Hydroxychloroquine-Mediated Cardiotoxicity With a False-Positive 99m Technetium–Labeled Pyrophosphate Scan for Transthyretin-Related Cardiac Amyloidosis
2017; Lippincott Williams & Wilkins; Volume: 11; Issue: 1 Linguagem: Inglês
10.1161/circimaging.117.007059
ISSN1942-0080
AutoresIan C Chang, John P. Bois, Melanie C. Bois, Joseph J. Maleszewski, Geoffrey B. Johnson, Martha Grogan,
Tópico(s)Pneumocystis jirovecii pneumonia detection and treatment
ResumoHomeCirculation: Cardiovascular ImagingVol. 11, No. 1Hydroxychloroquine-Mediated Cardiotoxicity With a False-Positive 99mTechnetium–Labeled Pyrophosphate Scan for Transthyretin-Related Cardiac Amyloidosis Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessCase ReportPDF/EPUBHydroxychloroquine-Mediated Cardiotoxicity With a False-Positive 99mTechnetium–Labeled Pyrophosphate Scan for Transthyretin-Related Cardiac Amyloidosis Ian C.Y. Chang, MD, John P. Bois, MD, Melanie C. Bois, MD, Joseph J. Maleszewski, MD, Geoffrey B. Johnson, MD, PhD and Martha Grogan, MD Ian C.Y. ChangIan C.Y. Chang From the Departments of Cardiovascular Diseases (I.C.Y.C., J.P.B., M.G.), Pathology (M.C.B., J.J.M.), and Radiology and Immunology (G.B.J.), Mayo Clinic, Rochester, MN. , John P. BoisJohn P. Bois From the Departments of Cardiovascular Diseases (I.C.Y.C., J.P.B., M.G.), Pathology (M.C.B., J.J.M.), and Radiology and Immunology (G.B.J.), Mayo Clinic, Rochester, MN. , Melanie C. BoisMelanie C. Bois From the Departments of Cardiovascular Diseases (I.C.Y.C., J.P.B., M.G.), Pathology (M.C.B., J.J.M.), and Radiology and Immunology (G.B.J.), Mayo Clinic, Rochester, MN. , Joseph J. MaleszewskiJoseph J. Maleszewski From the Departments of Cardiovascular Diseases (I.C.Y.C., J.P.B., M.G.), Pathology (M.C.B., J.J.M.), and Radiology and Immunology (G.B.J.), Mayo Clinic, Rochester, MN. , Geoffrey B. JohnsonGeoffrey B. Johnson From the Departments of Cardiovascular Diseases (I.C.Y.C., J.P.B., M.G.), Pathology (M.C.B., J.J.M.), and Radiology and Immunology (G.B.J.), Mayo Clinic, Rochester, MN. and Martha GroganMartha Grogan From the Departments of Cardiovascular Diseases (I.C.Y.C., J.P.B., M.G.), Pathology (M.C.B., J.J.M.), and Radiology and Immunology (G.B.J.), Mayo Clinic, Rochester, MN. Originally published29 Dec 2017https://doi.org/10.1161/CIRCIMAGING.117.007059Circulation: Cardiovascular Imaging. 2018;11:e007059IntroductionCardiac amyloidosis is a rare infiltrative process most commonly caused by abnormal deposition of precursor proteins from monoclonal light chain or transthyretin (ATTR).1 An accurate diagnosis of the amyloidosis subtype has crucial prognostic and therapeutic implications. Bone scintigraphy using 99mtechnetium-labeled pyrophosphate (99mTc-PYP) has been found to have a sensitivity and specificity of 68% and 100%, respectively, for ATTR in patients without evidence of plasma cell dyscrasia.2 Furthermore, high heart/contralateral ratio of ≥1.6 predicted worse survival.3 This has led to a proposed nonbiopsy diagnosis of ATTR using bone scintigraphy.2 However, without widely using 99mTc-PYP scan in various cardiac conditions, the true specificity for amyloidosis remains unclear. We present a case of hydroxychloroquine-mediated cardiotoxicity, a previously unrecognized cause of a false-positive PYP scan for ATTR.A 69-year-old woman with Sjogren syndrome on hydroxycholoquine for 15 years presented with congestive heart failure. On presentation, the patient's creatinine and estimated glomerular filtration rate were 1.2 mg/dL and 45 mL/min per m2, respectively. Transthoracic echocardiogram (Figure 1A and Movie I in the Data Supplement: parasternal long axis; Figure 1B: parasternal short axis; Figure 1C: strain imaging) showed concentric left ventricular wall thickening and abnormal global averaged longitudinal peak systolic strain at −10%, most preserved at the apex. Planar