Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors.

Long-term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting-state networks for predicting short and long-term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting-state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default-mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long-term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCAhospital-3M = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA3M-12M = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (ßDMN = 0.85, p = 0.03; ßSN = 1.48, p < 0.01; ßDAN = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long-term memory, attention, or executive functioning. Resting-state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short-term global, but not long-term global or domain-specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long-term cognitive performance after cardiac arrest.

Risk Factors for Inadequate Defibrillation Safety Margins Vary With the Underlying Cardiac Disease: Implications for Selective Testing Strategies.

INTRODUCTION: In view of the shift from routine toward no or selective defibrillation testing, optimization of the current risk stratification for inadequate defibrillation safety margins (DSMs) could improve individualized testing decisions. Given the pathophysiological differences in myocardial substrate between ischemic and nonischemic heart disease (IHD/non-IHD) and the accompanying differences in clinical characteristics, we studied inadequate DSMs and their predictors in relation to the underlying etiology. METHODS AND RESULTS: Cohort of routine defibrillation tests (n = 785) after first implantable cardioverter defibrillator (ICD)-implantations at the Radboud UMC (2005-2014). A defibrillation threshold >25 J was regarded as an inadequate DSM. In total, 4.3% of patients had an inadequate DSM; in IHD 2.5% versus 7.3% in non-IHD (P = 0.002). We identified a group of non-IHD patients at high risk (13-42% inadequate DSM); the remainder of the cohort (>70%) had a risk of only 2% (C-statistic entire cohort 0.74; C-statistic non-IHD 0.82). This was based upon two identified interaction terms: (1) non-IHD and age (aOR 0.94 [95% CI 0.91-0.97]); (2) non-IHD and the indexed left ventricular (LV) internal diastolic diameter (aOR 3.50 [95% CI 2.10-5.82]). CONCLUSION: The present study on risk stratification for an inadequate DSM not only confirms the importance of making a distinction between IHD and non-IHD, but also shows that risk factors in an entire cohort (LV dilatation, age) may only apply to a subgroup (non-IHD). Appreciation of this concept could favorably affect current risk stratification. If confirmed, our approach may be used to optimize individualized testing decisions in an upcoming era of non-routine testing.

Manual Cardiopulmonary Resuscitation Versus CPR Including a Mechanical Chest Compression Device in Out-of-Hospital Cardiac Arrest: A Comprehensive Meta-analysis From Randomized and Observational Studies.

STUDY OBJECTIVE: Mechanical chest compression devices have been developed to facilitate continuous delivery of high-quality cardiopulmonary resuscitation (CPR). Despite promising hemodynamic data, evidence on clinical outcomes remains inconclusive. With the completion of 3 randomized controlled trials, we conduct a meta-analysis on the effect of in-field mechanical versus manual CPR on clinical outcomes after out-of-hospital cardiac arrest. METHODS: With a systematic search (PubMed, Web of Science, EMBASE, and the Cochrane Libraries), we identified all eligible studies (randomized controlled trials and nonrandomized studies) that compared a CPR strategy including an automated mechanical chest compression device with a strategy of manual CPR only. Outcome variables were survival to hospital admission, survival to discharge, and favorable neurologic outcome. RESULTS: Twenty studies (n=21,363) were analyzed: 5 randomized controlled trials and 15 nonrandomized studies, pooled separately. For survival to admission, the pooled estimate of the randomized controlled trials did not indicate a difference (odds ratio 0.94; 95% confidence interval 0.84 to 1.05; P=.24) between mechanical and manual CPR. In contrast, meta-analysis of nonrandomized studies demonstrated a benefit in favor of mechanical CPR (odds ratio 1.42; 95% confidence interval 1.21 to 1.67; P<.001). No interaction was found between the endorsed CPR guidelines (2000 versus 2005) and the CPR strategy (P=.27). Survival to discharge and neurologic outcome did not differ between strategies. CONCLUSION: Although there are lower-quality, observational data that suggest that mechanical CPR used at the rescuer's discretion could improve survival to hospital admission, the cumulative high-quality randomized evidence does not support a routine strategy of mechanical CPR to improve survival or neurologic outcome. These findings are irrespective of the endorsed CPR guidelines during the study periods.

