SPC365

Transthyretin cardiac amyloidosis due to rare mutations in Portuguese patients

Session: Posters (Sessão 5 - Écran 3) - Doenças do Miocárdio e Pericárdio 2
Speaker: Catarina Costa

Congress: CPC 2022
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.3 Myocardial Disease – Diagnostic Methods
Session Type: Pósters Electrónicos
FP Number: ---
Authors: Catarina Martins da Costa; Ana Filipa Amador; João Calvão; Tânia Proença; Miguel Carvalho; Ricardo Alves Pinto; Catarina Amaral Marques; André Cabrita; Raquel Mota Garcia; Isabel Tavares; Goreti Moreira; Teresa Pinho; Susana Fernandes; Elisabete Martins; Filipe Macedo
<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Introduction</span></span></strong> <span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Transthyretin amyloidosis</span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"> (ATTR amyloidosis) is a heterogeneous disorder and a frequent cause of cardiac amyloidosis. The hereditary form is associated with&nbsp;more than 100 different </span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">transthyretin</span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"> (TTR)&nbsp;</span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">genetic variants</span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">. In Portugal, the Val50Met mutation is particularly frequent and associated with an early neurologic phenotype.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Another mutation, the ATTR Val122Ile variant, is predominantly associated with severe cardiomyopathy and is a well-known cause of&nbsp;</span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">cardiac amyloidosis</span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">&nbsp;between African-American patients frequently described in US cohorts. So far, very few cases of this mutation have been reported in Caucasian patients including Portuguese <span style="color:black">patients.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Objective</span></span></strong><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"> We aimed to study patients with hereditary cardiac ATTR amyloidosis in our center. Clinical data w<span style="color:black">ere </span>retrospectively obtained from electronic records. </span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Results</span></span></strong><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"> We identified <span style="color:black">4 </span>patients (72 years old mean age; 3 men) with cardiac amyloidosis, 3 with the Val122Ile variant and <span style="color:black">1 with His4Ile </span>(individual characteristics are described in table 1)<span style="color:black">. </span>All patients were Caucasian.</span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Patients 1 to 3 presented a variant in exon 4 (the most commonly affected exon<span style="color:black">). All imaging data </span>including bone cardiac scintigraphy (CS), were in accordance with <span style="color:black">ATTR</span> amyloidosis diagnosis. They presented with congestive heart failure or syncope. It took on average 2 years from diagnosis to <span style="color:black">the </span>first heart failure hospitalization. Patient 3 died with advanced heart failure after being considered no candida<span style="color:black">te </span>for heart transplanta<span style="color:black">tion</span>. Interestingly enough <span style="color:black">this </span>patient carries the Val122Ile variant in homozigoty.</span></span></span></span></p>

<p style="text-align:justify">&nbsp;</p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"><span style="color:black">Patient 4 was exceptional since she presented a <em>new </em>variant in exon 1. She was in NYHA I and had no hospitalization during follow-up. Echocardiogram showed left ventricular hypertrophy and the CS a Perugini score of 0. Cardiac magnetic resonance was suggestive of infiltrative cardiomyopathy and the myocardium biopsy confirmed amyloidosis. She had particularly exuberant hepatic amyloidosis. </span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">The family screening revealed that patient 1&rsquo;s 47 years old son, <span style="color:black">with hypertension, carries the </span>Val122Ile variant. At the time of diagnosis, he was asymptomatic; transthoracic echocardiogram showed basal interventricular septum moderate hypertrophy (15mm) and the Perugini score <span style="color:black">was 0</span>. Patient 2 has 1 daughter, who was negative for TTR </span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">gene variants</span></span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">, and one son who refused to perform family screening. </span></span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Conclusion:</span></span></strong><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif"> Four cases with rare ATTR variants (Val122Ile and <span style="color:black">His4Ile</span></span></span><span style="font-family:&quot;Calibri&quot;,sans-serif">) </span><span style="font-size:11.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">were identified in our center, and the family screening allowed <span style="color:black">the diagnosis of 2 asymptomatic carriers</span>. This study reinforces the <span style="color:black">importance of the genetic test in patients with cardiac ATTR </span>amyloidosis. Larger studies are needed to <span style="color:black">evaluate the prevalence of non Val50Met ATTR mutations in Portuguese patients with (cardiac) amyloidosis</span></span></span></span></span></p>