- Email: [email protected]
233
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Abstracts
graft to the subclavian artery and 3) a small rotary pump implanted in a pacemaker pocket. We sought to investigate the hemodynamic inand outflow conditions of such an approach. Methods: Pumps were implanted in seven sheep (mean 75 ⫾6 kg). The pump itself was positioned subcutaneously and the inflow cannula was inserted in the left atrium through a small thoracotomy. The outflow graft was sutured to the left carotid artery as a substitute for the human subclavian artery. Flow and pressure distribution was measured at implantation and on termination of the experiments (4 weeks). Pumps were operated on lowest flow conditions for worse case testing (20000 rpm). No anticoagulants or any other drugs were administered. Animals were euthanized and an autopsy was performed to investigate local histological effects and peripheral emboli. Results: At implantation, mean pump flow was 2.6 ⫾1L/min and 68 ⫾0.1 % of flow was directed toward the body. The blood pressure gradient between the left carotid artery and the rest of the body was 18 ⫾4 mmHg in systole and 27.6 ⫾7mmHg in diastole. At termination, 85 ⫾2% of pump flow was directed towards the body. The blood pressure gradient decreased to 5 ⫾8 mmHg in systole and 8 ⫾8 mmHg in diastole. Autopsies showed no specific cardiac findings or peripheral emboli. The carotid artery showed preserved anatomy and endothelium at the level of and proximal to the outflow. Conclusion: Partial support with inflow from the left atrium and outflow to a peripheral vessel is feasible. Vascular adaptation and compliance allow the flow to be more directed toward the body than toward the distal outflow of the vessel. This approach allows a minimal invasive support for patients in chronic heart failure. Disclosure: Circulite paid the cost of the research to investigate the hemodynamic performance of this device. 231 EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) FOR PRIMARY GRAFT DYSFUNCTION (PGD) AFTER LUNG TRANSPLANTATION: ANALYSIS OF THE EXTRACORPOREAL LIFE SUPPORT ORGANISATION (ELSO) REGISTRY S. Fischer,1 D. Bohn,2 P. Rycus,3 A.F. Pierre,1 M. de Perrot,1 T.K. Waddell,1 S. Keshavjee,1 1Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada; 2Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 3 Extracorporeal Life Support Organization (ELSO), University of Michigan, Ann Arbor, MI Some patients with severe primary graft dysfunction (PGD) after lung transplantation (LTx) require extracorporeal gas exchange using ECMO as a life saving treatment option. A few single center experiences have been reported with relatively few cases of ECMO after LTx. We reviewed the ELSO registry, which was established with the intention to improve quality and outcome of extracorporeal life support (ECLS) in pts treated with ECMO applied for all indications. Currently 31,340 pts are included; 151 were post-LTx ECMO pts with PGD (age 35⫾18 yrs). Indications for LTx were: ARDS (15%), CF (15%), IPF (8%), PPH (10%), emphysema (15%), acute lung failure (11%), and ‘other’ (23%) (unknown: 3%). Bilateral LTx was performed in 69 and single LTx in 74 pts (unknown: 8). ECMO run time was 140⫾212 hrs. Veno-ven. ECMO was used in 25, veno-art. in 89, and other modes in 15 pts (unknown: 22). ECMO was discontinued in 93 pts due to lung recovery. It was discontinued in: 29 pts with MOF, 22 pts that died with no further specification, and in 7 pts for other reasons. In total, 63 (42%) pts survived the hospital stay. Major complications during ECMO included hemorrhage (52%), hemodialysis/-filtration (42%), neurological (12%) and cardiac (28%) complications, inotropic support (77%), and sepsis (15%). Although the ELSO registry was not primarily established to study ECMO in LTx, it provides valuable insights and evidence that there is indeed an appreciable salvage rate with the use of ECMO for PGD after LTx.
