Light-chain cardiac amyloidosis: strategies to promote early diagnosis and cardiac response

Abstract

Amyloid light chain (AL) amyloidosis is a systemic disease characterised by the aggregation of misfolded immunoglobulin light chain (LC), predominantly in the heart and kidneys, causing organ failure. If untreated, the median survival of patients with cardiac AL amyloidosis is 6 months from the onset of heart failure. Protracted time to establish a diagnosis, often lasting >1 year, is a frequent factor in poor treatment outcomes. Cardiologists, to whom patients are often referred, frequently miss the opportunity to diagnose cardiac AL amyloidosis. Nearly all typical cardiac support measures, with the exception of diuretics, are ineffective and may even worsen clinical symptoms, emphasising the need for accurate diagnosis. Patients with severe cardiac involvement face poor outcomes; heart transplantation is rarely an option because of multiorgan involvement, rapid clinical decline and challenges in predicting which patients will respond to treatment of the underlying plasma cell disorder. Early diagnosis and prompt treatment with ‘source therapies’ that limit the production of amyloidogenic LC are associated with better survival and improvement in organ function after a median of 2.4 months following haematological complete response. However, organ recovery is often incomplete because these source therapies do not directly target deposited amyloid. Emerging amyloid-directed therapies may attenuate, and potentially reverse, organ dysfunction by clearing existing amyloid and inhibiting fibril formation of circulating aggregates. Improved recognition of AL amyloidosis by cardiologists allows for earlier treatment and improved outcomes.

Simplified apical four‐chamber view evaluation of relative apical sparing of longitudinal strain in diagnosing AL amyloid cardiomyopathy

“…In AL amyloidosis, amyloid cardiomyopathy is the major determinant of outcome. Early recognition and prompt initiation of therapy are thus of utmost importance as the median survival of untreated patients with AL amyloidosis is very poor, reaching only several months from the onset of heart failure …”

“…is very poor, reaching only several months from the onset of heart failure. 2 Echocardiography is still the mainstay for the noninvasive diagnosis of cardiac amyloidosis. However, concentric left ventricular (LV) wall thickening as the main finding suggestive of amyloid heart disease is regularly found in more prevalent heart pathologies including arterial hypertension and hypertrophic cardiomyopathy.…”

Kidney embolization induces prompt organ response in a 86‐year‐old patient with MGRS‐related AL‐amyloidosis

“…To underline its crucial pathophysiology, driven by an underlying B‐cell clone, renal AL‐amyloidosis has recently been included in the definition of monoclonal gammopathy of renal significance (MGRS) . Despite substantial improvements following the introduction of proteasome inhibitors (PI), immunomodulatory agents (IMiDs) and most recently the CD38 monoclonal antibody daratumumab, overall survival remains grim and 30% die of organ failure within the first year after diagnosis . Kidney dysfunction commonly presents as nephrotic syndrome with massive edema, proteinuria, and hypoalbuminemia .…”

“…2 Despite substantial improvements following the introduction of proteasome inhibitors (PI), immunomodulatory agents (IMiDs) and most recently the CD38 monoclonal antibody daratumumab, overall survival remains grim and 30% die of organ failure within the first year after diagnosis. 3,4 Kidney dysfunction commonly presents as nephrotic syndrome with massive edema, proteinuria, and hypoalbuminemia. 5 Renal improvement is closely associated with serological remission, but necessitates intensive systemic treatment for at least 6-12 months until recovery.…”

Pinch purpura unmasking systemic amyloidosis

“…1,2 Cardiac involvement represents a poor prognostic factor, with a reported median survival of 6 months from the onset of heart failure. 3 A clinical manifestation that is virtually pathognomonic of systemic amyloidosis is pinch purpura, observed mainly in the periocular area. Even though the latter finding develops in less than one-third of all cases, when present, it significantly facilitates early diagnosis.…”