Virtual reality to reduce periprocedural anxiety during invasive coronary angiography: rationale and design of the VR InCard trial.

INTRODUCTION: Patients undergoing invasive coronary angiography (ICA) experience anxiety due to various reasons. Procedural anxiety can lead to physiological and psychological complications, compromising patient comfort and overall procedural outcomes. Benzodiazepines are commonly used to reduce periprocedural anxiety, although the effect is modest. Virtual reality (VR) is a promising non-pharmacological intervention to reduce anxiety in patients undergoing ICA. METHODS AND ANALYSIS: A single-centre open-label randomised controlled trial is conducted assessing the effectiveness of add-on VR therapy on anxiety in 100 patients undergoing ICA and experiencing anxiety in a periprocedural setting. The primary outcome is the Numeric Rating Scale (NRS) anxiety score measured just before obtaining arterial access. Secondary outcomes include postarterial puncture and postprocedural anxiety, patient-reported outcome measures (PROMs) of anxiety and physiological measurements associated with anxiety. The NRS anxiety level and physiological measurements are assessed five times during the procedure. The PROM State-Trait Anxiety Inventory and Perceived Stress Scale are completed preprocedure, and the PROM STAI and the Igroup Presence Questionnaire are performed postprocedure. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the Research Ethics Committee of the Radboud University Medical Centre, the Netherlands (CMO Arnhem-Nijmegen, 2023-16586). Informed consent is obtained from all patients. The trial is conducted according to the principles of the Helsinki Declaration and in accordance with Dutch guidelines, regulations, and acts (Medical Research involving Human Subjects Act, WMO). REGISTRATION DETAILS: Trial registration number: NCT06215456.

Automated cardiac arrest detection using a photoplethysmography wristband: algorithm development and validation in patients with induced circulatory arrest in the DETECT-1 study.

BACKGROUND: Unwitnessed out-of-hospital cardiac arrest is associated with low survival chances because of the delayed activation of the emergency medical system in most cases. Automated cardiac arrest detection and alarming using biosensor technology would offer a potential solution to provide early help. We developed and validated an algorithm for automated circulatory arrest detection using wrist-derived photoplethysmography from patients with induced circulatory arrests. METHODS: In this prospective multicentre study in three university medical centres in the Netherlands, adult patients (aged 18 years or older) in whom short-lasting circulatory arrest was induced as part of routine practice (transcatheter aortic valve implantation, defibrillation testing, or ventricular tachycardia induction) were eligible for inclusion. Exclusion criteria were a known bilateral significant subclavian artery stenosis or medical issues interfering with the wearing of the wristband. After providing informed consent, patients were equipped with a photoplethysmography wristband during the procedure. Invasive arterial blood pressure and electrocardiography were continuously monitored as the reference standard. Development of the photoplethysmography algorithm was based on three consecutive training cohorts. For each cohort, patients were consecutively enrolled. When a total of 50 patients with at least one event of circulatory arrest were enrolled, that cohort was closed. Validation was performed on the fourth set of included patients. The primary outcome was sensitivity for the detection of circulatory arrest. FINDINGS: Of 306 patients enrolled between March 14, 2022, and April 21, 2023, 291 patients were included in the data analysis. In the development phase (n=205), the first training set yielded a sensitivity for circulatory arrest detection of 100% (95% CI 94-100) and four false positive alarms; the second training set yielded a sensitivity of 100% (94-100), with six false positive alarms; and the third training set yielded a sensitivity of 100% (94-100), with two false positive alarms. In the validation phase (n=86), the sensitivity for circulatory arrest detection was 98% (92-100) and 11 false positive circulatory arrest alarms. The positive predictive value was 90% (95% CI 82-94). INTERPRETATION: The automated detection of induced circulatory arrests using wrist-derived photoplethysmography is feasible with good sensitivity and low false positives. These promising findings warrant further development of this wearable technology to enable automated cardiac arrest detection and alarming in a home setting. FUNDING: Dutch Heart Foundation (Hartstichting).

