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Background Variation in outcomes by race/ethnicity in adults with heart failure (HF) has been previously observed. Identifying factors contributing to these variations could help target interventions. We evaluated the association of race/ethnicity with HF outcomes and potentially contributing factors within a contemporary HF cohort. Methods and Results We identified members of Kaiser Permanente Northern California, a large integrated healthcare delivery system, who were diagnosed with HF between 2012 and 2016 and had at least 1 year of prior continuous membership and left ventricular ejection fraction data. We used Cox regression with time‐dependent covariates to evaluate the association of self‐identified race/ethnicity with HF or all‐cause hospitalization and all‐cause death, with backward selection for potential explanatory variables. Among 34 621 patients with HF, compared with White patients, Black patients had a higher rate of HF hospitalization (adjusted hazard ratio [HR], 1.28; 95% CI, 1.18–1.38) but a lower rate of death (adjusted HR, 0.78; 95% CI, 0.72–0.85). In contrast, Asian/Pacific Islander patients had similar rates of HF hospitalization, but lower rates of all‐cause hospitalization (adjusted HR, 0.89; 95% CI, 0.85–0.93) and death (adjusted HR, 0.75; 95% CI, 0.69–0.80). Hispanic patients also had a lower rate of death (adjusted HR, 0.85; 95% CI, 0.80–0.91). Sensitivity analyses showed that effect sizes for Black patients were larger among patients with reduced ejection fraction. Conclusions In a contemporary and diverse population with HF, Black patients experienced a higher rate of HF hospitalization and a lower rate of death compared with White patients. In contrast, selected outcomes for Asian/Pacific Islander and Hispanic patients were more favorable compared with White patients. The observed differences were not explained by measured potentially modifiable factors, including pharmacological treatment. Future research is needed to identify explanatory mechanisms underlying ongoing racial/ethnic variation to target potential interventions.

Background The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF‐15 (growth differentiation factor‐15), galectin‐3, sST2 (soluble suppression of tumorigenesis‐2), hsTnT (high‐sensitivity troponin T), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score

Background The survival benefit associated with cumulative adherence to multiple clinical and lifestyle‐related guideline recommendations for secondary prevention after acute myocardial infarction (AMI) is not well established. Methods and Results We examined adults with AMI (mean age 68 years; 64% men) surviving at least 30 (N=25 778) or 90 (N=24 200) days after discharge in a large integrated healthcare system in Northern California from 2008 to 2014. The association between all‐cause death and adherence to 6 or 7 secondary prevention guideline recommendations including medical treatment (prescriptions for β‐blockers, renin‐angiotensin‐aldosterone system inhibitors, lipid medications, and antiplatelet medications), risk factor control (blood pressure

Background We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity troponin T, galectin‐3, growth differentiation factor‐15, and soluble ST‐2. Incident AF (“AF event”) was defined as a hospitalization for AF. During a median follow‐up of 8 years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log‐transformed NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log‐high‐sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose–response relationship in categorical analyses. Although log‐soluble ST‐2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log‐galectin‐3 (HR 1.05; 95% CI, 0.91, 1.22) and log‐growth differentiation factor‐15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and high‐sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease.

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation (AF). Methods and Results Using data from the ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti‐Clot Treatment Scale (ACTS) questionnaire, a validated metric of patient‐reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range (TTR; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all‐cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA2DS2‐VASc 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF, and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR (TTR ≥75%: odds ratio, 1.01 [95% CI, 0.99–1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI, 0.98–1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI, 0.97–1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR, warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.

Background Chronic kidney disease (CKD) is a common comorbidity in patients with atrial fibrillation. The presence of CKD complicates drug selection for stroke prevention and rhythm control. Methods and Results Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow‐up data were included (N=9019). CKD was defined as an estimated creatinine clearance

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these “low‐risk” patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low‐risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation (P

