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Long-term Outcome in Acute Vasodilator Responsive Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
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The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
Conclusion: These data demonstrate significant dynamic exercise based functional differences between PVH vs. PAH. The significant correlation of non-invasive GX indices to the TPG also suggests their clinical potential for quantitative serial tracking of WHO I and II PH therapy.
Table 1. Differences between PAH-WHO I and PH-WHO II
Invasive RHC (rest)
WHO I
PAPm 41.3 +/-13.3 PCWP 14.1+/-6.7 TPG 27.1+/-12.8 RVPs 66.5+/-22.8 Non-invasive GX (rest & exercise) VE slope 41.6+/-13.3 ETCO2 rest 32.4+/-8.0 ETCO2 peak 30.3+/-8.8 GX capacitance peak 240+/-124 (GXCap pk) Shape Multi-parametric 2.0+/-1.6 score
WHO II
Significance Level (t test)
34.7+/-10.4 22.8+/-7.2 11.4+/-7.0 50+/-14.1
p= .03 p< .0001 p< .0001 p< .0006
35.2+/-9.0 37.3+/-6.2 36.1+/-6.7 396+/-172
p= .03 p= .01 p= .005 p= .002
3.0+/-1.9
p= .05
1( 30) Long-term Outcome in Acute Vasodilator Responsive Connective Tissue Disease-Associated Pulmonary Arterial Hypertension E. Brittain , S. Halliday, M. Pugh, A. Hemnes, I. Robbins. Vanderbilt University Medical Center, Nashville, TN. Purpose: Acute response to vasodilator testing at the time of right heart catheterization (RHC) is associated with an excellent prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH). Vasodilator responsiveness (VR) requires a decrease in mean pulmonary artery pressure (mPA) of at least 10mmHg to an absolute value < 40mmHg. We sought to determine the prevalence and prognostic significance of VR in patients with connective tissue disease associated PAH (CTD-PAH). Methods: We analyzed hemodynamic and clinical data in consecutive PAH patients referred for RHC. Vasodilator testing was performed using inhaled nitric oxide (40ppm for 10 minutes). PAH diagnosis was made according to consensus guidelines. Patients with IPAH and CTD-PAH were included in the analysis. Results: One hundred seventeen patients were analyzed (56% IPAH, 44% CTDPAH). Criteria for VR were met in 13 (20%) IPAH patients and 8 (16%) CTDPAH patients. Among VR CTD-PAH patients, 6 had scleroderma and 2 had systemic lupus erythematosis (SLE). There were no clinical or hemodynamic differences in CTD-PAH patients meeting VR criteria and CTD-PAH patients who did not. Six of 8 CTD-PAH VR patients were treated with calcium channel blockers (CCB). One patient with SLE had a sustained clinical response to CCB monotherapy. The remaining 5 patients failed to respond clinically as indicated by worsening functional class. Survival among VR CTD-PAH patients was no different from non-vasodilator responsive IPAH and CTD-PAH patients whereas survival was improved in VR IPAH patients (Figure 1; log rank p < 0.001). Conclusion: A small percentage of CTD-PAH patients may demonstrate acute vasoreactivity, however sustained clinical response to CCB monotherapy in CTD-PAH is uncommon. Moreover, VR does not confer survival benefit in CTD-PAH compared to non-responders. These data confirm previous studies that routine acute vasodilator testing may be of little utility in patients with established CTD-PAH.
1( 31) Complete Pulmonary Artery Occlusion from Chronic Thromboembolic Disease: Outcomes Following Pulmonary Thromboendarterectomy Surgery A. Kitcher , V. Pretorius, K. Kerr, P. Fedullo, N.H. Kim, D. Poch, M. Madani, S. Jamieson, W. Auger. Pulmonary and Critical Care Medicine, UCSD, La Jolla, CA. Purpose: Characterize patients with chronic thromboembolic pulmonary hypertension (CTEPH) with complete main pulmonary artery occlusion, and their response to pulmonary thromboendarterectomy (PTE). Methods: Retrospective review of a patient database at a PTE referral center. Two independent reviewers evaluated radiographic data including ventilation/perfusion (V/Q) scans and chest radiographs. Demographic data, operative findings, hemodynamic changes and clinical outcomes were collected. Patients were included if the V/Q scan revealed nonperfusion of an entire lung. Presence of contralateral filling defects on V/Q scan was also noted. Results: Of 603 PTE patients operated between January 2009 and June 2013, 25 had complete main pulmonary artery occlusion; 13 patients had only unilateral disease and 12 had disease in the contralateral lung. Mean age was 41.8 years, 72% were female, and median time elapsed between PE or CTEPH diagnosis and surgery was 17 months. Average pre-operative pulmonary vascular resistance (PVR) was 508 dyne*sec/cm5. Patients with purely unilateral disease had an average pre-operative PVR of 349 dyne*sec/ cm5; 10 of 13 were female (77%). Following surgery, average PVR for all twenty five patients decreased to 229 dyne*sec/cm5. Hospital mortality was 0%. On post-operative V/Q scan, 7 patients (28%) had significant (> 75% estimated) reperfusion of the occluded lung, 10 patients (40%) had partial reperfusion (< 75% estimated), and 8 patients (32%) had minimal or no reperfusion. Seven (87%) reperfusion failure patients were female, and 4 (50%) had contralateral chronic thromboembolic (CTE) disease, compared to 47.1% in patients who reperfused. A median of 24 months had elapsed between CTE diagnosis and surgery, compared to 15 months in patients who reperfused. Three of four patients whose pre-operative chest radiograph showed moderate ipsilateral volume loss failed to reperfuse that lung postoperatively. Conclusion: Patients with main pulmonary artery occlusion from chronic thromboembolic disease appear to be at higher risk for reperfusion failure than what is reported in typical patients following PTE. Available data have been scarce in predicting patients at risk for this outcome. This study suggests that duration of main PA occlusion, female gender, and ipsilateral lung volume loss may be important. 