Exercise oscillatory ventilation in systolic heart failure: an indicator of impaired hemodynamic response to exercise

Abstract

Background: Exercise oscillatory ventilation (EOV) is a noninvasive parameter that potently predicts outcomes in systolic heart failure (HF). However, mechanistic insights into EOV have been limited by the absence of studies relating EOV to invasive hemodynamic measurements and blood gases performed during exercise.

Methods and results: Fifty-six patients with systolic HF (mean±SEM age, 59±2 years; left ventricular ejection fraction, 30±1%) and 19 age-matched control subjects were studied with incremental cardiopulmonary exercise testing. Fick cardiac outputs, filling pressures, and arterial blood gases were measured at 1-minute intervals during exercise. We detected EOV in 45% of HF (HF+EOV) patients and in none of the control subjects. The HF+EOV group did not differ from the HF patients without EOV (HF-EOV) in age, sex, body mass index, left ventricular ejection fraction, or origin of HF. Univariate predictors of the presence of EOV in HF, among measurements performed during exercise, included higher right atrial pressure and pulmonary capillary wedge pressure and lower cardiac index (CI) but not Paco2 or Pao2. Multivariate logistic regression identified that low exercise CI is the strongest predictor of EOV (odds ratio, 1.39 for each 1.0-L · min(-1) · m(-2) decrement in CI; 95% confidence interval, 1.14-1.70; P=0.001). Among HF patients with EOV, exercise CI was inversely related to EOV cycle length (R=-0.71) and amplitude (R=-0.60; both P<0.001). In 11 HF+EOV subjects treated with 12 weeks of sildenafil, EOV cycle length and amplitude decreased proportionately to increases in CI.

Conclusion: Exercise oscillatory ventilation is closely related to reduced CI and elevated filling pressures during exercise and may be an important surrogate for exercise-induced hemodynamic impairment in HF patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00309790.

Figure 1

Exercise oscillatory ventilation was defined as ≥3 cyclical fluctuations of minute ventilation (V_E) during exercise with an amplitude >25% of the mean trough-to-trough V_E during that interval. Cycle Length (C_L), and Amplitude (Amp).

Figure 2

Mean ± SEM hemodynamic measurements at rest (time 0), and during the first 6 minutes of exercise in HF patients with and without exercise oscillatory ventilation (EOV) and in controls. (Panel A) cardiac indices; (Panel B) mean pulmonary arterial pressures (PAP); (Panel C) right atrial pressures (RAP); (Panel D) pulmonary capillary wedge pressures (PCWP).

Figure 3

Mean ± SEM arterial blood gas and minute ventilation values at rest (time 0), and during the first 6 minutes of exercise in HF patients with and without exercise oscillatory ventilation (EOV) and in controls. (Panel A) arterial pH; (Panel B) arterial PaCO₂; (Panel C) arterial PaO₂; (Panel D) minute ventilation (V_E).

Figure 4

Correlations between EOV parameters and cardiac performance; EOV amplitude is inversely related to cumulative cardiac index during exercise (ΣCI, Panel A), and right ventricular ejection fraction (RVEF, Panel C). EOV cycle length is also inversely related to cumulative cardiac index during exercise (ΣCI, Panel B), and right ventricular ejection fraction (RVEF, Panel D).

Figure 5

Correlations between EOV parameters and arterial blood gases; EOV amplitude was not related to cumulative PaO₂ (ΣCI, Panel A) or PaCO₂ (Panel C) during exercise. EOV cycle length was also not related to PaO₂ (Panel B) or PaCO₂ (Panel D).

Figure 6

Effect of sildenafil treatment on EOV amplitude and cycle length. Graphical depiction of EOV in two representative patients indicates that amplitude and cycle length of ventilatory oscillations are reduced by treatment with sildenafil. Arrows on the X axis denote onset of exercise. Following sildenafil treatment, EOV amplitude and cycle length diminish and oscillations resolve during late exercise.