Silent Progression: Cardiac Amyloidosis Unmasking IgG Lambda Myeloma in an Elderly Patient

Silent Progression: Cardiac Amyloidosis Unmasking IgG Lambda Myeloma in an Elderly Patient | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Silent Progression: Cardiac Amyloidosis Unmasking IgG Lambda Myeloma in an Elderly Patient soufiane touiti, Meriem Bouali, Loubna El Bahri, lyasse Asfalou, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6498469/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Jan, 2026 Read the published version in The Egyptian Heart Journal → Version 1 posted 11 You are reading this latest preprint version Abstract Background: Cardiac amyloidosis is an underrecognized etiology of heart failure with preserved ejection fraction (HFpEF), particularly in elderly patients. Light-chain (AL) amyloidosis, when associated with multiple myeloma, is highly aggressive and portends a poor prognosis, especially in advanced cardiac stages. Case Presentation: We report the case of a 79-year-old male with type 2 diabetes, hypertension, and a history of pacemaker implantation for complete atrioventricular block in the context of atrial fibrillation. He was admitted with progressive exertional dyspnea and an episode of syncope. Clinical examination revealed fine basal crackles and signs of decompensated heart failure. ECG demonstrated a paced rhythm. Echocardiography and cardiac MRI revealed concentric left ventricular hypertrophy with a sparkling myocardial texture, biatrial dilation, restrictive filling pattern, and diffuse subendocardial late gadolinium enhancement—features highly suggestive of cardiac amyloidosis. Laboratory tests revealed anemia, renal dysfunction, elevated troponin and NT-proBNP, and a monoclonal IgG lambda spike. Bone marrow biopsy confirmed the diagnosis of multiple myeloma with plasma cell infiltration. Based on clinical and laboratory findings, the patient was classified as Mayo stage IIIB AL cardiac amyloidosis and ISS stage I multiple myeloma. He received bortezomib-cyclophosphamide-based chemotherapy and supportive care, but unfortunately died five months after diagnosis. Discussion: This case highlights the importance of early recognition of cardiac amyloidosis in elderly patients with unexplained heart failure and monoclonal gammopathy. Cardiac MRI and serum free light chain analysis are critical tools in the diagnostic pathway. Despite advances in treatment, outcomes remain poor in advanced cardiac involvement. Early intervention may improve prognosis, underscoring the need for heightened clinical awareness. Conclusion: Infiltrative cardiomyopathies like AL amyloidosis should be considered in elderly patients with heart failure and systemic red flags. Timely diagnosis and multidisciplinary management are essential but often insufficient in advanced stages. Cardiac amyloidosis AL amyloidosis Multiple myeloma Cardiac MRI Heart failure with preserved ejection fraction Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 INTRODUCTION Cardiac amyloidosis is an infiltrative cardiomyopathy caused by extracellular deposition of misfolded protein fibrils within the myocardium, leading to progressive diastolic dysfunction and restrictive physiology. Among its various forms, immunoglobulin light-chain (AL) amyloidosis is particularly aggressive, often associated with rapid deterioration when cardiac involvement occurs. More than 50% of patients with AL amyloidosis develop cardiac involvement, which is the main determinant of prognosis—median survival is often limited to a few months without treatment or when diagnosis is delayed ( 1 )( 2 ). The clinical presentation of cardiac amyloidosis is frequently nonspecific, often mimicking hypertensive heart disease or heart failure with preserved ejection fraction (HFpEF), especially in older adults ( 3 ). AL amyloidosis is typically associated with an underlying plasma cell dyscrasia, such as multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)( 4 ). In some cases, cardiac symptoms may precede hematologic signs, delaying diagnosis and treatment. We report a case of advanced AL cardiac amyloidosis revealing underlying IgG lambda multiple myeloma in a 79-year-old man. This case highlights the diagnostic and therapeutic challenges inherent to this often-overlooked condition. CASE REPORT A 79-year-old man with a medical history of type 2 diabetes mellitus, hypertension, and permanent atrial fibrillation with dual-chamber pacemaker implantation in 2022 for complete atrioventricular block, presented with progressive exertional dyspnea over three months. His symptoms progressed from NYHA class II to class III, and he experienced a brief syncope (~ 10 seconds) while climbing stairs, without post-ictal confusion or focal neurological deficit. This, along with a global decline in functional status, prompted hospital admission. On admission, he was alert and oriented. Respiratory rate was 23 breaths/min, heart rate was 65 bpm (regular), and blood pressure was 110/50 mmHg. Cardiac auscultation revealed regular heart sounds without murmurs or added sounds. Fine bibasilar crackles were noted on pulmonary examination; the remainder of the exam was unremarkable. Chest radiography was normal. Electrocardiogram (ECG) (Fig. 1 ) showed a ventricular-paced rhythm with a controlled rate of 65 bpm, without conduction or repolarization abnormalities. Transthoracic echocardiography (TTE) (Fig. 2 – 5 ) revealed a non-dilated left ventricle with concentric hypertrophy and a granular or "sparkling" myocardial appearance, highly suggestive of an infiltrative cardiomyopathy. Both the interventricular septum and the posterior wall were thickened, measuring 14 mm. Biatrial enlargement was noted. Doppler evaluation demonstrated a restrictive mitral