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Background: Genetic susceptibility to various chronic diseases has been shown to influence heart failure (HF) risk. However, the underlying biological pathways, particularly the role of leukocyte telomere length (LTL), are largely unknown. We investigated the impact of genetic susceptibility to chronic diseases and various traits on HF risk, and whether LTL mediates or modifies the pathways., Methods: We conducted prospective cohort analyses on 404 883 European participants from the UK Biobank, including 9989 incident HF cases. Multivariable Cox regression was used to estimate associations between HF risk and 24 polygenic risk scores (PRSs) for various diseases or traits previously generated using a Bayesian approach. We assessed multiplicative interactions between the PRSs and LTL previously measured in the UK Biobank using quantitative PCR. Causal mediation analyses were conducted to estimate the proportion of the total effect of PRSs acting indirectly through LTL, an integrative marker of biological aging., Results: We identified 9 PRSs associated with HF risk, including those for various cardiovascular diseases or traits, rheumatoid arthritis (P = 1.3E-04), and asthma (P = 1.8E-08). Additionally, longer LTL was strongly associated with decreased HF risk (P-trend = 1.7E-08). Notably, LTL strengthened the asthma-HF relationship significantly (P-interaction = 2.8E-03). However, LTL mediated only 1.13% (P < 0.001) of the total effect of the asthma PRS on HF risk., Conclusions: Our findings shed light onto the shared genetic susceptibility between HF risk, asthma, rheumatoid arthritis, and other traits. Longer LTL strengthened the genetic effect of asthma in the pathway to HF. These results support consideration of LTL and PRSs in HF risk prediction., (Published by Oxford University Press 2024.)

Background: Higher total serum cholesterol is associated with lower mortality in heart failure. Evaluating associations between lipoprotein subfractions and mortality among people with heart failure may provide insights into this observation., Methods: We prospectively enrolled a community cohort of people with heart failure from 2003 to 2012 and assessed vital status through 2021. Plasma collected at enrollment was used to measure lipoprotein subfractions via nuclear magnetic resonance spectroscopy. A composite score of 6 lipoprotein subfractions was generated using the lipoprotein insulin resistance index (LP-IR) algorithm. Using covariate-adjusted proportional hazards regression models, we evaluated associations between LP-IR score and all-cause mortality., Results: Among 1382 patients with heart failure (median follow-up 13.9 years), a one-standard-deviation (SD) increment in LP-IR score was associated with lower mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.97-0.99). Among LP-IR parameters, mean high-density lipoprotein (HDL) particle size was significantly associated with lower mortality (HR per 1-SD decrement in mean HDL particle size = 0.83; 95% CI, 0.78-0.89), suggesting that the inverse association between LP-IR score and mortality may be driven by smaller mean HDL particle size., Conclusions: LP-IR score was inversely associated with mortality among patients with heart failure and may be driven by smaller HDL particle size., (Published by Elsevier Inc.)

Background: Heart failure (HF) risk is greater in rural versus urban regions in the United States (US), potentially due to differences in healthcare coverage and access. Whether this excess risk applies to countries with universal healthcare is unclear and the underlying biological mechanisms are unknown. In the prospective United Kingdom (UK) Biobank, we investigated urban-rural regional differences in HF risk and the mechanistic role of biological aging., Methods: Multivariable Cox regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF in relation to residential urban-rural region and a Biological Health Score (BHS) that reflects biological aging from environmental, social, or dietary stressors. We estimated the proportion of the total effect of urban-rural region on HF mediated through BHS., Results: Among 417,441 European participants, 10,332 incident HF cases were diagnosed during the follow-up. Compared to participants in large urban regions of Scotland, those in England/Wales had significantly increased HF risk (smaller urban: HR = 1.83, 95%CI: 1.64-2.03; suburban: HR = 1.77, 95%CI: 1.56-2.01; very rural: HR = 1.61, 95%CI: 1.39-1.85). Additionally, we found a dose-response relationship between increased biological aging and HF risk (HR per 1 SD increase  = 1.14 (95%CI: 1.12-1.17). Increased biological aging mediated a notable 6.6% ( p  < 0.001) of the total effect of urban-rural region on HF., Conclusion: Despite universal healthcare in the UK, disparities in HF risk by region were observed and may be partly explained by environmental, social, or dietary factors related to biological aging. Our study contributes to precision public health by informing potential biological targets for intervention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wong, Blechter, Rodriquez, Shearer, Breeze, Pérez-Stable and Roger.)

Background: Heart failure (HF) and kidney disease frequently co-occur, increasing mortality risk. The cardiorenal syndrome results from damage to either the heart or kidney impacting the other organ. The epidemiology of cardiorenal syndrome among the general population is incompletely characterized and despite shared risk factors with HF, differences in mortality risk across key demographics have not been well described. Thus, the primary goal of this study was to analyze annual trends in cardiorenal-related mortality, evaluate if these trends differed by age, sex, and race or ethnicity, and describe these trends against a backdrop of HF mortality., Methods and Findings: The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database was used to examine cardiorenal- and HF-related mortality in the US between 2011and 2020. International Classification of Diseases, 10 Revision codes were used to classify cardiorenal-related deaths (I13.x) and HF-related deaths (I11.0, I13.0, I13.2, and I50.x), among decedents aged 15 years or older. Decedents were further stratified by age group, sex, race, or ethnicity. Crude and age-adjusted mortality rates (AAMR) per 100,000 persons were calculated. A total of 97,135 cardiorenal-related deaths and 3,453,655 HF-related deaths occurred. Cardiorenal-related mortality (AAMR, 3.26; 95% CI: 3.23-3.28) was significantly lower than HF-related mortality (AAMR, 115.7; 95% CI: 115.6-115.8). The annual percent change (APC) was greater and increased over time for cardiorenal-related mortality (2011-2015: APC, 7.1%; 95% CI: 0.7-13.9%; 2015-2020: APC, 19.7%, 95% CI: 16.3-23.2%), whereas HF-related mortality also increased over that time period, but at a consistently lower rate (2011-2020: APC, 2.4%; 95% CI: 1.7-3.1%). Mortality was highest among older and male decedents for both causes. Cardiorenal-related deaths were more common in non-Hispanic or Latino Blacks compared to Whites, but similar rates were observed for HF-related mortality. A larger proportion of cardiorenal-related deaths, compared to HF-related deaths, listed cardiorenal syndrome as the underlying cause of death (67.0% vs. 1.2%)., Conclusions: HF-related deaths substantially outnumber cardiorenal-related deaths; however, cardiorenal-related deaths are increasing at an alarming rate with the highest burden among non-Hispanic or Latino Blacks. Continued surveillance of cardiorenal-related mortality trends is critical and future studies that contain detailed biomarker and social determinants of health information are needed to identify mechanisms underlying differences in mortality trends., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: Most patients with heart failure (HF) have multimorbidity which may cause difficulties with self-management. Understanding the resources patients draw upon to effectively manage their health is fundamental to designing new practice models to improve outcomes in HF. We describe the rationale, conceptual framework, and implementation of a multi-center survey of HF patients, characterize differences between responders and non-responders, and summarize patient characteristics and responses to the survey constructs among responders., Methods: This was a multi-center cross-sectional survey study with linked electronic health record (EHR) data. Our survey was guided by the Chronic Care Model to understand the distribution of patient-centric factors, including health literacy, social support, self-management, and functional and mental status in patients with HF. Most questions were from existing validated questionnaires. The survey was administered to HF patients aged ≥ 30 years from 4 health systems in PCORnet® (the National Patient-Centered Clinical Research Network): Essentia Health, Intermountain Health, Mayo Clinic, and The Ohio State University. Each health system mapped their EHR data to a standardized PCORnet Common Data Model, which was used to extract demographic and clinical data on survey responders and non-responders., Results: Across the 4 sites, 10,662 patients with HF were invited to participate, and 3330 completed the survey (response rate: 31%). Responders were older (74 vs. 71 years; standardized difference (95% CI): 0.18 (0.13, 0.22)), less racially diverse (3% vs. 12% non-White; standardized difference (95% CI): -0.32 (-0.36, -0.28)), and had higher prevalence of many chronic conditions than non-responders, and thus may not be representative of all HF patients. The internal reliability of the validated questionnaires in our survey was good (range of Cronbach's alpha: 0.50-0.96). Responders reported their health was generally good or fair, they frequently had cardiovascular comorbidities, > 50% had difficulty climbing stairs, and > 10% reported difficulties with bathing, preparing meals, and using transportation. Nearly 80% of patients had family or friends sit with them during a doctor visit, and 54% managed their health by themselves. Patients reported generally low perceived support for self-management related to exercise and diet., Conclusions: More than half of patients with HF managed their health by themselves. Increased understanding of self-management resources may guide the development of interventions to improve HF outcomes., (© 2024. The Author(s).)

