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396: Late Rapidly Progressive Cardiac Allograft Vasculopathy Is Associated with Poor Outcome
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Abstracts
The Journal of Heart and Lung Transplantation February 2009
394 Dynamics of Pleural Effusions in the Presence of EverolimusBased Immunosuppression in De Novo Cardiac Transplant Recipients H. Ross1, H. Lehmkuhl, S.-S. Wang, M. Vigano, A. Zuckermann, S. Varnous, M. Frigerio, G. Laufer, L. Potena, A. Keogh, U. Livi 1 University Health Network, Toronto, ON, Canada; 2Deutsches Herzzentrum Berlin, Berlin, Germany; 3National Taiwan University Hospital, Taipei, Taiwan; 4Policlinico S. Matteo, IRCCS ¨r Universita degli Studi di Pavia, Pavia, Italy; 5Univ.-Klinik fu Chirurgie, Vienna, Austria; 6Ho ˆ pital La Pitie´ Salpe´trie`re, Paris, France; 7Ospedale Niguarda Ca’Granda, Milan, Italy; 8Univ.Klinik fu ¨ r Chirurgie, Innsbruck, Austria; 9Istituto di Malattie dell’apparato Cardiovascolare, Bologna, Italy; 10St Vincent’s Hospital, Sydney, Australia; 11Az. Ospedaliero-Universitaria S. Maria della Misericordia di Udine, Udine, Italy, Purpose: Proliferation signal inhibitors have been associated with the development of pleural effusions (PLE) following cardiac engraftment. Using data from two recent heart transplantation (Tx) studies, the dynamics of PLE in recipients on everolimus (EVL) vs. MMF were studied. Methods and Materials: Pooled data from 373 patients from two multicenter, randomized studies in de novo heart Tx were analyzed: 1) A2403 study: 6-month, open-label trial comparing renal function in patients treated with EVL (1.5mg/day, trough level 3– 8ng/mL) with reduced-exposure (RD) or standard-exposure (ST) CsA, both with steroids; 2) A2411 study: 12-month, open-label trial of renal function and efficacy comparing EVL (1.5mg/day, trough level 3– 8ng/mL) with RD CsA or MMF (3000mg/day) with ST CsA, both with steroids. 290 patients on EVL were compared to 83 on MMF, analyzing adverse and serious adverse events concerning time of initial occurrence, severity and recurrence rate of spontaneous PLE up to Day 120 post-Tx. Results: Altogether, 50 (17.2%) vs. 11 (13.3%) patients on EVL vs. MMF, respectively, were reported to have PLE post-Tx. Within 15 days after Tx, 32 (64%) vs. 8 (72.7%) of all initial PLE in the presence of EVL vs. MMF occurred.In total, 5 (12%) of the initial PLE in the EVL cohort occurred beyond Day 31 (at Days 37, 62, 68, 70, 115). There were 2 (4%) EVL recipients who experienced severe PLE (on Days 4 and 12), vs. none in the MMF arm. A total of 6 (12%) EVL-treatedrecipients had a recurrence vs. 1 (9.1%) MMF-treated recipient. Conclusions: Although incidence and recurrence rate of PLE are higher in the presence of EVL vs. MMF after de novo cardiac Tx, the clinical impact is comparable. Anticipating the possibility of PLE necessitating drainage up to Month 2 post-Tx will improve treatment of recipients on EVL-therapy following heart Tx.
