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637 Circulating Biomarkers of Reverse Remodeling during Support of a Continuous Flow LVAD
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The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
635 Use of Long-Term Ventricular Assist Devices in Bridging to Heart Transplantation – A UK National Survey A. Emin,1 C.A. Rogers,1 H.L. Thomas,3 S. Tsui,4 G. MacGowan,5 J. Parameshwar,4 N.R. Banner.2 1on behalf of the UK VAD Forum and UK Cardiothoracic Transplant Steering Group, Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, United Kingdom; 2Cardiopulmonary Transplantation, Harefield Hospital, Middlesex, United Kingdom; 3Statistics and Clinical Audit, NHS Blood and Transplant, Bristol, United Kingdom; 4Cardiopulmonary Transplantation, Papworth Hospital, Papworth Everard, Cambridgeshire, United Kingdom; 5Cardiopulmonary Transplantation, Freeman Hospital, Newcastle, United Kingdom. Purpose: There has been a decline in the number of hearts available for transplantation (HTx). Consequently waiting times have increased & ventricular assist devices (VADs) have been used to manage patients prior to HTx. Here, we report activity & outcome in UK patients receiving a long-term (LT) VAD as a bridge to HTx. Methods and Materials: All patients who received a LT VAD as a bridge to HTx between 5/2002 & 6/2010 were included using a comprehensive national database. We excluded patients who received prior short-term support (bridge to bridge). Activity is grouped into 3 eras: 5/2002-12/2004, 1/2005-12/2007 & 1/2008-6/2010. Results: 246 LVADs were implanted in 239 patients; 75 (31%) also received an RVAD. Median age at implant was 44 years (IQR 32-55) & 79% were male. Activity rose from 26 implants/year in era 1 to 41/year in era 3. Device choice has changed towards 2nd & 3rd generation devices; 81% were 1st generation in era 1 compared with 31% in era 2 & 4% in era 3. Duration of support ranged up to 1927 days, increasing from a median of 84 days (IQR 20-209) in era 1 to 280 days (IQR 86-661) in era 3 (p⬍0.01). Survival to 1 year after LVAD implant was 61% (95%CI 54-67), rising from 53% (95%CI 40-64) in era 1 to 66% (95%CI 54-75) in era 3 (p⫽0.10). Of the 239 patients implanted, 83 (35%) have received HTx, 52 (22%) are alive on a VAD & 84 (35%) died on support. The remaining 20 (8%) patients were explanted; 18 of these remain alive & 2 have died. 30-day mortality after HTx for patients with or without a pre-HTx VAD was 19% (95%CI 12-29) & 10% (95%CI 8-12) respectively (p⬍0.01). Early post-HTx mortality was similar for 1st, 2nd & 3rd generation LVADs (p⫽0.24). 1-year survival conditional on 30-day survival was similar with & without a pre-HTx VAD (93% vs. 91%, p⫽0.48). Conclusions: Use of LT VADs as a bridge to HTx has increased in the UK. There has been a switch from 1st to 2nd/3rd generation devices & duration of support has increased. Bridging may increase early HTx mortality but does not affect subsequent outcome. 636 Ventricular Assist Device Support as a Bridge to Heart Transplantation in Patients with Giant Cell Myocarditis L.K. Murray,1 S.N. Jonas,1 P.C. Colombo,1 D. Mancini,1 E. Joye,1 E. Horn,1 H. Takayama,2 Y. Naka,2 U.P. Jorde,1 U. Nir.1 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY. Purpose: Giant cell myocarditis (GCM) is a rare form of myocarditis which carries a poor prognosis. Treatment includes standard heart failure medication and immunosuppression, but many pts require end-stage therapies. This study sought to determine the outcome of pts bridged with ventricular assist devices (VAD) to heart transplantation (HTX). Methods and Materials: A retrospective chart review was performed to identify pts with GCM treated with VAD or HTX. Diagnosis was determined by endomyocardial or explanted heart biopsy. Results: 8 pts aged 44⫾16 years (4 female) were diagnosed with GCM between 2000-10 and treated with HTX or VAD. 6 pts received VADs and 2 pts went directly to HTX. 5 out of 6 pts were bridged with biventricular support (2 Centrimag BiVAD, 1 Abiomed BiVAD, 1 Heartmate I with Abiomed RVAD, 1 Heartmate II with Centrimag RVAD); 1 patient was supported by LVAD (Heartmate I) alone. All RVAD cannulation was performed from right atrium to pulmonary artery. LVAD cannulation was from left ventricle apex to ascending aorta. 2 pts died on device support (1
