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OBJECTIVES Right heart failure (RHF) is a major complication following left ventricular assist device (LVAD) implantation. Pulmonary artery pulsatility index (PAPi) has been evaluated as a haemodynamic marker for RHF, but PAPi is dependent on pulmonary vascular resistance (PVR). We conducted a systematic review to assess the relationship between PAPi and RHF and death in patients undergoing LVAD implantation and examined the relationship between PAPi cut-off and PVR. METHODS We searched PubMed, EMBASE, CENTRAL and manually screened retrieved references to identify all clinical studies reporting PAPi in adult patients with a durable LVAD. Eligibility criteria were prespecified and 2 reviewers independently screened and extracted data; the Newcastle–Ottawa Scale was used to assess quality of non-randomized studies. This study was prospectively registered on PROSPERO (CRD42021259009). RESULTS From 283 unique records, we identified 16 studies reporting haemodynamic assessment in 20 634 adult patients with an implanted durable LVAD. Only 2 studies reported on mortality and in both, a lower PAPi was significantly associated with death. Fifteen studies reported RHF data and, in 10 studies, a lower PAPi was significantly associated with RHF. Six studies reported on PAPi cut-offs ranging from 0.88 to 3.3; and the cut-offs were directly related to PVR (r = 0.6613, P = 0.019). CONCLUSIONS Lower PAPi was associated with RHF and death following LVAD implantation, but a single PAPi cut-off cannot be defined, as it is dependent on PVR.

The Fontan circulation predisposes to multiple morbidities typically associated with older age but occurring in their third and fourth decades, consistent with premature aging. In this pilot study, we evaluated whether the Fontan circulation is associated with premature epigenetic aging. We found that in whole blood, Δage, the difference between chronological age and estimated epigenetic DNAge™, was significantly higher in those living with a Fontan circulation than in a reference cohort (z=5.59, p

Background and AimsPrevious trials evaluating remote ischaemic preconditioning in children undergoing cardiac surgery showed mixed results. We sought to determine whether adequately delivered bilateral preconditioning is cardioprotective in young children, with or without cyanosis, undergoing surgery.MethodsProspective, double-blind, randomised controlled trial at two UK centres. Children aged 3-36 months undergoing tetralogy of Fallot repair or ventricular septal defect closure were randomised in a 1:1 ratio to receive either bilateral preconditioning or sham intervention. Participants were followed up until hospital discharge or 30 days. The primary outcome was area under the curve for high-sensitivity troponin-T in the first 24 hours after surgery, analysed by intention-to-treat. Right atrial biopsies were obtained in selected patients. Trial registration:ISRCTN12923441.ResultsBetween 24 October 2016 and 8 December 2020, 120 eligible children were randomised to receive either bilateral preconditioning (n=60) or sham intervention (n=60). Participants had a median age of 7 months and 42 (35%) were female. The primary outcome, area under the curve for hs-troponin-T was higher in the preconditioning group (mean: 70.0±50.9µg/L/hr, n=56) than in controls (mean: 55.6±30.1µg/L/hr, n=58), p=0.04. Sub-group analyses did not show a differential treatment effect by oxygen saturations (pinteraction=0.25) but showed evidence of differential treatment effect by underlying defect (pinteraction=0.04). Myocardial metabolism, quantified in atrial biopsies, and secondary outcomes were not different between randomised groups.ConclusionsBilateral remote ischemic preconditioning does not attenuate myocardial injury in children undergoing surgical repair for congenital heart defects, and there was evidence of potential harm in unstented tetralogy of Fallot.

ObjectiveTo bring together patients, parents, charities and clinicians in a Priority Setting Partnership to establish national clinical priorities for research in children and adults with congenital heart disease.MethodsThe established James Lind Alliance methodology was used to identify and prioritise research on the management of congenital heart disease, focusing on diagnosis, treatment and outcomes. An initial open survey was used to gather potential uncertainties which were filtered, categorised, converted into summary questions and checked against current evidence. In a second survey, respondents identified the unanswered questions most important to them. At two final workshops, patients, parents, charities and healthcare professionals agreed the top 10 lists of priorities for child/antenatal and adult congenital heart disease research.Results524 respondents submitted 1373 individual questions, from which 313 out of scope or duplicate questions were removed. The remaining 1060 questions were distilled into summary questions and checked against existing literature, with only three questions deemed entirely answered and removed. 250 respondents completed the child/antenatal survey (56 uncertainties) and 252 completed the adult survey (47 uncertainties). The questions ranked the highest by clinicians and non-clinicians were taken forward to consensus workshops, where two sets of top 10 research priorities were agreed.ConclusionsThrough an established and equitable process, we determined national clinical priorities for congenital heart disease research. These will be taken forward by specific working groups, a national patient and public involvement group, and through the establishment of a UK and Ireland network for collaborative, multicentre clinical trials in congenital heart disease.

