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Background: The absence of high quality, large-scale data that indicates definitive mortality benefits does not allow for firm conclusions on the role of intravenous vasodilators in acute heart failure. We aimed to investigate the associations between intravenous vasodilators and clinical outcomes in acute heart failure patients, with a specific focus on patient profiles and type of vasodilators., Methods: Data of 26,212 consecutive patients urgently hospitalised for a primary diagnosis of acute heart failure between 2009 and 2015 were extracted from a government-funded multicentre data registration system. Propensity scores were calculated with multiple imputations and 1:1 matching performed between patients with and without vasodilator use. The primary endpoint was inhospital mortality., Results: On direct comparison of the vasodilator and non-vasodilator groups after propensity score matching, there were no significant differences in the inhospital mortality rates (7.5% vs. 8.8%, respectively; P =0.098) or length of intensive/cardiovascular care unit stay and hospital stay between the two groups. However, there was a substantial difference in baseline systolic blood pressure by vasodilator type; favourable impacts of vasodilator use on inhospital mortality were observed among patients who had higher systolic blood pressures and those who had no atrial fibrillation on admission. Furthermore, when compared to nitrates, the use of carperitide (natriuretic peptide agent) was significantly associated with worse outcomes, especially in patients with intermediate systolic blood pressures., Conclusions: In acute heart failure patients, vasodilator use was not universally associated with improved inhospital outcomes; rather, its effect depended on individual clinical presentation: patients with higher systolic blood pressure and no atrial fibrillation seemed to benefit maximally from vasodilators., Trial Registration: UMIN-CTR identifier, UMIN000013128.

Objectives: Heart failure with preserved ejection fraction (HFpEF) is now recognized as a geriatric syndrome with multifactorial pathophysiology and clinical heterogeneity rather than a solely left ventricular diastolic dysfunction. Because the pathophysiology of HFpEF is suggested to differ by age, this study compared the clinical characteristics and prognostic factors between HFpEF patients aged 65 to 84 years and those aged 85 years or older., Design: Retrospective cohort study., Setting: The Tokyo CCU Network including 73 hospitals in Tokyo, Japan., Participants: Individuals aged 65 years or older with HFpEF (N = 4305)., Measurements: Very old patients were defined as those aged 85 years or older. Potential risk factors for in-hospital mortality were selected by univariate analyses, and those with a P value <.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors., Results: Prevalence of hypertension was significantly higher in very old patients, whereas prevalence of coronary artery disease, diabetes mellitus, hyperlipidemia, and smoking was significantly higher in patients aged 65 to 84 years. In very old patients, low systolic blood pressure (hazard ratio [HR] = .988), high serum creatinine level (HR = 1.34), and coexisting chronic obstructive pulmonary disease (COPD; HR = 2.01) were identified as independent risk factors for in-hospital mortality. In contrast, low systolic blood pressure (HR = .987) and low body mass index (HR = .935) were identified as independent risk factors in patients aged 65 to 84 years., Conclusion: Significant differences were observed in the clinical characteristics and prognostic factors for in-hospital mortality between HFpEF patients aged 65 to 84 and those 85 years and older. Of note, coexisting COPD was associated with significantly lower survival rate only in patients aged 85 years and older, suggesting the prognostic impact of concomitant pulmonary disease in HFpEF may increase with age. These results have implications for future research and management of older HFpEF patients. J Am Geriatr Soc 00:1-6, 2019. J Am Geriatr Soc 67:2123-2128, 2019., (© 2019 The American Geriatrics Society.)

