Prognostic benefits of His-Purkinje capture in physiological pacemakers for bradycardia.

INTRODUCTION: Clinical outcomes of long-term ventricular septal pacing (VSP) without His-Purkinje capture remain unknown. This study evaluated the differences in clinical outcomes between conduction system pacing (CSP), VSP, and right ventricular pacing (RVP). METHODS: Consecutive patients with bradycardia indicated for pacing from 2016 to 2022 were prospectively followed for the clinical endpoints of heart failure (HF)-hospitalizations and all-cause mortality at 2 years. VSP was defined as septal pacing due to unsuccessful CSP implant or successful CSP followed by loss of His-Purkinje capture within 90 days. RESULTS: Among 1016 patients (age 73.9 ± 11.2 years, 47% female, 48% atrioventricular block), 612 received RVP, 335 received CSP and 69 received VSP. Paced QRS duration was similar between VSP and RVP, but both significantly longer than CSP (p < .05). HF-hospitalizations occurred in 130 (13%) patients (CSP 7% vs. RVP 16% vs. VSP 13%, p = .001), and all-cause mortality in 143 (14%) patients (CSP 7% vs. RVP 19% vs. VSP 9%, p < .001). The association of pacing modality with clinical events was limited to those with ventricular pacing (Vp) > 20% (pinteraction < .05). Adjusting for clinical risk factors among patients with Vp > 20%, VSP (adjusted hazard ratio [AHR]: 4.74, 95% confidence interval [CI]: 1.57-14.36) and RVP (AHR: 3.08, 95% CI: 1.44-6.60) were associated with increased hazard of HF-hospitalizations, and RVP (2.52, 95% CI: 1.19-5.35) with increased mortality, compared to CSP. Clinical endpoints did not differ between VSP and RVP with Vp > 20%, or amongst groups with Vp < 20%. CONCLUSION: Conduction system capture is associated with improved clinical outcomes. CSP should be preferred over VSP or RVP during pacing for bradycardia.

Conduction system versus biventricular pacing in heart failure with non-left bundle branch block.

INTRODUCTION: The benefits of cardiac resynchronization therapy (CRT) with biventricular pacing (BiV) is significantly lower when applied to heart failure (HF) patients with non-left bundle branch block (LBBB) conduction delay. We investigated clinical outcomes of conduction system pacing (CSP) for CRT in non-LBBB HF. METHODS: Consecutive HF patients with non-LBBB conduction delay undergoing CSP were propensity matched for age, sex, HF-etiology, and atrial fibrillation (AF) in a 1:1 ratio to BiV from a prospective registry of CRT recipients. Echocardiographic response was defined as an increase in left ventricular ejection fraction (LVEF) by ≥10%. The primary outcome was the composite of HF-hospitalizations or all-cause mortality. RESULTS: A total of 96 patients were recruited (mean age 70 ± 11years, 22% female, 68% ischemic HF and 49% AF). Significant reductions in QRS duration and LV dimensions were seen only after CSP, while LVEF improved significantly in both groups (p < 0.05). Echocardiographic response occurred more frequently in CSP than BiV (51% vs. 21%, p < 0.01), with CSP independently associated with four-fold increased odds (adjusted odds ratio 4.08, 95% confidence interval [CI] 1.34-12.41). The primary outcome occurred more frequently in BiV than CSP (69% vs. 27%, p < 0.001), with CSP independently associated with 58% risk reduction (adjusted hazard ratio [AHR] 0.42, 95% CI 0.21-0.84, p = 0.01), driven by reduced all-cause mortality (AHR 0.22, 95% CI 0.07-0.68, p < 0.01), and a trend toward reduced HF-hospitalization (AHR 0.51, 95% CI 0.21-1.21, p = 0.12). CONCLUSIONS: CSP provided greater electrical synchrony, reverse remodeling, improved cardiac function and survival compared to BiV in non-LBBB, and may be the preferred CRT strategy for non-LBBB HF.

The information needs of patients with atrial fibrillation: A scoping review.

