Sedentary Time and Cumulative Risk of Preserved and Reduced Ejection Fraction Heart Failure: From the Multi-Ethnic Study of Atherosclerosis

BackgroundThis study examined the relationship between self-reported sedentary time (ST) and the cumulative risk of heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) in a diverse cohort of U.S. adults 45–84 years of age.Methods and ResultsUsing data from the Multi-Ethnic Study of Atherosclerosis (MESA), we identified 6,814 subjects, all free of baseline cardiovascular disease. Cox regression was used to calculate the hazard ratios (HR) associated with risk of HFpEF and HFrEF. Weekly ST was dichotomized based on the 75th percentile (1890 min/wk). During ～11.2 years of follow-up there were 178 first incident HF diagnoses: 74 HFpEF and 69 HFrEF. Baseline ST >1890 min/wk was significantly associated with an increased risk of HFpEF (HR 1.87, 95% confidence interval [CI] 1.13–3.09, P = .01), but not of HFrEF. The relationship with HFpEF remained significant in fully adjusted models including physical activity and waist circumference (HR 2.16, 95% CI 1.23–3.78, P < .01). In addition, every 60-minute increase in weekly ST was associated with a 3% increased risk of HFpEF (HR 1.03, 95% CI 1.01–1.05, P < .01).ConclusionsSedentary time >1890 min/wk (～4.5 h/d) is a significant predictor of HFpEF, independently from physical activity and adiposity.     

Sudden Cardiac Death in Heart Failure Patients With Preserved Ejection Fraction

BackgroundWhereas sudden cardiac death (SCD) risk has been recognized in heart failure (HF) patients with reduced ejection fraction (HFrEF), less is known about SCD risk in HF patients with preserved EF (HFpEF). We examined the incidence and predictors of SCD in HFpEF in a large population sample.Methods and ResultsMedical records of patients discharged with a primary diagnosis of HF from hospitals in Minneapolis–St Paul in 1995 and 2000 were abstracted. HFpEF was defined as EF ≥45%. SCD was defined as cardiac arrest or out-of-hospital death due to coronary heart disease (CHD) on death certificates. A total of 2,203 patients (age 70 ± 11 years, 53% male) were included. The 787 patients (36%) with HFpEF were older, more often female and more likely to have hypertension than the 1,416 (64%) with HFrEF. All-cause mortality (52% vs 58%; P = .01) and SCD (6% vs 14%; P < .0001) rates were lower in HFpEF than in HFrEF 5 years after hospital discharge. Age, sex, CHD, and length of index hospitalization were the only independent predictors of SCD in HFpEF.ConclusionsIncidence of SCD in HFpEF is lower than in HFrEF. Present markers of SCD in HFpEF are sparse and insufficient to identify the patient at risk.     

Trends in Heart Failure Hospitalizations in the US from 2008 to 2018

BackgroundHeart failure (HF) is a major driver of health care costs in the United States and is increasing in prevalence. There is a paucity of contemporary data examining trends among hospitalizations for HF that specifically compare HF with reduced or preserved ejection fraction (HFrEF or HFpEF, respectively).Methods and ResultsUsing the National Inpatient Sample, we identified 11,692,995 hospitalizations due to HF. Hospitalizations increased from 1,060,540 in 2008 to 1,270,360 in 2018. Over time, the median age of patients hospitalized because of HF decreased from 76.0 to 73.0 years (P < 0.001). There were increases in the proportions of Black patients (18.4% in 2008 to 21.2% in 2018) and of Hispanic patients (7.1% in 2008 to 9.0% in 2018; P < 0.001, all). Over the study period, we saw an increase in comorbid diabetes, sleep apnea and obesity (P < 0.001, all) in the entire cohort with HF as well as in the HFrEF and HFpEF subgroups. Persons admitted because of HFpEF were more likely to be white and older compared to admissions because of HFrEF and also had lower costs. Inpatient mortality decreased from 2008 to 2018 for overall HF (3.3% to 2.6%) and HFpEF (2.4% to 2.1%; P < 0.001, all) but was stable for HFrEF (2.8%, both years). Hospital costs, adjusted for inflation, decreased in all 3 groups across the study period, whereas length of stay was relatively stable over time for all groups.ConclusionsThe volume of patients hospitalized due to HF has increased over time and across subgroups of ejection fraction. The demographics of HF, HFrEF and HFpEF have become more diverse over time, and hospital inpatient costs have decreased, regardless of HF type. Inpatient mortality rates improved for overall HF and HFpEF admissions but remained stable for HFrEF admissions.     

