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496 Risk Factors for Nosocomial Infection in the Post-Operative Period after Heart Transplantation
Abstracts Conclusions: A measurement of pretransplant PAPP-A concentrations as an independent factor might be useful to identify patients at high risk of CAV development, as well as severe episodes of ACR and AMR after HTx. 493 Declining Incidence of Cardiac Allograft Vasculopathy: A Serial Angiographic Review R. Khan, K. Morant, P.W. Pflugfelder, W.J. Kostuk. Division of Cardiology, LHSC University Hospital, London, ON, Canada. Purpose: Coronary artery disease in the transplanted heart (cardiac allograft vasculopathy; CAV) develops insidiously and is the principal cause of death beyond 1 year of transplantation. We have previously shown a time dependent increasing prevalence of CAV such that by 10 years 60% of coronary angiograms demonstrate abnormalities (1/2 of those moderate to severe; ISHLT grades 2 or 3). To determine whether contemporary management practices post transplantation have resulted in improved early CAV outcomes, a large consecutive series of post transplant angiograms was reviewed. Methods and Materials: Between April 1981 and December 2010, all available serial angiograms on patients surviving at least one year were reviewed. In total, one year data from 264 patients and 3 year data from 228 patients were available. Patients in the time period 2000-2010 were compared to those before 2000. Results: After 2000, MMF was adopted for routine use (96% vs 42% before 2000, p⬍0.001), tacrolimus supplanted the use of cyclosporine (70% vs 7% before 2000, p⬍0.001), and aggressive lipid lowering regimens with statins were routinely employed (92% vs 52% before 2000, p⬍0.001). Total cholesterol before 2000 was 6.0⫾1.1 mmol/L and 4.0⫾ 1.2 mmol/L after 2000 (p⬍0.001). At the same time, donor age increased (36⫾16 yr vs 29⫾12 yr, p⬍0.001), recipient age increased (51⫾10 yr vs 46⫾12 yr, p⬍0.001) and total ischemic time increased (241⫾86 min vs 215⫾84 min, p⬍0.001). Nevertheless the incidence of CAV (any severity) has declined: 10.7% vs 6.4% (p⫽0.36) at one year and 24.3% vs 7.0% (p⬍0.001) at 3 years. At 3 years, the prevalence of ISHLT grade 2 to 3 abnormalities was 8.3% before 2000 and 0% after 2000 (p⫽0.03). Conclusions: This review has shown a significant decline in the early development of CAV over the last decade. Refinements in post transplant management may be an important factor for this change and merit further study. Whether onset of disease is prevented or merely delayed will be apparent with further follow-up.
S173 495 A Strong Thigh Can Make VO2 Go High – Predictors of VO2 peak in Heart Transplant Recipients K. Nytrøen,1 L.A. Rustad,1,2 E. Gude,1 A.E. Fiane,3,5 K. Rolid,1 I. Holm,4 S. Aakhus,1 L. Gullestad.1,5,6 1Department of Cardiology, Oslo University Hospital HF Rikshospitalet, Oslo, Norway; 2Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; 3Norwegian School of Sport Sciences, Oslo, Norway; 4Department of Cardiothoracic Surgery, Oslo University Hospital HF Rikshospitalet, Oslo, Norway; 5Division of Surgery and Clinical Neuroscience, Oslo University Hospital HF Rikshospitalet, Oslo, Norway; 6Faculty of Medicine, University of Oslo, Oslo, Norway. Purpose: Heart transplant (HTx) recipients have reduced exercise capacity with reported VO2 peak levels of 50-70% of predicted values. The aim of this study was to evaluate central and peripheral factors predictive of VO2 peak. Methods and Materials: 51 clinically stable HTx recipients ⬎ 18 years old and 1-8 years after HTx underwent VO2 testing on a treadmill. Clinical laboratory, hemodynamic and echocardiograpic data, lungfunction and isokinetic muscle strength were recorded. Results: Mean(SD) age was 52(16) years, 71 % men, and time from HTx was 4.1(2.2) years. Median VO2 peak was 27.3 ml/kg/min, corresponding to 80% of predicted values. Recipients with VO2⬎ median value had significantly lower body mass index (BMI), body fat and triglycerides, and significantly higher body water, muscle strength, HDL-cholesterol, lung function, mitral annular velocity, peak ventilation, O2 pulse and VE/VCO2 slope compared to VO2 ⱕ median value. Donor age, recipient age, sex, medication, ischemic time, cardiac dimensions, systolic function and chronotropic responses during exercise were similar. First corrected for age and gender, regression analysis showed that O2 pulse, as a surrogate of stroke volume, BMI and endurance strength in quadriceps and hamstrings, representing peripheral factors, explained 71% (p⬍0.001) of the variation in VO2 peak (ml/kg/min).
