Cardiac amyloidosis in a kidney transplant recipient

44-Year-Old Man With Exertional Dyspnea, Weight Loss, and Palpitations

Systemic amyloidosis is a relatively rare multisystem disease caused by the deposition of misfolded protein in various tissues and organs. It may present to almost any specialty, and diagnosis is frequently delayed.[1][1] Cardiac involvement is a leading cause of morbidity and mortality, especially

A 74-year-old man presented with decreasing exercise tolerance and mild ankle edema. He was previously fit but was now breathless on climbing 2 flights of stairs. He had no history of angina, orthopnea, or paroxysmal nocturnal dyspnea. His medical history included non–insulin-dependent diabetes mellitus treated for 10 years and mild hypertension. Six years earlier he had been diagnosed with a monoclonal gammopathy of unknown significance. At that time, a bone marrow biopsy showed 30% overall cellularity with 5% to 10% plasmacytosis (normal <4%) and immunoglobulin light-chain restriction. Approximately 3 years ago, he developed deep vein thrombosis and was treated with low-molecular-weight heparin. A year later, leg swelling occurred and was attributed to venous insufficiency. The following year, he developed progressive fatigue on exertion, and an abnormal ECG (Figure 1) led to a treadmill test that was considered normal. An echocardiogram showed concentric wall thickening (Movie 1 in the Data Supplement), and the possibility of cardiac amyloidosis was raised. A fat pad biopsy was negative for amyloid deposits. The bone marrow biopsy performed in 2005 (when his monoclonal gammopathy of unknown significance was diagnosed) was restained and was negative for amyloid. At that time, serum-free λ light chains were 108.9 mg/L (normal range, 5.7–26.3) with κ light chains of 13 mg/L (normal, 3.3–19) and an abnormal ratio of 0.12 (normal, 0.26–1.65). His brain natriuretic peptide measured 275 pcg/mL. He was treated with oral diuretics, which improved leg swelling, but because of persistent symptoms, he sought medical care at our institution. On review of symptoms, he denied jaw claudication, symptoms of postural hypotension, easy bruising, or tongue swelling. He did give a history suggestive of neuropathy with a leathery feeling in his feet but no numbness in his hands. Medications included metformin 500 mg twice a day, aspirin 80 mg daily, lisinopril …

Thrombospondin type-1 domain-containing 7A-related membranous nephropathy associated with glomerular AL amyloidosis

The Clinical Impact of Proteomics in Amyloid Typing

BackgroundThe prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis are substantially influenced by cardiac involvement. ATTR amyloidosis has better...

Systemic amyloidosis

Rationale:Cardiac amyloidosis is caused by extracellular deposition of amyloid proteins, with over 30 distinct forms identified based on protein composition. The predominant types are immunoglobulin light chain and transthyretin (ATTR) amyloidosis. This study presents an exceedingly rare case of concurrent light chain cardiac amyloidosis (AL-CA) and ATTR cardiac amyloidosis.Patient concerns:A 69-year-old Chinese woman was admitted to the hospital due to recurrent heart failure that had been present for the past 3 months. She presented with symptoms including fatigue, reduced exercise tolerance, and difficulty breathing when reclining flat. She exhibited inadequate response to anti-heart failure therapy.Diagnoses:The diagnosis of coexisting AL-CA and wild-type transthyretin cardiac amyloidosis was confirmed through a combination of echocardiography, blood tests, cardiovascular magnetic resonance imaging, technetium-99m pyrophosphate scintigraphy, invasive procedures (bone marrow and endomyocardial biopsies), mass spectrometry, and genetic testing.Interventions:Prior to diagnosis, the patient was treated for heart failure with preserved ejection fraction with diuretics, sodium-glucose cotransporter-2 inhibitors, and angiotensin receptor-neprilysin inhibitors. Following confirmation of cardiac amyloidosis, tafamidis was initiated to stabilize ATTR. Chemotherapy was subsequently attempted after hematologic referral but discontinued due to adverse effects. The patient later ceased most prescribed therapies in favor of unproven alternatives.Outcomes:After 3 months of comprehensive treatment, the patient discontinued tafamidis and other related therapies due to intolerance of adverse effects, opting instead for traditional Chinese medicine. Subsequent poor treatment adherence prevented regular follow-up and reassessment. Although the patient reported persistent exertional dyspnea during sporadic follow-up visits, no objective disease progression parameters (e.g., N-terminal pro-B-type natriuretic peptide levels, cardiac imaging changes) or standardized treatment response data were obtained.Lessons:We report a confirmed case of coexistent AL-CA and wild-type transthyretin cardiac amyloidosis, validated through comprehensive diagnostic evaluation. Although dual therapy targeting both amyloid types may be needed, the lack of guidelines and follow-up data highlights the need for standardized management approaches. Future studies should prioritize long-term outcome tracking.

