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Rubidium Positron Emission Tomography and Coronary Flow Reserve Predicts Graft Function After Heart Transplant
S48
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
Conclusion: Our findings suggest that DPD ≥ 7 mmHg and, in particular, PH may evolve into prognostic markers for long-term outcome after HT. The importance and prognostic value of repeated haemodynamic measurements the first year after HT is emphasized by its association with reduced outcome, illustrating that pulmonary vascular changes may be present.
Conclusion: Recipient liver dysfunction is associated with reduced early and late graft survival, however the negative influence of liver dysfunction is amplified in patients with CF-LVAD explantation. These findings may be important for OHT and CF-LVAD patient selection.
1( 06)
1( 05) Influence of Liver Dysfunction in Patients Undergoing Heart Transplantation With Left Ventricular Assist Device Explantation: Comparative Analysis Using the MELD Excluding INR (MELD-XI) Scoring System S. Maltais ,1 M.E. Davis,1 M.R. Danter,1 J.M. Stulak,2 N.A. Haglund.3 1Cardiac Surgery, Vanderbilt Univ Med Ctr, Nashville, TN; 2Cardiac Surgery, Mayo Clinic, Rochester, TN; 3Cardiovascular Medicine, Vanderbilt Univ Med Ctr, Nashville, TN. Purpose: The effects of liver dysfunction in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) explant at OHT is unknown. We investigated its effect on survival outcomes after CF-LVAD explantation-OHT. Methods: Adults undergoing OHT with or without CF-LVAD explantation between 2007 and 2014 were identified in the SRTR database. We utilized a Model for End-stage Liver Disease (MELD) eXcluding INR (MELD-XI) scoring system to define patients with liver dysfunction (score ≥ 17). Patients were stratified into four groups based liver dysfunction with or without CF-LVAD explantation at OHT and analyzed according to graft survival at 1 and 5 years. Results: Overall, 7598 patients with OHT were analyzed with an average MELD-XI score of 10.4±5.7. While 5838 patients (77%) underwent direct OHT during the study period, 1760 patients (23%) underwent OHT with CF-LVAD explantation (HeartMate II= 1661, 94%; HeartWare= 99, 6%). Liver dysfunction (MELD-XI ≥ 17) was identified in 693 patients (12%) undergoing direct OHT (Group A0) and 138 patients (8%) with LVAD explant-OHT (Group B0). For patients with MELD-XI < 17, direct OHT was performed in 5145 patients (Group A1), and CF-LVAD explant-OHT in 1622 patients (Group B1). Kaplan-Meier analysis revealed an association between a high MELD-XI score and decreased post-transplant graft survival in direct OHT and CF-LVAD explant-OHT groups (Figure; p< 0.001). After adjusting for covariates, Cox regression analysis revealed patients bridged with CF-LVADs, recipients with MELD-XI ≥ 17, higher BMI and higher creatinine had increased risk of graft failure (all p< 0.001).
Rubidium Positron Emission Tomography and Coronary Flow Reserve Predicts Graft Function After Heart Transplant J. Kawano , J. Patel, M. Kittleson, F. Liou, D. Wong, G. Jamero, B. Azarbal, D.H. Chang, L. Czer, A. Trento, J.A. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: Cardiac allograft vasculopathy (CAV) is a major factor limiting survival after heart transplant. CAV may present as small vessel or microvascular disease, which is correlated with reduced coronary flow reserve (CFR). CFR is commonly performed through intracoronary flow wire. Recently, rubidium positron emission tomography (PET) scanning has become a reliable test to demonstrate CFR. We reviewed patients with low CFR (CFR< 2) and assessed them for cardiac dysfunction as defined by decreased left ventricular ejection fraction (LVEF), increased left ventricular end diastolic volume index (LVEDVI) and left ventricular enlargement. Methods: We assessed 36 patients transplanted between 1994 and 2013 and who underwent routine rubidium PET scanning between 2011 and 2014 at their annual visit. Patients with established coronary disease were excluded. CFR was determined by rubidium PET scanning. Additional concomitant information of LVEF at rest and post stress, LVEDVI at rest and post-stress, and left ventricular enlargement was recorded. Results: 9 patients had a low CFR. The low CFR group had significantly decreased LVEF post-stress and a trend towards decreased LVEF at rest. The low CFR group also had significantly higher LVEDVI at rest and post-stress. A significantly larger percentage of patients had left ventricular enlargement in the low CFR group (see table). Conclusion: Low CFR is associated with cardiac dysfunction which may be due to small vessel coronary disease in the absence of epicardial CAV. Rubidium PET may have a role in determining small vessel disease in heart transplant patients.