Background: Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact., Methods and Results: In an HF community cohort (2003-2012), we measured frailty as a proportion of deficits present out of 32 physical limitations and comorbidities, MVX by nuclear magnetic resonance spectroscopy, and collected extensive longitudinal clinical data. Patients were categorized by frailty score (≤0.14, >0.14 and ≤0.27, >0.27) and MVX score (≤50, >50 and ≤60, >60 and ≤70, >70). Cox models estimated associations of frailty and MVX with death, adjusted for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Uno's C-statistic measured the incremental value of MVX beyond frailty and clinical factors. Weibull's accelerated failure time regression assessed whether MVX mediated the association between frailty and death. We studied 985 patients (median age, 77; 48% women). Frailty and MVX were weakly correlated (Spearman's ρ=0.21). The highest frailty group experienced an increased rate of death, independent of MVX, MAGGIC score, and NT-proBNP (hazard ratio, 3.3 [95% CI, 2.5-4.2]). Frailty improved Uno's c-statistic beyond MAGGIC score and NT-proBNP (0.69-0.73). MVX only mediated 3.3% and 4.5% of the association between high and medium frailty groups and death, respectively., Conclusions: In this HF cohort, frailty and MVX are weakly correlated. Both independently contribute to stratifying the risk of death, suggesting that they capture distinct domains of vulnerability in HF.

Background: Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure., Methods: Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed., Results: The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%-51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9-2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3-1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno's C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP., Conclusions: This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers., Competing Interests: Disclosures Dr Connelly is an employee of and holds stock in Labcorp. Dr Otvos is a consultant, stockholder, and former employee of Labcorp. The other authors report no conflicts.

Aims: Serum sex hormones have been linked to cardiovascular disease risk. However, their roles in the pathogenesis of heart failure (HF) in both men and women are unclear. We investigated the associations between free androgen, testosterone, and estradiol, and future risk of HF., Methods and Results: This prospective cohort study evaluated UK Biobank participants free of prevalent cardiovascular disease and HF at baseline. Unitless free androgen, testosterone, and estradiol indices were generated using serum concentrations of total testosterone (nmol/L), estradiol (pmol/L), sex hormone binding globulin (SHBG, nmol/L), and albumin (g/L) in blood collected at enrolment. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF in relation to quartiles (Q) of free androgen (FAI), testosterone (FTI), estradiol (FEI) indices, and potential confounders. There were 180 712 men (including 5585 HF cases with FAI and 571 HF cases with FEI), and 177 324 women (including 2858 HF cases with FAI and 314 HF cases with FEI) with complete data. Increased FAI was associated with decreased HF risk in both men (HR Q4 vs. Q1 : 0.86, 95% CI 0.79-0.94, p-trend continuous  < 0.0001) and post-menopausal women (HR Q4 vs. Q1 : 0.83, 95% CI 0.73-0.95). Similar inverse associations were observed for FTI only in men (HR Q4 vs. Q1 : 0.91, 95% CI 0.83-0.98). Higher FEI was significantly associated with decreased HF risk among men (HR Q4 vs. Q1 : 0.76, 95% CI 0.59-0.98), but was positively associated among pre-menopausal women (HR Q4 vs. Q1 : 2.16, 95% CI 1.11-4.18)., Conclusions: Sex hormones potentially influence HF pathogenesis and may offer pathways for interventions., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Inflammation and protein energy malnutrition are associated with heart failure (HF) mortality. The metabolic vulnerability index (MVX) is derived from markers of inflammation and malnutrition and measured by nuclear magnetic resonance spectroscopy. MVX has not been examined in HF., Objectives: The authors sought to examine the prognostic value of MVX in patients with HF., Methods: The authors prospectively assembled a population-based cohort of patients with HF from 2003 to 2012 and measured MVX scores with a nuclear magnetic resonance scan from plasma collected at enrollment. Patients were divided into 4 MVX score groups and followed until March 31, 2021., Results: The authors studied 1,382 patients (median age: 78 years; 48% women). The median MVX score was 64.6. Patients with higher MVX were older, more likely to be male, have atrial fibrillation, have higher NYHA functional class, and have HF duration of >18 months. Higher MVX was associated with mortality independent of Meta-analysis Global Group in Chronic Heart Failure score, ejection fraction, and other prognostic biomarkers. Compared to those with the lowest MVX, the HRs for MVX groups 2, 3, and 4 were 1.2 (95% CI: 0.9-1.4), 1.6 (95% CI: 1.3-2.0), and 1.8 (95% CI: 1.4-2.2), respectively (P trend  < 0.001). Measures of model improvement document the added value of MVX in HF for classifying the risk of death beyond the Meta-analysis Global Group in Chronic Heart Failure score and other biomarkers., Conclusions: In this HF community cohort, MVX was strongly associated with mortality independently of established clinical factors and improved mortality risk classification beyond clinically validated markers. These data underscore the potential of MVX to stratify risk in HF., Competing Interests: Funding Support and Author Disclosures The investigators were supported by the Intramural Research program of the National Heart, Lung, and Blood Institute of the National Institutes of Health. This study also used in part the resources from the Rochester Epidemiology Project medical records linkage system, which is supported by the National Institute on Aging (AG 058738), by the Mayo Clinic Research Committee, and by fees paid annually by Rochester Epidemiology Project users. The funding institution did not play a role in the design, conduct, analysis, or reporting or in the decision to submit this manuscript for publication. The study was approved by the Mayo Clinic and Olmsted Medical Center Institutional Review Boards. Dr Connelly is an employee of and holds stock in LabCorp. Dr Otvos is a consultant, stockholder, and former employee of LabCorp. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Published by Elsevier Inc.)

Background: Heart failure (HF) is a complex clinical syndrome with persistently high mortality. High-throughput proteomic technologies offer new opportunities to improve HF risk stratification, but their contribution remains to be clearly defined. We aimed to systematically review prognostic studies using high-throughput proteomics to identify protein signatures associated with HF mortality., Methods: We searched four databases and two clinical trial registries for articles published from 2012 to 2023. HF proteomics studies measuring high numbers of proteins using aptamer or antibody-based affinity platforms on human plasma or serum with outcomes of all-cause or cardiovascular death were included. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. A third reviewer resolved conflicts. We assessed the risk of bias using the Risk Of Bias In Non-randomized Studies-of Exposure tool., Results: Out of 5131 unique articles identified, nine articles were included in the review. The nine studies were observational; three used the aptamer platform, and six used the antibody platform. We found considerable heterogeneity across studies in measurement panels, HF definitions, ejection fraction categorization, follow-up duration, and outcome definitions, and a lack of risk estimates for most protein associations. Hence, we proceeded with a systematic review rather than a meta-analysis. In two comparable aptamer studies in patients with HF with reduced ejection fraction, 21 proteins were identified in common for the association with all-cause death. Among these, one protein, WAP four-disulfide core domain protein 2 was also reported in an antibody study on HFrEF and for the association with CV death. We proposed standardized reporting criteria to facilitate the interpretation of future studies., Conclusions: In this systematic review of nine studies evaluating the association of proteomics with mortality in HF, we identified a limited number of proteins common across several studies. Heterogeneity across studies compromised drawing broad inferences, underscoring the importance of standardized approaches to reporting., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Heart failure (HF) is a complex clinical syndrome with high mortality. Current risk stratification approaches lack precision. High-throughput proteomics could improve risk prediction. Its use in clinical practice to guide the management of patients with HF depends on validation and evidence of clinical benefit., Objective: To develop and validate a protein risk score for mortality in patients with HF., Design: Community-based cohort., Setting: Southeast Minnesota., Participants: Patients with HF enrolled between 2003 and 2012 and followed through 2021., Measurements: A total of 7289 plasma proteins in 1351 patients with HF were measured using the SomaScan Assay (SomaLogic). A protein risk score was derived using least absolute shrinkage and selection operator regression and temporal validation in patients enrolled between 2003 and 2007 (development cohort) and 2008 and 2012 (validation cohort). Multivariable Cox regression was used to examine the association between the protein risk score and mortality. The performance of the protein risk score to predict 5-year mortality risk was assessed using calibration plots, decision curves, and relative utility analyses and compared with a clinical model, including the Meta-Analysis Global Group in Chronic Heart Failure mortality risk score and N -terminal pro-B-type natriuretic peptide., Results: The development ( n = 855; median age, 78 years; 50% women; 29% with ejection fraction <40%) and validation cohorts ( n = 496; median age, 76 years; 45% women; 33% with ejection fraction <40%) were mostly similar. In the development cohort, 38 unique proteins were selected for the protein risk score. Independent of ejection fraction, the protein risk score demonstrated good calibration, reclassified mortality risk particularly at the extremes of the risk distribution, and showed greater clinical utility compared with the clinical model., Limitation: Participants were predominantly of European ancestry, potentially limiting the generalizability of the findings to different patient populations., Conclusion: Validation of the protein risk score demonstrated good calibration and evidence of predicted benefits to stratify the risk for death in HF superior to that of clinical methods. Further studies are needed to prospectively evaluate the score's performance in diverse populations and determine risk thresholds for interventions., Primary Funding Source: Division of Intramural Research at the National Heart, Lung, and Blood Institute of the National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2328.