Background Contemporary data about symptomatic paroxysmal supraventricular tachycardia (PSVT) epidemiology are limited. We characterized prevalence and correlates of symptomatic PSVT within a large healthcare delivery system and estimated national PSVT burden. Methods and Results We identified adults with an encounter for potential PSVT between 2010 and 2015 in Kaiser Permanente Northern California, excluding those with prior known atrial fibrillation or atrial flutter. We adjudicated medical records, ECGs, and other monitoring data to estimate positive predictive values for targeted International Classification of Diseases (ICD), 9th and 10th Revisions codes in inpatient, emergency department, and outpatient settings. Combinations of diagnosis codes and settings were used to calculate PSVT prevalence, and PSVT correlates were identified using multivariable regression. We estimated national rates by applying prevalence estimates in Kaiser Permanente to 2010 US Census data. The highest positive predictive values included codes for “PSVT” in the emergency department (82%), “unspecified cardiac dysrhythmia” in the emergency department (27%), “anomalous atrioventricular excitation” as a primary inpatient diagnosis (33%), and “unspecified paroxysmal tachycardia” as a primary inpatient diagnosis (23%). Prevalence of symptomatic PSVT was 140 per 100 000 (95% confidence interval, 100–179) and was higher for individuals who were older, women, white or black, or who had valvular heart disease, heart failure, diabetes mellitus, lung disease, or prior bleeding. We estimate the national prevalence of symptomatic PSVT to be 168 per 100 000 (95% confidence interval, 120–215). Conclusions Selected diagnostic codes in inpatient and emergency department settings may be useful to identify symptomatic PSVT episodes. We project that at least 0.168% of US adults experience symptomatic PSVT, and certain characteristics can identify people at higher risk.

BackgroundPrimary prevention implantable cardioverter‐defibrillators (ICDs) reduce mortality in selected patients with left ventricular systolic dysfunction by delivering therapies (antitachycardia pacing or shocks) to terminate potentially lethal arrhythmias; inappropriate therapies also occur. We assessed device therapies among adults receiving primary prevention ICDs in 7 healthcare systems. Methods and ResultsWe linked medical record data, adjudicated device therapies, and the National Cardiovascular Data Registry ICD Registry. Survival analysis evaluated therapy probability and predictors after ICD implant from 2006 to 2009, with attention to Centers for Medicare and Medicaid Services Coverage With Evidence Development subgroups: left ventricular ejection fraction, 31% to 35%; nonischemic cardiomyopathy

BackgroundAnxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. Methods and ResultsThe Cardiovascular Research Network WAVE (Community‐Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision (ICD‐9), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person‐years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01–2.28). Results were not materially changed after additional adjustment for patient‐level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03–2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. ConclusionsDiagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors or achieved anticoagulation quality.

BackgroundMineralocorticoid receptor antagonist (MRA) therapy may be beneficial to patients with atrial fibrillation (AF), but little is known about their use in patients with AF and subsequent outcomes. Methods and ResultsIn order to better understand MRA use and subsequent outcomes, we performed a retrospective cohort study of the contemporary ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry. AF progression and cardiovascular outcomes were compared using propensity‐matched Cox proportional hazards modeling according to MRA use at baseline and new MRA use at follow‐up versus patients with no MRA use. Among 7012 patients with nonpermanent AF, 320 patients were taking MRA at enrollment, and 416 patients initiated MRA use during follow‐up. The mean patient age was 72.5 years, 56.3% were men, and 70.4% had paroxysmal AF. Among all patients taking MRAs, 434 (59.0%) had heart failure, 655 (89.0%) had hypertension, and 380 (51.6%) had both. After adjustment, new MRA use was not associated with reduced AF progression (hazard ratio, 1.18; 95% confidence interval, 0.88–1.58; P=0.27) but showed a trend towards lower risk of stroke, transient ischemic attack, or systemic embolism (hazard ratio, 0.17; 95% confidence interval, 0.02–1.23; P=0.08). Results were similar for a comparison of new MRA users and baseline MRA users compared with nonusers. ConclusionsIn community‐based outpatients with AF, the majority of MRA use was for heart failure and hypertension. MRA use also trended towards lower adjusted stroke risk. Future studies should test the hypothesis that MRA use may decrease the risk of stroke in patients with AF.

