Tricuspid regurgitation in elderly patients with acute heart failure: insights from the KCHF registry.

AIMS: Several studies demonstrated that tricuspid regurgitation (TR) is associated with poor clinical outcomes. However, data on patients with TR who experienced acute heart failure (AHF) remains scarce. The purpose of this study is to evaluate the association between TR and clinical outcomes in patients admitted with AHF, using a large-scale Japanese AHF registry. METHODS AND RESULTS: The current study population consisted of 3735 hospitalized patients due to AHF in the Kyoto Congestive Heart Failure (KCHF) registry. TR grades were assessed according to the routine clinical practice at each participating centre. We compared the baseline characteristics and outcomes according to the severity of TR. The primary outcome was all-cause death. The secondary outcome was hospitalization for heart failure (HF). The median age of the entire study population was 80 (interquartile range: 72-86) years. One thousand two hundred five patients (32.3%) had no TR, while mild, moderate, and severe TR was found in 1537 patients (41.2%), 776 patients (20.8%), and 217 patients (5.8%), respectively. Pulmonary hypertension, significant mitral regurgitation, and atrial fibrillation/flutter were strongly associated with the development of moderate/severe of TR, while left ventricular ejection fraction <50% was inversely associated with it. Among 993 patients with moderate/severe TR, the number of patients who underwent surgical intervention for TR within 1 year was only 13 (1.3%). The median follow-up duration was 475 (interquartile range: 365-653) days with 94.0% follow-up at 1 year. As the TR severity increased, the cumulative 1 year incidence of all-cause death and HF admission proportionally increased ([14.8%, 20.3%, 23.4%, 27.0%] and [18.9%, 23.0%, 28.5%, 28.4%] in no, mild, moderate, and severe TR, respectively). Compared with no TR, the adjusted risks of patients with mild, moderate, and severe TR were significant for all-cause death (hazard ratio [95% confidence interval]: 1.20 [1.00-1.43], P = 0.0498, 1.32 [1.07-1.62], P = 0.009, and 1.35 [1.00-1.83], P = 0.049, respectively), while those were not significant for hospitalization for HF (hazard ratio [95% confidence interval]: 1.16 [0.97-1.38], P = 0.10, 1.19 [0.96-1.46], P = 0.11, and 1.20 [0.87-1.65], P = 0.27, respectively). The higher adjusted HRs of all the TR grades relative to no TR were significant for all-cause death in patients aged <80 years, but not in patients aged ≥80 years with significant interaction. CONCLUSIONS: In a large Japanese AHF population, the grades of TR could successfully stratify the risk of all-cause death. However, the association of TR with mortality was only modest and attenuated in patients aged 80 or more. Further research is warranted to evaluate how to follow up and manage TR in this elderly population.

Atrial fibrillation in patients with severe aortic stenosis.

BACKGROUND: There has been no previous report evaluating the long impact of atrial fibrillation (AF) on the clinical outcomes stratified by the initial management [conservative or aortic valve replacement (AVR)] strategies of severe aortic stenosis (AS). METHODS: We analyzed 3815 patients with severe AS enrolled in the CURRENT AS registry. Patients with AF were defined as those having a history of AF when severe AS was found on the index echocardiography. The primary outcome measure was a composite of aortic valve-related death or hospitalization for heart failure. RESULTS: The cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with AF than in those without AF (44.2 % versus 33.2 %, HR 1.54, 95 % CI 1.35-1.76). After adjusting for confounders, the risk of AF relative to no AF remained significant (HR 1.34, 95 % CI 1.16-1.56). The magnitude of excess adjusted risk of AF for the primary outcome measure was greater in the initial AVR stratum (N = 1197, HR 1.95, 95 % CI 1.36-2.78) than in the conservative stratum (N = 2618, HR 1.26, 95 % CI 1.08-1.47) with a significant interaction (p = 0.04). In patients with AF, there was a significant excess adjusted risk of paroxysmal AF (N = 254) relative to chronic AF (N = 528) for the primary outcome measure (HR 1.34, 95 % CI 1.01-1.78). CONCLUSIONS: In patients with severe AS, concomitant AF was independently associated with worse clinical outcomes regardless of the initial management strategies. In those patients with conservative strategy, paroxysmal AF is stronger risk factor than chronic AF.

Longitudinal changes in nailfold videocapillaroscopy findings differ by myositis-specific autoantibody in idiopathic inflammatory myopathy.

