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Background: Diagnostic rates and risk factors for the subsequent development of chronic thromboembolic pulmonary hypertension (CTEPH) following pulmonary embolism (PE) are not well defined., Methods: Over a 10-year period (2010-2020), consecutive patients attending a PE follow-up clinic in Sheffield, UK (population 554 600) and all patients diagnosed with CTEPH at a pulmonary hypertension (PH) referral centre in Sheffield (referral population estimated 15-20 million) were included., Results: Of 1956 patients attending the Sheffield PE clinic 3 months following a diagnosis of acute PE, 41 were diagnosed with CTEPH with a cumulative incidence of 2.10%, with 1.89% diagnosed within 2 years. Of 809 patients presenting with pulmonary hypertension (PH) and diagnosed with CTEPH, 32 were Sheffield residents and 777 were non-Sheffield residents. Patients diagnosed with CTEPH at the PE follow-up clinic had shorter symptom duration (p<0.01), better exercise capacity (p<0.05) and less severe pulmonary haemodynamics (p<0.01) compared with patients referred with suspected PH. Patients with no major transient risk factors present at the time of acute PE had a significantly higher risk of CTEPH compared with patients with major transient risk factors (OR 3.6, 95% CI 1.11-11.91; p=0.03). The presence of three computed tomography (CT) features of PH in combination with two or more out of four features of chronic thromboembolic pulmonary disease at the index PE was found in 19% of patients who developed CTEPH and in 0% of patients who did not. Diagnostic rates and pulmonary endarterectomy (PEA) rates were higher at 13.2 and 3.6 per million per year, respectively, for Sheffield residents compared with 3.9-5.2 and 1.7-2.3 per million per year, respectively, for non-Sheffield residents., Conclusions: In the real-world setting a dedicated PE follow-up pathway identifies patients with less severe CTEPH and increases population-based CTEPH diagnostic and PEA rates. At the time of acute PE diagnosis the absence of major transient risk factors, CT features of PH and chronic thromboembolism are risk factors for a subsequent diagnosis of CTEPH., Competing Interests: Conflict of interest: C. Durrington reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports lecture honoraria from Janssen Pharmaceuticals, outside the submitted work. C.A. Elliot reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D. De-Fonseka reports a leadership role on the Pleural Specialist Advisory Group and Pleural Disease Guideline Committee for the British Thoracic Society, outside the submitted work. A.J. Swift reports support for the present manuscript from a Wellcome Trust fellowship, and also reports grants from Janssen Pharmaceuticals, NIHR and Wellcome Trust, and consulting fees from Janssen Pharmaceuticals, outside the submitted work. K. Dwivedi reports support for the present manuscript from Wellcome 4Ward North fellowship, and also reports grants from Janssen, and lecture honoraria from Royal College of Radiologists, and is a committee member for the Royal College of Radiologists Artificial Intelligence Working Group and Royal College of Radiologists RADIANT group, outside the submitted work. A. Charalampopoulos reports lecture honoraria from Janssen and Boehringer, outside the submitted work. A. Hameed reports lecture honoraria and travel support from Janssen, outside the submitted work. A.M.K. Rothman reports grants from a Wellcome Trust Clinical Research Career Development Fellowship (206632/Z/17/Z), MRC (experimental medicine grant MR/W026279/1), Abbott Laboratories, Medtronic Inc., Endotronix, SoniVie, NXT Biomedical, Gradient and Neptune Medical, outside the submitted work. N. Hamilton reports consulting fees and travel support from Janssen, lecture honoraria from MSD and Janssen, advisory board participation with Bayer, MSD, Janssen and Vifor, and a leadership role as pharmacist for the NHS Specialist Respiratory Clinical Reference Group, outside the submitted work. A.A.R. Thompson reports grants from the British Heart Foundation and NIHR, and lecture honoraria and travel support from Janssen-Cilag Ltd, outside the submitted work. R. Condliffe reports lecture honoraria and travel support from Janssen Pharmaceuticals, outside the submitted work. D.G. Kiely reports support for the present manuscript from NIHR Sheffield Biomedical Research Centre, and also reports grants from Janssen Pharmaceuticals, NIHR Sheffield Biomedical Research Centre and Ferrer, consulting fees and lecture honoraria from Janssen Pharmaceuticals, Ferrer, Altavant, MSD and United Therapeutics, travel support from Janssen, Ferrer, MSD and United Therapeutics, advisory board membership for Janssen and MSD, and leadership roles as a member of the Clinical Reference Group for Specialised Respiratory Medicine (NHS England) and lead of the UK National Audit of Pulmonary Hypertension, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Cardiac magnetic resonance (CMR) is the gold standard technique to assess biventricular volumes and function, and is increasingly being considered as an end-point