Screening for Cardiac Amyloidosis With Nuclear Cardiology for Minority Populations
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 646
- 试验地点
- 4
- 主要终点
- Prevalence of Transthyretin Cardiac Amyloidosis (ATTR-CA) in Cohort of Caribbean Hispanics and Blacks With Heart Failure (HF)
研究概览
简要总结
In this study, the investigators recruited a cohort of elderly Black and Hispanic patients with heart failure to define the number of patients who have cardiac amyloidosis by utilizing highly sensitive heart imaging and blood tests. The investigators also explored differences in genetics and sex as they relate to heart failure disease progression in cardiac amyloidosis.
详细描述
Heart failure with preserved ejection fraction (HFpEF) disproportionately afflicts older Black and Hispanic Americans. Transthyretin cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin (TTR or prealbumin) protein and is classified by the genetics of TTR into wild-type (ATTRwt) or hereditary (hATTR or ATTRv). ATTR CA, irrespective of genotype, is an age-dependent, often unrecognized, mechanism underlying HFpEF. While hATTR CA results from point mutations that promote TTR misfolding and amyloid aggregation, factors that contribute to ATTRwt CA are not well defined. While previously thought to be untreatable, promising therapies that have been recently reported are most effective if administered early in disease course. Only a small proportion of individuals with wild-type TTR will develop ATTRwt CA, overwhelmingly reported in Caucasian males beyond age 60 years. However, as an autosomal protein, allele distribution is not sex specific. For hATTR, a substitution of isoleucine for valine (Val142Ile) is the most frequent TTR mutation in the US, observed almost exclusively in Black Americans with an allele frequency of 3.4%. But there are no data regarding the prevalence of ATTRwt CA in African Americans and no data for ATTR CA prevalence, irrespective of genotype, in the Hispanic population. One of the reasons for the knowledge deficit is the challenge of diagnosis. Endomyocardial biopsy, while nearly 100% sensitive and specific, is impractical as a screening test and genotyping alone of patients is insufficient to identify ATTR CA because wild-type patients develop disease. In this study, the investigators used a highly accurate technique for ATTR CA identification using Tc99m-pyrophosphate (PYP) imaging that avoids the need for biopsy. (Tc99m-HDP may have been used in cases of interrupted supply of PYP) Tc99m-PYP myocardial uptake can occur before echocardiographic or clinical changes, suggesting enhanced sensitivity. While studies using the technique have suggested that 10-15% of elderly hospitalized patients with heart failure may have ATTR CA, Tc99m-PYP had not been applied broadly in heart failure patients as a means to facilitate early diagnosis. The overall hypothesis is that a significant proportion of heart failure in elderly Blacks and Hispanics is caused ATTR CA. Using these non-invasive tests, the investigators will establish the prevalence of ATTR CA.
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
- •Black or Hispanic of Caribbean origin.
- •Age ≥ 60 years.
- •Diagnosis of heart failure, confirmed by one of two methods:
- •Modified criteria utilized by Rich et al. which include a history of acute pulmonary edema or the occurrence of at least two of the following that improved with diuretic therapy without another identifiable cause: dyspnea on exertion, paroxysmal nocturnal dyspnea, orthopnea, bilateral lower extremity edema or exertional fatigue, and
- •National Health and Nutrition Examination Survey (NHANES) congestive heart failure (CHF) criteria with a score ≥
- •Left ventricular septal OR inferolateral wall thickness ≥12 mm by echocardiography.
- •Left ventricular Ejection fraction >30% by echocardiography.
- •Able to understand and sign the informed consent document after the nature of the study has been fully explained.
排除标准
- •Primary amyloidosis (AL) or secondary amyloidosis (AA).
- •Prior liver or heart transplantation.
- •Active malignancy or non-amyloid disease with expected survival of less than 1 year.
- •Heart failure, in the opinion of the investigator, primarily caused by severe left-sided valve disease. Note: if valve was repaired, subject may be considered as no longer with severe valve disease.Heart failure, in the opinion of the investigator, primarily caused by either valve disease or ischemic heart disease.
- •Heart failure, in the opinion of the investigator, primarily caused by ischemic heart disease.
- •Ventricular assist device or anticipated within the next 6 months.
- •Impairment from stroke, injury or other medical disorder that precludes participation in the study.
- •Disabling dementia or other mental or behavioral disease.
- •Enrollment in a clinical trial not approved for co-enrollment.
- •Expected use of continuous intravenous inotropic therapy in the next 6 months.
- •High risk for non-adherence as determined by screening evaluation.
- •Inability or unwillingness to comply with the study requirements.
- •Chronic kidney disease with eGFR <15 mL/min/1.73 m2 or ESRD.
- •Weight >350 lb.
- •Nursing home resident.
- •Other reason that would make the subject inappropriate for entry into this study.
研究组 & 干预措施
Blacks/Hispanics with Heart Failure
Blacks/Hispanics with heart failure due to transthyretin cardiac amyloidosis were identified by 99mTc-PYP (or 99mTc-HDP) scintigraphy. Those with transthyretin cardiac amyloidosis were further subtyped into those with a genetic cause (ATTRv) and those with a non-genetic cause (ATTRwt - wild type transthyretin cardiac amyloidosis).
干预措施: 99mTc-PYP or 99m Tc-HDP (Drug)
结局指标
主要结局
Prevalence of Transthyretin Cardiac Amyloidosis (ATTR-CA) in Cohort of Caribbean Hispanics and Blacks With Heart Failure (HF)
时间窗: Study Participation of One Year
The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive. Determination of ATTR-CA was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.
Age Distribution of ATTR Cardiac Amyloidosis
时间窗: Study Participation of One Year
The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among participants ≤75 years or \>75 years enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.
Sex Distribution of ATTR Cardiac Amyloidosis
时间窗: Study Participation of One Year
The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among male and female participants enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.
Self-Identified Hispanic Ethnicity Distribution of ATTR Cardiac Amyloidosis.
时间窗: Study Participation of One Year
The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among those self-identified as Hispanic, enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.
ATTR Type Distribution of Cardiac Amyloidosis
时间窗: Study Participation of One Year
The prevalence of ATTR cardiac amyloidosis was calculated from among the number of subjects within the cohort determined to be ATTR-CA positive among those variant (v142i) and non-variant (wild-type) participants enrolled in this study. Determination of ATTR was defined as significant myocardial retention of Tc-99 PYP. The prevalence is expressed as a percentage of total enrollment. ATTR-CA prevalence is reported for two different groups: Self-identified as Black, subjects with Heart Failure and Self-identified as non-Black, subjects with Heart Failure.
次要结局
未报告次要终点
研究者
Mathew S. Maurer, MD
Arnold and Arlene Goldstein Professor of Cardiology
Columbia University