OBJECTIVE: To assess the longitudinal changes in nailfold videocapillaroscopy (NVC) in patients expressing myositis-specific autoantibodies [anti-aminoacyl-tRNA synthetase (ARS), anti-transcriptional intermediary factor 1 (TIF1), and anti-melanoma differentiation-associated gene 5 (MDA5)]. METHODS: This study was performed retrospectively, at a single site, on an observational cohort. Seventy-one idiopathic inflammatory myopathy patients were included (25 patients expressed anti-MDA5 Abs, 24 patients expressed anti-TIF1 Abs, and 22 patients expressed anti-ARS Abs). NVC findings included giant, enlarged, and reduced capillaries, haemorrhages, capillary ramification, disorganization of the vascular array, and capillary loss. NVC findings were compared from baseline to after disease activity stabilization. RESULTS: The frequency of enlarged capillaries at baseline was different among the three groups, and was significantly higher in patients with anti-TIF1 Abs compared with those with anti-ARS Abs (88% vs 55%, P < 0.05). Reduced capillaries were significantly increased in patients with anti-TIF1 Abs compared with those with anti-MDA5 (96% vs 44%, P < 0.0001) or anti-ARS Abs (96% vs 50%, P < 0.0005). Both enlarged and reduced capillaries improved after stabilization in patients with anti-MDA5 Abs (P < 0.0001 and P < 0.05, respectively). These improvements were not observed in patients expressing anti-TIF1 and anti-ARS Abs. However, a significant reduction in haemorrhages was observed in all three groups (P < 0.0001 for each group). CONCLUSIONS: The results of this study demonstrate that longitudinal changes in NVC findings may vary depending on myositis-specific Ab expression. Therefore, it is crucial to assess individual NVC findings separately, as each finding may impact disease activity in a different manner.

Cytokine-producing B-cell balance associates with skin fibrosis in patients with systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and lung fibrosis. Over 90% of patients with SSc are positive for autoantibodies. In addition, the serum levels of B-cell activating factor, a potent B-cell stimulator, are correlated with SSc severity and activity. Thus, B cells play an important role in SSc pathogenesis. However, two opposing B-cell subsets exist: effector B cells (Beff) and regulatory B cells (Breg). Interleukin (IL)-6-producing Beff have been shown to promote scleroderma in a mouse model, whereas IL-10-producing Breg inhibit scleroderma development. In the present study, we investigated the clinical association of effector and regulatory B cells in patients with SSc. The blood levels of IL-6-producing Beff and IL-10-producing Breg were measured in 30 patients with SSc and 21 healthy subjects by flow cytometry. The frequency of IL-6-producing Beff in the blood was significantly (p < 0.0001) elevated in patients with SSc (median, 56.2%; range, 35.3-81.3%) compared with that in healthy controls (median, 41.3%; range, 21.0-61.3%). In contrast, the frequency of IL-10-producing Breg in the blood was significantly (p < 0.05) decreased in patients with SSc (median, 1.4%; range, 0.5-2.8%) compared with that in healthy controls (median, 2.0%; range, 1.1-3.8%). The Beff/Breg ratio was significantly increased in patients with SSc. In addition, the Beff/Breg ratio was positively correlated with the skin score and extent of interstitial lung disease. These results suggest that dysregulation of effector and regulatory B-cell balance contributes to SSc pathogenesis.

Appetite loss at discharge from acute decompensated heart failure: Observation from KCHF registry.

OBJECTIVE: The complex link between nutritional status, protein and lipid synthesis, and immunity plays an important prognostic role in patients with heart failure. However, the association between appetite loss at discharge and long-term outcome remains unclear. METHODS: The Kyoto Congestive Heart Failure registry is a prospective cohort study that enrolled consecutive patients hospitalized for acute decompensated heart failure (ADHF) in Japan. We assessed 3528 patients alive at discharge, and for whom appetite and follow-up data were available. We compared one-year clinical outcomes in patients with and without appetite loss at discharge. RESULTS: In the multivariable logistic regression analysis using 19 clinical and laboratory factors with P value < 0.1 by univariate analysis, BMI < 22 kg/m2 (odds ratio (OR): 1.57, 95% confidence interval (CI): 1.11-2.24, P = 0.01), CRP >1.0mg/dL (OR: 1.49, 95%CI: 1.04-2.14, P = 0.03), and presence of edema at discharge (OR: 4.30, 95%CI: 2.99-6.22, P<0.001) were associated with an increased risk of appetite loss at discharge, whereas ambulatory status (OR: 0.57, 95%CI: 0.39-0.83, P = 0.004) and the use of ACE-I/ARB (OR: 0.70, 95% CI: 0.50-0.98, P = 0.04) were related to a decreased risk in the presence of appetite loss. The cumulative 1-year incidence of all-cause death (primary outcome measure) was significantly higher in patients with appetite loss than in those without appetite loss (31.0% vs. 15.0%, P<0.001). The excess adjusted risk of appetite loss relative to no appetite loss remained significant for all-cause death (hazard ratio (HR): 1.63, 95%CI: 1.29-2.07, P<0.001). CONCLUSIONS: Loss of appetite at discharge was associated with worse 1-year mortality in patients with ADHF. Appetite is a simple, reliable, and useful subjective marker for risk stratification of patients with ADHF.

