Fibrosing mediastinitis is caused by a proliferation of fibrous tissue in the mediastinum with encasement of mediastinal viscera and compression of mediastinal bronchovascular structures. Pulmonary hypertension (PH) is a severe complication of fibrosing mediastinitis caused by extrinsic compression of the pulmonary arteries and/or veins.We have conducted a retrospective observational study reviewing clinical, functional, hemodynamic, radiological characteristics, and outcome of 27 consecutive cases of PH associated with fibrosing mediastinitis diagnosed between 2003 and 2014 at the French Referral Centre for PH.Fourteen men and 13 women with a median age of 60 years (range 18-84) had PH confirmed on right heart catheterization. The causes of fibrosing mediastinitis were sarcoidosis (n=13), tuberculosis-infection confirmed or suspected (n=9), mediastinal irradiation (n=2), and idiopathic (n=3). Sixteen patients (59%) were in NYHA functional class III and IV. Right heart catheterization confirmed moderate to severe PH with a median mean pulmonary artery pressure of 42 mm Hg (range 27-90) and a median cardiac index of 2.8 L/min/m(2) (range 1.6-4.3). Precapillary PH was found in 22 patients, postcapillary PH in 2, and combined postcapillary and precapillary PH in 3. Severe extrinsic compression of pulmonary arteries (>60% reduction in diameter) was evidenced in 2, 8, and 12 patients at the main, lobar, or segmental levels, respectively. Fourteen patients had at least one severe pulmonary venous compression with associated pleural effusion in 6 of them. PAH therapy was initiated in 7 patients and corticosteroid therapy (0.5-1mg/kg/day) was initiated in 3 patients with sarcoidosis, with 9 other being already on low-dose corticosteroids. At 1-year follow-up, 3 patients had died and among the 21 patients evaluated, 3 deteriorated, 14 were stable, and only 4 patients with sarcoidosis improved (4 receiving corticosteroids and 1 receiving corticosteroids and PAH therapy). Survival was 88%, 73%, and 56% at 1, 3, and 5 years, respectively.We found no clear clinical improvement with the use of specific PAH therapy. Corticosteroid therapy may be associated with clinical improvement, in some patients with fibrosing mediastinitis due to sarcoidosis. Although never performed for this indication, lung transplantation may be proposed in eligible patients with severe PH and fibrosing mediastinitis.
Pulmonary hypertension (PH) is relatively common in connective tissue diseases. However, few studies have focused on the pulmonary hypertension (PH) associated with polymyositis (PM). Our aim is to investigate the prevalence of PH and determine the associated factors for PH in patients with PM. Multicenter study of 61 patients with PM underwent evaluation including general information, physical examination, laboratory indictors, thoracic high-resolution CT (HRCT) imaging, and transthoracic echocardiography (TTE). TTE was performed to estimate the pulmonary arterial pressure. PH was defined as resting systolic pulmonary artery pressure (sPAP) ≥40 mmHg. PH was identified in ten patients (16.39 %) who had few cardiopulmonary symptoms. PM patients with PH had higher prevalence of interstitial lung disease (ILD) and pericardial effusion (PE) compared with patients without PH (18 vs. 11.5 %, p = 0.005; 11.5 vs. 9.8 %, p = 0.004; respectively). After controlling for age, gender, and potential factors, ILD and PE were independently associated with PH in patients with PM in multivariate analysis (OR = 8.193, 95 % CI 1.241–54.084, p = 0.029; OR = 8.265, 95 % CI 1.298–52.084, p = 0.025; respectively). Depending on TTE, the possible prevalence of PH was 16.39 % in patients with PM. Both ILD and PE may contribute to the development of PH in PM.
Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies.
