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Sidney Aung,1 Eric Vittinghoff,2 Gregory Nah,1 Noah D Peyser,1 Mark J Pletcher,2 Jeffrey E Olgin,1 Gregory M Marcus1 1Division of Cardiology, University of California, San Francisco, San Francisco, CA, USA; 2Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USACorrespondence: Gregory M MarcusUniversity of California, San Francisco, 505 Parnassus Ave, M1180B, San Francisco, CA, 94143, USATel +1 415-476-3450Fax +1 415-476-6260Email greg.marcus@ucsf.eduIntroduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (Covid-19), has been a serious threat to global health. Previous work has focused primarily on hospitalized patients or on identifying risk factors for disease severity and mortality once the infection has taken place. We sought to leverage the ubiquity of smartphones and mobile applications to study risk factors for Covid-19 infection in a large, geographically heterogenous cohort.Methods: We analyzed data obtained from the Covid-19 Citizen Science (CCS) Study, a worldwide, mobile application-based cohort. After employing forward selection to identify variables with p values < 0.1, multivariable logistic regression models were utilized to identify independent risk factors associated with prevalent SARS-CoV-2 infection.Results: Among 36,041 participants in 113 countries and all 50 states in the US, 484 participants had prevalent SARS-CoV-2 infection. After multivariable adjustment, being a healthcare worker, living with at least one school-aged child, having pets at home, and having immunodeficiency were each associated with an increased odds of SARS-CoV-2. The association between pets and prevalent SARS-CoV-2 was driven by dog ownership. After adjustment for the same covariates, Asian or Pacific Islander race, receiving a flu shot within the past year, increased level of education, and smoking or vaping marijuana within the last 30 days were each associated with a lower odds of SARS-CoV-2.Conclusion: We identified various characteristics and behaviors, many of which are potentially modifiable, associated with prevalent SARS-CoV-2 infection in a world-wide mobile application-based cohort.Keywords: COVID-19, epidemiology, cohort study, digital health, mobile applications

Disability measures in multiple sclerosis (MS) rely heavily on ambulatory function, and current metrics fail to capture potentially important variability in walking behavior. We sought to determine whether remote step count monitoring using a consumer-friendly accelerometer (Fitbit Flex) can enhance MS disability assessment. 99 adults with relapsing or progressive MS able to walk ≥2-min were prospectively recruited. At 4 weeks, study retention was 97% and median Fitbit use was 97% of days. Substudy validation resulted in high interclass correlations between Fitbit, ActiGraph and manual step count tally during a 2-minute walk test, and between Fitbit and ActiGraph (ICC = 0.76) during 7-day home monitoring. Over 4 weeks of continuous monitoring, daily steps were lower in progressive versus relapsing MS (mean difference 2546 steps, p

Atrial flutter ablation is associated with a high rate of acute procedural success and symptom improvement. The relationship between ablation and other clinical outcomes has been limited to small studies primarily conducted at academic centers. We sought t

BackgroundGenome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans.ObjectiveTo identify novel genetic variants associated with resting heart rate in African Americans.MethodsTen cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)).ResultsFourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans.ConclusionsAn intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Implantable cardioverter-defibrillators (ICDs) are placed in patients at risk for sudden cardiac death, but the procedure may cause adverse events. Patient body habitus may be an important factor responsible for ICD implantation complications. We assessed

Background: Atrial fibrillation (AF) may be due to an inherited trait, particularly in lone AF patients. A family history of AF in lone AF patients has not previously been compared with a family history of patients with AF and established risk factors (non-lone AF).Objective: The purpose of this study was to compare the frequency of having a first-degree relative with AF in lone and non-lone AF patients.Methods: We performed a case-control study of consecutive subjects presenting to a single electrophysiology laboratory. A convenience sample of subjects with no known arrhythmias was also enrolled.Results: Four hundred twenty-nine subjects were enrolled: 136 had AF (54 with lone AF), 84 had atrial flutter, 158 had other supraventricular arrhythmias, and 51 had no known arrhythmias. Significantly more subjects with AF reported a first-degree family history of AF compared with the remainder of the cohort (25% vs. 5%; P <.001). In multivariable analysis adjusting for potential confounders, AF patients had a 6-fold greater odds of having a family member with AF (95% confidence interval [CI] 2.93-12.7; P <.001). Lone AF patients had a first-degree family member with AF substantially more often than those with non-lone AF (41% vs. 14%; P <.001). After adjusting for potential confounders, lone AF patients remained significantly more likely than other AF patients to have a first-degree relative with AF (OR 7.2; 95% CI 2.1-24.7; P = .002).Conclusion: Lone AF patients have a first-degree family member with AF substantially more often than other AF patients. This suggests that an inherited trait may be particularly important in this subgroup of patients. [ABSTRACT FROM AUTHOR]