Public assistance in patients with acute heart failure: a report from the KCHF registry.

AIMS: There is a scarcity of data on the post-discharge prognosis in acute heart failure (AHF) patients with a low-income but receiving public assistance. The study sought to evaluate the differences in the clinical characteristics and outcomes between AHF patients receiving public assistance and those not receiving public assistance. METHODS AND RESULTS: The Kyoto Congestive Heart Failure registry was a physician-initiated, prospective, observational, multicentre cohort study enrolling 4056 consecutive patients who were hospitalized due to AHF for the first time between October 2014 and March 2016. The present study population consisted of 3728 patients who were discharged alive from the index AHF hospitalization. We divided the patients into two groups, those receiving public assistance and those not receiving public assistance. After assessing the proportional hazard assumption of public assistance as a variable, we constructed multivariable Cox proportional hazard models to estimate the risk of the public assistance group relative to the no public assistance group. There were 218 patients (5.8%) receiving public assistance and 3510 (94%) not receiving public assistance. Patients in the public assistance group were younger, more frequently had chronic coronary artery disease, previous heart failure hospitalizations, current smoking, poor medical adherence, living alone, no occupation, and a lower left ventricular ejection fraction than those in the no public assistance group. During a median follow-up of 470 days, the cumulative 1 year incidences of all-cause death and heart failure hospitalizations after discharge did not differ between the public assistance group and no public assistance group (13.3% vs. 17.4%, P = 0.10, and 28.3% vs. 23.8%, P = 0.25, respectively). After adjusting for the confounders, the risk of the public assistance group relative to the no public assistance group remained insignificant for all-cause death [hazard ratio (HR), 0.97; 95% confidence interval (CI), 0.69-1.32; P = 0.84]. Even after taking into account the competing risk of all-cause death, the adjusted risk within 180 days in the public assistance group relative to the no public assistance group remained insignificant for heart failure hospitalizations (HR, 0.93; 95% CI, 0.64-1.34; P = 0.69), while the adjusted risk beyond 180 days was significant (HR, 1.56; 95% CI, 1.07-2.29; P = 0.02). CONCLUSIONS: The AHF patients receiving public assistance as compared with those not receiving public assistance had no significant excess risk for all-cause death at 1 year after discharge or a heart failure hospitalization within 180 days after discharge, while they did have a significant excess risk for heart failure hospitalizations beyond 180 days after discharge. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) and https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

Current use of inotropes according to initial blood pressure and peripheral perfusion in the treatment of congestive heart failure: findings from a multicentre observational study.

OBJECTIVES: Current guidelines restrict the use of inotropes for the treatment for heart failure (HF) unless the patients are hypotensive or hypoperfused because of safety concerns. This study sought to characterise the contemporary real-world use of inotropes and associated long-term outcomes according to systolic blood pressure (sBP) and perfusion status. DESIGN: A multicentre prospective cohort study. SETTING: This study was nested from the Kyoto Congestive Heart Failure registry, which included consecutive Japanese patients admitted for HF. PARTICIPANTS: We categorised 3995 patients into two groups: sBP ≥90 mm Hg and warm profile group, and sBP <90 mm Hg or cold profile group. In each group, patients were stratified across the use of inotropes within 24 hours of hospital presentation. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was all-cause death throughout follow-up. Secondary outcomes included cardiovascular death throughout follow-up, all-cause death during index hospitalisation and after discharge, and HF hospitalisation. RESULTS: A total of 793 patients (20%) presented with sBP <90 mm Hg or cold profile, whereas 3202 patients had sBP ≥90 mm Hg and warm profile; 276 patients (35%) in the sBP <90 mm Hg/cold group and 312 patients (10%) in the sBP ≥90 mm Hg/warm group received initial inotropic treatment. Adjusted excess risk of inotrope use relative to no inotrope for the primary outcome measure was significant in the sBP ≥90 mm Hg/warm group (adjusted HR), 1.36; 95% CI 1.09 to 1.72, p=0.006) but not in the sBP <90 mm Hg/cold group (adjusted HR, 1.28, 95% CI 0.96 to 1.69, p=0.09). Risk for postdischarge all-cause death and HF hospitalisation was not significantly different between the patients with inotropes and no inotropes in both groups. CONCLUSION: Inotrope use in the absence of hypotension and hypoperfusion is still common, but associated with a worse long-term prognosis. TRIAL REGISTRATION NUMBER: UMIN000015238.

