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Patients with persistent heart failure (HF) with reduced ejection fraction (HFrEF) have a poorer prognosis than those with HF with improved ejection fraction (HFimpEF). However, data on the predictive value of echocardiographic parameters for persistent HFrEF are lacking. We retrospectively studied 443 patients who were diagnosed with HFrEF (EF ≤ 40%) during hospitalization and underwent echocardiography at the 1-year follow-up. We divided them into the 2 groups: HFimpEF (EF > 40%) and persistent HFrEF group at 1-year follow-up, and assessed the predictive value of echocardiographic parameters at discharge for persistent HFrEF. In total, 301/443 patients (68%) were diagnosed with persistent HFrEF and 142/443 (32%) with HFimpEF at the 1-year follow-up. Kaplan-Meier analysis revealed that the persistent HFrEF group had a poorer prognosis than the HFimpEF group (log-rank, P < 0.001). Receiver operating characteristic curve analysis revealed that left ventricular end-systolic diameter (LVESD) had the highest area under the curve (AUC) (0.70; 95% confidence interval [CI]: 0.64-0.75; cutoff value: 55 mm) among various echocardiographic parameters. LVESD was an independent predictor of persistent HFrEF at the 1-year follow-up (odds ratio: 1.07, 95%CI: 1.02-1.12) upon multivariable logistic regression analysis. The incidence of persistent HFrEF was higher in patients with an LVESD ≥ 55 mm than in those with an LVESD < 55 mm (81% versus 55%, Fisher's exact test, P < 0.001). In conclusion, an LVESD (≥ 55 mm) was associated with persistent HFrEF. Focusing on LVESD in daily practice may help clinicians with risk stratification for decision-making regarding management in patients with advanced HF refractory to guideline-directed medical therapy.

We evaluated whether modified Model for End-Stage Liver Disease (MELD) scores are useful for predicting the postdischarge prognosis in hospitalized patients with heart failure (HF) who are discharged alive. The MELD-XI and MELD-Na scores were calculated at discharge for a total of 1156 patients in the HIJ-HF II study. We also studied 3 groups on the basis of the left ventricular ejection fraction (LVEF): the HFrEF (LVEF < 40%), HFmrEF (LVEF 40-49%) and HFpEF (LVEF ≥ 50%) groups. The primary outcome was all-cause mortality, and the secondary outcome was rehospitalization due to worsening HF. The median MELD-XI and MELD-Na scores were 12 and 14, respectively. After a median follow-up of 19 months, there were significantly higher rates of all-cause mortality in patients with MELD-XI scores ≥ 12 than in those with MELD-XI scores < 12; there were also higher rates of all-cause mortality in patients with MELD-Na scores ≥ 14 than in those with MELD-Na scores < 14 (both log-rank p < 0.001). The cumulative incidence function based on a competing risks model showed a higher rate of rehospitalization due to worsening HF in patients with MELD-XI scores ≥ 12 than in those with MELD-XI scores < 12 and a higher rate of rehospitalization due to worsening HF in those with MELD-Na scores ≥ 14 than in those with MELD-Na scores < 14 (both Gray's test p < 0.001). The adjusted hazard ratios (HRs) of all-cause mortality for patients with MELD-XI scores ≥ 12 and those with MELD-Na scores ≥ 14 were 2.07 [95% confidence interval (CI) 1.25-3.44] and 2.79 [95% CI 1.63-4.79], respectively, in the HFrEF group; however, the HRs were not significant in the HFmrEF or HFpEF groups. Thus, MELD-XI and MELD-Na scores may be useful for predicting prognosis in hospitalized HF patients who are discharged alive, especially for those in the HFrEF group., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Appropriate implantable cardioverter-defibrillator (ICD) shocks are associated with an increased risk of mortality and heart failure (HF) events. The first appropriate shock may occur late after implantation. However, whether the timing of the first appropriate shock influences prognosis is unknown. This study aimed to evaluate the clinical significance of the timing of the first appropriate shock in patients with ICD., Methods: This retrospective and observational study enrolled 565 consecutive ICD patients. Patients who received an appropriate shock were divided into the early group (first appropriate shock <1 year after ICD implantation) and late group (first appropriate shock ≥1 year after ICD implantation). All-cause mortality was compared between the two groups., Results: Over a median follow-up of 5.6 years, 112 (19.8%) patients received an appropriate shock, including 32 patients (28.6%) in the early group and 80 patients (71.4%) in the late group. Comparisons of baseline characteristics at ICD implantation revealed that the late group was more likely to receive cardiac resynchronization therapy (66.3% vs. 31.3%, p < 0.001), ICD for primary prevention (60.0% vs. 31.3%, p = 0.001), and angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker treatment (88.8% vs. 71.9%, p = 0.028). Survival after shock was significantly worse in the late group than in the early group (p = 0.027). In multivariable Cox proportional hazards analysis, the late group had an increased risk of all-cause mortality compared with the early group (HR: 2.22; 95% CI 1.01-4.53; p = 0.029). In both groups, the most common cause of death was HF., Conclusions: Late occurrence of the first appropriate ICD shock was associated with a worse prognosis compared with early occurrence of the first appropriate shock. Cardiac death was the most common cause of death in patients who experienced late occurrence of the first appropriate ICD shock, resulting from HF in most cases., (© 2022 Wiley Periodicals LLC.)

