Volume 10 Supplement 1

First European Congress on Hereditary ATTR amyloidosis

Open Access

Diflunisal therapy for cardiac ATTR amyloidosis: a longitudinal, prospective, single centre study

  • Candida C Quarta1,
  • Sevda Ozer1,
  • Carol J Whelan1,
  • Marianna Fontana1,
  • Dorota M Rowczenio1,
  • Janet A Gilbertson1,
  • Philip N Hawkins1 and
  • Julian D Gillmore1
Orphanet Journal of Rare Diseases201510(Suppl 1):O23

https://doi.org/10.1186/1750-1172-10-S1-O23

Published: 2 November 2015

Background

The transthyretin (TTR) stabilizer diflunisal has been shown to reduce the rate of progression of neurological manifestations in patients with hereditary ATTR amyloidosis. However, data on the effect of diflunisal on cardiac structure and function in amyloidotic hearts are lacking. We report the echocardiographic profiles and cardiac biomarkers of patients with either mutant (M) or wild-type (WT) TTR-related cardiac amyloidosis (ATTR-CA) who received treatment with diflunisal compared to matched untreated patients.

Methods

We included in the analysis patients with clearly defined ATTR-CA, who received diflunisal for at least 24 months. For comparison, we included a group of patients with similar age, left ventricular (LV) wall thickness and renal function who were not treated with diflunisal. Patients with coexistent rhythm abnormalities (e.g. atrial fibrillation) or pacemaker implantation were excluded. All subjects underwent a standardized comprehensive protocol of evaluations and follow-up.

Results

We identified 18 patients aged 70 [67-73] who received diflunisal for at least 24 months (9 WT; 9 M: 7 T60A, 1 S77Y, 1 G47R). For comparison we included 17 untreated patients, aged 70 [68-75] (p=0.43) (14 WT; 3 M: 2 T60A, 1 V122I). At baseline, treated and untreated patients did not show significant differences in terms of LV wall thickness (16.6±2 vs. 16.9±2 mm, p=0.45), LV ejection fraction (53±9 vs. 48±10 %, p=0.1), and global longitudinal strain (GLS, -11.4±4 vs. -10.9±4%, p=0.74). NT-proBNP (log transformed) was 5.9±0.9 and 6.2±0.7ng/L in the treated and untreated group respectively (p=0.41). Estimated glomerular filtration rate (eGFR) was mildly reduced in both treated and untreated patients (69±2 vs. 63±20 ml/min, p=0.3).

Over 42 [34-64] months, LV wall thickness remained stable and comparable in both groups (p=0.76). LV ejection fraction worsened within the untreated group (p=0.03), but remained stable in the treated one (p=0.2), although there was no significant difference in rate of decline between the groups (p=0.24). GLS worsened in the untreated group (from -10.9±4 to -8.7±3 %, p=0.03) but not in the treated one (from -11.4±4 to -11.2±3 %, p=0.88; generalized estimating equation p=0.02). NT-proBNP increased in both the untreated group (from 6.2±0.7 to 6.9±0.6 ng/L, p<0.001) and (less) in the treated one (from 5.9±0.9 to 6.2±0.7 ng/L, p=0.02; generalized estimating equation p<0.01), in the absence of a significant decrease of eGFR over time, both between groups (generalized estimating equation p=0.29) and within each group (from 69±17 to 65±20 ml/min in the treated group, p=0.19; from 63±20 to 55±22 ml/min in the untreated group, p=0.07).

Conclusion

The use of sensitive markers of change in cardiac function, such as GLS and NT-proBNP, suggests that diflunisal may slow or halt disease progression in mutant and wild-type ATTR-CA. These findings encourage further systematic study of diflunisal in ATTR-CA.

Authors’ Affiliations

(1)
Royal Free Hospital, Division of Medicine, University College of London, National Amyloidosis Centre

Copyright

© Quarta et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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