Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation Accepted Manuscript Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation Karolis Kluonaitis[.]
Accepted Manuscript Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation Karolis Kluonaitis, Sigita Glaveckaite, Giedre Balciunaite, Austeja Juskaite, Darius Palionis, Nomeda Valeviciene, Ugnius Mickys, Rimgaudas Katkus, Ricardo FontesCarvalho, Jelena Celutkiene PII: S1109-9666(16)30247-0 DOI: 10.1016/j.hjc.2017.02.003 Reference: HJC 141 To appear in: Hellenic Journal of Cardiology Received Date: 24 October 2016 Revised Date: 27 January 2017 Accepted Date: 10 February 2017 Please cite this article as: Kluonaitis K, Glaveckaite S, Balciunaite G, Juskaite A, Palionis D, Valeviciene N, Mickys U, Katkus R, Fontes-Carvalho R, Celutkiene J, Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation, Hellenic Journal of Cardiology (2017), doi: 10.1016/ j.hjc.2017.02.003 This is a PDF file of an unedited manuscript that has been accepted for publication As a service to our customers we are providing this early version of the manuscript The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain ACCEPTED MANUSCRIPT Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation RI PT Karolis Kluonaitis1, Sigita Glaveckaite2, Giedre Balciunaite2, Austeja Juskaite1, Darius Palionis3, Nomeda Valeviciene3, Ugnius Mickys4, Rimgaudas Katkus2, Ricardo FontesCarvalho5, Jelena Celutkiene2 Faculty of Medicine, Vilnius University, Vilnius, Lithuania Vilnius University, Clinic of Cardiovascular Diseases, Centre of Cardiology and Angiology, Vilnius, Lithuania SC Vilnius University, Department of Radiology, Nuclear Medicine and Medical Physics, Centre of Radiology and Nuclear Medicine, Vilnius, Lithuania National Center of Pathology, Vilnius, Lithuania University of Porto, Department of Physiology, Porto, Portugal M AN U Corresponding author: Austeja Juskaite, austejajusk@gmail.com, Faculty of Medicine, Vilnius AC C EP TE D University, Vilnius, Lithuania; phone +37069627307 ACCEPTED MANUSCRIPT Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation RI PT Letter to the Editor Keywords Cardiac sarcoidosis, cardiovascular magnetic resonance, positron emission tomography, SC prednisone A 34-year-old female presented to emergency room of our hospital, complaining of M AN U palpitation Electrocardiogram (ECG) showed regular narrow QRS complex tachycardia, of 170 bpm, which terminated spontaneously shortly after admission Her serum electrolytes, creatinine, glucose and complete blood count were all normal Transthoracic echocardiography (TTE) showed dilatation of the left ventricle (LV) with regional wall motion abnormalities in the lateral and inferior walls, LV apical aneurysm and reduced LV ejection fraction (LVEF) to 35% Although patient had no risk factors for coronary heart disease, coronary pathology had to be TE D excluded, so the patient underwent computed tomography (CT) coronary angiography, which demonstrated normal coronary arteries Incidentally, CT revealed pronounced bilateral mediastinal and perihilar lymphadenopathy with several small and non-specific focal lesions in both lungs (Fig 1A) As the cause of LV damage was not clear, cardiovascular magnetic EP resonance (CMR) was performed CMR confirmed echocardiographic findings, showing LV apical aneurysm, segmental wall motion abnormalities and the reduced LVEF to 37% (Fig 1B and 1C) Additionally, unusual late gadolinium enhancement (LGE) pattern was noticed LGE AC C was not completely typical for post-ischaemic scars, presenting with epicardial, mid-myocardial and even transmural distribution dominating in the lateral wall and apex with focal subendocardial sparing, especially in the lateral LV wall Slightly lower LGE signal intensity compared with a typical post-ischaemic scar was observed (Fig 1D and 1E) CMR also confirmed pronounced bilateral mediastinal and perihilar lymphadenopathy On basis