BACKGROUND: Pulmonary arterial hypertension is a progressive, fatal disease. Published treatment guidelines recommend treatment escalation on the basis of regular patient assessment with the goal of achieving or maintaining low-risk status. Various strategies are available to determine risk status. This analysis describes an update of the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk calculator (REVEAL 2.0) and compares it with recently published European Society of Cardiology/ Respiratory Society guideline-derived risk assessment strategies. METHODS: A subpopulation from the US-based registry REVEAL that survived >= 1 year postenrollment (baseline for this cohort) was analyzed. For REVEAL 2.0, point values and cutpoints were reassessed, and new variables were evaluated. The Kaplan-Meier method was used to estimate survival at 12 months postbaseline; discrimination was quantified using the c-statistic. Mortality estimates and discrimination were compared between REVEAL 2.0 and Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (COMPERA) and French Pulmonary Hypertension Registry (FPHR) risk assessment strategies. For this comparison, a three-category REVEAL 2.0 score was computed in which patients were classified as low-, intermediate-, or high-risk. RESULTS: REVEAL 2.0 demonstrated similar discrimination as the original calculator in this subpopulation (c-statistic = 0.76 vs 0.74), provided excellent separation of risk among the risk categories, and predicted clinical worsening as well as mortality in patients who were followed >= 1 year. The REVEAL 2.0 three-category score had greater discrimination (c-statistic = 0.73) than COMPERA (c-statistic = 0.62) or FPHR (c-statistic = 0.64). Compared with REVEAL 2.0, COMPERA and FPHR both underestimated and overestimated risk. CONCLUSION: REVEAL 2.0 demonstrates greater risk discrimination than the COMPERA and FPHR risk assessment strategies in patients enrolled in REVEAL. After external validation, the REVEAL 2.0 calculator can assist clinicians and patients in making informed treatment decisions on the basis of individual risk profiles.

The assessment of objective measurement of cardiopulmonary status has helped us achieve better clinical outcomes for patients and develop new therapies through to the point of market access; however, patient surveys indicate that more can be done to improve holistic care and patient engagement. In this multidisciplinary review, we examine how clinical teams can acknowledge and embrace the individual patient's perspective, and thus improve the care for individual patients suffering from pulmonary hypertension by cultivating the importance and relevance of health-related quality of life in direct clinical care. At the individual level, patients should be provided with access to accredited specialist centres which provide a multidisciplinary approach where there is a culture focused on narrative medicine, quality of life, shared decision making and timely access to palliative care, and where there is participation in education. On a larger scale, we call for the development, expansion and promotion of patient associations to support patients and carers, lobby for access to best care and treatments, and provide input into the development of clinical trials and registries, focusing on the patients’ perspective.

Background: Pulmonary arterial hypertension (PAH) is a progressive vascular disorder with a high mortality. Clinical experience and small case series suggest thrombocytopenia may be frequent in this population and associated with a poor prognosis. We sought to estimate the prevalence of thrombocytopenia in patients with PAH and characterize its association with disease characteristics and patient outcome. Methods: Single center cohort study of 714 incident adult patients with Group 1 PH who were evaluated for baseline platelet count at the time of diagnosis. Pts were stratified into three groups: normal platelet count (>150 x 10(9)/L), Grade 1 thrombocytopenia (75-149 x 10(9)/L) and Grade 2-4 thrombocytopenia (<75 x 10(9)/L). Results: The median platelet count was 209 x 10(9)/L (IQR 163, 264). There were 572 (80%) pts without thrombocytopenia, 107 (15%) with Grade 1 and 35 (5%) with Grade 2-4 thrombocytopenia. The median pt age was 55 years (IQR 44-65) with no difference between platelet groups (p = 0.85). Men were more likely to have thrombocytopenia (62, 34%) than women (80, 15%, p < 0.0001). Thrombocytopenia was frequent with portopulmonary PAH (84%) as opposed to idiopathic PAH (iPAH; 14%) or connective tissue disease associated PAH (12%). Platelet counts were not associated with functional class symptoms, the degree of right ventricular enlargement or dysfunction or tricuspid regurgitation by echocardiography. Invasive hemodynamics of right atrial pressure, mean pulmonary artery pressure and pulmonary vascular resistance were also similar between platelet groups. Thrombocytopenia was associated with higher mortality in iPAH patients (age- and sex-adjusted 5 year mortality [HR 1.95 (1.20, 3.08) p = 0.008] but not in other etiology groups. In a multivariate model of iPAH patients (adjusted for age, sex, DLCO, PVR, creatinine and 6MW distance) thrombocytopenia was most predictive of 5-year mortality [HR 1.68 (1.32, 2.12), p < 0.0001]. Conclusion: Thrombocytopenia in the context of iPAH portends a poor prognosis and is a simple independent factor to consider in judging severity of disease. (C) 2018 Elsevier Inc. All rights reserved.

