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BACKGROUND: Patients hospitalised with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with COVID-19 and coronary disease risk factors. PATIENTS/METHODS: A randomised controlled open-label trial across acute hospitals (UK and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. The trial terminated early due to low recruitment. At 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted OR 0.73, 95%CI 0.38 to 1.41, p=0.355). Significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR 1.46, 95% CrI 0.88 to 2.37, Pr(Beta>0)=93%; adjusted OR 1.50, 95% CrI 0.91 to 2.45, Pr(Beta>0)=95%) and median time to discharge home was two days shorter (95% CrI -4 to 0, 2% probability that it was worse). CONCLUSIONS: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

Aims Oxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. The aim of this analysis was to examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome and to determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI). Methods and results Patients with severe single-vessel coronary artery disease (CAD) were randomized 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomization treadmill CPET, dobutamine stress echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period. A total of 195 patients with CPET data were randomized (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score [+0.82 segments; 95% confidence interval (CI): 0.40 to 1.25, P = 0.0068] and lower fractional flow reserve (−0.07; 95% CI: −0.12 to −0.02, P = 0.011) compared with those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score [oxygen-pulse plateau presence (Pinteraction = 0.026) and oxygen-pulse gradient (Pinteraction = 0.023)] and Seattle angina physical-limitation score [oxygen-pulse plateau presence (Pinteraction = 0.037)]. Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse, and oxygen uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI. Conclusion Although selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel CAD.

Background: It is not known whether the optimal Atrioventricular delay (AV ) varies between left ventricular (LV) pacing site during endocardial biventricular pacing (BiVP) and may therefore needs consideration. Methods: We assessed the haemodynamic AV in patients with chronic heart failure undergoing endocardial LV lead implantation. AV was assessed during atrio-biventricular pacing (BVP) with a “roving LV lead”. Up to four locations were studied: mid lateral wall, mid septum (or a close alternative), site of greatest haemodynamic improvement and LV lead implant site. The AV was compared to a fixed AV delay of 180ms. Results: Seventeen patients were included (12 male, aged 66.5 +/- 12.8 years, ejection fraction 26 +/- 7%, 16 left bundle branch block or high percentage of right ventricular pacing (RVP), QRS duration 167 +/-27 ms). In most locations (62/63), AV increased systolic blood pressure during BiVP compared with RVP (relative improvement 6 mmHg, IQR 4-9mmHg). Compared to a fixed AV delay the haemodynamic improvement at AV was higher (1mmHg, IQR 0.2-2.6mmHg, pConclusion: Within a patient, different endocardial LV lead locations have slightly different haemodynamic AV which are superior to a fixed AV delay. The haemodynamic consequence of applying an optimum from a different lead location is small.

The large number of available MRI sequences means patients cannot realistically undergo them all, so the range of sequences to be acquired during a scan are protocolled based on clinical details. Adapting this to unexpected findings identified early on in the scan requires experience and vigilance. We investigated whether deep learning of the images acquired in the first few minutes of a scan could provide an automated early alert of abnormal features. Anatomy sequences from 375 CMR scans were used as a training set. From these, we annotated 1500 individual slices and used these to train a convolutional neural network to perform automatic segmentation of the cardiac chambers, great vessels and any pleural effusions. 200 scans were used as a testing set. The system then assembled a 3D model of the thorax from which it made clinical measurements to identify important abnormalities. The system was successful in segmenting the anatomy slices (Dice 0.910) and identified multiple features which may guide further image acquisition. Diagnostic accuracy was 90.5% and 85.5% for left and right ventricular dilatation, 85% for left ventricular hypertrophy and 94.4% for ascending aorta dilatation. The area under ROC curve for diagnosing pleural effusions was 0.91. We present proof-of-concept that a neural network can segment and derive accurate clinical measurements from a 3D model of the thorax made from transaxial anatomy images acquired in the first few minutes of a scan. This early information could lead to dynamic adaptive scanning protocols, and by focusing scanner time appropriately and prioritizing cases for supervision and early reporting, improve patient experience and efficiency. Electronic supplementary material The online version of this article (10.1007/s10554-020-02050-w) contains supplementary material, which is available to authorized users.