AIMS AND OBJECTIVES: To identify the atrial fibrillation (AF)-specific information needs of patients with AF. BACKGROUND: Patients' understanding of AF is pertinent to optimising treatment and outcomes, thus highlighting the need for effective patient education. The information required to deliver effective AF-specific patient education is less examined. METHODS: Guided by Arksey and O'Malley's framework, a scoping review was conducted for studies reporting the AF-specific information needs of patients with AF. Systematic searches were conducted across six databases (Medline, PubMed, CINAHL, Scopus, PsycINFO and ProQuest). All analyses were narrated in prose and outlined in tables. The PRISMA-ScR checklist was used to report this review. RESULTS: The systematic search yielded 3816 articles, of which 22 were included. Three major themes emerged from the thematic analysis. Each theme was supported by three subthemes. First, in 'Understanding AF', patients reported the need for 'Easy-to-understand information', information on the 'Screening and diagnosis' of AF and 'Trajectory of disease and its associated risks'. Second, in 'Treating AF', patients required information on the 'Role of anticoagulation', 'Existing or novel therapeutic options' and 'Monitoring effectiveness of treatment'. Lastly, in 'Living with AF', patients needed education in 'Symptom management', 'Secondary prevention of risks' and 'Recognition of emergency situations'. CONCLUSIONS: This review has identified the key AF-specific information needs of patients with AF. Being cognisant of the information needs of patients with AF, healthcare providers may become more effective in developing person-centred patient education interventions. RELEVANCE TO CLINICAL PRACTICE: Delivering relevant patient education is an important cornerstone for atrial fibrillation care. Nurses by convention play a professional role in patient education. It may be facilitative for nurses to refer to the review findings when developing and implementing patient education interventions. Being in the midst of an ongoing pandemic, patient education strategies may require the use of telecommunication technologies.

Assessment of the general public's knowledge of atrial fibrillation through social media: a cross-sectional study.

BACKGROUND: Early detection and timely treatment of atrial fibrillation (AF) remains pivotal to preventing AF-related complications. Public involvement in recognising potential AF symptoms and managing AF is vital for early detection and treatment of AF. OBJECTIVE: The aim of the study is to assess the general public's knowledge of AF using an online survey, disseminated via social media. METHODS: A cross-sectional online survey of the general public was conducted between November to December 2021. The survey's URL was shared on National University Heart Centre, Singapore's official Facebook page. Digital marketing strategies were employed to recruit members of the public. The 27-item survey assessed public's knowledge across five domains: basic information about AF, risk factors of AF, detection of AF, prevention of AF, and management of AF. RESULTS: The survey involved 620 participants. Approximately two-thirds were between the ages 21 to 40 years (64.5%), female (60%) and had at least a degree (64.7%) as their highest level of education. Participants obtained a mean percentage score of 63.3 ± 26.0 for their AF knowledge. One-way ANOVA was done to examine the associations between the participants' characteristics and their knowledge of AF. There were no statistically significant differences in the AF knowledge scores across the various sociodemographic subgroups. CONCLUSIONS: Members of the public recruited from Facebook and via digital marketing had moderately good knowledge of AF. However, public awareness pertaining to preventing AF has potential for improvement. The utility of social media in reaching the general public was illustrated through this study.

Ventricular tachycardia from myocarditis following COVID-19 vaccination with tozinameran (BNT162b2, Pfizer-BioNTech).

To combat the coronavirus disease 2019 (COVID-19) pandemic, many countries have started population vaccination programs using messenger ribonucleic acid (mRNA) vaccines. With the widespread use of such vaccines, reports are emerging worldwide, of the vaccine's association with the development of myocarditis. Younger men are more likely to develop postvaccine myocarditis, which usually presents as self-limiting chest pain within a week after the second dose. We present a case of myocarditis following vaccination with tozinameran (BNT162b2, Pfizer-BioNTech), which presented late, with ventricular tachycardia (VT) reduced left ventricular ejection fraction (LVEF).

Registered nurses' perceptions towards advanced practice nursing: A nationwide cross-sectional study.