Photoplethysmography and intracardiac pressures: early insights from a pilot study.

Aims: Invasive haemodynamic monitoring of heart failure (HF) is used to detect deterioration in an early phase thereby preventing hospitalizations. However, this invasive approach is costly and presently lacks widespread accessibility. Hence, there is a pressing need to identify an alternative non-invasive method that is reliable and more readily available. In this pilot study, we investigated the relation between wrist-derived photoplethysmography (PPG) signals and the invasively measured pulmonary capillary wedge pressure (PCWP). Methods and results: Fourteen patients with aortic valve stenosis who underwent transcatheter aortic valve replacement with concomitant right heart catheterization and PPG measurements were included. Six unique features of the PPG signals [heart rate, heart rate variability, systolic amplitude (SA), diastolic amplitude, crest time (CT), and large artery stiffness index (LASI)] were extracted. These features were used to estimate the continuous PCWP values and the categorized PCWP (low < 12 mmHg vs. high ≥ 12 mmHg). All PPG features resulted in regression models that showed low correlations with the invasively measured PCWP. Classification models resulted in higher performances: the model based on the SA and the model based on the LASI both resulted in an area under the curve (AUC) of 0.86 and the model based on the CT resulted in an AUC of 0.72. Conclusion: These results demonstrate the capability to non-invasively classify patients into clinically meaningful categories of PCWP using PPG signals from a wrist-worn wearable device. To enhance and fully explore its potential, the relationship between PPG and PCWP should be further investigated in a larger cohort of HF patients.

Long-term Effect of Face-to-Face vs Virtual Reality Cardiopulmonary Resuscitation (CPR) Training on Willingness to Perform CPR, Retention of Knowledge, and Dissemination of CPR Awareness: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Increased bystander cardiopulmonary resuscitation (CPR) is essential to improve survival after cardiac arrest. Although most studies focus on technical CPR skills, the randomized Lowlands Saves Lives trial prespecified a follow-up survey on other important aspects that affect the widespread performance of CPR. Objective: To investigate bystander willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness 6 months after undergoing short face-to-face and virtual reality (VR) CPR trainings. Design, Setting, and Participants: A prespecified 6-month posttraining survey was conducted among 320 participants in the Lowlands Saves Lives trial, a randomized comparison between 20-minute face-to-face, instructor-led CPR training and VR training. Participants were recruited at the Lowlands music festival, with a designated area to conduct scientific projects (August 16-18, 2019; the Netherlands). Statistical analysis was performed from March 1, 2020, to July 31, 2021. Interventions: Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training using CPR manikins or VR training using the Resuscitation Council (UK)-endorsed Lifesaver VR smartphone application and a pillow to practice compressions. Main Outcomes and Measures: Primary outcomes were willingness to perform CPR on a stranger, theoretical knowledge retention, and dissemination of CPR awareness as reported by the entire cohort. As secondary analyses, the results of the 2 training modalities were compared. Results: Of 381 participants, 320 consented to this follow-up survey; 188 participants (115 women [61%]; median age, 26 years [IQR, 22-32 years]) completed the entire survey and were accordingly included in the secondary analysis. The overall proportion of participants willing to perform CPR on a stranger was 77% (144 of 188): 81% (79 of 97) among face-to-face participants and 71% (65 of 91) among VR participants (P = .02); 103 participants (55%) reported feeling scared to perform CPR (P = .91). Regarding theoretical knowledge retention, a median of 7 (IQR, 6-8) of 9 questions were answered correctly in both groups (P = .81). Regarding dissemination of CPR awareness, 65% of participants (123 of 188) told at least 1 to 10 family members or friends about the importance of CPR, and 15% (29 of 188) had participated in certified, instructor-led training at the time of the survey, without differences between groups. Conclusions and Relevance: In this 6-month posttraining survey, young adult participants of short CPR training modules reported high willingness (77%) to perform CPR on a stranger, with slightly higher rates for face-to-face than for VR participants. Theoretical knowledge retention was good, and the high dissemination of awareness suggests that these novel CPR training modules staged at a public event are promising sensitizers for involvement in CPR, although further challenges include mitigating the fear of performing CPR. Trial Registration: ClinicalTrials.gov Identifier: NCT04013633.