Ischemic Stroke in Acute Decompensated Heart Failure: From the KCHF Registry.

Background Heart failure (HF) is a known risk factor for ischemic stroke, but data regarding ischemic stroke during hospitalization for acute decompensated HF (ADHF) are limited. Methods and Results We analyzed the data from a multicenter registry (Kyoto Congestive Heart Failure [KCHF] Registry) that enrolled 4056 consecutive patients with ADHF in Japan (mean age, 78 years; men, 2238 patients [55%]; acute coronary syndrome [ACS], 239 patients [5.9%]). We investigated the incidence and predictors of ischemic stroke during hospitalization for ADHF. During the hospitalization, 63 patients (1.6%) developed ischemic stroke. The median interval from admission to the onset of ischemic stroke was 7 [interquartile range: 2-14] days, and the most common underlying cause was cardioembolism (64%). Men (OR, 1.87; 95%CI, 1.11-3.24), ACS (OR, 2.31; 95%CI, 1.01-4.93), absence of prior HF hospitalization (OR, 2.21; 95%CI, 1.24-4.21), and high B-type natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) levels (above the median) at admission (OR, 3.15; 95%CI, 1.84-5.60) were independently associated with ischemic stroke. In patients without ACS, the independent risk factors for ischemic stroke were fully consistent with those in the main analysis. Higher quartiles of BNP/NT-proBNP levels were significantly associated with higher incidence of ischemic stroke (P for trend, <0.001). Patients with ischemic stroke showed higher in-hospital mortality, longer length of hospital stay, and poorer functional status at discharge. Conclusions During hospitalization for ADHF, 1.6% of the patients developed ischemic stroke. Men, ACS, absence of prior HF hospitalization, and high BNP/NT-proBNP levels at admission were independently associated with ischemic stroke.

Clinical outcome after surgical aortic valve replacement in low-risk Japanese patients with severe aortic stenosis.

Two randomized control trials demonstrated that transcatheter aortic valve implantation was associated with 1-2 year clinical outcomes comparable or even superior to surgical aortic valve replacement (SAVR) in low surgical risk patients with severe aortic stenosis (AS). However, no previous study has reported the clinical outcomes after SAVR in Japanese patients with low surgical risk. From 3815 consecutive patients enrolled in the CURRENT AS registry, we retrieved 220 patients who underwent SAVR in reference to the inclusion and exclusion criteria of the PARTNER 3 trial. Age and surgical risk score in the current study population were comparable to those in the PARTNER 3 trial (Age: 75 years versus 74 years, and STS-PROM score: 2.3 versus 1.9). The cumulative incidence of a composite all-cause death or stroke was comparable between the current study population and the SAVR patients in the PARTNER 3 trial both at 30-day (2.3% versus 3.3%), and at 1-year (4.1% versus 4.9%). The clinical outcomes of SAVR in low surgical risk patients with severe AS selected from a real world Japanese registry according to the inclusion and exclusion criteria of the PARTNER 3 trial was favorable and numerically comparable to those of SAVR patients in the PARTNER 3 trial.

Long-Term Impact of Diabetes Mellitus on Initially Conservatively Managed Patients With Severe Aortic Stenosis.

