Determining Potential Mechanisms of Worse Outcomes in Black HCM Patients
确定黑人 HCM 患者出现更糟糕结果的潜在机制
基本信息
- 批准号:10717764
- 负责人:
- 金额:$ 77.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-08-10 至 2028-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdultAgeArrhythmiaBiological AssayBiological MarkersBiological ModelsBlack PopulationsBlack raceCardiacCardiac MyocytesCessation of lifeClinicalClinical DataDataDevelopmentDiagnosisDiseaseDisparityDisparity in diagnosisEchocardiographyElectrocardiogramElectrophysiology (science)ExhibitsFibrosisFunctional disorderGeneticGenotypeGoalsHealth StatusHeartHeart DiseasesHeart failureHeritabilityHospitalizationHumanHypertensionHypertrophic CardiomyopathyHypertrophyImplantable DefibrillatorsIn VitroIndividualInterventionLeft Ventricular Ejection FractionLeft Ventricular HypertrophyMechanicsMedical GeneticsModelingMolecularMutationMyocardiumOutcomePathogenicityPathway interactionsPatient CarePatient-Focused OutcomesPatientsPhenotypePhysiciansPhysiologyPlasmaPopulationPredispositionProteomicsQuality of lifeResearch PersonnelResistanceRestRiskRisk FactorsSarcomeresTissue EngineeringVariantadverse outcomeblack patientcardiac tissue engineeringcardiogenesiscohortcourse developmentgenetic testinggenetic variantgenome editingimprovedin vitro Modelinduced pluripotent stem cellinduced pluripotent stem cell derived cardiomyocytesinduced pluripotent stem cell technologyinsightminiaturizemortalitymouse modelnovelpeerpressureracial disparityresearch clinical testingrisk stratificationsudden cardiac deathtoolvariant of interestvariant of unknown significanceyoung adult
项目摘要
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiac disease. Individuals with HCM have
adverse clinical outcomes, including heart failure, arrhythmias, and sudden cardiac death (SCD) It is estimated
.
that, in the U.S., 6 out of 7 individuals with HCM are unaware of their diagnosis. There are recognized racial
disparities in the diagnosis of HCM. While Black individuals have been observed to have more clinical and ECG
signs that should promote consideration of the diagnosis of HCM, HCM is underdiagnosed in Black patients.
Furthermore, even once diagnosed, there are well-recognized disparities between Black and White patients with
HCM; Black patients have lower rates of referral to HCM Centers, referral for genetic testing, referral for SCD
risk stratification, and referral for interventions such as septal reduction therapy and implantable cardioverter-
defibrillator (ICD) placement. The lower rates of referral are in direct opposition to the data that shows that,
compared to Whites, Black individuals with HCM have approximately 2-fold the risk of SCD and development of
class III or IV (moderate or severe) heart failure. There are several potential contributors to these racial
disparities. HCM is typically diagnosed using routine echocardiography and clinical genetic testing is used to
help diagnose ambiguous cases. Black individuals with HCM are more likely to have ambiguous presentations
and clinical testing is less useful as, compared to Whites, Black patients with HCM are ~40% less likely to have
a pathogenic or likely pathogenic (P/LP) sarcomeric variant identified and more than 40% more likely to have
variants of uncertain significance (VUS). Furthermore, hypertension (HTN) is more prevalent in Black individuals
and physicians may attribute the patient’s left ventricular hypertrophy to HTN and not consider HCM.
In addition,
recent evidence suggests that HTN may be an environmental modifier /”trigger” of worse disease in patients with
HCM. Dr. Huebsch, Co-investigator on this proposal, created an in vitro micro-heart (μHM) model system from
cardiomyocytes derived from human induced pluripotent stem cells (iPSC) harboring single sarcomere mutations
and has used this model system to help tease apart the contributions of afterload and genetics in HCM. We
hypothesize that the presence of (1) multiple sarcomeric variants and (2) HTN contribute to the worse outcomes
observed in Black HCM patients. AIM 1. To assess adverse outcomes in Black HCM patients with (vs without)
(A) more than one variant (i.e. 2 P/LP variants or 1 P/LP variant + 1 or more VUS) and (B) HTN, in 2 real-world
U.S. cohorts of HCM patients. An exploratory analysis using Somascan assays to identify novel plasma
proteomic biomarkers of adverse outcomes will also be performed. AIM 2. To characterize the effects of multiple
variants on cardiac physiology and fibrosis in our novel in vitro μHM model subjected to increased afterload.
Combining patient clinical data with powerful in vitro tools of iPSC technology, genome editing and tissue
engineering, will allow us to gain important insights and understanding of potential triggers and mechanisms
contributing to worse outcomes in Black HCM patients.
肥厚性心肌病(HCM)是最常见的遗传性心脏病。HCM患者有
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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SHARON CRESCI其他文献
SHARON CRESCI的其他文献
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{{ truncateString('SHARON CRESCI', 18)}}的其他基金
PREDICTION OF OUTCOMES IN HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF): A NEW PLASMA BIOMARKER
保留射血分数 (HFPEF) 的心力衰竭结果预测:一种新的血浆生物标志物
- 批准号:
9810249 - 财政年份:2019
- 资助金额:
$ 77.75万 - 项目类别:
Genomic variants associated with angina and health status outcome after MI
与心绞痛和心肌梗死后健康状况结果相关的基因组变异
- 批准号:
9197213 - 财政年份:2011
- 资助金额:
$ 77.75万 - 项目类别:
Genomic variants associated with angina and health status outcome after MI
与心绞痛和心肌梗死后健康状况结果相关的基因组变异
- 批准号:
8521389 - 财政年份:2011
- 资助金额:
$ 77.75万 - 项目类别:
Genomic variants associated with angina and health status outcome after MI
与心绞痛和心肌梗死后健康状况结果相关的基因组变异
- 批准号:
8258932 - 财政年份:2011
- 资助金额:
$ 77.75万 - 项目类别:
Genomic variants associated with angina and health status outcome after MI
与心绞痛和心肌梗死后健康状况结果相关的基因组变异
- 批准号:
8339338 - 财政年份:2011
- 资助金额:
$ 77.75万 - 项目类别:
Genomic variants associated with angina and health status outcome after MI
与心绞痛和心肌梗死后健康状况结果相关的基因组变异
- 批准号:
8818197 - 财政年份:2011
- 资助金额:
$ 77.75万 - 项目类别:
Association of PPAR-pathway gene polymorphisms with diabetic outcomes in BARI 2D
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7297134 - 财政年份:2007
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Association of PPAR-pathway gene polymorphisms with diabetic outcomes in BARI 2D
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