Background: Systolic time intervals measured by echocardiography and carotid artery tracings are validated methods of assessing left ventricular function. However, the clinical utility of phonoelectrocardiographic systolic time intervals for predicting heart failure using newer technology has not been evaluated.Methods: We enrolled 100 adult patients undergoing left heart catheterization. Participants underwent computerized phonoelectrocardiographic analysis, left ventricular end-diastolic pressure (LVEDP) measurement, transthoracic echocardiographic measurement of left ventricular ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. The heart rate-adjusted systolic time intervals included the time from the Q wave onset to peak S1 (electromechanical activation time, EMAT), Q wave onset to peak S2 (electromechanical systole, Q-S2), and peak S1 to peak S2 (left ventricular systolic time, LVST). Left ventricular dysfunction was defined as the presence of both LVEDP >15 mmHg and LVEF <50%.Results: EMAT (r =-0.51; P < 0.0001), EMAT/LVST (r =-0.41; P = 0.0001), and Q-S2 (r =-0.39; P = 0.0003) correlated with LVEF, but not with LVEDP. An abnormal EMAT > or =15 (odds ratio 1.38, P < 0.0001) and EMAT/LVST > or =0.40 (OR 1.13, P = 0.002) were associated with left ventricular dysfunction. EMAT > or =15 had 44% sensitivity, 94% specificity, and a 7.0 likelihood ratio for left ventricular dysfunction, while EMAT/LVST > or =0.40 had 55% sensitivity, 95% specificity, and a 11.7 likelihood ratio. In patients with an intermediate BNP (100-500 pg/mL), the likelihood ratio increased from 1.1 using the BNP result alone to 11.0 when adding a positive EMAT test for predicting left ventricular dysfunction.Conclusions: Phonoelectrocardiographic measures of systolic time intervals are insensitive but highly specific tests for detecting abnormalities in objective markers of left ventricular function. EMAT and EMAT/LVST provide diagnostic information independent of BNP for detecting patients with left ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Background: Previous studies relying on clinical care data have suggested that atrial fibrillation is less common in African Americans than Caucasians, but the mechanism remains unknown. Clinical care may itself vary by race, potentially affecting the accuracy of atrial fibrillation ascertainment in studies relying on clinical data. We sought to examine racial differences in atrial fibrillation prevalence determined by protocol-driven electrocardiograms (ECGs) obtained in prospective cohort studies and to study racial differences in echocardiographic characteristics.Methods: We pooled primary data from 3 cohort studies with atrial fibrillation adjudicated from study protocol ECGs and documentation of potentially important confounders: the Heart and Soul Study (n=1014), the Heart and Estrogen-Progestin Replacement Study (n=2673), and The Osteoporotic Fractures in Men Sleep Study (n=2911). Left atrial anatomic dimensions were compared among races from sinus rhythm echocardiograms in the Heart and Soul Study.Results: Of the 6611 participants, 268 (4%) had atrial fibrillation: Caucasians had the highest prevalence (5%), and African Americans had the lowest (1%; P<.001 for each compared with all other races). After adjustment for potential confounders, Caucasians had a 3.8-fold greater odds of having atrial fibrillation than African Americans (95% confidence interval, 1.6-8.8, P=.002). Although ventricular and atrial volumes and function were similar in Caucasians and African Americans, Caucasians had a 2 mm larger anterior-posterior left atrial diameter after adjusting for potential confounders (95% confidence interval, 1-3 mm, P<.001).Conclusion: ECG confirmed atrial fibrillation is more common in Caucasians than in African Americans, which might be related to the larger left atrial diameter observed in Caucasians. [ABSTRACT FROM AUTHOR]

