This study shows a similar response of LV diastolic properties to submaximal normoxic exercise in HAPE-S and control subjects, although the former group had a larger increase in pulmonary artery pressures. Similarly, at high altitude, the increase in pulmonary pressures and changes in LV diastolic function did not go in parallel, and pharmacologic reduction of pulmonary artery pressures by HAPE prophylaxis did not uniformly affect LV diastolic function. Therefore, impairment of LV filling by isolated acute pulmonary hypertension appears to be irrelevant in subjects with normal ventricles. Additionally, our data provide little evidence for diastolic dysfunction of the LV in this setting.
At high altitude, an abnormal LV filling pattern has been described in previous studies. Ventricular interaction due to a hypoxia-induced rise in pulmonary artery pressures has been supposed to represent the underlying mechanism. One study performed at low altitude supported this hypothesis: the E/A ratio decreased in HAPE-S subjects at peak exercise and during acute hypoxia at rest, which was interpreted as impairment of LV relaxation. In our study, we did not find any exercise-induced differences in LV diastolic filling between HAPE-S and control subjects at a moderate workload despite a significantly higher increase in RVPG in HAPE-S subject. The difference between the study by Grunig et al and our results could tentatively be explained by differences in exercise workload. Whereas in the former report, mitral inflow measurements were performed at peak exercise, we assessed RVPG and the E/A ratio simultaneously at a workload of 40% of the individual peak exercise capacity. However, Grunig et al only assessed E/A ratio as parameter of diastolic function, which is significantly influenced by heart rate and therefore not suitable as a sole measure of diastolic function. In addition, it is surprising that control subjects did not show any decrease in E/A in response to exercise. Furthermore, E/A fusion is likely to occur at peak exercise, which might complicate the interpretation of the mitral inflow pattern.
The difference between HAPE-S and control subjects in RVPG increase in response to exercise at low altitude was not observed between the study groups at high altitude. However, the absolute RVPG values at high altitude, at rest as well as during exercise, were significantly different between groups with highest values in the placebo group. The vanishing difference in increases caused by exercise may have resulted from the fact that particularly in patients treated with placebo, RVPG values were already elevated at rest, whereas the resting levels at low altitude were normal in all subjects.
The two prophylactic treatments against HAPE reduced pulmonary artery pressures comparably at 4,559 m. However, they had a different effect on LV filling. In HAPE-S subjects treated with dexameth-asone, E/A was unchanged at high altitude, whereas subjects receiving tadalafil showed changes similar to those observed in the placebo group. These differences contributed to the fact that changes in pulmonary artery pressures from 490 to 4,559 m did not correlate with corresponding changes in E/A. It is likely that this observation is primarily related to differences in heart rate. More medical news on My Canadian Pharmacy. It has been speculated that the effect of dexamethasone on heart rate is related to a favorable modulation of the increased sympathetic activity at high altitude. This hypothesis is supported by experimental evidence from hypobaric hypoxia. Irrespective of these pathophysiologic considerations, our data suggest that there is no relevant coupling between acute changes in pulmonary artery pressures and LV diastolic properties at high altitude.
In agreement with previous data, we found atrial reversal in the pulmonary veins to be increased at high altitude as a potential marker of LV diastolic dysfunction. However, this may not prove diastolic dysfunction because atrial contraction may be influenced by sympathetic stimulation and changes in heart rate. Therefore, an increase in atrial reversal may occur even without alteration of LV relaxation. Still, mild changes in diastolic properties at high altitude could represent compensated diastolic dysfunction. However, based on our data, a mechanism other than ventricular interaction due to acute changes in pulmonary artery pressures would have to be discussed as a contributing causative factor.
An important question is whether LV dysfunction might occur with physical stress at high altitude and therefore facilitate development of HAPE. In our study, LVEF significantly increased with exercise with no difference in response between the study groups. This is in accordance with previous data obtained under conditions simulating an altitude of 8,840 m, implying that LV systolic function is not hampered at high altitude.
According to our data, not only LVEF but also echocardiographically estimated LV filling pressures seem to be largely unaffected by altitude exposure, From low to high altitude, no increase in E/E’ was observed in our study. Interestingly, the ratio slightly increased at both altitudes in response to exercise, irrespective of whether subjects were susceptible to HAPE or not, and irrespective of the magnitude of the pulmonary artery pressure increase. The slight increase in E/E’ during exercise differs from previous data in middle-aged normal control subjects, in whom the ratio was reported to remain unchanged. The reason for this difference is not clear. Possible explanations might be the extraordinary training state and the young age of the investigated mountaineers. Athletes have been shown to exhibit higher E-wave velocities during exercise when compared to sedentary control subjects. Thus, a vigorous early LV filling phase might have contributed to the slightly increased E/E’ ratio. Of importance, the exercise-induced changes in E/E’ at 4,559 m were similar between the different groups, suggesting that LV diastolic function in HAPE-S subjects is not relevantly deteriorated by physical activity. Previously, an increase in LV filling pressures resulting from vigorous exercise at high altitude has been discussed as a possible contributor to development of HAPE. However, invasive hemodynamic stud-ies in patients with overt HAPE suggest no relevant pathomechanical role of increased LV filling pressures in the development of HAPE.
The noninvasive nature of Doppler echocardiography represents a limitation of our study. Although the use of Doppler echocardiography has been well established in the estimation of pulmonary artery pressures, the correlation with measurements derived from right-heart catheterization may vary depending on the underlying condition. In high-altitude medicine, however, echocardiographic and invasive measurements of pulmonary artery pressure have shown a good correlation. Furthermore, the increased pulmonary artery pressure reactivity observed in HAPE-S subjects in response to exercise is in agreement with previous noninvasive and invasive studies.
The assessment of E/E’ has been validated for prediction of LV end-diastolic pressure by comparison of echocardiographic data to simultaneously performed invasive measurements. Still, it could be argued that at high altitude, the situation may be different due to the effect of hypoxia on myocardial tissue velocity. Our observations, however, are in line with data derived from an invasive study at high altitude showing that left atrial pressures are low under resting conditions in untreated HAPE-S mountaineers with or without apparent HAPE.
Our study represents a unique model to investigate the hemodynamic impact of ventricular interaction due to isolated acute pulmonary hypertension in otherwise healthy subjects. LV diastolic dysfunction induced by exposure to high altitude was very mild at best or even nonexistent. Importantly, there appears to be no relevant coupling between acute increases in pulmonary artery pressures and changes in LV diastolic function. Thus, our data question the concept of significant ventricular interaction in the setting of acute pulmonary hypertension.