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.

摘要

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