screening for cardiac amyloidosis with nuclear imaging for minority populations

Conditions: Amyloid Cardiomyopathy, Transthyretin-Related

Summary: in this study, the investigators will recruit 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 will also explore differences in genetics and sex as they relate to heart failure disease progression in cardiac amyloidosis.

heart failure with preserved ejection fraction (hfpef) disproportionately afflicts older black and hispanic americans. attr cardiac amyloidosis (attr ca) is caused by myocardial deposition of misfolded transthyretin protein (ttr or prealbumin) and is classified by the genetics of ttr into wild-type (attrwt) or hereditary (hattr or attrm). 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 (val122ile) is the most frequent ttr mutation in the us, observed 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 will use a highly accurate technique for attr ca identification using tc99m-pyrophosphate (pyp) imaging that avoids the need for biopsy. (tc99m-hdp may be 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 hf may have attr ca, tc99m-pyp has not been applied broadly in hf patients as a means to facilitate early diagnosis. in addition, the investigators will test the diagnostic accuracy of a point-of-care diagnostic tool that utilizes a novel biomarker, retinol binding protein 4 (rbp4), and an assay to measure ttr stability. the overall hypothesis is that a significant proportion of hf in elderly blacks and hispanics is caused attr ca. using these non-invasive tests, the investigators will establish the prevalence of attr ca and explore the relationship between rbp4 concentration and ttr stability in a prospective cohort study of elderly black and hispanic americans with hf.

Eligibility criteria:
inclusion criteria: 1. black or hispanic of caribbean origin. 2. age ≥ 60 years. 3. diagnosis of heart failure, confirmed by one of two methods: 1. 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 2. national health and nutrition examination survey (nhanes) congestive heart failure (chf) criteria with a score ≥3. 4. left ventricular septal or inferolateral wall thickness ≥12 mm by echocardiography. 5. left ventricular ejection fraction \>30% by echocardiography. 6. able to understand and sign the informed consent document after the nature of the study has been fully explained. exclusion criteria: 1. primary amyloidosis (al) or secondary amyloidosis (aa). 2. prior liver or heart transplantation. 3. active malignancy or non-amyloid disease with expected survival of less than 1 year. 4. 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. 5. heart failure, in the opinion of the investigator, primarily caused by ischemic heart disease. 6. ventricular assist device or anticipated within the next 6 months. 7. impairment from stroke, injury or other medical disorder that precludes participation in the study. 8. disabling dementia or other mental or behavioral disease. 9. enrollment in a clinical trial not approved for co-enrollment. 10. expected use of continuous intravenous inotropic therapy in the next 6 months. 11. high risk for non-adherence as determined by screening evaluation. 12. inability or unwillingness to comply with the study requirements. 13. chronic kidney disease with egfr \<15 ml/min/1.73 m2 or esrd. 14. weight \>350 lb. 15. nursing home resident. 16. other reason that would make the subject inappropriate for entry into this study.

Keywords: heart failure cardiac amyloidosis ttr mutation blacks hispanics aging