The initial imaging evaluation comprises of two main 2D echocardiography parameters: left ventricle ejection fraction (LVEF) less than 40% or fractional shortening less than 25% [6]. However, the comprehensive diagnosis of DCM should consider aspects of the clinical presentation, patient examination and other test results. Dilatation of the LV, especially end-diastolic and end-systolic transverse diameter enlargement (spherical remodeling), associated with reduced wall thickness, is easily recognized with 2D echocardiography in parasternal long-axis view (See Fig. 1 and Appendix Video 1).

Fig. 1.

Echocardiographic aspect of DCM. Parasternal long-axis view showing a dilated left atrium and left ventricle in diastole. An online video of this patient with idiopathic dilated cardiomyopathy is available (Appendix Video 1).

Cardiac chamber enlargement is often present, but linear volumetric estimation is no longer recommended. According to the American Society of Echocardiography quantitative parameters should be obtained for an accurate assessment. Thus, DCM is defined by an LV end-diastolic volume index above 100 mL/m${}^2$ [4]. The upper normal volume is 74 mL/m${}^2$ in men and 61 mL/m${}^2$ in women [4]. The end-systolic volume of the LV is a defining feature, but also a prognostic parameter, an index greater than 35 mL/m${}^2$ is correlated with an unfavorable outcome [3, 4]. Another classic parameter is the LVEF, less than 40% and is specific to heart failure with reduced ejection fraction (HFrEF) (see Fig. 2). It is widely accepted that patient outcome is inversely related to the left ventricle ejection fraction. The hallmark of DCM is left ventricular cavity dilation, which may be associated with other cardiac chamber enlargements. Although the myocardial walls may be either of normal or reduced thickness, the total left ventricular mass is increased because of the overall increase in LV size. However, parameters related to the LV systolic function, such as fractional shortening, ejection fraction, stroke volume, and cardiac output are typically reduced. The normal range of the stroke volume is between 50 and 100 mL/beat. Although the stroke volume is reduced in some cases, LV cavity dilation may initially serve to compensate by restoring the stroke volume, thus it is recommended to guide the diagnosis by measuring the LV end-systolic volume index (ESVI) because it provides important information in several clinical settings.

Fig. 2.

Echocardiographic aspect of DCM in a patient with idiopathic dilated cardiomyopathy. (A) Parasternal short axis at the level of the mitral valve, diastolic frame showing a dilated left ventricle. (B) Parasternal short axis at the level of the mitral valve, systolic frame showing the small difference between the end-diastolic and end-systolic diameter of the left ventricle due to reduced contractility.

Left atrial volume index (LAVi) is estimated from 2D echocardiography 4 chamber-view. A value above 50 mL/m${}^2$ is a characteristic echocardiographic aspect of DCM [8]. This is due especially to the diastolic disfunction associated with different grades of mitral regurgitation. Data suggest that minimal atrial volume assessed at ventricular end-diastole has a better predictive value of outcomes than maximal left atrial volume measured at ventricular end-systole [9].

The evaluation of the anatomy and function of the right ventricle (RV) is mandatory, given the fact that the prognosis is considerably worse when there is RV dilatation and/or RV systolic dysfunction. RV systolic power is defined by the tricuspid annular plane systolic excursion (TAPSE) in 2D apical 4-chamber view, ejection fraction and fractional area change. For TAPSE, a reported value of 14 mm, is associated with poor prognostic in patients with DCM [3, 4]. RV dysfunction is not essential for the diagnosis of DCM but when present, it is an adverse prognostic marker.