Objective: No agents have been proven to improve survival in heart failure with preserved ejection fraction (HFpEF), but the phenotypic diversity of HFpEF suggests it may be possible to identify specific HFpEF phenotypes that will benefit from certain treatments. This study compared the risk factors for and prognostic impacts of treatments on in-hospital mortality between HFpEF patients with (+) and without (-) high blood pressure (HBP)., Methods: Data on 2238 consecutive HFpEF patients were extracted from Tokyo CCU Network data registry and analysed. HFpEF was defined as an ejection fraction greater than or equal to 50%; HBP was defined as elevated systolic blood pressure (>140 mmHg) at admission. Potential risk factors for in-hospital mortality were selected by univariate analyses and those with P < 0.10 were used in multivariate Cox regression analysis with forward selection (likelihood ratio) to identify significant factors., Results: In-hospital mortality was significantly lower for HFpEF + HBP than HFpEF - HBP patients (log-rank, P < 0.001). Independent risk factors for in-hospital mortality in HFpEF + HBP patients were older age (hazard ratio 1.069) and in-hospital treatment without beta-blockers (hazard ratio 7.946), whereas older age (hazard ratio 1.035), higher C-reactive protein (hazard ratio 1.047), higher B-type natriuretic peptide (hazard ratio 1.000) and in-hospital treatment without diuretics (hazard ratio 4.201) were identified as independent risk factors in HFpEF - HBP patients., Conclusion: There were significant differences in prognostic factors, including beta-blocker and diuretic treatments, for in-hospital mortality between HFpEF patients with and without HBP. These findings suggest possible individualized therapies for patients with HFpEF.

Obesity is known to be associated with the development of heart failure (HF). However, the relationship between the body mass index (BMI) and acute HF (AHF) remains to be elucidated. Eight hundred and eight AHF patients were enrolled in this study. The patients were assigned to four groups according to their BMI values: severely thin (n = 11, BMI <16), normal/underweight (n = 579, 16 ≤ BMI <25), overweight (n = 178, 25 ≤ BMI <30) and obese (n = 40, BMI ≥30). The patients in the severely thin group were more likely to be female, have systolic blood pressure (SBP) <100 mmHg and have valvular disease than normal/underweight patients. The patients in the overweight group were significantly younger than those in the normal/underweight, and those in the overweight group were more likely to have SBP ≥140 mmHg and hypertensive heart disease and less likely to have valvular disease than the patients in the normal/underweight group. The prognosis, including all-cause death, was significantly poorer among patients who were severely thin than those who were normal/underweight, overweight and significantly better among those who were overweight than those who were normal/underweight, severely thin and obese patients. A multivariate Cox regression model identified that severely thin [HR: 3.372, 95% confidence interval (CI) 1.362-8.351] and overweight (HR: 0.615, 95% CI 0.391-0.966) were independent predictors of 910-day mortality as the reference of normal/underweight. Overweight patients tended to have SBP ≥140 mmHg and be relatively young, while severely thin patients tended to have SBP <100 mmHg and be female. These factors were associated with a better prognosis of overweight patients and adverse outcomes in severely thin patients. These factors may contribute to the "obesity paradox" in severely decompensated AHF patients.

Atherosclerosis induces the elevation of uric acid (UA), and an elevated UA level is well known to lead to a poor prognosis in patients with acute heart failure (AHF). However, the prognostic value of atherosclerotic risk factors in hyperuricemic AHF patients remains to be elucidated. The data from 928 patients who were admitted to the intensive care unit (ICU) at Nippon Medical School Chiba Hokusoh Hospital between January 2001 and December 2014, and whose serum UA levels were measured were screened. A total of 394 AHF patients with hyperuricemia were enrolled in this study. The patients were assigned to a low-risk group (≤1 atherosclerosis risk factor) and a high-risk group (≥2 atherosclerosis risk factors) according to their number of risk factors. The patients in the low-risk group were more likely to have dilated cardiomyopathy, clinical scenario 3 than those in the high-risk group. The serum total bilirubin, blood urea nitrogen, C-reactive protein, and brain-type natriuretic peptide levels were significantly higher in the low-risk group than the high-risk group (p < 0.001, p = 0.005, p = 0.003, and p = 0.008, respectively). A multivariate Cox regression model revealed that the number of risk factors (number = 1, HR (hazard ratio) 0.243, 95 % CI 0.096-0.618, p = 0.003; number = 2, HR 0.253, 95 % CI 0.108-0.593, p = 0.002; number ≥3, HR 0.209, 95 % CI 0.093-0.472, p < 0.001), eGFR (per 1.0 mmol/l increase) (HR 0.977, 95 % CI 0.961-0.994, p = 0.007), and serum UA level (per 1 mg/dl increase) (HR 1.270, 95 % CI 1.123-1.435, p < 0.001) was an independent predictor of 1-year mortality. The prognosis, including all-cause death and HF events, was significantly poorer among the low-risk patients than among the high-risk patients. Atherosclerotic risk factors were not associated with a poor prognosis in patients with hyperuricemic AHF.

