Routine laboratory biomarkers as prognostic indicators of cardiac sarcoidosis outcomes
Main Article Content
Keywords
Sarcoidosis, Biomarkers, LVAD, Cardiac sarcoidosis, Heart transplant, Major adverse cardiac events
Abstract
Background: Biomarkers to monitor disease activity and predict major adverse cardiac events (MACE) in CS have not been described previously. We aimed to identify biomarkers to predict MACE in cardiac sarcoidosis (CS).
Methods: Patients (N=232) diagnosed with CS were retrospectively enrolled. Biomarkers including angiotensin-converting enzyme (ACE), N-terminal brain natriuretic peptide (NT-proBNP), troponin T, and creatinine levels were evaluated against a primary end point of left ventricular assist device implantation, heart transplantation, or death, and a secondary end point of cardiac hospitalization-free survival.
Results: Troponin T (hazard ratio [HR], 1.06 per 0.01 ng/mL; P=.006), NT-proBNP (HR, 1.31 per 1,000 pg/mL; P<.001), and creatinine (HR, 4.02 per mg/dL; P=.01) were associated with the primary end point, even after adjusting for ejection fraction. NT-proBNP, B-type natriuretic peptide (BNP), creatinine, albumin, and calcium were associated with the secondary end point (P<.05). ACE levels were associated with presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging (mean difference, 14.7; P=.03); 1,25 dihydroxyvitamin D (1,25-OHVit-D) was associated with uptake on cardiac 18F-flurodeoxyglucose position emission tomography (FDG-PET, P=.03).
Conclusions: Troponin T, NT-proBNP, and creatinine predict clinically significant outcomes in CS. ACE levels correlated with LGE on CMR, and 1,25-OHVit-D levels correlated with FDG-PET activity.
References
[2] Kiko T, Yoshihisa A, Kanno Y, Yokokawa T, Abe S, Miyata-Tatsumi M, et al. A Multiple Biomarker Approach in Patients with Cardiac Sarcoidosis. Int Heart J. 2018;59:996-1001.
[3] Muchtar E, Blauwet LA, Gertz MA. Restrictive Cardiomyopathy: Genetics, Pathogenesis, Clinical Manifestations, Diagnosis, and Therapy. Circ Res. 2017;121:819-37.
[4] Blauwet LA, Cooper LT. Idiopathic giant cell myocarditis and cardiac sarcoidosis. Heart Fail Rev. 2013;18:733-46.
[5] Yatsynovich Y, Dittoe N, Petrov M, Maroz N. Cardiac Sarcoidosis: A Review of Contemporary Challenges in Diagnosis and Treatment. Am J Med Sci. 2018;355:113-25.
[6] Arkema EV, Grunewald J, Kullberg S, Eklund A, Askling J. Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden. Eur Respir J. 2016;48:1690-9.
[7] Arkema EV, Cozier YC. Epidemiology of sarcoidosis: current findings and future directions. Ther Adv Chronic Dis. 2018;9:227-40.
[8] Hiraga H, Iwai K. Guidelines for diagnosis of cardiac sarcoidosis: study report on diffuse pulmonary disease (in Japanese). The Japanese Ministry of Health and Welfare. 1993;2.
[9] Birnie DH, Sauer WH, Bogun F, Cooper JM, Culver DA, Duvernoy CS, et al. HRS expert consensus statement on the diagnosis and management of arrhythmias associated with cardiac sarcoidosis. Heart Rhythm. 2014;11:1305-23.
[10] Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation. 1978;58:1204-11.
[11] Terasaki F, Yoshinaga K. New Guidelines for Diagnosis of Cardiac Sarcoidosis in Japan. Ann Nucl Cardiol. 2017;3:42-5.
[12] Cooper LT, Baughman KL, Feldman AM, Frustaci A, Jessup M, Kuhl U, et al. The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology. Eur Heart J. 2007;28:3076-93.
[13] Hulten E, Aslam S, Osborne M, Abbasi S, Bittencourt MS, Blankstein R. Cardiac sarcoidosis-state of the art review. Cardiovasc Diagn Ther. 2016;6:50-63.
[14] Blankstein R, Osborne M, Naya M, Waller A, Kim CK, Murthy VL, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol. 2014;63:329-36.