AIMS: To explore registered nurses' perceptions towards the role of advanced practice nurses and to examine registered nurses' interests in becoming advanced practice nurses. BACKGROUND: Globally, the development and implementation of advanced practice nurses have been deemed propitious. Advanced practice nurses are recruited and developed from the current pool of registered nurses. Empirical research is needed to inform practice on ensuring the sustainability of the advanced practice nurse workforce through the recruitment and development of the current population of registered nurses. METHODS: A nationwide cross-sectional online survey was conducted in Singapore. Registered nurses from all public health care institutions were surveyed. RESULTS: Respondents (n = 1,025) displayed optimism and acceptance towards advanced practice nurses. However, only 30.7% hoped to become advanced practice nurses. Nursing leaders were reported to have a low success rate in identifying registered nurses who were both suitable and interested in the advanced practice nurse role. CONCLUSIONS: Registered nurses' positive perspectives towards the role of advanced practice nurses do not translate into interests in the role. The study offers pragmatic applicability in ensuring the sustainability of the advanced practice nurse workforce. IMPLICATIONS FOR NURSING MANAGEMENT: Advanced practice nurse-specific residency programmes for pre-master registered nurses may be facilitative to retaining and recruiting registered nurses for the advanced practice nurse workforce.

Predictors of NOAC versus VKA use for stroke prevention in patients with newly diagnosed atrial fibrillation: Results from GARFIELD-AF.

INTRODUCTION: A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non-vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored. METHODS: Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ±â€¯antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016. RESULTS: The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP. CONCLUSION: GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome.

Characteristics of patients with atrial fibrillation prescribed antiplatelet monotherapy compared with those on anticoagulants: insights from the GARFIELD-AF registry.

Aims: Current atrial fibrillation (AF) guidelines discourage antiplatelet (AP) monotherapy as alternative to anticoagulants (ACs). Why AP only is still used is largely unknown. Methods and results: Factors associated with AP monotherapy prescription were analysed in GARFIELD-AF, a registry of patients with newly diagnosed (≤6 weeks) AF and ≥1 investigator-determined stroke risk factor. We analysed 51 270 patients from 35 countries enrolled into five sequential cohorts between 2010 and 2016. Overall, 20.7% of patients received AP monotherapy, 52.1% AC monotherapy, and 14.1% AP + AC. Most AP monotherapy (82.5%) and AC monotherapy (86.8%) patients were CHA2DS2-VASc ≥2. Compared with patients on AC monotherapy, AP monotherapy patients were frequently Chinese (vs. Caucasian, odds ratio 2.73) and more likely to have persistent AF (1.32), history of coronary artery disease (2.41) or other vascular disease (1.67), bleeding (2.11), or dementia (1.81). The odds for AP monotherapy increased with 5 years of age increments for patients ≥75 years (1.24) but decreased with age increments for patients 55-75 years (0.86). Antiplatelet monotherapy patients were less likely to have paroxysmal (0.67) or permanent AF (0.57), history of embolism (0.56), or alcohol use (0.90). With each cohort, AP monotherapy declined (P<0.0001), especially non-indicated use. AP + AC and no antithrombotic therapy were unchanged. However, even in 2015 and 2016, about 50% of AP-treated patients had no indication except AF (71% were CHA2DS2-VASc ≥2). Conclusion: Prescribing AP monotherapy in newly diagnosed AF has declined, but even nowadays a substantial proportion of AP-treated patients with AF have no indication for AP. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362.

Questionnaires Designed to Assess Knowledge of Atrial Fibrillation: A Systematic Review.

BACKGROUND: Atrial fibrillation (AF) is associated with high mortality and morbidity. Approximately half of patients with AF and at risk of stroke do not receive oral anticoagulation, despite its demonstrable reduction of stroke risk. Low adherence to anticoagulation medications may be a result of limited knowledge of AF among patients; hence, a validated instrument to assess AF knowledge is warranted. Cross-sectional surveys evaluating AF knowledge revealed the availability of instruments in the literature, but no systematic review has hitherto been conducted to characterize them. OBJECTIVE: The objective of this study is to collate all validated instruments assessing AF knowledge. METHODS: A systematic review was conducted. CINAHL, EMBASE, MEDLINE, and PsycINFO were searched from inception to May 25, 2018. Study selection and data extraction were conducted by 2 reviewers, from which results are presented narratively. RESULTS: Based on 407 records retrieved from the databases, 15 studies were included, from which 7 questionnaires assessing AF knowledge were identified. The number of items ranged from 8 to 58. All the questionnaires were content validated, and some also examined other validities and reliabilities. CONCLUSION: In the literature, 7 validated questionnaires are available for assessing AF knowledge, in which the items often cover knowledge of AF in general, symptoms, treatments, and complications.

