Remote Acute Assessment of Cardiac Patients Post-Acute Coronary Syndrome (TELE-ACS): A Randomized Controlled Trial.

BACKGROUND: Telemedicine programmes can provide remote diagnostic information to aid clinical decision that could optimize care and reduce unplanned re-admissions post ACS. OBJECTIVES: TELE-ACS is a randomized controlled trial which aims to compare a telemedicine-based approach versus standard care in patients following ACS. METHODS: Patients were suitable for inclusion with at least one cardiovascular risk factor and presenting with ACS and were randomized (1:1) prior to discharge. The primary outcome was time to first readmission at 6-months. Secondary outcomes included emergency department (ED) visits, major adverse cardiovascular events and patient reported symptoms. The primary analysis was performed according to intention to treat. The trial was registered on ClinicalTrial.gov (NCT05015634). RESULTS: 337 patients were randomized from January 2022 to April 2023, with a 3.6% drop-out rate. The mean age was 58.1 years. There was a reduced rate of readmission over 6-months (hazard ratio [HR] 0.24; 95% confidence interval [CI] 0.13 to 0.44; p < 0.001) and ED attendance (HR 0.59; 95% CI 0.59; 95% CI 0.40 to 0.89) in the telemedicine arm, and fewer unplanned coronary revascularizations (3% in telemedicine arm versus 9% in standard therapy arm). The occurrence of chest pain (9% versus 24%), breathlessness (21% versus 39%) and dizziness (6% versus 18%) at 6-months was lower in the telemedicine group. CONCLUSIONS: The TELE-ACS study has shown that a telemedicine-based approach for the management of patients following ACS was associated with a reduction in hospital readmission, ED visits, unplanned coronary revascularization and patient reported symptoms.

Automated echocardiographic left ventricular dimension assessment in dogs using artificial intelligence: Development and validation.

BACKGROUND: Artificial intelligence (AI) could improve accuracy and reproducibility of echocardiographic measurements in dogs. HYPOTHESIS: A neural network can be trained to measure echocardiographic left ventricular (LV) linear dimensions in dogs. ANIMALS: Training dataset: 1398 frames from 461 canine echocardiograms from a single specialist center. VALIDATION: 50 additional echocardiograms from the same center. METHODS: Training dataset: a right parasternal 4-chamber long axis frame from each study, labeled by 1 of 18 echocardiographers, marking anterior and posterior points of the septum and free wall. VALIDATION DATASET: End-diastolic and end-systolic frames from 50 studies, annotated twice (blindly) by 13 experts, producing 26 measurements of each site from each frame. The neural network also made these measurements. We quantified its accuracy as the deviation from the expert consensus, using the individual-expert deviation from consensus as context for acceptable variation. The deviation of the AI measurement away from the expert consensus was assessed on each individual frame and compared with the root-mean-square-variation of the individual expert opinions away from that consensus. RESULTS: For the septum in end-diastole, individual expert opinions deviated by 0.12 cm from the consensus, while the AI deviated by 0.11 cm (P = .61). For LVD, the corresponding values were 0.20 cm for experts and 0.13 cm for AI (P = .65); for the free wall, experts 0.20 cm, AI 0.13 cm (P < .01). In end-systole, there were no differences between individual expert and AI performances. CONCLUSIONS AND CLINICAL IMPORTANCE: An artificial intelligence network can be trained to adequately measure linear LV dimensions, with performance indistinguishable from that of experts.

Development of artificial intelligence tools for invasive Doppler-based coronary microvascular assessment.