BACKGROUND:Plasma brain natriuretic peptide (BNP) level is a prognostic biomarker in pulmonary arterial hypertension (PAH). Its impact on long-term overall survival (OS) was investigated in the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management (REVEAL), a 5-year observational, multicenter, US registry of patients with PAH. METHODS:Patients were ≥ 18 years of age, met right heart catheterization criteria at rest, had World Health Organization group I PAH, and had BNP measurement at enrollment. Optimal BNP threshold was obtained via receiver operating characteristic curve analysis. OS was compared in patients with low (≤ 340 pg/mL) vs high (> 340 pg/mL) BNP at baseline; changes between baseline and last assessment were also examined. Patients were categorized based on baseline (low or high) and follow-up (low or high) BNP values; hazard ratios (HRs) for OS were estimated and compared using Cox regression. RESULTS:Overall, 1,426 patients were analyzed. Mortality risk was significantly higher in patients with baseline high vs low BNP (HR, 3.6; 95% CI, 3.0-4.2). BNP change analysis at ≤ 1 year postenrollment demonstrated that the low-low group had the lowest and the high-high group had the highest 5-year mortality risk (HR, 0.23; 95% CI, 0.19-0.27). Changes in BNP score also correlated with change of risk of death. CONCLUSIONS:Baseline BNP threshold of 340 pg/mL strongly predicted survival up to 5 years in patients with PAH. A BNP reduction at 1 year since enrollment was associated with decreased mortality risk, whereas an increase in BNP at 1 year was associated with an increased mortality risk, supporting BNP as a surrogate marker of PAH survival.

BACKGROUND:Supplemental low-flow oxygen is recommended by treatment guidelines as supportive therapy for patients with pulmonary arterial hypertension (PAH), based largely on expert opinion. Reduced diffusing capacity of lung carbon monoxide (DLCO) is associated with increased mortality in PAH. Reduced DLCO is also associated with relative hypoxemia, making the effects of supplemental oxygen use of particular interest in this sub-population. METHODS:Patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a 5-year observational study of Group 1 PAH, were categorized by presence or absence of supplemental oxygen use and by degree of DLCO reduction. Kaplan-Meier survival estimates were calculated by group. RESULTS:Of 3,046 patients, 57% used supplemental oxygen and 43% did not. Supplemental oxygen users had worse prognostic factors and more PAH-specific medication use. Of the 424 patients with severe DLCO reduction (<40% of predicted), 76% used oxygen and 24% did not. Patients with severe DLCO reduction who used supplemental oxygen had a significantly lower risk of all-cause mortality than those who did not (hazard ratio 0.56; 95% confidence interval 0.39 to 0.83; p = 0.0033). This was true for newly diagnosed and previously diagnosed patients. There was no relationship between oxygen use and outcomes in patients with no, mild, or moderate DLCO reduction. CONCLUSIONS:In this observational study, the risk of death was significantly lower for patients with severe DLCO reduction who received supplemental oxygen compared with those who did not. A randomized trial is warranted to further investigate the relationship between supplemental oxygen use and outcomes in PAH.

Pulmonary arterial hypertension (PAH) is progressive and associated with early demise. Risk assessment tools help predict prognosis and optimize disease management. A PAH risk calculator from Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) was refined to allow better risk delineation and include new clinically useful variables.

Designing a randomized controlled trial (RCT) to investigate a survival benefit in a rare disease such as pulmonary arterial hypertension (PAH) has considerable logistical and ethical constraints. In the SERAPHIN RCT, a 23% non-significant reduction in the risk of all-cause mortality was observed with macitentan 10 mg vs. placebo. As SERAPHIN enrolled patients in the same time frame as the US REVEAL registry, a prediction model based on REVEAL data was used to further explore the effect of macitentan on mortality. From REVEAL (N = 3515), 734 patients who would have met SERAPHIN eligibility criteria were selected (REVEAL analysis cohort [RAC]). Using the RAC, a prediction model for time to death up to 3 years was constructed based on ten baseline prognostic variables. The model was used to predict survival of each of the 742 SERAPHIN patients had they received real-world treatment in the RAC. The average temporal profile of these patients was then compared with the observed survival of the macitentan 10 mg group (n = 242) using a log-rank test and Cox's proportional hazard model. Over 3 years, the risk of mortality observed with macitentan 10 mg was 35% lower than that predicted (p = 0.01) (Fig). Real-world observational data can complement RCT data to provide a means of evaluating survival benefits in rare diseases. Merits and limitations of this approach will be discussed.

