Incident Heart Failure With Mildly Reduced Ejection Fraction: Frequency, Characteristics, and Outcomes.

BACKGROUND: Heart failure (HF) with an ejection fraction (EF) of 41%-49% is recognized as HF with a mildly reduced EF (HFmrEF). However, existing knowledge of the HFmrEF phenotype is based on HF clinical trial and registry cohorts that may be limited by multiple forms of bias. METHODS AND RESULTS: In a community-based, retrospective cohort study, adult residents of Olmsted County, Minnesota, with validated (Framingham criteria) incident HF from 2007 to 2015 were categorized by echocardiographic EF at first HF diagnosis. Among 2035 adults with incident HF, 12.5% had HFmrEF, 29.9% had HF with reduced EF (HFrEF), and 57.6% had HF with preserved EF (HFpEF). Mean age and sex varied by EF group, with HFmrEF (75.6 years, 45.3% female), HFrEF (70.9 years, 36.5% female), and HFpEF (76.9 years, 59.7% female). Most comorbid conditions were more common in HFmrEF vs HFrEF, but similar in HFmrEF and HFpEF. After a mean follow-up of 4.6 ± 3.5 years, adjusting for age, sex, and comorbidities, the risks of hospitalization and cardiovascular mortality did not differ by EF category. Of patients who began as HFmrEF, 26.9% declined to an EF of 40% or less and 44.8% improved to an EF of 50% or greater. CONCLUSIONS: In this community cohort of incident HF, 12.5% have HFmrEF. Clinical characteristics in HFmrEF resemble HFpEF more than HFrEF. Adjusted hospitalization and mortality risks did not vary by EF group. Patients with incident HFmrEF usually transitioned to a different EF category on follow-up.

Associations of Atrial Fibrillation After Noncardiac Surgery With Stroke, Subsequent Arrhythmia, and Death : A Cohort Study.

BACKGROUND: Postoperative atrial fibrillation (AF) after noncardiac surgery confers increased risks for ischemic stroke and transient ischemic attack (TIA). How outcomes for postoperative AF after noncardiac surgery compare with those for AF occurring outside of the operative setting is unknown. OBJECTIVE: To compare the risks for ischemic stroke or TIA and other outcomes in patients with postoperative AF versus those with incident AF not associated with surgery. DESIGN: Cohort study. SETTING: Olmsted County, Minnesota. PARTICIPANTS: Patients with incident AF between 2000 and 2013. MEASUREMENTS: Patients were categorized as having AF occurring within 30 days of a noncardiac surgery (postoperative AF) or having AF unrelated to surgery (nonoperative AF). RESULTS: Of 4231 patients with incident AF, 550 (13%) had postoperative AF as their first-ever documented AF presentation. Over a mean follow-up of 6.3 years, 486 patients had an ischemic stroke or TIA and 2462 had subsequent AF; a total of 2565 deaths occurred. The risk for stroke or TIA was similar between those with postoperative AF and nonoperative AF (absolute risk difference [ARD] at 5 years, 0.1% [95% CI, -2.9% to 3.1%]; hazard ratio [HR], 1.01 [CI, 0.77 to 1.32]). A lower risk for subsequent AF was seen for patients with postoperative AF (ARD at 5 years, -13.4% [CI, -17.8% to -9.0%]; HR, 0.68 [CI, 0.60 to 0.77]). Finally, no difference was seen for cardiovascular death or all-cause death between patients with postoperative AF and nonoperative AF. LIMITATION: The population consisted predominantly of White patients; caution should be used when extrapolating the results to more racially diverse populations. CONCLUSION: Postoperative AF after noncardiac surgery is associated with similar risk for thromboembolism compared with nonoperative AF. Our findings have potentially important implications for the early postsurgical and subsequent management of postoperative AF. PRIMARY FUNDING SOURCE: National Institute on Aging.

Recent trends in cardiovascular disease deaths: a state specific perspective.

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.