Color and spectral Doppler echocardiography is of limited use in the diagnosis of DCM, except for atrioventricular valve incompetence. One constant feature is the presence of mitral regurgitation, secondary to the annulus dilation with abnormal leaflet tethering. Mitral regurgitation can present with different degrees of severity and is an additional prognostic factor (see Fig. 3 and Appendix Video 2 and 3). The pathophysiology of mitral regurgitation in DCM is usually due to abnormal leaflet tethering mandated by the change in LV shape from ellipsoid to spherical. As cardiomyopathy progresses, the point of leaflet coaptation migrates from its normal basal location to a spot deeper in the LV cavity this leading to also to an apposition defect with the generation of an eccentric regurgitant jet. Moreover, DCM patients present with an abnormally low diastolic function [5]. Restrictive or pseudo-normal diastolic inflow patterns impact the patients with DCM, with an associated poor prognosis [10, 11]. The assessment of the pulmonary vein flow signal as an adjunct to the mitral inflow pattern is very important in the echographic evaluation of DCM. Abnormal pulmonary venous systolic flow patterns have been shown to correlate with the future development of pulmonary hypertension. Loss of the systolic dominant flow pattern suggests elevated filling pressure and the difference between the pulmonary venous flow reversal duration and the mitral inflow duration during atrial contraction greater than 30 ms predicts mortality and hospitalization [9]. Studies evaluating diastolic compliance with Doppler echocardiography have shown also an altered mitral diastolic flow with a short deceleration time $\le$115 msec, and an E/A ratio $>$1 is a powerful independent predictor of mortality or the need for transplantation among patients with heart failure [9].

Fig. 3.

Echocardiographic aspect of DCM in a patient with idiopathic dilated cardiomyopathy. (A) Apical 4 chamber view, showing dilated left ventricle, dilated left atrium, and significant secondary mitral regurgitation flow with Coanda effect. (B) Parasternal long-axis view, showing dilated left ventricle, dilated left atrium, and significant secondary mitral regurgitation flow with Coanda effect. An online video of this patient with idiopathic dilated cardiomyopathy is available (Appendix Video 2 and 3).

TDI is a technique used to characterize diastolic dysfunction but also gives important information about the global and regional systolic function of the myocardium. By TDI can be assessed displacement velocities of small samples of the tissue, values which are directly proportional to the contractility force of the region of interest but it is also correlated with the global systolic function of the LV or RV. The mean normal value of the velocity contraction (S wave) for the septal annulus is 8.1 $\pm$ 1.5 (6.0–10.9) and for the lateral mitral annulus is 10.2 $\pm$ 2.4 (6.7–14.6) for a 35 to 75 years old study population [12]. Myocardial mitral annular or basal segmental (Sm) systolic and early diastolic (Ea or Em) velocities have been shown to predict mortality or cardiovascular events. In DCM the myocardial systolic velocity displacement is under the normal values. Several studies are comparing the S wave value among different age groups with no significant differences. Related to the diastolic dysfunction, Doppler tissue imaging exhibits patterns associated with elevated LV filling pressures. Mitral annular early diastolic velocity ratio (E/E TDI—annular or segmental) is a strong prognostic parameter, especially when E/E TDI is $\ge$15. Moreover, systolic intraventricular dyssynchrony measured by segmental analysis of myocardial velocities is another independent predictor of adverse clinical outcomes in heart failure subjects, even when the QRS duration is normal [12].

Speckle tracking is also useful in the evaluation of DCM. Left ventricle global longitudinal strain (GLS) is more sensitive compared to the ejection fraction in the detection of impaired systolic function. Moreover, the GLS is a prognostic parameter for the left ventricle reverse remodeling. A higher GLS is associated with a better reverse remodeling, even with a similar left ventricle ejection fraction. A GLS value more negative than –10%, which is reported as a cut-off, is related to better reverse remodeling and consequently with better long-term prognosis [13].

Some cases of DCM with severe systolic dysfunction (left ventricular ejection fraction $\le$35%) and wide QRS complex remain symptomatic, with chronic heart failure (NYHA class II–IV) despite optimal medical treatment. This subgroup of patients may benefit from cardiac resynchronization therapy (CRT) [14]. Patients who are CRT candidates may be evaluated by echocardiography to assess LV systolic and regional function and also cardiac dyssynchrony [15, 16]. Several echocardiographic modalities for dyssynchrony assessment are employed, such as conventional M-mode and pulsed-wave Doppler techniques [15, 16, 17]. While individual studies showed strong promise for the use of echo-derived mechanical dyssynchrony in determining response to CRT [15, 16, 17], multicenter studies failed to demonstrate prognostic benefit, hence echo is not currently used to assess mechanical dyssynchrony to determine CRT response [18].