Chronic kidney disease (CKD) and heart failure (HF) are the first and most frequent comorbidities associated with mortality risks in early-stage type 2 diabetes mellitus (T2DM). However, efficient screening and risk assessment strategies for identifying T2DM patients at high risk of developing CKD and/or HF (CKD/HF) remains to be established. This study aimed to generate a novel machine learning (ML) model to predict the risk of developing CKD/HF in early-stage T2DM patients. The models were derived from a retrospective cohort of 217,054 T2DM patients without a history of cardiovascular and renal diseases extracted from a Japanese claims database. Among algorithms used for the ML, extreme gradient boosting exhibited the best performance for CKD/HF diagnosis and hospitalization after internal validation and was further validated using another dataset including 16,822 patients. In the external validation, 5-years prediction area under the receiver operating characteristic curves for CKD/HF diagnosis and hospitalization were 0.718 and 0.837, respectively. In Kaplan-Meier curves analysis, patients predicted to be at high risk showed significant increase in CKD/HF diagnosis and hospitalization compared with those at low risk. Thus, the developed model predicted the risk of developing CKD/HF in T2DM patients with reasonable probability in the external validation cohort. Clinical approach identifying T2DM at high risk of developing CKD/HF using ML models may contribute to improved prognosis by promoting early diagnosis and intervention., (© 2022. The Author(s).)

Background: Appropriate shock therapy is associated with subsequent all-cause death in heart failure (HF) patients who receive an implantable cardioverter defibrillator (ICD) for the primary prevention of sudden cardiac death. To evaluate the impact of signal-averaged electrocardiography (SAECG) findings on appropriate shocks in prophylactic ICD patients with nonischemic systolic HF., Methods: We studied 86 patients with nonischemic HF and a left ventricular ejection fraction ≤ 35% who underwent new ICD implantation for the primary prevention of sudden cardiac death. We excluded patients who had a previously implanted permanent pacemaker and patients who received cardiac resynchronization therapy with an ICD. SAECG was performed before implantation. Abnormal SAECG findings were defined if 2 of the following 3 conditions were identified: filtered QRS duration (fQRS) ≥ 114 ms, root-mean-square voltage during the last 40 ms of the fQRS (RMS 40) < 20 μV, and duration of the low-amplitude potentials < 40 μV (LAS 40) > 38 ms; additionally, patients with a QRS complex ≥ 120 ms who met both the RMS 40 and LAS 40 criteria were also considered to have abnormal SAECG findings. The primary outcome was the first occurrence of appropriate shock after implantation of the ICD. The secondary outcomes were the first occurrence of inappropriate shock and all-cause mortality., Results: Forty-two patients met the criteria for abnormal SAECG findings (49%). During a median follow-up period of 61 months, 17 patients (20%) died, 24 (28%) received appropriate shock therapy, and 19 (22%) received inappropriate shock therapy. There was a significantly higher incidence of appropriate shocks in patients with abnormal SAECG findings than in those with normal SAECG findings (log-rank test, p = 0.025). Multivariate analysis revealed that abnormal SAECG findings were independently associated with the occurrence of appropriate shock (hazard ratio 2.67, 95% confidential interval 1.14-6.26). However, abnormal SAECG findings were not related to inappropriate shock. There was no difference in the incidence of all-cause death between patients with abnormal and normal SAECG findings., Conclusions: Our results suggest that abnormal SAECG findings are associated with a high probability of appropriate shocks in prophylactic ICD patients with nonischemic systolic HF., (© 2022. The Author(s).)

Objectives: Stroke is a substantial complication of left ventricular assist device (LVAD) implantation. The relationship between stroke and the anatomical position of the inflow cannula of patients who underwent LVAD implantation was investigated., Methods: We enrolled 15 patients with advanced-stage heart failure who underwent implantation of continuous-flow-LVAD. Data of patients who suffered a stroke within 6 months after LVAD implantation were retrospectively compared to those who remained free of stroke. The distance between the inflow duct and left ventricular (LV) septum (duct-sep distance) and its ratio to LV diastolic diameter (LVDd) were measured from echocardiography at 1 month after LVAD implantation. Receiver operating characteristic curves for the endpoint of stroke using the duct-sep distance to LVDd ratio was created and the cut-off value was calculated. The incidence of stroke during the 6 months after LVAD implantation according to this ratio was estimated using the Kaplan-Meier method., Results: At 1 month after LVAD implantation, there were no significant differences in baseline characteristics and echocardiography parameters between the stroke and stroke-free groups. Receiver operating characteristic curve analysis for the endpoint of stroke using the duct-sep distance to LVDd ratio revealed 0.217 as a cut-off value (sensitivity: 80%, specificity: 80%, area under the curve: 0.72). Stroke was more frequent in patients with a duct-sep distance to LVDd ratio ⩾0.217 at 1 month than in those with a lower ratio., Conclusion: The duct-sep distance to LVDd ratio was associated with the occurrence of stroke, suggesting that inflow cannula position influences the incidence of stroke.