Background: The serum level of uric acid (UA) is a well-known prognostic factor for heart failure (HF) patients. However, the prognostic impact of hyperuricemia and the factors that induce hyperuricemia in acute HF (AHF) patients are not well understood., Methods and Results: Eight hundred eighty-nine AHF patients were enrolled in this study. The patients were assigned into a low UA group (UA≤7.0mg/dl, n=495) or a high UA group (UA>7.0mg/dl, n=394) according to their UA level on admission. A Kaplan-Meier curve showed that the survival rate of the low UA group was significantly higher than that of the high UA group. A multivariate Cox regression model identified that a high UA level (HR: 1.192, 95%CI 1.112-1.277) was an independent predictor of 180-day mortality. A multivariate logistic regression model for a high serum UA level on admission indicated that chronic kidney disease (CKD) (OR: 2.030, 95%CI: 1.298-3.176, p=0.002) and the administration of loop diuretics before admission (OR: 1.556, 95%CI: 1.010-2.397, p=0.045) were independent factors. The prognosis, including all-cause death and HF events, was significantly poorer among patients who had a high UA level who had previously used loop diuretics and among CKD patients with a high UA level than among other patients., Conclusions: The serum UA level was an independent predictor in patients who were hospitalized during an emergent situation for AHF. An elevated serum UA level on admission was associated with the presence of CKD and the use of loop diuretics. These factors were also associated with adverse outcomes in hyperuricemic patients with AHF., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

There have been few reports discussing the clinical significance of the season of admission of acute heart failure (AHF) patients. The data of 661 patients with AHF admitted to the intensive care unit were analyzed. Patients were assigned to a summer admission (Group-S, n = 113, between July and September), a winter admission (Group-W, n = 214, between December and February), or to the other seasons admission group (Group-O, n = 334). We evaluated the relationships between the seasonal variations and the clinical profiles, and the long-term prognosis. There were significantly more patients with cardiomyopathy and New York Heart Association class 4, and the serum levels of total bilirubin were significantly higher in Group-S (85.8, 24.8 %, and 0.60 [0.50-0.90]) than in Group-W (75.2, 15.4 %, and 0.60 [0.40-0.78]). The left ventricular ejection fraction on admission was significantly reduced and intravenous administration of dobutamine was used more frequently in Group-S (30.0 [25.0-46.0], 31.9 %) than in Group-W (34.4 [25.2-48.0], 20.6 %) and Group-O (35.0 [25.0-46.0], 19.8 %). The multivariate Cox regression model found that summer admission was independently associated with cardiovascular death (HR: 1.58, 95 % CI 1.01-2.48; p = 0.044) and heart failure (HF) events (HR: 1.55, 95 % CI 1.05-2.28; p = 0.028). The Kaplan-Meier curves showed that the cardiovascular death rate was significantly higher in Group-S than in Group-W and Group-O, and the HF events were significantly higher in Group-S than in Group-O. The summer admission AHF patients included sicker patients, and the prognosis in these patients was worse than in the patients admitted at other times.