Increased glycolysis in the lung vasculature has been connected to the development of pulmonary hypertension (PH). We therefore investigated whether glycolytic regulator 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase (PFKFB3)-mediated endothelial glycolysis plays a critical role in the development of PH. Heterozygous global deficiency of protected mice from developing hypoxia-induced PH, and administration of the PFKFB3 inhibitor 3PO almost completely prevented PH in rats treated with Sugen 5416/hypoxia, indicating a causative role of PFKFB3 in the development of PH. Immunostaining of lung sections and Western blot with isolated lung endothelial cells showed a dramatic increase in PFKFB3 expression and activity in pulmonary endothelial cells of rodents and humans with PH. We generated mice that were constitutively or inducibly deficient in endothelial and found that these mice were incapable of developing PH or showed slowed PH progression. Compared with control mice, endothelial -knockout mice exhibited less severity of vascular smooth muscle cell proliferation, endothelial inflammation, and leukocyte recruitment in the lungs. In the absence of , lung endothelial cells from rodents and humans with PH produced lower levels of growth factors (such as PDGFB and FGF2) and proinflammatory factors (such as CXCL12 and IL1β). This is mechanistically linked to decreased levels of HIF2A in lung ECs following knockdown. Taken together, these results suggest that targeting PFKFB3 is a promising strategy for the treatment of PH.
Background Pulmonary hypertension (PH) is hemodynamically classified as pre-capillary (as seen in idiopathic pulmonary arterial hypertension [IPAH]) or post-capillary (as seen in heart failure with preserved ejection fraction [HFpEF]). Overlaps between these conditions exist. Some patients present with risk factors for left heart disease but pre-capillary PH, whereas patients with HFpEF may have combined pre- and post-capillary PH. Objectives This study sought to further characterize similarities and differences among patient populations with either PH-HFpEF or IPAH. Methods We used registry data to analyze clinical characteristics, hemodynamics, and treatment responses in patients with typical IPAH (<3 risk factors for left heart disease; n = 421), atypical IPAH (≥3 risk factors for left heart disease; n = 139), and PH-HFpEF (n = 226) receiving PH-targeted therapy. Results Compared with typical IPAH, patients with atypical IPAH and PH-HFpEF were older, had a higher body mass index, had more comorbidities, and had a lower 6-min walking distance, whereas mean pulmonary artery pressure (46.9 ± 13.3 mm Hg vs. 43.9 ± 10.7 mm Hg vs. 45.7 ± 9.4 mm Hg, respectively) and cardiac index (2.3 ± 0.8 l/min/m vs. 2.2 ± 0.8 l/min/m vs. 2.2 ± 0.7 l/min/m , respectively) were comparable among groups. After initiation of targeted PH therapies, all groups showed improvement in exercise capacity, functional class, and natriuretic peptides from baseline to 12 months, but treatment effects were less pronounced in patients with PH-HFpEF than typical IPAH; with atypical IPAH in between. Survival rates at 1, 3, and 5 years were almost identical for the 3 groups. Conclusions Patients with atypical IPAH share features of both typical IPAH and PH-HFpEF, suggesting that there may be a continuum between these conditions.
Anomalous origin of the pulmonary artery from the ascending aorta can lead to congestive heart failure in infancy, and with advancing age many patients will experience severe pulmonary hypertension. Surgical intervention has high mortality and morbidity risks if this happens. Strategies to manage these patients seem only limited to heart–lung transplantation or lung transplantation. Here, we successfully performed surgical intervention in an adult patient who had anomalous origin of the right pulmonary artery from the ascending aorta with high pressures in the ascending aorta and normally originating pulmonary artery.