Pilot study on VF-waveform based algorithms for early detection of acute myocardial infarction during out-of-hospital cardiac arrest.

INTRODUCTION: On-scene detection of acute coronary occlusion (ACO) during ongoing ventricular fibrillation (VF) may facilitate patient-tailored triage and treatment during cardiac arrest. Experimental studies have demonstrated the diagnostic potential of the amplitude spectrum area (AMSA) of the VF-waveform to detect myocardial infarction (MI). In follow-up, we performed this clinical pilot study on VF-waveform based discriminative models to diagnose acute MI due to ACO in real-world VF-patients. METHODS: In our registry of VF-patients transported to a tertiary hospital (Nijmegen, The Netherlands), we studied patients with high-quality VF-registrations. We calculated VF-characteristics prior to the first shock, and first-to-second shock changes (Δ-characteristics). Primary aim was to assess the discriminative ability of the AMSA to detect patients with ACO. Secondarily, we investigated the discriminative value of adding ΔAMSA-measures using machine learning algorithms. Model performances were assessed using C-statistics. RESULTS: In total, there were 67 VF-patients with and 34 without an ACO, and baseline characteristics did not differ significantly. Based on the AMSA prior to the first defibrillation attempt, discrimination between ACO and non-ACO was possible, with a C-statistic of 0.66 (0.56-0.75). The discriminative model using AMSA + ΔAMSA yielded a C-statistic of 0.80 (0.69-0.88). CONCLUSION: These clinical pilot data confirm previous experimental findings that early detection of MI using VF-waveform analysis seems feasible, and add insights on the diagnostic impact of accounting for first-to-second shock changes in VF-characteristics. Confirmative studies in larger cohorts and with a variety of VF-algorithms are warranted to further investigate the potential of this innovative approach.

The influence of timing of coronary angiography on acute kidney injury in out-of-hospital cardiac arrest patients: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication in cardiac arrest survivors and associated with adverse outcome. It remains unclear whether the incidence of AKI increases after the post-cardiac arrest contrast administration for coronary angiography and whether this depends on timing of angiography. Aim of this study was to investigate whether early angiography is associated with increased development of AKI compared to deferred angiography in out-of-hospital cardiac arrest (OHCA) survivors. METHODS: In this retrospective multicenter cohort study, we investigated whether early angiography (within 2 h) after OHCA was non-inferior to deferred angiography regarding the development of AKI. We used an absolute difference of 5% as the non-inferiority margin. Primary non-inferiority analysis was done by calculating the risk difference with its 90% confidence interval (CI) using a generalized linear model for a binary outcome. As a sensitivity analysis, we repeated the primary analysis using propensity score matching. A multivariable model was built to identify predictors of acute kidney injury. RESULTS: A total of 2375 patients were included from 2009 until 2018, of which 1148 patients were treated with early coronary angiography and 1227 patients with delayed or no angiography. In the early angiography group 18.5% of patients developed AKI after OHCA and 24.1% in the deferred angiography group. Risk difference was - 3.7% with 90% CI ranging from - 6.7 to - 0.7%, indicating non-inferiority of early angiography. The sensitivity analysis using propensity score matching showed accordant results, but no longer non-inferiority of early angiography. The factors time to return of spontaneous circulation (odds ratio [OR] 1.12, 95% CI 1.06-1.19, p < 0.001), the (not) use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (OR 0.20, 95% CI 0.04-0.91, p = 0.04) and baseline creatinine (OR 1.05, 95% CI 1.03-1.07, p < 0.001) were found to be independently associated with the development of AKI. CONCLUSIONS: Although AKI occurred in approximately 20% of OHCA patients, we found that early angiography was not associated with a higher AKI incidence than a deferred angiography strategy. The present results implicate that it is safe to perform early coronary angiography with respect to the risk of developing AKI after OHCA.

Cost Analysis From a Randomized Comparison of Immediate Versus Delayed Angiography After Cardiac Arrest.

