Atrial function and geometry differences in transthyretin versus immunoglobulin light chain amyloidosis: a cardiac magnetic resonance study

To determine the differences in left atrial (LA) function and geometry assessed by cardiac magnetic resonance (CMR) between transthyretin (ATTR) and immunoglobulin light chain (AL) cardiac amyloidosis (CA). We performed a retrospective analysis of 54 consecutive patients (68.5% male, mean age 67 ± 11 years) with confirmed CA (24 ATTR, 30 AL) who underwent comprehensive CMR examinations. LA structural and functional assessment including LA volume, LA sphericity index, and LA strain parameters were compared between both subtypes. In addition, 15 age-matched controls were compared to all groups. Patients with ATTR-CA were older (73 ± 9 vs. 62 ± 10 years, p < 0.001) and more likely to be male (83.3% vs. 56.7%, p = 0.036) when compared to AL-CA. No significant difference existed in LA maximum volume and LA sphericity index between ATTR-CA and AL-CA. LA minimum volumes were larger in ATTR-CA when compared with AL-CA. There was a significant difference in LA function with worse strain values in ATTR vs AL: left atrial reservoir [7.4 (6.3–12.8) in ATTR vs. 13.8 (6.90–24.8) in AL, p = 0.017] and booster strains [3.6 (2.6–5.5) in ATTR vs. 5.2 (3.6–12.1) in AL, p = 0.039]. After adjusting for age, LA reservoir remained significantly lower in ATTR-CA compared to AL-CA (p = 0.03), but not LA booster (p = 0.16). We demonstrate novel differences in LA function between ATTR-CA and AL-CA despite similar LA geometry. Our findings of more impaired LA function in ATTR may offer insight into higher AF burden in these patients.

Immunoglobulin Light Chain Amyloidosis Presenting as Inferior Vena Cava Thrombosis

Immunoglobulin light chain (AL) amyloidosis is a rare disease characterized by the deposition of misfolded extracellular proteins within various body tissues resulting in dysfunction of the cardiac, renal, gastrointestinal, hematologic, and nervous systems, among others. Systemic AL amyloidosis often presents with a constellation of vague symptoms such as fatigue, dyspnea, and abdominal pain. Untreated AL amyloidosis with cardiac involvement is rapidly fatal with a median survival of 6 months. In this report, we will highlight the case of a 43-year-old female who presented with generalized abdominal symptoms and fatigue. She was found to have extensive inferior vena cava (IVC) thrombosis extending into the renal veins bilaterally in the setting of nephrotic range proteinuria, new onset arrhythmia, diastolic heart failure, gastrointestinal, and autonomic dysfunction. She received systemic thrombolytic therapy for the IVC and renal vein thrombosis. The multiorgan involvement led us to consider the possibility of amyloidosis. Abdominal fat pad biopsy was performed as part of the diagnostic effort. The abdominal fat pad biopsy did not reveal AL amyloidosis. Ultimately, the diagnosis of systemic AL amyloidosis was made on the basis of pathology from luminal biopsies obtained during outpatient esophagogastroduodenoscopy that was performed days prior to her admission. Unique to our case is the patient presentation with extensive thrombotic disease of the IVC and renal veins. It is important to understand the disease process, presenting signs and symptoms as well as diagnostic essentials based on current literature in order to minimize the morbidity and mortality of this rare disease.

Light Chain Stabilization: A Therapeutic Approach to Ameliorate AL Amyloidosis

Non-native immunoglobulin light chain conformations, including aggregates, appear to cause light chain amyloidosis pathology. Despite significant progress in pharmacological eradication of the neoplastic plasma cells that secrete these light chains, in many patients impaired organ function remains. The impairment is apparently due to a subset of resistant plasma cells that continue to secrete misfolding-prone light chains. These light chains are susceptible to the proteolytic cleavage that may enable light chain aggregation. We propose that small molecules that preferentially bind to the natively folded state of full-length light chains could act as pharmacological kinetic stabilizers, protecting light chains against unfolding, proteolysis and aggregation. Although the sequence of the pathological light chain is unique to each patient, fortunately light chains have highly conserved residues that form binding sites for small molecule kinetic stabilizers. We envision that such stabilizers could complement existing and emerging therapies to benefit light chain amyloidosis patients.