Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making.

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.

Cardiac function in 10-year-old twins following different fetal therapies for twin-twin transfusion syndrome.

OBJECTIVES: To compare cardiac function at 10 years of age in four groups of monochorionic diamniotic (MCDA) twin pairs: uncomplicated MCDA twins (n = 6) (Group 1); twins that had had twin-twin transfusion syndrome (TTTS) managed by amnioreduction (TTTS-amnio, n = 9) (Group 2) or laser photocoagulation (TTTS-laser, n = 10) (Group 3); and dichorionic diamniotic controls (DCDA, n = 6) (Group 4). METHODS: Echocardiograms optimizing apical four-chamber and short-axis left ventricular views were stored for offline speckle-tracking analysis, blinded to twin type. Myocardial long-axis shortening and lengthening velocities were measured using pulsed Doppler ultrasound at the cardiac base. M-mode measurements of fractional shortening (short axis) and maximal excursion of the atrioventricular annulus (four-chamber) were recorded. Syngo Vector Velocity Imaging software tracked left ventricular myocardial motion offline to produce free wall strain, strain rate and rotation. Intertwin pair and group differences were investigated using ANOVA. RESULTS: Cardiac measurements were within the normal ranges for 10-year-olds. No significant within-twin-pair and intergroup differences were found in current size, heart rates, strain or strain rate. Compared to DCDA controls, TTTS twins showed less cardiac rotation (TTTS-laser, P < 0.001 and TTTS-amnio, P = 0.054) with significant intertwin reduction in the ex-recipient (TTTS-amnio, P = 0.006) and larger MCDA twins (P = 0.027) compared with their cotwins. A similar pattern was seen in left ventricular early diastolic mitral valve tissue velocity (MVE') in all monochorionic groups, but only achieving significance in TTTS-amnio twins (P = 0.037). Intrapair differences in rotation and MVE' were significantly different following treatment at Quintero stages III or IV. CONCLUSIONS: Within-twin-pair patterns of left ventricular rotation and diastolic function differ at 10 years of age in ex-recipients of TTTS twins treated with amnioreduction compared with those treated by laser photocoagulation and controls. .

A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC). METHODS: We conducted a randomised phase II/III trial in patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4-6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322. RESULTS: The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P=0.019). End-of-treatment RECIST response (CR+PR) was 13.2 and 32.6% (P=0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P=0.74) months and 7.2 vs 7.5 (P=0.59), respectively. CONCLUSION: Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.

Measuring implementation of evidence-based guidance on promoting workers' health.

BACKGROUND: The National Health Service (NHS) employs 1.4 million people in England. In health care, improved workforce health has been associated with improved outcomes for patients. The UK's National Institute for Health and Clinical Excellence (NICE) has produced evidence-based guidance on improving workers' health. However, the extent of implementation of evidence-based guidance has not previously been measured. AIMS: To measure progress with implementation of NICE guidance on workplace health and identify opportunities to improve this. METHODS: All NHS organizations in England were invited to participate in an audit of implementation of NICE guidance. A web-based tool was developed to collect information on the extent to which each organization had implemented NICE guidance addressing health promotion in the workplace. RESULTS: The number of organizations that participated was 282. These employed a total of 868 979 workers. Organizations were more likely to involve staff in planning and designing an organizational approach to each topic where health and well-being was a regular board agenda item. Those with an overarching strategy were more likely to have staff health and well-being as a regular board agenda item (P < 0.05) and more likely to have specific policies for obesity, physical activity and promoting mental well-being (all P <0.01). CONCLUSIONS: Implementation of NICE guidance on health at work is incomplete across the NHS in England. Implementation was more complete where boards were leading health and well-being plans and the workforce were actively involved. There is scope to improve the implementation of evidence-based guidance to improve workers' health.

Total anomalous pulmonary venous connection: impact of prenatal diagnosis.

