Differential Prognostic Impact of Clinical Congestion between Preserved versus Reduced Ejection Fraction in Patients Hospitalized for Acute Decompensated Heart Failure: Findings from the Japanese Kyoto Congestive Heart Failure Registry.

BACKGROUND: Most patients hospitalized for heart failure (HF) present with signs of congestion. Prognostic significance of clinical congestion may vary depending on left ventricular ejection fraction (LVEF). This study aims to investigate the prognostic impact of congestion across different LVEF categories. METHODS AND RESULTS: Composite congestion scores (CCSs; 0-9) derived from the severity of edema, jugular venous pressure, and orthopnea, were analyzed on admission and at discharge in 3787 patients hospitalized for HF (LVEF ≥ 40%: n = 2347, LVEF < 40%: n = 1440). The median admission CCS was 4 in both LVEF strata (P = .64). Adjusted hazard ratios (HRs; 95% confidence interval [CI]) of the moderate (CCS 4-6) and severe congestion [7-9] groups relative to the mild congestion [0-3] group on admission for a composite of all-cause death or HF rehospitalization were 1.20 (1.04-1.39, P = .01) and 1.54 (1.27-1.86, P < .001) in the LVEF ≥ 40% stratum, and 1.20 (1.01-1.44, P = .04) and 0.82 (0.61-1.07, P = .14) in the LVEF < 40% stratum, respectively (Pinteraction< .001). A total of 16% of the patients with LVEF ≥40% and 14% with LVEF <40% had residual congestion (CCS ≥ 1) at discharge, which was associated with a respective adjusted HR of 1.40 (1.18-1.65, P < .001) and 1.25 (0.98-1.58, P = .07) for postdischarge death or HF rehospitalization (Pinteraction = 0.63). CONCLUSION: The severity of clinical congestion on admission was associated with adverse clinical outcomes in patients with LVEF ≥ 40%, but not in those with LVEF < 40%. These findings warrant further studies to better understand the detailed profile of congestion across the LVEF spectrum.

Prognostic Value of the Severity of Clinical Congestion in Patients Hospitalized for Decompensated Heart Failure: Findings From the Japanese KCHF Registry.

BACKGROUND: Congestion is a leading cause of hospitalization and a major therapeutic target in patients with heart failure (HF). Clinical practice in Japan is characterized by a long hospital stay, which facilitates more extensive decongestion during hospitalization. We herein examined the time course and prognostic impact of clinical congestion in a large contemporary Japanese cohort of HF. METHODS AND RESULTS: Peripheral edema, jugular venous pressure, and orthopnea were graded on a standardized 4-point scale (0-3) in 3787 hospitalized patients in a Japanese cohort of HF. Composite Congestion Scores (CCS) on admission and at discharge were calculated by summing individual scores. The primary outcome was a composite of all-cause death or HF hospitalization. The median admission CCS was 4 (interquartile range, 3-6). Overall, 255 patients died during the median hospitalization length of 16 days, and 1395 died or were hospitalized for HF over a median postdischarge follow-up of 396 days. The cumulative 1-year incidence of the primary outcome increased at higher tertiles of congestion on admission (32.5%, 39.3%, and 41.0% in the mild [CCS ≤3], moderate [CCS = 4 or 5], and severe [CCS ≥6] congestion groups, respectively, log-rank P < .001). The adjusted hazard ratios of moderate and severe congestion relative to mild congestion were 1.205 (95% confidence interval [CI], 1.065-1.365; P = .003) and 1.247 (95% CI, 1.103-1.410; P < .001), respectively. Among 3445 patients discharged alive, 85% had CCS of 0 (complete decongestion) and 15% had a CCS of 1 or more (residual congestion) at discharge. Although residual congestion predicted a risk of postdischarge death or HF hospitalization (adjusted hazard ratio, 1.314 [1.145-1.509]; P < .001), the admission CCS correlated with the risk of postdischarge death or HF hospitalization, even in the complete decongestion group. No correlation was observed for postdischarge death or HF hospitalization between residual congestion at discharge and admission CCS (P for the interaction = .316). CONCLUSIONS: In total, 85% of patients were discharged with complete decongestion in Japanese clinical practice. Clinical congestion, on admission and at discharge, was of prognostic value. The severity of congestion on admission was predictive of adverse outcomes, even in the absence of residual congestion. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02334891 (NCT02334891) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017241 (UMIN000015238).

Demographics, Management, and In-Hospital Outcome of Hospitalized Acute Heart Failure Syndrome Patients in Contemporary Real Clinical Practice in Japan　- Observations From the Prospective, Multicenter Kyoto Congestive Heart Failure (KCHF) Registry.

BACKGROUND: There is a scarcity of reports on the clinical characteristics and management practice in contemporary all-comer patients with acute decompensated heart failure (ADHF). Methods and Results: The Kyoto Congestive Heart Failure (KCHF) registry is a prospective observational cohort study enrolling 4,056 consecutive patients who had hospital admission due to ADHF without any exclusion criteria between October 2014 and March 2016 in the 19 participating hospitals in Japan. Baseline characteristics, clinical presentations, management, and in-hospital outcomes were compared between heart failure (HF) with reduced left ventricular ejection fraction (LVEF; HFrEF, LVEF <40%), HF with mid-range LVEF (HFmrEF, LVEF 40-49%), and HF with preserved LVEF (HFpEF, LVEF ≥50%). Of the 4,041 patients with documented LVEF, 1,744 (43%) had HFpEF; 746 (19%), HFmrEF; and 1,551 (38%), HFrEF. The median age was 80 years (IQR, 72-86 years) in the entire population, and was higher with increasing LVEF (P<0.001). The in-hospital mortality rate was higher in the HFrEF than in the HFmrEF and HFpEF groups (9.2%, 4.8%, and 5.1%, respectively, P<0.001). CONCLUSIONS: This registry elucidated the clinical features and clinically relevant in-hospital outcomes in contemporary consecutive patients with ADHF in real-world clinical practice in Japan. When classified by LVEF, significant differences in characteristics and in-hospital outcomes existed between patients with HFrEF, HFmrEF, and HFpEF.

