Our study revealed an acceptable agreement of the cardiac output assessment determined by thermodilution and C2H2 uptake in PAH patients, although we observed a large splay of single measurements. These differences, however, were not larger than those reported from patients with other cardiopulmonary diseases . Our findings are in accordance with an earlier trial by Hoeper et al. who reported that thermodilution and C2H2 rebreathing are equally accurate in patients with idiopathic PAH when being compared with the direct Fick method . In contrast, our study demonstrated that the agreement between thermodilution and the C2H2 technique was poor in patients suffering from CTEPH.
Several issues need to be discussed in this context. In our study CTEPH patients had lower CI values compared to the PAH subgroup. As C2H2 uptake tends to underestimate cardiac output in our CTEPH cohort and thermodilution might overestimate cardiac output in the presence of a low CI , the poorer agreement of both methods could be explained by a wider divergence of measurements. However, another trial has challenged this hypothesis indicating that thermodilution is equally accurate in a broad spectrum of cardiac output values .
Furthermore, mean FEV1 and the averaged FEV1/FVC ratios were significantly reduced in the CETPH cohort, possibly explaining the poorer agreement of both methods. As patients with concurrent lung diseases were excluded from our trial and both groups had similar mean BMI values, these findings might be explained by the older mean age in the CETPH subgroup. As the alveolar distribution of C2H2 might be affected by the reduction of FEV1/FVC, cardiac output measurements obtained by the C2H2 uptake method are probably less accurate in the CTEPH cohort.
In addition to that, an impaired gas exchange might contribute to the poorer agreement of both techniques in the CTEPH cohort, as the C2H2 technique is expected to fail in the presence of a relevant mismatching of ventilation to perfusion. Indeed, we found evidence of an uneven distribution of ventilation to perfusion in CTEPH patients primarily due to two different mechanisms, increased dead space ventilation and heterogeneous pulmonary perfusion.
Although there are some reports indicating that ventilation/perfusion matching is relatively well preserved in both conditions [12–14], there is evidence that increased ventilation/perfusion ratios in CTEPH are primarily caused by augmented dead space fractions [15, 16]. In our study Vd/Vt at peak exercise was significantly increased in CTEPH compared to PAH. These findings are in accordance with the report of Zhai and colleagues, who were able to show that significant differences in gas exchange exist between CTEPH and PAH due to differences in Vd/Vt . Dead space ventilation in pulmonary thromboembolism increases the gradient between arterial and end-tidal CO2 . Correspondingly, we found the mean a-etCO2 gradient to be significantly elevated among CTEPH patients compared to the PAH subgroup in our study. Similar findings have recently been made by Scheidl and co-workers , who found increased capillary to end-tidal CO2 differences in patients with CTEPH compared to those suffering from idiopathic PAH. Increased dead space ventilation might be the result of a more uneven perfusion pattern in CTEPH patients, possibly due to additional thrombus formation and a more proximal vascular occlusion, leading to heterogeneous perfusion defects . Areas with diminished blood flow and areas with increased blood flow coexist, while ventilation is more or less homogeneously distributed. As a result, there are areas with an increased ventilation/perfusion ratio or even dead space ventilation and others with a low ventilation/perfusion ratio. In contrast, PAH is characterized by an obstructive vasculopathy that bilaterally involves distal, medium to small size muscular arteries , possibly resulting in a more balanced distribution of perfusion and ventilation. Therefore, we speculate that compared to PAH patients, increased heterogeneity in pulmonary blood flow in comparison to ventilation might contribute to an inaccurate determination of cardiac output by the C2H2 method in CTEPH.
Our study is limited by the fact that cardiac output measurements determined by thermodilution and the C2H2 method were not performed simultaneously. Thus, the splay of single measurements might partially be explained by the physiological variations of cardiac output during the day. However, both techniques were performed shortly after each other without any change of medication in all study participants in order to minimize substantial fluctuations. Moreover, the results might have been influenced by different body positions, as right heart catheterizations were performed in supine position while patients were sitting when the C2H2 technique was performed. Thus, measurements by the C2H2 uptake method might tend to underestimate cardiac output, as preload decreases when subjects sit up. This circumstance possibly explains some of the very low cardiac output values measured by C2H2 uptake. Finally, we didn't evaluate the degree of tricuspid regurgitation, which is commonly present in patients with PH and might have influenced the accuracy of thermodilution in our study participants . As a consequence, thermodilution might have underestimated the cardiac output in the presence of severe tricuspid regurgitation.