Light-chain (AL) cardiac amyloidosis should be considered in multiple myeloma with heart failure with preserved ejection fraction and left ventricular wall thickening even without classic ECG low voltage or diffuse subendocardial LGE.
Cardiac magnetic resonance tissue characterization combined with serum AL assays offers high diagnostic confidence when biopsy or scintigraphy is not feasible or non-diagnostic.
Bone-avid scintigraphy does not reliably rule in or rule out AL in the setting of multiple myeloma and may be misleading.
Introduction
Immunoglobulin light-chain (AL) amyloidosis is a life-threatening systemic disorder in which cardiac involvement is the principal determinant of prognosis. 1 , 2 In patients with multiple myeloma (MM), cardiac amyloid infiltration may masquerade as hypertensive remodelling or hypertrophic cardiomyopathy phenocopies, delaying recognition. 3-5 We report a patient with immunoglobulin A lambda (IgA-λ) MM who developed progressive heart failure with preserved ejection fraction (HFpEF), in whom integration of biomarkers and multimodality imaging enabled a high-confidence working diagnosis of AL cardiac amyloidosis when tissue diagnosis or scintigraphic subtyping was impractical. 1 , 6
Summary figure
| Date | Event/findings | Management/outcome |
| 17 November 2020 | Initial presentation: >5-year gingival/epistaxis history, anaemia, thrombocytopenia; ascites/pleural effusions on imaging | Work-up for haematologic disease |
| 19–23 November 2020 | Bone marrow: IgA-λ MM; diagnosed ITP (immune thrombocytopenic purpura); baseline echo: septal ∼13 mm, LVEF (left ventricular ejection fraction) is 59% | Methylprednisolone + cyclophosphamide + thalidomide; supportive care—bleeding improved |
| 25 June 2022 | Decompensation with exertional dyspnoea/oedema; N-terminal pro-B-type natriuretic peptide (NT-proBNP) is 7164 pg/mL | Initiated PCD (bortezomib–cyclophosphamide–dexamethasone) + heart failure care |
| May 2024 | Rising myeloma markers; recurrent congestion; adherence suboptimal | Regimen changed to KRd (carfilzomib–lenalidomide–dexamethasone) |
| 2 December 2024 | Echo: persistent thickening, preserved ejection fraction (EF) , elevated pulmonary artery systolic pressure (PASP) (49 mmHg) | Ongoing HF optimization |
| December 2024 | Cardiac magnetic resonance (CMR): non-ischaemic late gadolinium enhancement (LGE) pattern with diffuse involvement; supportive of AL cardiac amyloidosis (AL-CA) | Working diagnosis AL cardiac amyloidosis (AL-CA); continued clone-directed therapy |
| Follow-up | Biomarker improvement (NT-proBNP is 3431 pg/mL) though septal thickening/valvular regurgitation persisted | Continued multidisciplinary team (MDT) follow-up |
Case presentation
A 74-year-old man with a long history of mucocutaneous bleeding presented in 2020 with progressive dyspnoea and peripheral oedema. Physical examination revealed signs of congestion with ascites and pleural effusions. Laboratory testing demonstrated anaemia and thrombocytopenia consistent with immune thrombocytopenic purpura in the setting of MM, together with markedly elevated NT-proBNP.
Transthoracic echocardiography ( Figure 1 ) showed concentric left ventricular (LV) wall thickening (septal thickness ∼13 mm) with preserved LV ejection fraction (59%) and elevated pulmonary artery systolic pressure (∼49 mmHg), consistent with HFpEF physiology. Serial electrocardiograms ( Figure 2 ) demonstrated borderline QRS voltages in the limb leads with non-specific ST-segment-T-wave changes, illustrating the absence of classic low-voltage findings despite increased wall thickness.
Bone marrow examination ( Figure 3 ) confirmed IgA-λ MM. Initial therapy with corticosteroids, cyclophosphamide, and thalidomide improved bleeding manifestations. In 2022, the patient experienced decompensated heart failure with NT-proBNP peaking at 7164 pg/mL. According to the revised 2012 Mayo staging system, incorporating NT-proBNP and cardiac troponin, the patient was classified as Stage II, indicating an intermediate cardiac risk profile. 7
Clone-directed therapy with bortezomib-cyclophosphamide-dexamethasone (PCD) (bortezomib ∼1.3 mg/m 2 subcutaneously on Days 1, 8, and 15; cyclophosphamide 300–500 mg orally on Days 1–14; dexamethasone 20–40 mg weekly) was initiated for two cycles, alongside optimized heart failure therapy. In 2024, owing to rising myeloma markers and suboptimal adherence, treatment was escalated to KRd (carfilzomib 20→36 mg/m 2 on Days 1–2, 8–9, and 15–16; lenalidomide 10–15 mg on Days 1–21; dexamethasone 20–40 mg weekly), with three cycles completed and ongoing at the last follow-up.