inflow pattern, consistent with elevated left ventricular filling pressures. Speckle-tracking analysis showed a significantly reduced global longitudinal strain, with relative apical sparing—producing the classic “cherry-on-top” pattern on the bull’s-eye plot, strongly indicative of cardiac amyloidosis. Cardiac magnetic resonance imaging (CMR) (Fig. 6–8) reinforced the echocardiographic suspicion of infiltrative cardiomyopathy. It demonstrated marked concentric left ventricular hypertrophy with diffuse subendocardial late gadolinium enhancement (LGE), notably involving the interventricular septum and extending to all myocardial walls. Native T1 mapping revealed significantly elevated values (1310 ms in the lateral wall), and the calculated extracellular volume (ECV) was 38%—both highly consistent with diffuse myocardial amyloid infiltration. These findings, particularly the global subendocardial LGE pattern and abnormal parametric mapping, are hallmarks of advanced AL cardiac amyloidosis. Laboratory evaluation showed normocytic normochromic anemia (Hb 11.8 g/dL), chronic kidney disease (eGFR 49 mL/min/1.73m²), proteinuria (urine protein-to-creatinine ratio: 158 mg/mmol; albumin-to-creatinine ratio: 21 mg/mmol), and low serum albumin (13 g/L). Total 24-hour proteinuria was 29 g. Cardiac biomarkers were significantly elevated: troponin I at 132 ng/L (~ 3x upper limit of normal) and NT-proBNP at 8828 pg/mL. Serum protein electrophoresis (SPEP) showed a monoclonal spike in the gamma region (20.5 g/L). Serum immunofixation identified an IgG lambda monoclonal protein. Free light chain analysis revealed a kappa/lambda ratio of 0.23. Bence-Jones proteinuria was negative. Bone marrow aspiration revealed 10–12% dystrophic plasma cells. Immunohistochemical staining confirmed plasma cell infiltration expressing CD56, consistent with multiple myeloma. A skeletal survey, including skull X-rays and spinal/pelvic MRI, showed no lytic lesions. Serum calcium was normal (93 mg/dL). The International Staging System (ISS) score was 1 (β2-microglobulin 3.12 mg/L; serum albumin 41 g/L). Cardiac amyloidosis was staged as Mayo Clinic stage IIIB. The patient’s heart failure was managed with intravenous loop diuretics. Anticoagulation for atrial fibrillation was maintained. After multidisciplinary evaluation, chemotherapy with bortezomib and cyclophosphamide (VC protocol) was initiated, alongside valaciclovir 500 mg/day and levofloxacin 500 mg/day for infection prophylaxis. Despite optimal treatment, the patient’s condition progressively worsened, and he passed away five months after diagnosis. DISCUSSION Cardiac amyloidosis, particularly light-chain (AL) amyloidosis, represents a critical diagnostic and prognostic inflection point in patients presenting with heart failure with preserved ejection fraction (HFpEF). The disease results from the extracellular deposition of misfolded immunoglobulin light chains produced by clonal plasma cells, most commonly in the myocardium and kidneys, but often with systemic involvement ( 1 ). Cardiac amyloidosis may mimic or coexist with more common cardiovascular conditions, leading to frequent under-recognition and delayed treatment — delays that are often fatal ( 5 ). In this case, the patient’s presentation with progressive dyspnea, syncope, and signs of HFpEF in the context of preserved left ventricular ejection fraction (LVEF) but increased myocardial thickness was initially non-specific. However, several “red flag” findings ( 6 ) pointed toward an infiltrative process including unexplained LV hypertrophy, proteinuria, elevated cardiac biomarkers, and monoclonal gammopathy—pointed toward AL amyloidosis. These features, when considered together, strongly suggested AL amyloidosis, later confirmed by cardiac MRI and hematologic workup. ( 6 ) In elderly patients, cardiac amyloidosis is an increasingly recognized cause of HFpEF. In fact, a 2019 autopsy series found that up to 25% of patients over 80 years with HFpEF had evidence of cardiac transthyretin amyloidosis (ATTR) ( 2 ). While AL amyloidosis is less prevalent than ATTR in this age group, it carries a far worse prognosis, especially in the presence of cardiac involvement. Median survival for untreated AL cardiac amyloidosis is approximately 6 months ( 7 ). In clinical practice, AL amyloidosis should be suspected in any patient with unexplained heart failure, especially when accompanied by systemic signs such as macroglossia, periorbital purpura, weight loss, syncope, or nephrotic syndrome ( 8 ). Notably, in our patient, the history of conduction system disease requiring pacemaker implantation—in the absence of significant ischemia—should have raised earlier suspicion for amyloid infiltration. Cardiac MRI is instrumental in diagnosing infiltrative cardiomyopathies. The hallmark of AL cardiac amyloidosis is global subendocardial or transmural late gadolinium enhancement (LGE), along with elevated native T1 values and extracellular volume (ECV) on parametric mapping ( 9 )( 10 ). In this case, the patient’s MRI showed diffuse LGE and an ECV of 38%, consistent with severe myocardial amyloid infiltration. Elevated troponin and NT-proBNP are also strongly prognostic. The Mayo Clinic 2012 staging system incorporates these markers, and stage IIIB disease, as in this case, carries a median survival of only 3–4 months, even with therapy ( 11 ). Although AL amyloidosis is associated with underlying plasma cell dyscrasias, only ~ 10–15% of patients with multiple myeloma develop systemic AL amyloidosis ( 12 ). Conversely, AL amyloidosis can precede or co-exist with multiple myeloma in up to 30% of cases ( 13 ). This patient had IgG lambda multiple myeloma with moderate plasma cell infiltration (10–12%), fitting the diagnostic criteria for both disorders. The lack of bone lesions or hypercalcemia, coupled with renal and cardiac dysfunction, pointed toward amyloid organ damage as the primary manifestation. The prognostic scoring in multiple myeloma (ISS stage I in this case) does not capture the impact of cardiac amyloid, which often independently dictates outcome. This dichotomy between hematologic and cardiac severity complicates treatment planning.