BACKGROUND:Renal dysfunction is associated with abnormal cardiopulmonary hemodynamics, in-hospital death and poor survival in patients with pulmonary arterial hypertension (PAH), and thus it may be a prognostic biomarker. In our analysis we assess the relationship between change in estimated glomerular filtration rate (eGFR) and outcomes in PAH patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL). METHODS:Overall 2,368 patients were classified into chronic kidney disease (CKD) stages based on baseline eGFR: normal or Stages 1 or 2 (n = 1,699); Stage 3a (n = 399); Stage 3b (n = 196); and Stages 4 or 5 (n = 74). We evaluated the relationship between baseline CKD stage and survival, as well as the composite end-point of survival and freedom from all-cause hospitalization. The relationships between change in eGFR at ≥1 year and these clinical end-points were also evaluated. RESULTS:Patients with a ≥10% decline in eGFR from baseline over ≥1 year had a significantly increased risk of death (hazard ratio 1.66; p < 0.0001) and the composite of all-cause hospitalization and death (hazard ratio 1.33; p = 0.002). This decline predicted survival independently of changes in 6-minute walk distance and functional class. However, a ≥10% increase in eGFR was not significantly associated with either end-point. CONCLUSION:In REVEAL, a ≥10% decline in eGFR over ≥1 year independently predicted poorer survival. Thus, eGFR may be a simple and economical biomarker in PAH.

INTRODUCTION:Tricuspid valve regurgitation (TR) is a frequent finding in patients with pulmonary arterial hypertension (PAH). However, its prognostic significance and relation to PAH, while suspected, are poorly understood. We assessed 727 consecutive patients with newly diagnosed PAH who underwent transthoracic echocardiographic evaluation of tricuspid valve function.OBJECTIVES:The study objective was to determine the association of TR presence and severity with patient characteristics, pulmonary artery hemodynamics and outcome.METHODS:Consecutive patients with newly diagnosed PAH (N = 727 with group 1 pulmonary hypertension) underwent transthoracic echocardiographic evaluation of tricuspid valve function at diagnosis. The primary study end point was all-cause mortality or lung transplantation.RESULTS:In this population, 702 patients (96.5%) had TR; in 165 patients (23%), TR was severe. Compared with those with no or mild TR by echocardiography criteria, patients with severe TR had shorter mean (SD) 6-minute walk distances (285 [125] m vs 360 [121] m; P = .02) and higher levels of B-type natriuretic peptide (695 [672] pg/dL vs 328 [300] pg/dL; P < .05). Severe TR was associated with greater right atrial dilatation (91% vs 47%; P = .004) and right ventricular (RV) dilatation (92% vs 51%; P = .008), greater right atrial pressure (mean [SD] 15 [7] mm Hg vs 10 [6] mm Hg; P < .001) and lower cardiac index (mean [SD], 2.2 [0.7] L/min/m2 vs 2.8 [0.9] L/min/m2; P < .001). Severe TR was strongly predictive of greater 5-year mortality risk after adjustment for age, sex, functional class, 6-minute walk distance, diffusing capacity, RV size and pulmonary vascular resistance index (adjusted hazard ratio, 1.83; 95% CI, 1.38-2.41; P < .001).CONCLUSIONS:Severe TR was a significant predictor of long-term mortality rate in PAH, and TR severity correlated with PAH severity.

