Life After Surviving Fontan Surgery: A Meta-Analysis of the Incidence and Predictors of Late Death.

AIM: We now know that 20-40% of patients with a single ventricle will develop heart failure after the second decade post-Fontan surgery. However, we remain unable to risk-stratify the cohort to identify patients at highest risk of late failure and death. We conducted a systematic review of all reported late outcomes for patients with a Fontan circulation to identify predictors of late death. METHODS: We searched MEDLINE, Embase and PubMed with subject terms ("single ventricle", "Hypoplastic left heart syndrome", "congenital heart defects" or "Fontan procedure") AND ("heart failure", "post-operative complications", "death", "cause of death", "transplantation" or "follow-up studies") for relevant studies between January 1990 and December 2015. Variables identified as significant predictors of late death on multivariate analysis were collated for meta-analysis. Survival data was extrapolated from Kaplan-Meier survival curves to generate a distribution-free summary survival curve. RESULTS: Thirty-four relevant publications were identified, with a total of 7536 patients included in the analysis. Mean follow-up duration was 114 months (range 24-269 months). There were 688 (11%) late deaths. Predominant causes of death were late Fontan failure (34%), sudden death (19%) and perioperative death (16%). Estimated mean survival at 5, 10 and 20 years post Fontan surgery were 95% (95%CI 93-96), 91% (95%CI 89-93) and 82% (95%CI 77-85). Significant predictors of late death include prolonged pleural effusions post Fontan surgery (HR1.18, 95%CI 1.09-1.29, p<0.001), protein losing enteropathy (HR2.19, 95%CI 1.69-2.84, p<0.001), increased ventricular end diastolic volume (HR1.03 per 10ml/BSA increase, 95%CI 1.02-1.05, p<0.001) and having a permanent pacemaker (HR12.63, 95%CI 6.17-25.86, p<0.001). CONCLUSIONS: Over 80% of patients who survive Fontan surgery will be alive at 20 years. Developing late sequelae including protein losing enteropathy, ventricular dysfunction or requiring a pacemaker predict a higher risk of late death.

Cardiopulmonary bypass changes the plasma proteome in children undergoing tetralogy of Fallot repair.

INTRODUCTION: Cardiopulmonary bypass (CPB) can be associated with deleterious clinical effects. However, the impact of CPB on inflammatory, immunological and other homeostatic pathways remains poorly understood. We investigated the impact of CPB on the plasma proteome in children undergoing tetralogy of Fallot repair. METHODS: Blood samples were taken from 20 children prior to and at the end of CPB and 6h, 12h and 24h after CPB. Plasma was analysed by liquid chromatography-mass spectrometry (LC-MS) in a label-free, untargeted approach. Data were analysed using Genedata software to identify peptides that were differentially expressed (p<0.01 above a false discovery rate). Proteins were identified from peptides that demonstrated differential expression. RESULTS: The proteins that were found to be differentially expressed were haptoglobin isoform 1 preproprotein, isoform 2 of semaphorin-6C, vitamin D-binding protein, inter-alpha-trypsin inhibitor, ceruloplasmin, apolipoprotein B100 and fibrinogen alpha. CONCLUSION: CPB alters the plasma proteome with differences most apparent at 6h and 12h post CPB. There was a return to baseline with no proteins differentially regulated by 24h.

Extracorporeal membrane modality conversions.

