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Usefulness of Right-to-Left Shunting and Poor Exercise Gas Exchange for Predicting Prognosis in Patients With Pulmonary Arterial Hypertension

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We hypothesized that the longitudinal changes in peak oxygen uptake, ventilatory efficiency, and exercise-induced right-to-left shunting in patients with pulmonary arterial hypertension (PAH) would predict outcomes better than baseline measurements alone. Patients with PAH die prematurely. Identifying prognostic markers is critical for treating patients with PAH; however, longitudinal prognostic information of PAH is limited. We enrolled 103 patients with PAH into a long-term, prospective outcome study using serial cardiopulmonary exercise testing to measure the peak oxygen uptake, ventilatory efficiency (ratio of ventilation to carbon dioxide output at the anaerobic threshold), right-to-left shunting, and other factors in patients treated with optimal therapy. The patients were followed up for a mean of 4.7 years. During the study period, 20 patients died, and 3 underwent lung transplantation. The baseline peak oxygen uptake and ventilatory efficiency was 0.79 L/min and 49 (normal <34), respectively, reflecting severe disease. Poorer ventilatory efficiency and greater New York Heart Association classification were associated with poor outcome at baseline and at follow-up. On multivariate analysis, the persistence or development of an exercise-induced right-to-left shunt strongly predicted death or transplantation (p <0.0001), independent of the hemodynamics and all other exercise measures, including peak oxygen uptake and ventilatory efficiency. The absence of a shunt at baseline was associated with a 20% rate of nonsurvival, which decreased to 7% at follow-up. A poorer ventilatory efficiency appeared to be associated with a poor outcome in patients without a shunt. In conclusion, a persistent exercise-induced right-to-left shunt and poor ventilatory efficiency were highly predictive of poor outcomes in patients with pulmonary arterial hypertension.

Section snippets

Methods

We prospectively enrolled 103 patients with idiopathic PAH (IPAH), familial PAH, and associated PAH (APAH), as defined by currently accepted diagnostic World Health Organization group I criteria9 into a long-term, noninvasive outcome study evaluating serial CPET measurements. All patients underwent diagnostic right heart catheterization with measurements of the right atrial, right ventricular, pulmonary arterial, and pulmonary capillary wedge pressure and cardiac output. Patients with disorders

Results

All patients survived at least to their second CPET. The patients were followed up for a mean of 4.7 years after their first CPET. The baseline patient demographics, CPET findings, and invasive hemodynamics are listed in Table 1. Our population was mostly women, consistent with previously reported cohorts from our institution.2 The baseline peak oxygen uptake and ratio of ventilation to carbon dioxide output at the anaerobic threshold was 0.79 ± 0.26 L/min and 49 ± 13 (normal <34),

Discussion

Although previous studies have demonstrated the prognostic utility of CPET in patients with PAH,5 our study is the first to evaluate the prognostic value of repeated CPET measurements. In addition, our study is the first to show that an exercise-induced right-to-left shunt predicts a poorer outcome in patients with PAH. Moreover, we have shown that, beyond the traditional measurements of exercise capacity and ventilatory efficiency, assessing shunt status is useful for predicting the outcome in

Acknowledgment

We are grateful to Joy Beckmann, RN, and Daisy Camanga, RN, for their tireless efforts in treating patients and to Chase Kissling, BS, Kevin Chang, BS, and Daniel Dumitrescu, MD, for their help in database organization.

References (19)

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    Citation Excerpt :

    Very interestingly, decreased PetCO2 during exercise is associated with the blunted cardiac output response to exercise in patients with heart failure [12]. In addition, a sudden and abrupt decrease of PetCO2 may indicate exercise-induced shunt (EIS) [13], which is a finding that has prognostic implications in PAH [14]. Despite sharing some pathophysiological mechanisms [15], patients with chronic thromboembolic pulmonary hypertension (CTEPH) are more likely to have proximal vascular obstructive lesions, which may lead to poorer right ventricle–pulmonary vascular coupling [16–18] and worse gas exchange abnormalities compared to idiopathic PAH (IPAH).

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This research was supported by grant 1 K23 RR17596-01 from the National Institutes of Health, Bethesda, Maryland, grant M01-RR00425 from the National Institutes of Health/Harbor-UCLA General Clinical Research Center, Torrence, California, and Beginning Grant-in-Aid 0160126Y from the American Heart Association, Dallas, Texas.

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