Rationale: Prostacyclin‐associated leg pain is a potentially debilitating adverse effect of prostacyclin therapy for patients with pulmonary arterial hypertension (PAH). However, to our knowledge, this entity has not been systematically studied. Objectives: To characterize the clinical features and metabolic risk factors for prostacyclin‐associated leg pain. Methods: At one academic medical center, we assembled and analyzed a case series of patients with PAH and prostacyclin‐associated leg pain. Measurements and Main Results: Over a period of 2 years, we identified 11 patients with PAH and prostacyclin‐associated leg pain who agreed to participate in this study. Subjects underwent a standardized clinical evaluation, electrodiagnostic assessment, and serologic screen for metabolic causes of peripheral neuropathy. All 11 patients were female; their mean (SD) age was 50 (±9) years; their median (interquartile range) PAH duration was 56 (20‐96) months; and their prostacyclin therapy duration was a median (interquartile range) of 20 (14‐36) months. All patients reported leg pain beginning soon after prostacyclin initiation and varying with dose. All described a neuropathic pain in a symmetric, distal, stocking distribution. Neurologic examination revealed a sensory, small‐fiber, predominantly peripheral neuropathy in seven (78%) patients. Results of autonomic reflex testing and thermoregulatory sweat testing were abnormal in 82% and 90% of patients, respectively, suggesting small‐fiber neuropathy. Serologic evaluation identified a new, previously unrecognized contributor to neuropathy in eight (73%) patients, including vitamin B12 deficiency in six (55%), uncompensated hypothyroidism in three (27%), and diabetes mellitus in one (9%). Conclusions: Chronic prostacyclin‐associated leg pain is associated with a small‐fiber neuropathy. Treatable metabolic contributors (vitamin B12 deficiency, thyroid dysfunction, or diabetes) appear to be common possible “second hits” that may be underrecognized. We recommend screening for possible metabolic contributors in patients who have otherwise unexplained leg pain in the setting of PAH and current or anticipated prostacyclin therapy.

SESSION TITLE: Pulmonary Vascular Disease II SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are rare, progressive diseases characterized by increases in pulmonary artery pressure (PAP) and pulmonary vascular resistance with high morbidity and mortality. Despite advances in treatment and patient outcomes, recent studies have shown common diagnostic errors and an underutilization of consensus treatment guidelines. The Pulmonary Hypertension Association (PHA) launched the PH Care Centers (PHCC) initiative to identify centers with a focused interest in PH and to better understand adherence and barriers to consensus best practices. METHODS: Applicant PH programs underwent chart reviews of 96 clinical variables on 15 randomly selected PAH and CTEPH patients managed by the program within the past three years. Patients selected included those managed on oral, inhaled and parenteral therapies; CTEPH patients; and recently deceased patients. PHCC reviewers assessed adherence to expert consensus guidelines on PH diagnosis, hemodynamic assessment of PAH, disease treatment, and changes in treatment goals in response to disease progression. Data are presented as overall percent of items observed during the chart reviews (% ranges of individual centers). RESULTS: Between February 2014 and March 2016, PHCC reviewed 38 programs and subsequently accredited 30 adult and 4 pediatric Centers of Comprehensive Care (CCC). Data from 12% of the site reviews were excluded from analysis due to missing data or because the reviews were conducted during the pilot phase of accreditation. Regarding PH diagnostic guidelines, appropriate testing was found for the following tests: PFTs, 95.4% (62.5-100); Chest imaging, 99.6% (87.5-100); overnight oximetry or polysomnography, 78.8% (12.5-100); and VQ or CTA to rule out CTEPH, 96.0% (60.0-100). Hemodynamic assessments of patients on PAH-targeted therapy revealed: right heart catheterization in 100.0%; mPAP≥25mmHg, 99.7% (90-100); PAOP≤15mmHg, 99.3% (90-100); and appropriate acute vasoreactivity testing, 96.3% (62.5-100). Longitudinal management reviews showed WHO/NYHA functional class assessments, 96.7% (50-100); documented 6MW testing, 97.5% (62.5-100); referral for PTE evaluation in 100% of CTEPH cases. All patients reviewed who had died in the prior year had a documented transplantation discussion, and palliative medicine referral or discussion was documented in 98.3% (50-100). CONCLUSIONS: An initial cross-sectional analysis of CCCs accredited by the PHCC program revealed that accredited centers had strong adherence to expert consensus guidelines in the diagnosis and treatment of pulmonary hypertension. Areas for quality improvement within the surveyed items include inconsistent screening for sleep breathing disorders. CLINICAL IMPLICATIONS: The PHCC accreditation process can assist centers with their individual quality improvement programs through creating national benchmarks for care, inform healthcare providers of options for experienced PH co-management, and assist patients seeking high quality care. DISCLOSURE: Erika Berman Rosenzweig: Consultant fee, speaker bureau, advisory committee, etc.: Actelion Pharmaceuticals, Consultant fee, speaker bureau, advisory committee, etc.: Gilead Sciences, Consultant fee, speaker bureau, advisory committee, etc.: Ikaria, University grant monies: Actelion, University grant monies: United Therapeutics, University grant monies: Bayer HealthCare, University grant monies: Gilead Sciences Michael McGoon: Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Gilead, Consultant fee, speaker bureau, advisory committee, etc.: Lung Biotechnology Murali Chakinala: Consultant fee, speaker bureau, advisory committee, etc.: Actelion Pharmaceuticals, Consultant fee, speaker bureau, advisory committee, etc.: Gilead Sciences, Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: SteadyMed, Consultant fee, speaker bureau, advisory committee, etc.: Bayer HealthCare, Grant monies (from industry related sources): Actelion Pharmaceuticals, Grant monies (from industry related sources): Gilead Sciences, Grant monies (from industry related sources): United Therapeutics, Grant monies (from industry related sources): Bayer HealthCare, Grant monies (from industry related sources): MedTronic, Grant monies (from industry related sources): Reata, Grant monies (from industry related sources): Ikaria, Grant monies (from industry related sources): GlaxoSmithKline Joel Wirth: Grant monies (from industry related sources): Actelion Pharmaceuticals, Grant monies (from industry related sources): Arena, Grant monies (from industry related sources): Lung LLC, Grant monies (from industry related sources): Reata The following authors have nothing to disclose: Michael Gray, Olivia Onyeador No Product/Research Disclosure Information

