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This study aimed to report the real-world atrial fibrillation (AF) diagnostic yield of the implantable cardiac monitor (ICM) in patients with stroke or transient ischemic attack (TIA), and compare it to patients with an ICM for unexplained syncope.We used patient data from device clinics across the United States of America with ICM remote monitoring via PaceMate™, implanted for stroke or TIA, and unexplained syncope. Patients with known AF or atrial flutter were excluded. The outcome was AF lasting ≥2 min, adjudicated by International Board of Heart Rhythm Examiners certified cardiac device specialists.We included a total of 2469 patients, 51.1% with stroke or TIA (mean age: 69.7 [SD: 12.2] years, 41.1% female) and 48.9% with syncope (mean age: 67.0 [SD: 17.1] years, 59.4% female). The cumulative AF detection rate in patients with stroke or TIA was 5.5%, 8.9%, and 14.0% at 12, 24, and 36 months, respectively. The median episode duration was 73 (interquartile range: 10-456) min, ranging from 2 min to 40.9 days, with 52.3%, 28.6%, and 4.4% of episodes lasting at least 1, 6, and 24 h, respectively. AF detection was increased by age (adjusted hazard ratio [for every 1-year increase]: 1.024, 95% confidence interval: 1.008-1.040; p = .003), but was not influenced by sex (p = .089). For comparison, the cumulative detection rate at 12, 24, and 36 months were, respectively, 2.4%, 5.2%, and 7.4% in patients with syncope.Patients with stroke or TIA have a higher rate of AF detection. However, this real-world study shows significantly lower AF detection rates than what has been previously reported.

Aims This study aimed to investigate the impact of sex on the clinical profile, utilization of rhythm control therapies, cost of hospitalization, length of stay, and in-hospital mortality in patients admitted for atrial fibrillation (AF) in the United States. Methods and results We used data from the Nationwide Inpatient Sample for the year 2018. Regression analysis was performed to investigate differences between men and women. A P-value ≤ 0.05 was considered significant. We included 82592 patients with a primary diagnosis of of AF 50.8% women. Women were significantly older (mean age 74 vs. 67 years, P Conclusion There were differences in the risk profile, management, and outcomes between men and women hospitalized for AF. Further studies are needed to explore why women are treated differently regarding rhythm control procedures.

Aims The aim of this study is to summarize data from prospective cohort studies on clinical predictors of stroke and systemic embolism in anticoagulant-naïve atrial fibrillation (AF) patients. Methods and results EMBASE, MEDLINE, Global Index Medicus, and Web of Science were searched to identify all studies published by 28 November 2019. Forty-seven studies reporting data from 1 756 984 participants in 15 countries were included. The pooled incidence of stroke in anticoagulant-naïve AF patients was 23.8 per 1000 person-years (95% CI 19.7–28.2). Older age was associated with incident stroke or systemic embolism, with a pooled hazard ratio (HR) of 2.14 (95% CI 1.85–2.47), 2.83 (95% CI 2.27–3.51), and 6.87 (95% CI 6.33–7.44) for age 65–75, ≥75, and ≥85 years, respectively. Other predictors of stroke or systemic embolism included history of stroke or TIA (HR 2.84, 95% CI 2.19–3.67), hypertension (HR 1.60, 95% CI 1.37–1.86), diabetes (HR 1.28, 95% CI 1.20–1.37), heart failure (HR 1.25, 95% CI 1.11–1.40), peripheral artery disease (pooled HR 1.35, 95% CI 1.04–1.75), vascular disease (pooled HR 1.21, 95% CI 1.06–1.39), and prior myocardial infarction (pooled HR 1.08, 95% CI 1.03–1.14). Female sex was a predictor of thromboembolism in studies outside Asia (HR 1.35, 95% CI 1.15–1.59), but not in those done in Asia (HR 0.95, 95% CI 0.81–1.10). Conclusion This study confirms age and prior stroke as the strongest predictors of stroke or systemic embolism in anticoagulant-naive AF patients. Other predictors include hypertension, diabetes, heart failure, and vascular disease. Female sex seems not to be universally associated with stroke or systemic embolism.