( 14 ) Multidisciplinary collaboration is key. Treatment strategies must balance the aggressive nature of the plasma cell dyscrasia with the fragility imposed by cardiac dysfunction ( 15 ). In this patient, despite the appropriate chemotherapy and supportive management, disease progression was relentless due to the advanced cardiac amyloid infiltration. The mainstay of AL amyloidosis therapy is eliminating the amyloidogenic plasma cell clone, typically using bortezomib-based regimens ( 14 ). In this case, the patient was started on a bortezomib-cyclophosphamide regimen (VC protocol) with antimicrobial prophylaxis. Unfortunately, advanced cardiac involvement limits chemotherapy tolerability, and even well-selected patients with stage IIIB disease may not survive beyond a few months ( 11 ). Emerging therapies, such as daratumumab (anti-CD38 monoclonal antibody), have shown promise in AL amyloidosis when added to standard regimens (e.g., Dara-VCD), improving hematologic response and survival ( 16 ). However, such therapies may not be accessible or appropriate in elderly frail patients with multiorgan failure. This case poignantly illustrates the crucial role of early diagnosis. Had the diagnosis of amyloidosis been considered earlier—perhaps at the time of pacemaker implantation for idiopathic AV block—the patient might have received therapy before reaching irreversible cardiac decompensation. CONCLUSION Cardiac amyloidosis should be considered in elderly patients with unexplained HFpEF, conduction disturbances, or disproportionate LV hypertrophy. The presence of red flags such as proteinuria, low serum albumin, and monoclonal gammopathy should prompt thorough diagnostic workup. This case illustrates how cardiac involvement can serve as the initial manifestation of underlying multiple myeloma and highlights the severe prognosis associated with late-stage AL amyloidosis. Early diagnosis, multidisciplinary management, and access to novel therapies are key to improving survival in these patients. Abbreviations VC protocol: Bortezomib–cyclophosphamide protocol TTE: Transthoracic echocardiography SSFP: Steady-state free precession SPEP: Serum protein electrophoresis NYHA: New York Heart Association NT-proBNP: N-terminal pro–B-type natriuretic peptide MRI: Magnetic resonance imaging MGUS: Monoclonal gammopathy of undetermined significance LVEF: Left ventricular ejection fraction LV: Left ventricle / ventricular LGE: Late gadolinium enhancement ISS: International Staging System HFpEF: Heart failure with preserved ejection fraction GLS: Global longitudinal strain ESC: European Society of Cardiology EF: Ejection fraction ECV: Extracellular volume ECG: Electrocardiogram DARA-VCD: Daratumumab–bortezomib– cyclophosphamide–dexamethasone CR: Case report CMR: Cardiac magnetic resonance BPM: Beats per minute AV block: Atrioventricular block ATTR: Transthyretin amyloidosis AL: Amyloid light-chain Declarations CONSENT FOR PUBLICATION Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request. FUNDING DECLARATION This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. References Muchtar E, Dispenzieri A, Magen H, et al. Systemic Amyloidosis from A (AA) to T (ATTR): A Review. J Intern Med. 2021;289(3):268–292. 2021; Kyle RA, Gertz MA. Primary Systemic Amyloidosis: Clinical and Laboratory Features in 474 Cases. Semin Hematol. 1995;32(1):45–59. 1995; Tana M, Piccinini R, Moffa L, Tana C. Heart Failure with Preserved Ejection Fraction and Cardiac Amyloidosis in the Aging Heart. Int J Mol Sci. 2024;25(21):11519. Published 2024 Oct 26. doi:10.3390/ijms252111519. 2024; Staron, A., Kataria, Y., Murray, D.L., Sloan, J.M. and Sanchorawala, V. Systemic AL amyloidosis with an undetectable plasma cell dyscrasia: A zebra without stripes. Am J Hematol, 95: E45-E48. https://doi.org/10.1002/ajh.25685. 2020; Huan T Nguyen, Chuyen T H Nguyen,. Cardiac amyloidosis mimicking acute coronary syndrome: a case report and literature review, European Heart Journal - Case Reports, Volume 4, Issue 6, December 2020,. 2020; Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021, 42:1554-68. 2021; Gertz MA, Comenzo R, Falk RH, et al. Definition of Organ Involvement and Treatment Response in Immunoglobulin Light Chain Amyloidosis (AL): A Consensus Opinion from the 10th International Symposium on Amyloid and Amyloidosis. Am J Hematol. 2005;79(4):319–328. 2005; Donnelly JP, Hanna M. Cardiac Amyloidosis: An Update on Diagnosis and Treatment. Cleve Clin J Med. 2017;84(12 Suppl 3):12–26. 2017; Fontana M, Pica S, Reant P, et al. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. Circulation. 2015;132(16):1570–1579. 2015; Razvi Y, Patel RK, Fontana M, Gillmore JD. Cardiac Amyloidosis: A Review of Current Imaging Techniques. Front Cardiovasc Med. 2021;8:751293. Published 2021 Dec 10. doi:10.3389/fcvm.2021.751293. 2021; Kumar S, Dispenzieri A, Lacy MQ, et al. Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements. J Clin Oncol. 2012;30(9):989–995. 2012; Palladini G, Merlini G. Multiple myeloma and AL amyloidosis: Similarities and differences. Haematologica. 2020;105(3):562–564. 2020; Ríos-Tamayo R, Krsnik I, Gómez-Bueno M, Garcia-Pavia P, Segovia-Cubero J, Huerta A, Salas C, Silvestre RÁ, Sánchez A, Manso M, Delgado L, Lahuerta JJ, Martínez-López J, Duarte RF. AL Amyloidosis and Multiple Myeloma: A Complex Scenario in Which Cardiac Involvement Remains the Key Prognostic Factor. Life (Basel). 