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Continuous-Flow LVAD Support Alters Gastrointestinal Vascularity: A Likely Contributor to LVAD-Associated Gastrointestinal Bleeding
Abstracts S251 or pump thrombosis (group 1= 12.24% vs. group 2= 9.67%, p= 0.723) were found between the 2 groups. Conclusion: Our study showed a high prevalence of use of triple therapy in LVAD patients with no significant differences in bleeding, stroke or pump thrombosis risk when compared to patient receiving mono-antiplatelet therapy.
Methods: The medical records of 20 consecutive patients undergoing LVAD ex for thrombosis from January 2009 to July 2015 were reviewed. Thrombosis was defined as lactate dehydrogenase elevation 3x the upper limit of normal without alternative etiology. One patient with LVAD thrombosis who was exchanged to a BiVAD due to refractory VT was excluded. Results: Among 192 primary LVAD implants, the incidence of LVAD-T was 19.8% and VAD ex for LVAD-T was 53% (20/38). The mean time from initial LVAD surgery to LVAD-T requiring device exchange was 497 days (range 16-1486). In addition to hemolysis, 40% of pts presented with symptoms of HF, 60% with LVAD alarms or power spikes, and 15% with cardioembolic CVA. Peak LDH was higher for HVAD-related compared to HMII thrombotic events (3662±1492 vs. 1482±593, p< 0.001). Mean time from hospital admission to LVAD ex was 11 days (1-29). Primary exchanges included: 15 pts HMII to HMII; 4 HVAD to HVAD, 1 HMII to HVAD. 6 of 15 pts with HMII to HMII exchange had recurrent thrombosis. Median time to recurrences was 26 days. Recurrent thrombosis was not observed within 180 days in the HVAD to HVAD group. Among the HMII recurrent events, 2 pts were bridged to transplant with medical therapy and 4 pts underwent a second exchange from HMII to HVAD. No recurrences were observed in these 4 pts through 180 days. Survival to 180 days censored for heart transplant was 90%. 180 day survival free from thrombosis was 60%. The incidence of recurrent LVAD-T was 30 (FIGURE). Conclusion: Survival following LVAD exchange for thrombosis is good, however, recurrent thrombotic events are common. Further study of patient, surgical technique, and device specific factors predisposing to recurrence following exchange is required.
6( 82) Impact of Atrial Fibrillation on Pump Thrombosis and Thromboembolic Events in Long-Term Left Ventricular Assist Device Therapy D. Pedde , S. Soltani, F. Kaufmann, M. Müller, P. Pergantis, V. Falk, T. Krabatsch, E. Potapov. DHZB, Berlin, Germany. Purpose: Pump thrombosis (PT) and thromboembolic events (TEE) are severe complications in long-term left ventricular assist device (LVAD) therapy. The aim of the present study is the evaluation of impact of atrial fibrillation on these events in patients supported with HeartWare HVAD (HW). Methods: Incidence of visually confirmed PT and TEE such as peripheral arterial embolism and cerebral embolism was retrospectively analyzed in patients supported with primarily implanted HW (n= 250) that were implanted between 10/2012 and 06/2015 at our institute. Patients were divided into those suffering from atrial fibrillation (AF n= 185) and those showing sinus rhythm (SR n= 65) before surgery. Results: Median support time for all patients was 1.33 years (0-2.95) and 354 patient years. Patients with AF showed 0.05 events per patient year (EPPY) for PT vs. 0.08 EPPY in the SR group (p= 0.441). Patients with AF showed 0.1 EPPY for TEE vs 0.05 EPPY in the SR group (p= 0.120). Kaplan-Meier analysis of survival probability showed no difference between the two groups. Conclusion: Our preliminary study showed that preoperative AF has no impact on PT and TEE. We are currently evaluating 400 more patients to increase the power of our analysis and will present the results at the congress. 6( 83) A Single Center Experience of Device Exchange for Continuous Flow Left Ventricular Assist Device Thrombosis K.J. Morine ,1 D. Mehak,1 J.N. Upshaw,1 D.T. Pham,2 N.K. Kapur,1 A.R. Vest,1 D. DeNofrio,1 M.S. Kiernan.1 1Tufts Medical Center, Boston, MA; 2Northwestern Memorial Hospital, Chicago, IL. Purpose: Our goal was to review the management and outcomes of patients undergoing LVAD ex secondary to thrombosis.
