Manemann, Sheila M.

Abstract 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.

Background: Several chronic diseases can contribute to functional disability. However, little is known about functional disability and its progression overtime in chronic heart failure (HF). We aimed to investigate the prevalence and progression of difficulty with activities of daily living (ADLs) and its association with mortality in patients with HF. Methods: We enrolled Southeastern Minnesota residents with HF into a longitudinal study from September 2, 2003 through January 31, 2012. A patient’s difficulty with 9 ADLs (feeding themselves, dressing, toileting, housekeeping, climbing stairs, bathing, walking, using transportation, managing medications) was assessed by questionnaire. Patients were followed for all-cause mortality. Using Rasch analysis to determine the order of ADL difficulty, patients were divided into 3 categories (minimal, moderate, severe difficulty). Predictors of ADL difficulty were assessed using negative binomial regression and the association between ADL difficulty and death with Cox proportional hazard regression. Results: Among 1128 patients (mean age 74.7 years, 49.2% female), most (59.4%) reported difficulty with one or more ADLs at enrollment, with 272 (24.1%) and 146 (12.9%) reporting moderate and severe difficulty, respectively. The independent predictors of difficulty with ADLs were older age, female sex, diabetes, morbid obesity, cerebrovascular disease, dementia, anemia, and unmarried status. After a mean (SD) follow-up of 3.2 (2.4) years, 615 (54.5%) patients had died. There was a stepwise increase in the risk of death as difficulty with ADLs increased ( Figure ). After adjusting for age, sex, and comorbidity, the HR (95% CI) for mortality was 1.52 (1.25-1.83, p<0.001) for patients with moderate and 2.28 (1.82-2.85, p<0.001) for those with severe difficulty with ADLs compared to those with minimal difficulty (p for trend<0.001). In most patients (73.5%), difficulty with ADLs was stable over time. However, survivors reporting persistently severe or worsening ADL difficulty in a second assessment (median 9 months later) were at an increased risk of subsequent mortality (adjusted HR 2.08, 95% CI 1.70-2.55, p<0.001). Conclusions: Functional disability is common in patients with HF, can progress over time, and is independently associated with adverse prognosis.

Background: Heart failure (HF) patients are experiencing an epidemic of hospitalizations. Nevertheless, data on the frequency and distribution of hospitalizations over the course of the disease are lacking. Methods: We determined the rates of hospitalizations during periods of follow-up in Olmsted County, MN residents with incident HF from 2000-2010. HF was identified using ICD-9 code 428 and validated by the Framingham criteria. All hospitalizations were obtained for the 2 years following incident HF and each was categorized as due to HF, other cardiovascular (ICD-9 codes 390-427, 429-459), or non-cardiovascular causes. Follow-up was divided into discrete time periods (epochs): 0-30, 31-182, 183-365, and 366-730 days. Negative binomial regression examined associations between epochs of follow-up time and hospitalizations. Results: Among 1702 incident HF patients (mean age 76, 44% male), 1143 (67%) were hospitalized at index. Over the 2 year follow-up, 3008 hospitalizations were observed among 1136 patients, and 351 patients were hospitalized within 30 days of incident HF (median time from HF to hospitalization: 11 days). The majority of hospitalizations were due to non-cardiovascular causes (63% vs. 14% HF, 23% other cardiovascular); however, a larger proportion of HF and other cardiovascular hospitalizations were observed within the first 30 days (52% non-cardiovascular, 18% HF, 30% other cardiovascular) compared to the other time periods. The rate of hospitalization was highest within the first 30 days and was similar across sex, presentation of incident HF (inpatient, outpatient), and type of HF (preserved (≥50%), reduced (<50%) ejection fraction) (Table). Conclusions: HF patients experience high rates of hospitalizations, particularly within the first 30 days, and the majority of hospitalizations are for non-cardiovascular causes. Continued efforts to manage comorbid conditions and reduce hospitalizations in HF patients are needed.

Background: Whether age alone explains the comorbidity burden in heart failure (HF) is unclear. In particular, differences in the burden of co-morbid conditions in HF patients compared to population controls has not been well documented. Methods: The prevalence of 17 chronic conditions defined by the US Department of Health and Human Services were obtained in 1746 incident HF patients from 2000-2010 and controls matched 1:1 on sex and age from Olmsted County, MN. Conditions were ascertained requiring 2 occurrences of a diagnostic code. Logistic regression determined associations of each condition with HF. Results: Among the 1746 matched pairs (mean age 76.2 years, 43.5% men), the prevalence was higher in HF cases for all conditions (p<0.05) except dementia and osteoporosis. After adjusting for all conditions, hypertension, coronary artery disease, arrhythmia, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, hepatitis, and substance abuse were significantly more common in HF (figure). More than a 2-fold increased odds of hepatitis, arrhythmia, and coronary artery disease was observed among HF cases. Arrhythmia (34.2%), hypertension (31.1%), and coronary artery disease (27.8%) had the largest attributable risk of HF; for example, assuming a causal relationship, if arrhythmias were eliminated, 34% of HF would be avoided. Conclusions: Compared to age- and sex-matched controls, HF patients have a higher prevalence of many chronic conditions, indicating the excess comorbidity in HF is not due to age alone. Some cardiovascular conditions, including arrhythmia, coronary artery disease, and hypertension were more common in HF. Of the non-cardiovascular conditions, hepatitis had the strongest association with HF and was an unanticipated finding that deserves additional investigation. It is important to understand comorbidities as they play a key role in the excess mortality and healthcare utilization experienced by HF patients.