2023 Jul 6;13(7):1518. doi: 10.3390/life13071518. PMID: 37511893; PMCID: PMC10382070. 2023; Xu J, Wang M, Shen Y, et al. Effects of Amyloid Light-Chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-Center Retrospective Study. Cancer Manag Res. 2021;13:1343-1356. Published 2021 Feb 11. doi:10.2147/CMAR.S287922. 2021; Pour-Ghaz I, Bath A, Kayali S, et al. A Review of Cardiac Amyloidosis: Presentation, Diagnosis, and Treatment. Curr Probl Cardiol. 2022;47(12):101366. doi:10.1016/j.cpcardiol.2022.101366. 2022; Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021;385(1):46–58. 2021; Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Jan, 2026 Read the published version in The Egyptian Heart Journal → Version 1 posted Editorial decision: Revision requested 15 Dec, 2025 Reviews received at journal 15 Dec, 2025 Reviewers agreed at journal 13 Dec, 2025 Reviews received at journal 08 Aug, 2025 Reviewers agreed at journal 07 Aug, 2025 Reviewers agreed at journal 18 May, 2025 Reviewers agreed at journal 18 May, 2025 Reviewers invited by journal 29 Apr, 2025 Editor assigned by journal 23 Apr, 2025 Submission checks completed at journal 23 Apr, 2025 First submitted to journal 21 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6498469","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":449534973,"identity":"d23611de-05e7-4284-9297-5eefb8fd89b6","order_by":0,"name":"soufiane 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1","display":"","copyAsset":false,"role":"figure","size":491509,"visible":true,"origin":"","legend":"\u003cp\u003eventricular-paced rhythm with a controlled rate of 65 bpm\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/599696f9bb57e810c090bfff.png"},{"id":82164501,"identity":"1e398b72-2bc0-49c5-9c1e-dd60512099c2","added_by":"auto","created_at":"2025-05-07 09:06:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":511880,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eApical four-chamber view showing concentric LV hypertrophy with granular myocardial texture and biatrial enlargement.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/87b22efd21f0a2cc9bb3c926.png"},{"id":82164503,"identity":"d3cf227f-b74c-490e-9225-e3de3c4535a8","added_by":"auto","created_at":"2025-05-07 09:06:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":370531,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eParasternal short-axis view confirming concentric LV thickening.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/5b0f4ff3506d4c7442fea067.png"},{"id":82164504,"identity":"2e2550ae-386c-42a0-9eff-ff6a8524500d","added_by":"auto","created_at":"2025-05-07 09:06:36","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":361372,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eApical four-chamber view with similar findings.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/78554aae0144430465c333db.png"},{"id":82164508,"identity":"b6f82bea-3140-48bf-9530-b8fb573e5847","added_by":"auto","created_at":"2025-05-07 09:06:37","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":411113,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eBull’s-eye plot showing severely reduced global longitudinal strain with apical sparing—typical “cherry-on-top” pattern indicative of cardiac amyloidosis.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/d6797f7f63f502ecbde29572.png"},{"id":82164505,"identity":"175a9e71-b4a6-464d-a81a-98f61778dafc","added_by":"auto","created_at":"2025-05-07 09:06:36","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":342568,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e \u003cstrong\u003eAxial cine SSFP view showing concentric left ventricular hypertrophy\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/e0a10b41071219afdb616f2f.png"},{"id":82164510,"identity":"35b7109c-4ed6-4f22-b22a-6556c5e93dc2","added_by":"auto","created_at":"2025-05-07 09:06:37","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":242064,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eShort-axis T2-weighted image showing thickened myocardium without edema.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/2730c27b5c64f054e5aea19f.png"},{"id":82164506,"identity":"b057fc79-acc6-48a8-a576-a10c7f05a2ca","added_by":"auto","created_at":"2025-05-07 09:06:36","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":179768,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFour-chamber LGE view demonstrating diffuse subendocardial enhancement of both ventricles, consistent with advanced cardiac amyloid infiltration.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/2d2fdc31e7b13a0aa90d6370.png"},{"id":100069418,"identity":"fd4c97c2-1f51-4875-8eb6-d2d816619d86","added_by":"auto","created_at":"2026-01-12 16:13:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4068840,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6498469/v1/904d9f81-a574-4b9c-80ce-6cc75033d1df.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSilent Progression: Cardiac Amyloidosis Unmasking IgG Lambda Myeloma in an Elderly Patient\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCardiac amyloidosis is an infiltrative cardiomyopathy caused by extracellular deposition of misfolded protein fibrils within the myocardium, leading to progressive diastolic dysfunction and restrictive physiology. Among its various forms, immunoglobulin light-chain (AL) amyloidosis is particularly aggressive, often associated with rapid deterioration when cardiac involvement occurs. More than 50% of patients with AL amyloidosis develop cardiac involvement, which is the main determinant of prognosis\u0026mdash;median survival is often limited to a few months without treatment or when diagnosis is delayed (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe clinical presentation of cardiac amyloidosis is frequently nonspecific, often mimicking hypertensive heart disease or heart failure with preserved ejection fraction (HFpEF), especially in older adults (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). AL amyloidosis is typically associated with an underlying plasma cell dyscrasia, such as multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In some cases, cardiac symptoms may precede hematologic signs, delaying diagnosis and treatment.