Episode Of Acute Decompensated Heart Failure Research Articles

Plasma soluble fms-like tyrosine kinase-1, placental growth factor, and vascular endothelial growth factor system gene variants as predictors of survival in heart failure.

Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57-16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.

Factors related to early readmissions after acute heart failure: a nested case–control study

AimsTo describe the main characteristics of patients who were readmitted to hospital within 1 month after an index episode for acute decompensated heart failure (ADHF).Methods and resultsThis is a nested case–control study in the ReIC cohort, cases being consecutive patients readmitted after hospitalization for an episode of ADHF and matched controls selected from those who were not readmitted. We collected clinical data and also patient-reported outcome measures, including dyspnea, Minnesota Living with Heart Failure Questionnaire (MLHFQ), Tilburg Frailty Indicator (TFI) and Hospital Anxiety and Depression Scale scores, as well as symptoms during a transition period of 1 month after discharge. We created a multivariable conditional logistic regression model. Despite cases consulted more than controls, there were no statistically significant differences in changes in treatment during this first month. Patients with chronic decompensated heart failure were 2.25 [1.25, 4.05] more likely to be readmitted than de novo patients. Previous diagnosis of arrhythmia and time since diagnosis ≥ 3 years, worsening in dyspnea, and changes in MLWHF and TFI scores were significant in the final model.ConclusionWe present a model with explanatory variables for readmission in the short term for ADHF. Our study shows that in addition to variables classically related to readmission, there are others related to the presence of residual congestion, quality of life and frailty that are determining factors for readmission for heart failure in the first month after discharge.Trial Registration: ClinicalTrials.gov Identifier: NCT03300791. First registration: 03/10/2017.

Longitudinal Changes in Circulating Ketone Body Levels in Patients With Acute Heart Failure: A Post Hoc Analysis of the EMPA-Response-AHF Trial

BackgroundKetone bodies are endogenous fuels produced by the liver under conditions of metabolic or neurohormonal stress. Circulating ketone bodies are increased in patients with chronic heart failure (HF), yet little is known about the effect of acute HF on ketosis. We tested the hypothesis that ketogenesis is increased in patients with acute decompensated HF. Methods and resultsThis was a post hoc analysis of 79 patients with acute HF included in the EMPA-RESPONSE-AHF trial, which compared sodium-dependent glucose-cotransporter protein 2 inhibitor treatment with empagliflozin for 30 days with placebo in patients with acute HF [NCT03200860]. Plasma concentrations of ketone bodies acetone, β-hydroxybutyrate, and acetoacetate were measured at baseline and 5 different timepoints. Changes in ketone bodies over time were monitored using repeated measures analysis of variance. In the total cohort, median total ketone body concentration was 251 µmol/L (interquartile range, 178–377 µmol/L) at baseline, which gradually decreased to 202 µmol/L (interquartile range, 156–240 µmol/L) at day 30 (P = .041). Acetone decreased from 60 µmol/L (interquartile range, 34–94 µmol/L) at baseline to 30 µmol/L (interquartile range, 21–42 µmol/L) ( P < .001), whereas β-hydroxybutyrate and acetoacetate remained stable over time. Higher acetone concentrations were correlated with higher N-terminal pro brain natriuretic peptide levels (r = 0.234; P = .039). Circulating ketone bodies did not differ between patients treated with empagliflozin or placebo throughout the study period. A higher acetone concentration at baseline was univariately associated with a greater risk of the composite end point, including in-hospital worsening HF, HF rehospitalizations, and all-cause mortality after 30 days. However, after adjustment for age and sex, acetone did not remain an independent predictor for the combined end point. ConclusionsCirculating ketone body concentrations, and acetone in particular, were significantly higher during an episode of acute decompensated HF compared with after stabilization. Treatment with empagliflozin did not affect ketone body concentrations in patients with acute HF.

Renal function, electrolytes, and congestion monitoring in heart failure.

Congestion, renal function, and electrolyte imbalance (particularly potassium) are common problems in the management of the complex multi-morbid patient with heart failure (HF). Poor control of these fundamental clinical features is associated with adverse outcomes. Close monitoring of serum potassium and renal function is recommended by most current guidelines during the management of an episode of acute decompensated HF, yet the recommendations remain poorly implemented. Physicians are advised to treat a state of euvolaemia after an admission with decompensated HF and residual congestion is a marker of worse outcome, yet control of congestion is poorly assessed and managed in real-world practice. This document reflects the key points discussed by a panel of experts during a Heart Failure Association meeting on physiological monitoring of the complex multi-morbid HF patient, and here, we present to aspects related to renal function, electrolyte, and congestion monitoring.

