Association of the V122I Transthyretin Amyloidosis Genetic Variant With Cardiac Structure and Function in Middle-aged Black Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study | Cardiology | JAMA Cardiology | JAMA Network
[Skip to Navigation]
Sign In
Figure.  Coronary Artery Risk Development in Young Adults (CARDIA) Study Sample Population Flow Diagram
Coronary Artery Risk Development in Young Adults (CARDIA) Study Sample Population Flow Diagram

The flow diagram displays the sampling of Black adults for genetic analysis and those who had subsequent echocardiograms at year 25 and year 30.

Table 1.  Clinical Characteristics at Year 25 of Participants With Echocardiograms Stratified by V122I TTR Noncarrier and Carrier Status
Clinical Characteristics at Year 25 of Participants With Echocardiograms Stratified by V122I TTR Noncarrier and Carrier Status
Table 2.  Cardiac Structure and Function Parameters at Years 25 or 30 in Those Carrying vs Not Carrying the V122I TTR Varianta
Cardiac Structure and Function Parameters at Years 25 or 30 in Those Carrying vs Not Carrying the V122I TTR Varianta
1.
Jacobson  DR, Pastore  RD, Yaghoubian  R,  et al.  Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans.   N Engl J Med. 1997;336(7):466-473. doi:10.1056/NEJM199702133360703PubMedGoogle ScholarCrossref
2.
Buxbaum  J, Alexander  A, Koziol  J, Tagoe  C, Fox  E, Kitzman  D.  Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.   Am Heart J. 2010;159(5):864-870. doi:10.1016/j.ahj.2010.02.006PubMedGoogle ScholarCrossref
3.
Quarta  CC, Buxbaum  JN, Shah  AM,  et al.  The amyloidogenic V122I transthyretin variant in elderly black Americans.   N Engl J Med. 2015;372(1):21-29. doi:10.1056/NEJMoa1404852PubMedGoogle ScholarCrossref
4.
Damrauer  SM, Chaudhary  K, Cho  JH,  et al.  Association of the V122I hereditary transthyretin amyloidosis genetic variant with heart failure among individuals of African or Hispanic/Latino ancestry.   JAMA. 2019;322(22):2191-2202. doi:10.1001/jama.2019.17935PubMedGoogle ScholarCrossref
5.
Friedman  GD, Cutter  GR, Donahue  RP,  et al.  CARDIA: study design, recruitment, and some characteristics of the examined subjects.   J Clin Epidemiol. 1988;41(11):1105-1116. doi:10.1016/0895-4356(88)90080-7PubMedGoogle ScholarCrossref
6.
Lettre  G, Palmer  CD, Young  T,  et al.  Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.   PLoS Genet. 2011;7(2):e1001300. doi:10.1371/journal.pgen.1001300PubMedGoogle Scholar
7.
Armstrong  AC, Ricketts  EP, Cox  C,  et al.  Quality control and reproducibility in M-Mode, two-dimensional, and speckle tracking echocardiography acquisition and analysis: the CARDIA study, year 25 examination experience.   Echocardiography. 2015;32(8):1233-1240. doi:10.1111/echo.12832PubMedGoogle ScholarCrossref
8.
Pritchard  JK, Stephens  M, Donnelly  P.  Inference of population structure using multilocus genotype data.   Genetics. 2000;155(2):945-959.PubMedGoogle ScholarCrossref
9.
Plana  JC, Galderisi  M, Barac  A,  et al.  Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.   Eur Heart J Cardiovasc Imaging. 2014;15(10):1063-1093. doi:10.1093/ehjci/jeu192PubMedGoogle ScholarCrossref
10.
Choi  E-Y, Rosen  BD, Fernandes  VRS,  et al.  Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis.   Eur Heart J. 2013;34(30):2354-2361. doi:10.1093/eurheartj/eht133PubMedGoogle ScholarCrossref
11.
Phelan  D, Collier  P, Thavendiranathan  P,  et al.  Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis.   Heart. 2012;98(19):1442-1448. doi:10.1136/heartjnl-2012-302353PubMedGoogle ScholarCrossref
12.
Chirinos  JA, Segers  P, De Buyzere  ML,  et al.  Left ventricular mass: allometric scaling, normative values, effect of obesity, and prognostic performance.   Hypertension. 2010;56(1):91-98. doi:10.1161/HYPERTENSIONAHA.110.150250PubMedGoogle ScholarCrossref
13.
Dinulos  MBP, Vallee  SE.  The impact of direct-to-consumer genetic testing on patient and provider.   Clin Lab Med. 2020;40(1):61-67. doi:10.1016/j.cll.2019.11.003PubMedGoogle ScholarCrossref
14.
Müller  ML, Butler  J, Heidecker  B.  Emerging therapies in transthyretin amyloidosis—a new wave of hope after years of stagnancy?   Eur J Heart Fail. 2020;22(1):39-53. doi:10.1002/ejhf.1695PubMedGoogle ScholarCrossref
15.
Maurer  MS, Schwartz  JH, Gundapaneni  B,  et al; ATTR-ACT Study Investigators.  Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy.   N Engl J Med. 2018;379(11):1007-1016. doi:10.1056/NEJMoa1805689PubMedGoogle ScholarCrossref
Brief Report
December 23, 2020

