Incidence, characterization, and impact of newly detected donor-specific anti-HLA antibody in the first year after pediatric heart transplantation: A report from the CTOTC-04 study.

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.

Pediatric heart transplantation across a positive crossmatch: First year results from the CTOTC-04 multi-institutional study.

Sensitization is common in pediatric heart transplant candidates and waitlist mortality is high. Transplantation across a positive crossmatch may reduce wait time, but is considered high risk. We prospectively recruited consecutive candidates at eight North American centers. At transplantation, subjects were categorized as nonsensitized or sensitized (presence of ≥1 HLA antibody with MFI ≥1000 using single antigen beads). Sensitized subjects were further classified as complement-dependent cytotoxicity crossmatch (CDC-crossmatch) positive or negative and as donor-specific antibodies (DSA) positive or negative. Immunosuppression was standardized. CDC-crossmatch-positive subjects also received perioperative antibody removal, maintenance corticosteroids, and intravenous immunoglobulin. The primary endpoint was the 1 year incidence rate of a composite of death, retransplantation, or rejection with hemodynamic compromise. 317 subjects were screened, 290 enrolled and 240 transplanted (51 with pretransplant DSA, 11 with positive CDC-crossmatch). The incidence rates of the primary endpoint did not differ statistically between groups; nonsensitized 6.7% (CI: 2.7%, 13.3%), sensitized crossmatch positive 18.2% (CI: 2.3%, 51.8%), sensitized crossmatch negative 10.7% (CI: 5.7%, 18.0%), P = .2354. The primary endpoint also did not differ by DSA status. Freedom from antibody-mediated and cellular rejection was lower in the crossmatch positive group and/or in the presence of DSA. Follow-up will determine if acceptable outcomes can be achieved long-term.

Emotional well-being of living kidney donors: findings from the RELIVE Study.

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.

Morbidity and mortality of live lung donation: results from the RELIVE study.

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 (1993­2006), 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 < 0.001). No deaths occurred and no donors underwent lung transplantation during 4000+ person-years of follow-up (death: minimum 4, maximum 17 years; transplant: minimum 5, maximum 19). Live lung donation remains a potential option for recipients when using deceased donor lungs lacks feasibility. However, the use of two live donors for each recipient and the risk of morbidity associated with live lung donation do not justify this approach when deceased lung donors remain available. Center effects and long-term live donor outcomes require further evaluation.

Is third-time heart retransplantation justifiable?

Since repeat heart transplantation traditionally carries higher risk than primary engraftment, we tested the hypothesis that third-time cardiac allograft transplantation is associated with prohibitive mortality and morbidity. The cohort of all third-time cardiac retransplants performed at our institution (n=3) and reported to UNOS from 1987 to 2002 (n=10) was reviewed. The primary endpoints were early and late mortality. Extending the study frame through 2003 captures a total of 5 and 15 third-time heart transplant recipients in UCLA and UNOS databases, respectively. Of the 15 patients undergoing third-time retransplants, preoperatively one was ventricular assist device-dependent, four were on intravenous inotropes, and two had creatinine levels greater than 2.5. Additionally, four were male recipients of female donor hearts and the mean donor ischemic time was 2.6 hours. One patient was diagnosed with acute allograft rejection, 13 with coronary artery vasculopathy/chronic rejection, and one with primary graft failure. At our institution, five patients underwent a third heart transplant. There was no early or hospital mortality. One patient died late from transplant coronary artery disease and another following a fourth allograft. The mortality rate for third-time heart allograft recipients is acceptable. These results are influenced by small sample size, younger age, case selection, and operations at select, high-volume institutions with significant experience.

Delayed sternal closure: a lifesaving maneuver after early operation for complex congenital heart disease in the neonate.

Early repair of complex congenital heart malformations may lead to life-threatening respiratory and hemodynamic embarrassment on sternal closure. To avoid a fatal outcome in these situations, we postponed sternal closure in nine critically ill neonates by suturing silicone elastomer sheeting to the skin edges. This maneuver, in a setting of optimal inotropic and ventilatory support, allowed eight of the nine neonates to survive. The mean age at operation was 10.2 days (range 3 to 31). The mean preoperative weight was 3004.4 gm (range 1550 to 3780). The sternal wound was protected with an impervious silicone elastomer sheeting for a mean of 5.6 days (range 2 to 12). There was no instance of wound infection. The judicious application of this technique after operations for complex congenital heart disease can provide the necessary compliance vital for immediate cardiopulmonary performance and ultimate survival.

The incisional pulmonary artery band.

Occasionally early definitive repair of congenital heart disease carries prohibitive mortality, and interval pulmonary artery banding is necessary to protect the pulmonary arterial bed and improve systemic perfusion or prepare a systemic left ventricle for a later arterial switch operation. We describe our technique for effectively banding the pulmonary artery.

Spinal cord infarct after arterial switch associated with an umbilical artery catheter.

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.

Staged surgical approach to neonates with aortic obstruction and single-ventricle physiology.

