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A New Strategy after Lung Transplantation for Pulmonary Hypertension: Tapering Epoprostenol Administration
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The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
stolic pressure gradient; 3) combined (Ex-CPH) if both criteria are met; 4) hemodynamically Ex-Normal if neither criteria are met. Results: Preliminary data were available for 54 patients (50% male; Age = 59 § 14); exercise hemodynamic classifications comprised 23 ExNormal, 14 Ex-LHD, 12 Ex-PVD, and 5 Ex-CPH. At rest, Ees was similar in Ex-Normal, Ex-LHD, and Ex-PVD; Ea was higher in Ex-LHD and ExPVD compared to Ex-Normal (p<0.01), and so the Ees:Ea ratio was lower (p<0.01). With exercise, in Ex-Normal, Ees remained stable, Ea increased modestly (p<0.01) and the Ees:Ea ratio was preserved. In Ex-LHD, Ees and Ea both increased (p<0.05), and the Ees:Ea ratio was preserved. In Ex-PVD, Ees remained stable as Ea increased (p<0.01), and the Ees:Ea ratio trended modestly down (Fig. 1) Conclusion: In patients with pulmonary vascular and/or left heart disease, ventricular-vascular coupling is less favorable than in patients with normal hemodynamics, and abnormalities persist during exercise. 1225 A New Strategy after Lung Transplantation for Pulmonary Hypertension: Tapering Epoprostenol Administration A. Ohsumi, A. Aoyama, H. Kinoshita, T. Yoneda, M. Okuda, K. Yamazaki, K. Minatoya, Y. Yamada, Y. Yutaka, D. Nakajima, M. Hamaji, T.F. ChenYoshikawa and H. Date Kyoto University Hospital, Kyoto, Japan. Purpose: The perioperative survival of lung transplantation (LTx) for patients with idiopathic pulmonary arterial hypertension is known to be worse than for those with other underlying diseases because of difficulties in managing perioperative haemodynamic instability. High dose epoprostenol (PGI2) is frequently used for patients with end-stage pulmonary hypertension (PH) before transplantation, however, it is generally discontinued at the time of transplantation. We hypothesized that tapering epoprostenol rather than abrupt discontinuation after reperfusion would improve perioperative outcomes. Methods: We performed 193 LTxs since 2008 and 16 PH patients were on high dose epoprostenol (10-200 ng/kg/min) therapy. Epoprostenol was discontinued at the time of lung transplantation in 6 patients and it was tapered after reperfusion in ten patients. In the Discontinued group, epoprostenol was discontinued intraoperatively during extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass and was not resumed postoperatively. In the Tapered group, epoprostenol was discontinued during extracorporeal support and was resumed at the quarter of preoperative dose after reperfusion. It was then gradually tapered typically over the following two weeks according to the heart function on echocardiography. Results: One patient in the Discontinued group died on day 125 due to multiple organ failure, in contrast, no operative death was encountered in the Tapered group. Delayed chest closure and postoperative ECMO were more frequently required in the Discontinued group than the Tapered group (p = 0.0076, respectively). Primary graft dysfunction score was significantly lower in the Tapered group than the Discontinued group (0.6 § 1.3 vs 2.2 § 1.3 at 0h, p = 0.031; 0.4 § 0.8 vs 2.0 § 1.5 at 24h, p = 0.028; 0.3 § 0.7 and 1.8 § 1.5 at 48h, p = 0.033). Furthermore, the Tapered group required significantly shorter duration of postoperative mechanical ventilation (15.1 § 6.8 vs 41.5 § 41.9 days, p = 0.039). Conclusion: Tapering epoprostenol administration after reperfusion for PH may be a valuable new strategy which is associated with better perioperative outcomes. 1226 Clinical Course of Patients Transitioned from Another Prostacyclin Pathway Agent (PPA) to Selexipag in SPHERE K.M. Chin,1 V. McLaughlin,2 N.H. Kim,3 M.M. Chakinala,4 A.R. Hemnes,5 H.W. Farber,6 C. Zhao,7 J. Colvin,7 M. Shah,7 and K.B. Highland.8 1University of Texas, Southwestern Medical Center, Dallas, TX; 2University of Michigan Medical Center, Ann Arbor, MI; 3 University of California, San Diego, La Jolla, CA; 4Washington University School of Medicine, St. Louis, MO; 5Vanderbilt University Medical Center, Nashville, TN; 6Boston University School of Medicine, Boston, MA; 7Actelion, South San Francisco, CA; and the 8Cleveland Clinic, Cleveland, OH. Purpose: The selective oral IP receptor agonist selexipag is approved to delay disease progression and reduce the risk of hospitalization in patients with pulmonary arterial hypertension (PAH). SPHERE (SelexiPag: tHe
