Influence of improved antenatal detection on the outcomes of complete atrioventricular block diagnosed in fetal-neonatal life and childhood periods - a single-centre experience in South Wales for 55 years.

OBJECTIVE: This study aimed to analyse the influence of improved antenatal detection on the course, contemporary outcomes, and mortality risk factors of the complete atrioventricular block during fetal-neonatal and childhood periods in South Wales. METHODS: The clinical characteristics and outcomes of complete atrioventricular block in patients without structural heart disease at the University Hospital of Wales from January 1966 to April 2021 were studied. Patients were divided into two groups according to their age at diagnosis: I-fetal-neonatal and II-childhood. Contemporary outcomes during the post-2001 era were compared with historical data preceding fetal service development and hence earlier detection. RESULTS: There were 64 patients: 26 were identified in the fetal-neonatal period and the remaining 38 in the childhood period. Maternal antibodies/systemic lupus erythematosus disease (anti-Ro/Sjögren's-syndrome-related Antigen A and/or anti-La/Sjögren's-syndrome-related Antigen B) were present in 15 (57.7%) of the fetal-neonatal. Fetal/neonatal and early diagnosis increased after 2001 with an incidence of 1:25000 pregnancies. Pacemaker implantation was required in 34 patients, of whom 13 were diagnosed in the fetal-neonatal group. Survival rates in cases identified before 2001 were at 96.3% (26/27), whereas it was 83.8% (31/37) in patients diagnosed after 2001 (P > 0.05). Other mortality risk factors comprised a lower gestational week at birth, maternal antibodies, and an average ventricular heart rate of < 55 bpm. CONCLUSIONS: Fetal diagnosis of complete atrioventricular block is still portends high fetal and neonatal mortality and morbidity despite significantly improved antenatal detection after 2001. Pacemaker intervention is needed earlier in the fetal-neonatal group. Whether routine antenatal medical treatment might alter this outcome calls for further prospective multicentre studies.

Wide complex rhythm in a well neonate: Where are the P waves?

A neonate was seen for an evolving broad QRS complex rhythm initially captured at birth as intermittent escape beats on electrocardiogram. Continuous monitoring recorded features mimicking pre-excitation, but closer analysis revealed a regular broad QRS complex rhythm with isorhythmic atrioventricular dissociation, favouring a ventricular source. Treatment with flecainide and propranolol achieved successful control of the incessant arrhythmia with improvement in cardiac function on echocardiogram.

The influence of maturation on exercise-induced cardiac remodelling and haematological adaptation.

