Kappa-light Chain Amyloid Overlapping Hypertrophic Cardiomyopathy With Myocardial Noncompaction
2020; Lippincott Williams & Wilkins; Volume: 13; Issue: 7 Linguagem: Inglês
10.1161/circimaging.119.010379
ISSN1942-0080
AutoresAndrea Frustaci, Nicola Galea, Romina Verardo, Marco Francone, Maria Alfarano, Matteo Antonio Russo, Cristina Chimenti,
Tópico(s)Protein Tyrosine Phosphatases
ResumoHomeCirculation: Cardiovascular ImagingVol. 13, No. 7Kappa-light Chain Amyloid Overlapping Hypertrophic Cardiomyopathy With Myocardial Noncompaction Free AccessCase ReportPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessCase ReportPDF/EPUBKappa-light Chain Amyloid Overlapping Hypertrophic Cardiomyopathy With Myocardial Noncompaction Andrea Frustaci, MD, Nicola Galea, MD, Romina Verardo, PhD, Marco Francone, MD, Maria Alfarano, MD, Matteo Antonio Russo, MD and Cristina Chimenti, MD, PhD Andrea FrustaciAndrea Frustaci Prof Andrea Frustaci, Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, La Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy. Email E-mail Address: [email protected], Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences (A.F., M.A., C.C.), Sapienza University, Rome. Cellular and Molecular Cardiology Lab, IRCCS Lazzaro Spallanzani, Rome (A.F., R.V., C.C.). , Nicola GaleaNicola Galea Department of Experimental Medicine (N.G., M.F.), Sapienza University, Rome. , Romina VerardoRomina Verardo Cellular and Molecular Cardiology Lab, IRCCS Lazzaro Spallanzani, Rome (A.F., R.V., C.C.). , Marco FranconeMarco Francone Department of Experimental Medicine (N.G., M.F.), Sapienza University, Rome. , Maria AlfaranoMaria Alfarano Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences (A.F., M.A., C.C.), Sapienza University, Rome. , Matteo Antonio RussoMatteo Antonio Russo Cellular and Molecular Pathology Lab, IRCCS S. Raffaele Pisana, Rome, Italy (M.A.R.). and Cristina ChimentiCristina Chimenti Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences (A.F., M.A., C.C.), Sapienza University, Rome. Cellular and Molecular Cardiology Lab, IRCCS Lazzaro Spallanzani, Rome (A.F., R.V., C.C.). Originally published1 Jul 2020https://doi.org/10.1161/CIRCIMAGING.119.010379Circulation: Cardiovascular Imaging. 2020;13:e010379Coexistence of different biologically divergent myocardial entities is rare and of difficult recognition. Cardiac imaging can raise the suspicion of the unusual structural combination and solicit endomyocardial biopsy for confirmation.A 59-year old man known to be affected from age 30 years by a mildly symptomatic hypertrophic cardiomyopathy (HCM) was admitted because of recurrent long-lasting (3 months) fever. At admission, all microbiological investigations failed to identify an infectious agent. Eventually serological and hematologic studies diagnosed a monoclonal gammopathy paralleled by a pathological increase of bone marrow plasma cells >10%.Physical examination was unremarkable. Electrocardiogram was characterized by sinus rhythm 68 beats/min with elevated QRS voltages and inverted T wave in D1, AVL, and V6 leads suggesting left ventricular (LV) hypertrophy (Figure 1A). Two-dimensional electrocardiogram showed severe thickening of LV wall with maximal thickness of 21 mm located in the interventricular septum.Download figureDownload PowerPointFigure 1. Electrocardiographic, angiographic, histological, and ultrastructural findings of amyloid overlapping hypertrophic cardiomyopathy with myocardial noncompaction.A, 12-Lead electrocardiogram showing high QRS voltages with inverted T wave suggesting left ventricular (LV) hypertrophy. B, LV angiography denoting presence of transmural crypts. C, LV endomyocardial biopsy showing severe hypertrophy with disarray of cardiomyocytes compatible with hypertrophic cardiomyopathy. Large area of tissue replacement with fibrous tissue and pale-pink amorphous material is included (hematoxylin and eosin ×200). D, The endocardium is interrupted by deep unendothelialized channels indicating myocardial noncompaction (Masson trichrome ×100). E, Immunohistochemistry for kappa light chain showing intense interstitial positivity denoting light chain deposition (magnification ×200). F, Electron-micrograph showing the interstitial material to consist of amyloid fibrils.Cine-magnetic resonance images showed a severe LV hypertrophy (maximal wall thickness of 21 mm at basal septum), with reduced systolic function (LV ejection fraction: 49%), myocardial noncompaction at midapical segments, with multiple deep crypts at the antero-septal wall (Movies I and II in the Data Supplement). An increase of global extracellular volume reflects diffuse interstitial fibrosis, more pronounced in the hypertrophic segments and subendocardial layers. Late gadolinium-enhanced images relieved a diffuse enhancement of the septum, anterior and inferior walls of the left ventricle suggesting extensive amyloid infiltration (Figure 2).Download figureDownload PowerPointFigure 2. Cardiac magnetic resonance imaging in a patient Kappa-light chain amyloid overlapping hypertrophic cardiomyopathy with myocardial noncompaction.A, Cine-magnetic resonance images show a severe left ventricular (LV) hypertrophy (maximal wall thickness of 21 mm at basal