Association of New-Onset Atrial Fibrillation After Noncardiac Surgery With Subsequent Stroke and Transient Ischemic Attack.

Importance: Outcomes of postoperative atrial fibrillation (AF) after noncardiac surgery are not well defined. Objective: To determine the association of new-onset postoperative AF vs no AF after noncardiac surgery with risk of nonfatal and fatal outcomes. Design, Setting, and Participants: Retrospective cohort study in Olmsted County, Minnesota, involving 550 patients who had their first-ever documented AF within 30 days after undergoing a noncardiac surgery (postoperative AF) between 2000 and 2013. Of these patients, 452 were matched 1:1 on age, sex, year of surgery, and type of surgery to patients with noncardiac surgery who were not diagnosed with AF within 30 days following the surgery (no AF). The last date of follow-up was December 31, 2018. Exposures: Postoperative AF vs no AF after noncardiac surgery. Main Outcomes and Measures: The primary outcome was ischemic stroke or transient ischemic attack (TIA). Secondary outcomes included subsequent documented AF, all-cause mortality, and cardiovascular mortality. Results: The median age of the 452 matched patients was 75 years (IQR, 67-82 years) and 51.8% of patients were men. Patients with postoperative AF had significantly higher CHA2DS2-VASc scores than those in the no AF group (median, 4 [IQR, 2-5] vs 3 [IQR, 2-5]; P < .001). Over a median follow-up of 5.4 years (IQR, 1.4-9.2 years), there were 71 ischemic strokes or TIAs, 266 subsequent documented AF episodes, and 571 deaths, of which 172 were cardiovascular related. Patients with postoperative AF exhibited a statistically significantly higher risk of ischemic stroke or TIA (incidence rate, 18.9 vs 10.0 per 1000 person-years; absolute risk difference [RD] at 5 years, 4.7%; 95% CI, 1.0%-8.4%; HR, 2.69; 95% CI, 1.35-5.37) compared with those with no AF. Patients with postoperative AF had statistically significantly higher risks of subsequent documented AF (incidence rate 136.4 vs 21.6 per 1000 person-years; absolute RD at 5 years, 39.3%; 95% CI, 33.6%-45.0%; HR, 7.94; 95% CI, 4.85-12.98), and all-cause death (incidence rate, 133.2 vs 86.8 per 1000 person-years; absolute RD at 5 years, 9.4%; 95% CI, 4.9%-13.7%; HR, 1.66; 95% CI, 1.32-2.09). No significant difference in the risk of cardiovascular death was observed for patients with and without postoperative AF (incidence rate, 42.5 vs 25.0 per 1000 person-years; absolute RD at 5 years, 6.2%; 95% CI, 2.2%-10.4%; HR, 1.51; 95% CI, 0.97-2.34). Conclusions and Relevance: Among patients undergoing noncardiac surgery, new-onset postoperative AF compared with no AF was associated with a significant increased risk of stroke or TIA. However, the implications of these findings for the management of postoperative AF, such as the need for anticoagulation therapy, require investigation in randomized trials.

Multimorbidity and the risk of hospitalization and death in atrial fibrillation: A population-based study.

Patients with atrial fibrillation (AF) have many comorbidities and excess risks of hospitalization and death. Whether the impact of comorbidities on outcomes is greater in AF than the general population is unknown. METHODS: One thousand four hundred thirty patients with AF and community controls matched 1:1 on age and sex were obtained from Olmsted County, Minnesota. Andersen-Gill and Cox regression estimated associations of 19 comorbidities with hospitalization and death, respectively. RESULTS: AF cases had a higher prevalence of most comorbidities. Hypertension (25.4%), coronary artery disease (17.7%), and heart failure (13.3%) had the largest attributable risk of AF; these along with obesity and smoking explained 51.4% of AF. Over a mean follow-up of 6.3 years, patients with AF experienced higher rates of hospitalization and death than did population controls. However, the impact of comorbidities on hospitalization and death was generally not greater in patients with AF compared with controls, with the exception of smoking. Ever smokers with AF experienced higher-than-expected risks of hospitalization and death, with observed vs expected (assuming additivity of effects) hazard ratios compared with never smokers without AF of 1.78 (1.56-2.02) vs 1.52 for hospitalization and 2.41 (2.02-2.87) vs 1.84 for death. CONCLUSIONS: Patients with AF have a higher prevalence of most comorbidities; however, the impact of comorbidities on hospitalization and death is generally similar in AF and controls. Smoking is a notable exception; ever smokers with AF experienced higher-than-expected risks of hospitalization and death. Thus, interventions targeting modifiable behaviors may benefit patients with AF by reducing their risk of adverse outcomes.

