Published papers

© 2017, Japanese Circulation Society. All rights reserved. Background: Intracardiac echocardiography (ICE) and cardiac computed tomography (CCT), in addition to standard transesophageal echocardiography (TEE), have been used to identify left atrial (LA) thrombi prior to ablation for atrial fibrillation (AF). The clinical advantages of this, however, remain unclear. This study therefore investigated the advantages of additional pre-procedural LA appendage (LAA) thrombus evaluation using ICE and the clinical value of CCT in persistent and long-standing persistent AF. Methods and Results: We analyzed data from 108 consecutive patients with persistent and long-standing persistent AF who were scheduled to undergo AF ablation. TEE was performed within 24 h prior to ablation. ICE was performed for 97 patients in whom a thrombus was not detected on TEE. CCT was performed in 95 patients. Thrombus or sludge was detected on TEE in 11 patients (10.3%), for whom ablation was cancelled. Four additional patients were diagnosed with LAA thrombus on ICE. When TEE and ICE were used as the reference for thrombus detection, the sensitivity, specificity, positive predictive value, and negative predictive value of CCT for identifying contrast defects in the LAA were 100%, 81.0%, 40.7%, and 100%, respectively. Conclusions: ICE combined with TEE increased the detection rate of LAA thrombi in patients with persistent and long-standing persistent AF. Moreover, CCT had high sensitivity and negative predictive value for LAA thrombus detection.

© 2019, Springer Japan KK, part of Springer Nature. Heart failure (HF) is characterized by frequent rehospitalization and prolonged hospital stay. Although length of stay has been used as a surrogate marker for hospital performance, its association with early rehospitalization remains unknown. We investigated their precise association using contemporary Japanese HF registry. We analyzed the 2785 acute HF patients who were registered in the West Tokyo Heart Failure registry and discharged or transferred to the recuperation facilities (mean age, 73.8 ± 13.5 years; 60.8% were men). Median length of stay was 15 days (interquartile range, 10–23 days). One-hundred and fourteen patients (4.1%) were readmitted for worsening HF within 30 days after discharge. Thirty-day risk-adjusted HF readmission after a shorter length of stay (1–12 days; the lower tertile within the cohort) was higher than those after intermediate (13–19 days; the middle tertile) [HR 1.71, 95% confidence interval (CI) 1.05–2.77]. Even after a longer length of stay, there tended to be a higher risk of 30-day HF readmission (HR 1.59, 95% CI 0.96–2.65). In conclusion, the Japanese acute HF patients had low rates of early-HF readmission after quite a long length of stay at urban tertiary care centers. Shorter length of stay was associated with increased rates of 30-day HF readmission, while longer length of stay also the same trended. Clinical Trial Registration: https://www.umin.ac.jp/icdr/index-j.html. Unique identifier: UMIN000001171.

This observational study aimed to examine the extent of early invasive strategy (EIS) utilization in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) according to the National Cardiovascular Data Registry (NCDR) CathPCI risk score, and its association with clinical outcomes. Using a prospective multicenter Japanese registry, 2968 patients with NSTE-ACS undergoing percutaneous coronary intervention within 72 hours of hospital arrival were analyzed. Multivariable logistic regression analyses were performed to determine predictors of EIS utilization. Additionally, adverse outcomes were compared between patients treated with and without EIS. Overall, 82.1% of the cohort (n = 2436) were treated with EIS, and the median NCDR CathPCI risk score was 22 (interquartile range: 14-32) with an expected 0.3-0.6% in-hospital mortality. Advanced age, peripheral artery disease, chronic kidney disease or patients without elevation of cardiac biomarkers were less likely to be treated with EIS. EIS utilization was not associated with a risk of in-hospital mortality; yet, it was associated with an increased risk of acute kidney injury (AKI) (adjusted odds ratio: 1.42; 95% confidence interval: 1.02-2.01) regardless of patients’ in-hospital mortality risk. Broader use of EIS utilization comes at the cost of increased AKI development risk; thus, the pre-procedural risk-benefit profile of EIS should be reassessed appropriately in patients with lower mortality risk.