494 Tetranectin Is Associated with Cardiac Allograft Vasculopathy in Heart Transplant Recipients S. Aharinejad, M. Salama, R. Susanne, A. zuckermann, G. Laufer. Medical University of Vienna, Vienna, Austria. Purpose: The pathogenesis of cardiac allograft vasculopathy (CAV) in long-term survivors after heart transplantation (HTX) remains controversial. Histologically, CAV is characterized by intimal hyperplasia of the coronary arteries. Evidence suggests that hypercoagulability might play a role in CAV pathogenesis. Tetranectin (TN) is a homotrimeric C-type lectin, which is involved in the activation of tissue plasminogen activator and hepatocyte growth factor. Whether TN is associated with CAV pathogenesis, is unknown. Methods and Materials: Peripheral blood samples were obtained from 70 HTX patients and CAV was diagnosed in 35 recipients by coronary angiography and intravascular ultrasound. Results: Mixed serum samples were then analyzed using a protein array, which indicated downregulated circulating TN levels in CAV versus noCAV patients (p⬍0.0001). Subsequently, serum TN concentrations were determined by ELISA and were lower in CAV compared to no-CAV (p⬍0.01). Logistic regression analysis revealed that serum TN levels could diagnose CAV (OR⫽0.91; p⬍0.03). Conclusions: These results suggest that diminished TN levels are associated with CAV. Serum TN concentration could serve as a specific, easy to measure, quick and non-invasive marker in CAV diagnosis and monitoring.
Conclusions: Chronotropic incompetence was not a limiting factor for exercise capacity in a population of relatively fit HTx recipients. Predictors for VO2 peak were the same as factors determining exercise cpacity in normal subjects. Our findings emphasize the importance of normal BMI, low percentage of bodyfat and increased muscle mass and muscle strength in order to attain a sufficient VO2 peak level after HTx. 496 Risk Factors for Nosocomial Infection in the Post-Operative Period after Heart Transplantation P. Fernández-Ugidos,1 R. Gómez-López,1 M.J. Paniagua-Martin,2 R. Marzoa-Rivas,2 E. Barge-Caballero,2 J. Muñiz,3 J.J. Cuenca,4
S174
The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
M.T. Bouza-Vieiro,5 S. Fojon-Polanco,5 Z. Grille-Cancela,2 A. Castro-Beiras,2 M.G. Crespo-Leiro.2 1Intensive Care, Complexo Hospitalario Universitario de Ourense, Ourense, Spain; 2Cardiology, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain; 3 Instituto Universitario de Ciencias de la Salud, Universidade de A Coruña, A Coruña, Spain; 4Cardiac Surgery, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain; 5Intensive Care, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain. Purpose: Infection is a major cause of morbidity and mortality during post-operative period after heart transplantation (HT). Objective: To determine risk factors for nosocomial infection after HT and to identify patients who could benefit from profilactic or preemptive therapy. Methods and Materials: Historical cohort study that includes all patients who received a HT in a single institution from 1991 to 2009 followed until June, 2010. Epidemiological, surgical, clinical and microbiological variables were collected. The event of interest was nosocomial infection