Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)
10 août 2026 mis à jour par: Gianluca Di Bella, University of Messina
Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (ATTR-CA): New Horizons in Disease Staging and Follow-Up
Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive infiltrative cardiomyopathy caused by the deposition of misfolded transthyretin protein within the myocardium. Current disease staging and follow-up strategies mainly rely on cardiac biomarkers and renal function; however, the systemic nature of ATTR suggests that additional organ involvement may provide valuable prognostic information.
The purpose of this prospective observational study is to investigate liver dysfunction and coagulation abnormalities in patients with wild-type or hereditary ATTR-CA and to evaluate their potential role as novel markers of disease severity and progression. Patients with ATTR-CA will be compared with an age-matched control population with non-amyloid hypertrophic cardiomyopathy.
Clinical, laboratory, echocardiographic, hepatic ultrasound, liver stiffness, and coagulation parameters will be assessed at baseline and during follow-up. The study will also evaluate changes in these parameters after 6 and 12 months of treatment with tafamidis.
The results may improve the understanding of cardio-hepatic interactions in ATTR-CA and identify new tools for disease staging and longitudinal monitoring.
Aperçu de l'étude
Statut
Recrutement
Description détaillée
Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure and left ventricular hypertrophy in older adults. Although several prognostic models have been developed for ATTR-CA, most currently available staging systems are based primarily on cardiac biomarkers and renal function. These approaches may not fully capture the systemic nature of the disease.
Emerging evidence suggests that liver dysfunction and coagulation abnormalities may represent underexplored manifestations of ATTR-CA. Liver involvement may result from direct amyloid deposition, chronic venous congestion related to heart failure, or a combination of both mechanisms. Similarly, alterations in coagulation pathways may reflect hepatic dysfunction and systemic disease burden.
LICA2025 is a single-center, prospective, observational study designed to evaluate biochemical and instrumental markers of liver function and coagulation in patients with wild-type or hereditary ATTR-CA followed at the University Hospital G. Martino of Messina, Italy. A control population with non-amyloid hypertrophic cardiomyopathy will be enrolled for comparison.
The primary objective is to compare liver and coagulation parameters between ATTR-CA patients and controls. Secondary objectives include evaluating the relationship between hepatic/coagulation abnormalities and cardiac disease severity, assessing changes after 6±1 and 12±1 months of tafamidis therapy, and exploring potential interactions between liver dysfunction and coagulation disturbances.
Participants will undergo clinical evaluation, laboratory testing, electrocardiography, transthoracic echocardiography, hepatic ultrasound, liver elastography (FibroScan), and coagulation assessment according to the study protocol. Follow-up evaluations will be performed at baseline, 6 months, and 12 months.
The study aims to identify novel biomarkers and imaging parameters that may improve disease staging, risk stratification, and longitudinal monitoring in transthyretin cardiac amyloidosis.
Type d'étude
Observationnel
Inscription (Estimé)
70
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Coordonnées de l'étude
- Nom: Luigi Colarusso, MD, PhD Candidate
- Numéro de téléphone: +390902212341
- E-mail: luigi.colarusso@polime.it
Lieux d'étude
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Sicily
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Messina, Sicily, Italie, 98124
- Recrutement
- AOU Policlinico G. Martino, UOC Cardiologia con UTIC
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Contact:
- Luigi Colarusso, MD, PhD Candidate
- Numéro de téléphone: +390902212341
- E-mail: luigi.colarusso@polime.it
-
Sous-enquêteur:
- Roberto Licordari, MD, PhD
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Chercheur principal:
- Luigi Colarusso, MD, PhD Candidate
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Non
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
Adult patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) followed at the University Hospital G. Martino, Messina, Italy, and an age-matched control population with non-amyloid hypertrophic phenotype cardiomyopathy.
La description
Inclusion Criteria:
- Written informed consent obtained prior to study participation.
- Diagnosis of wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) according to current European recommendations.
- Ability to comply with study procedures and follow-up visits.
Exclusion Criteria:
- Age younger than 18 years.
- Severe liver dysfunction due to causes other than amyloidosis.
- Inability to comply with study procedures because of language barriers, cognitive impairment, or severe psychiatric disorders.
