It is characterized by LV dilation associated with global systolic dysfunction, in the absence of volume or pressure overload. The prevalence of dilated cardiomyopathy (DCM) is variable, reflecting the geographical and ethnic differences, as well as the methodologies used. A prevalence of 1:250 is estimated, based on the frequency of the left ventricular dysfunction as an expression of DCM.27 The criterion to define LV dilation is the final diastolic diameter > 2.7 cm/m². With increased gradual dilatation on the short axis, the LV cavity becomes spherical, with sphericity index (long/short axis dimension) close to 1 (normal value > 1.5).28 Wall thickness is usually normal, but the myocardial mass is increased. The degree of impairment of systolic function is variable, and systolic dysfunction is often progressive. LV volumes are calculated in a more reproducible and accurate way by using the 3D echocardiography. Abnormalities associated with diastolic function may be present, contributing to the variation in the clinical and hemodynamic presentation of DCM. The involvement of the RV can be evidenced, but it is not a criterion for the diagnosis of DCM.29 Notably, DCM is associated with an increased risk of severe arrhythmia, indicating the pathological involvement of the cardiac conduction system. Complex remodeling of one or both ventricles contributes to the secondary features of DCM, which include functional mitral and tricuspid regurgitation, enlarged atria, intracavitary thrombi, and evidence of low cardiac output.28 In the context of DCM, the analysis of diastolic function aims to estimate the filling pressures; and the mitral flow pattern is usually enough to identify patients with increased LA pressure. E-wave deceleration time is an important predictor of outcomes in these patients.30 Other diastolic dysfunction parameters, including the E/e’ ratio, have good correlation with pulmonary capillary pressure and have an additional prognostic value for LVEF.30

Echocardiography is the imaging method of choice for the evaluation of DCM patients, providing key data not only for diagnosis, risk stratification and treatment definition, but also plays a key role in the evaluation of family members.28 Key echocardiography indications in the evaluation of DCM are displayed in table 1. Transthoracic echocardiography (TTE) is indicated in the initial evaluation of patients with heart failure and suspected DCM. TTE is recommended in first-degree relatives of DCM patients due to the high incidence (20 to 50%) of familial DCM.28 Several echocardiographic parameters were used to assess mechanical desynchrony in patients with DCM. However, the broader role of echocardiography in the selection of patients for cardiac resynchronization therapy remains undefined. Currently, echocardiographies are limited to patients with borderline QRS duration (120 to 149 ms), whose presence of intra- or interventricular desynchrony may provide additional information.28 The echocardiography guiding the placement of electrodes at the site of greater mechanical activation delay (evaluation by speckle tracking) showed benefit in heart failure free survival, with a more favorable impact on ischemic heart disease compared to DCM.31

Chagasic dilated cardiomyopathy (CCM) presents similar characteristics to idiopathic DCM, but with predominance of segmental changes in contractility, especially in the basal segments of the inferior and inferolateral walls.32 Apical aneurysm is a typical CCM finding and is useful in the differential diagnosis of dilated cardiomyopathies.33 The morphology of aneurysms is variable and non-standard sections are often required for the identification of apical contractile changes. The presence of thrombi within the aneurysms is frequent and associated with cerebral thromboembolic events.34 Diastolic dysfunction is universally present in patients with CCM and heart failure.35 The main echocardiographic parameters previously studied with a prognostic value in CCM are LVEF, right ventricular function, LA volume and E/e’ ratio.33^,36 The contractile function of the LA evaluated by the negative peak of the global atrial strain was an independent predictor of clinical events in the CCM.35 The heterogeneity of systolic contraction, quantified by mechanical dispersion to speckle tracking, was associated with ventricular arrhythmias in patients with CCM, regardless of LVEF.37 Recommendations for performing TTE in CCM are set out in table 1.38

Cardiac resynchronization therapy is an established treatment option for patients with heart failure with marked reduction of LVEF. The echocardiography is fundamental in the indication, estimation of success and evaluation of the results of this procedure and may also contribute to the recovery of unfavorable results. This treatment is indicated as class I in patients with heart failure (New York Heart Association (NYHA) functional class II, III or IV), with LVEF lower than 35%, optimized medication and left bundle branch block with QRS duration above 150 ms.28 Also in class IIa and IIb indications, it is necessary to recognize the reduction of the LVEF below 35%, being contraindicated when this value is not present. Therefore, in the possibility of indication for cardiac resynchronization therapy, transthoracic echocardiography is a class I indication, level of evidence C. In this examination, it is mandatory that LVEF be obtained by the Simpson 2D method, with a description, in the report, of their volumes. It is also possible to use the 3D methodology, of less variability, although still unproven in this clinical scenario. Approximately 30% of patients do not present clinical improvement or significant reduction in LV final systolic volume.39 TTE can provide information that helps identify a greater probability of successful treatment response, such as the presence of mechanical, inter- and intraventricular desynchrony, the presence of myocardial reserve and determination of the last site of activation, which may be associated with higher degree of fibrosis. To this end, the use of a variety of methods is encouraged, from the visual evaluation of 2D echocardiography, M-mode,40 tissue Doppler and, especially, the use of a technique that evaluates longitudinal41 or radial myocardial deformation.42^,43 In the evaluation of successful response to treatment, it is expected, in regards to imaging, mainly negative remodeling to be observed, usually characterized by reduction of 15% of the initial systolic volume, analyzed between 3 and 6 months of the implant.39^,44 In case the negative remodeling and/or the clinical improvement of the patient is not met, one possibility is to adjust the pacemaker, guided by TTE, to optimize the atrial and ventricular stimulus intervals. The main correction in this case seems to be adjustment of the atrial and ventricular stimulus intervals, guided by the echocardiography, which allows for retrieval of the results.45^,46