Association of the V122I Transthyretin Amyloidosis Genetic Variant With Cardiac Structure and Function in Middle-aged Black Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study

Author Affiliations
  • 1Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 2Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 3Associate Editor, JAMA Cardiology
  • 4Deputy Editor, JAMA Cardiology
  • 5Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
  • 6Associate Editor for Translational Science, JAMA Cardiology
  • 7The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston
  • 8Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
JAMA Cardiol. 2021;6(6):718-722. doi:10.1001/jamacardio.2020.6623
Key Points

Question  Is there an association between the common transthyretin (TTR) genetic variant V122I and adverse cardiac mechanics among middle-aged Black adults without symptomatic heart failure?

Findings  In this population-based cohort study of 875 Black adults, there was a significant association of the TTR V122I variant with worse left ventricular structure and cardiac mechanics at a mean age of 54 years.

Meaning  In Black middle-aged adults with the TTR V122I variant, earlier screening with echocardiography may inform use of novel therapies targeting TTR amyloid deposition and intensification of risk factor modification to prevent or postpone heart failure, and this option should be studied.

Abstract

Importance  The variant V122I is commonly enriched in the transthyretin (TTR) gene in individuals of African ancestry and associated with greater risk of heart failure (HF) in older adulthood, after age 65 years. Prevention of HF may be most effective earlier in life, but whether screening with echocardiography can identify subclinical cardiac abnormalities during middle age to risk-stratify individuals appears to be unknown.

Objective  To examine the association between the V122I TTR variant and cardiac structure and function during middle age in those without prevalent HF.

Design, Setting, and Participants  This serial cross-sectional study of 875 Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort was conducted at 4 urban sites across the US. Recruiting was completed in 1985-1986, and follow-up examinations occurred 25 and 30 years later. A subset of Black adults from the CARDIA cohort who underwent TTR genotyping was included. Data analysis was completed from January 2020 to October 2020.

Exposures  The V122I TTR genotype.

Main Outcomes and Measures  Echocardiographic left ventricular (LV) circumferential and longitudinal systolic strain and LV structure, measured at years 25 and 30 of follow-up. The analyses were adjusted for age, sex, echocardiography quality, genetic ancestry, and field center.

Results  Among the 875 Black adults (mean [SD] age, 49.4 [3.8] years at year 25; 543 women [62.1%]), there were 31 individuals who were heterozygous and 1 who was homozygous for the V122I TTR variant. Of the adults who had an echocardiogram at year 25, rates of hypertension (312 [46%]), diabetes (102 [15%]), and current smoking (128 [19%]) were not significantly different between those who did and did not carry V122I TTR. At year 25, there was no difference in LV circumferential strain, longitudinal strain, or LV structure between those who did vs did not carry V122I TTR. At year 30, those who carried V122I TTR had significantly lower absolute LV circumferential strain (mean [SD], 12.4 [4.2] percentage units) compared with those who did not carry the variant (mean [SD], 14.5 [3.7] percentage units). Those who carried V122I TTR also had significantly higher LV mass index values (mean [SD], 97.5 [34.1] g/m2) compared with those who did not (mean [SD], 83.7 [22.6] g/m2) at year 30.

Conclusions and Relevance  Carrier status for the V122I TTR variant is associated with subclinical cardiac abnormalities in middle age (worse LV systolic function and higher LV mass) that have been associated with increased risk of incident HF. Midlife screening of individuals who carry V122I TTR with echocardiography may prognosticate risk of symptomatic HF and inform prevention strategies.

