HomeCirculation: Cardiovascular ImagingVol. 12, No. 2Clinical Value and Prognostic Impact of Pericardial Involvement in Acute Myocarditis Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBClinical Value and Prognostic Impact of Pericardial Involvement in Acute MyocarditisData From the ITAMY Gianluca Di Bella, MD, PhD, Massimo Imazio, MD, Jan Bogaert, MD, PhD, Fausto Pizzino, MD, Giovanni Camastra, MD, Lorenzo Monti, MD, Santo Dellegrottaglie, MD, PhD, Rocco Donato, MD, PhD, Claudio Moro, MD, Alessia Pepe, MD, Chiara Lanzillo, MD, PhD, Gianluca Pontone, MD, Martina Perazzolo Marra, MD, PhD, Armando Fusco, MD, Alessandra Scatteia, MD, Alessandro Pingitore, MD, PhD, Giovanni Donato Aquaro, MD and on behalf of the Cardiac Magnetic Resonance Working Group of the Italian Society of Cardiology Gianluca Di BellaGianluca Di Bella Correspondence to Gianluca Di Bella, MD, PhD, Clinical and Experimental Department of Medicine, University of Messina, Via Consolare Valeria 1, 98100 Messina, Italy. Email E-mail Address: [email protected] Clinical and Experimental Department of Medicine, University of Messina, Italy (G.D.B., R.D.). Search for more papers by this author , Massimo ImazioMassimo Imazio Cardiology Department, Maria Vittoria Hospital, Torino, Italy (M.I.). Department of Public Health and Pediatrics, University of Torino, Italy (M.I.). Search for more papers by this author , Jan BogaertJan Bogaert Department of Radiology, UZ Leuven, Belgium (J.B.). Search for more papers by this author , Fausto PizzinoFausto Pizzino Cardiology Department, Gabriele Monasterio Foundation-Consiglio Nazionale delle Ricerche Region Toscana, Pisa, Italy (F.P., G.D.A.). Scuola Superiore Sant’Anna di studi e di Perfezionamento Universiario, Institute of Life Sciences, Pisa, Italy (F.P.). Search for more papers by this author , Giovanni CamastraGiovanni Camastra Cardiac Department, Vannini Hospital Rome, Roma, Italy (G.C.). Search for more papers by this author , Lorenzo MontiLorenzo Monti Radiology Department, Humanitas Research Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan, Italy (L.M.). Search for more papers by this author , Santo DellegrottaglieSanto Dellegrottaglie Division of Cardiology, Villa dei Fiori, Acerra, Napoli, Italy (S.D.). Mount Sinai School of Medicine, New York, NY (S.D.). Search for more papers by this author , Rocco DonatoRocco Donato Clinical and Experimental Department of Medicine, University of Messina, Italy (G.D.B., R.D.). Search for more papers by this author , Claudio MoroClaudio Moro UO Cardiologia e UTIC, ASST Monza, PO Desio (C.M.). Search for more papers by this author , Alessia PepeAlessia Pepe Clinical and Experimental Department of Medicine, University of Messina, Italy (G.D.B., R.D.). Search for more papers by this author , Chiara LanzilloChiara Lanzillo Cardiology Department, Policlinico Casilino, Rome, Italy (C.L., A.F.). Search for more papers by this author , Gianluca PontoneGianluca Pontone Cardiac Department, Centro Cardiologico Monzino, Milano, Italy (G.P.). Search for more papers by this author , Martina Perazzolo MarraMartina Perazzolo Marra Division of Cardiology, Department of Cardiac, Thoracic, and Vascular Sciences, University of Padua, Italy (M.P.M.). Search for more papers by this author , Armando FuscoArmando Fusco Cardiology Department, Policlinico Casilino, Rome, Italy (C.L., A.F.). Search for more papers by this author , Alessandra ScatteiaAlessandra Scatteia Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy (A.S.). Search for more papers by this author , Alessandro PingitoreAlessandro Pingitore Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche, Pisa, Italy (A.P.). Search for more papers by this author , Giovanni Donato AquaroGiovanni Donato Aquaro Cardiology Department, Gabriele Monasterio Foundation-Consiglio Nazionale delle Ricerche Region Toscana, Pisa, Italy (F.P., G.D.A.). Search for more papers by this author and on behalf of the Cardiac Magnetic Resonance Working Group of the Italian Society of Cardiology Search for more papers by this author Originally published13 Feb 2019https://doi.org/10.1161/CIRCIMAGING.118.008504Circulation: Cardiovascular Imaging. 