Management of Ischemic Heart Disease, Heart Failure, and Pericarditis in Patients Undergoing Long-Term Dialysis

Introduction

Cardiovascular disease is exceedingly common in patients with kidney failure on maintenance dialysis and is the leading cause of death in this patient population. The rate of cardiovascular death in patients with kidney failure is substantially higher than that of the general population at all ages, but the disparity is particularly prominent within younger age groups. Cardiovascular disease is also a major contributor to the total morbidity of patients undergoing dialysis.

This chapter discusses the diagnosis and management of ischemic heart disease, heart failure, and pericarditis in patients with kidney failure undergoing dialysis. Recommendations based on evidence taken directly from the kidney failure population are discussed where possible. However, because the management of cardiovascular disease in patients with kidney failure has been relatively understudied and evidence from randomized clinical trials is limited, data from observational studies are included where necessary.

Ischemic Heart Disease

The prevalence of ischemic heart disease in patients on dialysis is estimated at 40%–50%. Also known as coronary artery disease, ischemic heart disease in patients on dialysis tends to be diffuse and multivessel and to have a high degree of calcification. The rate of acute myocardial infarction in patients on dialysis far exceeds the rate in the general population. The rate of acute myocardial infection in patients on dialysis was 73.1 per 1000 patient-years in 2011, compared to the rate in the general population of approximately 2 per 1000 patient-years. The high rates of ischemic heart disease in patients with kidney failure stem from the high prevalence of traditional and nontraditional risk factors ( Table 46.1 ).

Table 46.1

Risk Factors for Cardiac Disease in Dialysis Patients

Traditional	Nontraditional
Hypertension	Anemia
Dyslipidemia	Chronic inflammation
Diabetes	Oxidative stress
Smoking	Disordered bone and mineral metabolism
Sedentary lifestyle	Accelerated vascular calcification
Advanced age	Fluid overload
Left ventricular hypertrophy	Arteriovenous fistulae

Clinical Presentation

Patients with kidney failure can have typical presentations of stable ischemic heart disease (e.g., dyspnea or chest pain with exertion) or acute myocardial infarction (e.g., substernal chest pain and diaphoresis). However, they often present atypically with symptoms, such as epigastric pain, fatigue, or nausea, perhaps due in part to the high prevalence of concomitant diabetes mellitus or uremia-related neuropathies. Only 44% of dialysis patients complain of chest pain during acute myocardial infarction (compared with 68% of non-dialysis patients). Moreover, symptoms and signs of acute coronary syndrome can be mistakenly attributed to complications of dialysis or kidney failure, leading to its underrecognition. Therefore, a high index of suspicion is needed for an accurate diagnosis of ischemic heart disease and acute coronary syndromes.

Diagnosis

The hemodialysis procedure is a kind of “stress test” that can precipitate symptoms of ischemic heart disease. A variety of factors contribute to this phenomenon, including tachycardia, dialysis-related hypoxemia, and intradialytic hypotension. The emergence of symptoms of ischemic heart disease on dialysis is an indication for further evaluation.

One-third to over one-half of patients with kidney failure have significant ischemic heart disease (> 50% stenosis) by coronary angiography, despite having no symptoms. However, routine screening for ischemic heart disease in asymptomatic patients with kidney failure is generally not indicated because randomized trials (albeit in populations without kidney failure) have shown that coronary revascularization in asymptomatic patients does not reduce cardiovascular morbidity or mortality, except possibly in patients with unprotected left main disease. Moreover, kidney failure is considered an ischemic heart disease risk equivalent with indications for maximal medical management and, therefore, not reliant on the results of screening tests.

One notable exception is potential kidney transplant recipients, who often undergo noninvasive stress testing and subsequent revascularization. To date, there has been only one randomized trial of coronary revascularization in asymptomatic patients with kidney failure awaiting kidney transplantation, all of whom also had diabetes mellitus. Manske et al. randomized 26 patients with documented significant coronary lesions by angiography to medical management or revascularization; 10 of 13 patients in the medically treated group and 2 of 13 patients in the revascularization group experienced the composite cardiac endpoint of unstable angina, acute myocardial infarction, or cardiac death during a median of 8 months of follow-up ( P = 0.002). However, this study was conducted more than 25 years ago, and the medical management group received only aspirin and calcium channel blockers, making it difficult to apply these results to contemporary clinical practice. Despite the weakness of the available evidence, most clinical practice guidelines support screening asymptomatic patients awaiting kidney transplant who have additional risk factors, such as diabetes mellitus, known history of ischemic heart disease, older age, or longer dialysis vintage for ischemic heart disease with noninvasive testing followed by revascularization, if warranted. However, there is little consensus on the optimal timing for repeated screening tests, with some guidelines favoring annual testing, some recommending testing every 24 months, and others giving no specific interval for repeated testing. Some answers may be provided by the ongoing CARSK (Canadian Australasian Randomized Trial of Screening Kidney Transplant Candidates for Coronary Artery Disease) trial. After the CADScreening pilot trial demonstrated feasibility in 144 patients, the CARSK trial will randomize 3306 asymptomatic patients awaiting kidney transplant to noninvasive stress testing every 1–2 years or not (NCT03674307). Trial completion is projected for 2023.