The Journal of Heart and Lung Transplantation February 2006
Clearly this is a very high risk patient population and no single center can accumulate a large experience of ECMO for this specific indication. This data however underscores the importance of developing a specific registry for pts put on ECLS devices so that we can better study the outcomes, determine optimum treatment strategies, patient and device selection, and indications so as to improve the outcomes of pts requiring this unique therapy. 232 RIGHT VENTRICULAR ASSIST DEVICE IS BETTER THAN EXTRACORPOREAL MEMBRANE OXYGENATION FOR ISOLATED RIGHT VENTRICULAR FAILURE FOLLOWING HEART TRANSPLANTATION Y. Toyoda,1 K.R. McCurry,1 B.G. Hattler,1 M.A. Zenati,1 H. Tsukui,1 A.J. Boujoukos,2 R.L. Kormos,1 1Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA; 2 Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA Purpose: Mechanical circulatory support for primary graft failure after orthotopic heart transplantation (OHTx) includes extracorporeal membrane oxygenation (ECMO) or isolated right ventricular assist device (RVAD). The optimal strategy and subsequent outcome is not well documented. Methods: Between 4/1997– 4/2005, 34/285 consecutive OHTx recipients (12%) required mechanical circulatory support for primary graft failure (MS group), including veno-arterial ECMO (n⫽24), RVAD (n⫽9), or bi-ventricular assistance (n⫽1). These patients were compared to 251 patients who did not require support (Control). Results: ECMO was used for poor oxygenation (n⫽2), bi-ventricular failure (n⫽11) or isolated right ventricular failure (n⫽11), and RVAD for isolated right ventricular failure (n⫽9). The MS group received 78.4⫾8.2 hours of support, and had significantly (p⬍0.05 vs. Control) longer graft ischemic time (223⫾15 vs. 186⫾4 minutes), and increased preoperative systolic pulmonary artery pressure and pulmonary vascular resistance (55⫾3 vs. 48⫾1 mmHg and 3.4⫾0.5 vs. 2.6⫾0.1 Wood units). Thirty-day, 1-year, and 5-year actuarial survival was reduced to 41%, 34% and 34% in MS group compared to 97%, 89%, and 74% in Control (p⬍0.01). In those surviving mechanical support, there was no difference in 1-year and 5-year survival (84% and 84% in MS group) compared to control (91% and 76%). For patients with isolated right ventricular failure, 30-day, 1-year and 5-year survival was better (p⬍0.05) with RVAD (89%, 71% and 71%) compared to ECMO (18%, 9% and 9%). The incidence of complications including stroke, sepsis and multiple organ failure was higher with ECMO vs. RVAD (54% vs. 11%, p⬍0.05). Conclusion: These data indicate that mechanical circulatory support for isolated right ventricular failure following OHTx is better (p⬍0.05) with RVAD vs. ECMO, and its use does not affect long-term OHTx survival. 233 THE EFFECTS OF HYPERPERFUSION ON POSTOPERATIVE NEUROLOGIC DYSFUNCTION IN RECIPIENTS OF LEFTVENTRICULAR ASSIST DEVICE K. Lietz,1 K. Brown,2 R. John,3 D. Anderson,2 L. Joyce,3 L.W. Miller,1 1Cardiovascular Division, University of Minnesota, Minneapolis, MN; 2Division of Neurology, University of Minnesota, Minneapolis, MN; 3Division of Cardiothoracic Surgery, University of Minnesota, Minneapolis, MN Background: Cerebral hyperperfusion syndrome is a life-threatening condition described in pts with chronically hypoperfused cerebral vasculature whose normal cerebral circulation was reestablished after
The Journal of Heart and Lung Transplantation Volume 25, Number 2S
