patients. (See "Urine output and residual kidney function in kidney failure", section on 'Clinical importance of residual kidney function'.)

However, based on practice guidelines in the general population, some cardiologists recommend proceeding directly to coronary angiography without stress testing, particularly those ESKD patients at medium or high risk for CHD (eg, diabetic ESKD).

Patients with reduced ejection fraction also require additional medical therapy.

Evaluation of symptomatic patients — All dialysis patients who develop symptoms and/or signs of CHD should be evaluated for CHD and for clinically unsuspected valvular disease (such as aortic stenosis).

As noted above, signs and symptoms of CHD include classic angina symptoms that develop during exertion or hemodialysis, recurrent hypotension (on or off dialysis), heart failure that is unresponsive to changes in dry weight, and intradialytic hypotension that prevents attaining dry weight. Patients who have known CHD and chronic stable symptoms should be evaluated for CHD if any symptoms change [10,11].

The evaluation depends on the clinical stability of the patient. Patients who are not stable (ie, have persistent symptoms off dialysis and at rest and have persistent hemodynamic instability off dialysis) should be evaluated for acute coronary syndrome (ie, unstable angina or acute myocardial infarction [AMI]). (See 'Acute coronary syndrome' below.)

The optimal strategy for evaluating and treating ESKD patients with stable symptomatic CHD is not known. All such patients should undergo a history and physical examination and an ECG. Patients who have an ECG that is normal or unchanged from baseline and are clinically stable undergo noninvasive testing with stress imaging. (See 'Noninvasive testing' below.)

Depending upon the severity of ischemia, dialysis patients who have positive stress tests and are candidates for coronary revascularization should have coronary angiography. Coronary angiography is the gold standard for the diagnosis of coronary CHD in patients with or without advanced kidney disease. (See 'Coronary angiography' below.)

However, patients who have only mild ischemia suggested by noninvasive testing (in centers that have confidence in the accuracy for detection of CHD) and who have stable angina during exertion or during dialysis may be treated medically without angiography.

Patients with moderate or severe ischemia on stress testing may undergo angiography, provided that they are candidates for revascularization. However, the benefit of revascularization versus medical therapy in such patients is not clear. This issue is being addressed in the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease Trial (ISCHEMIA-CKD) [12]. This is a National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI)-sponsored, multicenter, randomized trial designed to determine whether an invasive strategy (optimal medical therapy plus coronary angiography plus optimal revascularization) reduces the incidence of death or nonfatal myocardial infarction (MI) compared with a conservative strategy (optimal medical therapy only) in patients with moderate or severe ischemia on stress testing, stable CHD, and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m², including those on maintenance dialysis.

Noninvasive testing — Noninvasive testing is not as accurate in the ESKD population as in the general population (figure 1) [10,13]. This is because commonly used methods in the general population involve exercise testing, which is often not able to be used accurately in ESKD patients, due to limitations in exercise capacity [10]. In addition, baseline abnormalities on the ECG and thallium scintigraphy induced by the abnormal metabolic milieu in advanced kidney disease may decrease the accuracy of different tests [14]. The accuracy of the different noninvasive imaging tests tends to be center specific and dependent upon the expertise of the examiner [10,13]. As a result, there is significant institutional variation in the approach to noninvasive evaluation of CHD in dialysis patients.

Commonly used noninvasive tests in the general population include exercise ECG, dobutamine stress echocardiography, adenosine- or dipyridamole-induced echocardiography, and stress by adenosine or dipyridamole plus nuclear scintigraphy. (See "Stress testing for the diagnosis of obstructive coronary heart disease".)

In general, among dialysis patients, we prefer dobutamine echocardiography rather than other noninvasive tests. Among dialysis patients, dobutamine-induced stress echocardiography appears to be more sensitive than other noninvasive tests, including vasodilator-induced stress nuclear scintigraphy. This is largely derived from studies in diabetic kidney transplant candidates (see "Kidney transplantation in adults: Kidney transplantation in diabetic kidney disease"):

●In one study of 125 candidates, all patients underwent coronary angiography, dobutamine stress echocardiography, and resting and exercise ECG [15]. Independent predictors of severe CHD (defined as luminal stenosis >70 percent by visual estimation in at least one epicardial artery) were a positive stress echocardiography result (odds ratio [OR] 23, 95% CI 6-88) or an abnormal resting ECG (OR 7, 95% CI 2-34). Overall, the sensitivity and specificity of dobutamine stress echocardiography were approximately 75 percent.