BackgroundIn US clinical practice, many patients who undergo placement of an implantable cardioverter‐defibrillator (ICD) for primary prevention of sudden cardiac death receive dual‐chamber devices. The superiority of dual‐chamber over single‐chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single‐ and dual‐chamber ICDs for primary prevention. Methods and ResultsWe identified patients receiving a single‐ or dual‐chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter‐Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all‐cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital‐level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single‐chamber device and 46.0% (n=479) received a dual‐chamber device. In a propensity‐weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59–1.38 [P=0.65]), all‐cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87–1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72–1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93–1.53 [P=0.17]). ConclusionsAmong patients who received an ICD for primary prevention without indications for pacing, dual‐chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single‐chamber devices. This study does not justify the use of dual‐chamber devices to minimize inappropriate shocks.

BackgroundAtrial fibrillation (AF) is the most common clinically significant arrhythmia in adults and a major risk factor for ischemic stroke. Nonetheless, previous research suggests that many individuals diagnosed with AF lack awareness about their diagnosis and inadequate health literacy may be an important contributing factor to this finding. Methods and ResultsWe examined the association between health literacy and awareness of an AF diagnosis in a large, ethnically diverse cohort of Kaiser Permanente Northern and Southern California adults diagnosed with AF between January 1, 2006 and June 30, 2009. Using self‐reported questionnaire data completed between May 1, 2010 and September 30, 2010, awareness of an AF diagnosis was evaluated using the question “Have you ever been told by a doctor or other health professional that you have a heart rhythm problem called atrial fibrillation or atrial flutter?” and health literacy was assessed using a validated 3‐item instrument examining problems because of reading, understanding, and filling out medical forms. Of the 12 517 patients diagnosed with AF, 14.5% were not aware of their AF diagnosis and 20.4% had inadequate health literacy. Patients with inadequate health literacy were less likely to be aware of their AF diagnosis compared with patients with adequate health literacy (prevalence ratio=0.96; 95% CI [0.94, 0.98]), adjusting for sociodemographics, health behaviors, and clinical characteristics. ConclusionsLower health literacy is independently associated with less awareness of AF diagnosis. Strategies designed to increase patient awareness of AF and its complications are warranted among individuals with limited health literacy.

BackgroundWarfarin reduces ischemic stroke risk in atrial fibrillation (AF) but increases bleeding risk. Novel anticoagulants challenge warfarin as stroke‐preventive therapy for AF. They are available at fixed doses but are more costly. Warfarin anticoagulation at a time in therapeutic range (TTR) ≥70% is similarly as effective and safe as novel anticoagulants. It is unclear whether AF patients with TTR ≥70% will remain stably anticoagulated and avoid the need to switch to a novel anticoagulant. We assessed stability of warfarin anticoagulation in AF patients with an initial TTR ≥70%. Methods and ResultsWithin the community‐based Anticoagulation and Risk Factors in AF (ATRIA) cohort followed from 1996 to 2003, we identified 2841 new warfarin users who continued warfarin over 9 months. We excluded months 1 to 3 to achieve a stable dose. For the 987 patients with TTR ≥70% in an initial 6‐month period (TTR1; months 4–9), we described the distribution of TTR2 (months 10–15) and assessed multivariable correlates of persistent TTR ≥70%. Of patients with TTR1 ≥70%, 57% persisted with TTR2 ≥70% and 16% deteriorated to TTR2

BackgroundThe clinical implications of ankle‐brachial index (ABI) cutpoints are not well defined in patients with chronic kidney disease (CKD) despite increased prevalence of high ABI attributed to arterial stiffness. We examined the relationship of ABI with cardiovascular disease (CVD) and all‐cause mortality among CKD patients. Methods and ResultsThree thousand six hundred twenty‐seven participants without clinical peripheral artery disease (PAD) at baseline from the Chronic Renal Insufficiency Cohort Study were included. ABI was obtained per standard protocol and CVD events were confirmed by medical record adjudication. A U‐shaped association of ABI with PAD, myocardial infarction (MI), composite CVD, and all‐cause mortality was observed. Individuals with an ABI between 1.0 and