© 2019 European Federation of Internal Medicine Purpose: Although guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) should be treated with renin-angiotensin system (RAS) inhibitors, the long-term efficacy of RAS inhibitors in HFrEF patients with moderate-to-severe chronic kidney disease (CKD) remains unclear. Methods: The present study included consecutive patients hospitalized for acute heart failure across five Japanese teaching hospitals. The impact of RAS inhibitors on 2-year all-cause mortality was evaluated in patients with an ejection fraction ≤40% and CKD, defined as an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m 2 , at discharge. Its severity was subclassified from 3B to 5 according to eGFR. Results: Overall, 553 patients (age, 76 ± 11 years; 68% male) were included. RAS inhibitors were prescribed more frequently in 227 patients with stage 3B (71.2%) than in 107 patients with stage 4 or 5 CKD (45.7%). All-cause mortality was recorded in 119 patients (23.4%) (55 [18.5%] patients with stage 3B; 64 [30.3%] patients with stage 4 or 5 CKD), within the median follow-up period of 609 (220–983) days. After many-to-one propensity score matching (87 pairs in stage 3; 60 pairs in stage 4 or 5 CKD), those with RAS inhibitors had reduced mortality rate in stage 3B (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.19–0.83) but not in stage 4 or 5 CKD (HR, 1.08; 95% CI, 0.57–2.03). Conclusions: In HFrEF patients with CKD, RAS inhibitors are associated with reduction in mortality in stage 3B CKD, but the association is less clear in stage 4 or 5 CKD.

In the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, an early invasive strategy did not decrease mortality compared to a conservative strategy for stable ischemic heart disease (SIHD) patients with moderate-to-severe ischemia, and the role of revascularization would be revised. However, the applicability and potential influence of this trial in daily practice remains unclear. Our objective was to assess the eligibility and representativeness of the ISCHEMIA trial on the patients with percutaneous coronary intervention (PCI). From a multicenter registry, we extracted a consecutive 13,223 SIHD patients with PCI (baseline cohort). We applied ISCHEMIA eligibility criteria and compared the baseline characteristics between the eligible patients and the actual study participants (randomized controlled trial (RCT) patients). In 3463 patients with follow-up information (follow-up cohort), the 2 year composite of major adverse cardiac events was evaluated between the eligible patients and RCT patients, as well as eligible and non-eligible patients in the registry. In the baseline cohort, 77.3% of SIHD patients with moderate-to-severe ischemia were eligible for the ISCHEMIA. They were comparable with RCT patients for baseline characteristics and outcomes unlike the non-eligible patients. In conclusion, the trial results seem applicable for the majority of PCI patients with moderate-to-severe ischemia except for the non-eligible patients.

The real-world evidence has been sparse on the impact of non-invasive positive pressure ventilation (NPPV) on the outcomes in acute decompensated heart failure (ADHF) patients. We aim to explore this issue in the prospective multicenter WET-HF registry. Among 3927 patients (77 (67–84) years, male 60%), the NPPV was used in 775 patients (19.7%). The association of NPPV use with in-hospital outcome and length of hospital stay (LOS) was examined by two methods, propensity score (PS) matching and multivariable analysis with adjustment for PS. In these analyses the NPPV group exhibited a lower endotracheal intubation (ETI) rate and a comparable in-hospital mortality, but longer LOS compared to the non-NPPV group. In the stratified analysis, the NPPV group exhibited a significantly lower ETI rate in patients with ischemic etiology, systolic blood pressure (sBP) > 140 mmHg and the Controlling Nutritional Status (CONUT) score ≤ 3, indicating better nutritional status. On the contrary, NPPV use was associated with longer LOS in patients with non-ischemic etiology, sBP < 100 mmHg and CONUT score > 3. In conclusion, NPPV use was associated with a lower incidence of ETI. Particularly, patients with ischemic etiology, high sBP, and better nutritional status might benefit from NPPV use.