The echocardiography is the main noninvasive imaging modality as well as the most versatile one in the evaluation and monitoring of patients after cardiac transplantation, providing accurate information on morphology and graft function. From the immediate postoperative period up to the moment of hospital discharge, serial echocardiographic exams are recommended both to identify and monitor surgical complications and early graft dysfunction, whether due to primary or secondary causes (e.g., reperfusion injury, non-responsive pulmonary hypertension (class I, level B).47^,48 In the presence of early graft dysfunction, the echocardiography usually shows an overall reduction in myocardial function (LVEF < 45%), loss of the contractile reserve, increase in RV volume with systolic dysfunction (tricuspid annular plane systolic excursion - TAPSE < 15 mm or RV ejection fraction < 45%).47 A comprehensive echocardiographic examination (class I, level B) is recommended in the sixth month after cardiac transplantation), which will serve as the baseline for assessing graft morphology and function during sequential and regular follow-up examinations (interval and frequency of exams in figure 1).47 Quantifications of cardiac chambers size and volumes, RV systolic function, LV diastolic and systolic parameters, and pulmonary arterial pressure should be performed on the sixth month and subsequent echocardiographies.47 It is recommended that such echocardiographic studies also include advanced methodologies, such as the study of myocardial deformation (strain) and 3D evaluation of the volumes and function of cardiac chambers and tricuspid valve (frequently injured during the endomyocardial biopsy procedure), for providing a more accurate and comprehensive analysis (class I, level B).47

Figure 1

^*Graft dysfunction: confirmed on echocardiographic examination by dropping the ejection fraction by more than 10% to a value lower than 50%, compared to the baseline examination of the sixth month; ^§patients with graft dysfunction suspected or confirmed; clinical symptoms of a possible new cardiac abnormality; alterations in the resting electrocardiogram.

Current cancer therapy is quite effective in some types of tumors, though it can induce cardiovascular complications. Cardiotoxicity (CT) induced by cancer treatment is recognized as the major cause of morbidity and mortality in cancer survivors.61 Before starting anti-neoplastic treatment, it is essential to access the risk of CT,62 taking into consideration: (a) the specific risk of the drug used in chemotherapy, as some of them may affect the cardiac function (anthracyclines, trastuzumab), while other ones, the vascular function (5-fluoracil, capecitabine), or both (bevacizumab); (b) the use of radiotherapy, as it increases the risk of heart failure when concomitant with anthracyclines, pericardial lesion (constrictive pericarditis) and coronary artery disease; (c) the presence of previous risk factors, such as age > 65 years, female gender, hypertension, diabetes mellitus, coronary artery disease and history of heart failure. All patients receiving potentially cardiotoxic drugs should be periodically monitored for CT signs, which can be classified according to the injury the drug used produces.63 CT Type I, potentially irreversible, anthracycline-related dose, is dose-dependent, mainly at > 250 to 300 mg/m² (often used in the treatment of breast cancer, lymphoma, leukemia, and sarcoma). It most commonly occurs in the first year of chemotherapy, or even two to three decades after completion of treatment, as progressive systolic dysfunction. It may rarely present as an acute systolic dysfunction, immediately after dosing. Type II CT, which is potentially reversible, mainly related to trastuzumab (used in the treatment of breast cancer in patients with increased HER2 receptor expression), has no relation to the cumulative dose.63 Such information is the basis for the algorithms of serial left ventricular function monitoring during and after treatment of cancer patients, published by the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE).3 The most historically used parameter is LVEF, calculated by TTE using the Simpson biplanar 2D method.4 LVEF values ​​between 53 and 73% should be considered normal in the evaluation. The main advantages of 2D TTE in relation to other imaging modalities, such as radioisotope ventriculography and magnetic resonance imaging (MRI), are: greater availability, lower cost, possibility of serial re-evaluations and greater safety (absence of radiation and limitation in patients with renal insufficiency). 3D TTE, used in sequential and comparative MRI evaluations for LVEF assessment, showed reproducibility comparable to MRI and better accuracy than 2D TTE,64 being more indicated, when available, in the serial evaluation of these patients.65

The definition of CT due to chemotherapy was defined by the consensus of these two societies3 as the decrease of LVEF > 10 percentage points to values < 53% and should be confirmed after 2 to 3 weeks of diagnosis by new imaging. This decrease may or may not be accompanied by symptoms of heart failure and may or may not be reversible. One of the major limitations of the use of LVEF for CT diagnosis in the follow-up of these patients is that changes in LVEF occur later. In order to minimize the risk of developing irreversible cardiomyopathy, it is essential to identify early signs of CT, since the administration of cardioprotective medication in this phase may result in an improvement in cardiac function.66 Thus, the search for a technique that allows subclinical and early detection of CT before LVEF decrease or the onset of clinical symptoms has been an area of intense investigation. In this scenario, the use of GLS gained importance, evaluating myocardial deformation. Such technique has inter- and intraobserver reproducibilities smaller than the LVEF obtained by the 2D TTE, but is limited by the variability of normal values ​​according to the brand of the equipment used, age and gender of the patients.67 Systematic review confirmed the prognostic value of the alterations in GLS for CT, preceding the LVEF decrease obtained by 2D or 3D TTE.15 The consensus recommends serial GLS evaluation in patients at risk of CT, with subclinical left ventricular dysfunction suggestive of a fall of > 15% of the baseline value, even without LVEF change.63 The relative decrease between 8 and 15% suggests a more rigorous follow-up. GLS Variation of < 8% is consistent with absence of subclinical dysfunction.63 Although some studies have drawn attention to changes in diastolic function following chemotherapy,68 there is no current evidence to support such parameters as indicative of CT.63 A use of biomarkers in the assessment integrated with imaging methods in chemotherapy patients evidenced the importance of troponin I (TnI) with a high negative predictive value in the detection of CT.69 It is probable that patients who do not evolve with TnI elevation have lower probability of events and perhaps less need for imaging tests in subsequent evaluations.69^,70 There is still no robust scientific evidence based on randomized clinical trials to support the algorithms proposed by the European Society of Oncology71 and the consensus of EACVI and ASE,63 in the follow-up of these patients; however, these documents represent current knowledge in the area. The orientation of the EACVI - ASE consensus63 to the present moment is:

