Mentoring and Research to Classify Atrial Cardiomyopathy

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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.