In-hospital Worsening Heart Failure Research Articles

Use of the ADHERE Risk Model as a Predictor of Risk of in-Hospital Worsening Heart Failure in a Cohort.

Patients admitted with acute decompensated heart failure (HF) are subject to developing worsening episodes that require more complex interventions. The Acute Decompensated Heart Failure National Registry (ADHERE) risk model was developed in the United States to predict the risk of in-hospital worsening HF. To use the ADHERE risk model in the assessment of risk of in-hospital worsening HF and to determine its sensitivity and specificity in hospitalized patients. This cohort study was conducted at a Brazilian public university hospital, and data from 2013 to 2020 were retrospectively collected. P values < 0.05 were considered statistically significant. A total of 890 patients with a mean age of 74 ± 8 years were included. The model showed that, in the group of 490 patients at risk, 254 (51.8%) developed in-hospital worsening HF. In the group of 400 patients not at risk, only 109 (27.2%) experienced worsening HF. The results demonstrated a statistically significant curve (area under the curve = 0.665; standard error = 0.018; P < 0.01; confidence interval = 0.609 to 0.701), indicating good accuracy. The model had a sensitivity of 69.9% and a specificity of 55.2%, with a positive predictive value of 52% and a negative predictive value of 72.7%. In this cohort, we showed that the ADHERE risk model was able to discriminate patients who in fact developed worsening HF during the admission period, from those who did not.

Development and validation of a nomogram to predict the risk of death within 1 year in patients with non-ischemic dilated cardiomyopathy: a retrospective cohort study

Predicting the chances mortality within 1 year in non-ischemic dilated cardiomyopathy patients can be very useful in clinical decision-making. This study has developed and validated a risk-prediction model for identifying factors contributing to mortality within 1 year in such patients. The predictive nomogram was constructed using a retrospective cohort study, with 615 of patients hospitalized in the First Affiliated Hospital of Guangxi Medical University between October 2012 and May 2020. A variety of factors, including presence of comorbidities, demographics, results of laboratory tests, echocardiography data, medication strategies, and instances of heart transplant or death were collected from electronic medical records and follow-up telephonic consultations. The least absolute shrinkage and selection operator and logistic regression analyses were used to identify the critical clinical factors for constructing the nomogram. Calibration, discrimination, and clinical usefulness of the predictive model were assessed using the calibration plot, C-index and decision curve analysis. Internal validation was assessed with bootstrapping validation. Among the patients from whom follow-up data were obtained, the incidence of an end event (deaths or heart transplantation within 1 year) was 171 cases per 1000 person-years (105 out of 615). The main predictors included in the nomogram were pulse pressure, red blood cell count, left ventricular end-diastolic dimension, levels of N-terminal pro b-type natriuretic peptide, medical history, in-hospital worsening heart failure, and use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The model showed excellent discrimination with a C-index of 0.839 (95% CI 0.799–0.879), and the calibration curve demonstrated good agreement. The C-index of internal validation was 0.826, which demonstrated that the model was quite efficacious. A decision curve analysis confirmed that our nomogram was clinically useful. In this study, we have developed a nomogram that can predict the risk of death within 1 year in patients with non-ischemic dilated cardiomyopathy. This will be useful in the early identification of patients in the terminal stages for better individualized clinical decisions.

A systematic review of in-hospital worsening heart failure as an endpoint in clinical investigations of therapy for acute heart failure.

In-hospital worsening heart failure (WHF) occurs frequently in patients hospitalized for acute heart failure (AHF) and has strongly negative prognostic associations. It may be a useful endpoint in studies of AHF management but important questions remain regarding optimization of its definition and variability in its incidence. Our objective was to survey the full extent of clinical interest in WHF and assess the impact of baseline variables and trial design on outcomes. PubMed, Embase, and BIOSIS were searched systematically for clinical studies that had in-hospital WHF as an endpoint. Differences in definitions of in-hospital WHF were reviewed for their potential impact on observed incidence of WHF and its associations with post-discharge outcomes. The search identified 35 publications representing 13 interventional trials, 3 observational studies, several different classes of therapeutic agent, and 78,752 patients overall. Incidence of in-hospital WHF varied greatly-from 4.2% to 37%. Concerning the impact of differences in the way in which WHF was defined, two important factors were physician determination of worsening and whether intensification of diuretic therapy alone was defined as a WHF event. Patients having in-hospital WHF were at substantially greater risk for death and longer length of stay during index hospitalizations, all-cause and heart-failure rehospitalization, cardiovascular complications, renal failure, all-cause death, cardiovascular death, and higher healthcare costs post-discharge. There is diverse interest in selecting in-hospital WHF as an endpoint in clinical trials. Differences in reported incidence are complexly related to differences in the way in which WHF is defined.

