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Rationale: Sepsis commonly results in elevated serum troponin levels and increased risk for postsepsis cardiovascular complications; however, the association between troponin levels during sepsis and cardiovascular complications after sepsis is unclear.Objectives: To evaluate the association between serum troponin levels during sepsis and 1 year after sepsis cardiovascular events.Methods: We analyzed adults aged ⩾40 years without preexisting cardiovascular disease within 5 years, admitted with sepsis across 21 hospitals from 2011 to 2017. Peak serum troponin I levels during sepsis were grouped as normal (⩽0.04 ng/ml) or tertiles of abnormal (>0.04 to ⩽0.09 ng/ml, >0.09 to ⩽0.42 ng/ml, or >0.42 ng/ml). Multivariable adjusted cause-specific Cox proportional hazards models with death as a competing risk were used to assess associations between peak troponin I levels and a composite cardiovascular outcome (atherosclerotic cardiovascular disease, atrial fibrillation, and heart failure) in the year following sepsis. Models were adjusted for presepsis and intrasepsis factors considered potential confounders.Measurements and Main Results: Among 14,046 eligible adults with troponin I measured, 2,012 (14.3%) experienced the composite cardiovascular outcome, including 832 (10.9%) patients with normal troponin levels, as compared with 370 (17.3%), 376 (17.6%), and 434 (20.3%) patients within each sequential abnormal troponin tertile, respectively (P < 0.001). Patients within the elevated troponin tertiles had increased risks of adverse cardiovascular events (adjusted hazard ratio [aHR]troponin0.04-0.09 = 1.37; 95% confidence interval [CI], 1.20-1.55; aHRtroponin0.09-0.42 = 1.44; 95% CI, 1.27-1.63; and aHRtroponin>0.42 = 1.77; 95% CI, 1.56-2.00).Conclusions: Among patients without preexisting cardiovascular disease, troponin elevation during sepsis identified patients at increased risk for postsepsis cardiovascular complications. Strategies to mitigate cardiovascular complications among this high-risk subset of patients are warranted. [ABSTRACT FROM AUTHOR]

Background: Multiple morbidity is the norm in advanced COPD and contributes to high symptom burden and worse outcomes.Research Question: Can distinct comorbidity profiles be identified and validated in a community-based sample of patients with COPD from a large integrated health care system using a standard, commonly used diagnostic code-based comorbidity index and downstream 2-year health care use data?Study Design and Methods: In this retrospective cohort study, we used latent class analysis (LCA) to identify comorbidity profiles in a population-based sample of 91,453 patients with a COPD diagnosis between 2011 and 2015. We included specific comorbid conditions from the Charlson Comorbidity Index (CCI) and accounted for variation in underlying prevalence of different comorbidities across the three study sites. Sociodemographic, clinical, and health-care use data were obtained from electronic health records (EHRs). Multivariate logistic regression analysis was used to compare rates of acute and postacute care use by class.Results: The mean age was 71 ± 11 years, 55% of patients were women, 23% of patients were people of color, and 80% of patients were former or current smokers. LCA identified four distinct comorbidity profiles with progressively higher CCI scores: low morbidity (61%; 1.9 ± 1.4), metabolic renal (21%; 4.7 ± 1.8), cardiovascular (12%; 4.6 ± 1.9), and multimorbidity (7%; 7.5 ± 1.7). In multivariate models, during 2 years of follow-up, a significant, nonoverlapping increase was found in the odds of having any all-cause acute (hospitalizations, observation stays, and ED visits) and postacute care use across the comorbidity profiles.Interpretation: Distinct comorbidity profiles can be identified in patients with COPD using standard EHR-based diagnostic codes, and these profiles are associated with subsequent acute and postacute care use. Population-based risk stratification schemes for end-to-end, comprehensive COPD management should consider integrating comorbidity profiles such as those found in this study. [ABSTRACT FROM AUTHOR]

Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF. [ABSTRACT FROM AUTHOR]

Background: To examine the individual and combined associations of noncardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF).Methods: We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of noncardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause.Results: Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 noncardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 noncardiac conditions/mobility limitation, ≥3 noncardiac conditions/no mobility limitation, ≥3 noncardiac conditions/mobility limitation (vs) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of noncardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age.Conclusions: There is an additive association of mobility limitation, beyond the burden of noncardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is an increasing epidemic globally that is associated with adverse health outcomes including end stage kidney disease (ESKD), cardiovascular disease (CVD), and death. American Indians (AIs) have a higher prevalence of CKD than most other racial/ethnic groups, due in part to a high prevalence of type 2 diabetes. Other genetic and environmental factors not yet identified may also contribute to the disproportionate burden of CKD in AIs.Method: We will establish 3 clinical centers to recruit AIs from the Southwest United States (US) to expand the Chronic Renal Insufficiency Cohort (CRIC) study. We will follow the current CRIC protocol for kidney and cardiovascular measures and outcomes, which include ambulatory monitoring of kidney function and the use of mobile health technologies for CVD sub-phenotyping, and compare the outcomes in AIs with those in other racial/ethnic groups in CRIC.Discussion: AI-CRIC will identify the role of various risk factors for rapid loss of kidney function among AIs of the Southwest US. In addition, to better understand the natural history of CKD and CVD in this high-risk population, we will identify unique risk factors for CKD and CVD progression in AIs. We will also compare event rates and risk factors for kidney and cardiovascular events in AIs with the other populations represented in CRIC. [ABSTRACT FROM AUTHOR]

This study evaluates changes in rates of patients hospitalized for acute myocardial infarction (AMI) or suspected stroke during COVID-19 surges in the US as a measure of willingness to seek care during the pandemic. [ABSTRACT FROM AUTHOR]

Objective: Chronic obstructive pulmonary disease (COPD) is associated with the development of atrial fibrillation (AF), and may complicate treatment of AF. We examined the association between COPD and symptoms, quality of life (QoL), treatment and outcomes among patients with AF.Methods: We compared patients with and without a diagnosis of COPD in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, a prospective registry that enrolled outpatients with AF not secondary to reversible causes, from both academic and community settings.Results: Among 9749 patients with AF, 1605 (16%) had COPD. Relative to patients without COPD, those with COPD were more likely to be older, current/former smokers (73% vs 43%), have heart failure (54% vs 29%) and coronary artery disease (49% vs 34%). Oral anticoagulant and beta blocker use were similar, whereas digoxin use was more common among patients with COPD. Symptom burden was generally higher, and QoL worse, among patients with COPD (median Atrial Fibrillation Effect on QualiTy-of-Life score 76 vs 83). Patients with COPD had higher risk of all-cause mortality (adjusted HR 1.52 (95% CI 1.32 to 1.74)), cardiovascular mortality (adjusted HR 1.51 (95% CI 1.24 to 1.84)) and cardiovascular hospitalisation (adjusted HR 1.15 (95% CI 1.05 to 1.26)). Patients with COPD also had higher risk of major bleeding events (adjusted HR 1.25 (95% CI 1.05 to 1.50)). There did not appear to be associations between COPD and AF progression, ischaemic events or new-onset heart failure.Conclusions: Among patients with AF, COPD is associated with higher symptom burden, worse QoL, and worse cardiovascular and bleeding outcomes. These associations were not fully explained by cardiovascular risk factors, AF treatment or smoking history.Clinical Registration Number: NCT01165710. [ABSTRACT FROM AUTHOR]

