- Email: [email protected]
399: Geometry of the Right Ventricle as Predictor of Right Ventricular Function after LVAD Implantation
S204
Abstracts
successfully treated rejection events. Eight patients were successfully treated for bronchitis or pneumonia and one for an invasive anastomotic fungal infection with Candida albicans. No patient developed CMV pneumonia. All subjects had normal renal function throughout the post-transplant course (mean creatinine 1.0⫾0.3mg/dL). The average tacrolimus level within 3 months post transplantation was 10.5⫾1.6ng/mL. T cell characteristics within 7 days post-transplant were on average; CD3 26.4⫾10/mcL (nl 700-2700), CD4 14.6⫾9/mcL (425-2000) and CD19 2.9/mcL⫾2.2 (120-520). Conclusions: Campath successfully reduces the need for systemic immunosuppression early after transplantation. The average rejection rate was acceptable on a low level maintenance immunosuppressive regimen.
397 Weaning from Left Ventricular Assist Devices in Patients with Idiopathic Dilated Cardiomyopathy: Prediction of PostWeaning Cardiac Stability M. Dandel,1 Y. Weng,1 H. Siniawski,1 E. Potapov,1 T. Drews,1 H. Lehmkuhl,1 C. Knosalla,1 R. Hetzer,1 1Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany Purpose: During unloading clinical recovery which allows weaning from VADs is possible. After 12 years of weaning experience, we searched for parameters that are predictive for post-weaning cardiac stability and thus helpful for future weaning decisions. Methods and Materials: With regard to potential prediction of weaning success we evaluated echocardiographic parameters obtained at final “off pump” trials before VAD explantation, histological changes, serum anti-1-adrenoreceptor autoantibody (A-1-AA) disappearance during unloading, duration of mechanical support and HF duration before VAD implantation. Among 80 patients weaned since 3/1995, a homogenous group of 35 patients with idiopathic dilated cardiomyopathy (IDCM) weaned from LVADs were evaluated. Results: The 8-year post-weaning survival was 78.1⫾8.2%. Freedom from HF recurrence at 4 years after weaning was 69.3⫾8.1%. Patients with cardiac stability were younger, history of HF and recovery time during unloading shorter, LV short/long axis ratio lower (less spherical) and systolic wall motion velocity higher (p⬍0.05). For LVEF ⱖ 45% at LV enddiastolic diameter (LVEDD) ⱕ55mm the positive predictive value for ⱖ4years cardiac stability reached 90.5%. There was no HF recurrence during the first 4 years in patients with LVEF ⱖ45%, LVEDD ⱕ55% and history of HF ⬍5 years. Time course of LVEF during the first 6 months also appeared predictive for long-term stability after weaning. History of HF ⬎ 5 years showed a predictive value of 90% for HF recurrence during the first 3 years. Neither reduction in myocardial hypertrophy and fibrosis nor serum A-1-AA disappearance during unloading were predictive for post-weaning cardiac stability. Conclusions: Off-pump LVEF and LVEDD, time course of LVEF during the first 6 post-weaning months and HF duration are predictive for the outcome after LVAD removal in IDCM patients. Patients’ age, altered LV geometry, low wall motion velocity and prolonged LVAD support until improvement (⬎ 6 months) are be risk factors for HF recurrence.
