Cardiomyopathies are a heterogenic group of diseases of the myocardium, which further classify into primary “confined to the heart, “or secondary “related to systemic disease.” The primary cardiomyopathies are divided into genetic “including hypertrophic, arrhythmogenic right ventricular, left ventricular noncompaction, Danon glycogen storage disease and others”; and acquired “including acute myocarditis, stress-induced (Takotsubo), peripartum, and tachycardia-induced cardiomyopathies." The secondary cardiomyopathies occur due to systemic diseases. These include infiltrative diseases such as amyloidosis, Gaucher disease, Hunter disease, and Hurler disease. Storage diseases, medication toxicity, inflammatory disease, and endocrinology diseases can also lead to secondary cardiomyopathy.[1]

Diagnosis of the etiology of cardiomyopathy starts with a thorough history and physical exam, including obtaining detailed social and family history, a careful review of medication and substance use, and followed by diagnostic tools including electrocardiogram, laboratory testing, imaging studies, and may require a myocardial biopsy to reach the definitive diagnosis. Echocardiogram, cardiac MRI, cardiac CT, and nuclear medicine imaging are the primary imaging modalities used for both work up and follow up on patients with cardiomyopathies.

Chest radiograph:

A chest radiograph is usually the initial imaging study to order, especially in an acute setting, to differentiate between cardiac and pulmonary etiologies of severe respiratory symptoms. The chest radiograph can also be used to distinguish different types of cardiomyopathy although it is not a sensitive test in the workup. In dilated cardiomyopathy, the chest radiograph will show increased left and right ventricular size. The chest radiograph can show evidence of cardiomegaly and increased cephalization, pleural effusion, and Kerley B-lines in the setting of acute congestive heart failure. Cardiomegaly on chest radiograph usually reflects the decreased ejection fraction, and the increased cephalization reflects increased preload. These can be helpful to establish a diagnosis of acute heart failure but are not adequate to confirm the diagnosis.[2]

In peripartum cardiomyopathy, findings are consistent with other dilated cardiomyopathies including enlargement of the heart silhouette and increased pulmonary venous congestion with or without interstitial edema. In contrast, the chest radiograph in Chagas heart disease usually shows an enlarged cardiac silhouette, which is typically due to pericardial effusion.[3] In restrictive cardiomyopathy, the chest radiograph shows increased atrium size resulting in cardiomegaly and associated with venous congestion. The presence of pericardial calcification can be used to differentiate chronic constrictive pericarditis “present” from restrictive cardiomyopathy.

Echocardiography

Echocardiogram remains the main imaging study in the workup for cardiomyopathy and to differentiate between the different types of cardiomyopathy. The ease of use and cost efficiency of echocardiogram comparing to other imaging studies has always made it the first choice in the evaluation of new-onset cardiomyopathy and follow up on the progress of the disease. The echocardiogram helps to evaluate the systolic and diastolic dysfunction, wall motion abnormalities, and valvular abnormalities. The sensitivity of the 2D echocardiogram is 81%, and the specificity is 100% in diagnoses of left ventricular dysfunction.[4] 

In dilated cardiomyopathy (DCM), the echocardiogram is an essential imaging test to make the diagnosis. The echocardiogram shows dilation with or without dysfunction of the left ventricle.[5] On 2D echocardiogram, the dilation of the left ventricle can be associated with reduced wall thickening and reduced inward systolic motion. Other common findings in DCM are reduced ejection fraction, left ventricular fractional shortening, four chambers dilation, left ventricular end diastolic volume index often exceeds 100ml/m^2 and the end systolic volume index of the left atrium usually increases to more than 50ml/m2. The enlargement of the left atrium in DCM can reflect the chronicity of the disease and can be a predictor of outcome.[6]

Abnormal global longitudinal strain (GLS) is a predictor of mortality in patients with systolic heart failure with decreased ejection fraction and is superior to other echocardiogram parameters as a prognostic measure.[7] The presence of abnormal GLS in patients who have recovered left ventricular ejection fraction is an indicator of increased risk of recurrence of decreased LVEF in the future follow up compared to patients with normal GLS.[8] Mitral regurgitation (MR) can be seen on the echocardiogram and can be primary or secondary. Primary MR can lead to increase preload on the left ventricle, and secondary MR can be a result of apical tenting of the mitral valve leaflets, annular dilatation of the valve, and ventricular dys-synchrony, which carries a poor prognosis.[5] The dilation of the right ventricle can be related to pulmonary hypertension or other pathologic involvement of the right ventricle. In idiopathic DCM, the presence of right ventricular dilation can indicate poor prognosis and higher mortality.[9] Reduced right ventricular ejection fraction is a predictor of poor survival in patients with moderate congestive heart failure.[10] 