Contemporary economic burden in a real‐world heart failure population with Commercial and Medicare supplemental plans

BackgroundLimited real‐world data exist on healthcare resource utilization (HCRU) and associated costs of patients with heart failure (HF) with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), including urgent HF visits, which are assumed to be less burdensome than HF hospitalizations (hHFs)HypothesisThis study aimed to quantify the economic burden of HFrEF and HFpEF, via a retrospective, longitudinal cohort study, using IBM® linked claims/electronic health records (Commercial and Medicare Supplemental data only).MethodsAdult patients, indexed on HF diagnosis (ICD‐10‐CM: I50.x) from July 2012 through June 2018, with 6‐month minimum baseline period and varying follow‐up, were classified as HFrEF (I50.2x) or HFpEF (I50.3x) according to last‐observed EF‐specific diagnosis. HCRU/costs were assessed during follow‐up.ResultsAbout 109 721 HF patients (22% HFrEF, 31% HFpEF, 47% unclassified EF; median 18 months'' follow‐up) were identified. There were 3.2 all‐cause outpatient visits per patient‐month (HFrEF, 3.3; HFpEF, 3.6); 69% of patients required inpatient stays (HFrEF, 80%; HFpEF, 78%). Overall, 11% of patients experienced hHFs (HFrEF, 23%; HFpEF, 16%), 9% experienced urgent HF visits (HFrEF, 15%; HFpEF, 12%); 26% were hospitalized less than 30 days after first urgent HF visit versus 11% after first hHF. Mean monthly total direct healthcare cost per patient was $9290 (HFrEF, $11 053; HFpEF, $7482).ConclusionsHF‐related HCRU is substantial among contemporary real‐world HF patients in US Commercial or Medicare supplemental health plans. Patients managed in urgent HF settings were over twice as likely to be hospitalized within 30 days versus those initially hospitalized, suggesting urgent HF visits are important clinical events and quality improvement targets.     

Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial

BackgroundIn the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.Methods and ResultsWe applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin's treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31–1.17], 0.79 [0.51–1.23], and 0.63 [0.50–0.78], respectively; P interaction = 0.62).ConclusionsIn EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF.     

Glycemic Markers and Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundAlthough diabetes increases heart failure (HF) risk, it is unclear how various dysglycemia markers (hemoglobin A_1C [HbA_1C], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance, and fasting insulin) are associated with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]). We assessed the relation of markers of dysglycemia and risks of HFpEF and HFrEF.Methods and ResultsWe included 6688 adults without prevalent cardiovascular disease who attended the first MESA visit (2000–2002) and were followed for incident hospitalized HF (HFpEF or HFrEF). Association of glycemic markers and status (normoglycemia, prediabetes, diabetes) with HFpEF and HFrEF were evaluated using adjusted Cox models. Over a median follow-up of 14.9 years, there were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events). Diabetes status conferred higher risks of HFpEF (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.57–2.68) and HFrEF (HR 2.02, 95% CI 1.38–2.97) compared with normoglycemia. Higher levels of FPG (≥126 mg/dL) and HbA_1C (≥6.5%) were associated with similarly higher risks of HFpEF (HR for FPG 1.96, 95% CI 1.21–3.17; HR for HbA_1C 2.00, 95% CI 1.20–3.31) and HFrEF (HR for FPG 1.84, 95% CI 1.18–2.88; HR for HbA_1C 1.99, 95% CI 1.28–3.09) compared with reference values. Prediabetic range HbA_1C (5.7%–6.4%) or FPG (100%–125 mg/dL), homeostasis model assessment of insulin resistance, and fasting insulin were not significantly associated with HFpEF or HFrEF.ConclusionsAmong community-dwelling individuals, HbA_1C and FPG in the diabetes range were each associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations.Lay AbstractHeart failure (HF) has 2 major subtypes (the heart's inability to pump or to fill up). Diabetes is known to increase HF risk, but its effects and that of markers of high glucose levels (fasting blood glucose and hemoglobin A_1C) on the occurrence of HF subtypes remains unknown. Among 6688 adults without known cardiovascular disease followed for nearly 15 years, diabetes conferred significantly higher risks of both HF types, compared with those with normal blood glucose levels. Higher levels of fasting blood glucose and hemoglobin A_1C were similarly associated with higher risks of both types of HF.     

