Myocardial contractile patterns predict future cardiac events in sarcoidosis

  • Jian Chen
  • Juan Lei
  • Ernest Scalzetti
  • Mary McGrath
  • David Feiglin
  • Robert Voelker
  • Jingfeng Wang
  • Michael C. IannuzziEmail author
  • Kan LiuEmail author
Original Paper


The poor prognosis of cardiac sarcoidosis (CS) underscores the need for risk stratification. We evaluated 84 consecutive sarcoidosis patients who were referred for echocardiographic studies for cardiac symptoms or abnormal electrocardiograms. In 54 patients without previous diagnosis of CS or other known structural heart disease, 13 reached endpoints during (median) 24 months follow up. Significantly impaired peak systolic longitudinal strain in their original echocardiograms were identified in 13 of 17 left ventricular segments, clustering in the free wall, interventricular septum and apex. The regional (including 13 clustered segments) peak systolic longitudinal strain (RPSLS) were significantly impaired in patients with endpoints, compared with those without [(−11.4 ± 4.45) vs. (−18.7 ± 3.76) %, P < 0.00001]. Cox multivariate regression analysis revealed that RPSLS was independently associated with endpoints (HR 1.24; 95% CI 1.08–1.42, P = 0.002). Receiver operating characteristic curve suggested a cut-off RPSLS value of −15.0% (84.6% sensitivity and 86.8% specificity) to predict the occurrence of endpoints. Impaired RPSLS correlates with risk of adverse cardiac events in patients with extra-cardiac sarcoidosis.


Risk stratification Regional peak systolic longitudinal strain Cardiac sarcoidosis 



Late peak diastolic velocities across mitral valve


Area under the receiver operating characteristic curve


Coronary artery disease


Cardiac magnetic resonance imaging


Cardiac sarcoidosis


Early peak diastolic velocities across mitral valve


Early diastolic mitral annulus (myocardial) velocity




18F-2-Fluoro-2-Deoxyglucose positron emission tomography


Heart Rhythm Society


Interventricular septal dimensions


Japanese Ministry of Health and Welfare


Left ventricular


Left ventricular end diastolic dimensions


Left ventricular end diastolic volumes


Left ventricular ejection fraction


Left ventricular end systolic dimensions


Left ventricular end systolic volumes


Regional peak systolic longitudinal strain


Posterior wall diameters


Receiver operating characteristic


Systolic mitral annulus (myocardial) velocity


Tissue Doppler imaging




Author contributions

KL, MCI, and JFW: Conception and design of the study; JC, JL, ES, MM, DF, RV: acquisition and analysis of data; JC, JL, ES, MM, DF: interpretation of data; KL, MCI, JFW, JL: drafting the work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

This study is approved by institutional research board of Human Subjects Committee of State University of New York Upstate Medical University.

Informed consent

Not applicable.


