Published papers

© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. Aims: The blood urea nitrogen (BUN)/creatinine ratio is a strong prognostic indicator in patients with acute decompensated heart failure (ADHF). However, the clinical impact of a high BUN/creatinine ratio at discharge with respect to renal dysfunction, neurohormonal hyperactivity, and different responsiveness to decongestion therapy remains unclear. Herein, we examined (i) the predictive value of a high BUN/creatinine ratio at discharge and (ii) its haemoconcentration-dependent effects, in patients with ADHF. Methods and results: The West Tokyo Heart Failure registry was a multicentre, prospective cohort registry-based study that enrolled patients hospitalized with a diagnosis of ADHF. The endpoint was post-discharge all-cause death. Based on the degree of haemoconcentration, patients (n = 2090) were divided into four subcategories. In multivariate proportional hazard analyses, a higher BUN/creatinine ratio was independently associated with higher all-cause mortality in the total population and in the extreme haemodilution (ΔHaemoglobin ≤ −0.9 g/dL) and haemoconcentration (0.8 g/dL ≤ ΔHaemoglobin) subcategories, but not in the modest haemodilution/haemoconcentration subcategories. Conclusions: A higher BUN/creatinine ratio at discharge was independently associated with higher post-discharge all-cause mortality in patients with ADHF. The predictive value of a high BUN/creatinine ratio at discharge was haemoconcentration dependent and may be an unfavourable predictor in patients showing excessive haemoconcentration and haemodilution, but not in those showing modest haemoconcentration/haemodilution.

© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology Aims: Clinical guidelines for improving the patients' quality of care vary in clinical practice, particularly in super-aging societies, like in Japan. We aimed to develop a set of appropriate-use criteria (AUC) for contemporary heart failure (HF) management to assist physicians in decision making. Methods and results: With the use of the RAND methodology, a multidisciplinary writing group developed patient-based clinical scenarios in 10 selected key topics, stratified mainly by HF stage, age, and renal function. Nine nationally recognized expert panellists independently rated the clinical scenario appropriateness twice on a scale of 1–9, as ‘appropriate’ (7–9), ‘may be appropriate’ (4–6), or ‘rarely appropriate’ (1–3). Decisions were based on clinical evidence and professional opinions in the context of available resource use and costs. An interactive round-table discussion was held between the first and second ratings; the median score of the nine experts was then assigned to an appropriate-use category. Most clinical scenarios without strong evidence were evaluated as ‘may be appropriate’. Frailty assessments in elderly patients (age ≥ 75 years), regardless of the HF stage, and advanced care planning in patients with stage C/D HF, regardless of age, were considered ‘appropriate’. For HF with reduced ejection fraction, beta-blocker administration in elderly patients (age ≥ 75 years) with heart rate < 50 b.p.m. and mineral corticosteroid receptor antagonist use in elderly patients (age ≥ 75 years) with an estimated glomerular filtration rate < 30 mL/min/1.73 m2 were considered ‘rarely appropriate’. Conclusions: The HF management AUC provide a practical guide for physicians regarding scenarios commonly encountered in daily practice.

We clarified the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure (HF) and post-discharge prognosis. We retrospectively analyzed a combined dataset from three large-scale registries of hospitalized patients with HF in Japan (NARA-HF, WET-HF, and REALITY-AHF) and patients diagnosed with HF with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes from admission to discharge: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor blockers. Primary endpoint was the combined endpoint of HF rehospitalization and all-cause death within 1 year of discharge. The cohort comprised 1113 patients, and 482 combined endpoints were observed. Overall, FMHF prescriptions increased in 413 (37.1%) patients (increased group), remained unchanged in 607 (54.5%) (unchanged group), and decreased in 93 (8.4%) (decreased group) at discharge compared with that during admission. In the multivariable analysis, the increased group had a significantly lower incidence of the primary endpoint than the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45–0.60; P < 0.001). In conclusion, increase in FMHF classes during HF hospitalization is associated with a better prognosis in patients with HFr/mrEF.