The Translation of Knowledge Into Practice in the Management of Atrial Fibrillation in Singapore.

BACKGROUND: Atrial fibrillation (AF) is a clinically significant cardiac arrhythmia known to increase the risk of stroke by at least four times. Stroke-risk assessment and thromboprophylaxis are vital components in AF management. Guidelines are available to standardise AF management, but physicians' adherence to the recommended guidelines has been low. The aims were to: 1. Examine and compare the level of knowledge and current practice in AF management between cardiologists and non-cardiologist physicians in Singapore; 2. Identify physicians' perceived barriers to prescribing oral anticoagulants (OACs) when indicated; 3. Identify strategies to optimise AF management. METHODS: From June 2017 to August 2017, a cross-sectional online survey involving physicians was conducted in Singapore. The survey instrument was adapted from a previously developed instrument, and validated locally by five cardiologists. It explored the physicians' stroke-risk assessment practices, estimation of stroke risk and benefits of anticoagulation, likelihood of prescribing anticoagulation when indicated, perceived barriers to anticoagulation, and strategies to optimise AF management. RESULTS: Sixty-three (63) physicians completed the survey (14 cardiologists and 49 non-cardiologist physicians). No significant difference was found between cardiologists and non-cardiologist physicians in their assessment and estimation of stroke risk for stable AF patients. However, when presented with an AF patient with stroke risk, cardiologists were more likely than non-cardiologist physicians to prescribe novel OACs (93% vs. 51%; χ2=7.933, p=0.004). Compared to cardiologists, the majority of the non-cardiologist physicians thought the risk of falls were usually or always barriers to prescribing OACs (29% vs 69%; χ2=7.579, p=0.006). Among the suggested strategies to support them in AF management, physicians have overwhelmingly rated two as "quite useful" and "very useful": the establishment of clinics for monitoring anticoagulated patients (100%); and involvement of pharmacists in managing patients on warfarin (98.4%). CONCLUSIONS: Physicians possess good knowledge about stroke-risk assessment in AF patients yet it is not translated into effective measures for stroke prevention. Physicians, especially non-cardiologist ones, were not anticoagulating AF patients when indicated. Although novel OACs are safer alternatives to warfarin, non-cardiologist physicians were less inclined to use them for stroke prevention. All physicians opined that establishing anticoagulation clinics and collaborating with pharmacists were useful strategies to optimise AF management. Existing barriers to anticoagulation impeded the translation of knowledge into practice in the management of AF patients in Singapore, for which optimal strategies to optimise AF management are ascertained.

Practice patterns and role perception of advanced practice nurses: A nationwide cross-sectional study.

AIMS: To provide an overview of the practice patterns of advanced practice nurses and to explore their perceptions of their role in Singapore. BACKGROUND: Role expansion of advanced practice nurses is increasingly popular in healthcare systems. However, their practice patterns remain variable, thereby introducing role ambiguity. Uncertainty revolves around how advanced practice nurses perceive their practice, competency and readiness for role expansion. METHODS: A nationwide survey of advanced practice nurses was conducted in Singapore. Statistical analyses of closed-ended responses and content analysis of open-ended responses were undertaken. RESULTS: A total of 87 participants were surveyed (42.8% response rate). Significant discrepancies existed between current practices and their expectations. Readiness for and acceptance of role expansion were discerned but multiple barriers to practice have remained. CONCLUSION: This pioneering study in Asia provides important evidence to support the call for greater clarity in the role of APNs and for review of existing institutional practice restrictions. It provides insights into healthcare systems in similar developmental stages of advanced practice nursing. IMPLICATIONS FOR NURSING MANAGEMENT: When outlining the goals and role priorities of advanced practice nurses APNs, nurse administrators can consider their best contributions in practice. This allows for long-term sustainability of their role.

High Incidence of Occult Atrial Fibrillation in Asian Patients with Cryptogenic Stroke.