OBJECTIVES Cardiac surgery with hypothermic circulatory arrest (HCA) is associated with neurological morbidity of variable severity and electroencephalography (EEG) is a sensitive proxy measure of brain injury. We conducted a narrative review of the literature to evaluate the role of perioperative EEG monitoring in cardiac surgery involving HCA. METHODS Medline, Embase, Central and LILACS databases were searched to identify studies utilizing perioperative EEG during surgery with HCA in all age groups, published since 1985 in any language. We aimed to compare EEG use with no use but due to the lack of comparative studies, we performed a narrative review of its utility. Two or more reviewers independently screened studies for eligibility and extracted data. RESULTS Fourty single-centre studies with a total of 3287 patients undergoing surgery were identified. Most were observational cohort studies (34, 85%) with only 1 directly comparing EEG use with no use. EEG continuity (18, 45%), seizures (15, 38%) and electrocerebral inactivity prior to circulatory arrest (15, 38%) were used to detect, monitor, prevent and prognose neurological injury. Neurological dysfunction was reported in almost all studies and occurred in 0–21% of patients. However, the heterogeneity of reported clinical and EEG outcome measures prevented meta-analysis. CONCLUSIONS EEG is used to detect cortical ischaemia and seizures and predict neurological abnormalities and may guide intraoperative cerebral protection. However, there is a lack of comparative data demonstrating the benefit of perioperative EEG monitoring. Use of a standardized methodology for performing EEG and reporting outcome metrics would facilitate the conduct of high-quality clinical trials.

Objective:The citation history of a published article reflects its impact on the literature over time. We conducted a comprehensive bibliometric analysis to identify the most cited papers on CHD in children.Methods:One-hundred and ninety journals listed in Journal Citation Reports were accessed via Web of Science. Publications with 250 or more citations were identified from Science Citation Index Expanded (1900–2020), and those relating to structural CHD in children were reviewed. Articles were ranked by citation count and the 100 most cited were analysed.Results:The number of citations ranged from 2522 to 309 (median 431, IQR 356–518), with 35 published since 2000. All were written in English, most originated from the United States (74%), and were published in cardiovascular journals, with Circulation (28%) the most frequent. There were 86 original research articles, including 50 case series, 14 cohort studies, and 10 clinical trials. The most cited paper was by Hoffman JI and Kaplan S on the incidence of CHD. Thirteen authors had 4 or more publications in the top 100, all of whom had worked in Boston, Philadelphia, San Francisco, or Dallas, and the most prolific author was Newburger JW (9 articles).Conclusions:Citation analysis provides a historical perspective on scientific progress by assessing the impact of individual articles. Our study highlights the dominant position of US-based researchers and journals in this field. Most of the highly cited articles remain case series, with few randomised controlled trials in CHD appearing in recent years.

The number of adults with congenital heart disease (ACHD) has increased over the last decades due to advancements in medical care, including interventional and surgical therapies. We are therefore more frequently challenged by the long-term consequences of palliative or corrective surgery carried out during childhood. Although patients with ACHD may develop conditions related to general cardiovascular risk factors, such as coronary artery disease, the most common complications leading to morbidity and mortality are arrhythmias, heart failure and thromboembolic events. For the management of arrhythmias, current recommendations regarding ablation and device therapy must be considered, whilst also taking into account the anatomical limitations of their congenital heart defect or surgical pathways. Heart failure treatment in acute and chronic settings must also consider the particular anatomy present, including the nature of the systemic ventricle. Treatments strategies for ACHD are typically extrapolated from the respective guidelines in non-ACHD patients, despite a lack of evidence to support this strategy. Right heart failure can be especially challenging to manage in conditions where either a systemic right ventricle or shunt lesions resulting in volume and/or pressure loading of the right ventricle are present. All physicians and cardiologists in particular should be acquainted with the most common diseases in ACHD, their complications and management regime, especially with regards to heart failure as this is a common reason for acute presentation in the emergency department.

