Left Ventricular Hypertrophy
LVH may be asymptomatic or patients may present with diastolic dysfunction, which is discussed in further detail in the next section.
On physical examination, hypertension is common. Particular attention should be paid to the pulse pressure as a surrogate measure of arterial stiffness, where “normal values” are <40–60 mm Hg. Precordial palpation may reveal a left ventricular heave and a sustained and diffuse cardiac apical impulse. On auscultation, a fourth heart sound may be heard.
Due to the lack of sensitivity of symptoms and physical examination findings, echocardiography is usually used for diagnosis and clinical follow-up of patients with LVH.
Heart failure may occur as a result of systolic dysfunction, diastolic dysfunction, or both. It may be asymptomatic or patients may present with shortness of breath, orthopnea, paroxysmal nocturnal dyspnea, reduced exercise tolerance, and progressive extracellular fluid volume expansion. In addition, patients with LV dysfunction on hemodialysis often tolerate dialysis treatments poorly and episodes of intradialytic hypotension may occur.
On physical examination, the signs of heart failure include pulmonary vascular congestion such as jugular venous distention and crackles due to pulmonary edema. LVH is the most common cause of diastolic dysfunction in CKD and these patients would be expected to have the cardiac findings discussed under that section. However, findings in patients with predominantly systolic heart failure include cardiomegaly, manifested by an inferiorly and laterally displaced apical pulsation, and the presence of a third heart sound on auscultation.
Due to the insensitivity of the physical examination, echocardiography is usually used for the diagnosis of heart failure. In addition to evaluating left ventricular function and geometry, echocardiography also has the advantage of providing other useful information, such as the presence of valvular heart disease, which may also contribute to left ventricular dysfunction.
The main symptom of cardiac ischemia is angina, which may be accompanied by symptoms of CHF. In CKD, the high proportion of patients with a concomitant diagnosis of diabetes mellitus means that atypical presentations of cardiac ischemia, such as shortness of breath without chest pain, may occur. In addition, patients with CKD may experience episodes of silent cardiac ischemia. For example, asymptomatic ST segment depression has been observed during hemodialysis treatments.
Findings on physical examination of acute cardiac ischemia may be relatively few. Signs of left and/or right heart failure may be observed depending on the size and location of the vascular territory affected. In general, the diagnosis of an acute coronary syndrome (ACS) relies on laboratory findings, including serial cardiac enzyme determinations and an electrocardiogram (ECG).
In the CKD population, a number of factors may interfere with the timely diagnosis of IHD, including diabetes, atypical presentations, and the relative lack of utility of specific tests in dialysis patients. Thus, a high index of suspicion in patients at high CVD risk is imperative.
Peripheral Vascular Disease
PVD, also a result of the atherosclerotic process, is common in CKD. The symptoms and signs depend on the vascular territory affected. Carotid artery disease causes neurologic changes during a transient ischemic attack or stroke. When the arteries supplying the lower extremities are affected, intermittent claudication with exertion may result. However, given the poor tolerance to exercise in the CKD population in general, this symptom probably lacks sensitivity. Chronic ischemia of the legs results in skin changes, hair loss, and muscle atrophy. Other signs include pallor, reduced or absent pulses, and bruits. Without treatment, skin ulceration and gangrene can occur when ischemia becomes critical.
The key to the diagnosis of PVD is serial assessment of peripheral arterial function through clinical examination and laboratory investigations. Reluctance to evaluate PVD in a timely manner may have led to an increase in morbidity and mortality in this particular cohort of patients.
Troponins comprise part of the contractile apparatus of myocytes in both cardiac and skeletal muscle. They consist of three subunits: Troponin C, troponin T, and troponin I. While cardiac and skeletal troponin C are identical, cardiac troponin T (cTnT) and I (cTnI) are encoded by genes different from their skeletal counterparts, and the molecules are also different. The assays currently in use for detection of cTnT and cTnI are specific for troponin released from the heart muscle. They are also highly sensitive to even small amounts of myocardial damage. The degree of troponin elevation in patients presenting with a suspected ACS provides important prognostic information, even in the presence of renal dysfunction. For these reasons, cTnT and cTnI are the preferred markers for the diagnosis of acute cardiac injury.
