Acute Effects of Coffee Consumption on Health among Ambulatory Adults.

BACKGROUND: Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. METHODS: We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits. RESULTS: The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, -0.41; 95% CI, -5.42 to 4.60). CONCLUSIONS: In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.).

Cannabis, cocaine, methamphetamine, and opiates increase the risk of incident atrial fibrillation.

AIMS: Atrial fibrillation (AF) is now regarded as a preventable disease, requiring a search for modifiable risk factors. With legalization of cannabis and more lenient laws regarding the use of other illicit substances, investigation into the potential effects of methamphetamine, cocaine, opiate, and cannabis exposure on incident AF is needed. METHODS AND RESULTS: Using Office of Statewide Health Planning and Development databases, a longitudinal analysis was performed of adult Californians ≥18 years of age who received care in an emergency department, outpatient surgery facility, or hospital from 1 January 2005 to 31 December 2015. Associations between healthcare coding for the use of each substance and a new AF diagnosis were assessed. Among 23,561,884 patients, 98 271 used methamphetamine, 48 701 used cocaine, 10 032 used opiates, and 132 834 used cannabis. Of the total population, 998 747 patients (4.2%) developed incident AF during the study period. After adjusting for potential confounders and mediators, use of methamphetamines, cocaine, opiates, and cannabis was each associated with increased incidence of AF: hazard ratios 1.86 [95% confidence interval (CI) 1.81-1.92], 1.61 (95% CI 1.55-1.68), 1.74 (95% CI 1.62-1.87), and 1.35 (95% CI 1.30-1.40), respectively. Negative control analyses in the same cohort failed to reveal similarly consistent positive relationships. CONCLUSION: Methamphetamine, cocaine, opiate, and cannabis uses were each associated with increased risk of developing incident AF. Efforts to mitigate the use of these substances may represent a novel approach to AF prevention.

Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events.

BACKGROUND: Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event. OBJECTIVE: To objectively ascertain whether alcohol consumption heightens risk for an AF episode. DESIGN: A prospective, case-crossover analysis. SETTING: Ambulatory persons in their natural environments. PARTICIPANTS: Consenting patients with paroxysmal AF. MEASUREMENTS: Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events. RESULTS: Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours. LIMITATION: Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population. CONCLUSION: Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur. PRIMARY FUNDING SOURCE: National Institute on Alcohol Abuse and Alcoholism.

Identifying Mitral Valve Prolapse at Risk for Arrhythmias and Fibrosis From Electrocardiograms Using Deep Learning.

BACKGROUND: Mitral valve prolapse (MVP) is a common valvulopathy, with a subset developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) is a marker of arrhythmic risk associated with myocardial fibrosis and increased mortality in MVP. OBJECTIVES: The authors sought to evaluate whether electrocardiogram (ECG)-based machine learning can identify MVP at risk for ComVE, death and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging. METHODS: A deep convolutional neural network (CNN) was trained to detect ComVE using 6,916 12-lead ECGs from 569 MVP patients from the University of California-San Francisco between 2012 and 2020. A separate CNN was trained to detect late gadolinium enhancement (LGE) using 1,369 ECGs from 87 MVP patients with contrast CMR. RESULTS: The prevalence of ComVE was 28% (160/569). The area under the receiver operating characteristic curve (AUC) of the CNN to detect ComVE was 0.80 (95% CI: 0.77-0.83) and remained high after excluding patients with moderate-severe mitral regurgitation [0.80 (95% CI: 0.77-0.83)] or bileaflet MVP [0.81 (95% CI: 0.76-0.85)]. AUC to detect all-cause mortality was 0.82 (95% CI: 0.77-0.87). ECG segments relevant to ComVE prediction were related to ventricular depolarization/repolarization (early-mid ST-segment and QRS from V1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 24% patients with available CMR; AUC for detection of LGE was 0.75 (95% CI: 0.68-0.82). CONCLUSIONS: CNN-analyzed 12-lead ECGs can detect MVP at risk for ventricular arrhythmias, death and/or fibrosis and can identify novel ECG correlates of arrhythmic risk. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.

Valvular disease burden in the modern era of percutaneous and surgical interventions: the UK Biobank.