Cardiovascular and haematological adaptations to endurance training facilitate greater maximal oxygen consumption ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ), and such adaptations may be augmented following puberty. Therefore, we compared left ventricular (LV) morphology (echocardiography), blood volume, haemoglobin (Hb) mass (CO rebreathing) and V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ in endurance-trained and untrained boys (n = 42, age = 9.0-17.1 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 61.6 ± 7.2 ml/kg/min, and n = 31, age = 8.0-17.7 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 46.5 ± 6.1 ml/kg/min, respectively) and girls (n = 45, age = 8.2-17.0 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 51.4 ± 5.7 ml/kg/min, and n = 36, age = 8.0-17.6 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 39.8 ± 5.7 ml/kg/min, respectively). Pubertal stage was estimated via maturity offset, with participants classified as pre- or post-peak height velocity (PHV). Pre-PHV, only a larger LV end-diastolic volume/lean body mass (EDV/LBM) for trained boys (+0.28 ml/kg LBM, P = 0.007) and a higher Hb mass/LBM for trained girls (+1.65 g/kg LBM, P = 0.007) were evident compared to untrained controls. Post-PHV, LV mass/LBM (boys: +0.50 g/kg LBM, P = 0.0003; girls: +0.35 g/kg LBM, P = 0.003), EDV/LBM (boys: +0.35 ml/kg LBM, P < 0.0001; girls: +0.31 ml/kg LBM, P = 0.0004), blood volume/LBM (boys: +12.47 ml/kg LBM, P = 0.004; girls: +13.48 ml/kg LBM, P = 0.0002.) and Hb mass/LBM (boys: +1.29 g/kg LBM, P = 0.015; girls: +1.47 g/kg LBM, P = 0.002) were all greater in trained versus untrained groups. Pre-PHV, EDV (R2adj  = 0.224, P = 0.001) in boys, and Hb mass and interventricular septal thickness (R2adj  = 0.317, P = 0.002) in girls partially accounted for the variance in V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ . Post-PHV, stronger predictive models were evident via the inclusion of LV wall thickness and EDV in boys (R2adj  = 0.608, P < 0.0001), and posterior wall thickness and Hb mass in girls (R2adj  = 0.490, P < 0.0001). In conclusion, cardiovascular adaptation to exercise training is more pronounced post-PHV, with evidence for a greater role of central components for oxygen delivery. KEY POINTS: It has long been hypothesised that cardiovascular adaptation to endurance training is augmented following puberty. We investigated whether differences in cardiac and haematological variables exist, and to what extent, between endurance-trained versus untrained, pre- and post-peak height velocity (PHV) children, and how these central factors relate to maximal oxygen consumption. Using echocardiography to quantify left ventricular (LV) morphology and carbon monoxide rebreathing to determine blood volume and haemoglobin mass, we identified that training-related differences in LV morphology are evident in pre-PHV children, with haematological differences also observed between pre-PHV girls. However, the breadth and magnitude of cardiovascular remodelling was more pronounced post-PHV. Cardiac and haematological measures provide significant predictive models for maximal oxygen consumption ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ) in children that are much stronger post-PHV, suggesting that other important determinants within the oxygen transport chain could account for the majority of variance in V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ before puberty.

The association of neurodevelopmental abnormalities, congenital heart and renal defects in a tuberous sclerosis complex patient cohort.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare multi-system genetic disorder characterised by the presence of benign tumours throughout multiple organs including the brain, kidneys, heart, liver, eyes, lungs and skin, in addition to neurological and neuropsychiatric complications. Intracardiac tumour (rhabdomyoma), neurodevelopmental disorders (NDDs) and kidney disorders (KD) are common manifestations of TSC and have been linked with TSC1 and TSC2 loss-of-function mutations independently, but the dynamic relationship between these organ manifestations remains unexplored. Therefore, this study aims to characterise the nature of the relationship specifically between these three organs' manifestations in TSC1 and TSC2 mutation patients. METHODS: Clinical data gathered from TSC patients across South Wales registered with Cardiff and Vale University Health Board (CAV UHB) between 1990 and 2020 were analysed retrospectively to evaluate abnormalities in the heart, brain and kidney development. TSC-related abnormalities such as tumour prevalence, location and size were analysed for each organ in addition to neuropsychiatric involvement and were compared between TSC1 and TSC2 mutant genotypes. Lastly, statistical co-occurrence between organ manifestations co-morbidity was quantified, and trajectories of disease progression throughout organs were modelled. RESULTS: This study found a significantly greater mutational frequency at the TSC2 locus in the cohort in comparison to TSC1. An equal proportion of male and female patients were observed in this group and by meta-analysis of previous studies. No significant difference in characterisation of heart involvement was observed between TSC1 and TSC2 patients. Brain involvement was seen with increased severity in TSC2 patients, characterised by a greater prevalence of cortical tubers and communication disorders. Renal pathology was further enhanced in TSC2 patients, marked by increased bilateral angiomyolipoma prevalence. Furthermore, co-occurrence of NDDs and KDs was the most positively correlated out of investigated manifestations, regardless of genotype. Analysis of disease trajectories revealed a more diverse clinical outcome for TSC2 patients: however, a chronological association of rhabdomyoma, NDD and KD was most frequently observed for TSC1 patients. CONCLUSIONS: This study marks the first empirical investigation of the co-morbidity between congenital heart defects (CHD), NDDs, and KDs in TSC1 and TSC2 patients. This remains a unique first step towards the characterisation of the dynamic role between genetics, heart function, brain function and kidney function during the early development in the context of TSC.