Initial evaluation of left ventricular function before the start of chemotherapy in patients who will use potentially cardiotoxic chemotherapeutics. If it is not possible in all patients, it is recommended in those at high risk for the development of CT: age > 65 years, previous left ventricular dysfunction, predicted use of high doses of anthracyclines (type I) or combination of type I and II drugs. To perform the LVEF assessment by the 3D TTE if available or, alternatively, by the 2D TTE (Simpson method). It is desirable that the evaluation by GLS and TnI is carried out. If not possible to perform GLS, report the S-wave of the medial and lateral tissue Doppler of the mitral annulus. Further monitoring of left ventricular function is recommended after this initial evaluation, depending on the chemotherapy to be initiated.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiovascular disease characterized by increased left ventricular wall thickness ≥ 15 mm in adults, with non-dilated ventricular cavity not explained by abnormal loading conditions, such as arterial hypertension or valve aortic stenosis.72 Minor hypertrophy degrees (13 to 14 mm) may also diagnose HCM, particularly among relatives of these patients. TTE is considered the initial imaging for diagnosis, stratification of the risk of cardiac events and management of patients with HCM. Among the parameters to be evaluated in HCM are: location and hypertrophy degree; identification of obstruction and intraventricular gradient at rest or intentionally caused; presence of magnitude of mitral reflux; systolic and diastolic function; and LA size. Any hypertrophy pattern may be found, though the asymmetric is the most frequent one (75% of cases), and it is more common at the confluence of the anterior interventricular septum with the LV free wall.73 Other forms of hypertrophy are: basal, concentric, apical and lateral wall. There is a linear association between maximum myocardial thickness and sudden death, with greater risk in patients with thickness ≥ 30 mm.72^,74 Gradual identification of the LV outflow tract is important in the management o symptoms and in the stratification of the risk of sudden death.72 TTE evaluation generally characterizes the presence of LV outflow tract obstruction (instantaneous gradient ≥ 30 mmHg) at rest (one third of patients) of after provocative maneuvers (one third), such as exercises (echocardiography under physical stress) or Valsalva maneuver. Echocardiography under physical stress can be very useful in patients with HCM, since in addition to detecting the presence and degree of obstruction during effort, it allows the objective evaluation of symptoms, functional capacity, systolic blood pressure response and the presence of secondary mitral regurgitation. Approximately 25% of HCM patients have abnormal blood pressure response during exercise, characterized by a drop in systolic pressure or by failure to increase in > 20 mmHg. This finding has been interpreted as a risk factor for unfavorable prognosis and sudden death.75 Stress echocardiography with dobutamine is not recommended. The cut-off value of the intraventricular gradient ≥ 50 mmHg at rest or after provocative maneuvers is considered when indicating surgical treatment or percutaneous intervention in symptomatic patients, despite therapy with optimized medication.72 Patients with HCM in general have diastolic dysfunction, commonly with altered relaxation (grade I), though without significant correlation between mitral flow data and LV filling pressures. Thus, the integrated approach of mitral Doppler data, tissue Doppler, pulmonary vein flow and LA volume is recommended in these patients.76 LVEF is normal or increased in most patients, giving the false impression of preserved systolic function. However, longitudinal strain assessment invariably shows a global and regional decrease (coincident with sites of greater hypertrophy) of contractility.77 Estimating the size of the LA is fundamental, as there is a significant correlation between the dilation of the chamber and an increased risk of cardiovascular events, such as atrial fibrillation and sudden death. The main complication of HCM is sudden cardiac death (SCD), especially in young and apparently healthy individuals.78^,79 Cardiac defibrillator implantation for primary or secondary prophylaxis may reduce mortality from this complication and is the only therapy with evidence of life-saving potential.80 TTE has a relevant role in the two most commonly used risk stratification scores form SCD in HCM, which determined the relationship between come clinical risk factors and prognosis. In the American model of primary prevention, one of the risk factors among 5 variables is the presence of interventricular septum thickness ≥ 30 mm.75 In the European model, of the seven variables analyzed, three of them are provided by TTE: septum thickness, LA and left ventricular outflow tract (LVOT) gradient at rest or after Valsalva maneuver.72 Family screening of first-degree relatives of HCM subjects should be performed periodically due to their risk of developing the disease. Recommendations for the use of echocardiography in HCM are summarized in table 2.