Background: The epidemiology of atrial fibrillation (AF)-associated thromboembolic complications outside of ischemic strokes has not been thoroughly elucidated., Objective: The aim of this study was to describe the epidemiology of AF-associated systemic infarcts and relevant interactions by sex and race/ethnicity., Methods: Using the Office of Statewide Health Planning and Development, we performed a longitudinal analysis of patients aged ≥18 years who received ambulatory surgery, emergency, or inpatient medical care in California between 2005 and 2015. We determined the distribution of infarct locations and risks of systemic infarcts for patients with AF. Interaction analyses by sex and race/ethnicity were conducted., Results: Of 1,321,694 patients with AF, the average annual rate of systemic infarct was 2.1% ± 0.18% compared with 0.56% ± 0.06% in the 22,944,488 patients without AF. The increased frequency of these infarcts was observed for every body area investigated. After adjustment for potential confounders and mediators, patients with AF experienced a 45% increased risk of a systemic infarct (hazard ratio, 1.45; 95% confidence interval, 1.44-1.47; P < .001). Women, Asians, Blacks, and Hispanics each exhibited a statistically significant heightened relative risk of systemic infarcts in the presence of AF., Conclusion: AF increases the risk of infarcts throughout the body. Susceptibility to these systemic infarcts varies by sex and race/ethnicity in patterns similar to differential risks for stroke. The presence of a systemic infarct in the absence of a clear cause should raise suspicion for AF, and the potential benefits of AF prevention and anticoagulation should be considered beyond only infarcts to the brain., Competing Interests: Disclosures Dr Marcus receives research funding from the National Institutes of Health and PCORI and is a consultant for and holds equity in InCarda. The remaining authors have nothing to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Prevalence estimates of atrial fibrillation (AF) from large populations have not been updated for >2 decades. Using data from 1996 to 1997, a previous study projected that there would be 3.3 million adults with AF in the United States in 2020., Objectives: The purpose of this study was to determine the contemporary age-, sex-, and race-standardized prevalence and the number of adults with diagnosed AF in the United States., Methods: We merged California's state-wide health care databases to assemble a cohort of adults aged ≥20 years who received hospital-based care in California from 2005 to 2019. International Classification of Diseases codes were used to identify AF and other comorbidities. After accounting for deaths, we utilized the U.S. Census to calculate the national age-, sex-, and race-standardized estimates of diagnosed AF., Results: Of 29,250,310 patients (mean age 50.6 ± 19.8 years, 53.8% women, 50.1% White), 2,003,867 (6.8%) had an AF diagnosis. The proportion of patients with diagnosed AF increased from 4.49% in 2005 to 2009 to 6.82% in 2015 to 2019. Over time, AF patients became relatively younger, were less likely to be female or White, and were more likely to have hypertension and diabetes. Standardizing based on age-, sex-, race-, and ethnicity-based proportions to the U.S. population, we estimate that the current national prevalence of diagnosed AF is at least 10.55 million (95% CI: 10.48-10.62 million), comprising 4.48% (95% CI: 4.47%-4.49%) of the adult population., Conclusions: The prevalence of diagnosed AF in the United States is higher than previously estimated. More efficient prevention and treatment strategies are needed to curb the burden of AF in the United States., Competing Interests: Funding Support and Author Disclosures This study was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute, Grant R01HL158825-01 (to Dr Marcus). Dr Marcus has received funding from the National Institutes of Health, PCORI, and the California Department of Cannabis Control; and is a consultant for and equity holder in InCarda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Ischemic heart disease (IHD) has been linked to an increased risk of atrial fibrillation (AF). However, data are sparse regarding the role of IHD in AF recurrence after catheter ablation., Objective: We sought to investigate whether preexisting or new-onset IHD is associated with a greater risk of AF recurrence after ablation., Methods: With use of Danish nationwide registries, all patients undergoing first-time AF ablation in Denmark from 2010 to 2020 were identified. The primary outcome was AF recurrence defined by AF-related hospital admission or antiarrhythmic drug use within 1 year after ablation excluding a 3-month blanking period. IHD was defined as an International Classification of Diseases, Tenth Revision diagnosis of IHD or prior coronary revascularization., Results: Of 12,162 patients undergoing first-time ablation for AF (mean age, 62 years; 30% female), 20% had preexisting IHD. Preexisting IHD was associated with an increased risk of AF recurrence in univariable log-binomial logistic regression (relative risk, 1.09; 95% CI, 1.04-1.14; P < .001). However, after multivariable adjustment including procedural year, preexisting IHD was no longer associated with an increased risk of AF recurrence (relative risk, 1.02; 95% CI, 0.97-1.06; P = .42). In a nested case-control study of those without preexisting IHD before ablation (n = 9778), newly diagnosed IHD after ablation was associated with an increased risk of AF recurrence in multivariable analysis (hazard ratio, 3.03; 95% CI, 1.84-4.99; P < .001)., Conclusion: The presence of IHD does not appear to reduce the effectiveness of AF ablation procedures. However, the emergence of IHD after AF ablation may serve as a trigger for AF that is insufficiently suppressed by prior ablation., Competing Interests: Disclosures T.B.-S.: steering committee member of the Amgen-financed GALACTIC-HF trial; steering committee member of the Boehringer Ingelheim–financed SHARP3 trial; chief investigator of the Boston Scientific–financed DANLOGIC-HF trial; chief investigator of the Sanofi Pasteur–financed NUDGE-FLU trial; chief investigator of the Sanofi Pasteur–financed DANFLU-1 trial; chief investigator of the Sanofi Pasteur–financed DANFLU-2 trial; steering committee member of LUX-Dx TRENDS Evaluates Diagnostics Sensors in Heart Failure Patients Receiving Boston Scientific's Investigational ICM System trial; advisory board: Sanofi Pasteur, Amgen, CSL Seqirus, and GSK; speaker honorarium: Bayer, Novartis, Sanofi Pasteur, GE Healthcare, and GSK; research grants: Boston Scientific, GE Healthcare, AstraZeneca, Novo Nordisk, and Sanofi Pasteur; consultant appointments: Novo Nordisk, IQVIA, and Parexel. All other authors report that they have no relevant conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Although smoking heightens the risk of AF, it remains unknown if that risk is amenable to modification after smoking cessation., Objectives: This study sought to evaluate the association between smoking cessation and atrial fibrillation (AF) risk in a large longitudinal cohort., Methods: After excluding those with prevalent AF and no history of smoking at baseline, we evaluated 146,772 UK Biobank participants with serial smoking assessments. We compared AF risk between former smokers at baseline and those who quit smoking during the study to current smokers. Incident AF was ascertained from outpatient and inpatient encounters and identified using International Classification of Diseases codes. Cox models were used to compare the risk of incident AF among current and former smokers as well as those who quit smoking during the study while controlling for age, sex, race, body mass index, education, cardiovascular comorbidities, alcohol use, and pack-years., Results: Among the 146,772 participants (48.3% female; age: 57.3 ± 7.9 years), 37,377 (25.5%) currently smoked; 105,429 (72.0%) were former smokers; and 3,966 (2.7%) quit smoking during the study. Over a mean 12.7 ± 2.0 years of follow-up, 11,214 (7.6%) participants developed AF. Compared to current smokers, the adjusted risk of AF was 13% lower in former smokers (HR: 0.87; 95% CI: 0.83-0.91) and 18% lower in those who quit smoking during the study (HR: 0.82; 95% CI: 0.70-0.95)., Conclusions: Compared to those who continue to smoke, smoking cessation was associated with a lower risk of AF., Competing Interests: Funding Support and Author Disclosures This research was conducted using the UK Biobank resource. UK Biobank is supported by its founding funders the Wellcome Trust and UK Medical Research Council, as well as the British Heart Foundation, Cancer Research UK, Department of Health, Northwest Regional Development Agency, and Scottish Government. Dr Marcus receives funding from the National Institutes of Health, Patient-Centered Outcomes Research Institute, and California Tobacco-Related Disease Research Program and is a consultant for and owns equity in InCarda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures G. Marcus is a consultant for InCarda and has equity in InCarda. K. Pundi is a consultant for Evidently and iRhythm.

Competing Interests: Disclosures Dr Marcus reports receiving funding from the National Institutes of Health, PCORI, and the California Department of Cannabis Control; he is a consultant for and holds equity in InCarda.

Developed in partnership with the European Heart Rhythm Association (EHRA), (a registered branch of the European Society of Cardiology (ESC)) the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin America Heart Rhythm Society (LAHRS)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Substantial data support a heritable basis for supraventricular tachycardias, but the genetic determinants and molecular mechanisms of these arrhythmias are poorly understood. We sought to identify genetic loci associated with atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular accessory pathways or atrioventricular reciprocating tachycardia (AVAPs/AVRT)., Methods: We performed multiancestry meta-analyses of genome-wide association studies to identify genetic loci for AVNRT (4 studies) and AVAP/AVRT (7 studies). We assessed evidence supporting the potential causal effects of candidate genes by analyzing relations between associated variants and cardiac gene expression, performing transcriptome-wide analyses, and examining prior genome-wide association studies., Results: Analyses comprised 2384 AVNRT cases and 106 489 referents, and 2811 AVAP/AVRT cases and 1,483 093 referents. We identified 2 significant loci for AVNRT, which implicate NKX2-5 and TTN as disease susceptibility genes. A transcriptome-wide association analysis supported an association between reduced predicted cardiac expression of NKX2-5 and AVNRT. We identified 3 significant loci for AVAP/AVRT, which implicate SCN5A , SCN10A , and TTN/CCDC141 . Variant associations at several loci have been previously reported for cardiac phenotypes, including atrial fibrillation, stroke, Brugada syndrome, and electrocardiographic intervals., Conclusions: Our findings highlight gene regions associated with ion channel function (AVAP/AVRT), as well as cardiac development and the sarcomere (AVAP/AVRT and AVNRT) as important potential effectors of supraventricular tachycardia susceptibility., Competing Interests: Disclosures Dr Lubitz is a full-time employee of Novartis as of July 2022. Previously, Dr Lubitz received research support from Bristol Myers Squibb/Pfizer, Bayer AG, Boehringer Ingelheim, Fitbit, IBM, Medtronic, and Premier, Inc, and consulted for Bristol Myers Squibb/Pfizer, Bayer AG, Blackstone Life Sciences, and Invitae. Dr Ellinor receives research support from Bayer AG, IBM, and Bristol Myers Squibb/Pfizer and has consulted for Novartis, MyoKardia, and Bayer AG. Dr Damrauer receives research support for RenalytixAI and has consulted for Calico Labs. Dr Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic outside this work. Dr Cutler has consulted for Janssen Scientific. Dr Roselli is supported by a grant from Bayer AG to the Broad Institute focused on the development of therapeutics for cardiovascular disease. The other authors report no conflicts.