Hepatic bridge and round ligament of the liver during cytoreductive surgery: a retrospective cohort.

PURPOSE: The hepatic bridge as an anatomical variation may lead to recurrence and treatment failure in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by constituting an obscure region during surgery. This report aimed to highlight the relationship between the hepatic bridge and various prognostic factors in peritoneal carcinomatosis. METHODS: Data of 101 patients who underwent CRS/HIPEC for peritoneal carcinomatosis in a single centre were retrospectively reviewed. Demographic characteristics, primary origin of peritoneal carcinomatosis, classification of hepatic bridge, Peritoneal Cancer Index (PCI) score, and completeness of cytoreduction (CC) score were analysed. RESULTS: The tumour was proven histopathologically in 18 (28.6%) of 63 patients who underwent distal round ligament (DRL) resection. The PCI score was found to be significantly higher in patients with tumour in DRL compared to the ones without tumour (p < 0.001). The median PCI score of patients with implant positive DRL was 18 (12-20) and this score was 3 (2-6) for patients with implant negative DRL (p < 0.001). The ROC curve concerning the risk of an implant penetrating the round ligament revealed the optimal cut-off value of PCI at 10 with 88.9% sensitivity and 79.3% specificity. CONCLUSION: The round ligament should be removed, regardless of the PCI score, as a standard in mucinous adenocarcinoma of the appendix and malignant peritoneal mesothelioma. DRL should be removed when PCI is equal or higher than 10 for PC due to colorectal and ovarian cancers.

Prenatal Diagnosis of the Right Aortic Arch: Change in Detection Rate, the Status of Associated Anomalies, and Perinatal Outcomes in 137 Fetuses.

To evaluate prenatal findings of the right aortic arch (RAA), associated cardiac, extracardiac, and genetic anomalies, its perinatal outcomes and the need for postnatal interventions in cases of isolated RAA with a view to facilitating appropriate counseling. This was a multicenter, cohort study, that was undertaken in two international major cardiac centers between 2009 and 2020. The study subjects were prenatally diagnosed RAA cases with and without other structural cardiac defects. A RAA was identified in 137 fetuses. There were 84 cases of isolated RAA. Associations with additional intracardiac malformations were found in 53 (38.7%) cases. An extracardiac anomaly was observed in 26/137 (18.9%) fetuses, 11/84 (13.0%) fetuses with isolated RAA, and 15/53 (28.3%) fetuses with an additional intracardiac anomaly. The incidence of extracardiac and chromosomal anomalies was significantly higher in cases of RAA with abnormal intracardiac anatomy (28.3-18.8%, respectively), compared with RAA with normal intracardiac anatomy (13.0-5.9%, respectively) (p < 0.05). 22q11.2 microdeletion was found higher in RAA with CHD (4/18 fetuses) than isolated RAA (2/24 fetuses) (22.2% vs. 8.3% respectively). ALSA was present in 19.3% of cases. ALSA was more frequently observed in cases of isolated RAA (23.6%), than in RAA with structural CHD (7.6%) (p < 0.05). The pregnancy was interrupted in six fetuses, and one died in utero. The mortality rate was higher in fetuses with intracardiac anomaly than RAA without cardiac anomaly (11/49 (22.4%) vs. 2/81 (2.4%). Vascular ring formation was revealed in 21/98 cases. The RAA caused symptoms of a vascular ring in only one patient (0.7%) requiring surgery in the follow-up. Overall survival after initial diagnosis in the total cohort was 85.4% with 38 of 53 (71%) RAA with CHD cases and 79 of 84 (94.0%) isolated RAA cases. Chromosomal and extracardiac anomalies are lower in isolated RAA but not negligible hence amniocentesis should be routinely offered in all cases. The requirement for postnatal intervention in the immediate neonatal period is remote, therefore delivery of these fetuses need not be undertaken at a cardiac or surgical center.