  1. 1.
    Hamzeh N, Steckman DA, Sauer WH, Judson MA (2015) Pathophysiology and clinical management of cardiac sarcoidosis. Nat Rev Cardiol 12(5):278–288. doi: 10.1038/nrcardio.2015.22 CrossRefPubMedGoogle Scholar
  2. 2.
    Youssef G, Beanlands RS, Birnie DH, Nery PB (2011) Cardiac sarcoidosis: applications of imaging in diagnosis and directing treatment. Heart 97(24):2078–2087. doi: 10.1136/hrt.2011.226076 CrossRefPubMedGoogle Scholar
  3. 3.
    Iannuzzi MC, Rybicki BA, Teirstein AS (2007) Sarcoidosis. N Engl J Med 357(21):2153–2165. doi: 10.1056/NEJMra071714 CrossRefPubMedGoogle Scholar
  4. 4.
    Kim JS, Judson MA, Donnino R, Gold M, Cooper LT Jr, Prystowsky EN, Prystowsky S (2009) Cardiac sarcoidosis. Am Heart J 157(1):9–21. doi: 10.1016/j.ahj.2008.09.009 CrossRefPubMedGoogle Scholar
  5. 5.
    Thomsen TK, Eriksson T (1999) Myocardial sarcoidosis in forensic medicine. Am J Forensic Med Pathol 20(1):52–56CrossRefPubMedGoogle Scholar
  6. 6.
    Yazaki Y, Isobe M, Hiroe M, Morimoto S, Hiramitsu S, Nakano T, Izumi T, Sekiguchi M, Central Japan Heart Study G (2001) Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone. Am J Cardiol 88 (9):1006–1010CrossRefPubMedGoogle Scholar
  7. 7.
    Nagai T, Nagano N, Sugano Y, Asaumi Y, Aiba T, Kanzaki H, Kusano K, Noguchi T, Yasuda S, Ogawa H, Anzai T (2015) Effect of corticosteroid therapy on long-term clinical outcome and left ventricular function in patients with cardiac sarcoidosis. Circ J 79(7):1593–1600. doi: 10.1253/circj.CJ-14-1275 CrossRefPubMedGoogle Scholar
  8. 8.
    Morgenthau AS, Iannuzzi MC (2011) Recent advances in sarcoidosis. Chest 139(1):174–182. doi: 10.1378/chest.10-0188 CrossRefPubMedGoogle Scholar
  9. 9.
    Viles-Gonzalez JF, Pastori L, Fischer A, Wisnivesky JP, Goldman MG, Mehta D (2013) Supraventricular arrhythmias in patients with cardiac sarcoidosis prevalence, predictors, and clinical implications. Chest 143(4):1085–1090CrossRefPubMedGoogle Scholar
  10. 10.
    Iannuzzi MC, Fontana JR (2011) Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA 305(4):391–399. doi: 10.1001/jama.2011.10 CrossRefPubMedGoogle Scholar
  11. 11.
    Soejima K, Yada H (2009) The work-up and management of patients with apparent or subclinical cardiac sarcoidosis: with emphasis on the associated heart rhythm abnormalities. J Cardiovasc Electrophysiol 20(5):578–583. doi: 10.1111/j.1540-8167.2008.01417.x CrossRefPubMedGoogle Scholar
  12. 12.
    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 (2014) HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm 11(7):1305–1323. doi: 10.1016/j.hrthm.2014.03.043 CrossRefPubMedGoogle Scholar
  13. 13.
    Uemura A, Morimoto S, Hiramitsu S, Kato Y, Ito T, Hishida H (1999) Histologic diagnostic rate of cardiac sarcoidosis: evaluation of endomyocardial biopsies. Am Heart J 138(2 Pt 1):299–302CrossRefPubMedGoogle Scholar
  14. 14.
    Nadel J, Lancefield T, Voskoboinik A, Taylor AJ (2015) Late gadolinium enhancement identified with cardiac magnetic resonance imaging in sarcoidosis patients is associated with long-term ventricular arrhythmia and sudden cardiac death. Eur Heart J Cardiovasc Imaging 16(6):634–641. doi: 10.1093/ehjci/jeu294 PubMedGoogle Scholar
  15. 15.
    Greulich S, Deluigi CC, Gloekler S, Wahl A, Zurn C, Kramer U, Nothnagel D, Bultel H, Schumm J, Grun S, Ong P, Wagner A, Schneider S, Nassenstein K, Gawaz M, Sechtem U, Bruder O, Mahrholdt H (2013) CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging 6(4):501–511. doi: 10.1016/j.jcmg.2012.10.021 CrossRefPubMedGoogle Scholar
  16. 16.
    Blankstein R, Osborne M, Naya M, Waller A, Kim CK, Murthy VL, Kazemian P, Kwong RY, Tokuda M, Skali H, Padera R, Hainer J, Stevenson WG, Dorbala S, Di Carli MF (2014) Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 63(4):329–336. doi: 10.1016/j.jacc.2013.09.022 CrossRefPubMedGoogle Scholar
  17. 17.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 28(1):1–39 e14. doi: 10.1016/j.echo.2014.10.003 CrossRefPubMedGoogle Scholar
  18. 18.
    Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelista A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 22(2):107–133. doi: 10.1016/j.echo.2008.11.023 CrossRefPubMedGoogle Scholar
  19. 19.
    Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, 3rd, Dokainish H, Edvardsen T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK, Popescu BA, Waggoner AD (2016) Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 29(4):277–314. doi: 10.1016/j.echo.2016.01.011 CrossRefPubMedGoogle Scholar
  20. 20.
    Wacholder S, McLaughlin JK, Silverman DT, Mandel JS (1992) Selection of controls in case-control studies. I. Principles. Am J Epidemiol 135(9):1019–1028CrossRefPubMedGoogle Scholar
  21. 21.
    Lei J, Dhamoon AS, Wang J, Iannuzzi M, Liu K (2016) Walking the tightrope: using quantitative Doppler echocardiography to optimize ventricular filling pressures in patients hospitalized for acute heart failure. Eur Heart J Acute Cardiovasc Care 5(2):130–140. doi: 10.1177/2048872615573517 CrossRefPubMedGoogle Scholar
  22. 22.
    Liu K, Krone R (2013) Evaluation of coronary steal in myocardium supplied by coronary collaterals: the role of speckle tracking analysis in resting and stress echocardiography. Echocardiography 30(9):1111–1117. doi: 10.1111/echo.12311 PubMedGoogle Scholar
  23. 23.
    Sun Z, Singh P, Wei T, Kozman H, Liu K (2016) Is the heart really stressed out of energy? JACC Cardiovasc Imaging 9(5):633–635. doi: 10.1016/j.jcmg.2015.02.030 CrossRefGoogle Scholar
  24. 24.
    Valeyre D, Soler P, Clerici C, Pre J, Battesti JP, Georges R, Hance AJ (1988) Smoking and pulmonary sarcoidosis: effect of cigarette smoking on prevalence, clinical manifestations, alveolitis, and evolution of the disease. Thorax 43(7):516–524CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chiu CZ, Nakatani S, Zhang G, Tachibana T, Ohmori F, Yamagishi M, Kitakaze M, Tomoike H, Miyatake K (2005) Prevention of left ventricular remodeling by long-term corticosteroid therapy in patients with cardiac sarcoidosis. Am J Cardiol 95(1):143–146. doi: 10.1016/j.amjcard.2004.08.083 CrossRefPubMedGoogle Scholar
  26. 26.
    Ise T, Hasegawa T, Morita Y, Yamada N, Funada A, Takahama H, Amaki M, Kanzaki H, Okamura H, Kamakura S, Shimizu W, Anzai T, Kitakaze M (2014) Extensive late gadolinium enhancement on cardiovascular magnetic resonance predicts adverse outcomes and lack of improvement in LV function after steroid therapy in cardiac sarcoidosis. Heart 100(15):1165–1172. doi: 10.1136/heartjnl-2013-305187 CrossRefPubMedGoogle Scholar
  27. 27.
    Bito V, Heinzel FR, Weidemann F, Dommke C, van der Velden J, Verbeken E, Claus P, Bijnens B, De Scheerder I, Stienen GJ, Sutherland GR, Sipido KR (2004) Cellular mechanisms of contractile dysfunction in hibernating myocardium. Circ Res 94(6):794–801. doi: 10.1161/01.RES.0000124934.84048.DF CrossRefPubMedGoogle Scholar
  28. 28.
    Patel MR, Cawley PJ, Heitner JF, Klem I, Parker MA, Jaroudi WA, Meine TJ, White JB, Elliott MD, Kim HW, Judd RM, Kim RJ (2009) Detection of myocardial damage in patients with sarcoidosis. Circulation 120(20):1969–1977. doi: 10.1161/CIRCULATIONAHA.109.851352 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Abraham TP, Dimaano VL, Liang HY (2007) Role of tissue Doppler and strain echocardiography in current clinical practice. Circulation 116(22):2597–2609. doi: 10.1161/CIRCULATIONAHA.106.647172 CrossRefPubMedGoogle Scholar
  30. 30.
    Rosner A, How OJ, Aarsaether E, Stenberg TA, Andreasen T, Kondratiev TV, Larsen TS, Myrmel T (2010) High resolution speckle tracking dobutamine stress echocardiography reveals heterogeneous responses in different myocardial layers: implication for viability assessments. J Am Soc Echocardiogr 23(4):439–447. doi: 10.1016/j.echo.2009.12.023 CrossRefPubMedGoogle Scholar
  31. 31.
    Biswas M, Sudhakar S, Nanda NC, Buckberg G, Pradhan M, Roomi AU, Gorissen W, Houle H (2013) Two- and three-dimensional speckle tracking echocardiography: clinical applications and future directions. Echocardiography 30(1):88–105. doi: 10.1111/echo.12079 CrossRefPubMedGoogle Scholar
  32. 32.
