Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Pediatric mechanical circulatory support.

Over the past two decades clinicians and researchers have sought to bring mechanical circulatory support (MCS) to pediatric patients with heart failure. ECMO, IABPs, and VADs have all been used in infants and children as a bridge to myocardial recovery or as a bridge to transplant. However, until recently, a commitment by industry, government, and researchers towards the development of pediatric MCS has not been present, especially in the United States. Advancements in adult VAD design to smaller, quieter, and fully implantable pumps capable of complete outpatient support have sparked curiosity in the application of this technology to children. Also, the increasing success of palliating congenital heart disease is creating an ever-growing cohort of children and adolescents with heart failure. These changing demographics and technological advances have caused a refocus of attention. This is most clearly demonstrated by the international use of several established MCS pediatric and neonatal systems, by the FDAOs increasing proclivity to allow the use of international pediatric VADs in the USA, and by the recent National Heart, Lung, and Blood Institute funding of several institutions to develop pediatric VADs. This review describes the different aspects of pediatric MCS including indications, the features of the various VADs, and their current application in children worldwide.

The effect of short-term prophylactic methylprednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: The aim of this study was to determine the effect of prophylactic immune suppression on the incidence and severity ofpostpericardiotomy syndrome (PPS) in children after cardiac surgery with cardiopulmonary bypass (CPB). BACKGROUND: Prophylactic suppression of the inflammatory response has an unknown effect on the incidence and severity of PPS in children undergoing surgery with CPB. METHODS: This randomized double-blind placebo controlled trial included two study groups. Group A received pre-CPB intravenous methylprednisolone (1 mg/kg) plus four additional intravenous doses over 24 h, and Group B received intravenous saline placebo at identical intervals. Data included patient demographics, cardiac diagnosis/operation, CPB time, incidence and severity of PPS. Noncomplicated PPS--temperature >100.5 degrees F, pericardial friction rub, patient irritability, small pericardial +/- pleural effusion. Complicated PPS--noncomplicated PPS plus hospital readmission +/- pericardiocentesis or thoracentesis. RESULTS: We randomized 266 children: 20 exclusions (6 perioperative deaths, 14 reasons unrelated to treatment) leaving Group A (n = 126) and Group B (n = 120). There were no significant group differences in gender, cardiac diagnosis or CPB time. Group mean age differed (p = 0.05) and was treated as a covariate with no substantive outcome effect. In total, 39/246 children (16%) developed PPS (noncomplicated: n = 30, complicated: n = 9). There was no inter-group difference in overall PPS incidence (p = 0.73). However, Group A had a marginally significant increase in complicated PPS (p = 0.05). CONCLUSIONS: Intravenous methylprednisolone at a standard anti-inflammatory dose administered pre-CPB and early post-CPB neither prevents nor attenuates PPS in children. Short-term pre-CPB and post-CPB methylprednisolone treatment may complicate PPS.

Naloxone, adrenalectomy, and steroid replacement: evidence against a role for circulating beta-endorphin in food intake.

Naloxone has a dose-dependent, significant anorectic effect when administered to normal rats, consistent with an antagonism of central or peripheral enkephalinergic or endorphinergic mechanisms. Mean levels of circulating immunoreactive beta-endorphin were similar in intact rats (0.5 ng/ml) and dexamethasone-treated adrenalectomized rats (0.5 ng/ml). In contrast, plasma levels were high in adrenalectomized rats with no replacement steroid (1.3 ng/ml) and in adrenalectomized rats given the mineralocorticoid deoxycorticosterone (0.9 ng/ml). In sharp distinction to the clear changes in circulating immunoreactive beta-endorphin produced by adrenalectomy and selective steroid replacement, no differences were seen in baseline food intake or anorectic response to naloxone. We conclude that a physiological role for circulating beta-endorphin in the regulation of food intake appears unlikely.

Metabolic changes preceding functional and morphologic indices of rejection in heterotopic cardiac allografts. A 31P nuclear magnetic resonance study.

