Different Types Of Pulmonary Hypertension Research Articles

Pulmonary embolism and deep venous thrombosis in China.

The Annual Report on Cardiovascular Health and Diseases in China (2022) intricate landscape of cardiovascular health in China. In connection with the previous section, this eighth section of the report offers a comprehensive analysis of pulmonary embolism and deep venous thrombosis. In recent years, research in the field of pulmonary vessel in China has made great progress. A number of nationwide multi-center registry research results have filled the gaps in the epidemiology, diagnosis and treatment of pulmonary hypertension and venous thromboembolism. Different types of pulmonary hypertension still need attention to the identification of risk factors and/or risk stratification, and venous thromboembolism needs attention in the prevention and the overall management inside and outside hospital. In the future, we look forward to the publication of more high-quality research in China, which could be able to improve relevant guidelines for pulmonary vascular diseases both domestically and internationally.

FAST ASSESSMENT OF PULMONARY HYPERTENSION TYPE IN DOGS USING BASIC ULTRASONOGRAPHY TECHNIQUES

"Pulmonary hypertension (PH) is a complex hemodynamic condition defined by increased pulmonary vasculature pressure. The precise diagnostic can be obtained by evaluating the clinical status of the patient, performing complex imaging methods and by direct assessment of pulmonary arterial pressure. Invasive methods are considered golden standard; however, these techniques are limited in animals with respiratory failure. Previous studies aimed to evaluate the cut-off value of the PV/PA ratio in different types of PH in dogs. Therefore, the aim of this study is to correlate the type of PH with the changes of the pulmonary vein to pulmonary artery ratio (PV/PA) in dogs assessed by transthoracic echocardiography. The ratio was assessed using the right parasternal long axis view of the heart in B-mode and Mmode. This retrospective study included thirty-nine dogs presented for cardiologic examination at our Veterinary Teaching Hospital. Dogs were divided in three groups as following: control group (n=10), precapillary PH group (n=16) and postcapillary PH group (n=13). The median and interquartile range (M±IQR) of the PV/PA ratio were 0.95 (0.79– 1.5) in the control group, 0.85 (0.55-0.92) in precapillary PH group and 1.86 (1.44-2.16) in the postcapillary PH group. The area under the curve (AUC) for the PV/PA ratio comparison between the control and postcapillary PH groups was 1 (P<0.05), suggesting a cut-off ratio of 1.17 for the postcapillary PH group. This value is lower than the previous suggested value (>1.7). The importance of this finding derives from the ability to observe early changes induced by PH in dogs diagnosed with different stages of myxomatous mitral valve disease (MMVD), even when the tricuspid regurgitating jet cannot be assessed."

Characterization of pulmonary arterial stiffness using cardiac MRI.

Pulmonary arterial stiffness (PAS) is a pathologic hallmark of all types of pulmonary hypertension (PH). Cardiac MRI (CMR), a gold-standard imaging modality for the evaluation of pulmonary flow, biventricular morphology and function has been historically reserved for the longitudinal clinical follow-up, PH phenotyping purposes, right ventricular evaluation, and research purposes. Over the last two decades, numerous indices combining invasive catheterization and non-invasive CMR have been utilized to phenotype the character and severity of PAS in different types of PH and to assess its clinically prognostic potential with encouraging results. Many recent studies have demonstrated a strong role of CMR derived PAS markers in predicting long-term clinical outcomes and improving currently gold standard risk assessment provided by the REVEAL calculator. With the utilization of a machine learning strategies, strong diagnostic and prognostic performance of CMR reported in multicenter studies, and ability to detect PH at early stages, the non-invasive assessment of PAS is on verge of routine clinical utilization. In this review, we focus on appraising important CMR studies interrogating PAS over the last 20 years, describing the benefits and limitations of different PAS indices, and their pathophysiologic relevance to pulmonary vascular remodeling. We also discuss the role of CMR and PAS in clinical surveillance and phenotyping of PH, and the long-term future goal to utilize PAS as a biomarker to aid with more targeted therapeutic management.

Significance of Hypocapnia in the Risk Assessment of Patients with Pulmonary Hypertension.