BACKGROUND: The surgical management of neonatal systemic outflow obstruction and complex single ventricle pathology is variable. METHODS: In 15 neonates (12 boys and 3 girls) with complex forms of single-ventricle pathology and aortic coarctation or interruption, an initial strategy of banding the pulmonary artery and repair of the obstruction from a left thoracotomy was undertaken. RESULTS: The median age at operation was 6 days (range 2 to 33 days) and the median weight was 3.3 kg (range 2 to 4.6 kg). There were no early deaths and one late death after the initial surgical palliation. Of the 14 survivors, 8 have undergone a bidirectional cavopulmonary anastomosis. The median age for bidirectional Glenn was 9.75 months (range 3.5 to 26 months). Seven infants have required Damus-Kaye-Stansel reconstruction for subaortic obstruction (one early death). The median age of the Damus-Kaye-Stansel procedure was 4 months (range 3 weeks to 9 months). Thirteen of 15 patients (87%) are alive and 6 have proceeded to a Fontan operation (median follow-up 68 months). A single failing Fontan required takedown to bidirectional Glenn and central shunt. CONCLUSIONS: Our experience suggests that this high-risk subgroup of neonates with aortic obstruction and single-ventricle pathophysiology is safely managed by initial pulmonary artery banding palliation and repair of aortic obstruction. This strategy, careful surveillance, and early relief of subaortic stenosis can maintain acceptable anatomy and hemodynamics for later bidirectional Glenn and Fontan procedures.

Retrieval of Silastic catheter fragment from heart in septic thromboembolism complicating aplastic anemia.

A 42-year-old man with aplastic anemia presented to hospital toxic and septic secondary to central Silastic catheter sepsis. The chronic indwelling catheter fractured during an attempt at removal and the distal remnant embolized to the right ventricular outflow tract and main pulmonary artery precipitating near cardiopulmonary collapse. The thrombosed catheter was successfully retrieved under fluoroscopy by an endovascular snare technique thus avoiding operative intervention in this immunosuppressed, thrombocytopenic and septic individual. The patient had an uneventful recovery.

Extracorporeal membrane oxygenation for cardiac support in pediatric patients.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

Primary antiphospholipid syndrome: a cause of catastrophic shunt thrombosis in the newborn.

This is a unique report of systemic-to-pulmonary artery shunt thromboses secondary to primary antiphospholipid syndrome and antithrombin III deficiency in a neonate with cyanotic congenital heart disease. This infant with tricuspid atresia experienced thromboses of two modified Blalock-Taussig shunts en route to a bidirectional cavo-pulmonary shunt and potential future Fontan operation. Chronic warfarin anticoagulation has prevented additional thrombo-embolic events.

Heart transplantation in the young and elderly.

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. METHODS: Between July 1994 and June 1998, 39 pediatric patients aged 16 days to 17.6 years (median 6.68 years) and 123 elderly patients aged 60 to 74.8 years (median 64.1 years) were transplanted at our institution. In the pediatric group, 19 had idiopathic dilated cardiomyopathy (DCM) (46 %), 14 had congenital heart disease (34 %), 4 had other etiologies of cardiomyopathy (10 %), 2 had transplant coronary artery disease (TCAD) (5 %), and 1 each had acute rejection and graft failure. In the elderly group, 71 had ischemic cardiomyopathy (58 %), 38 had DCM (31 %), 9 had other forms of cardiomyopathy (7 %), and 5 had TCAD (4 %). RESULTS: Thirty-day, 1-year, and 4-year survival was 97.4 %, 87.2 %, and 70.9 % for the pediatric group and 92.7 %, 81.3 %, and 79.3 % for the elderly group. One and 4-year freedom from TCAD was 100.0 % and 85.3 % for the pediatric group and 91.9 % and 83.3 % for the elderly group. CONCLUSIONS: [emsp3 ]Orthotopic heart transplantation is effective for the treatment of irreparable congenital and end-stage heart disease. It provides excellent long-term results in both the very young and elderly.

Transplantation for congenital heart disease.

Refinements in surgical technique, donor and recipient myocardial preservation, and immunosuppression have brought pediatric heart transplantation for end-stage heart failure (whatever the cause) from the heyday of clinical experimentation to the realm of a viable therapeutic. Heart transplantation in this subpopulation yields excellent early and midterm survival. Acute rejection remains an important cause of morbidity and mortality after heart transplantation in children. Future improvement in quality of life for these patients calls for newer immunosuppressive strategies to reduce acute rejection episodes and ultimately improve long-term graft survival.

Pericardiovascular approach to cardiac assist: acute feasibility study.

