Increased interbreath variability of gas exchange during exercise in children with cardiomyopathy

During exercise testing in patients with chronic heart failure and severely depressed left ventricular function, an increased variability of gas exchange with a phenomenon of periodic breathing with an oscillatory pattern in oxygen uptake (VO₂) has been recognised.¹ Previous studies were performed in adult patients with chronic heart failure related to ischaemic heart disease. The aim of the present study was to analyse whether an increased interbreath variability for gas exchange with an oscillatory pattern could also be identified during exercise in children with cardiomyopathy. Moreover, we also analysed whether this new parameter correlates with cardiac function.

Patients and methods

In all, 49 patients were used for this analysis. Twenty patients were studied with dilated cardiomyopathy (DCMP; mean (SD) age 11.7 (3.7) years). At a regular outpatient visit the patients were clinically investigated, and underwent an echocardiographic and electrocardiographic examination. Myocardial function was assessed by determination of the fractional shortening on the echocardiogram. The patients were compared with 29 age‐matched normal controls (Nl) (10.7 (2.8) years).

Maximal exercise test was performed on a treadmill. Speed was set at 5.6 km/h, and the inclination was increased by 2% every minute until exhaustion. Gas exchange was measured breath‐by‐breath. During exercise, the interbreath variability for VO₂ was calculated as the mean value of all absolute differences between the VO₂ of all single breaths during 1 min, and the mean of all these breaths and was expressed as a percentage of the mean value for VO₂ during that minute.²

Exercise capacity was assessed by determination of the maximal VO₂ or symptom‐limited VO₂ and was expressed as a percentage of the Nl mean value.²

Results

The left ventricular end diastolic diameter averaged 55.3 (9.3) mm in DCMP versus 41 (4.1) mm in Nl (p<0.001). The fractional shortening averaged 22.5 (7.4%) in DCMP versus 37.3 (4.2%) in Nl (p<0.001).

For submaximal exercise at 2% inclination, the variability for VO₂ amounted to 9.6 (5.4) for DCMP versus 7.1 (2.3%) for Nl (p = 0.006) and at 4% inclination 8.6 (3.9) for DCMP versus 6.2 (2) for Nl (p = 0.006).

In patients with DCMP an increased variability of VO₂ was found for four levels of exercise in half of the group, which exceeded the 95% confidence limit (CL) of Nl (variability >8%). In these patients an oscillatory pattern in VO₂ could also be observed. For the total group (patients with DCMP and Nl), at 2% inclination on the treadmill, significant negative correlations were found between the magnitude of the variability for the VO₂ and the VO₂ max (r = −0.47, p = 0.05) and the fractional shortening (r = −0.48; p = 0.05) as an estimate of myocardial function.

Maximal oxygen uptake in DCMP averaged 79.8 (17.3%) of Nl (p<0.005, patients v Nl).

Discussion

This study shows a high‐interbreath variability of VO₂ during graded exercise testing in patients with DCMP with a significantly increased variability of VO₂ in half of the patients. This increased variability with an oscillatory pattern for VO₂ correlates with a poor left ventricular function. In the present study, the prevalence of increased interbreath variability with an oscillatory pattern is higher than values reported in literature (10–20%).³,⁴ This may be explained by differences in methods such as duration of oscillations³,⁵ or comparing different time windows.⁴ In the present study, we defined an increased breath‐by‐breath variability as exceeding 8% (upper limit of 95% CL). In subjects with normal left ventricular function no oscillatory pattern of VO₂ was observed. A similar observation has been made in adult patients with DCMP and systolic dysfunction.¹ The underlying mechanism for an oscillatory pattern of VO₂ remains to be determined. Previous studies have shown that increased interbreath variability for VO₂ during exercise correlates with poor left ventricular function.⁵ Similarly, in the present study an increased interbreath variability of VO₂ was observed in the subjects with the lowest values for fractional shortening. Oscillatory changes of VO₂ during exercise correlate with an oscillatory pattern of pulmonary blood flow. In patients with reduced left ventricular function, Yajima³ showed during simultaneous breath‐by‐breath gas exchange measurements and beat‐to‐beat radionuclide recordings of ejection fraction oscillatory fluctuation for both parameters.

Increased interbreath variability with oscillatory changes of VO₂ may significantly influence the determination of the maximal value for VO₂. With modern gas analysis equipment data are often reported with a time window of 10–15 s. Therefore, if a patient has an increased interbreath variability of VO₂ with a periodic oscillatory breathing, the peak of this value may exceed the true VO₂max. The overestimation will depend upon the size of the oscillation and can amount up to 5 ml O₂/min/kg or up to 35% of the average VO₂.⁴ This can be equal to the effect of some interventions—for example, physical training, pharmacological treatment; such difference can therefore be important for managing patients during a work up for heart transplantation. To obviate these problems, a time interval of 60 s or minimally 30 s should be recommended.

Abbreviations

DCMP - dilated cardiomyopathy