In-hospital worsening heart failure in patients admitted for acute heart failure

BackgroundIn-hospital worsening heart failure (WHF) is predictive of worse post-discharge outcomes and has been recently used as an endpoint in clinical trials in acute heart failure (AHF). MethodsWe described the clinical and prognostic significance of WHF in consecutive patients hospitalized for AHF at our institute. WHF was defined as worsening signs and symptoms of HF requiring treatment intensification. We compared WHF events by day 7 (early WHF) with WHF occurring at any time during admission. The primary endpoint was cardiovascular (CV) death and HF rehospitalizations through day 60. ResultsWe included 387 consecutive patients. Median length of stay was 11days (interquartile range 8–18days). Forty-five patients (11.6%) had WHF, HF rehospitalization, or death through day 7 whereas 90 (23.3%) had WHF or died at any time during initial hospitalization. Patients with WHF occurring any time during admission were more symptomatic, had lower systolic blood pressure, worse renal function, and higher troponins at baseline. Both early WHF and WHF at any time during hospitalization were associated with a longer length of stay and higher CV death and HF rehospitalization rates at day 60, but only WHF at any time was associated with all-cause death at day 180 (adjusted HR 2.42 95% CI 1.30, 4.52; p=0.0055) and with all-cause death any time during the follow-up period (adjusted HR 1.60 95% CI 1.02, 2.53; p=0.0425). ConclusionsOur study confirms the prognostic significance of WHF and shows the independent prognostic value of WHF also for long-term mortality when assessed throughout hospitalization.

Implications of Using Different Definitions on Outcomes in Worsening Heart Failure.

In-hospital worsening heart failure (WHF) is an important event that has inconsistent definitions used across trials. We used data from 2 acute heart failure (HF) trials from the National Institutes of Health HF Network, DOSE (Diuretic Optimization Strategies Evaluation) and ROSE (Renal Optimization Strategies), to understand event rates associated with different WHF definitions. We pooled data from 668 patients in DOSE and ROSE and assessed the relationship between WHF and the composite end point of rehospitalization, emergency room visits for HF, and mortality through 60 days. We also assessed for a differential relationship between the timing of WHF development and outcomes. The overall incidence of WHF was 14.6% (24.1% in DOSE, 6.3% in ROSE, and 5.0% in DOSE using the ROSE definition). WHF was associated with an increase in the composite end point (hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.11-2.42; P=0.01). However, the association between WHF and outcomes was significantly stronger in ROSE than in DOSE (HR, 2.67; 95% CI, 1.45-4.91; P<0.01 and HR, 1.28; 95% CI, 0.79-2.08; P=0.31, respectively). Development of WHF between baseline to 24 hours compared with 24 to 48 hours or 48 to 72 hours demonstrated a trend toward improved outcomes (HR, 0.49; 95% CI, 0.21-1.17; P=0.11 and HR, 0.45; 95% CI, 0.20-1.04; P=0.06, respectively). A WHF definition that excluded the intensification of diuretics resulted in a lower event rate but a stronger association with outcomes. These data support the need for continued efforts to standardize WHF definitions in clinical trials. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00577135 (DOSE) and NCT01132846 (ROSE).