BACKGROUND: The burden of valvular heart disease (VHD) has increased significantly among ageing populations, yet remains poorly understood in the present-day context of percutaneous and surgical interventions. OBJECTIVE: To define the incidence, clinical correlates and associated mortality of VHD in the UK Biobank cohort. METHODS: We interrogated data collected in the UK Biobank between 1 January 2000 and 30 June 2020. VHD incidence was determined using International Classification of Disease-10 codes for aortic stenosis (AS), aortic regurgitation (AR), mitral stenosis, mitral regurgitation (MR) and mitral valve prolapse. We calculated HRs for incident VHD and all-cause mortality. Clinical correlates of VHD included demographics, coronary artery disease, heart failure and atrial fibrillation. Surgical and percutaneous interventions for mitral and aortic VHD were considered time-dependent variables. RESULTS: Among 486 187 participants, the incidence of any VHD was 16 per 10 000 person-years, with highest rates for MR (8.2), AS (7.2) and AR (5.0). Age, heart failure, coronary artery disease and atrial fibrillation were significantly associated with all types of VHD. In our adjusted model, aortic and mitral VHD had an increased risk of all-cause death compared with no VHD (HR 1.62, 95% CI 1.44 to 1.82, p<0.001 and HR 1.25, 95% CI 1.09 to 1.44, p=0.002 for aortic and mitral VHD, respectively). CONCLUSION: VHD continues to constitute a significant public health burden, with MR and AS being the most common. Age and cardiac comorbidities remain strong risk factors for VHD. In the modern era of percutaneous and surgical interventions, mortality associated with VHD remains high.

Clinical Correlates and Outcomes of Methamphetamine-Associated Cardiovascular Diseases in Hospitalized Patients in California.

Background Methamphetamine misuse affects 27 million people worldwide and is associated with cardiovascular disease (CVD); however, risk factors for CVD among users have not been well studied. Methods and Results We studied hospitalized patients in California, captured by the Healthcare Cost and Utilization Project database, between 2005 and 2011. We studied the association between methamphetamine use and CVD (pulmonary hypertension, heart failure, stroke, and myocardial infarction). Among 20 249 026 persons in the Healthcare Cost and Utilization Project, 66 199 used methamphetamines (median follow-up 4.58 years). Those who used were more likely younger (33 years versus 45 years), male (63.3% versus 44.4%), smoked, misused alcohol, and had depression and anxiety compared with nonusers. Methamphetamine use was associated with the development of heart failure (hazard ratio [HR], 1.53 [95% CI, 1.45-1.62]) and pulmonary hypertension (HR, 1.42 [95% CI, 1.26-1.60]). Among users, male sex (HR, 1.73 [95% CI, 1.37-2.18]) was associated with myocardial infarction. Chronic kidney disease (HR, 2.38 [95% CI, 1.74-3.25]) and hypertension (HR, 2.26 [95% CI, 2.03-2.51]) were strong risk factors for CVD among users. When compared with nonuse, methamphetamine use was associated with a 32% significant increase in CVD, alcohol abuse with a 28% increase, and cocaine use with a 47% increase in CVD. Conclusions Methamphetamine use has a similar magnitude of risk of CVD compared with alcohol and cocaine. Prevention and treatment could be focused on those with chronic kidney disease, hypertension, and mental health disorders.

Human Immunodeficiency Virus Infection and Out-of-Hospital Cardiac Arrest.

Patients with human immunodeficiency virus (HIV) infection are at increased risk of cardiovascular disease, but studies on HIV as a risk factor for cardiac arrest in the general population are lacking. We aimed to examine the association of HIV infection with out-of-hospital cardiac arrests (OHCAs). We used the Office of Statewide Health Planning and Development data to evaluate HIV infection as a predictor of OHCA in all California emergency department encounters from 2005 to 2015, adjusting for age, gender, race, income, obesity, smoking, alcohol, substance abuse, hypertension (HTN), diabetes, coronary artery disease, congestive heart failure (CHF), atrial fibrillation, and chronic kidney disease (CKD). We also determined patient characteristics modifying these associations by including interaction terms in multivariable-adjusted models. In 18,542,761 patients (mean age 47 ± 20 years, 53% women, 43,849 with HIV) followed for a median 6.8 years, 133,983 new OHCA events occurred. Incidence rates in patients with HIV were higher than in patients without HIV (1.99 vs 1.16 OHCA events per 1,000-person-years follow-up). After multivariable adjustment, HIV was associated with a 2.5-fold higher risk of OHCA (hazard ratio 2.47, 95% confidence interval 2.29 to 2.66, p <0.001). The risk of OHCA with HIV was disproportionately stronger in younger patients, women, and in those with HTN, CHF, and CKD. In this large prospective study, HIV was associated with a 2.5-fold increased risk of OHCA, with a greater vulnerability to this outcome in patients with HIV who were female or had HTN, CHF, or CKD.