Emergency department visits and hospitalizations attributable to recent Epstein-Barr virus infection.

OBJECTIVE: Infectious mononucleosis (IM) or mono is typically caused by primary infection with Epstein-Barr virus (EBV) and may have a months-long, complicated course. We utilized population-based data to add to the limited literature on health care utilization following EBV infection. METHODS: The Rochester Epidemiology Project includes medical records for ∼60% of residents living in 27 counties of Minnesota (MN) and Wisconsin (WI). Persons meeting a case definition of recent EBV infection from 1 January 1998 to 31 December 2021 were compared to three persons not meeting the definition, matched on case's sex, age, and index date. Emergency department (ED) visits and hospitalizations in the two groups were compared during 5-years' follow-up divided into three periods (short-term ≤3 months, mid-term >3 months-1 year, long-term >1-5 years). Adjusted hazard ratios (AHR) were estimated to account for the potential influence of confounding variables. RESULTS: In total, 6,423 persons had a recent EBV infection and were matched to 19,269 comparators. The risk of an ED visit was significantly higher among cases in the short-term period (24.3% vs referents: 7.6%, p <.001; AHR = 3.71, 95% CI = 3.41-4.03). Cases also had an increased risk of hospitalization in the short-term (5.2% vs 1.6%: referents, p <.001; AHR = 3.53, 95% CI = 2.94-4.24). For ED visits but not hospitalization, the excess risk persisted into the mid-term follow-up period. Persons without a concurrent clinical diagnosis of IM continued to have an increased risk of hospitalizations up to 1 year after index date (AHR = 1.45, 95% CI = 1.09-1.91) and an increased risk of ED visits up to 5 years after the index date (AHR = 1.29, 95% CI = 1.14-1.46). CONCLUSION: There is a substantial short- and mid-term increased risk of serious health care encounters associated with recent EBV infection. Mid- and long-term risks are increased in patients who do not have a concomitant diagnosis of IM.

The impact of multimorbidity and functional limitation on quality of life in patients with heart failure: A multi-site study.

BACKGROUND: Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health-related quality of life in patients with HF is not well understood. METHODS: Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF-related prescription drugs from four U.S. institutions were mailed a survey to measure patient-centric factors including functional status (activities of daily living [ADLs]) and health-related quality of life (PROMIS-29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non-cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS-29 sub-scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. RESULTS: A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66-4.45), depression (OR: 3.11, 95% CI: 2.39-4.06), and fatigue (OR: 4.19, 95% CI: 3.25-5.40); worse sleep (OR: 2.14, 95% CI: 1.69-2.72) and pain (OR: 6.73, 95% CI: 5.15-8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19-12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. CONCLUSION: Patients with only functional limitation have similar poor health-related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well-being of patients with HF.

The Importance of Estimating Excess Deaths Regionally During the COVID-19 Pandemic.