usErs dRug rEgistry) is a US registry accruing data on real-world selexipag use. Here we report interim data on patients transitioning from a different PPA to selexipag. Methods: Patients newly initiated on selexipag or previously initiated with a documented titration scheme are eligible for this ongoing study. Data are collected at routine visits (total follow-up: 18 months). Transitioned patients were defined as those taking a PPA for ≥30 days at selexipag initiation who had stopped the initial PPA ≤7 days before, or those continuing with the initial PPA at selexipag initiation. Assessments at the clinic visit closest to selexipag initiation were considered “baseline”. Results: Of the first 250 enrolled patients (data cut-off: August 21, 2018), 56 (22%) had transitioned to selexipag: 8 (14.3%), 28 (50.0%), 3 (5.4%), and 17 (30.4%) from an oral, inhaled, subcutaneous, or intravenous PPAs, respectively. 65% completed their transition within 60 days. There were no clear differences in baseline characteristics or clinical course in patients who had transitioned from inhaled or oral PPAs vs parenteral PPAs. Transitioned and non-transitioned patients had similar baseline characteristics, except transitioned patients had a longer median time from PAH diagnosis to selexipag initiation (5.6 vs 3.1 years) and more had idiopathic PAH (64% vs 49%). The median time to maintenance selexipag dose was similar (8.1 vs 8.6 weeks) but the median maintenance dose was higher (1400 vs 1200 mg BID) for transitioned patients. Of patients who had baseline and 12-month data (transitioned, n=39; non-transitioned n=112), 10.3% and 9.8% of transitioned and non-transitioned patients had worsened FC, 69.2% and 74.1% had stable FC, and 20.5% and 16.1% had improved FC. With similar median time on selexipag (19.7 vs 17.8 months), 29% of transitioned and 34% of non-transitioned patients discontinued selexipag with 19.6% in each group discontinuing due to adverse events. Conclusion: Baseline characteristics, clinical course, and selexipag tolerability were generally similar in transitioned vs non-transitioned patients. 1227 Secular Trends and Outcome of Isolated versus Combined Type 2 Pulmonary Hypertension in Patients with End-Stage Heart Failure A. Nasri,1 J. Dupuis,1 L. Hausermann,1 M. Tremblay-Gravel,1 M.C. Parent,1 M. Carrier,1 N. Racine,1 S. de Denus,1 A. Ducharme,1 A. Fortier,2 and M. White.1 1Montreal Heart Institute, Montreal, QC, Canada; and the 2Montreal Health Innovations Coordinating Centre, Montreal, QC, Canada. Purpose: The presence of pulmonary hypertension (PH) is associated with some adverse outcomes following cardiac transplantation (CTx). It is now suggested to diagnose group 2 PH when the mean pulmonary artery pressure (PAPm) is >20 mmHg. The characteristics and outcomes of patients with isolated post-capillary PH (Ipc-PH) versus combined pre- and postcapillary PH (Cpc-PH) diagnosed pre-CTx using this new definition and follow-up long-term after CTx have not been investigated. Methods: This study included 361 patients who received a first CTx at the Montreal Heart Institute between January 1983 and December 2014. Patients were classified as having PH based on the most recent right heart catheterization prior to CTx. Ipc-PH was defined by a pulmonary capillary wedge pressure (PCWP) >15 mmHg, PAPm >20 mmHg and pulmonary vascular resistance (PVR) ≤3 woods units, while Cpc-PH was defined by a PCWP >15 mmHg, PAPm >20 mmHg and PVR >3 woods units. Severe PH was defined as PAPm ≥35 mmHg. The cohort was analyzed in 2 groups according to the era of CTx (first: 1983 to 1998; second: 1999 to 2014). The primary outcome was all cause and cardiovascular mortality. The secondary outcomes included a selection of major adverse cardiac events. Results: The prevalence of PH was 90.71% in the first era (Ipc-PH=55.19% and Cpc-PH=35.52%) versus 83.71% in the second era (Ipc-PH=49.44% and Cpc-PH=34.27%); P=NS. Both severe Cpc-PH and severe Ipc-PH were less prevalent in the second era (20.22% vs 30.05% Cpc-PH and 16.29% vs 25.14% Ipc-PH; P=0.0016). However, there were no significant changes in PAPm values for all severity of Ipc-PH or Cpc-PH across the eras. The diagnosis of Ipc-PH or Cpc-PH yielded no impact on intra-hospital or 30 days mortality regardless of era of CTx. However, severe PH (severe Ipc-PH or Cpc-PH combined) was associated with an increased 30 days, 1 year and 3 years mortality (all P<0.05) regardless of the era of CTx. Conclusion: The prevalence of Ipc-PH or Cpc-PH is very high pre-CTx. Unless severe, the presence of group 2-PH has not modulated the early or late post-CTx mortality over 30 years. Accurate diagnosis and better
