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Orthotopic cardiac transplantation after failing Fontan procedure
114
Abstracts
The Journal of Heart and Lung Transplantation January 2002
(HED) to evaluate presynaptic catecholamine uptake and storage. 16 of the transplants displayed signs of incomplete RI confined to the anteroseptal wall, 13 pts were completely denervated. Within 24 hrs of PET imaging, all pts underwent radionuclide ventriculography(RNV)to determine LVEF at rest and during a standardized, symptom-limited Ex-test. 10 age- and gender-matched healthy volunteers served as control group. This study now reports about additional measurements of LVEF in the post-Ex state, determined 3 min after cessation of the stress test in subgroups of 26 transplant pts and 9 normals. Results for LVEF are summarized in the table. The increase during Ex was comparable between reinnervated pts and normals. Post stress, LVEF dropped in both groups. In contrast, in denervated pts, only a mild increase of LVEF was observed during Ex, followed by a mild further increase post Ex. In conclusion, additional data acquired after termination of Ex confirm that LV performance after HTx is significantly influenced by innervation status. Chronotropic and inotropic response during and after Ex parallels in reinnervated pts and controls. The different behavior in denervated pts with a further increase of LVEF after Ex, supports the notion that mechanisms other than direct innervation such as a (delayed) response to circulating catecholamines and the FrankStarling mechanism are responsible for regulation of the allograft inotropic state. † p⬍0.001 comparison with the control group ‡ p⬍0.01 comparison with the reinnervated group. LVEF
rest
50 W
peak
Post
denervated reinnervated control
67 ⫾ 6 66 ⫾ 7 68 ⫾ 6
69 ⫾ 7†‡ 76 ⫾ 6 80 ⫾ 6
70 ⫾ 8†‡ 78 ⫾ 6 82 ⫾ 5
72 ⫾ 8 74 ⫾ 8 73 ⫾ 3
† ‡
p ⬍ 0.001 comparison with the control group p ⬍ 0.01 comparison with the reinnervated group.
164 PREEMPTIVE ANTIVIRAL THERAPY IS HIGHLY EFFICIENT IN PREVENTING CYTOMEGALOVIRUS (CMV) DISEASE IN CMV-POSITIVE HEART TRANSPLANT RECIPIENTS B. Radovancevic, C.D. Thomas, R. Radovancevic, E.L. Ford, O.H. Frazier, Transplant Service, Texas Heart Institute, Houston, TX We retrospectively analyzed the effectiveness of preemptive antiviral therapy for prevention of CMV disease in CMV-positive HT recipients (Group I) and compared the resulting data with data from HT recipients who received transplants before introduction of this approach and did not receive any prophylaxis (Group II). Methods: Peripheral blood leukocytes (PBL) from patients in Group I (n⫽65) were assayed for the presence of CMV by CMV pp65 antigenemia assay and fluorescent microscopy. The assay utilized FITC-labeled monoclonal antibodies to CMV lowermatrix protein pp65 and was performed weekly for 12 weeks. A positive result was defined as ⬎1 antigen-positive cell per 5x104 PBL. Those patients in Group I who received a positive result (n⫽43) received either hyperimmune IVIG (Cytogam威; MedImmune) 200 mg/kg IV once or intravenous ganciclovir (Cytovene威; Roche Pharmaceuticals) 5 mg/kg every 12 hours for 7 days until a negative result was obtained. CMV disease was defined as a positive tissue culture, positive PCR tissue analysis, febrile illness involving a 4-fold increase in CMV IgG level and/or the presence of CMV IgM in the absence rheumatoid factor, or at least two of the following-(1) doubling of SGOT or LDH level, (2) leukope-
