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Use of PCSK9 Inhibitor Therapy in a Small Cohort of Heart Transplant Recipients with Statin Intolerance or Refractory Hyperlipidemia
Abstracts
675 Use of PCSK9 Inhibitor Therapy in a Small Cohort of Heart Transplant Recipients with Statin Intolerance or Refractory Hyperlipidemia R. Jackson, D. Jennings, M. Gaine, T. Fanek, A. Mabasa, J. Lee, A. Kleet, F. Latif, S. Restaino and M. Farr. Medicine, Columbia University Medical Center, New York, NY. Purpose: Use of statin therapy in heart transplant (HT) recipients offers the dual benefits of lipid control and as an anti-rejection agent. It is unknown whether PCSK9 inhibitors are safe and effective in transplant recipients and whether there might be similar anti-rejection or anti-inflammatory benefits in this patient population. Methods: We identified eight patients in our outpatient HT clinic who were either statin intolerant (defined by myositis or transaminitis) or with refractory hyperlipidemia (defined as LDL > 80 in patients with cardiac allograft vasculopathy [CAV] or LDL > 120 in patients without prior CAV). Baseline demographics including lipid parameters and presence or absence of CAV were collected. Descriptive statistical analysis were performed in Excel. Results: The mean age was 54 years. The average time after HT to PCSK9 initiation ranged from one month to 28 years. Two patients were treated for refractory hyperlipidemia, while the remaining were statin intolerant. All patients tolerated evolocumab 140 mg subcutaneously every two weeks, with no reported side effects. The average time on PCSK9 inhibitor therapy was 14 months. Six patients have follow up LDL values at 3 months after starting therapy. In this group the LDL decreased from a mean of 146.2 mg/ dL prior to therapy to 78.1 mg/ dL after 1-3 months of treatment (p = 0.016). One patient was intolerant to both statin therapy and everolimus. In this patient we saw an improvement in CAV at 1 year angiographic follow up. Conclusion: Use of PCSK9 inhibitors in this small single-center cohort appears to be safe and effective. While this therapy has known benefit for atherosclerosis, additional research is needed to understand whether there are anti-inflammatory properties that may stabilize or improve CAV in a larger cohort of HT recipients.
676 Desensitization in Patients Bridged to Urgent Heart Transplantation under Extracorporeal Membrane Oxygenation Support: A Preliminary Experience J. Guihaire, S. Davino, M. Kloeckner, R. Ramadan, A. Azmoun, F. Stephan and P. Deleuze. Adult Cardiac Surgery, Marie Lannelongue Hospital, Paris Sud University, Le Plessis Robinson, France. Purpose: High sensitization limits the access to organs and increases the risk of acute allograft rejection. Desensitization therapy remains a major challenge in patients with cardiogenic shock. We report our experience of plasmapheresis (PP) in patients bridged to heart transplantation under extracorporeal membrane oxygenation (ECMO). Methods: Patients who underwent PP under ECMO before heart transplantation between January 2017 and September 2018 in our institution were included. Mean fluorescence intensity (MFI) of HLA-specific antibodies was retrieved and reported as follow: score 4 for MFI lower than 1000, score 6 for MFI ranged from 1000 to 3000 and score 8 for MFI higher than
S275 3000. Complications during PP, perioperative events and post-transplantation outcomes were reviewed. Results: Six patients with a mean age of 37.5 years (16-70) underwent PP under ECMO before heart transplantation. The mean follow-up was 8.6 months (2-16). The mean duration of ECMO support was 29 days (1-74) and patients received a mean 6.8 PP sessions before heart transplantation (1-29). The mean of number of HLA-specific antibodies before heart transplantation was 9.6 for score 6 (4-13) and 5.8 for score 8 (1-12). Hemorrhagic shock occurred in two patients, leading to ECMO removal in one case. The mean number of blood transfusion products during the transplantation was 12.16 units of packed red blood cells (3-29), 7.3 fresh frozen plasma (0-25), 3.9 platelet concentrates (2-7.4), 5.4 gr of fibrinogen (0-10). Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% (79-100) for Class I and 44.2% for Class II (0-83). Hospital survival was 100% and antibody mediated rejection was diagnosed and successfully treated in two patients respectively at 7 and 23 days after heart transplantation. Conclusion: Plasmapheresis under ECMO support was associated with favorable early outcomes despite bleeding events before and during heart transplantation. Long-term incidence of acute and chronic rejections have to be further investigated in this population.