Background Heart failure (HF) is a complex disease that contributes to a high number of hospitalizations, deaths, and economic health care costs each year. However, among patients with HF, there is a lack of awareness of their HF diagnosis that has not been fully examined. Methods and Results Residents from 3 counties of southeast Minnesota with a first-ever International Classification of Diseases, Ninth Revision ( ICD-9 ) code 428 or Tenth Revision ( ICD-10 ) code I50 between January 1, 2013 and March 31, 2016 (N=2461) were prospectively surveyed to measure HF self-awareness. A total of 1114 patients returned the survey (response rate, 45%), and 787 had validated HF upon medical record review. Among these 787 patients with HF (mean age, 76 years; 53% men), 37% (n=293) were aware of their HF diagnosis. After adjustment, being a woman (odds ratio [OR], 1.56 [95% CI, 1.10-2.22]), having HF with reduced ejection fraction (OR, 1.58 [95% CI, 1.13-2.22]), attending the HF clinic (OR, 4.07 [95% CI, 2.25-7.36]), and having coronary artery disease (OR, 1.65 [95% CI, 1.16-2.37]) were all associated with increased awareness of an HF diagnosis. Conversely, having diabetes was associated with decreased awareness of an HF diagnosis (adjusted OR, 0.69 [95% CI, 0.50-0.95]). Conclusions Awareness of an HF diagnosis is low in a community population of patients with HF. Strategies to improve patient awareness of their diagnosis should be implemented to improve self-care behaviors and outcomes in patients with HF.

Background Among patients with heart failure (HF), social risk factors (SRFs) are associated with poor outcomes. However, less is known about how co-occurrence of SRFs affect all-cause health care utilization for patients with HF. The objective was to address this gap using a novel approach to classify co-occurrence of SRFs. Methods and Results This was a cohort study of residents living in an 11-county region of southeast Minnesota, aged ≥18 years with a first-ever diagnosis for HF between January 2013 and June 2017. SRFs, including education, health literacy, social isolation, and race and ethnicity, were obtained via surveys. Area-deprivation index and rural-urban commuting area codes were determined from patient addresses. Associations between SRFs and outcomes (emergency department visits and hospitalizations) were assessed using Andersen-Gill models. Latent class analysis was used to identify subgroups of SRFs; associations with outcomes were examined. A total of 3142 patients with HF (mean age, 73.4 years; 45% women) had SRF data available. The SRFs with the strongest association with hospitalizations were education, social isolation, and area-deprivation index. We identified 4 groups using latent class analysis, with group 3, characterized by more SRFs, at increased risk of emergency department visits (hazard ratio [HR], 1.33 [95% CI, 1.23-1.45]) and hospitalizations (HR, 1.42 [95% CI, 1.28-1.58]). Conclusions Low educational attainment, high social isolation, and high area-deprivation index had the strongest associations. We identified meaningful subgroups with respect to SRFs, and these subgroups were associated with outcomes. These findings suggest that it is possible to apply latent class analysis to better understand the co-occurrence of SRFs among patients with HF.

Importance: Rural populations experience an increased burden of heart failure (HF) mortality compared with urban populations. Whether HF incidence is greater among rural individuals is less known. Additionally, the intersection between racial and rural health inequities is understudied., Objective: To determine whether rurality is associated with increased risk of HF, independent of cardiovascular (CV) disease and socioeconomic status (SES), and whether rurality-associated HF risk varies by race and sex., Design, Setting, and Participants: This prospective cohort study analyzed data for Black and White participants of the Southern Community Cohort Study (SCCS) without HF at enrollment who receive care via Centers for Medicare & Medicaid Services (CMS). The SCCS is a population-based cohort of low-income, underserved participants from 12 states across the southeastern United States. Participants were enrolled between 2002 and 2009 and followed up until December 31, 2016. Data were analyzed from October 2021 to November 2022., Exposures: Rurality as defined by Rural-Urban Commuting Area codes at the census-tract level., Main Outcomes and Measures: Heart failure was defined using diagnosis codes via CMS linkage through 2016. Incidence of HF was calculated by person-years of follow-up and age-standardized. Sequentially adjusted Cox proportional hazards regression models tested the association between rurality and incident HF., Results: Among 27 115 participants, the median (IQR) age was 54 years (47-65), 18 647 (68.8%) were Black, and 8468 (32.3%) were White; 5556 participants (20%) resided in rural areas. Over a median 13-year follow-up, age-adjusted HF incidence was 29.6 (95% CI, 28.9-30.5) per 1000 person-years for urban participants and 36.5 (95% CI, 34.9-38.3) per 1000 person-years for rural participants (P < .001). After adjustment for demographic information, CV risk factors, health behaviors, and SES, rural participants had a 19% greater risk of incident HF (hazard ratio [HR], 1.19; 95% CI, 1.13-1.26) compared with their urban counterparts. The rurality-associated risk of HF varied across race and sex and was greatest among Black men (HR, 1.34; 95% CI, 1.19-1.51), followed by White women (HR, 1.22; 95% CI, 1.07-1.39) and Black women (HR, 1.18; 95% CI, 1.08-1.28). Among White men, rurality was not associated with greater risk of incident HF (HR, 0.97; 95% CI, 0.81-1.16)., Conclusions and Relevance: Among predominantly low-income individuals in the southeastern United States, rurality was associated with an increased risk of HF among women and Black men, which persisted after adjustment for CV risk factors and SES. This inequity points to a need for additional emphasis on primary prevention of HF among rural populations.

Background: The Framingham Heart Study Dementia Risk Score (FDRS) was developed in a general population of older persons. It is unknown how the FDRS variables predict Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) in heart failure and atrial fibrillation populations. We aimed to evaluate the predictive ability of the FDRS variables in population-based cohorts of heart failure and atrial fibrillation and to determine whether the addition of other comorbidities and risk factors improves risk prediction for AD/ADRD., Methods: Residents aged ≥50 years from 7 southeastern Minnesota counties with a first diagnosis of heart failure or atrial fibrillation between January 1, 2013, and December 31, 2017, were identified. Patients with AD/ADRD before or within 6 months after index atrial fibrillation or heart failure and patients who died within 6 months after index were excluded. For both cohorts, models were constructed to predict AD/ADRD after index including the variables in the FDRS. Additional comorbidities and risk factors were added to the models. For all models, c-statistics using 5-fold cross-validation were calculated., Results: Among 3052 patients with heart failure (mean age 75 years, 53% male), 626 developed AD/ADRD; among 4107 patients with atrial fibrillation (mean age 74 years, 57% male), 736 developed AD/ADRD. Among patients with heart failure, the FDRS variables predicted AD/ADRD with c-statistic = 0.69. Adding comorbidities and risk factors improved the c-statistic slightly to 0.70. The FDRS variables also performed well (c-statistic = 0.73) in patients with atrial fibrillation; adding comorbidities and risk factors slightly improved performance (c-statistic = 0.75)., Conclusions: The variables from the FDRS predict AD/ADRD well in both heart failure and atrial fibrillation populations. The addition of comorbidities and risk factors only modestly improved prediction, indicating that the FDRS variables are appropriate to predict AD/ADRD in patients with heart failure and atrial fibrillation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Functional debility is associated with worse outcomes in the general heart failure population, but the prevalence of difficulty with activities of daily living and clinical significance once patients develop advanced heart failure requires further examination., Methods: This was a population-based, retrospective cohort study of Olmsted County, Minnesota adults with advanced heart failure from 2007-2018. Difficulty with 9 activities of daily living was assessed by questionnaire. Predictors of difficulty were assessed by a proportional odds model. Associations of difficulty with activities of daily living with mortality and hospitalization were examined using Cox and Andersen-Gill models., Results: Among 765 patients with advanced heart failure, 565 (73.9%) reported difficulty with activities of daily living at diagnosis. Of those, 257 (45%) had moderate and 148 (26%) had severe difficulty. Independent predictors of difficulty included female sex (odds ratio [OR] 1.73; 95% confidence interval [CI], 1.26-2.36; P = .001), older age (OR per 10-year increase 1.17; 95% CI, 1.05-1.31; P = .005), dementia (OR 1.85; 95% CI, 1.06-3.24; P = .031), depression (OR 1.75; 95% CI, 1.28-2.40; P = .001), and morbid obesity (OR 1.49; 95% CI, 1.04-2.13; P = .031). Estimated 2-year mortality was 61.5%, 64.2%, and 67.6% in patients with no/minimal, moderate, and severe difficulty, respectively. The adjusted hazard ratios (95% CI) for death were 1.08 (0.90-1.28) and 1.17 (0.95-1.43) for moderate and severe difficulty, respectively, vs no/minimal difficulty (P = .33). There were no statistically significant associations of difficulty with activities of daily living and hospitalization risks., Conclusions: Most patients with advanced heart failure have difficulty completing activities of daily living and are at high risk of mortality regardless of impairment in activities of daily living., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Cognitive function is essential to effective self-management of heart failure (HF). Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) can coexist with HF, but its exact prevalence and impact on health care utilization and death are not well defined., Methods: Residents from 7 southeast Minnesota counties with a first-ever diagnosis code for HF between January 1, 2013 and December 31, 2018 were identified. Clinically diagnosed AD/ADRD was ascertained using the Centers for Medicare and Medicaid (CMS) Chronic Conditions Data Warehouse algorithm. Patients were followed through March 31, 2020. Cox and Andersen-Gill models were used to examine associations between AD/ADRD (before and after HF) and death and hospitalizations, respectively., Results: Among 6336 patients with HF (mean age [SD] 75 years [14], 48% female), 644 (10%) carried a diagnosis of AD/ADRD at index HF diagnosis. The 3-year cumulative incidence of AD/ADRD after HF diagnosis was 17%. During follow-up (mean [SD] 3.2 [1.9] years), 2618 deaths and 15,475 hospitalizations occurred. After adjustment, patients with AD/ADRD before HF had nearly a 2.7 times increased risk of death, but no increased risk of hospitalization compared to those without AD/ADRD. When AD/ADRD was diagnosed after the index HF date, patients experienced a 3.7 times increased risk of death and a 73% increased risk of hospitalization compared to those who remain free of AD/ADRD., Conclusions: In a large, community cohort of patients with incident HF, the burden of AD/ADRD is quite high as more than one-fourth of patients with HF received a diagnosis of AD/ADRD either before or after HF diagnosis. AD/ADRD markedly increases the risk of adverse outcomes in HF underscoring the need for future studies focused on holistic approaches to improve outcomes., (© 2022 The American Geriatrics Society.)

