Implication of modified MELD scores for postdischarge prognosis in hospitalized patients with heart failure.

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.

Impact of signal-averaged electrocardiography findings on appropriate shocks in prophylactic implantable cardioverter defibrillator patients with nonischemic systolic heart failure.

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.

Prognostic Impact of Landiolol in Patients with Acute Heart Failure and Atrial Fibrillation with Rapid Ventricular Rates: A Pilot Observational Study.

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.

Benefits and safety of landiolol for rapid rate control in patients with atrial tachyarrhythmias and acute decompensated heart failure.

Atrial tachyarrhythmias often occur in patients with worsening heart failure (HF), and the development of atrial tachyarrhythmias in acute decompensated HF (ADHF) causes an uncontrolled heart rate (HR) and leads to further exacerbation of HF and persistence of a decompensated HF state. Landiolol, a short-acting intravenous beta-1 blocker, shows very high cardiac beta-1 selectivity and has a very short elimination half-life of approximately 4 min. As shown in several reports, the benefit of intravenous landiolol is that it lowers the ventricular rate early after the start of use without markedly deteriorating haemodynamics. After the cardiac status is stabilized by rapid control of HR, subsequent basic HF pharmacotherapy and rhythm control therapies will be effective for improving outcomes. Because of the pharmacokinetic properties of landiolol, if the patient suffers an adverse reaction such as hypotension or bradycardia, such effects can be quickly reversed by tapering the dose or discontinuing use altogether. Based on several clinical studies, this review discusses the efficacy, safety and role of intravenous landiolol in acute HR control in patients with atrial tachyarrhythmias and ADHF.

Meta-analysis comparing inappropriately low dose versus standard dose of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: The appropriateness of direct oral anticoagulant (DOAC) dosing has been the issue in the real-world setting, and inappropriately lower DOAC dose may not be as effective or safe as the standard dose in patients with atrial fibrillation (AF). Multiple real-world studies compared the inappropriately lower DOAC dose versus the standard dose, but their main findings were contradictory. METHODS: A meta-analysis was performed to compare the efficacy and safety of the inappropriately lower DOAC dose with the standard DOAC dose in patients with AF. Database searches through May 30, 2021, were performed using Medline and Google Scholar. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. The secondary outcome was all-cause mortality. RESULTS: A total of 16 studies were included in this meta-analysis. It revealed that the inappropriately lower DOAC dose was significantly associated with a higher event rate of stroke or systemic embolism compared with the DOAC standard dose (odds ratio 1.21 [95% CI 1.02-1.43], P = 0.03, I2 = 66%). There was no significant difference in the major bleeding event rate between these groups (1.03, [0.92-1.15], P = 0.62; I2 = 27%). CONCLUSION: The inappropriately lower DOAC dose should be avoided to optimize DOAC effectiveness in patients with AF.

Left intraventricular pressure gradient in hypertrophic cardiomyopathy patients receiving implantable cardioverter-defibrillators for primary prevention.

BACKGROUND: Conventional risk factors for sudden cardiac death (SCD) justify primary prevention through implantable cardioverter-defibrillator (ICD) implantation in hypertrophic cardiomyopathy (HCM) patients. However, the positive predictive values for these conventional SCD risk factors are low. Left ventricular outflow tract obstruction (LVOTO) and midventricular obstruction (MVO) are potential risk modifiers for SCD. The aims of this study were to evaluate whether an elevated intraventricular pressure gradient (IVPG), including LVOTO or MVO, is a potential risk modifier for SCD and ventricular arrhythmias requiring ICD interventions in addition to the conventional risk factors among HCM patients receiving ICDs for primary prevention. METHODS: We retrospectively studied 60 HCM patients who received ICDs for primary prevention. An elevated IVPG was defined as a peak instantaneous gradient ≥ 30 mmHg at rest, as detected by continuous-wave Doppler echocardiography. The main outcome was a composite of SCD and appropriate ICD interventions, which were defined as an antitachycardia pacing or shock therapy for ventricular tachycardia or fibrillation. The Cox proportional hazards model was used to assess the relationships between risk factors and the occurrence of SCD and appropriate ICD interventions. RESULTS: Thirty patients met the criteria of elevated IVPG (50%). During the median follow-up period of 66 months, 2 patients experienced SCD, and 10 patients received appropriate ICD interventions. Kaplan-Meier curves showed that the incidence of the main outcome was higher in patients with an IVPG ≥ 30 mmHg than in those without an IVPG ≥ 30 mmHg (log-rank P = 0.03). There were no differences in the main outcome between patients with LVOTO and patients with MVO. The combination of nonsustained ventricular tachycardia (NSVT) and IVPG ≥ 30 mmHg was found to significantly increase the risk of the main outcome (HR 6.31, 95% CI 1.36-29.25, P = 0.02). Five patients experienced ICD implant-related complications. CONCLUSIONS: Our findings showed that a baseline IVPG ≥ 30 mmHg was associated with an increased risk of experiencing SCD or appropriate ICD interventions among HCM patients who received ICDs for primary prevention. Combined with NSVT, which is a conventional risk factor, a baseline IVPG ≥ 30 mmHg may be a potential modifier of SCD risk in HCM patients.

