Atrial fibrillation detection using insertable cardiac monitor after stroke: A real-world cohort study.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Decrement Evoked Potential (DEEP) Mapping of the Atria: Unmasking Atrial Fibrillation Substrate.

BACKGROUND: Atrial myopathy may underlie the progression of atrial fibrillation (AF) from a treatable disease to an irreversible condition with poor ablation outcomes. Electrophysiological methods to unmask areas prone to re-entry initiation could be key to defining latent atrial myopathy. METHODS: Consecutive patients referred for AF ablation were prospectively included at four institutions. Decrement evoked potential mapping (DEEP) was performed in eight left atrial sites and five right atrial sites, from two different pacing locations (endocardially from the left atrial appendage, epicardially from the proximal coronary sinus). The electrograms (EGMs) during S1 600 ms drive and after an extra stimulus (S2 at +30 ms above atrial refractoriness) were studied at each location and assessed for decremental properties. Follow-up was 12 months. RESULTS: Seventy-four patients were included and 85% had persistent AF. A total of 17,614 EGMs were individually analysed and measured. Nine percent of the EGMs showed DEEP properties (local delay of >10 ms after S2) with a mean decrement of 33±26 ms. DEEPs were more frequent in the left atrium than the right atrium (9.4% vs 8.0%; p<0.001) and more prevalent in persistent AF patients than paroxysmal AF patients (9.8% vs 4.6% p=0.001). Atrial DEEPs were more frequently unmasked in normal bipolar voltage areas and by epicardial pacing than endocardial pacing (9.6% vs 8.4%, respectively; p=0.004). Within the left atrium, the roof had the highest prevalence of DEEP EGMs. CONCLUSIONS: DEEP mapping of both atria is useful for highlighting areas with a tendency for unidirectional block and re-entry initiation. Those areas are more easily unmasked by epicardial pacing from the coronary sinus and more prevalent in persistent AF patients than in paroxysmal AF patients.

Sex disparities in enrollment and reporting of outcomes by sex in contemporary clinical trials of atrial fibrillation.

BACKGROUND: 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. METHODS: 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. 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. CONCLUSION: 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.

A meta-analysis of clinical risk factors for stroke in anticoagulant-naïve patients with atrial fibrillation.

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.

Rates, Predictors, and Impact of Smoking Cessation after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis.

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.

Late Potentials and Early Repolarisation Are Associated With Serious Mental Illness and May Portend Increased Arrhythmic Risk.

BACKGROUND: Patients with serious mental illness (SMI) have an increased risk of sudden death. Higher rates of signal-averaged electrocardiogram (SAECG) abnormal late potentials (LP), which may be a predictor of sudden death risk, have been shown in patients with schizophrenia. We aimed to assess the prevalence and predictors of electrocardiograph (ECG) and SAECG abnormalities in a mixed SMI population. METHODS: Consecutive consenting inpatients with SMI had 12-lead ECG and SAECG recorded in addition to demographics, diagnoses and medications. Standard criteria for abnormal SAECG were applied. Multivariate regression analysis was performed to determine predictors of SAECG abnormalities including diagnoses, body mass index, ECG parameters, psychotropic medication use, and medications associated with Long QT or Brugada syndromes. RESULTS: Eighty (80) patients, 49% male, mean age 39±17 years were included. SAECG criteria abnormality for 1, 2 or 3 criteria were seen in 19, 3 and 5 cases (34% in total) respectively. Early repolarisation pattern was seen in 19% of patients. SAECG abnormality was associated with male gender (OR 7.3; 95% CI 2.3-23.4), and schizophrenia/schizoaffective disorder diagnosis (OR 7.4; 95% CI 1.9-29.0), but not with medication type or dose. CONCLUSIONS: In the mixed SMI population studied, there was a high rate of SAECG-detected late potentials (34%) and early repolarisation pattern (19%). Schizophrenia/schizoaffective disorder diagnosis was the strongest multivariate predictor identified. Further studies are needed to define the mechanism and significance of these cardiac abnormalities in SMI patients.

Exercise echocardiography to assess left atrial function in patients with symptomatic AF.

