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• W2548156636 abstract "HomeCirculation: Cardiovascular ImagingVol. 9, No. 1Prognosis of Myocardial Damage in Sarcoidosis Patients With Preserved Left Ventricular Ejection Fraction Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBPrognosis of Myocardial Damage in Sarcoidosis Patients With Preserved Left Ventricular Ejection FractionAlways Look at the Bright Side of Cardiovascular Magnetic Resonance Simon Greulich, MD and Heiko Mahrholdt, MD Simon GreulichSimon Greulich From the Department of Cardiology, Robert Bosch Medical Center, Stuttgart, Germany. Search for more papers by this author and Heiko MahrholdtHeiko Mahrholdt From the Department of Cardiology, Robert Bosch Medical Center, Stuttgart, Germany. Search for more papers by this author Originally published13 Jan 2016https://doi.org/10.1161/CIRCIMAGING.115.004417Circulation: Cardiovascular Imaging. 2016;9Sarcoidosis is a systemic granulomatous inflammatory disease of unknown origin, in which myocardial involvement may be part of the systemic process or occur in isolation. The annual incidence of sarcoidosis in the United States has been estimated at 10.9 per 100 000 in whites and at 35.5 per 100 000 in blacks,1 and the prevalence of cardiac sarcoidosis (CS) in these patients ranges from 4% to 55%.2 This large range can, in part, be explained by patient selection criteria, different diagnostic methods, and different standards. Nevertheless, the main reason for the differences in the reported prevalence of CS is most likely the fact that the diagnosis of CS is challenging. Some patients may present with conduction abnormalities, ventricular arrhythmias, and symptoms of heart failure, pointing toward potential cardiac involvement of sarcoid disease. However, many patients present with nonspecific symptoms, no relevant ECG abnormalities, and preserved left ventricular ejection fraction (LVEF). Hence, ECG and echocardiography as criteria for CS in these patients might be misleading. Thus, there is a need for a reliable diagnostic tool to identify patients with CS. Cardiovascular magnetic resonance (CMR) as a noninvasive imaging technique delineates both functional and morphological aspects of the heart and, at the same time, provides excellent tissue characterization. One previous study comprising 81 consecutive patients with biopsy-proven extracardiac sarcoidosis and preserved LVEF compared cardiac involvement by late gadolinium enhancement (LGE) CMR with standard clinical evaluation using the consensus criteria (modified Japanese Ministry of Health guidelines 19933). LGE identified CS in 21 patients (26%) compared with 10 (12%; 8 overlapping) using Japanese Ministry of Health criteria resulting in a 2-fold higher rate for LGE. Pathology evaluation in 15 patients (19%) identified 4 with CS; all 4 were positive by LGE-CMR, whereas only 2 of them were positive by the Japanese Ministry of Health guidelines.4 This landmark study was one of the first to demonstrate the high value of CMR in detection of CS.See Article by Murtagh et alHowever, histological workup still remains the gold standard for diagnosing CS despite its limitations (eg, invasiveness and potential sampling error). The updated guideline for workup of CS by the Japanese Ministry of Health from 2006 recognized LGE as a minor criterion for the clinical diagnosis group only, requiring another minor criterion, and 1 additional major criterion before the clinical diagnosis of CS can be accepted.5 In contrast, a current expert consensus article from the Heart Rhythm Society states that CS is probable (and therefore considered adequate to establish a clinical diagnosis of CS) if there is (1) a histological diagnosis of extracardiac sarcoidosis and (2) LGE on CMR (in a pattern consistent with CS), and (3) other causes for the cardiac manifestation have been reasonably excluded.2 However, the authors had to concede that the LGE pattern in sarcoid patients can be variable, ranging from subepicardial or intramural nonischemic pattern to a more subendocardial, ischemic-type pattern, mimicking previous myocardial infarction.Perhaps of more relevance than merely diagnosing CS is the prognosis of patients with this disease. CS might result in heart failure, arrhythmias, and sudden cardiac death in these often young individuals. LGE-CMR seems to be a useful predictor of outcome in patients with CS, as well as in other nonischemic myocardial diseases.6,7 In the study mentioned above,4 patients with myocardial damage indicated by LGE-CMR had a 9-fold higher rate of adverse events and an 11.5-fold higher rate of cardiac death compared with patients without LGE. Our group has extended these findings in a larger, international multicenter setting consisting of 155 patients with systemic sarcoidosis who underwent CMR for workup of suspected CS. Patients were followed up for ≈2.6 years, and