Aims: Coronary flow reserve (CFR) assessment has proven clinical utility, but Doppler-based methods are sensitive to noise and operator bias, limiting their clinical applicability. The objective of the study is to expand the adoption of invasive Doppler CFR, through the development of artificial intelligence (AI) algorithms to automatically quantify coronary Doppler quality and track flow velocity. Methods and results: A neural network was trained on images extracted from coronary Doppler flow recordings to score signal quality and derive values for coronary flow velocity and CFR. The outputs were independently validated against expert consensus. Artificial intelligence successfully quantified Doppler signal quality, with high agreement with expert consensus (Spearman's rho: 0.94), and within individual experts. Artificial intelligence automatically tracked flow velocity with superior numerical agreement against experts, when compared with the current console algorithm [AI flow vs. expert flow bias -1.68 cm/s, 95% confidence interval (CI) -2.13 to -1.23 cm/s, P < 0.001 with limits of agreement (LOA) -4.03 to 0.68 cm/s; console flow vs. expert flow bias -2.63 cm/s, 95% CI -3.74 to -1.52, P < 0.001, 95% LOA -8.45 to -3.19 cm/s]. Artificial intelligence yielded more precise CFR values [median absolute difference (MAD) against expert CFR: 4.0% for AI and 7.4% for console]. Artificial intelligence tracked lower-quality Doppler signals with lower variability (MAD against expert CFR 8.3% for AI and 16.7% for console). Conclusion: An AI-based system, trained by experts and independently validated, could assign a quality score to Doppler traces and derive coronary flow velocity and CFR. By making Doppler CFR more automated, precise, and operator-independent, AI could expand the clinical applicability of coronary microvascular assessment.

Quality of Life Assessment in Trials of Revascularization for Chronic Stable Angina: Insights from ORBITA and the Implications of Blinding.

The main aims of therapy in chronic stable angina are to reduce the risk of myocardial infarction and death and improve symptoms and quality of life (QoL). Unblinded trials have shown that revascularization does not reduce the risk of myocardial infarction or death but does appear to improve symptoms. However, symptoms are susceptible to the placebo effect which can bias therapies to appear more effective than they are. To assess the true physical impact of a treatment on symptoms, placebo-controlled trials with patients and medical and research teams blinded to treatment allocation are necessary. Symptoms and QoL can be reported directly by the patient or indirectly by the physician. Patient-reported outcome measures in angina trials can include angina frequency, frequency of nitrate use, exercise capacity, and questionnaires such as the Seattle Angina Questionnaire (SAQ) and the generic EuroQOL-5D-5L (EQ-5D-5L) QoL questionnaire. Physician-assessed outcome measures include Canadian Cardiovascular Society Class. The Objective Randomised Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial was the first blinded placebo-controlled study investigating the role of percutaneous coronary intervention (PCI) in chronic stable angina. The trial showed a smaller than expected and not statistically significant effect of placebo-controlled PCI on the primary endpoint of change in exercise time at 6 weeks follow-up in single-vessel coronary artery disease. There was also no significant placebo-controlled treatment effect of PCI for the prespecified secondary endpoints of SAQ or EQ-5D-5L, although PCI did result in 20% more patients becoming free from angina than placebo in a non-prespecified secondary analysis. ORBITA has demonstrated the need for symptomatic and QoL effects of PCI to be studied using placebo control. Here, we describe ways of measuring QoL, the impact of the unblinded and blinded trials to date, what we have learned from ORBITA, and what is next for this common and complex condition.

Phasic flow patterns of right versus left coronary arteries in patients undergoing clinical physiological assessment.

BACKGROUND: Coronary blood flow in humans is known to be predominantly diastolic. Small studies in animals and humans suggest that this is less pronounced or even reversed in the right coronary artery (RCA). AIMS: This study aimed to characterise the phasic patterns of coronary flow in the left versus right coronary arteries of patients undergoing invasive physiological assessment. METHODS: We analysed data from the Iberian-Dutch-English Collaborators (IDEAL) study. A total of 482 simultaneous pressure and flow measurements from 301 patients were included in our analysis. RESULTS: On average, coronary flow was higher in diastole both at rest and during hyperaemia in both the RCA and LCA (mean diastolic-to-systolic velocity ratio [DSVR] was, respectively, 1.85±0.70, 1.76±0.58, 1.53±0.34 and 1.58±0.43 for LCArest, LCAhyp, RCArest and RCAhyp, p<0.001 for between-vessel comparisons). Although the type of RCA dominance affected the DSVR magnitude (RCAdom=1.55±0.35, RCAco-dom=1.40±0.27, RCAnon-dom=1.35; standard deviation not reported as n=3), systolic flow was very rarely predominant (DSVR was greater than or equal to 1.00 in 472/482 cases [97.9%] overall), with equal prevalence in the LCA. Stenosis severity or microvascular dysfunction had a negligible impact on DSVR in both the RCA and LCA (DSVR x hyperaemic stenosis resistance R2 =0.018, p=0.03 and DSVR x coronary flow reserve R2 <0.001, p=0.98). CONCLUSIONS: In patients with coronary artery disease undergoing physiological assessment, diastolic flow predominance is seen in both left and right coronary arteries. Clinical interpretation of coronary physiological data should therefore not differ between the left and the right coronary systems.