\u003c/p\u003e \u003cp\u003eWe report a case of advanced AL cardiac amyloidosis revealing underlying IgG lambda multiple myeloma in a 79-year-old man. This case highlights the diagnostic and therapeutic challenges inherent to this often-overlooked condition.\u003c/p\u003e"},{"header":"CASE REPORT","content":"\u003cp\u003eA 79-year-old man with a medical history of type 2 diabetes mellitus, hypertension, and permanent atrial fibrillation with dual-chamber pacemaker implantation in 2022 for complete atrioventricular block, presented with progressive exertional dyspnea over three months. His symptoms progressed from NYHA class II to class III, and he experienced a brief syncope (~\u0026thinsp;10 seconds) while climbing stairs, without post-ictal confusion or focal neurological deficit. This, along with a global decline in functional status, prompted hospital admission.\u003c/p\u003e\n\u003cp\u003eOn admission, he was alert and oriented. Respiratory rate was 23 breaths/min, heart rate was 65 bpm (regular), and blood pressure was 110/50 mmHg. Cardiac auscultation revealed regular heart sounds without murmurs or added sounds. Fine bibasilar crackles were noted on pulmonary examination; the remainder of the exam was unremarkable.\u003c/p\u003e\n\u003cp\u003eChest radiography was normal. Electrocardiogram (ECG) (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) showed a ventricular-paced rhythm with a controlled rate of 65 bpm, without conduction or repolarization abnormalities.\u003c/p\u003e\n\u003cp\u003eTransthoracic echocardiography (TTE) (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e) revealed a non-dilated left ventricle with concentric hypertrophy and a granular or \u0026quot;sparkling\u0026quot; myocardial appearance, highly suggestive of an infiltrative cardiomyopathy. Both the interventricular septum and the posterior wall were thickened, measuring 14 mm. Biatrial enlargement was noted. Doppler evaluation demonstrated a restrictive mitral inflow pattern, consistent with elevated left ventricular filling pressures. Speckle-tracking analysis showed a significantly reduced global longitudinal strain, with relative apical sparing\u0026mdash;producing the classic \u0026ldquo;cherry-on-top\u0026rdquo; pattern on the bull\u0026rsquo;s-eye plot, strongly indicative of cardiac amyloidosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCardiac magnetic resonance imaging (CMR)\u003c/strong\u003e (Fig. 6\u0026ndash;8) reinforced the echocardiographic suspicion of infiltrative cardiomyopathy. It demonstrated marked concentric left ventricular hypertrophy with diffuse subendocardial late gadolinium enhancement (LGE), notably involving the interventricular septum and extending to all myocardial walls. Native T1 mapping revealed significantly elevated values (1310 ms in the lateral wall), and the calculated extracellular volume (ECV) was 38%\u0026mdash;both highly consistent with diffuse myocardial amyloid infiltration. These findings, particularly the global subendocardial LGE pattern and abnormal parametric mapping, are hallmarks of advanced AL cardiac amyloidosis.\u003c/p\u003e\n\u003cp\u003eLaboratory evaluation showed normocytic normochromic anemia (Hb 11.8 g/dL), chronic kidney disease (eGFR 49 mL/min/1.73m\u0026sup2;), proteinuria (urine protein-to-creatinine ratio: 158 mg/mmol; albumin-to-creatinine ratio: 21 mg/mmol), and low serum albumin (13 g/L). Total 24-hour proteinuria was 29 g.\u003c/p\u003e\n\u003cp\u003eCardiac biomarkers were significantly elevated: troponin I at 132 ng/L (~\u0026thinsp;3x upper limit of normal) and NT-proBNP at 8828 pg/mL.\u003c/p\u003e\n\u003cp\u003eSerum protein electrophoresis (SPEP) showed a monoclonal spike in the gamma region (20.5 g/L). Serum immunofixation identified an IgG lambda monoclonal protein. Free light chain analysis revealed a kappa/lambda ratio of 0.23. Bence-Jones proteinuria was negative.\u003c/p\u003e\n\u003cp\u003eBone marrow aspiration revealed 10\u0026ndash;12% dystrophic plasma cells. Immunohistochemical staining confirmed plasma cell infiltration expressing CD56, consistent with multiple myeloma.\u003c/p\u003e\n\u003cp\u003eA skeletal survey, including skull X-rays and spinal/pelvic MRI, showed no lytic lesions. Serum calcium was normal (93 mg/dL). The International Staging System (ISS) score was 1 (\u0026beta;2-microglobulin 3.12 mg/L; serum albumin 41 g/L). Cardiac amyloidosis was staged as Mayo Clinic stage IIIB.\u003c/p\u003e\n\u003cp\u003eThe patient\u0026rsquo;s heart failure was managed with intravenous loop diuretics. Anticoagulation for atrial fibrillation was maintained. After multidisciplinary evaluation, chemotherapy with bortezomib and cyclophosphamide (VC protocol) was initiated, alongside valaciclovir 500 mg/day and levofloxacin 500 mg/day for infection prophylaxis.\u003c/p\u003e\n\u003cp\u003eDespite optimal treatment, the patient\u0026rsquo;s condition progressively worsened, and he passed away five months after diagnosis.