Hospitalized Patients With COVID-19 Have Higher Plasma Aldosterone-Renin Ratio and Lower ACE Activity Than Controls.

Context: SARS-CoV-2 infects cells via the angiotensin converting enzyme 2 (ACE2) receptor, whose downstream effects "counterbalance" the classical renin angiotensin aldosterone system (RAAS). Objective: We aimed to determine to what extent circulating RAAS biomarker levels differ in persons with and without COVID-19 throughout the disease course. Methods: We measured classical (renin, aldosterone, aldosterone/renin ratio [ARR], Ang2, ACE activity) and nonclassical (ACE2, Ang1,7) RAAS biomarkers in hospitalized COVID-19 patients vs SARS-CoV-2 negative controls. We compared biomarker levels in cases with contemporaneous samples from control patients with upper respiratory symptoms and a negative SARS-CoV-2 PCR test. To assess RAAS biomarker changes during the course of COVID-19 hospitalization, we studied cases at 2 different times points ∼ 12 days apart. We employed age- and sex-adjusted generalized linear models and paired/unpaired t tests. Results: Mean age was 51 years for both cases (31% women) and controls (50% women). ARR was higher in the first sample among hospitalized COVID-19 patients vs controls (P = 0.02). ACE activity was lower among cases at their first sample vs controls (P = <0.001). ACE2 activity, Ang 1,7, and Ang2 did not differ at the 2 COVID-19 case time points and they did not differ in COVID-19 cases vs controls. Additional adjustment for body mass index (BMI) did not change our findings. Conclusions: High ARR, independent of BMI, may be a risk marker for COVID-19 hospitalization. Serum ACE activity was lower in patients with COVID-19 vs controls at the beginning of their hospitalization and then increased to similar levels as controls, possibly due to lung injury, which improved with inpatient disease management.

Premature ventricular complexes and development of heart failure in a community-based population.

OBJECTIVE: A higher premature ventricular complex (PVC) frequency is associated with incident congestive heart failure (CHF) and death. While certain PVC characteristics may contribute to that risk, the current literature stems from patients in medical settings and is therefore prone to referral bias. This study aims to identify PVC characteristics associated with incident CHF in a community-based setting. METHODS: The Cardiovascular Health Study is a cohort of community-dwelling individuals who underwent prospective evaluation and follow-up. We analysed 24-hour Holter data to assess PVC characteristics and used multivariable logistic and Cox proportional hazards models to identify predictors of a left ventricular ejection fraction (LVEF) decline and incident CHF, respectively. RESULTS: Of 871 analysed participants, 316 participants exhibited at least 10 PVCs during the 24-hour recording. For participants with PVCs, the average age was 72±5 years, 41% were women and 93% were white. Over a median follow-up of 11 years, 34% developed CHF. After adjusting for demographics, cardiovascular comorbidities, antiarrhythmic drug use and PVC frequency, a greater heterogeneity of the PVC coupling interval was associated with an increased risk of LVEF decline and incident CHF. Of note, neither PVC duration nor coupling interval duration exhibited a statistically significant relationship with either outcome. CONCLUSIONS: In this first community-based study to identify Holter-based features of PVCs that are associated with LVEF reduction and incident CHF, the fact that coupling interval heterogeneity was an independent risk factor suggests that the mechanism of PVC generation may influence the risk of heart failure.

Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is the most common arrhythmia. Although patients have reported that various exposures determine when and if an AF event will occur, a prospective evaluation of patient-selected triggers has not been conducted, and the utility of characterizing presumed AF-related triggers for individual patients remains unknown. Objective: To test the hypothesis that n-of-1 trials of self-selected AF triggers would enhance AF-related quality of life. Design, Setting, and Participants: A randomized clinical trial lasting a minimum of 10 weeks tested a smartphone mobile application used by symptomatic patients with paroxysmal AF who owned a smartphone and were interested in testing a presumed AF trigger. Participants were screened between December 22, 2018, and March 29, 2020. Interventions: n-of-1 Participants received instructions to expose or avoid self-selected triggers in random 1-week blocks for 6 weeks, and the probability their trigger influenced AF risk was then communicated. Controls monitored their AF over the same time period. Main Outcomes and Measures: AF was assessed daily by self-report and using a smartphone-based electrocardiogram recording device. The primary outcome comparing n-of-1 and control groups was the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score at 10 weeks. All participants could subsequently opt for additional trigger testing. Results: Of 446 participants who initiated (mean [SD] age, 58 [14] years; 289 men [58%]; 461 White [92%]), 320 (72%) completed all study activities. Self-selected triggers included caffeine (n = 53), alcohol (n = 43), reduced sleep (n = 31), exercise (n = 30), lying on left side (n = 17), dehydration (n = 10), large meals (n = 7), cold food or drink (n = 5), specific diets (n = 6), and other customized triggers (n = 4). No significant differences in AFEQT scores were observed between the n-of-1 vs AF monitoring-only groups. In the 4-week postintervention follow-up period, significantly fewer daily AF episodes were reported after trigger testing compared with controls over the same time period (adjusted relative risk, 0.60; 95% CI, 0.43- 0.83; P < .001). In a meta-analysis of the individualized trials, only exposure to alcohol was associated with significantly heightened risks of AF events. Conclusions and Relevance: n-of-1 Testing of AF triggers did not improve AF-associated quality of life but was associated with a reduction in AF events. Acute exposure to alcohol increased AF risk, with no evidence that other exposures, including caffeine, more commonly triggered AF. Trial Registration: ClinicalTrials.gov Identifier: NCT03323099.

Coffee Consumption and Incident Tachyarrhythmias: Reported Behavior, Mendelian Randomization, and Their Interactions.

Importance: The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated. Objective: To assess the association between consumption of common caffeinated products and the risk of arrhythmias. Design, Setting, and Participants: This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses. Exposures: Daily coffee intake and genetic polymorphisms that affect caffeine metabolism. Main Outcomes and Measures: Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes. Results: A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism-related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia. Conclusions and Relevance: In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.

Association of Insurance Status With Emergent Versus Nonemergent Hospital Encounters Among Adults With Congenital Heart Disease.

Background Although the number of hospital visits has exponentially increased for adults with congenital heart disease (CHD) over the past few decades, the relationship between insurance status and hospital encounter type remains unknown. The purpose of this study was to evaluate the association between insurance status and emergent versus nonemergent encounters among adults with CHD ≥18 years old. Methods and Results We used California Office of Statewide Health Planning and Development Database from January 2005 to December 2015 to determine the trends of insurance status and encounters and the association of insurance status on encounter type among adults with CHD. A total 58 359 nonpregnancy encounters were identified in 6077 patients with CHD. From 2005 to 2015, the number of uninsured encounters decreased by 38%, whereas government insured encounters increased by 124% and private by 79%. Overall, there was a significantly higher proportion of emergent than nonemergent encounters associated with uninsured status (13.0% versus 1.8%; P<0.0001), whereas the proportion of nonemergent encounters associated with private insurance was higher than emergent encounters (35.8% versus 62.4%; P<0.0001). When individual patients with CHD became uninsured, they were ≈5 times more likely to experience an emergent encounter (P<0.0001); upon changing from uninsured to insured, they were significantly less likely to have an emergent encounter (P<0.001). After multivariate adjustment, uninsured status exhibited the highest odds of an emergent rather than nonemergent encounter compared with all other covariates (adjusted odds ratio, 9.20; 95% CI, 7.83-10.8; P<0.0001). Conclusions Efforts to enhance the ability to obtain and maintain insurance throughout the lifetime of patients with CHD might result in meaningful reductions in emergent encounters and a more efficient use of resources.

Characteristics and Behaviors Associated with Prevalent SARS-CoV-2 Infection.

INTRODUCTION: 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.

Emergency activations for chest pain and ventricular arrhythmias related to regional COVID-19 across the US.

Evidence that patients may avoid healthcare facilities for fear of COVID-19 infection has heightened the concern that true rates of myocardial infarctions have been under-ascertained and left untreated. We analyzed data from the National Emergency Medical Services Information System (NEMSIS) and incident COVID-19 infections across the United States (US) between January 1, 2020 and April 30, 2020. Grouping events by US Census Division, multivariable adjusted negative binomial regression models were utilized to estimate the relationship between COVID-19 and EMS cardiovascular activations. After multivariable adjustment, increasing COVID-19 rates were associated with less activations for chest pain and non-ST-elevation myocardial infarctions. Simultaneously, increasing COVID-19 rates were associated with more activations for cardiac arrests, ventricular fibrillation, and ventricular tachycardia. Although direct effects of COVID-19 infections may explain these discordant observations, these findings may also arise from patients delaying or avoiding care for myocardial infarction, leading to potentially lethal consequences.

