The association of positive antinuclear antibodies with the clinical and hemodynamic features of 43 patients with primary pulmonary hypertension and 16 patients with secondary pulmonary hypertension was investigated. Each patient had determinations of antinuclear antibodies using a KB cell substrate immunofluorescent test. Of the patients with primary pulmonary hypertension, 40% had positive antinuclear antibodies at titers of 1:80 dilutions or greater. There were no differences between patients with primary pulmonary hypertension and positive antinuclear antibodies compared with those with negative antinuclear antibodies in relation to clinical or hemodynamic status. A 6% incidence raie of antinuclear antibodies was found in patients with secondary pulmonary hypertension, similar to that in the normal population. The clinical, hemodynamic, serologic and histologic similarity between patients with primary pulmonary hypertension and those with unexplained pulmonary hypertension associated with collagen vascular disorders suggests that primary pulmonary hypertension in some patients may represent a collagen vascular disease confined to the lungs. The frequency of positive antinuclear antibody tests would place primary pulmonary hypertension between rheumatoid arthritis and scleroderma in the spectrum of collagen vascular diseases. Further studies are necessary, however, before one might expect that immunosuppressive therapy would be beneficial to these patients.
The duration of the acceleration phase of pulmonary systolic flow was measured by pulsed Doppler echocardiography in 39 normal subjects and 67 patients with heart disease to evaluate the reliability of this Doppler index as an estimate of pulmonary arterial pressure. The mean (SD) Doppler index in patients with abnormal mean pulmonary arterial pressure (greater than 15 mm Hg) was significantly shorter than that in normal subjects (110 (30) ms vs 150 (10) ms). The Doppler index was significantly related to the mean pulmonary arterial pressure (r = -0.75) the pulmonary blood flow (r = 0.46), and the total pulmonary vascular resistance (r = -0.68). Forty four of 45 patients with an abnormal index (less than or equal to 120 ms) showed abnormal mean pressure (greater than 15 mm Hg). Without exception patients with a low index (less than or equal to 90 ms) had distinct pulmonary hypertension (greater than or equal to 25 mm Hg). Twelve of 22 patients with a normal index (greater than or equal to 130 ms), however, also showed abnormal pressures. Nine of the 12 had an atrial septal defect and they had high pulmonary arterial pressure associated with high blood flow. Eighteen patients with valvar heart disease, whose mean pulmonary arterial pressure ranged from 16 mm Hg to 24 mm Hg, had a significantly shorter acceleration phase and a higher total vascular resistance than 11 patients with atrial septal defect in whom the pressure range was similar (120(20) ms vs 140 (20) ms, 3.8 (1.1) hybrid resistance unit vs 1.6 (0.5)). Thus although the acceleration time of the pulmonary systolic flow is useful for the evaluation of pulmonary hypertension, it is a complex index that is affected not only by pulmonary arterial pressure but also by pulmonary blood flow and pathological changes in the pulmonary vascular bed.,Myelopathy is a well recognised but rare association withMycobacterium tuberculosis infection, but has not been described with atypical mycobacteria. We report two cases of disabling myelopathy in association with pulmonary infection byMycobacterium kansasii andMycobacterium malmoense; the myelopathy is presumed to be a para-infectious phenomenon.
Factors predicting life expectancy in primary pulmonary hypertension have not been well defined. Thirty four cases of primary pulmonary hypertension that had been followed up until death or for at least five years were reviewed retrospectively. Patients were divided into three groups: 18 patients who died within five years of presentation to hospital; 12 who survived more than five years; and four who improved and who lived for more than five years. The age at onset was similar in the three groups and, like symptoms and sex, did not predict life expectancy. Right heart failure during the course of the disease was associated with a poor outcome. Radiographic evidence of cardiac enlargement and evidence of right heart strain on electrocardiogram at presentation was also predictive of survival for less than five years. Pulmonary arteriolar resistance was higher and cardiac output lower in those with the shortest survival times. There was no relation between pulmonary artery pressure and length of survival. Systemic resistance varied directly with pulmonary resistance and served to maintain systemic pressure. Presentation in or after pregnancy and patency of the foramen ovale were associated with longer survival. In four patients there was evidence of regression of the disease by cardiac catheterisation and lung histology. Primary pulmonary hypertension is a heterogeneous condition in which life expectancy varies widely.