1( 32) Muscularization of Pulmonary Arteries Is Reduced in Female Athymic Rats Exposed to Vascular Endothelial Growth Factor Receptor (VEGF-R) Blockade J. Guihaire ,1 E. Fadel,2 F. Haddad,3 T. Deuse,1 H. Reichenspurner,1 R.C. Robbins,3 S. Schrepfer.1 1Transplant and Stem Cell Immunobiology Lab, University Heart Center Hamburg, Hamburg, Germany; 2Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, University of Paris Sud, Le Plessis Robinson, France; 3Cardiothoracic Surgery, Stanford University, Palo Alto, CA. Purpose: The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share a higher severity of the disease. The influence of estrogens on the development of PH is not well documented. We sought to compare the severity of experimental PH between male and female athymic rats. Methods: PH was induced in 11 male and 11 female athymic rats (SU/M and SU/F, respectively) using the tyrosine kinase inhibitor of VEGF-R I and II, semaxinib (40 mg/kg, single subcutaneous injection). After 28 days, the right ventricular end-diastolic diameter (RVEDD) and tricuspid annular plane systolic excursion (TAPSE) were measured using cardiac echography, and right ventricular-pulmonary arterial (RV-PA) coupling was evaluated by a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and right ventricular (RV) myocardium were performed using respectively elastica von Gieson and hematoxylin-eosin stainings. Results: Four weeks after semaxinib injection, RV end-systolic pressure was higher in SU/M than in SU/F (66.3 ± 8.9 vs. 29.5 ± 13.4 mmHg, P< 0.001). Males developed marked RV enlargement and systolic dysfunction
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
Conclusion: These data demonstrate significant dynamic exercise based functional differences between PVH vs. PAH. The significant correlation of non-invasive GX indices to the TPG also suggests their clinical potential for quantitative serial tracking of WHO I and II PH therapy.
Table 1. Differences between PAH-WHO I and PH-WHO II
Invasive RHC (rest)
WHO I
PAPm 41.3 +/-13.3 PCWP 14.1+/-6.7 TPG 27.1+/-12.8 RVPs 66.5+/-22.8 Non-invasive GX (rest & exercise) VE slope 41.6+/-13.3 ETCO2 rest 32.4+/-8.0 ETCO2 peak 30.3+/-8.8 GX capacitance peak 240+/-124 (GXCap pk) Shape Multi-parametric 2.0+/-1.6 score
WHO II
Significance Level (t test)
34.7+/-10.4 22.8+/-7.2 11.4+/-7.0 50+/-14.1
p= .03 p< .0001 p< .0001 p< .0006
35.2+/-9.0 37.3+/-6.2 36.1+/-6.7 396+/-172
p= .03 p= .01 p= .005 p= .002
3.0+/-1.9
p= .05
1( 30) Long-term Outcome in Acute Vasodilator Responsive Connective Tissue Disease-Associated Pulmonary Arterial Hypertension E. Brittain , S. Halliday, M. Pugh, A. Hemnes, I. Robbins. Vanderbilt University Medical Center, Nashville, TN. Purpose: Acute response to vasodilator testing at the time of right heart catheterization (RHC) is associated with an excellent prognosis in patients with idiopathic pulmonary arterial hypertension (IPAH). Vasodilator responsiveness (VR) requires a decrease in mean pulmonary artery pressure (mPA) of at least 10mmHg to an absolute value < 40mmHg. We sought to determine the prevalence and prognostic significance of VR in patients with connective tissue disease associated PAH (CTD-PAH). Methods: We analyzed hemodynamic and clinical data in consecutive PAH patients referred for RHC. Vasodilator testing was performed using inhaled nitric oxide (40ppm for 10 minutes). PAH diagnosis was made according to consensus guidelines. Patients with IPAH and CTD-PAH were included in the analysis. Results: One hundred seventeen patients were analyzed (56% IPAH, 44% CTDPAH). Criteria for VR were met in 13 (20%) IPAH patients and 8 (16%) CTDPAH patients. Among VR CTD-PAH patients, 6 had scleroderma and 2 had systemic lupus erythematosis (SLE). There were no clinical or hemodynamic differences in CTD-PAH patients meeting VR criteria and CTD-PAH patients who did not. Six of 8 CTD-PAH VR patients were treated with calcium channel blockers (CCB). One patient with SLE had a sustained clinical response to CCB monotherapy. The remaining 5 patients failed to respond clinically as indicated by worsening functional class. Survival among VR CTD-PAH patients was no different from non-vasodilator responsive IPAH and CTD-PAH patients whereas survival was improved in VR IPAH patients (Figure 1; log rank p < 0.001). Conclusion: A small percentage of CTD-PAH patients may demonstrate acute vasoreactivity, however sustained clinical response to CCB monotherapy in CTD-PAH is uncommon. Moreover, VR does not confer survival benefit in CTD-PAH compared to non-responders. These data confirm previous studies that routine acute vasodilator testing may be of little utility in patients with established CTD-PAH.