Background: Understanding patient perspectives of self-care is critical for improving multidisciplinary education programs and adherence to such programs. However, perspectives of self-care for patients with heart failure (HF) as well as the association between patient perspectives and patient-physician communication remain unclear. Methods: Confidence levels regarding self-care behaviors (eight lifestyle behaviors and four consulting behaviors) and self-monitoring were assessed using a self-administered questionnaire survey, which was directly distributed by dedicated physicians and nurses to consecutive patients hospitalized with HF in a tertiary-level hospital. Patient-physician communication was evaluated according to the quality of physician-provided information regarding “treatment and treatment choices” and “prognosis” using the Prognosis and Treatment Perception Questionnaire. Out of 202 patients, 187 (92.6 %) agreed to participate, and 176 completed the survey [valid response rate, 87.1 %; male, 67.0 %; median age, 73 (63–81) years]. Multivariate logistic regression analyses were conducted to predict low confidence in self-care (score in the lowest quartile). Results: High confidence (confident or completely confident >75 % of patients) was observed for all self-care behavior categories except low-salt diet (63.1 %), regular exercise (63.1 %), and flu vaccination (65.9 %). Lower confidence in self-care behavior was associated with low quality of patient-physician communication. With regard to self-monitoring, 62.5 % of patients were not confident in distinguishing worsening symptoms of HF from other diseases; non-confidence was also associated with low quality of patient-physician communication. Conclusions: Hospitalized patients with HF had low confidence regarding regular exercise, salt restriction, and flu vaccination. The results also suggest patient-physician communication affects patient confidence.

Background: Sarcoidosis is a granulomatous disorder characterized by the formation of non-necrotizing granulomas in various organs. Cardiac sarcoidosis presents with various clinical, anatomical, and electrophysiological manifestations. As cardiac involvement is related to adverse outcomes, the early diagnosis of cardiac sarcoidosis is crucial and sometimes challenging. Case summary: A 65-year-old woman was initially treated for sick sinus syndrome (SSS) with normal cardiac function. Cardiac conduction defects and biventricular dysfunction continued to progress over a short clinical course, and the patient was eventually referred to our hospital for further investigation and treatment of cardiogenic shock due to pacemaker pacing failure. An echocardiography revealed a large thrombus formation in the right ventricle and atrium. An urgent thrombectomy was performed, and myocardial biopsy confirmed the diagnosis of cardiac sarcoidosis. Steroid pulse therapy was initiated and was effective in treating the cardiogenic shock. One year after discharge, the patient manifested with sustained ventricular tachycardia and ultimately died of severe cardiac pump failure. On autopsy, diffuse fibrotic tissues were noted in both ventricles and atria. Discussion: While conduction abnormalities, such as right bundle brunch block and atrioventricular block, are common clinical manifestations, SSS is rarely reported as a primary manifestation of cardiac sarcoidosis. Thus, clinicians should ensure that sufficient investigations are carried out when diagnosing idiopathic SSS.

Background The Japanese Hypertrophic Cardiomyopathy Registry Study was designed to provide comprehensive, real-world insights into the clinical characteristics and management of hypertrophic cardiomyopathy (HCM) in Japan. Methods This multicentre, prospective study enrolled consecutive patients with HCM from 24 referral hospitals across Japan starting in 2016. The baseline characteristics of 1485 patients enrolled by December 2019 are presented in this analysis. Results The median ages at registration and diagnosis were 69 and 60 years, respectively, with men accounting for 54% of the cohort. Familial HCM was confirmed in 18% of cases. Of the cohort, 36% had hypertrophic obstructive cardiomyopathy (HOCM), while 8% had mid-ventricular obstruction, 14% had apical HCM and 4% were in the end-stage phase. Atrial fibrillation was observed in 27% of patients, though the majority were asymptomatic or had mild symptoms at registration. Adverse outcomes included prior sustained ventricular tachycardia or fibrillation (6%), heart failure requiring hospitalisation (11%) and embolic events (5%). Defibrillator implantation was performed in 11% of patients. Differences in the defibrillator indications for primary prevention in the current three guidelines and status of defibrillator deployment at registration were clarified: the percentages of class IIa recommendation in the whole cohort and of patients with defibrillator implantation in class IIa were 22% and 19% in the Japanese guidelines, 4% and 39% in the European guidelines and 28% and 22% in the American guidelines, respectively. Beta blockers were prescribed to 90% of patients with HOCM, while 51% received cibenzoline. Septal reduction therapies were performed in 22% of patients with HOCM, with 6% undergoing surgical myectomy. Conclusions As the first large-scale, prospective HCM registry in Japan, this study provides valuable baseline data on the clinical characteristics and management of HCM. These findings will help address gaps between current practice and guideline recommendations, improving the care of patients with HCM.

