Published papers

Background: Interest in clinical course preceding heart failure (HF) exacerbation has grown, with a greater emphasis placed on patients' clinical factors including precipitant factor (PF). Large-scale studies with precise PF documentation and temporal-outcome variation remain limited. Methods: We reviewed prospectively collected 2412 consecutive patient-level records from a multicenter Japanese registry of hospitalized patients with HF (West Tokyo Heart Failure2 Registry: 2018–2020). Patients were categorized based on PFs: behavioral (i.e., poor adherence to physical activity, medicine, or diet regimen), treatment-required (i.e., anemia, arrhythmia, ischemia, infection, thyroid dysfunction or other conditions as suggested exacerbating factors), and no-PF. The composite outcomes of HF rehospitalization and death within 1 year after discharge and HF rehospitalization were individually assessed. Results: Median patient age was 78 years (interquartile range: 68–85 years), and 1468 (61%) patients had documented PFs, of which 356 (15%) were considered behavioral. The behavioral PF group were younger, more male and had past HF hospitalization history compared to those in the other groups (all p < 0.05). Although risk of in-hospital death was lower in the behavioral PF group, their risk of composite outcome was not significantly different from the treatment-required group (hazard ratio [HR] 1.19 [95% confidence interval {CI} 0.93–1.51]) and the no-PF group (HR 1.28 [95%CI 1.00–1.64]). Furthermore, the risk of HF rehospitalization was higher in the behavioral PF group than in the other two groups (HR 1.40 [95%CI 1.07–1.83] and HR 1.39 [95%CI 1.06–1.83], respectively). Conclusion: Despite a better in-hospital prognosis, patients with behavioral PFs were at significantly higher risk of HF rehospitalization.

Aims: The trajectories of systolic function after admission for acute heart failure (HF) and their effect on clinical outcomes have not been fully elucidated. We aimed to assess changes in left ventricular ejection fraction (LVEF) between the index and 1 year after discharge and to examine their prognostic implications. Methods and results: We extracted data from a prospective multicentre registry of patients hospitalized for acute HF and identified 1636 patients with LVEF data at admission and 1 year after discharge. We categorized them into five groups based on LVEF changes: HF with unchanged-preserved EF [HFunc-pEF (EF ≥ 50%); N = 527, 32.2%], unchanged-mildly reduced EF [HFunc-mrEF (EF 41–49%); N = 86, 5.3%], unchanged-reduced EF [HFunc-rEF (EF ≤ 40%); N = 377, 23.0%], worsened EF (HFworEF; N = 83, 5.1%), and improved EF (HFimpEF; N = 563, 34.4%). We then evaluated the subsequent composite outcome of cardiovascular death and HF readmission. During 1 year after discharge, 53% of patients with HF with reduced EF and 67% of those with HF with mildly reduced EF (HFmrEF) transitioned to other categories, whereas 92% of those with HF with preserved EF (HFpEF) remained within the same category. Patients with HFimpEF were more likely to be younger and had relatively preserved renal function, whereas those with HFworEF were the oldest and had more comorbidities among the five groups. After multivariable adjustment, patients with HFimpEF and HFunc-pEF had a lower risk for composite outcomes when referenced to patients with HFunc-rEF [hazard ratio (95% confidence interval), P-value: 0.28 (0.16–0.49), P < 0.001, and 0.40 (0.25–0.63), P < 0.001, respectively]. Conversely, patients with HFunc-mrEF and HFworEF had a comparable risk [0.44 (0.18–1.07), P = 0.07, and 0.63 (0.29–1.39), P = 0.26, respectively]. Conclusions: A substantial number of patients with HF experienced transitions to other categories after discharge. Notably, patients with decreased EF experienced a worse prognosis, even with slight decreases (e.g. HFpEF transitioning to HFmrEF). These findings emphasize the significance of longitudinal assessments of systolic function to better manage patients following acute decompensation.

Aims: The long-term outcome in patients with heart failure (HF) after hospitalization may vary substantially depending on their age and left ventricular ejection fraction (LVEF). We aimed to assess the relative rates of cardiovascular death (CVD) and non-CVD based on the age and how the rates differ under the updated LVEF classification system. Methods and results: Consecutively registered hospitalized patients with HF (N = 3558; 39.7% women with a mean age of 73.9 ± 13.3 years) were followed for a median of 2 (interquartile range, 0.8–3.1) years. The CVDs and non-CVDs were evaluated based on age [young (<65 years), older (65–84 years), and very old (≥85 years)] and LVEF classification [HF with preserved EF (HFpEF; LVEF ≥50%) and non-HFpEF (LVEF <50%)]. The adverse clinical events were adjudicated independently by a central committee. Overall, 1505 (42.3%) had HFpEF [young: n = 182 (12.1%), older: n = 894 (59.4%), very old: n = 429 (28.5%)], and 2053 (57.7%) had non-HFpEF [young: n = 575 (28.0%), older: n = 1159 (56.5%), very old: n = 319 (15.5%)]. During the follow-up, the crude incidence of all-cause death was higher in non-HFpEF than in HFpEF across all age groups (non-HFpEF vs. HFpEF, young: 10.4% vs. 5.5%, log-rank P = 0.10; older: 26.6% vs. 20.9%, log-rank P = 0.002; very old: 36.7% vs. 31.7%, log-rank P = 0.043). CVDs accounted for more than half of all deaths in non-HFpEF (young 65.0%, older 64.2%, and very old 55.6%), whereas the proportion of CVDs remained less than half in HFpEF (young 50.0%, older 41.2%, very old 38.2%). HF readmission was associated with subsequent all-cause death in non-HFpEF [hazard ratio (HR): 1.72, 95% confidence interval (CI): 1.41–2.09, P < 0.001], but not in HFpEF (HR: 1.12, 95% CI: 0.87–1.43, P = 0.39). Conclusions: The probability of a non-CVD increases in both LVEF categories with advancing age, but that it is greater in the HFpEF category. The findings indicate that mitigating CV-related outcomes alone may be insufficient for treating HF in older population, particularly in the HFpEF category.

