ß-blocker therapy is not associated with adverse outcomes in patients with pulmonary arterial hypertension: a propensity score analysis.

BACKGROUND: The safety of ß-blockers in patients with isolated right ventricular failure because of pulmonary arterial hypertension (PAH) is unclear. METHODS AND RESULTS: We studied 564 PAH patients (total cohort) referred to our center from 1982 to 2013. Propensity score-matching was used to match pairs of PAH patients with and without ß-blocker use (matched cohort). We compared all-cause mortality between the groups in the total cohort and the matched cohort using bootstrap validation, Kaplan-Meier, and Cox proportional hazard analyses. Seventy-one of the 564 patients in the total cohort were on ß-blockers. They were older, had higher prevalence of comorbidities, and were more often on diuretics, digoxin, and angiotensin converting enzyme inhibitors. The severity of PAH and right ventricular failure was similar between those with and without ß-blocker use. After propensity matching, 63 patients with ß-blocker use were compared with 51 patients without ß-blocker use. During a median follow-up time of 4.8 years, there were 339 (60%) deaths in the total cohort and 70 deaths (61%) in the matched cohort. There was no difference in absolute mortality between those with and without ß-blockers (P=0.71). ß-Blocker use was not associated with increased all-cause mortality in the total cohort after adjusting for propensity score (adjusted hazard ratio, 1.0; 95% confidence interval, 0.7-1.5) and in the matched cohort (hazard ratio, 1.2; 95% confidence interval, 0.8-2.0). CONCLUSIONS: There was no statistically significant difference in long-term mortality between propensity score-matched pairs of PAH patients with and without ß-blocker use. These findings need further validation in prospective clinical trials.

Survival in pulmonary arterial hypertension patients awaiting lung transplantation.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease with lung transplantation as the only option for those patients refractory to medical therapy. Although several equations have been developed to predict PAH patient survival, it is unclear whether they can predict survival for patients awaiting transplantation. METHODS: Data were analyzed on 827 patients listed since 1991 on the Scientific Registry of Transplant Recipients. Overall survival and survival for patients listed prior to and after January 1, 2006 was estimated using the Kaplan-Meier (K-M) method and compared with predicted survival from the pulmonary hypertension connection (PHC) and lung allocation system (LAS) equations. A new equation using a novel model selection algorithm for correlated covariates and missing data was developed using clinical factors and variables in the LAS score. Model validation statistics were calculated and averaged across 500 bootstrap resamples within each of 5 imputation data sets. K-M with 95% confidence intervals and receiver-operator characteristic (ROC) curves assessed model performance. RESULTS: PHC predicted overall survival but underestimated and overestimated survival for those listed pre- and post-2006, respectively. The best model included baseline 6-minute walk distance (6MWD), invasive cardiac output and resting oxygen requirement (O2). Factors associated with 1-year waitlist survival included: resting O2 amount; invasive hemodynamics; 6MWD; and functional class. The new equation by ROC analysis outperformed the LAS and PHC equations. CONCLUSIONS: Current prediction models overestimate survival for PAH patients listed for transplant in the LAS era. This new survival equation can help guide clinicians caring for PAH patients with progression of disease requiring transplant.

Long-term effects of continuous prostacyclin therapy in adults with pulmonary hypertension associated with congenital heart disease.

BACKGROUND: The continuous administration of prostacyclin analogs (PGI2) is a proven and effective therapy in patients with group 1 pulmonary arterial hypertension (PAH). However, few studies have addressed its use in adults with PAH associated with congenital heart disease (CHD-PAH). Concerns remain regarding the theoretical risk of worsening right-to-left intracardiac shunt. In this study, we present the hemodynamic and clinical effects of long-term, continuous PGI2 administration in eight adult patients with CHD-PAH. METHODS: We retrospectively reviewed the records of patients with CHD-PAH treated with continuous prostacyclin analogs epoprostenol and treprostinil. Nine patients were identified; one patient had no documentation of an intracardiac shunt and was excluded from this study. Hemodynamic, functional, laboratory, and clinical data were included. RESULTS: Mean duration of continuous PGI2 therapy was 1 year. Compared to baseline, patients exhibited significant improvements in mean pulmonary artery (PA) pressure and PA oxygen saturation, without a significant decline in systemic blood pressure or systemic oxygen saturation. Metabolic equivalents (METs) achieved on exercise testing increased, with an improvement in oxygen desaturation. World Health Organization functional classification remained the same. CONCLUSIONS: Long-term continuous PGI2 therapy in CHD-PAH patients resulted in hemodynamic and clinical improvements similar to those with group 1 PAH. The increase in PA oxygen saturation suggests that the net effect of PGI2 therapy did not result in increased right-to-left shunting, but, instead, diminished shunt. Though larger studies are needed, PGI2 should be considered as a potential treatment modality in adult patients with severe CHD-PAH who fail conventional therapy.

Referral of patients with pulmonary hypertension diagnoses to tertiary pulmonary hypertension centers: the multicenter RePHerral study.

IMPORTANCE: Pulmonary hypertension (PH) is a fatal disease. Although the prognosis of pulmonary arterial hypertension (PAH) has improved with targeted therapies, the outcome is dependent on early detection and an accurate diagnosis. OBJECTIVE: To determine the accuracy of PH diagnoses in patients referred to PH centers and the frequency of PAH-specific medication use despite an uncertain or incorrect diagnosis. DESIGN: Multicenter, descriptive, cross-sectional study. During a 10-month period in 2010 and 2011, data on newly referred patients were collected and entered into a secure Internet database. SETTING: Three large tertiary PH centers. PARTICIPANTS: One hundred forty consecutive patients newly referred to PH centers were invited to participate, and all consented to do so. RESULTS: Of 140 patients referred with a mean age of 56 years, 95 (68%) were referred by cardiologists or pulmonologists and 86 (61%) had disease classified as World Health Organization functional class III or IV. Fifty-six of the prereferral diagnoses (40%) were PAH, 42 (30%) unknown, and 22 (16%) PH secondary to lung disease or hypoxia. Of the 98 patients who received a definitive diagnosis before referral, 32 (33%) received a misdiagnosis. Fifty-nine patients underwent catheterization of the right and/or left side of the heart for the first time at the tertiary center. Of the 38 patients who underwent catheterization of the right side alone, 14 (37%) received a different diagnosis after undergoing the procedure; of the 21 patients who underwent catheterization of both sides of the heart, 11 (52%) received a different diagnosis after undergoing the procedures. Forty-two patients (30%) had started receiving PAH-specific medications before referral, with 24 of the prescriptions (57%) contrary to published guidelines. CONCLUSIONS AND RELEVANCE: Patients referred to PH centers for diagnosis and treatment are often referred late (with functional class III or IV disease), receive misdiagnoses, and are inappropriately prescribed medications. A reevaluation of educational efforts is required to improve awareness and the care and outcome of patients diagnosed as having PH.