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Is Doppler Echocardiography Useful for Estimating Ventricular Filling Pressures in Pediatric Heart Transplant Recipients?
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The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
Purpose: There is a paucity of data regarding orthotopic heart transplantation (OHT) among those with chromosomal anomalies (CA). The purpose of this study was to describe the incidence and outcomes of OHT in patients with CA. Methods: A multi-institutional, retrospective query of the Pediatric Health Information System database was used to identify all hospitalizations in which patients ≤ 21 years underwent OHT between 2004 and 2013. Mortality was the primary outcome measure. Measures of hospital utilization included readmission, length of stay (LOS), and hospital charge data. Descriptive statistics were reported using median and interquartile range or proportions. Intergroup differences were assessed by Chi-square analysis. Survival analyses were performed using Cox regression analysis, reported using odds ratio (OR) and 95% confidence intervals, and adjusted for age, gender, race, and presence of cardiomyopathy. Results: Out of 2181 total OHT patients, 40 (2%) had a CA. Recorded CA included DiGeorge syndrome and other chromosomal deletions (n= 15; 37.5%), unspecified CA (n= 14; 35%), Turner syndrome (n= 6; 15%) and Trisomy 21 (n= 5; 12.5%). Median age at OHT was similar between the CA and no-CA group (6.5 [0.7-12.4] vs. 5.1 [0.7-13.5] years, p= 0.989) as was gender (p= 0.121), race (p= 0.848), and the presence of cardiomyopathy (p= 0.292). Adjusted 1- and 5- year mortality was 20% and 25% in the CA group compared to 10% and 16% in the no-CA group (p= 0.087). The only CA significantly associated with higher mortality was Turner syndrome (50%, OR 17.6 [1.8-175.8]) at a median 14 (13 - 110) days after OHT. Thirtyday hospital readmission rate was 8% in the CA group versus 9% in the no-CA group (p= 0.242). Median hospital length of stay (LOS) was significantly longer in the CA group (76 [42-124] vs. 47 [21-91] days, p= 0.003) resulting in higher overall median hospital charge (US$1.1m [$721k-$1.7m] vs. $693k [$375k-$1.3m], p= 0.004) but similar hospital charge per day ($15.2k [$9.7k-$21.5k vs. $16.1k [$11.2k-$24.4k], p= 0.287). Conclusion: Patients with CA rarely undergo OHT but have similar survival to chromosomally normal patients except in Turner syndrome. Hospital utilization in these children is high. 8( 42) Home Milrinone Therapy in Pediatric Advanced Heart Failure L. Murray , L. Irby, A. Savage, R. Butts, M. Kavarana, A. Burnette, L. Haney. Pediatric Cardiology, Medical University of South Carolina, Charleston, SC. Purpose: Continuous home inotropic therapy for adult heart failure patients has been established as an effective bridge to heart transplantation. There is limited information about the use of this practice in pediatric patients. This study sought to describe the use of home inotropic therapy while awaiting pediatric heart transplant at our institution. Methods: A single center retrospective chart review was performed. All pediatric patients (age< 18) listed for heart transplant at our institution from 2002 to 2012 were included. Primary outcomes included death or delisting prior to transplant. Secondary outcomes included number of hospitalized days prior to transplant, PICC line changes, line infections, and change in kidney and liver function from time of listing to time of transplant. Results: 30 patients were included in study. 13/30 patients were treated with home milrinone with a median age of 3.75 years (range 3 months-16 years) and received a median infusion of 165 days (30-265) of home milrinone. 4/13 patients had cardiomyopathy, 8/13 had single ventricle congenital heart disease, and 1 patient had congenital heart disease with biventricular circulation. Two patients had no previous cardiac operation, 4 patients had 1, and 7 patients had 2 or more operations. Median distance from transplant center was 133 miles (range 14.1-246.5). Median serum creatinine at listing was 0.3mg/dL (0.1-1.6) and serum bilirubin 0.9 IU/dL (0.4-1.9). There were 17 total hospitalizations in the home milrinone group after milrinone initiation with a median of 1.3 admissions per patient; 4 patients had 0 admissions, 6 patients had 1, and 3 patients had more than one. Of the 13 home milrinone patients, 92% (12/13) survived to transplant, zero acquired line infections, there was a total of 10 PICC line changes (6 patients had 0, 6 patients had 1, and 1 patient had 4) and there was no significant change in renal or liver function while awaiting transplant. Of the 12 patients successfully bridged to transplant, there was a 100% 1 year survival and to date only one death at 8.7 years post-transplant (median follow-up 2.6 years, range 1.0-8.7 years). Conclusion: Home milrinone is a safe and effective bridge to heart transplant in the pediatric population even in the youngest and most complex