Blood gas analysis is part of the diagnostic work-up for pulmonary hypertension (PH). Although some studies have found that the partial pressure of carbon dioxide (PaCO2) is an independent marker of mortality in individuals with pulmonary arterial hypertension (PH Group 1), there is a lack of data regarding the significance of PaCO2 in individuals with different types of PH based on the new 2022 definitions. Therefore, this study analyzed data from 157 individuals who were undergoing PH work-up, including right heart catheterization, using PH definitions from the 2022 European Society of Cardiology/European Respiratory Society guidelines. At diagnosis, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels were significantly higher, but the time-course of NT-pro-BNP levels during treatment was significantly more favorable in individuals with pulmonary arterial hypertension (PH Group 1) who did versus did not have hypocapnia (p = 0.026 and p = 0.017, respectively). These differences based on the presence of hypocapnia were not seen in individuals with PH Groups 2, 3, or 4. In conclusion, using the new definition of PH, hypocapnia may correlate with worse risk stratification at diagnosis in individuals with pulmonary arterial hypertension. However, hypocapnic individuals with pulmonary arterial hypertension may benefit more from disease-specific therapy than those without hypocapnia.

Outcomes of pregnancy in women with different types of pulmonary hypertension

BackgroundPulmonary hypertension (PH) is considered to increase maternal and fetal risk, and we attempt to explore pregnancy outcomes in women with different types of PH.MethodsWe retrospectively analyzed the clinical data of pregnant women with PH who were admitted to Anzhen Hospital from January 2010 to December 2019, and followed up on these parturients and their offspring.ResultsThree hundred and sixty-six pregnant women with PH were collected, including 265 pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD), 65 PH caused by left heart disease, 12 idiopathic PH, and 24 PH associated with other diseases. Maternal mean age was 28.4 ± 4.4 years and 72.1% were nulliparous. The estimated systolic pulmonary artery pressure was < 50 mmHg in 40.2% of patients, 50–70 mmHg in 23.2%, and > 70 mmHg in 36.6%. In more than 94% of women, a diagnosis of PH was made before pregnancy. During pregnancy, heart failure occurred in 15% of patients. Cesarean section was performed in 90.5% (20.4% emergency). Complications included fetal mortality (0.5%), preterm delivery (40.4%), and low birth weight (37.7%). A total of 20 mothers died (5.5%). The highest mortality rate was found in patients with idiopathic PH (4/12, 33.3%). A total of 12 children died (3.3%), 5 (1.4%) of them after discharge from the hospital, and 7 (1.9%) were in hospital.ConclusionsAlthough most of these women are fertile, PH does increase maternal and fetal risk. Women with idiopathic PH and Eisenmenger syndrome are not recommended to have children.

Oxidative Stress and Antioxidant Therapy in Pulmonary Hypertension.

Pulmonary hypertension (PH) is a progressive disease characterized by elevated artery pressures and pulmonary vascular resistance. Underlying mechanisms comprise endothelial dysfunction, pulmonary artery remodeling and vasoconstriction. Several studies have shown evidence of the critical role of oxidative stress in PH pathophysiology. Alteration of redox homeostasis produces excessive generation of reactive oxygen species, inducing oxidative stress and the subsequent alteration of biological molecules. Exacerbations in oxidative stress production can lead to alterations in nitric oxide signaling pathways, contributing to the proliferation of pulmonary arterial endothelial cells and smooth muscle cells, inducing PH development. Recently, antioxidant therapy has been suggested as a novel therapeutic strategy for PH pathology. However, the favorable outcomes observed in preclinical studies have not been consistently reproduced in clinical practice. Therefore, targeting oxidative stress as a therapeutic intervention for PH is an area that is still being explored. This review summarizes the contribution of oxidative stress to the pathogenesis of the different types of PH and suggests antioxidant therapy as a promising strategy for PH treatment.

Pulmonary hypertension: Linking inflammation and pulmonary arterial stiffening.

