Abstract MP29: Patient Characteristics And Outcomes Associated With In-hospital Onset Of Acute Decompensated Heart Failure

Incidence and Survival of Hospitalized Acute Decompensated Heart Failure in Four US Communities (from the Atherosclerosis Risk in Communities Study)

Characteristics and Outcomes of Patients With Acute Decompensated Heart Failure Developing After Hospital Admission

Background The discovery of new markers for acute kidney injury (AKI) in acute decompensated heart failure (ADHF) has been hampered by an incomplete understanding of the pathological processes underlying AKI in ADHF. Purpose In a sheep model of ADHF, we investigated changes in kidney gene expression in response to the development of, and recovery from, ADHF. Methods We collected serial kidney biopsies from 6 sheep prior to rapid cardiac pacing (day 0), after development of ADHF (pacing @220bpm for 14 days), and at the end of a 25-day (non-pacing) recovery period. Serial biopsies were supplemented with kidney samples collected post-mortem from animals undergoing a similar pacing/recovery protocol, giving a total of 11 “baseline” (B), 13 “heart failure” (HF) and 8 “recovery” (R) samples. We prepared RNA-Sequencing libraries using total RNA and Illumina TruSeq stranded mRNA library kits. Hormonal, haemodynamic, biochemical and urine measurements were also performed in all sheep before, during, and after development of ADHF. The study followed the principles of laboratory animal care and was approved by our institution's Animal Ethics Committee. Results We observed profound changes in hormonal, haemodynamic, biochemical and urine measures of cardio-renal injury in all sheep, confirming simulation of the peripheral consequences of ADHF, including clinically-relevant kidney dysfunction. This occurred in conjunction with altered kidney expression of 982 genes during ADHF development and 1,807 genes during ADHF recovery (p adj.<0.05, Fig 1). During ADHF development, changes in kidney gene expression were associated with activation of the pro-inflammatory p38 MAPK pathway and repression of several anti-inflammatory and reno-protective pathways, including eNOS signalling (all p adj.<0.001). In contrast, during ADHF recovery, changes in kidney gene expression were associated with reactivation of reno-protective pathways repressed during ADHF development, activation of anti-fibrotic pathways (including PTEN signalling) and repression of pathways that mediate inflammation and renal injury (including NF-kB signalling, all p adj.<0.001). Among 431 ADHF “responsive” genes (i.e. those that increased during ADHF development and decreased during ADHF recovery, or vice versa, Fig. 1), 37 genes encoded proteins detectable in plasma or urine and may represent markers of kidney repair in ADHF. Although most gene expression changes were transient, 192 genes remained altered after 4-weeks recovery (p adj.<0.05, Fig 1). Of these, 13 genes were predicted to encode proteins detectable in plasma or urine and may represent persistent markers of kidney injury in ADHF. Conclusion Our data provide the first insight into the gene pathways associated with kidney injury and repair in ADHF, in an established ovine model. Understanding the pathological processes underlying AKI in ADHF may enable discovery of novel markers for monitoring kidney injury and repair in ADHF. Figure 1. Genes altered in the kidney in ADHF Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Health Research Council of New Zealand, Heart Foundation of New Zealand

Early Palliative Care Consultation Reduces Length Of Stay And Cost In Patients Hospitalized With Acute Decompensated Heart Failure

