# Multiscale Modeling of Clotting Risk in Atrial Fibrillation

> **NIH NIH U01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $551,580

## Abstract

This project will develop clinically validated multiscale models of cardiac dynamics that integrate fluid dynamics,
electromechanical coupling, and fluid-structure interaction (FSI) to simulate intracardiac flows and blood 
co-agulation in atrial fibrillation (AF). AF is the most common sustained arrhythmia in the U.S. and is associated
with serious complications, including thromboembolism and stroke. Anticoagulation is commonly prescribed to
patients who have an elevated stroke risk. However, current risk assessment indices, which lack individualization
based upon atrial structure or function, classify most AF patients as being at intermediate risk. The core 
hypothesis of this research is that treatment guidelines using current risk assessment metrics result in many AF patients
receiving unneeded anticoagulation and unnecessary monitoring for thrombosis. The long-term objective of this
research is to develop new, broad-spectrum approaches to clotting risk assessment in AF that provide 
personalized risk prediction. The scientific premise of this proposal is that comprehensive models of atrial dysfunction will
enable mechanistic studies of flow and clotting in AF that will ultimately facilitate individualized treatment.
In AF, most clinically significant thrombi form in the left atrial appendage (LAA). The anatomy of the LAA is
extremely heterogeneous, and although there is an emerging appreciation that LAA anatomy affects clotting risk,
anatomy is not considered in current guidelines. Computer models provide ideal platforms for studying the impact
of structural and functional variations on LAA flow patterns, but most existing cardiac fluid dynamics models focus
on the ventricles. Further, no existing FSI model of the atria includes a detailed description of the LAA, which, like
the ventricles and unlike the main LA cavity, is highly trabeculated. A key innovation of this project is that it will
develop clinically validated FSI models of cardiac flow in patient-specific descriptions of LA anatomies, including
realistic models of the LAA. These models will be extended to include biophysically detailed models of coagulation
dynamics and clot transport. This project aims both to establish these models and also to apply them to study
flows and clotting dynamics in two therapies for AF: (1) percutaneous LAA exclusion via the WATCHMAN device
and (2) electrically isolating the LAA in catheter ablation therapy. In the case of LAA exclusion, the incidence of
device-associated thrombosis is 3.4%; consequently, post-operative anticoagulation therapy is currently used in
all patients receiving these devices. Electrical isolation of the LAA is rarely performed because of concerns about
its effect on systolic flow and stroke risk, and the inability to identify patients who would benefit.
The core modeling approaches developed in this project can also be deployed to simulate thrombogenesis
in a range of significant medical conditions (venous thromboembolism, d...

## Key facts

- **NIH application ID:** 10226154
- **Project number:** 5U01HL143336-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Boyce Eugene Griffith
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $551,580
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10226154

## Citation

> US National Institutes of Health, RePORTER application 10226154, Multiscale Modeling of Clotting Risk in Atrial Fibrillation (5U01HL143336-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10226154. Licensed CC0.

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