Ventilation variability inversely correlates to ejection fraction in heart failure

To the Editors:

Heart failure is currently considered a systemic disease. In this context, there is growing interest in cardiopulmonary interactions during rest, sleep and exercise 1. Periodic breathing during exercise is characterised by regular waxing and waning of minute ventilation (V’_E) due to oscillations in central respiratory drive. Periodic breathing independently predicts mortality in heart failure patients 2, but is not directly correlated with low left ventricular ejection fraction. For example, the occurrence of periodic breathing could predict cardiac mortality in patients who were waiting for cardiac transplantation, independent of ejection fraction 2.

Clinical experience shows that some heart failure patients exhibit ventilatory oscillations during exercise testing without achieving the established criteria of periodic breathing (minimum of three regular oscillations; deviation of three consecutive cycle lengths within 20% of their average; and minimal ventilatory oscillation of 5 L) 2. We hypothesised that the analysis of time-domain variability of respiratory variables during exercise could add important clinical information, detecting changes of insufficient magnitude to be classified as periodic breathing. Cardiopulmonary exercise tests in 17 heart failure patients (53% male; mean±sd age 59±9 yrs; ejection fraction 23±6%) under standard treatment were retrospectively analysed following approval of the Research Ethics Committee of the National Institute of Traumatology and Orthopedics (Ministry of Health, Brasilia, Brazil). All maximal progressive cardiopulmonary exercise tests were performed on an electromagnetically braked cycle ergometer (Medifit 400L; Medical Fitness Equipment, Maarn, the Netherlands), with work-rate increments of 5 W every 1 min at 60 rpm until exhaustion. V’_E, respiratory frequency (f_R) and tidal volume (V_T) were registered on a breath-by-breath basis using a computerised system (Vmax 229; SensorMedics, Buena Vista, CA, USA). The sd and root mean square successive differences (RMSSD) of V’_E, f_R and V_T during exercise testing were calculated for each patient. Considering that the number of observations has a direct influence on measures of variability, and that patients had exercised until exhaustion and thus time to exhaustion was not the same for all patients, variability (sd and RMSSD) was normalised using the number of respiratory cycles, reducing the probability that variability could be greater due to a greater number of observations registered in longer tests (sd/n and RMSSD/n, respectively). A complete two-dimensional echocardiogram was obtained at rest. Left ventricular ejection fraction was calculated using a modified Simpson’s biplane method.

Ejection fraction was inversely correlated with V’_E and f_R variability but not with V_T variability (table 1).

Although time-domain variability of breathing variables during rest has previously been used to predict success of weaning from mechanical ventilation 3, to our knowledge, this is the first time that this analysis has been applied to exercise data from heart failure patients. The present results show that patients with lower ejection fractions exhibit greater variability in V’_E and f_R throughout exercise testing. The calculations presented can be easily performed, and may add important clinical information in heart failure patients. Further studies evaluating the prognostic value of time-domain variability of V’_E and f_R during exercise are warranted.

• ©ERS 2010