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Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

We conducted a randomized, placebo-controlled, double-blind study of pediatric lung transplant recipients, hypothesizing that rituximab plus rabbit anti-thymocyte globulin induction would reduce de novo donor-specific human leukocyte antigen antibodies (DSA) development and improve outcomes. We serially obtained clinical data, blood, and respiratory samples for at least one year posttransplant. We analyzed peripheral blood lymphocytes by flow cytometry, serum for antibody development, and respiratory samples for viral infections using multiplex PCR. Of 45 subjects enrolled, 34 were transplanted and 27 randomized to rituximab (n = 15) or placebo (n = 12). No rituximab-treated subjects versus five placebo-treated subjects developed de novo DSA with mean fluorescence intensity >2000. There was no difference between treatment groups in time to the primary composite outcome endpoint (death, bronchiolitis obliterans syndrome [BOS] grade 0-p, obliterative bronchiolitis or listing for retransplant). A post-hoc analysis substituting more stringent chronic lung allograft dysfunction criteria for BOS 0-p showed no difference in outcome (p = .118). The incidence of adverse events including infection and rejection episodes was no different between treatment groups. Although the study was underpowered, we conclude that rituximab induction may have prevented early DSA development in pediatric lung transplant recipients without adverse effects and may improve outcomes (Clinical Trials: NCT02266888).

Remote interventions are increasingly utilized in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥ 2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included 3 weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the sub-protocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥ 50% of participants completing the weekly calls. MLVI was compared pre- and 180 days post-enrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥ 3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days post-enrollment (2.9 ± 1.29) compared to pre-enrollment (4.6 ± 2.10), p=0.02. At 180 days, MLVI decreased by 1.6 points in the intervention group, but increased by 0.6 in the comparison group (p=0.054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.

Promoting immune tolerance to transplanted organs can minimize the amount of immunosuppressive drugs that patients need to take, reducing lifetime risks of mortality and morbidity. Regulatory T cells (T

Background Organ transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV (HIV D+/R+) presents risks of donor-derived infections. Understanding clinical, immunologic, and virologic characteristics of HIV-positive donors is critical for safety. Methods We performed a prospective study of donors with HIV-positive and HIV false-positive (FP) test results within the HIV Organ Policy Equity (HOPE) Act in Action studies of HIV D+/R+ transplantation (ClinicalTrials.gov NCT02602262, NCT03500315, and NCT03734393). We compared clinical characteristics in HIV-positive versus FP donors. We measured CD4 T cells, HIV viral load (VL), drug resistance mutations (DRMs), coreceptor tropism, and serum antiretroviral therapy (ART) detection, using mass spectrometry in HIV-positive donors. Results Between March 2016 and March 2020, 92 donors (58 HIV positive, 34 FP), representing 98.9% of all US HOPE donors during this period, donated 177 organs (131 kidneys and 46 livers). Each year the number of donors increased. The prevalence of hepatitis B (16% vs 0%), syphilis (16% vs 0%), and cytomegalovirus (CMV; 91% vs 58%) was higher in HIV-positive versus FP donors; the prevalences of hepatitis C viremia were similar (2% vs 6%). Most HIV-positive donors (71%) had a known HIV diagnosis, of whom 90% were prescribed ART and 68% had a VL Conclusion The use of HIV-positive donor organs is increasing. HIV DRMs are common, yet resistance that would compromise integrase strand transfer inhibitor–based regimens is rare, which is reassuring regarding safety.

Solid organ transplant remains a life-saving therapy for children with end-stage heart, lung, liver, or kidney disease; however, ∼25% of allograft recipients experience acute rejection within the first 12 months after transplant. Our ability to detect rejection early and to develop less toxic immunosuppressive agents is hampered by an incomplete understanding of the immune changes associated with rejection, particularly in the pediatric population. Here we used high-dimensional single-cell proteomic technologies (CyTOF) to generate the first detailed, multi-lineage analysis of the peripheral blood immune composition of pediatric solid organ transplant recipients. We report that the organ transplanted impacts the immune composition post-transplant. When taking these allograft-specific differences into account, we further observed that differences in the proportion of subsets of CD8 and CD4 T cells were significantly associated with allograft health. Together, these data form the basis for mechanistic studies into the pathobiology of rejection to develop less invasive tools to identify early rejection and new immunosuppressive agents with greater specificity and less toxicity.

BACKGROUND. Long-term survival after lung transplantation (LTx) is limited by chronic lung allograft dysfunction (CLAD). Methods. We report an analysis of cytokine profiles in bronchoalveolar lavage samples collected during a prospective multicenter non-interventional trial primarily designed to determine the impact of community-acquired respiratory viral infections (CARV) in outcomes after pediatric LTx. In this analysis, we identify potential biomarkers of auto-inflammation and auto-immunity associated with survival and risk of bronchiolitis obliterans (BOS) after LTx with cytokine analysis of bronchoalveolar lavage fluid (BALF) from 61 pediatric recipients. RESULTS. Higher IL23 (p=0.048) and IL31 (p=0.035) levels were associated with the risk of BOS, and lower levels of epithelial growth factor (EGF) (p=0.041) and eotaxin (EOX) (p=0.017) were associated with BOS. Analysis using conditional inference trees to evaluate cytokines at each visit associated with survival identified soluble CD30 (p

Introduction Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)–sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes. Methods APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. Results The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. Conclusion This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation., Graphical abstract

Adolescent transplant recipients may encounter a range of potentially traumatic events (PTEs) pre- and post-transplant, yet little is known about the relationship between posttraumatic stress symptoms (PTSS) and medication adherence in this population. In the present study, adolescent recipients and caregivers completed psychosocial questionnaires at enrollment. Outpatient tacrolimus trough level data were collected over one year to calculate the Medication Level Variability Index (MLVI), a measure of medication adherence. Nonadherence (MLVI ≥ 2) was identified in 34.8% of patients, and most (80.7%) reported ≥ 1 PTE exposure. Levels of PTSS indicating likely posttraumatic stress disorder (PTSD) were endorsed by 9.2% of patients and 43.7% of caregivers. PTSS and MLVI were significantly correlated in the liver subgroup (r=0.30, p=.04). Hierarchical multivariable linear regression analyses revealed overall patient PTSS were significantly associated with QoL (p

