This case–control study demonstrates a significant association between persistent pulmonary hypertension of the newborn and the use of selective serotonin-reuptake inhibitors (SSRIs) during the second half of pregnancy. There was no significant association between this outcome and the use of SSRIs during the first half of pregnancy or the use of non-SSRI antidepressants during pregnancy. This study demonstrated a significant association between persistent pulmonary hypertension of the newborn and the use of selective serotonin-reuptake inhibitors during the second half of pregnancy. Persistent pulmonary hypertension of the newborn (PPHN) occurs in an estimated 1 or 2 infants per 1000 live births and is associated with substantial morbidity and mortality. 1 – 4 Despite treatment, 10 to 20 percent of affected infants will not survive. 4 , 5 Newborns with PPHN are typically full-term or near-term infants without associated congenital anomalies who present shortly after birth with severe respiratory failure requiring intubation and mechanical ventilation. 6 This disruption of the normal fetal-to-neonatal circulatory transition is characterized by postnatal persistence of elevated pulmonary vascular resistance, resulting in right-to-left shunting of blood through fetal channels (the patent ductus arteriosus, foramen . . .
COPD is a systemic disorder that is associated with increases of inflammatory proteins in systemic circulation. However, no data on the potential role of systemic inflammation in pulmonary hypertension secondary to COPD are available. Therefore, our aim was to investigate the degree of systemic inflammation reflected by circulatory levels of C-reactive protein (CRP), tumor-necrosis factor (TNF)-α, and interleukin (IL)-6 in COPD patients with and without pulmonary hypertension. Cross-sectional study. University hospital, tertiary referral setting. In 43 consecutive patients with COPD (mean [± SD] age, 65.0 ± 10.5 years; mean FEV , 46.2 ± 18.1% predicted), lung function was assessed using body plethysmography; pulmonary artery pressure (Ppa) levels were measured by echocardiography. Serum TNF-α and IL-6 levels were assessed by enzyme-linked immunosorbent assay, and high-sensitivity serum CRP levels were measured by chemiluminescent immunoassay. Pulmonary hypertension was present in 19 patients and was absent in 24 patients. In patients with pulmonary hypertension, serum CRP and TNF-α levels were significantly higher than in those patients without hypertension (median, 3.6 mg/L [25th to 75th percentile, 1.4 to 13.0 mg/L] vs 1.8 mg/L [25th to 75th percentile, 0.8 to 2.8 mg/L; p = 0.034]; and median, 4.2 pg/mL [25th to 75th percentile, 3.4 to 10.9 pg/mL] vs 3.1 pg/mL [25th to 75th percentile, 2.1 to 4.2 pg/mL]; p = 0.042, respectively). No differences were seen in serum IL-6 (median, 10.4 pg/mL [25th to 75th percentile, 8.8 to 12.2 pg/mL] vs 10.5 pg/mL [25th to 75th percentile, 9.4 to 39.1 pg/mL]; p = 0.651) between the groups. In multiple linear regression analysis, the following two variables were independent predictors of systolic Ppa ( = 0.373): Pao (p = 0.011); and log-transformed serum CRP level (p = 0.044). We conclude that increases in Ppa in patients with COPD are associated with higher serum levels of CRP and TNF-α, raising the possibility of a pathogenetic role for low-grade systemic inflammation in the pathogenesis of pulmonary hypertension in COPD patients.
Complications of Right Heart Catheterization Procedures in Patients With Pulmonary Hypertension in Experienced Centers Marius M. Hoeper, Stephen H. Lee, Robert Voswinckel, Massimiliano Palazzini, Xavier Jais, Alessandro Marinelli, Robyn J. Barst, Hossein A. Ghofrani, Zhi-Cheng Jing, Christian Opitz, Hans-Juergen Seyfarth, Michael Halank, Vallerie McLaughlin, Ronald J. Oudiz, Ralf Ewert, Heinrike Wilkens, Stefan Kluge, Hinrich-Cordt Bremer, Eva Baroke, Lewis J. Rubin We performed a multicenter 5-year retrospective and 6-month prospective evaluation of serious adverse events related to right heart catheter procedures in patients with pulmonary hypertension. A total of 7,218 right heart catheter procedures were analyzed. The results from the retrospective and the prospective analyses were almost identical. The overall number of serious adverse events was 76 (1.1%, 95% confidence interval 0.8% to 1.3%). The most frequent complications were related to venous access, followed by arrhythmias and hypotensive episodes. Four fatal events were recorded, resulting in an overall procedure-related mortality of 0.055% (95% confidence interval 0.01% to 0.099%). This study sought to assess the risks associated with right heart catheter procedures in patients with pulmonary hypertension. Right heart catheterization, pulmonary vasoreactivity testing, and pulmonary angiography are established diagnostic tools in patients with pulmonary hypertension, but the risks associated with these procedures have not been systematically evaluated in a multicenter study. We performed a multicenter 5-year retrospective and 6-month prospective evaluation of serious adverse events related to right heart catheter procedures in patients with pulmonary hypertension, as defined by a mean pulmonary artery pressure >25 mm Hg at rest, undergoing right heart catheterization with or without pulmonary vasoreactivity testing or pulmonary angiography. During the retrospective period, 5,727 right heart catheter procedures were reported, and 1,491 were reported from the prospective period, for a total of 7,218 right heart catheter procedures performed. The results from the retrospective and the prospective analyses were almost identical. The overall number of serious adverse events was 76 (1.1%, 95% confidence interval 0.8% to 1.3%). The most frequent complications were related to venous access (e.g., hematoma, pneumothorax), followed by arrhythmias and hypotensive episodes related to vagal reactions or pulmonary vasoreactivity testing. The vast majority of these complications were mild to moderate in intensity and resolved either spontaneously or after appropriate intervention. Four fatal events were recorded in association with any of the catheter procedures, resulting in an overall procedure-related mortality of 0.055% (95% confidence interval 0.01% to 0.099%). When performed in experienced centers, right heart catheter procedures in patients with pulmonary hypertension are associated with low morbidity and mortality rates.