embolic stroke; 1 hemorrhagic stroke). 4 pts were bridged to HTX 77⫾42 days after device implantation. A total of 6 pts underwent HTX. All pts who survived to HTX are alive with a mean follow-up of 54.4⫾51.2 months. 3 pts were found to have recurrent GCM in the transplanted heart 1.8, 7.3 and 37.2 months after HTX, of which 1 patient was treated with OKT 3, 1 with dacluzimab, and 2 with cyclophosphamide. 2 of the 3 pts recovered while 1 required re-HTX. 5 pts experienced high grade (3a/3b) rejection episodes at 66⫾52 days post-HTX. Cardiac function was preserved in all pts (mean EF 61⫾3%) and only 1 patient had cardiac allograft vasculopathy (23 months after HTX). Conclusions: Pts with end-stage GCM can be successfully bridged to HTX with VADs. Post-HTX pts can have survival outcomes comparable to the overall HTX population. The proper immunosuppressive regimen for this group is a topic of further investigation given the frequency of high grade rejection and GCM recurrence. 637 Circulating Biomarkers of Reverse Remodeling during Support of a Continuous Flow LVAD S.I. Lok,1 P. van der Weide,2 J. Kuik,2 B. Winkens,3 M.E.I. Schipper,2 H. Kemperman,2 P.A.F. Doevendans,1 R. de Weger,2 N. de Jonge.1 1 Cardiology, University Medical Center Utrecht, Utrecht, Netherlands; 2 Pathology, University Medical Center Utrecht, Utrecht, Netherlands; 3 Department Methodology & Statistics, Academic Hospital Maastricht, Maastricht, Netherlands. Purpose: In patients with heart failure myocardial remodeling occurs. It is unknown whether continuous flow LVAD (C-LVAD) leads to reverse remodeling of the myocardium and to changes in plasma concentrations of proteins that correlated with tissue remodeling. The goal of this study was to analyze these plasma markers during C-LVAD support. Methods and Materials: We analyzed plasma samples of 22 patients with a dilated cardiomyopathy (DCM) on C-LVAD as bridge to transplantion. Of these patients, 5 were weaned from their LVAD support. Blood samples were taken before,1,3 and 6 months after implantation. Plasma concentrations of brain-natriuretic peptide (BNP), osteopontin (OPN) and galectin-3 (Gal-3) were determined. In addition, plasma of 5 healthy controls were analysed. The amount of mRNA of OPN, BNP and Gal-3 were measured by q-PCR in myocardial tissue. Results: OPN, Gal-3 and BNP were significantly elevated in patients with DCM compared to control. BNP and Gal-3 decreased significantly after 1 month of C-LVAD support (p⬍ 0,0001) and remained stable thereafter, but was elevated compared to control. OPN increased significantly during the first month of LVAD support (p⬍0,0001) and returned to the same concentration prior implantation, but was still elevated compared to control. The patients that were succesfully weaned did not show a different pattern regarding OPN, Gal and/or BNP expression. Only the amount of mRNA of OPN decreased significantly during C-LVAD treatment (OPN p⬍0,05). Conclusions: Our findings indicate that mechanical unloading in end-stage heart failure is reflected by a rapid reduction of circulating OPN, Gal and BNP. Future clinical research is necessary to investigate whether these biomarkers can be used for monitoring reverse remodeling during C-LVAD. 638 Correlation of Pre-Implant Norepinephrine Transporter Levels with Myocardial Recovery during Left Ventricular Assist Device Support R.S. George,1 M. Yacoub,2 P. Facer,3 A. Khaghani,1 P. Anand,3 E.J. Birks.1 1Imperial College London, London, United Kingdom; 2Heart Science Centre, Magdi Yacoub Institute, London, United Kingdom; 3 Peripheral Neuropahty Unit, Hammersmiths Hospital, London, United Kingdom. Purpose: Cardiac norepinephrine transporter (NET) uptake sites are markedly impaired in heart failure (HF) patients resulting in intra-cardiac abundance of norepinephrine (NE). LVADs have shown to improve NET activity and reduce NE levels. The bearing of NET, however, to determine which LVAD patients have favourable recovery has not been studied. The aims of this study were to quantify NET using immunostaining in the myocardium of HF patients acquired at time of LVAD implantation and to correlate the findings with recovery.