症例は84歳女性。2011年に閉塞性肥大型心筋症(HOCM)を偶発的に指摘され近医通院を開始した。その後2016年8月頃より労作時胸痛が出現し増悪傾向を認め、同年11月に当院循環器内科を紹介受診した。経胸壁心エコーにて最大圧較差119mmHgの左室潤出路狭窄を認め、シベンゾリン、ビソプロロール導入後も改善に乏しく、2017年1月に経皮的中隔心筋焼灼術(PTSMA)を施行した。心室中隔基部を灌流する合計4本の中隔枝に対しアルコール焼灼を施行し、術中にエコー上で最大圧較差19mmHgまで軽減を確認した。術後は症状も消失したため問題なく退院となったが、2ヵ月後の2017年3月頃より労作時胸痛が再燃し、心エコーで最大圧較差96mmHgと流出路狭窄の再増悪を認め、PTSMA再施行目的に同年4月に入院となった。冠動脈造影では初回治療時にアルコール焼灼した4本の中隔枝のうち最も近位部の枝に再灌流を認め、同枝に対し再度アルコール焼灼を施行した。術後心エコーで最大圧較差15mmHgまで改善を認め、症状も消失し、1年半後の現在も再燃なく経過している。今回、初回PTSMA施行後の遠隔期に有症候性の流出路狭窄が再燃し、2回目のPTSMAで治療し得た閉塞性肥大型心筋症の1例を経験したので文献的考察を交えて報告する。(著者抄録)

Background: Pulmonary hypertension (PH) is a common complication of heart failure (HF) that has two subtypes: isolated postcapillary PH (IpcPH) and combined postcapillary and precapillary PH (CpcPH). The definitions of these subtypes were revised in 2022, but the prognostic impacts of this change in hospitalized patients with HF remain unclear. Therefore, this study aimed to investigate how the current definitions of PH subtypes affect patient prognosis. Methods: Among 4,762 patients in the West Tokyo Heart Failure 2 registry, we analyzed 975 patients (age: 69 ± 14 years; 33% female). We analyzed patients who underwent right heart catheterization following clinical stabilization. Patients were divided into NonPH, IpcPH, or CpcPH groups according to the 2018 and 2022 definitions. We assessed the impact of PH subtypes on adverse events, defined as cardiac mortality or HF rehospitalization among those hospitalized for HF. Results: The proportion of patients with CpcPH increased to 34.8% in 2022 (from 19.8% under the 2018 definition). The 2018 definition stated that CpcPH and IpcPH were associated with an increased risk of the adverse events (CpcPH: HR 1.62, 95%CI 1.14-2.31; IpcPH: HR 1.50, 95%CI 1.07-2.10). However, according to the 2022 definition, only CpcPH was an independent risk factor for the adverse events (CpcPH: HR 1.75, 95%CI 1.30-2.36; IpcPH: HR 1.03, 95%CI 0.64-1.65). Conclusions: The prognostic impact of CpcPH was more evident with the 2022 definition among hospitalized patients with HF. This information will help create more personalized disease management strategies.

Background: Bleeding events remain relatively frequent in patients with atrial fibrillation (AF), posing significant clinical challenges in routine patient management. The recently developed direct oral anticoagulant (DOAC) score shows promise in predicting bleeding risk; however, its performance in East Asian patients is not well characterized. Objective: This study aimed to assess the performance of the DOAC score in a contemporary outpatient-based registry of Japanese patients with AF and evaluate potential modifications to enhance its predictive accuracy. Methods: The Keio Interhospital Cardiovascular Studies-Atrial Fibrillation registry is a multicenter prospective database designed according to international standards for newly diagnosed AF. Adjudicated bleeding events were prospectively collected, and we assessed each bleeding risk score's predictive capacity using the C-index and calibration analysis. Performance was evaluated at 1- and 5-year intervals. Results: Among 2101 patients (median age of 70 years; 67.9% men), the overall 1- and 5-year bleeding incidence was 2.1% and 4.7%, respectively. The DOAC score demonstrated acceptable discrimination at 1 year (C-index 0.704, 95% confidence interval [CI] 0.634–0.774), which was maintained over the extended 5-year follow-up (C-index 0.690, 95% CI 0.640–0.741). Calibration analysis showed acceptable performance across validation datasets. Notably, modifying antiplatelet scoring by distinguishing aspirin (2 points) from other antiplatelets (1 point) improved the performance (C-index 0.707, 95% CI 0.637–0.777). Conclusion: The DOAC score proved valuable for long-term bleeding risk assessment in Japanese patients with AF, with enhanced performance through antiplatelet stratification. These findings support its implementation in East Asian populations for individualized clinical decision making.