Immunosuppression strategies have changed over time in pediatric heart transplantation. Thus, comorbidity profiles may have evolved. Clinical Trials in Organ Transplantation in Children-04 is a multicenter, prospective, cohort study assessing the impact of pre-transplant sensitization on outcomes after pediatric heart transplantation. This sub-study reports 1-year outcomes among recipients without pre-transplant donor-specific antibodies (DSAs).We recruited consecutive candidates (21 years) at 8 centers. Sensitization status was determined by a core laboratory. Immunosuppression was standardized as follows: Thymoglobulin induction with tacrolimus and/or mycophenolate mofetil maintenance. Steroids were not used beyond 1 week. Rejection surveillance was by serial biopsy.There were 240 transplants. Subjects for this sub-study (n = 186) were non-sensitized (n = 108) or had no DSAs (n = 78). Median age was 6 years, 48.4% were male, and 38.2% had congenital heart disease. Patient survival was 94.5% (95% confidence interval, 90.1-97.0%). Freedom from any type of rejection was 67.5%. Risk factors for rejection were older age at transplant and presence of non-DSAs pre-transplant. Freedom from infection requiring hospitalization/intravenous anti-microbials was 75.4%. Freedom from rehospitalization was 40.3%. New-onset diabetes mellitus and post-transplant lymphoproliferative disorder (PTLD) occurred in 1.6% and 1.1% of subjects, respectively. There was no decline in renal function over the first year. Corticosteroids were used in 14.5% at 1 year.Pediatric heart transplantation recipients without DSAs at transplant and managed with a steroid avoidance regimen have excellent short-term survival and a low risk of first-year diabetes mellitus and PTLD. Rehospitalization remains common. These contemporary observations allow for improved caregiver and/or patient counseling and provide the necessary outcomes data to help design future randomized controlled trials.

Noninvasive biomarkers are needed to monitor stable patients after kidney transplant (KT), because subclinical acute rejection (subAR), currently detectable only with surveillance biopsies, can lead to chronic rejection and graft loss. We conducted a multicenter study to develop a blood‐based molecular biomarker for subAR using peripheral blood paired with surveillance biopsies and strict clinical phenotyping algorithms for discovery and validation. At a predefined threshold, 72% to 75% of KT recipients achieved a negative biomarker test correlating with the absence of subAR (negative predictive value: 78%‐88%), while a positive test was obtained in 25% to 28% correlating with the presence of subAR (positive predictive value: 47%‐61%). The clinical phenotype and biomarker independently and statistically correlated with a composite clinical endpoint (renal function, biopsy‐proved acute rejection, ≥grade 2 interstitial fibrosis, and tubular atrophy), as well as with de novo donor-specific antibodies. We also found that

BACKGROUND: Transplant recipients with HIV may have worse outcomes with coronavirus disease 2019 (COVID-19) due to impaired T-cell function coupled with immunosuppressive drugs. Alternatively, immunosuppression might reduce inflammatory complications and/or antiretrovirals could be protective. METHODS: Prospective reporting of all cases of SARS-CoV-2 infection was required within the HOPE in Action Multicenter Consortium, a cohort of kidney and liver transplant recipients with HIV who have received organs from donors with and without HIV at 32 transplant centers in the United States. RESULTS: Between March 20, 2020 and September 25, 2020, there were 11 COVID-19 cases among 291 kidney and liver recipients with HIV (4%). In those with COVID-19, median age was 59 y, 10 were male, 8 were kidney recipients, and 5 had donors with HIV. A higher proportion of recipients with COVID-19 compared with the overall HOPE in the Action cohort were Hispanic (55% versus 12%) and received transplants in New York City (73% versus 34%, P < 0.05). Most (10/11, 91%) were hospitalized. High-level oxygen support was required in 7 and intensive care in 5; 1 participant opted for palliative care instead of transfer to the intensive care unit. HIV RNA was undetectable in all. Median absolute lymphocyte count was 0.3 × 103 cells/µL. Median CD4 pre-COVID-19 was 298 cells/µL, declining to

HIV-positive donor to HIV-positive recipient (HIV D+/R+) transplantation is permitted in the United States under the HIV Organ Policy Equity Act. To explore safety and the risk attributable to an HIV+ donor, we performed a prospective multicenter pilot study comparing HIV D+/R+ vs HIV-negative donor to HIV+ recipient (HIV D-/R+) kidney transplantation (KT). From 3/2016 to 7/2019 at 14 centers, there were 75 HIV+ KTs: 25 D+ and 50 D- (22 recipients from D- with false positive HIV tests). Median follow-up was 1.7 years. There were no deaths nor differences in 1-year graft survival (91% D+ vs 92% D-, P = .9), 1-year mean estimated glomerular filtration rate (63 mL/min D+ vs 57 mL/min D-, P = .31), HIV breakthrough (4% D+ vs 6% D-, P > .99), infectious hospitalizations (28% vs 26%, P = .85), or opportunistic infections (16% vs 12%, P = .72). One-year rejection was higher for D+ recipients (50% vs 29%, HR: 1.83, 95% CI 0.84-3.95, P = .13) but did not reach statistical significance; rejection was lower with lymphocyte-depleting induction (21% vs 44%, HR: 0.33, 95% CI 0.21-0.87, P = .03). In this multicenter pilot study directly comparing HIV D+/R+ with HIV D-/R+ KT, overall transplant and HIV outcomes were excellent; a trend toward higher rejection with D+ raises concerns that merit further investigation.

The frequency, indications, and outcomes for readmission following pediatric heart transplantation are poorly characterized. A better understanding of this phenomenon will help guide strategies to address the causes of readmission. Data from the Clinical Trials in Organ Transplantation for Children (CTOTC-04) multi-institutional collaborative study were utilized to determine incidence of, and risk factors for, hospital readmission within 30 days and 1 year from initial hospital discharge. Among 240 transplants at 8 centers, 227 subjects were discharged and had follow-up. 129 subjects (56.8%) were readmitted within one year; 71 had two or more readmissions. The 30-day and 1-year freedom from readmission were 70.5% (CI: 64.1%, 76.0%) and 42.2% (CI: 35.7%, 48.7%), respectively. The most common indications for readmissions were infection followed by rejection and fever without confirmed infection, accounting for 25.0%, 10.6%, and 6.2% of readmissions, respectively. Factors independently associated with increased risk of first readmission within 1 year (Cox proportional hazard model) were as follows: transplant in infancy (P = .05), longer transplant hospitalization (P = .04), lower UNOS urgency status (2/IB vs 1A) at transplant (P = .04), and Hispanic ethnicity (P = .05). Hospital readmission occurs frequently in the first year following discharge after heart transplantation with highest risk in the first 30 days. Infection is more common than rejection as cause for readmission, with death during readmission being rare. A number of patient factors are associated with higher risk of readmission. A fuller understanding of these risk factors may help tailor strategies to reduce unnecessary hospital readmission.

