Mentoring and Research to ClassifyAtrial Cardiomyopathy

This K24 grant will provide the PI, Dr. Lin Yee Chen, a midcareer NIH-funded patient-oriented research (POR)
investigator, with the protected time and support needed to (1) accelerate his current trajectory in mentoring
junior clinicians and investigators who are conducting POR in cardiovascular (CV) science, (2) acquire
additional training in mentoring methods, machine learning, and omics science, (3) promote his current
research that aims to define the mechanisms underlying the relationship of the abnormal atrial substrate—atrial
cardiomyopathy—and atrial fibrillation (AF) to ischemic stroke and other CV outcomes. Trainees in his AF
Clinical Research Group will be recruited from the NIH-funded T32 training programs in the University of
Minnesota's Division of Cardiology, Division of Epidemiology, and Division of Biostatistics; Department of
Medicine Physician Scientist Training Program; KL2 and TL1 Programs of the CTSI; and graduate programs
(MS in Clinical Research, MPH, and PhD) in the School of Public Health. For his career development, Dr.
Chen will hone his mentoring skills and learn new skills in cutting-edge areas (machine learning and omics
science) through focused study, selected coursework, seminars, and guidance from senior collaborators with
domain expertise. Finally, this grant will support a research project that is based on the Atherosclerosis Risk in
Communities (ARIC) Study, which extends Dr. Chen’s ongoing work to elucidate the role of atrial
cardiomyopathy in driving AF-related outcomes. The specific aims are: (1) Identify atrial cardiomyopathy
subtypes by using machine learning approaches to analyze the extensive data at ARIC Visit 5 (2011-13):
clinical, 2D-echocardiographic, heart rate variability, arterial stiffness, ECG, and multi-omics data, (2) Evaluate
association of subtypes with ischemic stroke and other CV outcomes, and (3) Discover specific risk factors for
subtypes by analyzing risk factor measures collected at Visits 1-4 (1987-98). Crucially, findings will be
validated in 2 independent community-based cohorts: Cardiovascular Health Study (CHS) and Multi-Ethnic
Study of Atherosclerosis (MESA). This project has significant impact: (1) This K24 grant will provide the PI
with the protected time to enhance his current mentoring of trainees involved in POR. By assembling a team of
senior collaborators that comprise experts in mentoring, data science, and molecular epidemiology, the PI
provides an outstanding platform for his mentees to acquire cutting-edge skills in POR, (2) By resolving
heterogeneity in atrial cardiomyopathy, the team will advance the NIH’s Precision Medicine initiative by
personalizing current treatment for patients based on biological underpinnings, (3) The findings will lead to a
clinically meaningful improvement in classification of stroke risk in patients with AF, which will improve patient
outcomes, (4) By efficiently leveraging existing resources of deeply phenotyped NHLBI cohorts, this project will
fill critical knowledge gaps in prevention and treatment, thus achieving a sustained and powerful impact on
CV public health, clinical practice, and education of the next generation of researchers in POR.

Grant Number: 5K24HL155813-05
NIH Institute/Center: NIH
Principal Investigator: Lin Chen