Advertisement

Cardiac sarcoidosis outcome differences: A comparison of patients with de novo cardiac versus known extracardiac sarcoidosis at presentation

      Highlights

      • De novo cardiac sarcoidosis (CS) presents with more advanced cardiomyopathy, ventricular arrhythmia and heart block.
      • De novo CS patients have increased adverse cardiac outcomes compared to those with a prior extracardiac sarcoidosis (ECS).
      • In those with CS, de novo and prior ECS patients have similar mortality.
      • Improved awareness and diagnosis of CS is warranted for earlier recognition.

      Abstract

      Background

      Sarcoidosis is a systemic disease characterized by granulomatous inflammation. Cardiac involvement is associated with increased morbidity. However, differences in clinical characteristics and outcomes based on initial sarcoidosis organ manifestation in patients with cardiac sarcoidosis (CS) have not been described.

      Methods

      A retrospective cohort of 252 patients with CS at an urban, quaternary medical center was studied. Presentation, treatment and outcomes of de novo CS and prior ECS groups were compared. Survival free of primary composite outcome (left ventricular assist device implantation, orthotopic heart transplantation (OHT), or death) was assessed.

      Results

      There were 124 de novo CS patients and 128 with prior ECS at time of CS diagnosis. De novo CS patients were younger at CS diagnosis (p = 0.020). De novo CS patients had a more advanced cardiac presentation: lower left ventricular ejection fraction (LVEF) (p < 0.001), more frequent sustained ventricular arrhythmias (VA) (p = 0.001), and complete heart block (p = 0.001). During follow-up, new VA (p < 0.001), ventricular tachycardia ablation (p < 0.001), and OHT (p = 0.003) were more common in the de novo CS group. Outcome free survival was significantly shorter for de novo CS patients (p = 0.005), with increased hazard of primary composite outcome (p = 0.034) and development of new VA (p = 0.027) when compared to ECS patients. Overall mortality was similar between groups.

      Conclusion

      Patients presenting with CS as their first recognized organ manifestation of sarcoidosis have an increased risk of adverse cardiac outcomes as compared to those with a prior history of ECS. Improved awareness and diagnosis of CS is warranted for earlier recognition.