BACKGROUND: Occult atrial fibrillation (AF) is not uncommon in patients with stroke. In western cohorts, insertable loop recorders (ILRs) have been shown to be the gold-standard and are cost-effective for AF detection. Anticoagulation for secondary stroke prevention is indicated if AF is detected. The incidence of occult AF among Asian patients with cryptogenic stroke is unclear. METHODS: Patients with cryptogenic stroke referred between August 2014 and February 2017 had ILRs implanted. Episodes of AF >2 minutes duration were recorded using proprietary algorithms within the ILRs, whereupon clinicians and patients were alerted via remote monitoring. All AF episodes were adjudicated using recorded electrograms. Once AF was detected, patients were counseled for anticoagulation. RESULTS: Seventy-one patients with cryptogenic stroke, (age 61.9 ± 13.5 years, 77.5% male, mean CHA2DS2VASc score of 4.2 ± 1.3) had ILRs implanted. Time from stroke to the ILR implant was a median of 66 days. Duration of ILR monitoring was 345 ± 229 days. The primary endpoint of AF detection at 6 months was 12.9%; and at 12 months it was 15.2%. Median time to detection of AF was 50 days. The AF episodes were all asymptomatic and lasted a mean of 77 minutes (± 118.9). Anticoagulation was initiated in all but 1 patient found to have AF. CONCLUSIONS: The incidence of occult AF is high in Asian patients with cryptogenic stroke and comparable to western cohorts. The combination of ILR and remote monitoring is a highly automated, technologically driven, and clinically effective technique to screen for AF.

Association of Age, Sex, Body Size and Ethnicity with Electrocardiographic Values in Community-based Older Asian Adults.

BACKGROUND: Existing electrocardiographic (ECG) reference values were derived in middle-aged Caucasian adults. We aimed to assess the association of age, sex, body size and ethnicity on ECG parameters in a multi-ethnic Asian population. METHODS: Resting 12-lead ECG and anthropometric measurements were performed in a community-based cohort of 3777 older Asians (age 64.7±9.1 years, 1467 men, 88.8% Chinese, 7.7% Malay, 3.5% Indian, body mass index [BMI] 24.0±3.9kg/m(2)). RESULTS: Men had longer PR interval, wider QRS, shorter QTc interval and taller SV3. In both sexes, older age was associated with longer PR interval, wider QRS, larger R aVL and more leftward QRS axis, while higher BMI was associated with longer PR interval, wider QRS, larger RaVL and more negative QRS axis. There were significant inter-ethnic differences in QRS duration among men, as well as in PR and QTc intervals among women (all adjusted p<0.05). Findings were similar in a healthy subset of 1158 adults (age 61.2±9.1 years, 365 men) without cardiovascular risk factors. CONCLUSIONS: These first community-based ECG data in multi-ethnic older Asians highlight the independent effects of age, sex, body size and ethnicity on ECG parameters.

Clinical significance of early atrial arrhythmia type and timing after single ring isolation of the pulmonary veins.

AIMS: Early atrial arrhythmia following atrial fibrillation (AF) ablation is associated with higher recurrence rates. Few studies explore the impact of early AF (EAF) and atrial tachycardia (EAT) on long-term outcomes. Furthermore, EAF/EAT have not been characterized after wide pulmonary vein isolation. We aimed to characterize EAF and EAT and its impact on late AF (LAF) and AT (LAT) after single ring isolation (SRI). METHODS AND RESULTS: We recruited 119 (females 21, age 58 ± 10 years) consecutive patients with AF (paroxysmal 76, persistent 43) undergoing SRI. Early atrial fibrillation/ early atrial tachycardia was defined as AF/AT within 3 months post-procedure (blanking period). Patients were followed for median 2.8[2.2-4] years. Early atrial fibrillation occurred in 28% (n = 33) and EAT in 25% (n = 30). At follow-up, 25% (n = 30) had LAF and 28% (n = 33) had LAT. Patients with EAF and EAT had higher rates of LAF (48 vs. 16%, P<0.0001) and LAT (60 vs. 16%, P < 0.0001), respectively. Independent predictors of LAF were EAF (3.53(1.72-7.29) P = 0.001); and of LAT were EAT (5.62(2.88-10.95) P < 0.0001) and procedure time (1.38/ h(1.07-1.78) P = 0.04). Importantly, EAF did not predict LAT and EAT did not predict LAF. Early atrial fibrillation late in the blanking period was associated with higher rates of LAF (73% for month 3 vs. 25% for Months 1-2, P = 0.004). However, EAT timing did not predict LAT. CONCLUSION: Early atrial fibrillation and EAT are predictive of LAF and LAT, respectively. Early atrial fibrillation late in the blanking period has greater predictive significance for LAF. This timing is not relevant for LAT. Early arrhythmia type and timing have important prognostic significance following SRI. CLINICAL TRIAL REGISTRATION: http://www.anzctr.org.au;ACTRN12606000467538.

