# Computational Stability Analysis to Predict Heart Failure after Myocardial Infarction

> **NIH NIH K99** · STANFORD UNIVERSITY · 2023 · $157,356

## Abstract

PROJECT SUMMARY
Myocardial infarction (MI) can lead to heart failure (HF), which severely impacts the quality of life of millions of
Americans. MI triggers a cascade of cardiac growth and remodeling (G&R) patterns. They change ventricular
size, shape, and function, driven by biomechanical, neurohormonal, and genetic stimuli. Adaptive short-term
G&R can stabilize cardiac performance. Yet, in many patients, adverse long-term G&R is unstable and
progresses to HF. Unfortunately, those patients lack robust clinical predictors because the biomechanical
stimuli of adverse G&R patterns are still unclear. Computational models of full-heart biomechanics, informed by
cardiac magnetic resonance imaging (CMR), show high potential to fill this gap. The foundation of this project
is a novel microstructure-based model of cell-scale G&R based on the homogenized constrained mixture
theory, co-developed by the applicant, Dr. Pfaller. In addition, this research plan will leverage a multiscale
model that combines cell-scale G&R and organ-scale cardiac contraction and validation with CMR in swine
and humans to predict the propensity to develop HF with the mechanobiological stability theory. In Aim 1, Dr.
Pfaller will refine and validate a framework for subject-specific models of cardiac G&R. After calibrating the
model to pressure and kinematic CMR measurements in control swine, he will introduce MI to the multiscale
model and validate the prediction of G&R with matching measurements in post-MI swine. In Aim 2, Dr. Pfaller
will quantify the propensity of developing adverse G&R with the mechanobiological stability theory and identify
risk factors of post-MI HF from infarct properties. He will test the validity of his HF prediction with longitudinal
human CMR and clinical data from the UK Biobank. Dr. Pfaller has excellent prior training in cardiac
biomechanics, medical imaging, and computational engineering with an established publication record in
cardiac and cardiovascular biomechanics. His career development plan (K99-phase) will provide additional
training in cardiac biology and using CMR for human subjects. Dr. Pfaller will also receive a wealth of informal
and didactic training at Stanford University, which will be critical for Dr. Pfaller to gain autonomy and launch a
productive career as an independent engineering-scientist. Mentor Dr. Marsden is a leading expert in patient-
specific modeling of the cardiovascular system. Co-Mentor Dr. Ennis (CMR) and advisors Drs. Humphrey (cell-
scale modeling), Cyron (stability theory), Kuhl (organ-scale modeling), Yang (cardiac biology), Salerno (heart
failure) offer complementary expertise. Dr. Pfaller will receive the necessary guidance and resources to
accomplish these goals and efficiently transition to independence (R00-phase). In summary, the strong
mentoring environment and training plan will fully prepare Dr. Pfaller to launch his independent career. The
proposed studies promise to offer insights into biomechanical ...

## Key facts

- **NIH application ID:** 10669258
- **Project number:** 5K99HL161313-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Martin R Pfaller
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $157,356
- **Award type:** 5
- **Project period:** 2022-09-01 → 2024-06-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10669258

## Citation

> US National Institutes of Health, RePORTER application 10669258, Computational Stability Analysis to Predict Heart Failure after Myocardial Infarction (5K99HL161313-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10669258. Licensed CC0.

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