Pulmonary hypertension (PH) is a progressive disease that arises from multiple etiologies and ultimately leads to right heart failure as the predominant cause of morbidity and mortality. In patients, distinct inflammatory responses are a prominent feature in different types of PH, and various immunomodulatory interventions have been shown to modulate disease development and progression in animal models. Specifically, PH-associated inflammation comprises infiltration of both innate and adaptive immune cells into the vascular wall of the pulmonary vasculature—specifically in pulmonary vascular lesions—as well as increased levels of cytokines and chemokines in circulating blood and in the perivascular tissue of pulmonary arteries (PAs). Previous studies suggest that altered hemodynamic forces cause lung endothelial dysfunction and, in turn, adherence of immune cells and release of inflammatory mediators, while the resulting perivascular inflammation, in turn, promotes vascular remodeling and the progression of PH. As such, a vicious cycle of endothelial activation, inflammation, and vascular remodeling may develop and drive the disease process. PA stiffening constitutes an emerging research area in PH, with relevance in PH diagnostics, prognostics, and as a therapeutic target. With respect to its prognostic value, PA stiffness rivals the well-established measurement of pulmonary vascular resistance as a predictor of disease outcome. Vascular remodeling of the arterial extracellular matrix (ECM) as well as vascular calcification, smooth muscle cell stiffening, vascular wall thickening, and tissue fibrosis contribute to PA stiffening. While associations between inflammation and vascular stiffening are well-established in systemic vascular diseases such as atherosclerosis or the vascular manifestations of systemic sclerosis, a similar connection between inflammatory processes and PA stiffening has so far not been addressed in the context of PH. In this review, we discuss potential links between inflammation and PA stiffening with a specific focus on vascular calcification and ECM remodeling in PH.

Various factors contribute to death in patients with different types of pulmonary hypertension: A retrospective pilot study from a single tertiary center.

A few studies have focused on the cause of death from different types of pulmonary hypertension (PH). This study aimed to systematically analyze the primary and secondary causes of death and compare the profiles between different PH groups. The contribution of PH to death was assessed in precapillary PH (i.e., group 1 [pulmonary arterial hypertension], group 3 [PH associated with lung disease], and group 4 [chronic thromboembolic PH]) using specific criteria; death was classified into three categories: PH death (death due to PH only), PH-related death, and PH-unrelated death. Disorders other than PH that contributed to death were analyzed, and mortality profiles were compared between groups. Eighty deceased patients with PH were examined (group 1, n=28; group 3, n=39; and group 4, n=13). The contribution of PH to death was significantly different between the three groups. "PH death" was most common in group 1 (61%), "PH-related death" in group 3 (56%), and "PH-related death" and "PH-unrelated death" in group 4 (38% for both). The highest contributing factor to death other than PH was respiratory failure in group 3 and malignant disease in group 4. Significant variations in the causes of death were observed in groups 1, 3, and 4PH patients. In addition to PH, respiratory failure and malignant disease significantly contributed to death in group 3 and group 4PH, respectively. Understanding the precise death cause may be important in achieving better outcomes in PH patients.

Normalization of Four Different Types of Pulmonary Hypertension After Atrial Septal Defect Closure.

Pulmonary hypertension (PH) is an established risk factor in patients with atrial septal defect (ASD), and its persistence after ASD closure is associated with increased mortality. Therefore, predictors for PH normalization after defect closure are needed. Multiple hemodynamic types of PH exist, but little is known about their prevalence and prognostic value for PH normalization after ASD closure. We carried out a retrospective study on 97 patients (76% female, median age at ASD closure 58 years) with four types of PH determined predominantly by right heart catheterization: hyperkinetic, pulmonary arterial hypertension, isolated post-capillary, and combined pre- and post-capillary. We investigated the frequency of the PH types and their prognostic significance for PH normalization after ASD closure. Frequency of PH types before ASD closure in our study was: hyperkinetic 55%, pulmonary arterial hypertension 10%, isolated post-capillary PH 24%, and combined PH 11%. Hyperkinetic PH type was positively associated with PH normalization after ASD closure (78% patients normalized), remaining a significant independent predictor when adjusted for age at closure, sex, heart failure, and NYHA. Hyperkinetic PH patients also had significantly better survival prognosis versus patients with other PH types (p = 0.04). Combined PH was negatively associated with PH normalization, with no patients normalizing. Pulmonary arterial hypertension and isolated post-capillary PH had intermediate rates of normalization (60 and 52%, respectively). In summary, all four hemodynamic types of PH are found in adult patients with ASD, and they can be used to stratify patients by their likelihood of PH normalization and survival after ASD closure.

Pulmonary Hypertension Associated with Connective Tissue Disease.

Pulmonary hypertension (PH), a syndrome characterized by elevated pulmonary pressures, commonly complicates connective tissue disease (CTD) and is associated with increased morbidity and mortality. The incidence of PH varies widely between CTDs; patients with systemic sclerosis are most likely to develop PH. Several different types of PH can present in CTD, including PH related to left heart disease and respiratory disease. Importantly, CTD patients are at risk for developing pulmonary arterial hypertension, a rare form of PH that is associated with high morbidity and mortality. Future therapies targeting pulmonary vascular remodeling may improve outcomes for patients with this devastating disease.