Background: Heart failure (HF) patients with aortic stenosis (AS) constitute a high-risk population posing diagnostic and therapeutic challenges. Few studies have characterized the burden of AS in patients admitted with acute decompensated HF (ADHF), stratified by ejection fraction (EF). Methods: The Atherosclerosis Risk in Communities study conducted community-based surveillance of a random sample of ADHF hospitalizations for residents ≥55 years of age in four US communities. ADHF cases were subclassified as having reduced (HFrEF) or preserved (HFpEF) EF using a 50% cutoff. AS severity was determined from echocardiogram reports obtained during abstracted hospitalizations. Odds of moderate or severe AS in patients with varying sex and race, and odds of all-cause 1-year mortality in those with higher AS severity were estimated using multivariable logistic regression. Results: From 2005-2014, there were 14,289 weighted ADHF hospitalizations of whom 7,357 had HFrEF (45.0% female, 36.6% black) and 6,932 HFpEF (62.9% female, 26.5% black). The prevalence of moderate or severe AS was 5.67% in HFrEF and 9.43% in HFpEF. Patients with higher AS severity were older than those with none or mild AS in both HFrEF ([mean age] 79.7 vs. 74.4 years, p<0.0001) and HFpEF (81.7 vs. 76.3 years, p<0.0001). No difference in odds of higher AS severity was detected between females and males in both HFrEF (5.49% vs. 5.81%, OR: 1.03, 95% CI: 0.83-1.27) and HFpEF (9.10% vs. 9.99%, OR: 0.89, 95% CI: 0.75-1.06). Moderate or severe AS was more likely in whites than blacks in both HFrEF (8.32% vs. 1.67%, OR: 0.23, 95% CI: 0.17-0.32) and HFpEF (11.1% vs. 6.38%, OR: 0.70, 95% CI: 0.56-0.88). Higher AS severity was independently associated with increased all-cause 1-year mortality after ADHF hospitalization in both HFrEF (44.3% vs. 30.5%, OR: 1.25, 95% CI: 1.16-1.35) and HFpEF (33.4% vs. 26.1%, OR: 1.16, 95% CI: 1.08-1.24). Conclusion: In ADHF patients with HFrEF or HFpEF, whites are more affected by AS than blacks, as are older patients when compared to their younger counterparts. Higher AS severity in ADHF patients is independently associated with all-cause mortality at 1 year after hospitalization, regardless of EF.

Introduction: Multiple diagnostic HF classification have been used to identify heart failure (HF) events. Whether these classification criteria can be used for estimating prognosis is unknown. Research Question: This study compares multiple research-derived HF classification criteria for predicting mortality in the ARIC study cohort with validated hospitalized acute decompensated heart failure (ADHF) events. Methods: There were 1,954 ARIC cohort members with hospitalized HF events from 2005-2019, validated as ADHF by ARIC study classification/adjudication. These HF events were also classified as HF present/absent at the time of hospitalization by other HF classification criteria - Framingham, Modified Boston, NHANES, and Gothenburg. Hazard ratios (HRs) for all-cause mortality at 30 days, 1 year, and 5 years were calculated using logistic regression for all included HF classification criteria compared to ARIC, stratified by ejection fraction (EF), and adjusted for demographics and comorbidities. Results: For all ADHF events, Framingham, NHANES, and Gothenburg were prognostic for survival, but not modified Boston criteria (Table). ADHF patients who were also classified as HF by Framingham criteria had a 30% or more increased mortality at 30-day, 1-year, and 5-years regardless of EF, compared to those who were not classified as HF by Framingham (p<0.05). Framingham criteria were prognostic for 30-day survival for those with HFrEF, and also for 1-year and 5-year survival for those with HFpEF. Conclusion: The presence of HF as defined using different published criteria is associated with elevated risk of all-cause mortality. To our knowledge, this is a novel study comparing multiple research-derived HF classification criteria for clinical prognostication of mortality in ADHF. More studies are needed to assess the utility of these HF classification criteria for prognostication for HF morbidity and rehospitalization and by HF type.

Hypertension is the most prevalent modifiable factor for the development of heart failure. However, the optimal blood pressure (BP) target for preventing heart failure remains uncertain. The SPRINT (Systolic BP Intervention Trial) was a large, randomized open-label trial (n=9361 participants) that showed the superiority of a systolic BP target of <120 mm Hg compared with <140 mm Hg, with a 36% lower rate of acute decompensated heart failure (ADHF) events. This beneficial effect was consistent across all the key prespecified subgroups, including advanced age, chronic kidney disease, and prior cardiovascular disease. Participants who had an ADHF event had a markedly increased risk of subsequent cardiovascular disease events, including recurrent ADHF. Randomization to the intensive arm did not affect the recurrence of ADHF after the initial ADHF event (hazard ratio, 0.93 [95% CI, 0.50-1.67]; P=0.81). A separate analysis demonstrated that the reduction in ADHF events in the intensive treatment group in SPRINT was not due to the differential use of diuretics between the 2 treatment groups. Although intensive BP treatment resulted in a lower cardiovascular disease event rate, this was not significantly associated with changes in left ventricular mass, function, or fibrosis, as assessed in SPRINT HEART, an ancillary study to SPRINT. Intensive BP treatment, however, significantly attenuated increases in carotid-femoral pulse wave velocity. Overall, these data highlight the importance of preventing ADHF in high cardiovascular risk hypertensive patients by optimal BP reduction as tested in SPRINT.