Background Pulmonary hypertension (PHT) lacks community prevalence and outcome data. Objective To characterise minimum ‘indicative’ prevalences and mortality data for all forms of PHT in a selected population with an elevated estimated pulmonary artery systolic pressure (ePASP) on echocardiography. Design Observational cohort study. Setting Residents of Armadale and the surrounding region in Western Australia (population 165 450) referred to our unit for transthoracic echocardiography between January 2003 and December 2009. Results Overall, 10 314 individuals (6.2% of the surrounding population) had 15 633 echo studies performed. Of these, 3320 patients (32%) had insufficient TR to ePASP and 936 individuals (9.1%, 95% CI 8.6% to 9.7%) had PHT, defined as, ePASP>40 mm Hg. The minimum ‘indicative’ prevalence for all forms of PHT is 326 cases/100 000 inhabitants of the local population, with left heart disease-associated PHT being the commonest cause (250 cases/100 000). 15 cases of pulmonary arterial hypertension/100 000 inhabitants were identified and an additional 144 individuals (15%) with no identified cause for their PHT. The mean time to death for those with ePASP >40 mm Hg, calculated from the first recorded ePASP, was 4.1 years (95% CI 3.9 to 4.3). PHT increased mortality whatever the underlying cause, but patients with PHT from left heart disease had the worst prognosis and those with idiopathic pulmonary arterial hypertension receiving disease-specific treatment the best prognosis. Risk of death increased with PHT severity: severe pulmonary hypertension shortened the lifespan by an average of 1.1 years compared with mild pulmonary hypertension. Conclusions In this cohort, PHT was common and deadly. Left heart disease was the most common cause and had the worst prognosis and treated pulmonary arterial hypertension had the best prognosis.
Background Pulmonary hypertension (PH) is a severe progressive disease. Though five subgroups are recognised, reports on survival focus mainly on pulmonary arterial hypertension (PAH). Methods Long-term transplant-free survival, and its determinants, were investigated in patients with PH (diagnosed by right heart catheterization) within a prospective registry at a single referral center in Giessen, Germany. Results In total, 2067 patients were enrolled (PAH, 685 patients [33.1%]; pulmonary venous hypertension, 307 patients [14.9%]; PH due to lung diseases (LD-PH), 546 patients [26.4%; mainly interstitial lung disease and chronic obstructive pulmonary disease]; chronic thromboembolic PH, 459 patients [22.2%]; PH owing to miscellaneous/unknown causes, 70 patients [3.4%]). Median follow-up was 37 months. Differences in transplant-free survival between etiological groups were highly significant ( p < 0.001), with 1-, 3-, and 5-year survival rates of 88.2%, 72.2%, and 59.4%, respectively, for those with PAH compared with 79.5%, 52.7%, and 38.1%, respectively, for patients with LD-PH. Patients’ age, sex, and 6-minute walk distance (6MWD), but not New York Heart Association (NYHA) functional class, associated significantly with survival across all PH subtypes in multivariate Cox regression analyses. Conclusions This is the largest reported single-center PH cohort. Some parameters used in clinical practice do not independently predict survival. Age, sex, and 6MWD outperformed NYHA functional class in predicting survival across all etiologic groups.
Pulmonary hypertension (PH) is an uncommon but progressive condition, and much of what we know about it comes from specialized disease registries. With expanding research into the diagnosis and treatment of PH, it is important to provide updated surveillance on the impact of this disease on hospitalizations and mortality. This study, which builds on previous PH surveillance of mortality and hospitalization, analyzed mortality data from the National Vital Statistics System and data from the National Hospital Discharge Survey between 2001 and 2010. PH deaths were identified using International Classification of Diseases, Tenth Revision codes I27.0, I27.2, I27.8, or I27.9 as any contributing cause of death on the death certificate. Hospital discharges associated with PH were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes 416.0, 416.8, or 416.9 as one of up to seven listed medical diagnoses. The decline in death rates associated with PH among men from 1980 to 2005 has reversed and now shows a significant increasing trend. Similarly, the death rates for women with PH have continued to increase significantly during the past decade. PH-associated mortality rates for those aged 85 years and older have accelerated compared with rates for younger age groups. There have been significant declines in PH-associated mortality rates for those with pulmonary embolism and emphysema. Rates of hospitalization for PH have increased significantly for both men and women during the past decade; for those aged 85 years and older, hospitalization rates have nearly doubled. Continued surveillance helps us understand and address the evolving trends in hospitalization and mortality associated with PH and PH-associated conditions, especially regarding sex, age, and race/ethnicity disparities.