Interpretation of cardiac troponin concentration in the setting of ESRD is complicated by the fact that the levels, particularly of cTnT, may be elevated in apparently asymptomatic individuals. The reasons for elevations in troponin in the absence of cardiac symptoms and the significance of the levels are still debated, but the finding of an elevated troponin concentration in a patient with ESRD cannot necessarily be dismissed as a false-positive result even if unaccompanied by cardiac symptoms.
What is even less clear is why asymptomatic troponin elevations in ESRD are observed more frequently with cTnT than with cTnI. Proposed explanations for this include differences in release patterns from damaged cardiac myocytes, circulating half-life, and dialyzability, in addition to the particular characteristics of the assays themselves.
Despite these controversies and uncertainties, patients with renal failure suspected of having an ACS should be followed with serial cardiac troponin assessments. A troponin level rising over time suggests an acute injury, especially if accompanied by other cardiac symptoms or ECG changes. A positive but unchanging level may not indicate acute damage, but it has prognostic implications in ESRD patients nonetheless. On the other hand, obtaining serial “normal” or “negative” results has an excellent negative predictive value and is therefore useful for excluding an ACS.
All patients suspected of having an ACS should be evaluated with an ECG. However, the interpretation can be complicated by preexisting abnormalities on the baseline tracing. In the absence of acute cardiac ischemia, ST-T segment morphology can be altered by LVH, electrolyte disturbances, and medications such as digoxin. In a patient presenting with possible cardiac ischemia, obtaining an old ECG for comparison can be extremely helpful. Aside from abnormalities of the baseline study, ischemic changes are expected to have an appearance the same as in individuals without kidney disease.
Exercise Treadmill Testing
In screening for coronary artery disease (CAD), detection of exercise-induced ischemia with exercise treadmill testing is of limited utility in renal failure. Patients are often unable to attain their target heart rate for reasons that include poor exercise tolerance, autonomic neuropathy, and use of medications that impair the chronotropic response to exercise, such as β-blockers and calcium channel blockers. Abnormalities of the resting ECG further compromise the sensitivity and specificity of this test. For these reasons, pharmacologic stress testing is generally preferred in renal failure.
Two-dimensional echocardiography has multiple uses in the renal failure population. It can be used to assess for abnormalities of cardiac structure, such as LVH and valvular heart disease, and also provides a good estimate of systolic and diastolic LV function. Ideally, patients on dialysis should be as close to their estimated dry weight as possible at the time of this study or at least have studies performed at the same time in their dialysis cycle for comparison purposes.
Dobutamine stress echocardiography (DSE) can be used as a noninvasive screening test for ischemic heart disease. Studies in the renal failure population are limited in number and comparisons between studies are difficult because of inconsistencies in methodology. Overall, DSE appears to be a useful, but imperfect, screening test for CAD in CKD.
Nuclear scintigraphy has uses similar to echocardiography in patients with kidney disease: Assessment of ventricular function, screening for CAD, and prediction of future cardiac events.
To screen for myocardial ischemia, a radionuclide is injected and fixed or reversible perfusion defects are detected by comparing cardiac single-photon emission computed tomography (SPECT) images at rest and following stress (exercise or pharmacologic). Dipyridamole is a pharmacologic agent that acts by blocking the cellular reuptake of adenosine, thereby increasing its levels and causing vasodilation. In patients with markedly impaired kidney function, baseline levels of adenosine are increased, thus a reduced vasodilatory response to exogenously administered dipyridamole may occur, thereby potentially producing a false-negative result.
Several studies have evaluated the use of nuclear scintigraphy in patients with renal failure; however, the reported results are variable, likely due to inconsistencies in methodology. Like DSE, nuclear scintigraphy appears to be a moderately useful but suboptimal screening test for CAD in this group of patients.
Both thallium scintigraphy and DSE have prognostic implications in the renal failure population. In a recent meta-analysis of these myocardial perfusion studies for stratifying cardiac risk among patients with ESRD who were candidates for kidney or kidney–pancreas transplantation, compared to patients with negative test results, patients with positive tests had a relative risk of myocardial infarction of 2.73 and of cardiac death of 2.92 following transplantation.