6( 84) Continuous-Flow LVAD Support Alters Gastrointestinal Vascularity: A Likely Contributor to LVAD-Associated Gastrointestinal Bleeding J. Kang ,1 P. Kwiatkowski,2 M. Acker,1 P. Atluri,1 P. McConnell,2 C.R. Bartoli.1 1University of Pennsylvania, Philadelphia, PA, PA; 2The Ohio State University, Columbus, OH, OH. Purpose: Bleeding from gastrointestinal angiodysplasia is a major source of morbidity during prolonged mechanical circulatory support. We tested the hypothesis that continuous-flow left ventricular assist device (LVAD) support alters gastrointestinal vascularity and promotes gastrointestinal angiodysplasia. Methods: Small bowel was obtained from deceased humans (n= 2 HeartMate II, n= 1 HVAD, 242±50 days support; n= 4 controls), sheep (n= 3 HeartMate II, 38±2 days support; n= 2 controls), and cows (n= 2 MVAD, 90±0 days support; n= 4 controls) after continuous-flow LVAD support. Transmural tissue sections were stained with FITC-conjugated isolectin-B4 for endothelium to demarcate vascular structures. Vascular density was defined by the area occupied by isolectin-B4 stain to the area of tissue sampled. Images were viewed with epifluorescence microscopy and analyzed with ImageJ Imaging Software. Results: Gastrointestinal vascular density was significantly higher among LVAD samples versus controls (Figure 1, 5.1±1.0 vs. 2.3±0.4 %, p= 0.01). Human vascular density was greater in LVAD patients versus controls (4.8±1.5 vs. 2.3±0.3 %). Likewise, ovine (3.0±0.5 vs. 0.7±0.03 %) and bovine (8.9±1.4 vs. 2.9±0.5 %) gastrointestinal vascular density was greater in animals that underwent LVAD support than in controls. Conclusion: Gastrointestinal vascular density increased in humans, sheep, and cows during prolonged continuous-flow LVAD support. These are the
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The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
first data to demonstrate altered gastrointestinal angiogenesis during LVAD support, which likely plays a major role in the high incidence of LVADassociated gastrointestinal bleeding.
6( 86) Elevated Preoperative Plasma Free Hemoglobin and Hemin May Predict LVAD Thrombosis D. Zhang , J. Kang, G. Redline, J. Howard, M. Acker, P. Atluri, C.R. Bartoli. University of Pennsylvania, Philadelphia, PA, PA.
6( 85) Discharge Lactate Dehydrogenase (LDH) Level Predicts Early Device Thrombosis in Patients with HEARTMATE II Left Ventricular Assist Devices: A Retrospective Cohort Analysis V.K. Topkara ,1 A.R. Garan,1 M. Yuzefpolskaya,1 K. Takeda,2 H. Takayama,2 R.C. Givens,1 J.A. Fried,1 F. Castagna,1 B. Cagliostro,1 M. Flannery,2 J.Z. Willey,3 S. Restaino,1 F. Latif,1 M.A. Farr,1 M. Maurer,1 D.M. Mancini,1 Y. Naka,2 P.C. Colombo.1 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY; 3Neurology, Columbia University, New York, NY. Purpose: Serum lactate dehydrogenase (LDH) has been used as a biomarker for detection of hemolysis and pump thrombosis in patients with left ventricular assist devices (LVADs). However, its ability to predict future thrombotic events in this population has not been fully characterized. Methods: Study population consists of all adult patients who underwent Heartmate II implantation at a large tertiary center from January 1, 2008 and October 1, 2015 who were successfully discharged. Patients who did not have LDH data at the time of hospital discharge were excluded from the study. Patients with level above and below average at discharge were followed for occurrence of device thrombosis (suspected and confirmed) and stroke. Results: 244 HeartMate II patients who were successfully discharged from index hospitalization were identified. Mean follow-up on device support was 16.9 ± 15.6 months. LDH level at the time of discharge was 350± 14 U/L. Patients with high LDH (> 350U/L) at discharge had significantly higher incidence of device thrombosis (21.8% vs. 8.4% at 1 year, Figure 1A), particularly within 3 months after hospital discharge. Risk of stroke in the post-discharge period was comparable between high and low LDH groups. Discharge LDH level had excellent discrimination for early device thrombosis with an AUC of 0.833 (p< 0.001, Figure 1B). LDH cut-off of 400 provided 66.7% sensitivity and 82.7% specificity for early device thrombosis. Discharge LDH levels have failed to discriminate late device thrombosis events (AUC 0.484, p= 0.796). Conclusion: Elevated LDH level at discharge is highly predictive of early device thrombosis in HeartMate II patients, however does not provide long-term prognostic information. Intensification of antithrombotic strategies should be considered in these patients if the bleeding risk is acceptable.