4:2:1 conduction of an AF initiating trigger.

A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus.

Remote monitoring of cardiac implantable electronic devices using smart device interface versus radiofrequency-based interface: A systematic review.

Background: Guidelines recommended remote monitoring (RM) in managing patients with Cardiac Implantable Electronic Devices. In recent years, smart device (phone or tablet) monitoring-based RM (SM-RM) was introduced. This study aims to systematically review SM-RM versus bedside monitor RM (BM-RM) using radiofrequency in terms of compliance, connectivity, and episode transmission time. Methods: We conducted a systematic review, searching three international databases from inception until July 2023 for studies comparing SM-RM (intervention group) versus BM-RM (control group). Results: Two matched studies (21 978 patients) were retrieved (SM-RM arm: 9642 patients, BM-RM arm: 12 336 patients). There is significantly higher compliance among SM-RM patients compared with BM-RM patients in both pacemaker and defibrillator patients. Manyam et al. found that more SM-RM patients than BM-RM patients transmitted at least once (98.1% vs. 94.3%, p < .001), and Tarakji et al. showed that SM-RM patients have higher success rates of scheduled transmissions than traditional BM-RM methods (SM-RM: 94.6%, pacemaker manual: 56.3%, pacemaker wireless: 77.0%, defibrillator wireless: 87.1%). There were higher enrolment rates, completed scheduled and patient-initiated transmissions, shorter episode transmission time, and higher connectivity among SM-RM patients compared to BM-RM patients. Younger patients (aged <75) had more patient-initiated transmissions, and a higher proportion had ≥10 transmissions compared with older patients (aged ≥75) in both SM-RM and BM-RM groups. Conclusion: SM-RM is a step in the right direction, with good compliance, connectivity, and shorter episode transmission time, empowering patients to be in control of their health. Further research on cost-effectiveness and long-term clinical outcomes can be carried out.

Impact of patient selection in clinical trials: application of ROCKET AF and ARISTOTLE criteria in GARFIELD-AF.

BACKGROUND: The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry. METHODS: Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA. RESULTS: Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs. CONCLUSION: Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.

An updated analysis on myocarditis and pericarditis cases reported following mRNA SARS-CoV-2 vaccination in Singapore.

INTRODUCTION: Messenger ribonucleic acid (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been associated with myocarditis/pericarditis, especially in young males. We evaluated the risk of myocarditis/pericarditis following mRNA vaccines by brand, age, sex and dose number in Singapore. METHODS: Adverse event reports of myocarditis/pericarditis following mRNA vaccines received by the Health Sciences Authority from 30 December 2020 to 25 July 2022 were included, with a data lock on 30 September 2022. Case adjudication was done by an independent panel of cardiologists using the US Centers for Disease Control and Prevention case definition. Reporting rates were compared with expected rates using historical data from 2018 to 2020. RESULTS: Of the 152 adjudicated cases, males comprised 75.0%. The median age was 30 years. Most cases occurred after Dose 2 (49.3%). The median time to onset was 2 days. Reporting rates were highest in males aged 12-17 years for both primary series (11.5 [95% confidence interval [CI] 6.7-18.4] per 100,000 doses, post-Dose 2) and following booster doses (7.1 [95% CI 3.0-13.9] per 100,000 doses). In children aged 5-11 years, myocarditis remained very rare (0.2 per 100,000 doses). The reporting rates for Booster 1 were generally similar or lower than those for Dose 2. CONCLUSIONS: The risk of myocarditis/pericarditis with mRNA vaccines was highest in adolescent males following Dose 2, and this was higher than historically observed background rates. Most cases were clinically mild. The risk of myocarditis should be weighed against the benefits of receiving an mRNA vaccine, keeping in mind that SARS-CoV-2 infections carry substantial risks of myocarditis/pericarditis, as well as the evolving landscape of the disease.