during the post-operative period of HT. Chi-squared or t-Student test were used to determine bivariate associations. Logistic regression was used to assess the simultaneous effect of several factors. Results: From 594 HT performed, 75 (12.6%) suffered at least one infectious episode. The following conditions were more frequent in infected patients: history of diabetes mellitus, renal dysfunction or neoplasia, combined or urgent HT, fever or treated infection prior to HT, prolongued ICU stay, central venous catheter (CVC), circulatory assistance device, mechanical ventilation, vasopressor therapy, post-operative rejection, acute renal failure and renal replacement therapy after HT. Only diabetes mellitus [p⫽0.019, odds ratio(OR) 2.25; 95% confidence interval (CI) 1.142– 4.46], mechanical ventilation for more than three days [p⫽ 0.006, RR 2.425, 95% IC 1.290-4.557] and CVC for more than 5 days [p⫽0.000, RR 6.230, 95% IC 3.178-12.215] remained in the final logistic regresion model. Conclusions: In our series, diabetes mellitus, invasive mechanical ventilation for more than 3 days and CVC for more than 5 days are independent predictors of infection during the postoperative period of HT. 497 Rates of CMV Viremia and Treated CMV in Patients Receiving Alemtuzumab Induction Prior to Cardiac Transplantation M.A. Shullo,1 R. Zomak,2 C. Grabowski,2 M. Navoney,2 D. McNamara,2 C. Bermudez,2 R.L. Kormos,2 J.J. Teuteberg.2 1Pharmacy and Therapeutics, University of Pittsburgh, PA; 2Heart and Vascular Institute, University of Pittsburgh, PA. Purpose: Rates of CMV viremia and CMV requiring treatment after induction therapy with alemtuzumab (C-1H) in cardiac transplantation (CTX) is unknown, particularly for CMV mismatches. Methods and Materials: All patients with C-1H induction for CTX at a single institution from 10/06 until 9/11 for whom donor and recipient CMV status was known. CMV prophylaxis was for 6 months: (D⫹/R⫺) with valaganciclovir 900mg/D; (D⫹/R⫹) or (D⫺/R⫹) with valgancicolvir 450 mg/D; (D⫺/R⫺) with valacyclovir 500mg/D, all doses were adjusted for renal function. Results: A total of 195 patients were included who received C-1H. Baseline characteristics were: mean age 55 years, 76% male, 86% white, 52% ischemic, VAD 23%, CMV mismatch (D⫹/R⫺) 21%. Maintenance immunosuppression was with tacrolimus and mycophenolate in all patients. Median duration of f/u was 815 days. The four year freedom from CMV viremia was 68% for the overall group, but significantly worse for mismatch 51% v. nonmismatch 72%, p⫽0.02 (figure 1a). The four year freedom from treated CMV was 80% for the overall group, but also significantly worse for mismatch 55% v. nonmismatch 85%, p⫽0.0001 (figure 1b). Valganciclovir was the therapy in 95%. The percentage of patients with repeated episodes of treated CMV was higher in the mismatch group 40% v. nonmismatches 5%, p ⫽ 0.04. Treated CMV episodes after the end of prophylaxis: mismatches 87% and nonmismatches 74%; mean days after prophylaxis of 157 and 139 respectively, p⫽0.44. Conclusions: With C-1H induction prior to CTX, 20% will have at least one episode of CMV requiring treatment by four years, in comparison 45% of CMV mismatches will require treatment and also have more frequent disease recurrence.