Introduction

Amyloidogenic transthyretin cardiomyopathy (ATTR-CM) occurs because of cumulative deposition of misfolded transthyretin (TTR) amyloid fibrils in the heart.1 The most common pathogenic variant in the TTR gene in the US is a valine-to-isoleucine substitution at position 122 (V122I), which is present in 4% of American individuals of African ancestry.1 Longitudinal population-based and cross-sectional studies in those who carry V122I TTR identify a 2-fold higher risk of developing heart failure (HF) after age 65 years.2-4 However, it is not known how early in life, subclinical abnormalities in cardiac structure and function may be detectable in carriers prior to the onset of HF. Identifying early changes in this high-risk subgroup may be important, given the emergence of targeted TTR therapies with the potential for a precision medicine approach to HF prevention. Therefore, we leveraged the well-phenotyped Coronary Artery Risk Development in Young Adults (CARDIA) study to examine differences between those who did vs did not carry V122I TTR variant at 2 points in midlife.

Methods
Data Source: CARDIA Study

The CARDIA study is an observational cohort of Black and White adults across 4 urban sites in the US.5 Participants between 18 and 30 years were recruited in 1985-1986 and have been followed up at regular intervals for more than 30 years. A total of 1209 self-identified Black participants underwent genotyping, and genetic data from 875 adults was available after quality control and removal of missing identifications (Figure).6 Our study sample included those who underwent echocardiograms at year 25 or year 30 (eTable 1 in the Supplement). The study was approved by the institutional review boards at each site. All participants provided written informed consent.

Genotyping and Imputation

Genotyping was performed using the Affymetrix Genome-Wide Human 6.0 array (Thermo Fisher Scientific). The 1000 Genomes Project Phase 3 Integrated Release version 5 reference panel was used to impute the V122I variant, rs76992529, with high accuracy as measured by an R2 of 0.98 (eMethods in the Supplement).

Echocardiography

Echocardiograms were performed at year 25 and year 30, according to American Society of Echocardiography guidelines.7 Primary echocardiographic parameters of interest included mid-LV circumferential strain (CS) and longitudinal strain (LS). Secondary echocardiographic parameters of interest included LV ejection fraction (LVEF), mean early diastolic mitral annulus tissue velocity (e'), indexed LV end diastolic volume (LVEDVi), left atrial volume (LAVi), and LV mass (LVMi) (eMethods in the Supplement).

Statistical Analysis

Clinical characteristics at year 25 were compared between those who did vs did not carry the V122I TTR variant using univariate linear models for continuous and χ2 tests for categorical variables. Multivariate general linear models were used to determine the associations between V122I TTR carrier status and echocardiographic parameters at year 25 and year 30. The models were adjusted for age, sex, the first 3 principal components of genetic ancestry, echocardiography quality score, and field center. Principal component analysis was performed using EIGENSTRAT.8 Interaction between TTR genotype and genetic ancestry were assessed (eMethods in the Supplement). Multiple sensitivity analyses were performed including restricting the sample to those with echocardiograms at both year 25 and year 30 and excluding individuals with an LVEF less than 50% or individuals with HF prior to the echocardiogram. Primary analyses were also adjusted for body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and hypertension, individually. The significance threshold was set at P < .05. Data analyses were completed from January 2020 to October 2020.

Results

Of the 875 middle-aged Black adults included (mean [SD] age, 49.4 [3.8] years at year 25; 62% women), 31 were heterozygous and 1 was homozygous for the V122I TTR variant (minor allele frequency, 0.019). At year 25, 672 of 875 (76.8%) underwent echocardiography (eTable 2 in the Supplement). At year 25, there were no significant differences in clinical characteristics between those who did vs did not carry V122I TTR (Table 1); rates of hypertension (312 [46%]), diabetes (102 [15%]), and current smoking (128 [19%]) were not significantly different between the 2 groups. Furthermore, the systolic and diastolic blood pressures at the time of the echocardiogram were not different between those who did vs did not carry V122I TTR at year 25 or year 30 (eTable 3 in the Supplement).