Tailored risk assessment of 90‐day acute heart failure readmission or all‐cause death to heart failure with preserved versus reduced ejection fraction

BackgroundAfter incident heart failure (HF) admission, patients are vulnerable to readmission or death in the 90‐day post‐discharge. Although risk models for readmission or death incorporate ejection fraction (EF), patients with HF with preserved EF (HFpEF) and those with HF with reduced EF (HFrEF) represent distinct cohorts. To better assess risk, this study developed machine learning models and identified risk factors for the 90‐day acute HF readmission or death by HF subtype.Methods and ResultsApproximately 1965 patients with HFpEF and 1124 with HFrEF underwent an index admission. Acute HF rehospitalization or death occurred in 23% of HFpEF and 28% of HFrEF groups. Of the 101 variables considered, multistep variable selection identified 24 and 25 significant factors associated with 90‐day events in HFpEF and HFrEF, respectively. In addition to risk factors common to both groups, factors unique to HFpEF patients included cognitive dysfunction, low‐pulse pressure, β‐blocker, and diuretic use, and right ventricular dysfunction. In contrast, factors unique to HFrEF patients included a history of arrhythmia, acute HF on presentation, and echocardiographic characteristics like left atrial dilatation or elevated mitral E/A ratio. Furthermore, the model tailored to HFpEF (area under the curve [AUC] = 0.770; 95% confidence interval [CI] 0.767–0.774) outperformed a model for the combined groups (AUC = 0.759; 95% CI 0.756–0.763).ConclusionThe UF 90‐day post‐discharge acute HF Re admission or Death Risk Assessment (UF90‐RADRA) models help identify HFpEF and HFrEF patients at higher risk who may require proactive outpatient management.     

Hepatocyte Growth Factor and Incident Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA)

BackgroundHepatocyte growth factor (HGF) is a cytokine and marker of cardiovascular disease (CVD) risk. Less is known about HGF and incident heart failure (HF). We examined the association of HGF with incident HF and its subtypes in a multiethnic cohort.Methods and ResultsWe included 6597 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, free of clinical CVD and HF at baseline, with HGF measured at baseline. Incident hospitalized HF was assessed and adjudicated for HF with preserved ejection fracture (HFpEF) vs HF with reduced ejection fraction (HFrEF). Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for HF risk by HGF levels, adjusted for socio-demographics, CVD risk factors and N-terminal pro-B-type natriuretic peptide. The mean age was 62 ± 10 years. The median HGF level was 950 pg/mL (interquartile range, 758–1086 pg/mL); 53% were women. Over 14 years (IQR, 11.5–14.7 years), there were 324 cases of HF (133 HFpEF and 157 HFrEF). For the highest HGF tertile compared with lowest, adjusted HRs were 1.59 (95% CI, 1.10–2.31), 1.90 (95% CI, 1.03–3.51), and 1.09 (95% CI, 0.65–1.82) for overall HF, HFpEF, and HFrEF, respectively. For continuous analysis per 1-standard deviation log-transformed HGF, adjusted HRs were 1.22 (95% CI, 1.06–1.41), 1.35 (95% CI, 1.09–1.69), and 1.00 (95% CI, 0.81–1.24) for HF, HFpEF, and HFrEF, respectively.ConclusionsHGF was independently associated with incident HF. HGF remained significantly associated with HFpEF but not HFrEF upon subtype assessment. Future studies should examine the mechanisms underlying these associations and evaluate whether HGF can be used to improve HF risk prediction or direct therapy.     