A Case of Extended Mechanical Circulatory Support with Impella 5.0 in a Patient with Cardiogenic Shock Secondary to Left Ventricular Aneurysm

Introduction Data from the Nationwide Inpatient Sample (NIS) indicate that the incidence of cardiogenic shock (CS) has increased in the last two decades. Despite recent advances in mechanical circulatory support (MCS), CS-attributable morbidity remains high, portending a poor prognosis for patients at risk of developing CS acutely in the setting of percutaneous coronary intervention (PCI), cardiac surgery, or acute decompensated heart failure (ADHF). Herein, we describe the case of a patient maintained on 18 days of Impella 5.0 MCS, following ADHF and CS in the setting of a large LV aneurysm. Case Description A 66 year-old male patient with a history of ischemic cardiomyopathy with two-vessel coronary artery bypass grafts presented to an outside hospital for an episode of ADHF. Left heart catheterization performed at the outside hospital showed left anterior descending (LAD) and left circumflex (LCx) artery disease with patent grafts. There was severe disease of the mid-right coronary artery (RCA) which was treated with PCI. One week following intervention, the patient became acutely hypotensive and hypoxemic at rest. Echocardiography at that time showed possible LV aneurysm, though contained rupture of the LV free wall could not be excluded. The patient was intubated and transferred to our hospital for further management. Upon arrival to our institution, imaging was performed, which confirmed the presence of a large anterolateral/inferolateral LV aneurysm with severely reduced ejection fraction (EF) to 30% (Figure). The patient was noted to be in multiorgan failure secondary to CS, and the decision was made to place an Impella 5.0 as a bridge to decision. The patient was maintained on Impella 5.0 for hemodynamic support for 18 days post-operatively, until, on hospital day 32, the patient expired due to septic shock from C. difficile colitis. Conclusion Impella 5.0 is currently indicated for use in patients with cardiogenic shock and for high risk PCI. Scant literature exists to support the use of Impella as a bridge to decision or namely bridge to permanent left ventricular assist device or bridge to heart transplant; in these investigations, mean duration of support ranges from approximately 0 to 13 days. The utility of Impella has not been studied in patients with LV aneurysm. Our case suggests that the Impella 5.0 can be used in patients with LV aneurysm for hemodynamic support for an extended clinical course.

Evaluation of Neutrophil-lymphocyte and Platelet-lymphocyte Ratios as Predictors of 30-day Mortality in Patients Hospitalized for an Episode of Acute Decompensated Heart Failure.

SummaryBackgroundTo investigate the association between both neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and 30-day mortality in patients hospitalized for an episode of acute decompensated heart failure (ADHF).Methods439 patients admitted to emergency department (ED) for an episode of ADHF. Clinical history, demographic, clinical and laboratory data recorded at ED admission and then correlated with 30-day mortality.Results45/439 (10.3%) patients died within 30 days from ED admission. The median values of NLR (4.1 vs 11.7) and PLR (159.1 vs 285.9) were significantly lower in survivors than in patients who died. The area under the ROC curve of NLR was significantly higher than that of the neutrophil count (0.76 vs 0.59; p<0.001), whilst the AUC of PLR was significantly better than that of the platelet count (0.71 vs 0.51; p<0.001). In univariate analysis, both NLR and PLR were significantly associated with 30-day. In the fully-adjusted multivariate model, NLR (odds ratio, 3.63) and PLR (odds ratio, 3.22) remained independently associated with 30-day mortality after ED admission.ConclusionsRoutine assessment of NLR and PLR at ED admission may be a valuable aid to complement other conventional measures for assessing the medium-short risk of ADHF patients.

Early readmission for heart failure: An avoidable or ineluctable debacle?