398 Exercise Performance and Hemodynamic Unloading in Patients with an Axial Flow Pump in Comparison to Pulsatile Devices
The Journal of Heart and Lung Transplantation February 2008
N. De Jonge,1 H. Kirkels,1 C. Klopping,1 H.M. Nathoe,1 H. Kemperman,2 J.R. Lahpor,1 1Division Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands; 2Clinical Chemistry, University Medical Center Utrecht, Utrecht, Netherlands Purpose: Axial flow pumps like the HearMate-2 (HM-2) are increasingly used as bridge to transplant and for destination therapy. The physiology of the HM-2 is completely different than the pulsatile, pusher-plate pumps like the HeartMate-1 (HM-1). We sought to determine if this difference in pump physiology has impact on the unloading of the heart and the exercise performance after implantation. Methods and Materials: Treadmill exercise testing 3 months after LVAD implantation was performed in 40 patients (pts) (38⫾13 yrs) on a HM-1 and compared to 9 pts (48⫾11 yrs) on a HM-2. HM-1 pumps were operated in the automatic mode; HM-2 operated at a fixed rotor speed of 9400-9800 RPM. Peak VO2 was expressed in ml/kg/min and as percentage of predicted according to Jones, to compensate for the difference in age between groups. The degree of unloading of the heart was determined by BNP plasma levels pre and 3 months post LVAD implantation. Results: Functional class improved from IV to I in all pts. Peak VO2 was 20.2⫾4.8 ml/kg/min in HM-1, vs. 17.9⫾2.9 in HM-2 pts. Expressed as percentage of predicted, there was no difference between groups: 53⫾ 12 % in HM-1 pts, vs. 55⫾8 % in HM-2 pts (p NS). BNP levels in HM-1 pts decreased from 1981⫾1052 to 124⫾91 pg/ml between pre-implant and 3 months after implant. In HM-2 pts it decreased from 2136⫾1325 to 278⫾209. Conclusions: Despite a completely different physiology between both LVAD designs, exercise performance and hemodynamic unloading, as determined by plasma BNP levels, 3 months after implantation is similar between both pumps. 399 Geometry of the Right Ventricle as Predictor of Right Ventricular Function after LVAD Implantation E.V. Potapov,1 A. Stepanenko,1 M. Dandel,1 M. Kukucka,2 T. Krabatsch,1 R. Hetzer,1 1Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2Anesthesiology, Deutsches Herzzentrum Berlin, Berlin, Germany Purpose: Right ventricular failure develops in 20-50% of patients after left ventricular assist device (LVAD) implantation, limiting the success of LVAD support. Identifying factors for predicting right heart failure after LVAD implantation is crucial for clinical practice. Methods and Materials: The preoperative echocardiographic parameters tricuspid regurgitation (TR), RV end diastolic diameter (cut-off 35 mm), RV ejection fraction (cut-off 30%), right atrial dimension (cut-off 50 mm) and short/long axis ratio (cut-off 0.6) were analyzed retrospectively in 47 patients in whom an LVAD was implanted in our institution between 1.1.1998 and 1.1.2006. Patients were divided into two groups: RV failure (n⫽8), defined by the occurrence of two of the following criteria in the first 48 hours after surgery: mean arterial pressure ⱕ55 mmHg, central venous pressure ⱖ16 mmHg, mixed venous saturation ⱕ55%, cardiac index ⬍2 l/min/m2, inotropic support score ⬎20 units or need for an RVAD; and a non-RV-failure group (n⫽39). Results: The RV failure group had a significantly higher short/long axis ratio of the RV (0.62 vs. 0.52, p⫽0.009). In patients with TR grade III-IV, two thirds developed RV failure versus 11% in patients with TR grade 0-II (p⫽0.009). In patients with short/long axis ratio of the RV of ⬍0.6, RV failure occurred in 7% vs. 60% in patients with ratio ⱖ0.6 (p⫽0.003).
The Journal of Heart and Lung Transplantation Volume 27, Number 2S
Abstracts
Conclusions: Preoperative evaluation of tricuspid regurgitation and RV geometry may help to select patients who would benefit from biventricular support.
