SPC365

Cardiac Involvement After Liver Transplantation in Familial Amyloid Polyneuropathy - A Continuing Challenge

Session: Sessão de Posters 17 - Genética em Cardiologia 2
Speaker: Ana Beatriz Garcia

Congress: CPC 2024
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 20. Congenital Heart Disease and Pediatric Cardiology
Subtheme: 20.6 Congenital Heart Disease – Clinical
Session Type: Cartazes
FP Number: ---
Authors: Ana Beatriz Garcia; Catarina Simões de Oliveira; Ana Margarida Martins; Ana Abrantes; Miguel Raposo; João Fonseca; Catarina Gregório; Conceição Coutinho; Élia Mateus; Isabel Conceição; Fausto J. Pinto; João R. Agostinho

<p style="text-align:justify"><span style="font-family:Calibri"><strong><span style="font-size:11,0000pt"><span style="font-family:Calibri"><strong>Introduction:&nbsp;</strong></span></span></strong></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">Hereditary transthyretin (TTR) amyloidosis is an autosomal dominant disease caused by mutations in the TTR gene. Val30Met is the most common - the condition is called familial amyloidotic polyneuropathy (FAP). Individuals with the Val30Met mutation generally present early with neuropathy and may have late onset cardiac involvement. </span></span><span style="font-size:11,0000pt"><span style="background-color:#ffffff"><span style="font-family:Calibri"><span style="color:#333333">In light of evidence that the liver is the main source of circulating TTR, orthotopic liver transplantation (LT) was introduced as a radical treatment for FAP. However, current findings show that the cardiomyopathy associated with FAP may progress after LV in some patients.</span></span></span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><strong><span style="font-size:11,0000pt"><span style="background-color:#ffffff"><span style="font-family:Calibri"><span style="color:#333333"><strong>Purpose:&nbsp;</strong></span></span></span></span></strong></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">To evaluate cardiac involvement progression in liver transplanted Val30Met FAP patients. </span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><strong><span style="font-size:11,0000pt"><span style="font-family:Calibri"><strong>Methods:&nbsp;</strong></span></span></strong></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">A retrospective analysis was conducted by collecting data from clinical, laboratory, electrocardiographic, echocardiographic, and 24h-ambulatory blood pressure monitoring records. Descriptive and inferential statistics were performed to identify cardiac involvement in FAP patients submitted to liver transplantation that was suspected/assumed by the presence of left ventricular hypertrophy (LVH) in the absence of abnormal loading conditions such as arterial hypertension or significant valvular heart disease. LVH was defined by either 1) interventricular septum or posterior wall dimension &ge; 12 mm or 2) index left ventricular mass &ge; 95 g/m</span></span><sup><span style="font-size:11,0000pt"><span style="font-family:Calibri">2 </span></span></sup><span style="font-size:11,0000pt"><span style="font-family:Calibri">in females and &ge; 115 g/m</span></span><sup><span style="font-size:11,0000pt"><span style="font-family:Calibri">2</span></span></sup><span style="font-size:11,0000pt"><span style="font-family:Calibri">&nbsp;in males. </span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><strong><span style="font-size:11,0000pt"><span style="font-family:Calibri"><strong>Results:&nbsp;</strong></span></span></strong></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">We enrolled 114 FAP patients (56% male), submitted to LT at a mean age of 38 years and followed for a mean time of 14 years at a FAP Referral Centre.&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">Twenty-four percent of patients (27 patients) had LVH identified before LT (LT at a mean age of 40 years, mean baseline NT-proBNP of 211 pg/mL). Although not statistically significant, there was an increase in mean interventricular septum (from 12 to 13mm) and posterior wall (from 10 to 11mm) thickness after LT, possibly suggesting disease progression.&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">At the time of pre-LT evaluation, 56% of patients did not meet the criteria for LVH. Among them, 59% did not develop LVH during the follow-up period (LT was performed at a mean age of 35 years and mean baseline NT-proBNP was 104 pg/mL), while 41% (26 patients) met the LVH criteria (LT was performed at a mean age of 40 years and mean baseline NT-proBNP was 348 pg/mL). In patients where screening echocardiograms allowed for the identification of hypertrophy development, the median time from LT to LVH identification was 6.8 years.&nbsp;</span></span></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">Through univariate Cox regression analysis, it was possible to identify an increased risk of cardiac involvement in those who undergo transplantation later, with a Hazard Ratio of 1.072 (95% CI, 1.023-1.123; p=0.003). NT-proBNP did not predict LVH development. </span></span></span></p>

<p style="text-align:justify"><span style="font-family:Calibri"><strong><span style="font-size:11,0000pt"><span style="font-family:Calibri"><strong>Conclusion:&nbsp;</strong></span></span></strong></span><span style="font-family:Calibri"><span style="font-size:11,0000pt"><span style="font-family:Calibri">Our results showed that cardiac involvement is a reality in FAP. It can be present prematurely in patients with early onset phenotype even before LT and it can progress or even develop after LT. </span></span></span></p>

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