Usefulness of genetics for clinical reclassification and refinement of prognostic stratification in pulmonary arterial hypertension.

INTRODUCTION AND OBJECTIVES: Risk stratification in pulmonary arterial hypertension (PAH) is essential to provide more aggressive treatment for patients at higher risk. Nevertheless, recently introduced simplified prognostic tools neglect the genetic background. Additionally, pulmonary veno-oclusive disease (PVOD) has never been considered in risk assessment strategies. METHODS: We analyzed consecutive patients in the Spanish registry of PAH (REHAP) genetically tested, between 2011 and 2022. We applied the 4-strata COMPERA 2.0 model, comparing these results with an amplified score including genetics. Cox regression models were compared using Harrel c-statistics. The application of the model was specifically tested in PVOD before inclusion. RESULTS: We identified 298 patients tested genetically among the group of idiopathic, familial, drug-induced PAH and PVOD patients in the REHAP registry. When we analyzed only patients with all available variables of interest at baseline (World Health Organization functional class, 6-minute walk test, B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide) and included in the 4-strata model (n=142), after a median follow-up of 58.2 months, 17.6% of patients died and 11.3% underwent lung transplant. The application of the 4-strata model in our population demonstrated a good prognostic capacity (Harrel c of 0.689), which was not improved by the introduction of genetics (c-index 0.690). This last model showed a tendency for a better identification of patients at intermediate-low and intermediate-high risk, and no differences between intermediate-high and high-risk strata. CONCLUSIONS: In this work, the addition of genetics to the COMPERA 4-strata model achieved a similar global prognostic capacity but changed the identification of different risk strata in a cohort of young genetically tested patients.

Real-life experience of inhaled iloprost for patients with pulmonary arterial hypertension: Insights from the Spanish REHAP registry.

INTRODUCTION: REHAP is a voluntary, observational Spanish registry of patients with pulmonary arterial hypertension. We analyzed the experience (use and effectiveness) with inhaled iloprost (inh-ILO) in real-life conditions during a 3-year period. METHODS: Patients included were those with PAH ≥14 years recruited during 1998-2016 who had received inh-ILO. Variables were collected at the beginning of treatment (0 ±â€¯3 months) and 12 ±â€¯3/36 ±â€¯6 months follow-up. Effectiveness was assessed in the intent-to-treat population as changes in functional class and/or physical performance and transplant-free survival from the beginning of treatment. Stopping inh-ILO-related survival was also assessed. Subanalyses included treatment strategy (first-line therapy -monotherapy or upfront combination- or sequential therapy) and risk of clinical worsening/death. RESULTS: Inh-ILO was the most frequently used prostanoid in Spain, rendering 267 patients eligible for analysis. Median age was 54 years; 61% were WHO FC III. Sixty (23%) patients started inh-ILO as monotherapy, 27 (10%) as upfront combination and 180 (67%) sequentially. At 3-year follow-up significant clinical improvements were observed; however, transplant-free survival rate was 54%, being poorer in patients at high risk (63% vs. 85% in low risk patients; P < 0.001) and similar in the three treatment strategies. Only 25% patients remained on inh-ILO. Three-year after stopping inh-ILO-related survival rate was 24.7%. CONCLUSION: Data from the REHAP collected during 3 years shows that inh-ILO has low effectiveness independently of the treatment strategy used, with a 3-year survival rate of 54% despite significant clinical improvements, probably due to the use in high-risk patients. Discontinuation rate was as high as 75%.

Short-term clinical outcome of normotensive patients with acute PE and high plasma lactate.

BACKGROUND: Strategies for identifying normotensive patients with acute symptomatic PE at high risk of PE-related complications remain to be defined. METHODS: This prospective cohort study aimed to determine the role of plasma lactate levels in the risk assessment of normotensive patients with acute PE. Outcomes assessed over the 7 days after the diagnosis of PE included PE-related mortality and haemodynamic collapse, defined as need for cardiopulmonary resuscitation, systolic blood pressure <90 mm Hg for at least 15 min, need for catecholamine administration, or need for mechanical ventilation. RESULTS: Between December 2012 and January 2014, the study enrolled 496 normotensive outpatients with acute symptomatic PE. PE-related complications occurred in 20 (4.0%; 95% CI 2.5% to 6.2%) of the 496 patients. These patients had higher baseline lactate levels (median 2.66 mmol/L; IQR 1.56-5.96 mmol/L) than patients without complications (1.20 mmol/L; IQR 1.20-2.00 mmol/L) (p<0.001). Overall, 135 patients (27.2%) had plasma lactate ≥2 mmol/L. Fourteen (10.4%) of them had PE-related complications versus 6 of 361 patients with low lactate (negative predictive value 98.3%; p<0.001). Patients with elevated plasma lactate had an increased rate of PE-related complications (adjusted OR 5.3; 95% CI 1.9 to 14.4; p=0.001) compared with those with low lactate. The combination of elevated plasma lactate with markers of right ventricular dysfunction (by echocardiogram) and myocardial injury (by cardiac troponin) was a particularly useful prognostic indicator (positive predictive value 17.9%; 95% CI 6.1% to 36.9%). CONCLUSIONS: Plasma lactate represents a powerful predictor of short-term PE-related complications and may provide guidance for decision-making in PE care.