Background: Left atrial (LA) function contributes to the augmentation of cardiac output during exercise. However, LA response to exercise in patients with atrial fibrillation (AF) is unknown. We explored the LA mechanical response to exercise and the association between LA dysfunction and exercise intolerance. Methods: We recruited consecutive patients with symptomatic AF and preserved left ventricular ejection fraction (LVEF). Participants underwent exercise echocardiography and cardiopulmonary exercise testing (CPET). Two-dimensional and speckle-tracking echocardiography were performed to assess LA function at rest and during exercise. Participants were grouped according to presenting rhythm (AF vs sinus rhythm). The relationship between LA function and cardiorespiratory fitness in patients maintaining SR was assessed using linear regression. Results: Of 177 consecutive symptomatic AF patients awaiting AF ablation, 105 met inclusion criteria; 31 (29.5 %) presented in AF whilst 74 (70.5 %) presented in SR. Patients in SR augmented LA function from rest to exercise, increasing LA emptying fraction (LAEF) and LA reservoir strain. In contrast, patients in AF demonstrated reduced LAEF and reservoir strain at rest, with failure to augment either parameter during exercise. This was associated with reduced VO2Peak compared to those in SR (18.4 ± 5.6 vs 22.5 ± 7.7 ml/kg/min, p = 0.003). In patients maintaining SR, LAEF and reservoir strain at rest and during exercise were associated with VO2Peak, independent of LV function. Conclusion: The maintenance of SR in patients with AF is associated with greater LA reservoir function at rest and greater augmentation with exercise compared to patients in AF. In patients in SR, reduced LA function is associated with reduced exercise tolerance, independent of LV function.

Structural, Functional, and Electrical Remodeling of the Atria With Reduced Cardiorespiratory Fitness: Implications for AF.

BACKGROUND: Reduced cardiorespiratory fitness (CRF) is an independent risk factor for the progression of atrial fibrillation (AF). We hypothesized that reduced CRF is associated with structural, functional, and electrical remodeling of the left atrium. OBJECTIVES: This study sought to correlate objectively assessed CRF with functional and electrical left atrial (LA) parameters using invasive and noninvasive assessments. METHODS: Consecutive patients with symptomatic AF undergoing catheter ablation were recruited. CRF was objectively quantified pre-ablation by using cardiopulmonary exercise testing. Using peak oxygen consumption, participants were classified as preserved CRF (>20 mL/kg/min) or reduced CRF (<20 mL/kg/min). LA stiffness was assessed invasively with hemodynamic monitoring and imaging during high-volume LA saline infusion. LA stiffness was calculated as ΔLA diameter/ΔLA pressure over the course of the infusion. LA function was assessed with echocardiographic measures of LA emptying fraction and LA strain. Electrical remodeling was assessed by using high-density electroanatomical maps for LA voltage and conduction. RESULTS: In total, 100 participants were recruited; 43 had reduced CRF and 57 had preserved CRF. Patients with reduced CRF displayed elevated LA stiffness (P = 0.004), reduced LA emptying fraction (P = 0.006), and reduced LA reservoir strain (P < 0.001). Reduced CRF was also associated with reduced LA voltage (P = 0.039) with greater heterogeneity (P = 0.027) and conduction slowing (P = 0.04) with greater conduction heterogeneity (P = 0.02). On multivariable analysis, peak oxygen consumption was independently associated with LA stiffness (P = 0.003) and LA conduction velocities (P = 0.04). CONCLUSIONS: Reduced CRF in patients with AF is independently associated with worse LA disease involving functional and electrical changes. Improving CRF may be a target for restoring LA function in AF.