Restrictive cardiomyopathies (RCM) are a group of entities characterized by abnormalities in the ventricular filling pattern, which may be associated with thickened and rigid walls and generally preserved systolic function. RCMs comprise various entities, including, endomyocardial fibrosis (EMF), endomyocardial fibroelastosis, Löefler parietal endocarditis, infiltrative (such as amyloidosis and sarcoidosis), storage (such as hemochromatosis and Fabry disease), idiopathic and other forms secondary to different processes (scleroderma, carcinoid syndrome, metastases of systemic neoplasms, anthracycline toxicity and irradiation heart disease).81 Diagnosis by echocardiography is based on common anatomical and functional changes: ventricular cavities of normal or reduced size, usually with Doppler degree III diastolic function (restrictive type), generally preserved overall systolic function, and dilated atria. Tissue Doppler analysis shows velocity e’ obtained in the septal mitral annulus usually below 7.0 cm/s, a useful measure in constrictive pericarditis differentiation.82 In amyloidosis, there is thickening of the atrioventricular valves, myocardial walls, and eventually the atrial septum, with a more intense (ecorrefringence) reflection and “granular and sparkling” myocardial aspect.83 The GLS analysis of the LV with 2D echocardiography in amyloidosis observes very low values, especially in the mid and basal segments with relative “apical sparing” (it aids in the differential diagnosis with other diseases).84 In EMF, one may observe: obliteration of the apex by fibrosis, signs of ventricular restriction, and involvement of the atrioventricular valves. The fibrosis of the apical thrombi is differentiated due to absence of akinesia or dyskinesia in the left EMF. Another differential diagnosis is apical HCM, which presents no endocardial thickening or restrictive pattern and displays specific electrocardiographic changes. Cardiac sarcoidosis may present with regional contractile abnormalities and non-ischemic distribution aneurysms. GLS measure represents an early marker of myocardial involvement in sarcoidosis and the magnitude of the reduction is associated with poor prognosis.85 The recommendations for TTE in RCM are set out in table 3. Transesophageal echocardiography (TEE) is indicated when there are technical difficulties to TTE and in the transoperative monitoring of fibrosis and apical correction of valve defects.

Arrhythmogenic cardiomyopathy (AC) is considered an inherited cardiomyopathy with autosomal dominant transmission, predisposing to the emergence of ventricular arrythmias, sudden death in young people, ventricular dysfunction and heart failure. Due to the frequent involvement of the LV, the use of the term CA is currently recommended, which comprises both ventricles, replacing the term “arrhythmogenic dysplasia of the RV”.86 The disease is characterized by a progressive replacement of the ventricular myocardium by fibrous and adipose tissue, which can lead to thinning of the wall and aneurysm formation. In the RV, the process is typically located in the inferior, apical and infundibular walls (dysplasia triangle), and may be diffuse or segmental. LV involvement occurs in more than half of the cases, typically located in the subepicardium or mesocardium, and often confined to the inferolateral segment. Echocardiography is the imaging modality of choice in the initial assessment of AC (Table 4) and the most commonly used propaedeutic method for patient follow-up.87 Typical morphologic features in patients with CA include regional contractile abnormalities and/or dilation and right ventricular dysfunction. Among the traditional echocardiographic criteria, derived from 2D echocardiography, proposed for the diagnosis of AC,88 are: presence of akinesia, dyskinesia or right ventricular aneurysm; increased ventricular outflow tract diameter (measured on long and short parasternal axis); and reduction of the fractional variation of the RV area. Recently, the routine and systematic addition of other echocardiographic measurements and techniques was recommended in order to improve evaluation:89

Conventional parameters: basal RV diameter (normal ≤ 41 mm); systolic excursion of the annular tricuspid plane (TAPSE - normal ≥ 17 mm).

In short, TTE, preferably with analysis of conventional and advanced parameters, is indicated in patients with suspected or established AC (evaluation of disease progression), as well as in family screening of first-degree relatives.

Non-compaction cardiomyopathy (NCC) is considered a distinct cardiomyopathy, marked by genetic heterogeneity, with an overlapping of different phenotypes and great variability of clinical presentation. As a consequence, there is still controversy in the literature regarding its nomenclature: whereas for the American Heart Association (AHA)90 it is considered a primary cardiomyopathy, the European Society of Cardiology (ESC)81 considers it an unclassified disorder. Its pathogenesis implies early interruption of compaction of the trabecular meshwork of the LV during embryogenesis, resulting in the formation of two layers: a thin compacted epicardial layer and a thick endocardial one (similar to a “spongy” mesh) with marked trabeculations and deep intertrabecular recesses. The 2D echocardiography is the basis for diagnosis, follow-up, and better delineation of NCC phenotypic expressions.91 Several criteria have been employed in diagnosis, taking into account the increase in the proportion of the non compacted layer (for example, the non compacted/compacted ratio at the end of systole > 2), presence of excessive trabeculation, hypokinesia of non compacted areas (commonly located at the apex and lateral wall) and visualization of flow in the recess (via color Doppler). New techniques have recently been incorporated to aid in diagnosis, such as the use of echocardiographic contrast, 3D echocardiography and myocardial strain for the analysis of regional deformation and rotation (which assumes a characteristic pattern in this nosological entity).92 Therefore, it should be noted that the diagnosis of suspected cases has increased in recent years, due to advances and improvements in imaging methods, as well as the perception of the need to actively investigate first-degree relatives affected by the disease (described in 13 to 50% of this specific group).93 On the other hand, increasingly frequent “exam findings” (physiological versus pathological variants) have been reported in clinical practice, leading to the worrisome excess of diagnoses.7 Therefore, it is recommended to carry out a comprehensive evaluation, including clinical, electrocardiographic data and careful analysis of the findings in complementary imaging studies.94 The recommendations for performing the echocardiography in NCC are set out in table 5.