Importance: Individuals with congenital heart disease (CHD) are increasingly reaching childbearing age, are more prone to adverse pregnancy events, and uncommonly undergo recommended cardiac evaluations. Data to better understand resource allocation and financial planning are lacking., Objective: To examine health care use and costs for patients with CHD during pregnancy., Design, Setting, and Participants: This retrospective cohort study was performed from January 1, 2010, to December 31, 2016, using Merative MarketScan commercial insurance data. Participants included patients with CHD and those without CHD matched 1:1 by age, sex, and insurance enrollment year. Pregnancy claims were identified for all participants. Data were analyzed from September 2022 to March 2024., Exposures: Baseline characteristics (age, US region, delivery year, insurance type) and pregnancy-related events (obstetric, cardiac, and noncardiac conditions; birth outcomes; and cesarean delivery)., Main Outcomes and Measures: Health service use (outpatient physician, nonphysician, emergency department, prescription drugs, and admissions) and costs (total and out-of-pocket costs adjusted for inflation to represent 2024 US dollars)., Results: A total of 11 703 pregnancies (mean [SD] maternal age, 31.5 [5.4] years) were studied, with 2267 pregnancies in 1785 patients with CHD (492 pregnancies in patients with severe CHD and 1775 in patients with nonsevere CHD) and 9436 pregnancies in 7720 patients without CHD. Compared with patients without CHD, pregnancies in patients with CHD were associated with significantly higher health care use (standardized mean difference [SMD] range, 0.16-1.46) and cost (SMD range, 0.14-0.55) except for out-of-pocket inpatient and ED costs. After adjustment for covariates, having CHD was independently associated with higher total (adjusted cost ratio, 1.70; 95% CI, 1.57-1.84) and out-of-pocket (adjusted cost ratio, 1.40; 95% CI, 1.22-1.58) costs. The adjusted mean total costs per pregnancy were $15 971 (95% CI, $15 480-$16 461) for patients without CHD, $24 290 (95% CI, $22 773-$25 806) for patients with any CHD, $26 308 (95% CI, $22 788-$29 828) for patients with severe CHD, and $23 750 (95% CI, $22 110-$25 390) for patients with nonsevere CHD. Patients with vs without CHD incurred $8319 and $700 higher total and out-of-pocket costs per pregnancy, respectively., Conclusions and Relevance: This study provides novel, clinically relevant estimates for the cardio-obstetric team, patients with CHD, payers, and policymakers regarding health care and financial planning. These estimates can be used to carefully plan for and advocate for the comprehensive resources needed to care for patients with CHD.