Development and Practical Test of Quality Indicators for Palliative Care in Patients With Chronic Heart Failure.

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.

Long-term outcome of carvedilol therapy in Japanese patients with nonischemic heart failure.

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.

Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

PURPOSE: Plasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females. METHODS: Between 1 July 2014 and 31 December 2015, we screened 2,359 patients (1,324 males) referred from 168 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively. RESULTS: Of 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml-1) and low α-Gal A activity (≤4.0 nmol h-1 ml-1), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 14 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 7 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance). CONCLUSION: Plasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

The PDF and HTML versions of the article have been updated to include the Creative Commons Attribution 4.0 International License information.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

In the above article, we noticed that one female patient in the positive group (plasma lyso-Gb3 7.6 ng/ml, α-galactosidase A activity 4.9 nmol/h/ml) who presented at the neurology clinic was already diagnosed with Fabry disease before the current study. We excluded patients with a confirmed diagnosis of Fabry disease and those with relatives known to have Fabry disease. To accurately describe the information in the current study, we must exclude this patient from the analysis. We have accurately revised this information as follows.

Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

The HTML version of this Article contained errors in Supplementary Figure S2 "Flowchart of the lyso-Gb3 screening and gene analysis in female patients", which have been detailed in the associated Correction.

Efficacy and Safety of the Ultra-Short-Acting ß1-Selective Blocker Landiolol in Patients With Recurrent Hemodynamically Unstable Ventricular Tachyarrhymias　- Outcomes of J-Land II Study.

BACKGROUND: We aimed to investigate the efficacy and safety of landiolol in Japanese patients with recurrent hemodynamically unstable ventricular tachycardia or recurrent ventricular fibrillation (recurrent VT/VF).Methods and Results:This was an open-label, uncontrolled, multicenter study. Patients with hemodynamically unstable VT or VF 24 h prior to providing informed consent, and who were refractory to class III antiarrhythmic drugs, were enrolled. Landiolol was started at a dose of 1 µg/kg/min, after VT/VF was suppressed with electrical defibrillation. Landiolol was titrated up to 10 µg/kg/min in 1 h and adjusted between 1 and 40 µg/kg/min for the efficacy assessment (1-49 h). The primary efficacy endpoint was the proportion of patients free from recurrent VT/VF. Secondary efficacy endpoints included the number of recurrent VT/VF events and the survival rate 30 days after the start of landiolol treatment. Adverse events (AEs) were assessed for safety; 27 and 29 patients were analyzed for efficacy and safety, respectively. The proportion of patients free from recurrent VT/VF was 77.8% (95% CI 57.1-89.3). The mean (±standard deviation) number of recurrent VT/VF events was 9.3±7.9. The survival rate was 96.3%. The overall incidence of AEs and of serious AEs was 72.4% and 6.9%, respectively. CONCLUSIONS: Landiolol may be useful for Japanese patients with recurrent VT/VF who do not respond to class III antiarrhythmic drugs.

Impact of Recurrent Ventricular Tachyarrhythmia on Outcome in Japanese Heart Transplant Candidates With a Left Ventricular Assist Device.

BACKGROUND: Recurrent ventricular tachyarrhythmias (VTA) are "A factor" modifiers in the Interagency Registry for Mechanically Assisted Circulatory Support profile. The effect of recurrent VTA on clinical outcome, however, is controversial. We evaluated the impact of recurrent VTA on outcome in Japanese heart transplant candidates with a left ventricular assist device (LVAD). Methods and Results: Sixty-six adult patients with advanced heart failure who were listed for heart transplantation between January 2005 and October 2017 were enrolled in the study. Recurrent VTA (modifier A status) was defined as a sustained ventricular tachycardia or fibrillation that required implantable cardioverter defibrillator shocks or an external defibrillator more than twice weekly. The primary outcome was death from any cause. The secondary outcomes were the first occurrence of VTA and recurrent VTA after LVAD implantation. Sixteen patients (24%) met the criteria for modifier A status, and 15 patients had an LVAD implanted. During a median follow-up of 1,124 days, 21 of 60 patients with an LVAD died. There was a significantly higher mortality rate in LVAD patients with modifier A status than in those who did not meet the modifier A criteria. On multivariate analysis, patients with modifier A status had an increased risk of mortality (HR, 3.43; 95% CI: 1.30-8.61, P=0.001). CONCLUSIONS: Recurrent VTA might be a marker for worse outcome in Japanese heart transplant candidates with an LVAD.