Use of small pulmonary vascular alterations to identify different types of pulmonary hypertension: a quantitative computed tomography analysis.

The morphological alterations of small pulmonary vessels measured by computed tomography (CT) is increasingly used in evaluation of suspected pulmonary hypertension (PH). To investigate the significance alterations of quantitative assessment of small pulmonary vessels on chest CT in distinguishing different types of PH and their severity. We retrospectively analyzed a dataset of 120 healthy controls (HCs) and 91 PH patients, including 34 patients with connective tissue diseases-related PH (CTD-PH), 26 patients with idiopathic pulmonary arterial hypertension (iPAH), and 31 patients with chronic obstructive pulmonary disease-related PH (COPD-PH). The CTD-PH patients were divided into mild to moderate PH (CTD-LM-PH) group (n = 17) and severe PH (CTD-S-PH) group (n = 17). A total of 53 CTD patients without PH (CTD-nPH) were enrolled for comparison with the CTD-PH. We measured the cross-sectional area of small pulmonary vessels < 5 mm2 (%CSA<5) and between 5-10 mm2 (%CSA5-10) as a percentage of total lung area among the populations included above and compared %CSA in different types of PH groups and HCs group. The mean pulmonary arterial pressure (mPAP) was measured by right heart catheterization. The %CSA5-10 of COPD-PH, CTD-PH, and iPAH patients increased (0.21±0.09, 0.49±0.20 and 0.61±0.20, p < 0.02) sequentially, while the %CSA<5 of CTD-PH, iPAH, and COPD-PH patients decreased (0.79±0.65, 0.65±0.38 and 0.52±0.27, p < 0.05) sequentially. The %CSA5-10 was significantly higher in CTD-S-PH patients than CTD-LM-PH patients and CTD-nPH patients (0.51±0.21, 0.31±0.15 and 0.28±0.12, p < 0.01). The %CSA5-10 was positively correlated with mPAP in the CTD-PH group. The quantitative parameters %CSA<5 and %CSA5-10 assessed by chest CT are useful for distinguishing different types of PH. In addition, the %CSA5-10 can provide information for identification of CTD-PH severity.

The biventricular dysfunction evaluation in the different types of pulmonary hypertension

Abstract Background Right ventricular (RV) function is well-known prognostic factor in patients with pulmonary hypertension (PH). However, situation becomes critical when underfilling of left ventricle (LV) leads to systemic hypoperfusion and scenario worsening. Objective To evaluate the relationship of RV and LV dysfunction in patients with the different forms of PH. Methods We evaluated parameters of RV and LV function and their relationship during right heart catheterization (RHC) in 125 patients with different forms of pulmonary arterial hypertension (PAH) and 51 patients with chronic thromboembolic PH (CTEPH), 7 patients with PH associated with left heart disease (LHD) and 17 patients in whom PH was excluded after procedure. In all patients recommended echocardiography protocol (Echo) and NT-proBNP level evaluation were performed. Results In the group without PH the RV stroke work index (RVSWI) level and its ratio to the LV stroke work index (LVSWI) were lowest and in the normal range: 7,0±0,7 ml·mmHg/m2 and 0,13±0,02 respectively. In all patients with PH, we noted the significant elevation of RVSWI &amp;gt;20 ml·mmHg/m2. Patients with PAH and CTEPH had a smaller left atrium, LV volumes on Echo and decreased stroke volume and pulmonary artery wedge pressure. The underfilling of LV in IPAH and CTEPH groups accompanied by severe lowering of LWSWI to 35–45 ml·mmHg/m2 (p&amp;lt;0,05 compared with LHD group and patients without PH). In spite of the levels of cardiac index were similar in patients with LHD and without PH, the RVSWI (23,1±2,7 ml·mmHg/m2) and its RVSWI/LVSWI ratio (0,53±0,09) were significantly higher in LHD group and confirmed severe RV overload. Only in HIV infection group observed severe depression of the pumping function of both heart's sides and levels of RWSWI and LVSWI were lowest, but the ratio was elevated (0,53) and indicated RV overload. Similar data were observed when we compare pumping coefficients of RV and LV in different groups. We did not find any association between NT-proBNP level and the LV volume and function. Conclusion The simultaneous evaluation of parameters of RV and LV function and their ratio during RHC in patients with different types of PH allowed not just to estimate the degree of RV overload and dysfunction, but also LV underfilling and dysfunction. Funding Acknowledgement Type of funding sources: None.