S205
M. Strueber,1 F. Stefan,1 A.R. Simon,1 G. Warnecke,1 M. Dierich,2 A. Haverich,1 T. Welte,2 J. Gottlieb,2 1Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany; 2Pneumology, Hannover Medical School, Hannover, Germany
400 LVAD Risk Prediction Models: The Value of Getting Another Opinion J.C. Matthews,1 T.F. Dardas,1 T.M. Koelling,1 F.D. Pagani,2 K.D. Aaronson,1 1Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI; 2Section of Cardiac Surgery, University of Michigan, Ann Arbor, MI Purpose: To compare the performance of various LVAD risk prediction models in assessing postop death and morbidity. Methods and Materials: The Risk Factor Selection Scale (RFSS), Revised Screening (RSS) Scale, Right Ventricular Failure Risk Score (RVFRS) and Lietz-Miller Destination Therapy Score (LMDTS) (table 1) were used to estimate risk in 145 LVAD candidates. Subjects were dichotomized at published score thresholds. Hazard ratios (HR) for postop morbidities and 180 day death were calculated with Cox regression. Results: Mean scores for noncensored survivors (n⫽68) vs. deaths (n⫽20) were: RFSS⫽1.2⫾1.5 vs 2.8⫾2.2; RSS⫽0.87⫾1.7 vs 3.2⫾3.4; RVFRS⫽1.1⫾2.1 vs 3.5⫾2.9; and LMDTS⫽8.7⫾6.1 vs 13.3⫾5.2, respectively (all p⬍0.05). Table 2 shows the HR for postop death, renal and RV (RVAD) failure. Sensitivities (PPV) for the RFSS and LMDTS in identifying death were 15% (43%) and 60% (23%), while specificities for survival (NPV) were 97% (88%) and 68% (91%), respectively. The RVFRS was best for predicting renal and RV failure. Conclusions: The LVAD risk prediction models vary in their strengths and weaknesses. Implementation of more than one model may be useful for a full assessment of LVAD morbidity and mortality.
Table 1 RFSS
pts RSS
pts RVFRS
Urine ⬍30 cc/hr CVP ⬍16 Intubated
3
Intubated
4
2 2
Postcard shock 2 Preop LVAD 2
PT ⬎16 2 Redo Surgery 1
CVP ⬎16 PT ⬎16
1 1
pts LMDTS
Vasopressor 4 Cr ⱖ2.3 Bilirubin ⱖ2 AST ⱖ80
pts
Plateletsⱕ148 7
3 Albumin ⱕ3.3 5 2.5 INR ⬎1.1 4 2
Circulation 1995; J Thorac Cardiovasc JHLT 2007:26: 92: 169 Surg 2003;125:855 S104
Vasodilator 4 mPAP ⱕ25 3 AST ⬎45 2 HCT ⱕ34 2 BUN ⬎51 2 No inotrope 2 Circulation 2007; 116:497
Table 2 High-Risk Strata
RFSS ⬎5, N⫽7 RSS ⬎5, N⫽17 RVFRS ⬎5, N⫽19 LMDTS ⬎12, N⫽52
180 Day Death #(%) dead in HR strata
Renal Failure #(%) in HR strata
3(43) 7(41) 6(32) 12(23)
4(57) 7(41) 13(68) 14(27)
4.9 4.7 2.9 2.9
RVAD #(%) in strata
7.6 7(43) 4.0 7(41) 9.4 10(53) 2.1* 13(25)
HR 5.4 4.4 6.3 2.2*
*pⱖ0.05, all others ⬍0.05
401 Everolimus Versus Mycophenolatemofetil in De Novo Immunosuppression after Lung Transplantation – Interims Analysis of a Prospective, Randomized, Clinical Trial
Purpose: Triple drug immunosuppression is the established therapy for maintenance immunosuppression after lung transplantation (LTX). In this study Everolimus was compared to Mycophenolatemofetil (MMF) in combination with Ciclosporin A and corticosteroids in terms of adverse events and effectivity. Methods and Materials: In a prospective randomized single center trial patients were included on day 28 after successful LTX and randomized to the Everolimus or the MMF group. An Interims analysis was carried out after inclusion of 100 patients and a follow up of one year. Results: In the MMF group 4 of 50 patients expired within one year after LTX. There was no mortality in the Everolimus group (p⫽0.043). CMV Antigenemia was more common (p⫽0.012) in the MMF group (15 versus 3 cases). Bacterial infections were found more frequently (p⬍0.05) in the Everolimus group (23 versus 10 cases). The total incidence of acute rejection periods were comparable in both groups (60 Everolimus/ 52 MMF), as well as the incidence of BOS (1 case per group).The number of Pneumonias (5 versus 3) and the incidence of other lower respiratory tract infections (23 versus 31) were similar. Lung function increased to a best FeV1 of 77 ⫾ 18 % of predicted (Everolimus) and 83 ⫾ 20 % (MMF). Glomerular filtration rate (GFR) decreased significantly (p⬎0.001) within 12 months in both groups from 103 ⫾ 47 ml/min to 54 ⫾ 22 ml/min (Everolimus) and from 96 ⫾ 34ml/min to 48 ⫾ 18 ml/min (MMF). Drop outs due to severe side effects or recurrent acute rejections occurred in 12 patients of the Everolimus arm and in 13 of the MMF arm. Conclusions: A survival benefit in the Everolimus arm has to be verified by further follow up. CMV antigenemia was more frequent in the MMF group despite CMV prophylaxis. Bacterial infections were seen more often in the Everolimus treated patients. In both groups renal toxicity remains a major problem. Future studies should address the development of less (renal) toxic immunosuppressive therapies after successful LTX. 402 Complete 3 Year Analysis of a Prospective Randomized International Multi-Center Investigator Driven Study Comparing Tacrolimus and Cyclosporin A, Both in Combination with MMF and Steroids after Lung Transplantation in 249 Patients H. Reichenspurner,1 A. Glanville,3 A. Christina,3 R. Lama,7 B. Carlos,4 E. Marc,6 J.