Acute Heart Failure Syndromes Patients Research Articles

Dose Response Relationship of RAS Blockers and Beta-Blockers in Patients with Acute Heart Failure Syndrome: A Nationwide Prospective Cohort Study, on Behalf of KorAHF Investigators

<h3>Purpose</h3> It remains unclear if patients with acute heart failure syndrome (AHFS) need to reach the maximally tolerated doses of renin-angiotensin system blockers (RASBs) or beta-blockers (BBs) to obtain a survival benefit. This study evaluated the dose-response relationship between RASBs or BBs and survival in AHFS patients. <h3>Methods</h3> In total, 5,331 patients in the Korean Acute Heart Failure registry were analyzed based on the doses of RASBs and BBs at discharge. Also, an additional analysis of 4,613 patients with dosage information at the first post-discharge follow-up visit was done. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test, and independent predictors of mortality were identified with the multivariable Cox proportional hazards model. <h3>Results</h3> In patients hospitalized with AHFS, RASB use at discharge was associated with a significant reduction in the risk of all-cause mortality. This effect was dose dependent for heart failure with reduced ejection fraction (HFrEF) but did not attain statistical significance for heart failure with preserved ejection fraction (HFpEF). BB use at discharge was associated with a reduction in all-cause mortality in HFrEF but not for HFpEF patients, although this was not dose dependent. At the first post-discharge follow-up visit, a significantly higher risk of all-cause mortality was associated with the maintenance or withdrawal of RASBs compared to up-titration of dose in HFrEF patients. <h3>Conclusion</h3> Using RASBs or BBs at discharge was associated with improved survival. A dose-response relationship between RASB and all-cause mortality was evident in AHFS patients with a reduced ejection fraction but not BBs. It is important to initiate and up-titrate RASBs to the maximally tolerated dose in AHFS patients during the transition period, especially for patients with a reduced ejection fraction.

The Prescription Characteristics, Efficacy and Safety of Spironolactone in Real-World Patients With Acute Heart Failure Syndrome: A Prospective Nationwide Cohort Study.

BackgroundRandomized clinical trials of spironolactone showed significant mortality reduction in patients with heart failure with reduced ejection fraction. However, its role in acute heart failure syndrome (AHFS) is largely unknown.AimTo investigate the prescription characteristics, efficacy and safety of spironolactone in real-world patients with AHFS.Methods5,136 AHFS patients who survived to hospital discharge using a nationwide prospective registry in Korea were analyzed. The primary efficacy outcome was 3-year all-cause mortality.ResultsSpironolactone was prescribed in 2,402 (46.8%) at discharge: <25 mg in 890 patients (37.1%), ≥25 mg, and <50 mg in 1,154 patients (48.0%), and ≥50 mg in 358 patients (14.9%). Patients treated with spironolactone had a lower proportion of chronic renal failure and renal replacement therapy during hospitalization and had lower serum creatinine level than those who did not. In overall patients, 3-year mortality was not different in both groups (35.9 vs. 34.5%, P = 0.279). The incidence of renal injury and hyperkalemia was 2.2% and 4.3%, respectively, at the first follow-up visit. The treatment effect of spironolactone on mortality was different across subpopulations according to LVEF. The use of spironolactone was associated with a significant reduction in 3-year morality in patients with LVEF ≤ 26% (33.8 vs. 44.3%, P < 0.001; adjusted HR 0.79, 95% CI 0.64–0.97, P = 0.023), but not in patients with LVEF > 26%.ConclusionsAlthough spironolactone was frequently used at lower doses in real-world practice, use of spironolactone significantly reduced 3-year mortality in patients with severely reduced LVEF with acceptable safety profile. However, our findings remain prone to various biases and further prospective randomized controlled studies are needed to confirm these findings.

A dose-response relationship of renin-angiotensin system blockers and beta-blockers in patients with acute heart failure syndrome: a nationwide prospective cohort study.