Background: The prognosis for atrial fibrillation (AF) patients is based on data that is decades old. Given evolving standards of clinical practice, we sought to evaluate temporal trends in clinically important outcomes among patients with AF., Methods: California's Department of Health Care Access and Information databases were used to identify adults aged ≥ 18 years with AF receiving hospital-based care in California. We compared 3 time-periods: 2005-2009, 2010-2014, and 2015-2019. ICD codes were used to identify chronic diseases and acute events. The outcomes were incident ischemic stroke, intracranial hemorrhage, and overall mortality., Results: We included 2 009 832 patients with AF (52.7% males, 70.7% Whites, and mean age of 75.0 years), divided in 3 cohorts: 2005-2009 (n = 738 954), 2010-2014 (n = 609 447), and 2015-2019 (n = 661 431). Each outcome became substantially less common with time: compared to 2005-2009, AF patients diagnosed in 2015-2019 experienced a 34% (adjusted hazard ratio [HR] 0.66, 95% CI 0.64-0.69), 22% (HR 0.78, 0.75-0.82), and 24% (HR 0.76, 0.75-0.77) reduction in risk of incident ischemic stroke, intracranial hemorrhage, and mortality, respectively. Between 2005-2009 and 2015-2019, patients aged ≥ 65 years experienced more reductions in each outcome compared to younger patients (p < 0.001 for all), and declines in each outcome were significantly lower for Hispanics and Blacks compared to white patients., Conclusion: The risks of stroke, intracranial hemorrhage, and death have significantly declined among AF patients, although differences in the magnitude of improvement of these outcomes by demographic groups were observed. Commonly described estimates of the prognosis for AF patients should be updated to reflect contemporary care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cannabis use is increasing worldwide. While prior studies have reported an association between cannabis use and a higher risk of atrial fibrillation (AF), most were cross-sectional and generally relied on diagnostic coding to identify cannabis users, which may not be representative of the typical recreational cannabis user., Objective: The purpose of this study was to examine the association between recreational cannabis use and lifetime AF risk., Methods: We evaluated the AF risk of participants of the UK Biobank cohort who completed the cannabis use lifestyle questionnaire. Cannabis exposure was categorized as "Occasional Use" for less than 100 times used, "Frequent Use" for more than 100 times used, and "Never" users. AF events were identified using International Classification of Diseases codes. Cox models were used to estimate the hazard ratios (HRs) between cannabis use and incident AF and were subsequently adjusted for age, sex, race, alcohol, coffee, smoking, education, and baseline cardiovascular comorbidities., Results: A total of 150,554 participants (mean age 63.4 ± 7.7 years; 86,487 (57.4%) female; and 33,442 (22.2%) using cannabis at least once) were followed for a mean period of 6.1 ± 0.6 years. After multivariable adjustment, there were no statistically significant differences in incident AF among occasional users (HR 0.98; 95% confidence interval 0.89-1.08) nor frequent users (HR 1.03; 95% confidence interval 0.81-1.32) as compared with never users., Conclusion: In a large prospective cohort study, there was no evidence that cannabis use was associated with a higher risk of incident AF. An evaluation of cannabis ingestion methods and quantification was not possible using the current data set., Competing Interests: Disclosures Dr Marcus is a consultant for Johnson & Johnson and InCarda and owns equity in InCarda. The rest of the authors report no conflicts of interest., (Copyright © 2023 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Alcohol consumption is associated with a higher increased risk of atrial fibrillation (AF), but the acute effects on cardiac electrophysiology in humans remain poorly understood. The HOw ALcohol InDuces Atrial TachYarrhythmias (HOLIDAY) Trial revealed that alcohol shortened pulmonary vein atrial effective refractory periods, but more global electrophysiologic changes gleaned from the surface ECG have not yet been reported., Methods: This was a secondary analysis of the HOLIDAY Trial. During AF ablation procedures, 100 adults were randomized to intravenous alcohol titrated to 0.08% blood alcohol concentration versus a volume and osmolarity-matched, masked, placebo. Intervals measured from 12‑lead ECGs were compared between pre infusion and at infusion steady state (20 min)., Results: The average age was 60 years and 11% were female. No significant differences in the P-wave duration, PR, QRS or QT intervals, were present between alcohol and placebo arms. However, infusion of alcohol was associated with a statistically significant relative shortening of the JT interval (r: -14.73, p = 0.048) after multivariable adjustment., Conclusion: Acute exposure to alcohol was associated with a relative reduction in the JT interval, reflecting shortening of ventricular repolarization. These acute changes may reflect a more global shortening of refractoriness, suggesting immediate proarrhythmic effects pertinent to the atria and ventricles., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gregory M. Marcus reports financial support was provided by National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Premature ventricular complexes (PVCs) are encountered frequently in clinical practice. While PVCs may have various causes, a small number of individuals with PVCs develop cardiomyopathy in the absence of other potential etiologies. When correctly identified, patients with PVC-incuded cardiomyopathy can have dramatic improvement of their cardiomyopathy with treatment of their PVCs. In this focused review, we discuss potential predictors of PVC-induced cardiomyopathy, including PVC frequency, PVC characteristics, and modifiable patient risk factors. We also review some proposed mechanisms of PVC-induced cardiomyopathy and conclude with future directions for research and clinical practice., (© 2023 Wiley Periodicals LLC.)

Previous studies relying on alcohol sales, alcohol-related injuries, and surveys have suggested that alcohol consumption increased during the COVID-19 pandemic. We sought to leverage over 1 million Breath Alcohol Concentration (BrAC) measurements from Bluetooth-enabled breathalyzers to conduct an objective and longitudinal assessment of alcohol use during the pandemic. Serial BrAC measurements revealed a decrease in drinking between January 1, 2020 and March 30, 2020, an increase between March 30, 2020 and May 25, 2020, a statistically insignificant decrease between May 25, 2020 and January 1, 2021, and an increase again between January 1, 2021 and June 4, 2021. No statistically significant relationships between shelter-in-place orders and alcohol consumption were detected. These findings demonstrate the complex relationship between the pandemic and alcohol consumption patterns, providing insights that may be relevant to the use of this commonly consumed substance with implications relevant to long-term effects from the patterns observed., (© 2024. The Author(s).)

COVID-19 increased the prevalence of clinically significant anxiety in the United States. To investigate contributing factors we analyzed anxiety, reported online via monthly Generalized Anxiety Disorders-7 (GAD-7) surveys between April 2020 and May 2022, in association with self-reported worry about the health effects of COVID-19, economic difficulty, personal COVID-19 experience, and subjective social status. 333,292 anxiety surveys from 50,172 participants (82% non-Hispanic white; 73% female; median age 55, IQR 42-66) showed high levels of anxiety, especially early in the pandemic. Anxiety scores showed strong independent associations with worry about the health effects of COVID-19 for oneself or family members (GAD-7 score +3.28 for highest vs. lowest category; 95% confidence interval: 3.24, 3.33; p<0.0001 for trend) and with difficulty paying for basic living expenses (+2.06; 1.97, 2.15, p<0.0001) in multivariable regression models after adjusting for demographic characteristics, COVID-19 case rates and death rates, and personal COVID-19 experience. High levels of COVID-19 health worry and economic stress were each more common among participants reporting lower subjective social status, and median anxiety scores for those experiencing both were in the range considered indicative of moderate to severe clinical anxiety disorders. In summary, health worry and economic difficulty both contributed to high rates of anxiety during the first two years of the COVID-19 pandemic in the US, especially in disadvantaged socioeconomic groups. Programs to address both health concerns and economic insecurity in vulnerable populations could help mitigate pandemic impacts on anxiety and mental health., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. McMahill-Walraven and Dr. Djibo are employees of CVS Health. Dr. Beatty received a salary in 2018 and 2019 and stock from 2019 to 2021 from Apple Inc., outside the submitted work. Dr. Olgin received personal fees from Vivalnk and grants from Samsung outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Cozen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Frequent premature atrial complexes (PACs) are associated with future incident atrial fibrillation (AF), but whether PACs contribute to development of AF through adverse atrial remodeling has not been studied. This study aimed to explore the effect of frequent PACs from different sites on atrial remodeling in a swine model., Methods: Forty swine underwent baseline electrophysiologic studies and echocardiography followed by pacemaker implantations and paced PACs (50% burden) at 250-ms coupling intervals for 16 weeks in 4 groups: (1) lateral left atrium (LA) PACs by the coronary sinus (Lat-PAC; n=10), (2) interatrial septal PACs (Sep-PAC; n=10), (3) regular LA pacing at 130 beats/min (Reg-130; n=10), and (4) controls without PACs (n=10). At the final study, repeat studies were performed, followed by tissue histology and molecular analyses focusing on fibrotic pathways., Results: Lat-PACs were associated with a longer P-wave duration (93.0±9.0 versus 74.2±8.2 and 58.8±7.6 ms; P <0.001) and greater echocardiographic mechanical dyssynchrony (57.5±11.6 versus 35.7±13.0 and 24.4±11.1 ms; P <0.001) compared with Sep-PACs and controls, respectively. After 16 weeks, Lat-PACs led to slower LA conduction velocity (1.1±0.2 versus 1.3±0.2 [Sep-PAC] versus 1.3±0.1 [Reg-130] versus 1.5±0.2 [controls] m/s; P <0.001) without significant change in atrial ERP. The Lat-PAC group had a significantly increased percentage of LA fibrosis and upregulated levels of extracellular matrix proteins (lysyl oxidase and collagen 1 and 8), as well as TGF-β1 (transforming growth factor-β1) signaling proteins (latent and monomer TGF-β1 and phosphorylation/total ratio of SMAD2/3; P <0.05). The Lat-PAC group had the longest inducible AF duration (terminal to baseline: 131 [interquartile range 30, 192] seconds versus 16 [6, 26] seconds [Sep-PAC] versus 22 [11, 64] seconds [Reg-130] versus -1 [-16, 7] seconds [controls]; P <0.001)., Conclusions: In this swine model, frequent PACs resulted in adverse atrial structural remodeling with a heightened propensity to AF. PACs originating from the lateral LA produced greater atrial remodeling and longer induced AF duration than the septal-origin PACs. These data provide evidence that frequent PACs can cause adverse atrial remodeling as well as AF, and that the location of ectopic PACs may be clinically meaningful., Competing Interests: Disclosures Pacemakers and leads used in the study were donated by Medtronic, Inc. The authors report no disclosures.