IntroductionMyocardial protection against ischaemic-reperfusion injury is a key determinant of heart function and outcome following cardiac surgery in children. However, with current strategies, myocardial injury occurs routinely following aortic cross-clamping, as demonstrated by the ubiquitous rise in circulating troponin. Remote ischaemic preconditioning, the application of brief, non-lethal cycles of ischaemia and reperfusion to a distant organ or tissue, is a simple, low-risk and readily available technique which may improve myocardial protection. The Bilateral Remote Ischaemic Conditioning in Children (BRICC) trial will assess whether remote ischaemic preconditioning, applied to both lower limbs immediately prior to surgery, reduces myocardial injury in cyanotic and acyanotic young children.Methods and analysisThe BRICC trial is a two-centre, double-blind, randomised controlled trial recruiting up to 120 young children (age 3 months to 3 years) undergoing primary repair of tetralogy of Fallot or surgical closure of an isolated ventricular septal defect. Participants will be randomised in a 1:1 ratio to either bilateral remote ischaemic preconditioning (3×5 min cycles) or sham immediately prior to surgery, with follow-up until discharge from hospital or 30 days, whichever is sooner. The primary outcome is reduction in area under the time-concentration curve for high-sensitivity (hs) troponin-T release in the first 24 hours after aortic cross-clamp release. Secondary outcome measures include peak hs-troponin-T, vasoactive inotrope score, arterial lactate and central venous oxygen saturations in the first 12 hours, and lengths of stay in the paediatric intensive care unit and the hospital.Ethics and disseminationThe trial was approved by the West Midlands-Solihull National Health Service Research Ethics Committee (16/WM/0309) on 5 August 2016. Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings. Parents will be informed of the results through a newsletter in conjunction with a local charity.Trial registration numberNCT12923441.

To examine the role and outcomes of all interventions for aortic stenosis in children, with focus on freedom from reintervention and the aim to minimise prosthetic aortic valve replacement (pAVR) during childhood. Retrospective analysis of 194 consecutive children who underwent any aortic valve intervention for a biventricular repair strategy at a single institution between 1995 and 2017. Data were obtained from hospital records and follow-up was 100% complete. Over a 22-year period, 194 children underwent total 313 aortic valve procedures: Primary interventions were surgical valvotomy (SV)/surgical repair (SR) in 94 (48.5%), balloon valvuloplasty (BV) in 60 (30.9%), pAVR in 8 (4.1%) and Ross/Ross-Konno procedure in 32 (16.5%). Median age at first intervention was 1.1 years (interquartile range [IQR] 0.1-9.4) and varied with type of intervention: SV/SR were most common in neonates (33, 75%) and infants (35, 68%), whilst BV was most frequent in older children (42, 42%). Operative survival was 99% (2 early deaths, both in neonates with critical aortic stenosis and poor left ventricular function) and 15-year survival was 95%. A Ross procedure was performed in 79 (40.7%) patients over the 15-year study period, 1 of whom required late pAVR for autograft failure. Freedom from any reintervention after SV/SR and BV was 41% and 40% at 10 years, compared to 90% at 10 years with the Ross procedure (P0.001). Among neonatal SV/SR and BV, 98% required reintervention during childhood with no difference between groups. Valve morphology did not influence freedom from ultimate valve replacement. In patients who went on to have a Ross procedure, median time from initial intervention to Ross was 2.8 years (IQR 0.1-11.9) in neonates and 6.0 years (IQR 3.1-7.5) in all other age groups. Overall freedom from pAVR was 97% at 10 years and was similar in the SV/SR and BV groups. A strategy of simple valve repair and primary Ross procedure provides excellent survival and good freedom from pAVR. However, reintervention rates after simple interventions for congenital AS are high, especially in younger age groups. The Ross procedure offers the best freedom from reintervention of any technique and wider use of primary Ross in younger age groups should be considered.