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eCardiac amyloidosis, particularly light-chain (AL) amyloidosis, represents a critical diagnostic and prognostic inflection point in patients presenting with heart failure with preserved ejection fraction (HFpEF). The disease results from the extracellular deposition of misfolded immunoglobulin light chains produced by clonal plasma cells, most commonly in the myocardium and kidneys, but often with systemic involvement (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Cardiac amyloidosis may mimic or coexist with more common cardiovascular conditions, leading to frequent under-recognition and delayed treatment \u0026mdash; delays that are often fatal (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this case, the patient\u0026rsquo;s presentation with progressive dyspnea, syncope, and signs of HFpEF in the context of preserved left ventricular ejection fraction (LVEF) but increased myocardial thickness was initially non-specific. However, several \u0026ldquo;red flag\u0026rdquo; findings (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) pointed toward an infiltrative process including unexplained LV hypertrophy, proteinuria, elevated cardiac biomarkers, and monoclonal gammopathy\u0026mdash;pointed toward AL amyloidosis.\u003c/p\u003e \u003cp\u003eThese features, when considered together, strongly suggested AL amyloidosis, later confirmed by cardiac MRI and hematologic workup. (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eIn elderly patients, cardiac amyloidosis is an increasingly recognized cause of HFpEF. In fact, a 2019 autopsy series found that up to 25% of patients over 80 years with HFpEF had evidence of cardiac transthyretin amyloidosis (ATTR) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). While AL amyloidosis is less prevalent than ATTR in this age group, it carries a far worse prognosis, especially in the presence of cardiac involvement. Median survival for untreated AL cardiac amyloidosis is approximately 6 months (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn clinical practice, AL amyloidosis should be suspected in any patient with unexplained heart failure, especially when accompanied by systemic signs such as macroglossia, periorbital purpura, weight loss, syncope, or nephrotic syndrome (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Notably, in our patient, the history of conduction system disease requiring pacemaker implantation\u0026mdash;in the absence of significant ischemia\u0026mdash;should have raised earlier suspicion for amyloid infiltration.\u003c/p\u003e \u003cp\u003eCardiac MRI is instrumental in diagnosing infiltrative cardiomyopathies. The hallmark of AL cardiac amyloidosis is global subendocardial or transmural late gadolinium enhancement (LGE), along with elevated native T1 values and extracellular volume (ECV) on parametric mapping (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). In this case, the patient\u0026rsquo;s MRI showed diffuse LGE and an ECV of 38%, consistent with severe myocardial amyloid infiltration. Elevated troponin and NT-proBNP are also strongly prognostic. The Mayo Clinic 2012 staging system incorporates these markers, and stage IIIB disease, as in this case, carries a median survival of only 3\u0026ndash;4 months, even with therapy (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough AL amyloidosis is associated with underlying plasma cell dyscrasias, only\u0026thinsp;~\u0026thinsp;10\u0026ndash;15% of patients with multiple myeloma develop systemic AL amyloidosis (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Conversely, AL amyloidosis can precede or co-exist with multiple myeloma in up to 30% of cases (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This patient had IgG lambda multiple myeloma with moderate plasma cell infiltration (10\u0026ndash;12%), fitting the diagnostic criteria for both disorders. The lack of bone lesions or hypercalcemia, coupled with renal and cardiac dysfunction, pointed toward amyloid organ damage as the primary manifestation.\u003c/p\u003e \u003cp\u003eThe prognostic scoring in multiple myeloma (ISS stage I in this case) does not capture the impact of cardiac amyloid, which often independently dictates outcome. This dichotomy between hematologic and cardiac severity complicates treatment planning.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMultidisciplinary collaboration is key. Treatment strategies must balance the aggressive nature of the plasma cell dyscrasia with the fragility imposed by cardiac dysfunction (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In this patient, despite the appropriate chemotherapy and supportive management, disease progression was relentless due to the advanced cardiac amyloid infiltration.\u003c/p\u003e \u003cp\u003eThe mainstay of AL amyloidosis therapy is eliminating the amyloidogenic plasma cell clone, typically using bortezomib-based regimens (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In this case, the patient was started on a bortezomib-cyclophosphamide regimen (VC protocol) with antimicrobial prophylaxis. Unfortunately, advanced cardiac involvement limits chemotherapy tolerability, and even well-selected patients with stage IIIB disease may not survive beyond a few months (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEmerging therapies, such as daratumumab (anti-CD38 monoclonal antibody), have shown promise in AL amyloidosis when added to standard regimens (e.g., Dara-VCD), improving hematologic response and survival (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, such therapies may not be accessible or appropriate in elderly frail patients with multiorgan failure.\u003c/p\u003e \u003cp\u003eThis case poignantly illustrates the crucial role of early diagnosis. Had the diagnosis of amyloidosis been considered earlier\u0026mdash;perhaps at the time of pacemaker implantation for idiopathic AV block\u0026mdash;the patient might have received therapy before reaching irreversible cardiac decompensation.