The health benefits of physical activity have been widely recognized, yet there is limited information on associations between accelerometer-related parameters and established patient-re-ported health status. This study investigated the association between the waist-worn accelerometer measurements, cardiopulmonary exercise testing (CPX), and results of the Kansas City Cardiomy-opathy Questionnaire (KCCQ) in heart failure (HF) patients hospitalized for acute decompensation. A total of 31 patients were enrolled and wore a validated three-axis accelerometer for 2 weeks and completed the short version of the KCCQ after removing the device. Daily step counts, exercise time (metabolic equivalents × hours), and %sedentary time (sedentary time/device-equipped time) were measured. Among the measured parameters, the best correlation was observed between %seden-tary time and the KCCQ overall and clinical summary scores (r = −0.65 and −0.65, each p < 0.001). All of the individual domains of the KCCQ (physical limitation, symptom frequency, and quality of life), with the exception of the social limitation domain, showed moderate correlations with %sed-entary time. Finally, oxygen consumption assessed by CPX demonstrated only weak associations with the accelerometer-measured parameters. An accelerometer could complement the KCCQ results in accurately assessing the physical activity in HF patients immediately after hospitalization, albeit its correlation with CPX was at most moderate.

Abnormal liver function tests (LFTs) are known to be associated with impaired clinical outcomes in heart failure (HF) patients. However, this implication varies with each single LFT panel. We aim to evaluate the long-term outcomes of acute HF (AHF) patients by assessing multiple LFT panels in combination. From a prospective multicenter registry in Japan, 1158 AHF patients who were successfully discharged were analyzed (mean age, 73.9 ± 13.5 years; men, 58%). LFTs (i.e., total bilirubin, aspartate aminotransferase or alanine aminotransferase, and alkaline phosphatase) at discharge were assessed; borderline and abnormal LFTs were defined as 1 and ≥2 parameter values above the normal range, respectively. The primary endpoint was composite of all-cause death or HF readmission. At the time of discharge, 28.7% and 8.6% of patients showed borderline and abnormal LFTs, respectively. There were 196 (16.9%) deaths and 298 (25.7%) HF readmissions during a median 12.4-month follow-up period. The abnormal LFTs group had a significantly higher risk of experiencing the composite outcome (adjusted hazard ratio: 1.51, 95% confidence interval: 1.08–2.12, p = 0.017), whereas the borderline LFTs group was not associated with higher risk of adverse events when referenced to the normal LFTs group. Among AHF patients, the combined elevation of ≥2 LFT panels at discharge was associated with long-term adverse outcomes.

Early and rapid risk stratification of patients with acute heart failure (AHF) is crucial for appropriate patient triage and outcome improvements. We aimed to develop an easy-to-use, in-hospital mortality risk prediction tool based on data collected from AHF patients at their initial presentation. Consecutive patients’ data pertaining to 2006-2017 were extracted from the West Tokyo Heart Failure (WET-HF) and National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure (NaDEF) registries (n = 4351). Risk model development involved stepwise logistic regression analysis and prospective validation using data pertaining to 2014-2015 in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure Syndrome (REALITY-AHF) (n = 1682). The final model included data describing six in-hospital mortality risk predictors, namely, age, systolic blood pressure, blood urea nitrogen, serum sodium, albumin, and natriuretic peptide (SOB-ASAP score), available at the time of initial triage. The model showed excellent discrimination (c-statistic = 0.82) and good agreement between predicted and observed mortality rates. The model enabled the stratification of the mortality rates across sixths (from 14.5% to <1%). When assigned a point for each associated factor, the integer score’s discrimination was similar (c-statistic = 0.82) with good calibration across the patients with various risk profiles. The models’ performance was retained in the independent validation dataset. Promptly determining in-hospital mortality risks is achievable in the first few hours of presentation; they correlate strongly with mortality among AHF patients, potentially facilitating clinical decision-making.