Interventricular dyssynchrony is determined by the temporal phase shift between the contraction of the two ventricles. There are several useful parameters to define dyssynchrony at the level and they can be obtained by conventional pulsed-wave Doppler or Tissue Doppler imaging. A difference higher than 40 ms between left ventricular and right ventricular pre-ejection time (measured by pulsed-wave Doppler), and also a delay greater than 56 ms between the onset of systolic motion in the basal right ventricular free wall versus the most delayed basal LV segment (measured by tissue Doppler) are the most used parameters for defining the interventricular dyssynchrony, but they also have limited value for predicting CRT response.

Intraventricular dyssynchrony defined as inhomogeneity in myocardium contractility can be evaluated by conventional echocardiography, tissue velocity measurements, and deformation imaging. The temporal difference between septal to posterior wall contraction can be assessed by M-mode echocardiography, from a parasternal short-axis view at the papillary muscle level, by measuring the delay in systolic thickening of the myocardium [17, 19]. It is calculated as the interval between the maximal posterior displacement of the septum and the maximal displacement of the left posterior wall. Another parameter used for establishing intraventricular dyssynchrony is the value of the pre-ejection time, measured from QRS onset to aortic flow onset. The recognized cut-off values are septal to posterior wall motion delay above 130 ms and left ventricular pre-ejection time higher than 140 ms [8, 20]. There is no demonstrated predictive role for these parameters. In contrast to the described parameters related to the timing of myocardial velocity peaks, myocardial deformation parameters (strain, strain rate) may help in distinguishing active contraction from passive one caused by tethering of adjacent myocardial regions [8, 14, 15, 21]. These parameters may also be used during follow-up for highlighting the reverse remodeling process, and some of them as prognostic features for patients with DCM and LV systolic dysfunction [14, 15, 17, 20].

Ventricular remodeling describes structural changes in the left ventricle in response to chronic alterations in loading conditions. Current therapeutic strategies for systolic heart failure aim to slow or halt the remodeling process. Reverse remodeling refers to a concept, where progressive LV dilatation and deterioration in contractile function are not simply arrested, but partially reversed is defined as a process characterized by a reduction in LV volumes with improvement in systolic and diastolic function. Right ventricular function normalization is part of a global hemodynamic improvement induced by therapy and precedes LV reverse remodeling.

2D echocardiography in HCM detects a septal wall thickness higher than 14 mm as a diagnostic criterion for HCM, after excluding all the other causes of LV hypertrophy. The severity and distribution of hypertrophy in HCM are highly variable [23]. It may be concentric or localized (septal, apical, free LV wall, or right ventricle hypertrophy) with or without intraventricular obstruction (medio-ventricular, LV outflow). One pathognomonic echocardiographic feature is the asymmetric septal hypertrophy, with a ratio of septal to the posterior wall thickness of 1.5/1 [29]. The first echocardiographic criterion for the diagnosis of LV hypertrophy is the LV mass obtained by M-mode and defined by an LV mass index $\ge$134 g/m${}^2$ body surface area in men and $\ge$110 g/m${}^2$ in women. Current guidelines define severe hypertrophy with an LV mass above 130 g/m${}^2$ for men and $>$112 g/m${}^2$ for women [4]. An LV mass index having a value above 95 g/m${}^2$ indicates an abnormally hypertrophied LV [5, 28, 29, 30]. In obstructive HCM, another echocardiographic specific sign is an abnormal anterior motion of the mitral valve, which tractions the anterior mitral leaflet within the LV outflow tract against the IV septum due to anterolateral papillary muscle embedded in hypertrophic myocardium (see Fig. 5). The duration of the contact between the anterior mitral valve and the LV septum in systole determines the severity of the outflow pressure gradient [30]. Depending on the predominant localization of segmental myocardial hypertrophy, different HCM phenotypes can be distinguished including asymmetric (septal) involvement which is the most common form of the disease, and other variants including apical, symmetric, midventricular, mass-like, and noncontiguous HCM. According to the localization of the hypertrophy, the dynamic obstruction may be assessed at the outflow tract or medio-ventricular. One important prognostic parameter in patients with HCM is the dimension of the left atrium, its size is associated with a higher risk for adverse events. Enlarged LAVi in HCM is associated with the severity of diastolic dysfunction. A transverse diameter larger than 48 mm and a volume above 118 ml are related to a higher risk of atrial fibrillation onset and poor survival in patients with HCM [28, 30]. Malposition of the anterolateral papillary muscle with anterior displacement may be observed in HCM, causing the outflow tract gradient. Moreover, the calcification of the mitral annulus which is a sign frequently found in HCM is related to the dynamic outflow tract obstruction [28, 30].

