Restrictive Cardiomyopathy Workup

The accurate diagnosis of restrictive cardiomyopathy (RCM) is difficult given the similar clinical and hemodynamic presentation of constrictive pericarditis, but it is of utmost importance for treatment and prognosis. In years past, the diagnosis of RCM was often not made until surgical biopsy. However, with advances in diagnostic imaging, the necessity of surgical intervention for diagnosis should decrease. Investigative modalities that may aid in the differentiation of RCM and constrictive pericarditis appear in Table 2 below. 

A full evaluation of the heart often necessitates a multimodality approach, including radiography, echocardiography, computed tomography (CT) scanning, magnetic resonance imaging (MRI), and invasive angiography. ^[23]  With the current availability of nuclear imaging and cardiac MRI (CMRI), the diagnosis of RCM can be made noninvasively with a high degree of accuracy, but echocardiography remains the “front line” for diagnosis in early cases. Early diagnosis is crucial, given the advancements in therapeutic possibilities. ^[24]

See also Imaging in Restrictive Cardiomyopathy.

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

A complete blood cell (CBC) count with peripheral smear helps to 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, percentage 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 a nearly identical clinical and hemodynamic presentation. ^[25]

The findings on electrocardiography (ECG) depend on the stage of the disease and the specific diagnosis. The ECG recording is abnormal in more than 90% of patients with restrictive cardiomyopathy (RCM), especially idiopathic RCM. The ECG may be normal, however, or only show nonspecific ST-T wave changes. Rhythm disorders are common, and up to 74% of patients have atrial fibrillation. Case reports have shown Torsades de pointe. Significant ST depression mimicking ischemia has also been reported, especially in idiopathic RCM. ^[26]

In infiltrative disease, low-voltage QRS complexes have been described. ^[19] Conduction abnormalities are uncommon in amyloidosis. A pseudoinfarct pattern is possible, secondary to myocardial infiltration and/or small vessel–induced ischemia or infarction.

Chest radiography typically shows a normal cardiac silhouette and manifestations of pulmonary venous hypertension and pulmonary congestion. There may be other signs of congestive heart failure, such as pleural effusions. ^[19]  There is typically no pericardial calcification, which is seen in constrictive pericarditis.

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

Two-dimensional imaging

There is a significant body of literature demonstrating the utility and availability of two-dimensional transthoracic echocardiography (TTE). Therefore, it is a primary diagnostic modality in suspected restrictive cardiomyopathy (RCM). ^[27] In noninfiltrative RCM, TTE shows a left ventricle that is nondilated, nonhypertrophied, and normally contracting. There is typically marked dilatation of both atria.

In infiltrative RCM, such as amyloidosis and glycogen storage diseases, the primary finding is a concentrically increased left ventricular wall thickness with a normal or reduced chamber cavity size. Interatrial septal thickening is more specific to infiltrative cardiomyopathies. These changes are caused by myocardial amyloid deposition rather than true myocyte hypertrophy. Left atrial thrombi may occur in cardiac amyloidosis even in sinus rhythm. ^[24] Other common findings include biatrial dilatation, valvular thickening, and pericardial effusion. The ejection fraction (EF) typically remains preserved until advanced stages of the disease, and reduced EF is a marker of poor prognosis. ^[27]

The ratio of stroke volume to left ventricular myocardial volume, called myocardial contraction fraction, is a novel metric of left ventricular remodeling that has demonstrated prognostic significance superior to left ventricular EF in infiltrative disease. ^[27]

A granular myocardial appearance, or “sparkling” was initially reported using older ultrasonographic techniques. With current harmonic imaging, this finding is no longer validated and is considered nonspecific for infiltrative disease. ^[27]

Obliterative cardiomyopathy may reveal a mural thrombus and cavity obliteration. In contrast, dilated cardiomyopathy shows dilatation of all the chambers of the heart. Increased wall thickness, especially of the ventricular septum, is observed in hypertrophic cardiomyopathy.