TTE, in addition to diagnostic confirmation, provides information necessary for follow-up and decision making in mitral regurgitation(MR).127 TTE identifies dilation of cardiac cavities and dysfunction of both ventricles, in addition to allowing the classification of regurgitation into primary (due to valve lesions) or secondary (caused by changes in LV geometry). The 3D echocardiography is more accurate in volumetric measurements and left ventricular function; it can be useful in the evaluation of RV4 and allows better visualization of the valve apparatus and planning of interventions.12^,133 The evaluation of the regurgitation degree can be made by the integrated approach of multiple qualitative and quantitative parameters: cavity dilations, pulmonary artery pressure, mitral inflow velocity, pulmonary vein flow pattern, mitral regurgitation density and duration analysis, calculus of the jet area or regurgitant volume, vena contracta measurement and regurgitant orifice measurement (flow convergence method, or proximal isovelocity surface area - PISA).133 Challenging situations for echocardiography are the presence of multiple and/or eccentric jets, cardiac arrhythmias and acute MR. In these cases, special emphasis should be given to integrated analysis relating anatomical and hemodynamic parameters. The improvement of quantitative measures, such as PISA and vena contracta, through the 3D echocardiography, can aid in the evaluation of eccentric reflux.132^,134 Another important point is the measurement of left ventricular function, especially in asymptomatic patients, which can be overestimated by LVEF measurement, with implications for deciding the best time for intervention and for postoperative outcomes. Recently, measurement of myocardial deformation (strain) has been studied to more sensitively identify ventricular dysfunction, but despite good prospects, it still requires more studies and standardization.131^,135^,136

TEE, whether 2D or 3D, is indicated for evaluation of the regurgitation mechanism in the care of inappropriate transthoracic images or in discrepancies between echocardiographic and clinical parameters.4^,133 The general recommendations for the use of the various modalities of echocardiography in MR are contained in tables 11, 12 and 13.

The diagnosis of mitral stenosis (MS) using echocardiography makes it possible to define its probable etiology as a consequence of a wide evaluation of the valve anatomy.137 The hemodynamic characterization of the gradients and valvular area, together with the description of thickening, leaflet mobility, subvalvar involvement and degree of calcification of the commissures, determines the progression stage of the disease and defines the most appropriate type of treatment when the disease is symptomatic. The joint interpretation of the echocardiography and the clinical symptoms determines the indication of surgical intervention or balloon catheter valvuloplasty.137 Recently, MS has been grouped into four distinct categories, based on anatomy, Doppler evaluation, presence of pulmonary hypertension, repercussions on LA, and symptoms: stage A (patients at risk for MS); stages B and C (asymptomatic patients, but with hemodynamic changes); and stage D (symptomatic patients with hemodynamic changes). Table 14 describes the parameters that must be included in the echocardiography to make this evaluation complete.138^,139 The use of TTE usually defines the anatomy and severity of the lesion (Table 15), but there are indications for the use of TEE, such as in situations of technically difficult echocardiographic window or 24 hours before balloon catheter valvuloplasty to rule out the presence of thrombi in the LA (Table 16).138^,140^,141 3D echocardiography, in the TTE or TEE modalities, has been shown to allow better anatomical analysis and more accuracy in the valvar area calculated by planimetry.142^,143 Physical or pharmacological stress echocardiography (dobutamine) may be used in the discordance between symptoms and resting echocardiography data.138 Such phenomenon of incompatibility between symptoms and hemodynamic repercussion can result from the disproportion between the valve area and the patient’s body size, or the lack of complacency of the valve orifice (which should increase during exercise).144 On a low-dose dobutamine echocardiography, the mean mitral transvalvular gradient should increase above 18 mmHg145 in order for MS to be considered the cause of the symptoms, while on exercise echocardiography (treadmill), the significant cut-off value is one elevation above 15 mmHg.138^,144 The increase in systolic pressure in the pulmonary artery is considered of clinical value only during the exercise echocardiography and should reach at least 60 mmHg so that pulmonary hypertension is considered secondary to MS. Other less frequent indications of a stress echocardiography may be found in asymptomatic patients with marked stenosis (Table 17).144 Care should be taken to diagnose associated lesions in MS, whether it is a significant MI (which imposes a limitation on balloon catheter valvuloplasty) or lesions on other heart valves.

