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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Sarcoidosis is a multisystem inflammatory disease of unknown etiology&#44; with heterogeneous presentation and possible cardiovascular involvement&#46; Associated mortality is mainly due to respiratory&#44; neurological or cardiac complications&#46; Myocardial involvement&#44; which may manifest as heart block&#44; ventricular arrhythmias or heart failure from both systolic and diastolic dysfunction&#44; may have life-threatening consequences&#44; and cardiac sudden death may be the first presentation of cardiac sarcoidosis&#44; occurring independently of pulmonary or other organ involvement&#46; When sarcoidosis is fatal&#44; cardiac involvement is a frequent cause of death<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; Recently&#44; an association between sarcoidosis and pulmonary embolism has been described&#44; which is explained by inflammatory and other biochemical mechanisms<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; This could worsen the prognosis of both pulmonary and cardiovascular disease and makes it important to seek early identification of patients at risk&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">It has become clear that asymptomatic cardiac involvement is far more prevalent that previously thought&#46; Nevertheless&#44; there is a lack of consensus as to the diagnostic and cardiovascular imaging modalities to be used and their relative accuracy in identifying the presence of preclinical cardiac disease&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Conventional two-dimensional &#40;2D&#41; echocardiography is recommended for assessing sarcoidosis patients with suspicion of cardiac involvement&#46; However&#44; morphological changes and overt global ventricular dysfunction&#44; as assessed by left ventricular ejection fraction &#40;LVEF&#41;&#44; probably occur simultaneously with already established clinical cardiac manifestations&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Speckle tracking echocardiography &#40;STE&#41; is a valuable tool for the quantitative assessment of regional myocardial function&#46; As in its early stages cardiac sarcoidosis does not affect the myocardium uniformly or globally&#44; the disease could theoretically be identified by this technique&#44; possibly before overt deterioration in LVEF<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>&#46; In keeping with the mainly regional nature of the disease&#44; cardiac magnetic resonance &#40;CMR&#41; is currently one of the advanced high-resolution imaging techniques of choice in the assessment of sarcoidosis&#44; enabling rapid&#44; accurate&#44; and non-invasive diagnosis&#46; Some studies have set out to find correlations between functional myocardial changes as assessed by STE and scar distribution on contrast-enhanced &#40;CE&#41; CMR<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a>&#46; Furthermore&#44; as tissue regions are identified by individual anatomical features in CMR&#44; feature- and tissue-tracking CMR has been explored in 2D cine image stacks&#44; and a series of deformation parameters describing myocardium mechanics can also be derived<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We present a case report of cardiac sarcoidosis with a rare presentation&#44; preceded by extensive pulmonary embolism&#46; Although the diagnosis was made by CE-CMR&#44; we proceeded with further segmental functional analysis by STE&#44; investigating possible effects on regional function&#46; We also sought to assess myocardial deformation by tissue-tracking CMR and the extent of its agreement with STE&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 44-year-old black male with pulmonary sarcoidosis diagnosed at the age of 39&#44; under irregular corticosteroid therapy&#44; presented to the hospital with sudden onset of effort dyspnea&#46; On admission the patient was in no distress&#44; with tachycardia &#40;100 beats&#47;min&#41; and normal blood pressure and oxygen saturation &#40;ambient air&#41;&#46; Physical examination was negative except for the presence of bilateral inspiratory crackles in the middle third of both lung fields&#46; The electrocardiogram &#40;ECG&#41; revealed no changes other than sinus tachycardia&#44; and blood analysis was remarkable for D-dimer elevation with normal BNP levels&#46; The patient underwent pulmonary computed tomography &#40;CT&#41; angiography&#44; which revealed bilateral pulmonary embolism in addition to parenchymal nodular infiltration&#44; interstitial ground glass pattern and bilateral mediastinal lymphadenopathy with several lymph node conglomerates &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>A&#41;&#46; Transthoracic echocardiography was normal&#44; with no signs of acute right-sided pressure overload or of right ventricular dysfunction&#46; Lower limb Doppler ultrasound was positive for partial right popliteal vein thrombosis&#46; The patient was started on oral anticoagulation with rivaroxaban in addition to corticotherapy&#59; hospital stay was uneventful and he was discharged&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Six weeks after admission he returned to the emergency department complaining of sudden dizziness&#46; He was hypotensive and tachycardic&#44; with no other significant findings&#46; His ECG was notable for monomorphic ventricular tachycardia &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>B&#41;&#44; which was successfully cardioverted to sinus rhythm&#46; Blood tests were negative for both D-dimers and troponin&#46; Notwithstanding&#44; pulmonary CT was repeated&#44; which showed partial resolution of pulmonary thrombosis&#44; with similar parenchymal and lymph node changes&#46; Conventional transthoracic echocardiography revealed normal LVEF&#46; Owing to suspicion of cardiac sarcoidosis&#44; CE-CMR was requested&#46; It showed no myocardial edema but was positive for delayed enhancement sparing the subendocardial layers&#44; and confirmed normal biventricular volumes and LVEF &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>C-G&#41;&#46; The patient accordingly received an implantable cardioverter-defibrillator&#44; and was asymptomatic at six-month follow-up with no further ventricular tachycardia episodes&#44; under oral anticoagulation&#46; A detailed coagulation investigation conducted subsequently&#44; including screening for antiphospholipid antibodies&#44; was negative&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">After the CMR study a detailed echocardiographic analysis was performed&#46; Global longitudinal strain was assessed as normal despite slightly lower regional values at the basal and mid lateral &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>A&#41; and inferior-lateral walls&#44; and this abnormality was increasingly noticed when detailed mid and epicardial longitudinal strain were analyzed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>B&#41;&#44; with slightly abnormal global longitudinal strain at the latter layer&#46; In accordance with these findings&#44; and even more pronounced than the longitudinal strain&#44; we found abnormal circumferential strain values at the same segments&#44; with positive values for the mid left ventricular subepicardial layers&#44; fully matching the distribution of delayed enhancement &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>C and <a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41;&#46; Nevertheless&#44; radial strain values were normal at the same level and segments&#44; not indicating regional deformation abnormalities&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">At tissue tracking CMR&#44; regional longitudinal deformation also matched STE longitudinal strain alterations at the basal lateral wall &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>E and F&#41;&#44; although radial and circumferential strain were unchanged &#40;<a class="elsevierStyleCrossRef" href="#sec0030">Videos 1 and 2</a>&#41;&#46; However&#44; on global four-dimensional tissue tracking&#44; radial strain assessment was notable for slight alterations in basal lateral wall strain &#40;<a class="elsevierStyleCrossRef" href="#sec0030">Video 3</a>&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Sarcoidosis is a chronic granulomatous disease mainly affecting patients between the ages of 20 and 40 years&#46; Cardiac involvement has been demonstrated in 20-50&#37; of patients in autopsy studies but clinically manifest cardiac disease is observed in only about 5&#37; of those with cardiac involvement&#46; As in the case presented&#44; black individuals are more likely than other racial groups to suffer extrathoracic organ involvement and a chronic disease course<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a>&#46; It has also recently been demonstrated that sarcoidosis may predispose to venous embolic events and its association with pulmonary embolism is significant regardless of age&#44; gender or race&#46; In this case pulmonary embolism was the first clinical event raising suspicion of sarcoidosis involvement beyond merely the lung parenchyma and mediastinum&#46; The cause of this potential increase in risk of pulmonary embolism is the subject of speculation&#44; but could include effects of corticosteroid treatment&#44; the unrecognized presence of disease-specific procoagulant factors &#40;increased thrombin activation and fibrin formation derived from macrophages and activated leukocytes&#41;&#44; simultaneous presence of antiphospholipid antibodies &#40;found in up to 38&#37; of sarcoidosis patients&#41;&#44; which was not documented in this report&#44; and even local vein compression by lymphadenopathy&#44; resulting in blood stasis<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">This patient also presented with one of the most feared cardiac complications of the disease&#46; Symptomatic ventricular tachycardia was the episode that led to the diagnosis of cardiac sarcoidosis despite the previous normal findings at conventional 2D echocardiography&#46; Asymptomatic left ventricular dysfunction&#44; proving regional sarcoidosis involvement&#44; was only established following advanced imaging studies&#46; Although negative for edema&#44; CMR displayed delayed enhancement with a non-ischemic pattern&#44; which not only supported the diagnosis but also provided further evidence for scarring and substrate heterogeneity predisposing to ventricular arrhythmias&#46; Even so&#44; this delayed enhancement pattern was not typical&#44; as it is characteristically patchy&#44; with involvement of the basal septum&#44; in this context<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Global longitudinal strain assessed by STE as a measure of left ventricular function was within normal values&#46; However STE was remarkable for heterogeneity of regional