Purpose: Emerging evidence suggests a relationship between left ventricular assist device (LVAD)-associated hemolysis and LVAD thrombosis. Plasma iron species such as free hemoglobin, hemin, and free iron (Fe2+, Fe3+), which are produced during hemolysis, generate oxidative stress and may promote thrombogenesis. We determined whether plasma free iron species may be useful to predict patients at high risk for LVAD thrombosis. Methods: Patients undergoing continuous-flow LVAD support were studied (n= 23). Whole blood was obtained prior to LVAD implantation. Plasma free hemoglobin, hemin, Fe2+, and Fe3+ were measured. Plasma levels were compared between patients that developed LVAD thrombosis and those that did not. Results: Of the 23 patients studied, 8 patients developed LVAD thrombosis. In these 8 patients, preoperative plasma free hemoglobin (non-thrombosis patients 36±5 mg/dL vs. thrombosis patients 65±12 mg/dL, p= 0.01) and hemin (non-thrombosis patients 0.18±0.04 μ g/dL vs. thrombosis patients 0.42±0.15 μ g/dL, p= 0.05) were significantly elevated versus non-thrombosis patients. Preoperative Fe2+ and Fe3+ levels were not statistically different between non-thrombosis and thrombosis patients. Conclusion: Preoperative plasma free hemoglobin and hemin were significantly elevated in patients that developed LVAD thrombosis. Plasma free iron species may have utility to predict patients at high risk for LVAD thrombosis. 6( 87) The Use of Integrilin Alone or in Combination with Heparin or Argatroban for Suspected Pump Thrombosis in Patients with Left Ventricular Assist Devices A. Bitar , D. Abramov, R. Vijayakrishnan, A. Lenneman, J. Trivedi, T.H. Massey, A. Cheng, M. Slaughter, E.J. Birks. Jewish Hospital/ University of Louisville, Louisville, KY. Purpose: Pump thrombosis and hemolysis in patients with Left Ventricular Assist Devices (LVAD) are associated with significant morbidity. Intensification of medical therapy with anticoagulation has been suggested as potential therapy, with mixed results. The aim of the study is to assess the safety and efficacy of integrilin without or without an anticoagulation agent in managing patients with LVAD presenting with suspected pump thrombosis. Methods: This retrospective single center study was completed using the medical informatics system to identify patients who developed their first episode of suspected pump thrombosis post implantation between March 1st 2011 and July 30th 2015. The anticoagulation regiment and patient outcomes during the hospitalization for thrombosis/hemolysis were analyzed. Our anticoagulation protocol included integrilin with or without an anticoagulant. Successful medical therapy was defined as an improvement in LDH/pump parameters without death or pump exchange. Results: A total of 27 patients (23 HeartMateII, 4 HeartWare) were identified. The average age was 55 years (range 19-75) and time from implant to event averaged 513 days (range 35-1760). The average LDH on presentation was 1111 and 63% of patients had power elevations. The average INR on admission was INR 2.4, with INR of ≥ 2 in 21/27 patients. All patients received integrilin: 10 received integrilin only, 9 received integrilin and argatroban and 8 received integrilin and heparin. Warfarin was continued in 25/27 patients.