Acute decompensated heart failure (ADHF) was a frequent common outcome in SPRINT (Systolic Blood Pressure Intervention Trial). We examined whether there was differential reduction in ADHF events from intensive blood pressure [BP] treatment among the 6 key, prespecified subgroups in SPRINT: age ≥75 years, prior cardiovascular disease, chronic kidney disease, women, black race, and 3 levels of baseline systolic BP (≤132 versus >132 to <145 versus ≥145 mm Hg). ADHF was defined as hospitalization for ADHF, confirmed and formally adjudicated by a blinded events committee using standardized protocols. At 3.29 years follow-up, there were 103 ADHF events (2.2%) among 4683 standard arm participants and 65 ADHF events (1.4%) among 4678 intensive arm participants (Cox proportional hazards ratio, 0.63; 95% confidence interval, 0.46-0.85; P value =0.003). In multivariable analyses, including treatment arm, baseline covariates that were significant predictors for ADHF included chronic kidney disease, cardiovascular disease, age≥75 years, body mass index, and higher systolic BP. The beneficial effect of the intervention on incident ADHF was consistent across all prespecified subgroups. Participants who had incident ADHF had markedly increased risk of subsequent cardiovascular events, including a 27-fold increase (P<0.001) in cardiovascular death. Targeting a systolic BP<120 mm Hg, compared with <140 mm Hg, significantly reduced ADHF events, and the benefit was similar across all key, prespecified subgroups. Participants who developed ADHF had markedly increased risk for subsequent cardiovascular events and death, highlighting the importance of strategies aimed at prevention of ADHF, especially intensive BP reduction. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Introduction: Understanding population-based trends in heart failure incidence is important to evaluation and planning of prevention and treatment strategies. Hypothesis: Community trends of acute decompensated heart failure (ADHF) in racially diverse populations may differ by race and sex. Methods: The Atherosclerosis Risk in Communities (ARIC) Study conducted continuous and comprehensive surveillance of hospitalized ADHF events (age ≥55 years) in four US communities between 2005-2012 and estimated hospitalized ADHF incidence and survival by race and sex. 17,651 hospitalizations for ADHF were identified by ICD-9-CM codes, then validated by standardized physician review of hospital records, yielding a weighted sample of 31,006 hospitalizations after accounting for sampling design. HF with reduced EF (HFrEF) was defined as EF&lt;50%. Results: Of the ADHF hospitalizations, 16259 (52.4%) were HFrEF, 11835 (38.2%) were HF with preserved EF (HFpEF), and 2912 (9.4%) were HF with unknown EF. HFrEF (both incident and recurrent ADHF) was more common in men (black men 70.4%, white men 61.4%), whereas HFpEF was more common in women (white women 50.0%, black women 39.5%). Compared to whites, blacks were younger, with less coronary heart disease and atrial arrhythmias, and more hypertension, diabetes, and chronic kidney disease. Between 2005-2012, the incidence of hospitalized ADHF increased, which mostly reflected the increase in rates of HFpEF (average annual percent change of incident HFpEF: black women 16.6%, black men 13.2%, white women 8.0%, white men 8.3%), with higher age-adjusted average incident HFpEF rates in women (black women 6.2 per 1000 persons, white women 5.9/1000, black men 4.6/1000, white men 4.2/1000). Changes in HFrEF incidence and changes in 28-day and 1-year case fatality for HFpEF and HFrEF were modest and generally not statistically significant. Age-adjusted 1-year case fatality was similar across all race-sex groups (~30% after any incident ADHF). Similar trends were seen for recurrent ADHF (HFpEF and HFrEF). Conclusions: Incident ADHF rates increased between 2005 and 2012 in the ARIC Study communities, primarily because of incident HFpEF in women and blacks. Further study is needed to understand the differences by race and sex.