498 Combined Prophylactic and Pre-Emptive CMV Strategy with Valganciclovir in Heart Transplant Patients Is Efficacious and Safe M. Eriksson,1 J.J. Jokinen,2 P. Hammainen,2 J. Lommi,3 K. Lemstrom.2 1 infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland; 2Heart and Lung Transplantation Program, Helsinki University Central Hospital, Helsinki, Finland; 3Cardiology, Helsinki University Central Hospital, helsinki, Finland. Purpose: We execute a combined prophylactic and pre-emptive strategy to reduce the morbidity and mortality associated with CMV disease among heart transplant patients. Depending on donor/recipient (D/R) CMV status, the recipients receive valganciclovir (VGCV) prophylaxis either for 6 months 900mg od (D⫹/R) or 3 months 450mg OD (the rest). After discontinuation of the prophylaxis we monitor the blood CMV antigenemia or nucleic acid levels for 3 months and treat the patients pre-emptively. The aim of this retrospective study was to evaluate the efficacy and safety of this regimen. Methods and Materials: 105 consecutive heart transplant patients from January 2004 to December 2010 were included in the study. The median follow-up time was 4.3 years (range 0.9 to 7.8 years). 56.2% of patients were male and 43.8% women, the mean age was 48.7⫾13.0 years (range 18.8-67.3 years). All patients received triple drug immunosuppression (calcineurin inhibitor, antimetabolite and steroid), and 94.3% of patients received induction therapy with antithymocyteglobulin. High risk CMV D⫹/R- status was noted in 14 (13.3%) recipients, while the D⫹/R⫹, D-/R⫹ and D-/R- status were observed in 66 (62.9%), 23 (21.9%) and 2 (1.9%) recipients, respectively. Results: Prophylaxis was accomplished in 96% of patients. Four patients interrupted prophylaxis due to leukopenia. The median delay to the first positive CMV test after the discontinuation of the prophylaxis was 46 days in the D⫹/R- group and 68 days in the low-risk groups. The incidence of CMV disease was 9/105 (8.6%) patients. Three cases of CMV disease
S173 495 A Strong Thigh Can Make VO2 Go High – Predictors of VO2 peak in Heart Transplant Recipients K. Nytrøen,1 L.A. Rustad,1,2 E. Gude,1 A.E. Fiane,3,5 K. Rolid,1 I. Holm,4 S. Aakhus,1 L. Gullestad.1,5,6 1Department of Cardiology, Oslo University Hospital HF Rikshospitalet, Oslo, Norway; 2Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; 3Norwegian School of Sport Sciences, Oslo, Norway; 4Department of Cardiothoracic Surgery, Oslo University Hospital HF Rikshospitalet, Oslo, Norway; 5Division of Surgery and Clinical Neuroscience, Oslo University Hospital HF Rikshospitalet, Oslo, Norway; 6Faculty of Medicine, University of Oslo, Oslo, Norway. Purpose: Heart transplant (HTx) recipients have reduced exercise capacity with reported VO2 peak levels of 50-70% of predicted values. The aim of this study was to evaluate central and peripheral factors predictive of VO2 peak. Methods and Materials: 51 clinically stable HTx recipients ⬎ 18 years old and 1-8 years after HTx underwent VO2 testing on a treadmill. Clinical laboratory, hemodynamic and echocardiograpic data, lungfunction and isokinetic muscle strength were recorded. Results: Mean(SD) age was 52(16) years, 71 % men, and time from HTx was 4.1(2.2) years. Median VO2 peak was 27.3 ml/kg/min, corresponding to 80% of predicted values. Recipients with VO2⬎ median value had significantly lower body mass index (BMI), body fat and triglycerides, and significantly higher body water, muscle strength, HDL-cholesterol, lung function, mitral annular velocity, peak ventilation, O2 pulse and VE/VCO2 slope compared to VO2 ⱕ median value. Donor age, recipient age, sex, medication, ischemic time, cardiac dimensions, systolic function and chronotropic responses during exercise were similar. First corrected for age and gender, regression analysis showed that O2 pulse, as a surrogate of stroke volume, BMI and endurance strength in quadriceps and hamstrings, representing peripheral factors, explained 71% (p⬍0.001) of the variation in VO2 peak (ml/kg/min).