OBJECTIVES: To investigate whether prenatal screening is effective in the detection of total anomalous pulmonary venous connection (TAPVC) and to identify common prenatal features. METHODS: This was a retrospective collaborative study involving 19 pediatric cardiac centers in the UK, Ireland and Sweden. Cases with TAPVC born between January 1, 1998 and December 31, 2004, and prenatally diagnosed cases whose estimated dates of delivery were within this time frame, were identified. Cases with functionally univentricular circulation or atrial isomerism were excluded. All available data and stored images were reviewed. RESULTS: Four-hundred and twenty-four cases with TAPVC were identified prenatally or postnatally, of whom eight (1.9%) had a prenatal diagnosis of TAPVC. Median gestational age at fetal diagnosis was 26 + 6 (range, 22 + 4 to 32 + 0) weeks. Six further fetuses with TAPVC had an abnormality diagnosed on prenatal ultrasound, but not the TAPVC. This included other congenital heart defects (four cases) and isolated pleural effusion (two cases). Seventeen (4.0%) of the 422 liveborn infants had a first-degree relative with congenital heart disease; and six of 17 had a sibling with TAPVC. Two died in utero. Of the liveborn infants diagnosed prenatally with TAPVC, none required urgent intervention for pulmonary venous obstruction and all were alive and well at a median of 2.3 (range, 1.0-7.0) years after surgical repair. CONCLUSION: Prenatal diagnosis of TAPVC is infrequent using current screening methods. Where there is a family history of TAPVC, specialized fetal echocardiography at 20 and 28 weeks' gestation may be indicated.

On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure.

BACKGROUND: Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM) patients. Treatment effects with improved left ventricular (LV) ejection fraction (EF) have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. METHODS: This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR) to the relative risk (RR) of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM) and 63-70% (lower half of the normal range for TM). RESULTS: A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p < 0.001) and the higher EF stratum (EF 63-70%, RR 0.893 p = 0.001). CONCLUSION: These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

Cystic fibrosis and survival to 40 years: a study of cystic fibrosis transmembrane conductance regulator function.

Significant survival heterogeneity exists in cystic fibrosis. Our aim was to determine whether residual function of the cystic fibrosis transmembrane conductance regulator (CFTR) is present in long-term survivors with severe mutations. Nasal potential difference (PD) and sweat chloride were measured in 34 long-term survivors (aged ≥ 40 yrs) and compared with young patients (18-23 yrs) with severe (n = 30) and mild (n = 31) lung disease. Baseline PD was not significantly different across the three groups (long-term survivors, -42.8 (range -71.0- -20.5) mV; young/mild, -40.5 (-58.8- -19.5) mV; young/severe,-46.3 (-74.0- -20.0) mV). Response to amiloride (ΔAmil) was significantly different across the three groups (p = 0.01); long-term survivors had values (27.8 (range 8.5-46) mV) which were not different to either young group, but the young/severe group had significantly higher values (29.5 (11-47) mV) than those in the young/mild group (22.0 (7-39) mV; p<0.01). Baseline PD and ΔAmil were associated with forced expiratory volume in 1 s (FEV1) (co-efficient (95% CI) -0.13 (-0.23- -0.03); p = 0.009 and -0.12 (-0.20- -0.04); p = 0.003, respectively). Sweat chloride was lowest (p <0.05) in the young/severe group (93.5 (74-111) mmol·L⁻¹ versus 98.8 (76.5-116.0) mmol·L⁻¹; long-term survivors; and 99.5 (80.0-113.5) mmol·L⁻¹; young/mild). Δ Amil is associated with FEV1 but our findings indicate that long-term survival cannot be explained by residual CFTR function when measurements are taken in later life.

Predicting 22q11.2 deletion syndrome: a novel method using the routine full blood count.

BACKGROUND: 22q11.2 deletion syndrome is common affecting nearly 1 in 3000, including many with DiGeorge Syndrome and 5% of individuals with congenital heart disease. Diagnosis is important because affected patients have impaired immune function and may suffer high mortality rates if given non-irradiated blood products from graft versus host disease. Symptomatic hypocalcaemia may also occur. Our objective was to determine whether mean platelet volume (MPV), available from the routine full blood count, may be a useful and rapid indicator of 22q11.2 deletion. METHOD: A retrospective case control cohort study analysing MPV and 22q11.2 deletion status was performed in a paediatric population (n = 166) undergoing cardiac surgery between 1999 and 2005. RESULTS: Twenty children were 22q11.2 positive. The median MPV was significantly larger for the 22q11.2 positive patient group compared to the non-22q11.2 patients (10.9fL versus 8.6fL, p<0.001). The area under the curve of the receiver operating characteristics (ROC) curve of MPV was large enough (0.85) to enable the accurate prediction of 22q11.2 deletion using MPV. CONCLUSIONS: MPV is a useful screening test, involving no extra laboratory work, cost or patient discomfort. MPV>10fL is a positive predictor of the presence of 22q11.2 deletion in children with congenital heart disease (specificity 89.7%). This finding should aid rapid decision-making for ordering irradiated blood products to prevent potentially fatal transfusion-associated graft versus host disease. It will alert clinicians to monitor serum calcium levels closely to prevent hypocalcaemic seizures.

