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Background Prevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age. Dual disease (AS+myocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR). Objectives This study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis. Methods Symptomatic severe AS patients aged ≥65 years undergoing SAVR were enrolled. ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA. Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation. Results SAVR was performed in 46 AS patients (age 70 ± 5 years, 70% men). PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n = 3 of 32, 9.4%), suggestive of myocardial ATTR-CA. On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis. Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%]; P = 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms; P = 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%]; P = 0.030). At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%; P = 0.477). Conclusions Dual disease is not uncommon in India. Isolated valvular amyloidosis in severe AS is much more common.

Binding of anionic (sodium dodecyl sulfate, SDS), cationic (cetyl trimethyl ammonium bromide, CTAB), and nonionic (TX-100) surfactants to gelatin chains in aqueous buffer (pH = 7.0) medium has been studied by dynamic light-scattering technique performed at T = 30 °C. In the surfactant concentration range varying from 0 to 100 mM, SDS exhibited electrostatic binding to the charged groups of the polypeptide chain resulting in considerable reduction in the hydrodynamic radius (R h) of gelatin up to the critical association concentration (CAC), and at higher concentrations both the SDS micelles and gelatin−SDS complexes were found to be coexisting in equilibrium. In the case of CTAB, almost the opposite was observed:  the gelatin chains showed small increase in size up to the CAC. Beyond this, the gelatin−CTAB complexes were observed to grow significantly, and these were found to be in equilibrium with CTAB micelles. TX-100 exhibited little hydrophobic binding to gelatin, and no observable change in gelatin size was observed. The micellar shapes were found to be near-spherical for SDS and oblate ellipsoidal for CTAB micelles. Results have been explained through the necklace-bead model of polymer−surfactant interactions.

Impaired conformation underlies CFTR misprocessing in cystic fibrosis. Defective conformation interferes with ER export and post-ER stability. In ΔF508 CFTR, low temperature or R555K improves both through a global conformational reversion. The interplay between the ER exit code and domain conformation governs CFTR misprocessing and rescue.