It remains unclear if patients with acute heart failure syndrome (AHFS) need to reach the maximally tolerated doses of renin-angiotensin system blockers (RASBs) or beta-blockers (BBs) to obtain a survival benefit. This study evaluated the dose-response relationship between RASBs or BBs and survival in AHFS patients. In total, 5331 patients in the Korean Acute Heart Failure registry were analysed based on the doses of RASBs and BBs at discharge. In AHFS patients, RASB use at discharge was associated with a significant reduction in all-cause mortality risk. This effect was dose-dependent for heart failure with reduced ejection fraction (HFrEF) but did not attain statistical significance for heart failure with preserved ejection fraction (HFpEF). BB use at discharge was associated with reduced all-cause mortality in HFrEF patients but not in HFpEF patients. In an additional analysis of 4613 patients with dosage information at the first post-discharge follow-up visit, a significantly higher mortality risk was associated with the maintenance or withdrawal of RASBs compared with up-titrating the dose in HFrEF patients. Using RASBs or BBs at discharge was associated with improved survival. A dose-response relationship between RASBs and all-cause mortality was evident in AHFS patients with a reduced ejection fraction but not BBs. It is important to initiate and up-titrate RASBs to the maximally tolerated dose in AHFS patients during the transition period, especially for patients with a reduced ejection fraction.

Prognostic Significance of Left Axis Deviation in Acute Heart Failure Patients with Left Bundle branch block: an Analysis from the Korean Acute Heart Failure (KorAHF) Registry.

Background and ObjectivesThe prognostic impact of left axis deviation (LAD) on clinical outcomes in acute heart failure syndrome (AHFS) with left bundle branch block (LBBB) is unknown. The aim of this study was to determine the prognostic significance of axis deviation in acute heart failure patients with LBBB.MethodsBetween March 2011 and February 2014, 292 consecutive AHFS patients with LBBB were recruited from 10 tertiary university hospitals. They were divided into groups with no LAD (n=189) or with LAD (n=103) groups according to QRS axis <−30 degree. The primary outcome was all-cause mortality.ResultsThe median follow-up duration was 24 months. On multivariate analysis, the rate of all-cause death did not significantly differ between the normal axis and LAD groups (39.7% vs. 46.6%, adjusted hazard ratio, 1.01; 95% confidence interval, 0.66, 1.53; p=0.97). However, on the multiple linear regression analysis to evaluate the predictors of the left ventricular ejection fraction (LVEF), presence of LAD significantly predicted a worse LVEF (adjusted beta, −3.25; 95% confidence interval, −5.82, −0.67; p=0.01). Right ventricle (RV) dilatation was defined as at least 2 of 3 electrocardiographic criteria (late R in lead aVR, low voltages in limb leads, and R/S ratio <1 in lead V5) and was more frequent in the LAD group than in the normal axis group (p<0.001).ConclusionsAmong the AHFS with LBBB patients, LAD did not predict mortality, but it could be used as a significant predictor of worse LVEF and RV dilatation (Trial registry at KorAHF registry, ClinicalTrial.gov, NCT01389843).

Heterogeneous impact of body mass index on in-hospital mortality in acute heart failure syndromes: An analysis from the ATTEND Registry.

Although the obesity paradox may vary depending upon clinical background factors such as age, gender, aetiology of heart failure and comorbidities, the reasons underlying the heterogeneous impact of body mass index (BMI) on in-hospital cardiac mortality under various conditions in patients with acute heart failure syndromes (AHFSs) remain unclear. Among 4617 hospitalised patients with AHFSs enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, the patient characteristics and in-hospital cardiac mortality rates in those with low BMI (BMI <25 kg/m2, n = 3263) were compared to those with high BMI (BMI ⩾25 kg/m2, n = 1354). Compared to the high-BMI group, the low-BMI group was significantly older, less likely to be male and to have hypertensive or idiopathic dilated aetiologies and more likely to have valvular aetiologies and a history of prior hospitalisation for AHFS. The low-BMI group also had lower prevalence rates of diabetes, dyslipidaemia, hypertension and atrial fibrillation and higher prevalence rates of anaemia and chronic obstructive pulmonary disease. In addition, cardiac mortality was significantly higher in the low-BMI group than in the high-BMI group (5.5 vs. 1.5%, p < 0.001). Logistic regression analysis demonstrated that low BMI was a predictor of cardiac mortality (odds ratio: 3.89, 95% confidence interval: 2.44-6.21). In subgroup analyses, the impact of BMI on cardiac mortality differed depending on the presence of hypertensive aetiology, hypertension, chronic obstructive pulmonary disease and hyponatremia (all p < 0.05), although there were no interactions between the impacts of BMI and age, gender, other aetiologies, prior hospitalisation, diabetes, anaemia, cardio-renal function and in-hospital management. It is necessary to appreciate the obesity paradox in AHFS patients, and a patient's heterogeneous background should also be considered.