Based on reports in adult lung transplant recipients, we hypothesized that community-acquired respiratory viral infections (CARVs) would be a risk factor for poor outcome after pediatric lung transplant. We followed 61 pediatric lung transplant recipients for 2+ years or until they met a composite primary endpoint including bronchiolitis obliterans syndrome/obliterative bronchiolitis, retransplant, or death. Blood, bronchoalveolar lavage, and nasopharyngeal specimens were obtained with standard of care visits. Nasopharyngeal specimens were obtained from recipients with respiratory viral symptoms. Respiratory specimens were interrogated for respiratory viruses by using multiplex polymerase chain reaction. Donor-specific HLA antibodies, self-antigens, and ELISPOT reactivity were also evaluated. Survival was 84% (1 year) and 68% (3 years). Bronchiolitis obliterans syndrome incidence was 20% (1 year) and 38% (3 years). The primary endpoint was met in 46% of patients. CARV was detected in 156 patient visits (74% enterovirus/rhinovirus). We did not find a relationship between CARV recovery from respiratory specimens and the primary endpoint (hazard ratio 0.64 [95% confidence interval: 0.25-1.59], P = .335) or between CARV and the development of alloimmune or autoimmune humoral or cellular responses. These findings raise the possibility that the immunologic impact of CARV following pediatric lung transplant is different than that observed in adults.

Anti-HLA donor-specific antibodies are associated with worse outcomes after organ transplantation. Among sensitized pediatric heart candidates, requirement for negative donor-specific cytotoxicity crossmatch increases wait times and mortality. However, transplantation with positive crossmatch may increase posttransplantation morbidity and mortality. We address this clinical challenge in a prospective, multicenter, observational cohort study of children listed for heart transplantation (Clinical Trials in Organ Transplantation in Children-04 [CTOTC-04]). Outcomes were compared among sensitized recipients who underwent transplantation with positive crossmatch, nonsensitized recipients, and sensitized recipients without positive crossmatch. Positive crossmatch recipients received antibody removal and augmented immunosuppression, while other recipients received standard immunosuppression with corticosteroid avoidance. This first CTOTC-04 report summarizes study rationale and design and relates pretransplantation sensitization status using solid-phase technology. Risk factors for sensitization were explored. Of 317 screened patients, 290 were enrolled and 240 underwent transplantation. Core laboratory evaluation demonstrated that more than half of patients were anti-HLA sensitized. Greater than 80% of sensitized patients had class I (with or without class II) HLA antibodies, and one-third of sensitized patients had at least 1 HLA antibody with median fluorescence intensity of ≥8000. Logistic regression models demonstrated male sex, weight, congenital heart disease history, prior allograft, and ventricular assist device are independent risk factors for sensitization.

Data on the clinical importance of newly detected donor-specific anti-HLA antibodies (ndDSAs) after pediatric heart transplantation are lacking despite mounting evidence of the detrimental effect of de novo DSAs in solid organ transplantation. We prospectively tested 237 pediatric heart transplant recipients for ndDSAs in the first year posttransplantation to determine their incidence, pattern, and clinical impact. One-third of patients developed ndDSAs; when present, these were mostly detected within the first 6 weeks after transplantation, suggesting that memory responses may predominate over true de novo DSA production in this population. In the absence of preexisting DSAs, patients with ndDSAs had significantly more acute cellular rejection but not antibody-mediated rejection, and there was no impact on graft and patient survival in the first year posttransplantation. Risk factors for ndDSAs included common sensitizing events. Given the early detection of the antibody response, memory responses may be more important in the first year after pediatric heart transplantation and patients with a history of a sensitizing event may be at risk even with a negative pretransplantation antibody screen. The impact on late graft and patient outcomes of first-year ndDSAs is being assessed in an extended cohort of patients.

Following kidney donation, short-term quality of life outcomes compare favorably to US normative data but long-term effects on mood are not known. In the Renal and Lung Living Donors Evaluation Study (RELIVE), records from donations performed 1963–2005 were reviewed for depression and antidepressant use predonation. Postdonation, in a cross-sectional cohort design 2010–2012, donors completed the Patient Health Questionnaire (PHQ-9) depression screening instrument, the Life Orientation Test-Revised, 36-Item Short Form Health Survey and donation experience questions. Of 6909 eligible donors, 3470 were contacted and 2455 participated (71%). The percent with depressive symptoms (8%; PHQ-9 > 10) was similar to National Health and Nutrition Examination Survey participants (7%, p = 0.30). Predonation psychiatric disorders were more common in unrelated than related donors (p = 0.05). Postdonation predictors of depressive symptoms included nonwhite race OR = 2.00, p = 0.020), younger age at donation (OR = 1.33 per 10 years, p = 0.002), longer recovery time from donation (OR = 1.74, p = 0.0009), greater financial burden (OR = 1.32, p = 0.013) and feeling morally obligated to donate (OR = 1.23, p = 0.003). While cross-sectional prevalence of depression is comparable to population normative data, some factors identifiable around time of donation, including longer recovery, financial stressors, younger age and moral obligation to donate may identify donors more likely to develop future depression, providing an opportunity for intervention.