Development and validation of a risk model for in-hospital worsening heart failure from the Acute Decompensated Heart Failure National Registry (ADHERE)

A subset of patients hospitalized with acute heart failure experiences in-hospital worsening heart failure, defined as persistent or worsening signs or symptoms requiring an escalation of therapy. We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital worsening heart failure. Our definition of in-hospital worsening heart failure included events such as escalation of medical therapy (eg, inotropic medications) >12hours after admission. We considered candidate risk prediction variables routinely assessed at admission, including age, medical history, biomarkers, and renal function. We used logistic regression with robust standard errors to generate a risk model in a 66% random derivation sample; we validated the model in the remaining 34%. We evaluated the calibration and discrimination of the model in both samples. We evaluated 23,696 patients hospitalized with acute heart failure. Baseline characteristics were well matched in the derivation and validation samples, and the occurrence of in-hospital worsening heart failure was similar in both samples (15.4% and 15.6%, respectively). In the multivariable model, the strongest predictors of in-hospital worsening heart failure were increased troponin and creatinine. The model was well calibrated and had good discrimination in the derivation sample (c statistic, 0.74) and validation sample (c statistic, 0.72). The ADHERE worsening heart failure risk model is a clinical tool with good discrimination for use in patients hospitalized with acute heart failure to identify those at increased risk for in-hospital worsening heart failure. This tool may be useful to target treatment strategies for patients at high risk for in-hospital worsening heart failure.

Patient journey after admission for acute heart failure: length of stay, 30-day readmission and 90-day mortality.

The course of patients following admission for acute heart failure (AHF) is of major importance to patients and healthcare providers. We examined predictors and associations of length of stay (LOS), 30-day post-discharge readmission and 90-day post-discharge mortality in 1990 patients enrolled in the PROTECT study. PROTECT was a randomized study that examined the effect of the adenosine blocker rolofylline in patients within 24 h of admission for AHF with mild to moderate renal impairment. Geographic-region-adjusted multivariable models showed that LOS was only partly explained by the severity of heart failure (HF), comorbidities (diabetes mellitus, renal impairment, ischaemic heart disease) and degree of metabolic dysfunction (cholesterol and albumin) at baseline (adjusted R(2) 0.27). Addition of in-hospital worsening heart failure (WHF) and changes in metabolic markers contributed significantly to prediction of LOS [R(2) difference 0.050, 95% confidence interval (CI) 0.0282-0.072]. Thirty-day HF readmission was associated with more severe HF and previous HF admission but not with LOS (odds ratios 1.00, 95% CI 0.97-1.04). Death within 90 days after discharge was associated with older age, more severe HF, worse renal function, and lower sodium and bicarbonate at admission; LOS was a strong predictor of 90-day post-discharge mortality. In patients admitted for AHF, LOS is not well-predicted by traditional markers of disease severity, but strongly associated with the occurrence of in-hospital WHF. Longer LOS is a strong predictor of early mortality after discharge but not of readmission. These findings may help focus efforts to reduce LOS and post-discharge outcomes on patients' subgroups at increased risk.

Abstract 10990: Regulatory Implications of Different Definitions and Outcomes in Worsening Heart Failure

Introduction: Despite the use of different definitions for worsening heart failure (WHF) in prior clinical trials and registries, an in-hospital WHF event has consistently been associated with worse patient outcomes. WHF is being considered as a potential endpoint to support drug approval. We combined patients from two acute HF trials conducted by the HF Network (ROSE-AHF and DOSE-AHF) to understand how different WHF definitions are associated with event rates. Methods: WHF was defined as persistent or worsening HF requiring rescue therapy including IV vasoactive agents, ultrafiltration, or mechanical support over 72 hours after randomization in ROSE and also included additional open label loop or thiazide diuretic in DOSE. We assessed the relationship between WHF and the composite endpoint (CE) of re-hospitalization, emergency room visits for HF and mortality through 60 days. We also assessed for a differential relationship of WHF from 0-24 hours, 24-48 hours and 48-72 hours post-randomization. Results: The overall incidence of WHF was 14.6% (24.1% in DOSE and 6.3% in ROSE). Patients who developed WHF had lower baseline systolic blood pressure, less peripheral edema and higher BUN. In the combined dataset, WHF was associated with an increase in the CE (hazard ratio [HR] 1.64; 95% confidence interval [CI] 1.11-2.42; p-value 0.01). However, the association between WHF and 60-day outcomes was significant in ROSE but not in DOSE (Table). The development of WHF between 48-72 hours compared with 0-24 hours or 24-48 hours was associated with improved outcomes ([HR] 0.48, 95% CI 0.27 - 0.88, p-value 0.02 and [HR] 0.45, 95% CI 0.26 - 0.78, p-value 0.004, respectively). Conclusions: A WHF definition that incorporated intensification of diuretics increased the event rate but was not associated with worse 60-day outcomes. The timing of a WHF event also had a differential association with outcomes. These data support the use of a standardized WHF definition in clinical trials.

