Screening for pulmonary arterial hypertension in adults carrying a <i>BMPR2</i> mutation

Montani, David; Girerd, Barbara; Jaïs, Xavier; Laveneziana, Pierantonio; Lau, Edmund; Bouchachi, Amir; Hascoët, Sébastien; Günther, Sven; Godinas, Laurent; Parent, Florence; Guignabert, Christophe; Beurnier, Antoine; Chemla, Denis; Hervé, Philippe; Eyries, Mélanie; Soubrier, Florent; Simonneau, Gérald; Sitbon, Olivier; Savale, Laurent; Humbert, Marc

doi:10.1183/13993003.04229-2020

Cited by 61 publications

(55 citation statements)

References 41 publications

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“…CPET is an attractive option for screening asymptomatic carriers since ventilatory abnormalities may be present early in the development of PAH, before echocardiographic changes suggesting PH are seen or when disease features begin to manifest [45,46]. The results of the DELPHI-2 study, which used a multimodal screening approach for asymptomatic BMPR2 mutation carriers, suggested that a CPET-derived probability score including the V′ E /V′ CO 2 can help detect early disease in this at-risk group [47].…”

Section: Is Ventilatory Inefficiency Useful In the Diagnosis Of Pulmonary Hypertension?mentioning

confidence: 99%

Ventilatory efficiency in pulmonary vascular diseases

et al. 2021

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Cardiopulmonary exercise testing (CPET) is a frequently used tool in the differential diagnosis of dyspnoea. Ventilatory inefficiency, defined as high minute ventilation (V′E) relative to carbon dioxide output (V′CO2), is a hallmark characteristic of pulmonary vascular diseases, which contributes to exercise intolerance and disability in these patients. The mechanisms of ventilatory inefficiency are multiple and include high physiologic dead space, abnormal chemosensitivity and an altered carbon dioxide (CO2) set-point. A normal V′E/V′CO2 makes a pulmonary vascular disease such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) unlikely. The finding of high V′E/V′CO2 without an alternative explanation should prompt further diagnostic testing to exclude PAH or CTEPH, particularly in patients with risk factors, such as prior venous thromboembolism, systemic sclerosis or a family history of PAH. In patients with established PAH or CTEPH, the V′E/V′CO2 may improve with interventions and is a prognostic marker. However, further studies are needed to clarify the added value of assessing ventilatory inefficiency in the longitudinal follow-up of patients.

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Section: Is Ventilatory Inefficiency Useful In the Diagnosis Of Pulmonary Hypertension?mentioning

confidence: 99%

Ventilatory efficiency in pulmonary vascular diseases

et al. 2021

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“…In this heterogenous but contemporary PAH cohort, we were able to confirm the predictive value of recognized clinical variables such as 6MWD, WHO functional class, and NT-proBNP levels [ 1 ], and additionally identify less established variables like renal impairment and DLCO as predictors for adverse outcome in PAH. Results from screening of susceptible subjects, both genetically or due to an underlying condition such as systemic sclerosis, further emphasize the importance of DLCO for early detection of pulmonary vascular disease [ 30 , 31 ]. Overall, our results support findings from the REVEAL-study and highlight the importance of comorbidities and pulmonary function testing in clinical evaluation [ 6 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Non-Invasive Risk Prediction Based on Right Ventricular Function in Patients with Pulmonary Arterial Hypertension

Qaderi

Weimann

Harbaum

et al. 2021

JCM

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Background: Right ventricular dysfunction is a major determinant of outcome in pulmonary arterial hypertension (PAH). We aimed to identify echocardiographic right heart parameters associated with adverse outcome and to develop a non-invasive, echocardiography-based risk score for PAH patients. Methods and Results: In 254 PAH patients we analyzed functional status, laboratory results, and echocardiographic parameters. We included these parameters to estimate all-cause death or lung transplantation using Cox regression models. The analyses included a conventional model using guideline-recommended variables and an extended echocardiographic model. Based on the final model a 12-point risk score was derived, indicating the association with the primary outcome within five years. During a median follow-up time of 4.2 years 74 patients died or underwent lung transplantation. The conventional model resulted in a C-Index of 0.539, whereas the extended echocardiographic model improved the discrimination (C-index 0.639, p-value 0.017). Ultimately, the newly developed risk score included WHO functional class, 6-min walking distance, N-terminal brain natriuretic peptide concentrations, pericardial effusion, right atrial area, tricuspid annular plane systolic excursion, and fractional area change. Conclusion: Integrating right heart function assessed by echocardiography improves prediction of death or lung transplantation in PAH patients. Independent validation of this finding is warranted.

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“…Our (re-)contact approach identified 10 relatives at risk as carriers and these carriers will be screened annually to detect PAH in early stages. Asymptomatic BMPR2 mutation carriers have a significant risk of 2.3% per year of developing PAH (0.99% per year in males and 3.5% per year in females) [11]. As shown in the DELPHI-2 study of Montani et al, annual screening of unaffected mutation carriers could be beneficial: annual screening identified five PAH cases and all patients remained at low risk with oral PAH-specific therapy during follow-up [11].…”

Section: Discussionmentioning

confidence: 99%

“…Asymptomatic BMPR2 mutation carriers have a significant risk of 2.3% per year of developing PAH (0.99% per year in males and 3.5% per year in females) [11]. As shown in the DELPHI-2 study of Montani et al, annual screening of unaffected mutation carriers could be beneficial: annual screening identified five PAH cases and all patients remained at low risk with oral PAH-specific therapy during follow-up [11]. These findings highlight the importance of detecting pathogenic variants in PAH patients and their relatives at risk.…”

Section: Discussionmentioning

confidence: 99%

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Uptake and Patient Perspectives on Additional Testing for Novel Disease-Associated Genes: Lessons from a PAH Cohort

Jansen¹,

Heuvel

Houweling³

et al. 2021

Genes

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Background: Pulmonary arterial hypertension (PAH) has an identifiable genetic cause in 5% of all PAH cases. Due to health benefits conferred by the early detection of PAH and the recent identification of additional PAH-associated genes, we decided to offer (extended) genetic testing to all incident and prevalent idiopathic PAH (iPAH) and pulmonary veno-occlusive disease (PVOD) patients in our clinic. Here, we report the lessons learned from (re-)contacting iPAH/PVOD patients concerning the uptake and analysis of identified PAH-associated genes and patient perspectives of the approach. Methods: Between January 2018 and April 2020, all iPAH/PVOD patients who were not previously genetically tested (contact group) and those who tested negative on prior analysis of BMPR2 and SMAD9 variants (re-contact group) were (re-)contacted for (additional) genetic testing. Results: With our approach, 58% of patients (84 out of 165) opted for genetic counselling, and a pathogenic variant was found in 12% of cases (n = 10) (re-contact group, 11%, and contact group, 13%). Eighty-six percent of participants of the survey study appreciated being (re-)contacted for genetic testing. Mild psychosocial impacts were observed. Conclusions: Our report shows the importance of (re-)contact and interest of patients (as indicated by the uptake, mild psychosocial impact and appreciation) in PAH.

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Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation

Cited by 61 publications

References 41 publications

Ventilatory efficiency in pulmonary vascular diseases

Ventilatory efficiency in pulmonary vascular diseases

Non-Invasive Risk Prediction Based on Right Ventricular Function in Patients with Pulmonary Arterial Hypertension

Uptake and Patient Perspectives on Additional Testing for Novel Disease-Associated Genes: Lessons from a PAH Cohort

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