Background: Chronic sleep disruption is associated with incident atrial fibrillation (AF), but it is unclear whether poor sleep quality acutely triggers AF., Objectives: The aim of this study was to characterize the relationship between a given night's sleep quality and the risk of a discrete AF episode., Methods: Patients with symptomatic paroxysmal AF in the I-STOP-AFIB (Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation) trial reported sleep quality on a daily basis. Participants were also queried daily regarding AF episodes and were provided smartphone-based mobile electrocardiograms (ECGs) (KardiaMobile, AliveCor)., Results: Using 15,755 days of data from 419 patients, worse sleep quality on any given night was associated with a 15% greater odds of a self-reported AF episode the next day (OR: 1.15; 95% CI: 1.10-1.20; P < 0.0001) after adjustment for the day of the week. No statistically significant associations between worsening sleep quality and mobile ECG-confirmed AF events were observed (OR: 1.04; 95% CI: 0.95-1.13; P = 0.43), although substantially fewer of these mobile ECG-confirmed events may have limited statistical power. Poor sleep was also associated with longer self-reported AF episodes, with each progressive category of worsening sleep associated with 16 (95% CI: 12-21; P < 0.001) more minutes of AF the next day., Conclusions: Poor sleep was associated with an immediately heightened risk for self-reported AF episodes, and a dose-response relationship existed such that progressively worse sleep was associated with longer episodes of AF the next day. These data suggest that sleep quality may be a potentially modifiable trigger relevant to the near-term risk of a discrete AF episode., Competing Interests: Funding Support and Author Disclosures This study was funded by a Patient-Powered Research Network Demonstration Project award from the Patient-Centered Outcomes Research Institute and the National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering (grant IU2CEB021881-01). Dr Wong’s institution has received, on his behalf, lecture, travel, and/or research funding from Abbott Medical, Bayer, Boehringer Ingelheim, Medtronic, MicroPort, Novartis, Servier, St. Jude Medical, and Vifor Pharma. Dr Marcus has received personal fees and equity interest from InCarda; personal fees from Johnson & Johnson; and grants from Baylis Medical, Medtronic, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, and the California Tobacco-Related Disease Research Program during the conduct of the study. Drs Modrow and Pletcher have received grants from the Patient-Centered Outcomes Research Institute during the conduct of the study. Dr Olgin has received personal fees from AliveCor during the conduct of the study; personal fees from VivaLNK outside the submitted work; and grants from Samsung outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Oral nirmatrelvir/ritonavir is approved as treatment for acute COVID-19, but the effect of treatment during acute infection on risk of Long COVID is unknown. We hypothesized that nirmatrelvir treatment during acute SARS-CoV-2 infection reduces risk of developing Long COVID and rebound after treatment is associated with Long COVID. We conducted an observational cohort study within the Covid Citizen Science (CCS) study, an online cohort study with over 100 000 participants. We included vaccinated, nonhospitalized, nonpregnant individuals who reported their first SARS-CoV-2 positive test March-August 2022. Oral nirmatrelvir/ritonavir treatment was ascertained during acute SARS-CoV-2 infection. Patient-reported Long COVID symptoms, symptom rebound and test-positivity rebound were asked on subsequent surveys at least 3 months after SARS-CoV-2 infection. A total of 4684 individuals met the eligibility criteria, of whom 988 (21.1%) were treated and 3696 (78.9%) were untreated; 353/988 (35.7%) treated and 1258/3696 (34.0%) untreated responded to the Long COVID survey (n = 1611). Among 1611 participants, median age was 55 years and 66% were female. At 5.4 ± 1.3 months after infection, nirmatrelvir treatment was not associated with subsequent Long COVID symptoms (odds ratio [OR]: 1.15; 95% confidence interval [CI]: 0.80-1.64; p = 0.45). Among 666 treated who answered rebound questions, rebound symptoms or test positivity were not associated with Long COVID symptoms (OR: 1.34; 95% CI: 0.74-2.41; p = 0.33). Within this cohort of vaccinated, nonhospitalized individuals, oral nirmatrelvir treatment during acute SARS-CoV-2 infection and rebound after nirmatrelvir treatment were not associated with Long COVID symptoms more than 90 days after infection., (© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Web- or app-based digital health studies allow for more efficient collection of health data for research. However, remote recruitment into digital health studies can enroll nonrepresentative study samples, hindering the robustness and generalizability of findings. Through the comprehensive evaluation of an email-based campaign on recruitment into the Health eHeart Study, we aim to uncover key sociodemographic and clinical factors that contribute to enrollment., Objective: This study sought to understand the factors related to participation, specifically regarding enrollment, in the Health eHeart Study as a result of a large-scale remote email recruitment campaign., Methods: We conducted a cohort analysis on all invited University of California, San Francisco (UCSF) patients to identify sociodemographic and clinical predictors of enrollment into the Health eHeart Study. The primary outcome was enrollment, defined by account registration and consent into the Health eHeart Study. The email recruitment campaign was carried out from August 2015 to February 2016, with electronic health record data extracted between September 2019 and December 2019., Results: The email recruitment campaign delivered at least 1 email invitation to 93.5% (193,606/206,983) of all invited patients and yielded a 3.6% (7012/193,606) registration rate among contacted patients and an 84.1% (5899/7012) consent rate among registered patients. Adjusted multivariate logistic regression models analyzed independent sociodemographic and clinical predictors of (1) registration among contacted participants and (2) consent among registered participants. Odds of registration were higher among patients who are older, women, non-Hispanic White, active patients with commercial insurance or Medicare, with a higher comorbidity burden, with congestive heart failure, and randomized to receive up to 2 recruitment emails. The odds of registration were lower among those with medical conditions such as dementia, chronic pulmonary disease, moderate or severe liver disease, paraplegia or hemiplegia, renal disease, or cancer. Odds of subsequent consent after initial registration were different, with an inverse trend of being lower among patients who are older and women. The odds of consent were also lower among those with peripheral vascular disease. However, the odds of consent remained higher among patients who were non-Hispanic White and those with commercial insurance., Conclusions: This study provides important insights into the potential returns on participant enrollment when digital health study teams invest resources in using email for recruitment. The findings show that participant enrollment was driven more strongly by sociodemographic factors than clinical factors. Overall, email is an extremely efficient means of recruiting participants from a large list into the Health eHeart Study. Despite some improvements in representation, the formulation of truly diverse studies will require additional resources and strategies to overcome persistent participation barriers., (©Madelena Y Ng, Jeffrey E Olgin, Gregory M Marcus, Courtney R Lyles, Mark J Pletcher. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 22.12.2023.)

