Diastolic dysfunction predicts impaired aerobic capacity in older HIVinfected

Transcription

1 Diastolic dysfunction predicts impaired aerobic capacity in older HIVinfected men Hillary McClintic Virginia Tech Carilion School of Medicine John Gottdiener, MD Kristina Crothers, MD Adeel A. Butt, MD David Leaf, MD Alberta Warner, MD Matthew Freiberg, MD Kris Ann Oursler, MD

2 Diastolic Dysfunction General population: prevalence is 28% in adults >45 1 HIV infected persons have greater risk of diastolic dysfunction 2 OR = 2.4 compared with controls (P=0.019) Clinical factors associated with diastolic dysfunction in HIV-infected individuals 3 : Diagnosis of HTN Lower nadir CD4+ count Elevated fasting glucose level Elevated hscrp level 1 Redfield MM, Jacobson SJ, Mahoney DW, et al. JAMA Hsue PY, Hunt PW, Ho JE, et al. Circ Heart Fail Mondy KE, Gottdiener J, Overton ET, et al. Clin Infect Dis. 2011

3 Components of diastolic function: Left ventricular relaxation Left ventricular diastolic stiffness Left atrial function

4

5 How do we measure diastolic function?

6 E: velocity across mitral valve during early LV filling A: velocity across mitral valve during late LV filling (atrial contraction) E/A: reflection of LV relaxation normally

7 E : peak velocity of mitral annulus in the longitudinal plane during early diastolic filling - normally >8 cm/s E/e : reflects LV filling pressures normally <10

8 Diastolic Function Predicts Exercise Capacity in Non-HIV Infected LV filling pressure (E/e ) significantly correlated with peak oxygen uptake (VO 2 peak) in patients with isolated diastolic heart failure 1 Exercise capacity decreases with age As diastolic function becomes impaired, the decrease in exercise performance with age has greater magnitude 2 1 Guazzi M, Myers J, et al. J Cardiopulm Rehabil Prev Grewal J, Mccully RB, et al. JAMA. 2009

9 Peak oxygen uptake during exercise is reduced 40% in HIV-infected adults VO2 peak (ml/kg/min) Healthy HIV Age (year) K Oursler, AIDS HR, 2006

10 HTN is associated with Lower VO2peak in HIV * *p< 0.05 Oursler et al, AIDS Research HR, 2006

11 Objective of Study To investigate the association of diastolic function and aerobic capacity in HIVinfected men with no prior diagnosis or symptoms of coronary heart disease.

12 Methods Design: Cross-sectional study of HIV-infected veterans enrolled in the VACS CVD study at the Baltimore VA site Aerobic exercise capacity measured by gas exchange at peak exercise during treadmill testing (VO 2 peak) Diastolic function assessed using resting Doppler echocardiography to record measures such as: Early (E) and late (A) mitral inflow velocities Mitral annular longitudinal diastolic velocity (e or Em) Association of VO 2 peak with clinical characteristics was tested by linear regression models

13 Characteristic Age (mean (SD), years) 54.5 (6.5) Race Black 94% White 4% Other 2% Participants (n=101) BMI [median value (range), kg/m 2 ] 25 (17-40) Diagnosis of hypertension 59% Diagnosis of diabetes 18% Smoking status Current smoker 72% Former smoker 12% Never smoked 17% CD4+ count [median cells/mm 3 ] 428 HIV RNA non-detectable [ 400 copies/ml] 72% Receiving HAART 70%

14 LV relaxation is independently associated with VO2peak VO2 Peak (ml/(kg min)) VO 2 peak (ml/(kg min)) r = 0.30 p = <0.01 VO2 peak (ml/(kg min)) VO 2 peak (ml/(kg min)) r = 0.30 p = < E/A ratio Em = E' (based on medial measurement) (cm/sec) Ratio of early to late diastolic filling velocity Mitral annular velocity

15 VO2Peak and Mitral Annular Velocity (E ) Mean VO2 Peak (ml/(kg min)) VO 2 peak (ml/(kg min)) * E' >=8 cm/s E'<8 *p< 0.05 Older HIV-infected men with decreased mitral annular velocity (impaired LV relaxation) have significantly lower mean VO2Peak.

16 LV Filling Pressure is independently associated with VO2Peak VO 2 peak (ml/(kg min)) VO2 Peak (ml/(kg min)) E/e' medial r = p = 0.045

17 VO2 Peak (ml/(kg min)) VO 2 peak (ml/(kg min)) VO 2 peak (ml/(kg min)) VO2 Peak (ml/(kg min)) E/A ratio Em = E' (based on medial measurement) (cm/sec) p = p = VO2 Peak (ml/(kg min)) VO 2 peak (ml/(kg min)) E/e' medial p = 0.018

18 Conclusion Diastolic function is independently associated with aerobic exercise capacity in older HIV-infected men without history or symptoms of CHD. Easy to measure and detectable early allows opportunity for intervention Highlights importance of managing clinical factors associated with diastolic dysfunction in HIV-infected

19 Future Directions Investigation into the pathophysiologic mechanism of diastolic dysfunction in older HIV-infected men Markers of chronic inflammation (e.g. CRP, IL-6) Biomarkers of myocardial fibrosis Can exercise training improve diastolic function and aerobic exercise capacity in these individuals?

20 Acknowledgements Virginia Tech Carilion School of Medicine & Research Institute Leslie LaConte, Ph.D Michael Friedlander, Ph.D Salem VA Medical Center VACS ABC, R01HL (Freiberg)