To assess the incidence of chronic thromboembolic pulmonary hypertension (CTPH) after the first episode of objectively confirmed pulmonary embolism (PE). Prospective cohort study in 12 Italian medical centers. Consecutive patients treated with oral anticoagulants for the first episode of PE, either idiopathic or associated with temporary risk factors, were followed up for at least 3 years. Patients were excluded from the study if they had a known persistent risk factor for venous thromboembolism (VTE). At the follow-up visits, patients were evaluated for persistent dyspnea, either at rest or on exertion. All patients who were referred with dyspnea were assessed by transthoracic echocardiography, with evaluation of the systolic and mean pulmonary artery pressures. Patients with evidence of pulmonary hypertension on echocardiography underwent perfusion lung scans and pulmonary angiography to confirm the diagnosis of CTPH. Overall, 259 patients were included in the study. PE was idiopathic in 135 patients, while it was associated with at least a temporary risk factor for VTE in 124 patients. After an average follow-up period of 46 months, 37 patients were found to have persistent dyspnea that was unexplained in 5 patients. Among these patients, a diagnosis of CTPH was confirmed in two patients with idiopathic PE (0.8% of the overall study population [95% confidence interval (CI), 0.0 to 1.9]; 1.5% of patients with idiopathic PE [95% CI, 0.0 to 3.6]). The diagnosis was made 14 and 22 months, respectively, after the acute PE. The incidence of CTPH observed in this study was about 1%. CTPH was observed in two patients with idiopathic PE.
Objectives: To measure survival, haemodynamic function and functional class in patients with systemic sclerosis associated pulmonary arterial hypertension (SSc-PAH) in two treatment eras. Methods: Six year longitudinal study of 92 consecutive patients with SSc-PAH diagnosed by cardiac catheterisation. Data were collected both prospectively and retrospectively. Patients were given basic treatment (diuretics, digoxin, oxygen and warfarin). Where clinically indicated, a prostanoid was used as advanced treatment (historical control group). From 2002, the range of treatments available expanded to include bosentan, which was generally the preferred treatment (current treatment era group). Survival was measured from the date of diagnosis of pulmonary hypertension by cardiac catheterisation. Six minute walking distance and haemodynamic function were measured at the time of diagnosis and at least one month after treatment was started. Results: The historical control group comprised 47 patients, all of whom received basic treatment; 27 of these were also treated with prostanoids. The current treatment era group comprised 45 patients, all of whom received bosentan as preferred treatment. Kaplan–Meier survival in the historical control group was 68% at one year and 47% at two years. Survival in the current treatment era group was 81% and 71% (p = 0.016) at one and two years, respectively. Pulmonary vascular resistance increased in the historical control group (by 147 dyn·s·cm−5), whereas in the current treatment era group, it remained stable over an average of nine months (decrease of 16 dyn·s·cm−5, p < 0.006). Conclusion: Survival of selected patients with SSc-PAH has improved in the current treatment era. In contrast to patients treated historically with basic drugs and prostanoids, patients treated in the current treatment era had improved survival associated with a lack of deterioration in cardiac haemodynamic function.
Summary Although pulmonary hypertension (PHT) is a common complication in patients with sickle cell disease (SCD), the rate of development of PHT and the factors that affect disease progression are unknown. We observed 93 patients over a median follow-up period of 2·6 years (range 0·2–5·1 years). Data were censored at the time of death or loss to follow-up. Pulmonary hypertension was associated with an increased risk of death (relative risk, 9·24; 95% confidence interval: 1·2–73·3; P = 0·01). There was no difference in the risk of death when patients with different degrees of PHT were compared. Lactate dehydrogenase and blood urea nitrogen were significantly associated with PHT in a logistic regression model. Higher levels of fetal haemoglobin and treatment with hydroxycarbamide were observed more frequently in patients without PHT. Thirteen per cent of patients with no previous evidence of PHT developed PHT following 3 years of observation. In conclusion: (1) PHT, regardless of severity, is associated with an increased risk of death in SCD patients; (2) haemolysis is strongly associated with PHT in SCD; (3) high levels of fetal haemoglobin and hydroxycarbamide therapy may decrease the occurrence of PHT; (4) screening for PHT is indicated for SCD patients in their non-crisis, steady states.