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eCardiac amyloidosis should be considered in elderly patients with unexplained HFpEF, conduction disturbances, or disproportionate LV hypertrophy. The presence of red flags such as proteinuria, low serum albumin, and monoclonal gammopathy should prompt thorough diagnostic workup. This case illustrates how cardiac involvement can serve as the initial manifestation of underlying multiple myeloma and highlights the severe prognosis associated with late-stage AL amyloidosis. Early diagnosis, multidisciplinary management, and access to novel therapies are key to improving survival in these patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVC protocol: Bortezomib\u0026ndash;cyclophosphamide protocol\u003c/p\u003e\n\u003cp\u003eTTE: Transthoracic echocardiography\u003c/p\u003e\n\u003cp\u003eSSFP: Steady-state free precession\u003c/p\u003e\n\u003cp\u003eSPEP: Serum protein electrophoresis\u003c/p\u003e\n\u003cp\u003eNYHA: New York Heart Association\u003c/p\u003e\n\u003cp\u003eNT-proBNP: N-terminal pro\u0026ndash;B-type natriuretic peptide\u003c/p\u003e\n\u003cp\u003eMRI: Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003eMGUS: Monoclonal gammopathy of undetermined significance\u003c/p\u003e\n\u003cp\u003eLVEF: Left ventricular ejection fraction\u003c/p\u003e\n\u003cp\u003eLV: Left ventricle / ventricular\u003c/p\u003e\n\u003cp\u003eLGE: Late gadolinium enhancement\u003c/p\u003e\n\u003cp\u003eISS: International Staging System\u003c/p\u003e\n\u003cp\u003eHFpEF: Heart failure with preserved ejection fraction\u003c/p\u003e\n\u003cp\u003eGLS: Global longitudinal strain\u003c/p\u003e\n\u003cp\u003eESC: European Society of Cardiology\u003c/p\u003e\n\u003cp\u003eEF: Ejection fraction\u003c/p\u003e\n\u003cp\u003eECV: Extracellular volume\u003c/p\u003e\n\u003cp\u003eECG: Electrocardiogram\u003c/p\u003e\n\u003cp\u003eDARA-VCD: Daratumumab\u0026ndash;bortezomib\u0026ndash;\u003c/p\u003e\n\u003cp\u003ecyclophosphamide\u0026ndash;dexamethasone\u003c/p\u003e\n\u003cp\u003eCR: Case report\u003c/p\u003e\n\u003cp\u003eCMR: Cardiac magnetic resonance\u003c/p\u003e\n\u003cp\u003eBPM: Beats per minute\u003c/p\u003e\n\u003cp\u003eAV block: Atrioventricular block\u003c/p\u003e\n\u003cp\u003eATTR: Transthyretin amyloidosis\u003c/p\u003e\n\u003cp\u003eAL: Amyloid light-chain\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCONSENT FOR PUBLICATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal upon request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFUNDING DECLARATION\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e\u003cbr\u003e\u003c/strong\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMuchtar E, Dispenzieri A, Magen H, et al. Systemic Amyloidosis from A (AA) to T (ATTR): A Review. J Intern Med. 2021;289(3):268\u0026ndash;292. 2021; \u003c/li\u003e\n\u003cli\u003eKyle RA, Gertz MA. Primary Systemic Amyloidosis: Clinical and Laboratory Features in 474 Cases. Semin Hematol. 1995;32(1):45\u0026ndash;59. 1995; \u003c/li\u003e\n\u003cli\u003eTana M, Piccinini R, Moffa L, Tana C. Heart Failure with Preserved Ejection Fraction and Cardiac Amyloidosis in the Aging Heart. Int J Mol Sci. 2024;25(21):11519. Published 2024 Oct 26. doi:10.3390/ijms252111519. 2024; \u003c/li\u003e\n\u003cli\u003eStaron, A., Kataria, Y., Murray, D.L., Sloan, J.M. and Sanchorawala, V. Systemic AL amyloidosis with an undetectable plasma cell dyscrasia: A zebra without stripes. Am J Hematol, 95: E45-E48. https://doi.org/10.1002/ajh.25685. 2020; \u003c/li\u003e\n\u003cli\u003eHuan T Nguyen, Chuyen T H Nguyen,. Cardiac amyloidosis mimicking acute coronary syndrome: a case report and literature review, European Heart Journal - Case Reports, Volume 4, Issue 6, December 2020,. 2020; \u003c/li\u003e\n\u003cli\u003eGarcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021, 42:1554-68. 2021; \u003c/li\u003e\n\u003cli\u003eGertz MA, Comenzo R, Falk RH, et al. Definition of Organ Involvement and Treatment Response in Immunoglobulin Light Chain Amyloidosis (AL): A Consensus Opinion from the 10th International Symposium on Amyloid and Amyloidosis. Am J Hematol. 2005;79(4):319\u0026ndash;328. 2005; \u003c/li\u003e\n\u003cli\u003eDonnelly JP, Hanna M. Cardiac Amyloidosis: An Update on Diagnosis and Treatment. Cleve Clin J Med. 2017;84(12 Suppl 3):12\u0026ndash;26. 2017; \u003c/li\u003e\n\u003cli\u003eFontana M, Pica S, Reant P, et al. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. Circulation. 2015;132(16):1570\u0026ndash;1579. 2015; \u003c/li\u003e\n\u003cli\u003eRazvi Y, Patel RK, Fontana M, Gillmore JD. Cardiac Amyloidosis: A Review of Current Imaging Techniques. Front Cardiovasc Med. 2021;8:751293. Published 2021 Dec 10. doi:10.3389/fcvm.2021.751293. 2021; \u003c/li\u003e\n\u003cli\u003eKumar S, Dispenzieri A, Lacy MQ, et al. Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements. J Clin Oncol. 2012;30(9):989\u0026ndash;995. 2012; \u003c/li\u003e\n\u003cli\u003ePalladini G, Merlini G. Multiple myeloma and AL amyloidosis: Similarities and differences. Haematologica. 2020;105(3):562\u0026ndash;564. 2020; \u003c/li\u003e\n\u003cli\u003eR\u0026iacute;os-Tamayo R, Krsnik I, G\u0026oacute;mez-Bueno M, Garcia-Pavia P, Segovia-Cubero J, Huerta A, Salas C, Silvestre R\u0026Aacute;, S\u0026aacute;nchez A, Manso M, Delgado L, Lahuerta JJ, Mart\u0026iacute;nez-L\u0026oacute;pez J, Duarte RF. AL Amyloidosis and Multiple Myeloma: A Complex Scenario in Which Cardiac Involvement Remains the Key Prognostic Factor. Life (Basel). 2023 Jul 6;13(7):1518. doi: 10.3390/life13071518. PMID: 37511893; PMCID: PMC10382070. 2023; \u003c/li\u003e\n\u003cli\u003eXu J, Wang M, Shen Y, et al. Effects of Amyloid Light-Chain Amyloidosis on Clinical Characteristics and Prognosis in Multiple Myeloma: A Single-Center Retrospective Study. Cancer Manag Res. 2021;13:1343-1356. Published 2021 Feb 11. doi:10.2147/CMAR.S287922. 