Chest
Volume 115, Issue 5, May 1999, Pages 1321-1328
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Clinical Investigations
PULMONARY VASCULATURE
Pulmonary Hypertension and Cardiac Function in Adult Cystic Fibrosis: Role of Hypoxemia

https://doi.org/10.1378/chest.115.5.1321Get rights and content

Study objectives

To determine (1) the prevalence of pulmonary hypertension and cardiac dysfunction in adult cystic fibrosis (CF) patients with severe lung disease, (2) the relationship between these cardiovascular abnormalities and hypoxemia, and (3) the impact of subclinical pulmonary hypertension on survival.

Design

Single-blind, cross-sectional study.

Setting

Ambulatory clinic of the Adult CF program at a tertiary-level hospital.

Patients

Clinically stable patients with severe lung disease (FEV1 < 40% of predicted normal value) who were not receiving supplemental oxygen. A second cohort of patients in stable condition with less severe lung disease (FEV1 40 to 65% predicted) was also recruited to enable multivariate analysis for the determinants of pulmonary hypertension.

Measurements and results

Eighteen patients with severe lung disease (FEV1 28 ± 7% of predicted normal value) were initially studied. Each patient had overnight polysomnography, pulmonary function tests, and Doppler echocardiography. Arterial oxygen saturation (Sao2) was reduced during wakefulness (87.1 ± 6.1%) and fell during sleep (84.0 ± 6.6%) while transcutaneous Pco2 was normal during wakefulness (41.1 ± 6.9 mm Hg) and increased during sleep (46.6 ± 4.7 mm Hg). Left ventricular size, systolic function, and diastolic function were normal except in one patient who had had a previous silent myocardial infarction due to coronary artery disease. Qualitative assessment of right ventricular function was normal in all patients. Pulmonary artery systolic pressure (PASP) was increased (> 35 mm Hg) in seven patients without clinical evidence of cor pulmonale. Regression analysis was performed by combining these data with data from an additional 15 CF patients with moderately severe lung disease (FEV1 56.3 ± 8.9% predicted normal) who were recruited to a modified study protocol that included overnight oximetry, pulmonary function tests, and Doppler echocardiography. None of these patients had evidence of hypoxemia and only three had mild elevation of PASP (36, 37, and 39 mm Hg). Linear regression analysis revealed that PASP was significantly correlated with FEV1(r = −0.44; p = 0.013), and Sao2 during wakefulness (r = −0.60; p = 0.0003), during sleep (r = −0.56; p = 0.0008), and after 6 min of exercise (r = −0.75; p < 0.0001). Multivariate analysis revealed that awake Sao2 was a significantly better predictor of PASP than FEV1 (p = 0.0104). Clinical follow-up of the original cohort for up to 5 years revealed that mortality was significantly higher in those with pulmonary hypertension than those without pulmonary hypertension (p = 0.0129).

Conclusions

In adult CF patients with severe stable lung disease, left and right ventricular function is well maintained in the absence of significant coronary artery disease; pulmonary hypertension develops in a significant proportion of patients and is strongly correlated with oxygen status, independent of lung function; and subclinical pulmonary hypertension is associated with an increased mortality.

Section snippets

Patient Population

Adult patients (> 18 years old) with CF confirmed by an abnormal sweat test result were recruited from the Adult CF program at the Wellesley Hospital in Toronto. We recruited 18 patients with severe lung disease (FEV1 < 40% of the predicted normal value) and 15 patients with moderately severe lung disease (FEV1 40 to 65% predicted). All patients were in clinically stable condition over the month prior to the study with no exacerbations requiring antibiotic therapy or hospitalization. Patients

Patients With Severe Lung Disease

Four of the 18 patients studied were female and 14 were male. The average age was 30.2 years (range, 21 to 40) and the mean body mass index (BMI) was 21.9 kg/m2 (range, 18.3 to 31.2). Indices of pulmonary function are summarized in Table 1. All patients had severe, stable lung disease. Mild hypoxemia was present at rest, and two of our patients had evidence of CO2 retention with arterial Pco2 of 66 and 53 mm Hg.

Mean Sao2 and tco2 during wakefulness and sleep are summarized in Table 2. Mild

Discussion

Clinical cor pulmonale occurs in the terminal stages of CF and its onset carries a grave prognosis.28 The mean survival time from the onset of clinically apparent cor pulmonale has been reported to be as short as 8 months.2 The nearly universal finding of severe hypoxemia in association with clinical cor pulmonale is, therefore, not surprising. We chose to study patients with severe CF (FEV1 < 40% predicted) prior to the development of hypoxemia or clinically apparent cor pulmonale to

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