of these findings, sarcoidosis or lymphoma was suspected Fibrobronchoscopy was performed CD4/CD8 ratio of 2.03 in the bronchoalveolar lavage fluid was inadequate to diagnose sarcoidosis Therefore, we proceeded with endobronchial ultrasound needle aspiration biopsy of the mediastinal lymph node and bronchoscopic lung biopsy Epithelioid granulomas with Langhan’s type giant cells were detected on the histological ACCEPTED MANUSCRIPT specimen of the pulmonary tissue No infectious agents were revealed by Grocott (silver), PAS and Ziehl Neelsen staining The histologic evidence was therefore consistent with lung sarcoidosis Based on above results, together with clinical and cardiac imaging data suggesting cardiac involvement, patient was diagnosed with cardiac and pulmonary sarcoidosis Due to extensive and possibly irreversible damage to the LV, the decision was made to place RI PT an implantable cardioverter–defibrillator (ICD) for primary prevention of sudden cardiac death Immunosuppressive therapy with prednisone 60 mg was started, tapered each month by 10 mg A month after initiation of medical therapy, positron emission tomography was conducted using 18-fluorodeoxyglucose (18F-FDG), demonstrating metabolically active lesions in the SC mediastinal lymph nodes and the LV free wall (Fig 1F and 1G) Following months, despite medical therapy with prednisone and metoprolol, patient continued to experience brief episodes of arrhythmias Several months’ later patient was admitted to the M AN U hospital with suspected ICD discharge ICD interrogation revealed episodes of supraventricular tachycardia (SVT) but no evidence of ventricular tachycardia or inappropriate ICD shocks An electrophysiology study revealed typical AV node paroxysmal tachycardia Successful radiofrequency ablation of slow pathway was carried out There was no recurrence of arrhythmia at the follow-up visits TE D Figure A, Computed tomography showing pronounced (arrows) perihilar lymphadenopathy, PA – pulmonary artery, Ao – aorta B and C, CMR cine four chamber heart view (balanced steady state free pre-session sequence) in diastole (B) and systole (C), representing apical aneurysm and akinetic apical and partly mid-ventricular segment of anterolateral wall (arrows) LV – left ventricle D, late gadolinium enhancement CMR four chamber view (inversion EP recovery sequence) representing transmural LGE pattern in the LV apex, as well an epicardial to mid-myocardial and transmural LGE pattern in the anterolateral wall (arrows, white signal represents LGE foci) E, late gadolinium enhancement CMR short axis view (mid-ventricular level) showing epicardial, partly transmural and even mid- AC C myocardial LGE pattern with focal sub-endocardial sparing in the LV lateral wall (arrows) F and G, 18F-FDG PET scan shows metabolically active lesions in the mediastinal lymph nodes (arrows) and the heart (G, arrowhead) Sarcoidosis is a systemic, poorly understood disease, which is usually characterised by noncaseating granulomas Although the disease mostly affects the lungs, cardiac involvement can be detected Autopsy studies show that cardiac involvement is found from 19.5% to 28% of patients with sarcoidosis However, only 2-7% of sarcoidosis patients clinically present with cardiac symptoms [1] Clinically, cardiac sarcoidosis (CS) can manifest with arrhythmias, conduction disorders, heart failure, pericardial effusion or even sudden cardiac death [2] Complete heart block is the most common finding in patients with clinically evident CS Our patient presented ACCEPTED MANUSCRIPT with supraventricular arrhythmias, which is a rare manifestation of CS, occurring in only about 0-15% of the cases [3] As symptoms and syndromes are non-specific and can be fatal, diagnosis is often delayed or even missed Cardiac dysfunction seen on TTE, which include regional wall motion abnormalities, ventricular aneurysms, as in our patient, are usually seen in advanced stages