Introduction: Guidelines recommend ventricular rate control to <130 bpm during atrial fibrillation (AF) in patients with acute decompensated heart failure (ADHF) to avoid aggravating deteriorations in cardiac outputs. We aimed to evaluate the prognostic impact of landiolol in patients with ADHF and AF., Methods: This observational study included 60 patients who were urgently hospitalized with ADHF and presented with AF and a heart rate (HR) ≥130 bpm at admission. The patients were assigned to the landiolol group (n = 37) or the reference group (n = 23) based on their intravenous landiolol use within 24 h after admission. The primary endpoint was death from any cause., Results: The groups' baseline characteristics were similar. A significant HR reduction occurred in the landiolol group at 2 h after admission. Compared with the reference group, the HR was significantly lower (111.6 vs. 97.9 bpm, p = 0.02) and the absolute HR reduction was greater (-32.2 vs. -50.0 bpm, p = 0.006) in the landiolol group at 48 h after admission. The landiolol group's mortality rate was significantly lower than that in the reference group (log-rank test, p = 0.032). landiolol use within 24 h after admission was independently associated with lower all-cause mortality (adjusted hazard ratio: 0.15, 95% confidence interval: 0.02-0.92)., Conclusion: Patients with ADHF and AF who received landiolol for rate control during the acute phase had better prognoses than those who did not receive landiolol., (© 2022 S. Karger AG, Basel.)

Aims: The number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta-blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio-selective beta-blocker use on the long-term outcomes of patients with HF and COPD., Methods and Results: Among the 5232 patients with HFrEF (left ventricular ejection fraction of <40%) prospectively enrolled from 11 Asian regions in the ASIAN-HF registry, 412 (7.9%) had a history of COPD. We compared the clinical characteristics and long-term outcomes of the patients with HF and COPD according to the use and type of beta-blockers used: cardio-selective beta-blockers (n = 149) vs. non-cardio-selective beta-blockers (n = 124) vs. no beta-blockers (n = 139). The heart rate was higher, and the outcome was poorer in the no beta-blocker group than in the beta-blocker groups. The 2 year all-cause mortality was significantly lower in the non-cardio-selective beta-blocker group than in the no beta-blocker group. Further, the cardiovascular mortality significantly decreased in the non-cardio-selective beta-blocker group before (hazard ratio: 0.36; 95% confidence interval: 0.18-0.73; P = 0.004) and after adjustments (hazard ratio: 0.37; 95% confidence interval: 0.19-0.73; P = 0.005), but not in the cardio-selective beta-blocker group., Conclusions: Beta-blockers reduced the all-cause mortality of patients with HFrEF and COPD after adjusting for age and heart rate, although the possibility of selection bias could not be completely excluded due to multinational prospective registry., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective Current clinical guidelines have proposed heart failure (HF) with mid-range ejection fraction (HFmrEF), defined as a left ventricular ejection fraction (LVEF) of 40-49%, but the proportion and prognosis of patients transitioning toward HF with a reduced LVEF (LVEF <40%, HFrEF) or HF with a preserved LVEF (LVEF ≥50%, HFpEF) are not fully clear. The present study prospectively evaluated the changes in the LVEF one year after discharge and the outcomes of hospitalized patients with HFmrEF. Methods We prospectively studied 259 hospitalized patients with HFmrEF who were discharged alive at our institutions between 2015 and 2019. Among them, 202 patients with HFmrEF who underwent echocardiography at the one-year follow-up were included in this study. Patient characteristics, echocardiographic data and all-cause death were collected. Results Eighty-seven (43%) patients transitioned to HFpEF (improved group), and 35 (17%) transitioned to HFrEF (worsened group). During a median follow-up of 33 months, 27 (13%) patients died. After adjustment, patients in the worsened group had an increased risk of all-cause mortality compared with those in the improved group [hazard ratio 7.02, 95% confidence interval (CI) 1.13-43.48]. The baseline LVEF (per 1% decrease) and tricuspid annular plane systolic excursion (per 1 mm decrease) were independent predictors of the worsened LVEF category (odds ratio 2.13, 95% CI 1.25-3.63 and odds ratio 1.31, 95% CI 1.01-1.70, respectively). Conclusion Our study showed that a worsened LVEF one year after discharge was associated with a poor prognosis in hospitalized patients with HFmrEF.