677 Evaluation of Early Allograft Function in Donor HCV-Positive to Recipient HCV-Negative Cardiac Transplantation Managed with Preemptive Direct Acting Antiviral Therapy T.A. Lebeis,1 M.E. Afari,1 E.D. Bethea,2 K. Gaj,1 J.L. Gustafson,2 K. Turvey,1 E. Coglianese,1 S.S. Thomas,1 C. Newton-Cheh,1 N. Ibrahim,1 W.D. Carlson,1 J.E. Ho,1 M. Nayor,1 J.K. Steiner,1 A. Spahillari,1 M.A. Villavicencio-Theoduloz,3 D.A. D’Alessandro,3 C. Soydara,1 N. Lever,1 R.T. Chung,2 and G.D. Lewis.1 1Cardiology Division, Massachusetts General Hospital, Boston, MA; 2Liver Center and Gastrointestinal Divison, Massachusetts General Hospital, Boston, MA; and the 3Cardiothoracic Surgery Division, Massachusetts General Hospital, Boston, MA. Purpose: Donor availability has continued to be a major issue limiting the number of cardiac transplantations in the United States. Given this shortage, it is necessary to consider strategies aimed at increasing the donor pool. We sought to evaluate the expanded use of hepatitis C virus (HCV) donor hearts, and characterize early allograft function in HCV-negative patients receiving pre-emptive anti-viral therapy following receipt of an HCV-infected donor heart. Methods: Patients who underwent heart transplantation with HCV-positive donors at our institution between November 2017 and October 2018 were studied. Invasive hemodynamic and echocardiographic data were collected from routine scheduled post-transplant procedures. Intensive care unit (ICU) time, time on inotropes and time until discharge were evaluated from the index hospitalization for heart transplantation and compared to data from our center in patients receiving non-HCV hearts between January 2016 and June 2018. Results: In total, there have been 23 recipients of donor HCV-positive heart transplants. Cardiac allograft and patient survival has been 100% at a median of 114 (IQR 81-190) days post-transplant. The average time on inotropes was 4.7§3.3 days in recipients of donor HCV-positive heart transplants, average time spent in the ICU was 7.2§4 days in the study group compared with 7.8§7.8 days in patients receiving non-HCV hearts and the average time to discharge was 19 § 9 days in the study group compared with 21§22 days in patients receiving non-HCV hearts (both p>0.05). Among 80 echocardiograms done on or after post-operative day 2 in recipients of HCV-positive donor hearts, the ejection fraction (EF) was 65§9% with a single value falling below 50% (45%) that normalized 6 days later. One and 8-week hemodynamic values, respectively, were as follows: right atrial pressure of 7§5 and 5§3 mmHg, mean pulmonary arterial pressure of 20§7 and 20§6 mmHg, mean pulmonary capillary wedge pressure of 14§6 and 11§5 mmHg, and cardiac index of 2.8§0.8 and 2.9§0.4 L/min/m2. Conclusion: In this single-center prospective study, patients who received preemptive direct-acting antiviral therapy following receipt of an
675 Use of PCSK9 Inhibitor Therapy in a Small Cohort of Heart Transplant Recipients with Statin Intolerance or Refractory Hyperlipidemia R. Jackson, D. Jennings, M. Gaine, T. Fanek, A. Mabasa, J. Lee, A. Kleet, F. Latif, S. Restaino and M. Farr. Medicine, Columbia University Medical Center, New York, NY. Purpose: Use of statin therapy in heart transplant (HT) recipients offers the dual benefits of lipid control and as an anti-rejection agent. It is unknown whether PCSK9 inhibitors are safe and effective in transplant recipients and whether there might be similar anti-rejection or anti-inflammatory benefits in this patient population. Methods: We identified eight patients in our outpatient HT clinic who were either statin intolerant (defined by myositis or transaminitis) or with refractory hyperlipidemia (defined as LDL > 80 in patients with cardiac allograft vasculopathy [CAV] or LDL > 120 in patients without prior CAV). Baseline demographics including lipid parameters and presence or absence of CAV were collected. Descriptive statistical analysis were performed in Excel. Results: The mean age was 54 years. The average time after HT to PCSK9 initiation ranged from one month to 28 years. Two patients were treated for refractory hyperlipidemia, while the remaining were statin intolerant. All patients tolerated evolocumab 140 mg subcutaneously every two weeks, with no reported side effects. The average time on PCSK9 inhibitor therapy was 14 months. Six patients have follow up LDL values at 3 months after starting therapy. In this group the LDL decreased from a mean of 146.2 mg/ dL prior to therapy to 78.1 mg/ dL after 1-3 months of treatment (p = 0.016). One patient was intolerant to both statin therapy and everolimus. In this patient we saw an improvement in CAV at 1 year angiographic follow up. Conclusion: Use of PCSK9 inhibitors in this small single-center cohort appears to be safe and effective. While this therapy has known benefit for atherosclerosis, additional research is needed to understand whether there are anti-inflammatory properties that may stabilize or improve CAV in a larger cohort of HT recipients.