494 Tetranectin Is Associated with Cardiac Allograft Vasculopathy in Heart Transplant Recipients S. Aharinejad, M. Salama, R. Susanne, A. zuckermann, G. Laufer. Medical University of Vienna, Vienna, Austria. Purpose: The pathogenesis of cardiac allograft vasculopathy (CAV) in long-term survivors after heart transplantation (HTX) remains controversial. Histologically, CAV is characterized by intimal hyperplasia of the coronary arteries. Evidence suggests that hypercoagulability might play a role in CAV pathogenesis. Tetranectin (TN) is a homotrimeric C-type lectin, which is involved in the activation of tissue plasminogen activator and hepatocyte growth factor. Whether TN is associated with CAV pathogenesis, is unknown. Methods and Materials: Peripheral blood samples were obtained from 70 HTX patients and CAV was diagnosed in 35 recipients by coronary angiography and intravascular ultrasound. Results: Mixed serum samples were then analyzed using a protein array, which indicated downregulated circulating TN levels in CAV versus noCAV patients (p⬍0.0001). Subsequently, serum TN concentrations were determined by ELISA and were lower in CAV compared to no-CAV (p⬍0.01). Logistic regression analysis revealed that serum TN levels could diagnose CAV (OR⫽0.91; p⬍0.03). Conclusions: These results suggest that diminished TN levels are associated with CAV. Serum TN concentration could serve as a specific, easy to measure, quick and non-invasive marker in CAV diagnosis and monitoring.
Conclusions: Chronotropic incompetence was not a limiting factor for exercise capacity in a population of relatively fit HTx recipients. Predictors for VO2 peak were the same as factors determining exercise cpacity in normal subjects. Our findings emphasize the importance of normal BMI, low percentage of bodyfat and increased muscle mass and muscle strength in order to attain a sufficient VO2 peak level after HTx. 496 Risk Factors for Nosocomial Infection in the Post-Operative Period after Heart Transplantation P. Fernández-Ugidos,1 R. Gómez-López,1 M.J. Paniagua-Martin,2 R. Marzoa-Rivas,2 E. Barge-Caballero,2 J. Muñiz,3 J.J. Cuenca,4
S174
The Journal of Heart and Lung Transplantation, Vol 31, No 4S, April 2012
M.T. Bouza-Vieiro,5 S. Fojon-Polanco,5 Z. Grille-Cancela,2 A. Castro-Beiras,2 M.G. Crespo-Leiro.2 1Intensive Care, Complexo Hospitalario Universitario de Ourense, Ourense, Spain; 2Cardiology, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain; 3 Instituto Universitario de Ciencias de la Salud, Universidade de A Coruña, A Coruña, Spain; 4Cardiac Surgery, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain; 5Intensive Care, Complexo Hospitalario Universitario de A Coruña, A Coruña, Spain. Purpose: Infection is a major cause of morbidity and mortality during post-operative period after heart transplantation (HT). Objective: To determine risk factors for nosocomial infection after HT and to identify patients who could benefit from profilactic or preemptive therapy. Methods and Materials: Historical cohort study that includes all patients who received a HT in a single institution from 1991 to 2009 followed until June, 2010. Epidemiological, surgical, clinical and microbiological variables were collected. The event of interest was nosocomial infection during the post-operative period of HT. Chi-squared or t-Student test were used to determine bivariate associations. Logistic regression was used to assess the simultaneous effect of several factors. Results: From 594 HT performed, 75 (12.6%) suffered at least one infectious episode. The following conditions were more frequent in infected patients: history of diabetes mellitus, renal dysfunction or neoplasia, combined or urgent HT, fever or treated infection prior to HT, prolongued ICU stay, central venous catheter (CVC), circulatory assistance device, mechanical ventilation, vasopressor therapy, post-operative rejection, acute renal failure and renal replacement therapy after HT. Only diabetes mellitus [p⫽0.019, odds ratio(OR) 2.25; 95% confidence interval (CI) 1.142– 4.46], mechanical ventilation for more than three days [p⫽ 0.006, RR 2.425, 95% IC 1.290-4.557] and CVC for more than 5 days [p⫽0.000, RR 6.230, 95% IC 3.178-12.215] remained in the final logistic regresion model. Conclusions: In our series, diabetes mellitus, invasive mechanical ventilation for more than 3 days and CVC for more than 5 days are independent predictors of infection during the postoperative period of HT. 497 Rates of CMV Viremia and Treated CMV in Patients Receiving Alemtuzumab Induction Prior to Cardiac Transplantation M.A. Shullo,1 R. Zomak,2 C. Grabowski,2 M. Navoney,2 D. McNamara,2 C. Bermudez,2 R.L. Kormos,2 J.J. Teuteberg.2 1Pharmacy and Therapeutics, University of Pittsburgh, PA; 2Heart and Vascular Institute, University of Pittsburgh, PA. Purpose: Rates of CMV viremia and CMV requiring treatment after induction therapy with alemtuzumab (C-1H) in cardiac transplantation (CTX) is unknown, particularly for CMV mismatches. Methods and Materials: All patients with C-1H induction for CTX at a single institution from 10/06 until 9/11 for whom donor and recipient CMV status was known. CMV prophylaxis was for 6 months: (D⫹/R⫺) with valaganciclovir 900mg/D; (D⫹/R⫹) or (D⫺/R⫹) with valgancicolvir 450 mg/D; (D⫺/R⫺) with valacyclovir 500mg/D, all doses were adjusted for renal function. Results: A total of 195 patients were included who received C-1H. Baseline characteristics were: mean age 55 years, 76% male, 86% white, 52% ischemic, VAD 23%, CMV mismatch (D⫹/R⫺) 21%. Maintenance immunosuppression was with tacrolimus and mycophenolate in all patients. Median duration of f/u was 815 days. The four year freedom from CMV viremia was 68% for the overall group, but significantly worse for mismatch 51% v. nonmismatch 72%, p⫽0.02 (figure 1a). The four year freedom from treated CMV was 80% for the overall group, but also significantly worse for mismatch 55% v. nonmismatch 85%, p⫽0.0001 (figure 1b). Valganciclovir was the therapy in 95%. The percentage of patients with repeated episodes of treated CMV was higher in the mismatch group 40% v. nonmismatches 5%, p ⫽ 0.04. Treated CMV episodes after the end of prophylaxis: mismatches 87% and nonmismatches 74%; mean days after prophylaxis of 157 and 139 respectively, p⫽0.44. Conclusions: With C-1H induction prior to CTX, 20% will have at least one episode of CMV requiring treatment by four years, in comparison 45% of CMV mismatches will require treatment and also have more frequent disease recurrence.
498 Combined Prophylactic and Pre-Emptive CMV Strategy with Valganciclovir in Heart Transplant Patients Is Efficacious and Safe M. Eriksson,1 J.J. Jokinen,2 P. Hammainen,2 J. Lommi,3 K. Lemstrom.2 1 infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland; 2Heart and Lung Transplantation Program, Helsinki University Central Hospital, Helsinki, Finland; 3Cardiology, Helsinki University Central Hospital, helsinki, Finland. Purpose: We execute a combined prophylactic and pre-emptive strategy to reduce the morbidity and mortality associated with CMV disease among heart transplant patients. Depending on donor/recipient (D/R) CMV status, the recipients receive valganciclovir (VGCV) prophylaxis either for 6 months 900mg od (D⫹/R) or 3 months 450mg OD (the rest). After discontinuation of the prophylaxis we monitor the blood CMV antigenemia or nucleic acid levels for 3 months and treat the patients pre-emptively. The aim of this retrospective study was to evaluate the efficacy and safety of this regimen. Methods and Materials: 105 consecutive heart transplant patients from January 2004 to December 2010 were included in the study. The median follow-up time was 4.3 years (range 0.9 to 7.8 years). 56.2% of patients were male and 43.8% women, the mean age was 48.7⫾13.0 years (range 18.8-67.3 years). All patients received triple drug immunosuppression (calcineurin inhibitor, antimetabolite and steroid), and 94.3% of patients received induction therapy with antithymocyteglobulin. High risk CMV D⫹/R- status was noted in 14 (13.3%) recipients, while the D⫹/R⫹, D-/R⫹ and D-/R- status were observed in 66 (62.9%), 23 (21.9%) and 2 (1.9%) recipients, respectively. Results: Prophylaxis was accomplished in 96% of patients. Four patients interrupted prophylaxis due to leukopenia. The median delay to the first positive CMV test after the discontinuation of the prophylaxis was 46 days in the D⫹/R- group and 68 days in the low-risk groups. The incidence of CMV disease was 9/105 (8.6%) patients. Three cases of CMV disease