Treadmill testing improves survival prediction models in pulmonary arterial hypertension.

BACKGROUND: Six-minute walk distance (6MWD) is used in the REVEAL equation to predict 1-year survival for patients with pulmonary arterial hypertension. We sought to determine whether exercise treadmill testing (ETT) could be used in its place. METHODS: This was a single-center study in which 449 patients were enrolled. The variables predictive of survival in the REVEAL equation were evaluated and compared with survival predicted by the REVEAL equation without an exercise measure and a revised equation using ETT. RESULTS: The addition of ETT to the equation improved the predictive ability of the REVEAL equation in the high- and low-risk patient groups. CONCLUSION: The study findings suggest that the addition of ETT parameters to the REVEAL prognostic equation improves the predictive value of the equation when 6-minute walk distance is unavailable.

Validation of the pulmonary hypertension connection equation for survival prediction in pulmonary arterial hypertension.

OBJECTIVE: The pulmonary hypertension connection (PHC) equation predicts contemporary survival in idiopathic, heritable, and anorexigen-associated pulmonary arterial hypertension (PAH). The aim of this study is to validate the PHC equation in a prospective PAH population cohort and compare its predictability with the French equation. METHODS: We compared the rates of actual survival in patients prospectively followed for up to 3.5 years in four double-blind, randomized trials and their open-label extension studies with predicted survival calculated using the PHC equation [(P(t) = e((-A(x,y,z)t)), A(x,y,z) = e((-1.270-0.0148x + 0.0402y - 0.361z)), where P(t) is the probability of survival, t the time interval in years, x the mean pulmonary artery pressure, y the mean right atrial pressure, and z the cardiac index] and the French equation in patients with idiopathic, heritable, and anorexigen-associated PAH (n = 449). RESULTS: Mean age was 44 ± 15 years, 77% were women, and 80% had World Health Organization (WHO) functional class III/IV symptoms. The mean 6-min walk distance (6MWD) was 354 ± 95 m. The baseline hemodynamics were as follows: mean right atrial pressure 10 ± 6 mm Hg, mean pulmonary artery pressure 59 ± 15 mm Hg, and cardiac output 4.1 ± 1.5 L/min. The 1-, 2-, and 3-year Kaplan-Meier survival rates were 89%, 80%, and 70%, respectively; the nonadjusted survival rates were 91%, 87%, and 84%, respectively. The expected survival predicted by both the PHC and the French equations was similar to the actual observed Kaplan-Meier survival and was within its 95% confidence limits. The PHC equation also performed well when used in patients with WHO functional class III/IV, cardiac output < 4 L/min, or 6MWD < 380 m. CONCLUSION: Risk prediction equations (PHC and French) accurately predicted survival and may be useful for risk estimation in patients with idiopathic, heritable, and anorexigen-associated PAH in large cohort studies. Their use for survival prediction for individual patients needs further study.

The effect of diluent pH on bloodstream infection rates in patients receiving IV treprostinil for pulmonary arterial hypertension.

BACKGROUND: Recent studies have reported an increase in catheter-related bloodstream infections (BSIs) and gram-negative BSIs among patients with pulmonary arterial hypertension treated with IV treprostinil. One possible explanation is the neutral pH of the treprostinil diluent compared with the basic pH of epoprostenol. We hypothesized that administering IV treprostinil with epoprostenol diluent will lower the rate of gram-negative BSI. METHODS: We prospectively enrolled patients treated with IV treprostinil and changed the diluent from native diluent to epoprostenol diluent. We compared the incidence of BSI and gram-negative BSI between those receiving IV treprostinil with epoprostenol diluent (n = 25) and those actively receiving IV epoprostenol (n = 61), as well as with a cohort of patients who received IV treprostinil in native diluent (n = 34). Incidence rates of BSI were expressed as a fraction of 1,000 medicine treatment days. RESULTS: There were similar rates of BSI in those treated with treprostinil with epoprostenol diluent and those treated with epoprostenol (0.32 of 1,000 vs 0.40 of 1,000; P = .79). Also, there were similar rates of gram-negative BSI in these two cohorts (0.08 of 1,000 vs 0.20 of 1,000; P = .46). BSI rates were not statistically different between those treated with treprostinil with epoprostenol diluent and those treated with treprostinil (0.32 of 1,000 vs 0.90 of 1,000; P = .06). However, gram-negative BSIs were significantly lower in patients treated with treprostinil with epoprostenol diluent than in those treated with treprostinil (0.08 of 1,000 vs 0.71 of 1,000, respectively; P = .01). CONCLUSIONS: Patients treated with treprostinil with epoprostenol diluent have a lower incidence of gram-negative BSI than do those treated with treprostinil and a similar rate to those treated with epoprostenol. Changing the diluent of treprostinil to epoprostenol diluent, in combination with the use of water-tight seals throughout the delivery system, appears to be an effective safety measure.

Risk assessment in pulmonary hypertension associated with heart failure and preserved ejection fraction.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with left heart failure (HF), especially those with HF and preserved ejection fraction (HFpEF). However, there is limited data on risk stratification in these patients. METHODS: Baseline clinical and hemodynamic variables of 339 patients with World Health Organization (WHO) Group 2 PH, 90% of whom had HFpEF, were studied to derive a multivariate Cox proportional hazards model. A simplified prognostic risk score was created based on the outcome of all-cause mortality. Nine predictors, significant after stepwise multivariable regression (p < 0.05), were used to create the risk score. Components of the risk score were functional class, diastolic blood pressure, pulmonary artery saturation, interstitial lung disease, hypotension on initial presentation, right ventricular hypertrophy, diffusion capacity of the lung for carbon monoxide, and 2 serum creatinine variables (≤ 0.9 mg/dl and ≥ 1.4 mg/dl). RESULTS: Overall 2-year survival was 73.8% ± 2.4% in the derivation cohort, and 87.5% ± 2.3%, 66.4% ± 4.9%, and 24.4% ± 6.7% for risk scores of 0 to 2, 3 to 4, and 5+, respectively (p < 0.0001 for the trend), with a C-index of 0.76 (95% confidence interval [CI], 0.71-0.81). The risk score was validated in 2 independent PH-HFpEF cohorts: 179 patients with a C-index of 0.68 (95% CI, 0.55-0.80) and 117 patients with a C-index of 0.68 (95% CI, 0.53-0.83). For the 3 cohorts combined (N = 635), the overall C-index was 0.72 (95% CI 0.68-0.76). In all 3 cohorts individually and in the 3 cohorts combined, the risk score predicted death (hazard ratio, 1.4-1.6; p < 0.01). CONCLUSIONS: Several clinical factors independently predict death in PH-HFpEF confirmed by validation. A novel risk score composed of these factors can be used to determine prognosis and may be useful in making therapeutic decisions.