SPC365

Transthyretin-directed antisense oligonucleotide therapy effects on ATTRv myocardiopathy – a single-center experience

Session: Comunicações Orais - Sessão 26 - Doenças do Miocárdio
Speaker: Catarina Gregório

Congress: CPC 2023
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.7 Myocardial Disease - Other
Session Type: Comunicações Orais
FP Number: ---
Authors: Catarina Gregório; João R Agostinho; Ana Beatriz Garcia; Joana Brito; Pedro Alves da Silva; Beatriz Valente Silva; Ana Margarida Martins; Catarina Simões de Oliveira; Ana Abrantes; Miguel Azaredo Raposo; João Santos Fonseca; Miguel Santos; Catarina Campos; Conceição Coutinho; Isabel Conceição; Fausto J. Pinto

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><strong>Introduction: </strong></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff">Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic disease with a heterogenous presentation that includes cardiomyopathy and polyneuropathy. Important advances have been made regarding disease-modifying therapies. Inotersen and patisiran are transthyretin-directed antisense oligonucleotide approved for the treatment of polyneuropathy. However, their effects on cardiomyopathy related parameters are not well defined.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><strong>Objective: </strong></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">To study the effect of patisiran and inotersen on cardiac function and structure in a population with ATTRv and evidence of cardiac involvement at baseline.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><strong>Methods: </strong></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">Single center retrospective study of patients with ATTRv and definite or possible diagnosis of amyloid cardiomyopathy (defined either by a positive bone scintigraphy or interventricular septum or posterior wall dimension &ge; 12 mm or index left ventricular mass &ge; 95 g/m</span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><sup>2 </sup></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">in female and &ge; 115 g/m</span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><sup>2</sup></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"> in male in the absence of abnormal loading conditions). Demographic, clinical, therapeutic and echocardiographic data was recorded. Wilcoxon Test was used to evaluate disease progression.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><strong>Results: </strong></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">A total of 46 patients were treated with either patisiran (32) or inotersen (14). From those, 8 patients fulfilled criteria for amyloid cardiomyopathy (7 had a positive bone scintigraphy and 1 patient had left ventricle hypertrophy without an abnormal loading condition), 3 were medicated with inotersen and 5 with patisiran. The median age was 76 years (IQR 68.8-79) and 88% were male.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">Globally, at baseline, median left ventricular ejection fraction was 60% (IQR 54-60), index left ventricular mass (LVM), 168g/m</span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><sup>2</sup></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"> (IQR 120-182), posterior wall (PW) dimension, 13mm (IQR 12-15), interventricular septum (IVS), 17mm (IQR 13-19) and left atrial volume (LAV) 45mL/m</span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><sup>2</sup></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"> (IQR 38-67). Median NTproBNP was 1148 pg/ml (IQR 595-3397) and 7 patients were in NYHA functional class I and 1 in class II. At follow-up (FUP), a significant reduction in LVM was noted (145g/m</span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><sup>2</sup></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">; IQR 113/187; p &lt;0.043). NYHA class worsened (class I: 3; class II: 5; p=0.046), however, although not significantly, NTproBNP decreased (795 pg/ml; IQR 425-1726).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">The small sample size precluded any comparison between both medications. However, NTproBNP reduction was manly driven by patisiran group (3071pg/ml; IQR 1079-5891 vs 555 pg/ml; 425-555 pg/ml) and LVM reduction by inotersen&rsquo;s (142g/m</span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><sup>2</sup></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">; IQR 120-142 vs 115g/m</span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><sup>2</sup></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">; IQR 108-115).</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">During the FUP none of these patients had a heart failure related admission or died.</span></span></span></p>

<p><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"><strong>Conclusion: </strong></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000">This small sized sample study of patients with ATTRv myocardiopathy suggest that </span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#212121"><span style="background-color:#ffffff">transthyretin-directed antisense oligonucleotide therapy</span></span></span></span><span style="font-size:11pt"><span style="font-family:Arial"><span style="color:#000000"> may halt cardiac involvement progression and may even induce cardiac reverse remodeling. </span></span></span></p>