We report the case of a patient with cardiovascular and respiratory failure due to severe anaphylaxis requiring multiple extracorporeal membrane oxygenation (ECMO) cannulation strategies to provide adequate oxygen delivery and ventilatory support during a period of rapid physiological change. ECMO provides partial or complete support of oxygenation-ventilation and circulation. The choice of which ECMO modality to use is governed by anatomical (vessel size, cardiovascular anatomy and previous surgeries) and physiological (respiratory and/or cardiac failure) factors. The urgency with which ECMO needs to be implemented (emergency cardiopulmonary resuscitation (eCPR), urgent, elective) and the institutional experience will also influence the type of ECMO provided. Here we describe a 12-year-old schoolgirl who, having been resuscitated with peripheral veno-venous (VV) ECMO for severe hypoxemia due to status asthmaticus in the setting of acute anaphylaxis, required escalation to peripheral veno-arterial (VA) ECMO for precipitous cardiovascular deterioration. Insufficient oxygen delivery for adequate cellular metabolic function and possible cerebral hypoxia due to significant differential hypoxia necessitated ECMO modification. After six days of central (transthoracic) VA ECMO support and 21 days of intensive care unit (ICU) care, she made a complete recovery with no neurological sequelae. The use of ECMO support warrants careful consideration of the interplay of a patient's pathophysiology and extracorporeal circuit dynamics. Particular emphasis should be placed on the potential for mismatch between cardiovascular and respiratory support as well as the need to meet metabolic demands through adequate cerebral, coronary and systemic oxygenation. Cannulation strategies occasionally require alteration to meet and anticipate the patient's evolving needs.

Paediatric heart transplantation in Australia comes of age: 21 years of experience in a national centre.

BACKGROUND: Heart transplantation (HT) is established therapy for end-stage heart failure in children with cardiomyopathy or congenital heart disease. AIMS: This review summarises experience at a national referral centre since the first local transplant. METHODS: Medical records of children referred for HT between 1 April 1988 and 1 January 2010 were retrospectively reviewed. All patients listed for HT were included. Survival analysis was used to summarise wait-list time to death/transplant, and separately, time to death in HT patients. RESULTS: One hundred and thirty-nine children were accepted on to the HT waiting list during the study (median age 7.7 (interquartile range (IQR) 2.5, 13.6) years), of whom 93 underwent HT (median age 10.9 (IQR 4.4, 14.6) years). Wait-list mortality was 32% (45 of 139 patients), lowest among children aged >10 years at listing (P < 0.001). Median time to HT was 69 days (range 29-146). Survival post-transplantation was 90% (95% confidence interval 82-95) at 1 year, 82% (72-89%) at 5 years and 68% (50-80%) at 10 years. Increasing case complexity over the study period included pre- and post-transplant circulatory support, management of pulmonary hypertension and introduction of ABO-incompatible HT for infants. Post-transplant survival did not vary according to age, pre-transplant diagnosis or use of pre-transplant circulatory support (all P > 0.05). CONCLUSIONS: Results of paediatric HT in Australia are comparable with international results, despite limitations of geographic isolation, small population and low organ donation rate. Increasing case complexity has not impacted on post-transplant survival.

The Australia and New Zealand Fontan Registry: description and initial results from the first population-based Fontan registry.

BACKGROUND: The Fontan procedure is the final in a series of staged palliations for single-ventricle congenital heart disease, which encompasses rare and heterogeneous cardiac lesions. It represents an unusual and novel physiological state characterised by absence of a subpulmonary ventricle. AIMS: The population is growing steadily, prompting creation of this registry to study their epidemiology, demographic trends, treatment and outcomes. METHODS: This multicentre, binational, prospective and retrospective, web-based registry involving all congenital cardiac centres in the region has identified nearly all Fontan patients in Australia and New Zealand. Patients identified retrospectively were approached for recruitment. New recipients are automatically enrolled prospectively unless they choose to opt-out. Follow-up data are collected yearly. RESULTS: Baseline data were obtained in 1072 patients as at 1 January 2011. Ninety-nine patients died; 64 were lost to follow up. Forty-four per cent of patients lost were between 20 and 30 years of age. The size of the Fontan population is increasing steadily. Among 973 living patients, 541 (56%) gave consent for prospective collection of follow up. Between 1 January 2011 and 1 January 2013, an additional 47 subjects were enrolled prospectively. The current proportion of patients operated with hypoplastic left heart syndrome is currently 29% and is growing rapidly. CONCLUSION: The population surviving after the Fontan procedure has been growing in recent decades, especially since survival with hypoplastic left heart syndrome has improved. The Australia and New Zealand Fontan Registry provides population-based data, and only large databases like this will give opportunities for understanding the population and performing prospective trials.

