Pulsed field ablation with the pentaspline catheter compared with cryoablation for the treatment of paroxysmal atrial fibrillation in the UK NHS: a cost-comparison analysis.

OBJECTIVES: Pulsed field ablation (PFA) is a promising new ablation modality for the treatment of atrial fibrillation (AF) that has recently become available in the UK National Health Service (NHS). We provide the first known economic evaluation of the technology. METHODS: A cost-comparison model was developed to compare the expected 12-month costs of treating AF using the pentaspline PFA catheter compared with cryoablation for a single hypothetical patient. Model parameters were based on a recent cost-effectiveness analysis by the National Institute for Health and Care Excellence where possible or published literature otherwise. Deterministic sensitivity, scenario and threshold analyses were conducted. RESULTS: Costs for a single patient treated with PFA were -3% (-£343) less over 12 months than those who received treatment with cryoablation. PFA was associated with 16% higher catheter costs but repeat ablation costs were over 50% less, driven by a reduction in repeat ablations required. Costs of managing complications were -£211 less in total for PFA compared with cryoablation. CONCLUSIONS: Routine adoption of PFA with the pentaspline PFA catheter looks to be as affordable for the NHS as current treatment alternative cryoablation.

An illusion of predictability in scientific results: Even experts confuse inferential uncertainty and outcome variability.

Traditionally, scientists have placed more emphasis on communicating inferential uncertainty (i.e., the precision of statistical estimates) compared to outcome variability (i.e., the predictability of individual outcomes). Here, we show that this can lead to sizable misperceptions about the implications of scientific results. Specifically, we present three preregistered, randomized experiments where participants saw the same scientific findings visualized as showing only inferential uncertainty, only outcome variability, or both and answered questions about the size and importance of findings they were shown. Our results, composed of responses from medical professionals, professional data scientists, and tenure-track faculty, show that the prevalent form of visualizing only inferential uncertainty can lead to significant overestimates of treatment effects, even among highly trained experts. In contrast, we find that depicting both inferential uncertainty and outcome variability leads to more accurate perceptions of results while appearing to leave other subjective impressions of the results unchanged, on average.

Experiment aversion among clinicians and the public - an obstacle to evidence-based medicine and public health.

Background: Randomized controlled trials (RCTs) are essential for determining the safety and efficacy of healthcare interventions. However, both laypeople and clinicians often demonstrate experiment aversion: preferring to implement either of two interventions for everyone rather than comparing them to determine which is best. We studied whether clinician and layperson views of pragmatic RCTs for Covid-19 or other interventions became more positive early in the pandemic, which increased both the urgency and public discussion of RCTs. Methods: We conducted several survey studies with laypeople (total n=2,909) and two with clinicians (n=895; n=1,254) in 2020 and 2021. Participants read vignettes in which a hypothetical decision-maker who sought to improve health could choose to implement intervention A for all, implement intervention B for all, or experimentally compare A and B and implement the superior intervention. Participants rated and ranked the appropriateness of each decision. Results: Compared to our pre-pandemic results, we found no decrease in laypeople's aversion to non-Covid-19 experiments involving catheterization checklists and hypertension drugs. Nor were either laypeople or clinicians less averse to Covid-19 RCTs (concerning corticosteroid drugs, vaccines, intubation checklists, proning, school reopening, and mask protocols), on average. Across all vignettes and samples, levels of experiment aversion ranged from 28% to 57%, while levels of experiment appreciation (in which the RCT is rated higher than the participant's highest-rated intervention) ranged from only 6% to 35%. Conclusions: Advancing evidence-based medicine through pragmatic RCTs will require anticipating and addressing experiment aversion among both patients and healthcare professionals.

The Social Shapes Test as a Self-Administered, Online Measure of Social Intelligence: Two Studies with Typically Developing Adults and Adults with Autism Spectrum Disorder.