We tested the hypothesis that external synchronized compression of the cardiovascular system can achieve effective hemodynamic assistance while circumventing problems associated with the blood-polymer interface in traditional cardiac assist devices. Ten dogs were studied to develop and test prototype devices and evaluate their hemodynamic effectiveness. Copulsation assistance was studied in animals with fibrillating hearts using Anstadt pericardiac cups. Mean systolic arterial pressure of 81.2 mm Hg and cardiac output of 2.9 L/min were achieved. Counterpulsation assistance was studied by inflating during diastole a balloon placed between the thoracic aorta and periaortic sheath and deflating the balloon during systole. In 4 dogs, 25 +/- 8.6% (SEM) of diastolic augmentation and 8.3 +/- 1.2% of systolic unloading were achieved. These preliminary results indicate the feasibility of a pericardiovascular approach to cardiac assistance. Further device development and the integration of copulsation and counterpulsation may improve cardiac output, reduce cardiac afterload, augment coronary perfusion, and ultimately benefit patients with severe heart failure.

Hybrid biomechanical assist for acute biventricular failure.

It is now clear dynamic cardiomyoplasty alone will not be able to support patients in severe cardiogenic shock. On the other hand, implantable univentricular electromechanically driven devices for permanent circulatory support are undergoing early clinical trials. Because of the potential for existing or subsequent biventricular failure and to avoid the need to implant two space-occupying mechanical devices, hybrid biomechanical assist devices could have certain advantages. To evaluate the feasibility of supporting profound biventricular failure, utilizing the combination of dynamic cardiomyoplasty and mechanical ventricular assistance, six dogs underwent simultaneous right latissimus dorsi cardiomyoplasty and left heart bypass. Microspheres were embolized into the pulmonary artery resulting in pulmonary hypertension and acutely impairing the right ventricle. The left ventricle was unloaded via a centrifugal Biomedicus pump. To create severe biventricular failure, the aorta was cross-clamped and potassium cardioplegia was infused into the aortic root to achieve a flaccid diastolic arrest of the heart. Infusion of microspheres into the pulmonary artery resulted in a dose-dependent increase in pulmonary artery pressure. Stimulation of the cardiomyoplasty under these conditions showed a 25.9 +/- 7.9% (S.E.M.) (p less than 0.05, paired t-test) increase in mean pulmonary artery flow. There was a corresponding increase of 6.75 +/- 10.6% in the centrifugal pump flow. Following diastolic arrest, the mean pulmonary artery and centrifugal pump flows increased 90.8 +/- 11.5% (p less than 0.001) and 16.4 +/- 12.1%, respectively. These preliminary results suggest this approach could be a useful alternative to patients who require long-term biventricular support.

Pulmonary artery counterpulsation with a skeletal muscle power source.

We evaluated the feasibility of using skeletal muscle (SM) to provide pulmonary artery (PA) counterpulsation in an acute pulmonary hypertension (PHT) model. PA counterpulsation was achieved in six dogs with a dual chambered pump powered by the latissimus dorsi muscle. A rate-responsive stimulator was used to make the muscle contract in counterpulsation. Graded PHT was induced by infusing 150 microns glass beads into the PA, while RV and PA pressures were monitored. With PA pressures ranging from 19/10 to 115/62 mmHg, effective counterpulsation was observed. The degree of counterpulsation was influenced by the extent of PHT induced, with the amount of RV tension-time index (TTI) unloading correlated with the level of PA systole (r = 0.92). Therefore, results were divided into two groups (Group 1: PA systole less than or equal to 40 mmHg, and Group 2: PA systole greater than 40 mmHg). In Group 1, RV TTI decreased from 11.29 +/- 0.76 to 9.99 +/- 0.72 mmHg.sec, PA diastole increased from 20 +/- 2.3 to 31 +/- 3.0 mmHg, and PA mean increased from 24 +/- 2.2 to 2.9 +/- 2.2 mmHg (all p less than 0.05). In Group 2, RV TT1 decreased from 15.12 +/- 1.83 to 10.99 +/- 0.90 mmHg.sec, PA diastole increased from 41 +/- 3.5 to 64 +/- 6.2 mmHg, and PA mean increased from 49 +/- 4.8 to 55 +/- 5.7 mmHg (all p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The remodelling of skeletal muscle for indefatigable hemodynamic work.

Skeletal muscle possesses inherent plasticity of gene expression. Low frequency pulse-train stimulation can remodel the biochemical machinery that confers physiological expression and fatigue resistance approaching that of the myocardium. This fatigue-resistant muscle can generate sufficient force to meet the power requirements for useful cardiac work. This ultimate goal is currently being pursued in models of cardiomyoplasty and muscle-powered cardiac assist devices. In this article, we review the three major subcellular systems subserving canine skeletal muscle transformation and compare them to those of cardiac muscle. The magnitude of the problem of clinical heart failure and the feasibility of fatigue-resistant skeletal muscle joining the therapeutic armamentarium are addressed. The adaptation and transformation of fast-twitch skeletal muscle in response to chronic electrical stimulation augers therapeutic potential as an endogenous, readily available power source for myocardial assistance. The basis mechanisms of skeletal muscle fatigue require elucidation to gain a complete and thorough understanding of how to manipulate this property to provide continuous hemodynamic work.