Aims Our objective was to determine the ventricular arrhythmia burden in implantable cardioverter-defibrillator (ICD) patients during COVID-19. Methods and results In this multicentre, observational, cohort study over a 100-day period during the COVID-19 pandemic in the USA, we assessed ventricular arrhythmias in ICD patients from 20 centres in 13 states, via remote monitoring. Comparison was via a 100-day control period (late 2019) and seasonal control period (early 2019). The primary outcome was the impact of COVID-19 on ventricular arrhythmia burden. The secondary outcome was correlation with COVID-19 incidence. During the COVID-19 period, 5963 ICD patients underwent remote monitoring, with 16 942 episodes of treated ventricular arrhythmias (2.8 events per 100 patient-days). Ventricular arrhythmia burden progressively declined during COVID-19 (P < 0.001). The proportion of patients with ventricular arrhythmias amongst the high COVID-19 incidence states was significantly reduced compared with those in low incidence states [odds ratio 0.61, 95% confidence interval (CI) 0.54–0.69, P < 0.001]. Comparing patients remotely monitored during both COVID-19 and control periods (n = 2458), significantly fewer ventricular arrhythmias occurred during COVID-19 [incident rate ratio (IRR) 0.68, 95% CI 0.58–0.79, P < 0.001]. This difference persisted when comparing the 1719 patients monitored during both the COVID-19 and seasonal control periods (IRR 0.69, 95% CI 0.56–0.85, P < 0.001). Conclusions During COVID-19, there was a 32% reduction in ventricular arrhythmias needing device therapies, coinciding with measures of social isolation. There was a 39% reduction in the proportion of patients with ventricular arrhythmias in states with higher COVID-19 incidence. These findings highlight the potential role of real-life stressors in ventricular arrhythmia burden in individuals with ICDs. Trial registration Australian New Zealand Clinical Trial Registry; URL: https://www.anzctr.org.au/; Unique Identifier: ACTRN12620000641998, Graphical Abstract

Underrepresentation of females in randomized controlled trials (RCTs) limits generalizability and quality of the evidence guiding treatment of females. This study aimed to measure the sex disparities in participants' recruitment in RCTs of atrial fibrillation (AF) and determine associated factors, and to describe the frequency of outcomes reported by sex.MEDLINE was searched to identify RCTs of AF published between January 1, 2011, and November 20, 2021, in 12 top-tier journals. We measured the enrollment of females using the enrollment disparity difference (EDD) which is the difference between the proportion of females in the trial and the proportion of females with AF in the underlying general population (obtained from the Global Burden of Disease). Random-effects meta-analyses of the EDD were performed, and multivariable meta-regression was used to explore factors associated with disparity estimates. We also determined the proportion of trials that included sex-stratified results.Out of 1133 records screened, 142 trials were included, reporting on a total of 133 532 participants. The random-effects summary EDD was -0.125 (95% confidence interval [CI] = -0.143 to -0.108), indicating that females were under-enrolled by 12.5 percentage points. Female enrollment was higher in trials with higher sample size (250 vs.750, adjusted odds ratio [aOR] 1.065, 95% CI: 1.008-1.125), higher mean participants' age (aOR: 1.006, 95% CI: 1.002-1.009), and lower in trials conducted in North America compared to Europe (aOR: 0.945, 95% CI: 0.898-0.995). Only 36 trials (25.4%) reported outcomes by sex, and of these 29 (80.6%) performed statistical testing of the sex-by-treatment interaction.Females remain substantially less represented in RCTs of AF, and sex-stratified reporting of primary outcomes is infrequent. These findings call for urgent action to improve sex equity in enrollment and sex-stratified outcomes' reporting in RCTs of AF.