Percutaneous coronary intervention (PCI) is frequently performed for stable angina. However, the first blinded trial, ORBITA, did not show a placebo-controlled increment in exercise time in patients with single-vessel disease, at 6 weeks, on maximal antianginal therapy. ORBITA-2 will assess the placebo-controlled efficacy of PCI on angina frequency in patients with single- or multivessel disease, at 12 weeks, on no antianginal therapy. ORBITA-2 is a double-blind placebo-controlled trial randomising participants with (i) angina at presentation, (ii) documented angina during the 2-week pre-randomisation symptom assessment phase, (iii) objective evidence of ischaemia, (iv) single- or multivessel disease, and (v) clinical eligibility for PCI. At enrolment, antianginals will be stopped, and angina questionnaires completed. Participants will record their symptoms on a smartphone application daily throughout the trial and will undergo exercise treadmill testing and stress echocardiography at pre-randomisation. They will then undergo coronary angiography with unblinded invasive physiology assessment. Eligible participants will then be sedated to a deep level of conscious sedation and randomised 1:1 between PCI and placebo. After the 12-week blinded follow-up period, they will return for questionnaires, exercise testing and stress echocardiography assessment. If angina becomes intolerable, antianginals will be introduced using a prespecified medication protocol. The primary outcome is an angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include exercise treadmill time, angina frequency, angina severity and quality of life. Trial registration: ClinicalTrials.gov: NCT03742050.

Summary: Background: Most patients who have heart failure with a reduced ejection fraction, when left ventricular ejection fraction (LVEF) is 40% or lower, are diagnosed in hospital. This is despite previous presentations to primary care with symptoms. We aimed to test an artificial intelligence (AI) algorithm applied to a single-lead ECG, recorded during ECG-enabled stethoscope examination, to validate a potential point-of-care screening tool for LVEF of 40% or lower. Methods: We conducted an observational, prospective, multicentre study of a convolutional neural network (known as AI-ECG) that was previously validated for the detection of reduced LVEF using 12-lead ECG as input. We used AI-ECG retrained to interpret single-lead ECG input alone. Patients (aged ≥18 years) attending for transthoracic echocardiogram in London (UK) were recruited. All participants had 15 s of supine, single-lead ECG recorded at the four standard anatomical positions for cardiac auscultation, plus one handheld position, using an ECG-enabled stethoscope. Transthoracic echocardiogram-derived percentage LVEF was used as ground truth. The primary outcome was performance of AI-ECG at classifying reduced LVEF (LVEF ≤40%), measured using metrics including the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity, with two-sided 95% CIs. The primary outcome was reported for each position individually and with an optimal combination of AI-ECG outputs (interval range 0–1) from two positions using a rule-based approach and several classification models. This study is registered with ClinicalTrials.gov, NCT04601415. Findings: Between Feb 6 and May 27, 2021, we recruited 1050 patients (mean age 62 years [SD 17·4], 535 [51%] male, 432 [41%] non-White). 945 (90%) had an ejection fraction of at least 40%, and 105 (10%) had an ejection fraction of 40% or lower. Across all positions, ECGs were most frequently of adequate quality for AI-ECG interpretation at the pulmonary position (979 [93·3%] of 1050). Quality was lowest for the aortic position (846 [80·6%]). AI-ECG performed best at the pulmonary valve position (p=0·02), with an AUROC of 0·85 (95% CI 0·81–0·89), sensitivity of 84·8% (76·2–91·3), and specificity of 69·5% (66·4–72·6). Diagnostic odds ratios did not differ by age, sex, or non-White ethnicity. Taking the optimal combination of two positions (pulmonary and handheld positions), the rule-based approach resulted in an AUROC of 0·85 (0·81–0·89), sensitivity of 82·7% (72·7–90·2), and specificity of 79·9% (77·0–82·6). Using AI-ECG outputs from these two positions, a weighted logistic regression with l2 regularisation resulted in an AUROC of 0·91 (0·88–0·95), sensitivity of 91·9% (78·1–98·3), and specificity of 80·2% (75·5–84·3). Interpretation: A deep learning system applied to single-lead ECGs acquired during a routine examination with an ECG-enabled stethoscope can detect LVEF of 40% or lower. These findings highlight the potential for inexpensive, non-invasive, workflow-adapted, point-of-care screening, for earlier diagnosis and prognostically beneficial treatment. Funding: NHS Accelerated Access Collaborative, NHSX, and the National Institute for Health Research.