Severity of Tricuspid Regurgitation on the Long-term Outcomes In Patients with Group I Pulmonary Hypertension Vs. Group Ii Pulmonary Hypertension

Background Severity of tricuspid regurgitation (TR) is implicated in the prognosis of different cardiac diseases, however little is known about this association in different types of pulmonary hypertension (PH) patients. Methods Single center study where 80 patients were recruited (40 with group I PH and 40 with group II PH). Echocardiogram was performed at 6 months and 12 months intervals after starting pulmonary vasodilators. Right heart cath was done at the beginning and after 12 months follow up. RV free-wall speckle-tracking strain, s’, TAPSE were used to assess RV function. TR severity was measured by echocardiogram and confirmed by cardiac MRI. Non ischemic LGE pattern and RV insertion site LGE were assessed. Patients were followed for a total of 24 months. Results Kaplan-Meier curve showed that patients with more than moderate TR had overall worse outcomes especially in group II PH (log-rank p=0.06). There was noticeable reduction in severity of TR after starting pulmonary vasodilators in the 2 groups, however p value was not significant. RV function improved when TR severity went from severe to mild and this was confirmed both by echo and cardiac MRI especially in group II PH with p value of 0.09. The presence of LGE was associated with worse outcomes regardless of type of PH, p value was 0.001. RV free wall speckle tracking strain improved as severity of TR improves especially from severe to mild and this was mostly noticed in group II PH with overall better outcome. Conclusion Improvement of TR and RV free wall speckle tracking strain was associated with better outcomes especially in group II PH. The presence of LGE regardless of type of PH, was associated with worse outcomes in the long term.

The Effect of Exercise on Endothelin 1 Level in Patients with Pulmonary Hypertension

Endothelin-1 (ET-1), a potent vasoconstrictor, is elevated in heart failure as well as in pulmonary arterial hypertension (PAH). To our knowledge little is known about ET-1 level in exercise induced pulmonary hypertension when compared to group 1 and 2 pulmonary hypertension. We aim to assess effect of exercise on ET-1 levels in different types of pulmonary hypertension. A prospective study measuring ET-1 level in patient with PAH, heart failure induced pulmonary hypertension (D-PH), exercise induced PAH and exercise induced D-PH both at rest at peak exercise. Demographic and echo data were collected. Right heart cath was done to confirm diagnosis and type of pulmonary hypertension, which was followed by arm lifting exercise for 4 minutes (30 watts and decrease of MVO2 by >10%) using different weights. Exercise induced PAH defined as mean pulmonary pressure (mPA) <20 mmHg at rest, with exercise mPA >30 mmHg and pulmonary wedge (PW) <20 mmHg. Exercise induced D-PH was defined as mPA<20 mmHg at rest, with exercise mPA >30 mmHg and PW >20 mmHg. Blood samples were collected to measure ET-1 level using ET-1 ELISA. A total of 77 patients were included in this study. 5 study groups were divided into: 10 control subjects, 18 patients with D-PH, 22 patients with PAH, 15 patients with Exercise D-PH and 12 patients with Exercise PAH. At rest, ET-1 level was the highest in Exercise-PAH compared to other groups 3.6 +/- 2 with p valule 0.04. Whereas, at peak exercise, ET-1 level was the highest in PAH compared to other groups with, 2.91 +/- 1.8 with p value of 0.05 (figure 1). Patients with D-PH had more evidence of diabetes mellitus, Obesity, smoking, dilated right atrium, right ventricular failure and were more elderly male. At rest, ET-1 level is the highest in patients with exercise induced PAH, whereas at peak exercise, ET-1 is the highest in patients with PAH. Patients with heart failure induced pulmonary hypertension have more cardiac risk factors with evidence of right sided failure.

NUCLEAR IMAGING IN PULMONARY HYPERTENSION

The review describes current possibilities of nuclear imaging methods in different types of pulmonary hypertension (PH): lung ventilation-perfusion scintigraphy and single photon emission computed tomography (SPECT), radionuclide ventriculography and angiography, as well as new potentials of myocardial perfusion SPECT for the evaluation of right ventricle.

Is Right Ventricular Remodeling in Pulmonary Hypertension Dependent on Etiology? An Echocardiographic Study.

