External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry.

INTRODUCTION: Contemporary 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 four-stratum risk assessment approach categorising patients as low, intermediate-low, intermediate-high or high risk, as proposed by the Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) investigators. METHODS: We evaluated incident patients from the French PAH Registry and applied a four-stratum risk method at baseline and at first reassessment. We applied refined cut-points for three variables: World Health Organization functional class, 6-min 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 three-stratum and four-stratum risk approaches. RESULTS: At baseline (n=2879), the four-stratum approach identified four distinct risk groups and performed slightly better than a three-stratum method for predicting mortality. Four-stratum model discrimination was significantly higher than the three-stratum 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 four-stratum approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the three-stratum 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 risk. CONCLUSIONS: The four-stratum 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 three-stratum approach.

Quantitative CT assessment of bronchial and vascular alterations in severe precapillary pulmonary hypertension.

BACKGROUND: Little is known about in vivo alterations at bronchial and vascular levels in severe pulmonary hypertension (PH) of different etiologies. We aimed to compare quantitative computed tomography (CT) data from the following three groups of severe precapillary PH patients: COPD, idiopathic pulmonary arterial hypertension (iPAH), and chronic thromboembolic PH (CTEPH). PATIENTS AND METHODS: This study was approved by the institutional review board. Severe PH patients (mean pulmonary arterial pressure [mPAP] ≥35 mmHg) with COPD, iPAH, or CTEPH (n=24, 16, or 16, respectively) were included retrospectively between January 2008 and January 2017. Univariate analysis of mPAP was performed in each severe PH group. Bronchial wall thickness (WT) and percentage of cross sectional area of pulmonary vessels less than 5 mm2 normalized by lung area (%CSA<5) were measured and compared using CT, and then combined to arterial partial pressure of oxygen (PaO2) to generate a "paw score" compared within the three groups using Kruskal-Wallis and its sensitivity using Fisher's exact test. RESULTS: WT was higher and %CSA<5 was lower in the COPD group compared to iPAH and CTEPH groups. Mosaic pattern was higher in CTEPH group than in others. In severe PH patients secondary to COPD, mPAP was positively correlated to %CSA<5. By contrast, in severe iPAH, this correlation was negative, or not correlated in severe CTEPH groups. In the COPD group, "paw score" showed higher sensitivity than in the other two groups. CONCLUSION: Unlike in severe iPAH and CTEPH, severe PH with COPD can be predicted by "paw score" reflecting bronchial and vascular morphological differential alterations.

Risk assessment, prognosis and guideline implementation in pulmonary arterial hypertension.

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-1·m-21017 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 N-terminal 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.

Assessment of platelet function with light transmission aggregometry in 24 patients supported with a continuous-flow left ventricular assist device: a single-center experience.

OBJECTIVES: This study evaluated platelet function for an extended period of time in patients with a HeartMate II continuous-flow left ventricular assist device (Thoratec Corporation, Pleasanton, Calif) with light transmission aggregometry and investigated the potential role of this test in clinical management. METHODS: Twenty-four patients were studied prospectively after implantation. Mean duration of support was 8.5 months. Platelet functions were assessed with light transmission aggregometry induced by thrombin receptor agonist peptide, ristocetin, or arachidonic acid. All patients received an aspirin regimen that was progressively increased until arachidonic acid-triggered platelet aggregation dropped lower than 20%. Plasma levels of von Willebrand factor were also determined when ristocetin-induced platelet agglutination was impaired. RESULTS: Intensity of platelet aggregation with thrombin receptor agonist peptide was little changed in patients with a HeartMate II relative to control subjects. Aspirin dose greater than 160 mg/d was progressively required in 46% of patients. Ristocetin-induced platelet agglutination was impaired in 4 patients in association with a lack of high molecular weight von Willebrand factor multimers. Three patients had thromboembolic events (12.5%) and 8 (33%) suffered from major bleeding complications. CONCLUSIONS: High platelet reactivity during treatment with aspirin is common in patients with a HeartMate II. Moreover, light transmission aggregometry may detect impaired ristocetin-induced platelet agglutination, enabling dosage of aspirin to be adjusted. Our strategy showed no major improvements in terms of thrombosis rate when compared with published data, although bleeding frequency was somewhat reduced. Benefits of light transmission aggregometry testing need to be assessed in a larger randomized study with a longer follow-up.