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JAMA Neurol. 2018 Jan 1;75(1):80-87. doi: 10.1001/jamaneurol.2017.2853.

Association of Cardiac Hemodynamic Factors With Severity of White Matter Hyperintensities in Chronic Valvular Heart Disease.

Lee WJ1, Jung KH1,2, Ryu YJ3, Kim JM4, Lee ST1,2, Chu K1,2, Kim M1,2,5, Lee SK1,2, Roh JK1,6.

Author information

Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Program in Neuroscience, Neuroscience Research Institute of SNUMRC, College of Medicine, Seoul National University, Seoul, South Korea.
Department of Radiology, Seoul National University Hospital, Seoul, South Korea.
Department of Neurology, Chung-Ang University Hospital, Seoul, South Korea.
Protein Metabolism Research Center, Seoul National University College of Medicine, Seoul, South Korea.
Department of Neurology, The Armed Forces Capital Hospital, Sungnam, South Korea.



The cerebral white matter hyperintensity (WMH) is frequently noted in patients with chronic heart disease. Long-term alteration of cardiac hemodynamics might have an influence on the mechanism of cerebral WMH.


To investigate the association between chronically altered cardiac hemodynamics and severity of cerebral WMH in patients with chronic valvular heart disease.

Design, Setting, and Participants:

This cross-sectional analysis identified 303 consecutive patients at a tertiary referral center between 2008 and 2016 who were 50 years or older, and diagnosed with severe chronic valvular heart disease and underwent cardiac catherization, echocardiography, and received brain magnetic resonance imaging. Among these patients, 71 with other demonstrated cardiac disease, central nervous system disease, and/or without sufficient catheterization data were excluded, and the remaining 232 patients were included in further analyses.


The site and mechanism of valve diseases, as well as clinical and medication profiles, were reviewed. Cardiac catheterization parameters such as right atrial (RA) mean pressure, right ventricular pressure, and aortic mean pressure were obtained. Comprehensive echocardiographic hemodynamic markers such as left ventricular (LV) ejection fraction, LV mass index, LV end diastolic volume, cardiac index, and E/e' ratio were also obtained.

Main Outcomes and Measures:

White matter hyperintensity volume was quantitatively evaluated using volumetric analysis.


This study included 232 patients (103 men [44.4%] and 129 women [55.6%]; mean [SD] (range) age, 65.6 [8.8] (51-88) years) in the final analysis. The mean (SD) WMH volume was 5.93 (7.14) mL (median [interquartile range], 4.33 [1.33-8.62] mL), and mean (SD) RA pressure was 10.0 (4.7) mm Hg. From the catheterization data, 147 patients (63.4%) were classified as having a disease involving the mitral valve; 93 (40.1%), aortic valve; 37 (15.9%), tricuspid valve; and 4 (1.7%), pulmonary valve. In multivariate linear regression analysis, adjusting the type and mechanism of valve disease and clinical, echocardiographic, and/or other catheterization parameters, WMH volume was linearly associated with mean RA pressure (B coefficient, 0.702; 95% CI, 0.373-1.031; P = .001), along with age (B coefficient, 0.145; 95% CI, 0.029-0.261; P = .01) and mean aortic pressure (B coefficient, 0.112; 95% CI, 0.034-0.190; P = .005).

Conclusions and Relevance:

Mean RA pressure was independently associated with the WMH volume in chronic valvular heart disease. Chronically altered RA hemodynamics might have a distinct influence on the pathomechanism underlying the development of WMH.

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