Phenotyping and Characterization of Danish Wild-type Transthyretin Amyloidosis Cardiomyopathy Patients: A Cross-sectional Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Investigation of the relations between cardiac amyloid severity and patient quality of life in patients with Wild-type Transthyretin Amyloidosis Cardiomyopathy.
研究概览
简要总结
Descriptive cross-sectional study on 100 consecutive ATTRwt-CM patients reflecting all NAC stages aiming primarily to investigate ATTRwt-CM patient's quality of life (QoL) measures and their relation to ATTRwt-CM severity. Secondarily aiming to investigate the possibility to measure misTTR and fragTTR in plasma and urine and to detect fragTTR in endomyocardial biopsies from ATTRwt-CM patients. To investigate whether misTTR and fragTTR levels are correlated with ATTRwt-CM severity.
详细描述
Hypothesis:
- We hypothesize that more severe wild-type amyloidosis cardiomyopathy (ATTRwt-CM) according to clinical, biochemical, and diagnostic imaging parameters are correlated with worse quality of life (QoL) for patients.
- We expect misfolded (misTTR) and/or fragmented transthyretin (fragTTR) to be measurable in plasma and/or urine and fragTTR to be detectable in endomyocardial biopsies from patients with ATTRwt-CM. We expect the values of misTTR and fragTTR to be correlated with the severity of ATTRwt-CM according to clinical, biochemical, and diagnostic imaging parameters. We expect the level of fragTTR from endomyocardial biopsies to be correlated with plasma levels of fragTTR.
Method:
ATTRwt-CM patients: Prospective inclusion of 100 consecutive ATTRwt-CM patients reflecting all NAC stages (40 patients from NAC disease stage 1, 40 patients from NAC disease stage II and 20 patients from NAC disease stage III). Patients will be recruited from the out-patient amyloidosis clinic at Aarhus University hospital. Patients will be thoroughly clinically assessed.
Control patients:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients > 18 years diagnosed with ATTRwt-CM by:
- •endomyocardial biopsy
- •DPD scintigraphy with Perugini grade 2-3 where variant amyloidosis is ruled out due to genetic testing.
- •Informed oral and written consent
排除标准
- •AL amyloidosis (light-chain amyloidosis).
- •Myelomatosis
- •Waldenström macroglobulinemia
- •Group 2: Control group
- •Inclusion Criteria:
- •Patients > 18 years
- •Informed oral and written consent
- •Exclusion Criteria:
- •Known cardiovascular disease including ischemic heart disease, heart failure, atrial fibrillation, presence of a pacemaker, or malignant hypertension. Well-controlled hypertension is acceptable.
- •Suspicion of cardiac amyloidosis assessed through clinical history, physical examination, ECG, and echocardiography focusing on "red flags":
- •Echocardiography with:
- •Myocardial hypertrophy (septum >11 mm)
- •Apical sparing in LV-GLS
- •Infiltrative changes in the right ventricle free wall, thickened atrioventricular valves, or thickened atrial septum
- •Symptoms of polyneuropathy
- •Low voltage on ECG or discrepancy between left ventricular thickness and ECG amplitude indicative of low voltage
- •Atrioventricular block (AV block)
- •Bilateral carpal tunnel syndrome
- •Surgery for spinal stenosis
- •Elevated troponin I or NT-pro-BNP
结局指标
主要结局
Investigation of the relations between cardiac amyloid severity and patient quality of life in patients with Wild-type Transthyretin Amyloidosis Cardiomyopathy.
时间窗: Through study completion, 2 years.
Quality of life will be addressed using KCCQ summary score, EQ-5D Utility score and VAS ranging score and ATTR-QOL total score.
Investigation of cardiac amyloidosis severity in patients with Wild-type Transthyretin Amyloidosis Cardiomyopathy.
时间窗: Through study completion, 2 years.
Amyloid severity will be addressed using primarily NAC-stages and NYHA-class. Furthermore, we will use NT-pro-BNP, findings on echo (stroke volume, ejectionfraction and global longitudional strain) and finding on CMRI (LV mass, T1 myocardial values and extracellular volume).
Assessment of transthyretin and pathogenic fragments and relation to cardiac amyloid severity in patients with Wild-type Transthyretin Amyloidosis Cardiomyopathy
时间窗: Through study completion, 2 years.
Transthyretin (TTR) will be measured as follows: total TTR, misfolded TTR and fragmented TTR in plasma and misfolded TTR and fragmented TTR in urine.
次要结局
- Validation of a new amyloid specific questionnaire (ATTR-QoL) in comparison with Kansas City Cardiomyopathy Questionnaire (KCCQ)(Through study completion, 2 years.)
研究者
Steen Hvitfeldt Poulsen
Professor, DMSc.
Aarhus University Hospital Skejby