Dilated Cardiomyopathy Workup

The workup in a patient with suspected cardiomyopathy may include the following:

• Complete blood count
• Metabolic panel
• Thyroid function tests
• Cardiac biomarkers
• B-type natriuretic peptide assay
• Chest radiography
• Echocardiography
• Cardiac magnetic resonance imaging (MRI)
• Electrocardiography (ECG)

In addition, a urine toxicology screen is used to detect drugs associated with risk for dilated cardiomyopathy, including cocaine and methamphetamine.

The risks and costs of cardiac catheterization should be considered before conducting right- or left-sided heart catheterization. Little additional prognostic information can be obtained from cardiac catheterization that cannot be obtained from echocardiography. Consider whether the study outcome will influence treatment of the patient (eg, patients with ischemic etiologies).

The utility of cardiac catheterization in a person with dilated cardiomyopathy is very limited and should be undertaken only when a strong likelihood of an ischemic etiology (eg, Q waves with systolic dysfunction, angina, positive imaging stress test finding) is present.

Endomyocardial biopsy has limited usefulness in the evaluation of dilated cardiomyopathy. However, it may be helpful in diagnosing myocarditis, connective tissue disorders, and amyloidosis.

The principal use of the CBC in these patients is to document anemia. Anemia can be associated with a high-output state. However, angiotensin-converting enzyme (ACE) inhibitors can cause leukopenia.

Hyponatremia signifies a poor prognosis. An elevated creatinine level may represent a primary or drug-related etiology (eg, hypovolemia, azotemia from ACE inhibitors). A low bicarbonate level is a poor prognostic sign. Contraction alkalosis can be observed secondary to diuretic therapy. Magnesium levels should be closely followed because low levels may cause chronic hypokalemia.

Liver function test results can be elevated. Possible causes in these patients include one or more of the following:

• Alcoholic disease
• Hemochromatosis
• Hepatic congestion (nutmeg liver)
• Infarction in inotrope-dependent CHF

Cardiac enzymes are useful for assessing acute or recent myocardial injury. Serum markers for myocardial necrosis (eg, troponin, creatine kinase, creatine kinase-MB) may be acutely elevated in persons with myocarditis. levels are markedly elevated in persons with muscular dystrophy.

Elevated biomarker levels may indicate acute coronary syndrome, which should be considered as a potential etiology for acute decompensation in a patient with a history of heart failure. Further, while the precise role of cardiac biomarkers is still being defined, there is evidence that patients who present with elevated markers experience more severe heart failure and higher mortality.^{[4, 5]}

B-type natriuretic peptide (BNP) assays help monitor the presence and severity of fluid overload. Changes in BNP level can reflect response to treatment. A low level of BNP is helpful in ruling out the condition.

In one study, a serum BNP below 100 pg/mL proved useful in excluding heart failure as a cause of dyspnea in emergency department (ED) patients.^[6] An elevated BNP level may be difficult to interpret in patients with stable, compensated heart failure, because they often have chronically elevated levels of BNP.

Chest radiography

Assess for enlargement and configuration of the cardiac silhouette. A study investigating the specificity and sensitivity of physical and laboratory findings in patients with dyspnea in the ED suggests that cardiomegaly is one of the most sensitive and specific signs in diagnosing cardiomyopathies. The absence of cardiomegaly on chest radiographs decreases the likelihood of heart failure. Remember that patients with left ventricular hypertrophy and pericardial effusion can also present with an enlarged cardiac silhouette.

Pulmonary vascular congestion may be observed. Hilar vessels may appear more concave, with prominent vasculature of the upper lung fields. Kerley B lines may be present. Pleural effusion usually occurs first on the right side, but it can be bilateral. Abnormal calcifications may be valvular, atherosclerotic, or pericardial in nature. Congenital malformations may be noted. The presence of pulmonary vascular congestion and interstitial edema on chest radiograph increases the likelihood of acute decompensated heart failure about 12-fold.

Echocardiography

Echocardiography has become one of the most useful and most efficient diagnostic modalities in attaining a diagnosis and classification of cardiomyopathy. Echocardiography may be indicated in the ED when a patient has findings suggestive of failure (eg, jugular venous distention) but the cause of cardiac decompensation is unclear.