patients. It can serve as an alternative to in-hospital milrinone in a select patient population. 8( 43) Is Doppler Echocardiography Useful for Estimating Ventricular Filling Pressures in Pediatric Heart Transplant Recipients? F.I. Lunze , K. Gauvreau, S.D. Colan, S. Dillis, E.D. Blume, T.P. Singh. Cardiology, Boston Children’s Hospital, Boston, MA. Purpose: Left ventricular (LV) E/E’ ratio - the ratio of mitral inflow and annular tissue Doppler imaging (TDI) velocities- is accepted as a surrogate for LV filling pressure in adults but has performed poorly in children. We hypothesized that transforming raw Doppler velocities into z-scores using pediatric normative data will improve the reliability of echocardiographic measures to estimate LV filling pressure in pediatric heart transplant (HT) recipients. Methods: All echocardiograms with TDI performed within 24 hours of a heart catheterization during 2005-2011 were identified (N= 751 studies in 122 HT recipients, median 6/pt). Age-based normative values in 380 healthy children were used to transform biventricular inflow and TDI velocities into z-scores. Multivariable generalized estimating equation models - which account for multiple studies in individual patients - were developed to relate mitral inflow and TDI velocities to pulmonary capillary wedge pressure (PCWP). A similar analysis was performed for mean right atrial pressure (RAP) using right ventricular (RV) Doppler velocities. Results: The median age of the study cohort at first evaluation was 13.9 yrs (IQR 6.4-16.8 yrs). The median duration between HT and the first study was 1.9 yrs (IQR 0.1-6.4 yrs). Although LV E/E’ ratio was associated with PCWP in univariate analysis (R2 = 0.11, P< 0.001), the final multivariable model for PCWP included mitral inflow E and LV S’ velocities (R2= 0.17, P< 0.001) but not LV E/E’ ratio.Using z-scores for mitral E and LV S’ velocities modestly improved the model for estimating PCWP (R2= 0.20, P< 0.001) whereas LV E/E’ z-score ratio was not significant. A multivariable model for RAP included RV E’, RV A’ and septal A’ velocities (R2= 0.11, P< 0.001) but not RV E/E’ ratio. Transforming these velocities to z-scores did not strengthen the association. Conclusion: There is only a modest association between Doppler echocardiography velocities and PCWP (or RAP) in pediatric HT recipients which is not improved by using z-scores for LV E/E’ ratio or other velocities. Cardiac catheterization retains its value in pediatric HT recipients for accurate assessment of LV and RV filling pressures in clinical care. 8( 44) Impact of Pre-Sensitization and Positive Virtual Cross-Match on Outcomes in Pediatric Heart Transplantation W.A. Zuckerman , M.E. Richmond, R.K. Singh, T.M. Lee, J.M. McAllister, L.J. Addonizio. Division of Pediatric Cardiology, Columbia University Medical Center, New York, NY. Purpose: Pre-formed anti-HLA antibodies (Abs) are predictive of outcomes after pediatric heart transplantation (HT). Ab detection has evolved from CDCpanel reactive Ab testing (PRA) to newer techniques such as the LuminexTM assay (LM) that determines specific Abs and their intensities, and allows for virtual cross-matching (VXM) prior to HT. We seek to evaluate the impact of pre-sensitization (PS) and positive VXM on outcomes in pediatric HT. Methods: An institutional, retrospective review of demographics of all HT patients (pts) since LM was performed at our institution in 2011. We determined PS by PRA, as well as PS by LM and VXM at different Ab median fluorescence intensities (MFI). We compared these as predictors of early rejection (0-6 months), early Ab-mediated rejection (AMR), positive cross-match at HT (+XM), and graft status. Results: Since 2011, 64 pts underwent HT (36 for cardiomyopathy, 24 for congenital heart disease (CHD), and 4 re-HTs). Mechanical circulatory support was used pre-HT in 16 pts. By PRA (10% cut-off), 4 pts were PS. By LM, using MFI cut-offs of > 0, > 2000, > 6000, > 10000, PS was present in 24, 22, 12, 7 pts, and VXM was positive in 14, 10, 6, 6 pts, respectively. One pt had +XM at HT (PS by PRA and positive LM and VXM at MFI > 10000). There were 2 HT deaths (17 year-old CHD, not PS by PRA but positive LM and VXM at MFI > 10000, no rejection; and 6 year-old CHD, not PS by PRA but positive LM at MFI> 6000 and VXM at MFI< 2000, during treatment for AMR). Fourteen pts had early rejection, 7 of whom had AMR. The table demonstrates the impact of PRA, LM, and VXM on the development of early rejection.