Fig. 5.

Echocardiographic aspect of HCM. (A) Parasternal long-axis view diastolic frame showing increased thickness of septum and inferolateral wall. (B) Parasternal long-axis view systolic frame showing (arrow) systolic anterior motion of the anterior mitral valve. (C) Short axis view diastolic frame showing significant left ventricular hypertrophy. (D) Short axis view systolic frame showing reduced left ventricular end-systolic diameter.

Echocardiography may also identify a phenotype of HCM associated with small apical aneurysms, not due to ischemia. These patients frequently present with malignant ventricular arrhythmias and resuscitated cardiac death or systemic cardioembolism [31]. Thus, the presence of apical aneurysms in the setting of HCM is associated with an ominous outcome and needs prompt implantation of an ICD [32].

Doppler echocardiography allows assessment of the intraventricular gradient and associated mitral regurgitation. One specific feature is the variability of the LV outflow gradient according to the hydration status, heart rate, the Valsalva maneuver (preload), and blood pressure (afterload). Conditions or pharmacologic interventions that increase preload and increase LV end-diastolic volume may reduce LVOT obstruction. Reduced preload and tachycardia responsible for a reduction in LV end-diastolic volume are associated with an increase in intraventricular gradient. Stress echocardiography is a method that employs different agents (exercise, dobutamine, isoproterenol, amyl nitrite) which alter LV diastolic volume, to highlight the dynamic intraventricular gradient [5, 27, 33]. The degree of mitral regurgitation severity in HCM can vary from mild to severe. The mechanism of mitral regurgitation is related to the geometry change of the valve due to the malposition of the anterolateral papillary muscle, the abnormal attachment of primary chordae tendineae and SAM. The latter is favored by the elongated leaflets of the mitral valve which are a usual feature of the mitral valve in HCM. Moreover, some studies establish a direct linear relationship between the left ventricular outflow tract area and the mitral valve area, with a positive correlation with the severity of outflow tract obstruction (see Fig. 6) [27, 33].

Fig. 6.

Echocardiographic aspect of HCM. CW Doppler in a patient with obstructive hypertrophic cardiomyopathy shows typical systolic flow with a late peaking gradient of 85 mm Hg at end-systole. The aspect of the continuous Doppler curve is typical for obstructive HCM, with an early peak and major increase of meso-telesystolic velocities when intraventricular obstruction occurs. This is most obvious in relatively bradycardic patients who display the typical “pulsus bisferiens” pattern.

TDI offers important and early information about the subclinical systolic dysfunction showed by under normal values of the myocardium velocity contraction [34]. The explanation for this is the disarray among the myocytes and the increased fibrotic tissue. An early diagnosis and prognostic parameter assessing the systolic function of the LV in HCM is the longitudinal dysfunction by an S lateral value under 9 cm/s. This constitutes a criterion for differentiating pathological LV hypertrophy (HCM/hypertensive LV hypertrophy) from physiological LV hypertrophy. Moreover, a lateral mitral annular systolic velocity lower than 4 cm/s was found to have a prognostic value and independently predicted death or hospitalization for worsening heart failure [26, 35]. There are also data suggesting that systolic (Sa) and diastolic (Ea) myocardial velocities measured by TDI are decreased in subjects who have mutations causing HCM, but who do not have yet developed LV hypertrophy [26, 36].