Endpoints
CFR < 2.00 (n= 9)
CFR > 2.00 (n= 27) P-Value
Average LVEF Rest Average LVEF Post Stress Average EDVI Rest Average EDVI Post Stress % LV Enlargement
48.7 ± 23.1 51.3 ± 24.0 69.9 ± 46.6 74.6 ± 55.1 44.40%
59.7 ± 11.9 64.0 ± 11.9 46.6 ± 16.2 50.4 ± 15.8 7.40%
0.070 0.042 0.030 0.044 0.025
Abstracts S49 1( 07) Do Abnormal Regadenoson Scans Predict Subsequent Poor Outcome? J. Kawano , M. Kittleson, J. Patel, B. Azarbal, F. Liou, S. Siddiqui, D. Wong, D.H. Chang, D. Ramzy, L. Czer, J.A. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: Cardiac allograft vasculopathy (CAV) is one of the major factors limiting long-term survival after heart transplantation. The use of annual coronary angiograms is an invasive procedure with inherent potential complications. Non-invasive testing such as dobutamine stress echocardiography has been demonstrated to have prognostic outcome after heart transplant. The use of regadenoson nuclear scans has been of increasing use in the recent past as another non-invasive means to detect CAV. It is not clear whether these nuclear scans are predictive of subsequent poor outcome. Methods: Between 1994 and 2012 we assessed 225 of heart transplant patients who underwent a regadenoson scan. Patients were divided into those who had normal regadenoson scans and those with abnormal regadenoson scans. An abnormal regadenoson scan was defined as a scan with any fixed perfusion defects and/or reversible defects. Outcomes including 1-year subsequent survival, freedom from left ventricular (LV) dysfunction and freedom from percutaneous coronary intervention (PCI)/angioplasty were assessed. Results: 1-year subsequent survival and freedom from LV dysfunction and PCI/angioplasty were significantly lower in patients with abnormal scans (see table). There was no difference between fixed defects versus any reversible defects for outcome. Conclusion: Abnormal regadenoson scans are predictive of poor outcome after heart transplantation. Aggressive strategies such as more frequent angiograms or re-transplant for select patients should be considered.
Endpoints
Normal Regadeno- Abnormal Regadenoson Scan (n= 165) son Scan (n= 60) P-value
1-year Subsequent Actuarial 99.40% Survival 1-year Subsequent Actuarial 100.00% Freedom from LV Dysfunction 1-year Subsequent Actuarial 100.00% Freedom from PCI/Angioplasty
95.00%
0.027
90.90%
< 0.001
86.70%
< 0.001
1( 08) Prolonged LVAD Support Effects Morbidity But Not Mortality Following Heart Transplant J.C. Grimm ,1 A.S. Shah,1 G.J. Whitman,1 C.M. Sciortino,1 J. Magruder,1 S.D. Russell,2 G.A. Ewald,3 S.C. Silvestry.4 1Surgery, The Johns Hopkins Medical Institution, Baltimore, MD; 2Medicine, The Johns Hopkins Medical Institution, Baltimore, MD; 3Medicine, Barnes Jewish Hospital, St. Louis, MO; 4Surgery, Barnes Jewish Hospital, St. Louis, MO. Purpose: The impact of the duration of ventricular assist device (VAD) therapy on outcomes following orthotopic heart transplantation (OHT) is unknown. Accordingly, we reviewed the experience of two institutions to determine whether prolonged (> 1 year) VAD support adversely affected patient survival and clinical outcomes following OHT. Methods: All adult (≥ 18 years of age) patients that underwent OHT between 2005 and 2012 at two institutions were retrospectively reviewed. Primary stratification by duration of therapy (> 1 year) was performed. Demographics, comorbid conditions, intraoperative variables and postoperative outcomes were abstracted from each institution’s database and compared between the cohorts. Differences in survival were analyzed by Kaplan-Meier estimates. Cox-proportional hazards regression modeling was employed to investigate the impact of extended VAD therapy on mortality. Results: During the study period, 41.9% (142/339) of patients that underwent OHT were bridged with a VAD. Therapy > 1 year was identified in 40.9% (58/142) of that population. Baseline demographics and comorbid conditions were similar between the two cohorts. Patients undergoing OHT > 1 year following VAD implantation experienced longer bypass times (p< 0.001), prolonged postoperative ventilation (p< 0.001) and a greater incidence of reoperations for bleeding (p= 0.049) and renal failure requiring dialysis