of the RI PT disease and are not specific CMR is an accurate, non-invasive test potentially used for detecting subclinical or clinical cardiac involvement in sarcoidosis; this is currently the non-invasive technique of choice for the evaluation of sarcoidosis In our patient, CMR revealed an unusual LGE pattern together with pronounced bilateral mediastinal and perihilar lymphadenopathy SC Those findings made the diagnosis of pulmonary and CS very likely Use of 18F-FDG PET appears to have high sensitivity; meta-analysis comparing studies to the 1993 Ministry of M AN U Health, Labour, and Welfare (MHLW) guidelines showed 89% sensitivity and 78% specificity [4] 18F-FDG PET scan in our case showed metabolically active foci both in the mediastinal lymph nodes and LV free wall consistent with active inflammation There are no currently accepted international guidelines for the diagnosis of CS However, there are two proposed diagnostic guidelines One is the Japanese Ministry of Health and Welfare’s set of criteria for the diagnosis of CS [5] The second is the National Institutes of TE D Health’s A Case Control Etiology of Sarcoidosis Study set of criteria [6] It is recognised, that the only absolute test for organ involvement in sarcoidosis is histological examination of tissue for the presence of granulomatous inflammation (and exclusion of other known cause of granuloma) However, clinical features can suggest that an organ is involved even in the absence EP of organ-specific biopsy if (1) sarcoidosis has already been demonstrated histologically in another organ and (2) other causes for the clinical manifestation have been reasonably excluded AC C [6] Patients with CS require immediate treatment with corticosteroids as this can affect the recovery of atrioventricular block and improve survival [7] In conclusion, despite of a broad armamentarium of contemporary imaging modalities, the early diagnosis of cardiac sarcoidosis remains very challenging Screening with CMR or 18FFDG PET is appropriate in patients in whom cardiac sarcoidosis is suspected References Lynch JP 3rd, Hwang J, Bradfield J, et al Cardiac involvement in sarcoidosis: evolving concepts in diagnosis and treatment Semin Respir Crit Care Med 2014;35(3):372-90 ACCEPTED MANUSCRIPT Sugizaki Y, Tanaka H, Imanishi J, et al Isolated primary cardiac sarcoidosis presenting as acute heart failure Intern Med 2013;52(1):71–4 Viles-Gonzalez JF, Pastori L, Fischer A, et al Supraventricular arrhythmias in patients with cardiac sarcoidosis prevalence, predictors, and clinical implications Chest 2013;143(4):1085–90 RI PT Youssef G, Leung E, Mylonas I, et al The use of 18F-FDG PET in the diagnosis of cardiac sarcoidosis: a systematic review and meta-analysis including the Ontario experience J Nucl Med 2012;53(2):241–8 Hiraga A Guideline for Diagnosis of Cardiac Sarcoidosis: Study Report on Diffuse SC Pulmonary Diseases Tokyo, Japan: Ministry of Health, Labour and Welfare; 1993:23– 24 Judson MA, Baughman RP, Teirstein AS, et al Defining organ involvement in M AN U sarcoidosis: the ACCESS proposed instrument ACCESS Research Group A Case Control Etiologic Study of Sarcoidosis Sarcoidosis Vasc Diffuse Lung Dis 1999;16(1):75-86 Ipek E, Demirelli S, Ermis E, Inci S Sarcoidosis and the heart: A review of the literature AC C EP TE D Intractable Rare Dis Res 2015;4(4):170-80 AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT ... +37069627307 ACCEPTED MANUSCRIPT Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation RI PT Letter to the Editor Keywords Cardiac sarcoidosis, cardiovascular magnetic...ACCEPTED MANUSCRIPT Cardiac sarcoidosis – diagnostic challenges due to unusual clinical presentation RI PT Karolis Kluonaitis1, Sigita Glaveckaite2, Giedre... lung sarcoidosis Based on above results, together with clinical and cardiac imaging data suggesting cardiac involvement, patient was diagnosed with cardiac and pulmonary sarcoidosis Due to extensive