Epidemiology and clinical characteristics of hospitalized elderly patients for heart failure with reduced,mid-range and preserved ejection fraction

Introduction: Elderly patients hospitalized with heart failure (HF) have high mortality rates and requires specific evidence based theraphy, however there are few studies which have focused on patients older than 80 years hospitalized with HF. The aim of the present study is to evaluate the overall clinical characteristics, management, and in-hospital outcomes of elderly patients hospitalized with HF.Methods: Journey-HF study was conducted in 37 different centers in Turkey and recruited 1606 patients who were hospitalized with HF between September 2015 and September 2016. In this study, clinical profile of patients ≥ 80 years old and 65-79 years old hospitalized with HF were described and compared based on EF-related classification: HFrEF (HF with reduced ejection fraction), HFmrEF (HF with mid-range ejection fraction) and HFpEF (HF with preserved ejection fraction).Results: A total of 1034 elder patients (71.6% 65–79 years old and 28.4% ≥80 years old) were recruited. Of the 65–79 years old patients 67.4% had HFrEF, 16.2% had HFmrEF and 16.3% had HFpEF. Among patients ≥80 years old 61.6% had HFrEF, 15.6% had HmrEF and 22.8% had HFpEF.When compared with patients with HFrEF and HFmrEF, patients ≥80 years old with HFpEF were more likely to be older, have atrial fibrilation (AF), and less likely to have diabetes mellitus (DM), coronary artery disease (CAD) or to be recieving an angiotensin-converting enzyme inhibitor (ACEi) or beta blocker theraphy. When compared to patients 65–79 years old with HFpEF, patients ≥80 years with HFpEF had a higher rate of AF and less likely DM. Acute coronary syndrome was the most common precipitant factor for hospitalization in both age groups with HFrEF group. Arrhythmia was a major precipitant factor for hospitalization of patients ≥80 years old with HFpEF. Non-compliance with theraphy was a major problem of patients ≥80 years old with HFrEF.Conclusion: Elderly patients with HFrEF, HFmrEF and HFpEF each had characterized unique patient profiles and the guideline recommended medications were less likely to be used in these patient populations. In hospital mortality rate is worrisome and reflects a need for more specific tretment strategy.     

Characteristics and outcomes of patients with a history of cancer recruited to heart failure trials

Aims

Heart failure (HF) therapy trials usually exclude cancer patients. We examined the association between cancer history and outcomes in trial participants with HF and reduced (HFrEF) or preserved ejection fraction (HFpEF).

Methods and results

We combined PARADIGM-HF and ATMOSPHERE, which enrolled HFrEF patients (n = 15 415) and we pooled HFpEF patients (ejection fraction ≥45%) enrolled in PARAGON-HF and CHARM-Preserved (n = 7363). The associations between cancer history, cardiovascular (CV) death, HF hospitalization, non-CV and all-cause death in these trials were examined. Incident cancer diagnoses during these trials were also measured. There were 658 (4.3%) and 624 (8.5%) patients with a cancer history in the HFrEF and HFpEF trials, respectively. HFrEF patients with a cancer history had a higher risk of HF hospitalization (adjusted hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.07–1.52, p = 0.007) and non-CV death (adjusted HR 1.57; 95% CI 1.16–2.12, p = 0.003) than those without. The risks of other outcomes were similar. There were no differences in the risk of any outcome in HFpEF patients with and without a cancer history. Adjusting for age and sex, the incidence of new cancer in the HFrEF and HFpEF trials was 1.09 (95% CI 0.83–1.36) and 1.07 (95% CI 0.81–1.32) per 100 person-years, respectively.

Conclusions

Although participants in HFrEF trials with a cancer history had higher risks of HF hospitalization and non-CV death than those without, the risks of CV and all-cause death were similar. Outcomes in HFpEF patients with and without a cancer history were similar. Incident cancer diagnoses were similar in HFrEF and HFpEF trials.     