The Renal and Lung Living Donors Evaluation Study assesses outcomes of live lung (lobectomy) donors. This is a retrospective cohort study at University of Southern California (USC) and Washington University (WASHU) Medical Centers (1993–2006), using medical records to assess morbidity and national databases to ascertain postdonation survival and lung transplantation. Serious complications were defined as those that required significant treatment, were potentially life-threatening or led to prolonged hospitalization. The 369 live lung donors (287 USC, 82 WASHU) were predominantly white, non-Hispanic and male; 72% had a biological relationship to the recipient, and 30% were recipient parents. Serious complications occurred in 18% of donors; 2.2% underwent reoperation and 6.5% had an early rehospitalization. The two centers had significantly different incidences of serious complications (p

Objectives. We sought to establish whether there was a difference in outcome after aortic valve repair with autologous pericardial leaflet extension in pediatric and adult populations.Methods. In our study, 128 patients (pediatric and adult) underwent valvular pericardial extension repair at our institution from 1997 through 2006. The patients were divided into either the pediatric group (?18 years of age; n = 54/128, 42%), with a mean age of 8.4 ± 5.4 (range, 0-17 years), or the adult group (n = 74/128, 58%), with a mean age of 48.9 ± 19.7 (range, 19-85 years). The endpoints of the study were mortality and reoperation rates.Results. Thirty-day mortality for the adult group was 0, and for the pediatric group it was 1/54 (1.8%), with no statistical difference (P = .1) between the groups. Late mortality for the pediatric group was 2/54 (3.7%) and in the adult group was 2/74 (2.7%). There was no statistical difference (P = .12) between the groups. In the pediatric group, there were 6 total reoperations (6/54) in 5 patients, with one patient undergoing reoperation twice. From these 6 cases, 3 were re-repair and 3 had aortic valve replacement; the mean interval between original repair and reoperation was 4.3 ± 2.5 years (range, 0.1-7.7 years). In the adult group, there were 5 total reoperations (5/74). From these 5 cases, 3 had aortic valve replacement and 2 re-repair; the mean interval between original repair and reoperation was 3.5 ± 3 years (range, 0.1-7 years). There was no statistical difference in the reoperation rate between the 2 groups (P= .38). At late follow-up, 82% of all patients in the adult group had no aortic regurgitation or only a trace (grades 0 and 1) and 78% of all patients in the pediatric group had no aortic regurgitation or only a trace (grades 0 and 1). There was no statistical difference in either aortic regurgitation (P = .06) or aortic stenosis (P = .28) between the 2 groups.Conclusions. Aortic valve repair with autologous pericardial leaflet extension has low mortality and morbidity rates, as well as good mid-term durability in both the pediatric and the adult groups.

Objective: We sought to establish whether there was a difference in outcome after aortic valve repair with autologous pericardial leaflet extension in acquired versus congenital valvular disease.Methods: One hundred and twenty-eight patients underwent reparative aortic valve surgery at our institution from 1997 through 2005 for acquired or congenital aortic valve disease. The acquired group (43/128) (34%) had a mean age of 56.4 20.3 years (range, 7.8—84.6 years) and the congenital group (85/128) (66%) had a mean age of 16.9 19.2 years (range, 0.3—82 years). The endpoints of the study were mortality and reoperation rates.Results:Thirty-day mortality was 0/43 (0%) in the congenital group and 1/85 (1.1%) in the acquired group. Late mortality in the acquired group was 3/43 (7%) and 3/84 (3.5%) in the congenital group (neither early nor late proportion of mortality is significantly different between the two groups, according to the nonparametric Binomial test for proportions). There were 13 total reoperations among 11 patients: 1/43 (2.3%) in the acquired group and 10/85 (11.7%) in the congenital group (p = 0.07). Two patients from the congenital group were reoperated on twice. The mean interval between original repair and reoperation was 3.6 5 years (range, 0—7 years) for acquired and 3.5 2.5 years (range, 0—7 years) for the congenital group (Wilcoxon 2sample test, p = 0.7). Total early reoperation rate (

Background The management of the mildly to moderately dilated ascending aorta (3.5 to 4.9 cm) in cardiac surgery remains controversial. Therapeutic options have included radical aortic resection with synthetic graft substitution, external aortic reinforcement or wrap, with or without partial aortic wall excision, and a watch-and-wait approach. We reviewed our institutional experience with Dacron (DuPont, Wilmington, DE) mesh wrap support of dilated ascending aortas. Methods During the last 20 years, 102 patients with aneurysmal dilatation of the ascending aorta underwent wrapping of the ascending aorta with a fine Dacron mesh from the ventricular-aortic junction to the origin of the innominate artery. For the last 10 years, the wrap was anchored to the aortic annulus with pledgeted sutures. Aortic diameters up to 6 cm, without focal areas of thinning, were wrapped. Aortic diameters exceeding 6 cm, or with focal thinning, underwent tailored aortic wall resection and wrapping. Primary end points of the study included mortality, aortic diameter growth, dissection or rupture, or both. Results The mean age of the group was 54.7 ± 19 years (range, 12 to 90 years). A single patient underwent aortic wrapping without cardiopulmonary bypass. Sixty-six patients (65%) required additional aortic valve surgery. Five patients (5%) had reinforcement of dilated sinuses with glutaraldehyde-treated pericardial patches combined with wrapping. Twenty-seven patients (26%) had combined coronary and valve surgery, and 2 patients had coronary revascularization alone. There was neither early nor hospital mortality. Among the 81 patients (79%) we were able to contact, 7 (7%) late deaths had occurred at 0.5, 1, 3, and 9 years after operation that were unrelated to aortic pathology. Various levels of follow-up were obtained in the 88 patients (86.2%). In 78 patients, echocardiograms, computed tomography angiograms, or magnetic resonance angiograms were obtained. In 2 of these patients, aneurysmal dilatation of the sinuses developed below the wrap and reoperation was required. No patient in whom the mesh wrap was anchored to the aortic annulus required reoperation. All 81 patients that were contacted by us and monitored by referring physicians were asymptomatic and free of problems related to the aorta. The mean (± SD) preoperative diameter of the ascending aorta was 49.2 ± 7.8 mm (range, 35 to 87 mm), the postwrap intraoperative diameter was 32.9 ± 3.4 mm (range, 20 to 40 mm), and the follow-up postoperative aortic diameter was 35.6 ± 12.7 mm (range, 27 to 52 mm). The mean average change in the aortic diameter during the follow-up period was 2.6 ± 14.8 mm (range, −7 to 22 mm), a mean of 8%. The mean follow-up period was 5.7 years (median, 4.77 years; range, 9 days to 21 years). There were no infections or other early complications related to the wrap. Conclusions Dacron mesh support of the moderately dilated aneurysmal ascending aorta, alone or in conjunction with coronary revascularization, aortic root surgery, or valvular operations, or both, is safe and durable. Dacron mesh is transparent and stretchable, permitting tight girdling of the aorta. These properties prevent hematoma formation, facilitate proximal vein graft anastomoses, and provide visualization and access to aortic suture lines. Finally, this technique retards further aortic dilation, altering the natural history of aortic aneurysms.

