PRE-DETERMINE: Advancing Sudden Arrhythmic Death Prediction in Coronary Artery Disease in the Absence of Severe Systolic Dysfunction
预先确定:在没有严重收缩功能障碍的情况下推进冠状动脉疾病的心律失常性猝死预测
基本信息
- 批准号:10608859
- 负责人:
- 金额:$ 153.82万
- 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:2023-02-15 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAddressAreaArrhythmiaBiological AssayBiological MarkersBlood PlateletsBlood TestsCardiacCardiac DeathCause of DeathCessation of lifeClinicalCohort StudiesCollaborationsCoronary ArteriosclerosisCoronary heart diseaseDataDevelopmentDimensionsDisease OutcomeEicosanoidsElectrocardiogramEventFatty AcidsFunctional disorderFundingGeneral PopulationGeneticGenotypeGoalsHeart DiseasesImageImplantable DefibrillatorsIndividualInflammatoryInfrastructureInterventionInvestmentsKnowledgeLeft Ventricular Ejection FractionLifeLife ExpectancyMachine LearningMethodsModelingMolecular ProfilingNational Heart, Lung, and Blood InstitutePathway interactionsPatientsPersonsPhenotypePopulationPopulations at RiskPositioning AttributePreventionPrevention ResearchPrimary PreventionProceduresProspective StudiesProspective, cohort studyProteinsProteomicsPublic HealthResearch PersonnelResourcesResuscitationRiskRisk MarkerSudden DeathTherapeuticTimeUnited StatesValidationVentricular ArrhythmiaVentricular FibrillationVentricular TachycardiaWorkadjudicationadvanced analyticsbaseclinically relevantcohortcost effectivecost efficientdesignfollow-upgenome-wideheart damageheart rhythmhigh riskimprovedinnovationinsightmachine learning methodmortalitymortality riskmultimodal datamultimodalityneglectnovelnovel strategiespredictive modelingpreventrandomized trialretention raterisk predictionrisk prediction modelrisk stratificationtool
项目摘要
Sudden and/or arrhythmic death (SAD), which typically results from lethal ventricular arrhythmias (ventricular
tachycardia and ventricular fibrillation, VT/VF) in the setting of coronary heart disease (CHD), afflicts an
estimated 310,000 persons annually in the United States. Reductions in SAD have continued to lag those
observed for other coronary heart disease (CHD) outcomes despite advances in resuscitation therapies and
the use of implantable cardioverter-defibrillators (ICDs). Current approaches to SAD prevention remain
centered on placing ICDs in patients with left ventricular ejection fraction (LVEF) <30-35% – even though the
majority of SAD occurs in the setting of LVEF >30-35%. In effect, the proportionately larger segment of the
at-risk population has been understudied and thus undertreated. Despite this unmet need, there remain very
few, if any, prospective studies examining SAD risk prediction in individuals with CHD and LVEF >30-35% over
a long enough time horizon where ICD therapy might be cost-effective. For this very reason, the PRE-
DETERMINE Cohort Study was intentionally designed to address this scientific gap and prospectively
study clinically relevant approaches to SAD risk prediction in CHD patients with LVEF >30-35%. In this
application, we propose to leverage the originally NHLBI-funded base cohort resource to continue adjudication
of accruing SAD and VT/VF events, in addition to competing causes of death, to attain 10+ years of endpoint
adjudication to enable the development and validation of multi-marker SAD risk prediction models based on
combinations of multi-dimensional clinical, ECG, imaging, biomarker, and genetic data generated in this unique
multicenter cohort of 5761 CHD patients. We will also leverage the base cohort to interrogate novel fatty acid
derived eicosanoids and putative arrhythmia modulating proteomic analytes in relation to risk for SAD and
competing causes of mortality in patients with CHD. Novel methods of competing risk analyses will be used to
integrate absolute and proportional SAD risk into SAD risk prediction models and to elucidate separate
associations between SAD vs. non-SAD causes of death. Machine learning approaches will be applied to
uncover inter-relations and latent features from multi-modality data not easily detected by conventional models.
An overarching goal of our work is to accurately identify those individual subsets of the broader population who
have sufficiently high absolute and proportional risk for SAD that they warrant inclusion in randomized trials of
primary prevention ICD therapy. The aims of the current proposal also offer new opportunities to identify
potential mechanistic pathways underlying the genesis of lethal ventricular arrhythmias that could serve as
novel targets for SAD prevention – extending beyond ICD placement – in patients with CHD and possibly even
in the general population wherein CHD underlies most SAD events. The continuation and expansion of the
PRE-DETERMINE study will provide the scientific field with a one-of-a kind resource for investigators and
trainees collaborating toward the common goal of reducing the burden of SAD.
