Cardiovascular Abnormalities, Primary Biliary Cholangitis
Conditions
Keywords
Primary Biliary Cholangitis, Cardiac impairment, Cardiovascular Magnetic Resonance
Brief summary
Primary biliary cholangitis (PBC) is a chronic inflammatory liver disease leading to cirrhosis. Researches reported patients with PBC may involve abnormalities on skeleton, thyroid and exocrine glands. However, whether this autoimmune disease would cause cardiac impairment is scarcely investigated. Cardiovascular Magnetic Resonance(CMR) is recently developed as a reliable modality to evaluate the cardiac tissue characteristics and functions. This study aims to investigate the cardiac status in PBC patients based on CMR.
Detailed description
Primary biliary cholangitis (PBC) is a progressive and uncommon inflammatory autoimmune cholesteric liver disease，which will contribute to cirrhosis. Symptoms and course of primary biliary cholangitis can be diverse, wherefore the targets of the current treatment are focused on the prevention of end-stage liver disease. Researches reported patients with PBC may involve abnormalities on skeleton, thyroid and exocrine glands. However, whether this autoimmune disease would cause cardiac impairment is scarcely investigated. From our clinical practice, the cardiac structural abnormal can be found in certain patients with PBC detected by cardiovascular magnet resonance (CMR). CMR is the primary and emerging imaging modality for myocardial tissue characterization, and it is recommended as a gold standard for functional imaging and assessment. This three-center, multi-modality, prospective observational study plans to identify the type and the severity of cardiac changes in PBC.
Interventions
DIAGNOSTIC_TESTCMR examination
After recruiting participants and collecting the baseline information, a CMR scan and a post-processed imaging procedure will be carried on in order to detect the cardiac impairment.
Sponsors
RenJi Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
for PBC group: * Age between 18-80 years old. * Definite primary biliary cirrhosis diagnosis which is consistent with European Association for the Study of the Liver (EASL) \[Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis (2017)\]. The following three diagnostic factors, at least meet two: 1. History of elevated alkaline phosphatase (ALP) levels; 2. Liver biopsy consistent with PBC; 3. Positive antimitochondrial antibodies (AMA) or specific antinuclear antibodies; * Providing written informed consent
Exclusion criteria
* History or presence of other concomitant liver disease including: 1. cirrhosis or viral hepatitis; 2. Inherited metabolic liver disease; 3. Drug-induced liver injury; 4. Other systemic disease inducing liver change. * Subjects with life expectancy \< 6 months. * Subjects with known ischemic/non-ischemic cardiomyopathy or abnormal in cardiac-related examinations. * Subjects with standard metallic contraindications to CMR (i.e., estimated glomerular filtration rate \< 30 ml/min/1.73 m2, New York Heart Association functional capacity class IV) Inclusion Criteria for Control group: * Absence of known systemic diseases * Normal examinations in CMR/Echo/ECG * Age between 18-80 years old. * Providing written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of Cardiac Events | 7 months after first CMR scanning | All PBC patients are followed up through telephone or by retrieving outpatient medical record systems. Cardiac events include: 1. cardiac death; 2. myocardial infarction; 3. hospitalization for unstable angina. |
| Quantitative Assessment in Cardiac Injury | within 2 days of CMR scan | T1 mapping-derived extracellular volumes (ECV) were used to detect changes in the myocardium interstitial matrix. ECV was calculated according to the ECV formula consist of T1 mapping value. |
Countries
China
Participant flow
Recruitment details
This was a prospective, three-center, cardiac imaging observational study. The study was open for recruitment between September 2017 and January 2019. The first participant was enrolled on October 23, 2017 and last participant was enrolled on January 8, 2019
Pre-assignment details
Of 119 enrolled participants. 112 participants were included and randomized to observational study group.
Participants by arm
| Arm | Count |
|---|---|
| PBC Group Patients have a definite PBC diagnosis.
CMR examination: After recruiting participants and collecting the baseline information, a CMR scan and a post-processed imaging procedure will be carried on in order to detect the cardiac impairment. | 56 |
| Control Group The healthy volunteers.
CMR examination: After recruiting participants and collecting the baseline information, a CMR scan and a post-processed imaging procedure will be carried on in order to detect the cardiac impairment. | 56 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Uncertain diagnosis | 2 | 1 |
Baseline characteristics
| Characteristic | PBC Group | Total | Control Group |
|---|---|---|---|
| Age, Continuous | 52 years | 52 years | 48 years |
| BMI | 23 kg/m^2 | 23 kg/m^2 | 23 kg/m^2 |
| Heart rate | 71 beats/min | 71 beats/min | 71 beats/min |
| Hemoglobin | 124 g/L | 129 g/L | 133 g/L |
| Left Ventricular Ejection Fraction | 75 % | 72 % | 69 % |
| LGE positive | 20 Participants | 25 Participants | 5 Participants |
| Myocardium Strain GCS | -22.5 % | -21.8 % | -20.8 % |
| Myocardium Strain GLS | -18.4 % | -17.8 % | -17.4 % |
| Native myocardium T1 mapping | 1317 msec | 1299 msec | 1284 msec |
| NYHA classification of heart failure class III-IV | 0 Participants | 0 Participants | 0 Participants |
| Other autoimmune diseases | 5 Participants | 5 Participants | 0 Participants |
| Platelet | 173 platelets *10^9/L | 200 platelets *10^9/L | 225 platelets *10^9/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 56 Participants | 112 Participants | 56 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Serum creatinine | 55.1 μmol/L | 58 μmol/L | 60.5 μmol/L |
| Sex: Female, Male Female | 50 Participants | 96 Participants | 46 Participants |
| Sex: Female, Male Male | 6 Participants | 16 Participants | 10 Participants |
| T2 mapping | 50 msec | 48 msec | 48 msec |
| T2-STIR positive | 12 Participants | 13 Participants | 1 Participants |
| Volume parameters LVEDV | 103 mL | 105 mL | 107 mL |
| Volume parameters LVESV | 27 mL | 28 mL | 31 mL |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 56 | 0 / 56 |
| other Total, other adverse events | 0 / 56 | 0 / 56 |
| serious Total, serious adverse events | 0 / 56 | 0 / 56 |
Outcome results
Primary
Quantitative Assessment in Cardiac Injury
T1 mapping-derived extracellular volumes (ECV) were used to detect changes in the myocardium interstitial matrix. ECV was calculated according to the ECV formula consist of T1 mapping value.
Time frame: within 2 days of CMR scan
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PBC Group | Quantitative Assessment in Cardiac Injury | 30 percentage of interstitial matrix |
| Control Group | Quantitative Assessment in Cardiac Injury | 26 percentage of interstitial matrix |
p-value: <0.01t-test, 2 sided
Primary
The Incidence of Cardiac Events
All PBC patients are followed up through telephone or by retrieving outpatient medical record systems. Cardiac events include: 1. cardiac death; 2. myocardial infarction; 3. hospitalization for unstable angina.
Time frame: 7 months after first CMR scanning
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PBC Group | The Incidence of Cardiac Events | Cardiac death | 0 Participants |
| PBC Group | The Incidence of Cardiac Events | Myocardial infarction | 0 Participants |
| PBC Group | The Incidence of Cardiac Events | Hospitalization for unstable angina | 0 Participants |
| Control Group | The Incidence of Cardiac Events | Cardiac death | 0 Participants |
| Control Group | The Incidence of Cardiac Events | Myocardial infarction | 0 Participants |
| Control Group | The Incidence of Cardiac Events | Hospitalization for unstable angina | 0 Participants |
p-value: 0.001Chi-squared