Background and objectives Most kidney donors view their experience positively, but some may experience psychosocial and financial burdens. We hypothesized that certain donor characteristics, poor outcome of the recipient, negative perceptions of care, and lack of support may be associated with poor psychosocial outcomes for donors. Design, setting, participants, & measurements The Renal and Lung Living Donors Evaluation Study (RELIVE) examined long-term medical and psychosocial outcomes for kidney donors (at three U.S. transplant centers) who donated between 1963 and 2005. Standardized questionnaires evaluated donor perspectives, recovery time, social support, motivation, financial impact, insurability after donation, and current psychological status. Questionnaires were mailed to 6909 donors. Results Questionnaires were returned by 2455 donors, who had donated 17±10 years earlier (range, 5–48 years), a response rate of 36%. Most (95%) rated their overall donation experience as good to excellent. Rating the overall donor experience more negatively was associated with donor complications, psychological difficulties, recipient graft failure, and longer time since donation. Nine percent (n=231) reported one or more of the following poor psychosocial outcomes: fair or poor overall donor experience, financial burden, regret or discomfort with decision to donate, or psychological difficulties since donation. Recipient graft failure was the only predictor for reporting one or more of these poor psychosocial outcomes (odds ratio, 1.77; 95% confidence interval, 1.33 to 2.34). Donors with lower educational attainment experienced greater financial burden. One of five employed donors took unpaid leave; 2% reported health and life insurability concerns. Conclusions Although the majority of donors viewed their overall donation experience positively, almost 1 in 10 donors reported at least one negative consequence related to donation. Recipient graft failure was associated with poor psychosocial outcome, defined as one or more of these negative consequences. Some donors were financially disadvantaged, and some experienced insurance difficulties. Interventions to avoid negative psychosocial and financial consequences are warranted.

Objective: Since a functional right ventricle is desirable when repairing pulmonary atresia with intact ventricular septum, we sought to determine the factors that portend a successful biventricular repair in these children. Methods: A review of operative records at UCLA between 1982 and 2001 revealed 56 patients diagnosed with pulmonary atresia with intact ventricular septum that underwent either a partial (n = 26) or complete biventricular repair. Kaplan—Meier survival curves with log rank statistics were used to evaluate the influence of demographic, technical, and anatomic factors on survival and need for reoperation. Results: Five-year actuarial survival following biventricular repair was 91.5%. Non-Caucasian race (p = 0.011) and omission of palliative right ventricular outflow tract obstruction (RVOTO) relief (p = 0.042) were risk factors for early death. All patients with adequate follow-up required reoperation with median duration of 6.9 years. The most common cause of early reoperation (

We sought to validate a simple grading scheme for right ventricular hypoplasia in determining suitability for a biventricular repair.We reviewed the medical records for 106 patients with pulmonary atresia-intact ventricular septum (PA-IVS) treated between 1982 and 2001. Over this period, children were assigned to mild (2/3 normal size, 23.7% of patients), moderate (1/3 to 2/3, 41.2%), or severe (1/3, 35.1%) right ventricular hypoplasia, and this grouping, along with severity of coronary anomalies (45% right ventricle to coronary fistulae, 16% with right ventricle dependent coronary circulation [RVDCC]), triaged children to eventual single ventricle (severe) or two-ventricle (mild or moderate) repair.Actuarial 10-year survival was 86.3% with mortality predicted by severe hypoplasia (odds ratio [OR] 12.9, p0.001), RVDCC (OR 15.0, p0.001), and non-Caucasian race (OR 10.7, p0.001). Multivariate analysis with a Cox proportional hazards model confirmed only RVDCC (risk ratio [RR] 10.9, p = 0.0009} and non-Caucasian race (RR 6.9, p = 0.007) as significant. Although not an independent risk factor for survival, the degree of hypoplasia was the most important determinant for definitive repair. Severe hypoplasia virtually precluded two-ventricle repair (OR 33.1, p0.001 by chi2 analysis) and was the strongest risk factor for a one-ventricle system (OR 78.7, p0.001). Actuarial survival after either repair was 91%, and no biventricular repair later converted to a Fontan system.Surgical management of patients based on this three tier grade for right ventricular hypoplasia results in excellent survival and correctly predicts patients destined for eventual Fontan and biventricular repair.

Background: As better diagnostic techniques and new operative approaches are developed pathologists will be called upon more often for intraoperative consultation to render a pathologic diagnosis and assess adequacy of resection. Methods: We conducted a retrospective survey of all patients presenting to our institution from 1979 to 1999. The surgical pathology and cardiothoracic surgery databases were used to identify these patients. Results: Of the 29 patients with primary cardiac neoplasms, 15 were male and 14 female. The mean age at surgery was 51.9 years (range, 7 months to 84 years). Twenty-six of 29 patients had a benign pathological diagnosis. The majority (20/26) of the benign tumors were myxomas. Other benign pathologic diagnoses included rhabdomyoma, fibroma, papillary fibroelastoma, localized fibrous tumor and lipoma. Three out of 29 were malignant: 1 fibrosarcoma, 1 malignant mesenchymoma, and 1 rhabdomyosarcoma. Six of the patients presented with thrombo-embolism, 8 with congestive heart failure symptoms, and three with chest discomfort. Five were asymptomatic or the neoplasm was an incidental finding. 2-D echocardiography established the diagnosis in all of the patients except one. Twenty-two of the 29 tumors were located in the atria (LA=15, RA=6, biatrial=1) and 5 in the ventricles (LV=1, RV=2, biventricular=2). Two patients in this series were referred for reresection. A median sternotomy approach was used for tumor extirpation in all patients. Three of the 29 patients have died at a mean follow-up period of 757 days (median, 118 days). There were two late deaths and one hospital (early) death in a reoperation for recurrent malignancy employing cardiac autotransplantation. One additional patient required cardiac reoperation. Conclusions: Primary cardiac neoplasms are rare and occur less commonly than metastatic disease of the heart. Congestive heart failure symptoms and thrombo-embolism account for close to half of the presenting signs and symptoms. 2-D echocardiography remains the mainstay of detection. Distinguishing between benign and malignant, thrombus and vegetation, and extracardiac structure is usually established by the size, shape, mobility and attachment of the mass. Clinical presentation and transesophageal echocardiographic views are extremely helpful in sharpening the accuracy of the diagnosis. Since surgery is the only reliable therapy pathologists will be called upon for intraoperative consultation. The majority of the neoplasms are benign. Malignant neoplasms are difficult to excise completely and portend a grave prognosis.