Favourable outcome for hydrops or cardiac failure associated with fetal tachyarrhythmia: a 20-year review.

BACKGROUND: Prognosis of fetuses with hydrops and tachyarrhythmia has been portrayed as poor in most published reports. This might lead to biased counselling, unnecessary caesarean section, preterm delivery, and even termination of pregnancy. AIMS: To evaluate contemporary fetal and postnatal outcomes of hydropic fetuses with fetal tachyarrhythmia when it is treated effectively and monitored systematically. METHODS: This is a retrospective review of a single centre experience at the University Hospital of Wales over a 20-year period. All fetuses received high doses of flecainide and digoxin combination treatment. Tachycardia response rate, time to arrhythmia and hydrops resolution, fetal and postnatal morbidity, and mortality rates were analysed. RESULTS: Twenty fetuses were diagnosed with hydrops fetalis and received treatment. The mechanism of fetal tachyarrhythmia was supraventricular tachycardia in thirteen and atrial flutter in eight cases. Among the 20 fetuses treated, the overall tachycardia response rate was 90% (18/20) with the restoration of sinus rhythm in 85% (17/20) of the cases. The median time to restore sinus rhythm or to rate control of the arrhythmia was 1.5 days (range 12 hours to 13 days). Hydrops resolved in 17 of the 20 fetuses, with a median time of 12 days (range 3-21 days). Four fetuses went into spontaneous preterm birth and one fetus was delivered early due to worsening hydrops. No significant neurological morbidity was observed in surviving neonates and infants on clinical examination. There was one postnatal death due to respiratory complications of prematurity in the non-responsive supraventricular tachycardia case. CONCLUSIONS: High-dose flecainide and digoxin combination offers effective treatment strategy in fetuses with hydrops and tachyarrhythmia with favourable outcomes. This study may guide more realistic counselling for pregnancies complicated by tachyarrhythmia and hydrops.

Transplacental treatment of foetal supraventricular tachycardia with triple antiarrhythmic combination to avoid intra-foetal intervention.

Although a high percentage of foetuses with supraventricular tachycardia respond to single or dual antiarrhythmic therapy, on occasion when there is no response to these combination regimens, direct intra-foetal therapy remains the only choice, albeit such an approach carries a potential risk to the foetus.Data with regard to the safety and efficacy of triple antiarrhythmic combination have not been reported before. Here, we present a foetus with intractable tachycardia in whom arrhythmia termination was successfully achieved with triple oral antiarrhythmic therapy.

Clinical outcomes and programming strategies of implantable cardioverter-defibrillator devices in paediatric hypertrophic cardiomyopathy: a UK National Cohort Study.

AIMS: Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort. METHODS AND RESULTS: Data from 90 patients undergoing ICD insertion at a median age 13 (±3.5) for primary (n = 67, 74%) or secondary prevention (n = 23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children (<16 years) with HCM from the UK. Seventy-six (84%) had an endovascular system [14 (18%) dual coil], 3 (3%) epicardial, and 11 (12%) subcutaneous system. Defibrillation threshold (DFT) testing was performed at implant in 68 (76%). Inadequate DFT in four led to implant adjustment in three patients. Over a median follow-up of 54 months (interquartile range 28-111), 25 (28%) patients had 53 appropriate therapies [ICD shock n = 45, anti-tachycardia pacing (ATP) n = 8], incidence rate 4.7 per 100 patient years (95% CI 2.9-7.6). Eight inappropriate therapies occurred in 7 (8%) patients (ICD shock n = 4, ATP n = 4), incidence rate 1.1/100 patient years (95% CI 0.4-2.5). Three patients (3%) died following arrhythmic events, despite a functioning device. Other device complications were seen in 28 patients (31%), including lead-related complications (n = 15) and infection (n = 10). No clinical, device, or programming characteristics predicted time to inappropriate therapy or lead complication. CONCLUSION: In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

Association of Fetal Atrial Flutter with Neonatal Atrioventricular Re-entry Tachycardia Involving Accessory Pathway: A Link to be Remembered.