Características e Tendências na Mortalidade em Diferentes Fenótipos de Insuficiência Cardíaca na Atenção Primária

Background:The classification of heart failure (HF) by phenotypes has a great relevance in clinical practice.Objective:The study aimed to analyze the prevalence, clinical characteristics, and outcomes between HF phenotypes in the primary care setting.Methods:This is an analysis of a cohort study including 560 individuals, aged ≥ 45 years, who were randomly selected in a primary care program. All participants underwent clinical evaluations, b-type natriuretic peptide (BNP) measurements, electrocardiogram, and echocardiography in a single day. HF with left ventricular ejection fraction (LVEF) < 40% was classified as HF with reduced ejection fraction (HFrEF), LVEF 40% to 49% as HF with mid-range ejection fraction (HFmrEF) and LVEF ≥ 50% as HF with preserved ejection fraction (HFpEF). After 5 years, the patients were reassessed as to the occurrence of the composite outcome of death from any cause or hospitalization for cardiovascular disease.Results:Of the 560 patients included, 51 patients had HF (9.1%), 11 of whom had HFrEF (21.6%), 10 had HFmrEF (19.6%) and 30 had HFpEF (58.8%). HFmrEF was similar to HFpEF in BNP levels (p < 0.001), left ventricular mass index (p = 0.037), and left atrial volume index (p < 0.001). The HFmrEF phenotype was similar to HFrEF regarding coronary artery disease (p = 0.009). After 5 years, patients with HFmrEF had a better prognosis when compared to patients with HFpEF and HFrEF (p < 0.001).Conclusion:The prevalence of ICFEI was similar to that observed in previous studies. ICFEI presented characteristics similar to ICFEP in this study. Our data show that ICFEi had a better prognosis compared to the other two phenotypes.     

Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

BackgroundRetrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown.ObjectivesWe investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF.MethodsThrough the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HF-LT), 4,438 outpatients were identified and classified into: reduced (<40% HFrEF), mid-range (40–49% HFmrEF), and preserved (≥50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components.ResultsMedian sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11–2.54; 2.46: 95% CI 1.66–3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P<0.05 for all); after model-adjustment, significant association of sUA with outcome persisted among HFrEF in Q-IV, and HFpEF in Q-III-IV.ConclusionsIn a large, contemporary-treated cohort of HF outpatients, sUA is an independent prognosticator of adverse outcome, which can be appreciated in HErEF and HFpEF patients.     

Prevalence and Prognostic Significance of Polyvascular Disease in Patients Hospitalized With Acute Decompensated Heart Failure: The ARIC Study

BackgroundPolyvascular disease is associated with increased mortality rates and decreased quality of life. Whether its prevalence or associated outcomes differ for patients hospitalized with heart failure with reduced vs preserved ejection fraction (HFrEF vs HFpEF, respectively) is uncertain.MethodsThe Atherosclerosis Risk in Communities (ARIC) study conducted hospital surveillance of acute decompensated heart failure (ADHF) from 2005–2014. Polyvascular disease (coexisting disease in ≥ 2 arterial beds) was identified based on the finding of prevalent coronary artery disease, peripheral artery disease or cerebrovascular disease. Mortality risks associated with polyvascular disease were analyzed separately for HFpEF and HFrEF, with adjustment for potential confounders. All analyses were weighted by the inverse of the sampling probability.ResultsOf 24,937 weighted (5460 unweighted) hospitalizations due to ADHF (52% female, 32% Black, mean age 75 years), polyvascular disease was prevalent in 22% with HFrEF and in 17% with HFpEF. One-year mortality risks increased sequentially with 0, 1 and ≥ 2 arterial bed involvement, both for patients with HFrEF (29%–32%–38%; P trend = 0.0006) and for those with HFpEF (26%–32%–37%; P trend < 0.0001). After adjustments, polyvascular disease was associated with a 26% higher mortality hazard for patients with HFrEF (HR = 1.26; 95% CI: 1.07–1.50) and a 29% higher hazard for patients with HFpEF (HR = 1.29; 95% CI: 1.03–1.62), with no interaction by HF type (P interaction = 0.9).ConclusionPatients hospitalized with ADHF and coexisting polyvascular disease have an increased risk of death, irrespective of HF type. Clinical attention should be directed toward polyvascular disease, with implementation of secondary prevention strategies to improve the prognosis of this high-risk population.SummaryPolyvascular disease is known to be associated with myocardial infarction, stroke or cardiovascular death and is a major risk factor for decreased quality of life. This study sought to evaluate the relationship between polyvascular disease and mortality in patients hospitalized with acute decompensated heart failure (ADHF), and to understand whether the associations differ based on ejection fraction. Patients hospitalized with ADHF and coexisting polyvascular disease had an increased risk of death, irrespective of heart failure type, implying the need for increased clinical attention directed toward polyvascular disease, along with implementation of secondary prevention strategies to improve prognosis.TweetPatients hospitalized with acute HF and coexisting polyvascular disease face an increased risk of death, irrespective of HF type.     