carotid endaretectomy or implantation of left-ventricular assist device (LVAD). Neurologic dysfunction (ND) in these pts is believed to result from inability of cerebral vasculature to accommodate to rapidly increasing perfusion pressures. Patients: We describe the effects of increased blood flow on the incidence of ND in 40 consecutive LVAD HeartMate XVE recipients btw Jan 2002 and Mar 2004 (mean age: 52.4 yrs, male 82.5%, ischemic heart disease 80%). Perioperative ND was defined as permanent/ transient central neurologic deficit, confusion and unresponsive coma for ⬎ 24 hrs, which developed within 30 days after LVAD implantation. Result: Fourteen pts (25%) developed ND after LVAD implantation, including encephalopathy (n⫽10) and coma (n⫽4). By univariate analysis risk factors for ND included: LVAD rate ⬎ 65 bpm (RR⫽3.6, p⫽0.03), stroke volume ⬎ 77 mL (RR⫽3.86, p⫽0.04), flow ⬎ 5 L/min (RR⫽2.9, p⫽0.05), systolic blood pressure ⬎ 110 mmHg (RR⫽2.5, p⫽0.09) and increased cardiac output (CO) ⬎ 50% when compared to the preimplantation baseline. By multivariate analysis, the increase of CO ⬎ 50% after LVAD implantation was the single predictor of postoperative ND (RR⫽4.7, p⫽0.01), and was found in 58% of pts at the time of neurologic event vs. 4.3% of asymptomatic pts shortly after LVAD implant, p⬍0.001. Among 14 pts with ND, reduction of LVAD flow led to improvement of symptoms in all 11 pts, whereas 3 pts whose LVAD settings were not changed continued to deteriorate. Conclusion: Rapid and excessive increase of blood flow may overload cerebral autoregulation in susceptible heart failure pts following LVAD implantation. Slow postoperative titration of LVAD flow to target CO increase not greater than 50% from baseline may help prevent or reverse neurologic symptoms in LVAD recipients.
234 EFFECT OF CLENBUTEROL ON CARDIAC AND SKELETAL MUSCLE FUNCTION DURING LVAD SUPPORT I. George,1 S. Xydas,1 J. Lamanca,2 P. Colley,1 C. Petrilli,2 D. Mancini,2 M. DiTullio,2 C. Marboe,3 E. Shane,4 Y. Naka,1 M.C. Oz,1 S. Maybaum,2 1Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY; 2 Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY; 3Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY; 4 Department of Endocrinology, Columbia University College of Physicians and Surgeons, New York, NY Background: While clenbuterol may improve cardiac function during LVAD support, its effects on skeletal muscle and functional capacity are unknown. Methods: Eight subjects (5 ischemic, 3 non-ischemic) were enrolled 5– 46 weeks post-LVAD implantation. Subjects continued their standard CHF regimen and received clenbuterol to a maximal daily dose of 720 mcg. Echocardiography at reduced LVAD support (4 L/min), cardiopulmonary exercise testing, body composition analysis, and quadriceps maximal voluntary contraction (MVC) were performed at baseline and after 3 months of clenbuterol therapy. Myocyte size and collagen deposition were measured at device implantation and explantation in 4 subjects. Results: One subject dropped out before receiving clenbuterol. All remaining subjects reached target dose with no serious adverse events or arrhythmias. CPK was elevated in 4 subjects (range 314 – 1497 mg/dl). Ejection fraction (LVEF) was reduced in all but one subject, with a significant increase in ventricular dimension. Body weight, lean mass, and quadriceps cross-sectional area significantly increased during the study. Exercise capacity did not change, but MVC significantly improved. No significant change in myocyte size or collagen deposition was seen.
