John J. O’Sullivan

Long-term follow-up of pediatric cardiac transplant recipients on a steroid-free regime: the role of endomyocardial biopsy

BACKGROUND Endomyocardial biopsy is used in long-term follow-up of cardiac transplant recipients to detect sub-clinical rejection. The value of this for adults and children on triple-drug immunosuppression has been disputed. We investigated its value in children maintained on a steroid-free regime. METHODS We used a retrospective review of annual surveillance biopsy results from children younger than 13 years at the time of cardiac transplant. RESULTS In a series of 40 children older than 10 years, we found no evidence of rejection in 88/130 (67.7%) biopsies; 41/130 (31.5%) showed grade 1A rejection, and 1/130 (0.8%) showed grade 1B rejection. No grade 2, 3, or 4 biopsies were found. Nine patients with 1A rejection had subsequent grade 0 biopsies, without any adjustment in treatment. Seven children had treatment changes and repeat biopsies because of grade 1A biopsies. CONCLUSION Significant late rejection is rare even in children on steroid-free maintenance. It is unlikely to be detected unexpectedly, and the practice of indefinite routine biopsy in children who are well is not justified. Future use should focus on individuals at higher risk of rejection.

Hypertension after pediatric cardiac transplantation: Detection, etiology, implications and management

Roche SL, O’Sullivan JJ, Kantor PF. Hypertension after pediatric cardiac transplantation: Detection, etiology, implications and management. 
Pediatr Transplantation 2010:14: 159–168.

Changing cyclosporin A formulation: An analysis in paediatric cardiac transplant recipients

Abstract: Cyclosporin A is the primary immunosuppressive agent used in cardiac transplantation to maintain chronic immunosuppression. Absorption may be erratic and major side‐effects include nephrotoxicity. A recently introduced formulation (Neoral®) improves absorption in cystic fibrosis heart–lung transplant recipients, but episodes of rejection have been reported on conversion from the oil‐based formulation. A retrospective analysis of 21 paediatric cardiac transplant recipients who had been converted from the oil‐based formulation to the micro‐emulsified formulation was performed. No clinical rejection episodes occurred following conversion. There was a significant reduction in dose following conversion (p < 0.001). The mean trough level was less on the new formulation (p = 0.04), but there was no difference in coefficient of variation or standard deviation. Mean glomerular filtration rate (GFR) was significantly less, but there was no difference in the rate of change of GFR on the new formulation. Erratic absorption and deteriorating renal function remain as significant problems in paediatric cardiac transplant recipients despite conversion to the new formulation.

Successful Medical Treatment of Bioprosthetic Pulmonary Valve Endocarditis Caused by Methicillin-Resistant Staphylococcus aureus

The mortality risk of prosthetic valve endocarditis is known to be increased in cases in which staphylococci are the causative organisms. Previous recommendations have concentrated on early surgical management of this condition, but there are now reports that these infections can be treated medically, thus leaving prosthetic material in situ. We describe a case of methicillin-resistant Staphylococcusaureus endocarditis on a bovine pericardial pulmonary valve that responded to antibiotic therapy without the need for surgical intervention.

The forgotten Korotkoff phases: How often are phases II and III present, and how do they relate to the other Korotkoff phases?*

BACKGROUND There are no data on the pattern of the Korotkoff phases in the normal population. This study was designed to describe the pattern of Korotkoff phase distribution in adults and children; to measure the duration of each of the phases; and to describe the differences between adults and children. METHODS A total of 57 children (7 to 8 years old) and 59 adults (median age 47 years, range 30 to 62 years) were studied. The pressure in the arm cuff was deflated using a device to provide a consistent deflation rate. The Korotkoff sounds were recorded to MiniDisc from the bell of a stethoscope and each sound described as phase I, II, III, or IV. RESULTS The most common pattern of Korotkoff phase distribution was for all five phases to be present (children [23/57; 40%], adults [24/59; 41%]). Phases I and IV were more common in children than in adults (56/57 [98%] v 47/59 [80%]; P = .002 for phase I; 52/57 [91%] v 44/59 [75%]; P = .018 for phase IV). Phases II and III were less common in children than in adults (32/57 [56%] v 50/59 [85%], P = .001 for phase II; 27/57 [47%] v 45/59 [76%], P = .001 for phase III). Phases I and IV were longer in children (median 3.9 [interquartile range, IQR 2.1 to 6.7] and 6.7 [IQR 3.2 to 9.8] sec, respectively) compared with adults (1.3 [IQR 0.7 to 2.7] and 1.7 [IQR 0.3 to 2.6), P < .001). CONCLUSIONS There are clear differences in the Korotkoff phases between adults and children. The length of phases II and III increase with age with concomitant decrease in phases I and IV. These differences between adults and children remain unexplained.