The Journal of Heart and Lung Transplantation, Vol 38, No 4S, April 2019
stolic pressure gradient; 3) combined (Ex-CPH) if both criteria are met; 4) hemodynamically Ex-Normal if neither criteria are met. Results: Preliminary data were available for 54 patients (50% male; Age = 59 § 14); exercise hemodynamic classifications comprised 23 ExNormal, 14 Ex-LHD, 12 Ex-PVD, and 5 Ex-CPH. At rest, Ees was similar in Ex-Normal, Ex-LHD, and Ex-PVD; Ea was higher in Ex-LHD and ExPVD compared to Ex-Normal (p<0.01), and so the Ees:Ea ratio was lower (p<0.01). With exercise, in Ex-Normal, Ees remained stable, Ea increased modestly (p<0.01) and the Ees:Ea ratio was preserved. In Ex-LHD, Ees and Ea both increased (p<0.05), and the Ees:Ea ratio was preserved. In Ex-PVD, Ees remained stable as Ea increased (p<0.01), and the Ees:Ea ratio trended modestly down (Fig. 1) Conclusion: In patients with pulmonary vascular and/or left heart disease, ventricular-vascular coupling is less favorable than in patients with normal hemodynamics, and abnormalities persist during exercise. 1225 A New Strategy after Lung Transplantation for Pulmonary Hypertension: Tapering Epoprostenol Administration A. Ohsumi, A. Aoyama, H. Kinoshita, T. Yoneda, M. Okuda, K. Yamazaki, K. Minatoya, Y. Yamada, Y. Yutaka, D. Nakajima, M. Hamaji, T.F. ChenYoshikawa and H. Date Kyoto University Hospital, Kyoto, Japan. Purpose: The perioperative survival of lung transplantation (LTx) for patients with idiopathic pulmonary arterial hypertension is known to be worse than for those with other underlying diseases because of difficulties in managing perioperative haemodynamic instability. High dose epoprostenol (PGI2) is frequently used for patients with end-stage pulmonary hypertension (PH) before transplantation, however, it is generally discontinued at the time of transplantation. We hypothesized that tapering epoprostenol rather than abrupt discontinuation after reperfusion would improve perioperative outcomes. Methods: We performed 193 LTxs since 2008 and 16 PH patients were on high dose epoprostenol (10-200 ng/kg/min) therapy. Epoprostenol was discontinued at the time of lung transplantation in 6 patients and it was tapered after reperfusion in ten patients. In the Discontinued group, epoprostenol was discontinued intraoperatively during extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass and was not resumed postoperatively. In the Tapered group, epoprostenol was discontinued during extracorporeal support and was resumed at the quarter of preoperative dose after reperfusion. It was then gradually tapered typically over the following two weeks according to the heart function on echocardiography. Results: One patient in the Discontinued group died on day 125 due to multiple organ failure, in contrast, no operative death was encountered in the Tapered group. Delayed chest closure and postoperative ECMO were more frequently required in the Discontinued group than the Tapered group (p = 0.0076, respectively). Primary graft dysfunction score was significantly lower in the Tapered group than the Discontinued group (0.6 § 1.3 vs 2.2 § 1.3 at 0h, p = 0.031; 0.4 § 0.8 vs 2.0 § 1.5 at 24h, p = 0.028; 0.3 § 0.7 and 1.8 § 1.5 at 48h, p = 0.033). Furthermore, the Tapered group required significantly shorter duration of postoperative mechanical ventilation (15.1 § 6.8 vs 41.5 § 41.9 days, p = 0.039). Conclusion: Tapering epoprostenol administration after reperfusion for PH may be a valuable new strategy which is associated with better perioperative outcomes. 1226 Clinical Course of Patients Transitioned from Another Prostacyclin Pathway Agent (PPA) to Selexipag in SPHERE K.M. Chin,1 V. McLaughlin,2 N.H. Kim,3 M.M. Chakinala,4 A.R. Hemnes,5 H.W. Farber,6 C. Zhao,7 J. Colvin,7 M. Shah,7 and K.B. Highland.8 1University of Texas, Southwestern Medical Center, Dallas, TX; 2University of Michigan Medical Center, Ann Arbor, MI; 3 University of California, San Diego, La Jolla, CA; 4Washington University School of Medicine, St. Louis, MO; 5Vanderbilt University Medical Center, Nashville, TN; 6Boston University School of Medicine, Boston, MA; 7Actelion, South San Francisco, CA; and the 8Cleveland Clinic, Cleveland, OH. Purpose: The selective oral IP receptor agonist selexipag is approved to delay disease progression and reduce the risk of hospitalization in patients with pulmonary arterial hypertension (PAH). SPHERE (SelexiPag: tHe