- Comorbidities associated with life expectancy less than 12 months.
- Active alcohol or substance abuse.
- For coagulation analyses: congenital coagulation disorders, thrombotic disorders, active malignancy, or sepsis.
- Pregnancy or breastfeeding.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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ATTR-CA Patients
Patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) diagnosed according to current European recommendations and followed at the University Hospital G. Martino, Messina.
Participants will undergo clinical, laboratory, echocardiographic, hepatic ultrasound, liver elastography, and coagulation assessments at baseline and during follow-up.
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Hypertrophic Phenotype Controls
Age-matched patients with non-amyloid hypertrophic phenotype cardiomyopathy serving as a control population.
Participants will undergo the same clinical, laboratory, echocardiographic, hepatic, and coagulation evaluations as the ATTR-CA group.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Liver Stiffness Measured by Transient Elastography (FibroScan)
Délai: Baseline, 6 Months, 12 Months
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Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.
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Baseline, 6 Months, 12 Months
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Controlled Attenuation Parameter (CAP) Measured by FibroScan
Délai: Baseline, 6 months, 12 months
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Controlled attenuation parameter (CAP) measured by FibroScan as an instrumental measure of hepatic steatosis, expressed in decibels per meter (dB/m), compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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Serum Aspartate Aminotransferase (AST/GOT)
Délai: Baseline, 6 months, 12 months
|
Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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Serum Alanine Aminotransferase (ALT/GPT)
Délai: baseline, 6 months, 12 months
|
Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Gamma-Glutamyl Transferase (GGT)
Délai: baseline, 6 months, 12 months
|
Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Alkaline Phosphatase (ALP)
Délai: baseline, 6 months, 12 months
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Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Bile Acids
Délai: baseline, 6 months, 12 months
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Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Total Bilirubin (mg/dL)
Délai: baseline, 6 months, 12 months
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Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Direct Bilirubin (mg/dL)
Délai: baseline, 6 months, 12 months
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Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Albumin (g/dL)
Délai: baseline, 6 months, 12 months
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Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Gamma Globulins (g/dL)
Délai: baseline, 6 months, 12 months
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Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Immunoglobulin M (IgM) (g/L)
Délai: baseline, 6 months, 12 months
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Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Ferritin (ng/mL)
Délai: baseline, 6 months, 12 months
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Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Anti-Mitochondrial Antibodies
Délai: baseline, 6 months, 12 months
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U/ml
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baseline, 6 months, 12 months
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Fibrosis-4 (FIB-4) Index
Délai: baseline, 6 months, 12 months
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FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Portal Vein Diameter Assessed by Liver Ultrasound
Délai: baseline, 6 months, 12 months
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Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)
Délai: baseline, 6 months, 12 months
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Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Spleen Diameter Assessed by Ultrasound (mm)
Délai: baseline, 6 months, 12 months
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Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Prothrombin Time (PT) (s)
Délai: baseline, 6 months, 12 months
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Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Activated Partial Thromboplastin Time (aPTT) (s)
Délai: baseline, 6 months, 12 months
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Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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International Normalized Ratio (INR)
Délai: baseline, 6 months, 12 months
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International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasma Fibrinogen
Délai: baseline, 6 months, 12 months
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Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Fibrin/Fibrinogen Degradation Products
Délai: Baseline, 6 months, 12 months
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Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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D-Dimer
Délai: baseline, 6 months, 12 months
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D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Alpha-2-Antiplasmin
Délai: baseline, 6 months, 12 months
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Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Antithrombin
Délai: baseline, 6 months, 12 months
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Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasminogen
Délai: baseline, 6 months, 12 months
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Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Thrombin-Antithrombin Complex
Délai: baseline, 6 months, 12 months
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Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasmin-Alpha-2-Antiplasmin Complex
Délai: baseline, 6 months, 12 months
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Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Prothrombin Fragment 1+2
Délai: baseline, 6 months, 12 months
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Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Coagulation Factor X
Délai: baseline, 6 months, 12 months
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Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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von Willebrand Factor Antigen
Délai: baseline, 6 months, 12 months
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von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasminogen Activator Inhibitor-1 (PAI-1)
Délai: baseline, 6 months, 12 months
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Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
Délai: Baseline
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Correlation between liver stiffness measured by FibroScan (kPa) and plasma NT-proBNP concentration (ng/L) in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)
Délai: Baseline
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Correlation between liver stiffness measured by FibroScan (kPa) and interventricular septal thickness expressed in mm measured by transthoracic echocardiography in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)
Délai: Baseline
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Correlation between liver stiffness measured by FibroScan (kPa) and Global Longitudinal Strain (expressed in %) measured by transthoracic echocardiography in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)
Délai: Baseline
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Correlation between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L) measured by standard laboratory testing in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Change in Liver Stiffness During Disease-Modifying Treatment
Délai: Baseline, 6±1 months, and 12±1 months
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Change in liver stiffness measured by FibroScan and expressed in kPa from baseline to 6±1 months and 12±1 months after treatment initiation.
