Diastolic heart failure accounts for over 50% of heart failure cases in the population greater than 65 and is an important health care problem for older Americans. Our current research shows that elderly patients with diastolic heart failure have severe exercise intolerance and that this improves with exercise training. However, less than 30% of the improvement is attributable to increased cardiac output. This suggests a potential role for impaired peripheral vasoregulation by compromising muscle perfusion. Our pilot data suggest that in elderly diastolic heart failure patients endothelial dependent flow mediated arterial dilation (FMAD) is substantially impaired, correlates with exercise capacity, and is increased after exercise training. The primary aims of this study are to perform an initial cross-sectional comparison of 60 elderly diastolic heart failure patients (symptomatic heart failure, a normal LV ejection fraction and no significant coronary or valvular heart disease or pulmonary disease) with matched healthy normal subjects and then to enter the patients into a randomized, controlled, single blinded trial of aerobic exercise training in order to test the following specific hypotheses: 1. Elderly diastolic heart failure patients have decreased FMAD compared to age and gender matched healthy normal subjects. 2. Exercise intolerance in elderly diastolic heart failure patients is associated with decreased FMAD. 3. Exercise training in elderly heart failure patients will improve FMAD and exercise capacity. 4. Improvements in exercise capacity will correlate with improvements in FMAD. A secondary aim is to examine relationship between FMAD and other determinants of ventricular-vascular coupling. Principle measurements include brachial artery FMAD and indexes of carotid artery stiffness by high resolution ultrasound; pulse wave velocity by tonometry; maximal and submaximal oxygen consumption and ventilatory anerobic threshold by expired gas analysis, and cardiac volumes by digital echocardiography. This study will assess the contribution of endothelial dysfunction to exercise intolerance in diastolic heart failure using a physiologically rational, widely applicable intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
2R01AG012257-04
Application #
2393266
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Project Start
1994-09-01
Project End
2001-06-30
Budget Start
1997-08-01
Budget End
1998-06-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Kitzman, Dalane W; Brubaker, Peter H; Herrington, David M et al. (2013) Effect of endurance exercise training on endothelial function and arterial stiffness in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. J Am Coll Cardiol 62:584-92
Haykowsky, Mark J; Herrington, David M; Brubaker, Peter H et al. (2013) Relationship of flow-mediated arterial dilation and exercise capacity in older patients with heart failure and preserved ejection fraction. J Gerontol A Biol Sci Med Sci 68:161-7
Haykowsky, Mark J; Brubaker, Peter H; Stewart, Kathryn P et al. (2012) Effect of endurance training on the determinants of peak exercise oxygen consumption in elderly patients with stable compensated heart failure and preserved ejection fraction. J Am Coll Cardiol 60:120-8
Haykowsky, Mark J; Brubaker, Peter H; John, Jerry M et al. (2011) Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction. J Am Coll Cardiol 58:265-74
Kitzman, Dalane W; Hundley, W Gregory; Brubaker, Peter H et al. (2010) A randomized double-blind trial of enalapril in older patients with heart failure and preserved ejection fraction: effects on exercise tolerance and arterial distensibility. Circ Heart Fail 3:477-85
Kitzman, Dalane W; Brubaker, Peter H; Morgan, Timothy M et al. (2010) Exercise training in older patients with heart failure and preserved ejection fraction: a randomized, controlled, single-blind trial. Circ Heart Fail 3:659-67
John, Jerry M; Haykowsky, Mark; Brubaker, Peter et al. (2010) Decreased left ventricular distensibility in response to postural change in older patients with heart failure and preserved ejection fraction. Am J Physiol Heart Circ Physiol 299:H883-9
Arena, Ross; Myers, Jonathan; Abella, Joshua et al. (2009) Influence of etiology of heart failure on the obesity paradox. Am J Cardiol 104:1116-21
Brubaker, Peter H; Moore, J Brian; Stewart, Kathryn P et al. (2009) Endurance exercise training in older patients with heart failure: results from a randomized, controlled, single-blind trial. J Am Geriatr Soc 57:1982-9
Moore, Brian; Brubaker, Peter H; Stewart, Kathryn P et al. (2007) VE/VCO2 slope in older heart failure patients with normal versus reduced ejection fraction compared with age-matched healthy controls. J Card Fail 13:259-62

Showing the most recent 10 out of 29 publications