BACKGROUND: Although diabetes mellitus (DM) is a common comorbidity of aortic stenosis (AS), clinical evidence about the long-term effect of DM on patients with AS is insufficient.Methods and Results:Data were acquired from CURRENT AS, a large Japanese multicenter registry that enrolled 3,815 patients with severe AS. Patients without initial valve replacement were defined as the conservative group; among them, 621 (23.4%) had DM, whereas 1997 did not. The DM group was further divided into 2 groups according to insulin treatment (insulin-treated DM, n=130; non-insulin treated DM, n=491). The primary outcome was a composite of aortic valve (AV)-related death and heart failure (HF) hospitalization. Secondary outcomes were AV-related death, HF hospitalization, all-cause death, cardiovascular death, sudden death, and surgical or transcatheter AV replacement during follow up. As a result, DM was associated with higher risk for the primary outcome (52.8% vs. 42.9%, P<0.001), with a statistically significant adjusted hazard ratio (HR 1.33, 95% confidence interval: 1.14-1.56, P<0.001). All secondary outcomes were not significantly different between DM and non-DM patients after adjusting for confounding factors, except for HF hospitalization. Insulin use was not associated with higher incidence of primary or secondary outcome. CONCLUSIONS: In initially conservatively managed patients with AS, DM was independently associated with higher risk for a composite of AV-related death or HF hospitalization; however, insulin use was not associated with poor outcomes.

Association of an increase in serum albumin levels with positive 1-year outcomes in acute decompensated heart failure: A cohort study.

BACKGROUND: Despite the prognostic importance of hypoalbuminemia, the prognostic implication of a change in albumin levels has not been fully investigated during hospitalization in patients with acute decompensated heart failure (ADHF). METHODS: Using the data from the Kyoto Congestive Heart Failure registry on 3160 patients who were discharged alive for acute heart failure hospitalization and in whom the change in albumin levels was calculated at discharge, we evaluated the association with an increase in serum albumin levels from admission to discharge and clinical outcomes by a multivariable Cox hazard model. The primary outcome measure was a composite of all-cause death or hospitalization for heart failure. FINDINGS: Patients with increased albumin levels (N = 1083, 34.3%) were younger and less often had smaller body mass index and renal dysfunction than those with no increase in albumin levels (N = 2077, 65.7%). Median follow-up was 475 days with a 96% 1-year follow-up rate. Relative to the group with no increase in albumin levels, the lower risk of the increased albumin group remained significant for the primary outcome measure (hazard ratio: 0.78, 95% confidence interval: 0.69-0.90: P = 0.0004) after adjusting for confounders including baseline albumin levels. When stratified by the quartiles of baseline albumin levels, the favorable effect of increased albumin was more pronounced in the lower quartiles of albumin levels, but without a significant interaction effect (interaction P = 0.49). CONCLUSIONS: Independent of baseline albumin levels, an increase in albumin during index hospitalization was associated with a lower 1-year risk for a composite of all-cause death and hospitalization in patients with acute heart failure.

C-reactive protein at discharge and 1-year mortality in hospitalised patients with acute decompensated heart failure: an observational study.

OBJECTIVES: To examine the association of a high C-reactive protein (CRP) level at discharge from an acute decompensated heart failure (ADHF) hospitalisation with the 1-year clinical outcomes. DESIGN: A post-hoc subanalysis of a prospective cohort study of patients hospitalised for ADHF (using the Kyoto Congestive Heart Failure (KCHF) registry) between October 2014 and March 2016 with a 1-year follow-up. SETTING: A physician-initiated multicentre registry enrolled consecutive hospitalised patients with ADHF for the first time at 19 secondary and tertiary hospitals in Japan. PARTICIPANTS: Among the 4056 patients enrolled in the KCHF registry, the present study population consisted of 2618 patients with an available CRP value both on admission and at discharge and post-discharge clinical follow-up data. We divided the patients into two groups, those with a high CRP level (>10 mg/L) and those with a low CRP level (≤10 mg/L) at discharge from the index hospitalisation. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was all-cause death after discharge from the index hospitalisation. The secondary outcome measures were heart failure hospitalisations, cardiovascular death and non-cardiovascular death. RESULTS: The high CRP group and low CRP group included 622 patients (24%) and 1996 patients (76%), respectively. During a median follow-up period of 468 days, the cumulative 1-year incidence of the primary outcome was significantly higher in the high CRP group than low CRP group (24.1% vs 13.9%, log-rank p<0.001). Even after a multivariable analysis, the excess mortality risk in the high CRP group relative to the low CRP group remained significant (HR, 1.43; 95% CI, 1.19 to 1.71; p<0.001). The excess mortality risk was consistent regardless of the clinically relevant subgroup factors. CONCLUSIONS: A high CRP level (>10 mg/L) at discharge from an ADHF hospitalisation was associated with an excess mortality risk at 1 year. TRIAL REGISTRATION DETAILS: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

Determinants and prognostic implications of instantaneous wave-free ratio in patients with mild to intermediate coronary stenosis: Comparison with those of fractional flow reserve.