Repeat echocardiography in late 2024 demonstrated persistent LV wall thickening and pulmonary hypertension, with small pericardial effusion showing partial improvement. Cardiac magnetic resonance ( Figure 4 ) revealed diffuse non-ischaemic late gadolinium enhancement with concentric ventricular thickening and bi-atrial enlargement, supportive of an infiltrative cardiomyopathy. In the MM context, bone-avid scintigraphy was not relied upon for diagnostic confirmation. Considering the markedly abnormal free AL burden, HFpEF with LV thickening, serosal effusions, and diffuse CMR findings, a working diagnosis of highly likely AL cardiac amyloidosis was adopted. Despite persistent structural abnormalities, NT-proBNP improved to 3431 pg/mL with multidisciplinary management.
Discussion
Diagnostic challenges in multiple myeloma
In MM, HFpEF with increased LV wall thickness and modest electrocardiography (ECG) voltage changes may mimic hypertensive heart disease or hypertrophic cardiomyopathy phenocopies, delaying recognition of AL cardiac amyloidosis. 3-5 This case demonstrates that absence of classic low-voltage ECG findings does not exclude AL cardiac involvement. 1 , 8 , 9
Limitations of bone-avid scintigraphy in light-chain cardiac amyloidosis
Bone-avid scintigraphy is valuable for diagnosing transthyretin amyloidosis but is neither necessary nor sufficient for diagnosing AL amyloidosis. 1 , 6 In patients with MM, scintigraphy may be negative or misleading; thus, a negative scan cannot exclude AL, and positive uptake does not reliably confirm it. 3 , 6
Management priorities and chemotherapy-related cardiotoxicity
Management focused on maintaining euvolaemia with cautious use of vasodilators, reflecting the preload-sensitive physiology of amyloid cardiomyopathy. 1 Although proteasome inhibitors, such as carfilzomib, are associated with heart failure risk, 10 several features supported AL cardiac amyloidosis as the dominant mechanism in this case 3 , 10 : heart failure symptoms preceded intensified chemotherapy, CMR demonstrated a diffuse infiltrative pattern rather than focal toxic injury, and NT-proBNP improved with combined clone-directed and heart-failure therapy. 2 , 7 Nevertheless, chemotherapy-related cardiotoxicity cannot be completely excluded and warrants close monitoring.
Overall, this case highlights three key teaching messages: (i) AL cardiac amyloidosis should be suspected in MM patients with HFpEF and LV thickening even without classic ECG features, (ii) bone-avid scintigraphy has important limitations in this context, and (iii) early multidisciplinary management can improve biomarkers despite persistent structural disease. The diagnostic reasoning and management approach are summarized in Figure 5 .
The absence of endomyocardial or surrogate tissue biopsy remains a major limitation, and the diagnosis is therefore framed as ‘highly likely’ rather than histologically confirmed AL cardiac amyloidosis. Similar diagnostic challenges of AL cardiac amyloidosis secondary to MM have also been described in previously published case reports and case series. 11-15 Alternative explanations, including hypertensive remodelling or chemotherapy-related cardiotoxicity, cannot be fully excluded, although integrated clinical and imaging findings make these less likely. Older age and frailty further complicate diagnosis and management of cardiac amyloidosis. 16 And MM with secondary amyloidosis may present with diverse extracardiac manifestations 17
Conclusion
In patients with MM, integration of cardiac biomarkers and CMR enables timely recognition of AL cardiac amyloidosis and guides management when biopsy or scintigraphy is impractical. This case underscores real-world nuances beyond guideline algorithms, including non-classic ECG and imaging features, non-diagnostic scintigraphy, and discordance between biochemical and structural cardiac response. 1 , 8 , 9
Acknowledgements
This report adheres to the CARE guidelines; a completed checklist is available on request.
Lead author biography
For image description, please refer to the figure legend and surrounding text.
Dr Jie He, graduated from Chongqing Medical University, is currently a cardiologist at Nanchong Central Hospital. With many years of clinical experience, he has been dedicated to the diagnosis and treatment of cardiovascular diseases as well as research in this field. He is proficient in the diagnosis and individualized treatment of common and difficult cardiovascular diseases, such as hypertension, coronary heart disease, heart failure, and arrhythmia. Additionally, he has accumulated rich clinical experience in the emergency treatment of acute myocardial infarction and critical cases.
Author contributions
Jie He (Writing—original draft, Writing—review & editing [lead]), Gang Yang (Writing—review & editing [supporting]), and Jianping Deng (Writing—review & editing [supporting])
Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images in accordance with the COPE guidelines.
Funding
No funding was received for this work.
Data availability
All data underlying this article are included in the article and its supplementary material; additional de-identified data are available from the corresponding author upon reasonable request.
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