Objectives: The goal of this study was to evaluate the prevalence, characteristics, and outcomes of patients with advanced heart failure (HF) in a geographically defined population., Background: Some patients with HF progress to advanced HF, characterized by debilitating HF symptoms refractory to therapy. Limited data are available on the epidemiology and outcomes of patients with advanced HF., Methods: This was a population-based cohort study of all Olmsted County, Minnesota, adults with and without HF from 2007 to 2017. The 2018 European Society of Cardiology advanced HF diagnostic criteria were operationalized and applied to all patients with HF. Hospitalization and mortality in advanced HF, overall and according to ejection fraction (EF) type (reduced EF <40% [HFrEF], mid-range EF 40%-49% [HFmrEF], and preserved EF ≥50% [HFpEF]) were examined using Andersen-Gill and Cox models., Results: Of 6,836 adults with HF, 936 (13.7%) met criteria for advanced HF. The prevalence of advanced HF increased with age and was higher in men. At advanced HF diagnosis, 396 (42.3%) patients had HFrEF, 134 (14.3%) had HFmrEF, and 406 (43.4%) had HFpEF. The median (interquartile range) time from advanced HF diagnosis to death was 12.2 months (3.7-29.9 months). The mean rate of hospitalization was 2.91 (95% CI: 2.78-3.06) per person-year in the first year after advanced HF diagnosis. There were no differences in risks of all-cause mortality or hospitalization by EF. Patients with advanced HFpEF were at lower risk for cardiovascular mortality compared with advanced HFrEF (HR: 0.79; 95% CI: 0.65-0.97)., Conclusions: In this population-based study, more than one-half of patients with advanced HF had mid-range or preserved EF, and survival was poor regardless of EF., Competing Interests: Funding Support and Author Disclosures This study was funded by the National Institutes of Health (R01 HL144529; Principal Investigator: Dr Dunlay) and made possible by using the resources of the Rochester Epidemiology Project, which is supported by the National Institute on Aging of the National Institutes of Health (R01 AG034676). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The rate of decline in cardiovascular disease (CVD) mortality has lessened nationally. How these findings apply to specific states or causes of CVD deaths is not known. Examining these trends at the state level is important to plan local interventions., Methods: We analyzed CVD mortality trends in Minnesota (MN) using the U.S. Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Trends were analyzed by age, sex, type of CVD and location of death., Results: CVD mortality rates in MN declined in 2000-2009 and then leveled off in 2010-2018, paralleling national rates. Age- and sex-adjusted CVD mortality decreased by 3.7% per year in 2000-2009 (average annual percent changes [AAPC]: -3.7; 95% CI: - 4.8, - 2.6) with no change observed in 2010-2018. Those aged 65-84 years had the most rapid early decline in CVD mortality (AAPC: -5.9, 95% CI: - 6.2, - 5.7) and had less improvement in 2010-2018 (AAPC: -1.8, 95% CI: - 2.2, - 1.5), and the younger age group (25-64 years) now experiences the most adverse trends (AAPC: 1.2, 95% CI: 0.7-1.8). Coronary heart disease (CHD) and cerebrovascular disease had the largest relative decreases in mortality in 2000-2009 (CHD AAPC: -5.2; 95% CI: - 6.5,-3.9; cerebrovascular disease AAPC: -4.4, 95% CI: - 5.2, - 3.6) with no change 2010-2018. Heart failure (HF)/cardiomyopathy followed similar trends with a 2.5% decrease (AAPC 95% CI: - 3.5, - 1.5) per year in 2000-2009 and no change in 2010-2018. Deaths from other CVD also decreased in the early time period (AAPC: -1.6, 95% CI: - 2.7, - 0.5) but increased in 2010-2018 (AAPC: 1.9, 95% CI: 0.5, 3.3). In- and out-of-hospital death rates improved in 2000-2009 with a slowing in improvement for in-hospital death and no further improvement for out-of-hospital death in 2010-2018., Conclusion: Concerning CVD mortality trends occurred in MN. In the most recent decade (2010-2018) mortality from all CVD subtypes plateaued or even increased. CVD mortality among the younger age groups increased as well. These data are congruent with adverse national trends supporting their generalizability. These adverse trends underscore the urgent need for CVD prevention and treatment, as well as continued surveillance to assess progress at the state and national level.

Designated as an emerging epidemic in 1997, heart failure (HF) remains a major clinical and public health problem. This review focuses on the most recent studies identified by searching the Medline database for publications with the subject headings HF, epidemiology, prevalence, incidence, trends between 2010 and present. Publications relevant to epidemiology and population sciences were retained for discussion in this review after reviewing abstracts for relevance to these topics. Studies of the epidemiology of HF over the past decade have improved our understanding of the HF syndrome and of its complexity. Data suggest that the incidence of HF is mostly flat or declining but that the burden of mortality and hospitalization remains mostly unabated despite significant ongoing efforts to treat and manage HF. The evolution of the case mix of HF continues to be characterized by an increasing proportion of cases with preserved ejection fraction, for which established effective treatments are mostly lacking. Major disparities in the occurrence, presentation, and outcome of HF persist particularly among younger Black men and women. These disturbing trends reflect the complexity of the HF syndrome, the insufficient mechanistic understanding of its various manifestations and presentations and the challenges of its management as a chronic disease, often integrated within a context of aging and multimorbidity. Emerging risk factors including omics science offer the promise of discovering new mechanistic pathways that lead to HF. Holistic management approaches must recognize HF as a syndemic and foster the implementation of multidisciplinary approaches to address major contributors to the persisting burden of HF including multimorbidity, aging, and social determinants of health.

Background Prior reports indicate that living in a rural area may be associated with worse health outcomes. However, data on rurality and heart failure (HF) outcomes are scarce. Methods and Results Residents from 6 southeastern Minnesota counties with a first-ever code for HF ( International Classification of Diseases, Ninth Revision [ ICD-9 ], code 428, and International Classification of Diseases, Tenth Revision [ ICD-10 ] code I50) between January 1, 2013 and December 31, 2016, were identified. Resident address was classified according to the rural-urban commuting area codes. Rurality was defined as living in a nonmetropolitan area. Cox regression was used to analyze the association between living in a rural versus urban area and death; Andersen-Gill models were used for hospitalization and emergency department visits. Among 6003 patients with HF (mean age 74 years, 48% women), 43% lived in a rural area. Rural patients were older and had a lower educational attainment and less comorbidity compared with patients living in urban areas ( P <0.001). After a mean (SD) follow-up of 2.8 (1.7) years, 2440 deaths, 20 506 emergency department visits, and 11 311 hospitalizations occurred. After adjustment, rurality was independently associated with an increased risk of death (hazard ratio [HR], 1.18; 95% CI, 1.09-1.29) and a reduced risk of emergency department visits (HR, 0.89; 95% CI, 0.82-0.97) and hospitalizations (HR, 0.78; 95% CI, 0.73-0.84). Conclusions Among patients with HF, living in a rural area is associated with an increased risk of death and fewer emergency department visits and hospitalizations. Further study to identify and address the mechanisms through which rural residence influences mortality and healthcare utilization in HF is needed in order to reduce disparities in rural health.