nia (⬍4000 cells/ml), and (3) thrombocytopenia (⬍100,000 cells/ ml). Group II (n⫽148). Results: Groups I and II were comparable in terms of pretransplant and donor CMV status, immunosuppressive therapy, and incidence of rejections. No patients in Group I developed CMV disease, whereas 27 patients in Group II (18%) did (p⫽0.00013). On average, Group I patients converted to positive antigenemia at day 41 (range, 14-111 days). The mean duration of preemptive therapy was 1.5 weeks (range, 1-4 weeks). In Group I, 22 of 65 patients (34%) did not require any therapy since they remained CMV antigenemia-negative. Conclusion: Preemptive therapy is clearly superior to no prophylaxis in CMV-positive HT recipients. That one third of CMVpositive patients did not require any therapy implies that this approach is significantly more advantageous than prophylaxis to such patients. 165 BRIDGING WITH PROSTAGLANDIN E1 TO HIGH-DOSE BETA-BLOCKER THERAPY IN PATIENTS WITH DECOMPENSATED, ADVANCED, CHRONIC HEART FAILURE R. Berger, M. Huelsmann, A. Bojic, B. Stanek, R. Pacher, University of Vienna, Vienna, Austria Background: Up to now -blockers are contraindicated in patients with decompensated, advanced, chronic heart failure (CHF). Prostaglandin E1 (PGE1) improves clinical symptoms, the neurohumoral status and hemodynamics and reduces the risk of cardiac decompensation. Thus, we tried to iniciate or increase -blocker therapy via clinical stabilisation by PGE1 and investigated the efficasy of -blockers in patients with decompensated CHF despite high-dose ACE-inhibition. Methods and Results: 169 consecutive, decompensated CHF patients in NYHA class IV despite high-dose ACE-inhibition received continuous iv PGE1. Initiation or increase of -blockers was not intended in the first 54 patients (before 8/97-group A), but was intended in further 115 patients in case of clinical stabilisation (NYHA II) in the absence of contraindications (after 8/97-group B). LVEF (15⫹5 vs 16⫹5%), RRmean (74⫹13 vs 75⫹10mmHg), CI (1,8⫹0.3 vs 1,8⫹0.4L/min/m2) and big endothelin (7,6⫹2.8 vs 7,9⫹4,8fmol/ml) were similar between groups. In 40 patients of group B -blockers were iniciated or increased (group B1), in 75 patients of group B not (group B2) LVEF 17⫹5 vs 17⫹5%, RRmean 76⫹11 vs 74⫹10mmHg, CI 1,9⫹0.5 vs 1.7⫹0.3L/min/m2 (p⬍0.01); big endothelin 76.6⫹3.2 vs 8.4⫹5.7fmol/ml. Kaplan Meier survival analysis showed a significant difference between group A and group B excluding patients with HTx (56 vs 57%) (p⬍0.05) and a significant difference between group B1 and group B2 excluding patients with HTx (38 vs 68%, p⫽0.002) (p⫽0.0001). Conclusion: Initialisation or increase of -blockers is possible in a large proportion of patients with decompensated CHF. These patients have a significant better survival. 166 ORTHOTOPIC CARDIAC TRANSPLANTATION AFTER FAILING FONTAN PROCEDURE A.Gamba, C. Mammana, R. Fiocchi, L. Iamele, B. Carrara, P. Ferrazzi, Cardiovascular Department, Ospedali Riuniti di Bergamo, Bergamo, Italy
The Journal of Heart and Lung Transplantation Volume 21, Number 1 Purpose: The clinical features and outcome of patients who underwent orthotopic cardiac transplantation (OCT) after a failing Fontan circulation is still debated. Methods and Results: Twelve patients were submitted to OCT in our Institution for failing Fontan-type operations. Five were female, the mean age was 16,6 ⫾ 7,25 years, mean period from Fontan procedure to transplant was 9 years (range 1-16 yrs). Four previous cardiac operations were performed in one pts, three operations in five pts and two operations in six pts. The indications for cardiac transplantation were protein-losing enteropathy (PLE) in six cases, heart failure and/or intractable arrhythmia’s in six patients. All the pts received as basic immunosuppressive therapy cyclosporine and azathioprine and four patients had a short period (3 to 6 months) of steroid therapy for repeated acute rejections. In a high percentage of pts (six) azathioprine was definitively stopped for adverse events. There were two hospital deaths: one pts died after 10 days for low output syndrome (preoperative NYHA IV and undersized donor heart) and one died in 17TH p.o. day after acute neurological event. One patient died 2 years later for acute rejection and another pts died seven years later for chronic rejection and endocarditis. One patient was successfully operated one year later for pulmonary vein obstruction. All the 8 survivors with a mean follow-up of 60 months (range 104-14 months) are in NYHA class I and one delivered a healthy baby. Normalisation of the protein titres was observed in all the cases after a mean period of 7 months. Conclusion: The results show that cardiac transplantation is a good option for patients with a failed Fontan operation; we documented the reversibility of PLE in all the cases; the risk of previous operation didn’t increase significantly the hospital mortality. 