in clinical studies. Currently, with the exception of right ventricular (RV) stroke volume and RV end-diastolic volume, there is only limited data on minimally important differences (MIDs) reported for CMR metrics. Our study aimed to identify MIDs for CMR metrics based on US Food and Drug Administration recommendations for a clinical outcome measure that should reflect how a patient "feels, functions or survives"., Methods: Consecutive treatment-naïve patients with pulmonary arterial hypertension (PAH) between 2010 and 2022 who had two CMR scans (at baseline prior to treatment and 12 months following treatment) were identified from the ASPIRE registry. All patients were followed up for 1 additional year after the second scan. For both scans, cardiac measurements were obtained from a validated fully automated segmentation tool. The MID in CMR metrics was determined using two distribution-based (0.5sd and minimal detectable change) and two anchor-based (change difference and generalised linear model regression) methods benchmarked to how a patient "feels" (emPHasis-10 quality of life questionnaire), "functions" (incremental shuttle walk test) or "survives" for 1-year mortality to changes in CMR measurements., Results: 254 patients with PAH were included (mean±sd age 53±16 years, 79% female and 66% categorised as intermediate risk based on the 2022 European Society of Cardiology/European Respiratory Society risk score). We identified a 5% absolute increase in RV ejection fraction and a 17 mL decrease in RV end-diastolic or end-systolic volumes as the MIDs for improvement. Conversely, a 5% decrease in RV ejection fraction and a 10 mL increase in RV volumes were associated with worsening., Conclusions: This study establishes clinically relevant CMR MIDs for how a patient "feels, functions or survives" in response to PAH treatment. These findings provide further support for the use of CMR as a clinically relevant clinical outcome measure and will aid trial size calculations for studies using CMR., Competing Interests: Conflict of interest: A.J. Swift has received research grant funding from Janssen Pharmaceuticals, and consultancy fees from Janssen Pharmaceuticals and General Electric. D.G. Kiely has received grant funding from Ferrer and Janssen Pharmaceuticals, and speaker and consultancy fees and funding for travel from Acceleron, Altavant, Ferrer, Janssen, MSD and United Therapeutics. The other authors have no relationships relevant to the contents of this paper to disclose., (Copyright ©The authors 2023.)

There are limited published data defining survival and treatment response in patients with mild lung disease and/or reduced gas transfer who fulfil diagnostic criteria for idiopathic pulmonary arterial hypertension (IPAH).Patients diagnosed with IPAH between 2001 and 2019 were identified in the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Centre) registry. Using prespecified criteria based on computed tomography (CT) imaging and spirometry, patients with a diagnosis of IPAH and no lung disease were termed IPAH no-LD (n=303), and those with minor/mild emphysema or fibrosis were described as IPAH mild-LD (n=190).Survival was significantly better in IPAH no-LD than in IPAH mild-LD (1- and 5-year survival 95% and 70% versus 78% and 22%, respectively; p<0.0001). In the combined group of IPAH no-LD and IPAH mild-LD , independent predictors of higher mortality were increasing age, lower diffusing capacity of the lung for carbon monoxide ( D LCO ), lower exercise capacity and a diagnosis of IPAH mild-LD (all p<0.05). Exercise capacity and quality of life improved (both p<0.0001) following treatment in patients with IPAH no-LD , but not IPAH mild-LD A proportion of patients with IPAH no-LD had a D LCO <45%; these patients had poorer survival than patients with D LCO ≥45%, although they demonstrated improved exercise capacity following treatment.The presence of even mild parenchymal lung disease in patients who would be classified as IPAH according to current recommendations has a significant adverse effect on outcomes. This phenotype can be identified using lung function testing and clinical CT reports. Patients with IPAH, no lung disease and severely reduced D LCO may represent a further distinct phenotype. These data suggest that randomised controlled trials of targeted therapies in patients with these phenotypes are required., Competing Interests: Conflict of interest: R.A. Lewis reports non-financial support from Actelion Pharmaceuticals, outside the submitted work. Conflict of interest: A.A.R. Thompson reports grants from British Heart Foundation, during the conduct of the study; support for meeting attendance from Actelion Pharmaceuticals Ltd, outside the submitted work. Conflict of interest: C.G. Billings has nothing to disclose. Conflict of interest: A. Charalampopoulos reports grants, personal fees and non-financial support from Actelion Pharmaceuticals, personal fees and non-financial support from Novartis, grants from Bayer and GSK, outside the submitted work. Conflict of interest: C.A. Elliot reports personal fees for advisory board work and lectures from Actelion