To investigate prenatal and postnatal outcomes of atrial flutter and its association with the development of a second tachycardia, following restoration of sinus rhythm, in the fetus or newborn. This study is a retrospective review of all fetuses that presented with atrial flutter from January 2001 to December 2019 at the University Hospital of Wales, Cardiff, UK. The specific type of arrhythmia, its time of appearance and clinical characteristics, echocardiographic findings, medical management, and postnatal outcomes were evaluated. Sixteen fetuses were diagnosed with atrial flutter (AFL). Thirteen fetuses had persistent AFL and three fetuses had intermittent AFL. Seven patients had hydrops, of which one had Ebstein's anomaly and the other six had normal hearts. Three of the fetuses that presented with AFL were diagnosed at 20, 21, and 23 weeks' gestation and the remainder were diagnosed in the third trimester. Thirteen patients with AFL received antiarrhythmic drugs and three were delivered without any treatment. Five fetuses with AFL developed atrioventricular reciprocating tachycardia following DC cardioversion after birth, and four of them exhibited pre-excitation on the ECG. These five patients (31.3%) required postnatal antiarrhythmic treatment for up to 2 years. Pre-excitation disappeared in two patients during follow-up and two asymptomatic patients with neonatal pre-excitation required accessory pathway ablation. Fetal atrial flutter has a strong association with atrioventricular reciprocating tachycardia and ventricular pre-excitation in the neonatal period. Therefore, electrocardiograms should be carefully reviewed in newborns following the initial resolution of atrial flutter.

The impact of sarcopenia on pathologic complete response following neoadjuvant chemoradiation in rectal cancer.

PURPOSE: The role of sarcopenia in pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT) in non-metastatic locally advanced rectal cancer is currently unknown. The present study investigates the association between sarcopenia and post-nCRT pCR. METHODS: The data of patients operated on following nCRT between January 2013 and January 2020 were collected retrospectively. Sarcopenia was diagnosed based on the calculation of the skeletal muscle index (SMI) from computed tomography carried out at the time of the initial diagnosis. A statistical analysis was then conducted for predictors of pCR. RESULTS: The study included 61 patients with an average age of 57.3 years, 28 of whom formed the non-sarcopenic group (NSG) and 33 the sarcopenic group (SG). Of the patients, 32.7% were at clinical stage 2, and 67.3% were at clinical stage 3. Pathologic data following a mesorectal excision revealed a pCR rate of 21.4% in the NSG compared with 3% in the SG, which was a statistically significant difference (p = 0.025). The TNM downstaging rate was higher in the NSG than in the SG, although the difference was not statistically significant (50% vs. 33.3%, p = 0.28). A univariate analysis revealed the factors affecting pCR to be non-sarcopenia (p = 0.025), age < 61 years (p = 0.004), interval to surgery ≥ 8 weeks (p = 0.029), and serum CEA < 2.5 ng/ml (p = 0.035). CONCLUSION: Sarcopenia was found to be a negative marker of pCR following nCRT in non-metastatic locally advanced rectal cancer.

Clinical presentation and survival of childhood hypertrophic cardiomyopathy: a retrospective study in United Kingdom.