167 HEART TRANSPLANT AND LVAD CHARGES ARE SIMILAR P.L. DiGiorgi, E.H. Burton, M.C. Oz, Surgery, Columbia University, New York, NY Background: Despite increasing clinical success of left ventricular assist devices (LVADs), physicians need to measure device cost efficacy in order to determine the societal value of this technology. Today’s large clinical volume allows comparison of the costs of this innovation compared to orthotopic heart transplant (OHT). Methods: We evaluated the hospital charges for patients who were discharged after LVAD implantation and returned to the hospital for OHT. Length of stays (LOS), readmissions, and outpatient services were analyzed including their respective hospital charges. Equal time periods were analyzed for both LVAD and OHT. Results: From the LVAD population at Columbia Presbyterian, 49 patients were discharged following HeartMate implantation and readmitted for OHT. The average charges for LVAD vs. OHT over an equal period of time were $244,468.41 ⫾ $139,200.07 vs. $204,921.18 ⫾ $85,686.67 (p⫽0.09). The average postoperative LOSs were 35.3 ⫾ 23.8 vs. 18.7 ⫾ 12.1 days for the LVAD and OHT respectively (p⬍0.001). LVADs were implanted for an average of 118 ⫾ 72 days. Lastly, the average number of outpatient services needed during the LVAD period was 2.7 ⫾ 4.5 vs. 10.1 ⫾ 7.6 (OHT), generating an average total service cost of $20,326.11 ⫾
Abstracts
115
$27,068.57 vs. 15,701.34 ⫾ $11,097.03 (LVAD inpatient rehabilitation considered an outpatient service) (p⫽0.27). Conclusions: LVAD implantation is associated with similar costs to that of OHT. In addition, OHT is associated with a greater number of outpatient services. These data show LVAD therapy, at least in the short term, is similar in cost to OHT. 168 THE NEW IMPELLA INTRACARDIAC MICROAXIAL PUMP FOR TREATMENT OF RIGHT HEART FAILURE AFTER ORTHOTOPIC HEART TRANSPLANTATION J. Martin,1 C. Yerebakan,1 C. Benk,1 M. Krause,1 G. Derjung,2 F. Beyersdorf,1 1Department of Cardiovascular Surgery, AlbertLudwigs-University, Freiburg, Germany; 2Impella Kardiotechnik AG, Aachen, Germany Right heart failure is a common problem after heart transplantation and may result in graft failure. The use of available assist devices in this situation is associated with a high incidence of complications due to hemorrhage and infections. Smaller and less invasive assist systems could minimize the risk and improve the outcome of the patients. The new Impella system is a miniaturized axial pump (diameter 19.2 F) for intracardiac support. Different catheter types for left and right ventricular support are available. The right ventricular assist device has a right angled shape (Fig.1). It is introduced via a dacron vascular graft(A)into the pulmonary artery (B) and through the pulmonary valve with the top of the pump in the right ventricle (C). To provide safe bleeding control the pump was introduced via a 10 mm vascular Dacron graft. To induce right heart failure pig hearts were transplanted orthotopically with an ischemic time of 24 hours. One hour after start of reperfusion the right ventricular impella system was inserted and weaning from cardiopulmonary bypass was attempted. Right ventricular circulatory support was maintained by the Impella pump for 5 hours. The assist system provided continuous blood flow of 2.5 - 4.5 l/min over the observation period. Introduction, handling, and removal of the system was safe and easy. Animals maintained good oxygenation and diuresis. One hour after weaning from the assist system hemodynamics remained stable with epinephrine at 0.1 g/kg/ min. Introduction of these device into the clinical arena could open a new approach to prevention and treatment of right heart failure after heart transplantation.