Currently, there is no literature to guide the choice between nuclear scintigraphy and DSE in screening for CAD in CKD, as there are no studies directly comparing the two modalities. Therefore, it is reasonable to consider local expertise, availability, and cost to guide test selection.
Computerized Tomography Scanning
Electron beam computerized tomography (EBCT) and helical CT scanning methods can be used to assess the degree of coronary artery calcification (CAC). In the general population, where calcification occurs in the intima in association with atherosclerotic deposits, CAC scores have been found to correlate with angiographic plaque burden and to predict future cardiac events. However, their utility in CKD populations is less clear.
Vascular calcification of both the intimal and medical layers is common in renal failure. The CAC scores of ESRD patients in particular are often several times greater than those found in the general population. However, CT scanning cannot distinguish between intimal and medial calcification, and there are conflicting reports as to whether there is a correlation between CAC scores and atherosclerotic plaque burden. Furthermore, while data demonstrate an association between higher CAC scores and mortality in ESRD, debate still exists as to the utility of this test in routine clinical care or as an endpoint in clinical trials. Until the appropriate long-term and interventional studies are undertaken, CT scanning is not recommended as a screen for CAD in the CKD population.
Percutaneous Coronary Angiography
While IHD is most commonly a result of atherosclerotic CAD, a substantial proportion of patients with CKD experience cardiac ischemia without significant coronary artery stenosis. It is likely that these patients, particularly those with LVH, have microvascular insufficiency that limits myocardial perfusion and causes ischemia.
The gold standard for diagnosis of CAD is angiography; however, the cost and the potential for morbidity make it impractical as a screening test. In general, it is reserved for patients whose noninvasive screening tests are positive, those who present with an ACS, or those with known CAD who have developed recurrent symptoms despite optimal management.
In predialysis patients, angiography may worsen renal function by causing contrast nephropathy or cholesterol embolization. Invasive examinations should be undertaken only after careful consideration of their necessity, and whether the results will alter patient management. Contrast nephropathy generally produces a transient and reversible decline in renal function and in the modern era, with low osmolality contrast dyes, improved technology, and some evidence of renoprotective effects of specific agents, the risk may be lower than previously described. On the other hand, the decline in renal function caused by cholesterol emboli is usually permanent and can render patients with earlier stages of CKD dialysis dependent.
Peripheral Vascular Disease
In general, the initial approach to investigating PVD is with noninvasive testing, as is done in the general population. An ankle–brachial index (ABI)(at rest plus or minus postexercise) is a simple test that can be performed in the physician's office to confirm the suspicion of PVD. An ABI of <0.90 suggests PVD and further investigations with segmental limb pressures, plethysmography, and various ultrasound techniques or magnetic resonance angiography are indicated.
Conventional angiography is generally performed in patients with significant ischemia as part of the workup for a revascularization procedure in suitable candidates.
Aviles RJ et al: Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med 2002;346:2047.
Beciani M et al: Cardiac troponin I (2nd generation assay) in chronic haemodialysis patients: prevalence and prognostic value. Nephrol Dial Transplant 2003;18:942.
deFilippi C et al: Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA 2003;290:353.
Haydar AA et al: Coronary artery calcification is related to coronary atherosclerosis in chronic renal disease patients: a study comparing EBCT-generated coronary artery calcium scores and coronary angiography. Nephrol Dial Transplant 2004;19:2307.
Lamb EJ et al: The significance of serum troponin T in patients with kidney disease: a review of the literature. Ann Clin Biochem 2004;41(Pt 1):1.
Moe SM et al: Natural history of vascular calcification in dialysis and transplant patients. Nephrol Dial Transplant 2004;19:2387.
Rabbat CG et al: Prognostic value of myocardial perfusion studies in patients with end-stage renal disease assessed for kidney or kidney-pancreas transplantation: a meta-analysis. J Am Soc Nephrol 2003;14:431.
Saw J et al: Coronary artery disease in chronic kidney disease patients: assessing the evidence for diagnosis, screening and revascularization. Can J Cardiol 2004;20:807.
Sharples EJ et al: Coronary artery calcification measured with electron-beam computerized tomography correlates poorly with coronary artery angiography in dialysis patients. Am J Kidney Dis 2004;43:313.