Objective: To describe an early experience of treating 40 children with the dual endothelin receptor antagonist bosentan, which is known to be safe and effective in adults with pulmonary hypertension (PH). Design: In this retrospective, observational study the UK Service for Pulmonary Hypertension for children treated 40 children with bosentan, 20 with idiopathic pulmonary arterial hypertension (IPAH) (mean age 8.03 years, range 1.2–17) and 20 with PH associated with other conditions (congenital heart disease, parenchymal lung or connective tissue disease, or HIV). Their mean age was 8.3 years (range 0.6–16 years). Patients: 39 patients were in World Health Organization (WHO) class III and IV, and all had shown recent deterioration. In IPAH the mean pulmonary vascular resistance (PVR) was 21.7 units⋅m2 (range 5.6–42.8). In secondary PH the mean PVR was 18 units⋅m2 (range 4.9–49). No child had a positive response to vasodilator testing with nitric oxide. Interventions: Bosentan was given as first line treatment to 25. Nine were given intravenous epoprostenol. Children were treated for a mean of 12.7 months (range 2–24 months). Main outcome measures: Response to treatment was judged by WHO functional class, six minute walk test, weight, ECG and echocardiographic findings, and need to add additional treatment. Results: Bosentan was well tolerated. In the IPAH group 19 (95%) stabilised with bosentan treatment but 12 (60%) patients needed combined treatment with epoprostenol. In secondary PH, WHO class, six minute walk test, and weight gain improved significantly. Conclusion: Bosentan helped stabilise children with IPAH but intravenous epoprostenol was also needed by 60%. Children with secondary PH improved.
Aims We tested the hypothesis that: (i) obstructive sleep apnoea (OSA) by itself originates pulmonary hypertension (PH); and (ii) the application of continuous positive airway pressure (CPAP) can reduce pulmonary pressure. Methods and results In this randomized and cross-over trial, 23 middle-aged OSA (apnoea-hypopnoea index, 44.1 +/- 29.3 h(-1)) and otherwise healthy patients and 10 control subjects were included. OSA patients randomly received either sham or effective CPAP for 12 weeks. Echocardiographic parameters, blood pressure recordings, and urinary catecholamine levels were obtained at baseline and after both treatment modalities. At baseline, OSA patients had higher pulmonary artery systolic pressure than control subjects (29.8 +/- 8.8 vs. 23.4 +/- 4.1 mmHg, respectively, P=0.036). Ten out of 23 patients [43%, (95% CI: 23-64%)] and none of the control subjects had PH at baseline (P=0.012). Two patients were removed from the study because of inadequate CPAP compliance. Effective CPAP induced a significant reduction in the values for pulmonary systolic pressure (from 28.9 +/- 8.6 to 24.0 +/- 5.8 mmHg, P < 0.0001). The reduction was greatest in patients with either PH or left ventricular diastolic dysfunction at baseline. Conclusion Severe OSA is independently associated with PH in direct relationship with disease severity and presence of diastolic dysfunction. Application of CPAP reduces pulmonary systolic pressure levels.
This study sought to demonstrate that a novel speckle-tracking method can be used to assess right ventricular (RV) global and regional systolic function. Fifty-eight patients with pulmonary arterial hypertension (11 men; mean age 53 ± 14 years) and 19 age-matched controls were studied. Echocardiographic images in apical planes were analyzed by conventional manual tracing for volumes and ejection fractions and by novel software (Axius Velocity Vector Imaging). Myocardial velocity, strain rate, and strain were determined at the basal, mid, and apical segments of the RV free wall and ventricular septum by Velocity Vector Imaging. RV volumes and ejection fractions obtained with manual tracing correlated strongly with the same indexes obtained by the Velocity Vector Imaging method in all subjects (r = 0.95 to 0.98, p <0.001 for all). Peak systolic myocardial velocities, strain rate, and strain were significantly impaired in patients with pulmonary arterial hypertension compared with controls and were most altered in patients with the most severe pulmonary arterial hypertension (p <0.05 for all). Pulmonary artery systolic pressure and a Doppler index of pulmonary vascular resistance were independent predictors of RV strain (r = −0.61 and r = −0.65, respectively, p <0.05 for both). In conclusion, the new automated Velocity Vector Imaging method provides simultaneous quantitation of global and regional RV function that is angle independent and can be applied retrospectively to already stored digital images.