Clinical Characteristics,Comorbidities and Prognosis in Patients With Heart Failure With Mid-Range Ejection Fraction

BackgroundPatients with left ventricular ejection fractions between 40% and 49% either discovered de novo, having declined from ≥50%, or improved from <40% have been described as heart failure (HF) with mid-range ejection fraction (HFmrEF). Though clinical signs and symptoms are similar to other phenotypes, possible prognostic differences and therapeutic responses reinforce the need for further understanding of patients’ characteristics especially in a rural community based population. The purpose of this study is to evaluate the clinical characteristics, comorbidities and prognosis of a rural patient population with HFmrEF.Materials and MethodsWe queried the electronic medical record from a community based university practice for all patients with a HF diagnosis. We included only those patients with >3 months follow-up and interpretable Doppler echocardiograms. We recorded demographic, Doppler-echo, and outcome variables (up to 2,083 days).ResultsThere were 633 HF patients: 42.4% with preserved ejection fraction (HFpEF, EF ≥50%), 36.4% with HFmrEF, and 21.0% with reduced ejection fraction (HFrEF, EF <40%). HFmrEF patients were older, had greater coronary disease prevalence, lower systolic blood pressure, elevated brain natriuretic peptide, lower hemoglobin, and higher creatinine than HFpEF. All-cause mortality was intermediate between HFrEF and HFpEF but was not significantly different. Landmark analysis revealed a trend toward greater second readmission in HFmrEF as compared to HFpEF (hazard ratio: 1.43 [0.96-2.14],P = 0.0767).ConclusionsRural patients with HFmrEF without an ambulatory HF clinic represent a higher percentage of HF patients than previously reported with greater coronary disease prevalence with comparable readmission rates and nonsignificantly different all-cause mortality.     

Prevalence of Prediabetes and Undiagnosed Diabetes in Patients with HFpEF and HFrEF and Associated Clinical Outcomes

Purpose

The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF).

Methods

We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models.

Results

HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c < 6.0), 20 and 22% had prediabetes (HbA1c 6.0–6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63–1.65) for prediabetes, HR 1.18 (0.75–1.86) for undiagnosed diabetes and 2.75 (1.83–4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF.

Conclusions

These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF.

     

The Relationship Between Atrial Fibrillation,Mitral Regurgitation,and Heart Failure Subtype: The ARIC Study