In past decades, outcomes of chronic cardiac disease supported the irreversibility of ventricular remodeling, with cardiac transplantation the only option for extending life. The irrevocable rightward shift of the end-diastolic pressure-volume relationship (EDPVR) accompanying progressive end-stage heart failure promoted an imbalance between matrix metalloproteinases and their tissue inhibitors, ultimately altering myocyte shape and size and leading to gradual ventricular balloon dilation of the structural cardiac skeleton, increased fibrosis, impaired ventricular function, and terminal pump failure. Subsequent clinical blockade of the sympathetic nervous system and the rennin-angiotensin-aldosterone axis now forms the cornerstone of modern pharmacologic therapy implicating these biomarkers are part of the direct pathway causing cardiovascular system failure. The later emergence of mechanically unloading the failing heart has captured the potential for reversing pump remodeling and restoring a gradual shift, leftward, back toward normal—the EDPVR. In practice, left ventricular assist device (LVAD) support restores normal cardiac output and blood pressure, thereby diminishing inotropic and pressor support. In turn, secondary effects of LVAD therapy are LV pressure and volume unloading and reductions in pulmonary venous and arterial pressure and pulmonary vascular resistance. The consequences of these hemodynamic changes are improved endorgan perfusion and tissue oxygen delivery. Cellular resuscitation restores autonomic function and subdues the neurohormonal and cytokine storm accompanying heart failure, promoting system recovery. The arrival of LVAD therapy has provided some mechanistic insight to reverse myocardial remodeling, enabling an understanding of the

Introduction: Heart transplantation has become an acceptable treatment in pediatric patients with end-stage heart disease and complex congenital heart disease. The liberalization of recipient eligibility criteria, mainly age, along with the expansion of the donor pool has resulted in the acceptable transplantation of older recipients.

We describe a neonate with tricuspid atresia, absent pulmonary valve, right ventricular hypoplasia, small venrricular septal defect, left ventricular ourflow tract obstruction and a patent arterial duct. These finding were diagnosed by echocardiography and confirmed by cardiac catherterization and postmortem examination. This is a unique report of a functionally single ventricle variant of absent pulmonary valve syndrome and biventricular outlet obstuction.

m E ACEMAKER GENERATOR POUCH and lead infection occur in 1% to 7% of patients with permanent pacemaker mplants.1,2 The diagnosis of infective pacemaker endocarditis emains a challenge because strict defining criteria are lacking, lthough several small retrospective studies and case reports ave emerged in recent years.1-3 The accepted and recomended treatment for patients with an infected pacemaker ystem is removal of the generator and lead extraction. Howver, in patients in whom large intracardiac vegetations are resent, cardiac surgery with cardiopulmonary bypass (CPB) ay be required to safely remove the infected pacemaker leads. A case of tricuspid valve endocarditis with intracardiac vegtations initially missed by preoperative transthoracic (TTE) nd transesophageal echocardiography (TEE) is presented. onversion to cardiac surgery with CPB was required for atrial nd ventricular pacing lead removal when another TEE docuented intracardiac vegetations and a patent foramen ovale uring attempted percutaneous extraction under fluoroscopic uidance. Intraoperative TEE, a standard tool for cardiac surery, is extremely helpful in cases of suspected pacemaker ndocarditis.

Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.

In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.

We report a case of a 43-year-old man with dilated cardiomyopathy and intractable ventricular tachycardias who did not respond to percutaneous implantable cardioverter defibrillator therapy and required implantation of epicardial patches. An apical suctioning device was used to retract the apex of the heart outside the mediastinal domain. The device provided excellent exposure and hemodynamic stability to safely implant the posterior epicardial patch.

Immunosuppression after heart transplantation is implicated in development of post-transplant lymphoproliferative disorder (PTLD). Despite a higher prevalence of PTLD in children, there is scarce knowledge about incidence, pathophysiologic mechanisms and risk factors for PTLD in pediatric recipients of cardiac allografts. We examined retrospectively the medical records of all 143 pediatric patients (mean age 9.2 +/- 6.1 yr) who received donor allografts between 1984 and 2002 and survived over 30 days. Five children (3.5%) developed PTLD over a mean follow-up period of 41.1 +/- 46.0 months. Time from transplant to diagnosis of PTLD ranged from 3.9 to 112 months (mean 48.0 +/- 41.9 months). Excluding PTLD, no other malignancies were found in this population. Actuarial freedom from PTLD was 99.2%, 99.2% and 96.2% at 1, 2, and 5 yr, respectively. Children who developed PTLD were more likely (by univariate analysis) to have been Rh negative (p = 0.01), Rh mismatched (p = 0.003), Epstein-Barr virus (EBV) seronegative (p = 0.001) and transplanted for congenital heart disease (p < 0.02). PTLD was associated with significant morbidity and mortality with a mean survival following diagnosis of 21.2 months. PTLD is a serious complicating outcome of cardiac transplantation that occurs in approximately 3.5% of children. Aside of immunosuppression, risk factors in this series for developing PTLD include EBV seronegativity and Rh negative status and mismatch. Non-hematogenous malignancies are rare in light of short allograft half-life.