A response-adaptive design of initial therapy for emergency department patients with heart failure

Finding safe and effective treatments for acute heart failure syndrome (AHFS) is a high priority. More than 80% of patients with AHFS who present to emergency departments are treated identically with intravenous diuretics, despite recognition of the syndrome's heterogeneity. We hypothesize that matching patient profiles with “personalized” AHFS treatments will improve outcomes. Matching multiple heterogeneous clinical profiles with a number of potentially effective treatments requires an adaptive trial design that can adjust for these complexities. We propose a Bayesian response-adaptive randomization trial design for AHFS patients. Baseline information collected for each patient with AHFS prior to randomization includes blood pressure, renal function, and dyspnea severity. The primary outcome is discharge readiness within 23h of presentation and no unplanned emergency visits or admissions for acute heart failure within 7days of discharge. We use a Bayesian logistic regression model to characterize the association between primary outcome and patient profile. We adaptively randomize patients to one of five treatments, basing the randomization probability on the cumulative data from the ongoing trial and fitting results from the regression model. Simulations show high probability of selecting the best treatment corresponding to the patient's profile while allocating more patients to the efficacious treatments within the trial.

Association of anemia and renal dysfunction with in-hospital mortality among patients hospitalized for acute heart failure syndromes with preserved or reduced ejection fraction

The aim of this study was to evaluate the association of anemia and renal dysfunction with in-hospital outcomes in acute heart failure syndromes patients with preserved or reduced ejection fraction. Of the 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4693 patients were evaluated to investigate the association among anemia, renal dysfunction, a preserved or reduced ejection fraction and in-hospital mortality. They were divided into four groups based on hemoglobin and estimated glomerular filtration rate at admission. The in-hospital mortality rate was 5.9% and 6.9% of the preserved and reduced ejection fraction groups, respectively. After adjustment for multiple comorbidities, there was no association of either anemia or renal dysfunction alone with in-hospital mortality in preserved ejection fraction patients, but the combination of anemia and renal dysfunction was associated with a somewhat higher risk of in-hospital mortality than that without either condition (odds ratio (OR), 2.75; 95% confidence interval (CI), 0.72-10.41; p=0.137). In reduced ejection fraction patients, adjusted analysis showed that a significantly higher risk of in-hospital mortality was associated with anemia alone (OR, 2.56; 95% CI, 1.10 -5.94; p=0.029) and with anemia plus renal dysfunction (OR, 2.34; 95% CI, 1.09-5.03; p=0.029) relative to the risk without either condition. Our findings demonstrate that anemia combined with renal dysfunction is not a risk factor for in-hospital mortality in patients with a preserved ejection fraction, whereas anemia is an independent predictor of in-hospital mortality risk in reduced ejection fraction patients regardless of renal dysfunction.

Relationship of renal insufficiency and clinical features or comorbidities with clinical outcome in patients hospitalised for acute heart failure syndromes.

Renal insufficiency is a well-known predictor of adverse events in patients with acute heart failure syndromes (AHFS). However, it remains unclear whether there are subgroups of AHFS patients in whom renal insufficiency is related to a higher risk of adverse events because of the heterogeneity of this patient population. Therefore, we investigated the relationship between renal insufficiency, clinical features or comorbidities, and the risk of adverse events in patients with AHFS. Of 4842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 4628 patients (95.6%) were evaluated in the present study in order to assess the relationship of renal insufficiency and clinical features or comorbidities with all-cause mortality after admission. Renal insufficiency was defined as an estimated creatinine clearance of ⩽40 mL/min (calculated by the Cockcroft-Gault formula) at admission. The median follow-up period after admission was 524 (391-789) days. The all-cause mortality rate after admission was significantly higher in patients with renal insufficiency (36.7%) than in patients without renal insufficiency (14.4%). Stratified analysis was performed in order to explore the heterogeneity of the influence of renal insufficiency on all-cause mortality. This analysis revealed that an ischaemic aetiology and a history of diabetes, atrial fibrillation, serum sodium, and anaemia at admission had significant influences on the relationship between renal insufficiency and all-cause mortality. The present study demonstrated that the relationship between renal insufficiency and all-cause mortality of AHFS patients varies markedly with clinical features or comorbidities and the mode of presentation due to the heterogeneity of this patient population.