scintigraphy (Figure 1D) of 99mTc-PYP uptake allows count comparison between the heart (red circle) with the contralateral chest (blue circle) on 3-hour uptake anterior planar imaging. The high heart/contralateral ratio was 1.8 (>1.3 considered positive). A total right mastectomy could potentially affect (decrease or increase) the high heart/contralateral ratio, making visual assessment of the single photon emission tomographic images for myocardial uptake more critical. Axial single photon emission tomography (Figure 1E) and fused single photon emission tomography/computed tomography imaging (Figure 1F; Movie II in the Data Supplement) demonstrated myocardial uptake, most pronounced in the left ventricular lateral wall with a semiquantitative score of 2 (0=no cardiac uptake, 1=less than bone, 2=same as bone, and 3=greater than bone/rib) consistent with ATTR. An endomyocardial biopsy was performed. Hematoxylin and eosin–stained sections of the endomyocardial biopsy shows marked sarcoplasmic vacuolization of cardiac myocytes (Figure 2A and 2B; ×100 and ×400 original magnification, respectively). Amyloid was not present on special stains, including sulfated Alcian blue stain and Congo red stains (Figure 2C and 2D, respectively, ×100 original magnification). Toluidine blue–stained thick sections show dense sarcoplasmic inclusions (Figure 2E; ×400 original magnification). Electron microscopy demonstrates the presence of myelinoid and curvilinear bodies, the combination of which is in keeping with hydroxychloroquine-mediated cardiotoxicity (Figure 2F), instead of a presumed diagnosis of cardiac ATTR from a falsely positive 99mTc-PYP scan.Download figureDownload PowerPointFigure 1. A 69-y-old woman with Sjogren syndrome on hydroxycholoquine for 15 y presented with congestive heart failure.Download figureDownload PowerPointFigure 2. Pathology evidence of hydroxychloroquine-mediated cardiotoxicity.Deemed positive using the conventional high heart/contralateral ratio and semiquantitative scoring method, this case illustrates a previously unrecognized pathogenesis behind a positive cardiac uptake of bone scintigraphy 99mTc-PYP tracer in patients without ATTR or light chain amyloidosis. Further studies are needed to determine the mechanism of myocardial uptake of 99mTc-PYP and the true specificity for amyloidosis as the use of this diagnostic modality increases.DisclosuresDr Geoffrey Johnson receives research funding from Pfizer Inc (modest). The other authors report no conflicts.FootnotesThe Data Supplement is available at http://circimaging.ahajournals.org/lookup/suppl/doi:10.1161/CIRCIMAGING.117.007059/-/DC1.Correspondence to Martha Grogan, MD, Department of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail [email protected]References1. Gertz MA, Benson MD, Dyck PJ, Grogan M, Coelho T, Cruz M, Berk JL, Plante-Bordeneuve V, Schmidt HHJ, Merlini G. Diagnosis, prognosis, and therapy of transthyretin amyloidosis.J Am Coll Cardiol. 2015; 66:2451–2466. doi: 10.1016/j.jacc.2015.09.075.CrossrefMedlineGoogle Scholar2. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans AW, Rezk T, Fontana M, Palladini G, Milani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C, Hawkins PN. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis.Circulation. 2016; 133:2404–2412. doi: 10.1161/CIRCULATIONAHA.116.021612.LinkGoogle Scholar3. Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, Pozniakoff T, Ruberg FL, Miller EJ, Berk JL, Dispenzieri A, Grogan M, Johnson G, Bokhari S, Maurer MS. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis.JAMA Cardiol. 2016; 1:880–889. doi: 10.1001/jamacardio.2016.2839.