Pharmaceuticals, GlaxoSmithKline and Bayer, grants from Pfizer, Actelion Pharmaceuticals and Bayer, support for meeting attendance from Bayer and Actelion Pharmaceuticals, outside the submitted work. Conflict of interest: N. Hamilton reports personal fees from MSD and Actelion, grants and personal fees from Bayer, outside the submitted work. Conflict of interest: C. Hill has nothing to disclose. Conflict of interest: J. Hurdman has nothing to disclose. Conflict of interest: S. Rajaram has nothing to disclose. Conflict of interest: I. Sabroe reports grants and personal fees for advisory board from AstraZeneca, grants from GSK, outside the submitted work. Conflict of interest: A.J. Swift has nothing to disclose. Conflict of interest: D.G. Kiely reports grants, personal fees and non-financial support from Actelion, Bayer and GSK, personal fees and non-financial support from MSD, outside the submitted work. Conflict of interest: R. Condliffe reports grants, personal fees and non-financial support from Actelion Pharmaceuticals and Bayer, grants from GSK, outside the submitted work., (Copyright ©ERS 2020.)

Pulmonary endarterectomy (PEA) is the gold standard treatment for operable chronic thromboembolic pulmonary hypertension (CTEPH). However, a proportion of patients with operable disease decline surgery. There are currently no published data on this patient group. The aim of this study was to identify outcomes and prognostic factors in a large cohort of consecutive patients with CTEPH.Data were collected for consecutive, treatment-naive CTEPH patients at the Pulmonary Vascular Disease Unit of the Royal Hallamshire Hospital (Sheffield, UK) between 2001 and 2014.Of 550 CTEPH patients (mean±sd age 63±15 years, follow-up 4±3 years), 49% underwent surgery, 32% had technically operable disease and did not undergo surgery (including patient choice n=72 and unfit for surgery n=63), and 19% had inoperable disease due to disease distribution. The 5-year survival was superior in patients undergoing PEA (83%) versus technically operable disease who did not undergo surgery (53%) and inoperable due to disease distribution (59%) (p<0.001). Survival was superior in patients following PEA compared with those offered but declining surgery (55%) (p<0.001). In patients offered PEA, independent prognostic factors included mixed venous oxygen saturation, gas transfer and patient decision to proceed to surgery.Outcomes in CTEPH following PEA are excellent and superior to patients declining surgery, and strongly favour consideration of a surgical intervention in eligible patients., Competing Interests: Conflict of interest: A.A.R. Thompson reports nonfinancial support (travel grants) from Actelion Pharmaceuticals Ltd, outside the submitted work. Conflict of interest: C.A. Elliot reports personal fees for lecturing and advisory board work from Actelion Pharmaceuticals, GlaxoSmithKline and Bayer, grants for research from Pfizer, Actelion Pharmaceuticals and Bayer, and grants for travel and attendance at conferences from Bayer and Actelion Pharmaceuticals, outside the submitted work. Conflict of interest: J. Hurdman was part funded as a clinical research fellow by an unrestricted educational grant from Actelion, and has received funding to attend conferences from Actelion, GSK and Pfizer. Conflict of interest: A. Charalampopoulos has received honoraria for lecturing and taking part in advisory boards, as well as support to attend scientific events/congresses from Actelion, GSK, Servier and MSD. Conflict of interest: N. Hamilton has and continues to receive honoraria for participation in advisory boards and educational meetings, and has and continues to receive funding to attend educational meetings from a number of pharmaceutical companies including Actelion, Bayer, GSK and MSD (these companies manufacture drug therapies for a variety of indications, but include areas of clinical interest in pulmonary hypertension). Conflict of interest: J. Pepke-Zaba, or her institution, has received research, educational grants and speaker's honoraria from Actelion, Bayer Pharma AG, Merck and GSK. Conflict of interest: D.P. Jenkins reports personal fees for lecturing from Bayer, and personal fees for lecturing and consultancy work for the MERIT study from Actelion, outside the submitted work. Conflict of interest: A. Lawrie reports research grants from the British Heart Foundation, Medical Research Council UK, Actelion Pharmaceuticals and GSK, and conference travel and scientific meeting support from Actelion Pharmaceuticals, outside the submitted work. Conflict of interest: R. Condliffe has received honoraria for lecturing and advisory boards from Actelion, Bayer and GSK, outside the submitted work. Conflict of interest: D.G. Kiely has received funding to attend educational meetings, fees for giving educational lectures and participating in advisory boards, and institutional funding for research from Actelion, Bayer and GSK, and has received funding to attend educational meetings, and fees for giving educational lectures and participating in advisory boards from MSD, outside the submitted work., (Copyright ©ERS 2018.)