Background: The number of hospitalized patients with heart failure (HF) is increasing as a result of the increase in the elderly population in Japan. We evaluated changes in the characteristics and outcomes of HF patients hospitalized in the 2000s to the 2010s and discharged alive based on left ventricular ejection fraction (LVEF)., Methods: Pooled patient data were obtained from The Heart Institute of Japan Heart Failure studies (HIJ-HF I: 2001-2 and HIJ-HF II: 2013-4). We studied patients discharged alive from pooled data based on LVEF < 40% (HFrEF), 40-49% (HFmrEF), and ≥50% (HFpEF). The primary outcome was death from any cause, and the secondary outcomes were cardiac death and rehospitalization due to worsened HF., Results: The proportion of HFpEF increased (35%-43%, p < 0.01), and the median ages of patients with HFmrEF (72-76 years, p < 0.01) or HFpEF (72-80 years, p < 0.01) increased from HIJ-HF I to HIJ-HF II. The use of angiotensin II receptor blockers, beta-blockers, statins, amiodarone, and erythropoietin increased, but nitrate and digoxin usage decreased. The adjusted survival rate and cardiac death-free rate were not significantly different between the 2000s and 2010s in any LVEF group, and the incidence of rehospitalization due to worsened HF was reduced in patients discharged alive from HIJ-HF I to HIJ-HF II [HFrEF: hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.51-0.89; HFmrEF: HR 0.89, 95% CI 0.68-1.16; and HFpEF: HR 0.77, 95% CI 0.61-0.97] with no significant interaction by LVEF groups., Conclusion: Our study demonstrated that age, the proportion of HFpEF, and guideline-recommended drug therapy use increased among hospitalized Japanese HF patients from the 2000s to the 2010s. The adjusted survival rate was not improved in any LVEF group, although the incidence of rehospitalization due to worsened HF was reduced., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Nonischemic heart failure (HF) is common in Japan. We evaluated the long-term outcome of Japanese patients with nonischemic HF receiving carvedilol based on left ventricular ejection fraction (LVEF) category. We conducted a single-center observation study of 1550 patients with nonischemic HF who were initiated with carvedilol between 2005 and 2015. Of these patients, 38% had an LVEF < 40% (HFrEF, median age 57 years, 28% female) and 62% had an LVEF ≥ 40% (HFpEF, 64 years, 38% female). The primary outcome was all-cause.death The secondary outcomes were cardiac death and sudden cardiac death (SCD). After a median follow-up of 5.5 [interquartile range, 2.9-8.8] years, the median daily maintenance doses of carvedilol in patients with HFrEF and HFpEF were 7.5 [5-12.5] mg and 7.5 [5-10] mg, respectively. The cumulative survival rates of HFrEF patients at 1, 3 and 5 years were 96.1%, 90.2% and 85.5%, respectively, and the cumulative survival rates of HFpEF patients at 1, 3 and 5 years were 97.8%, 94.4% and 90.7%, respectively. The cumulative cardiac death-free rates at 5 years were 94.4% in HFrEF patients and 97.7% in HFpEF patients, and the cumulative SCD-free rates at 5 years were 96.7% in HFrEF patients and 97.9% in HFpEF patients. The adjusted survival rate showed that a higher dose (≥ 7.5 mg daily) was associated with more favourable outcomes than a lower dose (< 7.5 mg daily) in HFrEF patients, but not in HFpEF patients. The adjusted survival rate showed that a lower heart rate (< 75 bpm) was associated with favourable outcomes than a higher heart rate (≥ 75 bpm) in HFrEF patients, but not in HFpEF patients. Long-term survival was good in Japanese patients with nonischemic HF receiving carvedilol. Higher doses and lower heart rates were associated with favourable survival for HFrEF patients, but not in HFpEF patients.

Background: Palliative care is highly relevant for patients with heart failure (HF), and there is a need for quantitative information on quality of care. Accordingly, this study aimed to develop a set of quality indicators (QIs) for palliative care of HF patients, and to conduct a practical pilot measurement of the proposed QIs in clinical practice.Methods and Results:We used a modified Delphi technique, a consensus method that involves a comprehensive literature review, face-to-face multidisciplinary panel meeting, and anonymous rating in 2 rounds. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 9 (highest) for appropriateness. All indicators receiving a median score ≥7 without significant disagreement were included in the final set of QIs. Through the consensus-building process, 35 QIs were proposed for palliative care in HF patients. Practical measurement in HF patients (n=131) from 3 teaching hospitals revealed that all of the proposed QIs could be obtained retrospectively from medical records, and the following QIs had low performance (<10%): "Intervention by multidisciplinary team", "Opioid therapy for patients with refractory dyspnea", and "Screening for psychological symptoms"., Conclusions: The first set of QIs for palliative care of HF patients was developed and could clarify quantitative information and might improve the quality of care.

Background: Advance care planning (ACP) is recommended as part of the management of patients with heart failure (HF)., Aims: To develop and validate ACP support tools for patients with HF., Methods: An ACP support tool was developed based on a systematic literature review. A multi-center, prospective before and after study was conducted to evaluate the usefulness of the support tool. This study included 21 patients with HF, 11 patients formed the control group and 10 patients were part of the intervention group who received ACP from medical staff using the ACP support tools developed for this study. Participants of the study were surveyed about their experience of ACP using a 6-point Likert scale., Findings: All of the healthcare professionals (n=9) involved in the study found the ACP tool useful and about 90% of patients considered the support tool useful. The score for 'the patient did not feel anxious about the future after receiving ACP discussion' was significantly higher (3.5 [3.0, 4.0] vs 2.0 [1.0, 3.0]; P=0.04) in the intervention group that used the ACP tool., Conclusion: ACP support tools are useful to manage patients with HF and could enable effective ACP without increasing patient anxiety.