Incident Strokes Among American Indian Individuals With Atrial Fibrillation.

BACKGROUND American Indian individuals experience a relatively high risk for cardiovascular disease and have exhibited a higher risk of stroke compared with other racial and ethnic minorities. Although this population has the highest incidence of atrial fibrillation (AF) compared with other groups, the relationship between AF and nonhemorrhagic stroke among American Indian individuals compared with other groups has not been thoroughly studied. METHODS and RESULTS We used the Healthcare Cost and Utilization Project to evaluate risk of nonhemorrhagic stroke among American Indian individuals, with comparisons to White, Black, Hispanic, and Asian individuals, among all adult California residents receiving care in an emergency department, inpatient hospital unit, or ambulatory surgery setting from 2005 to 2011. Of 16 951 579 patients followed for a median 4.1 years, 105 822 (0.6%) were American Indian. After adjusting for age, sex, income level, insurance payer, hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, cardiac surgery, valvular heart disease, chronic kidney disease, smoking, obstructive sleep apnea, pulmonary disease, and alcohol use, American Indian individuals with AF exhibited the highest risk of nonhemorrhagic stroke when compared with either non-American Indian individuals with AF (hazard ratio, 1.38; 95% CI, 1.23-1.55; P<0.0001) or to each race and ethnicity with AF. American Indian individuals also experienced the highest overall risk for stroke, with no evidence that AF disproportionately heightened that risk in interaction analyses. CONCLUSIONS American Indian individuals experienced the highest risk of nonhemorrhagic stroke, whether in the presence or absence of AF. Our findings likely suggest an opportunity to further study, if not immediately address, guideline-adherent anticoagulation prescribing patterns among American Indian individuals with AF.

Heart Failure, Atrioventricular Block, and Ventricular Tachycardia in Sarcoidosis.

Background Sarcoidosis is a granulomatous disease usually affecting the lungs, although cardiac morbidity may be common. The risk of these outcomes and the characteristics that predict them remain largely unknown. This study investigates the epidemiology of heart failure, atrioventricular block, and ventricular tachycardia among patients with and without sarcoidosis. Methods and Results We identified California residents aged ≥21 years using the Office of Statewide Health Planning and Development ambulatory surgery, emergency, or inpatient databases from 2005 to 2015. The risk of sarcoidosis on incident heart failure, atrioventricular block, and ventricular tachycardia were each determined. Linkage to the Social Security Death Index was used to ascertain overall mortality. Among 22 527 964 California residents, 19 762 patients with sarcoidosis (0.09%) were identified. Sarcoidosis was the strongest predictor of heart failure (hazard ratio [HR], 11.2; 95% CI, 10.7-11.7), atrioventricular block (HR, 117.7; 95% CI, 103.3-134.0), and ventricular tachycardia (HR, 26.1; 95% CI, 24.2-28.1) identified among all risk factors. The presence of any cardiac involvement best predicted each outcome. Approximately 22% (95% CI, 18%-26%) of the relationship between sarcoidosis and increased mortality was explained by the presence of at least 1 of these cardiovascular outcomes. Conclusions The magnitude of risk associated with sarcoidosis as a predictor of heart failure, atrioventricular block, and ventricular tachycardia, exceeds all established risk factors. Surveillance for and anticipation of these outcomes among patients with sarcoidosis is indicated, and consideration of a sarcoidosis diagnosis may be prudent among patients with heart failure, atrioventricular block, or ventricular tachycardia.

Long-term outcomes of ablation for ventricular arrhythmias in mitral valve prolapse.