Background: Different mechanisms of acute kidney injury (AKI) may exist for acute heart failure (AHF) patients compared with other patients., Methods and Results: We analyzed data from 282 patients with AHF. The biomarkers were measured within 30 min of admission. Patients were assigned to a no-AKI (n=213) or AKI group (Class R (n=49), Class I (n=15) or Class F (n=5)) using the RIFLE classifications on admission. We evaluated the relationships between the biomarkers and AKI, in-hospital mortality, all-cause death and HF events (HF re-admission, all-cause death) within 90 days. The serum heart-type fatty acid-binding protein (s-HFABP) levels were significantly higher in the AKI than in the no-AKI group, and the predictive biomarker for AKI was s-HFABP (odds ratio: 6.709; 95% confidence interval: 3.362-13.391). s-HFABP demonstrated an optimal balance between sensitivity and specificity (71.0%, 79.3%; area under the receiver-operating characteristic curve [AUC]=0.790) at 22.8 ng/ml for AKI, at 22.8 ng/ml for Class I/F (90.0%, 71.4%; AUC=0.836) and at 21.0 ng/ml for in-hospital mortality (74.3%, 70.0%; AUC=0.726). The Kaplan-Meier survival curves showed a significantly poorer prognosis in the high s-HFABP group (≥22.9 ng/ml) than in other groups., Conclusions: The s-HFABP level can indicate AKI on admission, and a high s-HFABP level is associated with a poorer prognosis for AHF patients.

Background: No scoring system for assessing acute heart failure (AHF) has been reported., Methods and Results: Data for 824 AHF patients were analyzed. The subjects were divided into an alive (n=750) and a dead group (n=74). We constructed a predictive scoring system based on eight significant APACHE II factors in the alive group [mean arterial pressure (MAP), pulse, sodium, potassium, hematocrit, creatinine, age, and Glasgow Coma Scale (GCS); giving each one point], defined as the APACHE-HF score. The patients were assigned to five groups by the APACHE-HF score [Group 1: point 0 (n=70), Group 2: points 1 and 2 (n=343), Group 3: points 3 and 4 (n=294), Group 4: points 5 and 6 (n=106), and Group 5: points 7 and 8 (n=11)]. A higher optimal balance was observed in the APACHE-HF between sensitivity and specificity [87.8%, 63.9%; area under the curve (AUC)=0.779] at 2.5 points than in the APACHE II (47.3%, 67.3%; AUC=0.558) at 17.5 points. The multivariate Cox regression model identified belonging to Group 5 [hazard ratio (HR): 7.764, 95% confidence interval (CI) 1.586-38.009], Group 4 (HR: 6.903, 95%CI 1.940-24.568) or Group 3 (HR: 5.335, 95%CI 1.582-17.994) to be an independent predictor of 3-year mortality. The Kaplan-Meier curves revealed a poorer prognosis, including all-cause death and HF events (death, readmission-HF), in Group 5 and Group 4 than in the other groups, in Group 3 than in Group 2 or Group 1, and in Group 2 than in Group 1., Conclusions: The new scoring system including MAP, pulse, sodium, potassium, hematocrit, creatinine, age, and GCS (APACHE-HF) can be used to predict adverse outcomes of AHF., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background:  Tolvaptan, an oral selective vasopressin 2 receptor antagonist that acts on the distal nephrons to cause a loss of electrolyte-free water, is rarely used during the acute phase of acute heart failure (AHF)., Methods and Results:  We investigated 183 AHF patients admitted to the intensive care unit and administered tolvaptan (7.5mg) with continuous intravenous furosemide, and then additionally at 12-h intervals until HF was compensated. When intravenous furosemide was changed to peroral use, the administration of tolvaptan was stopped. The patients were assigned to tolvaptan (n=52) or conventional treatment (n=131) groups. The amount of intravenous furosemide was significantly lower (35.4 [16.3-56.0] mg vs. 80.0 [30.4-220.0] mg), the urine volume was significantly higher on days 1 and 2 (3,691 [3,109-4,198] ml and 2,953 [2,128-3,592] ml vs. 2,270 [1,535-3,258] ml and 2,129 [1,407-2,906] ml) and the numbers of patients with worsening-AKI (step-up RIFLE Class to I or F) and Class F were significantly fewer (5.8% and 1.9% vs. 19.1% and 16.0%) in the tolvaptan group than in the conventional group, respectively. One of the specific medications indicated worsening-AKI and in-hospital mortality was tolvaptan (odds ratio [OR] 0.155, 95% confidence interval [CI] 0.037-0.657 and OR 0.191, 95% CI 0.037-0.985). The Kaplan-Meier curves showed that the death rate within 6 months was significantly lower in the tolvaptan group. The same result was found after propensity matching of the data., Conclusions:  Early administration of tolvaptan could prevent exacerbation of AKI and improve the prognosis for AHF patients.