In peripartum cardiomyopathy, there is a global decrease in the left ventricular systolic function with or without evidence of dilated ventricles. A left ventricular thrombus may occur when LVEF is less than 35%.[11] Left atrium enlargement or thrombus can present in severe cases, and right ventricular dilation and hypokinesia may occur. In rare cases, there can be pericardial effusion. In ischemic cardiomyopathy, the findings in echocardiogram usually relate to left ventricular wall motion abnormality as a result of old or new infarcts. The dobutamine stress echocardiogram can distinguish between ischemic cardiomyopathy and other etiologies.[12] High left ventricular end-systolic volume index (ESVI) of 45ml/m^2  is a predictor of poor outcomes in patients with ischemic cardiomyopathy.[13] In Chagas cardiomyopathy, the left and right ventricular systolic function can be between normal and severely impaired. In moderate to severe Chagas cardiomyopathy, an echocardiogram can show left ventricular, right ventricular, or bilateral apical aneurysm.[14] Decreased LVEF in Chagas Disease on 2D echocardiogram is an important predictor of mortality.[15] Pericardial effusion and sometimes tamponade may be a feature on echocardiogram in acute Chagas disease.[16] Left ventricular and left atrial thrombus are common findings on echocardiogram in Chagas cardiomyopathy.[16]

All patients with suspected hypertrophic cardiomyopathy (HCM) should be evaluated with an echocardiogram, to check the LV wall thickness, systolic and diastolic function, left ventricular outflow tract (LVOT) obstruction, and presence of mitral regurgitation. Clinical diagnosis of HCM is possible with the finding of LV hypertrophy on echocardiogram.[17] In HCM, the Systolic anterior motion SAM of the mitral valve can result in obstruction in the left ventricular outflow tract. A left ventricular outflow tract gradient over 30mmHg is as common as 20 to 25% of patients. The left ventricular outflow tract obstruction is a predictor of the development of severe symptoms of heart failure and a predictor of death.[18] Other findings associated with LVOT obstruction can be asymmetric septal hypertrophy, partial early systolic closure of the aortic valve, calcification of the mitral annulus and mitral regurgitation. Symptomatic patients with HCM without evidence of LVOT obstruction at rest should undergo a stress echocardiogram to evaluate the possibility of an obstruction on exertion; this will help to start early treatment.[19] The presence of increased left atrial size is a predictor of a poor outcome in HCM and is associated with the development of atrial fibrillation.[20] Increased left atrial volume index (LAVI) and GLS are both associated with worse outcomes in HCM, and they can both be used to optimize the risk stratification in HCM patients. [21] Progression of both LAVI and GLS measures with repeated echocardiograms in non-obstructive HCM is related to the development of heart failure.[22]

Diagnosis of restrictive cardiomyopathy by echocardiogram is more difficult than the diagnosis of hypertrophic and dilated cardiomyopathies. The left ventricle usually is usually normal in size or small and associated with a normal left ventricular systolic function. These patients usually have an abnormal diastolic function with biatrial enlargement.[23],[24] Although the wall thickness is usually normal, it can increase in infiltrative diseases, such as sarcoidosis, amyloidosis, and hypereosinophilic syndrome.[25] In cardiac amyloidosis, the left ventricular wall thickness is increased, and associated with diastolic dysfunction as early findings on echocardiogram, right ventricular diastolic dysfunction can also occur. The left ventricular wall thickness in cardiac amyloidosis is symmetric, and outlet obstruction is rare.[26] One-third of the patients with cardiac amyloidosis can have diastolic dysfunction with normal left ventricular wall thickness.[27] The presence of normal ventricular wall thickness on echocardiogram cannot exclude the cardiac involvement in systemic amyloidosis.[28],[29] The presence of right ventricular dilation in cardiac amyloidosis is associated with a poor prognosis with a very low survival rate.[30]