Automated Identification of Orthopedic Implants on Radiographs Using Deep Learning.

Accurate identification of metallic orthopedic implant design is important for preoperative planning of revision arthroplasty. Surgical records of implant models are frequently unavailable. The aim of this study was to develop and evaluate a convolutional neural network for identifying orthopedic implant models using radiographs. In this retrospective study, 427 knee and 922 hip unilateral anteroposterior radiographs, including 12 implant models from 650 patients, were collated from an orthopedic center between March 2015 and November 2019 to develop classification networks. A total of 198 images paired with autogenerated image masks were used to develop a U-Net segmentation network to automatically zero-mask around the implants on the radiographs. Classification networks processing original radiographs, and two-channel conjoined original and zero-masked radiographs, were ensembled to provide a consensus prediction. Accuracies of five senior orthopedic specialists assisted by a reference radiographic gallery were compared with network accuracy using McNemar exact test. When evaluated on a balanced unseen dataset of 180 radiographs, the final network achieved a 98.9% accuracy (178 of 180) and 100% top-three accuracy (180 of 180). The network performed superiorly to all five specialists (76.1% [137 of 180] median accuracy and 85.6% [154 of 180] best accuracy; both P < .001), with robustness to scan quality variation and difficult to distinguish implants. A neural network model was developed that outperformed senior orthopedic specialists at identifying implant models on radiographs; real-world application can now be readily realized through training on a broader range of implants and joints, supported by all code and radiographs being made freely available. Supplemental material is available for this article. Keywords: Neural Networks, Skeletal-Appendicular, Knee, Hip, Computer Applications-General (Informatics), Prostheses, Technology Assess-ment, Observer Performance © RSNA, 2021.

Automated Left Ventricular Dimension Assessment Using Artificial Intelligence Developed and Validated by a UK-Wide Collaborative.

BACKGROUND: requires training and validation to standards expected of humans. We developed an online platform and established the Unity Collaborative to build a dataset of expertise from 17 hospitals for training, validation, and standardization of such techniques. METHODS: The training dataset consisted of 2056 individual frames drawn at random from 1265 parasternal long-axis video-loops of patients undergoing clinical echocardiography in 2015 to 2016. Nine experts labeled these images using our online platform. From this, we trained a convolutional neural network to identify keypoints. Subsequently, 13 experts labeled a validation dataset of the end-systolic and end-diastolic frame from 100 new video-loops, twice each. The 26-opinion consensus was used as the reference standard. The primary outcome was precision SD, the SD of the differences between AI measurement and expert consensus. RESULTS: In the validation dataset, the AI's precision SD for left ventricular internal dimension was 3.5 mm. For context, precision SD of individual expert measurements against the expert consensus was 4.4 mm. Intraclass correlation coefficient between AI and expert consensus was 0.926 (95% CI, 0.904-0.944), compared with 0.817 (0.778-0.954) between individual experts and expert consensus. For interventricular septum thickness, precision SD was 1.8 mm for AI (intraclass correlation coefficient, 0.809; 0.729-0.967), versus 2.0 mm for individuals (intraclass correlation coefficient, 0.641; 0.568-0.716). For posterior wall thickness, precision SD was 1.4 mm for AI (intraclass correlation coefficient, 0.535 [95% CI, 0.379-0.661]), versus 2.2 mm for individuals (0.366 [0.288-0.462]). We present all images and annotations. This highlights challenging cases, including poor image quality and tapered ventricles. CONCLUSIONS: Experts at multiple institutions successfully cooperated to build a collaborative AI. This performed as well as individual experts. Future echocardiographic AI research should use a consensus of experts as a reference. Our collaborative welcomes new partners who share our commitment to publish all methods, code, annotations, and results openly.