Differences in health care use and outcomes by the timing of in-hospital worsening heart failure

Patients hospitalized with acute heart failure may experience worsening symptoms requiring escalation of therapy. In-hospital worsening heart failure is associated with worse in-hospital and postdischarge outcomes, but associations between the timing of worsening heart failure and outcomes are unknown. Using data from a large clinical registry linked to Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for acute heart failure. We defined in-hospital worsening heart failure by the use of inotropes or intravenous vasodilators or initiation of mechanical circulatory support, hemodialysis, or ventilation. The study groups were early worsening heart failure (n = 1,990), late worsening heart failure (n = 4,223), complicated presentation (n = 15,361), and uncomplicated hospital course (n = 41,334). Among 62,908 patients, those with late in-hospital worsening heart failure had higher in-hospital and postdischarge mortality than patients with early worsening heart failure or complicated presentation. Those with early or late worsening heart failure had more frequent all-cause and heart failure readmissions at 30 days and 1 year, with resultant higher costs, compared with patients with an uncomplicated hospital course. Although late worsening heart failure was associated with the highest mortality, both early and late worsening heart failures were associated with more frequent readmissions and higher health care costs compared to uncomplicated hospital course. Prevention of worsening heart failure may be an important focus in the care of hospitalized patients with acute heart failure.

Comparative effectiveness of torsemide versus furosemide in heart failure patients: insights from the PROTECT trial.

The authors assessed the comparative effectiveness of torsemide versus furosemide in the PROTECT trial. The authors assessed the relationship between loop diuretic at discharge and death or cardiovascular/renal hospitalization within 30 days, and death through 150 days postdischarge using inverse probability weighting. Out of 1004 patients, 83.5% received furosemide and 16.5% torsemide. Torsemide patients had higher blood urea nitrogen, and more in-hospital worsening heart failure. Following adjustment, torsemide was associated with similar 30-day outcomes compared with furosemide (p = 0.93), but remained associated with increased 150-day death (hazard ratio: 2.26; 95% CI: 1.40-3.66; p < 0.001). Patients treated with torsemide had features of greater disease severity, similar 30-day outcomes but increased 150-day mortality. Prospective randomized trials are needed to investigate the effect of torsemide versus furosemide.

The Impact of Worsening Heart Failure in the United States.

In-hospital worsening heart failure represents a clinical scenario wherein a patient hospitalized for acute heart failure experiences a worsening of their condition, requiring escalation of therapy. Worsening heart failure is associated with worse in-hospital and postdischarge outcomes. Worsening heart failure is increasingly being used as an endpoint or combined endpoint in clinical trials, as it is unique to episodes of acute heart failure and captures an important event during the inpatient course. While prediction models have been developed to identify worsening heart failure, there are no known FDA-approved medications associated with decreased worsening heart failure. Continued study is warranted.

In-hospital worsening heart failure.

Acute worsening heart failure (WHF) is seen in a sizable portion of patients hospitalized for heart failure, and is increasingly being recognized as an entity that is associated with an adverse in-hospital course. WHF is generally defined as worsening heart failure symptoms and signs requiring an intensification of therapy, and is reported to be seen in anywhere from 5% to 42% of heart failure admissions. It is difficult to ascertain the exact epidemiology of WHF due to varying definitions used in the literature. Studies indicate that WHF cannot be precisely predicted on the basis of baseline variables assessed at the time of admission. Recent data suggest that some experimental therapies may reduce the risk of development of WHF among hospitalized heart failure patients, and this is associated with a reduction in risk of subsequent post-discharge cardiovascular mortality. In this respect, WHF holds promise as a endpoint for acute heart failure clinical trials to better elucidate the benefit of targeted novel therapies. Better understanding of the pathophysiology and a consensus on the definition of WHF will further improve our epidemiological and clinical understanding of this entity.