Effects of subthalamic stimulation on speech of consecutive patients with Parkinson disease.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for advanced Parkinson disease (PD). Following STN-DBS, speech intelligibility can deteriorate, limiting its beneficial effect. Here we prospectively examined the short- and long-term speech response to STN-DBS in a consecutive series of patients to identify clinical and surgical factors associated with speech change. METHODS: Thirty-two consecutive patients were assessed before surgery, then 1 month, 6 months, and 1 year after STN-DBS in 4 conditions on- and off-medication with on- and off-stimulation using established and validated speech and movement scales. Fifteen of these patients were followed up for 3 years. A control group of 12 patients with PD were followed up for 1 year. RESULTS: Within the surgical group, speech intelligibility significantly deteriorated by an average of 14.2%±20.15% off-medication and 16.9%±21.8% on-medication 1 year after STN-DBS. The medical group deteriorated by 3.6%±5.5% and 4.5%±8.8%, respectively. Seven patients showed speech amelioration after surgery. Loudness increased significantly in all tasks with stimulation. A less severe preoperative on-medication motor score was associated with a more favorable speech response to STN-DBS after 1 year. Medially located electrodes on the left STN were associated with a significantly higher risk of speech deterioration than electrodes within the nucleus. There was a strong relationship between high voltage in the left electrode and poor speech outcome at 1 year. CONCLUSION: The effect of STN-DBS on speech is variable and multifactorial, with most patients exhibiting decline of speech intelligibility. Both medical and surgical issues contribute to deterioration of speech in STN-DBS patients. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that STN-DBS for PD results in deterioration in speech intelligibility in all combinations of medication and stimulation states at 1 month, 6 months, and 1 year compared to baseline and to control subjects treated with best medical therapy.

Preoperative 6-minute walk test adds prognostic information to Euroscore in patients undergoing aortic valve replacement.

AIMS: The authors investigated the additive prognostic value of the 6-minute walk test (6MWT) to Euroscore in patients with severe aortic stenosis undergoing aortic valve replacement (AVR) METHODS AND RESULTS: 208 patients with severe AS underwent the 6MWT before AVR, as part of a randomised trial (ASSERT) comparing stented and stentless aortic valves. Clinical follow-up was available for 200 patients up to 12 months. The rate of death, myocardial infarction (MI) or stroke (time to first event) was 13% (n = 14) in patients walking <300 metres compared to 4% (n = 4) in those who walked > or =300 metres (p = 0.017). When rate of death, MI or stroke by Euroscore risk was stratified by 6-minute walking distance, the 6MWT added prognostic information. In a Cox regression analysis 6MWT distance was the only variable retained as an independent predictor of the composite outcome of death, MI or stroke at 12 months (HR 0.28 95% CI 0.09 to 0.85, p = 0.025). CONCLUSIONS: The 6MWT is safe and feasible to carry out in patients with severe aortic stenosis before AVR, and provides potentially important functional and prognostic information to clinical assessment and the Euroscore risk score.

Cardiac T2* magnetic resonance for prediction of cardiac complications in thalassemia major.

BACKGROUND: The goal of this study was to determine the predictive value of cardiac T2* magnetic resonance for heart failure and arrhythmia in thalassemia major. METHODS AND RESULTS: We analyzed cardiac and liver T2* magnetic resonance and serum ferritin in 652 thalassemia major patients from 21 UK centers with 1442 magnetic resonance scans. The relative risk for heart failure with cardiac T2* values <10 ms (compared with >10 ms) was 160 (95% confidence interval, 39 to 653). Heart failure occurred in 47% of patients within 1 year of a cardiac T2* <6 ms with a relative risk of 270 (95% confidence interval, 64 to 1129). The area under the receiver-operating characteristic curve for predicting heart failure was significantly greater for cardiac T2* (0.948) than for liver T2* (0.589; P<0.001) or serum ferritin (0.629; P<0.001). Cardiac T2* was <10 ms in 98% of scans in patients who developed heart failure. The relative risk for arrhythmia with cardiac T2* values <20 ms (compared with >20 ms) was 4.6 (95% confidence interval, 2.66 to 7.95). Arrhythmia occurred in 14% of patients within 1 year of a cardiac T2* of <6 ms. The area under the receiver-operating characteristic curve for predicting arrhythmia was significantly greater for cardiac T2* (0.747) than for liver T2* (0.514; P<0.001) or serum ferritin (0.518; P<0.001). The cardiac T2* was <20 ms in 83% of scans in patients who developed arrhythmia. CONCLUSIONS: Cardiac T2* magnetic resonance identifies patients at high risk of heart failure and arrhythmia from myocardial siderosis in thalassemia major and is superior to serum ferritin and liver iron. Using cardiac T2* for the early identification and treatment of patients at risk is a logical means of reducing the high burden of cardiac mortality in myocardial siderosis. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00520559.

