Cardiac Amyloidosis in Heart Failure Patients With Preserved Ejection Fraction
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- Prevalence of ATTRwt among patients with HFpEF in Taiwan
研究概览
简要总结
Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure cases with heterogenous cause and variable presentations. The diagnosis of HFpEF required clinical signs and symptoms of HF, normal left ventricular ejection fraction (LVEF) and evidence of diastolic dysfunction. No treatment has been shown in recent major clinical trials having benefits in these patients. One major reason of the poor response to medical treatment is the heterogeneity of HFpEF, which contains many different underline causes. To identify the underlying causes of HFpEF may improve the diagnosis and treatment in these patients.
Age-related amyloid deposition has first been reported in 1876 and the following autopsy studies showed the prevalence of senile cardiac amyloid is up to 25%. Recently, it has been recognized that the deposits in senile cardiac amyloid are derived from wild-type transthyretin (TTR). Transthyretin amyloidosis cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin protein. There are 2 types of ATTR classified by genetic mutation including wild-type ATTR (ATTRwt) and familial cardiac amyloid caused by TTR mutation (ATTRm).
Multimodality techniques have been developed to assist in the diagnosis of the diagnosis of TTR. Among them, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy is a non-invasive test and it can diagnose TTR from other cause diverse form of cardiac amyloidosis and cardiomyopathy. In the study of Gonzalez-Lopez et al, in 120 HFpEF patients, 16 (13.3%) had positive 99mTc-DPD scan. Four patients with positive 99mTc-DPD scan received endomyocardial biopsy and confirmed cardiac amyloid deposition.
ATTRwt could be an important cause of HFpEF and it was often under diagnosed. A recent study in Spain reported that 13% of patents over age of 60 years with HFpEF and left ventricular wall thickness of 12mm or more had ATTRwt. However, the prevalence of ATTRwt among patients with HFpEF is not well-established in Taiwan and Asia. The aim of this study is to determine the prevalence, clinical characteristics, risk factors and outcomes of ATTRwt related HFpEF patients in Taiwan.
详细描述
Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical situation with multiple underlying causes. The diagnosis of HFpEF is challenging which requires clinical signs/symptoms of HF, a normal or mildly impaired systolic function measured by left ventricular ejection fraction (LVEF), and evidence of diastolic dysfunction. There are no significant improvements in treatment of HFpEF in recent years and the results in the major clinical trials for HFpEF were disappointed. One major reason is the heterogeneity of HFpEF, which contains several diseases under the same entity.
Small deposits of amyloid are found in the elder hearts in up to 25% of the autopsies. These deposits are mainly composed by wild-type transthyretin (TTR). Transthyretin amyloidosis cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin protein. It is classified into 2 groups by the genetics of Transthyretin amyloidosis (ATTR): wild-type (ATTRwt) or hereditary (hATTR or ATTRm). ATTR CA, irrespective of genotype, is an unrecognized mechanism underlying HFpEF. It was reported wild-type TTR might be an underdiagnosed cause of HFpEF. However, the prevalence of wild-type ATTR among patients with HFpEF is not well-established in Taiwan and Asia.
One of the most convenient method to detect and diagnosis cardiac amyloidosis is 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy6. In the study of Gonzalez-Lopez et al, in 120 HFpEF patients, 16 (13.3%) had positive 99mTc-DPD scan6. Four patients with positive 99mTc-DPD scan received endomyocardial biopsy and confirmed cardiac amyloid deposition6. In addition, technetium-99m TC pyrophosphate (PYP) scintigraphy is also very useful in diagnosis of cardiac amyloidosis.
The propose of this study is to determine the prevalence of ATTRwt among elderly HFpEF patients in Taiwan. In this study, the investigators will recruit a cohort of HFpEF patients in Taiwan to define the number of patients who have cardiac amyloidosis by utilizing highly sensitive heart imaging and blood tests. The investigators will also explore differences in different risk factors as they relate to heart failure disease progression in cardiac amyloidosis. According our previous studies, the average age of HFpEF in Taiwan is 65 y/o. In this study, the investigators set age limitation as 60 y/o. However, because 5% ATTRwt were < 60 y/o9, therefore, the investigators also recruit patients >50y/o with risk factors of ATTRwt.
Hypothesis HFpEF is a heterogeneous clinical situation with multiple underlying causes. ATTRwt is an underdiagnosed cause of HFpEF but the prevalence is unknown in Taiwan. ATTRwt can be diagnosed non-invasively by 99mTc-PYP scintigraphy7. The investigators aimed to investigate the prevalence and clinical characteristics of ATTRwt among patients with HFpEF.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 60 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is ≥ 60 years old or 50 y/o with carpal tunnel syndrome or spinal stenosis
- •Patient has been diagnosed as HFpEF in their medical history or newly diagnosed as HFpEF. They have HF symptoms with NYHA Classification of I-IV when diagnosis. The criteria of HFpEF is according to our previous studies.
- •More than 50% of them have LVPW ≥12mm (when diagnosis).
- •Written informed consent could be obtained.
排除标准
- •Patients unwilling to join this projects.
- •Patients with unstable coronary artery disease, plan to receive coronary intervention within months.
- •Patients has previous history of HFrEF with a LVEF <40%.
结局指标
主要结局
Prevalence of ATTRwt among patients with HFpEF in Taiwan
时间窗: At enrollment
次要结局
未报告次要终点