The most specific feature of the myocardium in HCM is the reduced contractile stress (the force per unit area) because of the cardiomyocyte disarray and interstitial fibrosis [33, 37]. A maintained ejection fraction is explained by the increased end-diastolic wall thickness that produces an augmented thickening, but the histopathology of this disease is characterized by myocardial hypertrophy, fiber disarray, increased loose connective tissue, and fibrosis, which are all thought to interfere with force generation and relaxation of the cardiac muscle. Both speckle tracking and tissue Doppler highlight this feature, with a significantly lower longitudinal systolic strain, systolic strain rate, and early diastolic strain rate (see Fig. 7) [27, 28, 30, 37]. GLS is independently associated with outcomes in HCM patients. A GLS with a value higher than –10 percent is associated with a higher risk of adverse events. This depressed contractility function of the LV correlates also with myocardial fibrosis and predicts ventricular arrhythmias. Through strain echocardiography an important prognostic parameter can be obtained: the mechanical dispersion, defined as the standard deviation of time from the onset of the QRS to peak negative strain. This is related to the amount of fibrosis and is also an independent predictor for arrhythmias [28].

Fig. 7.

Echocardiographic aspect of HCM. (A) Apical 4 chamber view shows left ventricular hypertrophy. (B) The longitudinal strain bull’s eye plot derived from 2-D speckle tracking imaging shows a significantly reduced GLS (global longitudinal strain) of –8.1%, the most abnormal region is the basal septum, corresponding with the greatest wall thickness.

2D echocardiography, as mentioned before, highlights a low or normal diastolic volume of the LV associated with normal or only mildly reduced LV ejection fraction, as criteria for RCM. Also, one or both atrial enlargement is identified, with increased pressures, and normal pericardium. Once the typical pattern of RCM is identified, the echocardiogram can reveal also some features for a specific etiology. For example, in cardiac amyloidosis, the left and right ventricular walls are often mildly and symmetrically thickened, the myocardium may have a granular appearance, and myocardial strain imaging may show preserved apical function. However, it is not sufficient information neither to confirm, nor exclude cardiac amyloidosis [39, 40, 50], and further testing is needed. Moreover, in sarcoidosis global or regional (typically basal posterior and lateral) LV wall motion abnormalities may be observed. The most common finding is myocardial thinning, while less common findings include myocardial aneurysms, hypertrophy, and pericardial effusion [51, 52]. In eosinophilic inflammation of the myocardium or hypereosinophilic syndrome, the echocardiogram is often unrevealing during the initial necrotic stage. In the thrombotic stage of the disease, the damaged endocardium may have associated thrombus, predominantly involving the ventricular apex [3, 5, 38, 52, 53]. During the last, fibrotic stage, increased endomyocardial echogenicity is seen, affecting one or both ventricles, sometimes with overlying thrombus; the ventricular filling can be restricted, and atrioventricular valve leaflets may be tethered [53, 54, 55]. A pattern similar to hypereosinophilic syndrome can emerge in endomyocardial fibrosis. It may be characterized by LV, RV, or biventricular apical fibrosis [53, 54, 55]. In radiation-induced RCM the echocardiogram may show structural abnormalities within the field of radiation, such as calcified heart valves, a thickened pericardium, or focal wall motion abnormalities related or not to radiation-associated coronary artery disease [40, 42, 56, 57].

Doppler echocardiography and tissue Doppler imaging show diastolic dysfunction, frequently with a restrictive pattern. Different aspects of the diastolic function can be revealed, but usually more than grade 2 diastolic dysfunction, with increased filling pressures: an elevated peak mitral inflow velocity (high velocity of E wave), rapid early mitral inflow deceleration (low deceleration time). E/A ratio greater than 0.8, deceleration time of E wave lower than 200 milliseconds, and frequently lower than 160 milliseconds, E/e’ ratio with a value above 9, are features found in the echocardiographic examination of RCM (see Fig. 10 and Appendix Video 5) [1, 4].