Aerosolised fluorescein can quantify FFP mask faceseal leakage: a cost-effective adaptation to the existing point of care fit test.

BACKGROUND: A qualitative fit test using bitter-tasting aerosols is the commonest way to determine filtering face-piece (FFP) mask leakage. This taste test is subjective and biased by placebo. We propose a cheap, quantitative modification of the taste test by measuring the amount of fluorescein stained filter paper behind the mask using image analysis. METHODS: A bitter-tasting fluorescein solution was aerosolised during mask fit tests, with filter paper placed on masks' inner surfaces. Participants reported whether they could taste bitterness to determine taste test 'pass' or 'fail' results. Filter paper photographs were digitally analysed to quantify total fluorescence (TF). RESULTS: Fifty-six healthcare professionals were fit tested; 32 (57%) 'passed' the taste test. TF between the taste test 'pass' and 'fail' groups was significantly different (p<0.001). A cut-off (TF = 5.0 × 106 units) was determined at precision (78%) and recall (84%), resulting in 5/56 participants (9%) reclassified from 'pass' to 'fail' by the fluorescein test. Seven out of 56 (12%) reclassified from 'fail' to 'pass'. CONCLUSION: Fluorescein is detectable and sensitive at identifying FFP mask leaks. These low-cost adaptations can enhance exiting fit testing to determine 'pass' and 'fail' groups, protecting those who 'passed' the taste test but have high fluorescein leak, and reassuring those who 'failed' the taste test despite having little fluorescein leak.

Cost-effectiveness analysis of percutaneous coronary intervention for single-vessel coronary artery disease: an economic evaluation of the ORBITA trial.

OBJECTIVE: To evaluate the cost-effectiveness of percutaneous coronary intervention (PCI) compared with placebo in patients with single-vessel coronary artery disease and angina despite anti-anginal therapy. DESIGN: A cost-effectiveness analysis comparing PCI with placebo. A Markov model was used to measure incremental cost-effectiveness, in cost per quality-adjusted life-years (QALYs) gained, over 12 months. Health utility weights were estimated using responses to the EuroQol 5-level questionnaire, from the Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial and UK preference weights. Costs of procedures and follow-up consultations were derived from Healthcare Resource Group reference costs and drug costs from the National Health Service (NHS) drug tariff. Probabilistic sensitivity analysis was undertaken to test the robustness of results to parameter uncertainty. Scenario analyses were performed to test the effect on results of reduced pharmaceutical costs in patients undergoing PCI, and the effect of patients crossing over from placebo to PCI due to refractory angina within 12 months. SETTING: Five UK NHS hospitals. PARTICIPANTS: 200 adult patients with stable angina and angiographically severe single-vessel coronary artery disease on anti-anginal therapy. INTERVENTIONS: At recruitment, patients received 6 weeks of optimisation of medical therapy for angina after which they were randomised to PCI or a placebo procedure. OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) expressed as cost (in £) per QALY gained for PCI compared with placebo. RESULTS: The estimated ICER is £90 218/QALY gained when using PCI compared with placebo in patients receiving medical treatment for angina due to single-vessel coronary artery disease. Results were robust under sensitivity analyses. CONCLUSIONS: The ICER for PCI compared with placebo, in patients with single-vessel coronary artery disease and angina on anti-anginal medication, exceeds the threshold of £30 000 used by the National Institute of Health and Care Excellence when undertaking health technology assessment for the NHS context.Trial registration: The ORBITA study is registered with ClinicalTrials.gov, number NCT02062593.

How achievable are COVID-19 clinical trial recruitment targets? A UK observational cohort study and trials registry analysis.

OBJECTIVES: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. DESIGN: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. SETTING: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. PARTICIPANTS: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. MAIN OUTCOME MEASURES: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. RESULTS: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. CONCLUSIONS: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.

Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial.

AIMS: Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. METHODS AND RESULTS: We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients' symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46-2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67-4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). CONCLUSION: Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. CLINICAL TRIAL REGISTRATION: ISRCTN18250790 and ClinicalTrials.gov: NCT02755688.

Beta-blocker efficacy across different cardiovascular indications: an umbrella review and meta-analytic assessment.