Abstract Aims Worsening heart failure (WHF) events occurring in non‐inpatient settings are becoming increasingly recognized, with implications for prognostication. We evaluate the performance of a natural language processing (NLP)‐based approach compared with traditional diagnostic coding for non‐inpatient clinical encounters and left ventricular ejection fraction (LVEF). Methods and results We compared characteristics for encounters that did vs. did not meet WHF criteria, stratified by care setting [i.e. emergency department (ED) and observation stay]. Overall, 8407 (22%) encounters met NLP‐based criteria for WHF (3909 ED visits and 4498 observation stays). The use of an NLP‐derived definition adjudicated 3983 (12%) of non‐primary HF diagnoses as meeting consensus definitions for WHF. The most common diagnosis indicated in these encounters was dyspnoea. Results were primarily driven by observation stays, in which 2205 (23%) encounters with a secondary HF diagnosis met the WHF definition by NLP. Conclusions The use of standard claims‐based adjudication for primary diagnosis in the non‐inpatient setting may lead to misclassification of WHF events in the ED and overestimate observation stays. Primary diagnoses alone may underestimate the burden of WHF in non‐hospitalized settings.

Background There is a need to develop electronic health record–based predictive models for worsening heart failure (WHF) events across clinical settings and across the spectrum of left ventricular ejection fraction (LVEF). Methods and Results We studied adults with heart failure (HF) from 2011 to 2019 within an integrated health care delivery system. WHF encounters were ascertained using natural language processing and structured data. We conducted boosted decision tree ensemble models to predict 1‐year hospitalizations, emergency department visits/observation stays, and outpatient encounters for WHF and all‐cause death within each LVEF category: HF with reduced ejection fraction (EF) (LVEF

Background Clinical risk factors, a single blood pressure (BP) measurement, current biomarkers, and biophysical parameters can effectively identify risk of early‐onset preeclampsia but have limited ability to predict later‐onset preeclampsia and gestational hypertension. Clinical BP patterns hold promise to improve early risk stratification for hypertensive disorders of pregnancy. Methods and Results After excluding preexisting hypertension, heart, kidney, or liver disease, or prior preeclampsia, the retrospective cohort (n=249 892) all had systolic BP

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site. Subsequent dementia was identified through previously validated diagnosis codes. Fine‐Gray subdistribution hazard models were used to examine the association of incident AF (versus no AF) with risk of incident dementia, adjusting for sociodemographics and comorbidity and accounting for competing risk of death. Subgroup analyses by age, sex, race, ethnicity, and chronic kidney disease status were also performed. Among 196 968 matched adults, mean (SD) age was 73.6 (11.3) years, with 44.8% women, and 72.3% White. Incidence rates (per 100 person‐years) for dementia over a median follow‐up of 3.3 (interquartile range, 1.7–5.4) years were 2.79 (95% CI, 2.72–2.85) and 2.04 (95% CI, 1.99–2.08) per 100 person‐years in persons with versus without incident AF, respectively. In adjusted models, incident AF was associated with a significantly greater risk of diagnosed dementia (subdistribution hazard ratio [sHR], 1.13 [95% CI, 1.09–1.16]). With additional adjustment for interim stroke events, the association of incident AF with dementia remained statistically significant (sHR, 1.10 [95% CI, 1.07–1.15]). Associations were stronger for age

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF‐related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced‐based secondary prevention strategies. We report on a National Heart, Lung, and Blood Institute virtual workshop directed at identifying knowledge gaps and research opportunities in the secondary prevention of AF. Once AF has been detected, lifestyle changes and novel models of care delivery may contribute to the prevention of AF recurrence, AF progression, and AF‐related complications. Although benefits seen in small subgroups, cohort studies, and selected randomized trials are impressive, the widespread effectiveness of AF secondary prevention strategies remains unknown, calling for development of scalable interventions suitable for diverse populations and for identification of subpopulations who may particularly benefit from intensive management. We identified critical research questions for 6 topics relevant to the secondary prevention of AF: (1) weight loss; (2) alcohol intake, smoking cessation, and diet; (3) cardiac rehabilitation; (4) approaches to sleep disorders; (5) integrated, team‐based care; and (6) nonanticoagulant pharmacotherapy. Our goal is to stimulate innovative research that will accelerate the generation of the evidence to effectively pursue the secondary prevention of AF.