-D. Aubert,5 H. Treede,1 W. Klepetko,2 European and Australian Investigators in Lung Transplantation 1 Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany; 2University of Vienna, Vienna, Austria; 3University of Sydney, Sydney, Australia; 4University of Barcelona, Barcelona, Spain; 5University of Lausanne, Lausanne, Switzerland; 6University of Brussels, Brussels, Belgium; 7 University of Cordoba, Cordoba, Spain Purpose: This prospective randomized international investigator driven study was performed to compare the efficacy and safety of Tac, MMF, Steroids vs. CsA, MMF, Steroids after Lung Transplantation. Primary objective was the incidence of bronchiolitis obliterans syndrome (BOS). Secondary objectives were incidence of acute rejection and infection, survival and adverse events. Final data of 249 patients with a complete 3 year follow-up will be presented.
Abstracts
successfully treated rejection events. Eight patients were successfully treated for bronchitis or pneumonia and one for an invasive anastomotic fungal infection with Candida albicans. No patient developed CMV pneumonia. All subjects had normal renal function throughout the post-transplant course (mean creatinine 1.0⫾0.3mg/dL). The average tacrolimus level within 3 months post transplantation was 10.5⫾1.6ng/mL. T cell characteristics within 7 days post-transplant were on average; CD3 26.4⫾10/mcL (nl 700-2700), CD4 14.6⫾9/mcL (425-2000) and CD19 2.9/mcL⫾2.2 (120-520). Conclusions: Campath successfully reduces the need for systemic immunosuppression early after transplantation. The average rejection rate was acceptable on a low level maintenance immunosuppressive regimen.
397 Weaning from Left Ventricular Assist Devices in Patients with Idiopathic Dilated Cardiomyopathy: Prediction of PostWeaning Cardiac Stability M. Dandel,1 Y. Weng,1 H. Siniawski,1 E. Potapov,1 T. Drews,1 H. Lehmkuhl,1 C. Knosalla,1 R. Hetzer,1 1Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany Purpose: During unloading clinical recovery which allows weaning from VADs is possible. After 12 years of weaning experience, we searched for parameters that are predictive for post-weaning cardiac stability and thus helpful for future weaning decisions. Methods and Materials: With regard to potential prediction of weaning success we evaluated echocardiographic parameters obtained at final “off pump” trials before VAD explantation, histological changes, serum anti-1-adrenoreceptor autoantibody (A-1-AA) disappearance during unloading, duration of mechanical support and HF duration before VAD implantation. Among 80 patients weaned since 3/1995, a homogenous group of 35 patients with idiopathic dilated cardiomyopathy (IDCM) weaned from LVADs were evaluated. Results: The 8-year post-weaning survival was 78.1⫾8.2%. Freedom from HF recurrence at 4 years after weaning was 69.3⫾8.1%. Patients with cardiac stability were younger, history of HF and recovery time during unloading shorter, LV short/long axis ratio lower (less spherical) and systolic wall motion velocity higher (p⬍0.05). For LVEF ⱖ 45% at LV enddiastolic diameter (LVEDD) ⱕ55mm the positive predictive value for ⱖ4years cardiac stability reached 90.5%. There was no HF recurrence during the first 4 years in patients with LVEF ⱖ45%, LVEDD ⱕ55% and history of HF ⬍5 years. Time course of LVEF during the first 6 months also appeared predictive for long-term stability after weaning. History of HF ⬎ 5 years showed a predictive value of 90% for HF recurrence during the first 3 years. Neither reduction in myocardial hypertrophy and fibrosis nor serum A-1-AA disappearance during unloading were predictive for post-weaning cardiac stability. Conclusions: Off-pump LVEF and LVEDD, time course of LVEF during the first 6 post-weaning months and HF duration are predictive for the outcome after LVAD removal in IDCM patients. Patients’ age, altered LV geometry, low wall motion velocity and prolonged LVAD support until improvement (⬎ 6 months) are be risk factors for HF recurrence.
