# Human Mitochondrial Variation and Sudden Cardiac Arrest Risk and Resuscitation

> **NIH HL R01** · JOHNS HOPKINS UNIVERSITY · 2026 · $693,969

## Abstract

Sudden cardiac arrest (SCA) is a major public health concern, accounting for up to 400,000 deaths each year.
While SCA cases are heterogeneous in etiology, the most common underlying pathologic substrate is ischemic
heart disease and the most common electrophysiologic mechanism is ventricular fibrillation (VF). Survival
following VF-SCA is less than 20% in most communities with mortality due largely to fulminant injury of either
the heart or brain. Accordingly, there is a compelling case to identify novel modifiable SCA risk factors, to
elucidate its underlying pathophysiology, and to identify novel preventative and therapeutic targets. The
mitochondrion has primary function in energetics, oxidative stress, and apoptosis, and serves as both a target
and an effector of ischemia-reperfusion injury. Consequently, mitochondria have a fundamental role in
arrhythmia risk and in cardiac and brain resuscitation. Indeed, we have previously demonstrated that
mitochondrial DNA (mtDNA) copy number (-CN), which reflects the number of MT genomes per cell, is a novel
risk factor for SCA, independent of traditional SCA risk factors. MtDNA-CN, however, captures the quantity of
mitochondria. It does not capture their quality. We have recently identified a series of mtDNA haplotypes that
capture functional genetic variation, and developed a computational tool to accurately assess somatic mutations
in mitochondria (heteroplasmy), allowing for a comprehensive survey of mtDNA genetic variation. Thus, we
propose to test the hypothesis that mtDNA variation (mtDNA-CN, inherited mtDNA haplotypes and rare
mutations, mtDNA heteroplasmy [somatic variants]) will be associated with SCA risk and resuscitation outcomes.
We will examine the association of SCA with mtDNA characteristics in 2,600 SCA cases from a large population-
based case-control study of SCA and validate our findings in two population-based cohort studies where SCA
cases have been identified prospectively and two case-control stud

## Key facts

- **NIH application ID:** 11251647
- **Project number:** 5R01HL170579-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Dan E Arking; THOMAS D REA; Nona  Sotoodehnia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $693,969
- **Award type:** 5
- **Project period:** 2024-04-12T00:00:00 → 2028-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11251647

## Citation

> US National Institutes of Health, RePORTER application 11251647, Human Mitochondrial Variation and Sudden Cardiac Arrest Risk and Resuscitation (5R01HL170579-03). Retrieved via AI Analytics 2026-07-12 from https://api.ai-analytics.org/grant/nih/11251647. Licensed CC0.

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