Background: Little is known about the association between coronary artery disease (CAD) and the risk of heart failure (HF) after myocardial infarction (MI), and whether it differs by reduced (HFrEF) or preserved (HFpEF) ejection fraction (EF) has yet to be determined. Subjects and Methods: Olmsted County, Minnesota residents (n=1,924; mean age, 64 years; 66% male) with first MI diagnosed in 1990-2010 and no prior HF were followed through 2013. Framingham Heart Study criteria were used to define HF, which was further classified according to EF (applying a 50% cutoff). The extent of angiographic CAD was defined at index MI according to the number of major epicardial coronary arteries with ≥50% lumen diameter obstruction. Fine & Gray and Cox proportional hazards regression models were used to assess the association of CAD categories with incidence of HF, and multiple imputation methodology was applied to account for the 19% with missing EF data. Results: During a mean (SD) follow-up of 6.7 (5.9) years, 594 patients developed HF. Adjusted for age and sex, with death considered a competing risk, the cumulative incidence rates of HF among patients with 1- (n=581), 2- (n=622), and 3-vessel disease (n=721) were 11.2%, 14.6% and 20.5% at 30 days; and 18.1%, 22.3% and 29.4% at 5 years after MI, respectively. The increased risk of HF with greater number of occluded vessels was only modestly attenuated after further adjustment for patient and MI characteristics, and did not differ materially by EF (Table). Conclusions: The extent of angiographic CAD expressed by the number of diseased vessels is independently associated with HF incidence after MI. The association is evident promptly after MI and applies to both HFrEF and HFpEF.

Background: Differences in the prevalence and duration of co-morbid conditions in atrial fibrillation (AF) patients compared to population controls have not been well documented. Methods: The prevalence and duration of 17 chronic conditions defined by the US Department of Health and Human Services, as well as anxiety, obesity, and smoking status, was obtained in a random sample of 1430 patients with incident AF from 2000-2010 and 1430 controls from Olmsted County, MN. Controls were matched to cases 1:1 on sex and age (within 5 years). Chronic conditions were ascertained electronically requiring 2 occurrences of a diagnostic code; the duration of each condition (up to 25 years) was calculated. Logistic regression determined associations of each condition with AF after adjustment for all other conditions. Results: Among the 1430 matched pairs (median age 76 years, 48.6% men), the prevalence of chronic conditions was higher in AF cases compared to controls for all conditions except asthma, dementia, depression, hepatitis, and osteoporosis (figure). However, the duration of the conditions were similar in AF compared to controls, except for hypertension (median duration 12.3 and 9.9 years in AF cases and controls, respectively; p=0.002). After adjusting for all other conditions, obesity, hypertension, congestive heart failure, coronary artery disease, chronic kidney disease, and chronic obstructive pulmonary disease remained significantly more common in AF compared to controls (figure). Conditions with the largest attributable risk of AF were hypertension (25.4%), coronary artery disease (17.7%), and congestive heart failure (12.3%). Conclusions: AF patients have a higher prevalence of many chronic conditions compared to population controls. However, besides hypertension, these comorbidities do not develop earlier in AF. Nevertheless, the excess comorbidity burden in AF is important to characterize and understand as it may partly explain the excess mortality and healthcare utilization experienced by AF patients.

Background: Referral to a skilled nursing facility (SNF) should contribute to reducing hospital readmissions; however, a “revolving door” phenomenon after admission to SNF has been hypothesized to drive readmissions. The urgent need to study the impact of SNF on readmissions in heart failure (HF) was recently emphasized, yet this has never been studied in the community. Objectives: To evaluate the association between discharge to SNF and 30-day readmissions in a community cohort of hospitalized incident HF patients. Methods: Olmsted County, MN residents hospitalized with first ever (incident) HF (International Classification of Diseases-9 th Revision code 428) from 1995 through 2010 were identified. HF was validated by Framingham criteria. Patients residing in a SNF prior to hospitalization were excluded from the analysis. Logistic regression was used to examine the association between discharge to SNF and 30-day readmissions. Results: Among 1360 HF patients (mean age 74±14, 47% male), 241(18%) were referred to a SNF. Overall, 296 (22%) patients were readmitted within 30-days after index hospitalization. The proportion of 30-day readmissions was greater among patients discharged to a SNF compared to patients discharged home (27% vs 21%, p=0.031). After adjustment for age and sex, patients discharged to a SNF had a 40% increase in the odds of having a hospital readmission within 30 days post HF compared to those discharged home (OR: 1.42, 95% CI 1.01-1.99). Further adjustment for year of HF diagnosis, ejection fraction, anemia, renal function, dementia and cancer did not alter the strength of the association (OR: 1.43, 95% CI: 0.99-2.09). Conclusion: Among community patients with HF, 30-day readmissions remain frequent and are more likely to occur among patients discharged to a SNF compared to those discharged home. These data provide new insight into the drivers of HF readmissions and suggest that interventions targeted to HF patients in SNFs may be warranted.