Background: The long-term downward national U.S. trend in heart disease-related mortality slowed substantially during 2011-2014 before turning upward in 2015. Examining mortality trends in the major subgroups of heart disease may provide insight into potentially more targeted and effective prevention and treatment approaches to promote favorable trajectories. We examined national trends between 2000 and 2015 in mortality attributed to major heart disease subgroups including ischemic heart disease, heart failure, and all other types of heart disease.Methods: Using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) data system, we determined national trends in age-standardized mortality rates attributed to ischemic heart disease, heart failure, and other heart diseases from January 1, 2000, to December 31, 2011, and from January 1, 2011, to December 31, 2015. Annual rate of changes in mortality attributed to ischemic heart disease, heart failure, and other heart diseases for 2000-2011 and 2011-2015 were compared.Results: Death attributed to ischemic heart disease declined from 2000 to 2015, but the rate of decline slowed from 4.96% (95% confidence interval 4.77%-5.15%) for 2000-2011 to 2.66% (2.00%-3.31%) for 2011-2015. In contrast, death attributed to heart failure and all other causes of heart disease declined from 2000 to 2011 at annual rates of 1.94% (1.77%-2.11%) and 0.64% (0.44%-0.82%) respectively, but increased from 2011 to 2015 at annual rates of 3.73% (3.21% 4.26%) and 1.89% (1.33-2.46%). Differences in 2000-2011 and 2011-2015 decline rates were statistically significant for all 3 endpoints overall, by sex, and all race/ethnicity groups except Asian/Pacific Islanders (heart failure only significant) and American Indian/Alaskan Natives.Conclusions: While the long-term decline in death attributed to heart disease slowed between 2011 and 2014 nationally before turning upward in 2015, heterogeneity existed in the trajectories attributed to heart disease subgroups, with ischemic heart disease mortality continuing to decline while death attributed to heart failure and other heart diseases switched from a downward to upward trend. While systematic efforts to prevent and treat ischemic heart disease continue to be effective, urgent attention is needed to address the challenge of heart failure. [ABSTRACT FROM AUTHOR]

Objectives To prioritize research topics relevant to the care of the growing population of older adults with multiple chronic conditions ( MCCs). Design Survey of experts in MCC practice, research, and policy. Topics were derived from white papers, funding announcements, or funded research projects relating to older adults with MCCs. Setting Survey conducted through the Health Care Systems Research Network ( HCSRN) and Claude D. Pepper Older Americans Independence Centers ( OAICs) Advancing Geriatrics Infrastructure and Network Growth Initiative, a joint endeavor of the HCSRN and OAICs. Participants Individuals affiliated with the HCSRN or OAICs and national MCC experts, including individuals affiliated with funding agencies having MCC-related grant portfolios. Measurements A 'top box' methodology was used, counting the number of respondents selecting the top response on a 5-point Likert scale and dividing by the total number of responses to calculate a top box percentage for each of 37 topics. Results The highest-ranked research topics relevant to the health and healthcare of older adults with MCCs were health-related quality of life in older adults with MCCs; development of assessment tools (to assess, e.g., symptom burden, quality of life, function); interactions between medications, disease processes, and health outcomes; disability; implementation of novel (and scalable) models of care; association between clusters of chronic conditions and clinical, financial, and social outcomes; role of caregivers; symptom burden; shared decision-making to enhance care planning; and tools to improve clinical decision-making. Conclusion Study findings serve to inform the development of a comprehensive research agenda to address the challenges relating to the care of this 'high-need, high-cost' population and the healthcare delivery systems responsible for serving it. [ABSTRACT FROM AUTHOR]

Objective: Patients with chronic kidney disease (CKD) have higher risk of sudden cardiac death; however, they may not receive implantable cardioverter defibrillators (ICDs), in part due to higher risk of complications. We evaluated whether CKD is associated with greater risk of device-delivered shocks/antitachycardia pacing (ATP) therapies among patients receiving a primary prevention ICD.Methods: We studied participants in the observational Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter Defibrillators. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Outcomes included all delivered shocks/ATPs therapies and type of shock/ATP therapies (inappropriate or appropriate, determined by physician adjudication) within the 3 years. We evaluated the associations between CKD and time to first device therapy, burden of device therapy, and inappropriate versus appropriate device therapy, adjusting for demographics, comorbidity, laboratory values and medication use.Results: Among 2161 participants, 1066 (49.3%) had CKD (eGFR 44±11 mL/min/1.73 m2) at ICD implantation. During mean of 2.26±0.89 years, 9.8% and 18.5% of participants had at least one inappropriate and appropriate shock/ATP therapies, respectively. CKD was not associated with time to first shock/ATP therapies (adjusted HR 0.87, 95% CI 0.73 to 1.05), overall burden of shock/ATP therapies (adjusted relative rate 0.93, 95% CI 0.74 to 1.17) or inappropriate versus appropriate shock/ATP therapies (adjusted relative risk 0.88, 95% CI 0.68 to 1.14) compared with not having CKD.Conclusions: In adults receiving a primary prevention ICD, mild-to-moderate CKD was not associated with the timing, burden or appropriateness of subsequent device therapy. Potential concern for inappropriate ICD-delivered therapies should not preclude ICDs among eligible patients with CKD. [ABSTRACT FROM AUTHOR]

Background: Monitoring trends in cardiovascular events can provide key insights into the effectiveness of prevention efforts. Leveraging data from electronic health records provides a unique opportunity to examine contemporary, community-based trends in acute myocardial infarction hospitalizations.Methods: We examined trends in hospitalized acute myocardial infarction incidence among adults aged ≥25 years in 13 US health plans in the Cardiovascular Research Network. The first hospitalization per member for acute myocardial infarction overall and for ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction was identified by International Classification of Diseases, Ninth Revision, Clinical Modification primary discharge codes in each calendar year from 2000 through 2008. Age- and sex-adjusted incidence was calculated per 100,000 person-years using direct adjustment with 2000 US census data.Results: Between 2000 and 2008, we identified 125,435 acute myocardial infarction hospitalizations. Age- and sex-adjusted incidence rates (per 100,000 person-years) of acute myocardial infarction decreased an average 3.8%/y from 230.5 in 2000 to 168.6 in 2008. Incidence of ST-segment elevation myocardial infarction decreased 8.7%/y from 104.3 in 2000 to 51.7 in 2008, whereas incidence of non-ST-segment elevation myocardial infarction increased from 126.1 to 129.4 between 2000 and 2004 and then decreased thereafter to 116.8 in 2008. Age- and sex-specific incidence rates generally reflected similar patterns, with relatively larger decreases in ST-segment elevation myocardial infarction rates in women compared with men. As compared with 2000, the age-adjusted incidence of ST-segment elevation myocardial infarction in 2008 was 48% lower among men and 61% lower among women.Conclusions and Relevance: Among a large, diverse, multicenter community-based insured population, there were significant decreases in incidence of hospitalized acute myocardial infarction and the more serious ST-segment elevation myocardial infarctions between 2000 and 2008. Decreases in ST-segment elevation myocardial infarctions were most pronounced among women. While ecologic in nature, these secular decreases likely reflect, at least in part, results of improvement in primary prevention efforts. [ABSTRACT FROM AUTHOR]

Objectives To determine the association between cognition and levels of cystatin C in persons with chronic kidney disease ( CKD). Design Prospective observational study. Setting Chronic Renal Insufficiency Cohort Cognitive Study. Participants Individuals with a baseline cognitive assessment completed at the same visit as serum cystatin C measurement (N = 821; mean age 64.9, 50.6% male, 48.6% white). Measurements Levels of serum cystatin C were categorized into tertiles; cognitive function was assessed using six neuropsychological tests. Scores on these tests were compared across tertiles of cystatin C using linear regression and logistic regression to examine the association between cystatin C level and cognitive performance (1 standard deviation difference from the mean). Results After multivariable adjustment for age, race, education, and medical comorbidities in linear models, higher levels of cystatin C were associated with worse cognition on the modified Mini-Mental State Examination, Buschke Delayed Recall, Trail-Making Test Part (Trails) A and Part B, and Boston Naming ( P < .05 for all). This association remained statistically significant for Buschke Delayed Recall ( P = .01) and Trails A ( P = .03) after additional adjustment for estimated glomerular filtration rate (e GFR). The highest tertile of cystatin C was associated with greater likelihood of poor performance on Trails A (odds ratio ( OR) = 2.17, 95% confidence interval ( CI) = 1.16-4.06), Trails B ( OR = 1.89, 95% CI = 1.09-3.27), and Boston Naming ( OR = 1.85, 95% CI = 1.07-3.19) than the lowest tertile after multivariate adjustment in logistic models. Conclusion In individuals with CKD, higher serum cystatin C levels were associated with worse cognition and greater likelihood of poor cognitive performance on attention, executive function, and naming. Cystatin C is a marker of cognitive impairment and may be associated with cognition independent of e GFR. [ABSTRACT FROM AUTHOR]

