Total WBC count is confirmed to be an independent predictor of death/MI in patients with or at high risk for CAD, but greater predictive ability is provided by high N (Q4 >6.6 x 10(3)/microl) or low L counts. The greatest risk prediction is given by the N/L ratio, with Q4 versus Q1 (>4.71 versus <1.96) increasing the hazard 2.2-fold. These findings have important implications for CAD risk assessment.
Objectives
To determine the mechanisms responsible for reduced aerobic capacity (peak VO2) in heart failure patients with preserved ejection fraction (HFPEF).
Background
HFPEF is the predominant form of HF in older persons. Exercise intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with HF and reduced EF, the mechanism of exercise intolerance in HFPEF is less well understood.
Methods
Left ventricular volumes (2D echocardiography), cardiac output (CO), VO2 and calculated arterial-venous oxygen content difference (A-VO2 Diff) were measured at rest and during incremental, exhaustive upright cycle exercise in 48 HFPEF patients (age 69±6 years) and 25 healthy age-matched controls (HC).
Results
In HFPEF compared to HC, VO2 was reduced at peak exercise (mean±SE: 14.3±0.5 vs. 20.4±0.6 mL·kg min−1; p<0.0001) and was associated with a reduced peak CO (6.3±0.2 vs. 7.6±0.2 L·min−1, p<0.0001) and A-VO2 Diff (17±0.4 vs. 19±0.4 ml·dl−1, p<0.0007). The strongest independent predictor of peak VO2 was the change in A-VO2 Diff from rest to peak exercise (A-VO2 Diff reserve) for both HFPEF (partial correlant 0.58, standardized β coefficient 0.66; p=0.0002) and HC (partial correlant 0.61, standardized β coefficient 0.41; p=0.005)
Conclusions
Both reduced CO and A-VO2 Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-VO2 Diff reserve is an independent predictor of peak exercise VO2 suggests that peripheral, ‘non-cardiac’ factors are important contributors to exercise intolerance in these patients.
Most elderly persons with heart failure have a preserved left ventricular (LV) ejection fraction (HFPEF). The pathophysiology of this disorder is not well understood, and there are conflicting data regarding the role of decreased LV distensibility. To assess LV distensibility over a range of preload conditions while minimizing the large, confounding changes in contractility, afterload, and heart rate characteristic of exercise, we measured LV end-diastolic volume (EDV), stroke volume (SV), and cardiac output (CO) using two-dimensional echocardiography in 48 elderly (mean age, 69 yr) HFPEF patients and 25 healthy age-matched controls during quiet supine rest, 45 degrees head-up tilt (HUT), and 45 degrees head-down tilt (HDT). As a result, when compared with controls, HFPEF patients had reduced percent changes in EDV (-7 +/- 2 vs. -17 +/- 2%; P = 0.003), SV (-7 +/- 3 vs. -27 +/- 2%; P = 0.003), and CO (-6 +/- 4 vs. -34 +/- 4%; P = 0.001) during the transition from supine to HUT. HFPEF also had reduced percent changes in EDV (8 +/- 2 vs. 15 +/- 2%; P = 0.02), SV (11 +/- 3 vs. 21 +/- 3%; P = 0.002), and CO (1 +/- 4 vs. 12 +/- 4%; P = 0.04) during the transition from HUT to HDT. In conclusion, HFNEF patients have reduced LV distensibility in response to postural change, resulting in blunted EDV, SV, and CO. This provides further support for the hypothesis that a blunted Frank-Starling mechanism may contribute to the pathophysiology of HFPEF.
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