Abstracts
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Conclusion: Although no significant change in LVEF was seen, clenbuterol increased skeletal muscle mass and strength and prevented the expected reduction in myocyte size. Baseline and Post-Treatment Testing HR (bpm) LV EDD (cm) LV EF (%) LV Mass (g) Peak VO2 (ml/kg/min) MVC (kg) CSA (cm2) Body Weight (lbs) Lean Mass (kg) Fat Mass (kg)
Pre-Clenbuterol
Post-Clenbuterol
71 ⫾ 11 4.7 ⫾ 0.7 33.6 ⫾ 9.5 159 ⫾ 45 14.4 ⫾ 3.7 37.0 ⫾ 15.7 76.3 ⫾ 16.9 166 ⫾ 39 21.1 ⫾ 8.9 6.8 ⫾ 3.3
84 ⫾ 10 5.2 ⫾ 0.7ⴱ 30.6 ⫾ 8.2 185 ⫾ 66 14.5 ⫾ 3.5 45.8 ⫾ 20.6ⴱ 86.6 ⫾ 26.1ⴱ 177 ⫾ 46ⴱ 23.6 ⫾ 9.7ⴱ 7.4 ⫾ 3.7
ⴱ p ⬍ 0.05 vs pre-clenbuterol, HR, heart rate; LV, left ventricular; EDD, end-diastolic dimension; EF, ejection fraction; VO2, oxygen consumption; MVC, maximal voluntary contraction; CSA, Cross Sectional Area.
235 TACROLIMUS IN COMBINATION, TACROLIMUS ALONE COMPARED (TICTAC TRIAL): A PROSPECTIVE RANDOMIZED TRIAL OF MINIMIZED IMMUNOSUPPRESSION IN ADULT HEART TRANSPLANT RECIPIENTS D.A. Baran,1 M.J. Zucker,1 L.H. Arroyo,1 M.M. Alwarshetty,1 M.R. Ramirez,1 S. Pinney,2 S. Lubitz,2 A.L. Gass,2 J. McCahill,1 S. Pardi,1 J. Prevost-Fernandez,1 T.W. Prendergast,1 D.J. Goldstein,1 M. Camacho,1 S. Shah,1 M. Cohen,1 1Heart Transplant Center, Newark Beth Israel Medical Center, Newark, NJ; 2 Cardiovascular Institute, Mt. Sinai Medical Center, New York, NY Background: Previous retrospective studies have shown that tacrolimus monotherapy (TAC) is feasible in heart transplant patients (txp pts). We conducted a prospective, randomized, open-label, twocenter trial comparing TAC/mycophenolate mofetil (MMF) therapy to TAC monotherapy. It was hypothesized that allograft rejection would be similar between groups. Methods: From 4/04 – 8/05, 50 de novo adult txp patients were enrolled. Induction therapy was not utilized. All pts received TAC/MMF/ steroids and randomized to either discontinue MMF at 2 weeks post-txp (“MONO”), or remain on TAC /MMF (“COMBO”). Steroids were weaned in all pts, with a target of 4 –5 months in the first 25 pts and over 2–3 months thereafter. Target TAC levels were 9 –11 ng/dl in both groups. The primary endpoint was mean 6 month ISHLT biopsy score. Results: 25 pts were randomized to MONO and 25 to COMBO. Age, gender, and race were similar between groups. Left ventricular assist devices were required pre-txp in 16 pts; 8 pts in each group. The time to steroid discontinuation was not significantly different beween groups (mean 167⫾ 80 days with MONO vs. 150⫾ 75 days COMBO, p⫽0.50). Weaning was quicker in the 2nd half of the study (92⫾ 24 days MONO vs. 102⫾ 34 days COMBO, p⫽0.54). The primary endpoint, mean 6-month biopsy score was significantly lower in MONO pts (0.41⫾ 0.05, MONO vs. 0.55 ⫾ 0.05, COMBO, p⫽0.004, Wilcoxon). There was 1 asymptomatic rejection ⱖ 3A with MONO vs. 2 episodes with COMBO (one with hemodynamic compromise). Cytomegalovirus infection was not seen. One death which could not be attributed to rejection (negative biopsies and autopsy) occurred in the MONO group. Conclusion: TAC monotherapy was associated with significantly less allograft rejection as assessed by mean biopsy score. Steroid weaning was well tolerated in both groups, even with an accelerated course. Longer-term follow-up is awaited to confirm these findings. Disclosure: The author is the recipient of a research grant and speaker honorarium from Astellas.