398 Exercise Performance and Hemodynamic Unloading in Patients with an Axial Flow Pump in Comparison to Pulsatile Devices
The Journal of Heart and Lung Transplantation February 2008
N. De Jonge,1 H. Kirkels,1 C. Klopping,1 H.M. Nathoe,1 H. Kemperman,2 J.R. Lahpor,1 1Division Heart and Lungs, University Medical Center Utrecht, Utrecht, Netherlands; 2Clinical Chemistry, University Medical Center Utrecht, Utrecht, Netherlands Purpose: Axial flow pumps like the HearMate-2 (HM-2) are increasingly used as bridge to transplant and for destination therapy. The physiology of the HM-2 is completely different than the pulsatile, pusher-plate pumps like the HeartMate-1 (HM-1). We sought to determine if this difference in pump physiology has impact on the unloading of the heart and the exercise performance after implantation. Methods and Materials: Treadmill exercise testing 3 months after LVAD implantation was performed in 40 patients (pts) (38⫾13 yrs) on a HM-1 and compared to 9 pts (48⫾11 yrs) on a HM-2. HM-1 pumps were operated in the automatic mode; HM-2 operated at a fixed rotor speed of 9400-9800 RPM. Peak VO2 was expressed in ml/kg/min and as percentage of predicted according to Jones, to compensate for the difference in age between groups. The degree of unloading of the heart was determined by BNP plasma levels pre and 3 months post LVAD implantation. Results: Functional class improved from IV to I in all pts. Peak VO2 was 20.2⫾4.8 ml/kg/min in HM-1, vs. 17.9⫾2.9 in HM-2 pts. Expressed as percentage of predicted, there was no difference between groups: 53⫾ 12 % in HM-1 pts, vs. 55⫾8 % in HM-2 pts (p NS). BNP levels in HM-1 pts decreased from 1981⫾1052 to 124⫾91 pg/ml between pre-implant and 3 months after implant. In HM-2 pts it decreased from 2136⫾1325 to 278⫾209. Conclusions: Despite a completely different physiology between both LVAD designs, exercise performance and hemodynamic unloading, as determined by plasma BNP levels, 3 months after implantation is similar between both pumps. 399 Geometry of the Right Ventricle as Predictor of Right Ventricular Function after LVAD Implantation E.V. Potapov,1 A. Stepanenko,1 M. Dandel,1 M. Kukucka,2 T. Krabatsch,1 R. Hetzer,1 1Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 2Anesthesiology, Deutsches Herzzentrum Berlin, Berlin, Germany Purpose: Right ventricular failure develops in 20-50% of patients after left ventricular assist device (LVAD) implantation, limiting the success of LVAD support. Identifying factors for predicting right heart failure after LVAD implantation is crucial for clinical practice. Methods and Materials: The preoperative echocardiographic parameters tricuspid regurgitation (TR), RV end diastolic diameter (cut-off 35 mm), RV ejection fraction (cut-off 30%), right atrial dimension (cut-off 50 mm) and short/long axis ratio (cut-off 0.6) were analyzed retrospectively in 47 patients in whom an LVAD was implanted in our institution between 1.1.1998 and 1.1.2006. Patients were divided into two groups: RV failure (n⫽8), defined by the occurrence of two of the following criteria in the first 48 hours after surgery: mean arterial pressure ⱕ55 mmHg, central venous pressure ⱖ16 mmHg, mixed venous saturation ⱕ55%, cardiac index ⬍2 l/min/m2, inotropic support score ⬎20 units or need for an RVAD; and a non-RV-failure group (n⫽39). Results: The RV failure group had a significantly higher short/long axis ratio of the RV (0.62 vs. 0.52, p⫽0.009). In patients with TR grade III-IV, two thirds developed RV failure versus 11% in patients with TR grade 0-II (p⫽0.009). In patients with short/long axis ratio of the RV of ⬍0.6, RV failure occurred in 7% vs. 60% in patients with ratio ⱖ0.6 (p⫽0.003).