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured. In the total lesions, mean diameter stenosis was 48.6% ± 9.0%, and physiological significance, defined by FFR of 0.80 or less or by iFR of 0.92 or less, was observed in 32.5% or 33.5%, respectively. Mismatch between iFR and FFR was observed in 18.1% of the lesions. Clinical factors did not predict FFR value; however, gender, diabetes mellitus, aortic stenosis, anemia, high-sensitivity CRP value, and renal function predicted iFR value. In multivariate logistic analysis after adjustment for FFR value, gender (p < 0.001), diabetes mellitus (p = 0.005), aortic stenosis (p = 0.016), high-sensitivity CRP (p < 0.001), and renal function (p = 0.003) were all independent predictors of iFR value. In Kaplan-Meier analysis, the baseline iFR predicted the subsequent major cardiovascular events (MACE) (hazard ratio, 2.40; 95% CI, 1.16-4.93; p = 0.018) and the results of the iFR-guided strategy for predicting rates of MACE and myocardial infarction/revascularization were superior to those of the FFR-guided strategy. In conclusion, significant clinical factors predicted iFR value, which affected the prognostic capacity. The iFR-guided strategy may be superior in patients with mild to intermediate stenosis.

Sex differences in patients with acute decompensated heart failure in Japan: observation from the KCHF registry.

AIMS: The association between sex and long-term outcome in patients hospitalized for acute decompensated heart failure (ADHF) has not been fully studied yet in Japanese population. The aim of this study was to determine differences in baseline characteristics and management of patients with ADHF between women and men and to compare 1-year outcomes between the sexes in a large-scale database representing the current real-world clinical practice in Japan. METHODS AND RESULTS: Kyoto Congestive Heart Failure registry is a prospective cohort study enrolling consecutive patients hospitalized for ADHF in Japan among 19 centres. Baseline characteristics, clinical presentation, management, and 1-year outcomes were compared between men and women. A total of 3728 patients who were alive at discharge constituted the current study population. There were 1671 women (44.8%) and 2057 men. Women were older than men [median (IQR): 83 (76-88) years vs. 77 (68-84) years, P < 0.0001]. Hypertensive and valvular heart diseases were more prevalent in women than in men (28.0% vs. 22.5%, P = 0.0001; and 26.9% vs. 14.0%, P < 0.0001, respectively), whereas ischaemic aetiology was less prevalent in women than in men (20.0% vs. 32.5%, P < 0.0001). Women less often had reduced left ventricular ejection fraction (<40%) than men (27.5% vs. 45.1%, P < 0.0001). The cumulative incidence of all-cause death or hospitalization for heart failure was not significantly different between women and men (33.6% vs. 34.3%, P = 0.71), although women were substantially older than men. After multivariable adjustment, the risk of all-cause death or hospitalization for heart failure was significantly lower among women (adjusted hazard ratio: 0.84, 95% confidence interval: 0.74-0.96, P = 0.01). CONCLUSIONS: Women with heart failure were older and more often presented with preserved EF with a non-ischaemic aetiology and were associated with a reduced adjusted risk of 1-year mortality compared with men in the Japanese population.

Association with Controlling Nutritional Status (CONUT) Score and In-hospital Mortality and Infection in Acute Heart Failure.

The high controlling nutritional status (CONUT) score that represents poor nutritional status has been acknowledged to have prognostic implications in chronic heart failure. We aimed to investigate its role in acute decompensated heart failure (ADHF). Using the data from an multicenter registry that enrolled 4056 consecutive patients hospitalized for ADHF in Japan between 2014 and 2016, we analyzed 2466 patients in whom data on the components of the CONUT score at hospital presentation were available. The decrease of lymphocyte count and total cholesterol was assigned with 0, 1, 2, and 3 points and the decrease of albumin was assigned with 0, 2, 4, and 6 points according to the severity. We defined low CONUT score as 0-4 (N = 1568) and high CONUT score as 5-9 (N = 898). The patients in the high CONUT score group were older and more likely to have a smaller body mass index than those in the low CONUT score group. The high CONUT score group was associated with higher rate of death and infection during the index hospitalization compared to the low CONUT score group (9.0% versus 4.4%, and 21.9% versus 12.7%, respectively). After adjusting for confounders, the excess risk of high relative to low CONUT score for mortality and infection was significant (OR: 1.61, 95%CI: 1.05-2.44, and OR: 1.66, 95%CI: 1.30-2.12, respectively). The effect was incremental according to the score. High CONUT score was associated with higher risk for in-hospital mortality and infection in an incremental manner in patients hospitalized for ADHF.