CMR detected LGE in 39 patients (25.5%). Of note, the presence of LGE yields a Cox hazard ratio of 31.6 for death, aborted sudden cardiac death, or appropriate implantable cardioverter-defibrillator (ICD) discharge and of 33.9 for any event (including ventricular tachycardia [VT] and nonsustained VT). This was superior to functional or clinical parameters, such as LVEF, LV end-diastolic volume, or heart failure presentation, yielding hazard ratios between 0.99 (per % increase LVEF) and 1.004 (presentation as heart failure) and between 0.94 and 1.2 for potentially lethal or other adverse events, respectively.8In this issue of Circulation: Cardiovascular Imaging, Murtagh et al9 provide further support to the prognostic value of LGE-CMR, investigating 205 patients with extracardiac sarcoidosis and an LVEF of >50% by CMR, including LGE sequences.Aims were to (1) determine the prevalence of CS (defined by the presence of LGE), (2) quantify the risk of death/VT, and (3) identify imaging-based covariates that predict which patients are at the greatest risk of death/VT. They found that 41 patients (20%) were LGE positive and 12 patients (6%) died or had VT during follow-up. Of note, 10 of these 12 individuals (83%) were LGE positive. In contrast to previous studies, Murtagh et al9 quantified areas of LGE as percentage of LV mass and found that LGE burden was the best predictor of death/VT (area under the curve, 0.80). Interestingly, for every 1% increase of LGE burden, the hazard of death/VT increased by 8%. This finding is of high clinical interest because establishing a critical threshold of LGE burden would make risk stratification much more precise in patients with CS and would facilitate decision making about further patient management, such as whether to implant an ICD. Despite these encouraging results, the study from Murtagh et al9 has several limitations: first, although reaching statistical significance, SDs of the means of LGE burden demonstrate a wide range (14.1±10.7 versus 5.1±4.7%; P=0.004) in patients with and without events. Therefore, identifying a definite threshold of LGE burden for predicting serious events remains challenging. Second, the overall number of events is low because only 12 patients of 205 patients (6%) died or had VT during follow-up. Could one really recommend placement of an ICD based on the results of adverse events in 12 individuals? Third, patients with known coronary artery disease were not excluded: 7 of 41 (=17%) LGE-positive patients had coronary artery disease. Three of them reached the end point death/VT, which could be a consequence of their coronary artery disease rather than because of CS. Although the authors provide data that despite excluding patients with coronary artery disease, LGE-positive patients are still at increased risk of having events, it is a limitation of the present study and is in contrast to previous LGE-CMR studies dealing with prognosis in suspected CS.4,8 Fourth, this is a retrospective single-center study with all its associated limitations. Although VT was part of the end point, Holter ECG monitoring was performed in less than a third (29%) of the patients. Thus, in some patients, cardiac arrhythmias may have been missed, which is one possible explanation for the overall low event rate in this patient cohort. Furthermore, the specific cause of death could not be determined in the majority of patients who died. Consequently, it remains elusive if all deaths were from cardiac origin and if cardiac deaths resulted from CS.The second major finding of the study, beside the role of LGE, is the value of assessment of right ventricular function in patients with suspected CS. The authors state that individuals who died or had VT more frequently had a reduced right ventricular EF compared with patients not having death or VT (45.4±12.3 versus 52.7±27.5%; P=0.037). Again, there is a wide range of SD with the mean of right ventricular EF in patients with and without end point, attenuating the significance of this result.A key clinical question, thus, is whether sarcoid patients with LGE should receive primary prophylactic ICD implantation. In our opinion, this question cannot be answered on the basis of the data available today. Current American Heart Association guidelines consider CS only a class IIA indication for ICD implant.10 Further large multicenter studies dealing with LGE-CMR in patients with CS, including quantification of the LGE burden, are needed to sufficiently address this question.Despite its limitations, the authors should be congratulated on performing this study, which gives much insight into both diagnosis and prognosis of patients with sarcoidosis. Moreover, this group is the first to describe a threshold of LGE burden, by which patients with sarcoidosis are at increased risk of having adverse events.The future will show if a cutoff of LGE burden can be established to facilitate decision making about prophylactic ICD implant in this per se high-risk population for major adverse cardiovascular events. However, when discussing LGE imaging and its prognostic implications, it should be kept in mind that there is not a one-to-one relationship between the presence of LGE and the occurrence of adverse events in LGE-positive patients, although LGE-positive patients are at increased risk of having an event. Nevertheless, there is much evidence indicating that LGE-negative patients in nonischemic cardiomyopathies tend to have an excellent prognosis6,8,11,12 consolidating the role of LGE as a gatekeeper for risk stratification in nonischemic myocardial disease.