Eight beagles receiving heterotopic (cervical) cardiac allografts from outbred donors were evaluated by serial 31P NMR, septal endocardial biopsy, and left ventricular pressure measurements for signs of rejection. Early postoperative myocardial energy levels, as assessed by ratios of phosphocreatine to inorganic phosphate (PCr/Pi) and phosphocreatine to beta-ATP (PCr/B-ATP), were acceptable in all recipients. In these nonimmunosuppressed animals, the mean ratios of PCr/Pi and PCr/B-ATP progressively decreased, with a greater than 25% reduction noted by postoperative day two and greater than 50% reduction by day three. In sharp contrast, left ventricular end-diastolic pressures remained stable and at baseline levels for the first three postoperative days, and only then markedly increased. Likewise, histologic evidence of rejection did not become prominent until postoperative day four. These results suggest that metabolic abnormalities significantly precede either functional or histologic changes in rejecting allografts. The early detection of these metabolic changes by 31P NMR appears to have important potential for the noninvasive diagnosis of cardiac allograft rejection.

Effects of cyclosporine on cerebral blood flow and metabolism in dogs.

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Cardiopulmonary bypass with profound hypothermia. An optimal preservation method for multiorgan procurement.

Numerous techniques have been devised for the harvesting of individual organs during a multiorgan procurement operation. Cardiopulmonary bypass with profound hypothermia (PH) has been employed in successful harvesting of heart-lung, kidney, pancreas, and liver grafts. This report summarizes our experience using CPB-PH for the harvesting of multiple organs from 10 brain-dead donors during the period from July 1983 to January 1988. Organs harvested included 10 heart-lungs, 17 kidneys (3 kidneys were not harvested due to anatomy and elevated creatinine), 1 liver, and 1 pancreas. Mean ischemic time for the distantly procured heart-lung grafts was 281 +/- 10 min. Adequate pulmonary function, as assessed by arterial blood gases, was observed in each heart-lung recipient (mean PO2 was 119 +/- 46 mmHg, 164 +/- 47 mmHg, 130 +/- 30 mmHg, 114 +/- 26 mmHg at immediate post-CPB, 6 hr postop, 24 hr postop, and postextubation, respectively). Mean length of intubation was 34 +/- 8 hr. Mean creatinines of kidney recipients at days 2, 7, and current creatinine were 7.4 +/- 3.6 mg%, 3.6 +/- 2.4 mg%, and 1.6 +/- 0.66 mg%, respectively. Eight kidney recipients (47%) required dialysis, (2 patients required only a single dialysis). Ninety-four percent of the kidney transplant patients are alive, and 88% (15/17) have functioning kidneys. One liver and 1 pancreas were harvested during this time period. Preservation was satisfactory in both the pancreas (Johns Hopkins Hospital) and liver (Dr. Thomas Starzl, personal communication). The technique of CPB-PH has resulted in excellent function of heart-lung grafts. Follow-up of the transplanted kidneys, liver, and pancreas utilizing this technique shows equal or better function compared with standard techniques. This technique offers other advantages in addition to satisfactory multiorgan preservation. Placement of an unstable patient on CPB ensures adequate organ perfusion and allows for a gradual yet uniform cooling of all organ systems. Cooling to a core temperature of 10-15 degrees C requires 30 min, during which time preliminary intraabdominal and mediastinal dissection can be carried out. Following cessation of CPB and subsequent exsanguination, organs can be more easily dissected in a near-bloodless field. This technique does not preclude additional crystalloid organ flushing. Since multiorgan procurement occurs with virtually every donor, this technique may be the optimal method providing excellent preservation, ease of dissection, and better control of hemodynamics during the operation.

Inhibition of complement, neutrophil, and platelet activation by an anti-factor D monoclonal antibody in simulated cardiopulmonary bypass circuits.