The Social Shapes Test (SST) is a measure of social intelligence which does not use human faces or rely on extensive verbal ability. The SST has shown promising validity among adults without autism spectrum disorder (ASD), but it is uncertain whether it is suitable for adults with ASD. We find measurement invariance between adults with (n = 229) or without ASD (n = 1,049) on the 23-item SST. We also find that adults without ASD score higher on the SST than adults with ASD (d = 0.21). We also provide two, 14-item versions which demonstrated good parallel test-retest reliability and are positively related to scores on the Frith-Happé task. The SST is suitable for remote, online research studies.

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

OBJECTIVES: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription.

Objecting to experiments even while approving of the policies or treatments they compare.

We resolve a controversy over two competing hypotheses about why people object to randomized experiments: 1) People unsurprisingly object to experiments only when they object to a policy or treatment the experiment contains, or 2) people can paradoxically object to experiments even when they approve of implementing either condition for everyone. Using multiple measures of preference and test criteria in five preregistered within-subjects studies with 1,955 participants, we find that people often disapprove of experiments involving randomization despite approving of the policies or treatments to be tested.

Safety, Feasibility and Economic Impact of Same-Day Discharge Following Atrial Fibrillation Ablation.

BACKGROUND: The widely accepted model for atrial fibrillation (AF) ablation involves overnight hospital stay post-procedure. Day case AF ablation has been carried out at Royal Papworth Hospital (RPH) since early 2017. We evaluated the feasibility, safety and efficacy of day case AF ablation at RPH. METHOD: This was a retrospective, single-centre study of consecutive AF ablations at RPH between March 2017 and April 2018. Demographic, procedural and outcome data were analysed. RESULTS: Over the study period, 452 AF ablations were performed in 448 patients. One hundred and twenty-nine (129) (28.5%) were planned day cases; of these 128 were discharged on the same day. Two hundred and eighty-three (283) procedures resulted in at least one night admission. There was no significant difference in age or sex between the groups. Of note, day case procedures were significantly shorter, more likely to commence in the morning and less likely to require general anaesthetic than overnight stays. Patients listed as day cases also had less far to travel. The overall complication rate was 3.3%, with no significant difference between groups. Follow-up data was available for 448 cases (99.1%). Procedural success rates were comparable between groups. The overall cost saving attributable to providing AF ablation as a day case was £67,200 over the 13-month period. CONCLUSIONS: Day case AF ablation is efficacious and associated with a low event rate, even without strict standardisation of patient selection or procedural protocols, in a high-volume centre. Substantial reduction in health care expenditure can be achieved with more widespread implementation of outpatient AF ablation.

Ultra-High-Density Activation Mapping to Aid Isthmus Identification of Atrial Tachycardias in Congenital Heart Disease.

OBJECTIVES: A new electroanatomic mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) using a 64-electrode mapping basket is now available; we systematically assessed its use in complex congenital heart disease (CHD). BACKGROUND: The incidence of atrial arrhythmias post-surgery for CHD is high. Catheter ablation has emerged as an effective treatment, but is hampered by limitations in the mapping system's ability to accurately define the tachycardia circuit. METHODS: Mapping and ablation data of 61 patients with CHD (35 males, age 45 ± 14 years) from 8 tertiary centers were reviewed. RESULTS: Causes were as follows: Transposition of Great Arteries (atrial switch) (n = 7); univentricular physiology (Fontans) (n = 8); Tetralogy of Fallot (n = 10); atrial septal defect (ASD) repair (n = 15); tricuspid valve (TV) anomalies (n = 10); and other (n = 11). The total number of atrial arrhythmias was 86. Circuits were predominantly around the tricuspid valve (n = 37), atriotomy scar (n = 10), or ASD patch (n = 4). Although the majority of peri-tricuspid circuits were cavo-tricuspid-isthmus dependent (n = 30), they could follow a complex route between the annulus and septal resection, ASD patch, coronary sinus, or atriotomy. Immediate ablation success was achieved in all but 2 cases; with follow-up of 12 ± 8 months, 7 patients had recurrence. CONCLUSIONS: We demonstrate the feasibility of the basket catheter for mapping complex CHD arrhythmias, including with transbaffle and transhepatic access. Although the circuits often involve predictable anatomic landmarks, the precise critical isthmus is often difficult to predict empirically. Ultra-high-density mapping enables elucidation of circuits in this complex anatomy and allows successful treatment at the isthmus with a minimal lesion set.