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Correspondence to Simon Greulich, MD, Robert Bosch Medical Center, Auerbachstr. 110, 70376 Stuttgart, Germany, E-mail [email protected]References1. Statement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999.Am J Respir Crit Care Med. 1999; 160:736–755.CrossrefMedlineGoogle Scholar2. Birnie DH, Sauer WH, Bogun F, Cooper JM, Culver DA, Duvernoy CS, Judson MA, Kron J, Mehta D, Cosedis Nielsen J, Patel AR, Ohe T, Raatikainen P, Soejima K. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis.Heart Rhythm. 2014; 11:1305–1323. doi: 10.1016/j.hrthm.2014.03.043.CrossrefMedlineGoogle Scholar3. Hiraga H, Yuwa K, Hiroe M. Guideline for the diagnosis of cardiac sarcoidosis: study report on diffuse pulmonary disease (in japanese).Jpn Ministry Health Welfare. 1993: 23–24.Google Scholar4. Patel MR, Cawley PJ, Heitner JF, Klem I, Parker MA, Jaroudi WA, Meine TJ, White JB, Elliott MD, Kim HW, Judd RM, Kim RJ. Detection of myocardial damage in patients with sarcoidosis.Circulation. 2009; 120:1969–1977. doi: 10.1161/CIRCULATIONAHA.109.851352.LinkGoogle Scholar5. Tsuda T, Ishihara M, Okamoto H, Ohara K, Oritsu M, Sugisaki K. Diagnostic standard and guideline for sarcoidosis-2006.Jpn JSarcoidosis Granulomatous Disord. 2007; 27:89–102.Google Scholar6. Schumm J, Greulich S, Wagner A, Grün S, Ong P, Bentz K, Klingel K, Kandolf R, Bruder O, Schneider S, Sechtem U, Mahrholdt H. Cardiovascular magnetic resonance risk stratification in patients with clinically suspected myocarditis.J Cardiovasc Magn Reson. 2014; 16:14. doi: 10.1186/1532-429X-16-14.CrossrefMedlineGoogle Scholar7. Greulich S, Ferreira VM, Dall’Armellina E, Mahrholdt H. Myocardial inflammation-are we there yet?Curr Cardiovasc Imaging Rep. 2015; 8:6. doi: 10.1007/s12410-015-9320-6.CrossrefMedlineGoogle Scholar8. Greulich S, Deluigi CC, Gloekler S, Wahl A, Zürn C, Kramer U, Nothnagel D, Bültel H, Schumm J, Grün S, Ong P, Wagner A, Schneider S, Nassenstein K, Gawaz M, Sechtem U, Bruder O, Mahrholdt H. CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis.JACC Cardiovasc Imaging. 2013; 6:501–511. doi: 10.1016/j.jcmg.2012.10.021.CrossrefMedlineGoogle Scholar9. Murtagh G, Laffin LJ, Beshai JF, Maffessanti F, Bonham CA, Patel AV, Yu Z, Addetia K, Mor-Avi V, Moss JD, Hogarth DK, Sweiss NJ, Lang RM, Patel AR. Prognosis of myocardial damage in sarcoidosis patients with preserved left ventricular ejection fraction: risk stratification using cardiovascular magnetic resonance.Circ Cardiovasc Imaging. 2016; 9:e003738. doi: 10.1161/CIRCIMAGING.115.003738.LinkGoogle Scholar10. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices); American Association for Thoracic Surgery; Society of Thoracic Surgeons. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons.J Am Coll Cardiol. 2008; 51:e1–62. doi: 10.1016/j.jacc.2008.02.032.CrossrefMedlineGoogle Scholar11. Grün S, Schumm J, Greulich S, Wagner A, Schneider S, Bruder O, Kispert EM, Hill S, Ong P, Klingel K, Kandolf R, Sechtem U, Mahrholdt H. Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.J Am Coll Cardiol. 2012; 59:1604–1615. doi: 10.1016/j.jacc.2012.01.007.CrossrefMedlineGoogle Scholar12. Bruder O, Wagner A, Jensen CJ, Schneider S, Ong P, Kispert EM, Nassenstein K, Schlosser T, Sabin GV, Sechtem U, Mahrholdt H. Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy.J Am Coll Cardiol. 2010; 56:875–887. doi: 10.1016/j.jacc.2010.05.007.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ismail T, Hua A, Plein S, D’Cruz D, Fernando M, Friedrich M, Zellweger M, Giorgetti A, Caobelli F and Haaf P (2022) The role of cardiovascular magnetic resonance in the evaluation of acute myocarditis and inflammatory cardiomyopathies in clinical practice — a comprehensive review, European Heart Journal - Cardiovascular Imaging, 10.1093/ehjci/jeac021, 23:4, (450-464), Online publication date: 22-Mar-2022. January 2016Vol 9, Issue 1 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.115.004417PMID: 26763282 Originally publishedJanuary 13, 2016 KeywordssurvivalEditorialsprognosiscardiomyopathiesmagnetic resonance imagingPDF download Advertisement SubjectsCardiomyopathy" @default.
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