TTE is the first-line method (Table 18) for the diagnosis and assessment of the severity of aortic valve stenosis (AVS).128^,146^-148 The definition of the moment of surgical or percutaneous intervention depends on the integrated analysis of clinical and echocardiographic parameters (valvular anatomy, Doppler valvular hemodynamics and repercussion on cavity size and pulmonary artery pressure) that allow to classify aortic stenosis into four stages: stage A (risk of AVS); stage B (mild and moderate asymptomatic AVS); stage C (asymptomatic marked AVS), subdivided into C1 (with LVEF ≥ 50%) and C2 (LVEF < 50%); and stage D (classical symptomatic marked AVS).149 In some AVS subgroups, valve area is reduced in the low gradient and low flow periods, either due to the concomitance of left ventricular dysfunction (LVEF < 50%) or the presence of small and hypertrophied LV, despite preserved LVEF). These subgroups are designated as stage D2 (with decreased LVEF) or D3 (with normal LVEF).146^,147^,150 In these discrepancy situations, in which valve area is ≤ 1.0 cm², the gradient is < 40 mmHg and LVEF is preserved (AVS with low paradoxical gradient or with low gradient and normal flow), additional methods such as TEE (3D, if possible), computed tomography or cardiac resonance may be necessary to confirm the severity of AVS.147 TEE allows a better evaluation of the aortic valve anatomy (valvular calcification), etiology (degenerative, congenital or rheumatic), LV exit path (diameter and geometry, mainly 3D) and greater accuracy in the calculation of valvular area, either by continuity equation or by direct planimetry.147^,150 The absence of significant calcification should alert to the possibility of sub- or supravalvar obstruction. In good-quality images, 3D TTE also allows for a more accurate LVEF assessment and a calculation of ejection volume (aortic transvalvular flow) by subtraction of final diastolic and systolic volumes, without the need to use LV exit pathway measurement and Doppler. This calculation, however, should be analyzed along with the other parameters, once it may also underestimate aortic transvalvular flow.147^,150 If the calculation of the valve area is made during hypertension (blood pressure ≥ 140 x 90 mmHg), it should be repeated after blood pressure control because it may underestimate the transvalvar flow. Reduction in LV systolic function by GLS measurement, with no other explanation, in the presence of preserved LVEF, favors the diagnosis of severe AVS with low paradoxical gradient. Stress echocardiography with low dose of dobutamine, with calculation of the projected area of ​​the valve, if necessary,144^,147 should be performed if there is marked aortic stenosis with low-flow/low gradient and left ventricular dysfunction (stage D2) to distinguish truly marked stenosis from pseudostenosis and to evaluate the contractile reserve (Table 19). Echocardiography under physical stress is recommended to unmask symptoms or to provide prognostic information on moderate or marked asymptomatic AVS with preserved LVEF (stages B or C) (Table 19). An increase in the mean pressure gradient (> 18 to 20 mmHg), the absence of contractile reserve and the increase of pulmonary artery systolic pressure (PASP) > 60 mmHg during exercise are parameters of worse prognosis and require follow-up at shorter intervals.144 Stress echocardiography may also be useful in low-flow/low paradoxical gradient (with preserved LVEF), asymptomatic or with mild or doubtful symptoms, to confirm the severity of AVS using the same criteria.144 In suboptimal images, the evaluation of LVEF can be improved by the use of myocardial contrast, to better delineate endocardial borders.147 The invasive hemodynamic study is restricted to situations in which noninvasive imaging tests are inconclusive.146^,149 The follow-up interval with TTE depends on the stage of the disease and predictors of poor prognosis. Accentuated aortic valve calcification is another predictor of more severe stenosis and worse clinical progression.151 Marked AVS with low paradoxal gradient has worse prognosis when compared to classical AVS and the remaining AVS subgroups.150 The paradoxical low gradient and normal flow (LV > 35 mL/m²) seems to have a prognosis similar to that of moderate AVS, but should be accompanied by shorter intervals, particularly if symptomatic.147 In classical AVS, the maximum velocity ≥ 5m/s152 and an annual increase in maximum velocity ≥ 0.3cm/s151 in serial examinations (recorded in the same incidence and with the same quality) are predictors of worse prognosis and of faster progression.146^,147^,149

In patients who are candidates for percutaneous implantation of aortic prosthesis for the treatment of AVS, 3D TEE can be used to evaluate the diameter of the ring, but it depends on the operator and image quality and should be used only when there is contraindication to computed tomography. On the other hand, 3D TEE is recommended to monitor the procedure and to evaluate outcomes or complications (Table 20).148

Echocardiography is the first-choice method to confirm diagnosis and etiology and to assess the severity and hemodynamic consequences of aortic regurgitation (AR).133^,153 AR can be observed due to primary diseases of the aortic valve (AV) or to abnormalities of the aortic root and ascending aorta. Degeneration of AV and bicuspid aortic valve are the most common etiologies. Other causes include rheumatic fever, fibrosis or infection, alteration of the valvular apparatus support or dilatation of the valve ring. The integrated analysis of clinical and echocardiographic parameters (valve anatomy, aortic root and ascending aortic root diameters, Doppler valvular hemodynamics and repercussions on cavity size and pulmonary artery pressure) allows the classification of AR in four stages: stage A (risk of AR), stage B (mild to moderate asymptomatic AR), stage C [asymptomatic acute AR without (C1) or with dysfunction/dilation of LV (C2)]; and stage D (symptomatic acute AR).149 In suboptimal images, LVEF measurement may be more accurate with the use of myocardial contrast to delineate the endocardial borders.133 TEE (with 3D if available), tomography or cardiac resonance may be necessary to better assess the aortic root and ascending aorta (especially in the case of a bicuspid aortic valve), the severity of AR, or the quantification of LV ejection volumes and ejection fraction.133 The appearance of symptoms in AR drastically changes prognosis. Effortless echocardiography may be indicated to reveal the presence of symptoms or to investigate other causes not related to AR (diastolic dysfunction, pulmonary hypertension or dynamic MI).144 However, it should not be used to assess severity, once that increased heart rate shortens diastole, limiting quantification.144 The follow-up interval with TTE depends on the stage of the disease and the presence of aortic dilatation associated with bicuspid aortic valvopathy.148^,154 Recommendations for the use of the various modalities of echocardiography in AR are set out in tables 21 to 24.