AIMS: Understanding the spectrum of disease, symptom burden and natural history are essential for the management of children with hypertrophic cardiomyopathy (HCM). The effect of changing screening practices over time has not previously been studied. This study describes the clinical characteristics and outcomes of childhood HCM over four decades in a well-characterized United Kingdom cohort. METHODS AND RESULTS: Six hundred and eighty-seven patients with HCM presented at a median age of 5.2 years (range 0-16). Aetiology was: non-syndromic (n = 433, 63%), RASopathy (n = 126, 18.3%), Friedreich's ataxia (n = 59, 8.6%) or inborn errors of metabolism (IEM) (n = 64, 9%). In infants (n = 159, 23%) underlying aetiology was more commonly a RASopathy (42% vs. 11.2%, P < 0.0001) or IEM (18.9% vs. 6.4% P < 0.0001). In those with familial disease, median age of presentation was higher (11 years vs. 6 years, P < 0.0001), 141 (58%) presented <12 years. Freedom from death or transplantation was 90.6% (87.9-92.7%) at 5 years (1.5 per 100 patient years) with no era effect. Mortality was most frequently sudden cardiac death (SCD) (n = 20, 2.9%). Children diagnosed during infancy or with an IEM had a worse prognosis (5-year survival 80.5% or 66.4%). Arrhythmic events occurred at a rate of 1.2 per 100 patient years and were more likely in non-syndromic patients (n = 51, 88%). CONCLUSION: This national study describes a heterogeneous disease whose outcomes depend on the age of presentation and aetiology. Overall mortality and SCD rates have not changed over time, but they remain higher than in adults with HCM, with events occurring in syndromic and non-syndromic patients.

A validation study of the European Society of Cardiology guidelines for risk stratification of sudden cardiac death in childhood hypertrophic cardiomyopathy.

AIMS: Sudden cardiac death (SCD) is the most common cause of death in children with hypertrophic cardiomyopathy (HCM). The European Society of Cardiology (ESC) recommends consideration of an implantable cardioverter-defibrillator (ICD) if two or more clinical risk factors (RFs) are present, but this approach to risk stratification has not been formally validated. METHODS AND RESULTS: Four hundred and eleven paediatric HCM patients were assessed for four clinical RFs in accordance with current ESC recommendations: severe left ventricular hypertrophy, unexplained syncope, non-sustained ventricular tachycardia, and family history of SCD. The primary endpoint was a composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate ICD therapy, or sustained ventricular tachycardia), defined as a major arrhythmic cardiac event (MACE). Over a follow-up period of 2890 patient years (median 5.5 years), MACE occurred in 21 patients (7.5%) with 0 RFs, 19 (16.8%) with 1 RFs, and 3 (18.8%) with 2 or more RFs. Corresponding incidence rates were 1.13 [95% confidence interval (CI) 0.7-1.73], 2.07 (95% CI 1.25-3.23), and 2.52 (95% CI 0.53-7.35) per 100 patient years at risk. Patients with two or more RFs did not have a higher incidence of MACE (log-rank test P = 0.34), with a positive and negative predictive value of 19% and 90%, respectively. The C-statistic was 0.62 (95% CI 0.52-0.72) at 5 years. CONCLUSIONS: The incidence of MACE is higher for patients with increasing numbers of clinical RFs. However, the current ESC guidelines have a low ability to discriminate between high- and low-risk individuals.

Cardiovascular Collapse with Intravenous Amiodarone in Children: A Multi-Center Retrospective Cohort Study.

OBJECTIVE: To determine the incidence of cardiovascular collapse in children receiving intravenous (IV) amiodarone and to identify the population at risk. DESIGN: A multicenter study of patients ≤ 18 years of age who received intravenous amiodarone between January 2005 and December 2015. A retrospective analysis was performed to identify patients who developed cardiovascular collapse (bradycardia and/or hypotension). RESULTS: Of 456 patients who received amiodarone, cardiovascular collapse occurred in 47 patients (10%). Patient risk factors for collapse in a univariate analysis were as follows: age < 3 months (p = 0.04), depressed cardiac function (p < 0.001), blood pressure below 3rd percentile (p < 0.001), high lactate at baseline (p < 0.001). Administration risk factors included bolus administration (p = 0.04), and bolus administration over ≤ 20 min (p = 0.04). In multivariate analysis, age, baseline blood pressure less than 3rd percentile, and rapid bolus delivery were independent risk factors for cardiovascular collapse in the study group. The mortality rate was significantly higher in the collapse group (28% versus 8%). CONCLUSION: We found an association between IV amiodarone administration and the risk of developing cardiovascular collapse in a significant subset of children. Extreme caution and careful hemodynamic monitoring is recommended when using IV amiodarone in this population, especially in young infants, hemodynamically compromised patients, and in patients receiving rapid amiodarone bolus administration.