Abstracts
graft to the subclavian artery and 3) a small rotary pump implanted in a pacemaker pocket. We sought to investigate the hemodynamic inand outflow conditions of such an approach. Methods: Pumps were implanted in seven sheep (mean 75 ⫾6 kg). The pump itself was positioned subcutaneously and the inflow cannula was inserted in the left atrium through a small thoracotomy. The outflow graft was sutured to the left carotid artery as a substitute for the human subclavian artery. Flow and pressure distribution was measured at implantation and on termination of the experiments (4 weeks). Pumps were operated on lowest flow conditions for worse case testing (20000 rpm). No anticoagulants or any other drugs were administered. Animals were euthanized and an autopsy was performed to investigate local histological effects and peripheral emboli. Results: At implantation, mean pump flow was 2.6 ⫾1L/min and 68 ⫾0.1 % of flow was directed toward the body. The blood pressure gradient between the left carotid artery and the rest of the body was 18 ⫾4 mmHg in systole and 27.6 ⫾7mmHg in diastole. At termination, 85 ⫾2% of pump flow was directed towards the body. The blood pressure gradient decreased to 5 ⫾8 mmHg in systole and 8 ⫾8 mmHg in diastole. Autopsies showed no specific cardiac findings or peripheral emboli. The carotid artery showed preserved anatomy and endothelium at the level of and proximal to the outflow. Conclusion: Partial support with inflow from the left atrium and outflow to a peripheral vessel is feasible. Vascular adaptation and compliance allow the flow to be more directed toward the body than toward the distal outflow of the vessel. This approach allows a minimal invasive support for patients in chronic heart failure. Disclosure: Circulite paid the cost of the research to investigate the hemodynamic performance of this device. 231 EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO) FOR PRIMARY GRAFT DYSFUNCTION (PGD) AFTER LUNG TRANSPLANTATION: ANALYSIS OF THE EXTRACORPOREAL LIFE SUPPORT ORGANISATION (ELSO) REGISTRY S. Fischer,1 D. Bohn,2 P. Rycus,3 A.F. Pierre,1 M. de Perrot,1 T.K. Waddell,1 S. Keshavjee,1 1Toronto Lung Transplant Program, Toronto General Hospital, Toronto, ON, Canada; 2Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; 3 Extracorporeal Life Support Organization (ELSO), University of Michigan, Ann Arbor, MI Some patients with severe primary graft dysfunction (PGD) after lung transplantation (LTx) require extracorporeal gas exchange using ECMO as a life saving treatment option. A few single center experiences have been reported with relatively few cases of ECMO after LTx. We reviewed the ELSO registry, which was established with the intention to improve quality and outcome of extracorporeal life support (ECLS) in pts treated with ECMO applied for all indications. Currently 31,340 pts are included; 151 were post-LTx ECMO pts with PGD (age 35⫾18 yrs). Indications for LTx were: ARDS (15%), CF (15%), IPF (8%), PPH (10%), emphysema (15%), acute lung failure (11%), and ‘other’ (23%) (unknown: 3%). Bilateral LTx was performed in 69 and single LTx in 74 pts (unknown: 8). ECMO run time was 140⫾212 hrs. Veno-ven. ECMO was used in 25, veno-art. in 89, and other modes in 15 pts (unknown: 22). ECMO was discontinued in 93 pts due to lung recovery. It was discontinued in: 29 pts with MOF, 22 pts that died with no further specification, and in 7 pts for other reasons. In total, 63 (42%) pts survived the hospital stay. Major complications during ECMO included hemorrhage (52%), hemodialysis/-filtration (42%), neurological (12%) and cardiac (28%) complications, inotropic support (77%), and sepsis (15%). Although the ELSO registry was not primarily established to study ECMO in LTx, it provides valuable insights and evidence that there is indeed an appreciable salvage rate with the use of ECMO for PGD after LTx.