At year 25, parameters of LV structure and function were similar between those who did vs did not carry V122I TTR, but those with the variant had worse LV diastolic function as measured by mean (SD) e' (those without the variant, 10.2 [2.4] cm/s; those with the variant, 9.2 [2.1] cm/s; P = .04; Table 2). Five years later (year 30), at a mean (SD) age of 54.3 (3.8) years, those with the variant had worse mean (SD) LV systolic function (lower absolute mid-LV CS; 12.3% [4.2%] vs 14.5% [3.7%]; P = .04) and less favorable indices of LV structure (higher mean [SD] LVMi; 97.5 [34.1] g/m2 vs 83.7 [22.6] g/m2; P = .02) than those without the V122I TTR variant (Table 2). At year 30, LVEDVi was higher in those with V122I TTR compared with those without it, but this did not meet the significance threshold. Although mean e' at year 30 was lower in those carrying the V122I TTR variant compared with those not carrying the variant, the difference was no longer significant. There was an interaction between African ancestry and V122I TTR variant with LVMi (eFigure and eTable 4 in the Supplement). Among adults carrying the V122I TTR variant, those with greater African ancestry had a higher LVMi than those with less African ancestry (116.4 [40.6] g/m2 vs 80.1 [11.5] g/m2), while those without the variant had similar LVMi regardless of African ancestry (83.7 [22.0] g/m2 vs 83.8 [23.3] g/m2).

Results remained unchanged when the participant who was homozygous for the V122I TTR variant was removed. Sensitivity analyses, including restricting the sample to those with echocardiographic data at both year 25 and year 30 (eTable 5 in the Supplement), excluding individuals with LVEFs less than 50% (eTable 6 in the Supplement) or individuals with HF (eTable 7 in the Supplement), and adjusting for BMI (eTable 8 in the Supplement) or hypertension (eTable 9 in the Supplement) demonstrated similar findings. Because of the relatively young age of the cohort, there were only 25 HF cases in the noncarrier group and 1 HF case in the V122I TTR carrier group within the entire cohort, including those without echocardiograms.

Discussion

We observed abnormal subclinical cardiac structure and function among individuals carrying the V122I TTR variant in midlife compared with those not carrying the variant. By leveraging a cohort of younger Black adults with state-of-the-art echocardiograms, including strain assessment, our study adds to existing literature and challenges the prevailing dogma that those with the variant do not have detectable cardiac changes prior to age 65 years.2 While our findings may represent earlier detection of myocardial damage attributable to deposition of misfolded TTR protein, we were not able to explore the role of potential interaction between the V122I genotype and cardiovascular risk factors in our analyses.

Our findings of approximately 2% lower mid-LV CS and 14-g/m2 higher LVMi in those with the variant compared with those without the variant at year 30 are clinically significant and consistent with expected LV abnormalities in the early stages of TTR amyloid fibril deposition. The 2.1–percentage unit between-group difference in mid-LV CS at year 30 is consistent with progressive LV dysfunction,9 with each 1–percentage-unit lowering in LV CS known to be associated with a 15% higher risk of incident HF.10 The lack of difference in LV LS may be attributable to apical preservation of LV LS in ATTR-CM. While mid-LV CS was measured using the mid-LV short-axis regions, LV LS was measured using the apical 4-chamber view, which includes the LV apex.11 The mean LVMi of those with the variant was greater than the 95th percentile for both men and women, based on population-based normative values.12 While LVEDVi was higher in those with the variant at year 30, it did not meet the significance threshold, and the mean values in both groups were well within the normal range. The higher LVEDVi in those with the variant is contrary to what may be expected; the finding may be associated with an interaction between the TTR variant and clinical risk factors and needs to be further assessed in future studies. The mean e' velocity was lower in those with the variant at both points but not significant at year 30, likely because of limited power with a decrease in sample size at follow-up. In addition, the significance of the association between carrier status and e' velocity was attenuated at year 25 after adjusting for BMI.

Our results may inform screening strategies for asymptomatic individuals who carry the V122I TTR variant, using echocardiography with speckle tracking starting as early as the fifth or sixth decade of life. Since the V122I TTR risk variant is tested in both direct-to-consumer and clinical cardiomyopathy genetic panels, is present at birth, and affects 1.5 million individuals, these data can inform investigations of potential management strategies in individuals who are asymptomatic.13 Further studies are needed to determine whether aggressive risk-factor modification or early treatment with Food and Drug Administration–approved investigative TTR therapies could help prevent or delay incident HF in those carrying V122I TTR.14 Strengths of this study include use of a population-based cohort of Black adults ranging in age from 43 and 60 years with repeated measurements of echocardiography.