1( 31) Complete Pulmonary Artery Occlusion from Chronic Thromboembolic Disease: Outcomes Following Pulmonary Thromboendarterectomy Surgery A. Kitcher , V. Pretorius, K. Kerr, P. Fedullo, N.H. Kim, D. Poch, M. Madani, S. Jamieson, W. Auger. Pulmonary and Critical Care Medicine, UCSD, La Jolla, CA. Purpose: Characterize patients with chronic thromboembolic pulmonary hypertension (CTEPH) with complete main pulmonary artery occlusion, and their response to pulmonary thromboendarterectomy (PTE). Methods: Retrospective review of a patient database at a PTE referral center. Two independent reviewers evaluated radiographic data including ventilation/perfusion (V/Q) scans and chest radiographs. Demographic data, operative findings, hemodynamic changes and clinical outcomes were collected. Patients were included if the V/Q scan revealed nonperfusion of an entire lung. Presence of contralateral filling defects on V/Q scan was also noted. Results: Of 603 PTE patients operated between January 2009 and June 2013, 25 had complete main pulmonary artery occlusion; 13 patients had only unilateral disease and 12 had disease in the contralateral lung. Mean age was 41.8 years, 72% were female, and median time elapsed between PE or CTEPH diagnosis and surgery was 17 months. Average pre-operative pulmonary vascular resistance (PVR) was 508 dyne*sec/cm5. Patients with purely unilateral disease had an average pre-operative PVR of 349 dyne*sec/ cm5; 10 of 13 were female (77%). Following surgery, average PVR for all twenty five patients decreased to 229 dyne*sec/cm5. Hospital mortality was 0%. On post-operative V/Q scan, 7 patients (28%) had significant (> 75% estimated) reperfusion of the occluded lung, 10 patients (40%) had partial reperfusion (< 75% estimated), and 8 patients (32%) had minimal or no reperfusion. Seven (87%) reperfusion failure patients were female, and 4 (50%) had contralateral chronic thromboembolic (CTE) disease, compared to 47.1% in patients who reperfused. A median of 24 months had elapsed between CTE diagnosis and surgery, compared to 15 months in patients who reperfused. Three of four patients whose pre-operative chest radiograph showed moderate ipsilateral volume loss failed to reperfuse that lung postoperatively. Conclusion: Patients with main pulmonary artery occlusion from chronic thromboembolic disease appear to be at higher risk for reperfusion failure than what is reported in typical patients following PTE. Available data have been scarce in predicting patients at risk for this outcome. This study suggests that duration of main PA occlusion, female gender, and ipsilateral lung volume loss may be important. 1( 32) Muscularization of Pulmonary Arteries Is Reduced in Female Athymic Rats Exposed to Vascular Endothelial Growth Factor Receptor (VEGF-R) Blockade J. Guihaire ,1 E. Fadel,2 F. Haddad,3 T. Deuse,1 H. Reichenspurner,1 R.C. Robbins,3 S. Schrepfer.1 1Transplant and Stem Cell Immunobiology Lab, University Heart Center Hamburg, Hamburg, Germany; 2Thoracic and Vascular Surgery and Heart-Lung Transplantation, Marie Lannelongue Hospital, University of Paris Sud, Le Plessis Robinson, France; 3Cardiothoracic Surgery, Stanford University, Palo Alto, CA. Purpose: The epidemiology of pulmonary hypertension (PH) is characterized by a female preponderance, whereas males share a higher severity of the disease. The influence of estrogens on the development of PH is not well documented. We sought to compare the severity of experimental PH between male and female athymic rats. Methods: PH was induced in 11 male and 11 female athymic rats (SU/M and SU/F, respectively) using the tyrosine kinase inhibitor of VEGF-R I and II, semaxinib (40 mg/kg, single subcutaneous injection). After 28 days, the right ventricular end-diastolic diameter (RVEDD) and tricuspid annular plane systolic excursion (TAPSE) were measured using cardiac echography, and right ventricular-pulmonary arterial (RV-PA) coupling was evaluated by a pressure-volume admittance catheter. Morphometric analyses of lung vasculature and right ventricular (RV) myocardium were performed using respectively elastica von Gieson and hematoxylin-eosin stainings. Results: Four weeks after semaxinib injection, RV end-systolic pressure was higher in SU/M than in SU/F (66.3 ± 8.9 vs. 29.5 ± 13.4 mmHg, P< 0.001). Males developed marked RV enlargement and systolic dysfunction