Methods: The medical records of 20 consecutive patients undergoing LVAD ex for thrombosis from January 2009 to July 2015 were reviewed. Thrombosis was defined as lactate dehydrogenase elevation 3x the upper limit of normal without alternative etiology. One patient with LVAD thrombosis who was exchanged to a BiVAD due to refractory VT was excluded. Results: Among 192 primary LVAD implants, the incidence of LVAD-T was 19.8% and VAD ex for LVAD-T was 53% (20/38). The mean time from initial LVAD surgery to LVAD-T requiring device exchange was 497 days (range 16-1486). In addition to hemolysis, 40% of pts presented with symptoms of HF, 60% with LVAD alarms or power spikes, and 15% with cardioembolic CVA. Peak LDH was higher for HVAD-related compared to HMII thrombotic events (3662±1492 vs. 1482±593, p< 0.001). Mean time from hospital admission to LVAD ex was 11 days (1-29). Primary exchanges included: 15 pts HMII to HMII; 4 HVAD to HVAD, 1 HMII to HVAD. 6 of 15 pts with HMII to HMII exchange had recurrent thrombosis. Median time to recurrences was 26 days. Recurrent thrombosis was not observed within 180 days in the HVAD to HVAD group. Among the HMII recurrent events, 2 pts were bridged to transplant with medical therapy and 4 pts underwent a second exchange from HMII to HVAD. No recurrences were observed in these 4 pts through 180 days. Survival to 180 days censored for heart transplant was 90%. 180 day survival free from thrombosis was 60%. The incidence of recurrent LVAD-T was 30 (FIGURE). Conclusion: Survival following LVAD exchange for thrombosis is good, however, recurrent thrombotic events are common. Further study of patient, surgical technique, and device specific factors predisposing to recurrence following exchange is required.
6( 82) Impact of Atrial Fibrillation on Pump Thrombosis and Thromboembolic Events in Long-Term Left Ventricular Assist Device Therapy D. Pedde , S. Soltani, F. Kaufmann, M. Müller, P. Pergantis, V. Falk, T. Krabatsch, E. Potapov. DHZB, Berlin, Germany. Purpose: Pump thrombosis (PT) and thromboembolic events (TEE) are severe complications in long-term left ventricular assist device (LVAD) therapy. The aim of the present study is the evaluation of impact of atrial fibrillation on these events in patients supported with HeartWare HVAD (HW). Methods: Incidence of visually confirmed PT and TEE such as peripheral arterial embolism and cerebral embolism was retrospectively analyzed in patients supported with primarily implanted HW (n= 250) that were implanted between 10/2012 and 06/2015 at our institute. Patients were divided into those suffering from atrial fibrillation (AF n= 185) and those showing sinus rhythm (SR n= 65) before surgery. Results: Median support time for all patients was 1.33 years (0-2.95) and 354 patient years. Patients with AF showed 0.05 events per patient year (EPPY) for PT vs. 0.08 EPPY in the SR group (p= 0.441). Patients with AF showed 0.1 EPPY for TEE vs 0.05 EPPY in the SR group (p= 0.120). Kaplan-Meier analysis of survival probability showed no difference between the two groups. Conclusion: Our preliminary study showed that preoperative AF has no impact on PT and TEE. We are currently evaluating 400 more patients to increase the power of our analysis and will present the results at the congress. 6( 83) A Single Center Experience of Device Exchange for Continuous Flow Left Ventricular Assist Device Thrombosis K.J. Morine ,1 D. Mehak,1 J.N. Upshaw,1 D.T. Pham,2 N.K. Kapur,1 A.R. Vest,1 D. DeNofrio,1 M.S. Kiernan.1 1Tufts Medical Center, Boston, MA; 2Northwestern Memorial Hospital, Chicago, IL. Purpose: Our goal was to review the management and outcomes of patients undergoing LVAD ex secondary to thrombosis.