(p< 0.001). Despite the increased morbidity, duration of therapy did not affect, nor did it predict, 1- or 5-year survival. Conclusion: Bridge with a VAD > 1 year does not confer an increased risk of mortality after OHT. It does, however, appear to detrimentally impact the duration of mechanical ventilation and the occurrence of hemorrhage and renal dysfunction postoperatively. 1( 09) Effective Transcutaneous Energy Transfer Allows for More Than 6 Hours of Freedom From External Gear - The Future Is Here Y. Kassif ,1 M. Zilbershlag,2 M. Levy,2 S. Schueler.3 1Cardiac Surgery, Sheba Medical Center, Ramat Gan, Israel; 2Leviticus Cardio, Ramat Gan, Israel; 3cardiac surgery, Freeman Hospital, Newcastle upon Tyne, United Kingdom. Purpose: We have developed a unique Coplanar Energy Transfer (CET) system (Leviticus Cardio) which is a wireless energy transmission system to implantable Ventricular Assist Devices (VADs). Based upon previous successful in vitro testing, we have now tested the system in vivo. Methods: The CET system contains 3 parts: - The external gear (rechargeable batteries and an external controller attached to a belt, carrying a transmitter coil) - The implantable internal system ( receiver antenna, a small rechargeable battery, and a miniature controller) - The operator system enables programming and data acquisition using a tablet computer. The CET main features are: 1. Stable transmition and alignment over time despite animal rigorous movements 2. Prolonged internal battery operation The CET system was implanted in 5 pigs: in 3 pigs the Jarvik 2000 VADs were connected to the left ventricle and operated for 2, 9 and 24 hours, and in 2 pigs the HeartMate II LVADs were mounted on the animals’ back with an external mock circulation for up to 1 week. Results: Energy transmission was stable in all animals with no alignment interference (graph 1). While removing all external gear for 6-9 hours at 9000 RPM’s the power starts dropping, however, the LVAD was still operating successfully (Graph 3). Following reconnection the power returns to baseline levels (Graph 2). The fourth graph shows both observed and calculated times of freedom from external gear in different VADs. The latest experiments demonstrated stable energy transfer for up to 1 week until the experiment was terminated. Conclusion: The CET system is reliable and consistent thus providing high safety profile. Patients will not be troubled with malalignment, and enjoy prolonged internal battery operation that allows for more than 6 hours of freedom from external gear.
The Journal of Heart and Lung Transplantation, Vol 34, No 4S, April 2015
Conclusion: Our findings suggest that DPD ≥ 7 mmHg and, in particular, PH may evolve into prognostic markers for long-term outcome after HT. The importance and prognostic value of repeated haemodynamic measurements the first year after HT is emphasized by its association with reduced outcome, illustrating that pulmonary vascular changes may be present.
Conclusion: Recipient liver dysfunction is associated with reduced early and late graft survival, however the negative influence of liver dysfunction is amplified in patients with CF-LVAD explantation. These findings may be important for OHT and CF-LVAD patient selection.
1( 06)
1( 05) Influence of Liver Dysfunction in Patients Undergoing Heart Transplantation With Left Ventricular Assist Device Explantation: Comparative Analysis Using the MELD Excluding INR (MELD-XI) Scoring System S. Maltais ,1 M.E. Davis,1 M.R. Danter,1 J.M. Stulak,2 N.A. Haglund.3 1Cardiac Surgery, Vanderbilt Univ Med Ctr, Nashville, TN; 2Cardiac Surgery, Mayo Clinic, Rochester, TN; 3Cardiovascular Medicine, Vanderbilt Univ Med Ctr, Nashville, TN. Purpose: The effects of liver dysfunction in patients undergoing continuous-flow left ventricular assist device (CF-LVAD) explant at OHT is unknown. We investigated its effect on survival outcomes after CF-LVAD explantation-OHT. Methods: Adults undergoing OHT with or without CF-LVAD explantation between 2007 and 2014 were identified in the SRTR database. We utilized a Model for End-stage Liver Disease (MELD) eXcluding INR (MELD-XI) scoring system to define patients with liver dysfunction (score ≥ 17). Patients were stratified into four groups based liver dysfunction with or without CF-LVAD explantation at OHT and analyzed according to graft survival at 1 and 5 years. Results: Overall, 7598 patients with OHT were analyzed with an average MELD-XI score of 10.4±5.7. While 5838 patients (77%) underwent direct OHT during the study period, 1760 patients (23%) underwent OHT with CF-LVAD explantation (HeartMate II= 1661, 94%; HeartWare= 99, 6%). Liver dysfunction (MELD-XI ≥ 17) was identified in 693 patients (12%) undergoing direct OHT (Group A0) and 138 patients (8%) with LVAD explant-OHT (Group B0). For patients with MELD-XI < 17, direct OHT was performed in 5145 patients (Group A1), and CF-LVAD explant-OHT in 1622 patients (Group B1). Kaplan-Meier analysis revealed an association between a high MELD-XI score and decreased post-transplant graft survival in direct OHT and CF-LVAD explant-OHT groups (Figure; p< 0.001). After adjusting for covariates, Cox regression analysis revealed patients bridged with CF-LVADs, recipients with MELD-XI ≥ 17, higher BMI and higher creatinine had increased risk of graft failure (all p< 0.001).