Abstract 168: The ADHERE Risk Model for In-hospital Worsening Heart Failure

Background: A subset of patients hospitalized with acute heart failure (HF) experience in-hospital worsening heart failure (WHF), defined as persistent or worsening signs or symptoms requiring an escalation of therapy. These patients are at increased risk for mortality and readmission resulting in increased costs, yet predictors for the development of WHF remain poorly characterized and an in-hospital WHF risk model has not been derived and validated. Methods: We analyzed data from the Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims to develop and validate a risk model for in-hospital WHF. Based on previous work, in-hospital WHF was defined by any of the following: use of inotropes or vasodilators &gt;12 hours after admission; initiation of mechanical circulatory support, hemodialysis, or ventilation after the first inpatient day; or transfer to an intensive care unit. We considered candidate risk prediction variables routinely assessed on admission including age, medical history, biomarkers and renal function. Logistic regression with robust standard errors was used to generate a risk model for in-hospital WHF in a 66% random derivation sample; the model was validated in the remaining 34% sample. We evaluated the calibration and discrimination of the model in both samples. Results: We evaluated 23,696 patients hospitalized with acute HF. Baseline characteristics were well-matched in the derivation and validation samples. The mean age was 81 years (standard deviation [SD] 7.7), mean systolic BP was 145 mm Hg (SD 29.8), and mean creatinine was 1.5 mg/dL (SD 0.9). The occurrence of in-hospital WHF was similar in the derivation, 15.4% (2403 of 15,640), and validation samples, 15.6% (1257 of 8056). After multivariable adjustment, the strongest predictors of in-hospital WHF were positive admission troponin and admission creatinine (Table). The model was well-calibrated. The risk model had strong discrimination in the derivation (c statistic=0.74) and validation samples (c statistic=0.72). Conclusion: The ADHERE WHF risk model is a validated clinical tool with good discrimination for use in hospitalized acute HF patients to identify patients at risk for in-hospital WHF. This tool may be useful to target treatment strategies for patients at high risk for in-hospital WHF.

Abstract 342: Differences in Health Care Utilization and Outcomes Based on Timing of In-Hospital Worsening Heart Failure

Background: Patients admitted with acute heart failure (AHF) may experience worsening symptoms requiring escalation of therapy during hospitalization. In-hospital worsening heart failure (WHF) is associated with worse in-hospital and post-discharge outcomes, but the association between timing of in-hospital WHF (i.e. early or late during hospitalization) and outcomes is unknown. Methods: Using the Acute Decompensated Heart Failure National Registry (ADHERE) and Medicare claims, we examined characteristics, outcomes, and costs of patients hospitalized for AHF. Based on previous work, in-hospital WHF was defined by use of inotropes or intravenous vasodilators, or initiation of mechanical circulatory support, hemodialysis, or ventilation. Patients with in-hospital WHF were categorized as early WHF (12-24 h after presentation) or late WHF (&gt; 24 h after presentation). Patients were considered to have a complicated presentation if they required escalation of therapy within 12 h of presentation, or an uncomplicated hospital course if they did not require escalation of therapy during hospitalization. Results: Of 62,908 patients, 3.2% (1,990 of 62,908) had early WHF, 6.7% (4,223 of 62,908) had late WHF, 24.4% (15,361 of 62,908) had a complicated presentation, and 65.7% (41,334 of 62,908) had an uncomplicated hospital course. Patients with late WHF had the highest rate of in-hospital and post-discharge mortality, and the highest hospital costs. The complicated presentation group had lower mortality, readmissions, and Medicare payments than the early WHF group. In an adjusted analysis, late WHF was associated with higher mortality compared to early WHF, and both early and late WHF were associated with more readmissions and resultant higher costs compared to patients with an uncomplicated hospital course (Table). Conclusions: While late WHF was associated with higher mortality compared to the other groups, both early and late WHF were associated with more frequent readmissions and higher healthcare costs compared to those with an uncomplicated hospital course. Prevention of both early and late WHF may be an important focus in the care of hospitalized patients with AHF.