Abstracts
The Journal of Heart and Lung Transplantation January 2002
(HED) to evaluate presynaptic catecholamine uptake and storage. 16 of the transplants displayed signs of incomplete RI confined to the anteroseptal wall, 13 pts were completely denervated. Within 24 hrs of PET imaging, all pts underwent radionuclide ventriculography(RNV)to determine LVEF at rest and during a standardized, symptom-limited Ex-test. 10 age- and gender-matched healthy volunteers served as control group. This study now reports about additional measurements of LVEF in the post-Ex state, determined 3 min after cessation of the stress test in subgroups of 26 transplant pts and 9 normals. Results for LVEF are summarized in the table. The increase during Ex was comparable between reinnervated pts and normals. Post stress, LVEF dropped in both groups. In contrast, in denervated pts, only a mild increase of LVEF was observed during Ex, followed by a mild further increase post Ex. In conclusion, additional data acquired after termination of Ex confirm that LV performance after HTx is significantly influenced by innervation status. Chronotropic and inotropic response during and after Ex parallels in reinnervated pts and controls. The different behavior in denervated pts with a further increase of LVEF after Ex, supports the notion that mechanisms other than direct innervation such as a (delayed) response to circulating catecholamines and the FrankStarling mechanism are responsible for regulation of the allograft inotropic state. † p⬍0.001 comparison with the control group ‡ p⬍0.01 comparison with the reinnervated group. LVEF
rest
50 W
peak
Post
denervated reinnervated control
67 ⫾ 6 66 ⫾ 7 68 ⫾ 6
69 ⫾ 7†‡ 76 ⫾ 6 80 ⫾ 6
70 ⫾ 8†‡ 78 ⫾ 6 82 ⫾ 5
72 ⫾ 8 74 ⫾ 8 73 ⫾ 3
† ‡
p ⬍ 0.001 comparison with the control group p ⬍ 0.01 comparison with the reinnervated group.
164 PREEMPTIVE ANTIVIRAL THERAPY IS HIGHLY EFFICIENT IN PREVENTING CYTOMEGALOVIRUS (CMV) DISEASE IN CMV-POSITIVE HEART TRANSPLANT RECIPIENTS B. Radovancevic, C.D. Thomas, R. Radovancevic, E.L. Ford, O.H. Frazier, Transplant Service, Texas Heart Institute, Houston, TX We retrospectively analyzed the effectiveness of preemptive antiviral therapy for prevention of CMV disease in CMV-positive HT recipients (Group I) and compared the resulting data with data from HT recipients who received transplants before introduction of this approach and did not receive any prophylaxis (Group II). Methods: Peripheral blood leukocytes (PBL) from patients in Group I (n⫽65) were assayed for the presence of CMV by CMV pp65 antigenemia assay and fluorescent microscopy. The assay utilized FITC-labeled monoclonal antibodies to CMV lowermatrix protein pp65 and was performed weekly for 12 weeks. A positive result was defined as ⬎1 antigen-positive cell per 5x104 PBL. Those patients in Group I who received a positive result (n⫽43) received either hyperimmune IVIG (Cytogam威; MedImmune) 200 mg/kg IV once or intravenous ganciclovir (Cytovene威; Roche Pharmaceuticals) 5 mg/kg every 12 hours for 7 days until a negative result was obtained. CMV disease was defined as a positive tissue culture, positive PCR tissue analysis, febrile illness involving a 4-fold increase in CMV IgG level and/or the presence of CMV IgM in the absence rheumatoid factor, or at least two of the following-(1) doubling of SGOT or LDH level, (2) leukope-
nia (⬍4000 cells/ml), and (3) thrombocytopenia (⬍100,000 cells/ ml). Group II (n⫽148). Results: Groups I and II were comparable in terms of pretransplant and donor CMV status, immunosuppressive therapy, and incidence of rejections. No patients in Group I developed CMV disease, whereas 27 patients in Group II (18%) did (p⫽0.00013). On average, Group I patients converted to positive antigenemia at day 41 (range, 14-111 days). The mean duration of preemptive therapy was 1.5 weeks (range, 1-4 weeks). In Group I, 22 of 65 patients (34%) did not require any therapy since they remained CMV antigenemia-negative. Conclusion: Preemptive therapy is clearly superior to no prophylaxis in CMV-positive HT recipients. That one third of CMVpositive patients did not require any therapy implies that this approach is significantly more advantageous than prophylaxis to such patients. 