Outcomes and risk assessment in pulmonary veno-occlusive disease.

Introduction: Pulmonary veno-occlusive disease (PVOD) is a rare and severe subtype of pulmonary arterial hypertension (PAH). Although European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines advise assessing PAH severity at baseline and during follow-up, no existing risk assessment methods have been validated for PVOD. This study aimed to identify prognostic factors, examine the impact of treatment strategies and evaluate risk assessment methods for PVOD patients. Methods: The study analysed all incident PVOD patients included in the French Pulmonary Hypertension Registry between 2006 and 2021. Survival was assessed based on initial treatment strategy and risk status and compared to a matched (age, sex, pulmonary vascular resistance) PAH group. Six risk assessment methods (number of four low-risk and three noninvasive low-risk variables, ESC/ERS guidelines three-strata and four-strata models, REVEAL 2.0 and Lite 2) were applied at baseline and early follow-up, and their accuracy was compared using Harrell's c-statistic. Results: Among the 327 included PVOD patients, survival rates at 1, 3 and 5 years were 86%, 50% and 27%, respectively. Multivariate analysis showed that only 6-min walk distance was associated with survival, with no significant difference based on initial treatment strategy. All six risk assessment methods could discriminate mortality risk, and the ESC/ERS four-strata model was the most accurate at both baseline and follow-up (C-index 0.64 and 0.74). PVOD survival rates were consistently lower than PAH when comparing baseline risk status using the ESC/ERS four-strata model. Conclusion: PVOD is associated with poor outcomes, and initial treatment strategies do not significantly affect survival. Risk assessment methods can be useful in predicting survival for PVOD patients.

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.

Haemodynamics and serial risk assessment in systemic sclerosis associated pulmonary arterial hypertension.

The prognostic importance of follow-up haemodynamics and the validity of multidimensional risk assessment are not well established for systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH).We assessed incident SSc-PAH patients to determine the association between clinical and haemodynamic variables at baseline and first follow-up right heart catheterisation (RHC) with transplant-free survival. RHC variables included cardiac index, stroke volume index (SVI), pulmonary arterial compliance and pulmonary vascular resistance. Risk assessment was performed according to the number of low-risk criteria: 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-2Transplant-free survival from diagnosis (n=513) was 87%, 55% and 35% at 1, 3 and 5 years, respectively. At baseline, 6MWD was the only independent predictor. A follow-up RHC was available for 353 patients (median interval 4.6 months, interquartile range 3.9-6.4 months). The 6MWD, functional class, cardiac index, SVI, pulmonary arterial compliance and pulmonary vascular resistance were independently associated with transplant-free survival at follow-up, with SVI performing better than other haemodynamic variables. 1-year outcomes were better with increasing number of low-risk criteria at baseline (area under the curve (AUC) 0.63, 95% CI 0.56-0.69) and at first follow-up (AUC 0.71, 95% CI 0.64-0.78).Follow-up haemodynamics and multidimensional risk assessment had greater prognostic significance than at baseline in SSc-PAH.

Three-Dimensional Echocardiography for the Assessment of Right Ventriculo-Arterial Coupling.

BACKGROUND: The analysis of right ventriculo-arterial coupling (RVAC) from pressure-volume loops is not routinely performed. RVAC may be approached by the combination of right heart catheterization (RHC) pressure data and cardiac magnetic resonance (CMR)-derived right ventricular (RV) volumetric data. RV pressure and volume measurements by Doppler and three-dimensional echocardiography (3DE) allows another way to approach RVAC. METHODS: Ninety patients suspected of having pulmonary hypertension underwent RHC, 3DE, and CMR (RHC mean pulmonary artery pressure [mPAP] 37.9 ± 11.3 mm Hg; range, 15-66 mm Hg). Three-dimensional (3D) echocardiography was performed in 30 normal patients (echocardiographic mPAP 18.4 ± 3.1 mm Hg). Pulmonary artery (PA) effective elastance (Ea), RV maximal end-systolic elastance (Emax), and RVAC (PA Ea/RV Emax) were calculated from RHC combined with CMR and from 3DE using simplified formulas including mPAP, stroke volume, and end-systolic volume. RESULTS: Three-dimensional echocardiographic and RHC-CMR measures for PA Ea (3DE, 1.27 ± 0.94; RHC-CMR, 0.71 ± 0.52; r = 0.806, P < .001), RV Emax (3DE, 0.72 ± 0.37; RHC-CMR, 0.38 ± 0.19; r = 0.798, P < .001), and RVAC (3DE, 2.01 ± 1.28; RHC-CMR, 2.32 ± 1.77; r = 0.826, P < .001) were well correlated despite a systematic overestimation of 3DE elastance parameters. Among the whole population, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax were significantly lower in patients with mPAP < 25 mm Hg (n = 41) than in others (n = 79). Among the 90 patients who underwent RHC, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax increased significantly with increasing levels of pulmonary vascular resistance. CONCLUSIONS: Three-dimensional echocardiography-derived PA Ea, RV Emax, and RVAC correlated well with the reference RHC-CMR measurements. Ea and RVAC but not Emax were significantly different between patients with different levels of afterload, suggesting failure of the right ventricle to maintain coupling in severe pulmonary hypertension.

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.

Pulmonary hypertension in COPD: epidemiology, significance, and management: pulmonary vascular disease: the global perspective.

Pulmonary hypertension (PH) associated with parenchymal lung diseases is one of the most common forms of PH. Studies in patients with advanced COPD and hypoxemia have shown a very high prevalence of PH; however, prevalence in mild and moderate COPD is not known. Typical hemodynamic abnormalities include mild-to-moderate elevations in pulmonary artery pressure (PAP) and pulmonary vascular resistance with a preserved cardiac output. A small proportion (< 5%) of patients may have significant elevations in PAP (mean PAP > 35-40 mm Hg) in the presence of mild airflow limitation and are believed to have disproportionate PH. COPD-associated PH has significant clinical implications because it can produce functional limitation and has a negative impact on prognosis. Doppler echocardiography is the best noninvasive test, but noninvasive methods used for diagnosis are prone to error and cannot be relied on when making or refuting the diagnosis of PH. All patients require right-sided heart catheterization if treatment with PH-specific medications is contemplated. The most important steps in managing these patients are: (1) confirm the diagnosis; (2) optimize COPD management; (3) rule out comorbidities; (4) assess and treat hypoxemia; and (5) enroll the patient in pulmonary rehabilitation, if indicated. In patients with PH and advanced airflow limitation, lung transplantation offers the best opportunity for long-term benefit. The role of PH-specific medications remains poorly defined and requires further study but may be considered in patients with disproportionate PH.