- Email: [email protected]
QTC interval prolongation predicts mortality in patients with transplant coronary artery disease
S208
Abstracts
terized by progressive loss of pulmonary function caused by luminal fibrosis in the respiratory bronchioles which leads to small airway obstruction. Everolimus (Certican™), a potent immunosuppressant agent in renal and heart transplantation, is a proliferation inhibitor with the potential to target the major causes for BOS: acute rejection (an important risk factor for the development of BOS) and proliferation of fibroblasts. Methods: The aim of this three-year study, one of the biggest randomized, double-blind studies ever done in this indication, was to compare the efficacy (decline in pulmonary function as measured by spirometry) and safety of everolimus, a new investigational agent, vs azathioprine (AZA). Eligible patients had to demonstrate stable lung function and the absence of BOS (BOS 0, defined as FEV1 ⱖ80% of baseline) during a screening period. 223 stable lung or heart/lung transplant recipients were randomized to receive either everolimus 1.5 mg bid or AZA 1-3 mg/kg/day in the context of a cyclosporine/corticosteroid regimen. The major efficacy parameters were decline of FEV1 ⬎15% from the study entry value, graft loss or patient death (as a composite endpoint), decline in FEV1 over time, and incidence of BOS. Safety assessments were based on reporting of adverse events (including infections), vital signs, ECG, and laboratory parameters. Results: One-year clinical results on efficacy and safety will be available for presentation at the congress. 412 DIAGNOSTIC ACCURACY OF CORONARY ANGIOGRAPHY AND RISK FACTORS FOR POST-HEART TRANSPLANT CORONARY ARTERY VASCULOPATHY (CAV) L.D. Sharples,1 C.H. Jackson,1 J. Parameshwar,2 J. Wallwork,2 S.R. Large,2 1MRC Biostatistics Unit, Institute of Public Health, Cambridge, Cambridgeshire, United Kingdom; 2Transplant Unit, Papworth Hospital HNS Trust, Cambridge, Cambridgeshire, United Kingdom Background: CAV remains the most common cause of death amongst long term survivors of heart transplantation (HTx). Coronary angiography (QCA) is commonly used to monitor the progress of recipients. The diagnostic accuracy of QCA and identification of risk factors in this context has not been established. Methods: Between August 1979 and January 2002, 566 consecutive 1-year survivors of HTx underwent 2168 angiograms. Patients were classified as normal (0% stenosis), mild-moderate CAV (up to 70% stenosis) or severe CAV (⬎70% stenosis). We assumed that CAV is not spontaneously reversible and, in the absence of a gold standard, used serial measurements to estimate the diagnostic accuracy of QCA. The following risk factors for CAV onset, progression and survival were assessed: recipient and donor age and sex, pre-operative ischaemic heart disease (IHD), acute rejection, cytomegalovirus (CMV) infection and serological status. Results: CAV was diagnosed in 248/556 (45%) 1-year survivors, mean onset time 8.6 yrs. Patients spent mean 3.4 yrs with mild-moderate and 3.4 yrs with severe disease before death. Angiography was highly specific (97.8% false negative rate) but only moderately sensitive (79.3% true positive rate). The following variables significantly increased the risk of CAV onset: recipient age by16% per 10 years (1%, 34%); donor age by 27% per 10 years (13%, 43%); male recipient by 100% (11% to 257%); pre-transplant IHD by 75% (30%, 136%); cumulative rejection by 13% per episode (5%, 21%); CMV infection by 42% (6% to 92%). Cumulative acute rejections increased risk of death by 22% (3%, 44%). Conclusion: Angiography is a specific (97.8%) and moderately sensitive (79.3%) tool for diagnosis of post HTx CAV. CAV onset is related to
The Journal of Heart and Lung Transplantation January 2003 age of the donor, recipient’s history of IHD, and immune-related insults of acute rejection and CMV infection. 413 QTC INTERVAL PROLONGATION PREDICTS MORTALITY IN PATIENTS WITH TRANSPLANT CORONARY ARTERY DISEASE B. Vrtovec,1 B. Radovancevic, A.P. Yazdanbakhsh, R. Radovancevic, C.D. Thomas, O.H. Frazier, Cardiopulmonary Transplantation, Texas Heart Institute, Houston, TX Background: Prolonged QTc interval is associated with increased mortality in patients with pre-transplant coronary artery disease, but its significance in heart transplant recipients with coronary artery disease remains undefined. Methods: Of 527 patients who underwent heart transplantation between May 1982 and January 1996, we enrolled 239 recipients with transplant coronary artery disease (tCAD) documented by angiography within the first 5 years after transplantation. At the first tCAD occurrence, QT interval duration was determined by averaging 3 consecutive beats in all 12 leads of the standard ECG and corrected with the Bazett formula. Patients were followed for 