Objectives Cardioplegia is the primary method for myocardial protection during cardiac surgery. We conducted a systematic review of randomized controlled trials of cardioplegia in children to evaluate the current evidence base. Methods We searched MEDLINE, CENTRAL and LILACS and manually screened retrieved references and systematic reviews to identify all randomized controlled trials comparing cardioplegia solutions or additives in children undergoing cardiac surgery published in any language; secondary publications and those reporting inseparable adult data were excluded. Two or more reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. Results We identified 26 trials randomizing 1596 children undergoing surgery; all were single-centre, Phase II trials, recruiting few patients (median 48, interquartile range 30–99). The most frequent comparison was blood versus crystalloid in 10 (38.5%) trials, and the most common end points were biomarkers of myocardial injury (17, 65.4%), inotrope requirements (15, 57.7%) and length of stay in the intensive care unit (11, 42.3%). However, the heterogeneity of patients, interventions and reported outcome measures prohibited meta-analysis. Overall risk of bias was high in 3 (11.5%) trials, unclear in 23 (88.5%) and low in none. Conclusions The current literature on cardioplegia in children contains no late phase trials. The small size, inconsistent use of end points and low quality of reported trials provide a limited evidence base to inform practice. A core outcome set of clinically important, standardized, validated end points for assessing myocardial protection in children should be developed to facilitate the conduct of high-quality, multicentre trials.

Objective The most durable valved right ventricle to pulmonary artery conduit for the repair of congenital heart defects in patients of different ages, sizes, and anatomic substrate remains uncertain. Methods We performed a retrospective analysis of 4 common right ventricle to pulmonary artery conduits used in a single institution over 30 years, using univariable and multivariable models of time-to-failure to analyse freedom from conduit dysfunction, reintervention, and replacement. Results Between 1988 and 2018, 959 right ventricle to pulmonary artery conduits were implanted: 333 aortic homografts, 227 pulmonary homografts, 227 composite porcine valve conduits, and 172 bovine jugular vein conduits. Patients weighed 1.6 to 98.3 kg (median 15.3 kg), and median duration of follow-up was 11.4 years, with 505 (52.2%) conduits developing dysfunction, 165 (17.2%) requiring catheter intervention, and 415 (43.2%) being replaced. Greater patient weight, conduit z-score, type and position, as well as catheter intervention were predictors of freedom from replacement. Multivariable analysis demonstrated inferior durability for smaller composite porcine valve conduits, with excellent durability for larger diameter conduits of the same type. Bovine jugular vein conduit longevity was inferior to that of homografts in all but the smallest patients. Freedom from dysfunction at 8 years was 60.7% for aortic homografts, 72% for pulmonary homografts, 51.2% for composite porcine valve conduits, and 41.3% for bovine jugular vein conduits. Judicious oversizing of the conduit improved conduit durability in all patients, but to the greatest extent in patients weighing 5 to 20 kg. Conclusions Pulmonary and aortic homografts had greater durability than xenograft conduits, particularly in patients weighing 5 to 20 kg. Judicious oversizing was the most significant surgeon-modifiable factor affecting conduit longevity.

There is close interaction between the functions of the liver and heart affecting the presentation, diagnosis, and outcome of acute and chronic cardiac and liver disease. Conditions affecting both organ systems should be considered when proposing transplantation because the interaction between cardiac disease and liver disease has implications for diagnosis, management, selection for transplantation, and, ultimately, for longterm outcomes after liver transplantation (LT). The combination of cardiac and liver disease is well recognized in adults but is less appreciated in pediatric patients. The focus of this review is to describe conditions affecting both the liver and heart and how they affect selection and management of LT in the pediatric population.