Objectives To examine whether the total burden of comorbidity and pattern of co-occurring conditions varies in individuals with heart failure ( HF) with preserved left ventricular ejection fraction ( LVEF) ( HF-P) or HF with reduced LVEF ( HF-R). Design Cross-sectional cohort study. Setting Four participating health plans within the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Research Network. Participants All members aged 65 and older with HF based on hospital discharge and ambulatory visit diagnoses. Measurements Participants with a LVEF of 50% or greater were classified as having HF-P. Presence of cardiac and noncardiac comorbidities was obtained from health plan administrative databases. Results Of 23,435 individuals identified with HF and LVEF information, 53% (12,407) had confirmed HF-P (mean age 79.6; 60% female). More than three-quarters of the sample had three or more co-occurring conditions in addition to HF, and half had five or more cooccurring conditions. Participants with HF-P had a slightly higher burden of comorbidity than those with HF-R (mean 4.5 vs 4.4, P = .002). Patterns of how specific conditions co-occurred did not vary in participants with preserved or reduced systolic function. Conclusion There is a high degree of comorbidity and multiple morbidity in individuals with HF. The burden and pattern of comorbidity varies only slightly in individuals with preserved or reduced LVEF. [ABSTRACT FROM AUTHOR]

Background: The field of outcomes research seeks to define optimal treatment in practice and to promote the rapid full adoption of efficacious therapies into routine clinical care. The American Heart Association (AHA) formed the AHA Pharmaceutical Roundtable (PRT) Outcomes Research Centers Network to accelerate attainment of these goals. Participating centers were intended to carry out state-of-the-art outcomes research in cardiovascular disease and stroke, to train the next generation of investigators, and to support the formation of a collaborative research network.Program: After a competitive application process, 4 AHA PRT Outcomes Research Centers were selected: Duke Clinical Research Institute; Saint Luke's Mid America Heart Institute; Stanford University-Kaiser Permanente of Northern California; and University of California, Los Angeles. Each center proposed between 1 and 3 projects organized around a single theme in cardiovascular disease or stroke. Additionally, each center will select and train up to 6 postdoctoral fellows over the next 4 years, and will participate in cross-collaborative activities among the centers.Conclusions: The AHA PRT Outcomes Research Centers Network is designed to further strengthen the field of cardiovascular disease and stroke outcomes research by fostering innovative research, supporting high quality training, and encouraging center-to-center collaborations. [ABSTRACT FROM AUTHOR]

Hispanics are the fastest growing minority group in the United States. The incidence of end-stage renal disease (ESRD) in Hispanics is higher than non-Hispanic Whites and Hispanics with chronic kidney disease (CKD) are at increased risk for kidney failure. Likely contributing factors to this burden of disease include diabetes and metabolic syndrome, both are common among Hispanics. Access to health care, quality of care, and barriers due to language, health literacy and acculturation may also play a role. Despite the importance of this public health problem, only limited data exist about Hispanics with CKD. We review the epidemiology of CKD in US Hispanics, identify the factors that may be responsible for this growing health problem, and suggest gaps in our understanding which are suitable for future investigation. [ABSTRACT FROM AUTHOR]

The article provides information on a study on the comparative effectiveness of various β-blockers. It cites the statistics of chronic heart failure victims in the U.S. which affect more than 5 million Americans. The researchers compared mortality linked with different β-blockers after being hospitalized due to heart failure between 2001 and 2003. The patient characteristics were identified via administrative, state mortality, and Social Security Administration databases. Results showed that about 7976 out of 11,326 adults surviving a hospitalization for heart failure received β-blockers. It suggests that randomized trials within real-world settings be conducted to reassure the clinical effectiveness of β-blockers for heart failure.

CKD continues to be a growing problem in the United States, particularly among Hispanic individuals. The disproportionate growth of Hispanic ESRD patients is largely driven by this group's escalating population and by its increased prevalence of diabetes and other risk factors, such as the components of the metabolic syndrome and disparities in healthcare. Future studies should elucidate these and other nontraditional risk factors for CKD and CVD progression in the Hispanic population. This knowledge will provide the basis for developing prevention strategies and designing interventional clinical trials targeting the Hispanic population with earlier stages of CKD to both reduce the rates of progression on to ESRD and the burden of associated CVD and death. [ABSTRACT FROM AUTHOR]

Reports implications for rhythm management and stroke prevention in adults in the United States. Anticoagulation and risk factors in atrial fibrillation (ATRIA) study; Risk factors for stroke as well as reduction in quality of life, functional status, and cardiac performance; Atrial fibrillation to increase; Need for stroke prevention.

Purpose: To assess the effects of physician specialty on the knowledge, management, and outcomes of patients with coronary disease or heart failure.Materials and Methods: We performed a systematic search of MEDLINE from 1980 to 1997, as well as bibliographic references to articles about the effects of physician specialty on the knowledge, treatment, and outcomes of patients with coronary disease or heart failure in the United States.Results: Twenty-four articles met our criteria for inclusion (including eight that involved knowledge or self-reported practices, 14 that described actual practice patterns, and six that measured clinical outcomes). Cardiologists were more knowledgeable than generalist physicians about the optimal evaluation and management of coronary disease but not about the use of angiotensin-converting enzyme (ACE) inhibitors for heart failure. Patients with unstable angina or myocardial infarction were more likely to receive proven medical therapies, and possibly had improved outcomes, if they were treated by cardiologists. The use of lipid-lowering drugs after myocardial infarction was also more common among patients of cardiologists. ACE inhibitor use for heart failure was probably greater, and short-term readmission rates were lower, with cardiology care.Conclusions: Patients with coronary disease or heart failure in the United States who are treated by cardiologists appear more likely to receive evidence-based care and probably have better outcomes. Investigation of collaborative models of care and innovative efforts to improve the use of proven therapies by physicians are needed. [ABSTRACT FROM AUTHOR]

Hastings and colleagues ([1]) provide interesting data to support the finding that heart disease is more likely than cancer to be the leading cause of death in low-income counties in the United States. During this period, the crude mortality rate attributed to cancer declined by 0.6%; however, the mortality rate related to heart disease increased by 3.8%. Furthermore, data from Table 2 of the article do not support the statement that mortality from cancer was higher than that from heart disease in non-Hispanic white persons in 2015. [Extracted from the article]

This article reports on a study to test whether medical students at Harvard Medical School figure out the diagnosis of each case study featured in the journal from the Massachusetts General Hospital (MGH) more correctly than their counterparts at other medical institutions. These articles feature a case study and present dialogue on diagnosis and treatment options from experts. They are used to teach students and residents how to make a logical diagnosis. 260 case studies were reviewed and points were given for correct answers. Overall, physicians related to Harvard Medical School made the correct diagnosis 86 percent of the time. Physicians from MGH scored a 95 percent accuracy rate, while physicians unrelated to either institution were right 74 percent of the time.

Catheter ablation has brought major advances in the management of patients with atrial fibrillation (AF). As evidenced by multiple randomized trials, AF catheter ablation can reduce the risk of recurrent AF and improve quality of life. In some studies, AF ablation significantly reduced cardiovascular hospitalizations. Despite the existing data on AF catheter ablation, numerous knowledge gaps remain concerning this intervention. This report is based on a recent virtual workshop convened by the National Heart, Lung, and Blood Institute to identify key research opportunities in AF ablation. We outline knowledge gaps related to emerging technologies, the relationship between cardiac structure and function and the success of AF ablation in patient subgroups in whom clinical benefit from ablation varies, and potential platforms to advance clinical research in this area. This report also considers the potential value and challenges of a sham ablation randomized trial. Prioritized research opportunities are identified and highlighted to empower relevant stakeholders to collaborate in designing and conducting effective, cost-efficient, and transformative research to optimize the use and outcomes of AF ablation. [ABSTRACT FROM AUTHOR]