Background Real-world characteristics and outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF) treated with vericiguat remain unclear. We investigated patient characteristics, hypotension—the most relevant clinical event—, and outcomes after initiating vericiguat in patients with HFrEF. Methods In this nationwide, multicentre retrospective study involving 22 hospitals in Japan, we examined symptomatic or asymptomatic hypotension and drug discontinuation within 90 days after initiation of vericiguat in patients with left ventricular ejection fraction <45%. The association between hypotension and HF outcomes was also examined. Results Among the 799 patients with HFrEF, the mean age was 69.6 years, and 218 (27.3%) were female. Of them, 316 (39.5%) had New York Heart Association classification III or IV, and 329 (41.8%) had systolic blood pressure (sBP) <100 mm Hg. Hypotension was observed in 25.3% of patients within 90 days, with asymptomatic hypotension being the most common (17.9%). By contrast, drug discontinuation related to hypotension was less frequent (4.4%). After adjustment, sBP <100 mm Hg, low body mass index, and in-hospital vericiguat initiation were associated with the incidence of hypotension within 90 days. Patients who experienced hypotension had a greater risk of cardiovascular death or HF hospitalization than those who did not ( P = .01). Conclusions Although hypotension was relatively common soon after starting vericiguat, they were not often associated with drug discontinuation. Patients experiencing hypotension had a greater risk of HF outcomes, but this would be primarily associated with their vulnerability, given the infrequent discontinuation.

Background Although most established bleeding definitions primarily emphasize overt bleeding, endpoints from major clinical trials and studies have historically defined major bleeding to include a periprocedural hemoglobin drop of ≥3.0 g/dL. However, the clinical relevance of this laboratory-based criterion, particularly without overt bleeding, remains uncertain. Objectives The authors investigated the prognostic implication of a periprocedural hemoglobin drop of ≥3.0 g/dL, especially without overt bleeding. Methods Consecutive patients were analyzed from a Japanese registry between 2008 and 2021 after percutaneous coronary intervention (PCI). Patients were classified by hemoglobin drop (≥3.0 g/dL decrease between pre- and post-PCI) and overt bleeding. Cox regression assessed associations between these groups and 2-year major adverse cardiac events (MACE, such as all-cause mortality, acute coronary syndrome, heart failure hospitalization, and stroke). Results Among 7,145 patients (mean age: 69 years; 77.0% male), 73 (1.0%) had both overt bleeding and hemoglobin drop; 85 (1.2%) had overt bleeding only; 590 (8.3%) had hemoglobin drop only; and 6,397 (89.5%) had no bleeding (reference). MACE occurred in 872 (12.2%; 95% CI: 11.5-13.0) patients during the median follow-up period of 730 (Q1-Q3: 730-730) days. MACE incidence was 30.1% (95% CI: 19.9-42.0) in patients with overt bleeding and hemoglobin drop, with higher risk than those without bleeding (adjusted HR: 2.16; 95% CI: 1.37-3.42). Only those patients with hemoglobin drop were not at increased risk of MACE (adjusted HR: 1.20; 95% CI: 0.89-1.60). Conclusions Hemoglobin drop with overt bleeding after PCI was associated with increased 2-year MACE risk, whereas hemoglobin drop without overt bleeding had less prognostic relevance, highlighting the importance of clinical context in evaluating post-PCI bleeding.

Introduction: Heart failure substantially affects the quality of life of patients and imposes notable social and economic burdens. Despite the beneficial effects of cardiac rehabilitation, global participation rates remain low. Recent advances in wearable biometric technologies may improve patient adherence through real-time monitoring and personalized feedback. This study aimed to develop and evaluate an exercise-support program that integrates wearable devices to enhance rehabilitation outcomes in patients with heart failure. Methods: An innovative and practical cardiac rehabilitation program combined with a wearable device was developed based on patients and physicians’ feedback. A multicenter randomized controlled clinical trial was designed to evaluate the safety and effectiveness of the application in patients with heart failure in Japan from October 2022 to January 2025. Compared with traditional exercise-monitoring applications, the developed application offers an array of features that are designed to foster patient engagement and promote long-term adherence. These features include (1) individualized goal setting, (2) direct communication with healthcare providers, (3) education on heart failure through instructional videos, (4) automated motivational feedback, and (5) a curated library of research summaries on cardiac rehabilitation and self-care. Patients who meet the inclusion criteria (including those aged ≥18 years with a clinical diagnosis of heart failure) will be randomly assigned to one of two groups as follows: the integrated exercise-support app group or the standard care group, in which only a wearable device was implemented. The change in peak VO2 at 12 weeks, adjusted for baseline and allocation factors, will be analyzed as the primary endpoint. The secondary outcomes include quality-of-life measures and re-hospitalization rates. Data analysis will follow the intention-to-treat principle, with results reported as two-tailed 95 % confidence intervals and corresponding p-values. This study was approved by the relevant institutional ethics committee (approval number: DB23-001; iRCT: 2032230388). Informed consent will be obtained from all participants before study participation. The results of the study will be disseminated through peer-reviewed publications and presented at relevant scientific meetings.

