Development of interpretable machine learning models to predict in-hospital prognosis of acute heart failure patients.

AIMS: In recent years, there has been remarkable development in machine learning (ML) models, showing a trend towards high prediction performance. ML models with high prediction performance often become structurally complex and are frequently perceived as black boxes, hindering intuitive interpretation of the prediction results. We aimed to develop ML models with high prediction performance, interpretability, and superior risk stratification to predict in-hospital mortality and worsening heart failure (WHF) in patients with acute heart failure (AHF). METHODS AND RESULTS: Based on the Kyoto Congestive Heart Failure registry, which enrolled 4056 patients with AHF, we developed prediction models for in-hospital mortality and WHF using information obtained on the first day of admission (demographics, physical examination, blood test results, etc.). After excluding 16 patients who died on the first or second day of admission, the original dataset (n = 4040) was split 4:1 into training (n = 3232) and test datasets (n = 808). Based on the training dataset, we developed three types of prediction models: (i) the classification and regression trees (CART) model; (ii) the random forest (RF) model; and (iii) the extreme gradient boosting (XGBoost) model. The performance of each model was evaluated using the test dataset, based on metrics including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), Brier score, and calibration slope. For the complex structure of the XGBoost model, we performed SHapley Additive exPlanations (SHAP) analysis, classifying patients into interpretable clusters. In the original dataset, the proportion of females was 44.8% (1809/4040), and the average age was 77.9 ± 12.0. The in-hospital mortality rate was 6.3% (255/4040) and the WHF rate was 22.3% (900/4040) in the total study population. In the in-hospital mortality prediction, the AUC for the XGBoost model was 0.816 [95% confidence interval (CI): 0.815-0.818], surpassing the AUC values for the CART model (0.683, 95% CI: 0.680-0.685) and the RF model (0.755, 95% CI: 0.753-0.757). Similarly, in the WHF prediction, the AUC for the XGBoost model was 0.766 (95% CI: 0.765-0.768), outperforming the AUC values for the CART model (0.688, 95% CI: 0.686-0.689) and the RF model (0.713, 95% CI: 0.711-0.714). In the XGBoost model, interpretable clusters were formed, and the rates of in-hospital mortality and WHF were similar among each cluster in both the training and test datasets. CONCLUSIONS: The XGBoost models with SHAP analysis provide high prediction performance, interpretability, and reproducible risk stratification for in-hospital mortality and WHF for patients with AHF.

The characteristics and outcomes in patients with acute heart failure who used tolvaptan: from KCHF registry.

AIMS: The use of tolvaptan is increasing in clinical practice in Japan. However, the characteristics of patients who used tolvaptan and the timing of its use in patients with acute heart failure (AHF) are not fully elucidated. METHODS AND RESULTS: Among consecutive 4056 patients in the Kyoto Congestive Heart Failure registry, we analysed 3802 patients after excluding patients on dialysis, prior or unknown tolvaptan use at admission, and unknown timing of tolvaptan use, and we divided them into two groups: tolvaptan use (N = 773) and no tolvaptan use (N = 3029). The prevalence of tolvaptan use varied widely from 48.7% to 0% across the participating centres. Factors independently associated with tolvaptan use were diabetes, poor medical adherence, oedema, pleural effusion, hyponatraemia, estimated glomerular filtration rate < 30 mL/min/1.73 m2 , moderate/severe tricuspid regurgitation, dobutamine infusion within 24 h, and additional inotropes infusion beyond 24 h after admission. The mortality rate at 90 days after admission was significantly higher in the tolvaptan use group than in the no tolvaptan use group (14.3% vs. 8.6%, P = 0.049). However, after adjustment, the excess mortality risk of tolvaptan use relative to no tolvaptan use was no longer significant (hazard ratio = 1.53, 95% confidence interval = 0.77-3.02, P = 0.22). Patients with tolvaptan use had a longer hospital stay [median (interquartile range): 22 (15-34) days vs. 15 (11-21) days, P < 0.0001] and a higher prevalence of worsening renal failure (47.0% vs. 31.8%, P < 0.0001) and worsening heart failure (24.8% vs. 14.4%, P < 0.0001) than those without. CONCLUSIONS: AHF patients with tolvaptan use had more congestive status with poorer in-hospital outcomes and higher short-term mortality than those without tolvaptan use. 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).