National or statewide estimates of excess deaths have limited value to understanding the impact of the COVID-19 pandemic regionally. We assessed excess deaths in a 9-county geographically defined population that had low rates of COVID-19 and widescale availability of testing early in the pandemic, well-annotated clinical data, and coverage by 2 medical examiner's offices. We compared mortality rates (MRs) per 100,000 person-years in 2020 and 2021 with those in the 2019 reference period and MR ratios (MRRs). In 2020 and 2021, 177 and 219 deaths, respectively, were attributed to COVID-19 (MR = 52 and 66 per 100,000 person-years, respectively). COVID-19 MRs were highest in males, older persons, those living in rural areas, and those with 7 or more chronic conditions. Compared with 2019, we observed a 10% excess death rate in 2020 (MRR = 1.10 [95% CI, 1.04 to 1.15]), with excess deaths in females, older adults, and those with 7 or more chronic conditions. In contrast, we did not observe excess deaths overall in 2021 compared with 2019 (MRR = 1.04 [95% CI, 0.99 to 1.10]). However, those aged 18 to 39 years (MRR = 1.36 [95% CI, 1.03 to 1.80) and those with 0 or 1 chronic condition (MRR = 1.28 [95% CI, 1.05 to 1.56]) or 7 or more chronic conditions (MRR = 1.09 [95% CI, 1.03 to 1.15]) had increased mortality compared with 2019. This work highlights the value of leveraging regional populations that experienced a similar pandemic wave timeline, mitigation strategies, testing availability, and data quality.

Contemporary trends in heart failure with reduced and preserved ejection fraction after myocardial infarction: a community study.

Major changes have recently occurred in the epidemiology of myocardial infarction (MI) that could possibly affect outcomes such as heart failure (HF). Data describing trends in HF after MI are scarce and conflicting and do not distinguish between preserved and reduced ejection fraction (EF). We evaluated temporal trends in HF after MI. All residents of Olmsted County, Minnesota (n = 2,596) who had a first-ever MI diagnosed in 1990-2010 and no prior HF were followed-up through 2012. Framingham Heart Study criteria were used to define HF, which was further classified according to EF. Both early-onset (0-7 days after MI) and late-onset (8 days to 5 years after MI) HF were examined. Changes in patient presentation were noted, including fewer ST-segment-elevation MIs, lower Killip class, and more comorbid conditions. Over the 5-year follow-up period, 715 patients developed HF, 475 of whom developed it during the first week. The age- and sex-adjusted risk declined from 1990-1996 to 2004-2010, with hazard ratios of 0.67 (95% confidence interval (CI): 0.54, 0.85) for early-onset HF and 0.63 (95% CI: 0.45, 0.86) for late-onset HF. Further adjustment for patient and MI characteristics yielded hazard ratios of 0.86 (95% CI: 0.66, 1.11) and 0.63 (95% CI: 0.45, 0.88) for early- and late-onset HF, respectively. Declines in early-onset and late-onset HF were observed for HF with reduced EF (<50%) but not for HF with preserved EF, indicating a change in the case mix of HF after MI that requires new prevention strategies.

Atrial fibrillation in myocardial infarction patients: Impact on health care utilization.

BACKGROUND: Atrial fibrillation (AF) often complicates myocardial infarction (MI). While AF adversely impacts survival in MI patients, the impact of AF on health care utilization has not been studied. METHODS: The risk of hospitalizations, emergency department (ED) visits, and outpatient visits associated with prior, new-onset (<30 days post-MI), and late-onset (≥30 days post-MI) AF was assessed among incident MI patients from the Olmsted County, Minnesota, community. RESULTS: Of 1,502 MI patients, 237 had prior AF, 163 developed new-onset AF, 113 developed late-onset AF, and 989 had no AF. Over a mean follow-up of 3.9 years, 3,661 hospitalizations, 5,559 ED visits, and 80,240 outpatient visits occurred. After adjustment, compared with patients without AF, those with prior and new-onset AF exhibited a 1.6-fold and 1.3-fold increased risk of hospitalization, respectively. In contrast, late-onset AF carried a 2.2-fold increased risk of hospitalization. The hazard ratios were 1.4, 1.2, and 1.8 for ED visits and 1.4, 1.2, and 1.7 for outpatient visits for prior, new-onset, and late-onset AF. Additional adjustment for time-dependent recurrent MI and heart failure attenuated the results slightly for hospitalizations and ED visits; however, patients with late-onset AF still exhibited a >50% increased risk for both utilization measures. CONCLUSIONS: In MI patients, the risk of hospitalizations, ED visits, and outpatient visits differed by the timing of AF onset, with the greatest risk conferred by late-onset AF. Atrial fibrillation imparts an adverse prognosis after MI, underscoring the importance of its management in MI patients.