Background: The clinical importance of contrast-associated acute kidney injury (CA-AKI), the most common complication after percutaneous coronary intervention (PCI), is debated. Objectives: We aimed to assess the association between CA-AKI and long-term outcomes, overall and across the National Cardiovascular Data Registry (NCDR) AKI risk categories. Methods: We analyzed patients undergoing PCI between September 2008 and October 2021 from a Japanese registry aligned with the NCDR and categorized them by the NCDR AKI risk score tertiles (low-risk [<4.9%], intermediate-risk [4.9%-6.7%], and high-risk [≥6.7%]) groups. CA-AKI was defined as a 0.3 mg/dL increase or 50% increase in creatinine or the initiation of dialysis. Cox regression analyses assessed the association between CA-AKI and 2-year major adverse cardiovascular events (MACE; all-cause mortality, acute coronary syndrome, heart failure hospitalization, or stroke), and interactions were tested to examine whether preprocedural risk modified the association of CA-AKI with outcomes. Results: Of 7,916 patients, 723 (9.1%) developed CA-AKI; its incidence for low-risk, intermediate-risk, and high-risk groups was 2.3%, 7.3%, and 17.9%, respectively. CA-AKI was associated with an increased risk of MACE (adjusted HR [aHR]: 1.64; 95% CI: 1.37-1.97). The interaction between AKI risk profile and MACE was not significant (P interaction = 0.14), and a consistent association of CA-AKI and MACE across risk categories was observed (high-risk, aHR: 1.60; 95% CI: 1.30-1.98; intermediate, aHR: 1.64; 95% CI: 1.10-2.44; and low, aHR: 2.84; 95% CI: 1.43-5.65, respectively). Conclusions: CA-AKI was associated with long-term outcomes across all AKI risk profiles in PCI patients, underscoring the importance of interventions to reduce periprocedural CA-AKI.

Aims: The usefulness of catheter ablation (CA) for atrial fibrillation (AF) across a broad spectrum of heart failure (HF) patients remains to be established. We assessed the association of CA with both health-related quality of life (QoL) and cardiovascular events among HF patients with reduced and preserved left ventricular ejection fraction (LVEF) in an 'all-comer' outpatient-based AF registry. Methods and results: Of 3303 patients with AF consecutively enrolled in a retrospective multicentre registry that mandated the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) questionnaire at registration and 1-year follow-up, we extracted data from 530 patients complicating clinical HF. The association between CA and both 1-year change in AFEQT Overall Summary (AFEQT-OS) scores and 2-year composite clinical outcomes (including all-cause death, stroke, and HF hospitalization) was assessed by multivariable analyses. The median duration of AF was 108 days (52-218 days), and 83.4% had LVEF >35%. Overall, 75 patients (14.2%) underwent CA for AF within 1-year after registration. At 1-year follow-up, 67.2% in the ablation group showed clinically meaningful improvements of ≥ 5 points in AFEQT-OS score than 47.8% in the non-ablation group {adjusted odds ratio, 2.03 [95% confidence interval (CI): 1.13-3.64], P = 0.017}. Furthermore, the composite endpoint of all-cause death, stroke, and HF hospitalization occurred less frequently in the ablation group than the non-ablation group [adjusted hazard ratio, 0.27 (95% CI: 0.09-0.86), P = 0.027]. Conclusion: Among AF-HF patients, CA was associated with improved QoL and lower risk of cardiovascular events against drug therapy alone, even for patients with mildly reduced and preserved LVEF.