The phenotype and outcome of severe pulmonary hypertension in chronic obstructive pulmonary disease (COPD) is described in small numbers, and predictors of survival are unknown. Data was retrieved for 101 consecutive, treatment-naïve cases of pulmonary hypertension in COPD. Mean ± SD follow-up was 2.3 ± 1.9 years. 59 patients with COPD and severe pulmonary hypertension, defined by catheter mean pulmonary artery pressure ≥40 mmHg, had significantly lower carbon monoxide diffusion, less severe airflow obstruction but not significantly different emphysema scores on computed tomography compared to 42 patients with mild-moderate pulmonary hypertension. 1- and 3-year survival for severe pulmonary hypertension, at 70% and 33%, respectively, was inferior to 83% and 55%, respectively, for mild-moderate pulmonary hypertension. Mixed venous oxygen saturation, carbon monoxide diffusion, World Health Organization functional class and age, but not severity of airflow obstruction, were independent predictors of outcome. Compassionate treatment with targeted therapies in 43 patients with severe pulmonary hypertension was not associated with a survival benefit, although improvement in functional class and/or fall in pulmonary vascular resistance >20% following treatment identified patients with improved survival. Standard prognostic markers in COPD have limited value in patients with pulmonary hypertension. This study identifies variables that predict outcome in this phenotype. Despite poor prognosis, our data suggest that further evaluation of targeted therapies is warranted.

Pulmonary hypertension (PH) is a heterogeneous condition. To date, no registry data exists reflecting the spectrum of disease across the five diagnostic groups encountered in a specialist referral centre. Data was retrieved for consecutive, treatment-naïve cases diagnosed between 2001 and 2010 using a catheter-based approach. 1,344 patients were enrolled, with a mean follow-up of 2.9 yrs. The 3-yr survival was 68% for pulmonary arterial hypertension (PAH), 73% for PH associated with left heart disease, 44% for PH associated with lung disease (PH-lung), 71% for chronic thromboembolic PH (CTEPH) and 59% for miscellaneous PH. Compared with PAH, survival was inferior in PH-lung and superior in CTEPH (p<0.05). Multivariate analysis demonstrated that diagnostic group independently predicted survival. Within PAH, Eisenmenger's survival was superior to idiopathic PAH, which was superior to PAH associated with systemic sclerosis (p<0.005). Within PH-lung, 3-yr survival in sleep disorders/alveolar hypoventilation (90%) was superior to PH-lung with chronic obstructive pulmonary disease (41%) and interstitial lung disease (16%) (p<0.05). In CTEPH, long-term survival was best in patients with surgically accessible disease undergoing pulmonary endarterectomy. In this large registry of consecutive, treatment-naïve patients identified at a specialist PH centre, outcomes and characteristics differed between and within PH groups. The current system of classification of PH has prognostic value even when adjusted for age and disease severity, emphasising the importance of systematic evaluation and precise classification.

In patients with pulmonary hypertension, pregnancy is associated with a high risk of maternal death. Such patients are counselled to avoid pregnancy, or if it occurs, are offered early interruption. Some patients, however, decide to continue with their pregnancy and others may present with symptoms for the first time whilst pregnant. Pulmonary vasodilator therapy provides a treatment option for these high-risk patients. The present study describes three patients with pulmonary arterial hypertension of various aetiologies who were treated with the prostacyclin analogue iloprost during pregnancy, and the post-partum period. Nebulised iloprost commenced as early as 8 weeks of gestation and patients were admitted to hospital between 24-36 weeks of gestation. All pregnancies were completed with a duration of between 25-36 weeks and all deliveries were by caesarean section under local anaesthetic. All patients delivered children free from congenital abnormalities, and there was no post-partum maternal or infant mortality. In conclusion, although pregnancy is strongly advised against in those with pulmonary hypertension, the current authors have achieved a successful outcome for mother and foetus with a multidisciplinary approach and targeted pulmonary vascular therapy.