Background: Diabetes is a well-established risk factor for thromboembolism in patients with atrial fibrillation (AF), but less is known about how diabetes influences outcomes among AF patients.Objectives: This study assessed whether symptoms, health status, care, and outcomes differ between AF patients with and without diabetes.Methods: The cohort study included 9,749 patients from the ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, a prospective, nationwide, outpatient registry of patients with incident and prevalent AF. Outcomes included symptoms, health status, and AF treatment, as well as 2-year risk of death, hospitalization, thromboembolic events, heart failure (HF), and AF progression.Results: Patients with diabetes (29.5%) were younger, more likely to have hypertension, chronic kidney disease, HF, coronary heart disease, and stroke. Compared to patients without diabetes, patients with diabetes also had a lower Atrial Fibrillation Effects on Quality of Life score of 80 (interquartile range [IQR]: 62.5 to 92.6) versus 82.4 (IQR: 67.6 to 93.5; p = 0.025) and were more likely to receive anticoagulation (p < 0.001). Diabetes was associated with higher mortality risk, including overall (adjusted hazard ratio [aHR]: 1.63; 95% confidence interval [CI]: 1.04 to 2.56, for age <70 years vs. aHR: 1.25; 95% CI: 1.09 to 1.44, for age ≥70 years) and cardiovascular (CV) mortality (aHR: 2.20; 95% CI: 1.22 to 3.98, for age <70 years vs. 1.24; 95% CI: 1.02 to 1.51 for age ≥70 years). Diabetes conferred a higher risk of non-CV death, sudden cardiac death, hospitalization, CV hospitalization, and non-CV and nonbleeding-related hospitalization, but no increase in risks of thromboembolic events, bleeding-related hospitalization, new-onset HF, and AF progression.Conclusions: Among AF patients, diabetes was associated with worse AF symptoms and lower quality of life, and increased risk of death and hospitalizations, but not thromboembolic or bleeding events. [ABSTRACT FROM AUTHOR]

The National Heart, Lung, and Blood Institute convened a working group in January 2015 to explore issues related to an integrated data network for congenital heart disease research. The overall goal was to develop a common vision for how the rapidly increasing volumes of data captured across numerous sources can be managed, integrated, and analyzed to improve care and outcomes. This report summarizes the current landscape of congenital heart disease data, data integration methodologies used across other fields, key considerations for data integration models in congenital heart disease, and the short- and long-term vision and recommendations made by the working group. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess the pattern of the adoption of internal mammary artery (IMA) grafting in the United States, test its association with clinical outcomes, and assess whether its effectiveness differs in key clinical subgroups. Background: The effect of IMA grafting on major clinical outcomes has never been tested in a large randomized trial, yet it is now a quality standard for coronary artery bypass graft (CABG) surgery. Methods: We identified Medicare beneficiaries ≥66 years of age who underwent isolated multivessel CABG between 1988 and 2008, and we documented patterns of IMA use over time. We used a multivariable propensity score to match patients with and without an IMA and compared rates of death, myocardial infarction (MI), and repeat revascularization. We tested for variations in IMA effectiveness with treatment × covariate interaction tests. Results: The IMA use in CABG rose slowly from 31% in 1988 to 91% in 2008, with persistent wide geographic variations. Among 60,896 propensity score-matched patients over a median 6.8-year follow-up, IMA use was associated with lower all-cause mortality (adjusted hazard ratio: 0.77, p < 0.001), lower death or MI (adjusted hazard ratio: 0.77, p < 0.001), and fewer repeat revascularizations over 5 years (8% vs. 9%, p < 0.001). The association between IMA use and lower mortality was significantly weaker (p ≤ 0.008) for older patients, women, and patients with diabetes or peripheral arterial disease. Conclusions: Internal mammary artery grafting was adopted slowly and still shows substantial geographic variation. IMA use is associated with lower rates of death, MI, and repeat coronary revascularization. [Copyright &y& Elsevier]

Background. Widespread use of broad-spectrum antibiotics contributes to increasing rates of bacterial resistance to antibiotics. Second-generation macrolides have become popular for use among children because of their broad spectrum and favorable dosing and side-effect profiles, although experts do not generally recommend them for use as initial treatment of infections among younger children. Objective. To assess trends in second-generation macrolide use from 1996 to 2000 among children treated as outpatients in 9 US health plans, including associated diagnoses and use as initial treatment. Methods. We sampled claims data for 25 000 children, 3 months to <18 years of age, who were enrolled between September 1, 1995, and August 31, 2000, in each of 9 US health plans. Medications dispensed were linked with ambulatory visit claims to assign diagnoses. Dispensings without another antibiotic dispensing recorded in the previous 42 days were analyzed as initial treatment of a new illness episode. We analyzed trends in prescribing overall, for initial therapy, and, within specific diag-noses, for differences among health plans. Results. From 1995-1996 to 1999-2000, although overall antibiotic use decreased from 1.15 to 0.91 dispensings per person-year, second-generation macrolide use increased from 0.022 to 0.063 dispensings per person-year. Use as a proportion of all antibiotic dispensings in-creased from 1.9% to 6.9%, and use as initial therapy increased from 1.4% to 6%. For children <6 years of age, second-generation macrolide use as initial therapy increased from 0.9% to 5.0% for otitis media and from 5.2% to 24.0% for pneumonia. There was a wide range of prescribing rates among health plans during the last year of the study, from 0.006 to 0.135 dispensings per person-year. Conclusions. Despite recent trends toward decreased antibiotic use among children, the use of second-generation macrolides among children has increased dramatically, even among younger... [ABSTRACT FROM AUTHOR]

Background: Few studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States.Methods: A multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010 was established from 4 large, US-based integrated health care delivery systems. Computerized databases were accessed and medical records reviewed to collect information on patient demographics, clinical risk factors, initial antithrombotic treatment, and vital status. Multivariable Cox regression models were used to estimate the risk of death at 90 days.Results: The cohort comprised 5497 adults with acute venous thromboembolism. Pulmonary embolism was predominantly managed in the hospital setting (95.0%), while 54.5% of patients with lower extremity thrombosis were treated as outpatients. Anticoagulant treatment differed according to thromboembolism type: 2688 patients (92.8%) with pulmonary embolism and 1625 patients (86.9%) with lower extremity thrombosis were discharged on anticoagulants, compared with 286 patients (80.1%) with upper extremity thrombosis and 69 (54.8%) patients with other thrombosis. While 4.5% of patients died during the index episode, 15.4% died within 90 days. Pulmonary embolism was associated with a higher 90-day death risk than lower extremity thrombosis (adjusted hazard ratio 1.23; 95% confidence interval, 1.04-1.47), as was not being discharged on anticoagulants (adjusted hazard ratio 5.56; 95% confidence interval, 4.76-6.67).Conclusions: In this multicenter, community-based study of patients with acute venous thromboembolism, anticoagulant treatment and outcomes varied by thromboembolism type. Although case fatality during the acute episode was relatively low, 15.4% of people with thromboembolism died within 90 days of the index diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Heart disease and stroke remain among the leading causes of death nationally. We examined whether differences in recent trends in heart disease, stroke, and total mortality exist in the United States and Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system.Methods: The main outcome measures were comparisons of US and KPNC total, age-specific, and sex-specific changes from 2000 to 2015 in mortality rates from heart disease, coronary heart disease, stroke, and all causes. The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data system was used to determine US mortality rates. Mortality rates for KPNC were determined from health system, Social Security vital status, and state death certificate databases.Results: Declines in age-adjusted mortality rates were noted in KPNC and the United States for heart disease (36.3% in KPNC vs 34.6% in the United States), coronary heart disease (51.0% vs 47.9%), stroke (45.5% vs 38.2%), and all-cause mortality (16.8% vs 15.6%). However, steeper declines were noted in KPNC than the United States among those aged 45 to 65 years for heart disease (48.3% KPNC vs 23.6% United States), coronary heart disease (55.6% vs 35.9%), stroke (55.8% vs 26.0%), and all-cause mortality (31.5% vs 9.1%). Sex-specific changes were generally similar.Conclusions: Despite significant declines in heart disease and stroke mortality, there remains an improvement gap nationally among those aged less than 65 years when compared with a large integrated healthcare delivery system. Interventions to improve cardiovascular mortality in the vulnerable middle-aged population may play a key role in closing this gap. [ABSTRACT FROM AUTHOR]