Time post-Tx (d)
EVL n (%)
MMF n (%)
0–7 8–15 16–30 31–60 61–120
21(42) 11(22) 13(26) 1 (2) 4 (8)
6(54.5) 2(18.2) 2(18.2) 0 0
395 Relationship between Peripheral Blood Mononuclear Cell Gene Expression and QTc-Interval after Heart Transplantation in the Absence of Moderate or Severe Acute Cellular Rejection K. Shahzad1, M. Cadeiras1, M.M. John1, F. Latif1, A. Sinha2, S. Memon1, S. Restaino1, C.C. Marboe1, M.C. Deng1 1Columbia University Medical Center, New York, NY; 2Columbia University, New York, NY
Purpose: QTc-interval has been described as a potential noninvasive tool for detection of acute cardiac allograft rejection after heart transplantation (HTx). We have recently shown a correlation between QTc-interval and a gene expression profiling (GEP) test validated to rule out ISHLT grade 3A/2R acute cellular cardiac allograft rejection. We hypothesized that even in the absence of moderate to severe histologically defined cardiac allograft rejection there is a correlation between the GEP test score and QTc-interval. Methods and Materials: 76 patients (76% male, 67% Caucasians) were retrospectively analyzed who underwent GEP testing, at the time of their routine clinical follow up in our Institution between February 1st, 2006 and January 31st, 2007. Data was collected and analyzed using non-parametric tests and Spearman correlation. Samples were sorted by time post-HTx (⬍1year, 2-5 year and ⬎5 year) and correlation was calculated for these time points and overall. Results: The mean age was 42 19.9 years with a median time post-HTx of 1471 (476 - 2634) days at the time of sample collection. 50 samples had grade 0R rejection, 24 had grade 1R rejection and for two samples biopsy data was not available. Overall mean GEP score was 29.8 5.4. GEP score correlated positively with QTc-interval (r⫽ 0.377, p⫽0.001, n⫽63) at all time points post-HTx. Conclusions: We conclude that gene expression profiling of PBMC is a marker of early myocardial physiological changes during the rejection process and may help identify early forms of rejection which precede clinical signs of overt allograft rejection for timely intervention in HTx patients.
396 Late Rapidly Progressive Cardiac Allograft Vasculopathy Is Associated with Poor Outcome E. Shao1, M. Kawano1, K. Kiyosaki1, J. Patel1, M. Kittleson1, J. Moriguchi1, A. Ardehali2, J. Kobashigawa1 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2David Geffen School of Medicine at UCLA, Los Angeles, CA Purpose: Cardiac allograft vasculopathy (CAV) can have varied pathogenesis and clinical presentations. Early CAV (⬍ 2 yrs post transplant) can be mediated by vasculitis while late CAV (⬎2 yrs post transplant) may resemble native atherosclerosis. Some patients abruptly develop CAV even late after transplant. This severe, rapidly progressive disease is termed fulminant CAV. The purpose of the current study was to examine the outcomes of those heart transplant
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
patients (HTx pts) who developed fulminant CAV (ⱖ70% stenosis) within one year of a benign angiogram (⬍30% stenosis). Methods and Materials: Between 1994 and 2008, we identified 42 HTx pts with fulminant CAV ⱖ 2 yrs after heart transplant. Controls were matched 2:1 for age, gender and time from transplant to diagnosis of rapidly progressive CAV in the study group. Survival and non-fatal major adverse cardiac events (NF-MACE, myocardial infarction, heart failure, percutaneous intervention, stroke and new peripheral vascular disease) were assessed. Results: All HTx pts were on triple-drug immunosuppression, 95% were on statins, and none were on proliferation signal inhibitors.1-yr freedom from rejection after transplant (88.1% vs. 91.7%, p⫽NS) and hemodynamic compromise rejection (7.1% vs. 0%, p⫽NS) were comparable in the fulminant CAV and control groups. Mean time to fulminant CAV was 4.3 yrs from transplant (range 2-10 yrs). Outcomes were worse in patients with fulminant CAV compared with controls, including 1-yr survival from the time of diagnosis of fulminant CAV (83.3% vs. 97.6%; P⫽0.003), 5-yr survival (64.3% vs. 83.3%; P⫽0.009), and freedom from NF-MACE (54.8% vs. 91.7%, P⬍0.001). The major causes of death in patients with fulminant CAV was cardiac(n⫽6) and rejection (n⫽4). Conclusions: Late (ⱖ2 yrs after transplant), rapidly progressive angiographic CAV is a marker for poor outcome. Altered immunosuppression or retransplantation should be considered in these patients to improve morbidity and mortality. 