OBJECTIVES: We sought to define the early and late outcomes of unifocalization based on a classification of the native pulmonary artery (nPA) system and major aortopulmonary collateral arteries (MAPCAs) with a policy of combined recruitment and rehabilitation and to analyse the role of unifocalization by leaving the ventricular septal defect (VSD) open with a limiting right ventricle-pulmonary artery (RV-PA) conduit in borderline cases. METHODS: An analysis of 271 consecutive patients assessed for unifocalization at a single institution between 1988 and 2016 was performed. Patients were classified according to the pulmonary blood supply: group A, unifocalization based on nPA only; group B, based on nPA and MAPCAs; group C, MAPCAs only (absent nPAs). RESULTS: Unifocalization was achieved in 249 (91.9%) cases with an early mortality of 2.8%. Group A included 72 (28.9%) patients, group B 119 (47.8%) patients and group C 58 (23.3%) patients with no difference in early survival between groups. Survival at 5, 10 and 15 years was 90.0% (85.9–94.3), 87.2% (83.5–91.2) and 82.3% (75.2–89.9), respectively. Late survival in groups A and B was similar but 10- and 15-year survival in group C decreased to 79.2% (68.2–92.1) and 74.3% (61.1–90.4) (P = 0.02), respectively. A mean of 1.9 (±0.6) MAPCAs were recruited per patient (range 0–6). The VSD was left open with a limiting RV-PA conduit in 97 (39.0%) cases, but subsequently closed in 48 patients, giving a total of 200 (80.3%) patients achieving VSD closure (full repair). Delaying VSD closure was not associated with increased risk for early or late survival. A central shunt to rehabilitate the nPAs was used in 56 (22.5%) cases. This was associated with a reduction in the number of MAPCAs recruited, but still required a mean of 1.8 (±0.5) MAPCAs recruited per patient to achieve unifocalization. In multivariate risk analysis, those suitable for single-stage full repair had the best long-term outcomes. Group C anatomy was associated with poor late survival compared to groups A and B (hazard ratio 2.7). CONCLUSIONS: Survival is maximized by a combined approach of rehabilitation and recruitment. MAPCAs should always be recruited if they supply areas with absent nPA supply. A strategy of leaving the VSD open with a limiting RV-PA conduit is a safe and effective way of managing borderline cases.

OBJECTIVES Tetralogy of Fallot is characterized by anterocephalad deviation of the outlet septum, along with abnormal septoparietal trabeculations, which lead to subpulmonary infundibular stenosis. Archives of retained hearts are an important resource for improving our understanding of congenital heart defects and their morphological variability. This study aims to define variations in aortic override, coronary arterial patterns and ventricular septal defects in tetralogy of Fallot as observed in a morphological archive, highlighting implications for surgical management. METHODS The Birmingham Children’s Hospital archive contains 211 hearts with tetralogy of Fallot, of which 164 were analysed [69 (42.1%) unrepaired and 95 (57.9%) operated specimens]. A detailed morphological and geometric analysis was performed using a rigorous 5-layer review process. RESULTS Anomalies were observed in the orifices, origins and course of the coronary arteries: 20 hearts (13.0%) had more than 2 orifices and 3 hearts (1.9%) had a single orifice. In 7 hearts (4.3%), a coronary artery crossed the right ventricular outflow tract. The extent of aortic override ranged from 31.0% to 100% (median of 59.5%). The ventricular septal defect was most often perimembranous (139, 84.8%), but we also found muscular (14, 8.5%), atrioventricular (7, 4.3%) and doubly committed juxta-arterial (2, 1.2%) variants. CONCLUSIONS Anatomical variations are common and can impact surgical management. Anomalous coronary arteries may require a conduit rather than a transannular patch. Variability in aortic override determines the size of patch used to baffle blood to the aorta. The type of ventricular septal defect affects patch closure and the risk of postoperative conduction defects.

Importance A growing number of women are approaching childbearing age after arterial switch surgery for transposition of the great arteries. Prepregnancy counseling requires updated knowledge of the additional cardiovascular risks pregnancy poses for this cohort of women and the potential effect on their offspring; however, to our knowledge, this information is currently unknown. Objective To determine the pregnancy outcomes of women with transposition of the great arteries after an arterial switch operation, as well as the outcomes of their offspring. Design, Setting, and Participants This cohort study assessed women who had had arterial switch surgery from 1985 to the present and who were 16 years or older as of January 2018. All women with a previous arterial switch surgery for transposition of the great arteries with completed or ongoing pregnancy were included. Data were collected in a level 1 congenital cardiology center and joint obstetrics-cardiology clinic in Birmingham, United Kingdom. Exposures Patients were assessed before, during, and after pregnancy. Main Outcomes and Measures Adverse maternal cardiac events (arrhythmia, heart failure, aortic dissection, or acute coronary syndrome) and aortic root dilatation, aortic regurgitation, and left ventricular function before and after pregnancy were the main outcomes. Mode of delivery and fetal outcomes were considered secondary outcomes. Results A total of 25 pregnancies were identified in 15 women; 8 women had had 1 pregnancy, while 7 were multiparous. There were no adverse maternal cardiac events. Before pregnancy, 8 women (53%) had no aortic regurgitation, 1 (7%) had a trivial degree of regurgitation, 4 (26%) had mild regurgitation, and 2 (14%) had moderate regurgitation. After pregnancies, 1 woman (7%) had minor progression of aortic regurgitation. Five women (36%) had mild neoaortic root dilatation prepregnancy, but none developed progressive dilatation in the first year post-partum. A total of 24 pregnancies were completed by the end of the study, with all infants born alive and well. Nineteen modes of delivery were known; there were 7 cesarean deliveries (37%), of which 2 (11%) were recommended for aortic dilatation and 5 (26%) for obstetric indications or maternal choice. Conclusions and Relevance Pregnancy is well tolerated after arterial switch operation; no adverse maternal cardiac events or early progression of neoaortic root dilatation or aortic regurgitation were observed in this study. These results provide evidence to allow reassurance of women with previous arterial switch surgery who are planning pregnancies.