Background: Food insecurity is associated with poor glycemic control and increased risk for diabetes-related complications. The clinical benefit of addressing these challenges through a medically supportive grocery prescription (GRx) program in patients with type 2 diabetes mellitus (T2D) remains unclear. We report the aims and design of a randomized clinical trial to evaluate the effectiveness of a 6-month GRx intervention on hemoglobin A1c (HbA1c) levels among low-income adults with T2D., Methods: The Kaiser Permanente Evaluating Nutritional Interventions in Food-Insecure High-Risk Adults (KP ENRICH) Study is a pragmatic randomized trial enrolling 1100 participants within Kaiser Permanente Northern California and Southern California, two integrated health care delivery systems serving >9 million members. Medicaid-insured adults with T2D and baseline HbA1c ≥7.5% will be randomized at a 1:1 ratio to either GRx, delivered as $100 per month for select items from among a curated list of healthful food groups in an online grocery ordering and home-delivery platform along with biweekly digital nutrition educational materials, or control, consisting of free membership and deliveries from the online grocery platform but without curated food groups or purchasing dollars. The primary outcome is 6-month change in HbA1c. Secondary outcomes include 12-month change in HbA1c, and 6- and 12-month change in medical resource utilization, food security, nutrition security, dietary habits, diabetes-related quality of life, and dietary self-efficacy., Conclusions: The results of this large randomized clinical trial of GRx will help inform future policy and health system-based initiatives to improve food and nutrition security, disease management, and health equity among patients with T2D., Competing Interests: Declaration of competing interest Dr. Mozaffarian reports research funding from the National Institutes of Health, Gates Foundation, Kaiser Permanente Fund, National Association of Chain Drug Stores Foundation, and Rockefeller Foundation; personal fees from Acasti Pharma (ended); scientific advisory board, Beren Therapeutics, Brightseed, Calibrate, Elysium Health, Filtricine, HumanCo, Instacart Health, January Inc., Season Health, Validation Institute (ended: Perfect Day, Tiny Organics); an unrestricted gift from Google; stock ownership in Calibrate and HumanCo; and chapter royalties from UpToDate. Others at the Food is Medicine Institute have received research funding or gifts for investigator-initiated research from About Fresh, the American Diabetes Association, Kroger, and family foundations. The remaining authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Data on the epidemiology of aortic stenosis (AS) are primarily derived from single center experiences and administrative claims data that do not delineate by degree of disease severity., Methods: An observational cohort study of adults with echocardiographic AS was conducted January 1st, 2013-December 31st, 2019 at an integrated health system. The presence/grade of AS was based on physician interpretation of echocardiograms., Results: A total of 66,992 echocardiogram reports for 37,228 individuals were identified. The mean ± standard deviation (SD) age was 77.5 ± 10.5, 50.5% (N = 18,816) were women, and 67.2% (N = 25,016) were non-Hispanic whites. The age-standardized AS prevalence increased from 589 (95% Confidence Interval [CI] 580-598) to 754 (95% CI 744-764) cases per 100,000 during the study period. The age-standardized AS prevalences were similar in magnitude among non-Hispanic whites (820, 95% CI 806-834), non-Hispanic blacks (728, 95% CI 687-769), and Hispanics (789, 95% CI 759-819) and substantially lower for Asian/Pacific Islanders (511, 95% CI 489-533). Finally, the distribution of AS by degree of severity remained relatively unchanged over time., Conclusions and Relevance: The population prevalence of AS has grown considerably over a short timeframe although the distribution of AS severity has remained stable., Competing Interests: Declaration of Competing Interest APA is supported by a Mentored Patient-Oriented Research Career Development Award (K23HL150159) through the National Heart, Lung, and Blood Institute and has received relevant research support through grants to his institution from Abbott, Edwards Lifesciences, Lexicon, and Novartis. ASG has received relevant research support through grants to his institution from the National Heart, Lung and Blood Institute; National Institute of Diabetes, Digestive and Kidney Diseases; National Institute on Aging; Amarin Pharma, Inc.; Novartis; Janssen Research & Development; and CSL Behring. All other authors have no relevant conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not., Objective: To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD)., Design: Multicenter prospective cohort study., Setting: United States., Participants: Patients with CKD ( n  = 3150)., Measurements: Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits., Results: During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m 2 ) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m 2 ) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m 2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m 2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m 2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m 2 per year) also had CI bounds that included the possibility of no effect., Limitations: Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge., Conclusion: After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small., Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3617.

Atrial fibrillation (AF) is one of the strongest risk factors for ischemic stroke, which is a leading cause of disability and death. Given the aging population, increasing prevalence of AF risk factors, and improved survival in those with cardiovascular disease, the number of individuals affected by AF will continue increasing over time. While multiple proven stroke prevention therapies exist, important questions remain about the optimal approach to stroke prevention at the population and individual patient levels. Our report summarizes the National Heart, Lung, and Blood Institute virtual workshop focused on identifying key research opportunities related to stroke prevention in AF. The workshop reviewed major knowledge gaps and identified targeted research opportunities to advance stroke prevention in AF in the following areas: (1) improving risk stratification tools for stroke and intracranial hemorrhage; (2) addressing challenges with oral anticoagulants; and (3) delineating the optimal roles of percutaneous left atrial appendage occlusion and surgical left atrial appendage closure/excision. This report aims to promote innovative, impactful research that will lead to more personalized, effective use of stroke prevention strategies in people with AF.

Importance: Only modest attention has been paid to the contributions of social determinants of health to atrial fibrillation (AF) risk factors, diagnosis, symptoms, management, and outcomes. The diagnosis of AF provides unique challenges exacerbated by the arrhythmia's often paroxysmal nature and individuals' disparate access to health care and technologies that facilitate detection. Social determinants of health affect access to care and management decisions for AF, increasing the likelihood of adverse outcomes among individuals who experience systemic disadvantages. Developing effective approaches to address modifiable social determinants of health requires research to eliminate the substantive inequities in health care delivery and outcomes in AF., Observations: The National Heart, Lung, and Blood Institute convened an expert panel to identify major knowledge gaps and research opportunities in the field of social determinants of AF. The workshop addressed the following social determinants: (1) socioeconomic status and access to care; (2) health literacy; (3) race, ethnicity, and racism; (4) sex and gender; (5) shared decision-making in systemically disadvantaged populations; and (6) place, including rurality, neighborhood, and community. Many individuals with AF have multiple adverse social determinants, which may cluster in the individual and in systemically disadvantaged places (eg, rural locations, urban neighborhoods). Cumulative disadvantages may accumulate over the life course and contribute to inequities in the diagnosis, management, and outcomes in AF., Conclusions and Relevance: Workshop participants identified multiple critical research questions and approaches to catalyze social determinants of health research that address the distinctive aspects of AF. The long-term aspiration of this work is to eradicate the substantive inequities in AF diagnosis, management, and outcomes across populations.

Background: The approved use of transcatheter aortic valve replacement (TAVR) for aortic stenosis has expanded substantially over time. However, gaps remain with respect to accurately delineating risk for poor clinical and patient-centered outcomes. Our objective was to develop prediction models for 30-day clinical and patient-centered outcomes after TAVR within a large, diverse community-based population., Methods: We identified all adults who underwent TAVR between 2013-2019 at Kaiser Permanente Northern California, an integrated healthcare delivery system, and were monitored for the following 30-day outcomes: all-cause death, improvement in quality of life, all-cause hospitalizations, all-cause emergency department (ED) visits, heart failure (HF)-related hospitalizations, and HF-related ED visits. We developed prediction models using gradient boosting machines using linked demographic, clinical and other data from the Society for Thoracic Surgeons (STS)/American College of Cardiology (ACC) TVT Registry and electronic health records. We evaluated model performance using area under the curve (AUC) for model discrimination and associated calibration plots. We also evaluated the association of individual predictors with outcomes using logistic regression for quality of life and Cox proportional hazards regression for all other outcomes., Results: We identified 1,565 eligible patients who received TAVR. The risks of adverse 30-day post-TAVR outcomes ranged from 1.3% (HF hospitalizations) to 15.3% (all-cause ED visits). In models with the highest discrimination, discrimination was only moderate for death (AUC 0.60) and quality of life (AUC 0.62), but better for HF-related ED visits (AUC 0.76). Calibration also varied for different outcomes. Importantly, STS risk score only independently predicted death and all-cause hospitalization but no other outcomes. Older age also only independently predicted HF-related ED visits, and race/ethnicity was not significantly associated with any outcomes., Conclusions: Despite using a combination of detailed STS/ACC TVT Registry and electronic health record data, predicting short-term clinical and patient-centered outcomes after TAVR remains challenging. More work is needed to identify more accurate predictors for post-TAVR outcomes to support personalized clinical decision making and monitoring strategies., Competing Interests: Disclosures Dr. Ambrosy is supported by a Mentored Patient-Oriented Research Career Development Award (K23HL150159) through the National Heart, Lung, and Blood Institute, has received relevant research support through grants to his institution from Amarin Pharma, Inc., Abbott, and Novartis, and modest reimbursement for travel from Novartis. Dr. Go has received research funding through his institution from the National Heart, Lung and Blood Institute; National Institute on Aging; National Institute of Diabetes, Digestive and Kidney Diseases; Novartis; Janssen Research & Development; and Bristol Meyers-Squibb., (Copyright © 2022 Elsevier Inc. All rights reserved.)