Aims: There are regional differences in the patient characteristics, management, and outcomes of hospitalized patients with heart failure (HF). The aim of this study was to evaluate the clinical characteristics and outcomes of Japanese patients who are hospitalized with HF on the basis of the left ventricular ejection fraction (LVEF) stratum., Methods and Results: We retrospectively conducted a multicentre cohort study of 1245 hospitalized patients with decompensated HF between 2013 and 2014. Of these patients, 36% had an LVEF < 40% [HF with reduced ejection fraction (HFrEF), median age 72 years, 71% male], 21% had an LVEF 40-49% [HF with mid-range EF (HFmrEF), 77 years, 56% male], and 43% had an LVEF ≥ 50% [HF with preserved EF (HFpEF), 81 years, 44% male]. The primary outcome was death from any cause, and the secondary outcomes were cardiac death and re-hospitalization due to worsened HF after hospital discharge. There were high proportions of non-ischaemic cardiomyopathy (32%) in HFrEF patients, coronary artery disease (44%) in HFmrEF patients, and valvular disease (39%) in HFpEF patients. The frequencies of intravenous diuretic and natriuretic peptide administration during hospitalization were 66% and 30%, respectively. The median hospital stay for the overall population was 19 days, and the length of stay was >7 days for >90% of patients. In-hospital mortality was 7%, but was not different among the LVEF groups (HFrEF 7%, HFmrEF 6%, and HFpEF 8%). After a median follow-up of 19 months (range, 3-26 months), 192 (17%) of the 1156 patients who were discharged alive died, and 534 (46%) were re-hospitalized after hospital discharge. There were no significant differences in mortality after hospital discharge among the three LVEF groups (HFrEF 18%, HFmrEF 16%, and HFpEF 16%). There were no differences in cardiac death or re-hospitalization due to worsened HF after hospital discharge among the LVEF groups (cardiac death: HFrEF 8%, HFmrEF 7%, and HFpEF 7%; re-hospitalization due to worsened HF: HFrEF 19%, HFmrEF 16%, and HFpEF 17%). Multivariable-adjusted analyses showed that the HFmrEF and HFrEF groups, compared with the HFpEF group, were not associated with an increased risk for in-hospital death or death after hospital discharge. Non-cardiac causes of death and re-hospitalization after hospital discharge accounted for 35% and 38%, respectively., Conclusions: Our results revealed different clinical characteristics but similar mortality rates in the HFrEF, HFmrEF, and HFpEF groups. The most common cause of death and re-hospitalization after hospital discharge was HF, but non-cardiac causes also contributed to their prognosis. Integrated management approaches will be required for HF patients., (© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: To evaluate the impact of changes in the filtered QRS duration (fQRS) on signal-averaged electrocardiograms (SAECGs) from pre- to postimplantation on the clinical outcomes in nonischemic heart failure (HF) patients under cardiac resynchronization therapy (CRT)., Methods: We studied 103 patients with nonischemic HF and sinus rhythm who underwent CRT implantation. SAECGs were obtained within 1 week before and 1 week after implantation and narrowing fQRS was defined as a decrease in fQRS from pre- to postimplantation. Echocardiography was performed before and 6 months after CRT implantation. The primary outcome was death from any cause. The secondary outcomes were hospitalization due to worsened HF and occurrence of ventricular tachyarrhythmias., Results: Of the 103 CRT patients, 53 (51%) showed narrowing fQRS. Left ventricular end-diastolic volume and end-systolic volume were significantly reduced (both p < .001), and the left ventricular ejection fraction was significantly increased (p < .001) after CRT in patients with narrowing fQRS, but not in patients with nonnarrowing fQRS. During a median follow-up period of 33 months, patients with narrowing fQRS exhibited better survival than patients with nonnarrowing fQRS (p = .007). A lower incidence of hospitalization due to worsened HF (p < .001) and a lower occurrence of ventricular tachyarrhythmias (p = .071) were obtained in patients with narrowing fQRS. After adjusting for confounding variables, narrowing fQRS was associated with a low risk of mortality (HR 0.27, p = .006)., Conclusion: Our results suggested that narrowing fQRS on SAECG after CRT implantation predicts LV reverse remodeling and long-term outcomes in nonischemic HF patients., (© 2017 Wiley Periodicals, Inc.)

Additional risk stratification may provide more aggressive and focalized preventive treatment to high-risk hypertensive patients according to the Japanese hypertension guidelines. We prospectively investigated the predictive value of high-sensitivity troponin I (hsTnI), both independently and in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP), for incident heart failure (HF) in high-risk hypertensive patients with preserved left ventricular ejection fraction (LVEF). Baseline hsTnI and NT-proBNP levels and echocardiography data were obtained for 493 Japanese hypertensive outpatients (mean age, 68.5 years) with LVEF ≥ 50%, no symptomatic HF, and at least one of the following comorbidities: stage 3-4 chronic kidney disease, diabetes mellitus, and stable coronary artery disease. During a mean follow-up period of 86.1 months, 44 HF admissions occurred, including 31 for HF with preserved ejection fraction (HFpEF) and 13 for HF with reduced ejection fraction (HFrEF; LVEF <50%). Both hsTnI (p < 0.01) and NT-proBNP (p < 0.005) levels were significant independent predictors of HF admission. Furthermore, when the patients were stratified into 4 groups according to increased hsTnI (≥highest tertile value of 10.6 pg/ml) and/or increased NT-proBNP (≥highest tertile value of 239.7 pg/ml), the adjusted relative risks for patients with increased levels of both biomarkers versus neither biomarker were 13.5 for HF admission (p < 0.0001), 9.45 for HFpEF (p = 0.0009), and 23.2 for HFrEF (p = 0.003). Finally, the combined use of hsTnI and NT-proBNP enhanced the C-index (p < 0.05), net reclassification improvement (p = 0.0001), and integrated discrimination improvement (p < 0.05) to a greater extent than that of any single biomarker. The combination of hsTnI and NT-proBNP, which are individually independently predictive of HF admission, could improve predictions of incident HF in high-risk hypertensive patients but could not predict future HF phenotypes.

Background: Complete calcification of the left atrium (LA) is called "coconut atrium", which decreases the compliance of LA, leading to the elevation of LA pressure that is transmitted to the right-side of the heart. The pathogenesis of LA calcification in patients with rheumatic heart disease is unknown; however, possible mechanisms include chronic strain force in the atrial wall and inflammation. We report here a patient with long-standing rheumatic valvular heart disease with coconut atrium., Case Report: A 76-year-old man presented with breathlessness and leg edema due to right-sided heart failure. He was diagnosed with rheumatic fever at 8 years of age. Mitral commissurotomy and the mitral and aortic valve replacement were previously performed to treat mitral and aortic valvular stenosis. The profile view of the chest X-ray indicated a diffuse calcified outline of the LA wall. A transthoracic echocardiogram revealed pulmonary hypertension and dilatation of both atria. Moreover, computed tomography showed nearly circumferential calcification of the LA wall. Despite intense medical treatment, he succumbed to heart failure. An autopsy demonstrated that the LA was markedly dilated, its wall was calcified, and its appearance was similar to the surface of an atherosclerotic aorta. Microscopic examination revealed intensive calcification in the endocardium. Minimal accumulation of inflammatory cells was noted. Although slight fibrosis was observed, the cardiac musculature was preserved., Conclusions: To the best of our knowledge, this is the first report that identifies the histological changes of LA calcification associated with long-standing rheumatic valvular heart disease.