2019;12:e008504Acute myocarditis (AM) is often associated with pericardial involvement (PI). Previous studies showed that left ventricular (LV) ejection fraction (EF) and anteroseptal midwall late gadolinium enhancement (LGE) are strong prognostic independent predictors of long-term outcomes in AM.1,2We aimed to define the clinical and incremental prognostic role of PI in patients with AM enrolled in the ITAMY (Italian Study in Myocarditis). We included 467 patients (105 women; 34±14 years) with a definite cardiac magnetic resonance (CMR) diagnosis of AM according to ≥2 Lake Louise Criteria (myocardial edema, hyperemia, and LGE; Figure [A]).Download figureDownload PowerPointFigure. Summary of patient's selection and Kaplan-Meier curve analysis. Flowchart visualizing the derivation of the study population (A). Kaplan-Meier curve analysis of cardiac events (CEs) occurring with and without pericardial involvement (B) show a worse CE-free survival (P=0.001) in patients with pericardial involvement. Combining pericardial involvement and left ventricular ejection fraction <40% (no marker, only 1 or 2 markers; C) and combining pericardial involvement and anteroseptal midwall late gadolinium enhancement (LGE) involvement (no marker, only 1 or 2 markers; D) patients presenting with 2 markers had a worse CE-free survival in comparison with patients with only 1 marker (P<0.001) or none (P<0.01). CMR indicates cardiac magnetic resonance.Variables included traditional cardiovascular risk factors (age, smoking, sex, hypertension, dyslipidemia, diabetes mellitus, and family history of cardiovascular diseases) and CMR-derived parameters (right ventricular [RV] and LV indexed end-diastolic volumes [EDVi], reduced [<40%] LV-EF, LV mass index, number of LGE LV segments, anteroseptal LGE, and the presence of PI).PI was defined as pericardial inflammation (>50% pericardial hyperintensity on T2-weighted or LGE images) or pericardial effusion ≥5 mm on cine images in diastole.3,4A set of cardiac events (CEs) was used as a composite end point and included cardiac death, resuscitated cardiac arrest, cardiac transplantation, appropriate implantable cardioverter defibrillator shock, and heart failure hospitalization.The study was approved by the Institutional Ethics Committee, and informed consent of patients was obtained.Values are presented as mean±SD, median, and interquartile range. Qualitative data were expressed as numbers and percentages. Categorical variables were compared by χ2 test, whereas continuous variables were compared by t test or by Mann-Whitney U test. Univariate Cox proportional hazard regression analysis was used to identify the predictors of CEs. All the variables significantly associated to CEs at univariate analysis were included in a multivariate model. Kaplan-Meier curves and log-rank test were used to compare the CE-free survival. A 2-sided α-level <0.05 was considered significant.Deidentified data and materials of this study will made available on reasonable request.PI was detected in 111 patients who were included in PI-AM group. Among these, 67 patients showed pericardial effusion, 12 patients showed pericardial LGE, and 32 patients showed both. The remnant 356 patients were included in AM group.The PI-AM group showed significantly higher LV-EDVi (89±29 versus 81±16 mL/m2; P<0.0001) and RV-EDVi (72±23 versus 64±31 mL/m2; P<0.0001), lower LV-EF (56±13% versus 61±8%; P<0.001) and RV-EF (47±20% versus 54±18%; P<0.001), and greater myocardial involvement (LGE segments: 3.4±2.5 versus 2.9±2.5; P=0.04) than AM group. Anteroseptal LGE was similar between PI-AM (28%) and AM groups (30%).Follow-up median length was 860 days (interquartile range, 217–1789); interviewer was blinded to CMR results. Thirty-three CEs (7 sudden cardiac deaths, 3 resuscitated cardiac arrests, 4 appropriate implantable cardioverter defibrillator firings, 19 heart failure hospitalizations) occurred during follow-up with a higher incidence (P=0.007) in PI-AM (14 CEs; 12.6%) in respect to AM group (19 CEs; 5.4%). Patients with CEs showed lower prevalence of smoking status (3.1% versus 16.3%; P=0.04) and higher prevalence of LV-EF <40 (15.6% versus 2.8%; P=0.001), anteroseptal LGE (42.4% versus 21.8%; P=0.01), and PI (42.4% versus 22.5%; P=0.01). At Cox regression univariate analysis, LV-EF <40% (hazard ratio [HR], 11.139; CI, 4.188–29.629; P<0.001), anteroseptal LGE (HR, 2.463; CI, 1.225–4.954; P<0.01), and PI (HR, 2.920; CI, 1.462–5.829; P<0.01) resulted associated with CEs. Age, LV-EDVi, RV-EDVi, RV-EF, LV mass, and LGE segments did not show association with CEs at univariate analysis. At multivariate model, PI (HR, 2.483; CI, 1.205–5.118; P<0.05) was independently associated at CEs, as well as LV-EF <40% (HR, 6.251; CI, 2.217–17.625; P<0.001) and anteroseptal LGE (HR, 2.049; CI, 1.001–4.194; P<0.05).Patients with PI (Figure [B]) showed a worse CE-free survival (P=0.001). Patients with both PI and LV-EF <40% had a worse CE-free survival (P<0.001) in comparison with patients with only 1 parameter (PI or LV-EF <40%) or none. Similar findings (P<0.01) were observed combining PI with anteroseptal LGE (Figure [C] and [D]). No difference was found comparing patients with none in respect to one.Our main findings are (1) about a quarter of AM patients had PI; (2) worse CMR findings was observed in AM with PI; (3) the presence of PI was a long-term independent prognostic predictor of CEs in addition with anteroseptal LGE and reduced EF in AM.Previous studies showed that myopericarditis has always a good outcome.5 However, these studies investigated acute pericarditis alone and acute pericarditis with positive troponin with or without LV function abnormalities, whereas our population consisted of patients with elevated troponin with a CMR diagnosis of acute myocardial damage because of AM with or without PI. Moreover, combination of PI with LV dysfunction or anteroseptal LGE has also a worse prognostic impact, probably suggesting a more diffuse or severe disease.The main limitations were that endomyocardial biopsy was not performed; prognostic impact of pericardial effusion and pericardial inflammation was not investigated; T1 and T2 mapping were not performed.In conclusion, our data suggest that PI is an independent prognostic predictor of worse cardiac prognosis also in the setting of myocarditis with reduced EF or anteroseptal LGE.DisclosuresNone.FootnotesCorrespondence to Gianluca Di Bella, MD, PhD, Clinical and Experimental Department of Medicine, University of Messina, Via Consolare Valeria 1, 98100 Messina, Italy. Email gianluca.[email protected]itReferences1. Anzini M, Merlo M, Sabbadini G, Barbati G, Finocchiaro G, Pinamonti B, Salvi A, Perkan A, Di Lenarda A, Bussani R, Bartunek J, Sinagra G. Long-term evolution and prognostic stratification of biopsy-proven active myocarditis.Circulation. 2013; 128:2384–2394. doi: 10.1161/CIRCULATIONAHA.113.003092LinkGoogle Scholar2. Aquaro GD, Perfetti M, Camastra G, Monti L, Dellegrottaglie S, Moro C, Pepe A, Todiere G, Lanzillo C, Scatteia A, Di Roma M, Pontone G, Perazzolo Marra M, Barison A, Di Bella G; Cardiac Magnetic Resonance Working Group of the Italian Society of Cardiology. Cardiac MR with late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study.J Am Coll Cardiol. 2017; 70:1977–1987. doi: 10.1016/j.jacc.2017.08.044CrossrefMedlineGoogle Scholar3. Adler Y, Charron P, Imazio M, Badano L, Barón-Esquivias G, Bogaert J, Brucato A, Gueret P, Klingel K, Lionis C, Maisch B, Mayosi B, Pavie A, Ristic AD, Sabaté Tenas M, Seferovic P, Swedberg K, Tomkowski W; ESC Scientific Document Group. 2015 ESC guidelines for the diagnosis and management of pericardial diseases: the task force for the diagnosis and management of pericardial diseases of the European Society of Cardiology (ESC) endorsed by: the European Association for Cardio-Thoracic Surgery (EACTS).Eur Heart J. 2015; 36:2921–2964. doi: 10.1093/eurheartj/ehv318CrossrefMedlineGoogle Scholar4. Klein AL, Abbara S, Agler DA, Appleton CP, Asher CR, Hoit B, Hung J, Garcia MJ, Kronzon I, Oh JK, Rodriguez ER, Schaff HV, Schoenhagen P, Tan CD, White RD. American Society of Echocardiography clinical recommendations for multimodality cardiovascular imaging of patients with pericardial disease: endorsed by the Society for Cardiovascular Magnetic Resonance and Society of Cardiovascular Computed Tomography.J Am Soc Echocardiogr. 2013; 26:965.e15–1012.e15. doi: 10.1016/j.echo.2013.06.023CrossrefGoogle Scholar5. Imazio M, Brucato A, Barbieri A, Ferroni F, Maestroni S, Ligabue G, Chinaglia A, Cumetti D, Della Casa G, Bonomi F, Mantovani F, Di Corato P, Lugli R, Faletti R, Leuzzi S, Bonamini R, Modena MG, Belli R. Good prognosis for pericarditis with and without myocardial involvement: results from a multicenter, prospective cohort study.Circulation. 2013; 128:42–49. doi: 10.1161/CIRCULATIONAHA.113.001531LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Gatti M, Carisio A, D’Angelo T, Darvizeh F, Dell’Aversana S, Tore D, Centonze M and Faletti R (2020) Cardiovascular magnetic resonance in myocardial infarction with non-obstructive coronary arteries patients: A review, World Journal of Cardiology, 10.4330/wjc.v12.i6.248, 12:6, (248-261), Online publication date: 26-Jun-2020. Grigoratos C, Todiere G, Barison A and Aquaro G (2020) The Role of MRI in Prognostic Stratification of Cardiomyopathies, Current Cardiology Reports, 10.1007/s11886-020-01311-3, 22:8, Online publication date: 1-Aug-2020. February 2019Vol 12, Issue 2 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.118.008504PMID: 30755055 Originally publishedFebruary 13, 2019 Keywordsedemamyocarditisinflammationpericarditismagnetic resonance imagingPDF download Advertisement SubjectsCardiomyopathyInflammatory Heart DiseasePericardial Disease