Aim: It is not well known if advancing age influences normal rest or exercise pulmonary artery pressures. The purpose of the study was to evaluate the association of increasing age with measurements of pulmonary artery systolic pressure at rest and with exercise. Subjects and methods: A total of 467 adults without cardiopulmonary disease and normal exercise capacity (age range: 18–85 years) underwent symptom-limited treadmill exercise testing with Doppler measurement of rest and exercise pulmonary artery systolic pressure. Results: There was a progressive increase in rest and exercise pulmonary artery pressures with increasing age. Pulmonary artery systolic pressures at rest and with exercise were 25±5mmHg and 33±9mmHg, respectively, in those <40 years, and 30±5mmHg and 41±12mmHg, respectively, in those ≥70 years. While elevated left-sided cardiac filling pressures were excluded by protocol design, markers of arterial stiffness associated with the age-dependent effects on pulmonary pressures. Conclusion: These data demonstrate that in echocardiographically normal adults, pulmonary artery systolic pressure increases with advancing age. This increase is seen at rest and with exercise. These increases in pulmonary pressure occur in association with decreasing transpulmonary flow and increases in systemic pulse pressure, suggesting that age-associated blood vessel stiffening may contribute to these differences in pulmonary artery systolic pressure.

BACKGROUNDA subset of patients with hereditary hemorrhagic telangiectasia (HHT) develops pulmonary hypertension (PH) by mechanisms including pulmonary arterial hypertension, high flow, and elevated pulmonary arterial wedge pressure (PAWP). We aimed to describe echocardiographic and hemodynamic characteristics of patients with coexisting HHT and PH.METHODSWe conducted a single-center cohort study of patients with confirmed HHT who underwent right-sided heart catheterization (RHC) and transthoracic two-dimensional echocardiography for suspected PH between June 1, 2003 and September 1, 2013 at Mayo Clinic Rochester, Minnesota.RESULTSOf 38 patients with confirmed HHT who underwent RHC and echocardiography, 28 (74%) had a mean pulmonary artery pressure (MPAP) ≥ 25 mm Hg. Of those 28, 12 (43%) had pulmonary arterial hypertension. Two patients had normal PAWP and pulmonary vascular resistance (PVR), with PH secondary to either an atrial septal defect or high cardiac flow. Fourteen patients (50%) had elevated PAWP (≥ 15 mm Hg), nine with evidence of high flow. RHC in all 28 patients demonstrated a MPAP of 41 ± 11 mm Hg, PAWP of 17 ± 10 mm Hg, and PVR of 4.5 ± 4.2 Wood units. Echocardiography demonstrated moderate/severe right ventricular dysfunction in nine patients (32%). The presence of PH trended toward worse survival (P = .06).CONCLUSIONSPH in patients with HHT occurs by different mechanisms, and there is a trend toward worse survival in patients who develop PH despite the mechanism. The equal predilection toward all subtypes of PH illustrates the necessity of RHC to clarify the hemodynamics.