A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I–II (mean age: 63.5 years, interquartile range: 58.0–72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland–Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391–0.815) was achieved in 32/50 cases. The difference between sLT and VT was −4.9 ± 15.0 W. No comparative error was noted in the Bland–Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

Objective: To optimize workplace health promotion, a simple method for quantifying allostatic load response is needed. This study examines the feasibility of optimizing objective anxiety and presenteeism monitoring using daily smartwatch-measured ultra-short heart rate variability (HRV). Methods: Office workers without diagnosed disease prospectively performed 30 s HRV self-measurement each morning for two months and responded to the State-Trait Anxiety Inventory (STAI) and Work Limitation Questionnaire (WLQ). Logistic regression analysis examined daily HRV parameters in the high-trait anxiety group (HTA, STAI ≥ 40) using mean and variance HRV, age, self-reported gender, and body mass index (BMI). The ideal cutoff value enabled comparison of WLQ using the Mann–Whitney U test. Heart rate variability data were collected for 279 participants (male ratio, 83.9%; age, 42 ± 10 years) who completed questionnaires and monitored HRV for 30+ days. Results: Compared to the low-trait anxiety group, HTA exhibited higher variance of the log-transformed coefficient of component variance of high-frequency component (LnccvHF) and low-frequency per HF (Lnccv L/H), in addition to differences in the means of these HRV parameters. In addition to BMI (odds ratio [OR] = 0.92, p = 0.02) and mean LnccvL/H (OR = 10.75, p < 0.01), the variance of Lnccv L/H was an independent predictor of HTA (OR = 2.39E + 8, p = 0.011). The daily Lnccv L/H dispersion group had a lower WLQ productivity loss score (p = 0.02, r = 0.17). Conclusions: By focusing on HRV dispersion status, this simple and instantly applicable daily HRV monitoring system enables optimized quantitative monitoring of anxiety and productivity.

BACKGROUND: Despite recommendations from clinical practice guidelines to initiate and titrate guideline-directed medical therapy (GDMT) during their hospitalization, patients with acute heart failure (AHF) are frequently undertreated. In this study we aimed to clarify GDMT implementation and titration rates, as well as the long-term outcomes, in hospitalized AHF patients.Methods and Results: Among 3,164 consecutive hospitalized AHF patients included in a Japanese multicenter registry, 1,400 (44.2%) with ejection fraction ≤40% were analyzed. We assessed GDMT dosage (β-blockers, renin-angiotensin inhibitors, and mineralocorticoid-receptor antagonists) at admission and discharge, examined the contributing factors for up-titration, and evaluated associations between drug initiation/up-titration and 1-year post-discharge all-cause death and rehospitalization for HF via propensity score matching. The mean age of the patients was 71.5 years and 30.7% were female. Overall, 1,051 patients (75.0%) were deemed eligible for GDMT, based on their baseline vital signs, renal function, and electrolyte values. At discharge, only 180 patients (17.1%) received GDMT agents up-titrated to >50% of the maximum titrated dose. Up-titration was associated with a lower risk of 1-year clinical outcomes (adjusted hazard ratio: 0.58, 95% confidence interval: 0.35-0.96). Younger age and higher body mass index were significant predictors of drug up-titration. CONCLUSIONS: Significant evidence-practice gaps in the use and dose of GDMT remain. Considering the associated favorable outcomes, further efforts to improve its implementation seem crucial.

Exercise therapy at the aerobic level is highly recommended to improve clinical outcomes in patients with heart failure, in which cardiopulmonary exercise testing (CPX) is required to determine anaerobic thresholds (ATs) but is not available everywhere. This study aimed to validate a method to estimate the AT using heart rate variability (HRV) analysis from electrocardiography data in patients with heart failure. Between 2014 and 2019, 67 patients with symptomatic heart failure underwent CPXs in a single university hospital. During the CPX, RR intervals was measured continuously and the HRV threshold (HRVT), defined as the inflection point of <5 ms2 of a high-frequency component (HFC) using the power spectrum analysis, was determined. Patients were divided into two groups according to the mean HFC at rest (high-HFC group, n = 34 and low-HFC group, n = 33). The high-HFC group showed good correlation between the VO2 at AT and HRVT (r = 0.63, p < 0.001) and strong agreement (mean difference, −0.38 mL/kg, p = 0.571). The low-HFC group also showed modest correlation (r = 0.41, p = 0.017) but poor agreement (mean differences, 3.75 mL/kg, p < 0.001). In conclusion, the HRVT obtained from electrocardiography may be a useful indicator for estimating AT in patients with heart failure.