dysfunction&#44; largely of longitudinal strain measured at the mid myocardial and epicardial layers&#44; but particularly of circumferential strain&#44; epicardial values of which were clearly abnormal at the inferior and inferolateral left ventricular wall&#46; Notwithstanding&#44; radial strain analysis was within normal values at the same left ventricular level&#44; which did not identify regional dysfunction following this strain assessment&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">By definition&#44; STE is influenced by myocardial heterogeneity in laminar extension&#44; shear and thickening&#46; Coronary artery disease studies have demonstrated that the spatial sensitivity of high-resolution STE enables focused assessment of specific layers of the myocardium and a graded assessment of parts of the myocardial wall with different sensitivity to reduced coronary perfusion&#46; Although the relation between flow and transmural strain in three dimensions &#40;longitudinal&#44; circumferential and radial&#41; is non-linear&#44; different sensitivities can be attributed to a single strain dimension in order to assess a specific myocardial layer<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a>&#46; In agreement with this&#44; segmental strain analysis to investigate myocarditis revealed the predominantly subepicardial and intramyocardial involvement in this case&#44; mainly of oblique and circumferentially oriented fibers&#44; which would explain the circumferential strain abnormalities&#46; Both longitudinal and circumferential strain reduction in the acute phase have proved to be of prognostic value for the occurrence of events and subsequent recovery of LVEF<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a>&#46; Significant changes in both longitudinal and circumferential strain are thus to be expected in this case of sarcoidosis&#44; with a typical non-ischemic myocardial pattern of involvement&#44; although with no evidence of edema as in acute myocarditis&#46; However&#44; in contrast to our findings&#44; radial strain would need integrity of cross-fiber activation of all layers and should therefore have shown significant changes&#46; Moreover&#44; a single study with three-dimensional STE showed that only radial strain assessment had good potential to distinguish cardiac sarcoidosis from dilated cardiomyopathy&#44; which should increase interest in strain analysis in this condition<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a>&#46; This finding may bear some relation to previous contradictory data from assessment of possible overlap between areas of reduced strain and delayed late gadolinium enhancement&#46; Although we found obvious matching of distribution of changes in circumferential strain and delayed enhancement&#44; this has not generally been the case in previous reports on cardiac sarcoidosis&#44; and usually there are more areas of reduced strain than areas with enhancement&#46; As STE and tracking techniques reflect quantitative mechanics&#44; it is possible that subclinical cardiac involvement has subtle effects on myocardial contractility early&#44; before structural lesions such as granulomas or fibrosis occur with sufficient spatial resolution to be detected by available tissue characterization sequences that have limited sensitivity&#46; In addition&#44; if this was the case&#44; specific technical features of tracking algorithms&#44; such as temporal averaging and stronger endocardial weighing for CMR tissue tracking&#44; may explain the different findings for all other strain dimensions as assessed by echocardiography and CMR<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">5&#44;6</span></a>&#46; Although the issue is complex&#44; we should point out that possible correlation of strain analysis with delayed enhancement distribution is merely speculative in this case in particular and for cardiac involvement in sarcoidosis in general&#46; Data concerning these issues are scarce and the main findings are derived from studies on coronary artery disease and myocarditis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">One final point should be made concerning imaging data and prognosis&#46; Both left ventricular dilatation as assessed by echocardiography and myocardial delayed enhancement are independent predictors for overall mortality and risk of sudden cardiac death and arrhythmic events&#44; respectively&#46; In one study&#44; alterations in global longitudinal strain were the best independent echocardiographic predictor of worse outcome in cardiac sarcoidosis patients<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>&#46; However&#44; it should be noted that there are no specific data addressing cardiac structural and functional involvement in patients at different stages of the disease&#46; While identification of cardiac involvement before overt deterioration in LVEF could be improved&#44; it is still unknown whether regional alterations and delayed enhancement occur before left ventricular dilatation and heart failure&#46; Even so&#44; in this case&#44; ventricular arrhythmias occurred in the presence of normal volumes and LVEF&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Overall&#44; this case report is notable for the unusual clinical presentation and the value of the different available imaging tools for diagnosis of cardiac sarcoidosis&#46; Our experience shows that reliance should not be placed exclusively on