Risk stratification based on nutritional screening on admission: Three-year clinical outcomes in hospitalized patients with acute heart failure syndrome

BackgroundSeveral blood tests are commonly used to assess nutritional status, including serum albumin levels (SAL) and lymphocyte counts (LC). The aim of this study is to investigate whether nutritional screening on admission can be used to determine risk levels for adverse clinical events in acute heart failure syndrome (AHFS) patients. MethodsIn 432 consecutive AHFS patients, we measured SAL and LC and prospectively followed the patients for their combined clinical events (all-cause death and re-hospitalization for heart failure) for three years from admission. The classification and regression tree (CART) tool identified the cut-off criteria for SAL and LC to differentiate among patients with different risks of clinical events as 3.5g/dl and 963/mm3, respectively. ResultsThe CART tool classified 15.5% patients as high risk, 15.7% as intermediate risk, and 68.8% as low risk. The CART for nutritional status (CART-NS) values were strongly correlated with combined clinical events [hazard ratio of 2.13 (low vs high risk), 95% confidence interval of 1.42–3.16, p<0.001], even after adjusting for plasma brain natriuretic peptide levels. The CART-NS analysis improved the specificity (89.5%) of predictions of clinical outcomes with the comparable sensitivity (36.3%) compared with the use of a single criterion (SAL <3.5g/dl: 70.2, 42.4% or LC <963/mm3: 73.4, 41.7%, respectively). ConclusionA substantial proportion of AHFS patients are at risk of malnutrition, and this risk is associated with poor clinical outcomes. We demonstrate that this algorithm for nutritional screening, even in emergency clinical settings, can determine risk levels for further adverse events in AHFS patients.

Intravenous nicorandil for treatment of the urgent phase acute heart failure syndromes: A randomized, controlled trial.

Vasodilators, such as nitroglycerin, have long been first-line treatments for acute heart failure syndromes (AHFS). Nicorandil is a vasodilator with dual potassium channel opening and nitrate properties. However, there are no randomized controlled studies of intravenous nicorandil safety and efficacy in the urgent phase AHFS. We examined the symptomatic, hemodynamic, and echocardiographic effects and safety, and 60-day clinical outcomes of intravenous nicorandil, in addition to standard therapy, in patients with AHFS in the urgent phase. In this prospective, randomized controlled trial, 106 AHFS patients were randomized within one hour of arrival to receive either standard therapy (control group, n=56) or standard therapy plus simultaneous intravenous nicorandil (0.2 mg/kg bolus followed by 0.2 mg/kg/h for 24 h; nicorandil group, n=50). Outcomes were assessed at 60 days. Patients in the nicorandil group exhibited greater improvement of dyspnea as measured by change in a five-point Likert scale compared to those in the control group (after 1 h infusion: p=0.006, 6 h; p<0.001). The nicorandil group also showed significantly improved E/e', an estimate of left ventricular filling pressure, at 1 and 24 h ( p=0.001 and p=0.004, respectively). In addition, intravenous nicorandil therapy was safe and did not cause side effects such as excessive hypotension or reflex tachycardia. However, it did not reduce all-cause mortality and readmission rates at 60 days. Addition of intravenous nicorandil to standard therapy for urgent phase AHFS improved dyspnea and left ventricular diastolic function but not 60-day outcome.

Heterogeneity of the prognostic significance of B-type natriuretic peptide levels on admission in patients hospitalized for acute heart failure syndromes