PURPOSE: Prior studies reporting efficacy of radiofrequency catheter ablation for complex ventricular ectopy in mitral valve prolapse (MVP) are limited by selective inclusion of bileaflet MVP, papillary muscle only ablation, or short-term follow-up. We sought to evaluate the long-term incidence of hemodynamically significant ventricular tachycardia (VT) or fibrillation (VF) in patients with MVP after initial ablation. METHODS: We studied consecutive patients with MVP undergoing ablation for complex ventricular ectopy between 2013 and 2017 at our institution. Of 580 patients with MVP, we included 15 (2.6%, 10 women; mean age 50 ± 14 years, 53% bileaflet) with complex ventricular ectopy treated with initial ablation. RESULTS: Over a median follow-up of 3406 (1875-6551) days or 9 years, 5 of 15 (33%) patients developed hemodynamically significant VT/VF after their initial ablation and underwent placement of an implantable cardioverter defibrillator (ICD). Three of 5 also underwent repeat ablations. Sustained VT was inducible prior to index ablation in all 5 who developed VT/VF, compared to none of the 10 patients who did not develop VT/VF after index ablation (p = 0.002). Complex ventricular ectopy at index ablation was multifocal in all 5 patients who underwent repeat intervention versus 4 of 10 patients (40%) who did not (p = 0.04). All 3 patients with subsequent VT/VF who underwent repeat ablation had a new clinically dominant focus of ventricular arrhythmia and 3 of the patients with ICD had appropriate VT/VF therapies. CONCLUSIONS: In the long term, a subset of MVP patients treated with ablation for ventricular arrhythmias, all with multifocal ectopy on initial EP study, develop hemodynamically significant VT/VF. Our findings suggest the progressive nature of ventricular arrhythmias in patients with MVP and multifocal ectopy.

Predicting Incident Heart Failure in Women With Machine Learning: The Women's Health Initiative Cohort.

BACKGROUND: Heart failure (HF) is a leading cause of cardiac morbidity among women, whose risk factors differ from those in men. We used machine-learning approaches to develop risk- prediction models for incident HF in a cohort of postmenopausal women from the Women's Health Initiative (WHI). METHODS: We used 2 machine-learning methods-Least Absolute Shrinkage and Selection Operator (LASSO) and Classification and Regression Trees (CART)-to perform variable selection on 1227 baseline WHI variables for the primary outcome of incident HF. These variables were then used to construct separate Cox proportional hazard models, and we compared these results, using receiver-operating characteristic (ROC) curve analysis, against a comparator model built using variables from the Atherosclerosis Risk in Communities (ARIC) HF prediction model. We analyzed 43,709 women who had 2222 incident HF events; median follow-up was 14.3 years. RESULTS: LASSO selected 10 predictors, and CART selected 11 predictors. The highest correlation between selected variables was 0.46. In addition to selecting well-established predictors such as age, myocardial infarction, and smoking, novel predictors included physical function, number of pregnancies, number of previous live births and age at menopause. In ROC analysis, the CART-derived model had the highest C-statistic of 0.83 (95% confidence interval [CI], 0.81-0.85), followed by LASSO 0.82 (95% CI, 0.81-0.84) and ARIC 0.73 (95% CI, 0.70-0.76). CONCLUSIONS: Machine-learning approaches can be used to develop HF risk-prediction models that can have better discrimination compared with an established HF risk model and may provide a basis for investigating novel HF predictors.

Predictors of incident SARS-CoV-2 infections in an international prospective cohort study.

OBJECTIVE: Until effective treatments and vaccines are made readily and widely available, preventative behavioural health measures will be central to the SARS-CoV-2 public health response. While current recommendations are grounded in general infectious disease prevention practices, it is still not entirely understood which particular behaviours or exposures meaningfully affect one's own risk of incident SARS-CoV-2 infection. Our objective is to identify individual-level factors associated with one's personal risk of contracting SARS-CoV-2. DESIGN: Prospective cohort study of adult participants from 26 March 2020 to 8 October 2020. SETTING: The COVID-19 Citizen Science Study, an international, community and mobile-based study collecting daily, weekly and monthly surveys in a prospective and time-updated manner. PARTICIPANTS: All adult participants over the age of 18 years were eligible for enrolment. PRIMARY OUTCOME MEASURE: The primary outcome was incident SARS-CoV-2 infection confirmed via PCR or antigen testing. RESULTS: 28 575 unique participants contributed 2 479 149 participant-days of data across 99 different countries. Of these participants without a history of SARS-CoV-2 infection at the time of enrolment, 112 developed an incident infection. Pooled logistic regression models showed that increased age was associated with lower risk (OR 0.98 per year, 95% CI 0.97 to 1.00, p=0.019), whereas increased number of non-household contacts (OR 1.10 per 10 contacts, 95% CI 1.01 to 1.20, p=0.024), attending events of at least 10 people (OR 1.26 per 10 events, 95% CI 1.07 to 1.50, p=0.007) and restaurant visits (OR 1.95 per 10 visits, 95% CI 1.42 to 2.68, p<0.001) were associated with significantly higher risk of incident SARS-CoV-2 infection. CONCLUSIONS: Our study identified three modifiable health behaviours, namely the number of non-household contacts, attending large gatherings and restaurant visits, which may meaningfully influence individual-level risk of contracting SARS-CoV-2.