Chronological aging is one of the major risk factors of cardiovascular (CV) disease (CVD); however, the effect of biological aging on CVD and outcomes remain poorly understood. Herein, we evaluated the association between leukocyte telomere length (LTL), a marker of biological age, and CV outcomes.We searched PubMed, Embase, Ovid Medline, and Web of Science Core Collection for the studies on the association between LTL and myocardial infarction (MI), CV death, and/or CVD risk factors from inception to July 2020. Extracted data were pooled in a random-effects meta-analysis and summarized as risk ratio (RR) and corresponding 95% confidence interval (CI) per LTL tertile.A total of 32 studies (n = 144,610 participants) were included. In a pooled analysis of MI and LTL in a multivariate-adjusted model, the shortest LTL was associated with a 39% higher risk of MI (RR, 1.39; 95% CI, 1.16-1.67; P0.001). After adjusting for chronological age and traditional covariance, we showed a 28% increased risk of CV death in the shortest tertile of LTL (RR, 1.28; 95% CI, 1.05-1.56; P = 0.01). Analysis of the studies that investigated the association between CV risk factors and LTL (n = 7) showed that diabetes mellitus is associated with a 46% increased risk of LTL attrition (RR, 1.46; 95% CI, 1.46-2.09; P = 0.039).This study shows a strong association between LTL, a marker of biological aging, and the risk of MI and CV death. Cardiometabolic risk factors contribute to telomere attrition and therefore accelerates biological aging.

This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF).Efferent autonomic tone is not associated with atrial remodeling and AF persistence. However, the role of cardiac afferents is unknown.Individuals with nonpermanent AF (n = 48) were prospectively studied (23 in the in-AF group and 25 in sinus rhythm [SR]) with 12 matched control subjects. We performed: 1) low-level lower body negative pressure (LBNP), which decreases cardiac volume, offloading predominantly cardiac afferent (volume-sensitive) low-pressure baroreceptors; 2) Valsalva reflex (predominantly arterial high-pressure baroreceptors); and 3) isometric handgrip reflex (both baroreceptors). We measured beat-to-beat mean arterial pressure (MAP) and heart rate (HR). LBNP elicits reflex vasoconstriction, estimated using venous occlusion plethysmography-derived forearm blood flow (∝1/vascular resistance), maintaining MAP. To assess reversibility, we repeated LBNP (same day) after 1-hour low-level tragus stimulation (in n = 5 in the in-AF group and n = 10 in the in-SR group) and6 weeks post-cardioversion (n = 7).The 3 groups were well matched for age (59 ± 12 years, 83% male), body mass index, and risk factors (P = NS). The in-AF group had higher left atrial volume (P 0.001) and resting HR (P = 0.01) but similar MAP (P = 0.7). The normal LBNP vasoconstriction (-49 ± 5%) maintaining MAP (control subjects) was attenuated in the in-SR group (-12 ± 9%; P = 0.005) and dysfunctional in the in-AF group (+11 ± 6%; P 0.001), in which MAP decreased and HR was unchanged. Valsalva was normal throughout. Handgrip MAP response was lowest in the in-AF group (P = 0.01). Interestingly, low-level tragus stimulation and cardioversion improved LBNP vasoconstriction (-48 ± 15%; P = 0.04; and -32 ± 9%; P = 0.02, respectively).Cardiac afferent (volume-sensitive) reflexes are abnormal in AF patients during SR and dysfunctional during AF. This could contribute to AF progression, thus explaining "AF begets AF." (Characterisation of Autonomic function in Atrial Fibrillation [AF-AF Study]; ACTRN12619000186156).

Background Smoking cessation after a first cardiovascular event reduces the risk of recurrent vascular events and mortality. This systematic review and meta-analysis aimed to summarize data on the rates, predictors, and the impact of smoking cessation in patients after a stroke or transient ischemic attack (TIA). Methods MEDLINE, EMBASE and Web of Science were searched to identify all published studies providing relevant data through May 20, 2021. Random-effects meta-analysis method was used to pool proportions. Some findings were summarized narratively. Results Twenty-five studies were included. The pooled smoking cessation rates were 51.0% (8 studies, n = 1738) at 3 months, 44.4% (7 studies, n = 1920) at 6 months, 43.7% (12 studies, n = 1604) at 12 months, and 49.8% (8 studies, n = 2549) at 24 months or more of follow-up. Increased disability and intensive smoking cessation support programs were associated with a higher likelihood of smoking cessation, whereas alcohol consumption and depression had an inverse effect. Two studies showed that patients who quit smoking after a stroke or a TIA had substantially lower risk of recurrent stroke, death, and a composite of stroke, myocardial infarction, and death. Conclusion Smoking cessation in stroke survivors is associated with reduced recurrent vascular events and death. About half of smokers who experience a stroke or a TIA stop smoking afterwards. Those with low post-stroke disability, who consume alcohol, or have depression are less likely to quit. Intensive support programs can increase the likelihood of smoking cessation.