Survival in patients (pts) with pulmonary hypertension (PH) differs between subgroups at similar levels of pressure overload. We set to analyze right ventricular (RV) morphology and function in different types of PH using conventional and deformation imaging echocardiography. Thirty-four pts with PH: 12 pts with idiopathic pulmonary arterial hypertension (IPAH, 42.2 ± 13 years), 11 pts with chronic thromboembolic PH (CTEPH, 50.8 ± 12 years), 11 pts with Eisenmenger syndrome [ES 41.2 ± 15 years, 4 with atrial septal defect (ASD) and 7 with ventricular septal defect (VSD)], and 13 age-matched healthy individuals (38.1 ± 15 years) were evaluated. The following echocardiographic parameters were measured: echo-derived systolic pulmonary pressure (sPAPecho), RV end-diastolic diameter (RVEDD), RV wall thickness (RVWT), TAPSE, RV fractional area change (RVFAC), Tei index, peak systolic velocity of the tricuspid ring (S't), and speckle tracking-derived RV free wall strain. Furthermore, right heart catheterization (RHC) was performed in pts with PH and mean, and systolic pulmonary artery pressure (mPAPcath, sPAPcath), cardiac output (CO), cardiac index (COi), and pulmonary vascular resistance (PVR) were noted. The levels of mPAPcath and sPAPcath were similar between pts with PH (pANOVA = NS). Patients with ES had higher COi compared to other groups (2.94 ± 0.79, 2.28 ± 0.69, and 1.74 ± 0.46 L/min/m(2) for pts with ES, IPAH, and CTEPH respectively, pANOVA = 0.004, P post hoc ES versus all other groups < 0.05). TAPSE, Tei index, and S't were similar between groups and impaired versus controls (pANOVA < 0.001, P post hoc between groups of patients = NS). Patients with ES had better RVFAC (41.1 ± 9, 30.5 ± 10.8, 23.2 ± 9.8%) and RV free wall strain (-20.6 ± 3.5, -16.3 ± 7.5, -10.8 ± 5%), as well as an increased thickness of the RV free wall compared to other groups of patients (9.2 ± 1.5, 7.2 ± 1 and 7.2 ± 1.6 mm for pts with ES, IPAH and CTEPH, respectively) (pANOVA<0.001, P post hoc <0.05 ES versus all other groups). RVFAC and RV free wall strain significantly correlated with COi (r = 0.53, P = 0.006 and r = -0.77, P < 0.001, respectively). Patients with ES have a more hypertrophied RV free wall, better RV performance as assessed by RVFAC and RV free wall strain and increased COi compared to other types of PH. Furthermore, RV performance appears to be less dependent on the level of pressure overload. These findings could contribute to the better survival profile of patients with ES.

Anticoagulation therapy versus placebo for pulmonary hypertension.

Elevation of pulmonary pressure is no longer a rare disease, given its multifactorial etiology. However data on the actual incidence of this condition are still limited, and controversies regarding its management are ongoing. Use of anticoagulation in the management of pulmonary hypertension is based on the presence of in situ thrombosis in the patient with pulmonary arterial hypertension (PAH) and on retrospective evidence of clinical benefit. Current practice is dependent mostly on expert opinion and individualised experience. The real benefit of its use in different types of pulmonary hypertension is still debatable, and the therapeutic target of the international normalised ratio (INR) among treated patients remains inconclusive. Adverse outcomes associated with anticoagulants are significant and can include fatal haemorrhage. Justification for the use of this intervention requires critical evaluation of randomised controlled trials. 1. To evaluate the effectiveness of, and potential adverse events associated with, anticoagulation in the management of pulmonary hypertension (PH).2. To evaluate the effective therapeutic INR in pulmonary hypertensive patients receiving anticoagulants (North American centres 1.5 to 2.5, European centres 2.0 to 3.0). We identified trials through searches of the following databases.Cochrane Airways Group Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL), part of The Cochrane Library; MEDLINE (Ovid); EMBASE (Ovid); CINAHL (EBSCOhost); Clinical trials.gov and the World Health Organization (WHO) trials portal. The trial search date was 28 March 2014. We planned to include only randomised controlled trials. Participants with PH with co-morbidities including medical conditions requiring long-term anticoagulation were to be included. We also planned to include trials comparing any anticoagulant with placebo. Review authors (IE and HE) independently appraised all identified citations to establish their relevance for inclusion in the review. IE and HE independently screened the titles and abstracts of all identified potential studies for inclusion. No eligible trials were identified for inclusion in this review. No eligible studies were identified for inclusion in this review. Although our review of available non-randomised studies shows beneficial effect, this finding should be interpreted with caution since there are likely to be biases associated with their design and our methods were not designed to identify, appraise and summarise evidence from them. So that better decisions can be made regarding the effectiveness of this intervention, well-designed randomised controlled trials are needed.