Risk factors and clinical outcomes of functional decline during hospitalisation in very old patients with acute decompensated heart failure: an observational study.

OBJECTIVE: To investigate the prevalence and risk factors of functional decline during hospitalisation and its relationship with postdischarge outcomes in very old patients with acute decompensated heart failure (ADHF) hospitalisation. DESIGN: Prospective cohort study between 1 October 2014 and 31 March 2016. SETTING: A physician-initiated, multicentre study of consecutive patients admitted for ADHF in 19 hospitals throughout Japan. PARTICIPANTS: Among 3555 patients hospitalised for ADHF (median age (IQR), 80 (71-86) years; 1572 (44%) women), functional decline during the index hospitalisation occurred in 528 patients (15%). PRIMARY AND SECONDARY OUTCOMES: The primary outcome measure was a composite of all-cause death or heart failure (HF) hospitalisation after discharge. The secondary outcome measures were all-cause death, HF hospitalisation, and a composite of all-cause death or all-cause hospitalisation. RESULTS: The independent risk factors for functional decline included age ≥80 years (OR 2.71; 95% CI 2.09 to 3.51), female (OR 1.32; 95% CI 1.05 to 1.67), prior stroke (OR 1.67; 95% CI 1.28 to 2.19), dementia (OR 2.26; 95% CI 1.74 to 2.95), ambulatory before admission (OR 1.74; 95% CI 1.29 to 2.35), elevated body temperature (OR 1.91; 95% CI 1.31 to 2.79), New York Heart Association class III or IV on admission (OR 1.54; 95% CI 1.07 to 2.22), decreased albumin levels (OR 1.76; 95% CI 1.32 to 2.34), hyponatraemia (OR 1.49; 95% CI 1.10 to 2.03) and renal dysfunction (OR 1.55; 95% CI 1.22 to 1.98), after multivariable adjustment. The cumulative 1-year incidence of the primary outcome in the functional decline group was significantly higher than that in the no functional decline group (50% vs 31%, log-rank p<0.001). After adjusting for baseline characteristics, the higher risk of the functional decline group relative to the no functional decline group remained significant (adjusted HR 1.46; 95% CI 1.24 to 1.71; p<0.001). CONCLUSIONS: Independent risk factors of functional decline in very old patients with ADHF were related to both frailty and severity of HF. Functional decline during ADHF hospitalisation was associated with unfavourable postdischarge outcomes. TRIAL REGISTRATION NUMBER: NCT02334891, UMIN000015238.

Transcatheter Aortic Valve Implantation vs. Surgical Aortic Valve Replacement for Severe Aortic Stenosis in Real-World Clinical Practice.

BACKGROUND: There are no data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) outcomes in real clinical practice in Japan. METHODS AND RESULTS: We combined 2 independent registries, the K-TAVI Registry (a 6-center prospective registry of consecutive patients who underwent TAVI) and the CURRENT AS Registry (a large, 27-center registry of 3,815 consecutive patients with severe aortic stenosis [AS]). In the K-TAVI Registry, 338 patients underwent TAVI with SAPIEN XT balloon-expandable valves from October 2013 to January 2016, whereas in the CURRENT AS Registry 237 patients with severe AS underwent SAVR from January 2003 to December 2011. Propensity score matching was conducted, with final cohort comprising 306 patients. The cumulative 2-year incidence of all-cause death and heart failure (HF) hospitalization did not differ significantly between the TAVI and SAVR groups (13.7% vs. 12.4% [P=0.81] and 7.9% vs 3.9% [P=0.13], respectively). After adjusting for residual confounders, there were no significant differences between the TAVI and SAVR groups in the risk for all-cause death (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.35-1.58; P=0.43) or HF hospitalization (HR 1.27; 95% CI 0.40-4.59; P=0.69). CONCLUSIONS: These findings from 2 independent Japanese registries suggest that the 2-year risk of all-cause mortality and HF does not differ significantly between TAVI and SAVR groups in real-world practice in Japan.