397 REVEAL Registry: Pediatric IPAH Versus Pediatric Pulmonary Vascular Disease Associated with Congenital Heart Disease R.J. Barst1, D. Ivy2, D.B. Badesch3, R.L. Benza4, C.G. Elliott5, H.W. Farber6, A.E. Frost7, A. Krichman8, T.G. Liou9, G.E. Raskob10, P. Wason11, K. Feldkircher11, A.J. Foreman12, M.D. McGoon13 1 Columbia University College of Physicians & Surgeons, New York, NY; 2University of Colorado Denver School of Medicine, The Children’s Hospital, Aurora, CO; 3University of Colorado Health Sciences Center, Aurora, CO; 4Allegheny General Hospital, Pittsburgh, PA; 5Intermountain Medical Center, Murray, UT; 6 Boston University School of Medicine, Boston, MA; 7Baylor College of Medicine, Houston, TX; 8Duke University Medical Center, Durham, NC; 9University of Utah, Salt Lake City, UT; 10 University of Oklahoma Health Sciences Center, Oklahoma City, OK; 11Actelion Pharmaceuticals US, Inc., South San Francisco, CA, 12 ICON Clinical Research, San Francisco, CA; 13Mayo Clinic, Rochester, MN Purpose: The Registry to EValuate Early And Long-term PAH Disease Management (REVEAL), a multicenter, observational, U.S. study, is designed to provide information about demographics, clinical course and management of patients diagnosed with pulmonary arterial hypertension (PAH). Two PAH groups are idiopathic PAH (IPAH) and PAH associated with congenital heart disease (PAH-CHD). Methods and Materials: All consenting PAH patients are being enrolled at ⬃50 sites in the US (25 sites are providing pediatric patients defined as ⱖ 3 months of age at time of diagnostic right heart catheterization). Enrollment data include: clinical and treatment history, physical examination, and disease severity assessment. Results: Of 2977 patients enrolled in the registry between March 2006 and September 2007, 72 patients with CHD and 99 patients with IPAH have childhood-onset PAH (chPAH, age at diagnosis ⱕ18 years). The mean (SD) age at PAH diagnosis was 6.4 (5.8) years for PAH-CHD vs 8.1 (5.9) years for IPAH (p⫽0.071). chPAH-CHD had similar functional class (FC) at PAH diagnosis compared with chIPAH (CHD: FC I, 3%; FC II, 56%; FC III, 31%; and FC IV, 11% vs IPAH: FC I, 7%; FC II, 40%; FC III, 46%; and FC IV, 8% (p⫽0.29). Hemodynamics were also similar for the two pediatric populations at diagnosis. However,
Abstracts
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the time from PAH diagnosis to the start of PAH treatment was greater for PAH-CHD (mean, 75 [106] mos; median, 13 mos) than for IPAH (mean, 20 [46] mos; median, 1 mo, p⬍0.001). Finally, both groups of patients were equally likely to be treated with endothelin receptor antagonists (CHD, 43%; IPAH, 47%, p⫽0.61). However, the use of phosphodiesterase 5 inhibitors (PDE-5 I) and prostacyclin (PGI2) analogs was less for PAH-CHD than for IPAH (PDE-5 I, 43% vs 63%, respectively, p⫽0.012; PGI2 analogs, 27% vs 51%, respectively, p⫽0.002). Conclusions: Patients with chPAH-CHD and chIPAH have similar hemodynamics and FC at PAH diagnosis. However, patients with chPAH-CHD start treatment significantly later after PAH diagnosis than patients with chIPAH. 398 Plasma Matrix Metalloproteinase Levels and Disease Severity in Pulmonary Arterial Hypertension K. Jasti, S. Bhashyam, C. Melegari, D. Vido, L. Machen, R. Benza, S. Murali Gerald McGinnis Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA Purpose: Plasma levels of matrix metalloproteinase (MMP) - 2, MMP9 and tissue inhibitor of metalloproteinase (TIMP-1) are increased in pulmonary arterial hypertension (PAH) patients (pts). However the prognostic utility of these biomarkers is uncertain. The objective of this study was to assess if plasma MMP-2, 9 and TIMP-1 levels can discriminate disease severity in PAH pts. Methods and Materials: 29 pts with PAH (Idiopathic, n⫽18, Scleroderma, n⫽7, congenital shunt, n⫽4) had baseline plasma MMP-2, 9 and TIMP-1 levels, concurrent assessment of clinical data, hemodynamics, NYHA class, 6 minute walk distance (6MWD) and an echocardiogram (ECHO). Pts were classified into a high risk group (n⫽ 9; 6MWD ⬍ 300 meters, NYHA