In this trial, 261 patients with chronic thromboembolic pulmonary hypertension were assigned to placebo or to the soluble guanylate cyclase stimulator riociguat. At 16 weeks, riociguat had significantly improved the 6-minute walk distance and pulmonary vascular resistance. Chronic thromboembolic pulmonary hypertension is characterized by obstruction of the pulmonary vasculature by residual organized thrombi, 1 leading to increased pulmonary vascular resistance, progressive pulmonary hypertension, and right ventricular failure. 2 , 3 Patients with chronic thromboembolic pulmonary hypertension have a poor prognosis unless they receive treatment early. 4 Pulmonary endarterectomy is the standard treatment for chronic thromboembolic pulmonary hypertension and is the only potentially curative treatment. 5 However, surgery is not an option for all patients; some patients are ineligible for surgery owing to the occlusion of distal vessels or coexisting conditions, some decline surgery, and some do not have access to expert surgical . . .
SUMMARY POINTS Pulmonary hypertension has many causes so prognoses and treatments vary The condition is diagnosed by systematically evaluating the breathless patient and screening patients at high risk Patients at high risk of severe and treatable pulmonary hypertension include those with systemic sclerosis, portal hypertension, congenital heart disease, and previous pulmonary embolism Specialist centres provide access to tailored investigative and treatment pathways and support networks for patients Patients with severe pulmonary hypertension can deteriorate rapidly—do not delay referral to perform specialist investigations Only selected patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension benefit from interventions directed at pulmonary vasculature; for most patients treatment is aimed at the underlying condition
Patients with sickle cell disease underwent ECG with assessment of tricuspid valve regurgitant jet velocity (TRJV) to screen for pulmonary hypertension, followed by right heart catheterization if the TRJV was 2.5 m per second or more. Prevalence was 27% on the basis of ECG criteria but only 6% on the basis of catheterization. In several studies, pulmonary hypertension, particularly pulmonary arterial hypertension, has been reported as a frequent complication of sickle cell disease. 1 – 4 Pulmonary arterial hypertension is characterized by the presence of precapillary pulmonary hypertension in the absence of left-sided heart disease, lung disease, or chronic thromboembolism. On histopathological analysis, pulmonary arterial hypertension is characterized by the proliferation of medial smooth-muscle cells and endothelial cells in the small pulmonary arteries. 5 Pulmonary arterial hypertension may be idiopathic, heritable, or associated with other disorders, such as connective tissue diseases and congenital heart disease. 6 In the updated classification of pulmonary hypertension, sickle cell disease appears . . .
Pulmonary hypertension (PH) is an increasingly recognized cause of morbidity and mortality, and in the past 20 years, there has been a rapid expansion in research and available therapies. Although it is defined quite simply as a mean pulmonary arterial pressure of ≥ 25 mm Hg, PH encompasses a heterogeneous group of disease processes. In the past, PH was classified as primary or secondary, but as understanding of the various contributing diseases has increased, classification systems have attempted to group these diseases by clinical features and disease mechanism. The evaluation of patients with suspected PH can be cumbersome, and a careful and methodical approach is needed to ensure timely and accurate diagnosis, correct physiological classification, and appropriate treatment. In this review, we discuss the classification and diagnostic evaluation of PH in adults as well as some of the billing and coding considerations involved in this evaluation.
The number of effective, long-term treatments for pulmonary hypertension is limited. In this double-blind, randomized trial, an aerosolized form of iloprost, a stable analogue of the pulmonary vasodilator prostacyclin, was assessed over a 12-week period. Iloprost had a beneficial effect on the combined end point of the distance walked in six minutes and an improvement in the New York Heart Association functional class. A continuous infusion of prostacyclin was the first therapy shown to reduce mortality in a controlled study of patients with severe pulmonary hypertension. 1 However, its use is associated with a number of serious drawbacks. The lack of pulmonary selectivity results in systemic side effects, tolerance leads to progressive increases in the dose, and there may be recurrent infections of the intravenous catheter. 2 As an alternative, inhaled nitric oxide possesses pulmonary selectivity, but it is less potent than prostacyclin in the pulmonary vasculature. 3 , 4 Moreover, an interruption in the inhalation of continuous nitric oxide may cause rebound pulmonary hypertension. 5 , 6 Designed . . .