5 years from the time of first tCAD occurrence. Cardiac mortality included sudden cardiac death and death due to heart failure or myocardial infarction. Results: On average, tCAD first occurred at 2.4 ⫾ 1.5 years after transplantation. At this time, QTc interval was prolonged (⬎440 ms) in 130 patients (54%) and normal in 109 (46%). The groups did not differ in age, gender, incidence of rejection, or incidence of infection episodes. Graft ischemic time was longer in the prolonged QTc group (172 ⫾ 68 min) than the normal QTc group (151 ⫾ 63 min, p⫽0.02). The prolonged QTc group had a significantly higher 5-year cardiac mortality (46%) than the normal QTc group (21%) (p⫽0.002). The predictive value of QTc interval prolongation was more pronounced in patients with early (⬍2 years post-transplant) onset of tCAD: the 5-year cardiac mortality rates were 57% in the prolonged QTc group and 25% in the normal QTc group (p⫽0.001). On multivariate analysis, QTc interval prolongation was the only independent predictor of cardiac mortality (p⫽0.008). Conclusions: QTc interval prolongation (⬎440 ms) at the first occurrence of tCAD is predictive of cardiac mortality thereafter, especially if tCAD occurs within the first 2 years after transplantation. 414 IMPACT OF HEALTH INSURANCE AND BLACK RACE ON OUTCOME AFTER CARDIAC TRANSPLANTATION: ANALYSIS OF THE CARDIAC TRANSPLANT RESEARCH DATABASE M.C. Montpetit,2 R.N. Brown, S.V. Pamboukian, T. Stevens, G.W. Dec, C. Leier, A. VanBakel, B. Jaski, A. Heroux, J.K. Kirklin, for the Cardiac Transplant Research Database(CTRD), 1CTRD, University of Alabama at Birmingham, Birmingham, AL; 2Roche Young Investigator Award Background: Cardiac transplantation (CTx) is a treatment modality necessitating indefinite follow-up care, thus health insurance coverage may impact patient (pt) outcome. Methods: Insurance payer and other clinical variables were examined in pts receiving CTx from 1/96 to 12/01. Survival analyses and multivariable hazard function analyses were applied to 3578 pts from 33 institutions with private insurance, including HMO (P)(n⫽2425); Medicare (M)(n⫽327); Medicaid (A)(n⫽248); and Medicare⫹Medicaid (M⫹A)(n⫽110). Ill-defined payer groups were excluded (n⫽468). Results: Medicaid pts had the worst survival (p⬍0.01). Of the numerous risk factors for death post-CTx evaluated, only black race and CMV positivity were more prevalent in the M/A groups (p⬍0.01). By multi-variable analysis, survival was worse in black M or A pts (p⫽.003),
Abstracts
terized by progressive loss of pulmonary function caused by luminal fibrosis in the respiratory bronchioles which leads to small airway obstruction. Everolimus (Certican™), a potent immunosuppressant agent in renal and heart transplantation, is a proliferation inhibitor with the potential to target the major causes for BOS: acute rejection (an important risk factor for the development of BOS) and proliferation of fibroblasts. Methods: The aim of this three-year study, one of the biggest randomized, double-blind studies ever done in this indication, was to compare the efficacy (decline in pulmonary function as measured by spirometry) and safety of everolimus, a new investigational agent, vs azathioprine (AZA). Eligible patients had to demonstrate stable lung function and the absence of BOS (BOS 0, defined as FEV1 ⱖ80% of baseline) during a screening period. 223 stable lung or heart/lung transplant recipients were randomized to receive either everolimus 1.5 mg bid or AZA 1-3 mg/kg/day in the context of a cyclosporine/corticosteroid regimen. The major efficacy parameters were decline of FEV1 ⬎15% from the study entry value, graft loss or patient death (as a composite endpoint), decline in FEV1 over time, and incidence of BOS. Safety assessments were based on reporting of adverse events (including infections), vital signs, ECG, and laboratory parameters. Results: One-year clinical results on efficacy and safety will be available for presentation at the congress. 412 DIAGNOSTIC ACCURACY OF CORONARY ANGIOGRAPHY AND RISK FACTORS FOR POST-HEART TRANSPLANT CORONARY ARTERY VASCULOPATHY (CAV) L.D. Sharples,1 C.H. Jackson,1 J. Parameshwar,2 J. Wallwork,2 S.R. Large,2 1MRC Biostatistics Unit, Institute of Public Health, Cambridge, Cambridgeshire, United Kingdom; 2Transplant Unit, Papworth Hospital HNS Trust, Cambridge, Cambridgeshire, United Kingdom Background: CAV remains the most common cause of death amongst long term survivors of heart transplantation (HTx). Coronary angiography (QCA) is commonly used to monitor the progress of recipients. The diagnostic accuracy of QCA and identification of risk factors in this context has not been established. Methods: Between August 1979 and January 2002, 566 consecutive 1-year survivors of HTx underwent 2168 angiograms. Patients were classified as normal (0% stenosis), mild-moderate CAV (up to 