Sexual function is impaired in women and men with pulmonary hypertension

Background: Sexual health related quality of life (SHRQoL) is an important pillar of health related quality of life (HRQoL). The aim of this study was to investigate sexual functioning in men and women with pulmonary hypertension (PH). Methods and results: In this cross-sectional study, a total of 78 patients were included, 49 were diagnosed with pulmonary arterial hypertension and 29 with chronic thromboembolic pulmonary hypertension (median age 53 [IQR: 46–67 years], 66.7% female). All patients completed SHRQoL questionnaires; for women: ASEX, FSFI, and FSDS and for men: ASEX and IIEF. A PH-specific SHRQoL questionnaire was created based on 4 semi-structured interviews to investigate PH-specific barriers in sexuality. More than half of the patients experienced symptoms during sexual activity, mainly dyspnea (52.6%) and palpitations (32.1%). Sexual dysfunction was present, according to the FSFI-questionnaire, in 63.0% of women. All of the men experienced at least mild dysfunction in one of the domains of the IIEF and erectile dysfunction was present in 48.0%. Sexual dysfunction occurred more often in both men and women with PH than in the general population. PAH-specific medication was not associated with sexual dysfunction, nor was subcutaneous or intravenous pump therapy (OR 1.14, 95%-CI: 0.75–1.73). Diuretics were associated with sexual dysfunction in women (OR 4.01, 95%-CI: 1.04–15.41). Of all patients committed in a relationship, 69.0% would like to discuss sexuality with their healthcare provider. Conclusion: This study showed a high prevalence of sexual dysfunction in men and women with PH. It is important for healthcare providers to discuss sexuality with patients. Graphical abstract: [Figure not available: see fulltext.].</p

Central role of dendritic cells in pulmonary arterial hypertension in human and mice

The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is not fully understood, but evidence is accumulating that immune dysfunction plays a significant role. We previously reported that 31-week-old Tnfaip3(DNGR1-KO) mice develop pulmonary hypertension (PH) symptoms. These mice harbor a targeted deletion of the TNF alpha-induced protein-3 (Tnfaip3) gene, encoding the NF-kappa B regulatory protein A20, specifically in type I conventional dendritic cells (cDC1s). Here, we studied the involvement of dendritic cells (DCs) in PH in more detail. We found various immune cells, including DCs, in the hearts of Tnfaip3(DNGR1-KO) mice, particularly in the right ventricle (RV). Secondly, in young Tnfaip3(DNGR1-KO) mice, innate immune activation through airway exposure to toll-like receptor ligands essentially did not result in elevated RV pressures, although we did observe significant RV hypertrophy. Thirdly, PH symptoms in Tnfaip3(DNGR1-KO) mice were not enhanced by concomitant mutation of bone morphogenetic protein receptor type 2 (Bmpr2), which is the most affected gene in PAH patients. Finally, in human IPAH lung tissue we found co-localization of DCs and CD8+ T cells, representing the main cell type activated by cDC1s. Taken together, these findings support a unique role of cDC1s in PAH pathogenesis, independent of general immune activation or a mutation in the Bmpr2 gene

Central Role of Dendritic Cells in Pulmonary Arterial Hypertension in Human and Mice.

The pathogenesis of idiopathic pulmonary arterial hypertension (IPAH) is not fully understood, but evidence is accumulating that immune dysfunction plays a significant role. We previously reported that 31-week-old Tnfaip3DNGR1-KO mice develop pulmonary hypertension (PH) symptoms. These mice harbor a targeted deletion of the TNFα-induced protein-3 (Tnfaip3) gene, encoding the NF-κB regulatory protein A20, specifically in type I conventional dendritic cells (cDC1s). Here, we studied the involvement of dendritic cells (DCs) in PH in more detail. We found various immune cells, including DCs, in the hearts of Tnfaip3DNGR1-KO mice, particularly in the right ventricle (RV). Secondly, in young Tnfaip3DNGR1-KO mice, innate immune activation through airway exposure to toll-like receptor ligands essentially did not result in elevated RV pressures, although we did observe significant RV hypertrophy. Thirdly, PH symptoms in Tnfaip3DNGR1-KO mice were not enhanced by concomitant mutation of bone morphogenetic protein receptor type 2 (Bmpr2), which is the most affected gene in PAH patients. Finally, in human IPAH lung tissue we found co-localization of DCs and CD8+ T cells, representing the main cell type activated by cDC1s. Taken together, these findings support a unique role of cDC1s in PAH pathogenesis, independent of general immune activation or a mutation in the Bmpr2 gene