Background In patients with out-of-hospital cardiac arrest without ST-segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out-of-hospital cardiac arrest. Methods and Results A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost-prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND-36 and collected at 12-month follow-up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P=0.86). Generalized linear model: (ß, 0.991; 95% CI, 0.894-1.099; P=0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P<0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND-36 questionnaire did not differ between both groups. Conclusions The mean total costs between patients with out-of-hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl; Unique identifier: NL4857.

Optimal Combination of Chest Compression Depth and Rate in Virtual Reality Resuscitation Training: A Post Hoc Analysis of the Randomized Lowlands Saves Lives Trial.

Background Dissemination of cardiopulmonary resuscitation (CPR) skills is essential for cardiac arrest survival. Virtual reality (VR)-training methods are low cost and easily available, but to meet depth requirements adaptations are required, as confirmed in a recent randomized study on currently prevailing CPR quality criteria. Recently, the promising clinical performance of new CPR quality criteria was demonstrated, based on the optimal combination of compression depth and rate. We now study compliance with these newly proposed CPR quality criteria. Methods and Results Post hoc analysis of a randomized trial compared standardized 20-minute face-to-face CPR training with VR training using the Lifesaver VR smartphone application. During a posttraining test, compression depth and rate were measured using CPR mannequins. We assessed compliance with the newly proposed CPR criteria, that is, compression rate within ±20% of 107/minute and depth within ±20% of 47 mm. We studied 352 participants, age 26 (22-31) years, 56% female, and 15% with CPR training ≤2 years. Among VR-trained participants, there was a statistically significant difference between the proportions complying with newly proposed versus the currently prevailing quality criteria (52% versus 23%, P<0.001). The difference in proportions complying with rate requirements was statistically significant (96% for the new versus 50% for current criteria, P<0.001), whereas there was no significant difference with regard to the depth requirements (55% versus 51%, P=0.45). Conclusions Lifesaver VR training, although previously found to be inferior to face-to-face training, may lead to CPR quality compliant with recently proposed, new quality criteria. If the prognostic importance of these new criteria is confirmed in additional studies, Lifesaver VR in its current form would be an easily available vector to disseminate CPR skills.

Electrocardiographic recording direction impacts ventricular fibrillation waveform measurements: A potential pitfall for VF-waveform guided defibrillation protocols.

AIM: In cardiac arrest, ventricular fibrillation (VF) waveform analysis has identified the amplitude spectrum area (AMSA) as a key predictor of defibrillation success and favorable neurologic survival. New resuscitation protocols are under investigation, where prompt defibrillation is restricted to cases with a high AMSA. Appreciating the variability of in-field pad placement, we aimed to assess the impact of recording direction on AMSA-values, and the inherent defibrillation advice. METHODS: Prospective VF-waveform study on 12-lead surface electrocardiograms (ECGs) obtained during defibrillation testing in ICD-recipients (2010-2017). AMSA-values (mVHz) of simultaneous VF-recordings were calculated and compared between all limb leads, with lead II as reference (proxy for in-field pad position). AMSA-differences between leads I and II were quantified using Bland-Altman analysis. Moreover, we investigated differences between these adjacent leads regarding classification into high (≥15.5), intermediate (6.5-15.5) or low (≤6.5) AMSA-values. RESULTS: In this cohort (n = 243), AMSA-values in lead II (10.2 ± 4.8) differed significantly from the other limb leads (I: 8.0 ± 3.4; III: 12.9 ± 5.6, both p < 0.001). The AMSA-value in lead I was, on average, 2.24 ± 4.3 lower than in lead II. Of the subjects with high AMSA-values in lead II, only 15% were classified as high if based on assessments of lead I. For intermediate and low AMSA-values, concordances were 66% and 72% respectively. CONCLUSIONS: ECG-recording direction markedly affects the result of VF-waveform analysis, with 20-30% lower AMSA-values in lead I than in lead II. Our data suggest that electrode positioning may significantly impact shock guidance by 'smart defibrillators', especially affecting the advice for prompt defibrillation.

