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229: Clinical Benefits of Pharmacological Therapy in Exercise Induced Pulmonary Arterial Hypertension
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Abstracts
molecules activates pathways that are responsible for the regulation of PASMC proliferation. Demethylation of SOD2 may represent a novel approach for PAH therapy.
228 REVEAL Registry: Comparison of Patients with ChildhoodOnset and Adult-Onset Idiopathic Pulmonary Arterial Hypertension 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 meet the need for current and reliable information about demographics, clinical course and management of patients with pulmonary arterial hypertension (PAH). Methods and Materials: All consenting PAH patients are being enrolled at ⬃50 sites in the US (25 sites are providing pediatric patients defined as being ⱖ3 mos 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, 99 patients have childhood-onset idiopathic PAH (chIPAH, age at diagnosis ⱕ18 years) and 1295 patients have adult-onset IPAH (adIPAH, age at diagnosis ⱖ19 years). AdIPAH was associated with worse functional class (FC) at diagnosis compared with chIPAH: adult: FC I, 3%; FC II, 21%; FC III, 61%; and FC IV, 15% vs pediatric: FC I, 7%; FC II, 40%; FC III, 46%; and FC IV, 8% (p⬍0.001 adult vs pediatric). AdIPAH was also associated with worse hemodynamics at PAH diagnosis compared with chIPAH: mRAP 10.2 mmHg vs 6.6 mmHg, respectively (p⬍0.001); and CI 2.2 L/min/m2 vs 3.6 L/min/m2, respectively (p⬍0.001). AdIPAH was also associated with an earlier start of PAH treatment after diagnosis compared with chIPAH: mean time from diagnosis, 4 mos vs 20 mos, respectively (p⬍0.001). Finally, patients with adIPAH were less likely to be treated with phosphodiesterase-5 inhibitors compared with patients with chIPAH (48% vs 63%, respectively, p⫽0.005); however, the use of endothelin receptor antagonists and prostacyclin analogs was similar for both groups. Conclusions: Patients with adIPAH have worse hemodynamics and FC at diagnosis compared with patients with chIPAH. However, patients with adIPAH start treatment significantly earlier after diagnosis than patients with chIPAH.
229 Clinical Benefits of Pharmacological Therapy in Exercise Induced Pulmonary Arterial Hypertension M.H. Park, G.V. Ramani, W.J. Kop, P.A. Uber, M.R. Mehra University of Maryland, Baltimore, MD
The Journal of Heart and Lung Transplantation February 2009
Purpose: The pathophysiology and clinical significance of exerciseinduced pulmonary arterial hypertension (ePAH) remains contentious. Although screening for ePAH in selective indications (scleroderma) has been reported, little is known about its clinical implication in other disease forms; moreover, the response to treatment remains uncertain. Methods and Materials: Patients with exertional dyspnea were evaluated for PAH with a supine bicycle exercise right heart catheterization protocol (symptom limited or 85% of maximal HR) if they met the following criteria: normal resting echocardiographic and hemodynamic findings, no overt explanation for symptoms and ⬍80% predicted 6MWD or desaturation with activity. Exercise-induced PAH was defined as mPAPⱖ30 mmHg and PCWP ⱕ18 mmHg at peak exercise. Results: Ten patients were enrolled [55⫾10 years old, 7 women; FC III-IV; scleroderma (3), h/o pulmonary embolus (2), sarcoid (1), idiopathic (4)]. The LVEF was 0.62⫾0.04 and PASP 29⫾8mmHg. Exercise hemodynamics showed elevated PAP and depressed CI (sPAP 58⫾11, mPAP 37⫾5, PCWP 9⫾3 mmHg, CI 1.9⫾0.5 L/min/ m2). All patients were initially treated with bosentan (n⫽3 intolerant to bosentan switched to sildenafil). 6MWD increased significantly from pre-treatment levels to initial follow-up (median 189 days; range 62-355) with greater gain in the long-term (⬎1 year; median 416 days). These beneficial effects on exercise were accompanied by FC improvement (70% improved by at least 1 FC p ⬍ 0.05). Conclusions: These findings suggest that exercise induced PAH is an unique subset of the disease continuum that characterizes PAH. Importantly, we have demonstrated that this clinical entity is responsive to traditionally directed pharmacological therapy designed for PAH.
230 Pulmonary Hemodynamics in Patients with Obstructive Sleep Apnea Syndrome: Results in Patients Undergoing Right Heart Catheterization O.A. Minai, B. Ricaurte, R. Kaw, J.K. Stoller Cleveland Clinic, Cleveland, OH Purpose: Correlates and consequences of pulmonary hypertension (PH) associated with obstructive sleep apnea (OSA) are poorly understood. This study addresses the prevalence, nature, and prognosis of PH complicating OSA. Methods and Materials: Heart and Sleep Center databases between January 2000 and December 2005 were searched to identify patients who had undergone right-heart catheterization (RHC) within 6 months of an overnight polysomnography (PSG) showing obstructive sleep apnea. Results: 83 patients with complete PSG and RHC data were analyzed. No significant differences were observed between the PH and non-PH groups regarding age or AHI. Correlates of PH were elevated RVSP, BMI (p⫽0.026), female gender (p⫽0.01), nocturnal desaturation, and FVC ⬍70% by univariate analysis and female gender, age ⬍49 years,
Abstracts
molecules activates pathways that are responsible for the regulation of PASMC proliferation. Demethylation of SOD2 may represent a novel approach for PAH therapy.