The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2014
Purpose: There is a paucity of data regarding orthotopic heart transplantation (OHT) among those with chromosomal anomalies (CA). The purpose of this study was to describe the incidence and outcomes of OHT in patients with CA. Methods: A multi-institutional, retrospective query of the Pediatric Health Information System database was used to identify all hospitalizations in which patients ≤ 21 years underwent OHT between 2004 and 2013. Mortality was the primary outcome measure. Measures of hospital utilization included readmission, length of stay (LOS), and hospital charge data. Descriptive statistics were reported using median and interquartile range or proportions. Intergroup differences were assessed by Chi-square analysis. Survival analyses were performed using Cox regression analysis, reported using odds ratio (OR) and 95% confidence intervals, and adjusted for age, gender, race, and presence of cardiomyopathy. Results: Out of 2181 total OHT patients, 40 (2%) had a CA. Recorded CA included DiGeorge syndrome and other chromosomal deletions (n= 15; 37.5%), unspecified CA (n= 14; 35%), Turner syndrome (n= 6; 15%) and Trisomy 21 (n= 5; 12.5%). Median age at OHT was similar between the CA and no-CA group (6.5 [0.7-12.4] vs. 5.1 [0.7-13.5] years, p= 0.989) as was gender (p= 0.121), race (p= 0.848), and the presence of cardiomyopathy (p= 0.292). Adjusted 1- and 5- year mortality was 20% and 25% in the CA group compared to 10% and 16% in the no-CA group (p= 0.087). The only CA significantly associated with higher mortality was Turner syndrome (50%, OR 17.6 [1.8-175.8]) at a median 14 (13 - 110) days after OHT. Thirtyday hospital readmission rate was 8% in the CA group versus 9% in the no-CA group (p= 0.242). Median hospital length of stay (LOS) was significantly longer in the CA group (76 [42-124] vs. 47 [21-91] days, p= 0.003) resulting in higher overall median hospital charge (US$1.1m [$721k-$1.7m] vs. $693k [$375k-$1.3m], p= 0.004) but similar hospital charge per day ($15.2k [$9.7k-$21.5k vs. $16.1k [$11.2k-$24.4k], p= 0.287). Conclusion: Patients with CA rarely undergo OHT but have similar survival to chromosomally normal patients except in Turner syndrome. Hospital utilization in these children is high. 8( 42) Home Milrinone Therapy in Pediatric Advanced Heart Failure L. Murray , L. Irby, A. Savage, R. Butts, M. Kavarana, A. Burnette, L. Haney. Pediatric Cardiology, Medical University of South Carolina, Charleston, SC. Purpose: Continuous home inotropic therapy for adult heart failure patients has been established as an effective bridge to heart transplantation. There is limited information about the use of this practice in pediatric patients. This study sought to describe the use of home inotropic therapy while awaiting pediatric heart transplant at our institution. Methods: A single center retrospective chart review was performed. All pediatric patients (age< 18) listed for heart transplant at our institution from 2002 to 2012 were included. Primary outcomes included death or delisting prior to transplant. Secondary outcomes included number of hospitalized days prior to transplant, PICC line changes, line infections, and change in kidney and liver function from time of listing to time of transplant. Results: 30 patients were included in study. 13/30 patients were treated with home milrinone with a median age of 3.75 years (range 3 months-16 years) and received a median infusion of 165 days (30-265) of home milrinone. 4/13 patients had cardiomyopathy, 8/13 had single ventricle congenital heart disease, and 1 patient had congenital heart disease with biventricular circulation. Two patients had no previous cardiac operation, 4 patients had 1, and 7 patients had 2 or more operations. Median distance from transplant center was 133 miles (range 14.1-246.5). Median serum creatinine at listing was 0.3mg/dL (0.1-1.6) and serum bilirubin 0.9 IU/dL (0.4-1.9). There were 17 total hospitalizations in the home milrinone group after milrinone initiation with a median of 1.3 admissions per patient; 4 patients had 0 admissions, 6 patients had 1, and 3 patients had more than one. Of the 13 home milrinone patients, 92% (12/13) survived to transplant, zero acquired line infections, there was a total of 10 PICC line changes (6 patients had 0, 6 patients had 1, and 1 patient had 4) and there was no significant change in renal or liver function while awaiting transplant. Of the 12 patients successfully bridged to transplant, there was a 100% 1 year survival and to date only one death at 8.7 years post-transplant (median follow-up 2.6 years, range 1.0-8.7 years). Conclusion: Home milrinone is a safe and effective bridge to heart transplant in the pediatric population even in the youngest and most complex