Recent Trends in the Incidence, Treatment, and Prognosis of Patients With Heart Failure and Atrial Fibrillation (the Worcester Heart Failure Study)

We aimed to investigate the impact of obstructive coronary artery disease (CAD) in patients with acute decompensated heart failure (ADHF), and examine potential differences in prognostic utility for heart failure with reduced (HFrEF) versus preserved ejection fraction (HFpEF). The Atherosclerosis Risk in Communities study conducted hospital surveillance of ADHF from 2005 to 2014. Obstructive CAD was defined as ≥50% or ≥75% stenosis, respectively, for the left main and other major epicardial arteries. Adjusted associations between obstructive CAD and 30-, 60-, and 90-day mortality were analysed. A total of 934 (4146 weighted) patients admitted with ADHF (mean age 72 years, 46% women, 30% Black, 30% HFpEF) had available angiography (61% performed in hospital). Obstructive CAD was more prevalent with HFrEF than HFpEF, whether at the left main (15% vs. 11%), left anterior descending (LAD) (48% vs. 30%), left circumflex (37% vs. 32%), right coronary (42% vs. 32%), or multiple coronary arteries (45% vs. 33%). In-hospital revascularization was performed in 25% and 22% of patients with HFrEF and HFpEF, respectively. Obstructive CAD was associated with higher adjusted mortality, particularly with left main or LAD involvement, and had a more pronounced association with 90-day mortality in HFrEF (odds ratio [OR] 2.77; 95% confidence interval [CI] 1.53-5.02) than HFpEF (OR 0.94; 95% CI 0.36-2.41) (p-interaction=0.05). Patients hospitalized with ADHF and coexisting obstructive CAD have higher short-term mortality, warranting the need for effective interventions and secondary prevention.

To describe the clinical management of acute decompensated heart failure (ADHF) in patients receiving intravenous treatment with dobutamine, milrinone, or nesiritide, and to evaluate differences, based on treatment received, in the in-hospital mortality rate, length of stay (LOS), total health care costs, and 30-day hospital readmission rate. Retrospective cohort analysis. University HealthSystem Consortium (UHC) Clinical Database Pharmacy, a database with information from 32 academic hospitals. Two thousand one hundred thirty patients with ADHF who received dobutamine (1311 patients), milrinone (433), or nesiritide (386). Patients with ADHF were categorized according to the vasoactive therapy received. To evaluate baseline characteristics, chi(2) analysis was used; logistic regression was employed to assess the relationships between drug therapy and in-hospital mortality rates, and multivariate linear regression was used to assess whether drug therapy was related to LOS and total health care costs. All regression analyses controlled for age, sex, race, region of the United States where the hospital was located, primary payer for the hospital stay, UHC patient severity class, and chronic renal failure. In-hospital mortality rates were 10.2%, 7.9%, and 2.9% in the dobutamine, milrinone, and nesiritide groups, respectively. This resulted in an adjusted odds ratio for death of 3.5 (95% confidence interval [CI] 1.8-6.8) for dobutamine and 3.9 (95% CI 1.8-8.3) for milrinone (p<0.0001). Compared with inotropic therapy (dobutamine and milrinone), mean LOS in the hospital and the intensive care unit were lower with nesiritide (p<0.001). Total health care costs were lowest with nesiritide, but this reached statistical significance only when compared with milrinone (p<0.001). Thirty-day hospital readmission rates with dobutamine, milrinone, and nesiritide were 5.0%, 9.5%, and 3.9%, respectively (p=NS). Nesiritide therapy was associated with a lower in-hospital mortality rate and shorter LOS compared with dobutamine and milrinone. In addition, total health care costs with nesiritide were decreased compared with milrinone. These observations need to be validated by a randomized controlled trial.