Summary Background Paediatric pulmonary hypertension, is an important cause of morbidity and mortality, and is insufficiently characterised in children. The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension (TOPP) registry is a global, prospective study designed to provide information about demographics, treatment, and outcomes in paediatric pulmonary hypertension. Methods Consecutive patients aged 18 years or younger at diagnosis with pulmonary hypertension and increased pulmonary vascular resistance were enrolled in TOPP at 31 centres in 19 countries from Jan 31, 2008, to Feb 15, 2010. Patient and disease characteristics, including age at diagnosis and at enrolment, sex, ethnicity, presenting symptoms, pulmonary hypertension classification, comorbid disorders, medical and family history, haemodynamic indices, and functional class were recorded. Follow-up was decided by the patients' physicians according to the individual's health-care needs. Findings 362 of 456 consecutive patients had confirmed pulmonary hypertension (defined as mean pulmonary artery pressure ≥25 mm Hg, pulmonary capillary wedge pressure ≤12 mm Hg, and pulmonary vascular resistance index ≥3 WU/m−2 ). 317 (88%) patients had pulmonary arterial hypertension (PAH), which was idiopathic [IPAH] or familial [FPAH] in 182 (57%), and associated with other disorders in 135 (43%), of which 115 (85%) cases were associated with congenital heart disease. 42 patients (12%) had pulmonary hypertension associated with respiratory disease or hypoxaemia, with bronchopulmonary dysplasia most frequent. Finally, only three patients had either chronic thromboembolic pulmonary hypertension or miscellaneous causes of pulmonary hypertension. Chromosomal anomalies, mainly trisomy 21, were reported in 47 (13%) of patients with confirmed disease. Median age at diagnosis was 7 years (IQR 3–12); 59% (268 of 456) were female. Although dyspnoea and fatigue were the most frequent symptoms, syncope occurred in 31% (57 of 182) of patients with IPAH or FPAH and in 18% (eight of 45) of those with repaired congenital heart disease; no children with unrepaired congenital systemic-to-pulmonary shunts had syncope. Despite severe pulmonary hypertension, functional class was I or II in 230 of 362 (64%) patients, which is consistent with preserved right-heart function. Interpretation TOPP identifies important clinical features specific to the care of paediatric pulmonary hypertension, which draw attention to the need for paediatric data rather than extrapolation from adult studies. Funding Actelion Pharmaceuticals.
The effects of hypoxia on the human organism has been considered doubly fascinating by the scientific community. The knowledge of the discrete mechanisms allowing the acclimatization both at genetic level or through the cell mediators production in addition to the macroscopic responses of the cardio-circulatory and ventilatory systems to a hypoxic environment has been progressively developed since the last century; moreover granting a safer stay in hypoxic conditions not only for the residents but also for the different cathegories of workers, sportsmen and tourists has been considered a worthy aim of the medical activity. The effects of hypoxia were simulated in laboratory by means of an induced low pressure environment (normobaric hypoxia) or tested on the subjects at different levels of altitude (hypobaric hypoxia). Far from describing all the physiological and pathological responses of the organism, in this review, the authors expose the state of the art in the knowledge of the responsiveness of the pulmonary circle to the acute or chronic hypoxic condition, its possible progression to the pulmonary arterial hypertension, the latter being more appropriately named High-Altitude Pulmonary Hypertension. The currently available therapeutic options in the treatment of High-Altitude Pulmonary Hypertension are also reviewed.
Objectives Our goal was to investigate the effect of treatment with the oral dual endothelin receptor antagonist bosentan on the hemodynamics and exercise capacity of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Background CTEPH is characterized by vascular obstruction and remodeling, leading to increased pulmonary vascular resistance (PVR). Although pulmonary endarterectomy (PEA) is potentially curative, medical therapy is needed in patients with inoperable disease or persistent/recurrent pulmonary hypertension after PEA. Methods The BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension) study was a double-blind, randomized, placebo-controlled study in CTEPH including patients with either inoperable CTEPH or persistent/recurrent pulmonary hypertension after PEA (>6 months after PEA). Independent coprimary end points were change in PVR as a percentage of baseline and change from baseline in 6-min walk distance after 16 weeks of treatment with bosentan or placebo. Secondary end points included change from baseline in World Health Organization functional class and other hemodynamic parameters. Results One hundred fifty-seven patients were enrolled and randomized: 80 to placebo, 77 to bosentan. A statistically significant treatment effect (TE) of bosentan over placebo on PVR was demonstrated: −24.1% of baseline (95% confidence interval [CI]: −31.5% to −16.0%; p < 0.0001). Total pulmonary resistance (TE: −193 dyn·s·cm−5 ; 95% CI: −283 to −104 dyn·s·cm−5 ; p < 0.0001) and cardiac index (TE: 0.3 l·min−1 ·m−2 ; 95% CI: 0.14 to 0.46 l·min−1 ·m−2 ; p = 0.0007) improved. Mean TE on 6-min walk distance was +2.2 m (95% CI: −22.5 to 26.8 m; p = 0.5449). Bosentan treatment was well tolerated. Conclusions This study demonstrated a positive TE of bosentan on hemodynamics in this patient population. No improvement was observed in exercise capacity. Further trials are needed to define the role of medical therapy in patients with CTEPH (Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension; NCT00313222 ).
Chronic thromboembolic pulmonary hypertension is believed to be rare after an episode of acute pulmonary embolism. This study showed that the incidence of this serious complication was nearly 4 percent — substantially higher than previously reported — and was associated with previous pulmonary embolism, large perfusion defects, and an idiopathic presentation. Possible approaches to prevention are discussed. The incidence of this serious complication was nearly 4 percent. Chronic pulmonary hypertension is considered a relatively rare complication of pulmonary embolism but is associated with considerable morbidity and mortality. 1 – 3 It is commonly believed that symptoms become manifest only several years after the initial episode of pulmonary embolism. However, the true frequency (estimated at 0.1 percent among patients who survive a pulmonary embolism) and timing are not well established, and there is limited documentation concerning predisposing factors that could be addressed in an effort to prevent this feared complication. It has been hypothesized that in situ thrombosis and pulmonary arteriopathy are common causes of vascular occlusion leading to chronic . . .