A divergent transcriptional landscape underpins the development and functional branching of MAIT cells.

MR1-restricted mucosal-associated invariant T (MAIT) cells play a unique role in the immune system. These cells develop intrathymically through a three-stage process, but the events that regulate this are largely unknown. Here, using bulk and single-cell RNA sequencing-based transcriptomic analysis in mice and humans, we studied the changing transcriptional landscape that accompanies transition through each stage. Many transcripts were sharply modulated during MAIT cell development, including SLAM (signaling lymphocytic activation molecule) family members, chemokine receptors, and transcription factors. We also demonstrate that stage 3 "mature" MAIT cells comprise distinct subpopulations including newly arrived transitional stage 3 cells, interferon-γ-producing MAIT1 cells and interleukin-17-producing MAIT17 cells. Moreover, the validity and importance of several transcripts detected in this study are directly demonstrated using specific mutant mice. For example, MAIT cell intrathymic maturation was found to be halted in SLAM-associated protein (SAP)-deficient and CXCR6-deficient mouse models, providing clear evidence for their role in modulating MAIT cell development. These data underpin a model that maps the changing transcriptional landscape and identifies key factors that regulate the process of MAIT cell differentiation, with many parallels between mice and humans.

Initial results of primary device closure of large muscular ventricular septal defects in early infancy using perventricular access.

OBJECTIVES: To report our experience with the use of the Amplatzer muscular ventricular septal defect (VSD) occluder, using direct right ventricle free wall puncture for primary closure of muscular VSDs in infants. BACKGROUND: Young infants with heart failure due to large or multiple muscular VSDs often require intervention at a stage when percutaneous device closure is impractical due to delivery system limitations. There are considerable benefits to avoiding bypass in these infants. METHODS: Patients with suitable muscular VSDs, considered too small for transvenous closure, underwent periventricular muscular VSD closure under transesophageal echo (TEE) guidance. RESULTS: Eight infants underwent the procedure. The median age was 14 weeks (2-41) with median weight of 4 kg (3-6.6). Four patients had additional VSDs and one patient had previous repair of coarctation. One patient had dextrocardia and severe left ventricular impairment due to an associated cardiomyopathy. The median VSD size was 8 mm (range, 4-10 mm). A single device (6-12 mm) was deployed in each patient, the size chosen being 1-2 mm larger than the TEE measurement. Two patients had subsequent pulmonary artery banding, with absorbable bands, because of moderate residual shunting through additional VSDs. The latest echo study at a median of 7.2 weeks (0.5-66) post device implantation revealed no patients with a hemodynamically significant shunt. CONCLUSION: Perventricular muscular VSD closure can be safely and effectively undertaken in small infants with suitable muscular defects, and this strategy can avoid the need for bypass.

Tetralogy of Fallot: transannular and right ventricular patching equally affect late functional status.

