Amyloid light-chain amyloidosis with cardiac failure: a case description and literature analysis

Background

Amyloid light-chain (AL) amyloidosis is characterized by the deposition of insoluble amyloid fibrils in the extracellular matrix of various organs and tissues. These fibrils contain misfolded proteins and can cause severe organ dysfunction involving the heart, kidneys, liver, gastrointestinal tract, spleen, and nervous system (1). Clinical manifestations of AL amyloidosis vary according to the organs involved. Cardiac amyloidosis may be life-threatening, and early detection can increase the likelihood of survival (2). The main risk factor for AL amyloidosis is the presence of a plasma cell dyscrasia, such as monoclonal gammopathy of undetermined significance or multiple myeloma (3). In this report, we present a case of AL amyloidosis with severe cardiac failure and multi-organ involvement and describe the related imaging findings.

Case presentation

A 74-year-old man was admitted to hospital with chest tightness and shortness of breath. The symptoms had been present for 7 months, had worsened over the previous 2 weeks, and were associated with repeated episodes of heart failure. Echocardiography (ECHO) showed left ventricular systolic dysfunction with an ejection fraction (EF) of 32%. An electrocardiogram (ECG) showed sinus rhythm with ST-segment depression and T-wave inversion or flattening. No significant tachyarrhythmias or bradyarrhythmias were documented during the hospitalization.

The patient had a 10-year history of hypertension, but his blood pressure remained low after he stopped taking medication 6 months previously. Furthermore, renal insufficiency was diagnosed 6 months earlier. Six years previously, his coronary angiography, routine urine analysis, and kidney function tests showed no abnormalities.

The patient had a three-decade history of alcohol consumption but had abstained for the previous 6 months. He also had a significant smoking history but had quit 7 years prior. There was no significant family history. Physical examination revealed macroglossia (Figure 1), auscultation revealed fine inspiratory crackles at both lung bases, and mild-to-moderate edema was observed in both lower extremities.

Figure 1 Typical image of an enlarged tongue.

After a review of the patient’s history and examination, an initial diagnosis of an acute exacerbation of chronic heart failure was made. Nephrotic syndrome and acute coronary syndrome were considered the differential diagnoses.

Subsequent laboratory findings were as follows: cardiac troponin I (cTnI), 0.579 ng/mL; brain natriuretic peptide (BNP), 1,306 pg/mL; total cholesterol, 6.252 mmol/L; low-density lipoprotein cholesterol, 4.35 mmol/L; blood urea nitrogen, 11.01 mmol/L; and serum creatine, 178 µmol/L; uric acid, 623 µmol/L; albumin, 19.9 g/L; and hemoglobin, 117 g/L. Serum protein electrophoresis (SPEP) showed an M spike of 22.2%. Serum immunofixation electrophoresis was positive for immunoglobulin A and lambda light chain. The serum free light chain (FLC) assay revealed an abnormal kappa : lambda ratio. Urine immunofixation electrophoresis was positive for lambda light chain and immunoglobulin A. The 24-hour urine protein level was 8.83 g. These findings confirmed the presence of monoclonal lambda light chain-producing plasma cell dyscrasia.

The ECG revealed sinus rhythm with complete right bundle branch block; ST depression in leads II, III, and augmented vector foot (aVF); biphasic T waves in V4–6; and low voltage in the limb leads.

The ECHO showed dilation of the left ventricle and right atrium. The ventricular septum and left ventricular wall were hypertrophied and echogenic, with reduced systolic function [Simpson biplane ejection fraction (EF) 32%]. Valvular regurgitation and pericardial effusion were observed. Strain analysis revealed a severely decreased global longitudinal strain (GLS) (−6.6%), exhibiting the characteristic relative apical sparing pattern (Figure 2). Longitudinal strain in the middle and basal left ventricle was significantly reduced with relative apical preservation.

Figure 2 Bull’s-eye plot from two-dimensional speckle-tracking echocardiography illustrating both left ventricular strain and preservation of strain. ANT, anterior; GS, global strain; INF, inferior; LAT, lateral; SEPT, septal.