LVEF in this setting&#46; STE&#44; being less resource-intensive&#44; less costly&#44; portable and easily performed&#44; should be performed to detect alterations in regional strain that would suggest the diagnosis&#46; Moreover&#44; CMR can provide a definitive structural diagnosis if its findings correlate with strain values&#46; As a technique with many applications&#44; CMR with appropriate and experienced use of feature-tracking techniques may also provide functional data for regional strain analysis in the future&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Broadly speaking&#44; more work is needed using different applications and models for both functional and strain analysis and tissue characterization with different imaging modalities before they can be routinely used on a daily basis&#46; The aim should be a systematic analysis of how all these tools are to be applied&#44; not merely for optimizing the diagnosis of cardiac sarcoidosis but&#44; more importantly&#44; for detecting preclinical cardiac alterations before the occurrence of serious clinical events&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We report a case of sarcoidosis with an unusual presentation&#44; initially manifesting as bilateral pulmonary embolism and then as a cardiac form of the disease with an ominous clinical event consisting of sustained ventricular tachycardia&#46; The diagnosis was established by clinical and magnetic resonance criteria despite normal conventional echocardiographic study&#46; Detailed functional assessment provided by tracking techniques &#40;speckle tracking echocardiography and cardiac magnetic resonance tissue tracking&#41; enabled the detection of regional deformation abnormalities&#44; indicating prominent circumferential strain and epicardial layer alterations&#44; partly matching the structural changes depicted by distribution of delayed enhancement&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We find this case notable for various issues it raises concerning diagnosis and management of cardiac sarcoidosis&#46; These are mainly related to recent developments in imaging modalities that enable non-invasive identification of structural and functional abnormalities in this condition early&#44; before overt deterioration in left ventricular ejection fraction&#46; Information from different imaging modalities and tools provide information that could potentially assist preclinical diagnosis&#44; with possible prognostic implications&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Apresenta-se o caso de um doente de 44 anos com o diagn&#243;stico pr&#233;vio de sarcoidose pulmonar&#44; admitido consecutivamente no servi&#231;o de urg&#234;ncia por embolia pulmonar e taquicardia ventricular sintom&#225;tica&#46; Embora o estudo ecocardiogr&#225;fico mostrasse normal fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda&#44; o diagn&#243;stico de sarcoidose card&#237;aca foi estabelecido por elementos de ordem cl&#237;nica&#44; em conjuga&#231;&#227;o com os achados de resson&#226;ncia magn&#233;tica card&#237;aca&#46; Quando se efetuou estudo funcional detalhado do ventr&#237;culo esquerdo por <span class="elsevierStyleItalic">speckle</span> &#40;ecocardiografia&#41; e <span class="elsevierStyleItalic">tissue tracking</span> &#40;resson&#226;ncia magn&#233;tica&#41;&#44; detetaram-se altera&#231;&#245;es regionais da deforma&#231;&#227;o mioc&#225;rdica&#44; parcialmente coincidentes com a distribui&#231;&#227;o do realce tardio por resson&#226;ncia&#46; Para al&#233;m da apresenta&#231;&#227;o pouco habitual sob a forma de evento emb&#243;lico&#44; este caso de sarcoidose com subsequente documenta&#231;&#227;o de envolvimento card&#237;aco&#44; permitiu a aplica&#231;&#227;o de modalidades de imagem cardiovascular avan&#231;adas&#44; colocou em evid&#234;ncia a afe&#231;&#227;o estrutural e funcional mioc&#225;rdica&#44; na presen&#231;a de normal fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda&#46;</p></span>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Thoracic computed tomography&#58; pulmonary window with evidence of severe and diffuse parenchymal nodular infiltration &#40;asterisk&#41;&#44; also depicted in &#40;C&#41;&#44; and bilateral pulmonary artery thrombosis&#44; almost obstructive at the level of the right pulmonary artery &#40;white arrow&#41;&#59; &#40;B&#41; monomorphic ventricular tachycardia notable for a maximum deflection index of &#62;55&#37; in the precordium &#40;and an intrinsicoid deflection time of &#62;85 ms&#41;&#44; indicating epicardial origin&#46; Because there is right bundle branch block morphology in V1 and QS in leads II&#44; III and aVF&#44; the origin is in the inferior&#47;inferolateral left ventricle&#59; &#40;C&#41; cardiac magnetic resonance axial localizer&#59; &#40;D&#41; T2-weighted turbo-spin echo&#44; short-axis sequence&#44; negative for the presence of edema&#59; &#40;E-G&#41; phase-sensitive inversion recovery sequences depicting delayed enhancement sparing the subendocardium across the inferior&#44; lateral and inferolateral wall of the left ventricle &#40;arrowhead&#41;&#46;</p>"
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Case report
Rare presentation of sarcoidosis: Multimodal imaging diagnosis of cardiac involvement
Apresentação rara de sarcoidose: diagnóstico de envolvimento cardíaco por imagem multimoda
Joao Abecasisa,b,
Corresponding author
joaoabecasis@hotmail.com

Corresponding author.