Aims: Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low-dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. Methods and results: From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy-proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7–96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9–83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P < 0.001) between the two groups. Within the first year after HTx, 23 (59%) in the TAC group switched mycophenolate mofetil to everolimus, whereas 16 (48%) in the CsA group (P = 0.52). At 12 months, the rates of mortality and end-stage renal disease requiring renal replacement therapies were both 0%. In the instrumental variable analysis, no differences in renal function as well as graft rejection for 1 year after HTx existed between the TAC and CsA groups. These results were similar when taking into account of everolimus use. Conclusions: Irrespective of everolimus use with low-dose CNIs, our analysis using the instrumental variable method showed no differences in renal function as well as graft rejection during the first year after HTx between HTx recipients who received TAC or CsA.

© 2019, Springer Japan KK, part of Springer Nature. Patient-reported quality of life (PRQL) is a primary therapeutic target for patients with chronic heart failure (HF) and is associated with long-term prognosis. However, its utility in hospitalized HF (HHF) patients in the acute setting remains unclear. We aimed to assess the utility of PRQL (the Kansas City Cardiomyopathy Questionnaire [KCCQ]) in HHF patients and its association with long-term prognosis as well as with the clinical risk score (Get With The Guidelines-Heart Failure [GWTG-HF] risk score). PRQL was evaluated using the KCCQ in consecutive 114 HHF patients. Its association with the composite outcome of all-cause mortality or HF readmission within the first year after discharge was analyzed. Furthermore, its distribution by the clinical risk score (GWTG-HF) was evaluated using Pearson’s correlation coefficient. The median KCCQ was 34.9, but was widely distributed (interquartile range 23.7–56.8). After adjustment for known prognostic indicators, the KCCQ was not an independent predictor of the composite outcome within the first year (group with high vs. low KCCQ scores: hazard ratio, 0.67; 95% confidence interval 0.26–1.71). There was no significant correlation between the KCCQ and the GWTG-HF risk score. In conclusion, PRQL during the acute phase of HF was significantly impaired and also varied widely, irrespective of patient characteristics or severity. PRQL assessment and risk prediction for HHF patients in the acute setting seemed to provide two distinct types of information for health care providers.

© The Author(s) 2019. Background Atrial septal defect (ASD) and patent ductus arteriosus (PDA) are both common congenital heart diseases, but the combination of these two cardiac defects is extremely rare, and the therapeutic strategy is controversial. Case summary We treated an adult patient with combined ASD and PDA, and safely attained a successful outcome with two-stage transcatheter closure, which is PDA closure preceding ASD closure, to prevent serious complications. Discussion Transcatheter closure of one of the defects is now widely accepted as an alternative to surgical closure. In addition, adults with both ASD and PDA are better suited for transcatheter closure than surgical closure. One of the reasons is the difficulty to ligate the ductus arteriosus of an adult patient due to its friability and calcification. Meanwhile, simultaneous combined transcatheter closure of ASD and PDA can result in serious complications, such as thrombocytopenia and haemolysis, whose mechanism is considered to be the destruction of platelets and red blood cells by the residual shunt through implanted devices. Additionally, antiplatelet therapy that prevents device-related thrombus formation after ASD closure can possibly exacerbate thrombocytopenia and haemolysis. Therefore, the staged strategy is reasonable from the perspectives of antiplatelet therapy and haemodynamic changes.

Background: The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes. Methods: Consecutive patients hospitalized for acute heart failure between 2010 and 2014 were registered in a multicenter data registration system (72 institutions within Tokyo, Japan). Baseline demographics and in-hospital mortality were extracted from 17,473 patients. Patients with a trigger were grouped based on their triggering event: those with onset during (a) physical activity; (b) sleeping; (c) eating or watching television; (d) bathing or excretion (use of restrooms); and (e) engaging in other activities. These patients were compared with patients without identifiable triggers. Multiple imputation was used for missing data. Results: Patients were predominantly men (57.1%), with a mean age of 76.0 ± 13.0 years; a triggering event was present in 49.1%. No significant difference in baseline characteristics was noted between groups except for younger age, higher blood pressure, and prevalence of signs of congestion in the trigger-positive group. In-hospital mortality rate was 7.9%. Presence of triggers was positively associated with a reduced risk of in-hospital mortality (adjusted odds ratio 0.79; 95% confidence interval, 0.70-0.90; P =.0003). In a delta-adjusted pattern mixture model, the effect of a triggering event on in-hospital mortality remained consistently significant. Conclusion: Triggering events for acute heart failure can provide additional information for risk prediction. Efforts to identify the triggers should be made to classify patients according to risk group.

Background: It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real-time changes in the power spectrum of HRV during exercise and to investigate its relationship to the ventilatory threshold (VT). Methods and Results: Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO2 at the HRVT (HRVT-VO2) was substantially correlated with the VO2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P > 0.05). Furthermore, the HRVT-VO2 was also correlated with the VT-VO2 in these myocardial infarction patients (r=0.867), and the mean difference was -0.72 mL/kg per minute and was nonsignificant (P > 0.05). Conclusions: A HRV analysis with our method enabled real-time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.