猝死和/或心律失常死亡(SAD),通常由致死性室性心律失常(室性心律失常)引起
心动过速和室颤)在冠心病(CHD)的背景下,困扰着
据估计,美国每年有31万人。SAD的减少继续落后于
观察其他冠心病(CHD)预后,尽管复苏治疗和
植入型心律转复除颤器(ICD)的使用。目前预防SAD的方法仍然存在
中心是在左心室射血分数(LVEF)为30-35%的患者中放置ICD-即使
大多数SAD发生在LVEF>;30%-35%的设置中。实际上,比例较大的部分
高危人群一直没有得到充分的研究,因此也没有得到足够的治疗。尽管有这种未得到满足的需求,但仍有非常多的
很少有前瞻性研究检验CHD和LVEF>;30%-35%以上患者的SAD风险预测
ICD治疗可能具有成本效益的足够长的时间范围。正是因为这个原因,前-
确定队列研究是故意设计的,旨在解决这一科学差距,并具有前瞻性
研究LVEF和GT;30-35%的冠心病患者SAD风险预测的临床相关方法。在这
申请,我们建议利用最初由NHLBI资助的基本队列资源来继续裁决
除了相互竞争的死亡原因外,SAD和VT/VF事件的累积,以达到10年以上的终点
裁决,以使开发和验证多标记SAD风险预测模型基于
多维临床、心电、成像、生物标记物和遗传数据的组合在这个独特的
5761例冠心病患者的多中心队列研究。我们还将利用碱基队列来审问新型脂肪酸
衍生二十烷基类化合物和可能的心律失常调节蛋白质组分析与SAD和
冠心病患者死亡原因的相互竞争。竞争风险分析的新方法将被用于
将绝对SAD风险和比例SAD风险集成到SAD风险预测模型中,并阐明分开
SAD与非SAD死因之间的关系。机器学习方法将应用于
从多通道数据中发现传统模型不易检测到的相互关系和潜在特征。
我们工作的一个首要目标是准确地识别那些在更广泛的人口中
对SAD有足够高的绝对和比例风险,因此需要纳入
一级预防ICD治疗。目前提案的目标还提供了新的机会,以确定
致死性室性心律失常发生的潜在机制途径可作为
预防SAD的新目标--超越ICD安置--在CHD患者中,甚至可能
在普通人群中,冠心病是大多数SAD事件的基础。的延续和扩展
预先确定的研究将为科学领域的研究人员和
受训人员通力合作,朝着减轻SAD负担的共同目标努力。
项目成果
期刊论文数量(0)
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CHRISTINE M ALBERT其他文献
CHRISTINE M ALBERT的其他文献
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{{ truncateString('CHRISTINE M ALBERT', 18)}}的其他基金
Predisposing Factors for the Development of Atrial Fibrillation Among Women
女性房颤发生的诱发因素
- 批准号:
7739967 - 财政年份:2009
- 资助金额:
$ 153.82万 - 项目类别:
Predisposing Factors for the Development of Atrial Fibrillation Among Women
女性房颤发生的诱发因素
- 批准号:
7891235 - 财政年份:2009
- 资助金额:
$ 153.82万 - 项目类别:
PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study
预先确定:生物标志物和 MRI SCD 队列研究
- 批准号:
8090321 - 财政年份:2008
- 资助金额:
$ 153.82万 - 项目类别:
Pre-DETERMINE: Biologic Markers and MRI SCD Cohort Study
预确定:生物标志物和 MRI SCD 队列研究
- 批准号:
9462839 - 财政年份:2008
- 资助金额:
$ 153.82万 - 项目类别:
PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study
预先确定:生物标志物和 MRI SCD 队列研究
- 批准号:
8536353 - 财政年份:2008
- 资助金额:
$ 153.82万 - 项目类别:
Pre-DETERMINE: Biologic Markers and MRI SCD Cohort Study
预确定:生物标志物和 MRI SCD 队列研究
- 批准号:
9310983 - 财政年份:2008
- 资助金额:
$ 153.82万 - 项目类别:
PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study
预先确定:生物标志物和 MRI SCD 队列研究
- 批准号:
7866526 - 财政年份:2008
- 资助金额:
$ 153.82万 - 项目类别:
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