BackgroundWe hypothesized that variation in baseline characteristics of patients with acute heart failure syndromes (AHFS) affects the prognostic significance of B-type natriuretic peptide (BNP) levels because of heterogeneity of this patient population. We evaluated the association of elevated BNP levels on admission with an increased risk of adverse clinical outcomes in subgroups of patients hospitalized for AHFS. MethodsThis study included patients from the acute decompensated heart failure syndromes (ATTEND) study, a multicenter prospective cohort of 4501 AHFS patients with BNP data on admission. ResultsThe geometric mean BNP level was 654.9pg/mL (95% confidence interval: 636.1–674.2), and the optimal cut-off value for all-cause death was 1157pg/mL. All-cause mortality after admission was significantly higher in patients with high BNP levels (>1157pg/mL) than in those with low BNP levels (≤1157pg/mL) (median follow-up: 508days, log-rank P<0.001). Subgroup analyses were performed to evaluate the heterogeneity of the prognostic significance of BNP levels. The effect of high BNP levels on the risk of all-cause mortality was significantly greater in the subgroup of patients with a non-hypertensive etiology, low creatinine levels (<1.3mg/dL), and high sodium levels (≥135mEq/L) than in those without these factors (P=0.024, P<0.001, and P<0.001 for the interaction, respectively). ConclusionsThe present analysis shows that underlying etiology of heart failure (i.e., hypertensive), renal function, and sodium levels should be considered for assessing the clinical significance of elevated BNP levels on admission in relation to the risk of adverse outcome after hospitalization for AHFS.

Abstract 12552: A Novel Predictor of Weight Change During Hospitalization in Patients With Acute Heart Failure Syndromes in the Emergency Department

Introduction: Recent data showed acute heart failure syndromes (AHFS) could occur without weight gain, and often be triggered by rather a redistribution of fluids to the lungs without systemic congestion. In this subtype of AHFS, excessive diuretic and vasodilator therapy as first-line decongestion therapy in the emergency department (ED) may lead to dehydration and hypotension, subsequently resulting in serous organ hypoperfusion. Therefore, an accurate assessment of body fluid status is essential in AHFS. Methods: We studied 196 consecutive AHFS patients (77±12 years, 54% men, left ventricular ejection fraction 37±15%), who discharged after restoration of clinical stability (length of hospital stay 18±8 days). We collected clinical, laboratory, imaging and weight information. Measurements of total body water (TBW) and extracellular water (ECW) using bio-impedance analysis (BIA) were performed immediately at admission to the ED. Patients were divided into 2 groups according to the median % weight change (%WC) during hospitalization. Results: Weight and brain natriuretic peptide levels significantly decreased following decongestion therapy (from 59.0±14.3 to 52.9±12.9 kg, and from 779 [508-1289] to 285 [151-547] pg/ml, respectively, both p&lt;0.001). High-%WC group (≥9.4%) had lower systolic blood pressure (159±35 vs. 171±40 mmHg), and higher prevalence of day-time admission (79 vs. 54%), peripheral edema (82 vs. 43%) and pleural effusion on chest radiography (88 vs. 71%), and larger inferior vena cava diameter (20±5 vs. 17±5 mm) and lower tricuspid annular plane systolic excursion (14±4 vs. 16±4 mm) on echocardiography, and higher estimated glomerular filtration rate (eGFR) (58±29 vs. 46±21 ml/min/1.73m2), lower serum total protein level (6.5±0.6 vs. 6.8±0.7 g/dl), and higher ECW/TBW (0.423±0.015 vs. 0.405±0.013) compared with low-%WC group (p&lt;0.01 for all). Multiple linear regression analysis revealed that pleural effusion, eGFR, and ECW/TBW were significantly associated with %WC. ECW/TBW correlated most strongly with %WC (r=0.61, p&lt;0.0001). Conclusions: ECW/TBW helps enable emergency physicians to implement goal-directed treatment more rapidly and appropriately avoiding both dehydration and volume retention in AHFS.

Serial Changes in Serum ACE 2 and Plasma Ang (1-7) Concentration of Acute Heart Failure Syndrome Patients with Standard Therapy

Recently the existence of the ACE2-Ang(1-7)-Mas receptor-axis and the organ-protective effect by activating this axis have been revealed. We reported that serum ACE2 concentration level is higher and plasma Ang(1-7) concentration level is lower in AHFS-patients than healthy volunteers. Although there are no reports about its serial changes. To evaluate the serial changes of serum ACE2 concentration and plasma Ang(1-7) concentration for hospitalized AHFS-patients. Seventy-three patients hospitalized with acute heart failure at our institute between Nov. 2012 and May 2014. Plasma renin activity, serum ACE, plasma Ang II, serum ACE2, plasma Ang(1-7), and plasma aldosterone concentrations were measured immediately after the patient were able to sit up, and then one and three months after the onset of the standard therapy then evaluated the serial changes. Average age was 63±14 years old, 22% male, and the cause of acute AHFS was 29 ischemic heart disease, 43 non-ischemic heart disease. There were no serial changes in plasma renin activity, serum ACE, plasma Ang II, serum ACE2 and plasma aldosterone concentration. Plasma Ang(1-7) concentration significantly increased (2.43±1.18 ng/ml vs 3.02±1.98 ng/ml vs 3.35±2.01 ng/ml, p±0.05). Plasma Ang(1-7) concentration increased in AHFS patients with standard therapy.