TTE is the first-line method for evaluating tricuspid valve abnormalities (Table 25).146^,148^,149 In most cases, tricuspid regurgitation (TR) is secondary to tricuspid ring dilatation and leaflet pull due to distortion and right ventricular remodeling, which occur due to volume or pressure overload caused by diseases of the left side of the heart , pulmonary hypertension, pulmonary valve stenosis, among others. In this context, leaflets are structurally normal. Primary causes of TR are rarer and may be due to infective endocarditis (mainly drug users), rheumatic heart disease, carcinoid syndrome, myxomatous disease, endomyocardial fibrosis, corneal rupture related to endomyocardial biopsy, Ebstein’s anomaly, and congenital dysplasia, among others.133 Similar to mitral and aortic valve disease, it can be classified into four stages (A to D).149 A thorough analysis of valvular anatomy by TTE is fundamental for the diagnosis of the etiology and mechanisms involved. It is necessary to measure the diameter of the ring and the use of all indexes of RV systolic size and function.133 These measures help in decision making regarding the moment of the surgery and in the surgical planning. In situations of doubt regarding the RV, 3D TTE can be used, although it still requires more validation. Cardiac resonance remains the gold standard.146 In this context, TEE is not recommended due to the anterior location of the RV, which makes it difficult to see through the transesophageal route.148 Significant primary TR requires intervention before RV impairment.146^,149 Secondary TR is usually treated when left side valve disease is corrected. As in the other valvopathies, the echocardiographic follow-up interval depends on the stage of the disease, but the etiology of the disease must also be considered. In the case of secondary TR, it is appropriate to follow the recommendations described for left heart valve dysfunctions. Significant annular dilatation (≥ 40 or > 21 mm/m²) and dilatation or progressive RV dysfunction should alert for earlier follow-up.133 Tricuspid stenosis (TS) is an uncommon condition that, if present, is frequently associated with TR of rheumatic origin.146^,149 In this case, the presence of associated mitral stenosis is common, which is usually the predominant lesion. Other causes are rare, such as congenital diseases, drugs, Whipple’s disease, endocarditis, and large right atrial tumor.146 TS diagnosis of is often neglected. Careful analysis of the subvalvular apparatus is essential to predict valve repair.146 The integration of clinical and echocardiographic parameters related to TS (mean gradient > 5 to 10 mmHg, valve area ≤ 1.0 cm² and mean time of pressure drop ≥ 190 ms) classifies severity in stages C (marked asymptomatic) and D (marked symptomatic).149

TTE is the initial recommended method to diagnose and evaluate the severity of pulmonary stenosis (PS) or regurgitation (PR), its etiology and effects on cardiac structure and right ventricular function (class I).133^,149 In addition to assessing the valvular anatomy, investigation of the etiology requires a thorough evaluation of the RV, pulmonary ring, pulmonary artery trunk and its branches. Primary PS or PR (with leaflet involvement) are more often due to congenital diseases than acquired ones. Secondary PR occurs in situations of pulmonary hypertension. There is little literature on the quantification of the severity of PR on the echocardiography, but there is a consensus that it should be done in an integrated way with pulsed, continuous and color Doppler parameters; and graded as mild, moderate, or marked.133 PS and PR are classified, from the clinical-echocardiographic point of view, as stage C (marked asymptomatic) and D (marked symptomatic).149 Evaluation of the pulmonary valve may be difficult for TTE. In this situation, however, the TEE does not provide additional information and is not recommended (class III). There is little data on the value of 3D echocardiography. In cases of limited transthoracic imaging or severity parameters inconclusive or discordant with clinical data, cardiac resonance is recommended as the best method.133

Associated valvular lesions (AVL) in our setting are frequent due to the high prevalence of rheumatic fever (RF), which reaches 70% of valvular heart disease in Brazil.141 In the EuroHeart Survey, 51% of AVL patients had RF and 40% had degenerative valve disease.155 Pathophysiology is complex, because it depends on the specific combination of each valve lesion, and its diagnosis is challenging because the guidelines provide us with specific valvular parameters alone. AVL may result from two primary valvular diseases156 or from the combination of primary and secondary valvular disease.157 Despite the high prevalence of AVL, there is little evidence of the best course of action to be taken in each combination. The most common combinations and their most frequent changes are reported below:156

AS and MI: Increased LV pressure caused by aortic stenosis may increase the regurgitant orifice and decrease aortic transvalvular gradients, mimicking a low-flow state.156^,158 In some AS cases, there may be MR secondary to dilation and left ventricular dysfunction (tethering). Less frequent, but possible in these patients, is the presence of primary MR.

Recommendations for TTE and TEE in AVL are listed in tables 26 and 27, respectively. The frequency at which TTE should be performed is debatable and depends on the type of AVL and symptomatology; in general, the examination should be repeated according to the predominant valve lesion guideline.156 In the case of balanced lesions, TTE should be repeated with a shorter interval than the one suggested for a single valve lesion.156

In the scenario of a patient with acute chest pain and suspected coronary artery disease, echocardiography may be useful (Table 33) and should be routinely available in the emergency department and thoracic pain units.180 Evidence of new or presumably contractile change from LV to TTE is one of the parameters in the third universal definition of myocardial infarction181 and may in fact assist in the diagnosis/prognostic determination of an ACS. In addition, TTE may aid in the differential diagnosis of chest pain and/or associated conditions, such as acute aortic dissection, aortic stenosis, hypertrophic cardiomyopathy, and pulmonary embolism.180 By dividing LV into 16 or 17 segments, contractile segmental function is visually quantified based on systolic thickening (ST): hyperkinetic = 0 (ST > 70%); normal = 1 (ST = 50 to 70%); hypokinetic = 2 (ST < 40%); akinetic = 3 (ST < 10%); “dyskinetic = 4 (paradoxical movement/systolic expansion)”. The wall motion score index (WMSI) is the reference parameter to express the LV segmental function and its normality value is 1; values between 1 and 1.6 show a contractile alteration of mild degree; while WMSI values above 1.6 indicate greater involvement and worse prognosis.182 Obviously, the absence of alterations in segmental contractility in resting TTE does not exclude the presence of coronary artery disease.180 It should also be considered that the contractile alteration may occur in other conditions such as myocarditis, RV overload (volume/pressure), ventricular pre-excitation, Takotsubo type cardiomyopathy, left bundle branch block, chagasic cardiomyopathy or presence of pacemaker.180 TTE is the exam of choice in cases of hemodynamic instability with suspected cardiac origin, as well as in the identification of mechanical complications of AMI.179^,180 However, it is necessary to avoid requesting the examination for evaluation of patients with chest pain with a confirmed diagnosis of myocardial ischemia (ACS/AMI), since TTE should not delay the immediate onset of treatment.176^,177^,180 On the other hand, in the screening of symptomatic patients suspected of having coronary artery disease in the emergency room, recent evidence indicates the potential usefulness of GLS calculated by 2D speckle tracking. In the absence of preexisting structural heart disease, previous infarction or left bundle branch block, GLS (when < 16.5%) may complement existing diagnostic algorithms and act as an early adjunct marker of ischemia.183