Background: There have been few reports about the clinical significance of the time of admission for acute heart failure (AHF)., Methods: Five hundred thirty-one patients with AHF admitted to the intensive care unit (ICU) were analyzed. The patients were assigned to either the daytime HF group (n=195, visited from 08:00 to 20:00, Group D) or nighttime HF group (n=336, visited from 20:00 to 08:00, Group N). The clinical findings and outcomes were compared between these groups., Results: The systolic blood pressure (SBP), the number of patients with clinical scenario (CS) 1, and the heart rate (HR) were significantly higher in group N (SBP, 171.0±38.9mmHg; CS 1, 80.9%; HR, 116.9±28.0beats/min) than in group D (SBP, 154.2±37.1mmHg; CS 1, 66.2%; HR, 108.6±31.4beats/min). The patients in group N were more likely to have orthopnea (91.1%) than those in group D (70.3%). A multivariate logistic regression model identified a SBP ≥164mmHg [odds ratio (OR): 2.043; 95% confidence interval (CI): 1.383-3.109], HR ≥114beats/min (OR: 1.490; 95%CI: 1.001-2.218), and orthopnea (OR: 2.257; 95%CI: 1.377-3.701) to be independently associated with Group N. The length of ICU stay was shorter in group N (5.8±10.5 days) than in group D (7.8±11.5 days)., Conclusion: The nighttime HF was characterized by high SBP, high HR, and orthopnea, and the length of ICU stay was shorter in the nighttime HF group., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The relationship between acute kidney injury (AKI) in the acute phase of acute decompensated heart failure (ADHF) and patient outcome has not yet been reported., Methods and Results: Data for 625 patients with ADHF admitted to the intensive care unit were analyzed. No AKI occurred in 281 patients (no AKI) during the first 5 days. The AKI patients were assigned to 3 groups based on the timing: AKI present on admission and stable risk, injury, failure, loss, and endstage (RIFLE) class (stable early AKI; n=125), stepped-up RIFLE class (worsening early AKI; n=49), or AKI that occurred after admission (late AKI; n=170). The AKI patients were grouped into another 3 groups based on severity: class R (risk; n=214), class I (injury; n=73), or class F (failure; n=57). A multivariate logistic regression model found class I, class F, late AKI and worsening early AKI to be independently associated with in-hospital mortality. Kaplan-Meier survival curves showed that the survival rate in any-cause death during 2 years was significantly lower in class I, class F and the worsening early-AKI group, and there were significantly more HF events in class F and the worsening early-AKI group. There were significantly more class I and class F patients in the worsening early-AKI group., Conclusions: The presence of AKI on admission, worsening of AKI, and severe AKI (class I or class F) are associated with a poorer prognosis for ADHF patients.