Pulmonary vein stenosis: the UK, Ireland and Sweden collaborative study.

OBJECTIVE: To describe clinical features, morphology, management and outcome of pulmonary vein stenosis (PVS) in childhood. DESIGN AND SETTING: Retrospective international collaborative study involving 19 paediatric cardiology centres in the UK, Ireland and Sweden. PATIENTS: Cases of PVS presenting between 1 January 1995 and 31 December 2004 were identified. Cases where pulmonary veins connected to a morphological left atrium were included. Functionally univentricular hearts and total anomalous pulmonary venous connection were excluded. All available data and imaging were reviewed. RESULTS: 58 cases were identified. In 22 cases (38%) there was premature delivery. 46 (79%) had associated cardiac lesions; 16 (28%) had undergone previous cardiac surgery before PVS diagnosis. 16 children (28%) had a syndrome or significant extracardiac abnormality. 36 presented with unilateral disease of which 86% was on the left. Where there was adequate sequential imaging, disease progression was shown with discrete stenosis leading to diffusely small pulmonary veins. Collateral vessels often developed. 13 patients had no intervention. Initial intervention was by catheter in 17 and surgery in 28. Overall 3-year survival was 49% (95% CI 35% to 63%) with patients undergoing initial surgical intervention having greater freedom from death or re-intervention (hazard ratio 0.44, 95% CI 0.2 to 0.99, p = 0.023). CONCLUSIONS: PVS is a complex disease of uncertain cause and frequently associated with prematurity. Early intervention may be indicated to deter irreversible secondary changes.

Neural respiratory drive in obesity.

BACKGROUND: The load imposed on ventilation by increased body mass contributes to the respiratory symptoms caused by obesity. A study was conducted to quantify ventilatory load and respiratory drive in obesity in both the upright and supine postures. METHODS: Resting breathing when seated and supine was studied in 30 obese subjects (mean (SD) body mass index (BMI) 42.8 (8.6) kg/m(2)) and 30 normal subjects (mean (SD) BMI 23.6 (3.7) kg/m(2)), recording the electromyogram of the diaphragm (EMGdi, transoesophageal multipair electrode), gastric and oesophageal pressures. RESULTS: Ventilatory load and neural drive were higher in the obese group as judged by the EMGdi (21.9 (9.0) vs 8.4 (4.0)%max, p<0.001) and oesophageal pressure swings (9.6 (2.9) vs 5.3 (2.2) cm H(2)O, p<0.001). The supine posture caused an increase in oesophageal pressure swings to 16.0 (5.0) cm H(2)O in obese subjects (p<0.001) and to 6.9 (2.0) cm H(2)O in non-obese subjects (p<0.001). The EMGdi increased in the obese group to 24.7 (8.2)%max (p<0.001) but remained the same in non-obese subjects (7.0 (3.4)%max, p = NS). Obese subjects developed intrinsic positive end-expiratory pressure (PEEPi) of 5.3 (3.6) cm H(2)O when supine. Applying continuous positive airway pressure (CPAP) in a subgroup of obese subjects when supine reduced the EMGdi by 40%, inspiratory pressure swings by 25% and largely abolished PEEPi (4.1 (2.7) vs 0.8 (0.4) cm H(2)O, p = 0.009). CONCLUSION: Obese patients have substantially increased neural drive related to BMI and develop PEEPi when supine. CPAP abolishes PEEPi and reduces neural respiratory drive in these patients. These findings highlight the adverse respiratory consequences of obesity and have implications for the clinical management of patients, particularly where the supine posture is required.

NHS heart failure survey: a survey of acute heart failure admissions in England, Wales and Northern Ireland.