BACKGROUND: In tetralogy of Fallot, transannular patching is suspected to be responsible for late right ventricular dilatation. METHODS AND RESULTS: In our institution, 191 patients survived a tetralogy of Fallot repair between 1964 and 1984. Transannular patching was used in 99 patients (52%), patch closure of a right ventriculotomy in 35, and direct closure of a right ventriculotomy in 55. Two had a transatrial-transpulmonary approach. To identify predictive factors of adverse long-term outcome related to right ventricular dilatation, the following events were investigated: cardiac death, reoperation for symptomatic right ventricular dilatation, and NYHA class II or III by Cox regression analysis. Mean follow-up reached 22+/-5 years. The 30-year survival was 86+/-5%. Right ventricular patching, whether transannular or not, was the most significant independent predictor of late adverse event (improvement chi(2)=16.6, P:<0.001). In patients who had direct closure, the ratio between end-diastolic right and left ventricular dimensions on echocardiography was smaller (0.61+/-0.017 versus 0. 75+/-0.23, P:=0.007), with a smaller proportion presenting severe pulmonary insufficiency (9% versus 40%, P:=0.005). There was no difference between right ventricular and transannular patching concerning late outcome (log rank P: value=0.6), right ventricular size (0.70+/-0.28 versus 0.76+/-0.26, P:=0.4), or incidence of severe pulmonary insufficiency (30% versus 43%, P:=0.3). CONCLUSIONS: In tetralogy of Fallot, transannular patching does not result in a worse late functional outcome than patching of an incision limited to the right ventricle. Both are responsible for a similar degree of long-term pulmonary insufficiency and right ventricular dilatation.

Tricuspid valve repair for tricuspid valve endocarditis after Fallot repair.

Occurrence of endocarditis after surgical repair of tetralogy of Fallot is rare. A case of early postoperative endocarditis in a 1-year-old infant is described. At reoperation an abscess of the the tricuspid valve annulus was discovered at the site of implantation of the ventricular septal defect patch. After debridement of the annulus, the septal and the anterior leaflet of the tricuspid valve were found dehiscent from their annular insertion. The tricuspid annulus was reconstructed with a patch of autologous pericardium, and the preserved leaflets were reimplanted.

Ischemic gastric ulcer after coronary bypass using the right gastroepiploic artery.

The gastroepiploic artery has been widely used for complete arterial myocardial revascularization of young patients. Gastric complications related to the harvesting of this artery are exceptional. We describe here a case of ischemic gastric ulcer due to the use of a gastroepiploic artery in a patient with severe celiac trunk disease. The patient was cured by angioplasty completed by a stenting procedure.

Orthotopic heart transplantation in situs inversus.

The case of a successful orthotopic heart transplantation for complete situs inversus with double-inlet left ventricle and anomalies of the systemic venous return is reported. A piece of aortic homograft and a composite conduit made of the recipient right atrium and pericardium were used to connect, respectively, the left superior vena cava and the hepatic veins to the right-sided atrium of the donor heart.

Long-term results of operation for paravalvular abscess.

BACKGROUND: Operation for infective endocarditis with paravalvular abscess is reportedly associated with high mortality and morbidity rates. In an attempt to improve surgical outcome, an approach of radical resection of the abscess and inflamed tissues and reconstruction of the heart with either fresh or glutaraldehyde-fixed bovine pericardium was adopted by two surgeons at our institution. METHODS: From 1979 to 1995, 70 consecutive patients with active infective endocarditis and paravalvular abscess underwent operation. Their mean age was 49 years (range, 16 to 75 years), and 50 patients (71%) were men. Thirty-four patients had native and 36 had prosthetic valve endocarditis (8 had had composite replacement of the aortic valve and ascending aorta). Most patients (78%) were in New York Heart Association functional class IV. The principal indication for operation was cardiogenic or septic shock in 11 patients, or one or more of the following: persistent sepsis despite adequate antibiotic therapy in 36, congestive heart failure in 31, and recurrent emboli in 16. Staphylococci were responsible for the infection in 37 patients (53%). The abscess was in the mitral annulus in 11 patients, in the aortic root in 44, and in the aortic root and at least one other annulus in 15. After wide resection of the abscess, we reconstructed the heart and annuli with autologous or bovine pericardium. Mechanical heart valves were implanted in 36 patients, bioprostheses in 30, and aortic homografts in 2; valve repair was possible in 2. Sixteen patients required composite replacement of the ascending aorta and aortic valve. RESULTS: There were 9 operative deaths (13%). Infections caused by staphylococci and infections in multiple annuli were associated with increased operative mortality rates. Only 1 patient had persistent infection and required reoperation. The mean follow-up was 56 +/- 40 months. There were 12 late deaths, mostly cardiac. The actuarial survival including operative deaths was 64% +/- 8% at 8 years. In 8 patients, recurrent infective endocarditis developed 10 to 102 months after operation. The freedom from recurrent endocarditis was 76% +/- 10% at 8 years. CONCLUSIONS: This experience indicates that radical resection of the abscess and reconstruction of the heart with pericardium yield an excellent chance of eradicating the infection in patients with infective endocarditis and paravalvular abscess. The type of valve implanted may not be as important as radical resection of the abscess. These patients appear to have a greater than average risk of recurrent endocarditis.