The evidence of a new alteration of the segmental contractility at rest or its appearance before the induction of stress (exercise or pharmacological) suggests ischemic etiology.184 Stress echocardiography is an independent predictor of cardiovascular death, of additional value to the other methods and can avoid coronary angiography.175^,179 Its use may be recommended for risk stratification of patients in chest pain units (Table 34), especially when the electrocardiogram does not define the diagnosis and the exercise test is submaximal, non-feasible or inconclusive.179 Traditionally, stress echocardiography is performed after 24 hours of chest pain relief in low to moderate risk patients with no evident ischemic changes on the electrocardiogram and normal cardiac enzymes.

This echocardiographic modality allows the immediate and simultaneous access of LV segmental contraction and myocardial perfusion.179^,180 In patients with acute chest pain and non-diagnostic electrocardiogram, the use of contrast echocardiography increases sensitivity for the diagnosis of ACS (Table 35).180,185 Patients with normal perfusion and myocardial function at rest have good prognosis, while the presence of perfusion defects at rest identifies a subgroup at high risk for ACS.185

TTE, while providing important information on segmental contractility when performed at the time of acute chest pain, is limited in the investigation of patients with chronic coronary disease.175 Two situations of indication should be valued: the first one when there is a need for a differential diagnosis of chest pain with non-ischemic causes, such as pericarditis, valvular diseases (such as aortic stenosis) or cardiomyopathies that may occur with chest pain; the second is based on the knowledge of global left ventricular function as a prognostic factor in stable patients with chronic coronary disease (Table 36).175

Stress echocardiography is a useful investigative method for both suspected patients and those with an established diagnosis of stable coronary disease (Table 37). The method offers good accuracy in the ischemic investigation of patients from moderate to high risk, with a slight predominance of specificity compared to other non-invasive imaging methods, such as myocardial scintigraphy.179^,184^,186^,187 The stress-induced modality, whether physical, with treadmill or bicycle, or pharmacological, with dobutamine sensitized with atropine or even with dipyridamole, does not significantly change the diagnostic performance of the test.179 In general, in the investigation of stable coronary disease, stress echocardiography should be indicated for those patients with limited exercise performance, either by functional class or by non-interpretable electrocardiogram, such as in the presence of left bundle branch block.188 Thus, the method should not be considered as a substitute for the ergometric test. However, if available, it can be used as the first examination in the investigation of selected patients, with intermediate or high pretest probability. Furthermore, in the investigation of the risk of chronic coronary disease, it can be used as a sequential method to others such as coronary tomography, when the calcium score shows levels above 400.184^,186 Another important clinical situation for indication of stress echocardiography is the preoperative evaluation of patients undergoing intermediate-risk surgery.179^,187^,189 Even in this situation, the method can be used but it should not generally replace the exercise test when this is possible. However, in vascular surgeries, where there are one or more risk factors, the investigation may start from the echocardiographic examination under stress.184 Situations in which there is a need for the topographical definition of ischemia, such as those of a functional significance investigation of already known lesions, also induce the image examination under stress, which may be the echocardiography. However, the availability of the method in the region of medical practice and the technical ability and experience of the echocardiography laboratory for individualized application of the levels of recommendation suggested here should be considered.

The use of echocardiographic contrast agents consisting of microbubbles capable of overcoming the pulmonary barrier and remaining intact has become a powerful weapon for adequate visualization of the endocardium of all LV segments.185^,190 Thus, in the presence of two or more contiguous segments with limited technical quality, the use of any of these agents is indicated (Table 38).191^,192 The use of contrast agents for myocardial perfusion, although it is part of the same procedure, only with modifications in the acquisition and analysis of the images, remains considered off-label by the US and European health agencies. Guidelines on stable coronary disease already recognize the use of contrast agents to delineate endocardial borders, but they are still not based on myocardial perfusion evaluation.175 However, robust evidence supports the use of these agents for assessing myocardial perfusion both in the diagnosis of coronary disease in acute and chronic coronary syndromes,193 even showing its superiority over conventional stress echocardiography in predicting cardiovascular events.194 The accuracy of contrast agents has been compared with other methods such as myocardial scintigraphy and, in contrast, showed similarity, with greater sensitivity, mainly in the detection of uni-coronary lesions.195 However, the use of contrast agents for perfusion analysis is facilitated when stress is performed with dipyridamole; and the low use of dipyridamole in most Brazilian and worldwide echocardiography laboratories192 may be a barrier to the implementation of myocardial perfusion analysis.

Coronary flow reserve can also be assessed by contrast echocardiography under stress. Reduced values of coronary flow reserve are indicative of functional repercussion in lesions that anatomically have dubious expression. In addition, some studies have shown the role of this index in assessing viability and in predicting myocardial functional recovery in patients with stable coronary artery disease.196