Association between changes in loop diuretic dose and outcomes in acute heart failure.

AIMS: Little is known about the association between the starting of or dose changes in loop diuretics during acute heart failure (AHF) hospitalization and post-discharge outcomes. We investigated the clinical impact of starting loop diuretics and changing the loop diuretics dose during hospitalization on post-discharge outcomes. METHODS AND RESULTS: From the Kyoto Congestive Heart Failure registry, 3665 consecutive patients hospitalized for HF and discharged alive were included in this study. We analysed 1906 patients without loop diuretics on admission and were discharged alive and 1759 patients who received loop diuretics on admission and were discharged alive. The primary outcome measure was all-cause death. Of the 1906 patients without loop diuretics on admission, 1366 (71.7%) patients started loop diuretics during the index AHF hospitalization. Starting loop diuretics was not associated with lower post-discharge mortality [adjusted hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.68-1.25]. Of the 1759 patients who received loop diuretics on admission, loop diuretic dose was decreased in 23.8%, unchanged in 44.6%, and increased in 31.6% of the patients. Changes in the dose at discharge compared with no change in dose were not associated with lower risk of post-discharge mortality (decrease relative to no change: adjusted HR 0.98, 95% CI 0.76-1.28; increase relative to no change: adjusted HR 1.00, 95% CI 0.78-1.27). Compared with no loop diuretics at discharge, a loop diuretics dose of ≥80 mg at discharge was associated with higher post-discharge mortality risk. CONCLUSIONS: In patients with AHF, we found no association between the starting of loop diuretics and post-discharge outcomes and between dose changes and post-discharge outcomes.

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.

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).

Impact of catheter ablation on functional tricuspid regurgitation in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) plays the main role in atrial functional tricuspid regurgitation (TR). However, the effectiveness of catheter ablation (CA) for atrial functional TR together with the mechanisms of improvement of atrial functional TR have not been fully evaluated. METHODS: We retrospectively investigated consecutive 2685 patients with AF who received CA from February 2004 to December 2019 in Kyoto University Hospital, Kyoto, Japan. The current study population consisted of 2331 patients with available transthoracic echocardiographic (TTE) data before CA (2110 patients without significant TR and 221 patients with significant TR). Among the 221 patients with significant TR, there were 64 patients with functional TR and follow-up TTE at 6-18 months after CA for AF, in whom we compared echocardiographic parameters from baseline to follow-up. RESULTS: Patients with significant TR were older, and more often women, and had more persistent AF than those without significant TR. Among the 64 patients with functional TR, TR severity and TR jet area significantly improved at follow-up (TR jet area: 5.8 [4.0-7.6] cm2 to 2.1 [1.1-3.1] cm2, P < 0.001). Moreover, mitral regurgitation jet area, left atrial area, mitral valve diameter, right ventricular end-diastolic area, right atrial area, and tricuspid valve diameter decreased at follow-up. CONCLUSIONS: TR severity and jet area improved after CA in patients with AF and significant TR. The improvement of TR might be associated with reverse remodeling of the right heart.

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.

Prognostic impact of catheter ablation in patients with asymptomatic atrial fibrillation.