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
635 Use of Long-Term Ventricular Assist Devices in Bridging to Heart Transplantation – A UK National Survey A. Emin,1 C.A. Rogers,1 H.L. Thomas,3 S. Tsui,4 G. MacGowan,5 J. Parameshwar,4 N.R. Banner.2 1on behalf of the UK VAD Forum and UK Cardiothoracic Transplant Steering Group, Clinical Effectiveness Unit, The Royal College of Surgeons of England, London, United Kingdom; 2Cardiopulmonary Transplantation, Harefield Hospital, Middlesex, United Kingdom; 3Statistics and Clinical Audit, NHS Blood and Transplant, Bristol, United Kingdom; 4Cardiopulmonary Transplantation, Papworth Hospital, Papworth Everard, Cambridgeshire, United Kingdom; 5Cardiopulmonary Transplantation, Freeman Hospital, Newcastle, United Kingdom. Purpose: There has been a decline in the number of hearts available for transplantation (HTx). Consequently waiting times have increased & ventricular assist devices (VADs) have been used to manage patients prior to HTx. Here, we report activity & outcome in UK patients receiving a long-term (LT) VAD as a bridge to HTx. Methods and Materials: All patients who received a LT VAD as a bridge to HTx between 5/2002 & 6/2010 were included using a comprehensive national database. We excluded patients who received prior short-term support (bridge to bridge). Activity is grouped into 3 eras: 5/2002-12/2004, 1/2005-12/2007 & 1/2008-6/2010. Results: 246 LVADs were implanted in 239 patients; 75 (31%) also received an RVAD. Median age at implant was 44 years (IQR 32-55) & 79% were male. Activity rose from 26 implants/year in era 1 to 41/year in era 3. Device choice has changed towards 2nd & 3rd generation devices; 81% were 1st generation in era 1 compared with 31% in era 2 & 4% in era 3. Duration of support ranged up to 1927 days, increasing from a median of 84 days (IQR 20-209) in era 1 to 280 days (IQR 86-661) in era 3 (p⬍0.01). Survival to 1 year after LVAD implant was 61% (95%CI 54-67), rising from 53% (95%CI 40-64) in era 1 to 66% (95%CI 54-75) in era 3 (p⫽0.10). Of the 239 patients implanted, 83 (35%) have received HTx, 52 (22%) are alive on a VAD & 84 (35%) died on support. The remaining 20 (8%) patients were explanted; 18 of these remain alive & 2 have died. 30-day mortality after HTx for patients with or without a pre-HTx VAD was 19% (95%CI 12-29) & 10% (95%CI 8-12) respectively (p⬍0.01). Early post-HTx mortality was similar for 1st, 2nd & 3rd generation LVADs (p⫽0.24). 1-year survival conditional on 30-day survival was similar with & without a pre-HTx VAD (93% vs. 91%, p⫽0.48). Conclusions: Use of LT VADs as a bridge to HTx has increased in the UK. There has been a switch from 1st to 2nd/3rd generation devices & duration of support has increased. Bridging may increase early HTx mortality but does not affect subsequent outcome. 636 Ventricular Assist Device Support as a Bridge to Heart Transplantation in Patients with Giant Cell Myocarditis L.K. Murray,1 S.N. Jonas,1 P.C. Colombo,1 D. Mancini,1 E. Joye,1 E. Horn,1 H. Takayama,2 Y. Naka,2 U.P. Jorde,1 U. Nir.1 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY. Purpose: Giant cell myocarditis (GCM) is a rare form of myocarditis which carries a poor prognosis. Treatment includes standard heart failure medication and immunosuppression, but many pts require end-stage therapies. This study sought to determine the outcome of pts bridged with ventricular assist devices (VAD) to heart transplantation (HTX). Methods and Materials: A retrospective chart review was performed to identify pts with GCM treated with VAD or HTX. Diagnosis was determined by endomyocardial or explanted heart biopsy. Results: 8 pts aged 44⫾16 years (4 female) were diagnosed with GCM between 2000-10 and treated with HTX or VAD. 6 pts received VADs and 2 pts went directly to HTX. 5 out of 6 pts were bridged with biventricular support (2 Centrimag BiVAD, 1 Abiomed BiVAD, 1 Heartmate I with Abiomed RVAD, 1 Heartmate II with Centrimag RVAD); 1 patient was supported by LVAD (Heartmate I) alone. All RVAD cannulation was performed from right atrium to pulmonary artery. LVAD cannulation was from left ventricle apex to ascending aorta. 2 pts died on device support (1