The purpose of this analysis was to develop and validate computable phenotypes for heart failure (HF) with preserved ejection fraction (HFpEF) using claims-type measures using the Rochester Epidemiology Project. This retrospective study utilized an existing cohort of Olmsted County, Minnesota residents aged ≥ 20 years diagnosed with HF between 2007 and 2015. The gold standard definition of HFpEF included meeting the validated Framingham criteria for HF and having an LVEF ≥ 50%. Computable phenotypes of claims-type data elements (including ICD-9/ICD-10 diagnostic codes and lab test codes) both individually and in combinations were assessed via sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with respect to the gold standard. In the Framingham-validated cohort, 2,035 patients had HF; 1,172 (58%) had HFpEF. One in-patient or two out-patient diagnosis codes of ICD-9 428.3X or ICD-10 I50.3X had 46% sensitivity, 88% specificity, 84% PPV, and 54% NPV. The addition of a BNP/NT-proBNP test code reduced sensitivity to 35% while increasing specificity to 91% (PPV = 84%, NPV = 51%). Broadening the diagnostic codes to ICD-9 428.0, 428.3X, and 428.9/ICD-10 I50.3X and I50.9 increased sensitivity at the expense of decreasing specificity (diagnostic code-only model: 87% sensitivity, 8% specificity, 56% PPV, 30% NPV; diagnostic code and BNP lab code model: 61% sensitivity, 43% specificity, 60% PPV, 45% NPV). In an analysis conducted to mimic real-world use of the computable phenotypes, any one in-patient or out-patient code of ICD-9 428/ICD-10 150 among the broader population (N = 3,755) resulted in lower PPV values compared with the Framingham cohort. However, one in-patient or two out-patient instances of ICD-9 428.0, 428.9, or 428.3X/ICD-10 150.3X or 150.9 brought the PPV values from the two cohorts closer together. While some misclassification remains, the computable phenotypes defined here may be used in claims databases to identify HFpEF patients and to gain a greater understanding of the characteristics of patients with HFpEF., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)

Objectives: To measure the impact of patient-centered communication on mortality and hospitalization among patients with heart failure (HF)., Study Design: This was a survey study of 6208 residents of 11 counties in southeast Minnesota with incident HF (first-ever International Classification of Diseases, Ninth Revision code 428 or International Classification of Diseases, Tenth Revision code I50) between January 1, 2013, and March 31, 2016., Methods: Perceived patient-centered communication was assessed with the health care subscale of the Chronic Illness Resources Survey and measured as a composite score on three 5-point scales. We divided our cohort into tertiles and defined them as having fair/poor (score < 12), good (score of 12 or 13), and excellent (score ≥ 14) patient-centered communication. The survey was returned by 2868 participants (response rate: 45%), and those with complete data were retained for analysis (N = 2398). Cox and Andersen-Gill models were used to determine the association of patient-centered communication with death and hospitalization, respectively., Results: Among 2398 participants (median age, 75 years; 54% men), 233 deaths and 1194 hospitalizations occurred after a mean (SD) follow-up of 1.3 (0.6) years. Compared with patients with fair/poor patient-centered communication, those with good (HR, 0.70; 95% CI, 0.51-0.97) and excellent (HR, 0.70; 95% CI, 0.51-0.96) patient-centered communication experienced lower risks of death after adjustment for various confounders (Ptrend = .020). Patient-centered communication was not associated with hospitalization., Conclusions: Among community patients living with HF, excellent and good patient-centered communication is associated with a reduced risk of death. Patient-centered communication can be easily assessed, and consideration should be given toward implementation in clinical practice.

Objectives: The purpose of this study was to determine if health literacy is associated with mortality, hospitalizations, or emergency department (ED) visits among patients living with heart failure (HF)., Background: Growing evidence suggests an association between health literacy and health-related outcomes in patients with HF., Methods: We searched Embase, MEDLINE, PsycINFO, and EBSCO CINAHL from inception through January 1, 2019, with the help of a medical librarian. Eligible studies evaluated health literacy among patients with HF and assessed mortality, hospitalizations, and ED visits for all causes with no exclusion by time, geography, or language. Two reviewers independently selected studies, extracted data, and assessed the methodological quality of the identified studies., Results: We included 15 studies, 11 with an overall high methodological quality. Among the observational studies, an average of 24% of patients had inadequate or marginal health literacy. Inadequate health literacy was associated with higher unadjusted risk for mortality (risk ratio [RR]: 1.67; 95% confidence interval [CI]: 1.18 to 2.36), hospitalizations (RR: 1.19; 95% CI: 1.09 to 1.29), and ED visits (RR: 1.17; 95% CI: 1.03 to 1.32). When the adjusted measurements were combined, inadequate health literacy remained statistically associated with mortality (RR: 1.41; 95% CI: 1.06 to 1.88) and hospitalizations (RR: 1.12; 95% CI: 1.01 to 1.25). Among the 4 interventional studies, 2 effectively improved outcomes among patients with inadequate health literacy., Conclusions: In this study, the estimated prevalence of inadequate health literacy was high, and inadequate health literacy was associated with increased risk of death and hospitalizations. These findings have important clinical and public health implications and warrant measurement of health literacy and deployment of interventions to improve outcomes., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Differences in comorbid conditions in patients with heart failure compared with population controls, and whether differences exist by type of heart failure or age, have not been well documented., Methods: The prevalence of 17 chronic conditions were obtained in 2643 patients with incident heart failure from 2000 to 2013 and controls matched 1:1 on sex and age from Olmsted County, Minnesota. Logistic regression determined associations of each condition with heart failure., Results: Among 2643 matched pairs (mean age 76.2 years, 45.6% men), the comorbidities with the largest attributable risk of heart failure were arrhythmia (48.7%), hypertension (28.4%), and coronary artery disease (33.9%); together these explained 73.0% of heart failure. Similar associations were observed for patients with reduced and preserved ejection fraction, with the exception of hypertension. The risk of heart failure attributable to hypertension was 2-fold higher in patients with heart failure with preserved ejection fraction (38.7%) than in patients with heart failure with reduced ejection fraction (17.8%). Hypertension, coronary artery disease, arrhythmia, and diabetes were more strongly associated with heart failure in younger (≤75 years) compared to older (>75 years) persons., Conclusions: Patients with heart failure have a higher prevalence of many chronic conditions than controls. Similar associations were observed in patients with reduced and preserved ejection fraction, with the exception of hypertension, which was more strongly associated with heart failure with preserved ejection fraction. Finally, some cardiometabolic risk factors were more strongly associated with heart failure in younger persons, highlighting the importance of optimizing prevention and treatment of risk factors and, in particular, cardiometabolic risk factors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Myocardial infarction (MI) is associated with an increase in subsequent heart failure (HF), recurrent ischemic events, sudden cardiac arrest, and ventricular arrhythmias (SCA-VA). The primary objective of the study to determine the role of intercurrent HF and ischemic events on the development of SCA-VA following first type I MI., Methods and Results: A retrospective cohort study of patients experiencing first type 1 MI in Olmsted County, Minnesota (2002-2012) was conducted by identifying patients using the medical records linkage system (Rochester epidemiology project). Patients aged ≥18 years were followed from the time of MI till death or 31 July, 2017. Intercurrent HF and ischemic events were the primary exposures following MI and their association with outcome SCA-VA was assessed. Eight hundred and sixty-seven patients (mean age was 63 ± 14.5 years; 69% male; 49.8% ST-elevation myocardial infarction) who had their first type I MI during the study period were included. Majority of acute MI patients were revascularized using percutaneous coronary intervention and bypass surgery (628 [72.43%] and 87 [10.03%] respectively). During a mean follow-up of 7.69 ± 4.17 years, HF, recurrent ischemic events and SCA-VA occurred in 155 (17.9%), 245 (28.3%), and 40 (4.61%) patients respectively. Low ejection fraction (adjusted hazard ratio [HR] 0.95; 95% confidence interval [CI], 0.93-0.98; P < .001), intercurrent HF (adjusted HR 3.11; 95% CI, 1.39-6.95; P = .006) and recurrent ischemic events (adjusted HR 3.47; 95% CI, 1.68-7.18; P < .001) were associated with subsequent SCA-VA., Conclusion: SCA-VA occurred in a small proportion of patients after MI and is associated with intercurrent HF and recurrent ischemic events., (© 2019 Wiley Periodicals, Inc.)