Rubidium Positron Emission Tomography and Coronary Flow Reserve Predicts Graft Function After Heart Transplant J. Kawano , J. Patel, M. Kittleson, F. Liou, D. Wong, G. Jamero, B. Azarbal, D.H. Chang, L. Czer, A. Trento, J.A. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: Cardiac allograft vasculopathy (CAV) is a major factor limiting survival after heart transplant. CAV may present as small vessel or microvascular disease, which is correlated with reduced coronary flow reserve (CFR). CFR is commonly performed through intracoronary flow wire. Recently, rubidium positron emission tomography (PET) scanning has become a reliable test to demonstrate CFR. We reviewed patients with low CFR (CFR< 2) and assessed them for cardiac dysfunction as defined by decreased left ventricular ejection fraction (LVEF), increased left ventricular end diastolic volume index (LVEDVI) and left ventricular enlargement. Methods: We assessed 36 patients transplanted between 1994 and 2013 and who underwent routine rubidium PET scanning between 2011 and 2014 at their annual visit. Patients with established coronary disease were excluded. CFR was determined by rubidium PET scanning. Additional concomitant information of LVEF at rest and post stress, LVEDVI at rest and post-stress, and left ventricular enlargement was recorded. Results: 9 patients had a low CFR. The low CFR group had significantly decreased LVEF post-stress and a trend towards decreased LVEF at rest. The low CFR group also had significantly higher LVEDVI at rest and post-stress. A significantly larger percentage of patients had left ventricular enlargement in the low CFR group (see table). Conclusion: Low CFR is associated with cardiac dysfunction which may be due to small vessel coronary disease in the absence of epicardial CAV. Rubidium PET may have a role in determining small vessel disease in heart transplant patients.
Endpoints
CFR < 2.00 (n= 9)
CFR > 2.00 (n= 27) P-Value
Average LVEF Rest Average LVEF Post Stress Average EDVI Rest Average EDVI Post Stress % LV Enlargement
48.7 ± 23.1 51.3 ± 24.0 69.9 ± 46.6 74.6 ± 55.1 44.40%
59.7 ± 11.9 64.0 ± 11.9 46.6 ± 16.2 50.4 ± 15.8 7.40%
0.070 0.042 0.030 0.044 0.025
Abstracts S49 1( 07) Do Abnormal Regadenoson Scans Predict Subsequent Poor Outcome? J. Kawano , M. Kittleson, J. Patel, B. Azarbal, F. Liou, S. Siddiqui, D. Wong, D.H. Chang, D. Ramzy, L. Czer, J.A. Kobashigawa. Cedars-Sinai Heart Institute, Los Angeles, CA. Purpose: Cardiac allograft vasculopathy (CAV) is one of the major factors limiting long-term survival after heart transplantation. The use of annual coronary angiograms is an invasive procedure with inherent potential complications. Non-invasive testing such as dobutamine stress echocardiography has been demonstrated to have prognostic outcome after heart transplant. The use of regadenoson nuclear scans has been of increasing use in the recent past as another non-invasive means to detect CAV. It is not clear whether these nuclear scans are predictive of subsequent poor outcome. Methods: Between 1994 and 2012 we assessed 225 of heart transplant patients who underwent a regadenoson scan. Patients were divided into those who had normal regadenoson scans and those with abnormal regadenoson scans. An abnormal regadenoson scan was defined as a scan with any fixed perfusion defects and/or reversible defects. Outcomes including 1-year subsequent survival, freedom from left ventricular (LV) dysfunction and freedom from percutaneous coronary intervention (PCI)/angioplasty were assessed. Results: 1-year subsequent survival and freedom from LV dysfunction and PCI/angioplasty were significantly lower in patients with abnormal scans (see table). There was no difference between fixed defects versus any reversible defects for outcome. Conclusion: Abnormal regadenoson scans are predictive of poor outcome after heart transplantation. Aggressive strategies such as more frequent angiograms or re-transplant for select patients should be considered.