Limitations

Limitations of the study include a small sample size, missing data because of loss to follow-up, use of only 4-chamber views for volume assessment, and imputation of the V122I variant. Applicability of our results may be limited because measurement of LVMi and mid-LV CS are not routinely clinically measured. However, mid-LV CS is a sensitive marker that is impaired in TTR amyloid cardiomyopathy and has improved with tafamidis therapy in the Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) study. Mid-LV CS should be considered in those undergoing evaluation for TTR cardiac amyloidosis and can be measured offline with relative ease using standard short-axis images.15 These results are hypothesis generating and require replication in a larger cohort to inform clinically actionable threshold values.

Conclusions

In summary, V122I TTR carrier status is associated with subclinical cardiac abnormalities consistent with ATTR-CM at an earlier point in life than previously reported (at a mean age of 54 years). Midlife screening of those with the variant may identify risk of symptomatic HF and inform prevention strategies.

Back to top
Article Information

Accepted for Publication: November 2, 2020.

Published Online: December 23, 2020. doi:10.1001/jamacardio.2020.6623

Corresponding Author: Sadiya S. Khan, MD, MS, Division of Cardiology, Department of Medicine and Preventive Medicine, Northwestern University Feinberg School of Medicine, 680 N Lake Shore Dr, 14-002, Chicago, IL 60611 (s-khan-1@northwestern.edu).

Author Contributions: Drs Sinha and Khan had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sinha, Hou, Shah, Yancy, Lloyd-Jones, Rasmussen-Torvik, Khan.

Acquisition, analysis, or interpretation of data: Sinha, Zheng, Nannini, Qu, Hou, Shah, McNally, Fornage, Lima, Lloyd-Jones, Khan.

Drafting of the manuscript: Sinha, Hou, Lima.

Critical revision of the manuscript for important intellectual content: Sinha, Zheng, Nannini, Qu, Shah, Yancy, McNally, Fornage, Lima, Lloyd-Jones, Rasmussen-Torvik, Khan.

Statistical analysis: Sinha, Zheng, Nannini, Qu, Hou, Rasmussen-Torvik.

Obtained funding: Lima, Lloyd-Jones.

Administrative, technical, or material support: McNally, Lima.

Supervision: Sinha, Shah, Yancy, Lloyd-Jones, Khan.

Conflict of Interest Disclosures: Dr Shah has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer and received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Aria, Axon Therapeutics, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Cardiora, CVRx, Cyclerion, Cytokinetics, Eisai, GSK, Imara, Ionis, Ironwood, Keyto, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Shifamed, Tenax, and United Therapeutics, of which personal fees from Pfizer and Ionis and research grants from Pfizer were provided during the conduct of the study. Dr Yancy reported spousal employment at Abbott Inc. Dr McNally reported grants from National Institutes of Health and Northwestern University during the conduct of the study; personal fees from AstraZeneca, Avidity, Amgen, Cytokinetics, Invitae, Exonics/Vertex, Tenaya Therapeutics, Janssen, and Pfizer; grants from Solid Biosciences Grant and the Department of Defense to Northwestern outside the submitted work; and being a founder of Ikaika Therapeutics outside of the submitted work. Dr Lloyd-Jones reported grants from the National Institute of Health during the conduct of the study. Dr Khan reported grant KL2TR001424 from the National Center for Advancing Translational Sciences and grant 19TPA34890060 from the American Heart Association during the conduct of the study. No other disclosures were reported.

Funding/Support: Dr Sinha is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (grant T32HL069771). This research was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (grant KL2TR001424 [Dr Khan]) and the American Heart Association (grant AHA#19TPA34890060 [Dr Khan]). Research reported in this article was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences (grant KL2TR001424 [Dr Khan]). The Coronary Artery Risk Development in Young Adults Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (grants HHSN268201800005I and HHSN268201800007I), Northwestern University (grant HHSN268201800003I), University of Minnesota (grant HHSN268201800006I), and Kaiser Foundation Research Institute (grant HHSN268201800004I).

Role of the Funder/Sponsor: The manuscript has been reviewed by CARDIA for scientific content. The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. In addition, Drs Yancy, Shah, and McNally are editors of JAMA Cardiology, but they were not involved in any of the decisions regarding review of the manuscript or its acceptance.

