Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study.

BACKGROUND: Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the noninvasive French risk assessment approach (number of low-risk criteria based on the European Society of Cardiology and European Respiratory Society guidelines) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH. METHODS: GRIPHON randomized 1,156 patients with PAH to selexipag or placebo. Post-hoc analyses were performed on the primary composite end-point of morbidity/mortality by the number of low-risk criteria (World Health Organization functional class I-II; 6-minute walk distance >440 m; N-terminal pro-brain natriuretic peptide <300 ng/liter) and REVEAL 2.0 risk category. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazard models. RESULTS: Both the number of low-risk criteria and the REVEAL 2.0 risk category were prognostic for morbidity/mortality at baseline and any time-point during the study. Patients with 3 low-risk criteria at baseline had a 94% reduced risk of morbidity/mortality compared to patients with 0 low-risk criteria and were all categorized as low-risk by REVEAL 2.0. The treatment effect of selexipag on morbidity/mortality was consistent irrespective of the number of low-risk criteria or the REVEAL 2.0 risk category at any time-point during the study. Selexipag-treated patients were more likely to increase their number of low-risk criteria from baseline to week 26 than placebo-treated patients (odds ratio 1.69, p = 0.0002); similar results were observed for REVEAL 2.0 risk score. CONCLUSIONS: These results support the association between risk profile and long-term outcome and suggest that selexipag treatment may improve risk profile.

Comprehensive assessment of right ventricular function in patients with pulmonary hypertension with global longitudinal peak systolic strain derived from multiple right ventricular views.

BACKGROUND: Right ventricular (RV) function is a strong predictor of mortality in pulmonary hypertension (PH), but two-dimensional (2D) echocardiography-derived assessments of RV function that could aid in risk assessment and management of patients with PH are of limited utility. RV longitudinal peak systolic strain (RVLS) derived from 2D speckle-tracking echocardiography is a relatively novel method for quantifying RV function but typically is derived from a single apical four-chamber view of the right ventricle and may have inherent limitations. The objective of this study was to determine the utility of regional and global RVLS calculated from multiple views of the right ventricle to comprehensively assess RV function in a cohort of patients with PH. METHODS: Regional and global RVLS were obtained from multiple views of the right ventricle (centered on the right ventricle-focused apical position) in 40 patients with PH, defined as a mean pulmonary artery pressure ≥ 25 mm Hg, most of whom also had pulmonary capillary wedge pressures ≤ 15 mm Hg and were thus defined as having pulmonary arterial hypertension. This was compared with other 2D echocardiography-derived parameters of RV function and functional parameters. RESULTS: Global RVLS calculated from multiple views had a superior correlation with 6-min walk distance compared with other parameters of RV function, including tricuspid annular plane systolic excursion, RV myocardial performance index, and fractional area change. Although global RVLS calculated from multiple views displayed a similar correlation with 6-min walk distance as global RVLS calculated from a single four-chamber view, analysis of regional strains provided by multiple views identified distinct patterns of RV dysfunction, consisting of global, free wall, or septal dysfunction, that were associated with specific clinical characteristics. CONCLUSIONS: Global RVLS derived from multiple right ventricle-focused views yields a comprehensive quantitative assessment of regional and global RV function that correlates moderately with functional parameters and may be useful in the assessment of PH. Distinct patterns of regional RV dysfunction are associated with different clinical characteristics.

Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients.

Hospitalized patients with acute medical conditions are at significant risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Despite consensus-group recommendations that at-risk medical patients should receive thromboprophylaxis, there is currently no consensus as to which patients are at risk, and many patients may not receive appropriate thromboprophylaxis. This paper reviews evidence for the risk of VTE associated with different medical conditions and risk factors, and presents a risk-assessment model for risk stratification in medical patients. Medical conditions associated with a moderate to high risk of VTE include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Importantly, analyses of data from the MEDENOX study show that thromboprophylaxis significantly reduces the risk of VTE in these patient subgroups. Risk factors in medical patients include a history of VTE, history of malignancy, increasing age, thrombophilia, prolonged immobility, and obesity. These medical conditions and risk factors are included in a risk-assessment model which is hoped will provide a simple means of assisting clinicians in deciding whether thromboprophylaxis should be used in an individual patient.