Background: Galectin-3 (Gal-3) is implicated in cardiac fibrosis, but its association with adverse outcomes after myocardial infarction (MI) is unknown., Objectives: The purpose of this study was to examine the prognostic value of Gal-3 in a community cohort of incident MI., Methods: A population-based incidence MI cohort was prospectively assembled in Olmsted County, Minnesota, between 2002 and 2012. Gal-3 levels were measured at the time of MI. Patients were followed for heart failure (HF) and death., Results: A total of 1,342 patients were enrolled (mean age 67.1 years; 61.3% male; 78.8% non-ST-segment elevation MI). Patients with elevated Gal-3 were older and had more comorbidities. Over a mean follow-up of 5.4 years, 484 patients (36.1%) died and 368 (27.4%) developed HF. After adjustment for age, sex, comorbidities, and troponin, patients with Gal-3 values in tertiles 2 and 3 had a 1.3-fold (95% confidence interval [CI]: 0.9-fold to 1.7-fold) and a 2.4-fold (95% CI: 1.8-fold to 3.2-fold) increased risk of death, respectively (p trend  < 0.001) compared with patients with Gal-3 values in tertile 1. Patients with Gal-3 values in tertiles 2 and 3 had a higher risk of HF with hazard ratios of 1.4 (95% CI: 1.0 to 2.0) and 2.3 (95% CI: 1.6 to 3.2), respectively (p trend  < 0.001). With further adjustment for soluble suppression of tumorigenicity-2, elevated Gal-3 remained associated with increased risk of death and HF. The increased risk of HF did not differ by HF type and was independent of the occurrence of recurrent MI., Conclusions: Gal-3 is an independent predictor of mortality and HF post-MI. These findings suggest a role for measuring Gal-3 levels for risk stratification post-MI., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is a major clinical and public health problem, the management of which will benefit from large-scale pragmatic research that leverages electronic medical records (EMR). Requisite to using EMRs for HF research is the development of reliable algorithms to identify HF patients. We aimed to develop and validate computable phenotype algorithms to identify patients with HF using standardized data elements defined by the Patient Centered Outcomes Research Network (PCORnet) Common Data Model (CDM)., Methods: We built HF computable phenotypes utilizing the data domains of HF diagnosis codes, prescribed HF-related medications and N-terminal B-type natriuretic peptide (NT-proBNP). Algorithms were validated in a cohort (n = 76,254) drawn from Olmsted County, MN between 2010-2012 a sample of whose records were manually reviewed to confirm HF according to Framingham criteria., Results: The different algorithms we tested provided different tradeoffs between sensitivity and positive predictive value (PPV). The highest sensitivity (78.7%) algorithm utilized one HF diagnosis code and had the lowest PPV (68.5%). The addition of more algorithm components, such as additional HF diagnosis codes, HF medications or elevated NT-proBNP, improved the PPV while reducing sensitivity. When added to a diagnostic code, the addition of NT-proBNP (>450 pg/mL) had a similar impact compared to additional HF medication criteria, increasing PPV by ∼3-4% and decreasing sensitivity by ∼7-10%., Conclusions: Algorithms derived from PCORnet CDM elements can be used to identify patients with HF without manual adjudication with reasonable sensitivity and PPV. Algorithm choice should be driven by the goal of the research., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background As the population with cardiovascular disease ages, geriatric conditions are of increasing relevance. A possible geriatric prognostic indicator may be a fall risk score, which is mandated by The Joint Commission to be measured on all hospitalized patients. The prognostic value of a fall risk score on outcomes after dismissal is not well known. Thus, we aimed to determine whether a fall risk score is associated with death and hospital readmissions in patients with a recent incident cardiovascular disease event. Methods and Results In this retrospective cohort study, Olmsted County, MN patients with incident heart failure, myocardial infarction, or atrial fibrillation between August 1, 2005, and December 31, 2011, who were hospitalized within 180 days after the event were studied. Fall risk was measured by the Hendrich II fall risk model. Patients were followed for death or readmission within 30 days or 1 year. Among 2456 hospitalized patients with recent incident cardiovascular disease (549 heart failure, 784 myocardial infarction, 1123 atrial fibrillation; mean [SD] age, 71 [15] years; 55% men), the fall risk score was high in 22% of patients and moderate in 38%. The risk of death was increased if the fall risk score was increased, independent of age and comorbidities (moderate hazard ratio, 1.51; 95% CI, 1.09-2.08; high hazard ratio, 3.49; 95% CI, 2.52-4.85). Similarly, the risk of 30-day readmissions was substantially increased with a greater fall risk score (moderate hazard ratio, 1.29; 95% CI, 1.03-1.62; high hazard ratio, 1.63; 95% CI, 1.23-2.15). Results were similar for readmissions within 1 year. Conclusions More than half of hospitalized patients with recent incident cardiovascular disease have an elevated fall risk score, which is associated with an increased risk in readmissions and death. These results delineate an approach for risk stratification and management that may prevent readmissions and improve survival.

Objectives: To characterize the individual and combined effects of multimorbidity and functional limitation on healthcare use and mortality in a large, community cohort of individuals with heart failure (HF)., Design: Prospective cohort study., Setting: Eleven southeastern Minnesota counties., Participants: Individuals (mean age 74, 54% male) with a first-ever HF code (International Classification of Diseases, Ninth Revision code 428 or Tenth Revision code I50) between January 1, 2013 and March 31, 2016 (N=2,692)., Measurements: Eight activities of daily living measured using a survey on a Likert scale (1=without any difficulty, 5=unable to do; median=8). Participants with a score greater than 8 were categorized as having functional limitation. Multimorbidity was defined as having 2 or more noncardiac comorbidities., Results: Twenty-five percent of participants had neither multimorbidity nor functional limitation, 35% had multimorbidity, 9% had functional limitation, and 31% had both. After adjustment, participants with multimorbidity and functional limitation had greater risks of all outcomes (death: hazard ratio (HR)=4.92, 95% confidence interval (CI)=3.03-8.00; emergency department (ED) visit: HR=3.67, 95% CI=2.94-4.59; hospitalization: HR=3.66, 95% CI=2.85-4.70; outpatient visit: HR=1.73, 95% CI=1.52-1.96) than those with neither. Participants with functional limitation alone had greater risks of death (HR=4.84, 95% CI=2.78-8.43), ED visits (HR=2.35, 95% CI=1.75-3.16), and hospitalizations (HR=2.10, 95% CI=1.52-2.88) but not outpatient visits. Those with multimorbidity alone had similar risks of ED visits and hospitalizations as those with functional limitation alone but were more likely to have outpatient visits (HR=1.50, 95% CI=1.34-1.67)., Conclusion: Individuals with both multimorbidity and functional limitation have the highest risk of death and healthcare use. Individuals with only functional limitation have similar rates of hospitalizations and ED visits as those with only multimorbidity, underscoring the need to consider both when managing individuals with HF., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Background: Perceived social isolation has been shown to have a negative impact on health outcomes, particularly among older adults. However, these relationships have not been fully examined among patients with heart failure., Methods and Results: Residents from 11 southeast Minnesota counties with a first-ever International Classification of Diseases, Ninth Revision ( ICD-9 ) code 428 for heart failure between January 1, 2013, and March 31, 2015 (N=3867), were prospectively surveyed to measure perceived social isolation. A total of 2003 patients returned the survey (response rate, 52%); 1681 patients completed all questions and were retained for analysis. Among these patients (53% men; mean age, 73 years), ≈19% (n=312) had moderate perceived social isolation and 6% (n=108) had high perceived social isolation. After adjustment, patients reporting moderate perceived social isolation did not have an increased risk of death, hospitalizations, or emergency department visits compared with patients reporting low perceived social isolation; however, patients reporting high perceived social isolation had >3.5 times increased risk of death (hazard ratio, 3.74; 95% confidence interval [CI], 1.82-7.70), 68% increased risk of hospitalization (hazard ratio, 1.68; 95% CI, 1.18-2.39), and 57% increased risk of emergency department visits (hazard ratio, 1.57; 95% CI, 1.09-2.27). Compared with patients who self-reported low perceived social isolation, patients reporting moderate perceived social isolation had a 16% increased risk of outpatient visits (rate ratio, 1.16; 95% CI, 1.03-1.31), whereas those reporting high perceived social isolation had a 26% increased risk (rate ratio, 1.26; 95% CI, 1.04-1.53)., Conclusions: In patients with heart failure, greater perceived social isolation is associated with an increased risk of death and healthcare use. Assessing perceived social isolation during the clinical encounter with a brief screening tool may help identify patients with heart failure at greater risk of poor outcomes., (© 2018 The Authors, Mayo Clinic and Olmsted County Public Health Services. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: To examine the impact of health literacy on hospitalizations and death in a population of patients with heart failure (HF)., Patients and Methods: Residents from the 11-county region in southeast Minnesota with a first-ever International Classification of Diseases, Ninth Revision code 428 or Tenth Revision code 150 (n=5121) from January 1, 2013, through December 31, 2015, were identified and prospectively surveyed to measure health literacy using established screening questions. A total of 2647 patients returned the survey (response rate, 52%); 2487 patients with complete health literacy data were retained for analysis. Health literacy, measured as a composite score on three 5-point scales, was categorized as adequate (≥8) or low (<8). Cox proportional hazards regression and Andersen-Gill models were used to examine the association of health literacy with mortality and hospitalization., Results: Of 2487 patients (mean age, 73.5 years; 53.6% male [n=1333]), 10.5% (n= 261) had low health literacy. After mean ± SD follow-up of 15.5±7.2 months, 250 deaths and 1584 hospitalizations occurred. Low health literacy was associated with increased mortality and hospitalizations. After adjusting for age, sex, comorbidity, education, and marital status, the hazard ratios for death and hospitalizations in patients with low health literacy were 1.91 (95% CI, 1.38-2.65; P<.001) and 1.30 (95% CI, 1.02-1.66; P=.03), respectively, compared with patients with adequate health literacy., Conclusion: Low health literacy is associated with increased risks of hospitalization and death in patients with HF. The clinical evaluation of health literacy could help design interventions individualized for patients with low health literacy., (Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Recent data suggest that patient activation, or having the knowledge, skills, and confidence to engage and manage one's own health, favorably impacts patient behaviors and health outcomes. However, the role of activation in patients with heart failure is unknown., Objectives: The aims of this study are to measure the level of activation of patients hospitalized with acute decompensated heart failure (ADHF) and to determine whether activation is associated with in-hospital and early postdischarge outcomes., Methods: We prospectively recruited Southeastern Minnesota residents hospitalized at Mayo Clinic hospitals with ADHF from January 2014 to July 2015. Activation was measured using the Patient Activation Measure questionnaire., Results: Among the 302 patients enrolled, the mean age was 77.3 years, 57.3% were men, and 46.8% had preserved ejection fraction. The median (25th-75th percentile) length of stay was 4 (3-7) days. In total, 7 (2.3%) patients died before discharge. Most survivors were discharged to home (73.6%) or skilled nursing facilities (23.7%). The number of patients in each activation level from highest to lowest was 9 (3.0%), 121 (40.1%), 122 (40.4%), and 50 (16.6%). Patients with lower activation were older, were less educated, had lower patient satisfaction, and had worse health literacy. They were more often discharged to skilled nursing facilities and had higher 30-day mortality, although 30-day readmission did not differ by activation., Conclusions: Patients hospitalized with ADHF with lower activation are less satisfied, have worse health literacy, more often require skilled care, and are at increased risk for early postdischarge mortality. Activation can be easily measured and may help clinicians identify high-risk patients.