Worsening heart failure during hospitalization for acute heart failure: Insights from the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF)

Despite initial in-hospital treatment of acute heart failure (HF), some patients experience worsening HF (WHF). There are limited data about the outcomes and characteristics of patients who experience in-hospital WHF. We assessed the characteristics and outcomes of patients with and without WHF in the ASCEND-HF trial. Worsening HF was defined as at least 1 symptom or sign of new, persistent, or WHF requiring additional intravenous inotropic/vasodilator or mechanical therapy during index hospitalization. We assessed the relationship between WHF and 30-day mortality, 30-day mortality or HF hospitalization, and 180-day mortality. We also assessed whether there was a differential association between early (days 1-3) vs late (day ≥4) WHF and outcomes. Of 7,141 patients with acute HF, 354 (5%) experienced WHF. Patients with WHF were more often male and had a history of atrial fibrillation or diabetes, lower blood pressure, and higher creatinine. After risk adjustment, WHF was associated with increased 30-day mortality (odds ratio 13.37, 95% CI 9.85-18.14), 30-day mortality or HF rehospitalization (odds ratio 6.78, 95% CI 5.25-8.76), and 180-day mortality (hazard ratio 3.90, 95% CI 3.14-4.86) (all P values < .0001). There was no evidence of a difference in outcomes between early and late WHF (all P values for comparison ≥ .2). Worsening HF during index hospitalization was associated with worse 30- and 180-day outcomes. Worsening HF may represent an important patient-centered outcome in acute HF and a focus of future treatments.

In-hospital worsening heart failure and associations with mortality, readmission, and healthcare utilization.

BackgroundA subset of patients hospitalized with acute heart failure experiences worsening clinical status and requires escalation of therapy. Worsening heart failure is an end point in many clinical trials, but little is known about its prevalence in clinical practice and its associated outcomes.Methods and ResultsWe analyzed inpatient data from the Acute Decompensated Heart Failure National Registry linked to Medicare claims to examine the prevalence and outcomes of patients with worsening heart failure, defined as the need for escalation of therapy at least 12 hours after hospital presentation. We compared patients with worsening heart failure to patients with an uncomplicated hospital course and patients with a complicated presentation. Of 63 727 patients hospitalized with acute heart failure, 11% developed worsening heart failure. These patients had the highest observed rates of mortality, all‐cause readmission, and Medicare payments at 30 days and 1 year after hospitalization (P < 0.001 for all comparisons). The adjusted hazards of 30‐day mortality were 2.56 (99% CI, 2.34 to 2.80) compared with an uncomplicated course and 1.29 (99% CI, 1.17 to 1.42) compared with a complicated presentation. The adjusted cost ratios for postdischarge Medicare payments at 30 days were 1.35 (99% CI, 1.24 to 1.46) compared with an uncomplicated course and 1.11 (99% CI, 1.02 to 1.22) compared with a complicated presentation.ConclusionsIn‐hospital worsening heart failure was common and was associated with higher rates of mortality, all‐cause readmission, and postdischarge Medicare payments. Prevention and treatment of in‐hospital worsening heart failure represents an important goal for patients hospitalized with acute heart failure.

Abstract 109: In-Hospital Worsening Heart Failure is Associated With Poor Patient Outcomes and Increased Health Care Utilization

Background: A subset of patients hospitalized with acute heart failure (AHF) experiences worsening clinical status while hospitalized and require escalation of therapy. This phenomenon, termed in-hospital worsening heart failure (WHF), is an endpoint for many clinical trials but limited data exist on the prevalence of WHF in clinical practice and associated outcomes. Methods: We analyzed inpatient data from Acute Decompensated Heart Failure National Registry (ADHERE) linked to Medicare claims data to describe outcomes and health care utilization of patients that developed WHF. In-hospital WHF was defined by any of the following: use of inotropes or intravenous vasodilators &gt;12 hours after admission; initiation of mechanical circulatory support, hemodialysis, or ventilation after the first inpatient day; or transfer to the ICU after initial admission to a regular hospital ward. Patients with WHF were compared to those with an uncomplicated hospital course and those that had a complicated hospital presentation, defined as requiring the above advanced therapies on arrival. Results: The study population consisted of 63,727 patients hospitalized between 01/2001 and 12/2004. Of these, WHF developed in 7032 (11%), 15,361 (24%) presented with a complicated presentation and 41,334 (65%) with an uncomplicated hospital course. Observed mean length of stay was longest in the WHF cohort (10.0 days) followed by complicated presentation (6.3 days) and uncomplicated course (4.8 days). Patients with WHF also had higher observed rates of mortality and all-cause readmission at 30 days and 1 year after discharge (P&lt;0.001; Figure). The adjusted hazard ratio for 30-day mortality was 2.56 (99% CI 2.34-2.80) for WHF compared to an uncomplicated hospital course and 1.29 (1.17-1.42) compared to a complicated presentation. Medicare payments were also higher for patients with WHF with an adjusted cost ratio at 30 days of 1.35 (99% CI 1.24-1.46) for WHF compared to an uncomplicated hospital course and 1.11 (1.02-1.22) compared to a complicated presentation. Conclusion: In a large, multicenter registry, in-hospital WHF was common and associated with higher rates of mortality, all-cause readmission, and Medicare payments. Preventing and treating WHF represents an important therapeutic target among patients hospitalized with AHF.

