Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (ATTR-CA): New Horizons in Disease Staging and Follow-Up
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Liver Stiffness Measured by Transient Elastography (FibroScan)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
结局指标
主要结局
Liver Stiffness Measured by Transient Elastography (FibroScan)
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: baseline, 6 months, 12 months
Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Serum Ferritin (ng/mL)
时间窗: baseline, 6 months, 12 months
Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Anti-Mitochondrial Antibodies
时间窗: baseline, 6 months, 12 months
U/ml
Fibrosis-4 (FIB-4) Index
时间窗: 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
时间窗: 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)
时间窗: 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)
时间窗: baseline, 6 months, 12 months
Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
Prothrombin Time (PT) (s)
时间窗: 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)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: baseline, 6 months, 12 months
Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Plasminogen
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
时间窗: 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.
次要结局
- 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)
研究者
Gianluca Di Bella
MD, PhD
Azienda Ospedaliera Universitaria Policlinico "G. Martino"