Antimicrobial susceptibility of Escherichia coli isolates obtained from wild mammals between 2013 and 2017 in Japan.

The emergence and prevalence of antimicrobial-resistant bacteria in wild animals are a great concern for public health. A total of 963 Escherichia coli isolates from 475 wild mammals (242 sika deers, 112 wild boars, 113 small mammals, 4 Japanese badger, 2 Tokara cows, and 2 Amani rabbits), collected between 2013 and 2017, were examined for antimicrobial susceptibility. Resistance to at least one antimicrobial was observed in 92 of 963 isolates (9.3%). No isolates exhibited resistance to carbapenem (meropenem). Resistance to third-generation cephalosporin (cefotaxime) and fluoroquinolone (ciprofloxacin) was observed in less than 1% of the isolates. Thus, low prevalence of bacterial antimicrobial resistance was observed in wild mammals between 2013 and 2017 in Japan.

Age-Related Differences in the Effects of Initial Aortic Valve Replacement vs. Conservative Strategy on Long-Term Outcomes in Asymptomatic Patients With Severe Aortic Stenosis.

BACKGROUND: This study aimed to evaluate the effect of the initial aortic valve replacement (AVR) strategy relative to a conservative strategy on long-term outcomes stratified by age among asymptomatic patients with severe aortic stenosis (AS).Methods and Results:Among 1,808 asymptomatic severe AS patients in the CURRENT AS registry, there were 1,166 patients aged ≥75 years (initial AVR: n=124, and conservative: n=1,042), and 642 patients with age <75 years (initial AVR: n=167, and conservative: n=475). Median follow-up interval was 1,280 (interquartile range [IQR]: 1,012-1,611) days, and 1461 (IQR: 1,132-1,886) days in patients aged ≥ and <75 years, respectively. The favorable effect of the initial AVR strategy relative to conservative strategy for heart failure (HF) hospitalization was seen regardless of the age stratum (≥75 years: adjusted hazard ratio [HR] 0.13, 95% confidence interval [CI] 0.05-0.34, and <75 years: HR 0.37, 95% CI 0.14-0.99, interaction P=0.35). However, the lower mortality risk of the initial AVR strategy relative to conservative strategy was significant in patients aged ≥75 years, but not in patients <75 years, with significant interaction (HR 0.35, 95% CI 0.20-0.61, and HR 0.69, 95% CI 0.41-1.16, interaction P=0.016). CONCLUSIONS: The benefit of initial AVR in reducing HF hospitalization in asymptomatic patients with severe AS was consistently seen regardless of age. The magnitude of mortality benefit of initial AVR was greater in super-elder patients than in non-super-elder patients.

A risk prediction model in asymptomatic patients with severe aortic stenosis: CURRENT-AS risk score.

AIMS: Early aortic valve replacement (AVR) might be beneficial in selected high-risk asymptomatic patients with severe aortic stenosis (AS), considering their poor prognosis when managed conservatively. This study aimed to develop and validate a clinical scoring system to predict AS-related events within 1 year after diagnosis in asymptomatic severe AS patients. METHODS AND RESULTS: We analysed 1274 asymptomatic severe AS patients derived from a retrospective multicentre registry enrolling consecutive patients with severe AS in Japan (CURRENT AS registry), who were managed conservatively and completed 1-year follow-up without AVR. From a randomly assigned derivation set (N = 849), we developed CURRENT AS risk score for the AS-related event (a composite of AS-related death and heart failure hospitalization) within 1 year using a multivariable logistic regression model. The risk score comprised independent risk predictors including left ventricular ejection fraction <60%, haemoglobin ≤11.0 g/dL, chronic lung disease (2 points), diabetes mellitus, haemodialysis, and any concomitant valve disease (1 point). The predictive accuracy of the model was good with the area under the curve of 0.79 and 0.77 in the derivation and validation sets (N = 425). In the validation set, the 1-year incidence of AS-related events was much higher in patients with score ≥2 than in patients with score ≤1 (Score 0: 2.2%, Score 1: 1.9%, Score 2: 13.4%, Score 3: 14.3%, and Score ≥4: 22.7%, P < 0.001). CONCLUSION: The CURRENT-AS risk score integrating clinical and echocardiographic factors well-predicted the risk of AS-related events at 1 year in asymptomatic patients with severe AS and was validated internally.