Measuring frailty in heart failure: a community perspective.

BACKGROUND: Frailty, an important prognostic indicator in heart failure (HF), may be defined as a biological phenotype or an accumulation of deficits. Each method has strengths and limitations, but their utility has never been evaluated in the same community HF cohort. METHODS: Southeastern Minnesota residents with HF were recruited from 2007 to 2011. Frailty according to the biological phenotype was defined as 3 or more of: weak grip strength, physical exhaustion, slowness, low activity and unintentional weight loss >10 lb in 1 year. Intermediate frailty was defined as 1 to 2. The deficit index was defined as the proportion of deficits present out of 32 deficits. RESULTS: Among 223 patients (mean age 71 ± 14, 61% male), 21% were frail and 48% intermediate frail according to the biological phenotype. The deficit index ranged from 0.02-0.75, with a mean (SD) of 0.25 (0.13). Over a mean follow-up of 2.4 years, 63 patients died. After adjustment for age, sex and ejection fraction, patients categorized as frail by the biological phenotype had a 2-fold increased risk of death compared to those with no frailty, whereas a 0.1 unit increase in the deficit index was associated with a 44% increased risk of death. Both measures predicted death equally (C-statistics: 0.687 for biological phenotype and 0.700 for deficit index). CONCLUSION: The deficit index and the biological phenotype equally predict mortality. As the biological phenotype is not routinely assessed clinically, the deficit index, which can be ascertained from medical records, is a feasible alternative to ascertain frailty.

Heart failure performance measures: eligibility and implementation in the community.

BACKGROUND: The goal of heart failure (HF) performance measures is to improve quality of care by assessing the implementation of guidelines in eligible patients. Little is known about the proportion of eligible patients and how performance measures are implemented in the community. METHODS: We determined the eligibility for and adherence to performance measures and ß-blocker therapy in a community-based cohort of hospitalized HF patients from January 2005 to June 2011. RESULTS: All of the 465 HF inpatients (median age 76 years, 48% men) included in the study received an ejection fraction assessment. Only 164 had an ejection fraction <40% thus were candidates for ß-blocker and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB) therapy. Considering absolute contraindications, 99 patients were eligible to receive ACE inhibitors/ARB, and 162 to receive ß-blockers. Among these, 85% received ACE inhibitors/ARBs and 91% received ß-blockers. Among the 261 individuals with atrial fibrillation, 89 were eligible for warfarin and 54% received it. Of 52 current smokers, 69% received cessation counseling during hospitalization. CONCLUSION: In the community, among eligible hospitalized HF patients, the implementation of performance measures can be improved. However, as most patients are not candidates for current performance measures, other approaches are needed to improve care and outcomes.

Thirty-day rehospitalizations after acute myocardial infarction: a cohort study.