228 REVEAL Registry: Comparison of Patients with ChildhoodOnset and Adult-Onset Idiopathic Pulmonary Arterial Hypertension 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 meet the need for current and reliable information about demographics, clinical course and management of patients with pulmonary arterial hypertension (PAH). Methods and Materials: All consenting PAH patients are being enrolled at ⬃50 sites in the US (25 sites are providing pediatric patients defined as being ⱖ3 mos 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, 99 patients have childhood-onset idiopathic PAH (chIPAH, age at diagnosis ⱕ18 years) and 1295 patients have adult-onset IPAH (adIPAH, age at diagnosis ⱖ19 years). AdIPAH was associated with worse functional class (FC) at diagnosis compared with chIPAH: adult: FC I, 3%; FC II, 21%; FC III, 61%; and FC IV, 15% vs pediatric: FC I, 7%; FC II, 40%; FC III, 46%; and FC IV, 8% (p⬍0.001 adult vs pediatric). AdIPAH was also associated with worse hemodynamics at PAH diagnosis compared with chIPAH: mRAP 10.2 mmHg vs 6.6 mmHg, respectively (p⬍0.001); and CI 2.2 L/min/m2 vs 3.6 L/min/m2, respectively (p⬍0.001). AdIPAH was also associated with an earlier start of PAH treatment after diagnosis compared with chIPAH: mean time from diagnosis, 4 mos vs 20 mos, respectively (p⬍0.001). Finally, patients with adIPAH were less likely to be treated with phosphodiesterase-5 inhibitors compared with patients with chIPAH (48% vs 63%, respectively, p⫽0.005); however, the use of endothelin receptor antagonists and prostacyclin analogs was similar for both groups. Conclusions: Patients with adIPAH have worse hemodynamics and FC at diagnosis compared with patients with chIPAH. However, patients with adIPAH start treatment significantly earlier after diagnosis than patients with chIPAH.
229 Clinical Benefits of Pharmacological Therapy in Exercise Induced Pulmonary Arterial Hypertension M.H. Park, G.V. Ramani, W.J. Kop, P.A. Uber, M.R. Mehra University of Maryland, Baltimore, MD
The Journal of Heart and Lung Transplantation February 2009
Purpose: The pathophysiology and clinical significance of exerciseinduced pulmonary arterial hypertension (ePAH) remains contentious. Although screening for ePAH in selective indications (scleroderma) has been reported, little is known about its clinical implication in other disease forms; moreover, the response to treatment remains uncertain. Methods and Materials: Patients with exertional dyspnea were evaluated for PAH with a supine bicycle exercise right heart catheterization protocol (symptom limited or 85% of maximal HR) if they met the following criteria: normal resting echocardiographic and hemodynamic findings, no overt explanation for symptoms and ⬍80% predicted 6MWD or desaturation with activity. Exercise-induced PAH was defined as mPAPⱖ30 mmHg and PCWP ⱕ18 mmHg at peak exercise. Results: Ten patients were enrolled [55⫾10 years old, 7 women; FC III-IV; scleroderma (3), h/o pulmonary embolus (2), sarcoid (1), idiopathic (4)]. The LVEF was 0.62⫾0.04 and PASP 29⫾8mmHg. Exercise hemodynamics showed elevated PAP and depressed CI (sPAP 58⫾11, mPAP 37⫾5, PCWP 9⫾3 mmHg, CI 1.9⫾0.5 L/min/ m2). All patients were initially treated with bosentan (n⫽3 intolerant to bosentan switched to sildenafil). 6MWD increased significantly from pre-treatment levels to initial follow-up (median 189 days; range 62-355) with greater gain in the long-term (⬎1 year; median 416 days). These beneficial effects on exercise were accompanied by FC improvement (70% improved by at least 1 FC p ⬍ 0.05). Conclusions: These findings suggest that exercise induced PAH is an unique subset of the disease continuum that characterizes PAH. Importantly, we have demonstrated that this clinical entity is responsive to traditionally directed pharmacological therapy designed for PAH.
230 Pulmonary Hemodynamics in Patients with Obstructive Sleep Apnea Syndrome: Results in Patients Undergoing Right Heart Catheterization O.A. Minai, B. Ricaurte, R. Kaw, J.K. Stoller Cleveland Clinic, Cleveland, OH Purpose: Correlates and consequences of pulmonary hypertension (PH) associated with obstructive sleep apnea (OSA) are poorly understood. This study addresses the prevalence, nature, and prognosis of PH complicating OSA. Methods and Materials: Heart and Sleep Center databases between January 2000 and December 2005 were searched to identify patients who had undergone right-heart catheterization (RHC) within 6 months of an overnight polysomnography (PSG) showing obstructive sleep apnea. Results: 83 patients with complete PSG and RHC data were analyzed. No significant differences were observed between the PH and non-PH groups regarding age or AHI. Correlates of PH were elevated RVSP, BMI (p⫽0.026), female gender (p⫽0.01), nocturnal desaturation, and FVC ⬍70% by univariate analysis and female gender, age ⬍49 years,