B-Type Natriuretic Peptide in Low-Flow Aortic Stenosis: Relationship to Hemodynamics and Clinical Outcome. Results from the Multicenter TOPAS Study J. Bergler-Klein1, G. Mundigler1, P. Pibarot2, I. Burwash3, C. Fuchs1, J. G. Dumesnil2, C. Blais2, R. Beanlands3, Z. Hachicha2, D. Mohty-Eichahidi2, N. Loho1, F. Rader1, P. Eickhoff1, H. Baumgartner1 1Department of Cardiology, Medical University of Vienna, Austria; 2Laval Hospital/ Quebec Heart Institute, Laval University, Sainte Foy, Quebec, Canada; 3University of Ottawa Heart Institute, Ottawa, Ontario, Canada Background B-type natriuretic peptide (BNP) has been studied in aortic stenosis (AS), but no data have been reported for patients with low-flow/low-gradient AS. Therefore, we studied the relationship of BNP and Nt-BNP with rest and stress hemodynamics as well as clinical outcome in this group. Methods Plasma BNP and Nt-BNP were measured in 72 pts with AS undergoing dobutamine stress echocardiography (DSE). 63 pts had low-flow AS with indexed effective orifice area [EOA] < 0.6 cm/ m, mean gradient [MG] < 40 mmHg and LV ejection fraction [EF] ≤ 0.40 biplane Simpson technique. Nine pts with AS and normal EF served as controls. Pts were classified as truly severe [TS] or pseudo-severe AS [PS] based on their projected EOA at a normal flow rate of 250 mL/s ≤ or > 1.0 cm in DSE, as previously proposed in the TOPAS study. Results BNP and Nt-BNP were markedly elevated in low-flow AS (BNP 991 ± 1115 vs. controls 190 ± 183 pg/mL, p = 0.025; NtBNP 7330 ± 16,261 vs. 193 ± 199 pg/mL), but varied widely. Log BNP was inversely related to EF at rest (r = 0.60; p < 0.0001) and peak stress (r = 0.51; p < 0.0001), as well as to EOA at rest (r = 0.48, p < 0.0001) and peak stress (r = 0.47, p < 0.0001), stroke volume (BNP, r = 0.32, p = 0.012), mean transvalvular flow rate (r = 0.26, p = 0.04) and wall motion score index (r = 0.40, p = 0.001). Similar findings were observed for Nt-BNP. BNP was significantly higher in 25 TS compared to 38 PS pts (1162 ± 1229 vs. 680 ± 866 pg/mL, p = 0.008). Similarly, BNP was higher in 23 vs. 40 pts with a peak stress EOA ≤ or > 1.0 cm (1466 ± 1448 vs. 530 ± 467 pg/mL, p < 0.001). In the subgroup of 24 patients who underwent aortic valve replacement, BNP was higher in 6 pts who died postoperatively compared to 18 pts surviving valve replacement (1975 ± 2261 vs. 815 ± 492 pg/mL, p < 0.05). In the total cohort, cumulative 1-year survival of pts with BNP ≥ 550 pg/mL was significantly lower than of pts with BNP < 550 (51 ± 11 % vs. 92 ± 5 %, p = 0.04). Conclusion In pts with low-flow AS, BNP and Nt-BNP are markedly elevated and related to EF and EOA at rest and peak DSE. BNP is significantly higher in truly severe compared to pseudo-severe AS. BNP predicts poor postoperative outcome in the subset of patients undergoing valve replacement. Overall one-year survival is poor in pts with BNP ≥ 550, but reasonable in pts with BNP < 550 pg/mL. Exercise-Induced Pulmonary Hypertension in Patients after Successful Pulmonary Endarterectomy D. Bonderman, R. Hitsch, A. Martischnig, N. Skoro-Sajer, M. Kneußl, W. Klepetko, I. M. Lang Department of Internal Medicine II, Medical University of Vienna Background Pulmonary endarterectomy (PEA) provides potential cure for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Successfully operated patients have been shown to normalize exercise capacity and hemodynamic parameters in long-term studies. Abstracts in alphabetical order based on first authors’ last names. Methods To investigate whether pulmonary hypertension can be provoked by exercise, we studied patients at least one year after successful PEA with documented (near) normalization of exercise capacity and hemodynamics. Patients (n = 13) and age-matched nonpulmonary hypertensive controls (n = 14) underwent echocardiography at submaximal treadmill exercise.s in alphabetical order based on first authors’ last names. Methods To investigate whether pulmonary hypertension can be provoked by exercise, we studied patients at least one year after successful PEA with documented (near) normalization of exercise capacity and hemodynamics. Patients (n = 13) and age-matched nonpulmonary hypertensive controls (n = 14) underwent echocardiography at submaximal treadmill exercise. Results Resting mean pulmonary arterial pressure was 25 ± 9 mmHg, mean pulmonary vascular resistance was 291 ± 148 dynes × s × cm, mixed venous saturation was 71 ± 5 % and mean cardiac output was 5.2 ± 1.1 l/min at 63 ± 31 (range 16–120) months after PEA. There was no difference in age (61 ± 10 vs. 57 ± 13 years, p = 0.5) or 6-minute walking distance (489 ± 114 vs. 456 ± 45 meters, p = 0.32) between patients and controls. While the difference in resting systolic pulmonary arterial pressures (sPAP) reached only borderline significance (41 ± 18 vs. 30 ± 6 mmHg, p = 0.05), there was a significant difference in exercise-sPAP (71 ± 23 vs. 46 ± 11 mmHg, p = 0.001), resting pulmonic valve acceleration