Correction to: Adaptation and validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for the Netherlands

Unfortunately the original version of this article contained Electronic Supplementary Material which should not have been published with the article due to copyright reasons. The original version has been updated and the ESM has been removed

Genetic counselling and testing in pulmonary arterial hypertension:a consensus statement on behalf of the International Consortium for Genetic Studies in PAH

Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered.</p

36-month clinical outcomes of patients with venous thromboembolism:GARFIELD-VTE

Background: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. Methods: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. Findings: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0–8.1), 5.4 (4.9–5.9) and 2.7 (2.4–3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2–4.7), 3.5 (3.2–2.7) and 1.4 (1.3–1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). Interpretation: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population.</p

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Prognostic value of tricuspid valve regurgitation in patients with pulmonary arterial hypertension and CTEPH:A longitudinal study

Aims: The prognostic value of functional tricuspid valve regurgitation (TR) in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH) remains undetermined. This study primarily aims to quantify the prognostic role of TR in relation to right ventricle (RV) dysfunction on clinical outcomes and secondarily the evolution of TR and RV dysfunction over time. Methods: Adult PAH or CTEPH patients diagnosed by right heart catheterization were included. Exclusion criteria were prevalent patients and age &lt; 18 years. The primary endpoint was a composite of death or lung transplantation. Longitudinal evolution of TR and RV dysfunction were modelled with generalized mixed-effect models, which were inserted in a cox model under the joint-modelling framework in order to investigate the association of TR and RV dysfunction with the endpoint. Results: We included 76 PAH and 44 CTEPH patients (median age:59, females:62 %), with a mean follow-up of 3.2 ± 2.1 years. 31 patients reached the endpoint (2 transplant, 29 mortality). On average the probability of moderate-to-severe TR decreased during follow-up, whereas the probability of moderate-to-severe RV dysfunction remained stable. The cumulative effect of moderate-to-severe TR (HRper day 1.01 95 %CI[1.00–1.01],P &lt; 0.001) and moderate-to-severe RV dysfunction (HRper day: 1.01 95 %CI[1.00–1.01],P &lt; 0.001) was associated with the endpoint in univariable joint-models. In a multivariable joint-model with both the evolutions of TR and RV dysfunction only TR remained significant (HR per day: 1.01 95 %CI[1.00–1.01],P &lt; 0.001). Conclusion: Persistent moderate-to-severe tricuspid valve regurgitation during follow-up predicts adverse outcomes and might be a better predictor of lung transplantation and mortality compared to right ventricle dysfunction.</p

Adaptation and validation of the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) for the Netherlands

BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is the first disease-specific instrument for pulmonary arterial hypertension (PAH) to assess patient-perceived symptoms, activity limitations and quality of life. To be able to use this questionnaire in the Netherlands, the aim of the study was to translate and validate this instrument for the Dutch-speaking population. METHODS: First the CAMPHOR was translated into Dutch (by means of a bilingual and a lay panel) and field-tested by means of cognitive debriefing interviews with ten PAH patients. For psychometric evaluation, 80 patients with PAH or chronic thromboembolic pulmonary hypertension (CTEPH) were asked to complete the CAMPHOR twice over a two-week period. To test for construct validity, participants also completed the Nottingham Health Profile (NHP). RESULTS: The Dutch version of the CAMPHOR showed high internal consistency for all scales (Cronbach’s alpha 0.89–0.91) and excellent reproducibility over two weeks (reliability coefficients 0.87–0.91). Concurrent validity showed that the CAMPHOR scales correlated as expected with the NHP scales. The CAMPHOR was able to distinguish between patient groups based on self-reported general health status, disease severity and NYHA classification demonstrating evidence of known group validity. The CAMPHOR activity limitations scale correlated moderately with the distance walked during the 6‑minute walk test (r = −0.47, p < 0.01) and the symptoms scale with the Borg dyspnoea score (r = 0.51, p < 0.01). CONCLUSION: The Dutch version of the CAMPHOR is a reliable and valid measure of quality of life and health status in patients with PAH and CTEPH is recommended for use in routine care and in clinical research