Aims The aim of this study is to determine the association between the coronavirus disease 2019 (COVID-19) pandemic and atrial fibrillation (AF) occurrence in individuals with cardiac implantable electronic devices (CIEDs). Method and results Multi-centre, observational, cohort study over a 100-day period during the COVID-19 pandemic (COVID-19) in the USA. Remote monitoring was used to assess AF episodes in patients with a CIED (pacemaker or defibrillator; 20 centres, 13 states). For comparison, the identical 100-day period in 2019 was used (Control). The primary outcomes were the AF burden during the COVID-19 pandemic, and the association of the pandemic with AF occurrence, as compared with 1 year prior. The secondary outcome was the association of AF occurrence with per-state COVID-19 prevalence. During COVID-19, 10 346 CIEDs with an atrial lead were monitored. There were 16 570 AF episodes of ≥6 min transmitted (16 events per 1000 patient days) with a significant increase in proportion of patients with AF episodes in high COVID-19 prevalence states compared with low prevalence states [odds ratio 1.34, 95% confidence interval (CI) 1.21–1.48, P, Graphical Abstract Graphical Abstract

Background: Atrial fibrillation (AF) is a growing global epidemic, with its prevalence expected to significantly rise over coming decades. AF poses a substantial burden on health care systems, largely due to hospitalizations. Home-based clinical characterization has demonstrated improved outcomes in cardiac populations, but its impact on AF remains poorly defined. To test this hypothesis in AF, we developed the Home-Based Education and Learning Program for Patients With Atrial Fibrillation (HELP-AF) study. Methods: The HELP-AF study is a prospective multicentre randomized controlled trial that will recruit 620 patients presenting to hospital emergency departments (EDs) with symptomatic AF (ANZCTR Registration: ACTRN12611000607976). Patients will be randomized to either the HELP-AF intervention or usual care. The intervention consists of 2 home visits by a nurse or pharmacist trained in the structured educational visiting (SEV) method. Patients in the control group will receive usual discharge follow-up care. Results: The primary endpoints are total unplanned hospital admissions and quality of life. Secondary endpoints include AF symptom severity and burden score; time to first hospital admission; total unplanned days in hospital; total AF-related hospital admissions (including atrial flutter); total cardiac and noncardiac hospital admissions; total AF- or atrial flutter-related; cardiac- and noncardiac-related ED presentations; and all-cause mortality. An economic evaluation will also be performed. Clinical endpoints will be adjudicated by independent blinded assessors. Follow-up will be at 24 months. Conclusions: This study will assess the efficacy of a home-based structured patient-centred educational intervention in patients with AF. Refereed/Peer-reviewed

To summarize data on the prevalence/incidence, risk factors and prognosis of atrial fibrillation (AF) in patients with acute pulmonary embolism (aPE).MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through December 12, 2021. Random-effects meta-analysis method was used to pool estimates.We included 27 studies reporting data from a pooled population of 819,380 patients. The prevalence rates were 11.3% for pre-existing AF, 4.7% for newly diagnosed AF, and 13.2% for prevalent (total) AF. Predictors of newly diagnosed AF (from one study) included congestive heart failure (adjusted odds ratio [aOR] 3.33, 95% CI: 1.81-6.12), ischemic heart disease (aOR 3.25, 95% CI: 1.65-6.39), massive PE (aOR 2.67, 95% CI: 1.19-5.99). Overall, AF was associated with increased risk of short-term (aOR 1.54, 95% CI: 1.44-1.64) and long-term mortality (aOR 1.58, 95% CI: 1.26-1.97). In subgroup analyses, all types of AF were associated with increased risk of short-term mortality: pre-existing AF (aOR 1.90, 95% CI: 1.59-2.27), newly diagnosed AF (aOR 1.51, 95% CI: 1.18-1.93), and prevalent AF (aOR 1.50, 95% CI: 1.42-1.60). Pre-existing AF (aOR 2.08, 95% CI: 1.27-3.42) and prevalent AF (aOR 1.29, 95% CI: 1.02-1.63) were also associated with higher long-term mortality.AF is present in about one in eight patients with aPE, and is associated with increased short- and long-term mortality. AF might improve risk stratification in patients with aPE.