BackgroundAtrial fibrillation (AF) and mitral regurgitation (MR) are closely interrelated in the setting of heart failure (HF). Here we investigate the prevalence and prognostic significance of AF in patients with acute decompensated HF (ADHF) stratified by MR severity.Methods and ResultsThe Atherosclerosis Risk in Communities Study investigated ADHF hospitalizations in residents greater than or equal to 55 years of age in 4 US communities. ADHF cases were stratified by MR severity (none/mild or moderate/severe) and HF subtype (HF with reduced [HFrEF] or preserved [HFpEF] ejection fraction). The odds of AF in patients with increasing MR severity was estimated using multivariable logistic regression, adjusting for age, race, sex, diabetes, hypertension, coronary artery disease, hemodialysis, stroke, and anemia. Cox regression models were used to assess the association of AF with 1-year mortality in patients with HFpEF and HFrEF, stratified by MR severity and adjusted as described, also adjusting for the year of hospitalization. From 2005 to 2014, there were 3,878 ADHF hospitalizations (17,931 weighted). AF was more likely in those with higher MR severity regardless of HF subtype; more so in HFpEF (odds ratio [OR] 1.38, 95% confidence interval [CI], 1.31–1.45) than in HFrEF (OR, 1.19, 95% CI, 1.13–1.25) (interaction P [by HF subtype] < .01). When stratified by HF type, association between AF and 1-year mortality was noted in patients with HFpEF (OR, 1.28, 95% CI 1.04–1.56) but not HFrEF (OR 0.96, 95% CI 0.79–1.16) (interaction by EF subtype, P = .02).ConclusionsIn patients with ADHF, AF prevalence increased with MR severity and this effect was more pronounced in HFpEF compared with HFrEF. AF was associated with an increased 1-year mortality only in patients with HFpEF and concomitant moderate/severe MR.RegistrationNCT00005131, https://clinicaltrials.gov/ct2/show/NCT00005131     

Association of Midlife Cardiovascular Risk Factors With the Risk of Heart Failure Subtypes Later in Life

BackgroundIndependent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied.MethodsWe pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF.ResultsA total of 23,861 participants were included (mean age at first in-person visit, 61.8 ±1 0.2 years; 56.6% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF.ConclusionsMidlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.     

Outcomes and Predictors of Mortality Among Cardiac Intensive Care Unit Patients With Heart Failure

BackgroundLittle is known regarding the causes of critical illness and determinants of prognosis of patients with heart failure (HF) admitted to the modern cardiac intensive care unit (CICU). We sought to describe the epidemiology and outcomes of patients with HF admitted to the contemporary CICU.Methods and ResultsRetrospective cohort analysis of Mayo Clinic CICU patients admitted with HF from 2007 to 2018 who had left ventricular ejection fraction (LVEF) data. HF with reduced LVEF (HFrEF) was defined as a LVEF of less than 50%, and HF with preserved LVEF (HFpEF) as a LVEF of 50% or greater. In-hospital mortality was analyzed using multivariable logistic regression. Survival to 1 year was analyzed using a Kaplan–Meier analysis. We included 4012 patients, including 67.8% with HFrEF and 32.2% with HFpEF. Patients with HFrEF and HFpEF were comparable and had equivalent severity of illness. Critical care therapies were used in 59.4%, with a slight preponderance in patients with HFrEF. In-hospital mortality occurred in 12.5% of patients and was similar in HFrEF vs HFpEF. Shock and cardiac arrest were the strongest predictors of adjusted in-hospital mortality, followed by Braden skin score and serum chloride level; patients with HFrEF and HFpEF had similar adjusted mortality rates. The 1-year survival after hospital discharge was 74.5% and was slightly lower for patients with HFpEF. All-cause rehospitalization occurred in 36.6%, and 52.8% of hospital survivors died or were readmitted within 1 year.ConclusionsCICU patients with HF have a substantial burden of critical illness, high use of critical care therapies, and poor outcomes regardless of LVEF. This finding emphasizes the potential unmet care needs in this cohort.Lay summaryPatients with heart failure who require admission to the cardiac intensive care unit have high severity of illness and are at significant risk of death during and after hospitalization. These patients often require specialized critical care therapies to treat manifestations of critical illness. Patients who are admitted with cardiac arrest or shock, including those who require mechanical ventilation or vasopressors, are at particularly high risk of death. Patients’ left ventricular ejection fraction is not strongly associated with the risk of death when accounting for other major predictors including frailty and laboratory abnormalities.     