The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS)Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)

BACKGROUND: Clinical studies of pulmonary arterial hypertension have used the change in the 6-minute walk distance (6MWD) as a clinical end point; however, its association with survival outcomes has not been well established. In this analysis, we examined the prognostic value of the baseline 6MWD, absolute thresholds of the 6MWD, and change in the 6MWD.METHODS: Patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) with 6MVVD at enrollment, with or without a follow-up assessment within the first year of observation, were included. Kaplan-Meier survival estimates were computed for sub-sets with baseline 6MWD results that were above or below all possible thresholds and for sub-sets with a change in the 61VIWD that was 10 percentage points above or below all possible thresholds, including improvement thresholds and worsening thresholds. Multivariable Cox regression models assessed the effect of improvement and worsening in the 6MWD on 1-year survival, adjusted for baseline factors.RESULTS: One-year survival estimates were higher for patients with a baseline 6MV TD above vs below a threshold, although no specific threshold was more prognostic than another. In a model adjusted for the baseline 6MWD and risk score, worsening of the 6MWD over time significantly predicted decreased survival, but improvement in the 6MWD did not affect survival.CONCLUSIONS: No 6MWD improvement threshold carries particular prognostic value. Improvement in the 6MWD was not associated with survival, but worsening of the 6MWD was strongly and significantly associated with poor prognosis. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

To determine the hemodynamic profile of patients with hereditary hemorrhagic telangiectasia (HHT) referred for right heart catheterization and estimate the incidence of pulmonary hypertension (PH) and/or high output states in this setting. Single center cohort study of all patients with HHT and suspected PH who underwent right heart catheterization between 1/1/1995- 9/1/2013. Data reported as mean ± standard deviation. High output state was defined as cardiac index > 4.2 L/min/m2. Of 62 patients who underwent right heart catheterization for suspected HHT and PH, 38 patients (61 %) met Curacao criteria for HHT. The mean age at time of PH diagnosis was 56 ± 16 years. Baseline NT-BNP was 558 ± 1855 pg/ml and baseline hemoglobin was 11.6 ± 2.4 g/dL. At the time of right heart catheterization, 13 patients (34%) were World Health Organization functional class III/IV while 14 patients (37%) had class II symptoms. Pulmonary arteriovenous malformations, hepatic arteriovenous malformations, and gastrointestinal malformations were present in 17 (45 %), 29 (76 %), and 3 (8 %) respectively. Of those 38 patients with criteria-confirmed HHT, 24 (63%) had a pulmonary artery pressure > 25 mmHg and a cardiac index < 4.2 L/min/m2. The mean cardiac index for these patients was 3.25 ± 1.02 L/min/m2. Five (13%) had PAP >25 mmHg and cardiac index > 4.2 L/min/m2. The mean cardiac index for these patients was 4.65 ± 0.28 L/min/m2. Four (11%) of the 38 patients did not meet criteria for PH, but did have high output states with an index of > 4.2 L/min/m2. The mean cardiac index for these patients was 6.08 ± 0.78 L/min/m2. Five patients (13%) had neither PH nor high output states. Mean pulmonary vascular resistance for patients with both PH and HHT was 4.54 ± 4.19 Wood Units. In patients with hereditary hemorrhagic telangiectasia the coexistence of PH is common with the majority having hemodynamics compatible with pulmonary arterial hypertension rather than high-output mediated PH.

BACKGROUND Pulmonary arterial hypertension (PAH) is a rare, severe disease characterized by worsening right-sided heart failure, decreasing functional status, and poor survival. The present study characterizes the 5-year survival in the United States of a new and previous diagnosis of PAH in patients stratified by baseline functional class (FC). The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) is a 55-center observational US registry of the demographics, disease course, and management of patients with World Health Organization (WHO) group 1 PAH. METHODS The REVEAL Registry enrolled newly and previously diagnosed patients aged ≥ 3 months with WHO group 1 PAH consecutively from March 2006 to December 2009. Demographics, disease characteristics, and hemodynamic data were collected at enrollment. Survival analysis was conducted by FC and other subgroups in patients aged ≥ 18 years. RESULTS Survival differences between previously diagnosed and newly diagnosed patients at 1 year (90.4% vs 86.3%) were maintained to 5 years; 5-year survival for previously diagnosed patients was 65.4% compared with 61.2% for newly diagnosed patients. Previously diagnosed patients in FC I, II, III, and IV had an estimated 5-year survival rate of 88.0%, 75.6%, 57.0%, and 27.2%, respectively, compared with 72.2%, 71.7%, 60.0%, and 43.8% for newly diagnosed patients in FC I, II, III, and IV, respectively. CONCLUSIONS Patient survival of advanced PAH remains poor at 5 years despite treatment advances. New York Heart Association FC remains one of the most important predictors of future survival. These observations reinforce the importance of continuous monitoring of FC in patients with PAH. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.