Early hospital readmission after an episode of Acute Decompensated Heart Failure (ADHF) is an emerging issue that is causing a relevant clinical and economic burden. Although there might be several reasons for early readmissions, in many cases these might be effectively prevented by a more adequate post-discharge management, including recommendations on lifestyle and rehabilitation programs. However, almost half of hospitalizations are unrelated to specific cardiac causes and thus increases the difficulty in analyzing risks prediction. Many episodes are related to social environment, poor familiar assistance and inadequate followup program. In addition, the national and insurance companies constantly quest for a reduction of costs that could lead to inappropriately shortened hospital stays. Therefore, the suitability of early re-hospitalization as a correct target for good medical practice is highly debated. Nevertheless, the post-discharge phase after episodes of ADHF remains poorly analyzed in clinical trials and specific investigations should be considered during the transition period from acute to chronic status. A validated program, which focuses on an appropriate risk algorithm including cardiac and extracardiac precipitating factors is lacking. This is a necessary and it should become one of the most important targets to aim for in HF management and strategy.

Outcomes After Predischarge Initiation of β-Blocker in Patients Hospitalized for Severe Decompensated Heart Failure Requiring Inotropic Therapy

BackgroundThe optimal time for initiating β-blocker (BB) treatment in patients with severe acute decompensated heart failure requiring inotropic therapy has not been well defined. We evaluated the effect of predischarge initiation of BB treatment on clinical outcomes. MethodsAmong the 5625 patients enrolled in the Korean Acute Heart Failure (KorAHF) registry, 672 BB-naive patients suffering from heart failure with reduced ejection fraction (median, 67.0 years; 62.5% male; median left ventricular ejection fraction, 24.1%) who received inotropic support during hospitalization were evaluated. We compared the risk of post-discharge mortality and rehospitalization between groups with (n = 282) and without (n = 390) pre-discharge BB treatment. ResultsDuring a median follow-up of 2.6 years, all-cause mortality occurred in 252 patients (37.5%). Those who received pre-discharge BB treatment showed lower 2-year mortality rates compared with those who did not (21.3% vs 39.3%; P < 0.001). In a Cox proportional hazards model, all-cause mortality was consistently lower in pre-discharge BB groups after multivariable adjustment (hazard ratio, 0.69; 95% confidence interval, 0.50-0.95; P = 0.025) and adjustment for propensity score methods using the inverse probability of treatment weighting (hazard ratio, 0.70; 95% confidence interval, 0.52-0.93; P = 0.016). The same trend was observed for secondary outcomes of rehospitalization for any cause and rehospitalization for heart failure. Pre-discharge BB was associated with higher rates of BB prescription after 6 (90.1% vs 23.9%; P < 0.001) and 12 (88.9% vs 25.0%; P < 0.001) months. ConclusionsPre-discharge BB initiation is associated with better clinical outcomes after severe acute decompensated heart failure episodes requiring inotropic therapy.

The effect of intravenous isosorbide dinitrate in acute decompensated heart failure in hospital.

Background According to new recommendations for the management of acute decompensated heart failure (ADHF) in 2015, intravenous vasodilator therapy might be given as an early therapy when systolic blood pressure is normal to high (≥110mmHg). Only 29% of patients with ADHF are treated with vasodilators without medical contraindication. Objective To evaluate the effect of the systematic use of ISDN on ADHF without contraindication especially on rehospitalization rate. Settings The 600-bed hospital (Centre Hospitalier de l'Ouest Vosgien, Neufchâteau, France). Methods This is a retrospective study with data analysed from medical records. Patients with ADHF episodes and hospitalization in the cardiology department or intensive care unit (ICU) between November 2013 and December 2015 were included resulting in 199 hospitalizations in the analysis (37 were treated by ISDN, and 162 were not). Main outcome measure Effects of ISDN on 180-day hospital readmission for ADHF or acute myocardial infarction (AMI), in-hospital mortality, length of stay, number of ICU admissions, and ICU length of stay. Results Patients who received ISDN required more ICU admissions than the other patients (54.1 vs 33.3%, p=0.02). Nevertheless 180-day hospital readmission was lower for patients who were receiving ISDN (8.1 vs 22.8%, p=0.04). ISDN did not influence other clinical outcomes tested. Conclusion ISDN may minimize or prevent the consequences of altered haemodynamics. Lower rehospitalization rate with ISDN was seen in this study.