Background: Switzerland ranks among the top three healthcare systems in the world with regards to healthcare access, suggesting a high degree of health equity. However, Switzerland has few preventive strategies against smoking abuse. The aim of this study is to clarify whether educational level and citizenship status have an influence on the prevalence of smoking in Switzerland and whether there is health inequity related to a lack of preventive strategies., Methods: We based our analysis on publicly available health data published in the Swiss government's Swiss health survey (1992-2017). We compared the prevalence of smoking across the years and correlated these data with levels of educational attainment, citizenship status and age., Results: A continuous significant decline in smokers is observed in the highest education group (TERT). Over time, prevalence was reduced from 29% in 1992 to 23% in 2017 ( p < 0.001). The intermediate-level educational group (SEK 2) showed smaller but also significant decline on a 0.05 sigificance level over the same period, from 31% to 29% ( p = 0.003). The lowest educational group showed a nonsignificant decline from 28% to 27% ( p = 0.6). The population who holds Swiss citizenship showed a decrease in smoking from 28% to 26% within the time frame ( p < 0.001). People without Swiss citizenship had a much higher prevalence of smokers, at 38% in 1992 and declining to 32% in 2017 ( p < 0.001). All cohorts from age 15 to age 64 have a far higher prevalence of smokers than cohorts at an older age, with the highest prevalence in the 25-34 age group., Conclusion: In Switzerland, individuals with lower levels of education and non-Swiss populations are more susceptible to health risk of smoking. This is despite the existence of a high-quality healthcare system that has nevertheless failed to negated health inequities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wehrli, Gilljam, Koh, Matoori, Sartoretti, Boes, Hartmann, Roser, Ort, Wanner, Harder, Bech-Hohenberger, Froehlich, Fröhlich, Mutschler, Plümecke and Gutzeit.)

Background: Accurate, timely ascertainment of clinical end points, particularly hospitalizations, is crucial for clinical trials. The Tailored Antiplatelet Initiation to Lessen Outcomes Due to Decreased Clopidogrel Response after Percutaneous Coronary Intervention (TAILOR-PCI) Digital Study extended the main TAILOR-PCI trial's follow-up to 2 years, using a smartphone-based research app featuring geofencing-triggered surveys and routine monthly mobile phone surveys to detect cardiovascular (CV) hospitalizations. This pilot study compared these digital tools to conventional site-coordinator ascertainment of CV hospitalizations., Objective: The objectives were to evaluate geofencing-triggered notifications and routine monthly mobile phone surveys' performance in detecting CV hospitalizations compared to telephone visits and health record reviews by study coordinators at each site., Methods: US and Canadian participants from the TAILOR-PCI Digital Follow-Up Study were invited to download the Eureka Research Platform mobile app, opting in for location tracking using geofencing, triggering a smartphone-based survey if near a hospital for ≥4 hours. Participants were sent monthly notifications for CV hospitalization surveys., Results: From 85 participants who consented to the Digital Study, downloaded the mobile app, and had not previously completed their final follow-up visit, 73 (85.8%) initially opted in and consented to geofencing. There were 9 CV hospitalizations ascertained by study coordinators among 5 patients, whereas 8 out of 9 (88.9%) were detected by routine monthly hospitalization surveys. One CV hospitalization went undetected by the survey as it occurred within two weeks of the previous event, and the survey only allowed reporting of a single hospitalization. Among these, 3 were also detected by the geofencing algorithm, but 6 out of 9 (66.7%) were missed by geofencing: 1 occurred in a participant who never consented to geofencing, while 5 hospitalizations occurred among participants who had subsequently turned off geofencing prior to their hospitalization. Geofencing-detected hospitalizations were ascertained within a median of 2 (IQR 1-3) days, monthly surveys within 11 (IQR 6.5-25) days, and site coordinator methods within 38 (IQR 9-105) days. The geofencing algorithm triggered 245 notifications among 39 participants, with 128 (52.2%) from true hospital presence and 117 (47.8%) from nonhospital health care facility visits. Additional geofencing iterative improvements to reduce hospital misidentification were made to the algorithm at months 7 and 12, elevating the rate of true alerts from 35.4% (55 true alerts/155 total alerts before month 7) to 78.7% (59 true alerts/75 total alerts in months 7-12) and ultimately to 93.3% (14 true alerts/5 total alerts in months 13-21), respectively., Conclusions: The monthly digital survey detected most CV hospitalizations, while the geofencing survey enabled earlier detection but did not offer incremental value beyond traditional tools. Digital tools could potentially reduce the burden on study coordinators in ascertaining CV hospitalizations. The advantages of timely reporting via geofencing should be weighed against the issue of false notifications, which can be mitigated through algorithmic refinements., (©Robert Avram, Julia Byrne, Derek So, Erin Iturriaga, Ryan Lennon, Vishakantha Murthy, Nancy Geller, Shaun Goodman, Charanjit Rihal, Yves Rosenberg, Kent Bailey, Michael Farkouh, Malcolm Bell, Charles Cagin, Ivan Chavez, Mohammad El-Hajjar, Wilson Ginete, Amir Lerman, Justin Levisay, Kevin Marzo, Tamim Nazif, Jean-Francois Tanguay, Mark Pletcher, Gregory M Marcus, Naveen L Pereira, Jeffrey Olgin. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 10.11.2023.)