Endpoints
Normal Regadeno- Abnormal Regadenoson Scan (n= 165) son Scan (n= 60) P-value
1-year Subsequent Actuarial 99.40% Survival 1-year Subsequent Actuarial 100.00% Freedom from LV Dysfunction 1-year Subsequent Actuarial 100.00% Freedom from PCI/Angioplasty
95.00%
0.027
90.90%
< 0.001
86.70%
< 0.001
1( 08) Prolonged LVAD Support Effects Morbidity But Not Mortality Following Heart Transplant J.C. Grimm ,1 A.S. Shah,1 G.J. Whitman,1 C.M. Sciortino,1 J. Magruder,1 S.D. Russell,2 G.A. Ewald,3 S.C. Silvestry.4 1Surgery, The Johns Hopkins Medical Institution, Baltimore, MD; 2Medicine, The Johns Hopkins Medical Institution, Baltimore, MD; 3Medicine, Barnes Jewish Hospital, St. Louis, MO; 4Surgery, Barnes Jewish Hospital, St. Louis, MO. Purpose: The impact of the duration of ventricular assist device (VAD) therapy on outcomes following orthotopic heart transplantation (OHT) is unknown. Accordingly, we reviewed the experience of two institutions to determine whether prolonged (> 1 year) VAD support adversely affected patient survival and clinical outcomes following OHT. Methods: All adult (≥ 18 years of age) patients that underwent OHT between 2005 and 2012 at two institutions were retrospectively reviewed. Primary stratification by duration of therapy (> 1 year) was performed. Demographics, comorbid conditions, intraoperative variables and postoperative outcomes were abstracted from each institution’s database and compared between the cohorts. Differences in survival were analyzed by Kaplan-Meier estimates. Cox-proportional hazards regression modeling was employed to investigate the impact of extended VAD therapy on mortality. Results: During the study period, 41.9% (142/339) of patients that underwent OHT were bridged with a VAD. Therapy > 1 year was identified in 40.9% (58/142) of that population. Baseline demographics and comorbid conditions were similar between the two cohorts. Patients undergoing OHT > 1 year following VAD implantation experienced longer bypass times (p< 0.001), prolonged postoperative ventilation (p< 0.001) and a greater incidence of reoperations for bleeding (p= 0.049) and renal failure requiring dialysis
(p< 0.001). Despite the increased morbidity, duration of therapy did not affect, nor did it predict, 1- or 5-year survival. Conclusion: Bridge with a VAD > 1 year does not confer an increased risk of mortality after OHT. It does, however, appear to detrimentally impact the duration of mechanical ventilation and the occurrence of hemorrhage and renal dysfunction postoperatively. 1( 09) Effective Transcutaneous Energy Transfer Allows for More Than 6 Hours of Freedom From External Gear - The Future Is Here Y. Kassif ,1 M. Zilbershlag,2 M. Levy,2 S. Schueler.3 1Cardiac Surgery, Sheba Medical Center, Ramat Gan, Israel; 2Leviticus Cardio, Ramat Gan, Israel; 3cardiac surgery, Freeman Hospital, Newcastle upon Tyne, United Kingdom. Purpose: We have developed a unique Coplanar Energy Transfer (CET) system (Leviticus Cardio) which is a wireless energy transmission system to implantable Ventricular Assist Devices (VADs). Based upon previous successful in vitro testing, we have now tested the system in vivo. Methods: The CET system contains 3 parts: - The external gear (rechargeable batteries and an external controller attached to a belt, carrying a transmitter coil) - The implantable internal system ( receiver antenna, a small rechargeable battery, and a miniature controller) - The operator system enables programming and data acquisition using a tablet computer. The CET main features are: 1. Stable transmition and alignment over time despite animal rigorous movements 2. Prolonged internal battery operation The CET system was implanted in 5 pigs: in 3 pigs the Jarvik 2000 VADs were connected to the left ventricle and operated for 2, 9 and 24 hours, and in 2 pigs the HeartMate II LVADs were mounted on the animals’ back with an external mock circulation for up to 1 week. Results: Energy transmission was stable in all animals with no alignment interference (graph 1). While removing all external gear for 6-9 hours at 9000 RPM’s the power starts dropping, however, the LVAD was still operating successfully (Graph 3). Following reconnection the power returns to baseline levels (Graph 2). The fourth graph shows both observed and calculated times of freedom from external gear in different VADs. The latest experiments demonstrated stable energy transfer for up to 1 week until the experiment was terminated. Conclusion: The CET system is reliable and consistent thus providing high safety profile. Patients will not be troubled with malalignment, and enjoy prolonged internal battery operation that allows for more than 6 hours of freedom from external gear.