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Basso C and Stone J (2022) Autopsy in the era of advanced cardiovascular imaging, European Heart Journal, 10.1093/eurheartj/ehac220 Tahara N, Lairez O, Endo J, Okada A, Ueda M, Ishii T, Kitano Y, Lee H, Russo E and Kubo T (2021) 99m Technetium‐pyrophosphate scintigraphy: a practical guide for early diagnosis of transthyretin amyloid cardiomyopathy , ESC Heart Failure, 10.1002/ehf2.13693, 9:1, (251-262), Online publication date: 1-Feb-2022. Korosoglou G, Giusca S, André F, aus dem Siepen F, Nunninger P, Kristen A and Frey N (2021) Diagnostic Work-Up of Cardiac Amyloidosis Using Cardiovascular Imaging: Current Standards and Practical Algorithms, Vascular Health and Risk Management, 10.2147/VHRM.S295376, Volume 17, (661-673) Giblin G and Cuddy S (2021) Multimodality Imaging in Cardiac Amyloidosis, Current Cardiology Reports, 10.1007/s11886-021-01564-6, 23:10, Online publication date: 1-Oct-2021. Khalaf S, Khan N, Al-Mallah M, Kassi M and Shah D (2020) A positive PYP scan: Thinking beyond amyloid, Journal of Nuclear Cardiology, 10.1007/s12350-020-02149-6, 28:4, (1796-1797), Online publication date: 1-Aug-2021. Addison D, Slivnick J, Campbell C, Vallakati A, Jneid H and Schelbert E (2021) Recent Advances and Current Dilemmas in the Diagnosis and Management of Transthyretin Cardiac Amyloidosis, Journal of the American Heart Association, 10:9, Online publication date: 4-May-2021.Schafer E, Tushak Z, Trankle C, Rao K, Cartagena L and Shah K (2021) False-Positive 99mTechnetium-Pyrophosphate Scintigraphy in Two Patients With Hypertrophic Cardiomyopathy, Circulation: Heart Failure, 14:3, Online publication date: 1-Mar-2021. Naddaf E, Paul P and AbouEzzeddine O (2021) Chloroquine and Hydroxychloroquine Myopathy: Clinical Spectrum and Treatment Outcomes, Frontiers in Neurology, 10.3389/fneur.2020.616075, 11 Zhang K, Zhang R, Deych E, Stockerl-Goldstein K, Gorcsan J and Lenihan D (2021) A multi-modal diagnostic model improves detection of cardiac amyloidosis among patients with diagnostic confirmation by cardiac biopsy, American Heart Journal, 10.1016/j.ahj.2020.11.006, 232, (137-145), Online publication date: 1-Feb-2021. Chen C, Pan K, Wu B, Li X, Chen Z, Xu Q, Li X and Lv Q (2020) Safety of hydroxychloroquine in COVID-19 and other diseases: a systematic review and meta-analysis of 53 randomized trials, European Journal of Clinical Pharmacology, 10.1007/s00228-020-02962-5, 77:1, (13-24), Online publication date: 1-Jan-2021. Spencer-Bonilla G, Alexander K and Witteles R (2020) Advances in the Diagnosis and Management of Transthyretin Amyloid Cardiomyopathy, Current Treatment Options in Cardiovascular Medicine, 10.1007/s11936-020-00844-8, 22:11, Online publication date: 1-Nov-2020. Hanna M, Ruberg F, Maurer M, Dispenzieri A, Dorbala S, Falk R, Hoffman J, Jaber W, Soman P, Witteles R and Grogan M (2020) Cardiac Scintigraphy With Technetium-99m-Labeled Bone-Seeking Tracers for Suspected Amyloidosis, Journal of the American College of Cardiology, 10.1016/j.jacc.2020.04.022, 75:22, (2851-2862), Online publication date: 1-Jun-2020. Schrezenmeier E and Dörner T (2020) Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology, Nature Reviews Rheumatology, 10.1038/s41584-020-0372-x, 16:3, (155-166), Online publication date: 1-Mar-2020. (2019) Hydroxychloroquine, Reactions Weekly, 10.1007/s40278-019-65583-9, 1764:1, (159-159), Online publication date: 1-Aug-2019. Mendoza L Chloroquine and Hydroxychloroquine for the Treatment of COVID-19 patients: What Every Clinician Should Know, SSRN Electronic Journal, 10.2139/ssrn.3713810 January 2018Vol 11, Issue 1 Advertisement Article InformationMetrics © 2018 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.117.007059PMID: 29288196 Originally publishedDecember 29, 2017 Keywordstomography, emission-computed, single-photonamyloidosisSjogren's syndromeglomerular filtration ratecreatininePDF download Advertisement SubjectsCardio-OncologyCardiomyopathyImagingNuclear Cardiology and PET
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