Background: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 mm Hg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results after the addition of a recommended standardized stepped-care antihypertensive treatment to the randomized endovascular procedure under continued blinding to initial treatment. Methods: Patients with a daytime ambulatory BP ≥135/85 mm Hg and Results: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the standardized stepped-care antihypertensive treatment versus 84.5% in the sham group ( P =0.008), and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 versus 1.3±0.9, P =0.010 and 1.4±1.5 versus 2.0±1.8, P =0.018; respectively). Despite less intensive standardized stepped-care antihypertensive treatment, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (−18.1±12.2 versus −15.6±13.2 mm Hg, respectively; difference adjusted for baseline BP and number of medications: −4.3 mm Hg, 95% confidence interval, −7.9 to −0.6, P =0.024). There were no major adverse events in either group through 6 months. Conclusions: The BP-lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02649426.

The COVID-19 pandemic has altered our approach to inpatient echocardiography delivery. There is now a greater focus to address key clinical questions likely to make an immediate impact in management, particularly during the period of widespread infection. Handheld echocardiography (HHE) can be used as a first-line assessment tool, limiting scanning time and exposure to high viral load. This article describes a potential role for HHE during a pandemic. We propose a protocol with a reporting template for a focused core dataset necessary in delivering an acute echocardiography service in the setting of a highly contagious disease, minimising risk to the operator. We cover the scenarios typically encountered in the acute cardiology setting and how an expert trained echocardiography team can identify such pathologies using a limited imaging format and include cardiac presentations encountered in those patients acutely unwell with COVID-19.

Aims: A prolonged PR interval may adversely affect ventricular filling and therefore cardiac function. AV delay can be corrected using right-ventricular-pacing (RVP) but this induces ventricular dyssynchrony, itself harmful. Therefore, in intermittent heart-block, pacing-avoidance algorithms are often implemented. We tested His-bundle pacing (HBP) as an alternative. Methods: Out-patients with a long PR interval(>200ms) and intermittent need for ventricular pacing were recruited. We measured within patient differences in high-precision haemodynamics between AV-optimized RVP, and HBP, as well as a pacing-avoidance algorithm [Managed Ventricular Pacing (MVP)]. Results We recruited 18 patients. Mean left ventricular ejection fraction was 44.3±9%. Mean intrinsic PR interval was 266±42ms and QRS duration was 123±29ms. RVP lengthened QRS duration(+54 ms, 95%CI 42 to 67ms, p

Aims The efficacy of patent foramen ovale (PFO) closure for cryptogenic stroke has been controversial. We undertook a meta-analysis of randomized controlled trials (RCTs) comparing device closure with medical therapy to prevent recurrent stroke for patients with PFO. Methods and results We systematically identified all RCTs comparing device closure to medical therapy for cryptogenic stroke in patients with PFO. The primary efficacy endpoint was recurrent stroke, analysed on an intention-to-treat basis. The primary safety endpoint was new onset atrial fibrillation (AF). Five studies (3440 patients) were included. In all, 1829 patients were randomized to device closure and 1611 to medical therapy. Across all patients, PFO closure was superior to medical therapy for prevention of stroke [hazard ratio (HR) 0.32, 95% confidence interval (95% CI) 0.13–0.82; P = 0.018, I2 = 73.4%]. The risk of AF was significantly increased with device closure [risk ratio (RR) 4.68, 95% CI 2.19–10.00, P

Summary Background Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. Methods ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. Findings ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI −8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. Interpretation In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. Funding NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.