Background: Anxiety is often present in patients with depression. The aim of this study was to evaluate the impact of clustered depression and anxiety on mortality and rehospitalization in hospitalized patients with heart failure (HF)., Methods: A total of 221 hospitalized patients with HF, who completed the questionnaires, were analyzed in this prospective study (mean age 62±13 years; 28% female). One-third patients had implanted cardiac devices. Depression was defined as a Zung Self-Rating Depression Scale index score of ≥60 and anxiety was defined as a State-Trait Anxiety Inventory score of ≥40 (male) or ≥42 (female). The primary outcome was the composite of death from any cause or rehospitalization due to worsened HF and refractory arrhythmia., Results: Of the 221 HF patients, 29 (13%) had depression alone, 80 (36%) had anxiety alone, and 46 patients (21%) had both depression and anxiety. During an average follow-up of 41±21 months, patients with depression alone and those with clustered depression and anxiety were at an increased risk of the primary outcome [hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.17-4.28, p=0.01 and HR 2.75, 95% CI: 1.51-4.99, p=0.01, respectively] compared to patients with no symptoms. Multivariate analysis after adjusting for age, gender, New York Heart Association functional class, B-type natriuretic peptide, device implantation, renal dysfunction, and left ventricular dysfunction showed clustered depression and anxiety, but not depression alone or anxiety alone, was an independent predictor of the primary outcome (HR 1.96, 95% CI: 1.00-3.27, p=0.04)., Conclusions: Our results showed that clustered depression and anxiety were associated with worse outcomes in patients with HF., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Cardiac resynchronization therapy (CRT) improves the survival rates of patients with heart failure, but 30-40% of them do not respond to CRT, partially because of the position of the left ventricular (LV) lead. The relationship between the electrical and mechanical activation of the left ventricle is unknown. The aim of this study was to compare the electrical and mechanical dyssynchrony., Methods: We inserted electrode catheters into the coronary sinus (CS) and venous branches of the CS during CRT implantations and constructed electroanatomical contact maps in 16 patients using the EnSite NavX™ system. Mechanical activation was evaluated by speckle-tracking echocardiography and the latest mechanical and electrical sites were compared. The degrees of the electrical and mechanical delays of the implanted LV lead were also compared., Results: The electroanatomical maps revealed that the latest electrical sites were anterior in one, anterolateral in five, lateral in eight, and posterolateral in two. Echocardiographic imaging revealed that the latest mechanical sites were anteroseptal in two, anterior in four, lateral in five, posterior in two, and inferior in three. The latest electrical and mechanical sites matched in only three patients. The degree of the local mechanical delay for the LV lead was significantly larger in the responders than nonresponders, whereas the local electrical delay did not differ., Conclusion: A discrepancy between the electrical and mechanical dyssynchrony might affect an adequate LV lead positioning., (©2013 Wiley Periodicals, Inc.)

Tachycardia-induced cardiomyopathy (TIC) is a reversible form of the left ventricular (LV) systolic dysfunction and is believed to be a relatively acute process. We report a TIC case with a 30-year history of long-lasting persistent atrial tachycardia involving a 44-year-old man previously diagnosed with dilated cardiomyopathy and a low LV ejection fraction (LVEF) of 20%. ECG revealed atrial tachycardia at 110-120 bpm. He was hospitalised with a worsening heart failure. His clinical status was New York Heart Association functional class III, and echocardiography revealed LV dilation and an LVEF of 9%. A two-dimensional speckle-tracking strain measurement revealed LV mechanical dyssynchrony. He underwent radiofrequency ablation for atrial tachycardia. After restoring sinus rhythm, his cardiac symptoms improved immediately. The LV mechanical dyssynchrony decreased a week after ablation, without changes in the LV dilation or LVEF. Thereafter, the LV dilation and systolic function gradually improved, and atrial tachycardia and heart failure remained absent.

Aims: Cardiac resynchronization therapy (CRT) improves the clinical status of patients with congestive heart failure, although left ventricular epicardial pacing may increase transmural dispersion of repolarization (TDR). The aim of this study was to investigate the time-dependent effect of CRT on ventricular repolarization and ventricular arrhythmia at mid-term follow-up., Methods and Results: The study group consisted of 84 patients treated with CRT. Twelve-lead electrocardiogram was digitally recorded and Tpeak-to-Tend interval (Tp-e) was measured at baseline, 1 week, 1 month, and 3, 6, and 12 months after device implantation. We determined the time-dependent changes in Tp-e, ventricular tachycardia and ventricular fibrillation (VT/VF) during 12 months of follow-up, in both CRT responders and non-responders. Seventeen of 84 patients (20%) had VT/VF during first year. Six of those 17 patients (35%) experienced VT/VF within 1 month of implantation and diminished over time. Tp-e decreased significantly at 6 and 12 months after implantation compared with 1 week [108 ± 14 ms at 1 week vs. 97 ± 21 ms at 6 months (P = 0.03) and 95 ± 19 ms at 12 months (P = 0.01)]. Responders demonstrated a greater time-dependent reduction of Tp-e at 6 and 12 months of CRT and had a lower rate of VT/VF compared with non-responders (log-rank test, P = 0.004)., Conclusion: Transmural dispersion of repolarization and the number of patients with VT/VF decreased over time after CRT. Patients with reverse remodelling demonstrated a lower rate of VT/VF and a greater time-dependent reduction of TDR.