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 restriction of diastolic filling, as diastolic dysfunction precedes reductions in left ventricular EF in infiltrative disease. Studies have shown the degree of diastolic dysfunction correlates to the extent of wall thickening in amyloid infiltration. ^{[24, 27]} Accentuated early diastolic filling of the ventricles (E), shortened deceleration time, and diminished atrial filling (A) results in a high E-to-A ratio on mitral inflow velocities. Variations of this diastolic (transmitral) blood flow with respiration help differentiate between constrictive pericarditis and RCM.

In infiltrative disease, all valves are often thickened. However, color flow Doppler studies have revealed that valvular dysfunction is usually mild and rarely contributes to heart failure. In contrast, the progressive and severe diastolic dysfunction leads to low EF and restrictive Doppler filling patterns, which demonstrated a worse prognosis. ^[24]

In constrictive pericarditis, both 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 may be used as a noninvasive approach to distinguish RCM from constrictive pericarditis. In addition to the information obtained by standard Doppler imaging, pulsed-wave Doppler studies can determine the myocardial velocity gradient, which is a measure of myocardial contraction and relaxation. Small studies have suggested that the myocardial velocity gradient is a specific measurement to differentiate restrictive and constrictive physiology.

Strain imaging and speckle tracking

Strain imaging is a method of measuring myocardial deformation, and it has demonstrated high sensitivity for detecting more subtle changes in contractile function. Specific myocardial strain patterns may reveal earlier stages of a variety of cardiovascular disorders. Longitudinal systolic strain (deformation along the long-axis of the left ventricle) is particularly sensitive for detecting early changes of amyloidosis. ^[27]

Speckle-tracking echocardiography measures both global and segmental ventricular strain, and therefore evaluates different contractile directions beyond the longitudinal axis. This is yet another imaging method to differentiate amyloidosis from other conditions that cause increased myocardial wall thickness, such as hypertrophic cardiomyopathy. Amyloid infiltration shows a characteristic pattern of reduced basal and mid-wall left ventricular longitudinal systolic strain with relative preservation at the apex. ^[27]

Ventricular pressure tracings of increased right heart pressures, a 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 restrictive cardiomyopathy (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 the left and right ventricular filling pressures, with a difference of no more than 5 mm Hg between the two 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 the 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.

Radionuclide imaging

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

Cardiovascular magnetic resonance imaging (CMRI)

CMRI can be used to evaluate the myocardial structure/orientation, perfusion, function, and viability in cardiomyopathy, providing information such as the left ventricular mass, volume, and regional contractility, as well as myocardial strain analysis, tissue mapping, and extracellular volume estimation. ^[28]  

CMRI has been used to assess abnormal myocardial interstitium, and it has been shown to reliably identify the morphologic findings of cardiac amyloidosis. ^[27] Preliminary reports suggest a characteristic pattern of global subendocardial late gadolinium enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics in restrictive cardiomyopathy (RCM). Dynamic cine imaging provides a clear, unobstructed view of all cardiac chambers, which allows for high quality visualization and tracking of both the endocardial and epicardial borders in addition to valvular disease. ^[27]

CMRI-based strain analysis, like echocardiography, is a promising modality to improve the diagnostic sensitivity of early infiltrative disease and the specificity of imaging findings in the hypertrophic stage. ^[27]

Cardiac computed tomography (CCT) scanning

CCT scanning has primarily been used to investigate coronary artery disease in select RCM patients with anginal chest pain, and its diagnostic role has thus far been limited. Similar to CMRI, however, CCT scanning can track contrast medium distribution to healthy and unhealthy tissues. Despite the disadvantages with regard to renal insufficiency and radiation exposure, CCT scanning may be an alternative modality if CMRI is contraindicated or unavailable. ^[27]

Ventricular biopsy obtained from either the right or the left ventricle has proven to be useful in certain cases to establish 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, when viewed under a polarizing microscope. Fine-needle aspiration of abdominal fat is easier and safer to perform than myocardial biopsy for the determination of amyloidosis. Confirmation of the diagnosis of primary or amyloid light-chain (AL) amyloidosis demands a search for a plasma cell dyscrasia.

Liver biopsy is performed for diagnosis of hemochromatosis.