Computerized Analysis of the Ventricular Fibrillation Waveform Allows Identification of Myocardial Infarction: A Proof-of-Concept Study for Smart Defibrillator Applications in Cardiac Arrest.

Background In cardiac arrest, computerized analysis of the ventricular fibrillation (VF) waveform provides prognostic information, while its diagnostic potential is subject of study. Animal studies suggest that VF morphology is affected by prior myocardial infarction (MI), and even more by acute MI. This experimental in-human study reports on the discriminative value of VF waveform analysis to identify a prior MI. Outcomes may provide support for in-field studies on acute MI. Methods and Results We conducted a prospective registry of implantable cardioverter defibrillator recipients with defibrillation testing (2010-2014). From 12-lead surface ECG VF recordings, we calculated 10 VF waveform characteristics. First, we studied detection of prior MI with lead II, using one key VF characteristic (amplitude spectrum area [AMSA]). Subsequently, we constructed diagnostic machine learning models: model A, lead II, all VF characteristics; model B, 12-lead, AMSA only; and model C, 12-lead, all VF characteristics. Prior MI was present in 58% (119/206) of patients. The approach using the AMSA of lead II demonstrated a C-statistic of 0.61 (95% CI, 0.54-0.68). Model A performance was not significantly better: 0.66 (95% CI, 0.59-0.73), P=0.09 versus AMSA lead II. Model B yielded a higher C-statistic: 0.75 (95% CI, 0.68-0.81), P<0.001 versus AMSA lead II. Model C did not improve this further: 0.74 (95% CI, 0.67-0.80), P=0.66 versus model B. Conclusions This proof-of-concept study provides the first in-human evidence that MI detection seems feasible using VF waveform analysis. Information from multiple ECG leads rather than from multiple VF characteristics may improve diagnostic accuracy. These results require additional experimental studies and may serve as pilot data for in-field smart defibrillator studies, to try and identify acute MI in the earliest stages of cardiac arrest.

Diagnostic performance of the basic and advanced life support termination of resuscitation rules: A systematic review and diagnostic meta-analysis.

AIM: To minimize termination of resuscitation (TOR) in potential survivors, the desired positive predictive value (PPV) for mortality and specificity of universal TOR-rules are ≥99%. In lack of a quantitative summary of the collective evidence, we performed a diagnostic meta-analysis to provide an overall estimate of the performance of the basic and advanced life support (BLS and ALS) termination rules. DATA SOURCES: We searched PubMed/EMBASE/Web-of-Science/CINAHL and Cochrane (until September 2019) for studies on either or both TOR-rules in non-traumatic, adult cardiac arrest. PRISMA-DTA-guidelines were followed. RESULTS: There were 19 studies: 16 reported on the BLS-rule (205.073 patients, TOR-advice in 57%), 11 on the ALS-rule (161.850 patients, TOR-advice in 24%). Pooled specificities were 0.95 (0.89-0.98) and 0.98 (0.95-1.00) respectively, with a PPV of 0.99 (0.99-1.00) and 1.00 (0.99-1.00). Specificities were significantly lower in non-Western than Western regions: 0.84 (0.73-0.92) vs. 0.99 (0.97-0.99), p < 0.001 for the BLS rule. For the ALS-rule, specificities were 0.94 (0.87-0.97) vs. 1.00 (0.99-1.00), p < 0.001. For non-Western regions, 16 (BLS) or 6 (ALS) out of 100 potential survivors met the TOR-criteria. Meta-regression demonstrated decreasing performance in settings with lower rates of in-field shocks. CONCLUSIONS: Despite an overall high PPV, this meta-analysis highlights a clinically important variation in diagnostic performance of the BLS and ALS TOR-rules. Lower specificity and PPV were seen in non-Western regions, and populations with lower rates of in-field defibrillation. Improved insight in the varying diagnostic performance is highly needed, and local validation of the rules is warranted to prevent in-field termination of potential survivors.

Meta-Analysis Comparing Cardiac Arrest Outcomes Before and After Resuscitation Guideline Updates.