South Asian ethnicity is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk and has been identified as a "risk enhancer" in the 2018 American College of Cardiology/American Heart Association Guidelines. Risk estimation and statin eligibility in South Asians is not well understood; we studied the accuracy of 10-years ASCVD risk prediction by the pooled cohort equation (PCE), based on statin use, in a South Asian cohort. This is a retrospective cohort study of Kaiser Permanente Northern California South Asian members without existing ASCVD, age range 30-70, and 10-years follow up. ASCVD events were defined as myocardial infarction, ischemic stroke, and cardiovascular death. The cohort was stratified by statin use during the study period: never; at baseline and during follow-up; and only during follow-up. Predicted probability of ASCVD, using the PCE was calculated and compared to observed ASCVD events for low < 5.0%, borderline 5.0 to < 7.5%, intermediate 7.5 to < 20.0%, and high ≥ 20.0% risk groups. A total of 1835 South Asian members were included: 773 never on statin, 374 on statins at baseline and follow-up, and 688 on statins during follow-up only. ASCVD risk was underestimated by the PCE in low-risk groups: entire cohort: 1.8 versus 4.9%, p < 0.0001; on statin at baseline and follow-up: 2.58 versus 8.43%, p < 0.0001; on statin during follow-up only: 2.18 versus 7.77%, p < 0.0001; and never on statin: 1.37 versus 2.09%, p = 0.12. In this South Asian cohort, the PCE underestimated risk in South Asians, regardless of statin use, in the low risk ASCVD risk category., (© 2022. The Author(s).)

Background: Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF., Methods: The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care., Results: Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained., Conclusions: GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the "burden" of AF detected (percent time in AF, longest episode), and physicians' OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: At a given estimated glomerular filtration rate (eGFR), individuals who are Black have higher rates of mortality and kidney failure with replacement therapy (KFRT) compared with those who are non-Black. Whether the recently adopted eGFR equations without race preserve racial differences in risk of mortality and KFRT at a given eGFR is unknown., Objective: To assess whether eGFR equations with and without race and cystatin C document racial differences in risk of KFRT and mortality in populations including Black and non-Black participants., Design, Setting, and Participants: Retrospective individual-level data analysis of 62 011 participants from 5 general population and 3 chronic kidney disease (CKD) US-based cohorts with serum creatinine, cystatin C, and follow-up for KFRT and mortality from 1988 to 2018., Exposures: Chronic Kidney Disease Epidemiology Collaboration equation with serum creatinine (eGFRcr with and without race), cystatin C (eGFRcys without race), or both markers (eGFRcr-cys without race)., Main Outcomes and Measures: The prevalence of decreased eGFR at baseline and hazard ratios of KFRT and mortality in Black vs non-Black participants were calculated, adjusted for age and sex. Analyses were performed within each cohort and with random-effect meta-analyses of the models., Results: Among 62 011 participants (20 773 Black and 41 238 non-Black; mean age, 63 years; 53% women), the prevalence ratio (95% CI; percent prevalences) of eGFR less than 60 mL/min/1.73 m2 comparing Black with non-Black participants was 0.98 (95% CI, 0.93-1.03; 11% vs 12%) for eGFRcr with race, 0.95 (95% CI, 0.91-0.98; 17% vs 18%) for eGFRcys, and 1.2 (95% CI, 1.2-1.3; 13% vs 11%) for eGFRcr-cys but was 1.8 (95% CI, 1.7-1.8; 15% vs 9%) for eGFRcr without race. During a mean follow-up of 13 years, 8% and 4% of Black and non-Black participants experienced KFRT and 34% and 39% died, respectively. Decreased eGFR was associated with significantly greater risk of both outcomes for all equations. At an eGFR of 60 mL/min/1.73 m2, the hazard ratios for KFRT comparing Black with non-Black participants were 2.8 (95% CI, 1.6-4.9) for eGFRcr with race, 3.0 (95% CI, 1.5-5.8) for eGFRcys, and 2.8 (95% CI, 1.4-5.4) for eGFRcr-cys vs 1.3 (95% CI, 0.8-2.1) for eGFRcr without race. The 5-year absolute risk differences for KFRT comparing Black with non-Black participants were 1.4% (95% CI, 0.2%-2.6%) for eGFRcr with race, 1.1% (95% CI, 0.2%-1.9%) for eGFRcys, and 1.3% (95% CI, 0%-2.6%) for eGFRcr-cys vs 0.37% (95% CI, -0.32% to 1.05%) for eGFRcr without race. Similar patterns were observed for mortality., Conclusions and Relevance: In this retrospective analysis of 8 US cohorts including Black and non-Black individuals, the eGFR equation without race that included creatinine and cystatin C, but not the eGFR equation without race that included creatinine without cystatin C, demonstrated racial differences in the risk of KFRT and mortality throughout the range of eGFR. The eGFRcr-cys equation may be preferable to the eGFRcr equation without race for assessing racial differences in the risk of KFRT and mortality associated with low eGFR.

Background: The inclusion of race in equations to estimate the glomerular filtration rate (GFR) has become controversial. Alternative equations that can be used to achieve similar accuracy without the use of race are needed., Methods: In a large national study involving adults with chronic kidney disease, we conducted cross-sectional analyses of baseline data from 1248 participants for whom data, including the following, had been collected: race as reported by the participant, genetic ancestry markers, and the serum creatinine, serum cystatin C, and 24-hour urinary creatinine levels., Results: Using current formulations of GFR estimating equations, we found that in participants who identified as Black, a model that omitted race resulted in more underestimation of the GFR (median difference between measured and estimated GFR, 3.99 ml per minute per 1.73 m 2 of body-surface area; 95% confidence interval [CI], 2.17 to 5.62) and lower accuracy (percent of estimated GFR within 10% of measured GFR [P 10 ], 31%; 95% CI, 24 to 39) than models that included race (median difference, 1.11 ml per minute per 1.73 m 2 ; 95% CI, -0.29 to 2.54; P 10 , 42%; 95% CI, 34 to 50). The incorporation of genetic ancestry data instead of race resulted in similar estimates of the GFR (median difference, 1.33 ml per minute per 1.73 m 2 ; 95% CI, -0.12 to 2.33; P 10 , 42%; 95% CI, 34 to 50). The inclusion of non-GFR determinants of the serum creatinine level (e.g., body-composition metrics and urinary excretion of creatinine) that differed according to race reported by the participants and genetic ancestry did not eliminate the misclassification introduced by removing race (or ancestry) from serum creatinine-based GFR estimating equations. In contrast, the incorporation of race or ancestry was not necessary to achieve similarly statistically unbiased (median difference, 0.33 ml per minute per 1.73 m 2 ; 95% CI, -1.43 to 1.92) and accurate (P 10 , 41%; 95% CI, 34 to 49) estimates in Black participants when GFR was estimated with the use of cystatin C., Conclusions: The use of the serum creatinine level to estimate the GFR without race (or genetic ancestry) introduced systematic misclassification that could not be eliminated even when numerous non-GFR determinants of the serum creatinine level were accounted for. The estimation of GFR with the use of cystatin C generated similar results while eliminating the negative consequences of the current race-based approaches. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others.)., (Copyright © 2021 Massachusetts Medical Society.)