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.

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.

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).

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).

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.

Association of Previous Hospitalization for Heart Failure With Increased Mortality in Patients Hospitalized for Acute Decompensated Heart Failure.

Background: We sought to explore the effects of previous heart failure (HF) hospitalization on mortality in patients hospitalized for acute decompensated HF (ADHF) in a large Japanese contemporary observational database. Methods and Results: We prospectively enrolled consecutive patients with ADHF in 19 participating hospitals between October 2014 and March 2016. Of 4,056 patients, 1,442 patients (35.4%) had at least 1 previous HF hospitalization (previous hospitalization group), while 2,614 patients (64.5%) did not have a history of HF hospitalization (de novo hospitalization group). Patients with previous hospitalization were older and more often had comorbidities such as anemia, and renal failure than those without. The cumulative 1-year incidence of all-cause death was significantly higher in the previous hospitalization group than in the de novo hospitalization group (28% vs. 19%, P<0.001). After adjusting confounders, the excess risk of the previous hospitalization group relative to the de novo hospitalization group for all-cause death remained significant (HR, 1.28; 95% CI: 1.10-1.50, P=0.001). The excess risk was significant in patients without advanced age, anemia, or renal failure, but not significant in patients with these comorbidities, with significant interaction. Increase in the number of hospitalizations was associated with an increased risk for mortality. Conclusions: In a contemporary ADHF cohort in Japan, repeated hospitalization was associated with an increasing, higher risk for 1-year mortality.

Decline in Left Ventricular Ejection Fraction During Follow-Up in Patients With Severe Aortic Stenosis.

OBJECTIVES: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. BACKGROUND: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. METHODS: Among 3,815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. RESULTS: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p < 0.001). After adjusting for confounders, the excess risk of decline in LVEF over no decline for the primary outcome measure remained significant (hazard ratio: 1.98; 95% confidence interval: 1.29 to 3.06). When stratified by LVEF at index echocardiography (≥70%, 60% to 69%, and <60%), the risk of decline in LVEF on the primary outcome was consistently seen in all the subgroups, without any interaction (p = 0.77). CONCLUSIONS: Patients with severe AS with >10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140).

Malignant disease as a comorbidity in patients with severe aortic stenosis: clinical presentation, outcomes, and management.

Aim: To investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy. Methods and results: Using data of 3815 patients with severe AS in a retrospective multicentre registry [CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry], we compared 3-year clinical outcomes among three groups based on malignancy status: with malignancy currently under treatment including best supportive care (malignancy group), with a history of malignancy without any current treatment (past history group), or without history of malignancy (no malignancy group). Patients in the malignancy group (n = 124) were more often men and had higher prevalence of low body mass index, recurrence of malignancy, anaemia, and asymptomatic status, despite comparable surgical risks and echocardiographic parameters. The malignancy group or the past history group (n = 389) had significantly higher risk for all-cause death [hazard ratio (HR) 2.49, 95% CI (95% confidence interval) 1.98-3.14; HR 1.23, 95% CI 1.04-1.46] and for malignancy-related death (HR 16.2, 95% CI 10.64-24.54; HR 3.66, 95% CI 2.43-5.52) than that of the no malignancy group (n = 3302). The excess risk for aortic valve-related death was not observed in the malignancy group (HR 0.79, 95% CI 0.48-1.29) and was lower in the past history group (HR 0.72, 95% CI 0.53-0.96). In the malignancy group, the treatment strategy (surgery: n = 16, conservative management: n = 108) was determined based on the clinical status of AS or life expectancy. Conclusions: Malignancy had marked effect on all-cause death and malignancy-related death in patients with severe AS. History of malignancy also had a smaller but significant effect on mortality.

A rare case of hypertrophic cardiomyopathy with subendocardial late gadolinium enhancement in an apical aneurysm with thrombus.

The mechanisms responsible for the development of apical aneurysms in cases of hypertrophic cardiomyopathy (HCM) are currently unclear but likely involve multiple factors. Here, we present a case of HCM with marked subendocardial fibrosis involving the apical and proximal portions of the left ventricle. A 71-year-old man with left ventricular hypertrophy presented with signs and symptoms of heart failure. The presence of asymmetrical left ventricular hypertrophy and bilateral, thickened ventricular walls with an apical aneurysm on transthoracic echocardiography suggested a diagnosis of HCM with ventricular dysfunction. No intraventricular pressure gradients with obstruction were identified. Late gadolinium enhancement (LGE) with cardiac magnetic resonance imaging and endomyocardial biopsies showed subendocardial fibrosis involving the apical aneurysm and proximal portion. Whereas LGE in a transmural pattern is commonly observed in HCM apical aneurysms, subendocardial LGE, as noted in the present case, is a relatively rare occurrence. Thus, the present case may provide unique insights into the adverse remodeling process and formation of apical aneurysms in cases of HCM.

Diffuse homogeneous bone marrow uptake of FDG in patients with acute lymphoblastic leukemia.

PET (positron emission tomography) using FDG (¹8F-fluorodeoxyglucose) has been widely used in the evaluation of various malignancies, but its clinical application to leukemia remains limited. We report a case of leukemia in which diffuse bone marrow uptake of FDG was observed, and bone marrow aspiration subsequently revealed acute lymphoblastic leukemia. It is not easy to differentiate between physiological and pathologic uptake when diffuse homogeneous uptake in bone marrow is observed.