2021; \u003c/li\u003e\n\u003cli\u003ePour-Ghaz I, Bath A, Kayali S, et al. A Review of Cardiac Amyloidosis: Presentation, Diagnosis, and Treatment. Curr Probl Cardiol. 2022;47(12):101366. doi:10.1016/j.cpcardiol.2022.101366. 2022; \u003c/li\u003e\n\u003cli\u003eKastritis E, Palladini G, Minnema MC, et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. N Engl J Med. 2021;385(1):46\u0026ndash;58. 2021; \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-heart-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tehj","sideBox":"Learn more about [The Egyptian Heart Journal](https://tehj.springeropen.com)","snPcode":"43044","submissionUrl":"https://submission.springernature.com/new-submission/43044/3","title":"The Egyptian Heart Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cardiac amyloidosis, AL amyloidosis, Multiple myeloma, Cardiac MRI, Heart failure with preserved ejection fraction","lastPublishedDoi":"10.21203/rs.3.rs-6498469/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6498469/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eCardiac amyloidosis is an underrecognized etiology of heart failure with preserved ejection fraction (HFpEF), particularly in elderly patients. Light-chain (AL) amyloidosis, when associated with multiple myeloma, is highly aggressive and portends a poor prognosis, especially in advanced cardiac stages.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eWe report the case of a 79-year-old male with type 2 diabetes, hypertension, and a history of pacemaker implantation for complete atrioventricular block in the context of atrial fibrillation. He was admitted with progressive exertional dyspnea and an episode of syncope. Clinical examination revealed fine basal crackles and signs of decompensated heart failure. ECG demonstrated a paced rhythm. Echocardiography and cardiac MRI revealed concentric left ventricular hypertrophy with a sparkling myocardial texture, biatrial dilation, restrictive filling pattern, and diffuse subendocardial late gadolinium enhancement\u0026mdash;features highly suggestive of cardiac amyloidosis. Laboratory tests revealed anemia, renal dysfunction, elevated troponin and NT-proBNP, and a monoclonal IgG lambda spike. Bone marrow biopsy confirmed the diagnosis of multiple myeloma with plasma cell infiltration. Based on clinical and laboratory findings, the patient was classified as Mayo stage IIIB AL cardiac amyloidosis and ISS stage I multiple myeloma. He received bortezomib-cyclophosphamide-based chemotherapy and supportive care, but unfortunately died five months after diagnosis.\u003c/p\u003e\u003ch2\u003eDiscussion:\u003c/h2\u003e \u003cp\u003eThis case highlights the importance of early recognition of cardiac amyloidosis in elderly patients with unexplained heart failure and monoclonal gammopathy. Cardiac MRI and serum free light chain analysis are critical tools in the diagnostic pathway. Despite advances in treatment, outcomes remain poor in advanced cardiac involvement. Early intervention may improve prognosis, underscoring the need for heightened clinical awareness.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eInfiltrative cardiomyopathies like AL amyloidosis should be considered in elderly patients with heart failure and systemic red flags. Timely diagnosis and multidisciplinary management are essential but often insufficient in advanced stages.\u003c/p\u003e","manuscriptTitle":"Silent Progression: Cardiac Amyloidosis Unmasking IgG Lambda Myeloma in an Elderly Patient","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 09:06:32","doi":"10.21203/rs.3.rs-6498469/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-15T18:54:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-15T14:44:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"23587854923591559814287747160576283765","date":"2025-12-13T18:37:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-08T17:37:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144541756945952516305135130776756582866","date":"2025-08-07T12:13:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282844522690245676203498952101268284773","date":"2025-05-18T15:24:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99284704965841795247187539156497983597","date":"2025-05-18T12:42:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-29T07:46:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-23T09:54:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-23T09:51:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Heart Journal","date":"2025-04-21T19:48:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-heart-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tehj","sideBox":"Learn more about [The Egyptian Heart Journal](https://tehj.springeropen.com)","snPcode":"43044","submissionUrl":"https://submission.springernature.com/new-submission/43044/3","title":"The Egyptian Heart Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a8927539-4e85-467d-9c96-287a6c0bbeb2","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T16:05:53+00:00","versionOfRecord":{"articleIdentity":"rs-6498469","link":"https://doi.org/10.1186/s43044-026-00715-w","journal":{"identity":"the-egyptian-heart-journal","isVorOnly":false,"title":"The Egyptian Heart Journal"},"publishedOn":"2026-01-06 15:58:55","publishedOnDateReadable":"January 6th, 2026"},"versionCreatedAt":"2025-05-07 09:06:32","video":"","vorDoi":"10.1186/s43044-026-00715-w","vorDoiUrl":"https://doi.org/10.1186/s43044-026-00715-w","workflowStages":[]},"version":"v1","identity":"rs-6498469","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6498469","identity":"rs-6498469","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}