BACKGROUND Atrial fibrillation (AF) screening using mobile single-lead electrocardiogram (ECG) devices has demonstrated variable sensitivity and specificity. However, limited data exists on the use of such devices in low-resource countries. OBJECTIVE The goal of the research was to evaluate the utility of the KardiaMobile device’s (AliveCor Inc) automated algorithm for AF screening in a semirural Ethiopian population. METHODS Analysis was performed on 30-second single-lead ECG tracings obtained using the KardiaMobile device from 1500 TEFF-AF (The Heart of Ethiopia: Focus on Atrial Fibrillation) study participants. We evaluated the performance of the KardiaMobile automated algorithm against cardiologists’ interpretations of 30-second single-lead ECG for AF screening. RESULTS A total of 1709 single-lead ECG tracings (including repeat tracing on 209 occasions) were analyzed from 1500 Ethiopians (63.53% [953/1500] male, mean age 35 [SD 13] years) who presented for AF screening. Initial successful rhythm decision (normal or possible AF) with one single-lead ECG tracing was lower with the KardiaMobile automated algorithm versus manual verification by cardiologists (1176/1500, 78.40%, vs 1455/1500, 97.00%; PP100 bpm; 167/408, 40.93%). The sensitivity and specificity of rhythm decision using KardiaMobile automated algorithm were 80.27% (1168/1455) and 82.22% (37/45), respectively. CONCLUSIONS The performance of the KardiaMobile automated algorithm was suboptimal when used for AF screening. However, the KardiaMobile single-lead ECG device remains an excellent AF screening tool with appropriate clinician input and repeat tracing. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12619001107112; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378057&isReview=true

Atrial fibrillation (AF) and carotid stenosis (CS) can coexist and this association has been reported to result in a higher risk of stroke than attributed to either condition alone. Here we aimed to summarize the data on the association of CS and AF. MEDLINE and Embase were searched to identify all published studies providing relevant data through February 27, 2020. Random-effects meta-analysis method was used to pool estimates of prevalence. Heterogeneity was assessed by mean I-squared statistic. Forty-eight studies were included, 20 reporting on the prevalence of carotid disease in a pooled population of 49,070 AF patients, and 28 on the prevalence of AF in a total of 2,288,265 patients with carotid disease. The pooled prevalence of CS in AF patients was 12.4% (95% confidence interval [CI] 8.7 to 16.0, I2 93%; n = 3,919), ranging from 4.4% to 24.3%. The pooled prevalence of carotid plaque was 48.4% (95% CI 35.2 to 61.7, I2 = 99%; n = 4292). The prevalence of AF in patients with CS was 9.3% (95% CI 8.7 to 10.0, I2 99%; n = 2,286,518), ranging from 3.6% to 10.0%. This prevalence was much higher (p 0.05). In conclusion, AF and CS frequently coexist, with about one in ten patients with AF having CS, and vice versa. In addition, nonstenotic carotid disease is present in about half of AF patients. These findings have important implications for AF screening in patients with CS, stroke prevention, and the opportunities to intervene on common risk factors.

Atrial fibrillation (AF) is increasingly recognized as the cardiac electrophysiologic manifestation of a multifactorial systemic disease. Several risk factors for development of AF have been identified; many are modifiable. There is evidence to suggest that aggressive management of modifiable risk factors has potential to significantly reduce the burden of AF, before and after AF ablation. Specific risk factor management (RFM) clinics have been shown effective in conferring these benefits into tangible improvements in large cohorts of patients. This review discusses the evidence behind RFM as a key adjunctive management strategy alongside AF ablation and suggests a model for RFM in clinics.