165 BRIDGING WITH PROSTAGLANDIN E1 TO HIGH-DOSE BETA-BLOCKER THERAPY IN PATIENTS WITH DECOMPENSATED, ADVANCED, CHRONIC HEART FAILURE R. Berger, M. Huelsmann, A. Bojic, B. Stanek, R. Pacher, University of Vienna, Vienna, Austria Background: Up to now -blockers are contraindicated in patients with decompensated, advanced, chronic heart failure (CHF). Prostaglandin E1 (PGE1) improves clinical symptoms, the neurohumoral status and hemodynamics and reduces the risk of cardiac decompensation. Thus, we tried to iniciate or increase -blocker therapy via clinical stabilisation by PGE1 and investigated the efficasy of -blockers in patients with decompensated CHF despite high-dose ACE-inhibition. Methods and Results: 169 consecutive, decompensated CHF patients in NYHA class IV despite high-dose ACE-inhibition received continuous iv PGE1. Initiation or increase of -blockers was not intended in the first 54 patients (before 8/97-group A), but was intended in further 115 patients in case of clinical stabilisation (NYHA II) in the absence of contraindications (after 8/97-group B). LVEF (15⫹5 vs 16⫹5%), RRmean (74⫹13 vs 75⫹10mmHg), CI (1,8⫹0.3 vs 1,8⫹0.4L/min/m2) and big endothelin (7,6⫹2.8 vs 7,9⫹4,8fmol/ml) were similar between groups. In 40 patients of group B -blockers were iniciated or increased (group B1), in 75 patients of group B not (group B2) LVEF 17⫹5 vs 17⫹5%, RRmean 76⫹11 vs 74⫹10mmHg, CI 1,9⫹0.5 vs 1.7⫹0.3L/min/m2 (p⬍0.01); big endothelin 76.6⫹3.2 vs 8.4⫹5.7fmol/ml. Kaplan Meier survival analysis showed a significant difference between group A and group B excluding patients with HTx (56 vs 57%) (p⬍0.05) and a significant difference between group B1 and group B2 excluding patients with HTx (38 vs 68%, p⫽0.002) (p⫽0.0001). Conclusion: Initialisation or increase of -blockers is possible in a large proportion of patients with decompensated CHF. These patients have a significant better survival. 166 ORTHOTOPIC CARDIAC TRANSPLANTATION AFTER FAILING FONTAN PROCEDURE A.Gamba, C. Mammana, R. Fiocchi, L. Iamele, B. Carrara, P. Ferrazzi, Cardiovascular Department, Ospedali Riuniti di Bergamo, Bergamo, Italy
The Journal of Heart and Lung Transplantation Volume 21, Number 1 Purpose: The clinical features and outcome of patients who underwent orthotopic cardiac transplantation (OCT) after a failing Fontan circulation is still debated. Methods and Results: Twelve patients were submitted to OCT in our Institution for failing Fontan-type operations. Five were female, the mean age was 16,6 ⫾ 7,25 years, mean period from Fontan procedure to transplant was 9 years (range 1-16 yrs). Four previous cardiac operations were performed in one pts, three operations in five pts and two operations in six pts. The indications for cardiac transplantation were protein-losing enteropathy (PLE) in six cases, heart failure and/or intractable arrhythmia’s in six patients. All the pts received as basic immunosuppressive therapy cyclosporine and azathioprine and four patients had a short period (3 to 6 months) of steroid therapy for repeated acute rejections. In a high percentage of pts (six) azathioprine was definitively stopped for adverse events. There were two hospital deaths: one pts died after 10 days for low output syndrome (preoperative NYHA IV and undersized donor heart) and one died in 17TH p.o. day after acute neurological event. One patient died 2 years later for acute rejection and another pts died seven years later for chronic rejection and endocarditis. One patient was successfully operated one year later for pulmonary vein obstruction. All the 8 survivors with a mean follow-up of 60 months (range 104-14 months) are in NYHA class I and one delivered a healthy baby. Normalisation of the protein titres was observed in all the cases after a mean period of 7 months. Conclusion: The results show that cardiac transplantation is a good option for patients with a failed Fontan operation; we documented the reversibility of PLE in all the cases; the risk of previous operation didn’t increase significantly the hospital mortality. 