OBJECTIVES: Patients undergoing cardiopulmonary bypass frequently manifest generalized systemic inflammation and occasionally manifest serious multiorgan failure. Inflammatory responses of bypass are triggered by contact of blood with artificial surfaces of the bypass circuits, surgical trauma, and ischemia-reperfusion injury. We studied the effects of specific inhibition of the alternative complement cascade by using an anti-factor D monoclonal antibody (166-32) in extracorporeal circulation of human whole blood used as a simulated model of cardiopulmonary bypass. METHODS: Five healthy blood donors were used in the study. Monoclonal antibody 166-32 was added to freshly collected, heparinized human blood recirculated in a pediatric cardiopulmonary bypass circuit at a final concentration of 18 microg/mL. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets by immunofluorocytometric methods and enzyme-linked immunosorbent assays. RESULTS: Monoclonal antibody 166-32 inhibited the alternative complement activation and the production of Bb, C3a, sC5b-9, and C5a. Upregulation of CD11b on neutrophils and CD62P on platelets was also significantly inhibited by monoclonal antibody 166-32. This is consistent with the inhibition of the release of neutrophil-specific myeloperoxidase and elastase and platelet thrombospondin. The production of proinflammatory cytokine interleukin 8 was also suppressed by the antibody. CONCLUSIONS: The alternative complement cascade is predominantly activated during extracorporeal circulation. Anti-factor D monoclonal antibody 166-32 is effective in inhibiting the activation of complement, neutrophils, and platelets. Inhibition of the alternative complement pathway by targeting factor D could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.

Hemodynamic and physiologic changes during support with an implantable left ventricular assist device.

To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy.

Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants.

To evaluate changes in coronary blood flow during allograft rejection, 16 beagles with cervical cardiac allografts from mongrel donors were immunosuppressed postoperatively for 7 days with cyclosporine (20 mg/kg orally) and prednisone (0.5 mg/kg orally). They were weaned from immunosuppression over 3 days and then treated with methylprednisolone (30 mg/kg/day IV), cyclosporine (20 mg/kg orally), and prednisone (0.5 mg/kg orally) for 4 days. Previous experiments with this model have suggested the utility of phosphorus 31 nuclear magnetic resonance spectroscopy (31P NMR) in the diagnosis of rejection. Therefore in 10 dogs (NMR group) bioenergetic changes during rejection were assessed using the 31P NMR index of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). To correlate coronary blood flow and graft ischemia with allograft rejection, six dogs (FLOW group) underwent placement of a magnetic flow probe on the left anterior descending coronary artery to determine mean and peak coronary flow. In both NMR and FLOW groups, grafts were evaluated by endomyocardial biopsy (grading 0 to 8 for increasing rejection), and measurement of lactate production and left ventricular end-diastolic pressure. During the initial 7 days of immunotherapy, cellular rejection was effectively suppressed, and the bioenergetic status of the grafts remained stable (day 7: PCr/Pi = 70% of baseline, biopsy score = 2.0). During weaning of immunotherapy, however, the metabolic profile of the grafts decayed (day 10: PCr/Pi = 45% of baseline, biopsy score = 5.8; p less than 0.05 vs day 0). After 4 days of augmented immunosuppression, PCr/Pi recovered to 83% of baseline; this metabolic recovery corresponded with an improvement in mean biopsy score to 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and chronic pulmonary vasoconstriction after left lung autotransplantation in conscious dogs.

We investigated the acute and chronic effects of left lung autotransplantation (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in conscious dogs. Continuous LP/Q plots were generated in chronically instrumented conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented normal conscious dogs were studied at equal time points post-surgery. LLA had little or no effect on baseline systemic hemodynamics or blood gases. In contrast, compared with normal conscious dogs, striking active flow-independent pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/- 0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post-LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial blood gases were unchanged when total pulmonary blood flow was directed to exclusively perfuse the transplanted left lung. Thus, LLA results in both acute and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a useful stable experimental model to assess the specific effects of surgical transplantation on pulmonary vascular regulation.