The Journal of Heart and Lung Transplantation February 2006
Clearly this is a very high risk patient population and no single center can accumulate a large experience of ECMO for this specific indication. This data however underscores the importance of developing a specific registry for pts put on ECLS devices so that we can better study the outcomes, determine optimum treatment strategies, patient and device selection, and indications so as to improve the outcomes of pts requiring this unique therapy. 232 RIGHT VENTRICULAR ASSIST DEVICE IS BETTER THAN EXTRACORPOREAL MEMBRANE OXYGENATION FOR ISOLATED RIGHT VENTRICULAR FAILURE FOLLOWING HEART TRANSPLANTATION Y. Toyoda,1 K.R. McCurry,1 B.G. Hattler,1 M.A. Zenati,1 H. Tsukui,1 A.J. Boujoukos,2 R.L. Kormos,1 1Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA; 2 Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA Purpose: Mechanical circulatory support for primary graft failure after orthotopic heart transplantation (OHTx) includes extracorporeal membrane oxygenation (ECMO) or isolated right ventricular assist device (RVAD). The optimal strategy and subsequent outcome is not well documented. Methods: Between 4/1997– 4/2005, 34/285 consecutive OHTx recipients (12%) required mechanical circulatory support for primary graft failure (MS group), including veno-arterial ECMO (n⫽24), RVAD (n⫽9), or bi-ventricular assistance (n⫽1). These patients were compared to 251 patients who did not require support (Control). Results: ECMO was used for poor oxygenation (n⫽2), bi-ventricular failure (n⫽11) or isolated right ventricular failure (n⫽11), and RVAD for isolated right ventricular failure (n⫽9). The MS group received 78.4⫾8.2 hours of support, and had significantly (p⬍0.05 vs. Control) longer graft ischemic time (223⫾15 vs. 186⫾4 minutes), and increased preoperative systolic pulmonary artery pressure and pulmonary vascular resistance (55⫾3 vs. 48⫾1 mmHg and 3.4⫾0.5 vs. 2.6⫾0.1 Wood units). Thirty-day, 1-year, and 5-year actuarial survival was reduced to 41%, 34% and 34% in MS group compared to 97%, 89%, and 74% in Control (p⬍0.01). In those surviving mechanical support, there was no difference in 1-year and 5-year survival (84% and 84% in MS group) compared to control (91% and 76%). For patients with isolated right ventricular failure, 30-day, 1-year and 5-year survival was better (p⬍0.05) with RVAD (89%, 71% and 71%) compared to ECMO (18%, 9% and 9%). The incidence of complications including stroke, sepsis and multiple organ failure was higher with ECMO vs. RVAD (54% vs. 11%, p⬍0.05). Conclusion: These data indicate that mechanical circulatory support for isolated right ventricular failure following OHTx is better (p⬍0.05) with RVAD vs. ECMO, and its use does not affect long-term OHTx survival. 233 THE EFFECTS OF HYPERPERFUSION ON POSTOPERATIVE NEUROLOGIC DYSFUNCTION IN RECIPIENTS OF LEFTVENTRICULAR ASSIST DEVICE K. Lietz,1 K. Brown,2 R. John,3 D. Anderson,2 L. Joyce,3 L.W. Miller,1 1Cardiovascular Division, University of Minnesota, Minneapolis, MN; 2Division of Neurology, University of Minnesota, Minneapolis, MN; 3Division of Cardiothoracic Surgery, University of Minnesota, Minneapolis, MN Background: Cerebral hyperperfusion syndrome is a life-threatening condition described in pts with chronically hypoperfused cerebral vasculature whose normal cerebral circulation was reestablished after
The Journal of Heart and Lung Transplantation Volume 25, Number 2S