Resection of a chest chondrosarcoma invading the spine and the aorta.

A 34-year-old man presented with a large chondrosarcoma of the chest invading six ribs and the vertebral bodies of five adjacent thoracic vertebrae. En bloc resection of the tumor with six ribs, the anterior part of five vertebral bodies, and the thoracic aorta was performed through a thoracotomy and a paravertebral incision.

Early calcific stenosis of the aortic sorin pericarbon valve implanted in the elderly.

BACKGROUND: We reviewed our experience with the Sorin Pericarbon (Sorin, Saluggia, Italy) valve implanted in the aortic position. METHODS: From January 1990 to January 1996, 143 consecutive patients had a Pericarbon valve implanted in the aortic position. The mean age was 75+/-5 years. Seventy-eight patients (55%) were in New York Heart Association (NYHA) class III or IV. Sixty patients (42%) had one or more concomitant procedures (51 coronary artery bypass grafting [CABG], 7 carotid endarterectomies, 9 others). RESULTS: The hospital mortality rate was 12% (17 of 143 patients). The follow-up was 100% complete and the median time was 42 months (range, 2 to 79 months). There were 36 late deaths, 20 being cardiac-related: 5 non-valve-related, 11 valve-related, and 4 sudden unexpected deaths. The 5-year actuarial survival was 57%+/-5%. There were 6 early valve failures related to a calcific stenosis at a median time of 36 months (range, 5 to 66 months). Three patients had to undergo another operation and one of these patients died. One patient died the day before the planned reoperation and 2 patients are followed with a symptomatic aortic stenosis but refuse reoperation. Freedom from structural deterioration was 93%+/-3% at 4 years. Echocardiographic examination was obtained in 73 patients at a median time of 42 months (range, 4 to 79 months). Four additional asymptomatic patients were found to have calcifications of their prosthesis. The 5-year freedom from thromboembolic events and from endocarditis were, respectively, 87%+/-5% and 92%+/-3%. CONCLUSION: The surprisingly high rate of early failure due to calcific stenosis and of thromboembolic events of the Pericarbon valve implanted in the aortic position in the elderly made us discontinue its use in our institution.

Recycling of arterial grafts during reoperative coronary artery operations.

BACKGROUND: To overcome problems of lack of conduit and to maximize the number of arterial anastomoses in coronary reoperations we reused previously placed arterial grafts. METHODS: Sixteen patients were identified from February 1994 to July 1997. Mean age was 62.8 years (range, 44 to 75 years). Fifteen (94%) were in Canadian Cardiovascular Society angina class III or IV. The mean interval from primary to secondary operation was 8.5 years (range, 3 to 12 years). Eleven patients had a patent internal mammary artery graft used as the recipient for a proximal Y anastomosis. In 3 cases an arterial graft was reimplanted distally on the same coronary vessel and in 2 onto different coronary vessels. One patient had a combination of these techniques. Five patients required venous conduit. RESULTS: There were no deaths. Mean length of intensive care stay was 69 hours (range, 24 to 144) and mean hospital stay was 14 days (range, 10 to 28 days). All patients were discharged home. Follow-up averages 13 months (range, 2 to 43 months). Twelve patients (75%) are now in Canadian Cardiovascular Society angina class I and 3 (19%) in class II. CONCLUSIONS: Reusing arterial conduits during coronary reoperations is possible with minimal in-hospital morbidity and satisfactory results in terms of freedom from angina. Using these techniques can help overcome the problems of inadequate conduit and maximize the number of arterial anastomoses that can be made per patient.

