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Abstract Rationale Incident pulmonary arterial hypertension was underrepresented in most pulmonary hypertension registries and may have a different disease profile to prevalent disease. Objectives To determine the characteristics and outcome of a purely incident, treatment-naive cohort of idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension and to determine the changes in presentations and survival over the past decade in the United Kingdom and Ireland. Methods All consecutive newly diagnosed patients from 2001 to 2009 were identified prospectively. Measurements and Main Results A total of 482 patients (93% idiopathic, 5% heritable, and 2% anorexigen-associated pulmonary arterial hypertension) were diagnosed, giving rise to an estimated incidence of 1.1 cases per million per year and prevalence of 6.6 cases per million in 2009. Younger patients (age ≤ 50 yrs) had shorter duration of symptoms, fewer comorbidities, better functional and exercise capacity, higher percent diffusing capacity of carbon monoxide, more severe hemodynamic impairment, but better survival compared with older patients. In comparison with the earlier cohorts, patients diagnosed in 2007–2009 were older, more obese, had lower percent diffusing capacity of carbon monoxide,, and more comorbidities, but better survival. Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) equation, REVEAL risk score, and Pulmonary Hypertension Connection Registry survival equation accurately predicted survival of our incident cohort at 1 year. Conclusions This study highlights the influence of age on phenotypes of incident pulmonary arterial hypertension and has shown the changes in demographics and epidemiology over the past decade in a national setting. The results suggest that there may be two subtypes of patients: the younger subtype with more severe hemodynamic impairment but better survival, compared with the older subtype who has more comorbidities.

Patients classified as idiopathic pulmonary arterial hypertension (defined as Group 1 on European Respiratory Society (ERS)/European Cardiac Society (ESC) criteria) may have evidence of minor co-existing lung disease on thoracic computed tomography. We hypothesised that these idiopathic pulmonary arterial hypertension patients (IPAH lung disease) are a separate subgroup of idiopathic pulmonary arterial hypertension with different phenotype and outcome compared with idiopathic pulmonary arterial hypertension patients without co-existing lung disease (IPAH no lung disease). Patients with ‘IPAH lung disease’ have been eligible for all clinical trials of Group 1 patients because they have normal clinical examination and normal spirometry but we wondered whether they responded to treatment and had similar survival to patients with ‘IPAH no lung disease’. We described the outcome of the cohort of patients with ‘IPAH no lung disease’ in a previous paper. Here, we have compared incident ‘IPAH lung disease’ patients with ‘IPAH no lung disease’ patients diagnosed concurrently in all eight Pulmonary Hypertension centres in the UK and Ireland between 2001–2009. Compared with ‘IPAH no lung disease’ (n = 355), ‘IPAH lung disease’ patients (n = 137) were older, less obese, predominantly male, more likely to be current/ex-smokers and had lower six-minute walk distance, lower % predicted diffusion capacity for carbon monoxide, lower mean pulmonary arterial pressure and lower pulmonary vascular resistance index. After three months of pulmonary hypertension-targeted treatment, six-minute walk distance improved equally in ‘IPAH lung disease’ and ‘IPAH no lung disease’. However, survival of ‘IPAH lung disease’ was lower than ‘IPAH no lung disease’ (one year survival: 72% compared with 93%). This survival was significantly worse in ‘IPAH lung disease’ even after adjusting for age, gender, smoking history, comorbidities and haemodynamics. ‘IPAH lung disease’ patients had similar short-term improvement in six-minute walk distance with anti-pulmonary arterial hypertension therapy but worse survival compared with ‘IPAH no lung disease’ patients. This suggests that ‘IPAH lung disease’ are a separate phenotype and should not be lumped with ‘IPAH no lung disease’ in clinical trials of Group 1 pulmonary arterial hypertension.