Background Children requiring permanent pacing have a lifelong need for follow-up. Epicardial leads have traditionally fared worse than endocardial counterparts. We tested the hypothesis that steroid-eluting epicardial and endocardial leads had equivalent outcomes. Methods We reviewed medical records of 148 children, mean age 8.2 ± 4.8 years, in whom a dual-chamber pacemaker system with steroid-eluting leads from a single manufacturer was implanted. Primary outcome was mortality. Secondary outcomes included freedom from lead failure and pacemaker system reintervention. Loss of capture-sensing, lead displacement-fracture, exit block, and high thresholds constituted lead failure. Reintervention included need for lead revision or generator change. Results There was no early mortality. Late mortality occurred once (0.5 ± 0.5 deaths/1,000 patient-months) and eight times (3.4 ± 1.2 deaths/1,000 patient-months) in the endocardial and epicardial groups, respectively. The relative hazard of endocardial versus epicardial site for lead failure was 0.408 ( p = 0.038) and for reintervention was 0.629 ( p = 0.002). Endocardial and epicardial groups differed in important ways: concomitant cardiac surgery 5% (3 of 61) versus 27% (27 of 99); congenital heart disease 33% (20 of 61) versus 90% (89 of 99); single ventricle physiology 13% (8 of 61) versus 52% (51/99); and age (10.5 ± 4.5 years vs 5.5 ± 5.2 years). Adjusting for these covariants, the relative hazard for freedom from lead failure for endocardial versus epicardial leads was 0.546 ( p = 0.360). The adjusted relative hazard for freedom from reintervention was 0.157 ( p = 0.045). Conclusions Technologic advances attenuate important differences in lead failure rates between endocardial and epicardial steroid-eluting pacing leads and thus bridge the performance gap between these fixation modes.

Objective We tested the hypothesis that duration of donor brain injury and death would have an adverse effect on recipient rejection and mortality in pediatric heart transplantation. Methods Ninety-three cardiac transplants were performed at our center from July 1, 1997, through June 30, 2003. The primary study end points were the number of rejection episodes and the time to first rejection. Secondary outcomes were early and late mortality. Results Among 88 recipients of 93 cardiac allografts, 5 (6%) and 1 (1%) received second and third allografts, respectively. Overall patient mortality (3 early and 2 late) was 6% (5/88), and overall graft loss was 6% (6/93). Median time from donor brain injury to declaration of brain death (brain injury interval), time from brain death to donor cardiectomy (brain death interval), and graft ischemia time were 38, 24, and 3.3 hours, respectively. Cox regression analysis (adjusting for United Network for Organ Sharing status, ventilator dependence, extracorporeal membrane oxygenation and ventricular-assist device status, diagnosis of congenital heart disease, sex and cytomegalovirus mismatches, and type of immunosuppression) demonstrated that recipients of donor hearts with relatively long periods from brain injury to death declaration or from death to organ removal had significantly improved rejection-free survival (hazard ratios 0.3, P = .01, and 0.5, P = .05, for brain injury and brain death times, respectively). Prolonged donor heart ischemia did not impact rejection rate. Increasing brain injury interval, brain death interval, and graft ischemia time had no significant effect on mortality. Conclusion Longer brain injury and death intervals correlated with improved freedom from rejection but had no effect on mortality.

Background Cardiac repair for congenital heart disease in children awaiting liver transplantation presents unique therapeutic challenges and dilemmas. We tested the hypothesis that operations in these children requiring cardiopulmonary bypass (CPB) were not associated with prohibitive morbidity and mortality. Methods Over the last 10 years (1994–2004), five infants were identified in our database with end-stage liver disease and awaiting liver transplantation that required cardiac surgery. Primary end point for the study was mortality. Secondary end points included morbidity and time to liver transplantation. The new pediatric end-stage liver disease (PELD) model was used to score liver disease severity. Results Three boys and two girls with mean age of 8.6 months (range, 1.5–21 months) and mean PELD of 18.0 (range, 10–29) required CPB for repair. The only early mortality in the series occurred after cardiac arrest during creation of a central shunt. The child expired two days later despite extracorporeal membrane oxygenation support. The patient had important myocardial hypertrophy. All other patients survived and underwent successful liver transplantation. Conclusions Children with significant congenital heart disease awaiting liver transplantation can undergo safe cardiac repair with judicious perioperative support thereby reducing the risks of subsequent liver transplantation.

Paraplegia after an open heart operation in a neonate is a rare complication. We report a case of a infant in whom paraplegia developed after a successful arterial switch operation for transposition of the great arteries. The infant was monitored and resuscitated in the preoperative period with umbilical arterial and venous catheter tips located in the midthoracic region. He likely suffered a clinically silent thromboembolic event predisposing him to a localized hemorrhagic infarction during the repair.

Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. We sought to evaluate the relationship between renal function and outcomes after orthotopic heart transplantation (OHT).We conducted a retrospective review of 622 adults who underwent 628 consecutive OHTs between 1994 and 2001 at our institution. The recipients were divided into either normal (Group 1) or impaired (Group 2) pre-operative renal function. Impaired renal function was defined as creatinine clearance (CrCl)40 ml/min (Cockroft-Gault formula). Meanwhile, patients in Group 1 (normal) were defined by CrClor = 40 ml/min. The primary end points of the study were early and late mortality. The secondary end point included post-operative renal failure defined by the requirement of dialysis or renal allograft in the early post-operative period. The Kaplan-Meier method was used to determine actuarial survival.Early mortality was 7% (38/531) in Group 1 and 17% (16/96) in Group 2 (p = 0.002). Similarly, the death rate per 100 patient-years was 4.8 and 8.1 for the groups, respectively (p = 0.03). Nine percent of patients in Group 1 required post-operative dialysis (49/531), whereas 32% of recipients in Group 2 required this intervention (31/96) (p0.001). Early mortality was 41% for patients requiring post-operative dialysis and 3% for those not requiring such intervention (p0.001). Early mortality after post-operative dialysis was 41% (20/49) in Group 1 and 42% (13/31) in Group 2 (p = 0.2).CrCl40 ml/min is a useful marker for increased post-operative renal failure and mortality. Recipients who require post-operative dialysis have greatly increased mortality regardless of pre-operative CrCl. Dialysis in patients after heart transplantation carries a prohibitive risk. Dialysis as a bridge to renal transplantation may reduce this high mortality rate.

