Exercise intolerance

Abstract

Exercise intolerance is the primary symptom of chronic diastolic heart failure. It is part of the definition of heart failure and is intimately linked to its pathophysiology. Further, exercise intolerance affects the diagnosis and prognosis of heart failure. In addition, understanding the mechanisms of exercise intolerance can lead to developing and testing rational treatments for heart failure. This article focuses on the fundamental principles of exercise physiology and on the assessment, pathophysiology, and potential treatment of exercise intolerance in diastolic heart failure.

Figure 1

Excellent reproducibility of peak exercise VO2 in older heart failure patients, including those with LV ejection fraction. Group data shown in top panel; representative patient with 15 second averaged data shown in bottom. From Marburger et al, Am J. Cardiol 1998;82:905–909.

Figure 2

Exercise oxygen consumption (VO₂) during peak exhaustive exercise (left panel) and during submaximal exercise at the ventilatory anaerobic threshold (right panel) in age matched normal subjects (NO), elderly patients with heart failure due to systolic dysfunction (SD), and elderly patients with heart failure with normal systolic function, presumed diastolic dysfunction (DD). Exercise capacity is severely reduced in patients with diastolic heart failure compared to normals (p<0.001) and to a similar degree as in those with systolic heart failure. Overall, peak exercise VO₂ was 33% lower in the women compared to the men (not shown). Data from Kitzman DW, Little WC, Brubaker PH, Anderson RT, Hundley WG, Marburger CT et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 2002; 288(17):2144–2150.

Figure 3

Potential mechanisms of exercise intolerance from the factors of the Fick Equation.

Figure 4

Cardiovascular function assessed by invasive cardiopulmonary exercise testing in patients with heart failure and normal systolic function (open boxes) and age-matched normals (closed boxes). The primary components of the Fick equation for oxygen consumption, cardiac output and arteriovenous oxygen difference, are shown in panels A and B, respectively. The components of cardiac output, stroke volume and heart rate, are shown in panels C and D. The X-axis is exercise workload in kpm/min; 150 kpm/min is equivalent to 25 watts. From Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan M. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 1991; 17:1065–1072.

Figure 5

The components of the LV stroke volume response during exercise, LV ejection fraction, end-systolic volume, end-diastolic volume, and LV filling pressure, are shown in panels A–D. Not shown are systolic and mean arterial pressure, which was not different between groups. Key is same as for Figure 4. From Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan M. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 1991; 17:1065–1072.

Figure 6

LV diastolic function assessed by invasive cardiopulmonary exercise testing. Key is the same as for Figure 4. The pressure-volume relation was shifted upward and leftward at rest. In the patients with exercise, LV diastolic volume did not increase despite marked increase in diastolic (pulmonary wedge) pressure. Due to diastolic dysfunction, failure of the Frank-Starling mechanism resulted in severe exercise intolerance. From Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan M. Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 1991; 17:1065–1072.

Figure 7

Comparison of characteristic central and peripheral cardiovascular response to exercise in patients with heart failure associated with severe LV systolic dysfunction versus normal LV ejection fraction. See text for discussion.

Figure 8

Peak exercise oxygen consumption (y-axis, in ml/kg/min) in heart failure patients with and without chronotropic incompetence (CI). Those with chronotropic incompetence have more severe exercise intolernace, suggesting a contributory role for CI. Adapted from Brubaker et al, J Cardiopulm Rehab, 2006;26:86–89.

Figure 9

Heart rate acceleration during exercise in controls (CON) and patients with heart failure and preserved ejection fraction (HFPEF). From Kass et al; Circulation 2006;114:2138–2147.

Figure 10

Data and images from representative subjects from healthy young, healthy elderly, and elderly patients with diastolic heart failure. Maximal exercise oxygen consumption (V0₂max), aortic distensibility at rest, and left ventricular mass:volume ratio. Patients with diastolic heart failure have severely reduced exercise tolerance (V0₂max) and aortic distensibility and increased aortic wall thickness. Adapted from Hundley WG, Kitzman DW, Morgan TM, Hamilton CA, Darty S.N., Stewart KP et al. Cardiac cycle dependent changes in aortic area and aortic distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance. J Am Coll Cardiol 2001; 38(3):796–802.

Figure 11

There is a close relationship between peak exercise VO₂ (horizontal axis) and proximal aortic distensibility (vertical axis) in a group of 30 subjects (10 healthy young, 10 healthy old, and 10 elderly DHF patients). Each symbol represents the data from 1 participant. From Hundley WG, Kitzman DW, Morgan TM, Hamilton CA, Darty S.N., Stewart KP et al. Cardiac cycle dependent changes in aortic area and aortic distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance. J Am Coll Cardiol 2001; 38(3):796–802.

Figure 12

Flow mediated arterial dilation (FMAD) of the femoral artery by phase contrast magnetic resonance imaging in normal subjects, elderly patients with heart failure and normal ejection fraction (HFNEF) and patients with heart failure and reduced ejection fraction (HFREF). FMAD is severely reduced in HFREF but is relatively preserved in HFNEF compared to age matched healthy normal subjects. From Hundley WG, Bayram E, Hamilton CA, Hamilton EA, Morgan TM, Darty SN et al. Leg flow-mediated arterial dilation in elderly patients with heart failure and normal left ventricular ejection fraction. Am J Physiol Heart Circ Physiol 2007; 292(3):H1427–H1434.

Figure 13

Plots of peak systolic blood pressure and exercise duration during baseline, during placebo, and during losartan in a randomized, controlled, cross-over trial. Treatment with the angiotensin-II antagonist losartan increased exercise time. From Warner JG, Metzger C, Kitzman DW, Wesley DJ, Little WC. Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise. J Am Coll Cardiol 1999; 33:1567–1572.

Figure 14

Effect of alegebrium on left ventricular mass (top panel) and tissue Doppler early diastolic velocity at the mitral annulus in older patients with diastolic heart failure. From Little WC, Zile MR, Kitzman DW, Hundley WG, O’Brien T.X., deGroof RC. The Effect of Alagebrium Chloride (ALT-711), a Novel Glucose Cross-Link Breaker, in the Treatment of Elderly Patients with Diastolic Heart Failure. J Card Fail 2005 5 A.D.; 11(3):191–195.