usErs dRug rEgistry) is a US registry accruing data on real-world selexipag use. Here we report interim data on patients transitioning from a different PPA to selexipag. Methods: Patients newly initiated on selexipag or previously initiated with a documented titration scheme are eligible for this ongoing study. Data are collected at routine visits (total follow-up: 18 months). Transitioned patients were defined as those taking a PPA for ≥30 days at selexipag initiation who had stopped the initial PPA ≤7 days before, or those continuing with the initial PPA at selexipag initiation. Assessments at the clinic visit closest to selexipag initiation were considered “baseline”. Results: Of the first 250 enrolled patients (data cut-off: August 21, 2018), 56 (22%) had transitioned to selexipag: 8 (14.3%), 28 (50.0%), 3 (5.4%), and 17 (30.4%) from an oral, inhaled, subcutaneous, or intravenous PPAs, respectively. 65% completed their transition within 60 days. There were no clear differences in baseline characteristics or clinical course in patients who had transitioned from inhaled or oral PPAs vs parenteral PPAs. Transitioned and non-transitioned patients had similar baseline characteristics, except transitioned patients had a longer median time from PAH diagnosis to selexipag initiation (5.6 vs 3.1 years) and more had idiopathic PAH (64% vs 49%). The median time to maintenance selexipag dose was similar (8.1 vs 8.6 weeks) but the median maintenance dose was higher (1400 vs 1200 mg BID) for transitioned patients. Of patients who had baseline and 12-month data (transitioned, n=39; non-transitioned n=112), 10.3% and 9.8% of transitioned and non-transitioned patients had worsened FC, 69.2% and 74.1% had stable FC, and 20.5% and 16.1% had improved FC. With similar median time on selexipag (19.7 vs 17.8 months), 29% of transitioned and 34% of non-transitioned patients discontinued selexipag with 19.6% in each group discontinuing due to adverse events. Conclusion: Baseline characteristics, clinical course, and selexipag tolerability were generally similar in transitioned vs non-transitioned patients. 1227 Secular Trends and Outcome of Isolated versus Combined Type 2 Pulmonary Hypertension in Patients with End-Stage Heart Failure A. Nasri,1 J. Dupuis,1 L. Hausermann,1 M. Tremblay-Gravel,1 M.C. Parent,1 M. Carrier,1 N. Racine,1 S. de Denus,1 A. Ducharme,1 A. Fortier,2 and M. White.1 1Montreal Heart Institute, Montreal, QC, Canada; and the 2Montreal Health Innovations Coordinating Centre, Montreal, QC, Canada. Purpose: The presence of pulmonary hypertension (PH) is associated with some adverse outcomes following cardiac transplantation (CTx). It is now suggested to diagnose group 2 PH when the mean pulmonary artery pressure (PAPm) is >20 mmHg. The characteristics and outcomes of patients with isolated post-capillary PH (Ipc-PH) versus combined pre- and postcapillary PH (Cpc-PH) diagnosed pre-CTx using this new definition and follow-up long-term after CTx have not been investigated. Methods: This study included 361 patients who received a first CTx at the Montreal Heart Institute between January 1983 and December 2014. Patients were classified as having PH based on the most recent right heart catheterization prior to CTx. Ipc-PH was defined by a pulmonary capillary wedge pressure (PCWP) >15 mmHg, PAPm >20 mmHg and pulmonary vascular resistance (PVR) ≤3 woods units, while Cpc-PH was defined by a PCWP >15 mmHg, PAPm >20 mmHg and PVR >3 woods units. Severe PH was defined as PAPm ≥35 mmHg. The cohort was analyzed in 2 groups according to the era of CTx (first: 1983 to 1998; second: 1999 to 2014). The primary outcome was all cause and cardiovascular mortality. The secondary outcomes included a selection of major adverse cardiac events. Results: The prevalence of PH was 90.71% in the first era (Ipc-PH=55.19% and Cpc-PH=35.52%) versus 83.71% in the second era (Ipc-PH=49.44% and Cpc-PH=34.27%); P=NS. Both severe Cpc-PH and severe Ipc-PH were less prevalent in the second era (20.22% vs 30.05% Cpc-PH and 16.29% vs 25.14% Ipc-PH; P=0.0016). However, there were no significant changes in PAPm values for all severity of Ipc-PH or Cpc-PH across the eras. The diagnosis of Ipc-PH or Cpc-PH yielded no impact on intra-hospital or 30 days mortality regardless of era of CTx. However, severe PH (severe Ipc-PH or Cpc-PH combined) was associated with an increased 30 days, 1 year and 3 years mortality (all P<0.05) regardless of the era of CTx. Conclusion: The prevalence of Ipc-PH or Cpc-PH is very high pre-CTx. Unless severe, the presence of group 2-PH has not modulated the early or late post-CTx mortality over 30 years. Accurate diagnosis and better