Cervical esophago-esophageal anastomosis.

We describe our results with cervical esophagoesophageal anastomosis. This approach has been used with success in 4 patients. It has the advantage of avoiding esophagectomy in patients with benign disease and allows restoration of esophageal continuity in patients having limited options for esophageal replacement.

Modified Norwood procedure for hypoplastic left heart syndrome.

BACKGROUND: Since June 1994, we have used a modification of the Norwood technique in 13 patients presenting with the hypoplastic left heart syndrome or similar variants. METHODS: This technique involves coarctation repair, arch reconstruction, and creation of a neo-ascending aorta using autologous great vessel tissue only. Pulmonary blood flow is provided by a central shunt of 3.0- to 4.0-mm Gore-Tex. RESULTS: The mean age and weight at operation were 15 days (range, 1 to 77 days) and 3.2 kg (range, 1.7 to 4.6 kg), respectively. The mean circulatory arrest time was 32 minutes (range, 25 to 50 minutes). There was one operative death, and there have been no late deaths. Seven patients have gone on to conversion to a bidirectional cavopulmonary shunt at a mean age of 6 months. There have been no cases of recurrent coarctation, arch obstruction, or left pulmonary artery stenosis. Significant coronary insufficiency requiring revision of the ascending aortic reconstruction has developed in 2 patients. CONCLUSIONS: We believe this approach offers the advantage of using the patient's own native tissue for all great vessel reconstruction. This technique may also allow 10 to 15 minutes less of circulatory arrest time. The theoretic benefits include improved growth of repaired structures and avoidance of homograft or prosthetic material. The long-term results remain to be elucidated.

Prosthetic mitral valve replacement after atrioventricular septal defect repair: a technique for small children.

An 11-month-old girl was transferred for consideration of cardiac transplantation. She had previously undergone repair of complete atrioventricular septal defect at another institution. Her postoperative course was notable for severe mitral regurgitation, pulmonary hypertension, and heart failure. At reoperation, the left atrioventricular valve was considered irreparable with a very small (11 mm) annulus. Using a technique to enlarge the mitral annulus, a 17-mm prosthetic valve was placed. Her postoperative course was unremarkable and she is doing very well at 3 years follow-up.

Ross-Konno procedure with interrupted aortic arch repair in a premature neonate.

A 1,700-g premature baby who presented with interrupted aortic arch type B, hypoplastic aortic annulus, severe subaortic stenosis, and large ventricular septal defect underwent successful surgical repair. A Ross-Konno operation was used to address the left ventricular outflow tract obstruction, hypoplastic aortic annulus, and ventricular septal defect. The interruption was repaired with a direct anastomosis.

Correction of anomalous systemic venous drainage in heterotaxy syndrome.

A 3-month-old patient with heterotaxy syndrome, complex intracardiac malformations, and severe heart failure underwent surgical correction. Anatomy included an interrupted inferior vena cava with hemiazygous continuation to a persistent left superior vena cava draining to the left atrium. The presence of partial anomalous pulmonary venous drainage precluded an intraatrial baffle. Systemic venous reconstruction was achieved using the left atrial appendage along with an intracardiac repair of the other defects.

Surgical repair of severe bilateral branch pulmonary artery stenosis.

Management options for severe, bilateral branch pulmonary artery stenosis include percutaneous balloon dilation and direct surgical correction. Results with both balloon angioplasty and operation have been somewhat unpredictable. We report a case of staged surgical correction involving bilateral branch pulmonary artery reconstruction.

Tetralogy of Fallot: surgical management individualized to the patient.