The Journal of Heart and Lung Transplantation Volume 27, Number 2S
Abstracts
Conclusions: Preoperative evaluation of tricuspid regurgitation and RV geometry may help to select patients who would benefit from biventricular support.
S205
M. Strueber,1 F. Stefan,1 A.R. Simon,1 G. Warnecke,1 M. Dierich,2 A. Haverich,1 T. Welte,2 J. Gottlieb,2 1Cardiothoracic, Transplant, and Vascular Surgery, Hannover Medical School, Hannover, Germany; 2Pneumology, Hannover Medical School, Hannover, Germany
400 LVAD Risk Prediction Models: The Value of Getting Another Opinion J.C. Matthews,1 T.F. Dardas,1 T.M. Koelling,1 F.D. Pagani,2 K.D. Aaronson,1 1Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI; 2Section of Cardiac Surgery, University of Michigan, Ann Arbor, MI Purpose: To compare the performance of various LVAD risk prediction models in assessing postop death and morbidity. Methods and Materials: The Risk Factor Selection Scale (RFSS), Revised Screening (RSS) Scale, Right Ventricular Failure Risk Score (RVFRS) and Lietz-Miller Destination Therapy Score (LMDTS) (table 1) were used to estimate risk in 145 LVAD candidates. Subjects were dichotomized at published score thresholds. Hazard ratios (HR) for postop morbidities and 180 day death were calculated with Cox regression. Results: Mean scores for noncensored survivors (n⫽68) vs. deaths (n⫽20) were: RFSS⫽1.2⫾1.5 vs 2.8⫾2.2; RSS⫽0.87⫾1.7 vs 3.2⫾3.4; RVFRS⫽1.1⫾2.1 vs 3.5⫾2.9; and LMDTS⫽8.7⫾6.1 vs 13.3⫾5.2, respectively (all p⬍0.05). Table 2 shows the HR for postop death, renal and RV (RVAD) failure. Sensitivities (PPV) for the RFSS and LMDTS in identifying death were 15% (43%) and 60% (23%), while specificities for survival (NPV) were 97% (88%) and 68% (91%), respectively. The RVFRS was best for predicting renal and RV failure. Conclusions: The LVAD risk prediction models vary in their strengths and weaknesses. Implementation of more than one model may be useful for a full assessment of LVAD morbidity and mortality.