      Graphical abstract

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Respiratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Te H.S.
        • Perlman D.M.
        • Shenoy C.
        • et al.
        Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts.
        BMC Pulm. Med. 2020; 20 (Published 2020 Jun 1): 155https://doi.org/10.1186/s12890-020-01191-x
        • Trivieri M.G.
        • Spagnolo P.
        • Birnie D.
        • Liu P.
        • Drake W.
        • Kovacic J.C.
        • Baughman R.
        • Fayad Z.A.
        • Judson M.A.
        Challenges in cardiac and pulmonary sarcoidosis: JACC state-of-the-art review.
        J. Am. Coll. Cardiol. 2020 Oct 20; 76 (PMID: 33059834; PMCID: PMC7808240): 1878-1901https://doi.org/10.1016/j.jacc.2020.08.042
        • Grutters J.C.
        • van den Bosch J.M.M.
        Corticosteroid treatment in sarcoidosis.
        Eur. Respir. J. 2006; 28: 627-636https://doi.org/10.1183/09031936.06.00105805
        • Kinney E.L.
        • Jackson G.L.
        • Reeves W.C.
        • Zelis R.
        Thallium-scan myocardial defects and echocardiographic abnormalities in patients with sarcoidosis without clinical cardiac dysfunction. An analysis of 44 patients.
        Am. J. Med. 1980; 68 ([PubMed: 7369231]): 497-503
        • Tellier P.
        • Paycha F.
        • Antony I.
        • et al.
        Reversibility by dipyridamole of thallium-201 myocardial scan defects in patients with sarcoidosis.
        Am. J. Med. 1988; 85 ([PubMed: 3400694]): 189-193
        • Fahy G.J.
        • Marwick T.
        • McCreery C.J.
        • Quigley P.J.
        • Maurer B.J.
        Doppler echocardiographic detection of left ventricular diastolic dysfunction in patients with pulmonary sarcoidosis.
        Chest. 1996; 109 ([PubMed: 8549220]): 62-66
        • Perry A.
        • Vuitch F.
        Causes of death in patients with sarcoidosis. A morphologic study of 38 autopsies with clinicopathologic correlations.
        Arch. Pathol. Lab Med. 1995; 119 ([PubMed: 7848065]): 167-172
        • Mehta D.
        • Lubitz S.A.
        • Frankel Z.
        • Wisnivesky J.P.
        • Einstein A.J.
        • Goldman M.
        • Machac J.
        • Teirstein A.
        Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value of outpatient testing.
        Chest. 2008 Jun; 133 (Epub 2008 Mar 13. PMID: 18339784): 1426-1435https://doi.org/10.1378/chest.07-2784
        • Hulten E.
        • Aslam S.
        • Osborne M.
        • Abbasi S.
        • Bittencourt M.S.
        • Blankstein R.
        Cardiac sarcoidosis-state of the art review.
        Cardiovasc. Diagn. Ther. 2016; 6: 50-63https://doi.org/10.3978/j.issn.2223-3652.2015.12.13
        • Okada D.R.
        • Bravo P.E.
        • Vita T.
        • et al.
        Isolated cardiac sarcoidosis: a focused review of an under-recognized entity [published correction appears in J Nucl Cardiol. 2016 Sep 28;:].
        J. Nucl. Cardiol. 2018; 25: 1136-1146https://doi.org/10.1007/s12350-016-0658-1
        • Birnie D.H.
        • Sauer W.H.
        • Bogun F.
        • et al.
        HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis.
        Heart Rhythm. 2014; 11: 1304-1323https://doi.org/10.1016/j.hrthm.2014.03.043
        • Terasaki F.
        • Yoshinaga K.
        New guidelines for diagnosis of cardiac sarcoidosis in Japan.
        Ann Nucl. Cardiol. 2017; 3: 42-45https://doi.org/10.17996/anc.17-00042
        • Crouser E.D.
        • Maier L.A.
        • Wilson K.C.
        • Bonham C.A.
        • Morgenthau A.S.
        • Patterson K.C.
        • Abston E.
        • Bernstein R.C.
        • Blankstein R.
        • Chen E.S.
        • Culver D.A.
        • Drake W.
        • Drent M.
        • Gerke A.K.
        • Ghobrial M.
        • Govender P.
        • Hamzeh N.
        • James W.E.
        • Judson M.A.
        • Kellermeyer L.
        • Knight S.
        • Koth L.L.
        • Poletti V.
        • Raman S.V.
        • Tukey M.H.
        • Westney G.E.
        • Baughman R.P.
        Diagnosis and detection of sarcoidosis. An official American thoracic society clinical practice guideline.
        Am. J. Respir. Crit. Care Med. 2020 Apr 15; 201: e26-e51https://doi.org/10.1164/rccm.202002-0251ST
        • Okada D.R.
        • Saad E.
        • Wand A.L.
        • et al.
        Effect of corticosteroid dose and duration on 18-fluorodeoxyglucose positron emission tomography in cardiac sarcoidosis.
        JACC Cardiovasc Imaging. 2020; 13: 1280-1282https://doi.org/10.1016/j.jcmg.2019.12.013
        • Chareonthaitawee P.
        • Beanlands R.S.
        • Chen W.
        • et al.
        Joint SNMMI–ASNC expert consensus document on the role of 18F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring.
        J. Nucl. Cardiol. 2017; 24: 1741-1758https://doi.org/10.1007/s12350-017-0978-9
        • Griffin J.M.
        • Chasler J.
        • Wand A.L.
        • Okada D.R.
        • Smith J.N.
        • Saad E.
        • Tandri H.
        • Chrispin J.
        • Sharp M.
        • Kasper E.K.
        • Chen E.S.
        • Gilotra N.A.
        Management of cardiac sarcoidosis using mycophenolate mofetil as a steroid-sparing agent.
        J. Card. Fail. 2021 Jun 21; S1071–9164 (00246-3 Epub ahead of print. PMID: 34166800)https://doi.org/10.1016/j.cardfail.2021.06.010
        • RStudio Team
        RStudio.
        Integrated Development for R. RStudio, PBC, Boston, MA2020
        • Rabin D.L.
        • et al.
        Sarcoidosis: social predictors of severity at presentation.
        Eur. Respir. J. 2004; 24: 601-608
        • Judson M.A.
        • Boan A.D.
        • Lackland D.T.