Background Atrial fibrillation (AF) screening using mobile single-lead electrocardiogram (ECG) devices has demonstrated variable sensitivity and specificity. However, limited data exists on the use of such devices in low-resource countries. Objective The goal of the research was to evaluate the utility of the KardiaMobile device’s (AliveCor Inc) automated algorithm for AF screening in a semirural Ethiopian population. Methods Analysis was performed on 30-second single-lead ECG tracings obtained using the KardiaMobile device from 1500 TEFF-AF (The Heart of Ethiopia: Focus on Atrial Fibrillation) study participants. We evaluated the performance of the KardiaMobile automated algorithm against cardiologists’ interpretations of 30-second single-lead ECG for AF screening. Results A total of 1709 single-lead ECG tracings (including repeat tracing on 209 occasions) were analyzed from 1500 Ethiopians (63.53% [953/1500] male, mean age 35 [SD 13] years) who presented for AF screening. Initial successful rhythm decision (normal or possible AF) with one single-lead ECG tracing was lower with the KardiaMobile automated algorithm versus manual verification by cardiologists (1176/1500, 78.40%, vs 1455/1500, 97.00%; P100 bpm; 167/408, 40.93%). The sensitivity and specificity of rhythm decision using KardiaMobile automated algorithm were 80.27% (1168/1455) and 82.22% (37/45), respectively. Conclusions The performance of the KardiaMobile automated algorithm was suboptimal when used for AF screening. However, the KardiaMobile single-lead ECG device remains an excellent AF screening tool with appropriate clinician input and repeat tracing. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12619001107112; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378057&isReview=true

Type 2 Diabetes Mellitus is a serious disease with a long duration and considerable associated morbidity. It affects a significant proportion of populations around the world irrespective of economic status and its prevalence is increasing despite the efforts of clinicians, researchers, public health professionals and policy makers. Most epidemiologic research has focused on exploring the risk factors associated with this disease. However the present research aims to increase understanding of the progression of the disease from initial diagnosis to death. Aims The aims of this thesis, from a clinical perspective, are to (a) evaluate the trajectory of blood pressure as the disease progresses from initial diagnosis to death in a large longitudinal database of newly diagnosed type 2 diabetes mellitus patients;, (b) within sub-cohorts based on body mass index at time of diagnosis, explore HbA1c trajectories from diagnosis to death, particularly the association with treatment intensity; (c) examine the 'obesity paradox'; and (d) investigate gender specific effects of smoking on the risks of cardiovascular diseases. In addition the thesis explores methodological issues arising with the use of large longitudinal datasets, in particular issues relating to missing data and the effectiveness of multiple imputation as a technique to correct for this. Methods and ResultsThe thesis has used a dataset of 84596 newly diagnosed type 2 diabetes mellitus patients diagnosed between 1 January 1990 and 31 December 2005 and followed until April 2007 derived from the United Kingdom Clinical Practice Research Datalink. Generalised estimating equation models were used to explore the longitudinal trajectories. Cox regression models were used to evaluate the gender specific effects of smoking and the obesity paradox in relation to mortality risks. Separate models were created for patients with and without cardiovascular diseases prior to diagnosis of type 2 diabetes mellitus. All models were adjusted for the effects of other potential confounding factors. Elevated HbA1c trajectories were associated with use of intensive medication irrespective of body mass index at the time of diagnosis. Patients with normal body mass index at the time of diagnosis had increased mortality risk compared to obese patients confirming the obesity paradox in type 2 diabetes mellitus. Those who died during the study had an elevated trajectory of blood pressure compared to those who remained alive and this was statistically significant, but not clinically significant. Elevated mortality risks were observed in those with higher and lower levels of systolic blood pressure compared to those with normal (130-139 mmHg). Considering diastolic blood pressure of 80-84 mmHg as the reference level, diabetic patients with higher levels had significantly increased mortality risk. Women who smoked had a higher risk of cardiovascular diseases and mortality than men who smoked. Conclusion Clinical management, which aims to maintain good control over glycemic and blood pressure levels in patients with newly diagnosed type 2 diabetes mellitus, is the most important approach to avoid or to delay potential complications and improve survival. Special attention should be given to women who smoke as they are exposed to increased risks of cardiovascular diseases and mortality. Normal weight patients may also need to be managed differently due to the implications of the obesity paradox. Individualised management of this disease by joint efforts of clinicians and patients is the most important step in curbing this 21st century epidemic.