●A Cochrane meta-analysis reported pooled sensitivity and specificity estimates of 0.79 and 0.89 for dobutamine stress echocardiography and 0.74 and 0.70 for stress myocardial perfusion imaging [16]. The figure (figure 2) shows the receiver-operating characteristic (ROC) curves for the diagnosis of CHD in kidney transplant candidates by dobutamine stress echocardiography and myocardial perfusion imaging [17].

Dobutamine stress echocardiography is associated with arrhythmias (see "Overview of stress echocardiography", section on 'Safety of dobutamine administration'). The risk of dobutamine-associated transient atrial fibrillation may be higher among dialysis patients compared with the general population [18]. Among dialysis patients, the incidence of transient atrial fibrillation is estimated to be 2 to 3 percent, based on unpublished data from the Echocardiography Laboratory computerized stress echocardiography database at Hennepin County Medical Center, Minneapolis, MN, versus 0.5 percent in the general nonrenal population.

The increased incidence of atrial fibrillation associated with dobutamine stress echocardiography likely reflects the overall increased incidence and prevalence of atrial fibrillation in dialysis patients. (See "Epidemiology of and risk factors for atrial fibrillation", section on 'Chronic kidney disease' and "Atrial fibrillation in adults: Use of oral anticoagulants".)

Other tests that are used 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. Although generally not recommended for clinical decision making in the past, limited data [19] suggest that, in expert centers, CCTA might provide superior diagnostic accuracy to other noninvasive imaging techniques. (See "Coronary artery calcium scoring: Image acquisition and clinical utilization".)

This is consistent with the KDOQI guidelines, which state that further study is required prior to recommending the use of these modalities to screen for CHD in dialysis patients [20]. Drawbacks include the following:

●Although widely used in the general population for diagnostic evaluation of CHD, these tests are difficult to perform and interpret in ESKD patients, particularly those who have been on dialysis for an extended period of time or are older. This is because older patients or those with greater dialysis vintage often have extensive medial vascular calcification, which confounds the interpretation of the test. Medial vascular calcification may not be associated with luminal atherosclerotic coronary disease. (See "Vascular calcification in chronic kidney disease".)

●CCTA requires a minimum intravenous injection rate of iodinated radiocontrast media that may not be attainable in patients with poor peripheral venous access. If CCTA is being contemplated in a dialysis patient, the issue of obtaining adequate venous access should be anticipated and resolved. An arteriovenous fistula, when available, may be used for injection of the intravenous radiocontrast agent when attempts to secure a venous access have failed.

●Dialysis patients, particularly those who are just starting dialysis or are of relatively early vintage (ie, <2 years) may have significant residual kidney function. The loss of residual kidney function resulting from the administration of iodinated radiocontrast media could be deleterious and should be taken into consideration when deciding on CCTA. (See "Urine output and residual kidney function in kidney failure", section on 'Clinical importance of residual kidney function'.)

Definitive data on the risks of contrast-induced nephropathy and its consequence in the dialysis patient are not available at present.

Coronary angiography — Coronary angiography is the gold standard for the diagnosis of coronary disease in patients with or without advanced kidney disease. We refer for angiography patients who are candidates for coronary revascularization and have either positive stress tests or acute coronary syndromes (including unstable angina) or angina inadequately controlled by optimal medical therapy.

Among patients who have significant residual kidney function, we believe it is prudent to employ measures to prevent contrast-induced nephropathy in preparation for coronary angiography. This is because residual kidney function is associated with improved survival. (See "Patient survival and maintenance dialysis", section on 'Residual kidney function'.)

Methods to preserve residual kidney function among dialysis patients are the same as those in the nondialysis CKD population, with the exception of the volume of fluid administered. Among dialysis patients, fluids should be administered with caution, tailored to the fluid status of the patient, their residual urine output, and the temporal relationship of fluids to their next dialysis session. (See "Prevention of contrast-associated acute kidney injury related to angiography".)

The benefits of fluid administration for the preservation of residual kidney function have not been definitely demonstrated in dialysis patients.

ACUTE CORONARY SYNDROME — Chronic kidney disease (CKD) patients are more likely to present with acute myocardial infarction (AMI) than with stable angina as the initial manifestation of CHD [21]. As in the general population, the evaluation and diagnosis of dialysis patients with an acute coronary syndrome is based upon the constellation of symptoms and signs, findings on electrocardiogram (ECG), and levels of cardiac biomarkers. (See "Acute coronary syndrome: Terminology and classification".)

Clinical manifestations — ESKD patients with acute coronary syndrome generally present with the same symptoms as non-ESKD patients, including chest pain associated with dyspnea, nausea, vomiting, and diaphoresis. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Clinical presentation'.)

