Therapies for cardiac light chain amyloidosis: An update

Abstract

Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis, affecting around 10 people per million per year. This serious disorder is characterized by the presence of a clone of bone marrow plasma cells that produces monoclonal light chains (LCs) of the κ or predominantly λ type. These amyloidogenic LCs undergo extracellular misfolding and aggregation into proteotoxic soluble oligomers and amyloid fibrils that deposit within tissues. The lethal consequences of AL amyloidosis are due to the toxic products (the LCs) and not to the malignant behaviour of the plasma cell clone. Almost 80% of patients with AL amyloidosis have some degree of cardiac involvement, manifesting as heart failure (HF), and carrying a particularly poor prognosis. The past decade has seen major advances in the treatment of AL amyloidosis, and a rapidly fatal disease has become a treatable and possibly curable condition. The number of therapeutic options is rapidly expanding, offering hope to address currently unmet needs (most notably, the treatment of frail patients). The treatment of AL amyloidosis consists in a combination of agents targeting multiple steps of the amyloid cascade, associated with effective HF management, and there is ground for hope for dramatically improving the outcome in the near future. In the present review we will summarize our current knowledge on therapy for cardiac AL amyloidosis, targeting clinical cardiologists involved in the care of this serious disorder.

The Clinical Spectrum of Amyloidosis

“…Similarly, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) are sensitive (although not specific) markers of myocardial damage. The degree of elevation of these proteins are additional markers of myocardial cell damage in cardiac amyloidosis [34]. A characteristic finding on electrocardiogram is decreased voltage in the limb leads, as compared to normal; however, this is not a consistent finding even in patients with biopsy proven cardiac amyloidosis.…”

Analysis of gene expression profiling of amyloidogenic immunoglobulin light‑chains on cultured rat cardiomyocytes

“…Primary amyloidosis is a systematic disease characterized by the pathological deposition of misfolded proteins known as immunoglobulin light-chains (LCs) (1). Prognosis is closely associated with the organs involved, especially the heart, which is affected in 50-80% of patients with primary amyloidosis (2,3). Although this disease was identified in the mid-19th century, the mortality rate remains high, resulting from a difficult early diagnosis and few effective treatment options (4).…”

“…Although this disease was identified in the mid-19th century, the mortality rate remains high, resulting from a difficult early diagnosis and few effective treatment options (4). Patients with cardiac amyloidosis usually present with symptoms of heart failure, angina and conductive delays (3,5). Cardiac biomarkers, such as serum cardiac troponin and brain natriuretic peptide (BNP), are sensitive markers of cardiac dysfunction and the levels are elevated in amyloidosis (3,5,6).…”

“…Patients with cardiac amyloidosis usually present with symptoms of heart failure, angina and conductive delays (3,5). Cardiac biomarkers, such as serum cardiac troponin and brain natriuretic peptide (BNP), are sensitive markers of cardiac dysfunction and the levels are elevated in amyloidosis (3,5,6). Treatment of cardiac amyloidosis depends on a combination of therapies aimed at controlling hematologic disorders and relieving cardiac damage (5).…”

“…The routine therapeutic paradigm of heart failure cannot be simply translated to cardiac amyloidosis (5)(6)(7). Loop diuretics are central to the treatment for relieving congestion in cardiac amyloidosis (3,5). Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta blockers and mineralocorticoid receptor antagonists can cause hypotension, renal insufficiency, or other contraindications (3,5).…”