In this setting, the differential diagnosis may include pulmonary embolism or cardiac tamponade. On echocardiography, secondary findings associated with pulmonary embolism such as right ventricular distention or pericardial effusion with tamponade may be seen. Pericardial effusion can be easily excluded or characterized using this imaging modality.

Different forms of echocardiography offer different information. Two-dimensional echocardiography allows for assessment of overall function.

M-mode assists in measurement of chamber sizes (end-diastolic left ventricular dimensions are usually greater than 65 mm in patients with dilated cardiomyopathy) and wall thickness. Hypertrophy is defined as posterior wall or septal wall thickness greater than 11 mm, although this guideline is not absolute and must be viewed in the context of cavity size. Doppler echocardiography facilitates the measurement and assessment of flow and valvular pathologies. It also allows for measurements of diastolic and systolic dynamics.

The physician must look for the reversal of the E wave–to–A wave ratio (E/A) when evaluating left ventricular filling and pulmonary venous flow by Doppler echocardiography during left atrial filling. This suggests decreased compliance, which should be viewed in the context of whether the myocardium is dilated, hypertrophied, or both. For example, a restrictive process would show E/A reversal and normal to moderately enlarged cavitary dimensions.

More recently, tissue Doppler interrogation has been used in many cardiac ultrasound laboratories; this modality measures the velocity of portions of the heart wall, most often the left ventricular basilar annular area. Just as in the blood velocity parameters of E and A amplitudes, similar measurements of wall velocity—E' and A'—are made. Reversal of the E'/A' amplitude signifies likely diastolic dysfunction.

Segmental wall motion abnormalities may suggest an ischemic etiology for the cardiomyopathy. While ischemic cardiomyopathy is a common cause of such abnormalities, however, they can often be observed in association with other forms of cardiomyopathy, as well.

Echocardiography is used to help differentiate dilated cardiomyopathy from restrictive and hypertrophic cardiomyopathy. Dilated chambers and thin walls are the most prominent features of dilated cardiomyopathy.

Magnetic resonance imaging

MRI with gadolinium–diethylene-triamine pentaacetic acid (DTPA) has been used to evaluate the extent of mid-wall fibrosis, which may correlate with risk of arrhythmias and failure to respond to treatment. Further investigation is ongoing in the role that subendocardial sparing mid-wall fibrosis plays in the pathogenicity of arrhythmias. In the future, MRI with gadolinium may be used for the risk stratification of patients with dilated cardiomyopathy, as well as in the criteria for automatic implantable cardioverter-defibrillator placement.

An ECG is helpful in identifying left ventricular enlargement and estimating the other chamber sizes. ECG findings in Nonspecific ST-T wave changes and Q waves are characteristic of dilated cardiomyopathy. Atrial fibrillation or premature ventricular complexes are noted. Left ventricular hypertrophy or other chamber enlargement is observed. Conduction delay, particularly left bundle-branch block, can be observed. Varying degrees of atrioventricular block are noted.

An ECG showing atrial fibrillation increases the likelihood of heart failure. The absence of any ECG abnormality decreases the likelihood of heart failure. This is an important screening tool in differentiating ischemic heart disease from dilated cardiomyopathy.

Right-sided heart catheterization (RHC) can be beneficial in initially determining the volume status of a patient with equivocal clinical signs and symptoms of heart failure. RHC in a patient with dilated cardiomyopathy demonstrates elevated filling pressures (central venous pressure, pulmonary artery wedge pressure, right ventricular end-diastolic pressure) and decreased cardiac output.

In restrictive cardiomyopathy, RHC demonstrates a pattern in the ventricular hemodynamic tracing referred to as the "square root sign" or "dip-and-plateau pattern." This pattern is similar to that observed in patients with constrictive pericarditis, but in restrictive cardiomyopathy, the left ventricular end-diastolic pressure generally exceeds the right ventricular end-diastolic pressure by 6 mm Hg or more and the entire diastolic filling period is abnormal, while constrictive pericarditis is associated with normal or increased early filling.