676 Desensitization in Patients Bridged to Urgent Heart Transplantation under Extracorporeal Membrane Oxygenation Support: A Preliminary Experience J. Guihaire, S. Davino, M. Kloeckner, R. Ramadan, A. Azmoun, F. Stephan and P. Deleuze. Adult Cardiac Surgery, Marie Lannelongue Hospital, Paris Sud University, Le Plessis Robinson, France. Purpose: High sensitization limits the access to organs and increases the risk of acute allograft rejection. Desensitization therapy remains a major challenge in patients with cardiogenic shock. We report our experience of plasmapheresis (PP) in patients bridged to heart transplantation under extracorporeal membrane oxygenation (ECMO). Methods: Patients who underwent PP under ECMO before heart transplantation between January 2017 and September 2018 in our institution were included. Mean fluorescence intensity (MFI) of HLA-specific antibodies was retrieved and reported as follow: score 4 for MFI lower than 1000, score 6 for MFI ranged from 1000 to 3000 and score 8 for MFI higher than
S275 3000. Complications during PP, perioperative events and post-transplantation outcomes were reviewed. Results: Six patients with a mean age of 37.5 years (16-70) underwent PP under ECMO before heart transplantation. The mean follow-up was 8.6 months (2-16). The mean duration of ECMO support was 29 days (1-74) and patients received a mean 6.8 PP sessions before heart transplantation (1-29). The mean of number of HLA-specific antibodies before heart transplantation was 9.6 for score 6 (4-13) and 5.8 for score 8 (1-12). Hemorrhagic shock occurred in two patients, leading to ECMO removal in one case. The mean number of blood transfusion products during the transplantation was 12.16 units of packed red blood cells (3-29), 7.3 fresh frozen plasma (0-25), 3.9 platelet concentrates (2-7.4), 5.4 gr of fibrinogen (0-10). Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% (79-100) for Class I and 44.2% for Class II (0-83). Hospital survival was 100% and antibody mediated rejection was diagnosed and successfully treated in two patients respectively at 7 and 23 days after heart transplantation. Conclusion: Plasmapheresis under ECMO support was associated with favorable early outcomes despite bleeding events before and during heart transplantation. Long-term incidence of acute and chronic rejections have to be further investigated in this population.
677 Evaluation of Early Allograft Function in Donor HCV-Positive to Recipient HCV-Negative Cardiac Transplantation Managed with Preemptive Direct Acting Antiviral Therapy T.A. Lebeis,1 M.E. Afari,1 E.D. Bethea,2 K. Gaj,1 J.L. Gustafson,2 K. Turvey,1 E. Coglianese,1 S.S. Thomas,1 C. Newton-Cheh,1 N. Ibrahim,1 W.D. Carlson,1 J.E. Ho,1 M. Nayor,1 J.K. Steiner,1 A. Spahillari,1 M.A. Villavicencio-Theoduloz,3 D.A. D’Alessandro,3 C. Soydara,1 N. Lever,1 R.T. Chung,2 and G.D. Lewis.1 1Cardiology Division, Massachusetts General Hospital, Boston, MA; 2Liver Center and Gastrointestinal Divison, Massachusetts General Hospital, Boston, MA; and the 3Cardiothoracic Surgery Division, Massachusetts General Hospital, Boston, MA. Purpose: Donor availability has continued to be a major issue limiting the number of cardiac transplantations in the United States. Given this shortage, it is necessary to consider strategies aimed at increasing the donor pool. We sought to evaluate the expanded use of hepatitis C virus (HCV) donor hearts, and characterize early allograft function in HCV-negative patients receiving pre-emptive anti-viral therapy following receipt of an HCV-infected donor heart. Methods: Patients who underwent heart transplantation with HCV-positive donors at our institution between November 2017 and October 2018 were studied. Invasive hemodynamic and echocardiographic data were collected from routine scheduled post-transplant procedures. Intensive care unit (ICU) time, time on inotropes and time until discharge were evaluated from the index hospitalization for heart transplantation and compared to data from our center in patients receiving non-HCV hearts between January 2016 and June 2018. Results: In total, there have been 23 recipients of donor HCV-positive heart transplants. Cardiac allograft and patient survival has been 100% at a median of 114 (IQR 81-190) days post-transplant. The average time on inotropes was 4.7§3.3 days in recipients of donor HCV-positive heart transplants, average time spent in the ICU was 7.2§4 days in the study group compared with 7.8§7.8 days in patients receiving non-HCV hearts and the average time to discharge was 19 § 9 days in the study group compared with 21§22 days in patients receiving non-HCV hearts (both p>0.05). Among 80 echocardiograms done on or after post-operative day 2 in recipients of HCV-positive donor hearts, the ejection fraction (EF) was 65§9% with a single value falling below 50% (45%) that normalized 6 days later. One and 8-week hemodynamic values, respectively, were as follows: right atrial pressure of 7§5 and 5§3 mmHg, mean pulmonary arterial pressure of 20§7 and 20§6 mmHg, mean pulmonary capillary wedge pressure of 14§6 and 11§5 mmHg, and cardiac index of 2.8§0.8 and 2.9§0.4 L/min/m2. Conclusion: In this single-center prospective study, patients who received preemptive direct-acting antiviral therapy following receipt of an