123: REVEAL Registry: Prevalence, Demographics and Outcomes in Patients with Pulmonary Arterial Hypertension (PAH) Characterized by Higher Left Sided Pressures

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Abstracts

121 C-Reactive Protein in Broncho-Alveolar Lavage Is Associated with Airway Inflammation after Lung Transplantation R. Vos, B.M. Vanaudenaerde, S.I. De Vleeschauwer, L.J. Dupont, D. Van Raemdonck, G.M. Verleden Katholieke Universiteit and University Hospital Leuven, Leuven, Belgium Purpose: C-reactive protein (CRP), an acute phase marker of systemic inflammation, may also be part of the pulmonary immune system functioning as a local regulator of neutrophil chemotaxis, production of pro-inflammatory cytokines and interacting with surfactant activity. Its role in lung transplantation (LTx), however, is unclear. We hypothesized that CRP in broncho-alveolar lavage (BAL) fluid might be associated with airway inflammation or remodelling and therefore might also play a role in the development of Bronchiolitis Obliterans Syndrome (BOS). Methods and Materials: A total of 100 LTx recipients, transplanted between Aug 2001 and Aug 2005, were included in this crosssectional study. Patients were evaluated at 90 days after LTx and categorized as stable (n⫽36), colonized (n⫽25), suffering from infection (n⫽16) or acute rejection (n⫽23). Patients were free of suture problems or airway stenting, BOS and azithromycin therapy. BAL CRP, cell differentials and IL8, IL6, TGF␤, VEGF protein levels as well as blood leucocytosis, plasma CRP and FEV1 were evaluated. BAL CRP was compared between groups and its relationship with inflammatory or remodelling markers and FEV1 analyzed. Results: BAL CRP was increased in infection and acute rejection, but not in colonized patients, compared to stable LTx recipients (Figure 1). BAL CRP levels positively correlated with BAL total cell count, neutrophilia and IL8 levels as well as with plasma CRP levels. An inverse correlation with BAL VEGF and with FEV1 was also seen. For BAL IL6 and TGF␤, only a trend could be demonstrated (Table 1). Conclusions: The current data corroborate a possible role of CRP in airway inflammation after LTx. Its importance for BOS should therefore be further elucidated.

The Journal of Heart and Lung Transplantation February 2009

but the contribution of antibody mediated rejection to BOS is unclear. We hypothesised that a) Human leukocyte antigen (HLA) matching before lung transplantation (Tx) confers protection against BOS and b) development of donor specific HLA antibodies after lung Tx is associated with accelerated decline in FEV1from peak post Tx level. Methods and Materials: Lung Tx donors and recipients have HLA typing, but matching is not performed prior to Tx. Recipients are tested for HLA antibodies pre-Tx and with each post-Tx surveillance bronchoscopy. We classified subjects as ⫹ HLA if they developed new class I or II HLA antibodies post-Tx or had an increased % panel of reactive antibodies (PRA). Others were classified as – HLA. The percentage of class I and II HLA type matches and mean monthly decline in FEV1 was calculated for both groups. Results: 31 consecutive lung Txs performed between Nov 2004 and Sept 2008 were analysed; actuarial 2-year survival was 96.5%. 26 subjects more than five months post Tx (results from ⬎4 bronchoscopies) provided data. Donor-recipient class II HLA matching is associated with reduced likelihood of developing HLA antibodies after lung Tx (p⫽0.06, Fisher’s exact test). Development of positive HLA antibodies after lung Tx is associated with accelerated decline in FEV1 and more episodes of acute rejection. Conclusions: The presence of a donor-recipient HLA class II match prior to lung Tx is associated with a reduced likelihood of developing new HLA antibodies and a slower decline in lung function. This supports the hypothesis that HLA matching before lung Tx may protect against development of BOS. HLA matching, HLA antibodies, ⌬ FEV1 and acute rejection

⫹ HLA (n⫽9) - HLA (n⫽17)

Mean HLA Class I match/subject match

Class II match

Mean acute rejection episodes (>A1:>A2)

⌬FEV1 (ml/ month) mean (SD)

0.67

44.4%

22.2%

3.44:1.44

47.2(36)

1.31

41.2%

58.8 %

3.0 :1.18

32.4(25)