time (102 ± 24 vs. 132 ± 17 ms, p = 0.0008) and serum BNP levels (207 ± 134 vs. 70 ± 77 pg/ml, p = 0.007). Conclusions Patients with normal exercise capacity and resting hemodynamics after PEA demonstrate significant pulmonary hypertension at exercise. There is a need for studies investigating whether this patient population does additionally benefit from vasodilator therapies. Bacterial Infection is a Mechanism Underlying a Failure of Thrombus Resolution in Chronic Thromboembolic Pulmonary Hypertension D. Bonderman1, B. Redwan1, J. Jakowitsch1, H. Bergmeister2, H. Panzenböck1, M. K. Renner1, W. Klepetko3, U. Losert3, A. Georgopolos4 1Department of Internal Medicine II; 2Institute of Biomedical Research; 3Department of Cardiothoracic Surgery, Division of Cardiology; 4Department of Internal Medicine I, Medical University of Vienna Background Chronic thromboembolic pulmonary hypertension (CTEPH) results from single or recurrent pulmonary thromboemboli arising from sites of venous thrombosis. In patients with CTEPH, thromboemboli do not resolve but form endothelialized, fibrotic obstructions of the pulmonary vascular bed. Mechanisms underlying thrombus organisation are poorly understood. Because of the observation that infected intravenous leads enhance the likelihood of CTEPH, we tested the hypothesis that bacterial infection causes a failure of thrombus resolution. Methods Human thromboendarterectomy specimens were sterilly collected during surgery and analyzed with a bacterial 16S ribosomal DNA screening protocol. In a next step, a mouse model of venous thrombus formation was employed to investigate thrombus resolution in the absence and presence of low doses of staphylococcus aureus (0.15 ml of 10/ml injected as a single bolus into the tail vein). On days 1, 3, 7, 14 and 28 after thrombus induction, animals were sacrificed, thrombi were harvested, fixed and embedded in paraffin. Results 520 bp PCR products were obtained in 16 of 25 CTEPH thrombi, but in only 4 specimens derived from patients with acute pulmonary embolism. Cross-sectional area analysis demonstrated that thrombi from infected animals were larger than control thrombi (day 7: median cross-sectional area (CSA) 0.431 vs. 0.279 mm; day 28: median CSA 0.128 vs. 0.018 mm, n = 8, p < 0.05). Volumetry confirmed significantly larger thrombus volumes on days 3 and 28 (day 3: median thrombus volume 1.798 vs. 1.441 mm3; day 28 median thrombus volume 0.427 vs. 0.056 mm3, n = 8, p < 0.05). Realtime PCR demonstrated increasing expression of connective tissue growth factor (CTGF) in the thrombi over the observation period, contrasting the decline of CTGF expression in controls. For personal use only. Not to be reproduced without permission of Krause & Pachernegg GmbH. 366 J KARDIOL 2006; 13 (11–12) Cardiology 2006 – Abstracts Discussion The data demonstrate that infection with staphylococcus aureus enhances thrombus formation and persistence. CTGF expression analysis suggests that abnormal thrombus organization occurs after bacterial infection. Bosentan for the Treatment of Chronic Thromboembolic Pulmonary Hypertension – One-Year Experience D. Bonderman, N. Skoro-Sajer, M. Kneußl, W. Klepetko, I. Lang Department of Internal Medicine II, Medical University of Vienna Background Bosentan, an oral endothelin ETA/ETB-receptor antagonist, is effective in the short-term treatment of inoperable chronic thromboembolic pulmonary arterial hypertension (CTEPH). We investigated hemodynamics, safety and efficacy of bosentan therapy at one year of therapy in 21 patients (13 /8 , mean age 71 ± 12 years) who were treated off-label over 16 ± 6 months. Results After one year of treatment, NYHA functional class had improved by one class in 14 patients. Mean six-minute walking distances increased from 299 ± 131 m at baseline to 387 ± 121 m (p = 0.04). In parallel, proBNP decreased from 3365 ± 2923 pg/ml to 1579 ± 2103 pg/ml (p = 0.02). Overall, mean pulmonary arterial pressure (mPAP) decreased from 48 ± 10 to 43 ± 12 mmHg (p = 0.17), pulmonary vascular resistance (PVR) changed from 653 ± 247 to 468 ± 205 dynes × s × cm (p = 0.04). If hemodynamic nonresponders to therapy were excluded (n = 5), mPAP decreased from 50 ± 10 to 42 ± 11 mmHg (p = 0.17), and PVR changed from 757 ± 232 to 420 ± 137 dynes × s × cm (p = 0.015). Neither AST (25 ± 2 vs. 25 ± 2 U/l, p = 0.25) nor ALT (23 ± 12 vs. 24 ± 9 U/l, p = 0.57) changed significantly. Two deaths occurred from causes unrelated to pulmonary hypertension. Conclusions Our study suggests a beneficial long-term effect of the oral dual endothelin receptor antagonist, bosentan, in patients with inoperable CTEPH. Non-responders to bosentan therapy must be further characterized. Decreased Cardiac Remodeling after Combined (Intramyocardial and Intracoronary) Autologous Stem Cell Treatment in Chronic Heart Failure S. Charwat, M. Gyöngyösi, R. Jacob, G. Beran, I. Lang, M. Dettke, S. Graf, N. Nyolczas, H. Sochor, D. Glogar Department of