carotid endaretectomy or implantation of left-ventricular assist device (LVAD). Neurologic dysfunction (ND) in these pts is believed to result from inability of cerebral vasculature to accommodate to rapidly increasing perfusion pressures. Patients: We describe the effects of increased blood flow on the incidence of ND in 40 consecutive LVAD HeartMate XVE recipients btw Jan 2002 and Mar 2004 (mean age: 52.4 yrs, male 82.5%, ischemic heart disease 80%). Perioperative ND was defined as permanent/ transient central neurologic deficit, confusion and unresponsive coma for ⬎ 24 hrs, which developed within 30 days after LVAD implantation. Result: Fourteen pts (25%) developed ND after LVAD implantation, including encephalopathy (n⫽10) and coma (n⫽4). By univariate analysis risk factors for ND included: LVAD rate ⬎ 65 bpm (RR⫽3.6, p⫽0.03), stroke volume ⬎ 77 mL (RR⫽3.86, p⫽0.04), flow ⬎ 5 L/min (RR⫽2.9, p⫽0.05), systolic blood pressure ⬎ 110 mmHg (RR⫽2.5, p⫽0.09) and increased cardiac output (CO) ⬎ 50% when compared to the preimplantation baseline. By multivariate analysis, the increase of CO ⬎ 50% after LVAD implantation was the single predictor of postoperative ND (RR⫽4.7, p⫽0.01), and was found in 58% of pts at the time of neurologic event vs. 4.3% of asymptomatic pts shortly after LVAD implant, p⬍0.001. Among 14 pts with ND, reduction of LVAD flow led to improvement of symptoms in all 11 pts, whereas 3 pts whose LVAD settings were not changed continued to deteriorate. Conclusion: Rapid and excessive increase of blood flow may overload cerebral autoregulation in susceptible heart failure pts following LVAD implantation. Slow postoperative titration of LVAD flow to target CO increase not greater than 50% from baseline may help prevent or reverse neurologic symptoms in LVAD recipients.
234 EFFECT OF CLENBUTEROL ON CARDIAC AND SKELETAL MUSCLE FUNCTION DURING LVAD SUPPORT I. George,1 S. Xydas,1 J. Lamanca,2 P. Colley,1 C. Petrilli,2 D. Mancini,2 M. DiTullio,2 C. Marboe,3 E. Shane,4 Y. Naka,1 M.C. Oz,1 S. Maybaum,2 1Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY; 2 Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY; 3Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY; 4 Department of Endocrinology, Columbia University College of Physicians and Surgeons, New York, NY Background: While clenbuterol may improve cardiac function during LVAD support, its effects on skeletal muscle and functional capacity are unknown. Methods: Eight subjects (5 ischemic, 3 non-ischemic) were enrolled 5– 46 weeks post-LVAD implantation. Subjects continued their standard CHF regimen and received clenbuterol to a maximal daily dose of 720 mcg. Echocardiography at reduced LVAD support (4 L/min), cardiopulmonary exercise testing, body composition analysis, and quadriceps maximal voluntary contraction (MVC) were performed at baseline and after 3 months of clenbuterol therapy. Myocyte size and collagen deposition were measured at device implantation and explantation in 4 subjects. Results: One subject dropped out before receiving clenbuterol. All remaining subjects reached target dose with no serious adverse events or arrhythmias. CPK was elevated in 4 subjects (range 314 – 1497 mg/dl). Ejection fraction (LVEF) was reduced in all but one subject, with a significant increase in ventricular dimension. Body weight, lean mass, and quadriceps cross-sectional area significantly increased during the study. Exercise capacity did not change, but MVC significantly improved. No significant change in myocyte size or collagen deposition was seen.