70% stenosis) or severe CAV (⬎70% stenosis). We assumed that CAV is not spontaneously reversible and, in the absence of a gold standard, used serial measurements to estimate the diagnostic accuracy of QCA. The following risk factors for CAV onset, progression and survival were assessed: recipient and donor age and sex, pre-operative ischaemic heart disease (IHD), acute rejection, cytomegalovirus (CMV) infection and serological status. Results: CAV was diagnosed in 248/556 (45%) 1-year survivors, mean onset time 8.6 yrs. Patients spent mean 3.4 yrs with mild-moderate and 3.4 yrs with severe disease before death. Angiography was highly specific (97.8% false negative rate) but only moderately sensitive (79.3% true positive rate). The following variables significantly increased the risk of CAV onset: recipient age by16% per 10 years (1%, 34%); donor age by 27% per 10 years (13%, 43%); male recipient by 100% (11% to 257%); pre-transplant IHD by 75% (30%, 136%); cumulative rejection by 13% per episode (5%, 21%); CMV infection by 42% (6% to 92%). Cumulative acute rejections increased risk of death by 22% (3%, 44%). Conclusion: Angiography is a specific (97.8%) and moderately sensitive (79.3%) tool for diagnosis of post HTx CAV. CAV onset is related to
The Journal of Heart and Lung Transplantation January 2003 age of the donor, recipient’s history of IHD, and immune-related insults of acute rejection and CMV infection. 413 QTC INTERVAL PROLONGATION PREDICTS MORTALITY IN PATIENTS WITH TRANSPLANT CORONARY ARTERY DISEASE B. Vrtovec,1 B. Radovancevic, A.P. Yazdanbakhsh, R. Radovancevic, C.D. Thomas, O.H. Frazier, Cardiopulmonary Transplantation, Texas Heart Institute, Houston, TX Background: Prolonged QTc interval is associated with increased mortality in patients with pre-transplant coronary artery disease, but its significance in heart transplant recipients with coronary artery disease remains undefined. Methods: Of 527 patients who underwent heart transplantation between May 1982 and January 1996, we enrolled 239 recipients with transplant coronary artery disease (tCAD) documented by angiography within the first 5 years after transplantation. At the first tCAD occurrence, QT interval duration was determined by averaging 3 consecutive beats in all 12 leads of the standard ECG and corrected with the Bazett formula. Patients were followed for 5 years from the time of first tCAD occurrence. Cardiac mortality included sudden cardiac death and death due to heart failure or myocardial infarction. Results: On average, tCAD first occurred at 2.4 ⫾ 1.5 years after transplantation. At this time, QTc interval was prolonged (⬎440 ms) in 130 patients (54%) and normal in 109 (46%). The groups did not differ in age, gender, incidence of rejection, or incidence of infection episodes. Graft ischemic time was longer in the prolonged QTc group (172 ⫾ 68 min) than the normal QTc group (151 ⫾ 63 min, p⫽0.02). The prolonged QTc group had a significantly higher 5-year cardiac mortality (46%) than the normal QTc group (21%) (p⫽0.002). The predictive value of QTc interval prolongation was more pronounced in patients with early (⬍2 years post-transplant) onset of tCAD: the 5-year cardiac mortality rates were 57% in the prolonged QTc group and 25% in the normal QTc group (p⫽0.001). On multivariate analysis, QTc interval prolongation was the only independent predictor of cardiac mortality (p⫽0.008). Conclusions: QTc interval prolongation (⬎440 ms) at the first occurrence of tCAD is predictive of cardiac mortality thereafter, especially if tCAD occurs within the first 2 years after transplantation. 414 IMPACT OF HEALTH INSURANCE AND BLACK RACE ON OUTCOME AFTER CARDIAC TRANSPLANTATION: ANALYSIS OF THE CARDIAC TRANSPLANT RESEARCH DATABASE M.C. Montpetit,2 R.N. Brown, S.V. Pamboukian, T. Stevens, G.W. Dec, C. Leier, A. VanBakel, B. Jaski, A. Heroux, J.K. Kirklin, for the Cardiac Transplant Research Database(CTRD), 1CTRD, University of Alabama at Birmingham, Birmingham, AL; 2Roche Young Investigator Award Background: Cardiac transplantation (CTx) is a treatment modality necessitating indefinite follow-up care, thus health insurance coverage may impact patient (pt) outcome. Methods: Insurance payer and other clinical variables were examined in pts receiving CTx from 1/96 to 12/01. Survival analyses and multivariable hazard function analyses were applied to 3578 pts from 33 institutions with private insurance, including HMO (P)(n⫽2425); Medicare (M)(n⫽327); Medicaid (A)(n⫽248); and Medicare⫹Medicaid (M⫹A)(n⫽110). Ill-defined payer groups were excluded (n⫽468). Results: Medicaid pts had the worst survival (p⬍0.01). Of the numerous risk factors for death post-CTx evaluated, only black race and CMV positivity were more prevalent in the M/A groups (p⬍0.01). By multi-variable analysis, survival was worse in black M or A pts (p⫽.003),