embolic stroke; 1 hemorrhagic stroke). 4 pts were bridged to HTX 77⫾42 days after device implantation. A total of 6 pts underwent HTX. All pts who survived to HTX are alive with a mean follow-up of 54.4⫾51.2 months. 3 pts were found to have recurrent GCM in the transplanted heart 1.8, 7.3 and 37.2 months after HTX, of which 1 patient was treated with OKT 3, 1 with dacluzimab, and 2 with cyclophosphamide. 2 of the 3 pts recovered while 1 required re-HTX. 5 pts experienced high grade (3a/3b) rejection episodes at 66⫾52 days post-HTX. Cardiac function was preserved in all pts (mean EF 61⫾3%) and only 1 patient had cardiac allograft vasculopathy (23 months after HTX). Conclusions: Pts with end-stage GCM can be successfully bridged to HTX with VADs. Post-HTX pts can have survival outcomes comparable to the overall HTX population. The proper immunosuppressive regimen for this group is a topic of further investigation given the frequency of high grade rejection and GCM recurrence. 637 Circulating Biomarkers of Reverse Remodeling during Support of a Continuous Flow LVAD S.I. Lok,1 P. van der Weide,2 J. Kuik,2 B. Winkens,3 M.E.I. Schipper,2 H. Kemperman,2 P.A.F. Doevendans,1 R. de Weger,2 N. de Jonge.1 1 Cardiology, University Medical Center Utrecht, Utrecht, Netherlands; 2 Pathology, University Medical Center Utrecht, Utrecht, Netherlands; 3 Department Methodology & Statistics, Academic Hospital Maastricht, Maastricht, Netherlands. Purpose: In patients with heart failure myocardial remodeling occurs. It is unknown whether continuous flow LVAD (C-LVAD) leads to reverse remodeling of the myocardium and to changes in plasma concentrations of proteins that correlated with tissue remodeling. The goal of this study was to analyze these plasma markers during C-LVAD support. Methods and Materials: We analyzed plasma samples of 22 patients with a dilated cardiomyopathy (DCM) on C-LVAD as bridge to transplantion. Of these patients, 5 were weaned from their LVAD support. Blood samples were taken before,1,3 and 6 months after implantation. Plasma concentrations of brain-natriuretic peptide (BNP), osteopontin (OPN) and galectin-3 (Gal-3) were determined. In addition, plasma of 5 healthy controls were analysed. The amount of mRNA of OPN, BNP and Gal-3 were measured by q-PCR in myocardial tissue. Results: OPN, Gal-3 and BNP were significantly elevated in patients with DCM compared to control. BNP and Gal-3 decreased significantly after 1 month of C-LVAD support (p⬍ 0,0001) and remained stable thereafter, but was elevated compared to control. OPN increased significantly during the first month of LVAD support (p⬍0,0001) and returned to the same concentration prior implantation, but was still elevated compared to control. The patients that were succesfully weaned did not show a different pattern regarding OPN, Gal and/or BNP expression. Only the amount of mRNA of OPN decreased significantly during C-LVAD treatment (OPN p⬍0,05). Conclusions: Our findings indicate that mechanical unloading in end-stage heart failure is reflected by a rapid reduction of circulating OPN, Gal and BNP. Future clinical research is necessary to investigate whether these biomarkers can be used for monitoring reverse remodeling during C-LVAD. 638 Correlation of Pre-Implant Norepinephrine Transporter Levels with Myocardial Recovery during Left Ventricular Assist Device Support R.S. George,1 M. Yacoub,2 P. Facer,3 A. Khaghani,1 P. Anand,3 E.J. Birks.1 1Imperial College London, London, United Kingdom; 2Heart Science Centre, Magdi Yacoub Institute, London, United Kingdom; 3 Peripheral Neuropahty Unit, Hammersmiths Hospital, London, United Kingdom. Purpose: Cardiac norepinephrine transporter (NET) uptake sites are markedly impaired in heart failure (HF) patients resulting in intra-cardiac abundance of norepinephrine (NE). LVADs have shown to improve NET activity and reduce NE levels. The bearing of NET, however, to determine which LVAD patients have favourable recovery has not been studied. The aims of this study were to quantify NET using immunostaining in the myocardium of HF patients acquired at time of LVAD implantation and to correlate the findings with recovery.