BACKGROUND: Catheter ablation for asymptomatic atrial fibrillation (AF) remains controversial. The aim of the present study was to explore the prognostic impact of catheter ablation in asymptomatic AF patients. METHODS: We performed a post-hoc analysis of 537 risk-matched pairs of AF patients receiving first-time catheter ablation or conservative management. The primary outcome measure was a composite of cardiovascular death, heart failure (HF) hospitalization, ischemic stroke, or major bleeding. The study patients were divided into asymptomatic and symptomatic patients, and were further divided according to the presence or absence of previous AF-related complications (ischemic stroke or HF hospitalization). RESULTS: Most baseline characteristics were well balanced between the catheter ablation versus conservative management groups. The median follow-up period was 5.3 years. Catheter ablation as compared to conservative management was associated with significantly lower incidence of the primary outcome measure in the asymptomatic AF patients (14.7% versus 25.4% at 8-year, log-rank P = 0.008). However, the advantage of catheter ablation was significant only in the high-risk subset of patients with the previous AF-related complications (19.2% versus 55.6% at 8-year, log-rank P = 0.006), but not in those without (13.9% and 17.3%, P = 0.08). On the other hand, among the symptomatic AF patients, catheter ablation was associated with significantly lower incidence of the primary outcome measure regardless of the previous AF-related complications. CONCLUSIONS: In the post-hoc analysis of the matched AF cohort, catheter ablation as compared with conservative management was associated with better long-term clinical outcomes among asymptomatic AF patients only when the previous AF-related complications were present.

Stroke Risk Stratification With the CHADS2 Score in Patients Without Atrial Fibrillation Who Underwent Percutaneous Coronary Intervention.

The clinical significance of the CHADS2 score remains unclear in patients with coronary artery disease (CAD) without atrial fibrillation (AF). Therefore, the purpose of this study was to evaluate the association between the CHADS2 score and the long-term risk of ischemic stroke and its severity in patients with CAD with and without AF. Using the CREDO (Coronary Revascularization Demonstrating Outcome study)-Kyoto Registry Cohort-3, the present study population consisted of 11,516 patients with CAD who underwent percutaneous coronary intervention without oral anticoagulants at discharge. We divided the patients into 2 groups according to the presence (n = 721) or absence (n = 10,795) of AF. As the CHADS2 score increased from 0 or 1 to 6, the cumulative 5-year incidence of ischemic stroke incrementally increased from 2.1% to 17.1% in patients without AF and from 4.2% to 40.7% in patients with AF. The cumulative 5-year incidence of ischemic stroke in patients without AF and a CHADS2 score of 2 were numerically comparable to that in patients with AF and a CHADS2 score of 1 (3.4% and 3.7%). In the 423 patients who developed ischemic stroke, the modified Rankin Scale score was not significantly different between patients with and without AF (p for trend = 0.12). In patients with and without AF, the increase in the CHADS2 score was significantly associated with the greater prevalence of higher modified Rankin Scale scores (p for trend = 0.03 and <0.001, respectively). An increasing CHADS2 score was associated with an incrementally increased risk for ischemic stroke and greater severity of ischemic stroke in patients with and without AF.

Insomnia in patients with acute heart failure: from the KCHF registry.

AIMS: Insomnia is a known risk factor for heart failure (HF) and a predictor of cardiac events in HF patients, but the clinical significance of insomnia in patients with acute HF (AHF) is not adequately evaluated. This study aimed to investigate the association between insomnia and subsequent clinical outcomes in patients with AHF. METHODS: From the Kyoto Congestive Heart Failure registry, consecutive 3414 patients hospitalized for HF who were discharged alive were divided into the 2 groups at discharge: insomnia group and non-insomnia group. We compared baseline characteristics and 1 year clinical outcomes according to the presence of insomnia. The primary outcome measure was all-cause death. RESULTS: There were 330 patients (9.7%) and 3084 patients (90.3%) with and without insomnia, respectively. In the multivariable logistic regression analysis, brain-type natriuretic peptide above median value at discharge (OR = 1.50, 95% CI = 1.08-2.10, P = 0.02) and the presence of oedema at discharge (OR = 4.23, 95% CI = 2.95-6.07, P < 0.001) were positively associated with insomnia at discharge, whereas diuretics at discharge (OR = 0.60, 95% CI = 0.39-0.90, P = 0.01) were negatively associated with insomnia at discharge. The cumulative 1 year incidence of all-cause death was significantly higher in the insomnia group than in the non-insomnia group (25.1% vs. 16.2%, P < 0.001). Even after adjusting the confounders, the higher mortality risk of patients with insomnia relative to those without insomnia remained significant (HR = 1.55, 95% CI = 1.24-1.94; P < 0.001). CONCLUSIONS: Patients with insomnia at discharge were associated with a higher risk of mortality than those without insomnia at discharge.