123 REVEAL Registry: Prevalence, Demographics and Outcomes in Patients with Pulmonary Arterial Hypertension (PAH) Characterized by Higher Left Sided Pressures A. Frost1, D. Miller2, H. Farber3, M.D. McGoon4, R. Barst5, C.G. Elliott6 1Baylor College of Medicine, Houston, TX; 2ICON Clinical Research, Lifecycle Science Group, San Fransisco, CA; 3 Boston University School of Medicine, Boston, MA; 4Mayo Clinic, Rochester, MN; 5Columbia University College of Physicians & Surgeons, New York, NY; 6Intermountain Medical Center, University of Utah, Salt Lake, UT

122 The Relationship between Positive HLA Antibodies, Acute Rejection Episodes and Lung Function Decline Following Lung Transplantation C.I. Whale, A. Higton, N. Fernandez, S. Lawrence, C. Jary, E. Gabbay, M. Musk Royal Perth Hospital, Perth, WA, Australia Purpose: The relationship between recurrent acute cellular rejection and bronchiolitis obliterans syndrome (BOS) is established,

Purpose: The Registry to Evaluate Early And Long-term PAH Disease Management (REVEAL) a multicenter, observational, US-based study is designed to provide current information about demographics, course and management of WHO group I PAH patients (pts) and included an expanded definition: pulmonary artery occlusion pressures [PAOP] or LVEDP ⱕ 18mmHg at diagnostic right heart catheterization [RHC]. The prevalence, demographics, and outcomes of these pts were compared to those with strict WHO defined PAOP. Methods and Materials: Age, sex, race, functional class [FC] were compared between patients with PAOP ⱕ12 [Lw], 13-15 [Iw]; and 16-18 mmHg [Hw]. Post-enrollment: survival (1 yr), freedom from all-cause hospitalization and improvement in 6 minute walk distance [6MWD] from enrollment to 12 months were compared between groups as was the PAOP on subsequent RHC.

The Journal of Heart and Lung Transplantation Volume 28, Number 2S

Results: Between 3/2006 and 9/2007 2951 pts met inclusion criteria and had followup data. Lw pts tended to be younger at diagnosis than Iw or Hw pts (mean age 46 vs.52 and 53 yrs respectively) with a trend to more FCIV pts in Iw and Hw. Survival and freedom from hospitalization was the same in all groups. Enrollment 6MWD tended to be lower in Iw and Hw without significant difference in the frequency or degree of improvement in 6MWD at one year. Repeat RHC done in 1272 patients demonstrated that PAOP values normalized (ⱕ 12) in 50-65% of Iw and Hw patients and worsened in 21% of the previously Lw pts. Conclusions: There was no difference in survival or hospitalization between classical PAH pts and those with higher left sided pressures. The latter pts tended to be slightly older at diagnosis with slightly worse 6MWD at both enrollment and follow up at 12 months. The majority of patients outside the classical PAH definition at diagnosis had hemodynamcis in the classical range after treatment. Similar outcomes in all groups suggests that PAH diagnosis and PH specific therapy were appropriate in this expanded population. 124 Severe Pulmonary Hypertension in IPF: Characteristics and Implications O.A. Minai, J. Santacruz, M.M. Budev, K. McCarthy, L. Thuita, J. Alster Cleveland Clinic, Cleveland, OH Purpose: Pulmonary hypertension (PH) has been described as a complication of advanced IPF. The aim of our study was to characterize the prevalence, risk factors, and implications of severe PH in a large, well-characterized group of patients with advanced IPF. Methods and Materials: Patients with IPF who underwent right heart catheterization (RHC) as part of their lung transplant assessment were included. PH was defined as resting mean pulmonary artery pressure (mPAP) ⬎25mmHg and severe PH was defined as mPAPⱖ40 mmHg. Demographic, hemodynamic, and pulmonary function data for patients with severe PH were compared to those with mild/ moderate PH and those without PH (non-PH). Results: 148 patients [86M (58%); 128 Caucasians] with IPF that underwent RHC were identified. Of these 46% (68/148) met criteria for PH and 21 (14%) had severe PH. Compared to mild/mod PH and non-PH, patients with severe PH had lower cardiac index (2.2 vs 2.6 vs 2.9 l/min/m2; p⫽0.0003) and higher mean right atrial pressure (9.2 vs 7.7 vs 4.3 mmHg; p⫽⬍0.0001), pulmonary vascular resistance (7.5 vs 3.7 vs 2.2 Wood units; p⫽⬍0.0001), pulmonary artery pulse pressure (36 vs 26 vs 20 mmHg; p⫽⬍0.0001), BUN (p⫽0.06). Patients with severe PH had lower PaO2 (52 vs 59 vs 62 mmHg; p⫽0.03) and six-minute walk distance (6MWD) [294 vs 326 vs 368 meters; p⫽0.01] and higher mortality [43% (9/21) vs 28% (13/47) vs 20% (16/80)] compared to those with mild/moderate PH and the non-PH group. No significant differences between the groups were found in age, body mass index, forced vital capacity, or diffusion capacity for carbon monoxide. Conclusions: Patients with advanced IPF may have a very high prevalence of PH. In our group of patients, a significant proportion of patients had severe PH and the presence of PH did not correlate with severity of pulmonary function compromise. Patients with severe PH were more likely to have compromised hemodynamics, increased functional limitation, and higher mortality than patients with mild/ moderate PH and patients without PH. 125 Impact of Pulmonary Hypertension on Early Hemodynamics, Morbidity and Mortality after Orthotopic Heart Transplantation