Background and Objectives: The association of AKI after pediatric cardiac surgery with long-term CKD and hypertension development is unclear. The study objectives were to determine whether AKI after pediatric cardiac surgery is associated with incident CKD and hypertension., Design, Setting, Participants, & Measurements: This was a prospective cohort study of children of 1 month to 18 years old who were undergoing cardiac surgery at two tertiary care centers (Canada, United States). Participants were recruited before cardiac surgery and were followed during hospitalization and at 3, 12, 24, 36, and 48 months after discharge. Exposures were postoperative AKI, based on the Kidney Disease Improving Global Outcomes (KDIGO) definition, and age <2 years old at surgery. Outcomes and measures were CKD (low eGFR or albuminuria for age) and hypertension (per the 2017 American Academy of Pediatrics guidelines) at follow-up, with the composite outcome of CKD or hypertension., Results: Among 124 participants, 57 (46%) developed AKI. AKI versus non-AKI participants had a median (interquartile range) age of 8 (4.8-40.8) versus 46 (6.0-158.4) months, respectively, and higher preoperative eGFR. From the 3- to 48-month follow-up, the cohort prevalence of CKD was high (17%-20%); hypertension prevalence was also high (22%-30%). AKI was not significantly associated with the development of CKD throughout follow-up. AKI was associated with hypertension development at 12 months after discharge (adjusted relative risk, 2.16; 95% confidence interval, 1.18 to 3.95), but not at subsequent visits. Children aged <2 years old at surgery had a significantly higher prevalence of hypertension during follow-up than older children (40% versus 21% at 3-month follow-up; 32% versus 13% at 48-month follow-up)., Conclusions: CKD and hypertension burden in the 4 years after pediatric cardiac surgery is high. Young age at surgery, but not AKI, is associated with their development., (Copyright © 2020 by the American Society of Nephrology.)

While oral anticoagulation is a cornerstone of stroke prevention therapy in atrial fibrillation (AF), few studies have evaluated comparative discontinuation rates in clinical practice. The objective of this study is to evaluate discontinuation rates among patients on warfarin and direct oral anticoagulants (DOACs) in clinical practice., Methods: The ORBIT-AF II Registry enrolled 10,005 total AF patients with a CHA 2 DS 2 VASc score of ≥2 on warfarin or DOACs from 235 clinical practices across the US from February 13, 2013 and July 12, 2017. Descriptive statistics and multivariable Cox regression modeling were used to describe baseline characteristics and predictors of discontinuation. Unadjusted and adjusted discontinuation rates and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and propensity score adjustment, respectively., Results: At baseline, 16.4% (N = 1642/10,005) were treated with warfarin, 83.6% (N = 8363/10,005) with DOACs and 1498/10,005 patients (15.0%) discontinued therapy [warfarin = 236/1642 (14.4%) vs DOACs = 1262/8363 (15.1%)]. At 6 and 12 months respectively, among 7049 patients with a new diagnosis of AF within 6 months, adjusted discontinuation rates for warfarin versus DOACs were as follows: [6 months: 7.9%, 95%CI (6.8%-9.0%) vs 9.6% (8.4%-10.7%), P = .16]; [12 months: 12.7% (11.0%-14.3%) vs 15.3% (13.6%-16.9%), P = .02)]. Patients who discontinued therapy with warfarin or DOACs had higher risk of adverse clinical outcomes including: all-cause mortality and cardiovascular death (CV) than those who continued treatment., Conclusion: In a community based AF cohort, adjusted rates of discontinuation at 12-months were higher in DOAC-treated versus VKA-treated patients. Discontinuation of oral anticoagulation was associated with increased absolute risk of all-cause mortality and CV death., Clinical Trial Registration: URL:https://clinicaltrials.gov. Unique Identifier: NCT01701817., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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 <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross-sectional and longitudinal KCCQ scores. Among 2873 participants, GDF-15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19-1.68) and galectin-3 (1.28; 1.12-1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT-proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF-15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12-1.65), hsTnT (1.20; 1.01-1.44), and NT-proBNP (1.30; 1.08-1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin-3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF , GDF-15, galectin-3, NT-proBNP, and hsTnT were associated with low KCCQ either at baseline or during follow-up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.

The interrelationships between atrial fibrillation (AF) and heart failure (HF) are complex and poorly understood, yet the number of patients with AF and HF continues to increase worldwide. Thus, there is a need for initiatives that prioritize research on the intersection between AF and HF. This article summarizes the proceedings of a virtual workshop convened by the US National Heart, Lung, and Blood Institute to identify important research opportunities in AF and HF. Key knowledge gaps were reviewed and research priorities were proposed for characterizing the pathophysiological overlap and deleterious interactions between AF and HF; preventing HF in people with AF; preventing AF in individuals with HF; and addressing symptom burden and health status outcomes in AF and HF. These research priorities will hopefully help inform, encourage, and stimulate innovative, cost-efficient, and transformative studies to enhance the outcomes of patients with AF and HF.

Importance: The severity of acute kidney injury (AKI) is usually determined based on the maximum serum creatinine concentration. However, the trajectory of kidney function recovery could be an additional important dimension of AKI severity., Objective: To assess whether the trajectory of kidney function recovery within 72 hours after AKI is associated with long-term risk of clinical outcomes., Design, Setting, and Participants: This prospective, multicenter cohort study enrolled 1538 adults with or without AKI 3 months after hospital discharge between December 1, 2009, and February 28, 2015. Statistical analyses were completed November 1, 2018. Participants with or without AKI were matched based on demographic characteristics, site, comorbidities, and prehospitalization estimated glomerular filtration rate. Participants with AKI were classified as having resolving or nonresolving AKI based on previously published definitions. Resolving AKI was defined as a decrease in serum creatinine concentration of 0.3 mg/dL or more or 25% or more from maximum in the first 72 hours after AKI diagnosis. Nonresolving AKI was defined as AKI not meeting the definition for resolving AKI., Main Outcomes and Measures: The primary outcome was a composite of major adverse kidney events (MAKE), defined as incident or progressive chronic kidney disease, long-term dialysis, or all-cause death during study follow-up., Results: Among 1538 participants (964 men; mean [SD] age, 64.6 [12.7] years), 769 (50%) had no AKI, 475 (31%) had a resolving AKI pattern, and 294 (19%) had a nonresolving AKI pattern. After a median follow-up of 4.7 years, the outcome of MAKE occurred in 550 (36%) of all participants. The adjusted hazard ratio for MAKE was higher for patients with resolving AKI (adjusted hazard ratio, 1.52; 95% CI, 1.01-2.29; P = .04) and those with nonresolving AKI (adjusted hazard ratio 2.30; 95% CI, 1.52-3.48; P < .001) compared with participants without AKI. Within the population of patients with AKI, nonresolving AKI was associated with a 51% greater risk of MAKE (95% CI, 22%-88%; P < .001) compared with resolving AKI. The higher risk of MAKE among patients with nonresolving AKI was explained by a higher risk of incident and progressive chronic kidney disease., Conclusions and Relevance: This study suggests that the 72-hour period immediately after AKI distinguishes the risk of clinically important kidney-specific long-term outcomes. The identification of different AKI recovery patterns may improve patient risk stratification, facilitate prognostic enrichment in clinical trials, and enable recognition of patients who may benefit from nephrology consultation.