Prevalence of Pulmonary Hypertension in Systemic Sclerosis in European Caucasians and Metaanalysis of 5 Studies

To measure the prevalence of different types of pulmonary hypertension (PH) and to identify patients with systemic sclerosis (SSc) at highest risk in a multicenter European sample, with a metaanalysis of relevant studies. Consecutive patients with SSc recruited at 11 French and Italian centers underwent detailed evaluations, including Doppler echocardiography, chest computed tomography, pulmonary function tests, and right-heart catheterization (RHC), to detect the presence and causes of PH. A metaanalysis was performed, including data from 4 other studies. Among 206 patients in whom it was suspected, PH was confirmed by RHC in 83 patients (7%). Precapillary PH was found in 64 patients (5%), of whom 42 had pulmonary arterial hypertension (PAH) and 22 had PH secondary to interstitial lung disease (ILD). RHC identified 17 patients (1%) with postcapillary PH secondary to left-heart disease. Patients with DLCO/alveolar volume < 70% were more likely to have precapillary PH (87.5% vs 42%; p < 0.0001). Precapillary and postcapillary PH were associated with advanced age (68 ± 14 vs 59 ± 12 yrs, p < 0.0001, and 74 ± 16 vs 61.5 ± 10 yrs, p < 0.0001, respectively). The metaanalysis of 3818 patients showed a prevalence of precapillary PH of 9% (95% CI 6%-12%) and identified advanced age, longer disease duration, and limited cutaneous disease subset as risk factors for this condition. The prevalence of precapillary PH in our multicenter study of SSc was 5%, and in the metaanalysis 9%. Our observations support use of RHC to confirm the presence of precapillary PH suspected by noninvasive testing. We also identified patients at high risk who should be carefully monitored.

Different types of pulmonary hypertension require different treatment strategies

Different types of pulmonary hypertension require different treatment strategies

Recognition and management of pulmonary hypertension.

Pulmonary hypertension (mean pulmonary arterial pressure > 20mm Hg at rest or > 30mm Hg during exercise) occurs (i) as primary pulmonary hypertension (no known underlying cause), (ii) as persistent pulmonary hypertension of the newborn or (iii) secondary to a variety of lung and cardiovascular diseases. In the last 10 to 15 years there have been significant advances in the medical management of this debilitating and life-threatening disorder. The main drugs in current use are anticoagulants (warfarin, heparin) and vasodilators, especially oral calcium antagonists, intravenous prostacyclin (prostaglandin I2; epoprostenol) and inhaled nitric oxide. Calcium antagonists, (e.g. nifedipine, diltiazem) are used chiefly in primary pulmonary hypertension. They are effective in patients who give a pulmonary vasodilator response to an acute challenge with a short acting vasodilator (e.g. prostacyclin, nitric oxide or adenosine), and are used in doses greater than are usual in the treatment of other cardiovascular disorders. Prostacyclin, given by continuous intravenous infusion, is effective in patients even if they do not respond to an acute vasodilator challenge. The long term benefit in these patients is thought to reflect the antiproliferative effects of the drug and/or its ability to inhibit platelet aggregation. It is used either as long term therapy or as a bridge to transplantation. Inhaled nitric oxide, which is used mainly in persistent pulmonary hypertension of the newborn, has the particular benefit of being pulmonary selective, due to its route of administration and rapid inactivation. Anticoagulants have a specific role in the treatment of pulmonary thromboembolic pulmonary hypertension and are also used routinely in patients with primary pulmonary hypertension. Nondrug treatments for pulmonary hypertension include (i) supplemental oxygen (> or = 15 h/day), which is the primary therapy in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease and (ii) heart-lung or lung transplantation, which nowadays is regarded as a last resort. Different types of pulmonary hypertension require different treatment strategies. Future advances in the treatment of pulmonary hypertension may come from the use of drug combinations, the development of new drugs, such as endothelin antagonists, nitric oxide donors and potassium channel openers, or the application of gene therapy.