, Mariana Castrob, Regina Ribeirasa,b, Victor Gila
a Hospital dos Lusiadas, Cardiology Department, Lisbon, Portugal
b Hospital de Santa Cruz, Cardiology Department, Carnaxide, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Sarcoidosis is a multisystem inflammatory disease of unknown etiology&#44; with heterogeneous presentation and possible cardiovascular involvement&#46; Associated mortality is mainly due to respiratory&#44; neurological or cardiac complications&#46; Myocardial involvement&#44; which may manifest as heart block&#44; ventricular arrhythmias or heart failure from both systolic and diastolic dysfunction&#44; may have life-threatening consequences&#44; and cardiac sudden death may be the first presentation of cardiac sarcoidosis&#44; occurring independently of pulmonary or other organ involvement&#46; When sarcoidosis is fatal&#44; cardiac involvement is a frequent cause of death<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;2</span></a>&#46; Recently&#44; an association between sarcoidosis and pulmonary embolism has been described&#44; which is explained by inflammatory and other biochemical mechanisms<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3&#44;4</span></a>&#46; This could worsen the prognosis of both pulmonary and cardiovascular disease and makes it important to seek early identification of patients at risk&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">It has become clear that asymptomatic cardiac involvement is far more prevalent that previously thought&#46; Nevertheless&#44; there is a lack of consensus as to the diagnostic and cardiovascular imaging modalities to be used and their relative accuracy in identifying the presence of preclinical cardiac disease&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Conventional two-dimensional &#40;2D&#41; echocardiography is recommended for assessing sarcoidosis patients with suspicion of cardiac involvement&#46; However&#44; morphological changes and overt global ventricular dysfunction&#44; as assessed by left ventricular ejection fraction &#40;LVEF&#41;&#44; probably occur simultaneously with already established clinical cardiac manifestations&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Speckle tracking echocardiography &#40;STE&#41; is a valuable tool for the quantitative assessment of regional myocardial function&#46; As in its early stages cardiac sarcoidosis does not affect the myocardium uniformly or globally&#44; the disease could theoretically be identified by this technique&#44; possibly before overt deterioration in LVEF<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>&#46; In keeping with the mainly regional nature of the disease&#44; cardiac magnetic resonance &#40;CMR&#41; is currently one of the advanced high-resolution imaging techniques of choice in the assessment of sarcoidosis&#44; enabling rapid&#44; accurate&#44; and non-invasive diagnosis&#46; Some studies have set out to find correlations between functional myocardial changes as assessed by STE and scar distribution on contrast-enhanced &#40;CE&#41; CMR<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a>&#46; Furthermore&#44; as tissue regions are identified by individual anatomical features in CMR&#44; feature- and tissue-tracking CMR has been explored in 2D cine image stacks&#44; and a series of deformation parameters describing myocardium mechanics can also be derived<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We present a case report of cardiac sarcoidosis with a rare presentation&#44; preceded by extensive pulmonary embolism&#46; Although the diagnosis was made by CE-CMR&#44; we proceeded with further segmental functional analysis by STE&#44; investigating possible effects on regional function&#46; We also sought to assess myocardial deformation by tissue-tracking CMR and the extent of its agreement with STE&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case report</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 44-year-old black male with pulmonary sarcoidosis diagnosed at the age of 39&#44; under irregular corticosteroid therapy&#44; presented to the hospital with sudden onset of effort dyspnea&#46; On admission the patient was in no distress&#44; with tachycardia &#40;100 beats&#47;min&#41; and normal blood pressure and oxygen saturation &#40;ambient air&#41;&#46; Physical examination was negative except for the presence of bilateral inspiratory crackles in the middle third of both lung fields&#46; The electrocardiogram &#40;ECG&#41; revealed no changes other than sinus tachycardia&#44; and blood analysis was remarkable for D-dimer elevation with normal BNP levels&#46; The patient underwent pulmonary computed tomography &#40;CT&#41; angiography&#44; which revealed bilateral pulmonary embolism in addition to parenchymal nodular infiltration&#44; interstitial ground glass pattern and bilateral mediastinal lymphadenopathy with several lymph node conglomerates &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>A&#41;&#46; Transthoracic echocardiography was normal&#44; with no signs of acute right-sided pressure overload or of right ventricular dysfunction&#46; Lower limb Doppler ultrasound was positive for partial right popliteal vein thrombosis&#46; The patient was started on oral anticoagulation with rivaroxaban in addition to corticotherapy&#59; hospital stay was uneventful and he was discharged&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Six weeks after admission he returned to the emergency department complaining of sudden dizziness&#46; He was hypotensive and tachycardic&#44; with no other significant findings&#46; His ECG was notable for monomorphic ventricular tachycardia &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>B&#41;&#44; which was successfully cardioverted to sinus rhythm&#46; Blood tests were negative for both D-dimers and troponin&#46; Notwithstanding&#44; pulmonary CT was repeated&#44; which showed partial resolution of pulmonary thrombosis&#44; with similar parenchymal and lymph