Presentation blood glucose and death, hospitalization, and future diabetes risk in patients with acute heart failure syndromes.

PurposeThe prognostic implications of blood glucose on a wide range of outcomes including early mortality, hospitalizations, and incident diabetes diagnoses have not been fully elucidated in acute heart failure syndromes (AHFS).MethodsIn a population-based cohort of 16 524 AHFS patients presenting to the emergency department (ED) in Ontario, Canada between 2004 and 2007, we performed a competing risk analysis for 30-day mortality, new diabetes diagnoses, and hospitalization outcomes. Presentation blood glucose concentrations were categorized as follows: 3.9–6.1 [referent], >6.1–7.8, >7.8–9.4, >9.4–11.1, and >11.1 mmol/L.ResultsAmong AHFS patients without diabetes presenting to the ED (n = 9275), blood glucose >6.1 mmol/L (n = 5252, 56.6%) was associated with increased risks of all-cause death [hazard ratio (HR) range: 1.26 (95% CI 1.05–1.50) to 1.50 (95% CI 1.11–2.02)], and cardiovascular death [HR range: 1.28 (95% CI 1.03–1.59) to 1.64 (95% CI 1.16–2.33)]. Among AHFS patients with diabetes (n = 7249), presenting blood glucose >11.1 mmol/L (n = 2286, 31.5%) was associated with increased risks of all-cause death (HR 1.48, 95% CI 1.10–2.00) and diabetes-related hospitalizations (HR 1.39, 95% CI; 1.20–1.61). Presentation blood glucose >9.4 mmol/L was associated with increased risks of hospitalization for HF or cardiovascular causes [HR range: 1.09 (95% CI 1.02–1.17) to 1.15 (95% CI 1.07–1.24)] in all patients. With higher presentation blood glucose, the risk of incident diabetes diagnosis increased, with adjusted HRs of 1.61 (>6.1–7.8 mmol/L) to 3.61 (>11.1 mmol/L) among those without the condition at baseline (all P < 0.001).ConclusionsMildly elevated presentation blood glucose was associated with early death, future diabetes, and hospitalizations for diabetes, HF, and cardiovascular causes among patients with AHFS.

Positive hs-TnI at Emergency Department is an Independent Predictor for In-hospital Mortality in Acute Heart Failure Syndrome Patients

Positive hs-TnI at Emergency Department is an Independent Predictor for In-hospital Mortality in Acute Heart Failure Syndrome Patients

Impact of pulmonary artery catheter on outcome in patients with acute heart failure syndromes with hypotension or receiving inotropes: From the ATTEND Registry

BackgroundRandomized controlled trials concerning pulmonary artery catheters (PACs) use have yielded little evidence of their beneficial effects on survival. This study aimed to evaluate the association between PACs and in-hospital mortality in patients with acute heart failure syndromes (AHFS). MethodsThe Acute Decompensated Heart Failure Syndromes (ATTEND) Registry is a prospective, observational, multicenter cohort study performed in Japan, since April 2007. We analyzed data from the ATTEND Registry and evaluated the effectiveness of PAC in AHFS treatment using propensity score-matching and the Cox proportional hazards model. ResultsFinal follow-up examinations of the 4842 patients were conducted in December 2012. During the study period, 813 patients (16.8%) were managed with PACs, of which 502 patients (PAC group) were propensity score-matched with 502 controls (Control group). Of the 1004 score-matched patients, 22 (4.4%) patients from the Control group and 7 (1.4%) from the PAC group died. The risk of all-cause death was lower in the PAC group than that in the Control group [hazard ratio (HR), 0.3; 95% confidence interval (CI), 0.13–0.70; p=0.006]. PAC-guided therapy decreased all-cause mortality in patients with lower systolic blood pressure (SBP≤100mmHg; HR, 0.09; 95% CI, 0.01–0.70; p=0.021) or inotropic therapy (HR, 0.22; 95% CI, 0.08–0.57; p=0.002). ConclusionsThis study revealed that appropriate PAC use effectively decreases in-hospital mortality in AHFS patients, particularly those with lower SBP or receiving inotropic therapy, suggesting that real-world PAC use could improve AHFS management.