A multicentre study of patients with Timothy syndrome.

Aims: Timothy syndrome (TS) is an extremely rare multisystem disorder characterized by marked QT prolongation, syndactyly, seizures, behavioural abnormalities, immunodeficiency, and hypoglycaemia. The aim of this study was to categorize the phenotypes and examine the outcomes of patients with TS. Methods and results: All patients diagnosed with TS in the United Kingdom over a 24-year period were reviewed. Fifteen centres in the British Congenital Arrhythmia Group network were contacted to partake in the study. Six patients with TS were identified over a 24-year period (4 boys and 2 girls). Five out of the six patients were confirmed to have a CACNA1C mutation (p.Gly406Arg) and the other patient was diagnosed clinically. Early presentation with heart block, due to QT prolongation was frequently seen. Four are still alive, two of these have a pacemaker and two have undergone defibrillator implantation. Five out of six patients have had a documented cardiac arrest with three occurring under general anaesthesia. Two patients suffered a cardiac arrest while in hospital and resuscitation was unsuccessful, despite immediate access to a defibrillator. Surviving patients seem to have mild developmental delay and learning difficulties. Conclusion: Timothy syndrome is a rare disorder with a high attrition rate if undiagnosed. Perioperative cardiac arrests are common and not always amenable to resuscitation. Longer-term survival is possible, however, patients invariably require pacemaker or defibrillator implantation.

The Safety and Effectiveness of Flecainide in Children in the Current Era.

This retrospective study sought to determine the safety and effectiveness of flecainide in children with normal hearts and those with congenital heart disease (CHD) or cardiomyopathy (CMO). Baseline and follow-up data at two pediatric cardiology sites were queried (2000-2015); a total of 175 patients (20 with CHD and two with CMO) receiving flecainide were assessed. When comparing patients with CHD to those with normal hearts, patients with CHD were younger at diagnosis (median age 19 days; IQR 3-157.5 days vs normal heart patients median age 21 days; IQR 7-172 days, p = 0.4) and severe cardiac dysfunction was more prevalent (30% in CHD patients vs 8% in normal heart patients, p = 0.009). Treatment duration did not differ between the two groups (CHD patients median duration 52 weeks; IQR 27-91.5 weeks vs normal heart patients median duration 55 weeks; IQR 32-156 weeks, p = 0.5). Cardiac dysfunction resulting in flecainide discontinuation occurred in two patients (1%), one with CHD and one without. Three patients experienced proarrhythmia (2%) and there were no cardiac arrests during follow-up. There was one death in this cohort in a patient with severe CHD and an RSV infection (<1%). Arrhythmia control did not differ between the groups (90% in CHD patients vs 77% in normal heart patients, p = 0.2). Flecainide was well tolerated in this cohort, with fewer than 3% discontinuing medication due to flecainide-associated adverse events. Contrary to adult studies, there was no difference in the incidence of adverse events between patients with normal hearts and patients with CHD. Flecainide is a safe and effective antiarrhythmic medication, even for children with underlying CHD.

Influence of antenatal physical exercise on haemodynamics in pregnant women: a flexible randomisation approach.