Late homograft valve insertion after transannular patch repair of tetralogy of Fallot.

BACKGROUND AND AIMS OF THE STUDY: Transannular patch repair of tetralogy of Fallot leads to pulmonary insufficiency and progressive right ventricular dilatation responsible for a decreased exercise capacity. We studied the impact of late homograft insertion on the regression of the right ventricular volumes in symptomatic patients. METHODS: Between July 1992 and August 1996, 15 consecutive patients (age range: 4 to 24 years) were operated on at a median of 13 years (range: 3 to 20 years) after transannular patch repair of tetralogy of Fallot. All patients complained of exertional dyspnea and fatigue. Syncopes were reported in six patients and four patients had sustained episodes of ventricular tachycardia. Fourteen had pulmonary regurgitation grade 3 or 4 and one had an associated stenosis and insufficiency. All patients had a dilated right ventricle. At reoperation, no patients presented with major aneurysm. The patch was resected and the right ventricular outflow tract reconstructed with a cryopreserved pulmonary homograft. Right ventricular volumes were studied before the procedures and at the last follow up consultation. RESULTS: There was no operative death. One patient who had a concomitant patch repair of a hypoplastic left pulmonary artery needed extracorporeal circulatory support for eight days. After a median follow up of 25 months (range: 3 to 54 months) all patients but one are in NYHA class I. There were no late deaths. The mean end-diastolic diameter of the right ventricle decreased from 36 +/- 9 mm before surgery to 31 +/- 6 mm (not significant). The mean ratio between the end-diastolic diameter of the right and left ventricles decreased from 0.94 +/- 0.3 to 0.74 +/- 0.2 (p < 0.01). CONCLUSION: An increasing number of patients who had transannular patch repair for tetralogy of Fallot will require reoperation for symptomatic long-term pulmonary regurgitation. Homograft reconstruction of the right ventricular outflow tract of these patients induces regression of their right ventricular dilatation and leads to their functional recovery.

Transfer of the posterior leaflet of the tricuspid valve to the mitral valve.

BACKGROUND AND AIM OF THE STUDY: Coverage of large commissural defects may present a surgical challenge in mitral valve repair, for which the transfer of posterior tricuspid valve leaflet tissue is an attractive approach. METHODS: Five patients aged between 35 and 55 years underwent this procedure. After wide excision of the diseased mitral commissures, the posterior leaflet of the tricuspid valve was carefully checked, removed with its subvalvular apparatus, and transferred to the commissural area of the mitral valve. The stress on the papillary muscle suture was relieved by reinforcement of the free edge of the transferred leaflet by natural or artificial chordae. The tricuspid valve was repaired using either a sliding plasty or an annuloplasty. RESULTS: One patient who had no reinforcement of the subvalvular apparatus had a papillary muscle rupture and required mitral valve replacement during the early postoperative period. The four remaining patients remained asymptomatic and had no or trivial mitral regurgitation after a median of 13 months (range: 3-18 months), with excellent result at transesophageal echocardiography. CONCLUSION: We conclude that transfer of the tricuspid valve leaflet allows coverage of large commissural defect, and deserves a place among the surgeon's arsenal of reconstructive techniques for mitral valve repair.

Resection of the ascending aorta and aortic valve patch closure for type A aortic dissection after Novacor LVAD insertion.

A 60-year-old patient developed an acute type A aortic dissection in the postoperative course of a Novacor left ventricular assist device. We performed a resection of the ascending aorta with an aortic valve patch closure, end-to-end anastomosis of the outflow graft to the distal ascending aorta and two venous grafts to the coronary arteries, in order to avoid residual aortic insufficiency and bleeding related to exposure of the fragilized tissues to high pressures.