Background: A diagnosis of heart failure (HF) often requires a comprehensive lifestyle change to maintain disease stability. When patients with HF are married, the spouse frequently assumes the caregiving role. Our objectives were to describe the health of spouses of married patients with HF, and examine whether the health of a spouse impacts patient outcomes., Methods and Results: We identified 905 patients that were married at the time of incident HF diagnosis in Olmsted County, MN, from 2000 to 2012. Using Rochester Epidemiology Project resources, the patient and their spouse's comprehensive longitudinal health histories were linked. Spousal health at patient HF diagnosis was assessed by comorbidity burden, self-reported difficulty with activities of daily living and prior hospitalizations. The associations of spousal health with patient outcomes and patient death with spousal outcomes were examined using Cox and Andersen-Gill models. Spouses of patients with HF were elderly (mean age, 71 years), often had comorbid conditions, and 16% had difficulty with ≥1 activities of daily living. After adjustment for patient age, sex, and comorbidity, there were no independent associations of spousal health and patient risk of death or hospitalization after HF diagnosis. However, the risk of hospitalization (adjusted hazard ratio, 1.34; 95% confidence interval, 1.11-1.60; P =0.002) and death (hazard ratio, 2.10; 95% confidence interval, 1.60-2.75; P <0.001) increased in the surviving spouse after patient death., Conclusions: We found no evidence that the health of a spouse impacts patient outcomes after HF diagnosis. However, after a patient with HF dies, their surviving spouse's risk of hospitalization and death increases., (© 2017 American Heart Association, Inc.)

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome associated with poor quality of life, substantial health-care resource utilization, and premature mortality. We summarize the current knowledge regarding the epidemiology of HFpEF with a focus on community-based studies relevant to quantifying the population burden of HFpEF. Current data regarding the prevalence and incidence of HFpEF in the community as well as associated conditions and risk factors, risk of morbidity and mortality after diagnosis, and quality of life are presented. In the community, approximately 50% of patients with HF have HFpEF. Although the age-specific incidence of HF is decreasing, this trend is less dramatic for HFpEF than for HF with reduced ejection fraction (HFrEF). The risk of HFpEF increases sharply with age, but hypertension, obesity, and coronary artery disease are additional risk factors. After adjusting for age and other risk factors, the risk of HFpEF is fairly similar in men and women, whereas the risk of HFrEF is much lower in women. Multimorbidity is common in both types of HF, but slightly more severe in HFpEF. A majority of deaths in patients with HFpEF are cardiovascular, but the proportion of noncardiovascular deaths is higher in HFpEF than HFrEF.

Background: Soluble ST2 (sST2) is a marker of cardiac mechanical strain hypothesized to adversely impact short-term prognosis after myocardial infarction. We examined the association of sST2 with longer-term outcomes after myocardial infarction in a geographically defined community., Methods: Olmsted County, Minnesota residents who experienced an incident (first-ever) myocardial infarction between November 1, 2002 and December 31, 2012 were prospectively enrolled; sST2 levels were measured. Patients were followed for heart failure and death., Results: We studied 1401 patients with incident myocardial infarction (mean age 67 years; 61% men; 79% non-ST-elevation myocardial infarction). Median sST2 (ng/mL) was 48.7 (25 th -75 th percentile 32.5-103.3). Soluble ST2 was elevated in 51% of patients. Higher values of sST2 were associated with increased age, female sex, and comorbidities. During 5 years of follow-up, 388 persons died and 360 developed heart failure. After adjustment for age, sex, comorbidities, Killip class, and troponin T, the hazard ratios for death were 1.73 (95% confidence interval [CI], 1.22-2.45) and 3.57 (95% CI, 2.57-4.96) for sST2 tertiles 2 and 3, respectively (P trend <.001). For heart failure, the hazard ratios were 1.67 (95% CI, 1.18-2.37) and 2.88 (95% CI, 2.05-4.05), respectively (P trend <.001). Results were similar among 30-day survivors., Conclusions: In the community, sST2 elevation is present in half of myocardial infarctions. Higher values of sST2 are associated with a large excess risk of death and heart failure independently of other prognostic indicators. Measurement of sST2 should be considered for risk stratification after myocardial infarction., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Patients with atrial fibrillation (AF) experience an increased risk of heart failure (HF). However, data are lacking on current trends in the risk of HF after AF., Objective: The purpose of this study was to describe the temporal trends in HF occurrence after AF in a community cohort of patients with incident AF from 2000 to 2013., Methods: Cox regression was used to examine the association of year of AF diagnosis with HF and the predictors of developing HF after AF., Results: Among 3491 AF patients without prior HF, 750 (21%) developed incident HF over mean follow-up of 3.7 years. Among those with an echocardiogram, 422 (61%) had HF with preserved ejection fraction (HFpEF), and 270 (39%) had HF with reduced ejection fraction (HFrEF). After adjusting for demographics and comorbidities, the risk of developing HF did not change over time (hazard ratio [HR] (95% confidence interval [CI]) per year of AF diagnosis: 1.01 (0.98-1.03) overall; 1.00 (0.98-1.03) for HFpEF; 1.00 (0.96-1.03) for HFrEF). Increasing age, obesity, smoking, diabetes, chronic pulmonary disease, and renal disease were predictors of developing HF. Compared to the Olmsted County, Minnesota, population, a substantial excess risk of developing HF was observed after AF diagnosis [standardized morbidity ratio (95% CI): 9.60 (7.44-12.19), 2.13 (1.56-2.84), and 1.70 (1.34-2.14) at 90 days, 1 year, and 3 years after diagnosis]., Conclusion: In the community, HF is a frequent adverse outcome among patients with AF, and HFpEF is more common than HFrEF. The rates of HF after AF have not declined, thus highlighting the importance of continued efforts to improve outcomes in AF., (Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: To study the temporal distribution and causes of hospitalizations after heart failure (HF) diagnosis., Patients and Methods: Hospitalizations were studied in 1972 Olmsted County, Minnesota, residents with incident HF from January 1, 2000, to December 31, 2011. All hospitalizations were examined for the 2 years following incident HF, and each was categorized as due to HF, other cardiovascular causes, or noncardiovascular causes. Negative binomial regression examined associations between time periods (0-30, 31-182, 183-365, and 366-730 days after diagnosis) and hospitalizations., Results: During the 2 years after diagnosis, 3495 hospitalizations were observed among 1336 of the 1972 patients with HF. The age- and sex-adjusted rates of hospitalizations were highest in the first 30 days after diagnosis (3.33 per person-year vs 1.33, 1.07, and 1.00 per person-year for 31-182 days, 183-365 days, and 366-730 days, respectively). The rates of hospitalizations were similar across sex, presentation of HF (inpatient or outpatient), and type of HF (preserved or reduced ejection fraction). Patients diagnosed as inpatients who had long hospital stays (>5 days) experienced more than a 30% increased risk of rehospitalization within 30 days of dismissal. Importantly, most hospitalizations (2222 of 3495 [63.6%]) were due to noncardiovascular causes, and a minority (440 of 3495 [12.6%]) were due to HF. The rates of noncardiovascular hospitalizations were higher than those for HF or other cardiovascular hospitalizations across all follow-up for all time periods after HF., Conclusion: Patients with HF experience high rates of hospitalizations, particularly within the first 30 days, and mostly for noncardiovascular causes. To reduce hospitalizations in patients with HF, an integrated approach focusing on comorbidities is required., (Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) is associated with excess morbidity and mortality for which noncardiac causes are increasingly recognized. The authors previously described an increased risk of cancer among HF patients compared with community controls., Objectives: This study examined whether HF was associated with an increased risk of subsequent cancer among a homogenous population of first myocardial infarction (MI) survivors., Methods: A prospective cohort study was conducted among Olmsted County, Minnesota, residents with incident MI from 2002 to 2010. Patients with prior cancer or HF diagnoses were excluded., Results: A total of 1,081 participants (mean age 64 ± 15 years; 60% male) were followed for 5,327 person-years (mean 4.9 ± 3.0 years). A total of 228 patients developed HF, and 98 patients developed cancer (excluding nonmelanoma skin cancer). Incidence density rates for cancer diagnosis (per 1,000 person-years) were 33.7 for patients with HF and 15.6 for patients without HF (p = 0.002). The hazard ratio (HR) for cancer associated with HF was 2.16 (95% confidence interval [CI]: 1.39 to 3.35); adjusted for age, sex, and Charlson comorbidity index; HR: 1.71 (95% CI: 1.07 to 2.73). The HRs for mortality associated with cancer were 4.90 (95% CI: 3.10 to 7.74) for HF-free and 3.91 (95% CI: 1.88 to 8.12) for HF patients (p for interaction = 0.76)., Conclusions: Patients who develop HF after MI have an increased risk of cancer. This finding extends our previous report of an elevated cancer risk after HF compared with controls, and calls for a better understanding of shared risk factors and underlying mechanisms., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the effect of the number and type of comorbid conditions on death and hospitalizations in individuals with incident heart failure (HF)., Design: Population-based cohort study., Setting: Olmsted County, Minnesota., Participants: Olmsted County, Minnesota, residents with incident HF from 2000 to 2010 (mean age 76 ± 14, 56% female) (N = 1,714)., Measurements: The prevalence of 16 chronic conditions obtained at HF diagnosis classified into three groups: cardiovascular (CV) related, other physical, and mental., Results: The mean number of conditions per participant was 2.6 ± 1.5 for CV-related conditions, 1.3 ± 1.1 for other physical conditions, and 0.30 ± 0.61 for mental conditions. After a mean follow-up of 4.2 years, 1,073 deaths and 6,306 hospitalizations had occurred. After adjustment for age, sex, ejection fraction, in- or outpatient status, and number of other conditions, an increase of one other physical condition was associated with a 14% (HR = 1.14, 95% CI = 1.08-1.20) greater risk of death and a 26% (HR = 1.26, 95% CI = 1.20-1.32) greater risk of hospitalization, and an increase of one mental condition was associated with a 31% (HR = 1.31, 95% CI = 1.19-1.44) greater risk of death and an 18% (HR = 1.18, 95% CI = 1.07-1.29) greater risk of hospitalization. In contrast, an increase of one CV-related condition was not associated with greater risk of death and was associated with a 10% (HR = 1.10, 95% CI = 1.06-1.15) greater risk of hospitalization., Conclusion: CV-related conditions are the most common type of comorbid conditions in individuals with HF, but other physical and mental conditions are more strongly associated with death and hospitalizations. This underscores the effect of non-CV conditions on outcomes in HF., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Objective: To examine the association between depression and clinical outcomes in heart failure (HF) in a community cohort., Patients and Methods: HF patients in Minnesota, United States completed depression screening using the 9-item Patient Health Questionnaire (PHQ-9) between 1st Oct 2007 and 1st Dec 2011; patients with PHQ-9≥5 were labelled "depressed". We calculated the risk of death and first hospitalization within 2 years using Cox regression. Results were adjusted for 10 commonly used prognostic factors (age, sex, systolic blood pressure, estimated glomerular filtration rate, serum sodium, ejection fraction, blood urea nitrogen, brain natriuretic peptide, presence of diabetes and ischaemic aetiology). Area under the curve (AUC), integrated discrimination improvement (IDI) and net reclassification improvement (NRI) compared depression as a predictor against the aforementioned factors., Results: 425 patients (mean age 74, 57.6% males) were included in the study; 179 (42.1%) had PHQ-9≥5. The adjusted hazard ratio of death was 2.02 (95% CI 1.34-3.04) and of hospitalization was 1.42 (95% CI 1.13-1.80) for those with compared to those without depression. Adding depression to the models did not appreciably change the AUC but led to statistically significant improvements in both the IDI (p = 0.001 and p = 0.005 for death and hospitalization, respectively) and NRI (for death and hospitalization, 35% (p = 0.002) and 27% (p = 0.007) were reclassified correctly, respectively)., Conclusion: Depression is frequent among community patients with HF and associated with increased risk of hospitalizations and death. Risk prediction for death and hospitalizations in HF patients can be improved by considering depression.