Nitrates for acute heart failure syndromes

Current drug therapy for acute heart failure syndromes (AHFS) consists mainly of diuretics supplemented by vasodilators or inotropes. Nitrates have been used as vasodilators in AHFS for many years and have been shown to improve some aspects of AHFS in some small studies. The aim of this review was to determine the clinical efficacy and safety of nitrate vasodilators in AHFS. To quantify the effect of different nitrate preparations (isosorbide dinitrate and nitroglycerin) and the effect of route of administration of nitrates on clinical outcome, and to evaluate the safety and tolerability of nitrates in the management of AHFS. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (1950 to July week 2 2011) and EMBASE (1980 to week 28 2011). We searched the Current Controlled Trials MetaRegister of Clinical Trials (compiled by Current Science) (July 2011). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction. Randomised controlled trials comparing nitrates (isosorbide dinitrate and nitroglycerin) with alternative interventions (frusemide and morphine, frusemide alone, hydralazine, prenalterol, intravenous nesiritide and placebo) in the management of AHFS in adults aged 18 and over. Two authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using the Cochrane Collaboration tool for assessing risk of bias. Four studies (634 participants) met the inclusion criteria. Two of the included studies included only patients with AHFS following acute myocardial infarction (AMI); one study excluded patients with overt AMI; and one study included participants with AHFS with and without acute coronary syndromes.Based on a single study, there was no significant difference in the rapidity of symptom relief between intravenous nitroglycerin/N-acetylcysteine and intravenous frusemide/morphine after 30 minutes (fixed-effect MD -0.30, 95% CI -0.65 to 0.05), 60 minutes (fixed-effect MD -0.20, 95% CI -0.65 to 0.25), three hours (fixed-effect MD 0.20, 95% CI -0.27 to 0.67) and 24 hours (fixed-effect MD 0.00, 95% CI -0.31 to 0.31). There is no evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following outcome measures: requirement for mechanical ventilation, systolic blood pressure (SBP) change after three hours and 24 hours, diastolic blood pressure (DBP) change after 30, 60 and 90 minutes, heart rate change at 30 minutes, 60 minutes, three hours and 24 hours, pulmonary artery occlusion pressure (PAOP) change after three hours and 18 hours, cardiac output (CO) change at 90 minutes and three hours and progression to myocardial infarction. There is a significantly higher incidence of adverse events after three hours with nitroglycerin compared with placebo (odds ratio 2.29, 95% CI 1.26 to 4.16) based on a single study. There was no consistent evidence to support a difference in AHFS patients receiving intravenous nitrate vasodilator therapy or alternative interventions with regard to the following secondary outcome measures: SBP change after 30 and 60 minutes, heart rate change after 90 minutes, and PAOP change after 90 minutes. None of the included studies reported healthcare costs as an outcome measure. There were no data reported by any of the studies relating to the acceptability of the treatment to the patients (patient satisfaction scores).Overall there was a paucity of relevant quality data in the included studies. Assessment of overall risk of bias in these studies was limited as three of the studies did not give sufficient detail to allow assessment of potential risk of bias. There appears to be no significant difference between nitrate vasodilator therapy and alternative interventions in the treatment of AHFS, with regard to symptom relief and haemodynamic variables. Nitrates may be associated with a lower incidence of adverse effects after three hours compared with placebo. However, there is a lack of data to draw any firm conclusions concerning the use of nitrates in AHFS because current evidence is based on few low-quality studies.

Relationship between systolic blood pressure and preserved or reduced ejection fraction at admission in patients hospitalized for acute heart failure syndromes