ObjectiveInoperable chronic thromboembolic pulmonary hypertension (CTEPH) managed medically has a poor prognosis. Balloon pulmonary angioplasty (BPA) offers a new treatment for inoperable patients. The national BPA service for the UK opened in October 2015 and we now describe the treatment of our initial patient cohort.MethodsThirty consecutive, inoperable, anatomically suitable, symptomatic patients on stable medical therapy for CTEPH were identified and offered BPA. They initially underwent baseline investigations including Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) quality of life (QoL) questionnaire, cardiopulmonary exercise test, 6 min walk distance (6MWD), transthoracic echocardiography, N-terminal probrain natriuretic peptide (NT pro-BNP) and right heart catheterisation. Serial BPA sessions were then performed and after completion, the treatment effect was gauged by comparing the same investigations at 3 months follow-up.ResultsA median of 3 (IQR 1–6) BPA sessions per patient resulted in a significant improvement in functional status (WHO functional class ≥3: 24 vs 4, p<0.0001) and QoL (CAMPHOR symptom score: 8.7±5.4 vs 5.6±6.1, p=0.0005) with reductions in pulmonary pressures (mean pulmonary artery pressure: 44.7±11.0 vs 34.4±8.3 mm Hg, p<0.0001) and resistance (pulmonary vascular resistance: 663±281 vs 436±196 dyn.s.cm-5, p<0.0001). Exercise capacity improved (minute ventilation/carbon dioxide production: 55.3±12.2 vs 45.0±7.8, p=0.03 and 6MWD: 366±107 vs 440±94 m, p<0.0001) and there was reduction in right ventricular (RV) stretch (NT pro-BNP: 442 (IQR 168–1607) vs 202 (IQR 105–447) pg/mL, p<0.0001) and dimensions (mid RV diameter: 4.4±1.0 vs 3.8±0.7 cm, p=0.002). There were no deaths or life-threatening complications and the mild-moderate per-procedure complication rate was 10.5%.ConclusionsBPA is safe and improves the functional status, QoL, pulmonary haemodynamics and RV dimensions of patients with inoperable CTEPH.

Abstract Rationale The management of chronic thromboembolic pulmonary hypertension (CTEPH) has changed over recent years with the growth of pulmonary endarterectomy surgery and the availability of disease-modifying therapies. Objectives To investigate the prognosis of CTEPH in a national setting during recent years. Methods All incident cases diagnosed in one of the five pulmonary hypertension centers in the United Kingdom between January 2001 and June 2006 were identified prospectively. Information regarding baseline characteristics, treatment, and follow-up was subsequently collected from hospital records. Measurements and Main Results A total of 469 patients received a diagnosis, of whom 148 (32%) had distal, nonsurgical disease. One- and three-year survival from diagnosis was 82 and 70% for patients with nonsurgical disease and 88 and 76% for those treated surgically (P = 0.023). Initial functional improvement in patients with nonsurgical disease was noted but did not persist at 2 years. Significant functional and hemodynamic improvements were seen in surgically treated patients with an increase in six-minute-walk distance of 105 m (P < 0.001) at 3 months. Five-year survival from surgery in the 35% of patients who survived to 3 months but had persistent pulmonary hypertension was 94%. Conclusions The prognosis in nonsurgical disease has improved. We have confirmed the previously described good outcome in surgically treated disease. However, we have also demonstrated that the long-term prognosis for patients who have persistent pulmonary hypertension at 3 months after surgery is good. The observed improvements in outcome during the modern treatment era reinforce the importance of identifying patients with this increasingly treatable condition.

BackgroundAnaemia is common in left heart failure and is associated with a poorer outcome. Many patients with pulmonary arterial hypertension (PAH) are anaemic or iron-deficient. This study was performed to investigate the prevalence of iron deficiency in PAH and to identify possible causes.MethodsAll patients with idiopathic or heritable PAH diagnosed in 1995–2008 were identified. Controls were selected from patients with chronic thromboembolic pulmonary hypertension (CTEPH). Full blood counts were examined and any abnormality was investigated. Patients were excluded if they had a cause for iron deficiency. The prevalence study was based on 85 patients with idiopathic PAH and 120 with CTEPH. A separate group of 20 patients with idiopathic PAH and 24 with CTEPH with matching haemodynamics were prospectively investigated for serum factors affecting iron metabolism.ResultsThe prevalence study identified a point prevalence of unexplained iron deficiency of 50% in premenopausal women with idiopathic PAH compared with 8% in premenopausal women with CTEPH (p=0.002); 14% in postmenopausal women with idiopathic PAH compared with 6% in postmenopausal women with CTEPH (p=0.16); 28% in men with idiopathic PAH men compared with 2% in men with CTEPH (p=0.002); and 60% in patients with heritable PAH. The serum study showed that patients with idiopathic PAH had lower serum iron and transferrin saturations than those with CTEPH. Interleukin-6 levels correlated with iron levels(r=−0.6, p=0.006) and transferrin saturations (r=−0.68, p=0.001) in idiopathic PAH but not in CTEPH.ConclusionsThe prevalence of unexplained iron deficiency is significantly higher in idiopathic PAH than in CTEPH. This may be linked to interleukin-6.