Updates of resuscitation guidelines have limited high-level supporting evidence. Moreover, the overall effect of such bundled practice changes depends not only on the impact of the individual interventions but also on their interplay and swift functioning of the entire chain of survival. Therefore, real-world data monitoring is essential. We performed a meta-analysis of comparative studies on outcomes before and after successive guideline updates. On January 16, 2019, we searched for comparative studies (PubMed, Web-of-Science, Embase, and the Cochrane Libraries) reporting outcomes before and after resuscitation guidelines 2005, 2010, and 2015. We followed PRISMA, Cochrane, and Moose-recommendations. Studies on outcomes during the 2005 versus 2000 guideline period (n = 23; 40,859 patients) reported significantly higher ROSC (odds ratio [OR] 1.21 [1.04 to 1.42], p = 0.014), survival to admission (OR 1.34 [1.09 to 1.65], p = 0.005), survival to discharge (OR 1.46 [1.25 to 1.70], p <0.001), and favorable neurologic outcome (OR 1.35 [1.01 to 1.81], p = 0.040). Studies on outcomes during the 2010 versus 2005 guideline period (n = 11; 1,048,112 patients) indicated no difference in ROSC (OR 1.25 [95% confidence interval 0.95 to 1.63], p = 0.11), whereas survival to discharge improved significantly (OR 1.30 [1.17 to 1.45], p <0.001). Only 2 studies reported on neurologic outcomes, both showing improved outcome after the 2010 guideline update. No data on the 2015 guidelines were available. This meta-analysis on real-world data of >1 million patients demonstrates improved outcomes after the 2005 and 2010 resuscitation guideline updates, and a lack of data on the 2015 guideline. In conclusion, although limited in terms of causality, this study suggests that the sum of all efforts to improve outcomes, including updated CPR guidelines, contributed to increased survival after cardiac arrest.

Effect of Face-to-Face vs Virtual Reality Training on Cardiopulmonary Resuscitation Quality: A Randomized Clinical Trial.

Importance: Bystander cardiopulmonary resuscitation (CPR) is crucial for survival after cardiac arrest but not performed in most cases. New, low-cost, and easily accessible training methods, such as virtual reality (VR), may reach broader target populations, but data on achieved CPR skills are lacking. Objective: To compare CPR quality between VR and face-to-face CPR training. Design, Setting, and Participants: Randomized noninferiority trial with a prospective randomized open blinded end point design. Participants were adult attendees from the science section of the Lowlands Music Festival (August 16 to 18, 2019) in the Netherlands. Analysis began September 2019. Interventions: Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training or VR training using a smartphone app endorsed by the Resuscitation Council (United Kingdom). Main Outcomes and Measures: During a standardized CPR scenario following the training, we assessed the primary outcome CPR quality, measured as chest compression depth and rate using CPR manikins. Overall CPR performance was assessed by examiners, blinded for study groups, using a European Resuscitation Council-endorsed checklist (maximum score, 13). Additional secondary outcomes were chest compression fraction, proportions of participants with mean depth (50 mm-60 mm) or rate (100 min-1-120 min-1) within guideline ranges, and proportions compressions with full release. Results: A total of 381 participants were randomized: 216 women (57%); median (interquartile range [IQR]) age, 26 (22-31) years. The VR app (n = 190 [49.9%]) was inferior to face-to-face training (n = 191 [50.1%]) for chest compression depth (mean [SD], VR: 49 [10] mm vs face to face: 57 [5] mm; mean [95% CI] difference, -8 [-9 to -6] mm), and noninferior for chest compression rate (mean [SD]: VR: 114 [12] min-1 vs face to face: 109 [12] min-1; mean [95% CI] difference, 6 [3 to 8] min-1). The VR group had lower overall CPR performance scores (median [IQR], 10 [8-12] vs 12 [12-13]; P < .001). Chest compression fraction (median [IQR], 61% [52%-66%] vs 67% [62%-71%]; P < .001) and proportions of participants fulfilling depth (51% [n = 89] vs 75% [n = 133], P < .001) and rate (50% [n = 87] vs 63% [n = 111], P = .01) requirements were also lower in the VR group. The proportion of compressions with full release was higher in the VR group (median [IQR], 98% [59%-100%] vs 88% [55%-99%]; P = .002). Conclusions and Relevance: In this randomized noninferiority trial, VR training resulted in comparable chest compression rate but inferior compression depth compared with face-to-face training. Given the potential of VR training to reach a larger target population, further development is needed to achieve the compression depth and overall CPR skills acquired by face-to-face training. Trial Registration: ClinicalTrials.gov identifier: NCT04013633.