6( 84) Continuous-Flow LVAD Support Alters Gastrointestinal Vascularity: A Likely Contributor to LVAD-Associated Gastrointestinal Bleeding J. Kang ,1 P. Kwiatkowski,2 M. Acker,1 P. Atluri,1 P. McConnell,2 C.R. Bartoli.1 1University of Pennsylvania, Philadelphia, PA, PA; 2The Ohio State University, Columbus, OH, OH. Purpose: Bleeding from gastrointestinal angiodysplasia is a major source of morbidity during prolonged mechanical circulatory support. We tested the hypothesis that continuous-flow left ventricular assist device (LVAD) support alters gastrointestinal vascularity and promotes gastrointestinal angiodysplasia. Methods: Small bowel was obtained from deceased humans (n= 2 HeartMate II, n= 1 HVAD, 242±50 days support; n= 4 controls), sheep (n= 3 HeartMate II, 38±2 days support; n= 2 controls), and cows (n= 2 MVAD, 90±0 days support; n= 4 controls) after continuous-flow LVAD support. Transmural tissue sections were stained with FITC-conjugated isolectin-B4 for endothelium to demarcate vascular structures. Vascular density was defined by the area occupied by isolectin-B4 stain to the area of tissue sampled. Images were viewed with epifluorescence microscopy and analyzed with ImageJ Imaging Software. Results: Gastrointestinal vascular density was significantly higher among LVAD samples versus controls (Figure 1, 5.1±1.0 vs. 2.3±0.4 %, p= 0.01). Human vascular density was greater in LVAD patients versus controls (4.8±1.5 vs. 2.3±0.3 %). Likewise, ovine (3.0±0.5 vs. 0.7±0.03 %) and bovine (8.9±1.4 vs. 2.9±0.5 %) gastrointestinal vascular density was greater in animals that underwent LVAD support than in controls. Conclusion: Gastrointestinal vascular density increased in humans, sheep, and cows during prolonged continuous-flow LVAD support. These are the
S252
The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016
first data to demonstrate altered gastrointestinal angiogenesis during LVAD support, which likely plays a major role in the high incidence of LVADassociated gastrointestinal bleeding.
6( 86) Elevated Preoperative Plasma Free Hemoglobin and Hemin May Predict LVAD Thrombosis D. Zhang , J. Kang, G. Redline, J. Howard, M. Acker, P. Atluri, C.R. Bartoli. University of Pennsylvania, Philadelphia, PA, PA.
6( 85) Discharge Lactate Dehydrogenase (LDH) Level Predicts Early Device Thrombosis in Patients with HEARTMATE II Left Ventricular Assist Devices: A Retrospective Cohort Analysis V.K. Topkara ,1 A.R. Garan,1 M. Yuzefpolskaya,1 K. Takeda,2 H. Takayama,2 R.C. Givens,1 J.A. Fried,1 F. Castagna,1 B. Cagliostro,1 M. Flannery,2 J.Z. Willey,3 S. Restaino,1 F. Latif,1 M.A. Farr,1 M. Maurer,1 D.M. Mancini,1 Y. Naka,2 P.C. Colombo.1 1Medicine, Columbia University, New York, NY; 2Surgery, Columbia University, New York, NY; 3Neurology, Columbia University, New York, NY. Purpose: Serum lactate dehydrogenase (LDH) has been used as a biomarker for detection of hemolysis and pump thrombosis in patients with left ventricular assist devices (LVADs). However, its ability to predict future thrombotic events in this population has not been fully characterized. Methods: Study population consists of all adult patients who underwent Heartmate II implantation at a large tertiary center from January 1, 2008 and October 1, 2015 who were successfully discharged. Patients who did not have LDH data at the time of hospital discharge were excluded from the study. Patients with level above and below average at discharge were followed for occurrence of device thrombosis (suspected and confirmed) and stroke. Results: 244 HeartMate II patients who were successfully discharged from index hospitalization were identified. Mean follow-up on device support was 16.9 ± 15.6 months. LDH level at the time of discharge was 350± 14 U/L. Patients with high LDH (> 350U/L) at discharge had significantly higher incidence of device thrombosis (21.8% vs. 8.4% at 1 year, Figure 1A), particularly within 3 months after hospital discharge. Risk of stroke in the post-discharge period was comparable between high and low LDH groups. Discharge LDH level had excellent discrimination for early device thrombosis with an AUC of 0.833 (p< 0.001, Figure 1B). LDH cut-off of 400 provided 66.7% sensitivity and 82.7% specificity for early device thrombosis. Discharge LDH levels have failed to discriminate late device thrombosis events (AUC 0.484, p= 0.796). Conclusion: Elevated LDH level at discharge is highly predictive of early device thrombosis in HeartMate II patients, however does not provide long-term prognostic information. Intensification of antithrombotic strategies should be considered in these patients if the bleeding risk is acceptable.