Long-Term Survival for Patients With Acute Decompensated Heart Failure According to Ejection Fraction Findings

Limited data exist about the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to ejection fraction (EF) findings. The primary objective of this population-based observational study was to characterize and compare trends in long-term prognosis after an episode of ADHF across 3 EF strata. Hospital medical records were reviewed for 3,604 residents of the Worcester, Massachusetts, metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004 and had EF measurements during their index hospitalizations. The average age of this population was 75 years, most were white, and 44% were men. Approximately 49% of the population had heart failure (HF) with preserved EF (EF ≥ 50%), 37% had HF with reduced EF (EF ≤ 40%), and 14% had HF with borderline EF (EF 41% to 49%). Patients with HF with preserved EF experienced higher postdischarge survival rates than patients with either HF with reduced EF or HF with borderline EF at 1, 2, and 5 years after discharge from all central Massachusetts medical centers. Although prognosis at 1 year after hospital discharge improved for all patient groups during the years under study, especially for those with HF with reduced EF and HF with preserved EF, these encouraging trends decreased with increasing duration of follow-up. In conclusion, although improvements in 1-year postdischarge survival were observed for patients in each of the 3 EF groups examined to varying degrees, the postdischarge prognosis of all patients with ADHF remains guarded.

Recent Acute Decompensated Heart Failure Predicts Postoperative Cardiovascular Events

Acute decompensated heart failure (ADHF) is considered a major perioperative risk factor. Vascular surgery, excluding carotid endarterectomy, is a high risk procedure. Current guidelines do not address the optimal timing of elective, vascular surgery following an episode of ADHF. We hypothesized that ADHF occurring within 30 days prior to elective vascular surgery, independently predicts postoperative cardiovascular events. The American College of Surgeons - National Surgical Quality Improvement Program (NSQIP) database is a prospectively validated dataset of a sample of all non-cardiac surgical procedures. All elective vascular surgical patients from our institutional NSQIP from 2006 to 2010 were studied. The primary exposure was a history of ADHF within 30 days prior to surgery. The primary outcome was a composite of death, heart failure, postoperative MI, and ischemic stroke. Concomitant comorbidities, surgical and anesthetic data were evaluated. NSQIP data definitions were used for all data elements except “history of HF”, which was extracted from the electronic medical record using a previously validated search. The primary hypothesis was tested using logistic regression. Of 1291 study patients, 13 (1.0%) had ADHF within 30 days prior to surgery. Patients with ADHF were older, had a greater incidence of diabetes and ESRD (Table 1). Indices of surgical complexity including duration of surgery, and estimated blood loss were similar between the two groups. The primary outcome occurred in 3/13 (23.1%) patients with ADHF compared to 64/1278 (5.0%) patients without (p 0.004). After multivariate adjustment, ADHF was a strong predictor of postoperative cardiovascular events [OR 5.4, 95% CI 1.1 - 22.8] (Table 2). ADHF occurring within 30 days prior to elective vascular surgery is independently associated with increased risk of postoperative cardiovascular events. These data suggest that elective vascular surgery should be delayed for at least 30 days following an episode of ADHF.Table 1Baseline characteristicsVariablesRecent ADHF - NORecent ADHF - YESN1278 (99%)13 (1%)Age (years)∗Mean (SD).66.5 (14.3)75.1 (7.1)Weight (kg)∗Mean (SD).84.0 (20.2)76.5 (17.4)Current smoking334 (26.1%)4 (30.8%)Diabetes216 (16.9%)5 (38.5%)‡Statistically significant.Hypertension894 (70.0%)11 (84.6%)Cerebrovascular disease214 (16.7%)4 (30.8%)ESRD24 (1.9%)2 (15.4%)‡Statistically significant.CAD410 (32.1%)6 (46.2%)Duration of surgery (minutes)∗Mean (SD).247.8 (147.0)175.5 (105.2)Estimated surgical blood loss (ml)∗Mean (SD).884.3 (1510.0)1083.3 (1528.3)∗ Mean (SD).‡ Statistically significant. Open table in a new tab Table 2Adjusted odds ratios for Postoperative Cardiovascular Complications or DeathOR∗- Odds Ratio per unit change. (95% CI)p valueADHF within 30 days prior to surgery5.4 (1.1-22.8)0.04ESRD4.8 (1.6-12.5)0.01Age (per decade)1.6 (1.2-2)<0.01Length of surgery (per 30 minutes)1.1 (1-1.1)<0.01History of Diabetes1.6 (0.8-2.8)0.15History of CVA or TIA1.5 (0.8-2.7)0.16History of HF1.6 (0.7-4.1)0.27History of CAD1.3 (0.8-2.2)0.32Hypertension1.1 (0.6-2.4)0.7Abbreviations: CVA, CerebroVascular Accident; TIA, Transient Ischemic Attack; CAD, Coronary Artery Disease.∗ - Odds Ratio per unit change. Open table in a new tab