Cardiac magnetic resonance imaging (MRI) (Figure 3) revealed an enlarged left ventricle with wall thickening. The left ventricular myocardium exhibited impaired contractility and compliance. The right ventricle wall and atrial septum were thickened, with a small pericardial effusion. Quantitative T1 mapping and extracellular volume (ECV) calculation were not performed. Technetium-99m pyrophosphate (PYP) scintigraphy was also not performed due to logistical constraints.

Figure 3 Four-chamber cardiac MRI (A,B). MRI, magnetic resonance imaging.

These imaging findings were pivotal in raising the initial suspicion of cardiac amyloidosis. The combination of left ventricular hypertrophy with a granular, sparkling appearance on ECG, severely reduced GLS (−6.6%) with the characteristic relative apical sparing pattern, and the findings on cardiac MRI strongly suggested myocardial infiltration by amyloid deposits. This imaging profile, particularly a strain pattern highly specific to amyloidosis, guided the subsequent diagnostic workup toward confirming AL amyloidosis.

To confirm the diagnosis, biopsies were performed. Amyloid typing was confirmed via immunohistochemical staining of the tongue (Figure 4) and renal (Figure 5) biopsies, which showed strong positivity for lambda light chains and negativity for kappa light chains and transthyretin.

Figure 4 Histopathological findings of AL amyloidosis of the tongue. (A) Representative images of AL amyloidosis of the tongue with HE staining at 200× magnification. (B) Congo red staining at 200× magnification. AL, amyloid light chain; HE, hematoxylin and eosin.

Figure 5 Renal biopsy findings confirming AL amyloidosis. (A) Representative images of renal AL amyloidosis with HE staining at 200× magnification. (B) Congo red staining at 400× magnification. (C) Immunofluorescence staining of renal tissue biopsy showing kappa light-chain deposition at 200× magnification. (D) Immunofluorescence staining for lamba light-chain deposition at 200× magnification. AL, amyloid light-chain; HE, hematoxylin and eosin.

Ultimately, the patient was diagnosed with AL amyloidosis of the lambda light chain subtype, with critical involvement of the heart, kidneys, and tongue.

The patient was transferred to the hematology department. Due to financial constraints, he was treated with a regimen of daratumumab and methylprednisolon and not the preferred triple therapy (daratumumab, bortezomib, and dexamethasone). After three cycles of this suboptimal regimen, the patient’s clinical condition and biochemical markers (BNP and creatinine) failed to improve. The treatment was therefore deemed ineffective, and the patient decided to self-discharge for palliative care.

All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of The Second Affiliated Hospital of Jiaxing University. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

This case report illustrates a challenging clinical course of histologically confirmed multi-organ AL amyloidosis and focuses on the role of quantitative cardiac imaging. Although rare, with an estimated incidence of 8–12 cases per million people annually (4), cardiac involvement is associated with the poorest prognosis. Late diagnosis entails ineffective treatment, making it a leading cause of death (5). Our patient had severe cardiac dysfunction and no improvement with chemotherapy.

The central role of quantitative imaging in diagnosis

Diagnosing AL amyloidosis presents significant challenges, often leading to underdiagnosis due to the lack of specific clinical manifestations (6). Differentiating the type of amyloidosis is essential, as this determines the clinical course and selection of treatment strategy.

ECG abnormalities such as decreased voltage in limb leads and ST-segment changes are important indicators of amyloidosis, although not all patients exhibit these changes (7). Amyloid deposits infiltrate the heart, causing atrioventricular block (second and third degrees) and other arrhythmias, including atrial fibrillation (8).

ECG can often be the first modality to indicate cardiac involvement. The quantitative assessment of myocardial deformation via speckle-tracking ECHO (STE) is critical, as it can detect systolic impairment before a visible decline in left ventricular EF occurs (2,9). In our patient, the severely impaired GLS of −6.6% far exceeded the reduction in EF (32%), underscoring the superior sensitivity of STE in detecting early myocardial dysfunction in amyloid infiltration. The relative apical sparing pattern, quantified by a regional strain ratio, is a hallmark feature with high diagnostic accuracy and can effectively differentiate amyloidosis from other causes of concentric hypertrophy (10). In our case, the apical sparing pattern was a key quantitative imaging biomarker that significantly increased the confidence in the diagnosis.