        The clinical course of sarcoidosis: presentation, diagnosis, and treatment in a large white and black cohort in the United States, Sarcoidosis Vasc.
        Diffuse Lung Dis. 2012; 29: 119-127
        • Takashige N.
        • Naruse T.K.
        • Matsumori A.
        • et al.
        Genetic polymorphisms at the tumour necrosis factor loci (TNFA and TNFB) in cardiac sarcoidosis.
        Tissue Antigens. 1999; 54 ([PubMed: 10488747]): 191-193
        • Naruse T.K.
        • Matsuzawa Y.
        • Ota M.
        • et al.
        HLA-DQB1*0601 is primarily associated with the susceptibility to cardiac sarcoidosis.
        Tissue Antigens. 2000; 56 ([PubMed: 10958356]): 52-57
        • Valentonyte R.
        • Hampe J.
        • Huse K.
        • et al.
        Sarcoidosis is associated with a truncating splice site mutation in BTNL2.
        Nat. Genet. 2005; 37 ([PubMed: 15735647]): 357-364
        • Kandolin R.
        • Lehtonen J.
        • Airaksinen J.
        • Vihinen T.
        • Miettinen H.
        • Ylitalo K.
        • et al.
        Cardiac sarcoidosis: epidemiology, characteristics, and outcome over 25 years in a nationwide study.
        Circulation. 2015 Feb 17; 131: 624-632
        • Tezuka D.
        • Terashima M.
        • Kato Y.
        • Toriihara A.
        • Hirasawa K.
        • Sasaoka T.
        • Yoshikawa S.
        • Maejima Y.
        • Ashikaga T.
        • Suzuki J.
        • Hirao K.
        • Isobe M.
        Clinical characteristics of definite or suspected isolated cardiac sarcoidosis: application of cardiac magnetic resonance imaging and 18F-Fluoro-2-deoxyglucose positron-emission tomography/computerized tomography.
        J. Card. Fail. 2015; 21: 313-322
        • Tavora F.
        • Cresswell N.
        • Li L.
        • Ripple M.
        • Solomon C.
        • Burke A.
        Comparison of necropsy findings in patients with sarcoidosis dying suddenly from cardiac sarcoidosis versus dying suddenly from other causes.
        Am. J. Cardiol. 2009; 104: 571-577
        • Nagai T.
        • Nagano N.
        • Sugano Y.
        • Asaumi Y.
        • Aiba T.
        • Kanzaki H.
        • Kusano K.
        • Noguchi T.
        • Yasuda S.
        • Ogawa H.
        • Anzai T.
        Effect of corticosteroid therapy on long‐term clinical outcome and left ventricular function in patients with cardiac sarcoidosis.
        Circ. J. 2015; 79: 1593-1600
        • Okada D.R.
        • Saad E.
        • Wand A.L.
        • et al.
        Effect of corticosteroid dose and duration on 18-fluorodeoxyglucose positron emission tomography in cardiac sarcoidosis.
        JACC Cardiovasc Imaging. 2020; 13: 1280-1282https://doi.org/10.1016/j.jcmg.2019.12.013
        • Yazaki Y.
        • Isobe M.
        • Hiroe M.
        • et al.
        Prognostic determinants of long-term survival in Japanese patients with cardiac sarcoidosis treated with prednisone.
        Am. J. Cardiol. 2001; 88: 1006-1010https://doi.org/10.1016/S0002-9149(01)01978-6
        • Rosenthal D.G.
        • Parwani P.
        • Murray T.O.
        • Petek B.J.
        • Benn B.S.
        • De Marco T.
        • Gerstenfeld E.P.
        • Janmohamed M.
        • Klein L.
        • Lee B.K.
        • Moss J.D.
        • Scheinman M.M.
        • Hsia H.H.
        • Selby V.
        • Koth L.L.
        • Pampaloni M.H.
        • Zikherman J.
        • Vedantham V.
        Long-term corticosteroid-sparing immunosuppression for cardiac sarcoidosis.
        J. Am. Heart Assoc. 2019 Sep 17; 8 (Epub 2019 Sep 6. PMID: 31538835; PMCID: PMC6818011)e010952https://doi.org/10.1161/JAHA.118.010952
        • Sharp M.
        • Brown T.
        • Chen E.S.
        • Rand C.S.
        • Moller D.R.
        • Eakin M.N.
        Association of medication adherence and clinical outcomes in sarcoidosis.
        Chest. Feb 2020; (S0012369220302397)https://doi.org/10.1016/j.chest.2020.01.026
        • Baker M.C.
        • Sheth K.
        • Witteles R.
        • Genovese M.C.
        • Shoor S.
        • Simard J.F.
        TNF-alpha inhibition for the treatment of cardiac sarcoidosis [published correction appears in Semin Arthritis Rheum. 2021 Jun 22;:].
        Semin. Arthritis Rheum. 2020; 50: 546-552https://doi.org/10.1016/j.semarthrit.2019.11.004
        • Gilotra N.A.
        • Griffin J.M.
        • Pavlovic N.
        • Houston B.A.
        • Chasler J.
        • Goetz C.
        • Chrispin J.
        • Sharp M.
        • Kasper E.K.
        • Chen E.S.
        • Blankstein R.
        • Cooper L.T.
        • Joyce E.
        • Sheikh F.H.
        Sarcoidosis-related cardiomyopathy: current knowledge, challenges, and future perspectives state-of-the-art review.
        J. Card. Fail. 2021 Jul 11; S1071–9164 (Epub ahead of print. PMID: 34260889): 264-265https://doi.org/10.1016/j.cardfail.2021.06.016
        • Crawford T.C.
        • Okada D.R.
        • Magruder J.T.
        • Fraser C.
        • Patel N.
        • Houston B.A.
        • Whitman G.J.
        • Mandal K.
        • Zehr K.J.
        • Higgins R.S.
        • Chen E.S.
        • Tandri H.
        • Kasper E.K.
        • Tedford R.J.
        • Russell S.D.
        • Gilotra N.A.
        A contemporary analysis of heart transplantation and bridge-to-transplant mechanical circulatory support outcomes in cardiac sarcoidosis.
        J. Card. Fail. 2018 Jun; 24: 384-391
        • Jackson K.C.
        • Youmans Q.R.
        • Wu T.
        • Harap R.
        • Anderson A.S.
        • Chicos A.
        • Ezema A.
        • Mandieka E.
        • Ohiomoba R.
        • Pawale A.
        • Pham D.T.
        • Russell S.
        • Sporn P.H.S.
        • Yancy C.W.
        • Okwuosa I.S.
        Heart transplantation outcomes in cardiac sarcoidosis.
        J. Heart Lung Transplant. 2022 Jan; 41: 113-122