Noninvasive Wireless Bioimpedance Monitoring Tracks Patients with Healthcare Utilization Following Discharge from Acute Decompensated Heart Failure: Results from the ACUTE Pilot Study

Heart Failure (HF) remains a significant healthcare challenge characterized by recurrent episodes of acute decompensated HF (ADHF) and frequent hospitalizations. To date, remote monitoring in HF has largely relied on information from implanted devices that are only available in select patients with therapeutic indications or on remote disease management programs with variable outcome benefits.

Implantable Sensors for Heart Failure

Heart failure (HF) affects more than 5 million Americans, and acute decompensated heart failure (ADHF) has emerged as the leading cause of hospitalization among people over the age of 65 years.1 Importantly, HF is a leading public health concern, and hospitalization expenses related to management of ADHF impose a substantial financial burden on the health care system. Additionally, readmission rates after hospitalization for ADHF may be as high as 50% at 6 months,2 and insights from the ADHERE registry suggest that a majority of patients admitted with ADHF have a history of heart failure.1 These data demonstrate that the majority of patients admitted with ADHF are known to the medical system and to medical providers, thereby creating an opportunity for upstream strategies that may be capable of detecting early HF destabilization and implementing therapies to restabilize the patient and avert hospitalization. The anticipated changes in the health care system—with a focus on bundled payments for disease management—will necessitate robust disease management programs to optimize therapy and minimize recurrent admissions once patients have been diagnosed with HF. Perhaps even more importantly, averting repeat episodes of ADHF is likely to have a stabilizing effect on the progression of HF and may improve long-term morbidity and mortality. The transition from chronic HF to ADHF involves perturbations in multiple intersecting processes including neurohormonal circuits, inflammatory mediators, cardiorenal interactions, and myocardial performance. Concurrently, derangements in comorbid illnesses such as coronary disease, atrial and ventricular arrhythmias, and hypertension also contribute to the pathophysiology of ADHF.3 Ultimately, these multiple pathways lead to an elevation in ventricular filling pressures and signs of vascular congestion, which, in concert with symptoms from impaired cardiac output, lead to the clinical constellation of ADHF. This pathophysiologic paradigm highlights multiple opportunities for detecting early changes in the processes that …

Characteristics and outcomes in African American patients with decompensated heart failure.

Outcomes in patients with chronic heart failure vary by race. Racial differences in the characteristics and outcomes of patients with acute decompensated heart failure (ADHF) have not been well characterized. Therefore, we assessed race-related differences in presentation, treatment, in-patient experiences, and short-term mortality due to ADHF before and after accounting for known covariates. The Acute Decompensated Heart Failure National Registry database was analyzed to evaluate demographic and mortality differences in African American and white patients with ADHF entered into the database from its initiation in September 2001 to December 31, 2004. Stratified analyses by cause, age, left ventricular function, and history of heart failure subgroups were also conducted. A total of 105,872 episodes of ADHF occurred in white patients and 29,862 occurred in African American patients. African American patients with ADHF were younger than white patients (mean [SD] age, 63.5 [15.4] vs 72.5 [12.5] years) and had lower mean left ventricular ejection fractions. The prevalence of hypertension, diabetes mellitus, and obesity was higher in African American patients. African American race was associated with lower in-hospital mortality after adjustment for known predictors (2.1% vs 4.5%; adjusted odds ratio [OR], 0.79; 95% confidence interval [CI], 0.72-0.87; P < .001). This association persisted for all age cohorts, was independent of the use of intravenous vasoactive drugs, and was especially present in African American patients in the nonischemic subgroup (adjusted OR, 0.74; 95% CI, 0.57-0.96) but not the ischemic subgroup (adjusted OR, 0.91; 95% CI, 0.76-1.09). In ADHF, African American race is associated with lower in-hospital mortality compared with white race, despite certain indicators of increased disease severity.

