# Heart Rate Fragmentation: New Biomarker of Atrial Fibrillation Risk

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $586,845

## Abstract

PROJECT SUMMARY / ABSTRACT
Atrial fibrillation (AF), a common arrhythmia, is associated with substantially elevated risks of stroke, cognitive
decline, dementia, arterial emboli, heart failure, and cardiovascular death. Existing studies of AF generally
investigate AF that has been clinically recognized, but studies in patients with implanted monitoring devices
such as pacemakers or defibrillators indicate that a large proportion of AF episodes produce no symptoms at
all and are undetected clinically. Furthermore, complications commonly attributed to AF, including embolic
stroke, often occur in individuals with alterations of left atrial structure and function (atrial myopathy) but in the
absence of clinically recognized AF. Therefore, clinical presentation with AF may represent a late stage in the
pathophysiologic process linking atrial myopathy with serious complications including stroke and cognitive
decline. New biomarkers are needed that reflect atrial myopathy and are highly predictive of AF and its
complications. In the proposed research project, we will study newly developed heart rate (HR) fragmentation
metrics computed from long-term electrocardiographic (ECG) recordings. Our preliminary data support the
hypothesis that these new HR fragmentation metrics, developed by members of our investigative team, reflect
breakdown of the neuroautonomic-electrophysiologic network controlling the sino-atrial node and its regulation
of heart rate, and are highly predictive of both AF and cognitive impairment. In the setting of the Multi-Ethnic
Study of Atherosclerosis (MESA), we propose to compute HR fragmentation indices from overnight ECG
recordings and determine the association of HR fragmentation with cardiac structure assessed by MRI, with
incident AF, and with brain structure and function assessed by MRI and cognitive testing. In exploratory
analyses, we will use data from 14-day ambulatory ECG monitors to determine the short-term relationship of
paroxysmal AF with HR fragmentation. Data from the Sleep Heart Health Study cohorts will be used to
replicate findings from MESA for our primary aim. Our research will determine the extent to which HR
fragmentation is a biomarker of altered left atrial structure and function, clinically recognized AF, and
neurological complications of AF including impaired cognitive function and microvascular ischemia. With recent
developments in mobile monitoring technology, noninvasive ambulatory ECG monitoring overnight or for longer
periods is now practical. The measurement of HR fragmentation from these ECG recordings can be
automated. Thus, if HR fragmentation is indeed a biomarker of atrial myopathy, AF, and its complications,
information from noninvasive ECG monitoring may inform clinical care, including decisions about therapy to
reduce the risk of stroke.

## Key facts

- **NIH application ID:** 10215280
- **Project number:** 5R01HL144510-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Madalena D Costa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $586,845
- **Award type:** 5
- **Project period:** 2019-08-10 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215280

## Citation

> US National Institutes of Health, RePORTER application 10215280, Heart Rate Fragmentation: New Biomarker of Atrial Fibrillation Risk (5R01HL144510-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215280. Licensed CC0.

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