patients. It can serve as an alternative to in-hospital milrinone in a select patient population. 8( 43) Is Doppler Echocardiography Useful for Estimating Ventricular Filling Pressures in Pediatric Heart Transplant Recipients? F.I. Lunze , K. Gauvreau, S.D. Colan, S. Dillis, E.D. Blume, T.P. Singh. Cardiology, Boston Children’s Hospital, Boston, MA. Purpose: Left ventricular (LV) E/E’ ratio - the ratio of mitral inflow and annular tissue Doppler imaging (TDI) velocities- is accepted as a surrogate for LV filling pressure in adults but has performed poorly in children. We hypothesized that transforming raw Doppler velocities into z-scores using pediatric normative data will improve the reliability of echocardiographic measures to estimate LV filling pressure in pediatric heart transplant (HT) recipients. Methods: All echocardiograms with TDI performed within 24 hours of a heart catheterization during 2005-2011 were identified (N= 751 studies in 122 HT recipients, median 6/pt). Age-based normative values in 380 healthy children were used to transform biventricular inflow and TDI velocities into z-scores. Multivariable generalized estimating equation models - which account for multiple studies in individual patients - were developed to relate mitral inflow and TDI velocities to pulmonary capillary wedge pressure (PCWP). A similar analysis was performed for mean right atrial pressure (RAP) using right ventricular (RV) Doppler velocities. Results: The median age of the study cohort at first evaluation was 13.9 yrs (IQR 6.4-16.8 yrs). The median duration between HT and the first study was 1.9 yrs (IQR 0.1-6.4 yrs). Although LV E/E’ ratio was associated with PCWP in univariate analysis (R2 = 0.11, P< 0.001), the final multivariable model for PCWP included mitral inflow E and LV S’ velocities (R2= 0.17, P< 0.001) but not LV E/E’ ratio.Using z-scores for mitral E and LV S’ velocities modestly improved the model for estimating PCWP (R2= 0.20, P< 0.001) whereas LV E/E’ z-score ratio was not significant. A multivariable model for RAP included RV E’, RV A’ and septal A’ velocities (R2= 0.11, P< 0.001) but not RV E/E’ ratio. Transforming these velocities to z-scores did not strengthen the association. Conclusion: There is only a modest association between Doppler echocardiography velocities and PCWP (or RAP) in pediatric HT recipients which is not improved by using z-scores for LV E/E’ ratio or other velocities. Cardiac catheterization retains its value in pediatric HT recipients for accurate assessment of LV and RV filling pressures in clinical care. 8( 44) Impact of Pre-Sensitization and Positive Virtual Cross-Match on Outcomes in Pediatric Heart Transplantation W.A. Zuckerman , M.E. Richmond, R.K. Singh, T.M. Lee, J.M. McAllister, L.J. Addonizio. Division of Pediatric Cardiology, Columbia University Medical Center, New York, NY. Purpose: Pre-formed anti-HLA antibodies (Abs) are predictive of outcomes after pediatric heart transplantation (HT). Ab detection has evolved from CDCpanel reactive Ab testing (PRA) to newer techniques such as the LuminexTM assay (LM) that determines specific Abs and their intensities, and allows for virtual cross-matching (VXM) prior to HT. We seek to evaluate the impact of pre-sensitization (PS) and positive VXM on outcomes in pediatric HT. Methods: An institutional, retrospective review of demographics of all HT patients (pts) since LM was performed at our institution in 2011. We determined PS by PRA, as well as PS by LM and VXM at different Ab median fluorescence intensities (MFI). We compared these as predictors of early rejection (0-6 months), early Ab-mediated rejection (AMR), positive cross-match at HT (+XM), and graft status. Results: Since 2011, 64 pts underwent HT (36 for cardiomyopathy, 24 for congenital heart disease (CHD), and 4 re-HTs). Mechanical circulatory support was used pre-HT in 16 pts. By PRA (10% cut-off), 4 pts were PS. By LM, using MFI cut-offs of > 0, > 2000, > 6000, > 10000, PS was present in 24, 22, 12, 7 pts, and VXM was positive in 14, 10, 6, 6 pts, respectively. One pt had +XM at HT (PS by PRA and positive LM and VXM at MFI > 10000). There were 2 HT deaths (17 year-old CHD, not PS by PRA but positive LM and VXM at MFI > 10000, no rejection; and 6 year-old CHD, not PS by PRA but positive LM at MFI> 6000 and VXM at MFI< 2000, during treatment for AMR). Fourteen pts had early rejection, 7 of whom had AMR. The table demonstrates the impact of PRA, LM, and VXM on the development of early rejection.