Restrictive Cardiomyopathy Workup

Laboratory studies are performed to establish the diagnosis of restrictive cardiomyopathy (RCM), to quantitate the severity of the disease, and to monitor the patient.

Other investigative modalities are also employed in the workup, in particular to facilitate differentiation between RCM and constrictive cardiomyopathy (see Table 2 below).

Table 2. Investigation of Constrictive Cardiomyopathy and Restrictive Cardiomyopathy (Open Table in a new window)

A complete blood count (CBC) with peripheral smear helps establish eosinophilia. Blood gas analysis is performed to monitor hypoxia. Serum electrolyte, blood urea nitrogen (BUN) and creatinine levels should be obtained, as well as a liver function profile.

Serum iron concentrations, percent saturation of total iron-binding capacity, and serum ferritin levels are all increased in hemochromatosis.

Serum brain natriuretic peptide (BNP) levels should be assessed. Data suggest that serum BNP levels are nearly normal in patients with constrictive physiology of heart failure and grossly elevated in patients with restrictive physiology, despite nearly identical clinical and hemodynamic presentation.^[8]

Chest radiograph typically shows cardiomegaly with bilateral pleural effusions, absence of cardiomegaly, normal cardiac silhouette, no pericardial calcification (seen in constrictive pericarditis), and manifestations of pulmonary venous hypertension and pulmonary congestion

Angiography may show a small, thick-walled cavity in eosinophilic endomyocardial disease, which may be distorted significantly by a mural thrombus.

Two-dimensional imaging

Two-dimensional echocardiography shows a nondilated, normally contracting, nonhypertrophied left ventricle and marked dilatation of both atria. However, amyloidosis typically shows diffuse increased left ventricular thickening.

The ventricular cavity size may be normal or reduced. The wall thickness may be increased in patients with infiltrative diseases. Mural thrombus and cavity obliteration are features of obliterative cardiomyopathy. In contrast, dilated cardiomyopathy shows dilatation of all the chambers of the heart, and increased wall thickness, especially of the ventricular septum, is observed in hypertrophic cardiomyopathy.

Abnormal myocardial textures can also be appreciated using echocardiography. For example, granular speckling of the ventricular walls suggests the presence of infiltrative disease, such as amyloidosis.

Pericardial thickening is not reliably observed on echocardiography; magnetic resonance imaging (MRI) is suggested for exclusion of a thick pericardium.

Doppler imaging

Doppler echocardiography shows features of restriction to diastolic filling. Accentuated early diastolic filling of the ventricles (E), shortened deceleration time, and diminished atrial filling (A), which results in a high E-to-A ratio on the mitral inflow velocities, are present. Variations of this diastolic (transmitral) blood flow with respiration help differentiate between constrictive pericarditis and RCM.

Because both of the ventricles are encased in a common constricting pericardial sac, an inspiratory increase in inflow to the right ventricle causes a reciprocal reduction in the transmitral inflow to the left ventricle. Thus, a pattern of respiratory variation, with a diminished peak transmitral diastolic flow during inspiration, is characteristic of pericardial constriction but not of RCM. In contrast, in RCM, the left-sided filling pressures are elevated further in inspiration.

Pulsed-wave tissue Doppler imaging

The use of pulsed-wave Doppler imaging is used in some centers as a noninvasive approach to distinguishing RCM from constrictive pericarditis. In addition to the information obtained by standard Doppler imaging, pulsed-wave Doppler imaging can define myocardial contraction and relaxation. This results in a measure referred to as the myocardial velocity gradient. Small studies have suggested that the myocardial velocity gradient is a specific measure that distinguishes these 2 entities well.

Ventricular pressure tracings of increased right heart pressures, typical venous wave pattern, and the dip-and-plateau or square-root contour of the ventricular diastolic pressures (deep and rapid early decline in ventricular pressure at the onset of diastole, with a rapid rise to a plateau in early diastole) obtained by cardiac catheterization are the same in pericardial constriction and in RCM. This dip-and-plateau or square-root sign of ventricular pressure is manifested in the atrial pressure tracing as a prominent descent followed by a rapid rise to a plateau.

A few criteria favor the pericardial disorder, as follows:

• Equalization of left and right ventricular filling pressures, with a difference of no more than 5 mm Hg between the 2 sides
• Right ventricular end-diastolic pressure (RVEDP) equal to or exceeding one third of the level of the right ventricular systolic pressure (RVSP)
• RVSP lower than 50 mm Hg
• Persistence of diastolic equalization of pressures under stress or exercise or fluid challenge

In RCM, the variance between right and left ventricular diastolic pressures is more likely to be greater than 5 mm Hg, RVEDP is more likely to be less than one third the RVSP, and RVSP is more likely to be higher than 50 mm Hg.

The findings on electrocardiography (ECG) depend on the stage of the disease and the specific diagnosis. The ECG may be normal or just show some nonspecific ST-T wave changes, but rhythm disorders (notably atrial fibrillation) are common.

Conduction abnormalities are uncommon in amyloidosis. Low QRS voltage is common in amyloidosis, out of proportion to the thick left ventricle on echocardiography. A pseudoinfarct pattern is possible, secondary to myocardial infiltration and/or small vessel–induced ischemia or infarction.

Radionuclide imaging

Radionuclide imaging shows increased diffuse uptake of technetium-99m (^99m Tc) pyrophosphate and indium-111 (¹¹¹ In) antimyosin in cardiac amyloidosis.

Cardiovascular magnetic resonance (CMR)

Cardiovascular magnetic resonance (CMR) has been used to assess abnormal myocardial interstitium. Preliminary reports suggest a characteristic pattern of global subendocardial late gadolinium enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics in RCM.

Ventricular biopsy obtained from either the right or the left ventricle has proved useful in certain cases in establishing whether endocardial or myocardial disease is present. Growing experience in this technique indicates a high diagnostic yield in diseases that may present with restriction hemodynamics, when noninvasive studies have failed to establish a clear-cut diagnosis.

Amyloidosis demonstrates apple-green birefringence, stained with Congo red, viewed under a polarizing microscope. Fine-needle aspiration of abdominal fat is easier and safer than myocardial biopsy for determination of amyloidosis. Confirmation of the diagnosis of AL amyloidosis demands a search for a plasma cell dyscrasia.

Liver biopsy is performed for diagnosis of hemochromatosis.