Echocardiogram has low sensitivity when used for workup of cardiac sarcoidosis. In systemic sarcoidosis, an echocardiogram can show abnormal findings in up to 46% of patients even if they are asymptomatic for cardiac disease; findings can include: diastolic dysfunction, abnormal wall motion, and wall thickness (increased in acute cardiac sarcoidosis and decreased in chronic).[31] The presence or absence of systolic dysfunction and left ventricular dilation are mortality predictors.[31] Decreased LVEF and dilation of the left ventricle can present in up to 30% of patients.[32] In 10% of patients, an echocardiogram will show ventricular aneurysms, mainly in the septum and anterior wall.[32] Abnormal GLS can be a feature in sarcoidosis patients who have otherwise normal echocardiogram findings; the impaired GLS correlates with worse outcomes.[31] In hypereosinophilic cardiomyopathy, the echocardiogram can be normal in the acute stage, but as the disease progresses, the echocardiogram can show severe restrictive ventricular disease and intraventricular thrombus. In diabetes mellitus, an echocardiogram can show evidence of diastolic dysfunction and left ventricular hypertrophy with normal LVEF.[33]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy that is caused by the fibrous-fatty replacement of myocardium of the right ventricle. Echocardiogram has limited sensitivity in the diagnosis of ARVC, it can show regional RV akinesia, dyskinesia, or aneurysm, [24] it can help in detection of the RV fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE), these two measures are strong predictors of a major advanced cardiac event.[34] An echocardiogram can be a diagnostic modality for other unclassified cardiomyopathies. In Takotsubo stress cardiomyopathy, an echocardiogram can show hypokinesia or dyskinesia with reduced left ventricular systolic function; these patients have no evidence of coronary artery obstructive disease.[35] Right ventricular dysfunction may occur in one-third of the cases and is associated with more severe disease and worse left ventricular wall motion abnormality.[36] In isolated left ventricular noncompaction (LVNC), an echocardiogram can show evidence of cardiomyopathy, the main type seen is dilated cardiomyopathy,[37] but restrictive or hypertrophic features may be visible. The echocardiogram shows numerous prominent trabeculations of the endocardium of the left ventricle.[5] Color Doppler echocardiogram may show direct blood flow into the intertrabecular recesses from the ventricle; this finding does not present in any other type of cardiomyopathy.[38]

Multidetector computed tomography can be used in the workup of cardiomyopathy to differentiate between ischemic and nonischemic dilated cardiomyopathy etiology.[39] The coronary CTA is highly sensitive and specific in the diagnosis of CAD; it can also help in predicting the prognosis of ischemic cardiomyopathy[40]. In nonischemic dilated cardiac myopathy (DCM), the cardiac CT (CCT) can be used to measure the left ventricular internal diameter and left ventricular ejection fraction. Cardiac CT can predict poor prognosis depending on the LVEF,[24] but cardiac CT cannot differentiate between different types of nonischemic DCM.[40]

In HCM, the cardiac CT can help to identify the hypertrophy of the myocardium and the LVOT obstruction and can show an enlarged mitral valve, systolic anterior motion (SAM) of the mitral valve or mitral valve regurgitation. The CCT can demonstrate the asymmetry of the ventricular hypertrophy.[24] CCT can show atypical forms of HCM including apical hypertrophy, concentric hypertrophy or sometimes mid ventricular hypertrophy.[40] On delayed iodine enhancement (DIE), images fibrosis of the myocardium can be seen, mostly focal in the right ventricle but can be diffuse. The presence of this fibrosis can be related to life-threatening arrhythmia and cardiac death.[40]

In restrictive cardiomyopathy, the CCT can show the ventricular sizes similar to the echocardiogram findings. In cardiac sarcoidosis, the cardiac CT with contrast can demonstrate the enhancement of the sub-epicardium with global or regional hypokinesia.[24]. In the acute phase, focal wall thickening is visible due to focal areas of granulomas, but in chronic cardiac sarcoidosis wall thinning is seen.[40] Fibrosis can be seen on the DIE images and can be related to poor outcomes.[40] Multidetector CT can show cardiomegaly, pericardial effusion, and ventricular aneurysms.[32] In cardiac amyloidosis, CCT is not usually used due to the low sensitivity in the detection of myocardial infiltration,[24] but it can show ventricular wall thickening and biatrial enlargement.[40] On the DIE images, a pattern of diffuse transmural or sub-endocardial enhancement may present.[40]

In ARVC, cardiac CT can show dilation of the right ventricle with a bulging appearance in the right ventricular wall due to fatty deposition.[24][40] This fibro-fatty replacement in the right ventricular wall can cause thinning of the RV wall that detectable on the CCT. [41], these changes can cause RV dilation and systolic dysfunction. [40] The CCT can assess left ventricular involvement, the ventricular wall motion, and the ventricular function.[41] In Takotsubo stress cardiomyopathy (TTC), the cardiac CT can show the apical ballooning with a hyperdynamic contracting base of the left ventricle.[24][40] In 25% of patients with Takotsubo, right ventricular apex involvement is visible.[24] In LVNC, the CT can show the trabeculated to non-trabeculated myocardium in end diastole ratio to be greater than 2.3, which usually involves the anterior and inferolateral segments of the left ventricle.[24][40] 

