# The Clinical Relevance of Anthracycline-Related Cardiac Remodeling in Childhood Cancer Survivors

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $196,591

## Abstract

PROJECT SUMMARY/ABSTRACT
 Anthracycline antibiotics are essential, lifesaving chemotherapies used in ~60% of pediatric cancer
patients, but they confer a substantial dose-dependent risk of cardiac dysfunction and heart failure in long-term
survivors. The standard heart failure management approach -- waiting for left ventricular ejection fraction decline
and then starting afterload reduction therapy -- has been used for decades despite its limited success.
Alternatively, an early, targeted treatment strategy guided by specific disease manifestations could improve
outcomes. Adverse left ventricular remodeling (i.e., change in size and shape) precedes and may precipitate
heart failure and could be used to guide such a strategy. However, there is a critical need to define the specific
adverse features of left ventricular shape and to determine the relationship between remodeling and both
modifiable risk factors and long-term dysfunction in childhood cancer survivors treated with anthracyclines.
 The overall objectives of this proposal are to define the anthracycline-related adverse features of left
ventricular shape in childhood cancer survivors and to determine the associations between remodeling and both
modifiable risk factors, including reduced physical activity, and dysfunction over time. The central hypothesis of
this project is that anthracyclines cause specific adverse changes in 3D left ventricular shape; moderate to
vigorous physical activity mitigates this remodeling process; and adverse remodeling is prognostic
of subsequent dysfunction. To achieve these objectives, we will comprehensively analyze cardiac magnetic
resonance imaging in cross-sectional and longitudinal cohorts of adolescent and young adult childhood cancer
survivors. The Specific Aims are to 1) define the adverse features of left ventricular shape associated with
anthracycline dose exposure; 2) determine the associations between left ventricular remodeling and modifiable
risk factors, and 3) determine the relationship between left ventricular remodeling and subsequent dysfunction.
The expected contributions of this research will yield new imaging-based disease markers; improve early
detection, risk assessment, and clinical prognostication; and inform a future targeted intervention.
 Dr. Hari K. Narayan seeks this career development award to achieve his long-term goal of becoming an
independent physician scientist focused on preventing anthracycline-related heart failure in childhood cancer
survivors. Through the proposed training, he seeks to expand beyond his cardiovascular imaging and
epidemiology background by developing skills in computational modeling and machine learning analysis, patient-
oriented and physical activity research, and academic leadership. The mentorship team, which includes
expertise in pediatric clinical trials, computational cardiac image analysis, physical activity in survivorship, and
pediatric survivorship oncology, is optimally suited to guide hi...

## Key facts

- **NIH application ID:** 10901989
- **Project number:** 5K23HL163456-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Hari Kope Narayan
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,591
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901989

## Citation

> US National Institutes of Health, RePORTER application 10901989, The Clinical Relevance of Anthracycline-Related Cardiac Remodeling in Childhood Cancer Survivors (5K23HL163456-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10901989. Licensed CC0.

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