The amyloidoses are a group of protein-folding disorders in which ≥1 organ is infiltrated by proteinaceous deposits known as amyloid. The deposits are derived from 1 of several amyloidogenic precursor proteins, and the prognosis of the disease is determined both by the organ(s) involved and the type of amyloid. Amyloid involvement of the heart (cardiac amyloidosis) carries the worst prognosis of any involved organ, and light-chain (AL) amyloidosis is the most serious form of the disease. The last decade has seen considerable progress in understanding the amyloidoses. In this review, current and novel approaches to the diagnosis and treatment of cardiac amyloidosis are discussed, with particular reference to AL amyloidosis in the heart.

Wild-type transthyretin amyloidosis (ATTRwt) is increasingly recognized as an important cause of heart failure with preserved ejection fraction (HFpEF), affecting 13% in a consecutive series of cardiology and internal medicine patients admitted to a university hospital. 1 However, the diagnosis is often not considered due to the perceived rarity of the disease. Although the primary manifestation of ATTRwt is cardiac, approximately 50% of patients have a history of carpal tunnel syndrome, 2 with amyloid deposits in the flexor tenosynovium. 3 Spontaneous rupture of the distal biceps tendon (RBT) is uncommon, with an estimated prevalence of less than 1 per 1000 persons aged 56 to 74 years. 4 We observed RBT in several patients with ATTRwt cardiomyopathy, and performed a cross-sectional study to further evaluate.Methods | From December 2013 through January 2016, all patients with ATTRwt cardiomyopathy presenting to the Cardiac Amyloidosis Program at Brigham and Women's Hospital were systematically evaluated. The diagnosis of cardiac ATTRwt was based on histopathology of endomyocardial biopsy or positive result from technetium pyrophosphate scanning in the absence of a plasma cell dyscrasia. 5 Genetic testing was conducted to exclude mutant ATTR amyloidosis.Patients were asked about symptoms of RBT, date of onset, and associated trauma. RBT was defined as bunching of the biceps

Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding of gp120 to receptors on the target cell alters the gp120-gp41 relationship and activates the membrane-fusing capacity of gp41. Interaction of gp120 with the primary receptor, CD4, results in the exposure of the gp120 third variable (V3) loop, which contributes to binding the CCR5 or CXCR4 chemokine receptors. We show here that insertions in the V3 stem or polar substitutions in a conserved hydrophobic patch near the V3 tip result in decreased gp120-gp41 association (in the unliganded state) and decreased chemokine receptor binding (in the CD4-bound state). Subunit association and syncytium-forming ability of the envelope glycoproteins from primary HIV-1 isolates were disrupted more by V3 changes than those of laboratory-adapted HIV-1 envelope glycoproteins. Changes in the gp120 ␤2, ␤19, ␤20, and ␤21 strands, which evidence suggests are proximal to the V3 loop in unliganded gp120, also resulted in decreased gp120-gp41 association. Thus, a gp120 element composed of the V3 loop and adjacent beta strands contributes to quaternary interactions that stabilize the unliganded trimer. CD4 binding dismantles this element, altering the gp120-gp41 relationship and rendering the hydrophobic patch in the V3 tip available for chemokine receptor binding.