node changes&#46; Conventional transthoracic echocardiography revealed normal LVEF&#46; Owing to suspicion of cardiac sarcoidosis&#44; CE-CMR was requested&#46; It showed no myocardial edema but was positive for delayed enhancement sparing the subendocardial layers&#44; and confirmed normal biventricular volumes and LVEF &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>C-G&#41;&#46; The patient accordingly received an implantable cardioverter-defibrillator&#44; and was asymptomatic at six-month follow-up with no further ventricular tachycardia episodes&#44; under oral anticoagulation&#46; A detailed coagulation investigation conducted subsequently&#44; including screening for antiphospholipid antibodies&#44; was negative&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">After the CMR study a detailed echocardiographic analysis was performed&#46; Global longitudinal strain was assessed as normal despite slightly lower regional values at the basal and mid lateral &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>A&#41; and inferior-lateral walls&#44; and this abnormality was increasingly noticed when detailed mid and epicardial longitudinal strain were analyzed &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>B&#41;&#44; with slightly abnormal global longitudinal strain at the latter layer&#46; In accordance with these findings&#44; and even more pronounced than the longitudinal strain&#44; we found abnormal circumferential strain values at the same segments&#44; with positive values for the mid left ventricular subepicardial layers&#44; fully matching the distribution of delayed enhancement &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>C and <a class="elsevierStyleCrossRef" href="#fig0015">Figure 3</a>&#41;&#46; Nevertheless&#44; radial strain values were normal at the same level and segments&#44; not indicating regional deformation abnormalities&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">At tissue tracking CMR&#44; regional longitudinal deformation also matched STE longitudinal strain alterations at the basal lateral wall &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>E and F&#41;&#44; although radial and circumferential strain were unchanged &#40;<a class="elsevierStyleCrossRef" href="#sec0030">Videos 1 and 2</a>&#41;&#46; However&#44; on global four-dimensional tissue tracking&#44; radial strain assessment was notable for slight alterations in basal lateral wall strain &#40;<a class="elsevierStyleCrossRef" href="#sec0030">Video 3</a>&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">Sarcoidosis is a chronic granulomatous disease mainly affecting patients between the ages of 20 and 40 years&#46; Cardiac involvement has been demonstrated in 20-50&#37; of patients in autopsy studies but clinically manifest cardiac disease is observed in only about 5&#37; of those with cardiac involvement&#46; As in the case presented&#44; black individuals are more likely than other racial groups to suffer extrathoracic organ involvement and a chronic disease course<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a>&#46; It has also recently been demonstrated that sarcoidosis may predispose to venous embolic events and its association with pulmonary embolism is significant regardless of age&#44; gender or race&#46; In this case pulmonary embolism was the first clinical event raising suspicion of sarcoidosis involvement beyond merely the lung parenchyma and mediastinum&#46; The cause of this potential increase in risk of pulmonary embolism is the subject of speculation&#44; but could include effects of corticosteroid treatment&#44; the unrecognized presence of disease-specific procoagulant factors &#40;increased thrombin activation and fibrin formation derived from macrophages and activated leukocytes&#41;&#44; simultaneous presence of antiphospholipid antibodies &#40;found in up to 38&#37; of sarcoidosis patients&#41;&#44; which was not documented in this report&#44; and even local vein compression by lymphadenopathy&#44; resulting in blood stasis<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">This patient also presented with one of the most feared cardiac complications of the disease&#46; Symptomatic ventricular tachycardia was the episode that led to the diagnosis of cardiac sarcoidosis despite the previous normal findings at conventional 2D echocardiography&#46; Asymptomatic left ventricular dysfunction&#44; proving regional sarcoidosis involvement&#44; was only established following advanced imaging studies&#46; Although negative for edema&#44; CMR displayed delayed enhancement with a non-ischemic pattern&#44; which not only supported the diagnosis but also provided further evidence for scarring and substrate heterogeneity predisposing to ventricular arrhythmias&#46; Even so&#44; this delayed enhancement pattern was not typical&#44; as it is characteristically patchy&#44; with involvement of the basal septum&#44; in this context<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Global longitudinal strain assessed by STE as a measure of left ventricular function was within normal values&#46; However STE was remarkable for heterogeneity of regional dysfunction&#44; largely of longitudinal strain measured at the mid myocardial and epicardial layers&#44; but particularly of circumferential strain&#44; epicardial values of which were clearly abnormal at the inferior and inferolateral left ventricular wall&#46; Notwithstanding&#44; radial strain analysis was within normal values at the same left ventricular level&#44; which did not identify regional dysfunction following this strain assessment&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">By definition&#44; STE is influenced by myocardial heterogeneity in laminar extension&#44; shear and thickening&#46; Coronary artery disease studies have demonstrated that the spatial sensitivity of high-resolution STE enables focused assessment of specific layers of the myocardium and a graded assessment of parts of the myocardial wall with different