[15] Hulten E, Agarwal V, Cahill M, Cole G, Vita T, Parrish S, et al. Presence of Late Gadolinium Enhancement by Cardiac Magnetic Resonance Among Patients With Suspected Cardiac Sarcoidosis Is Associated With Adverse Cardiovascular Prognosis: A Systematic Review and Meta-Analysis. Circ Cardiovasc Imaging. 2016;9:e005001.
[16] Ning N, Guo HH, Iagaru A, Mittra E, Fowler M, Witteles R. Serial Cardiac FDG-PET for the Diagnosis and Therapeutic Guidance of Patients With Cardiac Sarcoidosis. J Card Fail. 2019;25:307-11.
[17] Gungor S, Ozseker F, Yalcinsoy M, Akkaya E, Can G, Eroglu H, et al. Conventional markers in determination of activity of sarcoidosis. Int Immunopharmacol. 2015;25:174-9.
[18] Ungprasert P, Carmona EM, Crowson CS, Matteson EL. Diagnostic Utility of Angiotensin-Converting Enzyme in Sarcoidosis: A Population-Based Study. Lung. 2016;194:91-5.
[19] Casanova N, Zhou T, Knox KS, Garcia JGN. Identifying Novel Biomarkers in Sarcoidosis Using Genome-Based Approaches. Clin Chest Med. 2015;36:621-30.
[20] Yasutake H, Seino Y, Kashiwagi M, Honma H, Matsuzaki T, Takano T. Detection of cardiac sarcoidosis using cardiac markers and myocardial integrated backscatter. Int J Cardiol. 2005;102:259-68.
[21] Handa T, Nagai S, Ueda S, Chin K, Ito Y, Watanabe K, et al. Significance of plasma NT-proBNP levels as a biomarker in the assessment of cardiac involvement and pulmonary hypertension in patients with sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2010;27:27-35.
[22] Kandolin R, Lehtonen J, Airaksinen J, Vihinen T, Miettinen H, Kaikkonen K, et al. Usefulness of Cardiac Troponins as Markers of Early Treatment Response in Cardiac Sarcoidosis. Am J Cardiol. 2015;116:960-4.
[23] Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med. 1975;59:365-72.
[24] Coleman GC, Shaw PW, Balfour PC, Jr., Gonzalez JA, Kramer CM, Patel AR, et al. Prognostic Value of Myocardial Scarring on CMR in Patients With Cardiac Sarcoidosis. JACC Cardiovasc Imaging. 2017;10:411-20.
[25] Ise T, Hasegawa T, Morita Y, Yamada N, Funada A, Takahama H, et al. 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. 2014;100:1165-72.
[26] Tanada Y, Sato Y, Sawa T, Fujiwara H, Takatsu Y. Serial measurement of high-sensitivity cardiac troponin I and N-terminal proB-type natriuretic peptide in a patient presenting with cardiac sarcoidosis. Intern Med. 2012;51:3379-81.
[27] Baba Y, Kubo T, Kitaoka H, Okawa M, Yamanaka S, Kawada Y, et al. Usefulness of high-sensitive cardiac troponin T for evaluating the activity of cardiac sarcoidosis. Int Heart J. 2012;53:287-92.
[28] Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296-305.
[29] Wannamethee SG, Shaper AG, Perry IJ. Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke. Stroke. 1997;28:557-63.
[30] Smith GL, Shlipak MG, Havranek EP, Foody JM, Masoudi FA, Rathore SS, et al. Serum urea nitrogen, creatinine, and estimators of renal function: mortality in older patients with cardiovascular disease. Arch Intern Med. 2006;166:1134-42.
[31] Tuegel C, Bansal N. Heart failure in patients with kidney disease. Heart. 2017;103:1848-53.
[32] Ahmadzai H, Loke WSJ, Huang S, Herbert C, Wakefield D, Thomas P. Biomarkers in sarcoidosis: a review. Curr Biomark Find. 2014;4:93-106.
[33] Burke RR, Rybicki BA, Rao DS. Calcium and vitamin D in sarcoidosis: how to assess and manage. Semin Respir Crit Care Med. 2010;31:474-84.
[34] Letilovic T, Perkov S, Mestric ZF, Vrhovac R. Differences in routine laboratory parameters related to cachexia between patients with hematological diseases and patients with solid tumors or heart failure - is there only one cachexia? Nutr J. 2013;12:6.
[35] Huizar JF, Ellenbogen KA, Tan AY, Kaszala K. Arrhythmia-Induced Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73:2328-44.
Article Sidebar
Article Details
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