septum); B, with reduced systolic function (LV ejection fraction: 49%), myocardial noncompaction at midapical segments; C, multiple deep crypts at the antero-septal wall (arrow); D, an increase of global extracellular volume reflects a diffuse interstitial fibrosis, more pronounced in the hypertrophic segments and subendocardial layers. E and F, Late gadolinium-enhanced images relieve a diffuse enhancement of the septum, anterior, and inferior walls of the left ventricle suggesting extensive amyloid infiltration.Due to clinical manifestation of fever with monoclonal gammopathy and to cardiac magnetic resonance findings raising the suspicion of cardiac amyloid overlapping HCM, the patient underwent cardiac catheterization with coronary, LV angiography, and endomyocardial biopsy. Coronary arteries were normal. LV angiography showed the presence of transmural crypts (Figure 1B) associated with LV myocardial noncompaction.At histology, severely hypertrophied disarrayed cardiomyocytes were fragmented in short runs by interstitial and replacement fibrosis (Figure 1C), suggesting a sarcomeric HCM.The endocardium was frequently interrupted by deep unendothelialized channels denoting LV myocardial noncompaction (Figure 1D).Paraffin sections were tested with immunohistochemistry for transthyretin, apolipoprotein 1 and 2, serum amyloid A, and Kappa and lambda light chains. Strong positivity for deposition of kappa light chain was documented on the interstitium and intramural vessel wall (Figure 1E).At ultrastructural examination, the interstitial space was focally widened by both connective and amyloid fibrils (Figure 1F).No other organ localization of amyloid was apparent judging from normal kidney and liver scan and function tests.The patient was treated with steroids and Alkeran to control the monoclonal gammopathy being followed by fever remittance.Identification of cardiac amyloid is easy when it occurs in the context of a normal heart. Indeed, presence of hypoatrophic myocytes surrounded by a dielectric material generates low QRS voltages that contrast with progressive thickening of cardiac walls raising a strong diagnostic suspicion. The sparkling like appearance at 2-dimensional echocardiogram makes the diagnosis of amyloid very likely soliciting endomyocardial biopsy for confirmation and molecular characterization. In our case with an established HCM, deposition of amyloid material was difficult to raise as the severe LV hypertrophy abolished its usual manifestation. Nevertheless, cardiac magnetic resonance imaging was still able to recognize zebroid areas highlighting the clinical manifestation of fever and monoclonal gammopathy. Histology and electron microscopy of endomyocardial biopsy samples recognized the strange combination of kappa light chain amyloid with HCM. Although impossible to prove, the large intercellular spaces derived by myocardial noncompaction may have favored amyloid deposition.Finally, the recognition of cardiac amyloid in HCM has important clinical implications. Treatment with immunosuppression of monoclonal gammopathy may revert or halt LV dysfunction, knowing the inhibitory action of light chain on cardiomyocytes1 extending sometimes to a real myocarditis.2Sources of FundingThis work was supported by European Project ERA-CVD (European Research Area Network on Cardiovascular Diseases) Transnational Research Projects on Cardiovascular Diseases (JTC 2016 IKDT-IGCM) and Italian Ministry of Health (Ricerca corrente) given to IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Spallanzani and IRCCS San Raffaele Pisana.DisclosuresNone.FootnotesThe Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.119.010379.Prof Andrea Frustaci, Department of Cardiovascular, Respiratory, Nephrologic, Anesthesiologic and Geriatric Sciences, La Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy. Email [email protected]it,References1. Imperlini E, Gnecchi M, Rognoni P, Sabidò E, Ciuffreda MC, Palladini G, Espadas G, Mancuso FM, Bozzola M, Malpasso G, et alProteotoxicity in cardiac amyloidosis: amyloidogenic light chains affect the levels of intracellular proteins in human heart cells.Sci Rep. 2017; 7:15661. doi: 10.1038/s41598-017-15424-3CrossrefMedlineGoogle Scholar2. Siegismund CS, Escher F, Lassner D, Kühl U, Gross U, Fruhwald F, Wenzel P, Münzel T, Frey N, Linke RP, et alIntramyocardial inflammation predicts adverse outcome in patients with cardiac AL amyloidosis.Eur J Heart Fail. 2018; 20:751–757. doi: 10.1002/ejhf.1039CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Chimenti C, Lavalle C, Magnocavallo M, Alfarano M, Mariani M, Bernardini F, Della Rocca D, Galardo G, Severino P, Di Lullo L, Miraldi F, Fedele F and Frustaci A (2021) A proposed strategy for anticoagulation therapy in noncompaction cardiomyopathy, ESC Heart Failure, 10.1002/ehf2.13694, 9:1, (241-250), Online publication date: 1-Feb-2022. July 2020Vol 13, Issue 7 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.119.010379PMID: 32605379 Originally publishedJuly 1, 2020 Keywordsparaproteinemiascardiomyopathieshypertrophy, left ventricularmagnetic resonance imagingPDF download Advertisement SubjectsCardiomyopathyHeart Failure
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