Objective: Expansion of potential donor pool may be facilitated by using cardiac allografts with long ischemic time. Early graft failure and potential relation to transplant coronary artery disease remains a concern. We sought to evaluate outcomes of heart transplantation in recipients of donor allografts with prolonged ischemia time. Methods: The study group consisted of 46 (mean age, 52 years) consecutive patients at UCLA from 1994 to 2002 that underwent heart transplantation with ischemia time O300 min. This group was compared to a casematched control group of 46 (mean age, 51 years) patients identified from our database during this time frame for the following factors: UNOS status, congenital heart disease diagnosis, preop inotropes, pretransplantation creatinineO1.5 and recipient age. Primary endpoint was mortality and secondary were rejection rate and transplant coronary artery disease. Allografts were perfused and stored in cold University of Wisconsin solution. Results: Mean donor ages of the study and case-matched control group were 34G15 and 34G14 years, respectively. Mean ischemia times were 388 (range, 301‐600 min) and 173 (range, 96‐236 min), respectively. The death incidence rate per 100 transplants per year was 9% for the study group and 7.4% for the matched group (PZ0.50). Thirty-day mortality for the study and case-matched groups were 4.3 and 2.1%, respectively (PZ0.9). Late mortality was 16.5 and 18.5%, respectively (PZ0.9). The risk of death after 30 days was 7.5 and 5.8%, respectively (PZ0.5, log-rank). One-year incidence of acute cellular rejection in the study and case-matched groups were 2 and 4.5% (PZ0.36), respectively. One-year incidence of transplant coronary artery disease in the study and case-matched groups were 4.3 and 5.4%, respectively (PZ0.68). Conclusions: Donor hearts with ischemia time greater than 300 min provide comparable early and intermediate outcomes given judicious and careful donor and recipient matching and our current techniques of myocardial preservation and modified reperfusion. Q 2005 Published by Elsevier B.V.

Background Minimally invasive and cosmetically attractive approaches are fashionable in conducting cardiac operations. Methods We reviewed retrospectively our experience in patients undergoing cardiac operations by means of redo submammary incisions. Results Fifteen consecutive female patients with a mean age of 13.2 years (range, 0.7 to 44 years) underwent reoperation through a former submammary incision. Seventy-three percent (11 of 15) had median sternotomy, cardiopulmonary bypass, and cardiac repairs. The mean aortic cross-clamp and cardiopulmonary bypass times were 78 ± 49.7 minutes (range, 16 to 182 minutes) and 114.4 ± 66.4 minutes (range, 27 to 261 minutes), respectively. Twenty-seven percent (4 of 15) had off-pump procedures; 3 for pacemaker-related issues (1 a third time reentry) and 1 for removal of sternal wires. Mean time interval between the primary submammary incision and reoperation was 5.4 ± 5.6 years (range, 0.01 to 20 years). Mean first 24 hours Hemovac drainage was 3.2 ± 2.4 mL/kg (range, 0.4 to 8.5 mL/kg). Mean intensive care unit and hospital stays were 2.1 ± 1.7 days (range, 0.0 to 5 days) and 5.5 ± 3.6 days (range, 0.80 to 13 days), respectively. One patient exhibited a chylothorax requiring ligation of her thoracic duct. Another patient had an infected seroma requiring incision and drainage 2 months postoperatively. Skin necrosis and infection were absent in this group. Breast development and lactation were normal. The cosmetic results were satisfactory. There was no mortality. Conclusions Redo sternotomies performed through redo transverse submammary incisions are safe for cardiac repair and result in acceptable cosmetic and functional results.

Background The purpose of this study is to evaluate the efficacy of aortic valve-sparing repair with glutaraldehyde-treated autologous pericardium in congenital valvular pathology. Methods Sixty-two patients underwent reparative aortic valve surgery from January 1997 through December 2003. The mean age was 25 ± 20 years (± standard deviation) (range, 10 days to 81 years). Fifty percent (31 of 62) were less than 19 years old at operation. The diagnoses included bicuspid aortic valve (39 patients), ventricular septal defect (14 patients), severe aortic stenosis (6 patients), subaortic stenosis (7 patients), bacterial endocarditis (7 patients), neonatal truncus arteriosus (2 patients), Shone's complex (2 patients), transposition complex (1 patient), double-chambered right ventricle (1 patient), and Marfan's syndrome (1 patient). Twelve patients (19 %) had prior sternotomy and cardiac operations. Valve-sparing techniques included pericardial leaflet extensions in 62 patients, creation of one or more pericardial neoaortic sinuses in 8, subcommissuroplasty in 8, pericardial patch of perforated leaflets in 9, Dacron mesh wrap (Boston Scientific, Wayne, NJ) of dilated ascending aorta in 12, and concomitant tricuspid and mitral valve repairs in 3 and 4 patients, respectively. Results There was one early death (1.6%). There were no late deaths at a mean follow-up of 25 ± 16 (range, 0.1 to 72.5 months). Six patients required reoperation and prosthetic or homograft replacement for aortic valve incompetence. One out of 6 reoperations required re-repair. The remaining patients are well with a mean aortic regurgitation grade by echocardiography of 1.3 ± 0.9 (scale, 0 to 4). Conclusions Aortic valve repair with pericardial leaflet extension is a promising technique for the growing child.

Background— Remodeling occurs in both ventricle and atrium in dilated cardiomyopathy and heart failure. However, the alteration of atrial extracellular matrix components during remodeling and its effect on the electrical remodeling and atrial arrhythmia have never been explored. Methods and Results— Atrial tissue samples of 53 explanted hearts from patients with dilated cardiomyopathy and end-stage heart failure who underwent heart transplantation were examined. Nineteen patients had permanent atrial fibrillation (PmAF), 18 had persistent AF (PsAF), and 16 had no documented AF (NAF). Sixteen donor left atria (LA) were used as controls (CNs). Western Blot analysis revealed a selective downregulation of tissue inhibitor of metalloproteinase (TIMP)-2 in PmAF and PsAF groups compared with the NAF and CN groups and an upregulation of atrial metalloproteinase (MMP)-2 that was most pronounced in the PmAF group followed by the PsAF and NAF groups. Immunofluorescent staining revealed that in the LA, type I collagen volume fraction (CVF-I) increased significantly in the PmAF group followed by the PsAF and NAF groups compared with that in CN. LA CVF-I significantly correlated with LA dimension and TIMP-2 to MMP-2 ratio. In the PsAF group, CVF-I/CVF-III ratio was significantly correlated with AF duration and the frequency of AF recurrence. Conclusions— Atrial extracellular matrix remodeling manifested by the selective downregulation of TIMP-2 along with upregulation of MMP-2 and CVF-I in the atrium is associated with the development of sustained atrial fibrillation in patients with cardiomyopathy and heart failure.