@ERSpublicationsSimplified risk assessment using the number of low-risk criteria predicts prognosis at baseline and follow-up in PAH http://ow.ly/KMsj30cPNbmCite this article as: Boucly A, Weatherald J, Savale L, et al. Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension. Eur Respir J 2017; 50: 1700889 [https://doi.org/ 10.1183/13993003.00889-2017.ABSTRACT Current European guidelines recommend periodic risk assessment for patients with pulmonary arterial hypertension (PAH). The aim of our study was to determine the association between the number of low-risk criteria achieved within 1 year of diagnosis and long-term prognosis.Incident patients with idiopathic, heritable and drug-induced PAH between 2006 and 2016 were analysed. The number of low-risk criteria present at diagnosis and at first re-evaluation were assessed: World Health Organization (WHO)/New York Heart Association (NYHA) functional class I or II, 6-min walking distance (6MWD) >440 m, right atrial pressure <8 mmHg and cardiac index ⩾2.5 L·min. 1017 patients were included (mean age 57 years, 59% female, 75% idiopathic PAH). After a median follow-up of 34 months, 238 (23%) patients had died. Each of the four low-risk criteria independently predicted transplant-free survival at first re-evaluation. The number of low-risk criteria present at diagnosis ( p<0.001) and at first re-evaluation ( p<0.001) discriminated the risk of death or lung transplantation. In addition, in a subgroup of 603 patients with brain natriuretic peptide (BNP) or Nterminal pro-brain natriuretic peptide (NT-proBNP) measurements, the number of three noninvasive criteria (WHO/NYHA functional class, 6MWD and BNP/NT-proBNP) present at first re-evaluation discriminated prognostic groups ( p<0.001).A simplified risk assessment tool that quantifies the number of low-risk criteria present accurately predicted transplant-free survival in PAH.

Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated.Data from newly diagnosed NYHA FC III/IV PAH patients (n519) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry.Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p,0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean¡SD 32¡19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68-82%), 60% (95% CI 50-70%) and 49% (95% CI 38-60%) at 1, 2 and 3 years, respectively.This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH.@ERSpublications Upfront triple combination therapy shows promising long-term efficacy in severe pulmonary arterial hypertension

Aim This study aimed at evaluating the effects of sacubitril/valsartan on neprilysin (NEP), and the metabolism of natriuretic peptides in heart failure (HF) and providing additional mechanistic information on the mode of action of the drug. Methods and results We enrolled 73 chronic HF patients who were switched from angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker to sacubitril/valsartan. In addition to clinical and echocardiographic assessment, plasma biomarkers were measured at baseline, day 30 and day 90 after initiation of treatment. Sacubitril/valsartan led to decrease in New York Heart Association class and improvement of echocardiographic parameters, as well as a dose‐dependent decrease in soluble NEP (sNEP) activity, while sNEP concentration remained unchanged. Neprilysin inhibition translated into an increase in its substrates such as atrial natriuretic peptide (ANP), substance P, and glucagon‐like peptide 1, the latter translating into a decrease in fructosamine. Cardiac troponin and soluble ST2 levels, biomarkers of HF severity unrelated to NEP metabolism also decreased. While there was a ∼4‐fold increase in ANP, we observed no change in plasma brain natriuretic peptide (BNP) and plasma BNP activity, and a mild decrease in N‐terminal proBNP (NT‐proBNP) concentrations. Finally, we found a progressive increase in the relationship between BNP and NT‐proBNP, which strongly correlated with an increase in T71 proBNP glycosylation (R2 = 0.94). Conclusion Sacubitril/valsartan rapidly and strongly reduced sNEP activity, leading to an increase in levels of NEP substrates. These data suggest a pleiotropic favourable impact of sacubitril/valsartan on the metabolism of HF patients with ANP rather than BNP as major effectors amongst natriuretic peptides.

• Chronic thromboembolic pulmonary hypertension (CTEPH) is potentially treatable by surgery. • Dual-energy computed tomography (DECT) allows angiography and perfusion using a single acquisition. • Both DECT perfusion and angiography showed satisfactory diagnostic performance in CTEPH. • DECT perfusion was more accurate than angiography in identifying segmental abnormalities.

IntroductionContemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate, or high-risk. A minority of patients achieve low-risk status with most remaining intermediate-risk. Our aim was to validate a 4-strata risk assessment approach categorising patients as low, intermediate-low, intermediate-high, or high risk, as proposed by the COMPERA Registry investigators.MethodsWe evaluated incident patients from the French PAH Registry and applied a 4-strata risk method at baseline and at first reassessment. We applied refined cut-points for 3 variables: World Health Organization functional class, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide. We used Kaplan-Meier survival analyses and Cox proportional hazards regression to assess survival according to a 3-strata and 4-strata risk approach.ResultsAt baseline (n=2879), the 4-strata approach identified 4 distinct risk groups and performed better than a 3-strata method for predicting mortality. The 4-strata model discrimination was higher than the 3-strata method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. Using the 4-strata approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the 3-strata approach. Those who achieved or maintained a low-risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high.ConclusionsThe 4-strata risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the 3-strata approach.