Sarcoidosis is a systemic condition, of unclear etiology, with a probable autoimmune component, associated with the formation of non-necrotizing granulomas in several organs and tissues.
Clinical manifestations are diverse, as well as the clinical course of the disease, which can be self-limited or chronic. Thoracic involvement occurs in 90% of the cases, with hilar adenopathy and/or diffuse pulmonary micronodules, especially along lymphatic structures.
Cardiac impairment is clinically detected in about 10% of the patients; however, prevalence reaches 25% in autopsy studies.
Cardiac impairment is associated with granulomatous infiltration, and progressive evolution to cicatricial fibrosis. It is responsible for about 50% of the deaths in patients with sarcoidosis,
There are specific criteria for the diagnosis of cardiac sarcoidosis, both in its isolated form and associated with systemic impairment.
From the diagnostic point of view, the most important findings are reduced left ventricle ejection fraction (LVEF) < 50% and the presence of abnormal tapering of the basal interventricular septum. Other segmental changes, especially if not correspondent to coronary territories, including the presence of aneurisms, are also relevant. Such findings, despite being associated with more advanced impairment, are contemplated as larger criteria by the main diagnostic algorithm used nowadays.
Diastolic dysfunction, despite not being specific for diagnosis, appears in earlier stages in comparison to the previously mentioned findings, and may suggest an additional investigation in patients with an established systemic diagnosis, or at the presence of suggestive clinical condition. According to a study published in 2019, diastolic dysfunction of the left ventricle was present in 26% of the 77 patients with confirmed diagnosis of systemic sarcoidosis.
Another important aspect is the analysis of the pericardium, once its direct involvement, after primary myocardial dysfunction, is described in 20% of the patients with cardiac sarcoidosis.
Left ventricular impairment may be primary, due to granulomatous myocardial infiltration, or secondary, due to pulmonary hypertension associated with lung impairment; its analysis is essential using quantitative parameters. The estimated systolic pressure of the pulmonary artery, in echocardiography, showed correlation with the measurements shown by the right catheterization in patients with pulmonary sarcoidosis.
The central illustration represents the main echocardiography findings associated with cardiac sarcoidosis.
Despite theoretically affecting any portion of the heart, endocardial and valve impairment is less reported. However, a recently published study demonstrated that 68% of the patients with cardiac sarcoidosis and moderate or major mitral insufficiency, presented hypercaptation of some level in papillary muscles, usually both, even when mitral insufficiency was classified as functional.
Among the advanced echocardiography techniques, the evaluation of myocardial strain using the speckle tracking technique is the most analyzed one. Absolute left ventricular global longitudinal strain (LV GLS) lower than 16.3% showed 82.2% sensitivity and 81.2% specificity for the diagnosis of cardiac sarcoidosis in patients with confirmed systemic diagnosis, whereas absolute right ventricular global longitudinal strain (RV GLS) lower than 19.9% showed 88.1% sensitivity and 86.7% specificity.
A meta-analysis published in 2020 assessed 589 patients with confirmed extracardiac sarcoidosis and 378 controls, showing consistent reduction of longitudinal and circumferential global strain in this group of patients, associated with cardiovascular outcomes, such as all-cause mortality, hospitalization due to heart failure, implantable cardioverter defibrillator (ICD) or appropriate therapy with that device.
Myocardial strain was also compared with other imaging methods, and had correlation with the late enhancement findings in CMR.
These data strengthen the use of the strain as a diagnostic and prognostic evaluation tool in these patients, with potential for earlier detection in relation to conventional echocardiographic findings.
Other advanced techniques are currently being analyzed by the Cardiomyopathy Group at Instituto do Coração (InCor). The evaluation of myocardial work and myocardial elastography in patients with confirmed cardiac sarcoidosis and sarcoidosis with no cardiac involvement is ongoing.
Myocardial elastography is an ultrasound modality that allows non-invasive assessment of myocardial stiffness by measuring the speed of propagation of shear waves naturally generated by the closure of the mitral valve. In media with a known density, it is known that this speed is directly proportional to the tissue stiffness.
Myocardial work is an approach deriving from myocardial strain, which represents the volume-pressure curve area of the left ventricle, built with data from LV GLS and the non-invasive blood pressure verification. Thus, it incorporates the effects of load variation, not contemplated by other methods, such as LVEF and LV GLS,
Tridimensional echocardiography (3D Echo) is still little available in transthoracic studies due to the learning curve to perform the examination, besides the costs associated with the specific transducer. The 3D Echo provides more accurate measurements of heart chambers and LVEF, with numbers that are comparable with those obtained in the CMR. This technique was used in patients with sarcoidosis and no diagnosed cardiac impairment, and showed reduction in the left atrial emptying fraction,
The most important prognostic factor is the presence of left ventricular dysfunction, related to the extension of cardiac impairment. Besides reduced LVEF, the extension of late myocardial enhancement through CMR and the number of segments with changes in perfusion in PET follow the same reasoning and are associated with negative cardiovascular outcomes.
Another prognostic data that is easy to verify is the thickness measurement of the interventricular septum basal portion < 4 mm, which was considered as an independent predictor of adverse events (all-cause mortality, heart failure leading to hospitalization and severe symptomatic arrhythmias).
As previously discussed, myocardial strain presents prognostic value in many studies. LVEF lower than 14% was significantly related to hospitalization and heart failure.
Conventional echocardiography findings are often unspecific or late. Besides, the differential diagnosis with other cardiomyopathies, or even with coronary artery disease, can be challenging. Therefore, the development of advanced techniques that can be incorporated to conventional examination, without substantial increase in cost, is very relevant.
Some technical aspects related to the method also made evaluation difficult, such as limitation in the acoustic window of patients with excess weight, often associated with the chronic use of corticoids, or extensive lung impairment. In these situations, the use of ultrasound enhancement agents can facilitate the evaluation of segmental dysfunction, tapering and aneurism, and should be used when available.