BACKGROUND: Over the past four decades, the surgical trend has been toward early, complete repair of tetralogy of Fallot (TOF). Many centers currently promote all neonates for total correction irrespective of anatomy and symptoms, with some surgeons advocating hypothermic circulatory arrest for repair in small infants. We believe this approach increases morbidity. METHODS: Based on approximately 40 years' experience in 2,175 patients, we developed a management protocol focused on patient size, systemic arterial saturations, and anatomy. Symptomatic patients (hypercyanotic spells, ductal dependent pulmonary circulation) weighing less than 4 kg undergo palliative modified Blalock-Taussig shunt (BTS) followed by complete repair at 6 to 12 months. Asymptomatic patients, weighing less than 4 kg who have threatened pulmonary artery isolation, undergo BTS and repair at 6 to 12 months. All other patients undergo complete repair after 6 months. RESULTS: From July 1, 1995, to December 1, 1999, 144 patients underwent operation for TOF (129 patients) or TOF with atrioventricular septal defect (TOF/AVSD, 15 patients). Ninety-four patients underwent one stage complete repair (88 TOF, 6 TOF/AVSD). Thirty-nine patients underwent repair after initial BTS (32 TOF, 7 TOF/AVSD). Ten patients are awaiting repair after BTS. The mean age and weight at complete repair were 18 months and 9 kg. There were no operative deaths. There have been 3 late deaths with complete follow-up (mortality 3 of 144 [2.1%]). Four of 133 patients (3%) have required reoperation after total correction. CONCLUSIONS: This management strategy optimizes outcomes by individualizing the operation to the patient. Advantages include avoidance of circulatory arrest, low morbidity and mortality, and low incidence of reoperation after complete repair.

Right-to-left interatrial shunt after pneumonectomy.

BACKGROUND: Platypnea and Orthodeoxia have been described with congenital heart and severe lung diseases. METHODS: We report 4 patients in whom platypnea and orthodeoxia developed after pneumonectomy. In these patients the mean oxygen saturation on room air was 65% (range, 45% to 79%) in the supine position. On O2 therapy it improved to 94% (range, 80% to 99%). When the patients assumed the erect position and were receiving O2 therapy the saturation dropped to a mean of 76% (range, 56% to 82%) and the patients complained of shortness of breath. Cardiac catheterization revealed a mean pulmonary capillary wedge pressure of 11.6 mm Hg (range, 7 to 18 mm Hg). All patients had normal right atrial pressure. A right-to-left interatrial shunt through a patent foramen ovale was documented by transesophageal echocardiography and dynamic ultrafast magnetic resonance imaging. The patients underwent surgical closure of the patent foramen ovale. RESULTS: In the erect position, the room air O2 saturation improved to a mean of 95% (range, 92% to 99%), and the shortness of breath disappeared. CONCLUSIONS: Postpneumonectomy patients complaining of shortness of breath should be assessed for platypnea and orthodeoxia. A right-to-left interatrial shunt through a patent foramen ovale can occur even in the absence of elevated right heart pressures, especially after right pneumonectomy, and is accentuated in the upright posture. Surgical correction of the patent foramen ovale can produce dramatic improvement.

Airway management during bilateral sequential lung transplantation for cystic fibrosis.

Bilateral sequential lung transplantation is now an accepted therapy for patients with end-stage cystic fibrosis. In our experience, the use of a standard double-lumen endotracheal tube to establish one-lung ventilation during bilateral lung transplantation has been associated with difficulty in clearing the airway of the thick, tenacious secretions characteristically seen in these patients. Intraoperatively, retained secretions have resulted in inadequate ventilation with subsequent hypercarbia, hypoxia, and the need for cardiopulmonary bypass support. We therefore changed our airway management to a single-lumen endotracheal tube combined with a bronchial blocker to establish one-lung ventilation during bilateral lung transplantation. The lumen of a single-lumen tube accommodates larger suction catheters and an adult bronchoscope, which has a larger suction port. We have used this technique in our last five transplantations, finding easier clearing of airway secretions along with markedly improved ventilation compared with management with a double-lumen tube. We recommend this technique of airway management when performing a bilateral single-lung transplantation for end-stage cystic fibrosis.