sensitivity to reduced coronary perfusion&#46; Although the relation between flow and transmural strain in three dimensions &#40;longitudinal&#44; circumferential and radial&#41; is non-linear&#44; different sensitivities can be attributed to a single strain dimension in order to assess a specific myocardial layer<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a>&#46; In agreement with this&#44; segmental strain analysis to investigate myocarditis revealed the predominantly subepicardial and intramyocardial involvement in this case&#44; mainly of oblique and circumferentially oriented fibers&#44; which would explain the circumferential strain abnormalities&#46; Both longitudinal and circumferential strain reduction in the acute phase have proved to be of prognostic value for the occurrence of events and subsequent recovery of LVEF<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a>&#46; Significant changes in both longitudinal and circumferential strain are thus to be expected in this case of sarcoidosis&#44; with a typical non-ischemic myocardial pattern of involvement&#44; although with no evidence of edema as in acute myocarditis&#46; However&#44; in contrast to our findings&#44; radial strain would need integrity of cross-fiber activation of all layers and should therefore have shown significant changes&#46; Moreover&#44; a single study with three-dimensional STE showed that only radial strain assessment had good potential to distinguish cardiac sarcoidosis from dilated cardiomyopathy&#44; which should increase interest in strain analysis in this condition<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a>&#46; This finding may bear some relation to previous contradictory data from assessment of possible overlap between areas of reduced strain and delayed late gadolinium enhancement&#46; Although we found obvious matching of distribution of changes in circumferential strain and delayed enhancement&#44; this has not generally been the case in previous reports on cardiac sarcoidosis&#44; and usually there are more areas of reduced strain than areas with enhancement&#46; As STE and tracking techniques reflect quantitative mechanics&#44; it is possible that subclinical cardiac involvement has subtle effects on myocardial contractility early&#44; before structural lesions such as granulomas or fibrosis occur with sufficient spatial resolution to be detected by available tissue characterization sequences that have limited sensitivity&#46; In addition&#44; if this was the case&#44; specific technical features of tracking algorithms&#44; such as temporal averaging and stronger endocardial weighing for CMR tissue tracking&#44; may explain the different findings for all other strain dimensions as assessed by echocardiography and CMR<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">5&#44;6</span></a>&#46; Although the issue is complex&#44; we should point out that possible correlation of strain analysis with delayed enhancement distribution is merely speculative in this case in particular and for cardiac involvement in sarcoidosis in general&#46; Data concerning these issues are scarce and the main findings are derived from studies on coronary artery disease and myocarditis&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">One final point should be made concerning imaging data and prognosis&#46; Both left ventricular dilatation as assessed by echocardiography and myocardial delayed enhancement are independent predictors for overall mortality and risk of sudden cardiac death and arrhythmic events&#44; respectively&#46; In one study&#44; alterations in global longitudinal strain were the best independent echocardiographic predictor of worse outcome in cardiac sarcoidosis patients<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">2</span></a>&#46; However&#44; it should be noted that there are no specific data addressing cardiac structural and functional involvement in patients at different stages of the disease&#46; While identification of cardiac involvement before overt deterioration in LVEF could be improved&#44; it is still unknown whether regional alterations and delayed enhancement occur before left ventricular dilatation and heart failure&#46; Even so&#44; in this case&#44; ventricular arrhythmias occurred in the presence of normal volumes and LVEF&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Overall&#44; this case report is notable for the unusual clinical presentation and the value of the different available imaging tools for diagnosis of cardiac sarcoidosis&#46; Our experience shows that reliance should not be placed exclusively on LVEF in this setting&#46; STE&#44; being less resource-intensive&#44; less costly&#44; portable and easily performed&#44; should be performed to detect alterations in regional strain that would suggest the diagnosis&#46; Moreover&#44; CMR can provide a definitive structural diagnosis if its findings correlate with strain values&#46; As a technique with many applications&#44; CMR with appropriate and experienced use of feature-tracking techniques may also provide functional data for regional strain analysis in the future&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Broadly speaking&#44; more work is needed using different applications and models for both functional and strain analysis and tissue characterization with different imaging modalities before they can be routinely used on a daily basis&#46; The aim should be a systematic analysis of how all these tools are to be applied&#44; not merely for optimizing the diagnosis of cardiac sarcoidosis but&#44; more importantly&#44; for detecting preclinical cardiac alterations before the occurrence of serious clinical events&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflicts of interest</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2016-06-29"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">We report a case of sarcoidosis with an unusual presentation&#44; initially manifesting as bilateral pulmonary