Chronic Valvular Heart Disease Linked To White Matter Brain Changes Interview with:
Dr. Keun-Hwa Jung MD PhD

Program in Neuroscience, Neuroscience Research Institute of SNUMRC
College of Medicine
Seoul National University
First author: Dr. Woo-Jin Lee MD
Department of Neurology
Seoul National University Hospital
Seoul, South Korea What is the background for this study? What are the main findings?

Response: Cerebral white matter hyperintensity is a prevalent consequence of brain aging process and associated with various complications. One of the main mechanisms underlying the progression of white matter hyperintensity is chronic dysfunction of the glymphatic system which maintains metabolic homeostasis in brain. Glymphatic system is the route where the cerebrospinal fluid enters into the brain parenchyma and is cleared out with soluble wastes to the perivascular space of the cerebral small veins, peri-meningeal lymphatic vessels, deep cervical lymph nodes, and finally to the right atrium.

Although the integrity of the glymphatic system is dependent on the adequate drainage of cerebral veins and lymphatics to the downstream chamber, the right atrium, the impact of hemodynamic changes in right-sided cardiac chambers on the development of white matter hyperintensity have not been elucidated.  What are the main findings?

Response: As valvular heart disease is a chronic disease which induces an alteration in cardiac hemodynamics, evaluation of the long-term hemodynamic changes in a valve disease in relation with the white matter hyperintensity volume may help us to elucidate the pathophysiological role of the heart in the development of white matter hyperintensity.

In this cross-sectional study, patients were diagnosed with a severe chronic heart valve disease with durations of more than 1 year from the initial diagnosis. The cerebral white matter hyperintensity volume was linearly associated with mean right atrial pressure on cardiac catheterization, along with age, and mean aortic pressure. Additionally, the highest tertile of the mean right atrial pressure (≥10.9mmHg) had a mean cerebral white matter hyperintensity volume of (10.32±9.32 mL), which is associated with 10.5/100 (person x years) incidence of disability and 2.1/100 (person x years) incidence of death according to a large sized cohort study. What should clinicians and patients take away from your report?

Response: Based on the result of this study, chronic elevation of the right atrial pressure should also be considered as a distinct motive of the development of cerebral white matter hyperintensity. As chronic valvular heart disease is a prevalent disorder in aged population, patients with a moderate to severe heart valve disease and a significantly elevated right atrial pressure should also check the presence or the severity of the white matter disease on brain MRI. What recommendations do you have for future research as a result of this study?

Response: It is important that the result of our study is replicated in prospective long-term cohort studies applying a predefined evaluation protocol.

Second, experimental studies using rodent models should endeavor to reveal the direct association between the long term elevation of right atrial pressure and the progression of cerebral small vessel disease. Studies to demonstrate the effect of the elevated pressure of cerebral venules or the stagnation of the cerebral glymphatic outflow on the integrity of cerebral blood brain barrier, water content in brain parenchyma, or the accumulation of cerebral soluble metabolites should also be performed. Thank you for your contribution to the community.


Lee W, Jung K, Ryu YJ, Kim J, Lee S, Chu K, Kim M, Lee SK, Roh J. Association of Cardiac Hemodynamic Factors With Severity of White Matter Hyperintensities in Chronic Valvular Heart Disease. JAMA Neurol. Published online November 06, 2017. doi:10.1001/jamaneurol.2017.2853

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions. 

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