Dyskalemia (hypokalemia and hyperkalemia) is a common comorbidity of heart failure (HF). Although dyskalemia is associated with poor prognosis, different prognostic impacts of hypo- and hyperkalemia remain vastly unclear. This study investigated the association of dyskalemia with prognosis in HF patients, especially the mode of death and left ventricular ejection fraction (LVEF). The multicenter study included 3398 patients hospitalized for HF. Patients were divided into three groups based on serum potassium levels at discharge: hypokalemia (<3.5 mEq/L; n = 115 (3.4%)), normokalemia (3.5–5.0 mEq/L; n = 2960 (87.1%)), and hyperkalemia (≥5.0 mEq/L; n = 323 (9.5%)). Two-year all-cause, cardiac, and non-cardiac mortality was evaluated. Association of serum potassium with two-year mortality demonstrated a U-shaped curve, with a worse prognosis for patients with hypokalemia. All-cause mortality at two-years did not differ among the three groups. Hypokalemia was associated with 2-year cardiac death (adjusted hazard ratio (HR), 2.60; 95% confidence interval (CI), 1.20–5.64) in HF with reduced ejection fraction (HFrEF; LVEF < 40%), but not in non-HFrEF. Regardless of LVEF, hyperkalemia was not independently associated with any mortality. Hypokalemia was independently associated with cardiac death, particularly in HFrEF patients. Such an association was not observed in hyperkalemia regardless of LVEF.

The optimal heart rate (HR) in patients with heart failure with reduced ejection fraction (HFrEF) has been ill-defined. Recently, a formula was proposed for estimating the target heart rate (THR), which eliminates the overlap between the E and A wave (E-A overlap). We aim to validate its prognostic significance in the multicenter WET-HF registry. This study used data from 647 patients with HFrEF hospitalized for acute decompensated HF (ADHF). The patients were divided into the 2 groups by THR. The primary endpoint was defined as the composite of all-cause death and ADHF readmission. The THR successfully discriminated the incidence of the primary endpoint, whereas no significant difference was observed in the primary endpoint when dividing the patients by uniform cutoff 70 bpm. HR at discharge ≤ THR was inversely associated with the primary endpoint. Restricted cubic spline analysis demonstrated the difference between HR at discharge, and THR (∆HR) from −10 to ±0 was associated with a lower risk of primary endpoint and ∆HR from ±0 to +15 was associated with a higher risk. THR discriminated long-term outcomes in patients with HFrEF more efficiently than the uniform cutoff, suggesting that it may aid in tailored HR reduction strategies.

Background: Understanding sex differences is critical for improving outcomes in patients with cardiovascular conditions. Sleep and psychological disturbances contribute to the development and progression of cardiovascular diseases, and important sex differences persist in their incidence and association with clinical outcomes. Methods: Sex-based variation in sleep and psychological disturbances were assessed in consecutive patients with cardiovascular diseases in a single university hospital. The prevalence of insomnia, sleep disordered breathing (SDB), anxiety, and depression was assessed using the Pittsburgh Sleep Quality Index (PSQI), nocturnal pulse oximeter, and the Hospital Anxiety and Depression Scale (HADS). The effect of sex on the prevalence of sleep and psychological disturbances as well as their associations was quantified using multivariate logistic regression models. Results: Among 1,233 patients (mean age 63.6 years, 25% women), women were significantly less likely than men to experience SDB (17.5% vs 31.5%, p < 0.001), but more likely to report an increased burden of insomnia (54.7% vs 43.3%, p = 0.001) and depression (23.9% vs 16.7%, p = 0.004). Insomnia was associated with depression, which was more remarkable among women (p value for interaction: 0.039). SDB was associated with anxiety among women but not men (p value for interaction: 0.003). There was no significant difference in the prevalence of anxiety between women and men. Conclusions: Among patients with cardiovascular disease, women reported an increased burden of insomnia and depression compared to men. The association between sleep and psychological disturbances may be more pronounced in women, suggesting that cardiologists should increase efforts for identification of such comorbidities and administer corresponding treatment, especially in women.

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

© 2020 The Author(s). Background: Many patients with emergent heart failure (HF) readmission have a delay between symptom onset and hospitalization. The present study aimed to characterize the interval between symptom onset and hospitalization in patients being readmitted for HF and to compare the clinical phenotypes of patients with delay before emergent readmission with those who presented to the hospital earlier. Methods: Data for a total of 2073 consecutive patients was collected from the Tokyo CCU Network database; the patients were divided into delayed (those who sought medical help > 2 days after symptom onset; n = 271) and early groups (remaining patients; n = 1802), and their clinical characteristics and mode of presentation were compared. Results: Age, sex, and laboratory findings including brain natriuretic peptide and serum creatinine levels were not significantly different between the two groups. Patients in the delayed group had greater chronic fluid retention and symptoms not associated with respiratory failure, whereas those in the early group were more likely to have acute respiratory distress, faster heart and respiration rates, and higher systolic blood pressure. Conclusions: More than one in ten patients with HF readmission delay seeking treatment > 2 days after symptom onset. Patients who delayed seeking treatment showed the phenotype of chronic fluid retention, whereas those who presented to the hospital earlier had the phenotype of acute respiratory failure.