Cardiac MRI offers unparalleled tissue characterization. Although late gadolinium enhancement (LGE) images suggestive of amyloidosis were acquired, the absence of T1 mapping and ECV quantification was a limitation to confirming the diagnosis, as these are established quantitative biomarkers for amyloid burden (11,12). Beyond diagnosis, cardiac MRI is being increasingly used to monitor treatment response (13). The lack of PYP scintigraphy, a valuable noninvasive test for differentiating subtypes, was another notable absence in this case (14,15). In cases such as this, in which there was confirmed monoclonal gammopathy, scintigraphy can still be useful for assessing a potential dual pathology. When scintigraphy is equivocal or unavailable, and clinical suspicion remains high, endomyocardial biopsy (EMB) remains the definitive diagnostic standard, as discussed in recent literature (16). In our patient, the combination of multi-organ involvement and positive lambda light chain staining on renal and tongue biopsies provided sufficient diagnostic certainty for a diagnosis of AL amyloidosis, obviating the need for EMB. Cardiac MRI further contributes through tissue characterization; although T1 mapping and ECV quantification were not performed in this case, the pattern of LGE and myocardial thickening provided high specificity. The integration of these quantitative imaging parameters is essential for noninvasive diagnosis and for monitoring disease progression and response to therapy.

The severity of the imaging findings, particularly the very low GLS and the extensive involvement on cardiac magnetic resonance, correlated with the patient’s poor prognosis and limited response to therapy, highlighting the prognostic value of these quantitative parameters.

Treatment

The treatment of AL amyloidosis is aimed at inhibiting FLC production to thereby suppress amyloid fibril formation and maintain organ function (17). Treatment decisions should account for age, organ function (e.g., that of the heart, lungs, liver, and kidneys), the side effects and toxicities of treatments (18), and the most suitable pretransplant induction drug, which should be fast-acting and have minimal side effects; alkylating drugs should be avoided. Bortezomib combined with dexamethasone has demonstrated high rates of hematological and organ response in AL amyloidosis treatment, along with rapid action and relatively mild side effects, making it a promising component in the pretransplantation induction chemotherapy regimen (18). For patients not eligible for stem cell transplantation, regimens with alkylating drugs, such as melphalan plus prednisone or melphalan plus dexamethasone, have demonstrated efficacy and safety (19). The high incidence of early death due to cardiac dysfunction in patients with AL amyloidosis underscores the critical importance of effective cardiac management. In patients with cardiac amyloidosis and heart failure, volume control, diuresis, and symptom control are vital. Due to common autonomic nerve dysfunction and low blood pressure, digitalis and dihydropyridine calcium channel blockers are generally discouraged. A cardiac pacemaker may be installed for symptomatic bradyarrhythmias or atrioventricular block (20). Furthermore, although less common than atrial arrhythmias, malignant ventricular arrhythmias can occur in amyloidosis and contribute to sudden cardiac death, necessitating careful monitoring and consideration of implantable cardioverter-defibrillator therapy in select patients (21,22). Heart transplantation may be an option in patients with severe heart failure. A significant limitation in this case was the administration of a suboptimal treatment regimen due to financial constraints, which undoubtedly impacted the outcome.

Conclusions

AL amyloidosis is underdiagnosed and warrants heightened attention. Early diagnosis is critical. This case highlights the importance of maintaining a high index of suspicion for AL amyloidosis in patients with multi-organ dysfunction. Furthermore, it demonstrates the indispensable role of multimodal cardiac imaging, particularly echocardiographic strain analysis and cardiac MRI, in raising diagnostic suspicion, guiding biopsy, and assessing disease severity. It is important that these advanced imaging techniques are applied early in the diagnostic algorithm of unexplained heart failure.

Acknowledgments

None.

Footnote

Funding: This work was supported by the Bureau of Science and Technology of JiaXing (No. 2023AY40033), Educational Commission of ZheJiang Province of China (No. Y202557593) and Jiaxing Municipal Health Commission (No. JWKD25003).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1-2712/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of The Second Affiliated Hospital of Jiaxing University. Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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