class III/IV, severe right ventricular (RV) systolic dysfunction on ECHO, right atrial pressure ⱖ 15 mm Hg and cardiac index ⬍ 2.0 lit/min/m2) or a low risk group (n⫽ 20; 6MWD ⬎300 meters, NYHA classs II, mild-moderate RV systolic dysfunction, right atrial pressure ⬍ 15 mm Hg, cardiac index ⬎ 2.0 l/min/m2) Group comparisons were done using one-way ANOVA. Results: High risk PAH pts had increased plasma MMP-2 levels (282⫾ 73 vs. 229 ⫾ 66 ng/ml; p⫽0.07) compared to low risk pts. Plasma MMP-9, and TIMP-1 levels in the 2 groups were not statistically different. Plasma MMP-2 levels were also increased (322⫾107 vs. 239⫾76 ng/ml; p⫽0.007) among pts who died (n⫽4) during the subsequent 1 year of follow-up, compared to the group that survived (n⫽25). Conclusions: These preliminary results demonstrate that plasma MMP-2 level in PAH pts correlates with disease severity. Whether this biomarker can reliably predict prognosis in PAH pts merits further investigation. 399 Endothelin-1 (ET-1) across the Lung Circulation in Patients with Pulmonary Arterial Hypertension and Influence of Epoprostenol Infusion N. Selimovic1, C.-H. Bergh1, B. Andersson1, E. Sakiniene2, H. Carlsten2, B. Rundqvist1 1Sahlgrenska University Hospital, Gothenburg, Sweden; 2Sahlgrenska University Hospital, Gothenburg, Sweden Purpose: To assess the transpulmonary gradient of ET-1 in patients with pulmonary arterial hypertension (PAH) and controls and to examine the acute effect of epoprostenol on the transplumonary ET-1 gradient.
Abstracts
The Journal of Heart and Lung Transplantation February 2009
394 Dynamics of Pleural Effusions in the Presence of EverolimusBased Immunosuppression in De Novo Cardiac Transplant Recipients H. Ross1, H. Lehmkuhl, S.-S. Wang, M. Vigano, A. Zuckermann, S. Varnous, M. Frigerio, G. Laufer, L. Potena, A. Keogh, U. Livi 1 University Health Network, Toronto, ON, Canada; 2Deutsches Herzzentrum Berlin, Berlin, Germany; 3National Taiwan University Hospital, Taipei, Taiwan; 4Policlinico S. Matteo, IRCCS ¨r Universita degli Studi di Pavia, Pavia, Italy; 5Univ.-Klinik fu Chirurgie, Vienna, Austria; 6Ho ˆ pital La Pitie´ Salpe´trie`re, Paris, France; 7Ospedale Niguarda Ca’Granda, Milan, Italy; 8Univ.Klinik fu ¨ r Chirurgie, Innsbruck, Austria; 9Istituto di Malattie dell’apparato Cardiovascolare, Bologna, Italy; 10St Vincent’s Hospital, Sydney, Australia; 11Az. Ospedaliero-Universitaria S. Maria della Misericordia di Udine, Udine, Italy, Purpose: Proliferation signal inhibitors have been associated with the development of pleural effusions (PLE) following cardiac engraftment. Using data from two recent heart transplantation (Tx) studies, the dynamics of PLE in recipients on everolimus (EVL) vs. MMF were studied. Methods and Materials: Pooled data from 373 patients from two multicenter, randomized studies in de novo heart Tx were analyzed: 1) A2403 study: 6-month, open-label trial comparing renal function in patients treated with EVL (1.5mg/day, trough level 3– 8ng/mL) with reduced-exposure (RD) or standard-exposure (ST) CsA, both with steroids; 2) A2411 study: 12-month, open-label trial of renal function and efficacy comparing EVL (1.5mg/day, trough level 3– 8ng/mL) with RD CsA or MMF (3000mg/day) with ST CsA, both with steroids. 290 patients on EVL were compared to 83 on MMF, analyzing adverse and serious adverse events concerning time of initial occurrence, severity and recurrence rate of spontaneous PLE up to Day 120 post-Tx. Results: Altogether, 50 (17.2%) vs. 11 (13.3%) patients on EVL vs. MMF, respectively, were reported to have PLE post-Tx. Within 15 days after Tx, 32 (64%) vs. 8 (72.7%) of all initial PLE in the presence of EVL vs. MMF occurred.In total, 5 (12%) of the initial PLE in the EVL cohort occurred beyond Day 31 (at Days 37, 62, 68, 70, 115). There were 2 (4%) EVL recipients who experienced severe PLE (on Days 4 and 12), vs. none in the MMF arm. A total of 6 (12%) EVL-treatedrecipients had a recurrence vs. 1 (9.1%) MMF-treated recipient. Conclusions: Although incidence and recurrence rate of PLE are higher in the presence of EVL vs. MMF after de novo cardiac Tx, the clinical impact is comparable. Anticipating the possibility of PLE necessitating drainage up to Month 2 post-Tx will improve treatment of recipients on EVL-therapy following heart Tx.