The administration of beta-blockers is challenging and their efficacy is unclear in heart failure (HF) patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the association of beta-blockers with mortality in such patients. This multicenter observational cohort study included hospitalized HF patients with a left ventricular ejection fraction <50% and evaluated them retrospectively. COPD was diagnosed based on medical records and/or the clinical judgment of each investigator. The study endpoints were two-year all-cause, cardiac, and non-cardiac mortality. This study included 83 patients with COPD and 1760 patients without. Two-year all-cause, cardiac, and non-cardiac mortality were observed in 315 (17%), 149 (8%), and 166 (9%) patients, respectively. Beta-blockers were associated with lower all-cause mortality regardless of COPD (COPD: hazard ratio [HR] 0.39, 95% CI 0.16–0.98, p = 0.044; non-COPD: HR 0.62, 95% CI 0.46–0.83, p = 0.001). This association in HF patients with COPD persisted after multivariate analysis and inverse probability weighting and was due to lower non-cardiac mortality (HR 0.40, 95% CI 0.14–1.18. p = 0.098), not cardiac mortality (HR 0.37, 95% CI 0.07–2.01, p = 0.248). Beta-blockers were associated with lower all-cause mortality in HF patients with COPD due to lower non-cardiac mortality. This may reflect selection biases in beta-blocker prescription.

Background: The prognostic implication of elevated or decreased blood glucose (BG) level in acute decompensated heart failure (ADHF) has been still controversial. Indices of stress hyperglycemia, expressed by the ratio of BG and chronic BG control, has been reported to be associated with poor outcome in different disease population. We sought to assess BG at admission and %ΔBG, an index of BG deviation from estimated average BG calculated from glycated hemoglobin (HbA1c), on the long-term outcome in ADHF patients. Methods and results: The West Tokyo Heart Failure (WET-HF) Registry is a prospective multicenter registry enrolling consecutive hospitalized ADHF patients. Among the patients (N = 3078, 77 [67–84] years, male 59%), BG at admission discriminated the long-term (1000 days) incidence of ADHF rehospitalization, but not cardiac death. BG at admission showed a U-shape relationship with the long-term incidence of ADHF rehospitalization after adjustment for covariates. Especially, in patients with HbA1c ≥ 6.5%, the lowest quartile showed the highest risk of ADHF rehospitalization. On the contrary, %ΔBG showed U-shape relationship with the long-term incidence of cardiac death after discharge, rather than ADHF rehospitalization after adjustment for covariates. In addition, elevated %ΔBG was associated with the long-term risk of sudden cardiac death (SCD) even after adjustment for covariates. Conclusions: For ADHF patients, BG at admission and %ΔBG might be a simple, useful tool for predicting and stratifying long-term risk of cardiac events. Especially, elevated %ΔBG might be an important in predicting hard events such as cardiac death or SCD.

© 2020 Elsevier Inc. Background: Heart failure (HF) is a highly prevalent, heterogeneous, and life-threatening condition. Precise prognostic understanding is essential for effective decision making, but little is known about patients’ attitudes toward prognostic communication with their physicians. Methods and Results: We conducted a questionnaire survey, consisting of patients’ prognostic understanding, preferences for information disclosure, and depressive symptoms, among hospitalized patients with HF (92 items in total). Individual 2-year survival rates were calculated using the Seattle Heart Failure Model, and its agreement level with patient self-expectations of 2-year survival were assessed. A total of 113 patients completed the survey (male 65.5%, median age 75.0 years, interquartile range 66.0–81.0 years). Compared with the Seattle Heart Failure Model prediction, patient expectation of 2-year survival was matched only in 27.8% of patients; their agreement level was low (weighted kappa = 0.11). Notably, 50.9% wished to know “more,” although 27.7% felt that they did not have an adequate prognostic discussion. Compared with the known prognostic variables (eg, age and HF severity), logistic regression analysis demonstrated that female and less depressive patients were associated with patients’ preference for “more” prognostic discussion. Conclusions: Patients’ overall prognostic understanding was suboptimal. The communication process requires further improvement for patients to accurately understand their HF prognosis and be involved in making a better informed decision.