Infants with persistent pulmonary hypertension have severe cyanosis even when they breathe high concentrations of oxygen. Although the pulmonary hypertension can be associated with other conditions (such as aspiration of meconium and sepsis), it may be idiopathic. Cardiac ultrasonography often reveals shunting of venous blood to the systemic circulation through the ductus arteriosus and the foramen ovale and no structural heart disease. Treatment with high fractions of inspired oxygen (FiO 2 ) and mechanical ventilation improves oxygenation in some infants with pulmonary-artery hypertension, but in many others it does not. Unless other treatments are used, the infants often die. Although . . .
ObjectivesThis study investigated the effects of dose step-down in patients with rheumatoid arthritis (RA) who achieved sustained disease control with baricitinib 4 mg once a day.MethodsPatients who completed a baricitinib phase 3 study could enter a long-term extension (LTE). In the LTE, patients who received baricitinib 4 mg for ≥15 months and maintained CDAI low disease activity (LDA) or remission (REM) were blindly randomised to continue 4 mg or taper to 2 mg. Patients could rescue (to 4 mg) if needed. Efficacy and safety were assessed through 48 weeks.ResultsPatients in both groups maintained LDA (80% 4 mg; 67% 2 mg) or REM (40% 4 mg; 33% 2 mg) over 48 weeks. However, dose reduction resulted in small, statistically significant increases in disease activity at 12, 24 and 48 weeks. Dose reduction also produced earlier and more frequent relapse (loss of step-down criteria) over 48 weeks compared with 4 mg maintenance (23% 4 mg vs 37% 2 mg, p=0.001). Rescue rates were 10% for baricitinib 4 mg and 18% for baricitinib 2 mg. Dose reduction was associated with a numerically lower rate of non-serious infections (30.6 for baricitinib 4 mg vs 24.9 for 2 mg). Rates of serious adverse events and adverse events leading to discontinuation were similar across groups.ConclusionsIn a large randomised, blinded phase 3 study, maintenance of RA control following induction of sustained LDA/REM with baricitinib 4 mg was greater with continued 4 mg than after taper to 2 mg. Nonetheless, most patients tapered to 2 mg could maintain LDA/REM or recapture with return to 4 mg if needed.,OBJECTIVE: To compare the visualisation of bronchopulmonary collaterals and bronchopulmonary collateral blood flow in patients with chronic thromboembolic pulmonary hypertension 2nd primary pulmonary hypertension. SETTING: Referral centre for cardiology at an academic hospital. PATIENTS: Nine patients with chronic thromboembolic pulmonary hypertension and 17 with primary pulmonary hypertension. INTERVENTIONS: Bronchopulmonary collaterals were visualised by selective bronchial arteriography or thoracic aortography. Bronchopulmonary collateral blood flow was estimated by injecting indocyanine green into the ascending aorta and sampling below the mitral valve from the left ventricle. RESULTS: The degree of pulmonary hypertension was comparable in the two groups. Large bronchopulmonary collaterals were visualised in all the patients with thromboembolic pulmonary hypertension who had bronchial arteriography or aortography or both. None of the primary pulmonary hypertension group studied by aortography had bronchopulmonary collaterals (P < < 0.001). All the patients with chronic thromboembolic pulmonary hypertension had significant bronchopulmonary collateral blood flow, which was (mean (SD)) 29.8 (18.6)% of the systemic blood flow. There was no recordable collateral blood flow in 11 of 15 patients with primary pulmonary hypertension. In the remaining four patients the mean value was 1.1 (1.8)% of the systemic blood flow (P < < 0.001). CONCLUSIONS: Visualisation of bronchopulmonary collaterals by thoracic aortography or by bronchial arteriography, or the demonstration of an increased bronchopulmonary collateral flow, helps to distinguish patients with chronic thromboembolic pulmonary hypertension from those with primary pulmonary hypertension.