Innovative multi-site photoplethysmography measurement and analysis demonstrating increased arterial stiffness in paediatric heart transplant recipients

OBJECTIVE It has been documented that heart transplantation in children is often complicated by arterial hypertension and increased arterial stiffness. We use innovative multi-site photoplethysmography (MPPG) pulse measurement and analysis technology to assess changes in arterial stiffness in paediatric heart transplant recipients (HTRs) in comparison with healthy control (HC) children. APPROACH A group of 20 HTRs (median age 13.5 years, eight male) were compared to an overall age- and gender-matched group of 161 HCs (median age 11.6 years, 74 male). Peripheral pulse was recorded bilaterally using MPPG at the ear lobe, index finger and great toe sites, along with an electrocardiogram cardiac timing reference. Segmental pulse arrival times between peripheral sites (finger-ear, PATf-e; toe-finger, PATt-f; and toe-ear PATt-e) were calculated as arterial stiffness measures, and differences between subject groups were tested using multivariate analysis. Normalised ear, finger and toe pulse shapes were also studied and compared between groups. MAIN RESULTS After correction for heart rate and diastolic and mean arterial blood pressures, the HTR group was found to have significantly lower segmental PATt-e and PATt-f measurements, with median values of 150 ms versus 172 ms in the HC group (p  =  0.02), and 104 ms versus 118 ms in the HC group (p  =  0.01), respectively, consistent with increased arterial stiffness in the patient group. The normalised ear, finger and toe sites showed only a mild elongation in each pulse rise time for the transplant group. SIGNIFICANCE This study shows that innovative and easy-to-do MPPG gives further evidence for increased arterial stiffness in children who have undergone successful cardiac transplantation.

Novel Management of Atrial Septal Defect at Time of Lung Transplantation

We present a case of a young female patient with end-stage lung failure because of pulmonary arterial hypertension who was failing maximal medical therapy and was listed for a single sequential lung transplantation. The challenge of the case was a concomitant presence of a large atrial septal defect. The novelty of our approach was a device closure of atrial septal defect before performing transplantation with the use of intraoperative venoarterial extracorporeal membrane oxygenation.

49 Outcome after Adult Heart Transplantation following Failure of Atrial Switch Procedure

Objective To investigate the outcome of orthotopic heart transplant (OHT) in adult population for failing atrial switch operation in childhood. Methods Between 2001 and March 2013, 230 OHT were performed at our institution. Of these twenty patients (8.7%) had undergone previous atrial inversion procedures (7 Senning, 13 Mustard) for simple Transposition of Great Arteries (TGA) or TGA with ventricular septal defect (VSD) Mean age of atrial switch procedure was 22.9 ± 24.3 months. Two patients were mechanically supported to OHT with Heartware HVAD. Mean age at OHT was 27.2 ± 9.6 years, medium time from atrial switch was 25.3 years. Donor ischaemic time and CPB were 192.4 ± 50 and 207.2 ± 88.5 min respectively. Lenght of stay in ITU was 6.5 days (1–25 days). Four patients required renal replacement therapy (CVVH) and one needed tracheostomy. Median follow up is 4.7 ± 3.6 years. Five deaths occurred (25%): 3 early deaths (one cerebro-vascular accident and 2 acute rejections), 2 late deaths (a EBV-related lymphoproliferative disorder and a late rejection). All deaths occurred before 2003. Conclusions Heart transplantation in patients with failing systemic ventricle following atrial switch procedure is associated with a medium and long term good outcome in the modern era. However the recent development of mechanical cardiac support has allowed us to bridge more efficiently these patients to OHT with better selection of donors and improved outcome.

140 Evolving Technical Approach and Results in Hypoplastic Left Heart Syndrome with Intact or Highly Restrictive Atrial Septum

Background We describe our current unit approach and report interstage results in the HLHS with Intact atrial septum (IAS) or highly restrictive interatrial communication (HRIC). Method A retrospective review of the institutional HLHS programme (2005–2014). Advances in fetal diagnosis lead to delivery planning in hybrid theatre: median sternotomy and interventional defect creation/enlargement. Results 9 neonates (4 IAS and 5 HRIC) and 5 required immediate intervention postnatally. Delayed/insufficient septostomy in 3 HRIC resulted in death before stage I Norwood even with ECMO support in 2/3. Of the other 6, 2 had trans-atrial stent placement and 1 trans-atrial balloon septostomy (3 had surgical septectomy). 5/6 underwent concomitant bilateral pulmonary artery banding. All the 6 patients reached the Norwood procedure after 27 ± 21 days and 50% required ECMO postoperatively. Trans-atrial stenting resulted in less pre Norwood morbidities. There was no stent-related complications. There was no hospital mortality after Norwood and current inter-stage survival is 100%: 5 patients underwent successfully second-stage palliation, 1 of them had the Fontan completion and subsequently transplanted. Conclusion Together with advanced fetal diagnosis, effective left atrial decompression especially with trans-atrial stunting using hybrid technique and availability of mechanical support can improve the outcome of HLHS/IAS/HRIC with low interstage morbidity and excellent survival.

Reply to the correspondence letter by M. Unolt “Congenital heart disease, genetic syndromes and major non-cardiac malformations”

We appreciate the interest shown in our paper by Dr. Unolt and colleagues and agree with their comments about the influence of non-cardiac malformations and genetic abnormalities on the outcome of cardiac surgery. In our paper, we chose to look at the whole population of infants with cardiovascular malformations—including those not undergoing cardiac surgery—to look at mortality from all causes. We looked at data for 20 years from 1987–2006, and obviously, clinical management changed during that time and has continued to do so since. The very large majority of infants with significant cardiovascular malformations now undergo surgery, and the operative risk for most of them is now very low [2]. This means that the adverse effect on outcome for those with serious non-cardiac malformations is likely to have become more marked. Conversely, results have improved greatly for those with common chromosomal abnormalities, and there is