Carol Act Supplement to Data-driven optimization of therapy for heart failure

卡罗尔法案对数据驱动的心力衰竭治疗优化的补充

• 批准号: 10851206
• 负责人: Kenneth S Campbell
• 金额: $ 12.86万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10851206
• 关键词: 3-Dimensional; Administrative Supplement; Algorithms; Aortic Valve Insufficiency; Baroreflex; Beds; Blood; Cardiac; Circulation; Clinical; Computer Models; Computer software; Data; Dilated Cardiomyopathy; Disease; Exercise; Filament; Goals; Growth; Heart; Heart Diseases; Heart Valve Diseases; Heart failure; Hypertension; Hypertrophic Cardiomyopathy; Laws; Left ventricular structure; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Prolapse; Mitral Valve Stenosis; Modeling; Mutation; Myocardial; Myosin ATPase; Parents; Patients; Pattern; Physiological; Postdoctoral Fellow; Pregnancy; Proteins; Qualifying; Relaxation; Research; Signal Transduction; Stenosis; Stress; Supervision; System; Techniques; Testing; Therapeutic; Therapeutic Intervention; Thinness; Time; Work; aortic valve; blood pump; clinical phenotype; clinically relevant; computer program; connectin; constriction; experience; parent grant; response; simulation; therapeutic evaluation; treatment optimization

ABSTRACT This proposal is submitted in response to NOT-HL-23-078 “Administrative supplements to encourage research in valvular heart disease” and seeks 12 months of additional support for HL163977, Data-driven optimization of therapy for heart failure. The parent R01 is active until 2026. The overarching goal of HL163977 is to develop a computer model of the heart that can be used to test therapeutic strategies and optimize treatments for patients who have heart failure. Aim 1 develops a system called MyoVent as a test-bed for implementing baroreflex control and myocardial growth. Aims 2 and 3 use the techniques developed with MyoVent and deploy them in a more sophisticated 3D framework called MyoFE to create patient-specific personalized models. The team has made rapid progress and Aim 1 is now mostly complete. The breakthrough was accomplished by developing algorithms that modulate concentric (wall thickening / thinning) and eccentric (chamber dilation / constriction) growth in response to physiologic signals. Specifically, the model assumes that hearts grow concentrically to stabilize the intracellular ATP concentration while eccentric growth is sensitive to the passive intracellular stress sensed by titin filaments. These growth laws reproduce the patterns of cardiac growth observed in clinically-relevant conditions including hypertension, exercise, and destabilization of the myosin super-relaxed state. This supplement will extend the simulations to valvular heart disease. The objective is focused. The team will test whether the growth laws predict the patterns of eccentric and concentric growth observed clinically in patients with mitral valve insufficiency (including mitral valve prolapse) and stenosis, and aortic valve insufficiency and stenosis. This will be accomplished in a single year by a highly-qualified and experienced post-doc who will work under the supervision of the contact PI.

抽象的 该提案是针对非HL-23-078提交的，“行政补充剂以鼓励研究 在瓣膜心脏病中”，并为HL163977寻求12个月的额外支持，数据驱动的优化 心力衰竭的治疗。直到2026年，父r01一直处于活动状态。 HL163977的总体目标是开发可用于测试的心脏的计算机模型 治疗策略并优化患有心力衰竭的患者的治疗方法。 AIM 1开发系统 称Myovent为实施压力反射控制和心肌生长的测试床。目标2和3使用 用Myovent开发的技术，并将它们部署在更复杂的3D框架中，称为Myofe 创建特定于患者的个性化模型。 该团队已经取得了迅速的进步，而AIM 1现在已经完成了。突破是由 开发算法调节同心（壁增厚 /变薄）和偏心（腔室扩张 / 收缩）响应生理信号的生长。具体而言，该模型假设心脏成长 综合以稳定细胞内ATP浓度，而偏心生长对被动敏感 细胞内应力是由钛丝所感应的。这些增长法重现了心脏增长的模式 在与临床相关的疾病中观察到，包括高血压，运动和肌球蛋白不稳定 超级宽带状态。 该补充剂将将模拟扩展到瓣膜心脏病。目标是集中的。团队会 测试生长法律是否预测患者临床观察到的偏心和同心生长的模式 二尖瓣功能不全（包括二尖瓣脱垂）和狭窄，主动脉瓣功能不全和 狭窄。这将在一年内由高素质和经验丰富的大多数人完成 在联系人的监督下。

项目成果

An in silico study of the effects of left ventricular assist device on right ventricular function and inter-ventricular interaction.

左心室辅助装置对右心室功能和心室间相互作用影响的计算机研究。

• DOI: 10.1111/aor.14649
• 发表时间: 2023
• 期刊: Artificial organs
• 影响因子: 2.4
• 作者: Fan,Lei;Choy,JennyS;Lee,Sangjin;Campbell,KennethS;Wenk,JonathanF;Kassab,GhassanS;Burkhoff,Daniel;Lee,LikChuan
• 通讯作者: Lee,LikChuan