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.

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.

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.

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.

Improved outcome and cost effectiveness in ablation of persistent atrial fibrillation under general anaesthetic.

Aims: Outcome of persistent atrial fibrillation (AF) ablation remains suboptimal. Techniques employed to reduce arrhythmia recurrence rate are more likely to be embraced if cost-effectiveness can be demonstrated. A single-centre observational study assessed whether use of general anaesthesia (GA) in persistent AF ablation improved outcome and was cost-effective. Methods and results: Two hundred and ninety two patients undergoing first ablation procedures for persistent AF under conscious sedation or GA were followed. End points were freedom from listing for repeat ablation at 18 months and freedom from recurrence of atrial arrhythmia at 1 year. Freedom from atrial arrhythmia was higher in patients who underwent ablation under GA rather than sedation (63.9% vs. 42.3%, hazard ratio (HR) 1.87, 95% confidence interval (CI): 1.23-2.86, P = 0.002). Significantly fewer GA patients were listed for repeat procedures (29.2% vs. 42.7%, HR 1.62, 95% CI: 1.01-2.60, P = 0.044). Despite GA procedures costing slightly more, a saving of £177 can be made per patient in our centre for a maximum of two procedures if all persistent AF ablations are performed under GA. Conclusions: In patients with persistent AF, it is both clinical and economically more effective to perform ablation under GA rather than sedation.

Patients upgraded to cardiac resynchronization therapy due to pacing-induced cardiomyopathy are at low risk of life-threatening ventricular arrhythmias: a long-term cause-of-death analysis.

Aims: Upgrade to cardiac resynchronization therapy (CRT) should be offered to patients who have developed pacing-induced cardiomyopathy with conventional right ventricular pacing. The extent to which these patients would also benefit from defibrillator back-up at the time of CRT upgrade is, however, unknown. Methods and results: Retrospective observational cohort study of 199 patients with pacing-induced cardiomyopathy and no history of sustained ventricular arrhythmia, including 104 upgraded to CRT-Pacemaker (CRT-P) and 95 upgraded to CRT-Defibrillator (CRT-D). The incidence of ventricular arrhythmias and the risk of sudden arrhythmic death obtained through a cause-of-death analysis based on clinical data and necropsy results were assessed and compared between the two groups. During a mean follow-up of 66 ± 24 months, 40 (38.5%) CRT-P patients died: three from primary arrhythmic death, while the remaining died of different causes (especially progressive heart failure), giving an incidence of 6.2 sudden arrhythmic deaths per 1000 patient-years. No episode of sustained VT was observed in the study group. There were no sudden arrhythmic deaths in the CRT-D group during a shorter follow-up, but the small and non-significant difference in all-cause mortality between CRT-Pacemaker (CRT-P) and CRT-D groups was mostly accounted for by an increase in non-sudden death. Women upgraded to CRT were at particularly low risk of all-cause mortality compared with men (HR 0.232, P = 0.048). Conclusion: Our findings suggest that patients who develop pacing-induced cardiomyopathy and are upgraded to CRT may not derive any significant benefit from the addition of the defibrillator in the absence of a history of ventricular arrhythmias.

A minimal or maximal ablation strategy to achieve pulmonary vein isolation for paroxysmal atrial fibrillation: a prospective multi-centre randomized controlled trial (the Minimax study).

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation of atrial fibrillation (AF). The intervenous ridge (IVR) may be incorporated into ablation strategies to achieve PVI; however, randomized trials are lacking. We performed a randomized multi-centre international study to compare the outcomes of (i) circumferential antral PVI (CPVI) alone (minimal) vs. (ii) CPVI with IVR ablation to achieve individual PVI (maximal). METHODS AND RESULTS: Two hundred and thirty-four patients with paroxysmal AF underwent CPVI and were randomized to a minimal or maximal ablation strategy. The primary outcome of recurrent atrial arrhythmia was assessed with 7-day Holter monitoring at 6 and 12 months. PVI was achieved in all patients. Radiofrequency ablation time was longer in the maximal group (46.6 ± 14.6 vs. 41.5 ± 13.1 min; P < 0.01), with no significant differences in procedural or fluoroscopy times. At mean follow-up of 17 ± 8 months, there was no difference in freedom from AF after a single procedure between a minimal (70%) and maximal ablation strategy (62%; P = 0.25). In the minimal group, ablation was required on the IVR to achieve electrical isolation in 44%, and was associated with a significant reduction in freedom from AF (57%) compared with the minimal group without IVR ablation (80%; P < 0.01). CONCLUSION: There was no statistically significant difference in freedom from AF between a minimal and maximal ablation strategy. Despite attempts to achieve PVI with antral ablation, IVR ablation is commonly required. Patients in whom antral isolation can be achieved without IVR ablation have higher long-term freedom from AF (the Minimax study; ACTRN12610000863033).

