UNASSIGNED: Transthyretin amyloid (ATTR) cardiomyopathy is slowed by tafamidis, which stabilizes the TTR molecule and reduces the formation of amyloidogenic oligomers. Stabilizers in clinical doses raise serum TTR, which may be a surrogate for the degree of stabilization.
UNASSIGNED: This study aims to determine, in a non-trial, unselected population of patients with ATTR cardiomyopathy, the effect of tafamidis on serum levels of TTR, and to compare these with published data of changes in TTR.
UNASSIGNED: TTR levels were measured before therapy and 3 to 12 months following initiation of tafamidis therapy in all patients seen between May 20, 2019, and March 1, 2021, who had a follow-up visits within 12 months of therapy initiation.
UNASSIGNED: Among 72 patients with ATTR cardiomyopathy (67 patients with wild-type and 5 patients with variant TTR), administration of tafamidis increased serum TTR from 21.8 mg ± 0.7 mg/dL to 29.3 ± 0.86 mg/dL, an increase of 34.5%. In 5 patients with variant TTR, the increase was 70.9%, compared to 32.0% in the wild-type patients. Mean N-terminal pro-brain natriuretic peptide increased over a mean follow-up of 21 ± 1.2 weeks, but the change was not statistically significant. Over the same period there was a small increase in high-sensitivity troponin T that was of borderline statistical significance (P = 0.057).
UNASSIGNED: Tafamidis consistently increases serum TTR levels in patients with ATTR cardiomyopathy, consistent with its effect on stabilizing TTR. Measurement of TTR level change post-TTR stabilizing therapy might be a surrogate for stabilization and could be a more accurate measure of drug efficacy than an in vitro nonphysiologic test of stabilization.

UNASSIGNED: Cardiac amyloidosis (CA) has been associated with poor outcomes. Screening studies suggest that CA is overlooked-especially in the elderly. Recent advances in treatment have brought attention to the disease, but data on temporal changes in CA epidemiology are sparse.
UNASSIGNED: The aim of this work was to describe all patients with CA in Denmark, examining changes in patient characteristics from 1998 to 2017.
UNASSIGNED: All patients with any form of amyloidosis diagnosed from 1998 to 2017, as well as their comorbidities and pharmacotherapy, were identified in Danish nationwide registries. CA was defined as any diagnosis code for amyloidosis combined with a diagnosis code for heart failure, cardiomyopathy, or atrial fibrillation or a procedural code for pacemaker implantation, regardless of the order. The index date was defined as the date of meeting those criteria. Patients were divided into 5-year periods by index date. For comparison, we also included control subjects (1:4 ratio) from the general population.
UNASSIGNED: CA criteria were met by 619 patients. Comparing 1998-2002 vs 2013-2017, the median age at baseline increased from 67.4 years (interquartile range [IQR]: 53.9-75.2 years) to 72.3 years (IQR: 66.0-79.3 years). The frequency of male patients increased from 62.1% to 66.2%. The incidence of CA rose from 0.88 to 3.56 per 100,000 person-years in the Danish population aged ≥65 years, and the 2-year mortality decreased from 82.6% (IQR: 69.9%-90.5%) to 50.2% (IQR: 43.1%-56.9%). Compared with control subjects, the mortality among CA patients was significantly higher (log-rank test: P < 0.0001).
UNASSIGNED: CA, as defined in this study, was increasingly diagnosed on a national scale. The increasing frequency of male patients and median age suggest that wild-type transthyretin amyloidosis is driving this increase. Greater recognition of earlier, less advanced cases might explain decreasing mortality.