Abstracts
S125
Conclusion: Although no significant change in LVEF was seen, clenbuterol increased skeletal muscle mass and strength and prevented the expected reduction in myocyte size. Baseline and Post-Treatment Testing HR (bpm) LV EDD (cm) LV EF (%) LV Mass (g) Peak VO2 (ml/kg/min) MVC (kg) CSA (cm2) Body Weight (lbs) Lean Mass (kg) Fat Mass (kg)
Pre-Clenbuterol
Post-Clenbuterol
71 ⫾ 11 4.7 ⫾ 0.7 33.6 ⫾ 9.5 159 ⫾ 45 14.4 ⫾ 3.7 37.0 ⫾ 15.7 76.3 ⫾ 16.9 166 ⫾ 39 21.1 ⫾ 8.9 6.8 ⫾ 3.3
84 ⫾ 10 5.2 ⫾ 0.7ⴱ 30.6 ⫾ 8.2 185 ⫾ 66 14.5 ⫾ 3.5 45.8 ⫾ 20.6ⴱ 86.6 ⫾ 26.1ⴱ 177 ⫾ 46ⴱ 23.6 ⫾ 9.7ⴱ 7.4 ⫾ 3.7
ⴱ p ⬍ 0.05 vs pre-clenbuterol, HR, heart rate; LV, left ventricular; EDD, end-diastolic dimension; EF, ejection fraction; VO2, oxygen consumption; MVC, maximal voluntary contraction; CSA, Cross Sectional Area.
235 TACROLIMUS IN COMBINATION, TACROLIMUS ALONE COMPARED (TICTAC TRIAL): A PROSPECTIVE RANDOMIZED TRIAL OF MINIMIZED IMMUNOSUPPRESSION IN ADULT HEART TRANSPLANT RECIPIENTS D.A. Baran,1 M.J. Zucker,1 L.H. Arroyo,1 M.M. Alwarshetty,1 M.R. Ramirez,1 S. Pinney,2 S. Lubitz,2 A.L. Gass,2 J. McCahill,1 S. Pardi,1 J. Prevost-Fernandez,1 T.W. Prendergast,1 D.J. Goldstein,1 M. Camacho,1 S. Shah,1 M. Cohen,1 1Heart Transplant Center, Newark Beth Israel Medical Center, Newark, NJ; 2 Cardiovascular Institute, Mt. Sinai Medical Center, New York, NY Background: Previous retrospective studies have shown that tacrolimus monotherapy (TAC) is feasible in heart transplant patients (txp pts). We conducted a prospective, randomized, open-label, twocenter trial comparing TAC/mycophenolate mofetil (MMF) therapy to TAC monotherapy. It was hypothesized that allograft rejection would be similar between groups. Methods: From 4/04 – 8/05, 50 de novo adult txp patients were enrolled. Induction therapy was not utilized. All pts received TAC/MMF/ steroids and randomized to either discontinue MMF at 2 weeks post-txp (“MONO”), or remain on TAC /MMF (“COMBO”). Steroids were weaned in all pts, with a target of 4 –5 months in the first 25 pts and over 2–3 months thereafter. Target TAC levels were 9 –11 ng/dl in both groups. The primary endpoint was mean 6 month ISHLT biopsy score. Results: 25 pts were randomized to MONO and 25 to COMBO. Age, gender, and race were similar between groups. Left ventricular assist devices were required pre-txp in 16 pts; 8 pts in each group. The time to steroid discontinuation was not significantly different beween groups (mean 167⫾ 80 days with MONO vs. 150⫾ 75 days COMBO, p⫽0.50). Weaning was quicker in the 2nd half of the study (92⫾ 24 days MONO vs. 102⫾ 34 days COMBO, p⫽0.54). The primary endpoint, mean 6-month biopsy score was significantly lower in MONO pts (0.41⫾ 0.05, MONO vs. 0.55 ⫾ 0.05, COMBO, p⫽0.004, Wilcoxon). There was 1 asymptomatic rejection ⱖ 3A with MONO vs. 2 episodes with COMBO (one with hemodynamic compromise). Cytomegalovirus infection was not seen. One death which could not be attributed to rejection (negative biopsies and autopsy) occurred in the MONO group. Conclusion: TAC monotherapy was associated with significantly less allograft rejection as assessed by mean biopsy score. Steroid weaning was well tolerated in both groups, even with an accelerated course. Longer-term follow-up is awaited to confirm these findings. Disclosure: The author is the recipient of a research grant and speaker honorarium from Astellas.