Chest
Volume 147, Issue 4, April 2015, Pages 1072-1079
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Original Research Pulmonary Vascular Disease
Exaggerated Pulmonary Hypertension and Right Ventricular Dysfunction in High-Altitude Dwellers With Patent Foramen Ovale

https://doi.org/10.1378/chest.14-1353Get rights and content

Abstract

BACKGROUND: There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems.

METHODS: We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure.

RESULTS: The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg,P< .001) and a blunted increase in fractional area change of the right ventricle (3% [−1%, 5%] vs 7% [3%, 16%],P= .008) during mild exercise.

CONCLUSIONS: These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov

Section snippets

Study Design and Participants

The study population consisted of 35 male patients with CMS and 22 healthy male HA dwellers living permanently in the city of La Paz or its surroundings (3,600-4,000 m altitude), enrolled consecutively in the study. All participants had typical Aymara surnames and self-identified themselves as Aymaras (the major indigenous population living in this region).

The patients with CMS were recruited at the Instituto Boliviano de Biologia de Altura, where the diagnosis of CMS was established based on

Baseline Characteristics

A PFO was found in 18 of the 57 participants (32%), of whom four had a PFO grade I, four had grade II, and 10 had grade III. Age, proportion of patients with CMS, and other baseline characteristics were similar between participants with and without a PFO (Table 1). A PFO grade I or II was found in four of 35 patients with CMS (11%) and in four of 22 healthy HA dwellers (18%), whereas a PFO grade III was found in six of 35 patients with CMS (17%) and four of 22 healthy subjects (18%) (P= .96).

Arterial Oxygen Saturation, Pulmonary Hemodynamic, and RV Variables at Rest

Discussion

In disease states associated with hypoxemia at low altitude, a PFO is associated with increased pulmonary artery pressure.6, 7 Surprisingly, in HA dwellers there is no information on the prevalence of PFO and its potential consequences on pulmonary artery pressure and RV function. Here, we believe for the first time, we show that although the prevalence of PFO in HA dwellers (32%) was similar to the one reported in low-altitude populations,24 its presence was associated with important

Conclusions

In conclusion, we show, for the first time to our knowledge, that in HA dwellers, the presence and the size of a PFO appear to have important hemodynamic consequences. At rest it's presence was associated with RV enlargement and, even more importantly, during mild exercise expected to be frequently associated with daily activity, a PFO in HA dwellers was related to exaggerated pulmonary hypertension and pulmonary vasoconstriction that was associated with RV enlargement and dysfunction.

Acknowledgments

Author contributions:R. B. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. S. F. R., E. R., Y. A., and U. S. contributed to the study concept and design; R. B., L. P., S. F. R., E. R., and Y. A. contributed to the acquisition of the data; R. B., L. P., S. F. R., and U. S. contributed to the analysis and interpretation of data; R. B. and U. S. contributed to the drafting of the manuscript; L. P., S. F. R.,

References (32)

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    Cardiovascular changes in individuals living at high altitudes include PH, right ventricular hypertrophy, and polycythemia [12,14,15]. In addition, the presence of a PFO in humans living at high altitude has been associated with increased pulmonary vasoconstriction and right ventricular systolic dysfunction compared with those without PFO [16]. It has also been reported that in mountaineers susceptible to high altitude pulmonary edema, there is a 4-fold increase in the frequency of PFO compared with those resistant to this condition, with more substantial hypoxemia appreciated in those with PFO [17].

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    2016, Chest
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    For technical reasons, echocardiography could not be performed in three patients with CMS and three control subjects. To evaluate the presence of a PFO, in 11 patients with CMS and 4 control subjects, transesophageal echocardiography was performed as previously described,24 in combination with injection of echocardiographic contrast medium.34,35 The diagnosis of PFO required the crossing of bubbles from the right to the left atrium within four heart beats after the release of the strain.

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Funding/Support:The authors have reported toCHESTthat no funding was received for this study. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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