Objectives. This study sought to analyze the determinants of pulmonary hypertension in patients with left ventricular dysfunction. Background. Pulmonary hypertension in patients with left ventricular dysfunction is a predictor of poor outcome. The independent role of cardiac functional abnormalities in the genesis of pulmonary hypertension is unclear. Methods. In 102 consecutive patients with primary left ventricular dysfunction (ejection fraction
Objectives. This study sought to determine the long-term effects of continuous infusion of epoprostenol (epo) therapy on survival and pulmonary artery pressure in patients with primary pulmonary hypertension (PPH). Background. PPH is a progressive disease for which there are few effective therapies. Methods. Patients with PPH and New York Heart Association functional class III or IV symptoms of congestive heart failure underwent right heart catheterization and Doppler-echocardiography to measure the maximal systolic pressure gradient between the right ventricle and right atrium (ΔP) and cardiac output (CO). Doppler-echocardiography and catheterization data were compared. Patients were followed up long term with Doppler-echocardiography. Results. Of 69 patients who went on to receive epo, 18 were followed up for >330 days (range 330 to 700). During long-term follow-up, there was a significant reduction in ΔP, which decreased from 84.1 ± 24.1 to 62.7 ± 18.2 (mean ± SD, p < 0.01). A Kaplan-Meier plot of survival of our study patients demonstrated improved survival compared with that of historical control subjects. The 1-, 2- and 3-year survival rates for our patients were 80% (n = 36), 76% (n = 22) and 49% (n = 6) compared with 10- (88%, n = 31), 20- (56%, n = 27) and 30-month (47%, n = 17) survival rates in historical control subjects. Conclusions. Patients receiving continuous infusion of epo for treatment of PPH experience a decrease in pulmonary artery pressure. Long-term follow-up of this single-center patient group demonstrated improved long-term survival during epo therapy compared with that in historical control subjects and confirms predicted improved outcomes based on shorter follow-up periods.
Although inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in newborn infants with persistent pulmonary hypertension, its effects are variable. We hypothesized (1) that the response to iNO therapy is dependent on the primary disease associated with persistent pulmonary hypertension of the newborn (PPHN) and (2) that the combination of high-frequency oscillatory ventilation (HFOV) with iNO would be efficacious in patients for whom either therapy alone had failed. To determine the relative roles of iNO and HFOV in the treatment of severe PPHN, we enrolled 205 neonates in a randomized, multicenter clinical trial. Patients were stratified by predominant disease category: respiratory distress syndrome ( = 70), meconium aspiration syndrome ( = 58), idiopathic PPHN or pulmonary hypoplasia (excluding congenital diaphragmatic hernia) (“other”: = 43), and congenital diaphragmatic hernia ( = 34); they were then randomly assigned to treatment with iNO and conventional ventilation or to HFOV without iNO. Treatment failure (partial pressure of arterial oxygen [Pa ] <60 mm Hg) resulted in crossover to the alternative treatment; treatment failure after crossover led to combination treatment with HFOV plus iNO. Treatment response with the assigned therapy was defined as sustained Pa of 60 mm Hg or greater. Baseline oxygenation index and Pa were 48 ± 2 and 41 ± 1 mm Hg, respectively, during treatment with conventional ventilation. Ninety-eight patients were randomly assigned to initial treatment with HFOV, and 107 patients to iNO. Fifty-three patients (26%) recovered with the initially assigned therapy without crossover (30 with iNO [28%] and 23 with HFOV [23%]; = 0.33). Within this group, survival was 100% and there were no differences in days of mechanical ventilation, air leak, or supplemental oxygen requirement at 28 days. Of patients whose initial treatment failed, crossover treatment with the alternate therapy was successful in 21% and 14% for iNO and HFOV, respectively ( = not significant). Of 125 patients in whom both treatment strategies failed, 32% responded to combination treatment with HFOV plus iNO. Overall, 123 patients (60%) responded to either treatment alone or combination therapy. By disease category, response rates for HFOV plus iNO in the group with respiratory syndrome and the group with meconium aspiration syndrome were better than for HFOV alone or iNO with conventional ventilation ( <0.05). Marked differences in outcomes were noted among centers (percent death or treatment with extracorporeal membrane oxygenation = 29% to 75%). We conclude that treatment with HFOV plus iNO is often more successful than treatment with HFOV or iNO alone in severe PPHN. Differences in responses are partly related to the specific disease associated with PPHN. (J Pediatr 1997;131:55-62)