Climbing the Mountain of Acute Decompensated Heart Failure

IN THIS ISSUE OF JAMA, 2 ARTICLES REPORT FINDINGS FROM the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) clinical trials program. Konstam et al report the overall longterm effects of tolvaptan in terms of safety and clinical outcomes for patients with worsening heart failure (HF) requiring hospitalization. Gheorghiade et al report shortterm effects of tolvaptan for acute symptom relief in these same patients, but presented as 2 trials that were based on study center assignment following completion of patient enrollment and randomization in the long-term trial. The aggregate findings demonstrate that tolvaptan relieves some symptoms associated with acute decompensated heart failure (ADHF) and has no demonstrable evidence of harm such as worsening of renal failure, but importantly, does not reduce mortality or HF-related morbidity at 1 year. In the context of ADHF, these are noteworthy findings. To date, no other therapeutic intervention has been demonstrated in large-scale randomized, placebo-controlled studies to positively influence symptoms in ADHF without generating a question of harm. Inotropes have been associated with increased mortality risk, and calcium sensitizers have been associated with increased cardiovascular mortality. Nesiritide was shown to relieve dyspnea and to reduce pulmonary congestion over the short term, but also was associated with increased intermediate-term mortality risks. Traditional vasodilator therapy relieves HF symptoms, but neither nitroglycerin nor nitroprusside has been subjected to prospective randomized controlled study, and effects on mortality are unknown. Even diuretics, which clearly relieve congestion, have uncertain effects on outcomes. Addressing the challenge of ADHF has been daunting. Acute decompensated HF accounts for more than 1 million acute hospitalizations per year in the United States at an annual cost of more than $30 billion and is associated with significant mortality. The risk of inpatient death is approximately 4% (but ranges from 2%-22%), and the risk of death/rehospitalization at 60 to 90 days after an episode of ADHF is 36%. At the core of this challenge, however, is the limited understanding of the pathophysiology of ADHF. While hemodynamic disturbances are clearly responsible for the observed signs and symptoms, plausible causative mechanisms that trigger acute decompensation, eg, ventricular injury and augmented neurohormonal activation, remain uncertain. Thus, therapy for ADHF is relegated to correcting perturbed hemodynamics. Comparison is made with the evolution of therapy for chronic HF—targeting hemodynamic abnormalities did not yield meaningful clinical benefits, but elucidation of relevant pathophysiological mechanisms followed by appropriately focused interventions in largescale trials resulted in salutary improvements. A similar approach is needed for ADHF. Another challenge of ADHF involves clinical trial design and construct. The studies to date have been small to moderate short-term hemodynamic or symptom-focused designs, constructed primarily to meet regulatory requirements. Important questions, including mechanistic hypotheses and the effect of interventions on rehospitalizations/mortality, have been inadequately studied. Trials in ADHF have also been confounded by considerable heterogeneity of the patient phenotype. Patients with ADHF are older, represent a mix of new-onset HF and decompensated chronic HF, have both reduced and preserved ejection fraction HF, have equal gender representation, and frequently have a number of important comorbidities, especially renal insufficiency. Moreover, “standard therapy” does not truly exist, as there are no evidence-based interventions proven to reduce morbidity and mortality associated with ADHF. Guidelines for ADHF have recently been put forward, but the treatment algorithms are sparse and focus on hemodynamic targets. The strategy is to relieve symptoms preferentially with diuretic use, including high-dose loop diuretics and continuous diuretic infusions (the safety of which is not known in HF), and to add vasodilator therapy (nitroglycerin or nitroprusside) if adjunctive approaches are needed. Inotropes are reserved for impending or frank shock but are otherwise dissuaded. Ultrafiltration represents at best an emerging technology with intriguing preliminary data but limited applications.

Treatment options for acute decompensated heart failure.

The benefits of nesiritide for the treatment of acute decompensated heart failure (ADHF) are discussed. In order to understand the goals of ADHF therapy, it is important to recognize the complex interplay between hemodynamic and neurohormonal abnormalities in patients suffering from heart failure. Goals of therapy include improvement in hemodynamic parameters, relief of symptoms, and minimization of adverse effects. Until recently, therapy with diuretics, positive inotropes, and intravenous vasodilators was the standard of care for treating ADHF. Nesiritide is the newest agent available for treating ADHF and may offer several benefits over standard of care therapy. It is important to remember that therapy for ADHF should not replace chronic oral heart failure therapy, nor should focus on prevention of ADHF episodes be lost.