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H. Bedanova, M. Orban, E.D. Petrikovits, J. Ondrasek, P. Nemec, J. Cerny Center of Cardiovascular and Transplant Surgery, Brno, Czech Republic Purpose: To determine the effect of pre-existing pulmonary hypertension (PHT) on early hemodynamics, morbidity and mortality after heart transplantation (HTx). Methods and Materials: A total of 149 patients, who underwent HTx between January 2000 and December 2007, were enrolled into the follow-up. According to preoperative pulmonary vascular resistance (PVR), the subjects were divided into 3 groups: Group A (n⫽84) without pulmonary hypertension (PH) with PVR ⬍ 3 Wood’ units (WU), group B (n⫽50) with mild to moderate PH with PVR 3-5 WU and group C (n⫽15) with severe PH with PVR ⬎ 5 WU. We studied hemodynamic profile early after transplantation, tricuspid valve regurgitation (TR) as a marker of right ventricle failure, incidence of acute cellular rejections (AR), infections, duration of hospitalization, 30-day mortality and a long-term survival. Results: Baseline characteristics were similar in all groups. Using vasodilator treatment (nitric oxide or alprostadil or their combination), PVR was successfully brought down to normal range (2.5 ⫾ 0.6 WU) on the day 1 following the surgery in all groups. Over 80% of patients were treated in Group C, 32% in Group A and 46% in Group B. There was no significant difference in the severity of TR among the 3 groups early after HTx (severe TR was observed in 46%, 54%, 33%, respectively). There was no significant difference in incidence of AR (G ⬎2 ISHLT classification) (23%, 23%, 33%, respectively), infections (28%, 32%, 33%, respectively), duration of hospitalization (30, 30, 28 days, respectively). There was no correlation between pre-transplant PHT and 30-day mortality or a long-term survival. Conclusions: In our cohort, PHT dropped very quickly after HTx, and was not associated with acute right heart failure following the surgery. Reversible PTH does not have a negative impact on short- and long-term survival after HTx. 126 Exercise Pulmonary Hypertension-Systemic Sclerosis: Four Distinct Entities R. Saggar1, D. Khanna2, S. Shapiro1, D.E. Furst2, D.J. Ross1, J.A. Belperio1, D.A. Zisman1, P.J. Clements2, N. Chauhan, J.P. Lynch1, S. Weigt1, R. Saggar1 1David Geffen School of Medicine, UCLA, Los Angeles, CA; 2David Geffen School of Medicine, UCLA, Los Angeles, CA Purpose: Define the prevalence and potentially heterogeneous subgroups of systemic sclerosis (SSc)-associated pulmonary hypertension (PH) based on exercise RHC. Methods and Materials: We conducted a retrospective study at a single university medical center among patients with SSc who underwent exercise RHC for dyspnea on exertion. The exercise RHC was performed while the patient was supine and awake using a lower extremity bicycle ergometer. Results: 32 patients were identified with normal resting pulmonary pressures. Mean age 53.9 yrs; 75% female; 62.5% limited/28.2% diffuse/9.3% SSc overlap; mean FVC% predicted of 76.6%, DLCO% predicted of 59.8%.Resting and Exercise hemodynamics: Conclusions: The exercise hemodynamic response in patients with SSc without resting PAH and dyspnea was variable. Four distinct groups were identified during exercise: normal hemodynamics; exercise PH;diastolic dysfunction(DD); diastolic dysfunction with precapillary pulmonary hypertension (DD-PcPH). These have potentially different prognosis and treatment options.