Utility and Validity of the HFA-PEFF and H2FPEF Scores in Patients With Symptomatic Atrial Fibrillation.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with atrial fibrillation (AF) represents a significant clinical challenge. Two diagnostic scoring tools have been developed to aid the noninvasive diagnosis of HFpEF: the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology) and the H2FPEF scoring systems. OBJECTIVES: The purpose of this study was to evaluate the performance of these 2 scoring tools for the diagnosis of HFpEF against a gold standard of invasive evaluation in a cohort of patients with AF. METHODS: The authors recruited consecutive patients with symptomatic AF and preserved ejection fraction who were scheduled for an AF ablation procedure. Gold-standard invasive diagnosis of HFpEF was performed at the AF ablation procedure using mean left atrial pressure at rest and following infusion of 500 mL fluid. Each participant was scored according to the noninvasive HFA-PEFF and H2FPEF scoring systems. Sensitivity and specificity analyses were performed to assess the accuracy of these scoring systems in diagnosing HFpEF. RESULTS: In total, 120 participants were recruited. HFpEF was diagnosed invasively in 88 (73.3%) participants, whereas 32 (26.7%) had no HFpEF. Using the HFA-PEFF score, 38 (31.7%) participants had a high probability of HFpEF and 82 (68.3%) had low/intermediate probability of HFpEF. Using the H2FPEF tool, 72 (60%) participants had a high probability of HFpEF and 48 (40%) had intermediate probability. A high HFA-PEFF (≥5 points) score could diagnose HFpEF with a sensitivity of 40% and a specificity of 91%, and a high H2FPEF score (≥6 points) could diagnose HFpEF with a sensitivity of 69% and specificity of 66%. Overall diagnostic accuracy was similar using both tools (AUC: 0.663 vs 0.707, respectively; P = 0.636). CONCLUSIONS: Against a gold standard of invasively diagnosed HFpEF, the HFA-PEFF and H2FPEF scores demonstrate only moderate accuracy in patients with AF and should be utilized with caution in this cohort of patients. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).

Social impact bonds and their application to preventive health.

Although preventive health in Australia has been acknowledged as central to national health and wellbeing, efforts to reform the delivery of preventive health have to date produced limited results. The financing of preventive health at a national level is based on outcome- or performance-based funding mechanisms; however, delivery of interventions and activities at a state level have not been subjected to outcome-based funding processes. A new financing tool being applied in the area of social services (social impact bonds) has emerged as a possible model for application in the prevention arena. This paper explores key issues in the consideration of this funding model in the prevention arena. When preventive health is conceptualised as a merit good, the role of government is clarified and outcome measures fully articulated, social impact bonds may be a viable funding option to supplement core public health activities. WHAT IS KNOWN ABOUT THE TOPIC? The complexities of outcome monitoring in preventive health are well understood.Likewise, the problem of linking funding to outcomes from preventive health practice has also been debated at length in health policy. However, not much is known about the application of social impact bonds into the preventive health arena.WHAT DOES THIS PAPER ADD? This paper discusses the limitations and opportunities facing the application of the social impact bond financing model in the preventive health arena. This has not been undertaken previously.WHAT ARE THE IMPLICATIONS FOR PRACTITIONERS? Social impact bonds have received significant recent attention from federal and state government treasury departments as potential financing tools for government. Health policy practitioners are watching this space very closely to see the outcomes of a New South Wales trial. Health promotion practitioners and primary care practitioners who deliver preventive services will need to keep abreast of this issue as it will have significant impact on their practice if states and territories introduce outcome-based funding processes.

Identification of Subclinical Heart Failure With Preserved Ejection Fraction in Patients With Symptomatic Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. We hypothesize that patients with symptomatic AF but without overt clinical HF commonly exhibit subclinical HFpEF according to established hemodynamic criteria. OBJECTIVES: The authors sought to use invasive hemodynamics to investigate the prevalence and implications of subclinical HFpEF in AF ablation patients. METHODS: Consecutive symptomatic AF ablation patients were prospectively recruited. Diagnosis of subclinical HFpEF was undertaken by invasive assessment of left atrial pressure (LAP). Participants had HFpEF if the baseline mean LAP was >15 mm Hg and early HFpEF if the mean LAP was >15 mm Hg after a 500-mL fluid challenge. LA compliance was assessed invasively by monitoring the LAP and LA diameter during direct LA infusion of 15 mL/kg normal saline. LA compliance was calculated as Δ LA diameter/ΔLAP. LA cardiomyopathy was further studied with exercise echocardiography and electrophysiology study. Functional impact was evaluated using cardiopulmonary exercise testing and the AF Symptom Severity questionnaire. RESULTS: Of 120 participants, 57 (47.5%) had HFpEF, 31 (25.8%) had early HFpEF, and 32 (26.7%) had no HFpEF. Both HFpEF and early HFpEF were associated with lower LA compliance compared with those without HFpEF (P < 0.001). Participants with HFpEF and early HFpEF also displayed decreased LA emptying fraction (P = 0.004), decreased LA voltage (P = 0.001), decreased VO2peak (P < 0.001), and increased AF symptom burden (P = 0.002) compared with those without HFpEF. CONCLUSIONS: Subclinical HFpEF is common in AF ablation patients and is characterized by a LA cardiomyopathy, decreased cardiopulmonary reserve and increased symptom burden. The diagnosis of HFpEF may identify patients with AF with the potential to benefit from novel HFpEF therapies. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).

