Multiscale Models for Predicting Short and Long-term Outcome of Cardiac Resynchronization Therapy

用于预测心脏再同步治疗的短期和长期结果的多尺度模型

• 批准号: 10673868
• 负责人: Kenneth C Bilchick
• 金额: $ 64.05万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-13 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673868
• 关键词: Acute; Adrenergic beta-Antagonists; American; Anatomy; Angiotensin Receptor; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Blood Tests; Body Surface Potential Mapping; Brain natriuretic peptide; Bundle-Branch Block; Canis familiaris; Cardiac; Cardiac Electrophysiologic Techniques; Cardiac Myocytes; Cells; Cicatrix; Circulation; Clinical; Clinical Data; Complex; Computer Models; Data; Devices; Disease; Electric Stimulation; Electrocardiogram; Electrophysiology (science); Elements; Goals; Growth; Heart; Heart Hypertrophy; Heart failure; Hormonal; Human; Infarction; Ischemia; Lead; Left; Left ventricular structure; Life; Location; Magnetic Resonance Imaging; Measurement; Mechanics; Methods; Modeling; Myocardial Contraction; Myocardial Infarction; Myocardial dysfunction; Myocardium; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Physiology; Procedures; Protocols documentation; Publishing; Regimen; Research Personnel; Signal Pathway; Signal Transduction; Symptoms; Testing; Time; Ventricular; Ventricular Remodeling; blood pump; cardiac resynchronization therapy; design; effective therapy; experience; hormonal signals; imaging study; implantation; improved; improved outcome; individual patient; individualized medicine; innovation; mechanical signal; mortality; multi-scale modeling; network models; predictive modeling; response; routine care; simulation; standard of care; success; therapy outcome; treatment planning; virtual therapy

Project Summary Heart failure is associated with an annual mortality rate of 300,000 Americans, while over a million experience a myocardial infarction. Many patients with both heart failure and myocardial infarction also develop ventricular dyssynchrony, which exacerbates cardiac dysfunction and worsens symptoms. Cardiac resynchronization therapy (CRT) has emerged as an effective therapy for patients who suffer from heart failure and dyssynchrony, such as left bundle branch block (LBBB). When CRT is successful, it improves survival by stopping and even reversing the progression of heart failure. CRT immediately restores electrical and mechanical synchrony of the healthy myocardium, and over time it reverses dilation of the left ventricle (LV). However, 35-50% of patients fail to respond to CRT. A major strength of CRT is the ability to tailor the therapy to individual patients with patient- specific lead locations, timing, and/or pacing protocol, which promises to improve outcome. However, it also presents a dilemma: there are far too many possible strategies to test during the implantation surgery. Given the complex interactions and patient-to-patient differences in anatomy, electrophysiology, infarct location, myocardial remodeling, and drug regimens, individualized computational models have the potential to improve CRT outcome by enabling virtual treatment planning and guidance. While computational models of the acute impact of CRT on electrical or mechanical synchrony exist, none are capable of predicting patient-specific outcomes and long-term post-CRT cardiac remodeling, and most are too computationally expensive for routine clinical use. Thus, the specific objective of this proposal is to develop a fast multiscale modeling approach for patient-specific prediction of CRT outcome in ischemic and non-ischemic LBBB patients that can be integrated into the existing, standard of care routine. This objective will be accomplished in three specific aims. In Aim 1, we will develop and validate a rapid electrophysiology model to identify patient-specific CRT pacing protocols that lead to improved LV synchrony based on pre-procedure measurements. In Aim 2, we will develop and validate a rapid strain-driven growth model to predict patient-specific long-term (6 months) outcomes of CRT in ischemic and non-ischemic LBBB patients. In Aim 3, we will test the hypothesis that incorporating patient-specific drug data through a multiscale model of cardiomyocyte hypertrophic signaling improves CRT remodeling predictions. All model predictions will be validated against pre- intra- and post-CRT clinical data we collected from 100 patients treated in our center, including comprehensive MRI studies, ECGs, blood pressure, and blood tests. Together, the proposed studies will enable researchers and clinicians to understand why CRT fails in many patients, taking into account patient-specific electromechanics, scar, long-term remodeling, and drug regimen, as well as explore patient-specific CRT strategies in order to improve the current 50-65% response rate.

项目总结

项目成果

A systemic congestive index (systemic pulse pressure to central venous pressure ratio) predicts adverse outcomes in patients undergoing valvular heart surgery.

• DOI: 10.1111/jocs.16772
• 发表时间: 2022-10
• 期刊: JOURNAL OF CARDIAC SURGERY
• 影响因子: 1.6
• 作者: Knio, Ziyad O.;Morales, Frances L.;Shah, Kajal P.;Ondigi, Olivia K.;Selinski, Christian E.;Baldeo, Cherisse M.;Zhuo, David X.;Bilchick, Kenneth C.;Mehta, Nishaki K.;Kwon, Younghoon;Breathett, Khadijah;Thiele, Robert H.;Hulse, Matthew C.;Mazimba, Sula
• 通讯作者: Mazimba, Sula

Noninvasive Electrical Mapping Compared with the Paced QRS Complex for Optimizing CRT Programmed Settings and Predicting Multidimensional Response.

• DOI: 10.1007/s12265-023-10418-1
• 发表时间: 2023-12
• 期刊: Journal of cardiovascular translational research
• 影响因子: 3.4

First-in-human noninvasive left ventricular ultrasound pacing: A potential screening tool for cardiac resynchronization therapy.

• DOI: 10.1016/j.hroo.2022.10.008
• 发表时间: 2023-03
• 期刊: HEART RHYTHM O2
• 作者: Bilchick, Kenneth C.;Morgounova, Ekaterina;Oomen, Pim;Malhotra, Rohit;Mason, Pamela K.;Mangrum, Mike;Kim, David;Gao, Xu;Darby, Andrew E.;Monfredi, Oliver J.;Aso, Joy A.;Franzen, Peter M.;Stadler, Robert W.
• 通讯作者: Stadler, Robert W.

Association of colchicine use for acute gout with clinical outcomes in acute decompensated heart failure.

• DOI: 10.1002/clc.23830
• 发表时间: 2022-07
• 期刊: CLINICAL CARDIOLOGY
• 影响因子: 2.7
• 作者: Roth, Mary E.;Chinn, Melissa E.;Dunn, Steven P.;Bilchick, Kenneth C.;Mazimba, Sula
• 通讯作者: Mazimba, Sula

Machine learning for multidimensional response and survival after cardiac resynchronization therapy using features from cardiac magnetic resonance.

• DOI: 10.1016/j.hroo.2022.06.005
• 发表时间: 2022-10
• 期刊: HEART RHYTHM O2
• 作者: Bivona, Derek J.;Tallavajhala, Srikar;Abdi, Mohamad;Oomen, Pim J. A.;Gao, Xu;Malhotra, Rohit;Darby, Andrew E.;Monfredi, Oliver J.;Mangrum, J. Michael;Mason, Pamela K.;Mazimba, Sula;Salerno, Michael;Kramer, Christopher M.;Epstein, Frederick H.;Holmes, Jeffrey W.;Bilchick, Kenneth C.
• 通讯作者: Bilchick, Kenneth C.