Migraine and atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Patients with migraines, particularly those with auras, may present with stroke. Atrial fibrillation is a known risk factor for stroke. With common pathophysiological factors between migraines and atrial fibrillation, we aimed to clarify the association between migraine and atrial fibrillation in this systematic review and meta-analysis. METHODS: A literature search was conducted in EMBASE, PubMed, Scopus and Cochrane electronic bibliographic databases from inception to 5 September 2022 with the following inclusion criteria: (a) cohort or cross-sectional studies; (b) studies that included only patients aged ≥18 years; and (c) studies that examined the association between atrial fibrillation and migraines. Exclusion criteria were case-control studies and the studies that included patients with previous diagnosis of atrial fibrillation or nonmigrainous headache. The Newcastle-Ottawa Scale was used to assess the quality of studies. RESULTS: Six studies were included, demonstrating a pooled prevalence of atrial fibrillation of 1.61% (95% confidence interval [CI] 0.51, 3.29) in migraine with aura and 1.32% (95% CI 0.17, 3.41) in migraine without aura. The overall prevalence of atrial fibrillation in migraine was 1.39% (95% CI 0.24, 3.46). CONCLUSION: In this systematic review and meta-analysis, the overall prevalence of atrial fibrillation in patients with migraine was low. Further studies are needed to clarify this relationship.

Predictors and outcomes of withholding and withdrawal of life-sustaining treatments in intensive care units in Singapore: a multicentre observational study.

BACKGROUND: Clinical practice guidelines on limitation of life-sustaining treatments (LST) in the intensive care unit (ICU), in the form of withholding or withdrawal of LST, state that there is no ethical difference between the two. Such statements are not uniformly accepted worldwide, and there are few studies on LST limitation in Asia. This study aimed to evaluate the predictors and outcomes of withholding and withdrawal of LST in Singapore, focusing on the similarities and differences between the two approaches. METHODS: This was a multicentre observational study of patients admitted to 21 adult ICUs across 9 public hospitals in Singapore over an average of three months per year from 2014 to 2019. The primary outcome measures were withholding and withdrawal of LST (cardiopulmonary resuscitation, invasive mechanical ventilation, and vasopressors/inotropes). The secondary outcome measure was hospital mortality. Multivariable generalised mixed model analysis was used to identify independent predictors for withdrawal and withholding of LST and if LST limitation predicts hospital mortality. RESULTS: There were 8907 patients and 9723 admissions. Of the former, 80.8% had no limitation of LST, 13.0% had LST withheld, and 6.2% had LST withdrawn. Common independent predictors for withholding and withdrawal were increasing age, absence of chronic kidney dialysis, greater dependence in activities of daily living, cardiopulmonary resuscitation before ICU admission, higher Acute Physiology and Chronic Health Evaluation (APACHE) II score, and higher level of care in the first 24 h of ICU admission. Additional predictors for withholding included being of Chinese race, the religions of Hinduism and Islam, malignancy, and chronic liver failure. The additional predictor for withdrawal was lower hospital paying class (with greater government subsidy for hospital bills). Hospital mortality in patients without LST limitation, with LST withholding, and with LST withdrawal was 10.6%, 82.1%, and 91.8%, respectively (p < 0.001). Withholding (odds ratio 13.822, 95% confidence interval 9.987-19.132) and withdrawal (odds ratio 38.319, 95% confidence interval 24.351-60.298) were both found to be independent predictors of hospital mortality on multivariable analysis. CONCLUSIONS: Differences in the independent predictors of withholding and withdrawal of LST exist. Even after accounting for baseline characteristics, both withholding and withdrawal of LST independently predict hospital mortality. Later mortality in patients who had LST withdrawn compared to withholding suggests that the decision to withdraw may be at the point when medical futility is recognised.