To evaluate the pulmonary artery pressure in patients with thalassemia major, Doppler echocardiography was performed in 33 patients with thalassemia major (aged 2 to 24 years) and 33 normal controls. Pulmonary artery pressure was estimated by (1) measuring the systolic transtricuspid gradient from tricuspid regurgitation and adding it to the right atrial pressure, estimated by the response of the inferior vena cava to deep inspiration, and (2) measuring the time to peak velocity of pulmonary flow. The results showed that of 33 patients, 28 had tricuspid regurgitation with a pulmonary systolic pressure ranging from 18 to 94 mm Hg (47 ± 15 mm Hg). Pulmonary systolic pressure was >30 mm Hg in all 22 patients >10 years old and in four of six patients <10 years old. Pressure correlated with left ventricular ejection fraction ( = –0.74), the ratio of mitral peak early diastolic flow velocity and peak velocity during the atrial contraction ( = 0.52), age ( = 0.56), and total blood transfusion units ( = 0.59). The pulmonary time to peak velocity was shortened compared with controls ( < 0.05). We concluded that pulmonary hypertension, as another cardiovascular complication of multiple factors of cause, seems to occur more frequently and at an early stage of the cardiac involvement in patients with thalassemia major. (Am Heart J 1997;134:532-7.)
Pulmonary hypertension (PHT) is an important complication of systemic sclerosis (SSc). Echocardiography can be used to detect PHT and, with Doppler echocardiography, the pulmonary arterial systolic pressure (PASP) can often be estimated. We have undertaken a study to compare echocardiographic assessment with right heart catheterization (RHC) in 33 SSc patients in whom clinical assessment [including EGG, chest X-ray, lung function tests and high-resolution computed tomography (HRCT)] had raised strong suspicion of PHT. The mean (S.D.) interval between echocardiography and RHC was 1.8 (2.3) months. Twenty-one patients (64%) had PHT (PASP greater than or equal to 30 mmHg) on RHC, and echocardiography correctly identified 19 of these (sensitivity 90%). Of the 12 patients without PHT on RHC, nine were correctly identified by echocardiography (specificity 75%). The five incorrectly classified patients all had PASP in the borderline normal/abnormal range. The presence of tricuspid regurgitation allowed Doppler measurement of PASP in 20 patients (61%) and this correlated significantly with RHC values (r = 0.83, P < 0.001). We conclude that echocardiography is a reliable method for detecting PHT and it map be particularly useful for the early detection and monitoring of this potentially fatal complication in SSc.
Objectives. To identify patients with hyperthyroidism and coincidental pulmonary hypertension and to document reversibility of pulmonary hypertension after treatment of hyperthyroidism. Design. Patients with hyperthyroidism referred for transthoracal echocardiography for any reason that showed elevated pulmonary arterial pressures were collected. After therapy for the thyreotoxic state with documented normalization of thyroid hormone (fT4), pulmonary arterial pressure was measured again noninvasively. Setting. An out-patient tertiary referral centre. Subjects. The medical records were used to identify, retrospectively patients with hyperthyroidism and pulmonary hypertension over a three-year period (April 1993 to April 1996). Interventions and main outcome measures. Systolic pulmonary artery pressure (PAPs) was determined by adding up right ventricular systolic pressure (RVSP) and mean right atrial pressure (RAP) measured by continuous-wave Doppler echocardiography according to standard techniques. All patients were treated for hyperthyroidism to normal fT4 levels. After successful therapy, Doppler echocardiography was repeated. Results. Four patients with pulmonary hypertension showing elevated PAPs of 40 +/- 11 mmHg were identified. After therapy, PAPs decreased in all patients to a mean of 25 +/- 6 mmHg. Conclusion. The observation of four patients with pulmonary hypertension and hyperthyroidism is striking and suggests a possible pathogenetic link of these disorders.