Rationale & Objectives: Few studies have investigated racial disparities in survival among dialysis patients in a manner that considers risk factors and mortality during the phase of kidney disease before maintenance dialysis. Our objective was to explore racial variations in survival among dialysis patients and relate them to racial differences in comorbid conditions and rates of death in the setting of kidney disease not yet requiring dialysis therapy., Study Design: Retrospective cohort study., Settings & Participants: 3,288 black and white participants in the Chronic Renal Insufficiency Cohort (CRIC), none of whom were receiving dialysis at enrollment., Exposure: Race., Outcome: Mortality., Analytic Approach: Cox proportional hazards regression was used to examine the association between race and mortality starting at: (1) time of dialysis initiation and (2) entry into the CRIC., Results: During 7.1 years of median follow-up, 678 CRIC participants started dialysis. Starting from the time of dialysis initiation, blacks had lower risk for death (unadjusted HR, 0.67; 95% CI, 0.51-0.87) compared with whites. Starting from baseline CRIC enrollment, the strength of the association between some risk factors and dialysis was notably stronger for whites than blacks. For example, the HR for dialysis onset in the presence (vs absence) of heart failure at CRIC enrollment was 1.30 (95% CI, 1.01-1.68) for blacks versus 2.78 (95% CI, 1.90-4.50) for whites, suggesting differential severity of these risk factors by race. When we included deaths occurring both before and after dialysis, risk for death was higher among blacks (vs whites) starting from CRIC enrollment (HR, 1.41; 95% CI, 1.22-1.64), but this finding was attenuated in adjusted models (HR, 1.08; 95% CI, 0.91-1.28)., Limitations: Residual confounding., Conclusions: The apparent survival advantage among blacks over whites treated with dialysis may be attributed to selected transition of a subset of whites with more severe comorbid conditions onto dialysis., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The association between statins and diabetes mellitus (DM) remains controversial. The Kaiser Permanente CHAMP Study identified adults without DM who had cardiovascular (CV) risk factors and no previous lipid lowering therapy (LLT) between 2008 and 2010. The CV risk factors included known atherosclerotic CV disease (ASCVD), elevated low-density lipoprotein cholesterol ≥190 mg/dl, or a low-density lipoprotein cholesterol between 70 and 189 mg/dl and an estimated 10-year ASCVD risk ≥7.5%. Incident DM was defined as ≥2 abnormal tests (i.e., A1C ≥6.5% or a fasting blood glucose ≥126 mg/dl) or ≥1 abnormal test result plus a new diagnostic code or medication for DM. Among 213,289 eligible adults, 28,149 patients initiating statins were carefully matched to an equal number of patients who remained off LLT during follow-up. Compared with matched patients not receiving statins, those initiating statin therapy had the same mean age (67.9 ± 9.4 years) and gender (42.8% women). The crude rate (per 100 person-years) of incident DM was low (0.55, 95% confidence interval [CI] 0.52 to 0.59) but was marginally higher in patients who were treated with a statin (0.69, 95% CI 0.64 to 0.74) versus no LLT (0.42, 95% CI 0.38 to 0.46). After additional adjustment, statin therapy was associated with a modestly increased risk of incident DM (adjusted hazard ratio 1.17, 95% CI 1.02 to 1.34). In conclusion, in adults without DM at increased ASCVD risk, initiation of statin therapy was independently associated with a modestly higher risk of incident DM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Importance: A deceleration in the rate of decrease of heart disease (HD) mortality between 2011 and 2014 has been reported. In the context of the rapid increase in the population of adults aged 65 years and older, extending the examination of HD mortality through 2017 has potentially important implications for public health and medical care., Objective: To examine changes in the age-adjusted mortality rate and the number of deaths within subcategories of HD from 2011 to 2017 in conjunction with the change in the size of the US population during the same period., Design, Setting, and Participants: In this quality improvement study, the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) data set was used to identify national changes in the US population aged 65 years and older and in the age-adjusted mortality rates and number of deaths that were listed with an underlying cause of HD, coronary heart disease (CHD), heart failure, and other HDs from January 1, 2011, to December 31, 2017., Main Outcomes and Measures: Changes from 2011 to 2017 in the US population and in age-adjusted mortality rates and number of deaths that were listed with an underlying cause of HD, CHD, heart failure (both as an underlying and a contributing cause), and other HDs overall, by sex and race/ethnicity., Results: The total size of this population of US adults aged 65 years and older increased 22.9% from 41.4 million to 50.9 million between January 1, 2011, and December 31, 2017, while the population of adults younger than 65 years increased by only 1.7%. During this period, the age-adjusted mortality rate decreased 5.0% for HD and 14.9% for CHD while increasing 20.7% for heart failure and 8.4% for other HDs. The number of deaths increased 8.5% for HD, 38.0% for heart failure, and 23.4% for other HDs while decreasing 2.5% for CHD. A total of 80% of HD deaths occurred in the group of adults aged 65 years and older., Conclusions and Relevance: The substantial increase in the growth rate of the group of adults aged 65 years and older who have the highest risk of HD was associated with an increase in the number of HD deaths in this group despite a slowly declining HD mortality rate in the general population. With the number of adults aged 65 years and older projected to increase an additional 44% from 2017 to 2030, innovative and effective approaches to prevent and treat HD, particularly the substantially increasing rates of heart failure, are needed.

Background: Studies evaluating the effects of atrial fibrillation (AF) catheter ablation versus antiarrhythmic therapy on outcomes have shown mixed results. In addition, guidelines recommend continuing oral anticoagulation (OAC) after ablation for those at risk of stroke, but real-world data are lacking., Methods: We evaluated outcomes including death, myocardial infarction, stroke or systemic embolism, intracranial bleeding, major bleeding, and hospitalization in patients undergoing AF ablation compared with a propensity score matched cohort of patients treated with anti-arrhythmic medications only in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registries. Cox proportional hazards regression was performed to evaluate the association between AF ablation and outcomes. We then evaluated patterns of treatment with OAC among AF ablation patients., Results: Among 21 595 patients, 1190 (6%) underwent de novo AF ablation. Our propensity score-matched cohort included 1087 patients who underwent AF ablation matched 1:1 with 1087 patients treated with antiarrhythmic medications only. There were no significant differences in the risk of all-cause and cardiovascular death, and most other major adverse cardiovascular and neurological events. AF catheter ablation was associated with an increased risk of all-cause hospitalization during follow-up (hazard ratio, 1.24 [95% CI, 1.05-1.46]), particularly in the first 3 months (the standard blanking period) after the procedure. Among those who underwent AF ablation with a CHA 2 DS 2 VASc score ≥2 for men and ≥3 for women, 23% had OAC discontinued after ablation. Among those who discontinued OAC, the median time to discontinuation was 6.2 months., Conclusions: In this large US national registry, we found no difference in adjusted rates of cardiovascular or all-cause death between patients treated with AF catheter ablation and antiarrhythmic medications only. Notably, discontinuation of OAC after ablation remains relatively common despite guideline recommendations for continued stroke prevention therapy in patients at risk of stroke.

Rationale & Objective: An elevated fibroblast growth factor 23 (FGF-23) level is independently associated with adverse outcomes in populations with chronic kidney disease, but it is unknown whether FGF-23 testing can improve clinical risk prediction in individuals., Study Design: Prospective cohort study., Setting & Participants: Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,789)., Exposure: Baseline carboxy-terminal FGF-23 (cFGF-23) level., Outcomes: All-cause and cardiovascular (CV) mortality, incident end-stage renal disease (ESRD), heart failure (HF) admission, and atherosclerotic events at 3, 5, and 8 years., Analytical Approach: We assessed changes in model performance by change in area under the receiver operating characteristic curve (ΔAUC), integrated discrimination improvement (IDI), relative IDI, and net reclassification index (NRI) above standard clinical factors. We performed sensitivity analyses, including an additional model comparing the addition of phosphate rather than cFGF-23 level and repeating our analyses using an internal cross-validation cohort., Results: Addition of a single baseline value of cFGF-23 to a base prediction model improved prediction of all-cause mortality (ΔAUC, 0.017 [95% CI, 0.001-0.033]; IDI, 0.021 [95% CI, 0.006-0.036]; relative IDI, 32.7% [95% CI, 8.5%-56.9%]), and HF admission (ΔAUC, 0.008 [95% CI, 0.0004-0.016]; IDI, 0.019 [95% CI, 0.004-0.034]; relative IDI, 10.0% [95% CI, 1.8%-18.3%]), but not CV mortality, ESRD, or atherosclerotic events at 3 years of follow-up. The NRI did not reach statistical significance for any of the 3-year outcomes. The incremental predictive utility of cFGF-23 level diminished in analyses of the 5- and 8-year outcomes. The cFGF-23 models outperformed the phosphate model for each outcome., Limitations: Power to detect increased CV mortality likely limited by low event rate. The NRI is not generalizable without accepted prespecified risk thresholds., Conclusions: Among individuals with CKD, single measurements of cFGF-23 improve prediction of risks for all-cause mortality and HF admission but not CV mortality, ESRD, or atherosclerotic events. Future studies should evaluate the predictive utility of repeated cFGF-23 testing., (Copyright © 2019 National Kidney Foundation, Inc. All rights reserved.)