The transesophageal echo probe may contribute to esophageal injury after catheter ablation for paroxysmal atrial fibrillation under general anesthesia: a preliminary observation.

INTRODUCTION: The transesophageal echo probe (TEE) is commonly used before and during atrial fibrillation (AF) ablation under general anesthesia (GA). We sought to determine the potential contribution of the TEE probe to esophageal injury after pulmonary vein isolation (PVI) alone for paroxysmal AF. METHODS AND RESULTS: Seventy-six patients undergoing PVI with TEE, PVI/TEE, 16 undergoing PVI without TEE (PVI/No TEE), and 27 undergoing TEE without any left atrial ablation (TEE/No LA ablation) under GA were included. Posterior wall ablation was power (20-25 W) and time limited (electrogram attenuation or ≤30 s). Esophageal capsule endoscopy (n = 206) was performed pre- and post-procedure and at 2 weeks. Esophageal lesions were seen in 30% of PVI/TEE, 0% of patients in the PVI/No TEE (P = 0.009), and 22% of TEE/No LA ablation groups (P = 0.47 vs. PVI/TEE). There were no instances of esophageal bleeding, perforation, or need for gastrointestinal intervention. Self-resolving dysphagia was the only reported symptom (5%). All lesions healed within 2 weeks. There was no significant difference in the location or morphological appearance of esophageal lesions seen in the PVI/TEE versus TEE/No LA ablation groups. CONCLUSIONS: Esophageal lesions were seen in 30% of patients undergoing PVI alone under GA with use of TEE and in a similar proportion (22%) of patients undergoing TEE in the absence of left atrial ablation. This study makes the preliminary observation that one must be cognizant of the TEE probe as a potential contributor to esophageal injury after AF ablation. Larger studies are needed to confirm these findings.

Glucagon-like peptide-1 protects against ischemic left ventricular dysfunction during hyperglycemia in patients with coronary artery disease and type 2 diabetes mellitus.

BACKGROUND: Enhancement of myocardial glucose uptake may reduce fatty acid oxidation and improve tolerance to ischemia. Hyperglycemia, in association with hyperinsulinemia, stimulates this metabolic change but may have deleterious effects on left ventricular (LV) function. The incretin hormone, glucagon-like peptide-1 (GLP-1), also has favorable cardiovascular effects, and has emerged as an alternative method of altering myocardial substrate utilization. In patients with coronary artery disease (CAD), we investigated: (1) the effect of a hyperinsulinemic hyperglycemic clamp (HHC) on myocardial performance during dobutamine stress echocardiography (DSE), and (2) whether an infusion of GLP-1(7-36) at the time of HHC protects against ischemic LV dysfunction during DSE in patients with type 2 diabetes mellitus (T2DM). METHODS: In study 1, twelve patients underwent two DSEs with tissue Doppler imaging (TDI)-one during the steady-state phase of a HHC. In study 2, ten patients with T2DM underwent two DSEs with TDI during the steady-state phase of a HHC. GLP-1(7-36) was infused intravenously at 1.2 pmol/kg/min during one of the scans. In both studies, global LV function was assessed by ejection fraction and mitral annular systolic velocity, and regional wall LV function was assessed using peak systolic velocity, strain and strain rate from 12 paired non-apical segments. RESULTS: In study 1, the HHC (compared with control) increased glucose (13.0 ± 1.9 versus 4.8 ± 0.5 mmol/l, p < 0.0001) and insulin (1,212 ± 514 versus 114 ± 47 pmol/l, p = 0.01) concentrations, and reduced FFA levels (249 ± 175 versus 1,001 ± 333 µmol/l, p < 0.0001), but had no net effect on either global or regional LV function. In study 2, GLP-1 enhanced both global (ejection fraction, 77.5 ± 5.0 versus 71.3 ± 4.3%, p = 0.004) and regional (peak systolic strain -18.1 ± 6.6 versus -15.5 ± 5.4%, p < 0.0001) myocardial performance at peak stress and at 30 min recovery. These effects were predominantly driven by a reduction in contractile dysfunction in regions subject to demand ischemia. CONCLUSIONS: In patients with CAD, hyperinsulinemic hyperglycemia has a neutral effect on LV function during DSE. However, GLP-1 at the time of hyperglycemia improves myocardial tolerance to demand ischemia in patients with T2DM. TRIAL REGISTRATION: http://www.isrctn.org . Unique identifier ISRCTN69686930.