Time post-Tx (d)
EVL n (%)
MMF n (%)
0–7 8–15 16–30 31–60 61–120
21(42) 11(22) 13(26) 1 (2) 4 (8)
6(54.5) 2(18.2) 2(18.2) 0 0
395 Relationship between Peripheral Blood Mononuclear Cell Gene Expression and QTc-Interval after Heart Transplantation in the Absence of Moderate or Severe Acute Cellular Rejection K. Shahzad1, M. Cadeiras1, M.M. John1, F. Latif1, A. Sinha2, S. Memon1, S. Restaino1, C.C. Marboe1, M.C. Deng1 1Columbia University Medical Center, New York, NY; 2Columbia University, New York, NY
Purpose: QTc-interval has been described as a potential noninvasive tool for detection of acute cardiac allograft rejection after heart transplantation (HTx). We have recently shown a correlation between QTc-interval and a gene expression profiling (GEP) test validated to rule out ISHLT grade 3A/2R acute cellular cardiac allograft rejection. We hypothesized that even in the absence of moderate to severe histologically defined cardiac allograft rejection there is a correlation between the GEP test score and QTc-interval. Methods and Materials: 76 patients (76% male, 67% Caucasians) were retrospectively analyzed who underwent GEP testing, at the time of their routine clinical follow up in our Institution between February 1st, 2006 and January 31st, 2007. Data was collected and analyzed using non-parametric tests and Spearman correlation. Samples were sorted by time post-HTx (⬍1year, 2-5 year and ⬎5 year) and correlation was calculated for these time points and overall. Results: The mean age was 42 19.9 years with a median time post-HTx of 1471 (476 - 2634) days at the time of sample collection. 50 samples had grade 0R rejection, 24 had grade 1R rejection and for two samples biopsy data was not available. Overall mean GEP score was 29.8 5.4. GEP score correlated positively with QTc-interval (r⫽ 0.377, p⫽0.001, n⫽63) at all time points post-HTx. Conclusions: We conclude that gene expression profiling of PBMC is a marker of early myocardial physiological changes during the rejection process and may help identify early forms of rejection which precede clinical signs of overt allograft rejection for timely intervention in HTx patients.