BACKGROUND: Beta-blockers are widely used for many cardiovascular conditions; however, their efficacy in contemporary clinical practice remains uncertain. METHODS: We performed a prospectively designed, umbrella review of meta-analyses of randomised controlled trials (RCTs) investigating the evidence of beta-blockers in the contemporary management of coronary artery disease (CAD), heart failure (HF), patients undergoing surgery or hypertension (registration: PROSPERO CRD42016038375). We searched MEDLINE, EMBASE and the Cochrane Library from inception until December 2018. Outcomes were analysed as beta-blockers versus control for all-cause mortality, myocardial infarction (MI), incident HF or stroke. Two independent investigators abstracted the data, assessed the quality of the evidence and rated the certainty of evidence. RESULTS: We identified 98 meta-analyses, including 284 unique RCTs and 1,617,523 patient-years of follow-up. In CAD, 12 meta-analyses (93 RCTs, 103,481 patients) showed that beta-blockers reduced mortality in analyses before routine reperfusion, but there was a lack of benefit in contemporary studies where ≥ 50% of patients received thrombolytics or intervention. Beta-blockers reduced incident MI at the expense of increased HF. In HF with reduced ejection fraction, 34 meta-analyses (66 RCTs, 35,383 patients) demonstrated a reduction in mortality and HF hospitalisation with beta-blockers in sinus rhythm, but not in atrial fibrillation. In patients undergoing surgery, 23 meta-analyses (89 RCTs, 19,211 patients) showed no effect of beta-blockers on mortality for cardiac surgery, but increased mortality in non-cardiac surgery. In non-cardiac surgery, beta-blockers reduced MI after surgery but increased the risk of stroke. In hypertension, 27 meta-analyses (36 RCTs, 260,549 patients) identified no benefit versus placebo, but beta-blockers were inferior to other agents for preventing mortality and stroke. CONCLUSIONS: Beta-blockers substantially reduce mortality in HF patients in sinus rhythm, but for other conditions, clinicians need to weigh up both benefit and potential risk.

Difference in functional assessment of individual stenosis severity in serial coronary lesions between resting and hyperemic pressure-wire pullback: Insights from the GIFT registry.

BACKGROUND: Identifying the individual hemodynamic significance of tandem coronary artery lesions can be complicated by the crosstalk phenomenon which occurs between serial stenoses under hyperemic conditions. Physiological assessments performed under resting conditions are considered to be, theoretically, less affected by the hemodynamic interaction between serial coronary stenoses. The purpose of this study was to assess whether pressure-wire (PW) pullback measurements at rest and during hyperemia provided different information as to which stenosis appeared to be most functionally significant. METHODS: In consecutive patients with angiographically discrete serial lesions, physiological lesion predominance (i.e. proximal or distal) was defined according to the pressure gradient along the vessels on PW-pullback trace. We used instantaneous wave-free ratio (iFR) based assessment as the reference standard and compared fractional flow reserve (FFR) based and hyperemic-iFR based lesion predominance. RESULTS: Eighty-eight vessels (70 patients, mean age 70.3 ± 9.4 years, 80% male) were included in this study. Median iFR, FFR and hyperemic-iFR were 0.85 (interquartile range [IQR]: 0.74 to 0.91), 0.73 (IQR: 0.65 to 0.80) and 0.60 (IQR: 0.49 to 0.71), respectively. When judged against iFR-pullback based physiological assessment, lesion predominance changed in 22.7% (20/88) in FFR and in 20.5% (18/88) in hyperemic-iFR, respectively. There was no statistical difference between FFR and hyperemic-iFR for the impact on these changes (p = 0.77). CONCLUSIONS: In serial coronary lesions, hyperemic PW-pullback disagreed with resting PW-pullback on the lesion-specific identification of ischemia in approximately 20% of cases, either in whole cardiac cycle or in wave-free period.

Mortality From Ischemic Heart Disease.