Summary Background Early studies suggest that radiofrequency-based renal denervation reduces blood pressure in patients with moderate hypertension. We investigated whether an alternative technology using endovascular ultrasound renal denervation reduces ambulatory blood pressure in patients with hypertension in the absence of antihypertensive medications. Methods RADIANCE-HTN SOLO was a multicentre, international, single-blind, randomised, sham-controlled trial done at 21 centres in the USA and 18 in Europe. Patients with combined systolic–diastolic hypertension aged 18–75 years were eligible if they had ambulatory blood pressure greater than or equal to 135/85 mm Hg and less than 170/105 mm Hg after a 4-week discontinuation of up to two antihypertensive medications and had suitable renal artery anatomy. Patients were randomised (1:1) to undergo renal denervation with the Paradise system (ReCor Medical, Palo Alto, CA, USA) or a sham procedure consisting of renal angiography only. The randomisation sequence was computer generated and stratified by centres with randomised blocks of four or six and permutation of treatments within each block. Patients and outcome assessors were blinded to randomisation. The primary effectiveness endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Patients were to remain off antihypertensive medications throughout the 2 months of follow-up unless specified blood pressure criteria were exceeded. Major adverse events included all-cause mortality, renal failure, an embolic event with end-organ damage, renal artery or other major vascular complications requiring intervention, or admission to hospital for hypertensive crisis within 30 days and new renal artery stenosis within 6 months. This study is registered with ClinicalTrials.gov, number NCT02649426. Findings Between March 28, 2016, and Dec 28, 2017, 803 patients were screened for eligibility and 146 were randomised to undergo renal denervation (n=74) or a sham procedure (n=72). The reduction in daytime ambulatory systolic blood pressure was greater with renal denervation (−8·5 mm Hg, SD 9·3) than with the sham procedure (−2·2 mm Hg, SD 10·0; baseline-adjusted difference between groups: −6·3 mm Hg, 95% CI −9·4 to −3·1, p=0·0001). No major adverse events were reported in either group. Interpretation Compared with a sham procedure, endovascular ultrasound renal denervation reduced ambulatory blood pressure at 2 months in patients with combined systolic–diastolic hypertension in the absence of medications. Funding ReCor Medical.

Background Patients presenting with ST-elevation myocardial infarction commonly have multi-vessel coronary artery disease. After the culprit artery is treated, the optimal treatment strategy for the residual disease is not yet defined. Large observational studies suggest that treatment of residual disease should be deferred but smaller randomised controlled trials (RCTs) suggest multi-vessel primary percutaneous coronary intervention (MV-PPCI) at the time of STEMI is safe. We examine if allocation bias of high-risk patients could explain the conflicting results between observational studies and RCTs and aim to resolve the paradox between the two. Methods A meta-analysis of registries comparing culprit-only PPCI to MV-PPCI was performed. We then determined if high-risk patients were more likely to be allocated to MV-PPCI. A meta-regression was performed to determine if any allocation bias of high-risk patients could explain the difference in outcomes between therapies. Results 47,717 patients (19 studies) were eligible. MV-PPCI had higher mortality than culprit-only PPCI (OR 1.59, 95% CI 1.12 to 2.24, p=0.03). However, higher risk patients were more likely to be allocated to MV-PPCI (OR 1.45, 95% CI 1.18 to 1.78, p=0.0005). When this was accounted for, there was no difference in mortality between culprit-only PPCI and MV-PPCI (OR 0.99, 95% CI 0.69 to 1.41, p=0.94). Discussion Clinicians preferentially allocate higher-risk patients to MV-PPCI at the time of STEMI, resulting in observational studies reporting higher mortality with this strategy. When this is accounted for, these large observational studies in ‘real world' patients support the conclusion of the smaller RCTs in the field: MV-PPCI has equivalent mortality to a culprit-only approach.

Aortic stenosis represents a growing health care burden in high-income countries. Currently, the only definitive treatment is surgical or transcatheter valve intervention at the end stages of disease. As the understanding of the underlying pathophysiology evolves, many promising therapies are being investigated. These seek to both slow disease progression in the valve and delay the transition from hypertrophy to heart failure in the myocardium, with the ultimate aim of avoiding the need for valve replacement in the elderly patients afflicted by this condition. Noninvasive imaging has played a pivotal role in enhancing our understanding of the complex pathophysiology underlying aortic stenosis, as well as disease progression in both the valve and myocardium. In this review, the authors discuss the means by which contemporary imaging may be used to assess disease progression and how these approaches may be utilized, both in clinical practice and research trials exploring the clinical efficacy of novel therapies.