396 Late Rapidly Progressive Cardiac Allograft Vasculopathy Is Associated with Poor Outcome E. Shao1, M. Kawano1, K. Kiyosaki1, J. Patel1, M. Kittleson1, J. Moriguchi1, A. Ardehali2, J. Kobashigawa1 1David Geffen School of Medicine at UCLA, Los Angeles, CA; 2David Geffen School of Medicine at UCLA, Los Angeles, CA Purpose: Cardiac allograft vasculopathy (CAV) can have varied pathogenesis and clinical presentations. Early CAV (⬍ 2 yrs post transplant) can be mediated by vasculitis while late CAV (⬎2 yrs post transplant) may resemble native atherosclerosis. Some patients abruptly develop CAV even late after transplant. This severe, rapidly progressive disease is termed fulminant CAV. The purpose of the current study was to examine the outcomes of those heart transplant
The Journal of Heart and Lung Transplantation Volume 28, Number 2S
patients (HTx pts) who developed fulminant CAV (ⱖ70% stenosis) within one year of a benign angiogram (⬍30% stenosis). Methods and Materials: Between 1994 and 2008, we identified 42 HTx pts with fulminant CAV ⱖ 2 yrs after heart transplant. Controls were matched 2:1 for age, gender and time from transplant to diagnosis of rapidly progressive CAV in the study group. Survival and non-fatal major adverse cardiac events (NF-MACE, myocardial infarction, heart failure, percutaneous intervention, stroke and new peripheral vascular disease) were assessed. Results: All HTx pts were on triple-drug immunosuppression, 95% were on statins, and none were on proliferation signal inhibitors.1-yr freedom from rejection after transplant (88.1% vs. 91.7%, p⫽NS) and hemodynamic compromise rejection (7.1% vs. 0%, p⫽NS) were comparable in the fulminant CAV and control groups. Mean time to fulminant CAV was 4.3 yrs from transplant (range 2-10 yrs). Outcomes were worse in patients with fulminant CAV compared with controls, including 1-yr survival from the time of diagnosis of fulminant CAV (83.3% vs. 97.6%; P⫽0.003), 5-yr survival (64.3% vs. 83.3%; P⫽0.009), and freedom from NF-MACE (54.8% vs. 91.7%, P⬍0.001). The major causes of death in patients with fulminant CAV was cardiac(n⫽6) and rejection (n⫽4). Conclusions: Late (ⱖ2 yrs after transplant), rapidly progressive angiographic CAV is a marker for poor outcome. Altered immunosuppression or retransplantation should be considered in these patients to improve morbidity and mortality. 397 REVEAL Registry: Pediatric IPAH Versus Pediatric Pulmonary Vascular Disease Associated with Congenital Heart Disease R.J. Barst1, D. Ivy2, D.B. Badesch3, R.L. Benza4, C.G. Elliott5, H.W. Farber6, A.E. Frost7, A. Krichman8, T.G. Liou9, G.E. Raskob10, P. Wason11, K. Feldkircher11, A.J. Foreman12, M.D. McGoon13 1 Columbia University College of Physicians & Surgeons, New York, NY; 2University of Colorado Denver School of Medicine, The Children’s Hospital, Aurora, CO; 3University of Colorado Health Sciences Center, Aurora, CO; 4Allegheny General Hospital, Pittsburgh, PA; 5Intermountain Medical Center, Murray, UT; 6 Boston University School of Medicine, Boston, MA; 7Baylor College of Medicine, Houston, TX; 8Duke University Medical Center, Durham, NC; 9University of Utah, Salt Lake City, UT; 10 University of Oklahoma Health Sciences Center, Oklahoma City, OK; 11Actelion Pharmaceuticals US, Inc., South San Francisco, CA, 12 ICON Clinical Research, San Francisco, CA; 13Mayo Clinic, Rochester, MN Purpose: The Registry to EValuate Early And Long-term PAH Disease Management (REVEAL), a multicenter, observational, U.S. study, is designed to provide information about demographics, clinical course and management of patients diagnosed with pulmonary arterial hypertension (PAH). Two PAH groups are idiopathic PAH (IPAH) and PAH associated with congenital heart disease (PAH-CHD). Methods and Materials: All consenting PAH patients are being enrolled at ⬃50 sites in the US (25 sites are providing pediatric patients defined as ⱖ 3 months of age at time of diagnostic right heart