BACKGROUND: Rehospitalization is a quality-of-care indicator, yet little is known about its occurrence and predictors after myocardial infarction (MI) in the community. OBJECTIVE: To examine 30-day rehospitalizations after incident MI. DESIGN: Retrospective cohort study. SETTING: Population-based registry in Olmsted County, Minnesota. PATIENTS: 3010 patients who were hospitalized in Olmsted County with first-ever MI from 1987 to 2010 and survived to hospital discharge. MEASUREMENTS: Diagnoses, therapies, and complications during incident and subsequent hospitalizations were identified. Manual chart review was performed to determine the cause of all rehospitalizations. The hazard ratios and cumulative incidence of 30-day rehospitalizations were determined by using Cox proportional hazards regression models. RESULTS: Among 3010 patients (mean age, 67 years; 40.5% female) with incident MI (31.2% ST-segment elevation), 643 rehospitalizations occurred within 30 days in 561 (18.6%) patients. Overall, 30.2% of rehospitalizations were unrelated to the incident MI and 42.6% were related; the relationship was unclear in 27.2% of rehospitalizations. Angiography was performed in 153 (23.8%) rehospitalizations. Revascularization was performed in 103 (16.0%) rehospitalizations, of which 46 (44.7%) had no revascularization during the index hospitalization. After adjustment for potential confounders, diabetes, chronic obstructive pulmonary disease, anemia, higher Killip class, longer length of stay during the index hospitalization, and a complication of angiography or reperfusion or revascularization were associated with increased rehospitalization risk. The 30-day incidence of rehospitalization was 35.3% in patients who experienced a complication of angiography during the index MI hospitalization and 31.6% in those who experienced a complication of reperfusion or revascularization during the index MI hospitalization, compared with 16.8% in patients who had reperfusion or revascularization without complications. LIMITATION: This study represents the experiences of a single community. CONCLUSION: Comorbid conditions, longer length of stay, and complications of angiography and revascularization or reperfusion are associated with increased 30-day rehospitalization risk after MI. Many rehospitalizations seem to be unrelated to the incident MI. PRIMARY FUNDING SOURCE: National Institutes of Health.

Diastolic stiffness as assessed by diastolic wall strain is associated with adverse remodelling and poor outcomes in heart failure with preserved ejection fraction.

AIMS: The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex but increased left ventricular (LV) diastolic stiffness plays a key role. A load-independent, non-invasive, direct measure of diastolic stiffness is lacking. The diastolic wall strain (DWS) index is based on the linear elastic theory, which predicts that impaired diastolic wall thinning reflects resistance to deformation in diastole and thus, increased diastolic myocardial stiffness. The objectives of this community-based study were to determine the distribution of this novel index in consecutive HFpEF patients and healthy controls, define the relationship between DWS and cardiac structure and function and determine whether increased diastolic stiffness as assessed by DWS is predictive of the outcome in HFpEF. METHODS AND RESULTS: Consecutive HFpEF patients (n = 327, EF ≥ 50%) and controls (n = 528) from the same community were studied. Diastolic wall strain was lower in HFpEF (0.33 ± 0.08) than in controls (0.40 ± 0.07, P < 0.001). Within HFpEF, those with DWS ≤ median (0.33) had higher LV mass index, relative wall thickness, E/e', Doppler-estimated LV end-diastolic pressure to LV end-diastolic volume ratio, left atrial volume index, and brain natriuretic peptide (BNP) levels than those with DWS > median. Heart failure with preserved ejection fraction patients with DWS ≤ median had higher rate of death or HF hospitalization than those with DWS > median (P = 0.003) even after the adjustment for age, gender, log BNP, LV geometry, or log E/e' (P < 0.01). CONCLUSION: These data suggest that DWS, a simple index, is useful in assessing diastolic stiffness and that more advanced diastolic stiffness is associated with worse outcomes in HFpEF.

Co-Occurrence of Social Risk Factors and Associated Outcomes in Patients With Heart Failure.

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.

Predicting Alzheimer's Disease and Related Dementias in Heart Failure and Atrial Fibrillation.

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.

Patient Awareness of Heart Failure Diagnosis: A Community Study.

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.

Cohort study examining associations between ceramide levels and risk of multimorbidity among persons participating in the Mayo Clinic Biobank.

