AL Amyloidosis for Cardiologists: Awareness, Diagnosis, and Future Prospects: JACC: CardioOncology State-of-the-Art Review

Abstract

Amyloid light chain (AL) amyloidosis is a rare, debilitating, often fatal disease. Symptoms of cardiomyopathy are common presenting features, and patients often are referred to cardiologists. Cardiac amyloid infiltration is the leading predictor of death. However, the variable presentation and perceived rarity of the disease frequently lead to delay in suspecting amyloidosis as a cause of heart failure, leading to misdiagnoses and a marked delay in diagnosis, with devastating consequences for the patient. A median time from symptom onset to correct diagnosis of about 2 years is often too long when median survival from diagnosis for patients with AL amyloidosis and cardiomyopathy is 4 months to 2 years. The authors highlight the challenges to diagnosis, identify gaps in the current knowledge, and summarize novel treatments on the horizon to raise awareness about the critical need for early recognition of symptoms and diagnosis of AL amyloidosis aimed at accelerating treatment and improving outcomes for patients.

Keywords: AL amyloidosis; AL, amyloid light chain; ASCT, autologous stem cell transplantation; ATTR, transthyretin; CMR, cardiac magnetic resonance imaging; CR, complete response; CyBorD, cyclophosphamide-bortezomib-dexamethasone; FLC, free light chain; Ig, immunoglobulin; LGE, late gadolinium enhancement; NT-proBNP, N-terminal pro–brain natriuretic peptide; PCD, plasma cell dyscrasia; QoL, quality of life; VGPR, very good partial response; awareness; diagnosis; future therapies.

Graphical abstract

Figure 1

Common Pathologies Among Patients With Amyloid Light Chain Amyloidosis This figure illustrates the systemic nature of amyloid light chain amyloidosis, the number of organs and tissues that are affected, the percentage of patients in whom these organs are affected at diagnosis, and some commonly observed symptoms for the affected organ or system. LVEF = left ventricular ejection fraction; NT-proBNP = N-terminal pro–brain natriuretic peptide; TnT = troponin T.

Central Illustration

Current Treatment, Knowledge Gaps, and Emerging Therapies for Amyloid Light Chain Amyloidosis This figure summarizes (A) the current treatment paradigm, (B) the gaps that still exist in treatment and in relevant endpoints, and (C) emerging therapies that target removal of existing amyloid fibril deposits from organs and tissues. AL = amyloid light chain; ASCT = autologous stem cell transplantation; CR = complete response; IgG = immunoglobulin G; PCD = plasma cell dyscrasia; QoL = quality of life.

Figure 2

Algorithm for Diagnosing AL Amyloidosis This figure illustrates the current systematic, stepwise process for diagnosing amyloid light chain (AL) amyloidosis and differentiating it from other cardiomyopathies. It identifies each type of test that is essential for suspicion of AL amyloidosis, diagnosing the disease and typing of the amyloidogenic free light chains (FLCs). ACR = albumin/creatinine ratio; DPD = ^99mTc-3-diphosphono-1,2-propanodicarboxylic acid; Echo = echocardiography; EKG = electrocardiography; LFT = liver function test; MRI = magnetic resonance imaging; NT-proBNP = N-terminal pro–brain natriuretic peptide; PYP = ^99mTc-pyrophosphate; SIFE = serum immunofixation electrophoresis; UIFE = urine immunofixation electrophoresis.

Figure 3

Algorithm for Treating Patients With AL Amyloidosis This figure illustrates the current approaches to treatment after diagnosis of amyloid light chain (AL) amyloidosis. It includes the decision process in determining which first-line treatment to administer and what to do on the basis of the outcomes of that treatment regimen. ASCT = autologous stem cell transplantation; BMPC = bone marrow plasmacytosis; CR = complete response; CyBorD. = cyclophosphamide-bortezomib-dexamethasone; PCD = plasma cell dyscrasia; VGPR = very good partial response.

Figure 4

Hematologic Response of Patients With Amyloid Light Chain Amyloidosis to First-Line Therapies This figure compares the efficacies of different first-line treatments on the basis of hematologic response criteria of very good partial response (VGPR) or better and using autologous stem cell transplantation (ASCT) as the benchmark. The numbers in parentheses indicate the number of patients on which these data are based. CyBorD = cyclophosphamide-bortezomib-dexamethasone; Dara = daratumumab.