Implantable cardioverter-defibrillators in the elderly: rationale and specific age-related considerations.

Despite the increasingly high rate of implantation of cardioverter-defibrillators (ICD) in elderly patients, data supporting their clinical and cost-effectiveness in this age stratum are ambiguous and contradictory. We comprehensively reviewed the state-of-the-art data regarding the applicability, safety, clinical- and cost-effectiveness of the ICD in elderly patients, and analysed which patients in this age stratum are more likely to get a survival benefit from this therapy. Although peri-procedural risk may be slightly higher in the elderly, this procedure is still relatively safe in this age group. In terms of correcting potentially life-threatening arrhythmias, the effectiveness of ICD therapy is comparable in older and younger individuals. However, the assumption of persistent ICD benefit in the elderly population is questionable, as any advantage of the device on arrhythmic death may be largely attenuated by a higher total non-arrhythmic mortality. While septuagenarians and octogenarians have higher annual all-cause mortality rates, ICD therapy may remain effective in highly selected patients at high risk of arrhythmic death and with minimum comorbidities despite advanced age. ICD intervention among the elderly, as a group, may not be cost-effective, but the procedure may reach cost-effectiveness in those expected to live >5-7 years after implantation. Biological age rather than chronological age per se should be the decisive factor in making a decision on ICD selection for survival benefit.

Cardioverter-defibrillator implantation and generator replacement in the octogenarian.

AIMS: Increase in life expectancy has led to increased rate of implantable cardioverter-defibrillator (ICD) implantation in patients in their 80s, but there are no current formal recommendations to guide physicians when elderly patients with ICDs require elective unit replacement (EUR). This study aims at assessing survival and rates of ICD therapies in patients who have had ICD implantation or EUR above the age of 80, focusing on the latter. METHODS AND RESULTS: Retrospective analysis of a prospectively kept database of all ICD-related procedures carried out in a single tertiary centre. Patients 80 years of age or older submitted to ICD implantation (n = 42) or EUR (n = 34) between November 1991 and May 2012 were included. Using collected baseline and outcome data from this cohort, we assessed survival of these patients and the rates of ICD therapies. Median additional years of life after ICD implantation and ICD EUR in patients who died before data retrieval was 2.5 and 1.2, respectively, and while 65% of deceased patients after ICD implantation died in the first 3 years after the procedure, 50% of deceased post-ICD EUR patients died within the first year. Mortality rates at 1 and 2 years post-EUR were 23.1 and 38.1%, respectively. Furthermore, ventricular tachycardia occurred in a small minority of patients after EUR (16.7%) and no ventricular fibrillation-triggered ICD therapies were reported in both groups. CONCLUSION: In octogenarians who are due for an ICD EUR, careful thought should be given to the current clinical status, comorbidities, and general frailty prior to considering them for the procedure. A survival benefit from ICD EUR in this age stratum is not likely.

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.

Atrial fibrillation in heart failure in the older population.

Atrial fibrillation (AF) is an important and often-underrecognized cause of cardiovascular morbidity and mortality. It is an arrhythmia that is commonly seen in the older patient; the median age of patients with AF in early studies was 75 years. Heart failure (HF) is also more frequently seen in the older patient with an approximate doubling of HF prevalence with each decade of life. There is clear interaction between AF and HF, with evidence that HF can lead to AF and AF exacerbates HF. This review focuses on the specific aspect of AF management in elderly patients with HF.