Serelaxin: A Novel Therapy for Acute Heart Failure with a Range of Hemodynamic and Non-Hemodynamic Actions

Acute heart failure (AHF) is characterized by high morbidity and mortality and high costs. Although the treatment of AHF has not changed substantially in recent decades, it is becoming clear that treatment strategies for AHF need to address both the immediate hemodynamic abnormalities giving rise to congestion as well as prevent organ damage that can influence long-term prognosis. Serelaxin, the recombinant form of human relaxin-2, a naturally occurring peptide hormone, has been found to significantly improve symptoms and signs of AHF, prevent in-hospital worsening heart failure, as well as significantly improve 180-day cardiovascular and all-cause mortality after a 48-h infusion commenced within 16 h of presentation (RELAX-AHF study). Available data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via anti-inflammatory, anti-cell death, anti-fibrotic, anti-hypertrophic, and pro-angiogenic effects. This manuscript describes the short- and long-term effects of serelaxin in AHF patients, analyzing how these effects can be explained by taking into account the range of hemodynamic and non-hemodynamic actions of serelaxin. In addition, this paper also addresses several aspects related to the role of serelaxin in the therapy of AHF that remain to be clarified and warrant further investigation.

Diuretic response in acute heart failure: clinical characteristics and prognostic significance

Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome. We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was -0.38 (-0.80 to -0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11-1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14-1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24-2.01, P < 0.001) in multivariable models. The proposed metric-weight loss indexed to diuretic dose-better captures a dose-response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal. Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.

Ivabradine Versus Beta-Blockers in Patients with Conduction Abnormalities or Left Ventricular Dysfunction Undergoing Cardiac Surgery.

IntroductionIn patients with conduction abnormalities or left ventricle (LV) dysfunction the use of β-blockers for post cardiac surgery rhythm control is difficult and controversial, with a paucity of information about other drugs such ivabradine used postoperatively. The objective of this study was to compare the efficacy and safety of ivabradine versus metoprolol used perioperatively in cardiac surgery patients with conduction abnormalities or LV systolic dysfunction.MethodsThis was an open-label, randomized clinical trial enrolling 527 patients with conduction abnormalities or LV systolic dysfunction undergoing coronary artery bypass grafting or valvular replacement, randomized to take ivabradine or metoprolol, or metoprolol plus ivabradine. The primary endpoints were the composites of 30-day mortality, in-hospital atrial fibrillation (AF), in-hospital three-degree atrioventricular block and need for pacing, in-hospital worsening heart failure (HF; safety endpoints), duration of hospital stay and immobilization and the above endpoint plus in-hospital bradycardia, gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus safety endpoint).ResultsHeart rate reduction and prevention of postoperative AF or tachyarrhythmia with combined therapy was more effective than with metoprolol or ivabradine alone during the immediate postoperative management of cardiac surgery patients. In the Ivabradine group, the frequency of early postoperative pacing and HF worsening was smaller than in the Metoprolol group and in combined therapy group. The frequency of primary combined endpoint was lower in the combined Ivabradine + Metoprolol group compared with the monotherapy groups.ConclusionConsidering efficacy and safety, the cardiac rhythm reduction after open heart surgery in patients with conduction abnormalities or LV dysfunction with ivabradine plus metoprolol emerged as the best treatment in this trial.Electronic supplementary materialThe online version of this article (doi:10.1007/s40119-013-0024-1) contains supplementary material, which is available to authorized users.