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ObjectivesLow cardiac output state is the principal cause of morbidity after surgical intervention for congenital heart disease. Myocardial ischemia–reperfusion injury, apoptosis, capillary leak syndrome, and myocardial edema are associated factors. We established a clinically relevant model to examine relationships between myocardial ischemia, edema, and cardiac dysfunction and to assess the role of the water transport proteins aquaporins.MethodsSixteen lambs were studied. Seven were control animals not undergoing cardiopulmonary bypass, and 9 underwent bypass. Six had 90 minutes of aortic crossclamping with blood cardioplegia and moderate hypothermia. The remaining 3 underwent cardiopulmonary bypass without aortic crossclamping. Hemodynamic and biochemical data were recorded, and myocardial edema, apoptotic markers, and aquaporin expression were determined after death.ResultsThe group undergoing cardiopulmonary bypass with aortic crossclamping had a low cardiac output state, with early postoperative tachycardia, hypotension, increased serum lactate levels, and impaired tissue oxygen delivery (P < .05) compared with the group undergoing cardiopulmonary bypass without aortic crossclamping. The lambs undergoing cardiopulmonary bypass with aortic crossclamping had increased myocardial water (P < .05) compared with those not undergoing cardiopulmonary bypass and a 2-fold increase in aquaporin 1 mRNA expression (P < .05) compared with those not undergoing cardiopulmonary bypass and those undergoing cardiopulmonary bypass without aortic crossclamping.ConclusionsA temporal association between hemodynamic dysfunction, myocardial edema, and increased aquaporin 1 expression was demonstrated. Cardiopulmonary bypass without ischemia was associated with minimal edema, negligible myocardial dysfunction, and static aquaporin expression. Ischemic reperfusion injury is the main cause of myocardial edema and myocardial dysfunction, but a causal relationship between edema and dysfunction remains to be proved.

Introduction: Primary allograft failure (PAF) is the leading cause of death within 30 days of cardiac transplantation. The aim of this study was to evaluate the outcome of patients with PAF managed with veno-arterial ECMO. Methods: Data were reviewed on 53 consecutive heart transplants performed at our institution between 1 June 2005 and 31 January 2008. Nine patients (17%) who required ECMO in order to wean from cardiopulmonary bypass (group 1) were compared with the remaining patients in the cohort (group 2). Results: There were no significant differences in preoperative recipient characteristics. Group 1 patients were more likely to receive hearts with abnormal ventricular function on echocardiography prior to retrieval (4/5 vs. 4/38, p= 0.033). Eight (89%) patients requiring ECMO were weaned off support following a mean of 91.3 h, and the Ross procedure between 1994 and 2005 (8.9± 4.7 years post-Ross operation). Subjects performed a bicycle exercise test, had 2D-echocardiography and cardiac MR imaging. 76% of subjects had aortic stenosis (including 12 cases of biscuspid aortic valve), 14% had aortic regurgitation and 10% had mixed disease. In 67% of subjects a valvotomy was performed prior to the Ross procedure. Freedom from re-do aortic and/or pulmonary valve surgery was 74%. The majority of subjects were classed as NYHA I (74%) with the remainder being NYHA II. On exercise testing, the mean predicted exercise capacity achieved was 85± 22%. On echocardiography the peak velocity across the aortic valve and homograft was 1.3± 0.4m/s and 2.5± 0.6m/s respectively. Cardiac MR imaging identified only trivial aortic valve and homograft regurgitation (6.3± 8.3% and 6.6± 9.5%, respectively). Biventricular systolic function was normal (LV EF 62± 7% and RV EF 61± 6%). The indexed LV mass was 83± 19 g/m2. Of note, in 30% of cases there was evidence of late gadolinium enhancement within the left ventricle. In the main this was noted in the subendocardium of the interventricular septum. The mean aortic sinus root dimension was 40± 8mm. There is excellent autograft and homograft functionmany years post Ross procedure. The finding of septal wall infarctionmaybe related to coronary re-implantationduring the procedure.

54 The New Zealand Heart Failure Registry: Early observations G.P. Devlin ∗, R. Troughton, M. Lund, R. Doughty, on behalf of the NZHFR Investigators Department of Cardiology, Waikato Hospital, New Zealand Background: The New Zealand Heart Failure Registry (NZHFR) commenced enrolment mid 2006 with the primary aim to improve the medical care of heart failure patients, through a better understanding of patient demographics, management, and in-hospital and postdischarge outcomes. Methods: The NZHFR is a national prospective observational web –based registry. All hospitals in New Zealand admitting patients with acute heart failure have been invited to participate with a minimum and maximum requirement of 5 and 15 consecutive patients recruited per month respectively. Results: At 14/2/2007 118 patients had been enrolled with 90 day follow up data available in 69% (81/118). The mean patient age was 67 years with 2/3rds male .CXR was performed in all patients. Natriuretic peptides were assayed in less than half (55/118) .Recent echocardiography was available in 83% (98/118).Systolic dysfunction was present in 60% (71/118) .In-hospital death was infrequent (3% ( i h (

The role of nitric oxide in heart failure is unknown. The high-capacity inducible isoform of nitric oxide synthase is present in the myocardium of patients with idiopathic dilated cardiomyopathy. Plasma nitrate, the stable end-product of nitric oxide production, was significantly increased in patients with heart failure compared with normal controls (means 51·3 and 24·6 μmol/L). Vasodilation caused by increased nitric oxide may compensate for the vasoconstrictor effect of neurohumoral adaptions to heart failure. Alternatively, excess production may be detrimental to the heart by a direct negative inotropic effect.