Purpose: Emerging evidence suggests a relationship between left ventricular assist device (LVAD)-associated hemolysis and LVAD thrombosis. Plasma iron species such as free hemoglobin, hemin, and free iron (Fe2+, Fe3+), which are produced during hemolysis, generate oxidative stress and may promote thrombogenesis. We determined whether plasma free iron species may be useful to predict patients at high risk for LVAD thrombosis. Methods: Patients undergoing continuous-flow LVAD support were studied (n= 23). Whole blood was obtained prior to LVAD implantation. Plasma free hemoglobin, hemin, Fe2+, and Fe3+ were measured. Plasma levels were compared between patients that developed LVAD thrombosis and those that did not. Results: Of the 23 patients studied, 8 patients developed LVAD thrombosis. In these 8 patients, preoperative plasma free hemoglobin (non-thrombosis patients 36±5 mg/dL vs. thrombosis patients 65±12 mg/dL, p= 0.01) and hemin (non-thrombosis patients 0.18±0.04 μ g/dL vs. thrombosis patients 0.42±0.15 μ g/dL, p= 0.05) were significantly elevated versus non-thrombosis patients. Preoperative Fe2+ and Fe3+ levels were not statistically different between non-thrombosis and thrombosis patients. Conclusion: Preoperative plasma free hemoglobin and hemin were significantly elevated in patients that developed LVAD thrombosis. Plasma free iron species may have utility to predict patients at high risk for LVAD thrombosis. 6( 87) The Use of Integrilin Alone or in Combination with Heparin or Argatroban for Suspected Pump Thrombosis in Patients with Left Ventricular Assist Devices A. Bitar , D. Abramov, R. Vijayakrishnan, A. Lenneman, J. Trivedi, T.H. Massey, A. Cheng, M. Slaughter, E.J. Birks. Jewish Hospital/ University of Louisville, Louisville, KY. Purpose: Pump thrombosis and hemolysis in patients with Left Ventricular Assist Devices (LVAD) are associated with significant morbidity. Intensification of medical therapy with anticoagulation has been suggested as potential therapy, with mixed results. The aim of the study is to assess the safety and efficacy of integrilin without or without an anticoagulation agent in managing patients with LVAD presenting with suspected pump thrombosis. Methods: This retrospective single center study was completed using the medical informatics system to identify patients who developed their first episode of suspected pump thrombosis post implantation between March 1st 2011 and July 30th 2015. The anticoagulation regiment and patient outcomes during the hospitalization for thrombosis/hemolysis were analyzed. Our anticoagulation protocol included integrilin with or without an anticoagulant. Successful medical therapy was defined as an improvement in LDH/pump parameters without death or pump exchange. Results: A total of 27 patients (23 HeartMateII, 4 HeartWare) were identified. The average age was 55 years (range 19-75) and time from implant to event averaged 513 days (range 35-1760). The average LDH on presentation was 1111 and 63% of patients had power elevations. The average INR on admission was INR 2.4, with INR of ≥ 2 in 21/27 patients. All patients received integrilin: 10 received integrilin only, 9 received integrilin and argatroban and 8 received integrilin and heparin. Warfarin was continued in 25/27 patients.