BACKGROUND: Normal pregnancy is associated with marked changes in haemodynamic function, however the influence and potential benefits of antenatal physical exercise at different stages of pregnancy and postpartum remain unclear. The aim of this study was therefore to characterise the influence of regular physical exercise on haemodynamic variables at different stages of pregnancy and also in the postpartum period. METHODS: Fifty healthy pregnant women were recruited and randomly assigned (2 × 2 × 2 design) to a land or water-based exercise group or a control group. Exercising groups attended weekly classes from the 20th week of pregnancy onwards. Haemodynamic assessments (heart rate, cardiac output, stroke volume, total peripheral resistance, systolic and diastolic blood pressure and end diastolic index) were performed using the Task Force haemodynamic monitor at 12-16, 26-28, 34-36 and 12 weeks following birth, during a protocol including postural manoeurvres (supine and standing) and light exercise. RESULTS: In response to an acute bout of exercise in the postpartum period, stroke volume and end diastolic index were greater in the exercise group than the non-exercising control group (p = 0.041 and p = 0.028 respectively). Total peripheral resistance and diastolic blood pressure were also lower (p = 0.015 and p = 0.007, respectively) in the exercise group. Diastolic blood pressure was lower in the exercise group during the second trimester (p = 0.030). CONCLUSIONS: Antenatal exercise does not appear to substantially alter maternal physiology with advancing gestation, speculating that the already vast changes in maternal physiology mask the influences of antenatal exercise, however it does appear to result in an improvement in a woman's haemodynamic function (enhanced ventricular ejection performance and reduced blood pressure) following the end of pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov NCT02503995. Registered 20 July 2015.

Diagnostic ultrasound features and outcome of restrictive foramen ovale in fetuses with structurally normal hearts.

Intrauterine foramen ovale (FO) restriction in association with congenital heart disease (CHD) carries a poor prognosis. However, in the absence of CHD, the clinical importance of restrictive FO in the fetus is not well understood. We evaluated the antenatal prevalence, clinical presentation, diagnostic ultrasound features, and outcome of restrictive FO in fetuses without CHD. We reviewed the echocardiographic and clinical records of 23 fetuses diagnosed with a restrictive FO and structurally normal heart between 2001 and 2012. The atrial septum, dimensions of cardiac structures, left and right cardiac output and Doppler interrogation of cardiac flows were examined. The clinical outcomes of all fetuses with restrictive FO were analysed. Restrictive FO was identified in 23 of 1,682 (1.4%) fetuses with no CHD. Enlarged right heart structures (100%), hypermobile or redundant primum atrial septum (91%), increased right-to-left ventricular cardiac output ratio (91%), and posteriorly angulated ductus arteriosus (68%) were the most common echocardiographic findings associated with this rare phenomenon. Additional noncardiac systemic abnormalities were identified in 13 (56%) babies. Seven (30%) neonates developed persistent pulmonary hypertension, and 7 infants died. Antenatal restrictive FO is an underrecognised entity despite being a common cause of right heart dilatation in the fetus. In the absence of CHD, restrictive FO is well tolerated antenatally, but its frequent association with noncardiac abnormalities and pulmonary hypertension in the neonate are noteworthy.

Preoperative serum tumor marker levels in gastric cancer.

OBJECTIVE: Tumor markers have shown little benefit as a method for screening. However, they can be used clinically for the monitoring of tumor recurrence and used as prognostic factors because higher levels have been observed in advanced disease. This study aimed to investigate the relationship between the preoperative tumor marker levels and different clinical aspects of gastric cancer. METHODS: One hundred and six consecutive patients with confirmed diagnosis of gastric cancer and 106 subjects (age and sex matched) with no malignancy as control group were included prospectively in this study in 3 years. The relationships between tumor markers CEA, CA 19-9 and stage of disease, tumor differentiation, presence of ringlet cell type, presence of peritoneal carcinomatozis were investigated. RESULTS: The serum CEA and CA 125 levels were found to be significantly elevated in gastric cancer patients than in controls. The serum level of CEA had showed a significant elevation with the presence of distant metastasis. The CA 19-9 and CA 125 levels had showed significant elevations with the presence of peritoneal carcinomatozis. Conclusions : This study showed that there is a limited clinical benefit of preoperative tumor marker measurements in gastric cancer such as estimation of peritoneal dissemination.