Background and Purpose: The role of an arterial blood gas analysis in acute heart failure (AHF) remains unclear. The acid-base balance could help to treat AHF, and it might help to distinguish different types of AHF, while it might be associated with the AHF prognosis. The present study was conducted to determine the relationship between the arterial blood gas sample at the time of hospital admission and clinical findings on admission, outcomes., Methods and Results: Six hundred twenty-one patients with AHF admitted to the intensive care unit were analyzed. Patients were assigned to an alkalosis group (n=99, pH>7.45), normal group (n=178, 7.35≤ pH≤ 7.45), and acidosis group (n=344, pH<7.35). The clinical findings on admission and outcomes (in-hospital mortality and any-cause death within 2 years) were compared between the three groups. The white blood cell counts (WBC), serum levels of total protein, albumin, and glucose were significantly lower, and the serum levels of C-reactive protein (CRP) and total bilirubin were significantly higher in the alkalosis group. Patients with orthopnea were significantly fewer, and the systolic blood pressure (SBP) and heart rate (HR) were significantly lower in the alkalosis group. The results of a multivariate logistic regression model for in-hospital mortality found that alkalosis was an independent risk factor (p=0.017, odds ratio: 2.589; 95% confidence interval: 1.186-5.648). The Kaplan-Meier curves showed the prognosis for any-cause death to be significantly poorer in the alkalosis group than in the normal group (p=0.026)., Conclusions: The factors associated with alkalosis AHF were high CRP, bilirubin, and low WBC, glucose, total protein, and albumin. The patients with alkalosis AHF were less likely to have orthopnea with low SBP and HR. They suggested that the patients with alkalosis AHF might have experienced AHF for a few days and were associated with high mortality., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The relationship between the short-term prognosis of acute heart failure (AHF) and acute kidney injury (AKI) using the risk, injury, failure, and end stage (RIFLE) criteria has already been reported, however, the relationship between the long-term prognosis and AKI has not. We investigated the relationship between the long-term prognosis after discharge and AKI using the RIFLE criteria. Five hundred patients with AHF admitted to our intensive care unit were analyzed. Patients were assigned to a no AKI (n = 156), Class R (risk; n = 201), Class I (injury; n = 73), or Class F (failure; n = 70) using the most severe RIFLE classifications during hospitalization. We evaluated the relationships between the RIFLE classifications and any-cause death, and HF events including death and readmission for HF within 1 year. A multivariate logistic regression model found that Class I (P = 0.013, OR: 2.768; 95% CI: 1.236-6.199) and Class F (P < 0.001, OR: 7.920; 95% CI: 3.497-17.938) were independently associated with any-cause death, and Class F was associated with HF events (P = 0.001, OR: 3.486; 95% CI: 1.669-7.281). The Kaplan-Meier survival curves showed the prognosis, including death, to be significantly poorer in Class I than in no AKI and Class R, to be significantly poorer in Class F than in no AKI, Class R, and Class I, and the prognosis including HF events to be significantly poorer in Class F than in no AKI, Class R, and Class I. The presence of severe AKI (Class I and F) was independently associated with long-term mortality for AHF.

Background: There have been few reports about the clinical significance of the time of admission for acute heart failure (AHF). Methods: Five hundred thirty-one patients with AHF admitted to the intensive care unit (ICU) were ana-lyzed. The patients were assigned to either the daytime HF group (n = 195, visited from 08:00 to 20:00, Group D) or nighttime HF group (n = 336, visited from 20:00 to 08:00, Group N). The clinical findings and outcomes were compared between these groups. Results: The systolic blood pressure (SBP), the number of patients with clinical scenario (CS) 1, and the heart rate (HR) were significantly higher in group N (SBP, 171.0±38.9mmHg; CS 1, 80.9%; HR, 116.9±28.0beats/min) than in group D (SBP, 154.2±37.1 mmHg; CS 1, 66.2%; HR, 108.6 ± 31.4 beats/min). The patients in group N were more likely to have orthopnea (91.1%) than those in group D (70.3%). A multivariate logistic regression model identified a SBP >164 mmHg [odds ratio (OR): 2.043; 95% confidence interval (CI): 1.383-3.109], HR >114beats/min (OR: 1.490; 95%CI: 1.001-2.218), and orthopnea (OR: 2.257; 95%CI: 1.377-3.701) to be independently associated with Group N. The length of ICU stay was shorter in group N (5.8 ± 10.5 days) than in group D (7.8 ± 11.5 days). Conclusion: The nighttime HF was characterized by high SBP, high HR, and orthopnea, and the length of ICU stay was shorter in the nighttime HF group. [ABSTRACT FROM AUTHOR]