References
1.
Jacobson  DR, Pastore  RD, Yaghoubian  R,  et al.  Variant-sequence transthyretin (isoleucine 122) in late-onset cardiac amyloidosis in black Americans.   N Engl J Med. 1997;336(7):466-473. doi:10.1056/NEJM199702133360703PubMedGoogle ScholarCrossref
2.
Buxbaum  J, Alexander  A, Koziol  J, Tagoe  C, Fox  E, Kitzman  D.  Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies.   Am Heart J. 2010;159(5):864-870. doi:10.1016/j.ahj.2010.02.006PubMedGoogle ScholarCrossref
3.
Quarta  CC, Buxbaum  JN, Shah  AM,  et al.  The amyloidogenic V122I transthyretin variant in elderly black Americans.   N Engl J Med. 2015;372(1):21-29. doi:10.1056/NEJMoa1404852PubMedGoogle ScholarCrossref
4.
Damrauer  SM, Chaudhary  K, Cho  JH,  et al.  Association of the V122I hereditary transthyretin amyloidosis genetic variant with heart failure among individuals of African or Hispanic/Latino ancestry.   JAMA. 2019;322(22):2191-2202. doi:10.1001/jama.2019.17935PubMedGoogle ScholarCrossref
5.
Friedman  GD, Cutter  GR, Donahue  RP,  et al.  CARDIA: study design, recruitment, and some characteristics of the examined subjects.   J Clin Epidemiol. 1988;41(11):1105-1116. doi:10.1016/0895-4356(88)90080-7PubMedGoogle ScholarCrossref
6.
Lettre  G, Palmer  CD, Young  T,  et al.  Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.   PLoS Genet. 2011;7(2):e1001300. doi:10.1371/journal.pgen.1001300PubMedGoogle Scholar
7.
Armstrong  AC, Ricketts  EP, Cox  C,  et al.  Quality control and reproducibility in M-Mode, two-dimensional, and speckle tracking echocardiography acquisition and analysis: the CARDIA study, year 25 examination experience.   Echocardiography. 2015;32(8):1233-1240. doi:10.1111/echo.12832PubMedGoogle ScholarCrossref
8.
Pritchard  JK, Stephens  M, Donnelly  P.  Inference of population structure using multilocus genotype data.   Genetics. 2000;155(2):945-959.PubMedGoogle ScholarCrossref
9.
Plana  JC, Galderisi  M, Barac  A,  et al.  Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.   Eur Heart J Cardiovasc Imaging. 2014;15(10):1063-1093. doi:10.1093/ehjci/jeu192PubMedGoogle ScholarCrossref
10.
Choi  E-Y, Rosen  BD, Fernandes  VRS,  et al.  Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis.   Eur Heart J. 2013;34(30):2354-2361. doi:10.1093/eurheartj/eht133PubMedGoogle ScholarCrossref
11.
Phelan  D, Collier  P, Thavendiranathan  P,  et al.  Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis.   Heart. 2012;98(19):1442-1448. doi:10.1136/heartjnl-2012-302353PubMedGoogle ScholarCrossref
12.
Chirinos  JA, Segers  P, De Buyzere  ML,  et al.  Left ventricular mass: allometric scaling, normative values, effect of obesity, and prognostic performance.   Hypertension. 2010;56(1):91-98. doi:10.1161/HYPERTENSIONAHA.110.150250PubMedGoogle ScholarCrossref
13.
Dinulos  MBP, Vallee  SE.  The impact of direct-to-consumer genetic testing on patient and provider.   Clin Lab Med. 2020;40(1):61-67. doi:10.1016/j.cll.2019.11.003PubMedGoogle ScholarCrossref
14.
Müller  ML, Butler  J, Heidecker  B.  Emerging therapies in transthyretin amyloidosis—a new wave of hope after years of stagnancy?   Eur J Heart Fail. 2020;22(1):39-53. doi:10.1002/ejhf.1695PubMedGoogle ScholarCrossref
15.
Maurer  MS, Schwartz  JH, Gundapaneni  B,  et al; ATTR-ACT Study Investigators.  Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy.   N Engl J Med. 2018;379(11):1007-1016. doi:10.1056/NEJMoa1805689PubMedGoogle ScholarCrossref
×