Background: Differences in the impact of comorbid conditions on outcomes in atrial fibrillation (AF) patients compared to population controls have not been well documented. Methods: The prevalence of 19 chronic conditions and smoking status was obtained in 1430 patients with incident AF from 2000-2010 and 1430 controls matched 1:1 on sex and age (within 5 years) from Olmsted County, MN. Andersen-Gill models determined associations of each condition with all-cause hospitalizations in AF cases and controls after adjusting for all other conditions and accounting for the matching. Cox regression determined associations of each condition with death. Results: Among 1430 matched pairs (median age 76 years, 48.6% men), the prevalence of chronic conditions was higher in AF cases compared to controls for all conditions except asthma, dementia, depression, hepatitis, and osteoporosis. Over a mean follow-up of 6.3 years, 2678 hospitalizations and 812 deaths occurred. The rates of hospitalization were 59 and 26 per 100 person-years and the rates of death were 10 and 5 per 100 person-years in AF cases and controls, respectively. After adjusting for all other conditions, the risk of hospitalization was lower in AF patients compared to controls for those with coronary artery disease, arthritis, cancer, chronic obstructive pulmonary disease, and osteoporosis (figure). In contrast, the risk of hospitalization was higher in AF cases for those with diabetes and substance abuse. For deaths, the only comorbidity with different associations between AF cases and controls was depression. The hazard ratios (95% CI) for death were 2.02 (1.26-3.24) in AF cases and 0.90 (0.58-1.38) in controls (p-value for interaction=0.008). Conclusions: AF patients have a higher prevalence of chronic conditions compared to population controls. The associations of comorbidities with hospitalizations differed between AF cases and controls, suggesting that management of comorbidities in patients with AF may need to be tailored to this specific patient population.

Background: A decline in all forms of coronary revascularization has been previously reported. Whether the decline has continued after the turn of the century is unknown as well as whether it is influenced by trends in the use and results of coronary angiography. Methods: All diagnostic and therapeutic coronary procedures performed among Olmsted County, MN residents from 2000-2015 were analyzed. Standardized rates (per 100,000 population) were calculated applying the direct method and temporal trends compared using Poisson regression models. Trends in disease severity, defined as 3-vessel and/or left main coronary artery disease (CAD), were assessed using logistic regression models. Results: Between 2000 and 2015, 11,691 coronary angiographies were performed (63% men; 54% ≥ 65 years of age). The age- and sex-standardized rates of angiography decreased over time (p trend < 0.001; Figure). Overall, 30% of the subjects had 3-vessel and/or left main CAD, and this proportion decreased over time (age- and sex-adjusted odds ratios (95% CI) for severe CAD: 0.68 (0.62-0.76) in 2005-2009 and 0.69 (0.63-0.77) in 2010-2015 compared with 2000-2004). Among 5,222 coronary revascularization procedures performed, 78% were PCI and 22% CABG. The age- and sex-standardized rates of any revascularization declined during the study period, reflecting temporal decreases in both PCI and CABG (all p trend < 0.001; Figure). The declines in angiography rates, CAD severity, and revascularization utilization were consistently greater in women than men (all P for interactions < 0.01). Conclusions: Declines in all forms of coronary revascularization, which were greater in women than men, have occurred in Olmsted County, MN, from 2000-2015. The declines occurred in the context of fewer angiograms performed in the population and reduced severity of anatomic CAD.

Introduction: Little is known about the characteristics and resources that enable patients with heart failure (HF) to engage in effective self-management. To address this gap in knowledge, we measured personal and health care resources for self-management and examined associations with mortality among patients with HF. Methods: We surveyed 5543 residents of 11 counties in Southeast Minnesota with a first-ever code for HF [International Classification of Disease, Ninth Revision code 428 or Tenth Revision code I50] between 1/1/2013 and 3/31/2016. Self-management resources were measured with the health care and personal subscales of the Chronic Illness Resources Survey (CIRS), both of which included 3 questions on a 5-point scale. The responses were averaged and participants were categorized as low if the mean score was below the median of the distribution (range from 1 to 5). The survey was returned by 2866 participants (response rate 52%) and those with complete data on the main items of interest were retained for analysis (N=2212). Cox proportional hazards regression was used to determine the association between each subscale and mortality. Results: Among 2212 participants (mean age 72.8 years, 54.1% men) the median health care score was 4, while the personal score was 3. Those with low health care resources were older and less educated than those with a higher score (p<0.05), while those with low personal resources had less comorbidities and lower education attainment compared to those with a higher score (p<0.05). After a mean (SD) follow-up of 1.3 ± 0.6 years, 207 deaths occurred. Low levels of both self-management resources were associated with an increased risk of death compared with patients with high levels (Table). Conclusions: Having limited self-management resources is associated with an increased risk of mortality among patients with HF. Thus, interventions aimed at supporting self-management among patients with HF may improve outcomes.