IntroductionHeart failure increases morbidity and mortality in patients admitted for cirrhosis. Our objective was to determine if patients with acute decompensated heart failure (ADHF) and cirrhosis would have increased mortality, hospital length of stay (LOS), and total hospital charges compared to patients with only ADHF. There is also a paucity of data regarding the influence of gender, race, ethnicity, insurance, and cirrhosis-related complications on mortality, hospital length of stay, and total hospitalization charges. In this study, we aim to identify risk factors in a national population cohort from 2016.MethodsAll patients above 18 years old with cirrhosis and ADHF admitted in 2016 were identified from the Nationwide Inpatient Sample (NIS). Multivariate regression analysis was used to estimate the odds ratio of in-hospital mortality, average length of stay (LOS), and total hospital charges after adjusting for the following factors: age, gender, race, Charlson and Elixhauser scores, primary insurance payer status, hospital type, hospital bed size, hospital region, and hospital teaching status. Statistical analysis was performed by using the survey procedures function in the statistical analysis system (SAS) software. Statistical significance was defined by the two-sided t-test with a p value < 0.05.ResultsThe overall sample contained 363,050 patients. A total of 355,455 patients were admitted with ADHF and 2% of these patients had concomitant cirrhosis (n = 7595) in 2016. The total mortality rate was 3.4%, hospital LOS was 6.6 days (with a median of 6.5 days), and the mean total hospital charge was $63,120.20. Patients with both ADHF and cirrhosis compared to patients without ADHF had increased mortality, hospital LOS, and cirrhosis-related complications.ConclusionsAs the incidence and prevalence of ADHF and cirrhosis increases worldwide, we urge the medical community to increase surveillance of patients with both diseases and perform rigorous cardiovascular risk assessments as well to improve patient outcomes.

Recurrent Acute Decompensated Heart Failure Admissions for Patients With Reduced Versus Preserved Ejection Fraction (from the Atherosclerosis Risk in Communities Study)

Background: Magnet® designated hospitals demonstrate excellence in nursing practice. Acute decompensated heart failure (ADHF) is a critical condition characterized by the sudden worsening of heart failure symptoms, leading to high in-hospital mortality and extended hospital stays. While prior studies have linked Magnet status to better general patient outcomes, its specific impact on ADHF management remains underexplored. This study aims to investigate whether Magnet designation independently predicts lower in-hospital mortality and shorter length of stay (LOS) for patients admitted with ADHF. Methods: We conducted a retrospective analysis of ADHF hospitalization between 2013-2020 across two large hospital systems in New York and Texas. Eligible cases included adults aged 18 or older with ADHF who received intravenous loop diuretics &lt; 24 hours of admission. Magnet designation was assessed at the hospital level. Two multilevel models were used: a logistic mixed-effects model to compute odds ratio (OR) for in-hospital mortality and a linear mixed-effects model to compute β for LOS. Both models included fixed effects for Magnet status, sex, ethnicity, year of admission, number of hospital beds, guideline-directed medical therapy (GDMT), Get with The Guidelines–Heart Failure (GWTG-HF) score, and Modified Charlson Comorbidity Index. Random intercepts were included for subject and hospital. All continuous predictors were standardized prior to model entry. Analyses were conducted in R (version 4.3.1) using packages lme4, lmer, and bobyqa . Results: The cohort included 26,004 ADHF patients (52.7% female; 79.2% White, 91.0% non-Hispanic), with mean age of 73+14 years and 28.3% of hospitalizations occuring at Magnet-designated hospitals. After adjusting for covariates, Magnet designation was associated with significantly lower odds of in-hospital mortality (OR = 0.21, 95% 0.06–0.78, p = 0.012). Mortality risk increased with higher GWTG-HF scores (p = 0.006). Magnet status was not associated with LOS (β = –3.18, p = 0.96). Longer LOS was observed in hospitals with more beds (β = 3.08, p &lt; 0.001), and among patients with higher GDMT (β = 5.56, p &lt; 0.001) and GWTG-HF scores (β = 6.24, p &lt; 0.001). Conclusion: Magnet designation was significantly associated with lower in-hospital mortality but not with shorter LOS among ADHF patients. These findings suggest that while Magnet hospitals may improve survival outcomes through high-quality care processes.