Population Whole Exome Screening: Primary Care Provider Attitudes About Preparedness, Information Avoidance, and Nudging.

Compared to clinicians previously surveyed, primary care providers employed in a health system known for clinical genomics were more likely to have ordered or referred a patient for genetic testing, but had only modestly more genetics training and reported similarly low levels of comfort answering patient questions about genetic risk. Most supported population genomic screening, reported willingness to get screened themselves, and judged a hypothetical patient's decision to be screened favorably relative to a similar patient's decision to decline screening. Stakeholder perceptions of the ethical appropriateness of nudging at-risk patients to discuss testing with counselors were mixed.

Targeting Nonpulmonary Vein Sources in Persistent Atrial Fibrillation Identified by Noncontact Charge Density Mapping: UNCOVER AF Trial.

Background Identification and elimination of nonpulmonary vein targets may improve clinical outcomes in patients with persistent atrial fibrillation (AF). We report on the use of a novel, noncontact imaging and mapping system that uses ultrasound to reconstruct atrial chamber anatomy and measures timing and density of dipolar, ionic activation (ie, charge density) across the myocardium to guide ablation of atrial arrhythmias. Methods The prospective, nonrandomized UNCOVER AF trial (Utilizing Novel Dipole Density Capabilities to Objectively Visualize the Etiology of Rhythms in Atrial Fibrillation) was conducted at 13 centers across Europe and Canada. Patients with persistent AF (>7 days, <1 year) aged 18 to 80 years, scheduled for de novo catheter ablation, were eligible. Before pulmonary vein isolation, AF was mapped and then iteratively remapped to guide each subsequent ablation of charge density-identified targets. AF recurrence was evaluated at 3, 6, 9, and 12 months using continuous 24-hour ECG monitors. The primary effectiveness outcome was freedom from AF >30 seconds at 12 months for a single procedure with a secondary outcome being acute procedural efficacy. The primary safety outcome was freedom from device/procedure-related major adverse events. Results Between October 2016 and April 2017, 129 patients were enrolled, and 127 underwent mapping and catheter ablation. Acute procedural efficacy was demonstrated in 125 patients (98%). At 12 months, single procedure freedom from AF on or off antiarrhythmic drugs was 72.5% (95% CI, 63.9%-80.3%). After 1 or 2 procedures, freedom from AF was 93.2% (95% CI, 87.1%-97.0%). A total of 29 (23%) retreatments because of arrhythmia recurrence were performed with average time from index procedure to first retreatment being 7 months. The primary safety outcome was 98% with no device-related major adverse events reported. Conclusions This novel ultrasound imaging and charge density mapping system safely guided ablation of nonpulmonary vein targets in persistent AF patients with 73% single procedure and 93% second procedure freedom from AF at 12 months. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT02825992 EU/NCT02462980 CN.

Objecting to experiments that compare two unobjectionable policies or treatments.

