Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (ATTR-CA): New Horizons in Disease Staging and Follow-Up
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University of Messina
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Liver Stiffness Measured by Transient Elastography (FibroScan)
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Observational
- Observational Model
- Case Control
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
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.
Outcomes
Primary Outcomes
Liver Stiffness Measured by Transient Elastography (FibroScan)
Time Frame: Baseline, 6 Months, 12 Months
Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.
Controlled Attenuation Parameter (CAP) Measured by FibroScan
Time Frame: Baseline, 6 months, 12 months
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.
Serum Aspartate Aminotransferase (AST/GOT)
Time Frame: Baseline, 6 months, 12 months
Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Serum Alanine Aminotransferase (ALT/GPT)
Time Frame: baseline, 6 months, 12 months
Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Serum Gamma-Glutamyl Transferase (GGT)
Time Frame: 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.
Serum Alkaline Phosphatase (ALP)
Time Frame: baseline, 6 months, 12 months
Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Serum Bile Acids
Time Frame: baseline, 6 months, 12 months
Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.
Total Bilirubin (mg/dL)
Time Frame: baseline, 6 months, 12 months
Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Direct Bilirubin (mg/dL)
Time Frame: baseline, 6 months, 12 months
Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Serum Albumin (g/dL)
Time Frame: baseline, 6 months, 12 months
Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Serum Gamma Globulins (g/dL)
Time Frame: baseline, 6 months, 12 months
Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Serum Immunoglobulin M (IgM) (g/L)
Time Frame: baseline, 6 months, 12 months
Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Serum Ferritin (ng/mL)
Time Frame: baseline, 6 months, 12 months
Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Anti-Mitochondrial Antibodies
Time Frame: baseline, 6 months, 12 months
U/ml
Fibrosis-4 (FIB-4) Index
Time Frame: baseline, 6 months, 12 months
FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.
Portal Vein Diameter Assessed by Liver Ultrasound
Time Frame: baseline, 6 months, 12 months
Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.
Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)
Time Frame: baseline, 6 months, 12 months
Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.
Spleen Diameter Assessed by Ultrasound (mm)
Time Frame: baseline, 6 months, 12 months
Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
Prothrombin Time (PT) (s)
Time Frame: baseline, 6 months, 12 months
Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Activated Partial Thromboplastin Time (aPTT) (s)
Time Frame: baseline, 6 months, 12 months
Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
International Normalized Ratio (INR)
Time Frame: baseline, 6 months, 12 months
International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Plasma Fibrinogen
Time Frame: baseline, 6 months, 12 months
Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Fibrin/Fibrinogen Degradation Products
Time Frame: Baseline, 6 months, 12 months
Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
D-Dimer
Time Frame: baseline, 6 months, 12 months
D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Alpha-2-Antiplasmin
Time Frame: baseline, 6 months, 12 months
Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Antithrombin
Time Frame: baseline, 6 months, 12 months
Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Plasminogen
Time Frame: baseline, 6 months, 12 months
Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Thrombin-Antithrombin Complex
Time Frame: baseline, 6 months, 12 months
Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Plasmin-Alpha-2-Antiplasmin Complex
Time Frame: baseline, 6 months, 12 months
Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Prothrombin Fragment 1+2
Time Frame: baseline, 6 months, 12 months
Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Coagulation Factor X
Time Frame: baseline, 6 months, 12 months
Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
von Willebrand Factor Antigen
Time Frame: baseline, 6 months, 12 months
von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Plasminogen Activator Inhibitor-1 (PAI-1)
Time Frame: baseline, 6 months, 12 months
Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Secondary Outcomes
- Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)(Baseline)
- Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)(Baseline)
- Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)(Baseline)
- Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)(Baseline)
- Change in Liver Stiffness During Disease-Modifying Treatment(Baseline, 6±1 months, and 12±1 months)
- Change in Controlled Attenuation Parameter During Disease-Modifying Treatment(Baseline, 6±1 months, and 12±1 months)
Investigators
Gianluca Di Bella
MD, PhD
Azienda Ospedaliera Universitaria Policlinico "G. Martino"