Abstract Background Cardiac involvement is the main determinant of prognosis in immunoglobulin light-chain (AL) amyloidosis, but may be under-recognized in patients with multiple myeloma (MM), particularly when classic electrocardiographic or cardiac magnetic resonance (CMR) features are absent. Early recognition therefore relies on integration of cardiac biomarkers and multimodality imaging when tissue biopsy or scintigraphic subtyping is impractical. Case summary A 74-year-old man with IgA-λ MM and immune thrombocytopenic purpura developed progressive heart failure with preserved ejection fraction (HFpEF), increased left-ventricular (LV) wall thickness, and markedly elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP; 7,164 pg/mL). Serial electrocardiograms did not demonstrate classic low voltage. CMR revealed diffuse non-ischaemic late gadolinium enhancement consistent with an infiltrative cardiomyopathy. Bone-avid scintigraphy was non-contributory in the context of MM. A working diagnosis of highly likely AL cardiac amyloidosis was established. Clone-directed therapy (two cycles of PCD followed by three ongoing cycles of KRd), together with volume-guided heart-failure management, resulted in biochemical improvement (NT-proBNP 3,431 pg/mL), although structural cardiac abnormalities persisted on follow-up imaging. Conclusion This case highlights real-world diagnostic and management challenges of AL cardiac amyloidosis in MM, particularly when electrocardiography and scintigraphy are equivocal, underscoring the importance of early suspicion, multimodality imaging, and close cardio-haematologic collaboration. Discussion This case illustrates real-world diagnostic challenges of AL-CA in MM when ECG and scintigraphy are equivocal. Clinicians should suspect AL-CA when HFpEF coexists with LV thickening and abnormal light-chain burden. Management emphasizes euvolaemia, cautious afterload reduction, and early haematology-cardiology co-management.
He et al. (2026) studied this question.