Importance: Whether the extent of coronary artery disease (CAD) is associated with the occurrence of heart failure (HF) after myocardial infarction (MI) is not known. Furthermore, whether this association might differ by HF type according to preserved or reduced ejection fraction (EF) has yet to be determined., Objectives: To evaluate in a community cohort of patients with incident (first-ever) MI the association of angiographic CAD with subsequent HF and to examine the prognostic role of CAD according to HF subtypes: HF with reduced EF and HF with preserved EF., Design, Setting, and Participants: A population-based cohort study was conducted in 1922 residents of Olmsted County, Minnesota, with incident MI diagnosed between January 1, 1990, and December 31, 2010, and no prior HF; study participants were followed up through March 31, 2013. The extent of angiographic CAD was determined at baseline and categorized according to the number of major epicardial coronary arteries with 50% or more lumen diameter obstruction., Main Outcomes and Measures: The primary end point was time to incident HF. The primary exposure variable was the extent of CAD as expressed by the number of major coronary arteries with significant obstruction (0-, 1-, 2-, or 3-vessel disease) obtained from coronary angiograms performed no more than 1 day after the MI. Heart failure was ascertained by the Framingham criteria and classified by type according to EF (50% cutoff)., Results: Of the 1922 participants, 1258 (65.4%) were men (mean [SD] age, 64 [13] years). During a mean follow-up period of 6.7 (5.9) years, 588 patients (30.6%) developed HF. With death and recurrent MI modeled as competing risks, the cumulative incidence rates of post-MI HF among patients with 0 or 1, 2, and 3 diseased vessels were 10.7%, 14.6%, and 23.0% at 30 days; and 14.7%, 20.6%, and 29.8% at 5 years, respectively (P < .001 for trend). After adjustment for clinical characteristics in a Cox proportional hazards regression model, the hazard ratios (95% CIs) for HF were 1.25 (0.99-1.59) and 1.75 (1.40-2.20) in patients with 2 and 3 vessels vs 0 or 1 occluded vessel, respectively (P < .001 for trend). The increased risk with a greater number of occluded vessels was independent of the occurrence of a recurrent MI and did not differ appreciably by HF type., Conclusions and Relevance: The extent of angiographic CAD is an indicator of post-MI HF regardless of HF type and independent of recurrent MI. These data underscore the need to further investigate the processes taking place in the transition from myocardial injury to HF.

Background: Contemporary data are lacking on the prognostic importance of heart failure (HF) after myocardial infarction (MI). We evaluated the prognostic impact of HF post MI according to preserved/reduced ejection fraction and the timing of its occurrence., Methods and Results: All Olmsted County, Minnesota, residents (n=2596) with incident MI diagnosed in 1990 to 2010 and no prior HF were followed through March 2013. Cox models were used to examine (1) the hazard ratios for death associated with HF type and timing and (2) secular trends in survival by HF status. During a mean follow-up of 7.6 years, there were 1116 deaths, 634 in the 902 patients who developed HF (70%) and 482 in the 1694 patients who did not develop HF (28%). After adjustment for age and sex, HF as a time-dependent variable was strongly associated with mortality (hazard ratio =3.31, 95% confidence interval: 2.93-3.75), particularly from cardiovascular causes (hazard ratio =4.20, 95% confidence interval: 3.50-5.03). Further adjustment for MI severity and comorbidity, acute treatment, and recurrent MI moderately attenuated these associations (hazard ratio =2.49 and 2.94 for all-cause and cardiovascular mortality, respectively). Mortality did not differ by ejection fraction, but was higher for delayed- versus early-onset HF (P for heterogeneity =0.002). The age- and sex-adjusted 5-year survival estimates in 2001 to 2010 versus 1990 to 2000 were 82% and 81% among HF-free and 61% and 54% among HF patients, respectively (P for heterogeneity of trends =0.05)., Conclusions: HF markedly increases the risk of death after MI. This excess risk is similar regardless of ejection fraction but greater for delayed- versus early-onset HF. Mortality after MI declined over time, primarily as a result of improved HF survival., (© 2015 American Heart Association, Inc.)

Identifying populations of heart failure (HF) patients is paramount to research efforts aimed at developing strategies to effectively reduce the burden of this disease. The use of electronic medical record (EMR) data for this purpose is challenging given the syndromic nature of HF and the need to distinguish HF with preserved or reduced ejection fraction. Using a gold standard cohort of manually abstracted cases, an EMR-driven phenotype algorithm based on structured and unstructured data was developed to identify all the cases. The resulting algorithm was executed in two cohorts from the Electronic Medical Records and Genomics (eMERGE) Network with a positive predictive value of >95 %. The algorithm was expanded to include three hierarchical definitions of HF (i.e., definite, probable, possible) based on the degree of confidence of the classification to capture HF cases in a whole population whereby increasing the algorithm utility for use in e-Epidemiologic research.