Randomized experiments have enormous potential to improve human welfare in many domains, including healthcare, education, finance, and public policy. However, such "A/B tests" are often criticized on ethical grounds even as similar, untested interventions are implemented without objection. We find robust evidence across 16 studies of 5,873 participants from three diverse populations spanning nine domains-from healthcare to autonomous vehicle design to poverty reduction-that people frequently rate A/B tests designed to establish the comparative effectiveness of two policies or treatments as inappropriate even when universally implementing either A or B, untested, is seen as appropriate. This "A/B effect" is as strong among those with higher educational attainment and science literacy and among relevant professionals. It persists even when there is no reason to prefer A to B and even when recipients are treated unequally and randomly in all conditions (A, B, and A/B). Several remaining explanations for the effect-a belief that consent is required to impose a policy on half of a population but not on the entire population; an aversion to controlled but not to uncontrolled experiments; and a proxy form of the illusion of knowledge (according to which randomized evaluations are unnecessary because experts already do or should know "what works")-appear to contribute to the effect, but none dominates or fully accounts for it. We conclude that rigorously evaluating policies or treatments via pragmatic randomized trials may provoke greater objection than simply implementing those same policies or treatments untested.

Atrial Tachycardia Arising From the Crista Terminalis, Detailed Electrophysiological Features and Long-Term Ablation Outcomes.

OBJECTIVES: The goal of this study was to characterize, in detail, focal atrial tachycardia (AT) arising from the crista terminalis to investigate associations with other atrial arrhythmia and to define long-term ablation outcomes. BACKGROUND: The crista terminalis is known to be the most common site of origin for focal AT, but it is not well characterized. METHODS: This study retrospectively identified a total of 548 ablation procedures for AT performed at a single center over a 16-year period, of which 171 were arising from the crista terminalis. RESULTS: Compared with patients with other AT sites of origin, crista terminalis AT patients were older (57.3 vs. 47.3 years), more commonly female (72.9% vs. 59.1%), were more commonly associated with coexistent atrioventricular nodal re-entry tachycardia (17.1% vs. 9.7%), and were more likely to be inducible with programmed stimulation (81.5% vs. 58.9%). There was preferential conduction in the superior-inferior axis along the crista terminalis. Acute ablation success rate was high (92.2%) and improved significantly when three-dimensional mapping was used (98.5%). Recurrence in the first 12 months after a successful ablation was 9.7%. Only 2 patients developed atrial fibrillation over the long-term follow-up of >7 years. CONCLUSIONS: This large series characterized the clinical and electrophysiological features and immediate and long-term ablation outcomes for AT originating from the crista terminalis. Features of the tachycardia suggest that age-related localized remodeling of the crista terminalis causes a superficial endocardial zone of conduction slowing leading to re-entry. Ablation outcomes were good, with long-term freedom from atrial arrhythmia.

High-resolution noncontact charge-density mapping of endocardial activation.

BACKGROUND: Spatial resolution in cardiac activation maps based on voltage measurement is limited by far-field interference. Precise characterization of electrical sources would resolve this limitation; however, practical charge-based cardiac mapping has not been achieved. METHODS: A prototype algorithm, developed from first principles of electrostatic field theory, derives charge density (CD) as a spatial representation of the true sources of the cardiac field. The algorithm processes multiple, simultaneous, noncontact voltage measurements within the cardiac chamber to inversely derive the global distribution of CD sources across the endocardial surface. RESULTS: Comparison of CD to an established computer-simulated model of atrial conduction demonstrated feasibility in terms of spatial, temporal, and morphologic metrics. Inverse reconstruction matched simulation with median spatial errors of 1.73 mm and 2.41 mm for CD and voltage, respectively. Median temporal error was less than 0.96 ms and morphologic correlation was greater than 0.90 for both CD and voltage. Activation patterns observed in human atrial flutter reproduced those established through contact maps, with a 4-fold improvement in resolution noted for CD over voltage. Global activation maps (charge density-based) are reported in atrial fibrillation with confirmed reduction of far-field interference. Arrhythmia cycle-length slowing and termination achieved through ablation of critical points demonstrated in the maps indicates both mechanistic and pathophysiological relevance. CONCLUSION: Global maps of cardiac activation based on CD enable classification of conduction patterns and localized nonpulmonary vein therapeutic targets in atrial fibrillation. The measurement capabilities of the approach have roles spanning deep phenotyping to therapeutic application. TRIAL REGISTRATION: ClinicalTrials.gov NCT01875614. FUNDING: The National Institute for Health Research (NIHR) Translational Research Program at Royal Papworth Hospital and Acutus Medical.