OBJECTIVES: To obtain national data on demographics, investigation, treatment and short-term outcome for patients admitted with acute heart failure. DESIGN: Retrospective survey of emergency admissions with acute heart failure from October 2005 to March 2006. SETTING: Acute NHS trusts in England, Wales and Northern Ireland. MAIN OUTCOME MEASURES: Patient demographics, referral source, admission characteristics, admission pathway, patient heart failure treatment on admission, length of stay, short-term mortality, discharge heart failure treatment, specialist follow-up and delayed discharge. RESULTS: 176/177 (99%) acute trusts responded and 9387 records were surveyed. Patients mean age was 77 (SD 11) years, 50% were women and 56% had prior history of heart failure. On average, women were 5 years older than men (80 vs 75 years, p<0.001), were less likely to have had echocardiography (52% vs 60%, p<0.001), and if previously diagnosed with heart failure less likely to be treated with ACE inhibitors (58.3% vs 66.8%, p<0.001), beta-blockers (30.1% vs 35.5%, p = 0.033) or aldosterone antagonists (18.9% vs 22.5%, p<0.001) at admission. In-hospital mortality was 15%. Age-adjusted mortality was higher in men (16% vs 14%, p = 0.042). 75% of patients were admitted with moderate to severe symptoms (NYHA class III or IV). Women were less likely to be prescribed anti-failure medication, except diuretics, on discharge (ACE-I/AIIRA 66.5% vs 73.4%, beta-blocker 31.3% vs 37.5%, aldosterone antagonists 23.4% vs 30.1%, all p<0.001). Only 20% of patients had planned specialist heart failure follow-up, with <1% referred for rehabilitation or specialist palliative care. CONCLUSION: Many patients admitted to acute hospitals in England, Wales and Northern Ireland are not being managed fully in accordance with international evidence-based guidelines. In comparison with earlier UK studies, the use of echocardiography and ACE-I and beta-blockers has increased, and length of stay reduced. Only a minority of patients are seen, or followed up, by a specialist service. Women seem to be less well managed against recommended guidelines. Significant and sustained effort is required to address gender inequalities in the provision of heart failure care.

Z-scores of the fetal aortic isthmus and duct: an aid to assessing arch hypoplasia.

OBJECTIVE: Prenatal diagnosis of isolated coarctation of the aorta suffers from high false positive and false negative rates. The aim of our study was to develop Z-scores for the aortic isthmus in normal fetuses as a reference for fetuses with suspected coarctation. METHODS: The aortic isthmal diameter, immediately proximal to the insertion of the arterial duct, was measured prospectively in the transverse (three vessel and trachea) and sagittal views in 221 normal fetuses at 18 to 37 weeks' gestation. The ductal diameter was measured immediately before it entered the descending aorta in the same view. All measurements were repeated three times by a single investigator and averaged. A second investigator re-measured the images of 50 cases to assess interobserver variability. Z-scores were created relating isthmal and ductal diameters to femur length and gestational age. The ratio between the isthmal and ductal diameters was calculated. RESULTS: The formula used to calculate Z-scores for the three diameters was: [ln(measured isthmal diameter) - (m ln(femur length or gestational age) + c)]/root MSE, where c is the intercept, m is a multiplier and MSE is the mean squared error. The ratio between isthmal and ductal diameters was close to a constant value of 1 (95% CI 0.97-1.01), regardless of the value of femur length or gestational age. CONCLUSION: We have defined Z-scores for the fetal aortic isthmus and arterial duct measured in the three vessels and trachea view and for the isthmus in the sagittal plane. In suspected coarctation, these Z-scores and the isthmal to ductal ratio may help in longitudinal assessment of the aortic arch and aid in the prenatal diagnosis of coarctation.

Bispectral index values during elective rigid bronchoscopy: a prospective observational pilot study.

Rigid bronchoscopy is associated with a high incidence of haemodynamic disturbance and awareness under anaesthesia. Anaesthetic agents are given both to attenuate the sympathetic response to bronchoscopy and to prevent awareness. Use of the Bispectral index to guide anaesthesia has shown to reduce awareness and improve recovery times from general anaesthesia. We undertook a prospective observational study of BIS values in 50 patients during routine anaesthesia for rigid bronchoscopy. BIS values were found to be between 40-60 during bronchoscopy for only 0.5% of the time (0-11.5%[0-98.7%]), median (interquartile range [range]). Patients had a BIS < 40 for 99.6% (87.9-100%[0-100%]) of the duration of bronchoscopy. We identified one case of possible awareness. Few of our patients undergoing general anaesthesia for rigid bronchoscopy had BIS scores in the suggested range of between 40 and 60. BIS < 40 was more frequent than in previous studies of different surgical populations. There was no difference in the BIS values of patients anaesthetised with intermittent boluses or target controlled infusions of propofol.

A randomized, placebo-controlled, double-blind trial of the effect of combined therapy with deferoxamine and deferiprone on myocardial iron in thalassemia major using cardiovascular magnetic resonance.

BACKGROUND: Cardiac complications secondary to iron overload are the leading cause of death in beta-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect. METHODS AND RESULTS: Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P=0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P=0.05), and absolute endothelial function (8.8% versus 3.3%; P=0.02). There was also a significantly greater improvement in serum ferritin in the combined group (-976 versus -233 microg/L; P<0.001). CONCLUSIONS: In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.