Influence of Parasympathetic Modulation in Doppler Mitral Inflow Velocity in Individuals without Heart Disease Ivana Antelmi, MD, Alice Tatsuko Yamada, MD, Chang Nan Hsin, MD, Jeane M. TsuTsui, MD, Cesar Jose ´ Grupi, MD, and Alfredo Jose ´ Mansur, MD, Sa˜o Paulo, Brazil Background: The relation between left ventricular filing velocities determined by Doppler echocardiography and autonomic nervous system function assessed by heart rate variability (HRV) is unclear. The aim of this study was to evaluate the influence of the autonomic nervous system assessed by the time and frequency do- main indices of HRV in the Doppler indices of left ventricular diastolic filling velocities in patients without heart disease. Methods: We studied 451 healthy individuals (255 female [56.4%]) with normal blood pressure, electrocardio- gram, chest x-ray, and treadmill electrocardiographic exercise stress test results, with a mean age of 43 6 12 (range 15-82) years, who underwent transthoracic Doppler echocardiography and 24-hour electrocardio- graphic ambulatory monitoring. We studied indices of HRV on time (standard deviation [SD] of all normal sinus RR intervals during 24 hours, SD of averaged normal sinus RR intervals for all 5-minute segments, mean of the SD of all normal sinus RR intervals for all 5-minute segments, root-mean-square of the successive normal si- nus RR interval difference, and percentage of successive normal sinus RR intervals > 50 ms) and frequency (low frequency, high frequency, very low frequency, low frequency/high frequency ratio) domains relative to peak flow velocity during rapid passive filling phase (E), atrial contraction (A), E/A ratio, E-wave deceleration time, and isovolumic relaxation time. Statistical analysis was performed with Pearson correlation and logistic regression. Results: Peak flow velocity during rapid passive filling phase (E) and atrial contraction (A), E/A ratio, and de- celeration time of early mitral inflow did not demonstrate a significant correlation with indices of HRV in time and frequency domain. We found that the E/A ratio was < 1 in 45 individuals (10%). Individuals with an E/A ratio < 1 had lower indices of HRV in frequency domain (except low frequency/high frequency) and lower indices of the mean of the SD of all normal sinus RR intervals for all 5-minute segments, root-mean-square of the successive normal sinus RR interval difference, and percentage of successive normal sinus RR intervals > 50 ms in time domain. Logistic regression demonstrated that an E/A ratio < 1 was associated with lower HF. Conclusion: Individuals with no evidence of heart disease and an E/A ratio < 1 demonstrated a significant decrease in indexes of HRV associated with parasympathetic modulation. (J Am Soc Echocardiogr 2010;23:762-5.) Keywords: Autonomic nervous system, E/A ratio, Diastolic function, Heart rate variability Heart rate variability (HRV) indices are useful noninvasive tools for the evaluation of autonomic activity and interplay between the sym- pathetic and parasympathetic nervous systems. 1 HRV has been widely applied for evaluating cardiovascular autonomic diabetic neu- ropathy and assessing risk of sudden death in patients with heart fail- ure. 2,3 In patients without evidence of cardiac disease, HRV indexes decrease with gender and increasing age, and increase in patients with higher functional capacity. 4 Doppler echocardiography provides information on left ventricu- lar filling and in asymptomatic individuals may reveal changes relative to the typically normal E/A ratio. 5,6 The frequency and clinical implications of this finding are less well understood. In medical practice, E/A < 1 is considered to represent a mild degree of diastolic dysfunction. 7,8 The identification of variables related to diastolic function represents an area of clinical interest. Doppler indices of left ventricular diastolic filling rates have been demonstrated to vary in different degrees with age, body mass index, and heart rate. 9-13 There is scant information on the relationship between left ventricular filling pattern and autonomic nervous system activity. In a sample of 31 healthy subjects, a poor correlation was observed between the mitral diastolic flow velocities and the HRV indices. 14 From the Heart Institute (Incor), University of Sa ˜ o Paulo Medical School, Sa ˜o Paulo, Brazil. Reprint requests: Alice Tatsuko Yamada, MD, Heart Institute (InCor), University of Sa ˜ o Paulo Medical School, General Outpatient Clinics, Dr. Ene ´ as de Carvalho Aguiar, 44, CEP 05403-000, Sa ˜ o Paulo, Brazil (E-mail: alice.yamada@incor.usp. br). 0894-7317/$36.00 Copyright 2010 by the American Society of Echocardiography. doi:10.1016/j.echo.2010.04.007 762