Robotically guided radiofrequency (RF) ablation offers greater catheter stability that may improve lesion depth. We performed a non-randomised comparison of patients undergoing ventricular tachycardia (VT) ablation either manually or robotically using the Hansen Sensei system for recurrent implantable defibrillator (ICD) therapy. Patients with infarct-related scar underwent VT ablation using the Hansen system to assess feasibility compared with patients undergoing manual VT ablation during a similar time period. Power delivery during robotic ablation was restricted to 30 W at 60 s. VT inducibility was checked at the end of the procedure. Pre-ablation ICD therapy burdens over 6 months were compared with post-ablation therapy averaged to a 6-month period. Twelve consecutive patients who underwent robotic VT ablation were compared to 12 consecutive patients undergoing a manual ablation. Patient demographics and comorbidities were similar in the two groups. A higher proportion of robotic cases were urgent (9/12 (75 %)) vs. manual (4/12 (33 %)) (p = 0.1). Post-ablation VT stimulation did not induce clinical VT in 11/12 (92 %) in each group. There were no peri-procedural complications related to ablation delivery. Patients were followed up for approximately 2 years. Averaged over 6 months, robotic ICD therapy burdens fell from 32 (5–400) events to 2.5 (0–11) (p = 0.015). Therapy burden fell from 14 (10–25) to 1 (0–5) (p = 0.023) in the manual group. There was no difference in long-term outcome (p = 0.60) and mortality (4/12 (33 %), p = 1.0). Robotically guided VT ablation is both feasible and safe when compared to manual ablation with good acute and long-term outcomes.

Background: During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed. Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children. Search methods: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011). Selection criteria: Double-blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies. Data collection and analysis: Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir. Main results: Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near-patient influenza testing were included. Of these 2356 children, 1255 had laboratory-confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory-confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory-confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir-resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory-confirmed influenza (risk difference (RD) -0.14, 95% confidence interval (CI) -0.24 to -0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD -0.08, 95% CI -0.12 to -0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Authors' conclusions: Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir-resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high-quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups. © 2012 The Cochrane Collaboration.

Background: During epidemics, influenza attack rates in children may exceed 40%. Options for prevention and treatment currently include the neuraminidase inhibitors zanamivir and oseltamivir. Laninamivir octanoate, the prodrug of laninamivir, is currently being developed. Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza in children. Search methods: For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1) which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January week 2, 2011) and EMBASE (January 2010 to January 2011). Selection criteria: Double‐blind, randomised controlled trials (RCTs) comparing neuraminidase inhibitors with placebo or other antiviral drugs in children aged up to and including 12 years. We also included safety and tolerability data from other types of studies. Data collection and analysis: Four review authors selected studies, assessed study quality and extracted data for the current and previous versions of this review. We analysed data separately for oseltamivir versus placebo, zanamivir versus placebo and laninamivir octanoate versus oseltamivir. Main results: Six treatment trials involving 1906 children with clinical influenza and 450 children with influenza diagnosed on rapid near‐patient influenza testing were included. Of these 2356 children, 1255 had laboratory‐confirmed influenza. Three prophylaxis trials involving 863 children exposed to influenza were also included. In children with laboratory‐confirmed influenza oseltamivir reduced median duration of illness by 36 hours (26%, P < 0.001). One trial of oseltamivir in children with asthma who had laboratory‐confirmed influenza showed only a small reduction in illness duration (10.4 hours, 8%), which was not statistically significant (P = 0.542). Laninamivir octanoate 20 mg reduced symptom duration by 2.8 days (60%, P < 0.001) in children with oseltamivir‐resistant influenza A/H1N1. Zanamivir reduced median duration of illness by 1.3 days (24%, P < 0.001). Oseltamivir significantly reduced acute otitis media in children aged one to five years with laboratory‐confirmed influenza (risk difference (RD) ‐0.14, 95% confidence interval (CI) ‐0.24 to ‐0.04). Prophylaxis with either zanamivir or oseltamivir was associated with an 8% absolute reduction in developing influenza after the introduction of a case into a household (RD ‐0.08, 95% CI ‐0.12 to ‐0.05, P < 0.001). The adverse event profile of zanamivir was no worse than placebo but vomiting was more commonly associated with oseltamivir (number needed to harm = 17, 95% CI 10 to 34). The adverse event profiles of laninamivir octanoate and oseltamivir were similar. Authors' conclusions: Oseltamivir and zanamivir appear to have modest benefit in reducing duration of illness in children with influenza. However, our analysis was limited by small sample sizes and an inability to pool data from different studies. In addition, the inclusion of data from published trials only may have resulted in significant publication bias. Based on published trial data, oseltamivir reduces the incidence of acute otitis media in children aged one to five years but is associated with a significantly increased risk of vomiting. One study demonstrated that laninamivir octanoate was more effective than oseltamivir in shortening duration of illness in children with oseltamivir‐resistant influenza A/H1N1. The benefit of oseltamivir and zanamivir in preventing the transmission of influenza in households is modest and based on weak evidence. However, the clinical efficacy of neuraminidase inhibitors in 'at risk' children is still uncertain. Larger high‐quality trials are needed with sufficient power to determine the efficacy of neuraminidase inhibitors in preventing serious complications of influenza (such as pneumonia or hospital admission), particularly in 'at risk' groups.

