Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis

NCT07766135 | Recruiting

• 2 other identifiers: CEL Messina Prot. 28-25Delibera n. 63/2026
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Transthyretin (TTR) Amyloid Cardiomyopathy; Cardiac Amyloidosis; Cardiomyopathies; Wild-Type Transthyretin Cardiac Amyloidosis; Hereditary Transthyretin Amyloidosis (ATTRv)

Keywords

ATTR; ATTR-CA; Cardiac Amyloidosis; Transthyretin Amyloidosis; Tafamidis; Acoramidis; Liver Stiffness; Fibroscan; Liver Dysfunction; Hepatic Congestion; Coagulation Disorder; Hemostasis; Cardiohepatic Syndrome; Biomarkers; Disease Staging; Echocardiography; Heart Failure; Wild-Type ATTR; Hereditary ATTR

Outcome Measures

Primary Outcomes (33)

• Liver Stiffness Measured by Transient Elastography (FibroScan)

  Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.

  Baseline, 6 Months, 12 Months

• Controlled Attenuation Parameter (CAP) Measured by FibroScan

  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.

  Baseline, 6 months, 12 months

• Serum Aspartate Aminotransferase (AST/GOT)

  Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.

  Baseline, 6 months, 12 months

• Serum Alanine Aminotransferase (ALT/GPT)

  Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Serum Gamma-Glutamyl Transferase (GGT)

  Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Serum Alkaline Phosphatase (ALP)

  Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Serum Bile Acids

  Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Total Bilirubin (mg/dL)

  Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Direct Bilirubin (mg/dL)

  Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Serum Albumin (g/dL)

  Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Serum Gamma Globulins (g/dL)

  Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Serum Immunoglobulin M (IgM) (g/L)

  Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Serum Ferritin (ng/mL)

  Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Anti-Mitochondrial Antibodies

  U/ml

  baseline, 6 months, 12 months

• Fibrosis-4 (FIB-4) Index

  FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Portal Vein Diameter Assessed by Liver Ultrasound

  Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)

  Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Spleen Diameter Assessed by Ultrasound (mm)

  Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Prothrombin Time (PT) (s)

  Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Activated Partial Thromboplastin Time (aPTT) (s)

  Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• International Normalized Ratio (INR)

  International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Plasma Fibrinogen

  Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Fibrin/Fibrinogen Degradation Products

  Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  Baseline, 6 months, 12 months

• D-Dimer

  D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Alpha-2-Antiplasmin

  Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Antithrombin

  Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Plasminogen

  Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Thrombin-Antithrombin Complex

  Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Plasmin-Alpha-2-Antiplasmin Complex

  Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Prothrombin Fragment 1+2

  Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Coagulation Factor X

  Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• von Willebrand Factor Antigen

  von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

• Plasminogen Activator Inhibitor-1 (PAI-1)

  Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.

  baseline, 6 months, 12 months

Secondary Outcomes (6)

• 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

Other Outcomes (3)

• Correlation Between Liver Stiffness and Prothrombin Fragment 1+2

  Baseline

• Correlation Between FIB-4 Index and Prothrombin Fragment 1+2

  Baseline

• Correlation Between Liver Stiffness and Fibrinogen

  Baseline

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Messina: lead
• Azienda Ospedaliera Universitaria Policlinico "G. Martino": collaborator

Study Sites (1)

AOU Policlinico G. Martino, UOC Cardiologia con UTIC

Messina, Sicily, 98124, Italy

RECRUITING

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Cardiomyopathies; Amyloidosis, Hereditary, Transthyretin-Related; Liver Diseases; Hemostatic Disorders; Heart Failure

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Amyloidosis, Familial; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies; Heart Diseases; Cardiovascular Diseases; Digestive System Diseases; Vascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Gianluca Di Bella, MD, PhD

  University of Messina and AOU Policlinico G. Martino

  STUDY CHAIR

• Luigi Colarusso, MD, PhD Candidate

  AOU Policlinico G. Martino

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luigi Colarusso, MD, PhD Candidate

CONTACT

+390902212341; luigi.colarusso@polime.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 12, 2026
• First Posted: August 14, 2026
• Study Start: January 30, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: August 14, 2026

Record last verified: 2026-06

Locations

IT (1)