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).

Starting Neurohormonal Antagonists in Patients With Acute Heart Failure With Mid-Range and Preserved Ejection Fraction.

BACKGROUND: The clinical benefits of neurohormonal antagonists for patients with heart failure (HF) with mid-range and preserved ejection fraction (HFmrEF and HFpEF) are uncertain.Methods and Results: This study analyzed 858 consecutive patients with HFmrEF (EF: 40-49%) or HFpEF (EF ≥50%), who were hospitalized for acute HF, and who were discharged alive, and were not taking angiotensin-converting enzyme inhibitors (ACE)-I/ angiotensin II receptor blockers (ARB) or ß-blockers at admission. The study population was classified into 4 groups according to the status of prescription of ACE-I/ARB and ß-blocker at discharge: no neurohormonal antagonist (n=342, 39.9%), ACE-I/ARB only (n=128, 14.9%), ß-blocker only (n=189, 22.0%), and both ACE-I/ARB and ß-blocker (n=199, 23.2%) groups. The primary outcome measure was a composite of all-cause death or HF hospitalization. The cumulative 1-year incidence of the primary outcome measure was 41.2% in the no neurohormonal antagonist group, 34.0% in the ACE-I/ARB only group, 28.6% in the ß-blocker only group, and 16.4% in the both ACE-I/ARB and ß-blocker group (P<0.001). Compared with the no neurohormonal antagonist group, both the ACE-I/ARB and ß-blocker groups were associated with a significantly lower risk for a composite of all-cause death or HF hospitalization (HR: 0.46, 95% CI: 0.28-0.76, P=0.002). CONCLUSIONS: In hospitalized patients with HFmrEF and HFpEF, starting both ACE-I/ARB and a ß-blocker was associated with a reduced risk of the composite of all-cause death or HF hospitalization compared with patients not starting on an ACE-I/ARB or ß-blocker.

Matched comparison of catheter ablation versus conservative management for atrial fibrillation.

It is still controversial whether catheter ablation for atrial fibrillation (AF) could improve clinical outcomes in general AF population. Among 4398 patients with diagnosis of AF in the outpatient department of Kyoto University Hospital between January 2005 and March 2015, we identified 537 pairs of patients who received first-time catheter ablation (ablation group) or conservative management (conservative group), matched for age, gender, AF duration, AF type, AF symptoms, and previous heart failure (HF). The primary outcome measure was a composite of cardiovascular death, HF hospitalization, ischemic stroke, or major bleeding. Most baseline characteristics were well balanced between the 2 groups, except for the higher prevalence of low body weight, history of malignancy, and severe chronic kidney disease in the conservative group. Median follow-up duration was 5.3 years. The cumulative 5-year incidence of the primary outcome measure was significantly lower in the ablation group than in the conservative group (5.2% versus 15.6%, log-rank P < 0.001). Even after adjusting for the imbalances in the baseline characteristics, the lower risk of the ablation group relative to the conservative group for the primary outcome measure remained highly significant (HR 0.32, 95% CI 0.21-0.47, P < 0.001). Ablation compared with conservative management was also associated with significantly lower risks for the individual components of the primary outcome. In this matched analysis in AF patients, ablation as compared with conservative management was associated with better long-term clinical outcomes, although we could not deny the possibility of selection bias and unmeasured confounding.

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.

Coronary angiography in patients with acute heart failure: from the KCHF registry.