Objective: To examine the associations between specific dietary patterns and incident atrial fibrillation (AF)., Methods: Using data from the UK Biobank, dietary intakes were calculated from 24-hour diet recall questionnaires. Indices representing adherence to dietary patterns (Mediterranean-style, Dietary Approaches to Stop Hypertension (DASH) and plant-based diets) were scored, and ultra-processed food consumption was studied as a percentage of total food mass consumed. Incident AF hospitalisations were assessed in Cox regression models., Results: A total of 121 300 individuals were included, with 4 579 incident AF cases over a median follow-up of 8.8 years. Adherence to Mediterranean-style or DASH diets was associated with a lower incidence of AF in minimally adjusted analyses (HR for highest vs lowest quintile 0.87 (95% CI 0.80-0.96) and HR 0.78 (95% CI 0.71-0.86), respectively). However, associations were no longer significant after accounting for lifestyle factors (HR 0.95 (95% CI 0.87-1.04) and 0.94 (95% CI 0.86-1.04) respectively), with adjustment for body mass index responsible for approximately three-quarters of the effect size attenuation. Plant-based diets were not associated with AF risk in any models. Greatest ultra-processed food consumption was associated with a significant increase in AF risk even in fully adjusted models (HR 1.13 (95% CI 1.02-1.24)), and a 10% increase in absolute intake of ultra-processed food was associated with a 5% increase in AF risk (HR 1.05 (95% CI 1.01-1.08))., Conclusion: With the possible exception of reducing ultra-processed food consumption, these findings suggest that attention to other modifiable risk factors, particularly obesity, may be more important than specific dietary patterns for the primary prevention of AF., Competing Interests: Competing interests: GMM has received research funding from Baylis Medical, is a consultant for Johnson and Johnson and InCarda and holds equity in InCarda. DHL reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott Medical, Biotronik, Medtronic and MicroPort CRM. JH is an International Advisory Board member for BMJ Heart and reports that Flinders University has received on his behalf lecture and/or consulting feels from Biotronik. PS reports having served on the Advisory Board of Boston Scientific, CathRx, Medtronic, PaceMate and Abbott Medical. PS also reports that the University of Adelaide has received on his behalf lecture, consulting fees and/or research funding from Medtronic, Boston Scientific, Abbott Medical and LivaNova. CXW reports that the University of Adelaide has received on his behalf lecture, travel and/or research funding from Abbott Medical, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Servier, St Jude Medical and Vifor Pharma., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Little is known about whether people who use both tobacco and cannabis (co-use) are more or less likely to have mental health disorders than single substance users or non-users. We aimed to examine associations between use of tobacco and/or cannabis with anxiety and depression., Methods: We analyzed data from the COVID-19 Citizen Science Study, a digital cohort study, collected via online surveys during 2020-2022 from a convenience sample of 53,843 US adults (≥ 18 years old) nationwide. Past 30-day use of tobacco and cannabis was self-reported at baseline and categorized into four exclusive patterns: tobacco-only use, cannabis-only use, co-use of both substances, and non-use. Anxiety and depression were repeatedly measured in monthly surveys. To account for multiple assessments of mental health outcomes within a participant, we used Generalized Estimating Equations to examine associations between the patterns of tobacco and cannabis use with each outcome., Results: In the total sample (mean age 51.0 years old, 67.9% female), 4.9% reported tobacco-only use, 6.9% cannabis-only use, 1.6% co-use, and 86.6% non-use. Proportions of reporting anxiety and depression were highest for the co-use group (26.5% and 28.3%, respectively) and lowest for the non-use group (10.6% and 11.2%, respectively). Compared to non-use, the adjusted odds of mental health disorders were highest for co-use (Anxiety: OR = 1.89, 95%CI = 1.64-2.18; Depression: OR = 1.77, 95%CI = 1.46-2.16), followed by cannabis-only use, and tobacco-only use. Compared to tobacco-only use, co-use (OR = 1.35, 95%CI = 1.08-1.69) and cannabis-only use (OR = 1.17, 95%CI = 1.00-1.37) were associated with higher adjusted odds for anxiety, but not for depression. Daily use (vs. non-daily use) of cigarettes, e-cigarettes, and cannabis were associated with higher adjusted odds for anxiety and depression., Conclusions: Use of tobacco and/or cannabis, particularly co-use of both substances, were associated with poor mental health. Integrating mental health support with tobacco and cannabis cessation may address this co-morbidity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)