catheterization). Enrollment data include: clinical and treatment history, physical examination, and disease severity assessment. Results: Of 2977 patients enrolled in the registry between March 2006 and September 2007, 72 patients with CHD and 99 patients with IPAH have childhood-onset PAH (chPAH, age at diagnosis ⱕ18 years). The mean (SD) age at PAH diagnosis was 6.4 (5.8) years for PAH-CHD vs 8.1 (5.9) years for IPAH (p⫽0.071). chPAH-CHD had similar functional class (FC) at PAH diagnosis compared with chIPAH (CHD: FC I, 3%; FC II, 56%; FC III, 31%; and FC IV, 11% vs IPAH: FC I, 7%; FC II, 40%; FC III, 46%; and FC IV, 8% (p⫽0.29). Hemodynamics were also similar for the two pediatric populations at diagnosis. However,
Abstracts
S203
the time from PAH diagnosis to the start of PAH treatment was greater for PAH-CHD (mean, 75 [106] mos; median, 13 mos) than for IPAH (mean, 20 [46] mos; median, 1 mo, p⬍0.001). Finally, both groups of patients were equally likely to be treated with endothelin receptor antagonists (CHD, 43%; IPAH, 47%, p⫽0.61). However, the use of phosphodiesterase 5 inhibitors (PDE-5 I) and prostacyclin (PGI2) analogs was less for PAH-CHD than for IPAH (PDE-5 I, 43% vs 63%, respectively, p⫽0.012; PGI2 analogs, 27% vs 51%, respectively, p⫽0.002). Conclusions: Patients with chPAH-CHD and chIPAH have similar hemodynamics and FC at PAH diagnosis. However, patients with chPAH-CHD start treatment significantly later after PAH diagnosis than patients with chIPAH. 398 Plasma Matrix Metalloproteinase Levels and Disease Severity in Pulmonary Arterial Hypertension K. Jasti, S. Bhashyam, C. Melegari, D. Vido, L. Machen, R. Benza, S. Murali Gerald McGinnis Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA Purpose: Plasma levels of matrix metalloproteinase (MMP) - 2, MMP9 and tissue inhibitor of metalloproteinase (TIMP-1) are increased in pulmonary arterial hypertension (PAH) patients (pts). However the prognostic utility of these biomarkers is uncertain. The objective of this study was to assess if plasma MMP-2, 9 and TIMP-1 levels can discriminate disease severity in PAH pts. Methods and Materials: 29 pts with PAH (Idiopathic, n⫽18, Scleroderma, n⫽7, congenital shunt, n⫽4) had baseline plasma MMP-2, 9 and TIMP-1 levels, concurrent assessment of clinical data, hemodynamics, NYHA class, 6 minute walk distance (6MWD) and an echocardiogram (ECHO). Pts were classified into a high risk group (n⫽ 9; 6MWD ⬍ 300 meters, NYHA class III/IV, severe right ventricular (RV) systolic dysfunction on ECHO, right atrial pressure ⱖ 15 mm Hg and cardiac index ⬍ 2.0 lit/min/m2) or a low risk group (n⫽ 20; 6MWD ⬎300 meters, NYHA classs II, mild-moderate RV systolic dysfunction, right atrial pressure ⬍ 15 mm Hg, cardiac index ⬎ 2.0 l/min/m2) Group comparisons were done using one-way ANOVA. Results: High risk PAH pts had increased plasma MMP-2 levels (282⫾ 73 vs. 229 ⫾ 66 ng/ml; p⫽0.07) compared to low risk pts. Plasma MMP-9, and TIMP-1 levels in the 2 groups were not statistically different. Plasma MMP-2 levels were also increased (322⫾107 vs. 239⫾76 ng/ml; p⫽0.007) among pts who died (n⫽4) during the subsequent 1 year of follow-up, compared to the group that survived (n⫽25). Conclusions: These preliminary results demonstrate that plasma MMP-2 level in PAH pts correlates with disease severity. Whether this biomarker can reliably predict prognosis in PAH pts merits further investigation. 399 Endothelin-1 (ET-1) across the Lung Circulation in Patients with Pulmonary Arterial Hypertension and Influence of Epoprostenol Infusion N. Selimovic1, C.-H. Bergh1, B. Andersson1, E. Sakiniene2, H. Carlsten2, B. Rundqvist1 1Sahlgrenska University Hospital, Gothenburg, Sweden; 2Sahlgrenska University Hospital, Gothenburg, Sweden Purpose: To assess the transpulmonary gradient of ET-1 in patients with pulmonary arterial hypertension (PAH) and controls and to examine the acute effect of epoprostenol on the transplumonary ET-1 gradient.