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Baseline, 6±1 months, and 12±1 months
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Change in Controlled Attenuation Parameter During Disease-Modifying Treatment
Délai: Baseline, 6±1 months, and 12±1 months
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Change in controlled attenuation parameter (CAP) measured by FibroScan and expressed in dB/m from baseline to 6±1 months and 12±1 months after treatment initiation.
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Baseline, 6±1 months, and 12±1 months
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Correlation Between Liver Stiffness and Prothrombin Fragment 1+2
Délai: Baseline
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Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between FIB-4 Index and Prothrombin Fragment 1+2
Délai: Baseline
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Correlation between FIB-4 and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
|
Baseline
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Correlation Between Liver Stiffness and Fibrinogen
Délai: Baseline
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Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma fibrinogen concentration in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino
- Chercheur principal: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
30 janvier 2026
Achèvement primaire (Estimé)
1 janvier 2028
Achèvement de l'étude (Estimé)
1 janvier 2028
Dates d'inscription aux études
Première soumission
12 juin 2026
Première soumission répondant aux critères de contrôle qualité
10 août 2026
Première publication (Réel)
14 août 2026
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
14 août 2026
Dernière mise à jour soumise répondant aux critères de contrôle qualité
10 août 2026
Dernière vérification
1 juin 2026
Plus d'information
Termes liés à cette étude
Mots clés
- Insuffisance cardiaque
- Hémostase
- Biomarqueurs
- Échocardiographie
- Dysfonctionnement du foie
- ATTR
- Fibroscan
- Amylose à transthyrétine
- Amylose cardiaque
- Tafamidis
- Raideur du foie
- Acoramidis
- Trouble de la coagulation
- Stade de la maladie
- ATTR-CA
- Hepatic Congestion
- Cardiohepatic Syndrome
- Wild-Type ATTR
- Hereditary ATTR
Termes MeSH pertinents supplémentaires
- Maladies du système nerveux
- Maladies vasculaires
- Maladies cardiovasculaires
- Maladies cardiaques
- Maladies neuromusculaires
- Métabolisme, erreurs innées
- Maladies génétiques, innées
- Maladies métaboliques
- Maladies du système nerveux périphérique
- Maladies du système digestif
- Maladies hématologiques
- Maladies neurodégénératives
- Troubles hérédodégénératifs, système nerveux
- Troubles hémorragiques
- Déficits de protéostase
- Neuropathies amyloïdes
- Amylose familiale
- Amylose
- Maladies et anomalies congénitales, héréditaires et néonatales
- Maladies nutritionnelles et métaboliques
- Maladies hémiques et lymphatiques
- Insuffisance cardiaque
- Maladies du foie
- Cardiomyopathies
- Troubles hémostatiques
- Neuropathies amyloïdes, familiales
- Amylose, héréditaire, liée à la transthyrétine
Autres numéros d'identification d'étude
- CEL Messina Prot. 28-25
- Delibera n. 63/2026 (Autre identifiant: AOU Policlinico G. Martino)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
INDÉCIS
Description du régime IPD
The decision regarding IPD sharing has not yet been finalized.
Any future data sharing will be considered in accordance with applicable ethical approvals, participant consent, institutional policies, and data protection regulations.
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Non
Étudie un produit d'appareil réglementé par la FDA américaine
Non
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