Early recognition and diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is crucial for improving prognosis and reducing the disease burden. Established clinical practice guidelines describe interventions for the diagnosis and evaluation of CTEPH, yet limited insight remains into clinical practice variation and barriers to care. The CTEPH global cross‐sectional scientific survey (CLARITY) was developed to gather insights into the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the recognition and diagnosis of CTEPH and the referral and evaluation of these patients. The survey was offered to hospital‐based medical specialists through Scientific Societies and other medical organizations, from September 2021 to May 2022. Response data from 353 physicians showed that self‐reported awareness of CTEPH increased over the past 10 years among 96% of respondents. Clinical practices in acute pulmonary embolism (PE) follow‐up and CTEPH diagnosis differed among respondents. While 50% of respondents working in a nonexpert center reported to refer patients to an expert pulmonary hypertension/CTEPH center when CTEPH is suspected, 51% of these physicians did not report referral of patients with a confirmed diagnosis for further evaluation. Up to 50% of respondents involved in the evaluation of referred patients have concluded a different operability status than that indicated by the referring center. This study indicates that early diagnosis and timely treatment of CTEPH is challenged by suboptimal acute PE follow‐up and patient referral practices. Nonadherence to guideline recommendations may be impacted by various barriers to care, which were shown to vary by geographical region.

The 6 minutes walk test (6MWT) is often shown to be the best predictor of mortality in pulmonary hypertension (PH) probably because it challenges the failing heart to deliver adequate cardiac output. We hypothesised that the 6MWT elicits maximal cardiac output as measured during a maximal cardiopulmonary exercise testing (CPET). 18 patients with chronic thromboembolic pulmonary hypertension (n = 12) or pulmonary arterial hypertension (n = 6) and 10 healthy subjects performed a 6MWT and CPET with measurements of cardiac output (non invasive rebreathing device) before and directly after exercise. Heart rate was measured during 6MWT with a cardiofrequence meter. Cardiac output and heart rate measured at the end of the 6MWT were linearly related to 6MW distance (mean±SD: 490±87 m). Patients with a high NT-pro-BNP achieve a maximum cardiac output during the 6MWT, while in normal subjects and in patients with a low-normal NT-proBNP, cardiac output at the end of a 6MWT was lower than achieved at maximum exercise during a CPET. In both cases, heart rate is the major determinant of exercise-induced increase in cardiac output. However, stroke volume increased during CPET in healthy subjects, not in PH patients. Maximal cardiac output is elicited by 6MWT in PH patients with failing right ventricle. Cardiac output increase is dependent on chronotropic response in patients with PH.

Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross‐sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients. The survey was circulated to hospital‐based medical specialists through Scientific Societies and other medical organizations from September 2021 to May 2022. The majority of the 212 respondents involved in the treatment of CTEPH were from centers performing up to 50 pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedures per year. Variation was observed in the reported proportion of patients deemed eligible for PEA/BPA, as well as those that underwent the procedures, including multimodal treatment and subsequent follow‐up practices. Prescription of pulmonary arterial hypertension‐specific therapy was reported for a variable proportion of patients in the preoperative setting and in most nonoperable patients. Reported use of vitamin K antagonists and direct oral anticoagulants was similar (86% vs. 82%) but driven by different factors. This study presents heterogeneity in treatment approaches for CTEPH, which may be attributed to center‐specific experience and region‐specific barriers to care, highlighting the need for new clinical and cohort studies, comprehensive clinical guidelines, and continued education.

Acute pulmonary embolism (PE) is a disease frequently encountered in clinical practice. While the management of haemodynamically stable, low risk patients with acute PE is well established, managing intermediate disease often presents a therapeutic dilemma. In this review, we discuss the various therapeutic options available in this patient group. This includes thrombolysis, surgical embolectomy and catheter directed techniques. We have also explored the role of specialist PE response teams in the management of such patients. ​

Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post‐PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA—89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6‐minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)‐quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (−27.9 ± 20.2% vs. −13.9 ± 23.9%, p  < 0.05) and ΔmPAP (−17.1 ± 14.4% vs. −8.5 ± 18.0%, p  < 0.05). There was a negative correlation between pre‐BPA PVR and TTTL ( r  = −0.47, p  < 0.05) which persisted post‐BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post‐BPA in PP patients. BPA response was not related to TTTL terciles or CTPA‐quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.