Cardiac Troponins

Up to 70% of asymptomatic patients with kidney failure have chronic elevations of cardiac troponins (troponin T and troponin I). These chronic elevations do not seem to be due solely to decreased kidney clearance, as troponins are large molecules that would not be filtered intact by the kidney. Moreover, the elimination of troponins after an acute myocardial infarction is similar in patients with and without kidney failure. Instead, the troponin elevations seen in asymptomatic patients with kidney failure may reflect subacute ischemia, underlying cardiac structural disease, or recurrent myocardial stunning. Troponin elevations in patients on dialysis are associated with a two to fourfold higher risk of all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events, and the U.S. Food and Drug Administration approved troponin T testing in patients with kidney failure for purposes of cardiac risk stratification over a decade ago. However, how best to use troponin values for clinical risk stratification and prognostication in stable patients with kidney failure remains unclear.

For diagnosis of acute myocardial infarction, cardiac troponins are the standard biomarkers, but their interpretation in patients with kidney failure is complicated by the high prevalence of chronically elevated values. A majority of patients with kidney failure have high-sensitivity troponin values greater than the 99th percentile of a normal reference population at baseline. The National Academy of Clinical Biochemistry recommends using a change of ≥ 20% in troponin values 6–9 hours after presentation with ≥ 1 value exceeding the 99th percentile to define acute myocardial infarction in patients with kidney failure. However, a systematic review found little evidence to support this recommendation and could not identify clear cut-points that would maximize sensitivity and specificity and thus the positive and negative predictive values for cardiac troponins to diagnose acute myocardial infarction in kidney failure. Thus, troponins alone cannot be used to diagnose an acute myocardial infarction but rather should be placed in the broader context of presenting symptoms, electrocardiographic (ECG) findings, and other clinical factors.

Noninvasive Stress Testing

Exercise ECG has been the traditional method of noninvasive diagnosis of ischemic heart disease. The sensitivity of this test is only 50%–60% for single-vessel disease but is greater than 85% for triple-vessel disease in the general population. These figures are based on the assumption that the patient reaches an adequate exercise level (i.e., 85% of the age-adjusted predicted maximal heart rate). A large proportion of patients with kidney failure are unable to achieve this target because of poor exercise tolerance or the use of beta-blockers, and many have abnormal baseline ECGs. Therefore, pharmacologic agents with imaging are often used for noninvasive testing in these patients.

The sensitivity of radionuclide testing in kidney failure patients ranges from 29% to 92%, with a specificity of 68%–88%. Dobutamine stress echocardiography may be the method of choice, as it avoids radiation exposure, has comparable sensitivity, and specificity in patients with kidney failure (35%–89% and 71%–94%, respectively). Patients with kidney failure have a much higher prevalence of coronary artery calcification compared to age-matched controls, which can be measured using electron beam computed tomography (EBCT). Studies of EBCT in patients with kidney failure have shown that higher coronary artery calcification scores are associated with higher risks of death and cardiovascular events. However, patients with kidney failure often have medial, rather than intimal, calcification, which may not have a causative role in ischemic heart disease. EBCT and other tests such as coronary CT angiography, coronary flow reserve assessment using positron emission tomography, and hybrid imaging approaches require further study in patients with kidney failure before they can be routinely used to screen for ischemic heart disease.

Coronary Angiography

Coronary angiography remains the gold standard for the diagnosis of ischemic heart disease. The major side effects associated with this procedure in dialysis patients are the potential precipitation of pulmonary edema due to volume overload and possible nephrotoxicity in patients with residual kidney function. The risk of both of these complications is minimized with the use of smaller volumes of contrast. In general, however, coronary angiography should be limited to those patients who have persistent symptoms of myocardial ischemia despite maximal medical therapy and in whom revascularization would be considered reasonable.

Medical Management

The treatment for acute coronary syndrome in patients with kidney failure is similar to that of the general population and includes timely administration of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs), and nitroglycerin, provided that there are no contraindications. Antithrombotic agents are often administered, particularly prior to percutaneous coronary interventions (PCIs), but special care to avoid renally cleared agents is required to reduce bleeding risks. A 2009 study showed that 22% of patients on dialysis undergoing PCI received a contraindicated antithrombotic agent (e.g., enoxaparin or eptifibatide), which was associated with a significantly higher risk of major in-hospital bleeding. Alternative antithrombotic agents are unfractionated heparin, abciximab, or bivalirudin.

For stable ischemic heart disease, the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines, published in 2005, recommend treating patients on dialysis in the same way as for the general population: aspirin, beta-blockers, ACE inhibitors or ARBs, and statins. However, the evidence on which these guidelines are based is weak (level C), as many studies are observational rather than randomized trials, and not all studies focused exclusively on secondary prevention. Consequently, whether to use these agents in patients with established stable ischemic heart disease requires individual risk-benefit assessments by the physician and the patient.

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