Background: Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively., Methods: We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2., Results: We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3 mg/dL., Conclusions: TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.

Background: The effectiveness of cardiac resynchronization therapy (CRT) in preventing sudden cardiac death is controversial. Epicardial left ventricular pacing reverses the direction of activation of the left ventricular wall from the epicardium to the endocardium. We evaluated whether the interlead difference between T-peak to T-end (Tp-e) intervals determined by a 187-channel repolarization interval-difference mapping electrocardiograph (187-ch RIDM-ECG) is related to the occurrence of ventricular tachyarrhythmia requiring implantable cardioverter-defibrillator (ICD) therapy in heart failure patients receiving CRT with a defibrillator (CRT-D)., Methods and Results: Repolarization interval-difference mapping electrocardiograph (187-channel) was performed on 61 patients who received CRT-D. Twenty-one patients experienced appropriate ICD therapy. The interlead difference between corrected recovery time intervals was not significantly different between patients with and without appropriate ICD therapy (98 ± 24 milliseconds versus 88 ± 24 milliseconds). The interlead difference between corrected Tp-e intervals was significantly higher in patients with appropriate ICD therapy than in those without (88 ± 22 milliseconds versus 59 ± 23 milliseconds, P < .001)., Conclusion: The interlead difference between corrected Tp-e intervals determined by 187-ch RIDM-ECG may be related to appropriate ICD therapy in heart failure patients receiving CRT-D., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Several protein kinase C (PKC) isoforms may play important roles in cellular signaling pathways. Recent reports have suggested that PKC plays critical isoform-specific roles in the development of cardiac hypertrophy and heart failure. The purpose of the present study was to examine the expression profiles of PKC isoforms in models of cardiac hypertrophy and heart failure. We examined the cardiac expression of individual PKC isoforms at the cardiac hypertrophy stage and the heart failure stage in Dahl salt-sensitive rats by Western blot analysis. The levels of all PKC isoforms increased at the cardiac hypertrophy stage and the heart failure stage, but the pattern of increase differed among PKC isoforms at the heart failure stage. The expressions of PKCalpha, beta, and delta increased at the cardiac hypertrophy stage and remained elevated at the heart failure stage. On the other hand, the expression of PKCepsilon and atypical PKCs (aPKCs) increased at the cardiac hypertrophy stage, but this increase tended to decline at the congestive heart failure stage. These results suggest that there are two groups of PKC isoforms. Several reports have shown that PKCalpha, beta, and delta are involved in the development of cardiac hypertrophy and heart failure, and that PKCepsilon plays a role in the physiological hypertrophic responses and cardioprotective actions. These facts suggest that all PKC isoforms (PKCalpha, beta, delta, epsilon, and aPKCs) expressed in the heart may have similar functions at the cardiac hypertrophy stage, but that two groups of PKC isoforms (PKCalpha, beta, delta, and PKCepsilon, aPKCs) have different functions at the congestive heart failure stage.

Background: The long‐term relationship between fracture‐prone implantable cardioverter‐defibrillator (ICD) leads and poor prognosis remains unclear in Japanese patients. Methods: We conducted a retrospective review of the records of 445 patients who underwent implantation of advisory/Linox leads (Sprint Fidelis, 118; Riata, nine; Isoline, 10; Linox S/SD, 45) and non‐advisory leads (Endotak Reliance, 33; Durata, 199; Sprint non‐Fidelis, 31) between January 2005 and June 2012 at our hospital. The primary outcomes were all‐cause mortality and ICD lead failure. The secondary outcomes were cardiovascular mortality, heart failure (HF) hospitalization, and the composite outcome of cardiovascular mortality and HF hospitalization. Results: During the follow‐up period (median, 8.6 [4.1–12.0] years), there were 152 deaths: 61 (34%) in patients with advisory/Linox leads and 91 (35%) in those with non‐advisory leads. There were 32 ICD lead failures: 27 (15%) in patients with advisory/Linox leads and five (2%) in those with non‐advisory leads. Multivariate analysis for ICD lead failure demonstrated that the advisory/Linox leads had a 6.65‐fold significantly greater risk of ICD lead failure than non‐advisory leads. Congenital heart disease (hazard ratio 2.51; 95% confidence interval 1.08–5.83; p =.03) could also independently predict ICD lead failure. Multivariate analysis for all‐cause mortality demonstrated no significant association between advisory/Linox leads and all‐cause mortality. Conclusions: Patients who have implanted fracture‐prone ICD leads should be carefully followed up for ICD lead failure. However, these patients have a long‐term survival rate comparable with that of patients with non‐advisory ICD leads in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure (HF) and low left ventricular ejection fraction (LVEF) are at high risk of sudden cardiac death (SCD). Optimal HF treatment can improve LVEF and reduce the risk of SCD. The aim of this study was to evaluate the incidence and predictors of SCD in Japanese patients with new‐onset systolic HF and to investigate factors that affect LVEF improvement. Methods: We retrospectively studied 174 consecutive hospitalized patients with new‐onset HF and LVEF ≤35% (median age, 66 years; men, 71%). The primary outcome was a composite of SCD, sustained ventricular arrhythmias, and appropriate implantable cardioverter‐defibrillator therapy. Results: The cumulative rates of meeting of the primary outcome at 3, 12, and 36 months after discharge were 3.9%, 8.1%, and 10.5%, respectively. Atrial fibrillation was a significant predictor of the primary outcome within 12 months after discharge (odds ratio, 5.87; 95% confidence interval [CI], 1.60–21.57). Among 104 patients who completed follow‐up echocardiography within 12 months after discharge, changes in LVEF were inversely associated with SCD (odds ratio/1% increase, 0.78; 95% CI, 0.65–0.93). A QRS duration <130 ms and a B‐type natriuretic peptide level <170 pg/mL were predictors of LVEF improvement to >35% (odds ratio, 3.69; 95% CI, 1.15–11.77; odds ratio, 3.19; 95% CI, 1.33–7.69, respectively). Conclusions: Our results showed a high incidence of meeting of the primary outcome within 12 months after discharge in hospitalized patients with new‐onset systolic HF. An improved LVEF may reduce the risk of late SCD. [ABSTRACT FROM AUTHOR]