AIMS: Little is known about the characteristics and outcomes of patients who undergo coronary angiography during heart failure (HF) hospitalization, as well as those with coronary stenosis, and those who underwent coronary revascularization. METHODS AND RESULTS: We analysed 2163 patients who were hospitalized for HF without acute coronary syndrome or prior HF hospitalization. We compared patient characteristics and 1 year clinical outcomes according to (i) patients with versus without coronary angiography, (ii) patients with versus without coronary stenosis, and (iii) patients with versus without coronary revascularization. The primary outcome measure was the composite of all-cause death or HF hospitalization. Coronary angiography was performed in 37.0% of patients. In the multivariable logistic regression analysis, factors independently associated with coronary angiography were age < 80 years [adjusted odds ratio (OR) = 1.76, 95% confidence interval (CI) = 1.41-2.20, P < 0.001], men (adjusted OR = 1.28, 95% CI = 1.03-1.59, P = 0.02), diabetes (adjusted OR = 1.27, 95% CI = 1.02-1.60, P = 0.04), no atrial fibrillation or flutter (adjusted OR = 1.45, 95% CI = 1.17-1.82, P < 0.001), no prior device implantation (adjusted OR = 1.81, 95% CI = 1.13-2.91, P = 0.01), current smoking (adjusted OR = 1.40, 95% CI = 1.05-1.87, P = 0.02), no cognitive dysfunction (adjusted OR = 1.90, 95% CI = 1.34-2.69, P < 0.001), ambulatory status (adjusted OR = 2.89, 95% CI = 2.03-4.10, P < 0.001), HF with reduced ejection fraction (adjusted OR = 1.55, 95% CI = 1.24-1.93, P < 0.001), estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 (adjusted OR = 1.93, 95% CI = 1.45-2.58, P < 0.001), no anaemia (adjusted OR = 1.27, 95% CI = 1.02-1.59, P = 0.04), and no prescription of ß-blockers prior to admission (adjusted OR = 1.32, 95% CI = 1.03-1.68, P = 0.03). Patients who underwent coronary angiography had a lower risk of the primary outcome [adjusted hazard ratio (HR) = 0.70, 95% CI = 0.58-0.85, P < 0.001]. Among the patients who underwent coronary angiography, those with coronary stenosis (38.9%) did not have lower risk of the primary outcome measure than those without coronary stenosis (adjusted HR = 0.93, 95% CI = 0.65-1.32, P = 0.68). Among the patients with coronary stenosis, those with coronary revascularization (54.3%) did not have higher risk of the primary outcome measure than those without coronary revascularization (adjusted HR = 1.36, 95% CI = 0.84-2.21, P = 0.22). CONCLUSIONS: In patients with acute HF, patients who underwent coronary angiography had a lower risk of clinical outcomes and were significantly different from those who did not undergo coronary angiography.

Newly Diagnosed Infection After Admission for Acute Heart Failure: From the KCHF Registry.

Background No studies have explored the association between newly diagnosed infections after admission and clinical outcomes in patients with acute heart failure. We aimed to explore the factors associated with newly diagnosed infection after admission for acute heart failure, and its association with in-hospital and post-discharge clinical outcomes. Methods and Results Among 4056 patients enrolled in the Kyoto Congestive Heart Failure registry, 2399 patients without any obvious infectious disease upon admission were analyzed. The major in-hospital and post-discharge outcome measures were all-cause deaths. There were 215 patients (9.0%) with newly diagnosed infections during hospitalization, and 2184 patients (91.0%) without infection during hospitalization. The factors independently associated with a newly diagnosed infection were age ≥80 years, acute coronary syndrome, non-ambulatory status, hyponatremia, anemia, intubation, and patients who were not on loop diuretics as outpatients. The newly diagnosed infection group was associated with a higher incidence of in-hospital mortality (16.3% and 3.2%, P<0.001) and excess adjusted risk of in-hospital mortality (odds ratio, 6.07 [95% CI, 3.61-10.19], P<0.001) compared with the non-infection group. The newly diagnosed infection group was also associated with a higher 1-year incidence of post-discharge mortality (19.3% in the newly diagnosed infection group and 13.6% in the non-infection group, P<0.001) and excess adjusted risk of post-discharge mortality (hazard ratio, 1.49 [95% CI, 1.08-2.07], P=0.02) compared with the non-infection group. Conclusions Elderly patients with multiple comorbidities were associated with the development of newly diagnosed infections after admission for acute heart failure. Newly diagnosed infections after admission were associated with higher in-hospital and post-discharge mortality in patients with acute heart failure. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02334891.