Introduction: Many techniques are available for cardioplegic arrest in children, but there is a lack of late phase clinical trials to guide practice. We surveyed paediatric cardiac surgeons and perfusionists to establish current practice and willingness to change within a clinical trial. Methods: An online survey was sent to all consultant paediatric cardiac surgeons and chief perfusionists in paediatric centres in the UK and Ireland. Information was sought on cardioplegia type, composition, temperature, topical cooling, dosing for induction and maintenance, interval between doses, whether practice changed with patient age or complexity and whether respondents would be willing and able to use different cardioplegia solutions within a randomised trial. Results: Responses were obtained from 32 (78.0%) surgeons and 12 (100%) perfusionists. Twenty-seven (84.4%) surgeons use blood cardioplegia in infants, with St. Thomas’ Harefield preparation the most popular (19, 59.4%), used routinely in eight (66.7%) centres. Twenty-two (68.8%) administer at 4-6°C, 18 (56.3%) use topical cooling, 18 (56.3%) give 30 ml/kg induction and 15 ml/kg maintenance, with 23 (71.9%) re-dosing every 20-25 minutes. Thirty (93.8%) surgeons were open to randomising patients in a trial, with del Nido (29, 90.6%) the most popular. Conclusions: This survey demonstrates heterogeneity in cardioplegia practice. Whilst most surgeons use blood cardioplegia, there is variation in type, temperature, topical cooling, dosing and intervals. Combined with a lack of evidence from late phase trials, our findings support the presence of clinical equipoise. Surgeons are willing to change practice, suggesting that a pragmatic, multi-centre, randomised, controlled trial of cardioplegia in children is feasible.

OBJECTIVES Randomized controlled trials are the gold standard for evaluating health care interventions, yet are uncommon in children’s heart surgery. We conducted a systematic review of clinical trials in paediatric cardiac surgery to evaluate the scope and quality of the current international literature. METHODS We searched MEDLINE, CENTRAL and LILACS, and manually screened retrieved references and systematic reviews to identify all randomized controlled trials reporting the effect of any intervention on the conduct or outcomes of heart surgery in children published in any language since January 2000; secondary publications and those reporting inseparable adult data were excluded. Two reviewers independently screened studies for eligibility and extracted data; the Cochrane Risk of Bias tool was used to assess for potential biases. RESULTS We identified 333 trials from 34 countries randomizing 23 902 children. Most were early phase (313, 94.0%), recruiting few patients (median 45, interquartile range 28–82), and only 11 (3.3%) directly evaluated a surgical intervention. One hundred and nine (32.7%) trials calculated a sample size, 52 (15.6%) reported a CONSORT diagram, 51 (15.3%) were publicly registered and 25 (7.5%) had a Data Monitoring Committee. The overall risk of bias was low in 22 (6.6%), high in 69 (20.7%) and unclear in 242 (72.7%). CONCLUSIONS The recent literature in children’s heart surgery contains few late-phase clinical trials. Most trials did not conform to the accepted standards of reporting, and the overall risk of bias was low in few studies. There is a need for high-quality, multicentre clinical trials to provide a robust evidence base for contemporary paediatric cardiac surgical practice.