Cardiovascular magnetic resonance (CMR) is used in cardiomyopathy to assess ventricular volumes, ejection fraction, myocardial mass, and wall thickness. The high resolution of CMR helps in assessment of the ventricle systolic function and differentiate between ischemic and non-ischemic cardiomyopathy. Late gadolinium enhancement (LGE) can identify the fibrosis of the myocardium which helps to differentiate between types of cardiomyopathy. LGE CMR can be used to check for the arrhythmogenic substrate; this helps for future treatment options including ablation.[42]

In DCM, the dilated ventricles and decreased ejection fraction are the main findings.[43] In peripartum cardiomyopathy, CMR can be helpful to predict outcome in peripartum cardiomyopathy, an improvement in LGE can predict recovery of the systolic dysfunction.[44][45] In Chagas disease, myocardial delayed enhancement by CMR can quantify myocardial fibrosis, which is significantly helpful in early diagnosis of Chagas cardiomyopathy in asymptomatic patients. This measurement is useful as a predictor factor for disease prognosis.[46] The CMR with LGE can assess the presence of myocardial fibrosis, which is a marker of the severity of the disease and predicts the development of malignant ventricular arrhythmias, which can lead to sudden cardiac death. CMR can detect ventricular aneurysms and intraventricular thrombus in Chagas cardiomyopathy.[42] It can also detect right ventricular dysfunction which is a poor prognostic factor in Chagas cardiomyopathy.[16]

In HCM, the CMR can show the septal and left ventricular hypertrophy and helps in the assessment of variant types of HCM. CMR is more sensitive than echocardiogram to identify areas of segmental left ventricular hypertrophy. Myocardial fibrosis can be detected when using IV gadolinium.[47] The intraventricular septum is usually asymmetric on CMR, but it can be symmetric occasionally. CMR can show apical hypertrophy or mass like left ventricular hypertrophy.[42] Both mitral valve and papillary muscles are part of the etiology of the LVOT obstruction. CMR can early detect the SAM of the mitral valve, which is the main etiology for the LVOT obstruction.[48] Left ventricular papillary muscles play an important role in the LVOT obstruction. CMR can detect the mass of the papillary muscle and can be helpful in pre-op planning for septal reduction therapy.[49] CMR can also help to detect right ventricular hypertrophy in HCM.[50] In carriers and early asymptomatic HCM patients, the CMR can detect left ventricular myocardial crypts that precede myocardial wall thickening and early changes of HCM.[51] 

CMR is essential in the diagnosis of restrictive cardiomyopathy and the differential diagnosis of etiology of this type of cardiomyopathies; it helps to differentiate the restrictive cardiomyopathy from the constrictive pericarditis.[42] Features of cardiac amyloidosis on CMR are concentric hypertrophy, increased septal thickness, atrial dilation bilaterally, and normal or impaired contractility.[42] In cardiac amyloidosis, LGE-CMR can detect early myocardial abnormalities in patients with normal left ventricular thickness.[52] LGE is an indicator of the severity of the cardiac amyloidosis related heart failure, and the severity is consistent with the BNP levels.[53]

In cardiac sarcoidosis, the typical findings on CMR are biventricular dilation and thinning of the septum.[42] The CMR detects cardiac sarcoidosis by identifying areas of LGE in the mid-wall, and subepicardial areas, LGE in the subendocardium is rare. These LGE areas are likely to be multifocal, especially in the anterior and inferior septum.[31] Presence of LGE was shown to be related to increased ventricular arrhythmia in cardiac sarcoidosis and can be related to cardiovascular death.[54] LGE-CMR is useful also in the evaluation of response to steroids treatment of the sarcoidosis.[42] In ARVC, the CMR can detect wall motion defects, right ventricular dilation, right ventricular dysfunction, and focal aneurysms. Right ventricular outflow tract enlargement, intramyocardial fatty infiltrates and focal wall thinning or wall hypertrophy are some of the morphological abnormalities that CMR can detect.[42]

CMR can be used as part of the workup for other unclassified cardiomyopathies. In stress cardiomyopathy, the CMR can show the left ventricular wall motion dyskinesia or akinesia in the mid and apical areas of the left ventricle in up to 75% of patients.[55] It can also show right ventricular involvement, and left ventricular thrombus.[55] LGE CMR does not show scarring of the myocardium, but CMR on the T2 weighted images shows wall edema.[42] In LVNC, the CMR can help to differentiate the true LVNC from other prominent hypertrabeculation that can present in normal individuals.[56]