Candida C Quarta

Carol J Whelan

Dorota M Rowczenio

Janet A Gilbertson

Julian D Gillmore

Marianna Fontana

Philip N Hawkins

Sevda Ozer

Orphanet Journal of Rare Diseases

Springer - Publisher Connector

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

ORAL PRESENTATION Open Access
Diflunisal therapy for cardiac ATTR amyloidosis: a
longitudinal, prospective, single centre study
Candida C Quarta*, Sevda Ozer, Carol J Whelan, Marianna Fontana, Dorota M Rowczenio, Janet A Gilbertson,
Philip N Hawkins, Julian D Gillmore
From First European Congress on Hereditary ATTR amyloidosis
Paris, France. 2-3 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 amyloi-
dosis. However, data on the effect of diflunisal on cardiac
structure and function in amyloidotic hearts are lacking.
We report the echocardiographic profiles and cardiac bio-
markers 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 fibrilla-
tion) or pacemaker implantation were excluded. All
subjects underwent a standardized comprehensive proto-
col 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 thick-
ness (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 trea-
ted 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 ejec-
tion 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.
Royal Free Hospital, Division of Medicine, University College of London,
National Amyloidosis Centre, NW3 2PF, London, UK
Quarta et al. Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):O23
http://www.ojrd.com/content/10/S1/O23
© 2015 Quarta et al. 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.
Published: 2 November 2015
doi:10.1186/1750-1172-10-S1-O23
Cite this article as: Quarta et al.: Diflunisal therapy for cardiac ATTR
amyloidosis: a longitudinal, prospective, single centre study. Orphanet
Journal of Rare Diseases 2015 10(Suppl 1):O23.
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Quarta et al. Orphanet Journal of Rare Diseases 2015, 10(Suppl 1):O23
http://www.ojrd.com/content/10/S1/O23
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Diflunisal therapy for cardiac ATTR amyloidosis: a longitudinal, prospective, single centre study

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