The HEART Camp Exercise Intervention Improves Exercise Adherence,Physical Function,and Patient-Reported Outcomes in Adults With Preserved Ejection Fraction Heart Failure

BackgroundDespite exercise being one of few strategies to improve outcomes for individuals with heart failure with preserved ejection fraction (HFpEF), exercise clinical trials in HFpEF are plagued by poor interventional adherence. Over the last 2 decades, our research team has developed, tested, and refined Heart failure Exercise And Resistance Training (HEART) Camp, a multicomponent behavioral intervention to promote adherence to exercise in HF. We evaluated the effects of this intervention designed to promote adherence to exercise in HF focusing on subgroups of participants with HFpEF and heart failure with reduced ejection fraction (HFrEF).Methods and ResultsThis randomized controlled trial included 204 adults with stable, chronic HF. Of those enrolled, 59 had HFpEF and 145 had HFrEF. We tested adherence to exercise (defined as ≥120 minutes of moderate-intensity [40%–80% of heart rate reserve] exercise per week validated with a heart rate monitor) at 6, 12, and 18 months. We also tested intervention effects on symptoms (Patient-Reported Outcomes Measurement Information System-29 and dyspnea-fatigue index), HF-related health status (Kansas City Cardiomyopathy Questionnaire), and physical function (6-minute walk test). Participants with HFpEF (n = 59) were a mean of 64.6 ± 9.3 years old, 54% male, and 46% non-White with a mean ejection fraction of 55 ± 6%. Participants with HFpEF in the HEART Camp intervention group had significantly greater adherence compared with enhanced usual care at both 12 (43% vs 14%, phi = 0.32, medium effect) and 18 months (56% vs 0%, phi = 0.67, large effect). HEART Camp significantly improved walking distance on the 6-minute walk test (η² = 0.13, large effect) and the Kansas City Cardiomyopathy Questionnaire overall (η² = 0.09, medium effect), clinical summary (η² = 0.16, large effect), and total symptom (η² = 0.14, large effect) scores. In the HFrEF subgroup, only patient-reported anxiety improved significantly in the intervention group.ConclusionsA multicomponent, behavioral intervention is associated with improvements in long-term adherence to exercise, physical function, and patient-reported outcomes in adults with HFpEF and anxiety in HFrEF. Our results provide a strong rationale for a large HFpEF clinical trial to validate these findings and examine interventional mechanisms and delivery modes that may further promote adherence and improve clinical outcomes in this population.Clinical Trial Registration: URL: https://clinicaltrials.gov/. Unique identifier: NCT01658670     

Validation and Recalibration of Seattle Heart Failure Model in Japanese Acute Heart Failure Patients

BackgroundPrecise risk stratification in heart failure (HF) patients enables clinicians to tailor the intensity of their management. The Seattle Heart Failure Model (SHFM), which uses conventional clinical variables for its prediction, is widely used. We aimed to externally validate SHFM in Japanese HF patients with a recent episode of acute decompensation requiring hospital admission.Methods and ResultsSHFM was applied to 2470 HF patients registered in the West Tokyo Heart Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart Failure databases from 2006 to 2016. Discrimination and calibration were assessed with the use of the c-statistic and calibration plots, respectively, in HF patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection fraction (HFpEF; ≥40%). In a perfectly calibrated model, the slope and intercept would be 1.0 and 0.0, respectively. The method of intercept recalibration was used to update the model. The registered patients (mean age 74 ± 13 y) were predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow-up of 2.1 years. Among HFrEF patients, SHFM showed good discrimination (c-statistic = 0.75) but miscalibration, tending to overestimate 1-year survival (slope = 0.78; intercept = −0.22). Among HFpEF patients, SHFM showed modest discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1-year survival (slope = 1.18; intercept = 0.16). Intercept recalibration (replacing the baseline survival function) successfully updated the model for HFrEF (slope = 1.03; intercept = −0.04) but not for HFpEF patients.ConclusionsIn Japanese acute HF patients, SHFM showed adequate performance after recalibration among HFrEF patients. Using prediction models to tailor the care for HF patients may improve the allocation of medical resources.