To evaluate pulmonary vasoreactivity in children and young adults with primary pulmonary hypertension, we performed cardiac catheterizations on nine patients with primary pulmonary hypertension (nine months to 23 years old) and made hemodynamic measurements: 1) before and after infusing prostacyclin, and 2) before and after administering sublingual nifedipine. Based upon the response to prostacyclin, patients were divided into responders and nonresponders using the following criteria: 1) 20 percent or greater decrease in mean pulmonary arterial pressure; 2) an increase in cardiac index; and 3) no change, or a decrease in the pulmonary vascular resistance to systemic vascular resistance ratio. By these criteria, five of the nine patients had a reactive pulmonary vascular bed and responded to prostacyclin administration. In addition, they all responded to nifedipine. The remaining four did not respond to either drug. There was a close correlation (r=0.85, p<0.01) between the magnitude of the pulmonary vasodilator response to treatment with prostacyclin and nifedipine. There was also a significant inverse correlation between the age of the patient at the time of the study and the pulmonary vasodilator response to administration of prostacyclin (r=0.91, p<0.01) and nifedipine (r=0.82, p<0.01); , both drugs produced a greater fall in pulmonary arterial pressure in younger patients with primary pulmonary hypertension than in older ones.
In patients with primary pulmonary hypertension, competition between the right and left ventricles for the limited pericardial space results in distortion of left ventricular geometry reflected in displacement of the ventricular septum toward the left ventricular cavity. Left ventricular shape is most dramatically deranged at end-systole and early diastole, suggesting the possibility that the distribution of left ventricular diastolic filling might be altered. To investigate this hypothesis, nine patients with primary pulmonary hypertension and nine normal individuals were studied with echocardiographic techniques. Left ventricular isovolumic relaxation time was significantly prolonged in patients with primary pulmonary hypertension by comparison with normal individuals (129 ± 36 versus 53 ± 9 ms, p < 0.005) and the fraction of the transmitral flow velocity integral occurring in the first half of diastole was significantly less than in normal individuals (38 ± 14% versus 70 ± 9%, p < 0.005). Measurement of fractional changes in short-axis left ventricular cavity area similarly demonstrated that in patients with primary pulmonary hypertension fractional early diastolic cavity expansion (32 ± 11%) was significantly less than in normal individuals (78 ± 9%, p < 0.005). In patients with primary pulmonary hypertension, the ventricular septum was abnormally flattened toward the left ventricular cavity at end-systole (normalized septal curvature 0.04 ± 0.19) and remained that way throughout early diastolic filling but returned toward normal at end-diastole (normalized septal curvature 0.68 ± 0.19, p < 0.005). Thus, in patients with primary pulmonary hypertension end-systolic and early diastolic deformation of the left ventricle by septal flattening toward the left ventricular cavity is associated with relative underfilling of the left ventricle in early diastole and redistribution of left ventricular filling into late diastole. The reliance on late diastolic filling and atrial systole to maintain left ventricular preload in primary pulmonary hypertension may have important implications for the use of vasodilators in this disease.
Extracorporeal membrane oxygenation (ECMO) has been available since 1975 as a therapy of last resort to provide adequate oxygenation for term infants with acute lung disorders that do not respond to maximal medical therapy. Virtually all term infants with serious lung disease have persistent pulmonary hypertension of the newborn (PPHN) characterzied by significant right-to-left shunting of blood and severe diffusion defects manifested as increased alveolar-arterial oxygen gradients (AaDO ). Criteria for initiation of ECMO therapy have been developed in several institutions but at the present time there are no universal criteria applicable to all infants with PPHN. We have attempted to establish entry criteria that may be used for different populations of infants with PPHN. Based on a retrospective review of 30 infants with PPHN in our institution, we have defined standards of maximal medical therapy. An alveolar-arterial oxygen difference (AaDO ) of ≥610 for 8 hours has been shown to be associated with 79% mortality in this population. This AaDO /time interval is established as a major criterion for institution of extracorporeal membrane oxygenation.
Despite the preponderance of primary pulmonary hypertension (PPH) in young female subjects, documented cases of PPH in association with pregnancy are uncommon. During a 12-month period, 73 female patients with PPH were evaluated as potential recipients of a heart-lung transplant; and in six (8 percent), PPH appeared to be related to pregnancy. Histologic confirmation of the diagnosis was available in four patients, and other causes of pulmonary hypertension were excluded as far as possible in the remaining two patients.