embolism and then as a cardiac form of the disease with an ominous clinical event consisting of sustained ventricular tachycardia&#46; The diagnosis was established by clinical and magnetic resonance criteria despite normal conventional echocardiographic study&#46; Detailed functional assessment provided by tracking techniques &#40;speckle tracking echocardiography and cardiac magnetic resonance tissue tracking&#41; enabled the detection of regional deformation abnormalities&#44; indicating prominent circumferential strain and epicardial layer alterations&#44; partly matching the structural changes depicted by distribution of delayed enhancement&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We find this case notable for various issues it raises concerning diagnosis and management of cardiac sarcoidosis&#46; These are mainly related to recent developments in imaging modalities that enable non-invasive identification of structural and functional abnormalities in this condition early&#44; before overt deterioration in left ventricular ejection fraction&#46; Information from different imaging modalities and tools provide information that could potentially assist preclinical diagnosis&#44; with possible prognostic implications&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Apresenta-se o caso de um doente de 44 anos com o diagn&#243;stico pr&#233;vio de sarcoidose pulmonar&#44; admitido consecutivamente no servi&#231;o de urg&#234;ncia por embolia pulmonar e taquicardia ventricular sintom&#225;tica&#46; Embora o estudo ecocardiogr&#225;fico mostrasse normal fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda&#44; o diagn&#243;stico de sarcoidose card&#237;aca foi estabelecido por elementos de ordem cl&#237;nica&#44; em conjuga&#231;&#227;o com os achados de resson&#226;ncia magn&#233;tica card&#237;aca&#46; Quando se efetuou estudo funcional detalhado do ventr&#237;culo esquerdo por <span class="elsevierStyleItalic">speckle</span> &#40;ecocardiografia&#41; e <span class="elsevierStyleItalic">tissue tracking</span> &#40;resson&#226;ncia magn&#233;tica&#41;&#44; detetaram-se altera&#231;&#245;es regionais da deforma&#231;&#227;o mioc&#225;rdica&#44; parcialmente coincidentes com a distribui&#231;&#227;o do realce tardio por resson&#226;ncia&#46; Para al&#233;m da apresenta&#231;&#227;o pouco habitual sob a forma de evento emb&#243;lico&#44; este caso de sarcoidose com subsequente documenta&#231;&#227;o de envolvimento card&#237;aco&#44; permitiu a aplica&#231;&#227;o de modalidades de imagem cardiovascular avan&#231;adas&#44; colocou em evid&#234;ncia a afe&#231;&#227;o estrutural e funcional mioc&#225;rdica&#44; na presen&#231;a de normal fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda&#46;</p></span>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Thoracic computed tomography&#58; pulmonary window with evidence of severe and diffuse parenchymal nodular infiltration &#40;asterisk&#41;&#44; also depicted in &#40;C&#41;&#44; and bilateral pulmonary artery thrombosis&#44; almost obstructive at the level of the right pulmonary artery &#40;white arrow&#41;&#59; &#40;B&#41; monomorphic ventricular tachycardia notable for a maximum deflection index of &#62;55&#37; in the precordium &#40;and an intrinsicoid deflection time of &#62;85 ms&#41;&#44; indicating epicardial origin&#46; Because there is right bundle branch block morphology in V1 and QS in leads II&#44; III and aVF&#44; the origin is in the inferior&#47;inferolateral left ventricle&#59; &#40;C&#41; cardiac magnetic resonance axial localizer&#59; &#40;D&#41; T2-weighted turbo-spin echo&#44; short-axis sequence&#44; negative for the presence of edema&#59; &#40;E-G&#41; phase-sensitive inversion recovery sequences depicting delayed enhancement sparing the subendocardium across the inferior&#44; lateral and inferolateral wall of the left ventricle &#40;arrowhead&#41;&#46;</p>"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Pathophysiology and clinical management of cardiac sarcoidosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "N&#46; Hamzeh"
                            1 => "D&#46;A&#46; Steckman"
                            2 => "W&#46;H&#46; Sauer"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1038/nrcardio.2015.22"
                      "Revista" => array:6 [
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                        "fecha" => "2015"
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                        "paginaInicial" => "278"
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                        "link" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25707386"
                            "web" => "Medline"
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                      ]
                    ]
                  ]
                ]
              ]
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            1 => array:3 [
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                          "etal" => true
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                            1 => "D&#46; Snipelisky"
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/ehjci/jev142"
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                  ]
                ]
              ]
            ]
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              "identificador" => "bib0045"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46;P&#46; Crawshaw"
                            1 => "C&#46;J&#46; Wotton"
                            2 => "D&#46;G&#46;R&#46; Yeates"
                          ]
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                    ]
                  ]
                  "host" => array:1 [
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ISSN: 21742049
Original language: English
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Idiomas
Revista Portuguesa de Cardiologia (English edition)
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