However, compared with the general population, ESKD patients are more likely to have only atypical symptoms, such as isolated dyspnea, weakness, syncope, palpitations, or cardiac arrest [22-26] (see "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Atypical symptoms'). In a retrospective, cohort-matched study, dialysis patients were compared with nondialysis patients using data from the United States Renal Data System (USRDS) and National Registry of Myocardial Infarction databases [23]. Compared with nondialysis patients with an AMI, dialysis patients with an AMI were significantly less likely to present with chest pain (68 versus 44 percent, respectively) or have ST elevation (36 versus 19 percent, respectively). ESKD patients were also less likely to have an initial diagnosis of acute coronary syndrome on admission (55 versus 79 percent in non-ESKD patients).

The increased incidence of atypical presentations may result in under-diagnosis and under-treatment [22,23]. Symptoms are commonly attributed to causes other than myocardial ischemia. As an example, the presence of dyspnea alone due to an AMI in an individual scheduled to undergo a regular chronic hemodialysis procedure may be mistakenly attributed to volume overload.

Evaluation and diagnosis — The approach to the patient suspected of having an acute coronary syndrome is generally the same as in patients without kidney disease. It is based upon the clinical presentation, ECG, and relevant laboratory tests, including a time-appropriate (with respect to the episode of suspected acute coronary syndrome) rise and fall in cardiac biomarkers. A detailed discussion of the diagnosis of AMI in patients without kidney disease is presented elsewhere. (See "Diagnosis of acute myocardial infarction".)

Among ESKD patients, ECG manifestations of acute coronary syndrome are similar to the general population (see "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department", section on 'Electrocardiogram assessment'). 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 [27].

In addition, compared with the general population, ESKD patients with AMI are less likely to have ST elevation [23,24,26]. In the study cited above, only 19 percent of ESKD patients with AMI presented with ST elevation compared with 36 percent in nondialysis patients with AMI [23].

The serologic diagnosis of AMI is more difficult in patients with ESKD because of elevations in cardiac biomarkers that are unrelated to acute coronary syndrome. This is discussed in detail separately. (See "Cardiac troponins in patients with kidney disease".)

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

●Cardiovascular disease (CVD) is common among patients with end-stage kidney disease (ESKD). Angina may be provoked by hemodialysis. Patients may also present with exertional angina or dyspnea, intradialytic or interdialytic hypotension, sudden cardiac arrest or death, and arrhythmias. Silent myocardial ischemia is common. (See 'Introduction' above and 'Clinical manifestations' above.)

●We obtain baseline electrocardiography (ECG) at the initiation of maintenance dialysis and a transthoracic echocardiogram within one to three months of initiation of maintenance dialysis. Patients with a reduced ejection fraction of <40 percent generally require further evaluation including noninvasive stress imaging and often coronary angiography. (See 'Screening at dialysis initiation' above.)

●All dialysis patients who develop symptoms and/or signs of coronary heart disease (CHD) should be evaluated for CHD and for clinically unsuspected valvular disease (such as aortic stenosis). Stable patients are evaluated with an ECG, noninvasive testing with stress imaging, and, depending upon the severity of ischemia and patient candidacy for revascularization, coronary angiography. (See 'Evaluation of symptomatic patients' above.)

●Among dialysis patients, we prefer dobutamine echocardiography rather than other noninvasive tests. Among dialysis patients, dobutamine-induced stress echocardiography appears to be more sensitive than other noninvasive tests. (See "Kidney transplantation in adults: Kidney transplantation in diabetic kidney disease" and 'Noninvasive testing' above.)

●Coronary angiography is the gold standard for the diagnosis of coronary disease in patients with or without advanced kidney disease. We refer for angiography patients who are candidates for coronary revascularization and have either positive stress tests or acute coronary syndromes (including unstable angina) or angina inadequately controlled by optimal medical therapy. (See 'Coronary angiography' above.)

●Dialysis patients with acute coronary syndrome generally present with the same symptoms as non-ESKD patients, including chest pain associated with dyspnea, nausea, vomiting, and diaphoresis. However, dialysis patients are more likely than nondialysis patients to have only atypical symptoms, such as isolated dyspnea, weakness, syncope, palpitations, or cardiac arrest. Atypical presentations may result in under-diagnosis and under-treatment. (See 'Clinical manifestations' above.)

●The approach to the dialysis patient suspected of having an acute coronary syndrome is based upon the clinical presentation, ECG, and relevant laboratory tests, including a time-appropriate rise and fall in cardiac biomarkers. ECG manifestations of acute coronary syndrome are similar to the general population, although baseline abnormalities on the ECG may mask characteristic changes of ischemia and ESKD patients may not have ST elevation. (See 'Evaluation and diagnosis' above.)