Introduction: Robotically-guided ablation offers theoretical advantages with greater catheter stability that can improve lesion depth. We performed a non-randomised comparison of patients undergoing ventricular tachycardia (VT) ablation either manually or using the Hansen robotic system. Methods: Consecutive patients with infarct-related scar underwent VT ablation using the Hansen system to assess feasibility, and were compared with patients undergoing manual VT ablation during the study period. All cases underwent a transeptal endocardial approach, using CARTO™ and irrigated catheter ablation guided by activation and entrainment manoeuvres if VT was sustained and tolerated, or substrate modification. The 6 month pre-ablation Implantable Cardioverter Defibrillator (ICD) therapy (Anti-tachycardia pacing (ATP) + shocks) was compared with the post ablation burden represented as a 6 monthly rate of each patient's total therapy burden during follow up ((6/follow-up duration (mths)) x total therapies post ablation)). Results: 25pts had VT ablations for infarct related scar during the study period. 13 pts had robotically guided ablation and 12 pts had manual ablation. Patients in both the robotic and manual groups had significantly impaired left ventricular function (EF 27±14% vs. 32 + /-11% respectively; p=0.32). The previous coronary revascularisationapproach, use of cardiac resynchronisation and amiodarone were similar in both groups. However 31% (4/13) of patients undergoing robotic ablation had been referred due to a failed manual approach and persisting high therapy burden as compared to 8% (1/12) redo procedures in the manual group (p=0.37). This was reflected by a trend towards higher pre-ablation therapy burden in the robotic as compared to the manual group (mean 312±566 vs. 11±9, p=0.08; median 11 vs. 9.5, p=0.50). In each group, 1 patient presented with slow incessant VT below the device therapy zone, and 1 patient had their device implanted post ablation. Post-procedure, the clinical VT was non-inducible in 85% (11/13) of the robotic group and in 92% (11/12) of the manual group. There were no peri-procedural complications. Mean follow-up was 23.5 months. Long-term mortality rates were similar (31%, 4/13 vs. 25%, 3/12; p=1.0). Post ablation, the 6 monthly therapy burden fell in both the robotic (mean reduction=290±560, median 3, p=0.047 Wilcoxon signed rank test) and manual (mean reduction=5.3±19, median 6.5, p=0.03) group. The overall reduction in therapy across all patients was 93% in the robotic and by 48% in the manual group. Conclusions: In this feasibility study, robotic VT ablation had a similar safety profile to manual ablation and a trend towards greater therapy reduction in a sicker cohort of patients. Table comparing acute procedural outcomes, 6 month pre/post ablation ICD therapies, and mortality rates between the robotic and manual groups. †Students t-test. §Fisher's exact test. ‖ Wilcoxon signed rank test. ![Graphic][1] [1]: /embed/inline-graphic-1.gif