59-Year-Old Man With Fatigue, Weight Loss, and Hepatomegaly

For the immunohistochemical detection of immunoglobulin (Ig) light chain amyloidosis on formalin-fixed, paraffin-embedded tissue sections, we prepared polyclonal antibodies against synthetic peptides corresponding to positions 118-134 of Ig lambda light chain and positions 116-133 of Ig kappa light chain. Nineteen cases of systemic Ig lambda light chain amyloidosis (Alambda amyloidosis), 10 cases of systemic Ig kappa light chain amyloidosis (Akappa amyloidosis), one case of immunohistochemically unclassified systemic amyloidosis and five cases of localized Alambda amyloidosis were tested with these antibodies. Anti-lambda (118-134) antiserum and the affinity-purified antibody both reacted with 18 of the 19 cases of systemic Alambda amyloidosis and all cases of localized Alambda amyloidosis, although the immunoexpression was somewhat variable in intensity in different areas within the same specimen in both systemic and localized amyloidosis. The signal intensities in plasma cells and serum reacted for anti-lambda (118-134) antiserum were weaker than signals obtained with commercially available anti-Ig lambda light chain antibodies. Anti-kappa (116-133) antiserum and the affinity-purified antibody reacted with nine of the 10 cases of systemic Akappa amyloidosis. We conclude that these antibodies against synthetic peptides corresponding to the Ig light chain constant region are useful for the classification of amyloidosis on formalin-fixed, paraffin-embedded tissue sections.

Clinical Characteristics and Outcome of Patients with Wild-Type Transthyretin and AL Cardiac Amyloidosis Confirmed By Mass Spectrometry

Cardiac amyloidosis detected on tc-99m bone scan.

Comparison of lambda and kappa light-chain cardiac amyloidosis in Polish patients diagnosed in cardiology department

Background Isolated cardiac amyloidosis (CA) is a complex diagnostic scenario, highlighting the need for physician awareness in differential diagnosis. Among the different types of amyloidosis, nearly all cases of CA are caused by light chain (AL) and transthyretin amyloidosis (ATTR). Patients with suspect CA without monoclonal components (MC) in both serum and urine and normal free light chain (FLC) ratio can have a non-biopsy diagnosis of ATTR amyloidosis with bone scintigraphy (1). However, in all suspected CA with a MC (approximately 20% of patients with ATTR amyloidosis), amyloid typing is mandatory. Thus, the diagnostic pathway of CA diverges based on MC-studies. We aim to assess if different sequence of diagnostic tests can affect outcomes in patients with cardiac AL amyloidosis. Methods Pavia Amyloidosis prospectively maintained database was searched for patients with isolated cardiac AL amyloidosis referred to our Centre from January 2016 to December 2020. Patients with a known monoclonal gammopathy (MG) and with multiple organ involvement were excluded. We searched for the date of symptom onset and first suspect of CA (i.e. recognition of clinical, imaging or laboratory signs of CA). In addition, we recorded the date of the different diagnostic tests performed: i.e. echocardiogram; serum and urine immunofixation and FLC measurement (MC-study); bone scintigraphy and cardiac magnetic resonance (defined as advanced cardiac imaging). We calculated the interval between those time-points and the final diagnosis: (a) from symptom onset to diagnosis, (b) from first suspect to final diagnosis, (c) from first suspect to MC-study and (d) to advanced cardiac imaging tests. We then searched for possible intervals of time amongst those, that were able to predict death at 3 months, by means of a ROC analysis. Results A total of 94 patients were included in the analysis (25% of all patients with cardiac AL amyloidosis diagnosed in the study period). Six (6%) patients died &amp;lt;1 month from diagnosis, and 27 (29%) died &amp;lt;3 months. Median overall survival (OS) of the whole cohort was 8 months, and the median follow-up of living patients was 39 months (range 16-73). The median time from symptom onset to diagnosis was 9 months (range 1-44) and the median time from the first suspect to diagnosis was 2 months (range 0-9). An interval from the first suspect to MC-study ≥6 weeks was the only predictor of death at 3 months. None of the other tested periods were associated with a significant ability to predict survival. A delay in MC-study ≥6 weeks identified patients with more advanced cardiac stage (50% vs. 25% were stage IIIb, P=0.02) and was associated with a significantly worse outcome (median survival 13 months vs. 4 months, P=0.012). In the whole cohort, a total of 76 (81%) patients underwent at least one advanced imaging examination. Amongst those, 37 (49%) performed the imaging tests before MC-study with a higher percentage of patients who had a delay in MC-studies evaluation (69% vs. 27%; P&amp;lt;0.001). Conclusion In patients who present with isolated cardiac AL amyloidosis with previously unknown MG, a relatively short delay in identifying the amyloid MC results in a considerable reduction of survival. A delay in MC-study was associated with more advanced cardiac stage. MC studies should be the first step in the work-up of patients with suspected CA to guide biopsy vs. non-biopsy diagnostic approach.

Patterns of Treatment Failure in Systemic Light Chain Amyloidosis with Long-Term Survival after Chemotherapy