Fig. 10.

Echocardiographic aspect of RCM. (A) Apical 4c view of an elderly patient with idiopathic restrictive cardiomyopathy, severe biatrial enlargement (left atrium $>$right atrium) with atrial fibrillation. (B) PW tissue Doppler recording of the septal mitral annulus showing mildly reduced myocardial velocities (systolic velocity of 5 cm/sec). A video of the apical 4 chamber view is available online (Appendix Video 5).

TDI is a valuable method of analysis of the systolic function in patients with suspected RCM, helping in the differential diagnosis between RCM and constrictive pericarditis. It offers information related to the contraction power of regional and global LV myocardium. Reductions in TDI systolic and diastolic parameters typically occur earlier in the natural history of the amyloid disease and other types of RCM compared to other traditional echocardiographic measurements. The diastolic function in TDI assessment has restrictive pattern, with low e’, and E/e’ (average of septal and lateral mitral annulus) $>$13 [58, 59]. Moreover, earlier in the natural history of the restrictive disease, abnormalities of mitral annular TDI parameters may classify the patient in the mild or moderate categories of diastolic dysfunction [38, 44, 60].

Strain echocardiography reveals low myocardial velocities with regional function inhomogeneity. In RCM due to cardiac amyloidosis, both LV and right ventricle (RV) walls are often moderately, or even severely, and symmetrically thickened and the myocardium may have a granular aspect. This aspect cannot be explained by secondary causes such as hypertension. In this case, strain echocardiography may show preserved apical function [45, 46, 47]. Regarding the LA function, strain echocardiography may help in the differential diagnosis between RCM and constrictive pericarditis (CP). In both RCM and CP, the reservoir function of the left atrium is normal or may be increased compared to normal due to higher filling pressure. Contrary to this, both active and passive functions are decreased in RCM. This can be evidenced using global and regional strain, which highlights a lower value compared to normal of the septal LA strain rate [61].

Arrhythmogenic cardiomyopathy (AC) is defined by fibrous and fibro-fatty replacement especially of the RV myocardium, affecting the inflow and outflow tract, but also the apex. This process most commonly affects the posterior and inferior areas of the right ventricular inflow tract adjacent to the tricuspid valve, but it also affects the anterior infundibulum and the apex, thus forming what is known as the “triangle of dysplasia”. According to recent data, there is also involvement of the postero-lateral wall of the LV. In the LV the fibro-fatty replacement determines a transmural lesion but the process starts from the subepicardial to the subendocardial LV layers. It has been demonstrated that in left ACM, the scar tissue tends to localize in the inferolateral subepicardial LV wall. In the initial assessment of AC, these typical regional wall motion abnormalities may be detected. Later changes may involve the RV free wall and become global, producing RV dilation (Fig. 11 and Appendix Video 6). Echocardiography is the first line and sometimes a sufficient method of evaluation in patients with AC.

Fig. 11.

Echocardiographic aspect of AC. Apical 4 chamber view showing dilation and thick right ventricular free wall. A video of the apical 4 chamber view is available online (Appendix Video 6).

The current guideline for a positive diagnosis involves the cardiac evaluation through echocardiography, magnetic resonance, or angiography to detect global or regional dysfunction of the RV and/or structural changes (Table 1, Ref. [62]). The right ventricle myocardial performance index (RV MPI) can be used in the baseline evaluation and follow-up for patients with AC, as it was shown to be a strong predictor for major cardiovascular adverse events, with a cut-off of 0.67.

TAPSE and fractional area change, as parameters of RV systolic function assessment, are prognostic factors in AC. RV ejection fraction estimation through 3D echocardiography, lateral systolic myocardium velocities by TDI and regional systolic strain have lower values in patients with AC [62, 63, 64, 65]. However, layer-specific GLS can predict arrhythmic risk in AC [66].