Narrowing filtered QRS duration on signal-averaged electrocardiogram predicts outcomes in cardiac resynchronization therapy patients with nonischemic heart failure.

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.

Risk factors for rhabdomyolysis with HMG-CoA reductase inhibitors identified using a postmarketing surveillance database in Japan
.

OBJECTIVE: To investigate quantitatively the risk factors for rhabdomyolysis or related symptoms associated with HMG-CoA reductase inhibitors (statins), we used the lipid-lowering drug database (32,157 patients) developed by the RAD-AR Council, Japan, based on the postmarketing surveillance (PMS) data of pharmaceutical companies to perform a nested case-control study. MATERIALS AND METHODS: Of 26,849 patients taking statins, the case group was composed of 51 patients who experienced rhabdomyolysis or related symptoms while taking statins, and the control group was 1,020 patients randomly selected from patients who did not experience rhabdomyolysis or related symptoms while taking statins. Relevant factors that can be extracted from the database were: sex, age, body mass index (BMI), statin use duration, complications, concomitant medication, and clinical laboratory test values. RESULTS: Among those taking statins, 51 experienced rhabdomyolysis or related symptoms. Factors differing significantly between the two groups by univariate analysis were age, duration of statin intake, combination drugs (Ca antagonists, angiotensin II receptor blocker (ARB), cardiac drugs, benzodiazepines, mucoprotective drugs, insulin, α-glucosidase inhibitors), clinical laboratory results (high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase, alkaline phosphatase, total bilirubin), and complications (alcoholic hepatitis). Conditional multivariate logistic analysis of these factors yielded adjusted/odds ratios of 8.82 for the concomitant administration of an ARB and 3.45 for increased AST and 3.20 for increased total bilirubin levels. CONCLUSION: Risk factors for rhabdomyolysis or related symptoms associated with taking statins were combination with ARB and increases in AST or total bilirubin levels.
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Surface electromyography of myopotential oversensing provoked by simultaneous straining and leftward twisting in a patient with an implantable cardioverter defibrillator.

An important step in diagnosing myopotential oversensing is to confirm its reproducibility using specific provocation maneuvers. Although most maneuvers involve the co-contraction of many muscles, no attempt has been made to assess relevant muscle activities by electromyography. We describe a case with an implantable cardioverter defibrillator (ICD) whose myopotential oversensing was provoked by simultaneous straining and leftward twisting. Simultaneous recordings from real-time ICD telemetry and myopotentials of the rectus abdominis, oblique abdominis, and diaphragm on electromyography during the provocation maneuvers were conducted. It was shown that all three muscles contracted simultaneously during the provocation maneuvers; the diaphragm activity was the main source of noise oversensing, and the twist itself caused oversensing possibly due to the change in the position of the lead. In conclusion, the electromyographic assessment of relevant muscle activities may be useful in assessing each muscle's role and its contribution to myopotential oversensing, especially in a patient whose myopotential oversensing requires complex maneuvers to be provoked.

Depression and Outcomes in Japanese Outpatients With Cardiovascular Disease　- A Prospective Observational Study.

BACKGROUND: The aim of this study was to determine the prevalence of depression assessed by the 9-item test from the Patient Health Questionnaire (PHQ-9) and the effect of depression on adverse cardiovascular outcomes in Japanese outpatients with cardiovascular disease (CVD).Methods and Results:This prospective observational study enrolled 1,453 outpatients with CVD (mean age 67±13 years; 31.3% female; 32.6% ischemic heart disease). Depression was defined as a PHQ-9 score ≥10. The main composite outcome was the time to death from any cause or a cardiovascular event. 81 patients (5.6%) were diagnosed with depression (PHQ-9 ≥10). NYHA class III, living alone, and unemployment were independently associated with depression. During an average follow-up of 584±80 days, the main outcome occurred in 85 patients (5.8%). There was a higher incidence of the main outcome in patients with depression than in those without depression (P<0.001). Depression was an independent predictor of the primary outcome (hazard ratio 4.64, 95% confidence interval 2.24-9.09, P<0.001). CONCLUSIONS: Depression assessed by the PHQ-9 was found in 5.6% of Japanese outpatients with CVD and was an important risk factor for adverse outcomes. (UMIN-CTR No. UMIN 000023514) (Circ J 2016; 80: 2482-2488).