Objective Reduced myocardial performance invariably follows pediatric cardiac surgery and is manifested by a low cardiac output state in its severest form. The role of myocardial membrane proteins in this setting is unknown. Dystrophin and dysferlin are involved in membrane integrity, whereas aquaporins selectively transport water. These proteins were examined in a model of pediatric cardiac surgery, together with a trial of poloxamer 188, which may reduce membrane injury. Methods Eight lambs were randomized to saline with or without poloxamer 188. Lambs underwent 2 hours of cardiopulmonary bypass and aortic crossclamping. After a further 9 hours of monitoring, the hearts were assessed for water content, capillary leak, and protein expression. Results Dystrophin expression was unaffected by ischemia/reperfusion, but dysferlin expression was reduced. Aquaporin 1 protein increased after ischemia/reperfusion. Poloxamer 188 administration was associated with supranormal levels of dystrophin, preservation of dysferlin expression, and normalization of aquaporin 1 expression. Poloxamer 188 was associated with less capillary leak, maintained colloid osmotic pressure, and less hemodilution. Poloxamer 188 was associated with an improved hemodynamic profile (higher blood pressure, higher venous saturation, and lower lactate), although the heart rate tended to be higher. Conclusions Changes in protein expression within the myocardial membrane were found in a clinically relevant model of pediatric cardiac surgery. Indicators of reduced performance, such as lower blood pressure and lower oxygen delivery, were lessened in association with the administration of the membrane protecting poloxamer 188. Poloxamer 188 was also associated with potentially beneficial changes in membrane protein expression, reduced capillary leakage, and less hemodilution.

Objective: This study was undertaken to determine the outcomes of patients with congenitally corrected transposition of the great arteries after restoration of the morphologically left ventricle to the systemic circulation. Methods Between November 1991 and June 2001, a total of 54 patients (median age 3.2 years, range 7 weeks–40 years) with either congenitally corrected transposition of the great arteries (n = 51) or atrioventricular discordance with double-outlet right ventricle (n = 3) underwent anatomic repair. This comprised a Senning procedure in all cases plus arterial switch (double-switch group) in 29 cases (53.7%), plus a Rastelli procedure (Rastelli-Senning group) in 22 cases (40.7%), and plus intraventricular rerouting (Senning-tunnel group) in 3 cases (5.6%). Left ventricular training by PA banding was performed before the double-switch operation in 9 of 29 cases (31%). Follow-up is complete (median 4.4 years). Results Early mortality was 5.6% (n = 3), with 2 late deaths. Kaplan-Meier survivals (± SEM) were 94.4% ± 3.1% at 1 year and 89.7% ± 4.4% at 9 years. Survivals at 7 years were 84.9% ± 7.1% in the double-switch group and 95.5% ± 4.4% in the Rastelli-Senning group ( P = .32). Of the 49 survivors, 46 (94%) were in New York Heart Association functional class I. Six have acquired new left ventricular dilatation or impaired systolic ventricular function. Four patients in the double-switch group had moderate aortic valve regurgitation develop, and 2 of them required valve replacement. Overall freedoms from reoperation at 1 and 9 years were 94.2% ± 3.3% and 77.5% ± 9.0%, with no significant difference between the groups ( P = .60). Conclusions Anatomic repair of congenitally corrected transposition of the great arteries can be carried out with low early mortality. Excellent functional status can be achieved, with good midterm survival. Continued surveillance is necessary for patents with valved conduits and to determine the longer-term function of the aortic valve and the morphologically left ventricle in the systemic circulation.

BackgroundMany genes have been implicated in the development of congenital heart disease (CHD). Next-generation sequencing offers opportunities for genetic testing but is often complicated by logistic and interpretative hurdles.ObjectivesThis study sought to apply next-generation sequencing technology to CHD families with multiple affected members using a purpose-designed gene panel to assess diagnostic potential for future clinical applications.MethodsWe designed a targeted next-generation sequencing gene panel for 57 genes previously implicated in CHD. Probands were screened in 16 families with strong CHD histories and in 15 control subjects. Variants affecting protein-coding regions were classified in silico using prediction programs and filtered according to predicted mode of inheritance, minor allele frequencies, and presence in databases such as dbSNP (Single Nucleotide Polymorphism Database) and ESP (Exome Sequencing Project). Disease segregation studies were conducted in variants identified in CHD cases predicted to be deleterious and with minor allele frequencies

Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392

Objectives Recovery from pediatric cardiac surgery is affected by ischemia–reperfusion injury, cardiac edema, and in some cases a low cardiac output syndrome. Although association has been made between the development of edema and dysfunction, modeling is confounded by intercurrent injurious stimuli that also cause cardiac edema and dysfunction. We tested whether a true causal relationship exists between edema and cardiac dysfunction. Methods We induced either ischemia or edema alone in isolated cardiomyocytes and whole Langendorff-perfused hearts. Function was measured as shortening dynamics and developed pressure, respectively. Results Ischemic injury impaired function in both cardiomyocytes and whole hearts. Isolated cells showed significant reduction in peak shortening and departure and relaxation velocities. Whole hearts displayed severely reduced developed pressures. Hyposmotic solution forced cardiomyocytes to swell to 7% greater than their normal size. No significant effect on shortening was seen. Similarly, Langendorff-perfused hearts were induced to take on 3% more water than control-perfused hearts and 9% more water than nonperfused hearts. This additional water was associated with mild dysfunction. Conclusions We demonstrate the capacity of the heart to tolerate edema greater than that seen in clinical settings without residual effect. Ischemia results in ongoing contractile dysfunction of both isolated cardiomyocytes and whole hearts. We conclude that dysfunction resulting from edema in ex vivo cardiac models is mild and suggest review of the importance given to edema-mediated dysfunction after cardiac surgery.