Background: Despite the effectiveness of implantable cardioverter defibrillators (ICDs) in the prevention of sudden cardiac death, shock therapy causes patients to experience pain and psychological distress, which contradicts the purpose of palliative care. It is difficult to predict the time course for heart failure (HF) patients, unlike that for cancer patients. The aim of this study was to evaluate the deactivation status of ICD therapy in Japanese patients with end‐stage HF. Methods: We retrospectively studied 51 ICD patients who died due to worsening HF at Tokyo Women's Medical University Hospital from 2010 to 2019. The frequency of ICD therapy delivered before death and information about the discussion of deactivation and do not attempt resuscitation (DNAR) decisions were reviewed using medical charts. Results: Of 51 patients, 12 (24%) patients deactivated ICD therapy and seven patients underwent deactivation within 24 hours of a DNAR order. The median time from deactivation to death was 3 days (range, 0‐56). Of 39 patients with DNAR orders, 27 (69%) did not undergo deactivation. A relatively high proportion of patients (n = 14, 27%) experienced ICD shocks within 1 month of death. The frequency of electrical storms within 1 month of death was also high (n = 12, 24%). Conclusions: Our study showed that only one‐fourth of Japanese patients with end‐stage HF underwent deactivation of ICD therapy. A relatively high frequency of shock therapy was observed in the last month before death. [ABSTRACT FROM AUTHOR]

Objective: Atrial tachyarrhythmias (ATAs) lead to clinical deterioration and worsening heart failure (HF) in patients with acute decompensated HF (ADHF). We evaluated the effects of the ultrashort-acting intravenous β1-blocker landiolol on the heart rate, hemodynamics, and outcome in patients with ATAs and ADHF.Methods: A total of 67 consecutive hospitalized patients with ATAs and ADHF who were treated with landiolol (36 males, 67 ± 12 years) were included in this single-center retrospective study. The primary endpoints were changes in heart rate and systolic blood pressure from baseline during intravenous landiolol administration. The secondary endpoints included restoration of sinus rhythm and outcomes.Results: The median maintenance dose of intravenous landiolol was 3.0 (range 1.0-12.0) μg/kg/min and the median treatment duration was 5 (range 1-24) days. Intravenous landiolol reduced heart rate (141 ± 17 beats/min at baseline to 99 ± 20 beats/min at 6 h, P < 0.001) without a marked reduction in blood pressure or deterioration of HF. During landiolol treatment, 15 (22%) patients had spontaneously restored sinus rhythm. Eight patients experienced in-hospital death, and 41 (69%) were discharged with sinus rhythm. During the follow-up of 16 ± 12 months, patients with sinus rhythm showed a lower frequency of rehospitalization due to worsening HF than patients with ATAs (5/41 vs. 7/18, P = 0.019).Conclusions: Our results showed that intravenous landiolol reduces the heart rate without markedly decreasing blood pressure in patients with ATAs and ADHF. Approximately 70% of the discharged patients were in sinus rhythm, and these patients showed a lower frequency of rehospitalization due to worsening HF (UMIN-CTR no. UMIN000033650). [ABSTRACT FROM AUTHOR]

Background We reviewed the effectiveness and safety of cardiac resynchronization therapy (CRT) for patients with New York Heart Association (NYHA) class IV non-ambulatory heart failure (NAHF). Methods From 2006 to 2011, 310 patients underwent CRT at Kobe University Hospital and Himeji Cardiovascular Center because of heart failure. Of these, 29 NAHF patients were retrospectively analyzed. The control group comprised 21 age- and ejection fraction-matched patients with NAHF who did not undergo CRT from the ICU database of Kobe University Hospital. The primary endpoint was all-cause death and hospitalization for heart failure. Response was defined as a >15% reduction in left ventricular end-systolic volume (LVESV). Results CRT was performed successfully without serious complications in all patients. Twenty-three patients (79%) were discharged 19±15 days after CRT implantation, while 6 (21%) died during their hospital stay due to progressive heart failure. Compared with the control group, patients in the CRT group showed significant improvements in the primary endpoint (log-rank p =0.04). Six patients (21%) were defined as responders and the Kaplan–Meier curve showed that responders experienced a better outcome than non-responders (log-rank p =0.029). LV dyssynchrony before implantation was significantly related to the occurrence of the primary endpoint ( p =0.02). Conclusions CRT can be safely used in patients with NAHF and can improve long-term patient outcomes, especially in treatment responders. [ABSTRACT FROM AUTHOR]