Patients undergoing cardiac surgery require adequate myocardial protection. Manipulating myocardial metabolism may improve the extent of myocardial protection. Perhexiline has been shown to be an effective anti-anginal agent due to its metabolic modulation properties by inhibiting the uptake of free fatty acids into the mitochondrion, and thereby promoting a more efficient carbohydrate-driven myocardial metabolism. Metabolic modulation may augment myocardial protection, particularly in patients with left ventricular hypertrophy (LVH) known to have a deranged metabolic state and are at risk of poor postoperative outcomes. This study aimed to evaluate the role of perhexiline as an adjunct in myocardial protection in patients with LVH secondary to aortic stenosis (AS), undergoing an aortic valve replacement (AVR).In a multicentre double-blind randomized controlled trial of patients with AS undergoing AVR ± coronary artery bypass graft surgery, patients were randomized to preoperative oral therapy with either perhexiline or placebo. The primary end point was incidence of inotrope use to improve haemodynamic performance due to a low cardiac output state during the first 6 h of reperfusion, judged by a blinded end points committee. Secondary outcome measures included haemodynamic measurements, electrocardiographic and biochemical markers of new myocardial injury and clinical safety outcome measures.The trial was halted early on the advice of the Data Safety and Monitoring Board. Sixty-two patients were randomized to perhexiline and 65 to placebo. Of these, 112 (54 perhexiline and 48 placebo) patients received the intervention, remained in the trial at the time of the operation and were analysed. Of 110 patients who achieved the primary end point, 30 patients (16 perhexiline and 14 placebo) had inotropes started appropriately; there was no difference in the incidence of inotrope usage OR of 1.65 [confidence interval (CI): 0.67-4.06] P = 0.28. There was no difference in myocardial injury as evidenced by electrocardiogram odds ratio (OR) of 0.36 (CI: 0.07-1.97) P = 0.24 or postoperative troponin release. Gross secondary outcome measures were comparable between the groups.Perhexiline as a metabolic modulator to enhance standard myocardial protection does not provide an additional benefit in haemodynamic performance or attenuate myocardial injury in the hypertrophied heart secondary to AS. The role of perhexiline in cardiac surgery is limited.

Intramural coronary arteries remain a major risk factor and technical challenge of the arterial switch operation for transposition of the great arteries. We report a 27-year-old woman who presented with acute coronary syndrome late after arterial switch with a complex coronary pattern (intramural left and right coronary from sinus 2). Computed tomography demonstrated that the pericardial 'saddle bag' used to reconstruct the intramural coronary was compressed between the neoaortic root and the neopulmonary trunk. During surgery, the coronary system was laid open into the neoaorta with patch enlargement, and the patient made an uneventful recovery.

A 74-year-old man presented with dyspnoea and reduced exercise tolerance (Medical Research Council grade 4). He was a current smoker with a history of paroxysmal atrial fibrillation and COPD for which he was on bronchodilators. There was no history of previous chest trauma or surgery and physical examination was unremarkable. CT thorax showed a 3.2 cm mass in the anterior mediastinum with two foci of coarse calcification (figure 1A). Positron emission tomography (PET)/CT demonstrated significant uptake (maximum standardised uptake ratio of 13.7) in the mass with a central area of inactivity (figure 1B); there was no significant activity elsewhere. His gas transfer was reduced at 63% predicted. Figure 1 CT sagittal plane showing a 3.2 cm lesion in the anterior mediastinum with areas of focal …

Background— Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. Methods and Results— Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5′ adenosine monophosphate–activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked β- N -acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P =0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P =0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. Conclusions— Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis. Clinical Trial Registration— URL: http://www.controlled-trials.com . Reference number: ISRCTN 05758301.

A 38-year-old man presented with a history of influenza-like symptoms and a persistent dry cough. He had been previously fit and well, other than a road traffic collision 20 years ago, in which he sustained bilateral pneumothoraces, left hemidiaphragm injury with herniation of the stomach into the left hemithorax and splenic injury. He therefore had undergone an emergency laparotomy, splenectomy and repair of the left hemidiaphragm. He was a non-smoker and denied contact with TB or asbestos. Physical examination was unremarkable other than a laparotomy scar. Chest radiograph showed a large opacity behind the cardiac silhouette suspicious for primary lung cancer (figure 1A). CT of the thorax and abdomen confirmed a 41 mm soft tissue mass in the left lower …

Purpose: Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. Method: Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. Results: Myocardial uptake of both (+) and (−) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (−) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (−) perhexiline were the plasma concentrations [(+) perhexiline: β = −0.256, p = 0.015; (−) perhexiline: β = −0.347, p = 0.001] and patients’ age [(+) perhexiline: β = 0.300, p = 0.004; (−) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (−) perhexiline varied inversely with simultaneous heart rate (β = −0.240, p = 0.015). Conclusion: (1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (−) perhexiline may selectively modulate heart rate reduction.