Table 1 RFSS
pts RSS
pts RVFRS
Urine ⬍30 cc/hr CVP ⬍16 Intubated
3
Intubated
4
2 2
Postcard shock 2 Preop LVAD 2
PT ⬎16 2 Redo Surgery 1
CVP ⬎16 PT ⬎16
1 1
pts LMDTS
Vasopressor 4 Cr ⱖ2.3 Bilirubin ⱖ2 AST ⱖ80
pts
Plateletsⱕ148 7
3 Albumin ⱕ3.3 5 2.5 INR ⬎1.1 4 2
Circulation 1995; J Thorac Cardiovasc JHLT 2007:26: 92: 169 Surg 2003;125:855 S104
Vasodilator 4 mPAP ⱕ25 3 AST ⬎45 2 HCT ⱕ34 2 BUN ⬎51 2 No inotrope 2 Circulation 2007; 116:497
Table 2 High-Risk Strata
RFSS ⬎5, N⫽7 RSS ⬎5, N⫽17 RVFRS ⬎5, N⫽19 LMDTS ⬎12, N⫽52
180 Day Death #(%) dead in HR strata
Renal Failure #(%) in HR strata
3(43) 7(41) 6(32) 12(23)
4(57) 7(41) 13(68) 14(27)
4.9 4.7 2.9 2.9
RVAD #(%) in strata
7.6 7(43) 4.0 7(41) 9.4 10(53) 2.1* 13(25)
HR 5.4 4.4 6.3 2.2*
*pⱖ0.05, all others ⬍0.05
401 Everolimus Versus Mycophenolatemofetil in De Novo Immunosuppression after Lung Transplantation – Interims Analysis of a Prospective, Randomized, Clinical Trial
Purpose: Triple drug immunosuppression is the established therapy for maintenance immunosuppression after lung transplantation (LTX). In this study Everolimus was compared to Mycophenolatemofetil (MMF) in combination with Ciclosporin A and corticosteroids in terms of adverse events and effectivity. Methods and Materials: In a prospective randomized single center trial patients were included on day 28 after successful LTX and randomized to the Everolimus or the MMF group. An Interims analysis was carried out after inclusion of 100 patients and a follow up of one year. Results: In the MMF group 4 of 50 patients expired within one year after LTX. There was no mortality in the Everolimus group (p⫽0.043). CMV Antigenemia was more common (p⫽0.012) in the MMF group (15 versus 3 cases). Bacterial infections were found more frequently (p⬍0.05) in the Everolimus group (23 versus 10 cases). The total incidence of acute rejection periods were comparable in both groups (60 Everolimus/ 52 MMF), as well as the incidence of BOS (1 case per group).The number of Pneumonias (5 versus 3) and the incidence of other lower respiratory tract infections (23 versus 31) were similar. Lung function increased to a best FeV1 of 77 ⫾ 18 % of predicted (Everolimus) and 83 ⫾ 20 % (MMF). Glomerular filtration rate (GFR) decreased significantly (p⬎0.001) within 12 months in both groups from 103 ⫾ 47 ml/min to 54 ⫾ 22 ml/min (Everolimus) and from 96 ⫾ 34ml/min to 48 ⫾ 18 ml/min (MMF). Drop outs due to severe side effects or recurrent acute rejections occurred in 12 patients of the Everolimus arm and in 13 of the MMF arm. Conclusions: A survival benefit in the Everolimus arm has to be verified by further follow up. CMV antigenemia was more frequent in the MMF group despite CMV prophylaxis. Bacterial infections were seen more often in the Everolimus treated patients. In both groups renal toxicity remains a major problem. Future studies should address the development of less (renal) toxic immunosuppressive therapies after successful LTX. 402 Complete 3 Year Analysis of a Prospective Randomized International Multi-Center Investigator Driven Study Comparing Tacrolimus and Cyclosporin A, Both in Combination with MMF and Steroids after Lung Transplantation in 249 Patients H. Reichenspurner,1 A. Glanville,3 A. Christina,3 R. Lama,7 B. Carlos,4 E. Marc,6 J.-D. Aubert,5 H. Treede,1 W. Klepetko,2 European and Australian Investigators in Lung Transplantation 1 Department of Cardiovascular Surgery, University Heart Center Hamburg, Hamburg, Germany; 2University of Vienna, Vienna, Austria; 3University of Sydney, Sydney, Australia; 4University of Barcelona, Barcelona, Spain; 5University of Lausanne, Lausanne, Switzerland; 6University of Brussels, Brussels, Belgium; 7 University of Cordoba, Cordoba, Spain Purpose: This prospective randomized international investigator driven study was performed to compare the efficacy and safety of Tac, MMF, Steroids vs. CsA, MMF, Steroids after Lung Transplantation. Primary objective was the incidence of bronchiolitis obliterans syndrome (BOS). Secondary objectives were incidence of acute rejection and infection, survival and adverse events. Final data of 249 patients with a complete 3 year follow-up will be presented.