    Montgomery DE, Puthumana JJ, Fox JM, Ogunyankin KO (2012) Global longitudinal strain aids the detection of non-obstructive coronary artery disease in the resting echocardiogram. Eur Heart J Cardiovasc Imaging 13(7):579–587. doi: 10.1093/ejechocard/jer282 CrossRefPubMedGoogle Scholar
  33. 33.
    Aggeli C, Felekos I, Tousoulis D, Gialafos E, Rapti A, Stefanadis C (2013) Myocardial mechanics for the early detection of cardiac sarcoidosis. Int J Cardiol 168(5):4820–4821. doi: 10.1016/j.ijcard.2013.07.010 CrossRefPubMedGoogle Scholar
  34. 34.
    Sareen N, Ananthasubramaniam K (2016) Strain imaging: from physiology to practical applications in daily practice. Cardiol Rev 24(2):56–69. doi: 10.1097/CRD.0000000000000067 CrossRefPubMedGoogle Scholar
  35. 35.
    Orii M, Hirata K, Tanimoto T, Shiono Y, Shimamura K, Yamano T, Ino Y, Yamaguchi T, Kubo T, Tanaka A, Imanishi T, Akasaka T (2015) Myocardial damage detected by two-dimensional speckle-tracking echocardiography in patients with extracardiac sarcoidosis: comparison with magnetic resonance imaging. J Am Soc Echocardiogr 28(6):683–691. doi: 10.1016/j.echo.2015.02.018 CrossRefPubMedGoogle Scholar
  36. 36.
    Murtagh G, Laffin LJ, Patel KV, Patel AV, Bonham CA, Yu Z, Addetia K, El-Hangouche N, Maffesanti F, Mor-Avi V, Hogarth DK, Sweiss NJ, Beshai JF, Lang RM, Patel AR (2016) Improved detection of myocardial damage in sarcoidosis using longitudinal strain in patients with preserved left ventricular ejection fraction. Echocardiography 33(9):1344–1352. doi: 10.1111/echo.13281 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Joyce E, Ninaber MK, Katsanos S, Debonnaire P, Kamperidis V, Bax JJ, Taube C, Delgado V, Ajmone Marsan N (2015) Subclinical left ventricular dysfunction by echocardiographic speckle-tracking strain analysis relates to outcome in sarcoidosis. Eur J Heart Fail 17(1):51–62. doi: 10.1002/ejhf.205 CrossRefPubMedGoogle Scholar
  38. 38.
    Schouver ED, Moceri P, Doyen D, Tieulie N, Queyrel V, Baudouy D, Cerboni P, Gibelin P, Leroy S, Fuzibet JG, Ferrari E (2017) Early detection of cardiac involvement in sarcoidosis with 2-dimensional speckle-tracking echocardiography. Int J Cardiol 227:711–716. doi: 10.1016/j.ijcard.2016.10.073 CrossRefPubMedGoogle Scholar
  39. 39.
    Hung CL, Verma A, Uno H, Shin SH, Bourgoun M, Hassanein AH, McMurray JJ, Velazquez EJ, Kober L, Pfeffer MA, Solomon SD, Investigators V (2010) Longitudinal and circumferential strain rate, left ventricular remodeling, and prognosis after myocardial infarction. J Am Coll Cardiol 56 (22):1812–1822. doi: 10.1016/j.jacc.2010.06.044 CrossRefPubMedGoogle Scholar
  40. 40.
    Cheung YF (2012) The role of 3D wall motion tracking in heart failure. Nat Rev Cardiol 9(11):644–657. doi: 10.1038/nrcardio.2012.128 CrossRefPubMedGoogle Scholar
  41. 41.
    Sperry BW, Ibrahim A, Negishi K, Negishi T, Patel P, Popovic ZB, Culver D, Brunken R, Marwick TH, Tamarappoo B (2017) Incremental prognostic value of global longitudinal strain and 18F-fludeoxyglucose positron emission tomography in patients with systemic sarcoidosis. Am J Cardiol 119(10):1663–1669. doi: 10.1016/j.amjcard.2017.02.010 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2017

Authors and Affiliations

  • Jian Chen
    • 1
    • 2
  • Juan Lei
    • 1
    • 3
  • Ernest Scalzetti
    • 4
  • Mary McGrath
    • 4
  • David Feiglin
    • 4
  • Robert Voelker
    • 1
  • Jingfeng Wang
    • 3
  • Michael C. Iannuzzi
    • 5
    Email author
  • Kan Liu
    • 1
    Email author
  1. 1.Division of CardiologyState University of New York, Upstate Medical University HospitalSyracuseUSA
  2. 2.Department of Cardiology, The Fifth Affiliated HospitalSun Yat-Sen UniversityZhuhaiChina
  3. 3.Department of Cardiology, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
  4. 4.Department of RadiologyState University of New York, Upstate Medical University HospitalSyracuseUSA
  5. 5.Department of Internal MedicineState University of New York, Upstate Medical University HospitalSyracuseUSA

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