BackgroundAmong patients with acute heart failure syndromes (AHFS), it has been reported that those with a reduced left ventricular ejection fraction (LVEF) tend to be hypotensive or normotensive, whereas those with a preserved LVEF tend to be hypertensive. However, it is unclear whether the systolic blood pressure (SBP) is actually associated with the LVEF in AHFS patients. Therefore, we evaluated the relationship between the SBP at admission and LVEF in patients hospitalized for AHFS. MethodsData from the Acute Decompensated Heart Failure Syndromes (ATTEND) registry were analyzed to investigate the relationship between the admission SBP and a preserved or reduced LEF in AHFS patients. Of the 4,842 patients enrolled in this registry, 4,831 patients (99.8%) were evaluated. They were divided into SBP quartiles (SBP <120, 120 to <140, 140 to <160, and ≥160mmHg), and LVEF was compared among the quartiles. ResultsPatients with an admission SBP <120mmHg were more likely to have a reduced LVEF than a preserved LVEF. In contrast, patients with an admission SBP ≥120mmHg were equally likely to have a preserved or reduced LVEF, indicating that there was no relation between a higher admission SBP and the LVEF. ConclusionsOur data indicated that an elevated SBP at admission may not be useful to distinguish between a preserved or reduced LVEF in the urgent phase of AHFS. However, taking geographical differences of AHFS into consideration, further investigations are needed to clarify the relationship between admission SBP and LVEF in patients hospitalized for AHFS.

Prognostic Impact of Blood Urea Nitrogen Changes During Hospitalization in Patients With Acute Heart Failure Syndrome

Elevated blood urea nitrogen (BUN) observed in patients hospitalized for acute heart failure syndrome (AHFS) may represent increased neurohumoral activation. The purpose of this study was to examine the prognostic impact of BUN changes during hospitalization on the long-term prognosis of AHFS patients. The Tohoku Acute Heart Failure Registry (n=497) is a multicenter retrospective cohort study enrolling AHFS patients who were admitted in 2007. The 337 survivors (mean age, 76 years; 52% male) were divided into 3 groups according to tertiles of BUN change during hospitalization: Decreased (D-BUN, ΔBUN (BUN level at discharge-BUN level at hospitalization)≤-1.63 mg/dl, n=112); Unchanged (U-BUN, ΔBUN-1.64 to 5.73 mg/dl, n=113); Increased (I-BUN, ΔBUN>5.73 mg/dl, n=112). The D-BUN group had higher prevalence of lowest glomerular filtration rate during hospitalization, whereas the I-BUN group had higher systolic blood pressure. During a median follow-up period of 2.3 years after discharge, the Kaplan-Meier curve showed that D-BUN and I-BUN had worse prognosis compared with U-BUN. Multivariable logistic model showed that all-cause death was more frequent in I-BUN (hazard ratio, 2.94; 95% confidence interval, 1.51-5.73; P<0.001). Subgroup analysis revealed that BUN increase during hospitalization was associated with all-cause death, regardless of renal function. AHFS patients with a BUN increase during hospitalization have worse long-term prognosis, independent of renal function.

Excessive wave reflections on admission predict post‐discharge events in patients hospitalized due to acute heart failure

The role of wave reflections in the pathogenesis of acute heart failure syndrome (AHFS) remains unclear. The present study investigated the long-term prognostic values of the carotid augmentation index (cAI), carotid augmented pressure (cAP), amplitude of the reflected pressure wave from a decomposed carotid pressure wave (Pb), and carotid pulse pressure (PP) on admission in patients hospitalized due to AHFS. A total of 120 patients (72 ± 14 years, 83.3% men) hospitalized due to AHFS (55.8% with systolic heart failure) were enrolled. Measures of cAI, cAP, Pb, carotid PP, and carotid-femoral pulse wave velocity (cf-PWV) by tonometry and thoracic fluid content (TFC) by impedance cardiography were obtained within 24 h of admission. N-terminal pro brain natriuretic peptide (NT-proBNP) levels were determined before discharge. Patients were followed up for a median of 601 days, accruing 66 adverse events including re-hospitalization for heart failure, non-fatal myocardial infarction, non-fatal stroke, and death. In univariate Cox analysis, all measures significantly predicted post-discharge events (all P < 0.05). In multivariate analysis, cAP [hazard ratio per SD and 95% confidence interval: 1.32 (1.051-1.67), P = 0.017], Pb [1.44 (1.13-1.84), P = 0.004] and carotid PP [1.35 (1.05-1.73), P = 0.019], but not cAI, TFC, or cf-PWV, significantly independently predicted events with adjustments for age, estimated glomerular filtration rate, haemoglobin, and NT-proBNP. On-admission measures of wave reflection magnitude, including cAP, Pb, and carotid PP, may be useful for predicting long-term outcomes in AHFS patients. The results support a major role for wave reflection in the pathogenesis of AHFS.