In many cases of cardiomyopathy, endomyocardial biopsy is class II (uncertain efficacy and may be controversial) or class III (generally not indicated). The exception to this is in cardiac transplant recipients, in whom routine periodic assessment of transplant rejection is necessary.

Class II indications for endomyocardial biopsy include the following:

• Recent onset of rapidly deteriorating cardiac function
• Patients receiving chemotherapy with doxorubicin
• Patients with systemic diseases with possible cardiac involvement (eg, hemochromatosis, sarcoidosis, amyloidosis, Löffler endocarditis, endomyocardial fibroelastosis)

Evidence does not indicate a benefit for performing myocardial biopsy when evaluating the likelihood of patient survival with current therapies.

Findings may include myocardial injury with inflammatory mediators (eg, macrophage derived, antibody/complement). Physical disruption of myocytes by inflammatory cells, proliferation of interstitial cells, and increased fibrous matrix may also be found.

Lymphocytic myocarditis is the most common finding in human cardiac tissue biopsy specimens. Myocyte necrosis, degeneration, or both with adjacent inflammatory infiltrate may be present. Significant coronary artery disease may be present. A predominance of lymphocytes and some monocytes without significant eosinophils may be present. Lymphocytic myocarditis is likely related to viral or other infections.

Eosinophilic myocarditis, sometimes called Löffler or Loeffler myocarditis, is usually due to the effects of a drug allergy. Perivascular infiltrates with eosinophil predominance, lymphocytes, and macrophages may be present. Eosinophilic myocarditis usually occurs with peripheral eosinophilia, rash, and/or fever.

Giant cell myocarditis is a rare condition usually associated with systemic illnesses such as the following:

• Infections (eg, tuberculosis, endocarditis, fungi, syphilis, leprosy)
• Rheumatologic illnesses (eg, rheumatoid arthritis, lupus, vasculitides, polymyositis, dermatomyositis)
• Gastrointestinal conditions (eg, Crohn disease, ulcerative colitis, chronic hepatitis)
• Autoantibody-associated conditions (eg, myasthenia gravis, Hashimoto thyroiditis)
• Sarcoidosis

Giant cell myocarditis is often associated with conduction abnormalities and may progress rapidly. Necrotizing or nonnecrotizing granulomas are found, often with eosinophilia. T-cell infiltrates have been documented, and anti-CD3 antibody therapy may be effective. The idiopathic type is most often progressive and may require cardiac transplantation. Patients are usually young and present with heart failure or ventricular arrhythmias.

Peripartum myocarditis may be a variant of lymphocytic myocarditis and worsens during pregnancy. In AIDS-related myocarditis, inflammatory infiltrates are observed in cardiac tissue, usually consisting of CD8⁺ T lymphocytes.

Hypothyroidism, hyperthyroidism, and thyroid hormone toxicity are all problems to be considered in the differential diagnosis of cardiomyopathy. For example, thyrotoxicosis is associated with a high-output state that may predispose to dilated cardiomyopathy. Results of thyroid function tests are not usually available to assist in decision making in the ED but may be sent for convenience.

On oxygen consumption testing, an oxygen consumption per minute (VO₂) maximum of less than 14 mL/kg/min signifies a poor prognosis. Such patients should be given early consideration to heart transplantation.

A central venous line or pulmonary artery catheter provides a good measure of filling pressures, and the latter can be used to estimate cardiac output. However, neither has been shown to improve outcomes when used in acute decompensated heart failure.

Classic staging of heart failure is based on the New York Heart Association (NYHA) system. A newer approach to the classification of heart failure is the American College of Cardiology/American Heart Association system, which is as follows^[7] :

• Stage A (high risk for developing heart failure): hypertension, coronary artery disease, diabetes mellitus, family history of cardiomyopathy
• Stage B (asymptomatic heart failure): previous myocardial infarction, left ventricular systolic dysfunction, asymptomatic valvular disease
• Stage C (symptomatic heart failure): structural heart disease, dyspnea, fatigue, reduced exercise tolerance
• Stage D (refractory end-stage heart failure): marked symptoms at rest despite maximal medical therapy, recurrent hospitalizations