Lifestyle Modification and Atrial Fibrillation: Critical Care for Successful Ablation.

Management of atrial fibrillation (AF) requires a comprehensive approach due to the limited success of medical or procedural approaches in isolation. Multiple modifiable risk factors contribute to the development and progression of the underlying substrate, with a heightened risk of progression evident with inadequate risk factor management. With increased mortality, stroke, heart failure and healthcare utilisation linked to AF, international guidelines now strongly support risk factor modification as a critical pillar of AF care due to evidence demonstrating the efficacy of this approach. Effective lifestyle management is key to arrest and reverse the progression of AF, in addition to increasing the likelihood of freedom from arrhythmia following catheter ablation.

Sex differences in clinical profile, management, and outcomes of patients hospitalized for atrial fibrillation in the United States.

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 < 0.001) and had a higher CHA2DS2-VASc score (median 4 vs. 2, P < 0.001) than men. Women had relatively higher in-hospital mortality (0.9% vs. 0.8%, P = 0.070); however, after adjustment for known risk factors female sex was no longer a predictor of mortality (P = 0.199). In sex-specific regression analyses, increased age, chronic obstructive pulmonary disease, previous stroke, heart failure, and chronic kidney disease were risk factors for in-hospital mortality in both sexes, vascular disease only in women, and race and alcohol abuse only in men. After adjusting for potential confounders, female sex was associated with lower likelihood of receiving catheter ablation [adjusted odds ratio (aOR) 0.69, 95% confidence interval (CI) 0.64-0.74] and electrical cardioversion (aOR 0.69, 95% CI 0.67-0.72), and with longer hospitalization (aOR 1.33, 95% CI 1.28-1.37), whereas sex had no influence on hospitalization costs (P = 0.339). 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.

Frequency and prognostic significance of atrial fibrillation in acute pulmonary embolism: A pooled analysis.

OBJECTIVE: To summarize data on the prevalence/incidence, risk factors and prognosis of atrial fibrillation (AF) in patients with acute pulmonary embolism (aPE). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Trace residue identification, characterization, and longitudinal monitoring of the novel synthetic opioid ß-U10, from discarded drug paraphernalia.

Empirical data regarding dynamic alterations in illicit drug supply markets in response to the COVID-19 pandemic, including the potential for introduction of novel drug substances and/or increased poly-drug combination use at the "street" level, that is, directly proximal to the point of consumption, are currently lacking. Here, a high-throughput strategy employing ambient ionization-mass spectrometry is described for the trace residue identification, characterization, and longitudinal monitoring of illicit drug substances found within >6,600 discarded drug paraphernalia (DDP) samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia from August 2020 to February 2021, while significant COVID-19 lockdown conditions were imposed. The utility of this approach is demonstrated for the de novo identification and structural characterization of ß-U10, a previously unreported naphthamide analog within the "U-series" of synthetic opioid drugs, including differentiation from its α-U10 isomer without need for sample preparation or chromatographic separation prior to analysis. Notably, ß-U10 was observed with 23 other drug substances, most commonly in temporally distinct clusters with heroin, etizolam, and diphenhydramine, and in a total of 182 different poly-drug combinations. Longitudinal monitoring of the number and weekly "average signal intensity" (ASI) values of identified substances, developed here as a semi-quantitative proxy indicator of changes in availability, relative purity and compositions of street level drug samples, revealed that increases in the number of identifications and ASI for ß-U10 and etizolam coincided with a 50% decrease in the number of positive detections and an order of magnitude decrease in the ASI for heroin.

Autonomic Afferent Dysregulation in Atrial Fibrillation.