Background Ischemic heart disease (IHD) has been considered the top cause of mortality globally. However, countries differ in their rates and there have been changes over time. Methods and Results We analyzed mortality data submitted to the World Health Organization from 2005 to 2015 by individual countries. We explored patterns in relationships with age, sex, and income and calculated age-standardized mortality rates for each country in addition to crude death rates. In 5 illustrative countries which provided detailed data, we analyzed trends of mortality from IHD and 3 noncommunicable diseases (lung cancer, stroke, and chronic lower respiratory tract diseases) and examined the simultaneous trends in important cardiovascular risk factors. Russia, United States, and Ukraine had the largest absolute numbers of deaths among the countries that provided data. Among 5 illustrative countries (United Kingdom, United States, Brazil, Kazakhstan, and Ukraine), IHD was the top cause of death, but mortality from IHD has progressively decreased from 2005 to 2015. Age-standardized IHD mortality rates per 100 000 people per year were much higher in Ukraine (324) and Kazakhstan (97) than in United States (60), Brazil (54), and the United Kingdom (46), with much less difference in other causes of death. All 5 countries showed a progressive decline in IHD mortality, with a decline in smoking and hypertension and in all cases a rise in obesity and type II diabetes mellitus. Conclusions IHD remains the single largest cause of death in countries of all income groups. Rates are different between countries and are falling in most countries, indicating great potential for further gains. On the horizon, future improvements may become curtailed by increasing hypertension in some developing countries and more importantly global growth in obesity.

Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial.

BACKGROUND: Atrial fibrillation is the commonest arrhythmia which raises the risk of heart failure, thromboembolic stroke, morbidity and death. Pharmacological treatments of this condition are focused on heart rate control, rhythm control and reduction in risk of stroke. Selective ablation of cardiac tissues resulting in isolation of areas causing atrial fibrillation is another treatment strategy which can be delivered by two minimally invasive interventions: percutaneous catheter ablation and thoracoscopic surgical ablation. The main purpose of this trial is to compare the effectiveness and safety of these two interventions. METHODS/DESIGN: Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF) is a prospective, multi-centre, randomised controlled trial within three NHS tertiary cardiovascular centres specialising in treatment of atrial fibrillation. Eligible adults (n = 120) with symptomatic, long-standing, persistent atrial fibrillation will be randomly allocated to either catheter ablation or thoracoscopic ablation in a 1:1 ratio. Pre-determined lesion sets will be delivered in each treatment arm with confirmation of appropriate conduction block. All patients will have an implantable loop recorder (ILR) inserted subcutaneously immediately following ablation to enable continuous heart rhythm monitoring for at least 12 months. The devices will be programmed to detect episodes of atrial fibrillation and atrial tachycardia ≥ 30 s in duration. The patients will be followed for 12 months, completing appropriate clinical assessments and questionnaires every 3 months. The ILR data will be wirelessly transmitted daily and evaluated every month for the duration of the follow-up. The primary endpoint in the study is freedom from atrial fibrillation and atrial tachycardia at the end of the follow-up period. DISCUSSION: The CASA-AF Trial is a National Institute for Health Research-funded study that will provide first-class evidence on the comparative efficacy, safety and cost-effectiveness of thoracoscopic surgical ablation and conventional percutaneous catheter ablation for long-standing persistent atrial fibrillation. In addition, the results of the trial will provide information on the effects on patients' quality of life. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN18250790 . Registered on 24 April 2015.

Doppler assessment of aortic stenosis: a 25-operator study demonstrating why reading the peak velocity is superior to velocity time integral.

Aims: Measurements with superior reproducibility are useful clinically and research purposes. Previous reproducibility studies of Doppler assessment of aortic stenosis (AS) have compared only a pair of observers and have not explored the mechanism by which disagreement between operators occurs. Using custom-designed software which stored operators' traces, we investigated the reproducibility of peak and velocity time integral (VTI) measurements across a much larger group of operators and explored the mechanisms by which disagreement arose. Methods and results: Twenty-five observers reviewed continuous wave (CW) aortic valve (AV) and pulsed wave (PW) left ventricular outflow tract (LVOT) Doppler traces from 20 sequential cases of AS in random order. Each operator unknowingly measured each peak velocity and VTI twice. VTI tracings were stored for comparison. Measuring the peak is much more reproducible than VTI for both PW (coefficient of variation 10.1 vs. 18.0%; P < 0.001) and CW traces (coefficient of variation 4.0 vs. 10.2%; P < 0.001). VTI is inferior because the steep early and late parts of the envelope are difficult to trace reproducibly. Dimensionless index improves reproducibility because operators tended to consistently over-read or under-read on LVOT and AV traces from the same patient (coefficient of variation 9.3 vs. 17.1%; P < 0.001). Conclusion: It is far more reproducible to measure the peak of a Doppler trace than the VTI, a strategy that reduces measurement variance by approximately six-fold. Peak measurements are superior to VTI because tracing the steep slopes in the early and late part of the VTI envelope is difficult to achieve reproducibly.