Ablation of Complex Fractionated Electrograms Improves Outcome in Persistent Atrial Fibrillation of Over 2 Year's Duration.

AIM: There is controversy and sparse data on whether substrate based techniques in addition to pulmonary vein isolation (PVI) confer benefit in the catheter ablation of persistent atrial fibrillation (AF), especially if long standing. We performed an observational study to assess whether substrate based ablation improved freedom from atrial arrhythmia. METHODS: A total of 286 patients undergoing first ablation procedures for persistent AF with PVI only(n = 79), PVI plus linear ablation(n = 85), or PVI plus complex fractionated electrogram (CFAE) and linear ablation(n = 107) were followed. Primary end point was freedom from atrial arrhythmia at one year. RESULTS: Mean duration of pre-procedure time in AF was 28+/-27 months.There were no differences in baseline characteristics between groups except a higher proportion of patients with a severely dilated LA in those receiving PVI+CFAEs+lines. Freedom from atrial arrhythmia was higher with a PVI+CFAE+lines strategy then for PVI alone (HR 1.56, 95% CI: 1.04-2.34, p=0.032) but was not higher with PVI+lines. Benefit of substrate modification was conferred for preprocedure times in AF of over 30 months. The occurrence of atrial tachycardia was higher when lines were added to the ablation strategy (HR 0.08, 95% CI: 0.01-0.59, p=0.014). Freedom from atrial arrhythmia at 1 year was higher with lower patient age, use of general anaesthetic (GA), normal or mildly dilated left atrium and decreasing time in AF. CONCLUSIONS: In patients with long standing persistent AF of over 30 months duration,CFAE ablation resulted in improved freedom from atrial arrhythmia. Increased freedom from atrial arrhythmia occurs in patients who are younger and have smaller atria, and with GA procedures. Linear ablation did not improve outcome and resulted in a higher incidence of atrial tachycardia.

Premature Ventricular Complex-induced Cardiomyopathy.

Premature ventricular complex-induced cardiomyopathy is a potentially reversible condition in which left ventricular dysfunction is induced by the occurrence of frequent premature ventricular complexes (PVCs). Various cellular and extracellular mechanisms and risk factors for developing cardiomyopathy in this context have been suggested but the exact pathophysiological mechanism remains unclear. The suppression of PVCs is usually indicated in symptomatic patients with frequent PVCs and also those with left ventricular dysfunction. Antiarrhythmic drugs are a useful non-invasive treatment to eliminate PVCs, but the side effect profile, including the risk of pro-arrhythmia, along with suboptimal clinical effectiveness, should be weighed against the usually more effective but not risk-free treatment with catheter ablation. The latter has progressively become first line therapy in many patients with PVC-induced cardiomyopathy and should be particularly considered in specific scenarios.

65% of Americans believe they are above average in intelligence: Results of two nationally representative surveys.

Psychologists often note that most people think they are above average in intelligence. We sought robust, contemporary evidence for this "smarter than average" effect by asking Americans in two independent samples (total N = 2,821) whether they agreed with the statement, "I am more intelligent than the average person." After weighting each sample to match the demographics of U.S. census data, we found that 65% of Americans believe they are smarter than average, with men more likely to agree than women. However, overconfident beliefs about one's intelligence are not always unrealistic: more educated people were more likely to think their intelligence is above average. We suggest that a tendency to overrate one's cognitive abilities may be a stable feature of human psychology.

Association of catheter ablation for atrial fibrillation with mortality and stroke: A systematic review and meta-analysis.