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.

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.

Electroanatomic remodeling of the left atrium in paroxysmal and persistent atrial fibrillation patients without structural heart disease.

INTRODUCTION: The nature of the atrial substrate thought to contribute toward maintaining atrial fibrillation (AF) outside the pulmonary veins remains poorly defined. Therefore, our objective was to determine whether patients with paroxysmal and persistent AF have an abnormal electroanatomic substrate within the left atrium (LA). METHODS AND RESULTS: Thirty-one patients with AF (17 paroxysmal AF and 14 persistent AF) were compared with 15 age-matched controls with left-sided supraventricular tachycardia (SVT). High-density 3-dimensional electroanatomic maps were created and the LA was divided into 8 segments for regional analysis. Bipolar voltage, conduction, and effective refractory periods (ERPs) of the posterior LA, left atrial appendage (LAA), and distal coronary sinus (CSd) and percentage complex signals were assessed. In the majority of LA regions, compared with controls, AF patients had: (1) lower mean voltage and a higher percentage low voltage; (2) slower conduction; and (3) more prevalent complex signals. Many of these changes were more marked in the persistent than the paroxysmal AF group. CONCLUSIONS: Patients with AF have lower regional voltage, increased proportion of low voltage, slowed conduction, and increased proportion of complex signals compared to controls. Many of these changes are more pronounced in persistent AF patients, suggesting there may be a progressive nature to the changes. Differences occurred in the absence of structural heart disease. These substrate abnormalities provide further insight into the progressive nature of atrial remodeling and the mechanisms involved in maintenance of AF.

Electroanatomic remodelling of the pulmonary veins associated with age.

AIMS: Increasing age is a significant risk factor for developing atrial fibrillation (AF). Pulmonary vein (PV) triggers are critical in the mechanism of AF, but little is known of the substrate changes that occur within the PVs with ageing. Therefore, we sought to identify whether ageing is associated with electroanatomic changes within the pulmonary veins. METHODS AND RESULTS: Twenty-five patients undergoing ablation for left-sided supraventricular tachycardia had high-density 3D electroanatomic maps of all four PVs created. Patients were divided into two groups: group 1 aged <50 years and group 2 aged >50 years. Mean-voltage (MV), % low-voltage (LV < 0.5 mV), conduction, signal complexity, and PV muscle sleeve length and diameter were assessed. Age was 33 ± 8 vs. 66 ± 8 years for groups 1 and 2, respectively (P < 0.001). Group 2 demonstrated: (i) lower MV within the PVs (1.66 ± 1.1 vs. 1.88 ± 1.1 mV, P < 0.001); (ii) increased % LV (5.0 vs. 1.1%, P < 0.001), and increased voltage heterogeneity within the PVs (65 ± 14 vs. 55 ± 8%, P < 0.05); (iii) regional and global conduction slowing in the PVs; and (iv) increased % complex signals within the PVs (1.4 vs. 0.4%, P = 0.009). There was no difference in PV sleeve length or diameter. CONCLUSION: Increasing age is associated with PV electroanatomic changes characterized by a significant reduction in PV voltage, conduction slowing, and increasing signal complexity. These observations provide new insights into the potential mechanisms behind the increased prevalence of AF with advancing age.

The challenging face of focal atrial tachycardia in the post AF ablation era.

Radiofrequency ablation (RFA) for atrial fibrillation (AF) has become one of the most common catheter ablation procedures performed worldwide. As experience and success in treating patients with paroxysmal AF have increased, more centers are performing ablation for persistent AF. Optimal results may require ablation beyond the pulmonary veins with extensive biatrial substrate modification required in some cases to restore sinus rhythm. On the road to sinus rhythm atrial tachycardias are generally encountered either acutely within the index procedure or following. This has led to an increase in the frequency of focal atrial tachycardia and a need to review our understanding and approach to this and how it differs following substrate modification in contrast with the de novo setting. This review aims to describe the differences in responsible mechanism and its translation to mapping and ablation of focal AT particularly in the post ablation atria (paAT).