The annual global economic burden of heart failure.

BACKGROUND: Heart failure (HF) imposes both direct costs to healthcare systems and indirect costs to society through morbidity, unpaid care costs, premature mortality and lost productivity. The global economic burden of HF is not known. METHODS: We estimated the overall cost of heart failure in 2012, in both direct and indirect terms, across the globe. Existing country-specific heart failure costs analyses were expressed as a proportion of gross domestic product and total healthcare spend. Using World Bank data, these proportional values were used to interpolate the economic cost of HF for countries of the world where no published data exists. Countries were categorized according to their level of economic development to investigate global patterns of spending. RESULTS: 197 countries were included in the analysis, covering 98.7% of the world's population. The overall economic cost of HF in 2012 was estimated at $108 billion per annum. Direct costs accounted for ~60% ($65 billion) and indirect costs accounted for ~40% ($43 billion) of the overall spend. Heart failure spending varied widely between high-income and middle and low-income countries. High-income countries spend a greater proportion on direct costs: a pattern reversed for middle and low-income countries. CONCLUSIONS: Heart failure imposes a huge economic burden, estimated at $108 billion per annum. With an aging, rapidly expanding and industrializing global population this value will continue to rise.

Hemodynamic response to intravenous adenosine and its effect on fractional flow reserve assessment: results of the Adenosine for the Functional Evaluation of Coronary Stenosis Severity (AFFECTS) study.

BACKGROUND: We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. METHODS AND RESULTS: A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both ΔPa and ΔPd were decreased (ΔPa, -10.2±10.5 mm Hg; ΔPd, -18.2±10.8 mm Hg; P<0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, -12.9±15.7 mm Hg; P<0.001; r=0.9; P<0.001). ΔPa and ΔPd were closely related under conditions of peak (r=0.75; P<0.001) and stable hyperemia (r=0.83; P<0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ≤0.80 and 5.2% with FFR threshold <0.75 when comparing Pd/Pa at peak and stable hyperemia. CONCLUSIONS: Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher.

Limitations of augmentation index in the assessment of wave reflection in normotensive healthy individuals.

OBJECTIVES: Augmentation index (AIx) is widely used as a measure of wave reflection. We compared the relationship between AIx and age, height and sex with 'gold standard' measures of wave reflection derived from measurements of pressure and flow to establish how well AIx measures wave reflection. MATERIALS AND METHODS: Measurements of carotid pressure and flow velocity were made in the carotid artery of 65 healthy normotensive individuals (age 21-78 yr; 43 male) and pulse wave analysis, wave intensity analysis and wave separation was performed; waveforms were classified into type A, B or C. AIx, the time of the first shoulder (T(s)), wave reflection index (WRI) and the ratio of backward to forward pressure (P(b)/P(f)) were calculated. RESULTS: AIx did not correlate with log WRI or P(b)/P(f). When AIx was restricted to positive values AIx and log WRI were positively correlated (r = 0.33; p = 0.04). In contrast log WRI and P(b)/P(f) were closely correlated (r = 0.66; p<0.001). There was no correlation between the T(s) and the timing of Pb or the reflected wave identified by wave intensity analysis. Wave intensity analysis showed that the morphology of type C waveforms (negative AIx) was principally due to a forward travelling (re-reflected) decompression wave in mid-systole. AIx correlated positively with age, inversely with height and was higher in women. In contrast log WRI and P(b)/P(f) showed negative associations with age, were unrelated to height and did not differ significantly by gender. CONCLUSIONS: AIx has serious limitations as a measure of wave reflection. Negative AIx values derived from Type C waves should not be used as estimates of wave reflection magnitude.