OBJECTIVES: This study sought to evaluate the role of cardiac afferent reflexes in atrial fibrillation (AF). BACKGROUND: Efferent autonomic tone is not associated with atrial remodeling and AF persistence. However, the role of cardiac afferents is unknown. METHODS: 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) and >6 weeks post-cardioversion (n = 7). RESULTS: 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). CONCLUSIONS: 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).

Stroke risk associated with carotid and aortic atherosclerosis in patients with atrial fibrillation: A systematic review.

OBJECTIVE: This review aimed to summarize the evidence on the risk of thromboembolism associated with carotid and aortic atherosclerosis in patients with AF, and the potential impact of their inclusion in current stroke risk stratification scores. METHODS: MEDLINE, Web of Science and EMBASE were systematically searched to identify all published studies providing relevant data through 28 February 2021. RESULTS: We identified 10 eligible studies. There was high heterogeneity across studies, precluding a meta-analysis. Carotid stenosis was not associated with incident ischemic stroke in three prospective studies, including the SPAF II trial and the ROCKET-AF trial. An association between carotid stenosis and thromboembolism was found in two studies, with a potential reporting bias due to their retrospective design. The evidence suggesting that carotid plaque predicts stroke or transient ischemic attack in AF patients were more consistent in the four studies evaluating this association. The inclusion of carotid plaque and carotid intima-media thickness (cIMT) into stroke risk stratification tools for AF patients improved their performance. Data on the association of aortic plaque with thromboembolism is scarce in patients with AF. The two studies reporting on this association suggest that aortic plaque alone does not predict incident ischemic stroke. CONCLUSION: Available data suggest an association of carotid atherosclerosis with the risk of stroke and transient ischemic attack in patients with AF. Future studies should evaluate whether incorporating cIMT and characteristics of carotid and aortic plaques into scoring systems would improve stroke prediction and prevention in patients with AF.

Rhythm monitoring strategies for atrial fibrillation detection in patients with cryptogenic stroke: A systematic review and meta-analysis.

OBJECTIVE: To summarize data on atrial fibrillation (AF) detection rates and predictors across different rhythm monitoring strategies in patients with cryptogenic stroke (CS) or embolic stroke of undetermined source (ESUS). METHODS: MEDLINE, Embase, and Web of Science were searched to identify all published studies providing relevant data through July 6, 2020. Random-effects meta-analysis method was used to pool estimates. RESULTS: We included 47 studies reporting on a pooled population of 8,215 patients with CS or ESUS. Using implantable cardiac monitor (ICM), the pooled rate of AF was 12.2% (95% CI 9.4-15.0) at 3 months, 16.0% (95% CI 13.2-18.8) at 6 months, 18.7% (95% CI 15.7-21.7) at 12 months, 22.8% (95% CI 19.1-26.5) at 24 months, and 28.5% (95% CI 17.6-39.3) at 36 months. AF rates were significantly higher in patients with ESUS vs CS (22.0% vs 14.2%; p < 0.001) at 6 months, and in studies using Reveal LINQ vs Reveal XT ICM (19.1% vs 13.0%; p = 0.001) at 12 months. Using mobile cardiac outpatient telemetry (MCOT), the pooled rate of AF was 13.7% (95% CI 10.2-17.2) at 1 month. Predictors of AF detection with ICM included older age, CHA2DS2-VASc score, left atrial enlargement, P wave maximal duration and prolonged PR interval. CONCLUSION: The yield of ICM increases with the duration of monitoring. More than a quarter of patients with CS or ESUS will be diagnosed with AF during follow-up. About one in seven patients had AF detected within a month of MCOT, suggesting that a non-invasive rhythm monitoring strategy should be considered before invasive monitoring.

Meta-Analysis Comparing the Frequency of Carotid Artery Stenosis in Patients With Atrial Fibrillation and Vice Versa.

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 <0.001) in patients undergoing carotid artery stenting (12.7%, 95% CI 11.3 to 14.02, I2 38.3%) compared with those undergoing carotid endarterectomy (6.9%, 95% CI 8.3 to 10.4, I2 94.1%). There was no difference in AF prevalence between patients with CS, with and without previous cerebrovascular event (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.