OBJECTIVE: Ceramides have been associated with several ageing-related conditions but have not been studied as a general biomarker of multimorbidity (MM). Therefore, we determined whether ceramide levels are associated with the rapid development of MM. DESIGN: Retrospective cohort study. SETTING: Mayo Clinic Biobank. PARTICIPANTS: 1809 persons in the Mayo Clinic Biobank ≥65 years without MM at the time of enrolment, and with ceramide levels assayed from stored plasma. PRIMARY OUTCOME MEASURE: Persons were followed for a median of 5.7 years through their medical records to identify new diagnoses of 20 chronic conditions. The number of new conditions was divided by the person-years of follow-up to calculate the rate of accumulation of new chronic conditions. RESULTS: Higher levels of C18:0 and C20:0 were associated with a more rapid rate of accumulation of chronic conditions (C18:0 z score RR: 1.30, 95% CI: 1.10 to 1.53; C20:0 z score RR: 1.26, 95% CI: 1.07 to 1.49). Higher C18:0 and C20:0 levels were also associated with an increased risk of hypertension and coronary artery disease. CONCLUSIONS: C18:0 and C20:0 were associated with an increased risk of cardiometabolic conditions. When combined with biomarkers specific to other diseases of ageing, these ceramides may be a useful component of a biomarker panel for predicting accelerated ageing.

Health Care Utilization and Death in Patients With Heart Failure During the COVID-19 Pandemic.

Objective: To compare the 1-year health care utilization and mortality in persons living with heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. Patients and Methods: Residents of a 9-county area in southeastern Minnesota aged 18 years or older with a HF diagnosis on January 1, 2019; January 1, 2020; and January 1, 2021, were identified and followed up for 1-year for vital status, emergency department (ED) visits, and hospitalizations. Results: We identified 5631 patients with HF (mean age, 76 years; 53% men) on January 1, 2019, 5996 patients (mean age, 76 years; 52% men) on January 1, 2020, and 6162 patients (mean age, 75 years; 54% men) on January 1, 2021. After adjustment for comorbidities and risk factors, patients with HF in 2020 and patients with HF in 2021 experienced similar risks of mortality compared with those in 2019. After adjustment, patients with HF in 2020 and 2021 were less likely to experience all-cause hospitalizations (2020: rate ratio [RR], 0.88; 95% CI, 0.81-0.95; 2021: RR, 0.90; 95% CI, 0.83-0.97) compared with patients in 2019. Patients with HF in 2020 were also less likely to experience ED visits (RR, 0.85; 95% CI, 0.80-0.92). Conclusion: In this large population-based study in southeastern Minnesota, we observed an approximately 10% decrease in hospitalizations among patients with HF in 2020 and 2021 and a 15% decrease in ED visits in 2020 compared with those in 2019. Despite the change in health care utilization, we found no difference in the 1-year mortality between patients with HF in 2020 and those in 2021 compared with those in 2019. It is unknown whether any longer-term consequences will be observed.

Biomarkers of cellular senescence and risk of death in humans.

A robust and heterogenous secretory phenotype is a core feature of most senescent cells. In addition to mediators of age-related pathology, components of the senescence associated secretory phenotype (SASP) have been studied as biomarkers of senescent cell burden and, in turn, biological age. Therefore, we hypothesized that circulating concentrations of candidate senescence biomarkers, including chemokines, cytokines, matrix remodeling proteins, and growth factors, could predict mortality in older adults. We assessed associations between plasma levels of 28 SASP proteins and risk of mortality over a median follow-up of 6.3 years in 1923 patients 65 years of age or older with zero or one chronic condition at baseline. Overall, the five senescence biomarkers most strongly associated with an increased risk of death were GDF15, RAGE, VEGFA, PARC, and MMP2, after adjusting for age, sex, race, and the presence of one chronic condition. The combination of biomarkers and clinical and demographic covariates exhibited a significantly higher c-statistic for risk of death (0.79, 95% confidence interval (CI): 0.76-0.82) than the covariates alone (0.70, CI: 0.67-0.74) (p < 0.001). Collectively, these findings lend further support to biomarkers of cellular senescence as informative predictors of clinically important health outcomes in older adults, including death.