167 HEART TRANSPLANT AND LVAD CHARGES ARE SIMILAR P.L. DiGiorgi, E.H. Burton, M.C. Oz, Surgery, Columbia University, New York, NY Background: Despite increasing clinical success of left ventricular assist devices (LVADs), physicians need to measure device cost efficacy in order to determine the societal value of this technology. Today’s large clinical volume allows comparison of the costs of this innovation compared to orthotopic heart transplant (OHT). Methods: We evaluated the hospital charges for patients who were discharged after LVAD implantation and returned to the hospital for OHT. Length of stays (LOS), readmissions, and outpatient services were analyzed including their respective hospital charges. Equal time periods were analyzed for both LVAD and OHT. Results: From the LVAD population at Columbia Presbyterian, 49 patients were discharged following HeartMate implantation and readmitted for OHT. The average charges for LVAD vs. OHT over an equal period of time were $244,468.41 ⫾ $139,200.07 vs. $204,921.18 ⫾ $85,686.67 (p⫽0.09). The average postoperative LOSs were 35.3 ⫾ 23.8 vs. 18.7 ⫾ 12.1 days for the LVAD and OHT respectively (p⬍0.001). LVADs were implanted for an average of 118 ⫾ 72 days. Lastly, the average number of outpatient services needed during the LVAD period was 2.7 ⫾ 4.5 vs. 10.1 ⫾ 7.6 (OHT), generating an average total service cost of $20,326.11 ⫾
Abstracts
115
$27,068.57 vs. 15,701.34 ⫾ $11,097.03 (LVAD inpatient rehabilitation considered an outpatient service) (p⫽0.27). Conclusions: LVAD implantation is associated with similar costs to that of OHT. In addition, OHT is associated with a greater number of outpatient services. These data show LVAD therapy, at least in the short term, is similar in cost to OHT. 168 THE NEW IMPELLA INTRACARDIAC MICROAXIAL PUMP FOR TREATMENT OF RIGHT HEART FAILURE AFTER ORTHOTOPIC HEART TRANSPLANTATION J. Martin,1 C. Yerebakan,1 C. Benk,1 M. Krause,1 G. Derjung,2 F. Beyersdorf,1 1Department of Cardiovascular Surgery, AlbertLudwigs-University, Freiburg, Germany; 2Impella Kardiotechnik AG, Aachen, Germany Right heart failure is a common problem after heart transplantation and may result in graft failure. The use of available assist devices in this situation is associated with a high incidence of complications due to hemorrhage and infections. Smaller and less invasive assist systems could minimize the risk and improve the outcome of the patients. The new Impella system is a miniaturized axial pump (diameter 19.2 F) for intracardiac support. Different catheter types for left and right ventricular support are available. The right ventricular assist device has a right angled shape (Fig.1). It is introduced via a dacron vascular graft(A)into the pulmonary artery (B) and through the pulmonary valve with the top of the pump in the right ventricle (C). To provide safe bleeding control the pump was introduced via a 10 mm vascular Dacron graft. To induce right heart failure pig hearts were transplanted orthotopically with an ischemic time of 24 hours. One hour after start of reperfusion the right ventricular impella system was inserted and weaning from cardiopulmonary bypass was attempted. Right ventricular circulatory support was maintained by the Impella pump for 5 hours. The assist system provided continuous blood flow of 2.5 - 4.5 l/min over the observation period. Introduction, handling, and removal of the system was safe and easy. Animals maintained good oxygenation and diuresis. One hour after weaning from the assist system hemodynamics remained stable with epinephrine at 0.1 g/kg/ min. Introduction of these device into the clinical arena could open a new approach to prevention and treatment of right heart failure after heart transplantation.