Rationale and design of the Lowlands Saves Lives trial: a randomised trial to compare CPR quality and long-term attitude towards CPR performance between face-to-face and virtual reality training with the Lifesaver VR app.

INTRODUCTION: Layperson cardiopulmonary resuscitation (CPR) is a key aspect in the chain of survival after cardiac arrest. New, low-cost, easily accessible training methods such as virtual reality (VR) training with a smartphone application may reach broader populations, but data on CPR performance are scarce. METHODS AND ANALYSIS: The Lowlands Saves Lives trial is a prospective randomised open-blinded end-point evaluation study, comparing two 20 min CPR training protocols: standardised, certified instructor-led face-to-face training complying with current education guidelines (using Laerdal Little Anne manikins), and VR training, using the UK Resuscitation Council endorsed Lifesaver VR app. In the latter, chest compressions are practiced on a pillow.During VR training, participants learn to resuscitate by completing a filmed CPR scenario while wearing VR goggles and headphones. Eligible for inclusion are adult attendees of Lowlands Science, a specific section of the 3-day Lowlands music festival (50 000 attendees), dedicated exclusively to science. Following the training, all participants will perform a CPR test on a Laerdal Resusci Anne QCPR manikin. Primary outcome measures are depth and rate of chest compressions, measured using CPR manikins. The key secondary outcome is overall CPR performance, with real-time examination (blinded for study group) of all items of a European Resuscitation Council endorsed checklist, and evaluation of a sample of videotaped CPR tests by a blinded event committee.Given the unique setting of a festival, the primary additional analysis will address the impact of alcohol levels on CPR quality parameters and overall performance. Follow-up questionnaires will evaluate the attitude towards performing CPR. This unique study may provide important insights into innovative CPR training methods, factors that impact CPR performance and the impact on long-term attitude towards resuscitation. ETHICS AND DISSEMINATION: This study received approval from the research ethics committee of the Radboudumc. All participants will provide written informed consent. The results of this study will be published in peer-reviewed journals and presented at (inter)national conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov registry (NCT04013633).

Ventricular fibrillation waveform characteristics of the surface ECG: Impact of the left ventricular diameter and mass.

BACKGROUND: Despite a promising association between VF waveform characteristics and prognosis after resuscitation, studies with VF-guided treatment have so far not improved outcomes. While driven by the idea that the VF waveform reflects arrest duration, increasing evidence suggests that pre-existent disease-related changes of the myocardium affect ECG-characteristics of VF as well. In this context, we studied the impact of the left ventricular (LV) diameter and mass. METHODS: Cohort of 193 ICD-patients with defibrillation testing at the Radboudumc (2010-2014). Surface ECG-recordings (leads I,II,aVF,V1,V3,V6) were analysed to study amplitude and frequency characteristics of the induced VF. Both for LV diameter and mass, patients were categorised in two groups, using echocardiographic data (ASE-guidelines). RESULTS: In all ECG-leads, dominant and median frequencies were significantly lower in patients with (n=40) than in patients without (n=151) an increased LV diameter. The mean amplitude and amplitude spectrum area (AMSA) did not differ. In contrast, we observed no differences in frequency characteristics in relation to the LV mass, whereas mean amplitude (I,aVF,V3) and AMSA (I,V3) were significantly higher in patients with (n=57) than in patients without (n=120) an increased LV mass. CONCLUSIONS: Frequency characteristics of VF were consistently lower in case of an increased LV diameter. Whereas LV mass does not affect the frequency of the VF waveform, amplitudes seem higher with increasing mass. These findings add to the current knowledge of factors that modulate VF characteristics of the surface ECG and provide insight into factors which may be accounted for in future studies on VF-guided resuscitative interventions.