BACKGROUND: Maintenance of sinus rhythm has been associated with lower mortality, but whether atrial fibrillation (AF) ablation per se benefits hard outcomes such as mortality and stroke is still debated. OBJECTIVE: To determine whether AF ablation is associated with a reduction in all-cause mortality and stroke compared with medical therapy alone. METHODS: Literature search looking for both randomized and observational studies comparing AF catheter ablation vs. medical management. Data pooled using random-effects. Risk ratios (RR) with 95% confidence intervals (CI) used as a measure of treatment effect. The primary and secondary outcomes were all-cause mortality and occurrence of cerebrovascular events during follow-up, respectively. RESULTS: Thirty studies were eligible for inclusion, comprising 78,966 patients (25,129 receiving AF ablation and 53,837 on medical treatment) and 233,990patient-years of follow-up. The pooled data of studies revealed that ablation was associated with lower risk of all-cause mortality: 5.7% vs. 17.9%; RR=0.44, 95% CI 0.32-0.62, p<0.001. In a sensitivity analysis by study design, a survival benefit of AF ablation was seen in randomized studies, with no heterogeneity (mortality risk 4.2% vs. 8.9%; RR=0.55, 95% CI 0.39-0.79, p=0.001, I2=0%), and also in observational studies, but with marked heterogeneity (6.1% vs. 18.3%; RR=0.39, 95% CI 0.26-0.59, p<0.001, I2=95%). The mortality benefit in randomized studies was mainly driven by trials performed in patients with left ventricular (LV) dysfunction and heart failure. The pooled risk of a cerebrovascular event was lower in patients receiving AF ablation (2.3% vs. 5.5%; RR=0.57, 95% CI 0.46-0.70, p<0.001, I2=62%), but no difference was seen in randomized trials (2.2% vs. 2.1%; RR=0.94, 95% CI 0.46-1.94, p=0.87, I2=0%). CONCLUSIONS: Ablation of atrial fibrillation associates with a survival benefit compared with medical treatment alone, although evidence is restricted to the setting of heart failure and LV systolic dysfunction.

Device complications with addition of defibrillation to cardiac resynchronisation therapy for primary prevention.

OBJECTIVE: In patients indicated for cardiac resynchronisation therapy (CRT), the choice between a CRT-pacemaker (CRT-P) versus defibrillator (CRT-D) remains controversial and indications in this setting have not been well delineated. Apart from inappropriate therapies, which are inherent to the presence of a defibrillator, whether adding defibrillator to CRT in the primary prevention setting impacts risk of other acute and late device-related complications has not been well studied and may bear relevance for device selection. METHODS: Observational multicentre European cohort study of 3008 consecutive patients with ischaemic or non-ischaemic dilated cardiomyopathy and no history of sustained ventricular arrhythmias, undergoing CRT implantation with (CRT-D, n=1785) or without (CRT-P, n=1223) defibrillator. Using propensity score and competing risk analyses, we assessed the risk of significant device-related complications requiring surgical reintervention. Inappropriate shocks were not considered except those due to lead malfunction requiring lead revision. RESULTS: Acute complications occurred in 148 patients (4.9%), without significant difference between groups, even after considering potential confounders (OR=1.20, 95% CI 0.72 to 2.00, p=0.47). During a mean follow-up of 41.4±29 months, late complications occurred in 475 patients, giving an annual incidence rate of 26 (95% CI 9 to 43) and 15 (95% CI 6 to 24) per 1000 patient-years in CRT-D and CRT-P patients, respectively. CRT-D was independently associated with increased occurrence of late complications (HR=1.68, 95% CI 1.27 to 2.23, p=0.001). In particular, when compared with CRT-P, CRT-D was associated with an increased risk of device-related infection (HR 2.10, 95% CI 1.18 to 3.45, p=0.004). Acute complications did not predict overall late complications, but predicted device-related infection (HR 2.85, 95% CI 1.71 to 4.56, p<0.001). CONCLUSIONS: Compared with CRT-P, CRT-D is associated with a similar risk of periprocedural complications but increased risk of long-term complications, mainly infection. This needs to be considered in the decision of implanting CRT with or without a defibrillator.