Optimal Targeted Temperature Management for Patients with Post-Cardiac Arrest Syndrome.

Background: To prevent hypoxic-ischemic brain damage in patients with post-cardiac arrest syndrome (PCAS), international guidelines have emphasized performing targeted temperature management (TTM). However, the most optimal targeted core temperature and cooling duration reached no consensus to date. This study aimed to clarify the optimal targeted core temperature and cooling duration, selected according to the time interval from collapse to return of spontaneous circulation (ROSC) in patients with PCAS due to cardiac etiology. Methods: Between 2014 and 2020, the targeted core temperature was 34 °C or 35 °C, and the cooling duration was 24 h. If the time interval from collapse to ROSC was within 20 min, we performed the 35 °C targeted core temperature (Group A), and, if not, we performed the 34 °C targeted core temperature (Group B). Between 2009 and 2013, the targeted core temperature was 34 °C, and the cooling duration was 24 or 48 h. If the interval was within 20 min, we performed the 24 h cooling duration (Group C), and, if not, we performed the 48 h cooling duration (Group D). Results: The favorable neurological outcome rates at 30 days following cardiac arrest were 45.7% and 45.5% in Groups A + B and C + D, respectively (p = 0.977). In patients with ROSC within 20 min, the favorable neurological outcome rates at 30 days following cardiac arrest were 75.6% and 86.4% in Groups A and C, respectively (p = 0.315). In patients with ROSC ≥ 21 min, the favorable neurological outcome rates at 30 days following cardiac arrest were 29.3% and 18.2% in Groups B and D, respectively (p = 0.233). Conclusions: Selecting the optimal target core temperature and the cooling duration for TTM, according to the time interval from collapse to ROSC, may be helpful in patients with PCAS due to cardiac etiology.

Clinical picture of the duration of venoarterial extracorporeal membrane oxygenation: analysis from JROAD-DPC.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for critically ill patients all over the world; however, comprehensive survey regarding the relationship between VA-ECMO duration and prognosis is limited. We conducted a survey of VA-ECMO patients in the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC), which was a health insurance claim database study among cardiovascular centers associated with the Japan Circulation Society, between April 2012 and March 2016. Out of 13,542 VA-ECMO patients, we analyzed 5766 cardiovascular patients treated with VA-ECMO. 68% patients used VA-ECMO only for 1 day and 93% had VA-ECMO terminated within 1 week. In multivariate analysis, the hazard ratio of 1-day support was significantly high at 1.72 (95% confidence intervals; 95% CI 1.53-1.95) (p < 0.001), while that of 2-day [0.60 (95% CI 0.49-0.73)], 3-day [0.75 (95% CI 0.60-0.94)], 4-day [0.43 (95% CI 0.31-0.60)] and 5-day support [0.62 (95% CI 0.44-0.86)] was significantly low. Comprehensive database analysis of JROAD-DPC revealed that cardiovascular patients who were supported with VA-ECMO for 2-5 days showed lower mortality. The optimal VA-ECMO support window should be investigated in further studies.

Impact of the COVID-19 pandemic on the hospitalizations, time course, presenting symptoms, and mid-term outcomes in patients with myocardial infarctions in a Japanese multi-center registry.

To investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on myocardial infarctions (MIs), consecutive MI patients were retrospectively reviewed in a multi-center registry. The patient characteristics and 180-day mortality for both ST-segment elevation myocardial infarctions (STEMIs) and non-STEMIs (NSTEMIs) in the after-pandemic period (7 April 2020-6 April 2021) were compared to the pre-pandemic period (7 April 2019-6 April 2020). Inpatients with MIs, STEMIs, and NSTEMIs decreased by 9.5%, 12.5%, and 4.1% in the after-pandemic period. The type of the presenting symptoms (as classified as typical symptoms, atypical symptoms, and out-of-hospital cardiac arrests [OHCAs]) did not differ between the two time periods for both STEMIs and NSTEMIs, while the rate of OHCAs was numerically higher in the after-pandemic period for the STEMIs (12.1% vs. 8.0%, p = 0.30). The symptom-to-admission time (STAT) did not differ between the two time periods for both STEMIs and NSTEMIs, but the door-to-balloon time (DTBT) for STEMIs was significantly longer in the after-pandemic period (83.0 [67.0-100.7] min vs. 70.0 [59.0-88.7] min, p = 0.004). The 180-day mortality did not significantly differ between the two time periods for both STEMIs (15.9% vs. 11.4%, p = 0.14) and NSTEMIs (9.9% vs. 8.0%, p = 0.59). In conclusion, hospitalizations for MIs decreased after the COVID-19 pandemic. Although the DTBTs were significantly longer in the after-pandemic period, the mid-term outcomes for MIs were preserved.

Edoxaban Monotherapy in Nonvalvular Atrial Fibrillation Patients with Coronary Artery Disease.

Background: Current guidelines recommend an oral anticoagulant (OAC) monotherapy in patients with nonvalvular atrial fibrillation (NVAF) and stable coronary artery disease (CAD) 1 year postpercutaneous coronary intervention (PCI). It might be possible to shorten the time for de-escalation from a dual therapy to monotherapy, but data regarding de-escalation to an edoxaban monotherapy are lacking. This study aimed to assess the clinical safety of an edoxaban monotherapy in patients with NVAF and stable CAD. Methods: A multicenter, prospective, randomized, open-label, and parallel group study was established to investigate the safety of an edoxaban monotherapy in patients with NVAF and stable CAD including over 6 months postimplantation of a third-generation DES and 1 year postimplantation of other stents (PRAEDO AF study). Between March 2018 and June 2020, 147 patients from 8 institutions in Japan were randomized to receive either an edoxaban monotherapy (n = 74) or combination therapy (edoxaban plus clopidogrel, n = 73). The primary study endpoint was the composite incidence of major bleeding and clinically significant bleeding, defined according to the ISTH criteria. Results: Major or clinically significant bleeding occurred in 2 patients in the monotherapy group (1.67% per patient-year) and in 5 patients in the combination therapy group (4.28% per patient-year) (hazard ratio, 0.39; 95% confidence interval, 0.08-2.02). There was no incidence of a myocardial infarction, stent thrombosis, unstable angina requiring revascularization, ischemic stroke, systemic stroke, or hemorrhagic stroke in either of the groups. Conclusions: The edoxaban monotherapy was shown to have acceptable clinical safety in patients with NVAF and stable CAD. The study was registered with the Japan Registry of Clinical Trials (jRCTs031180119).

Clinical outcomes for intracoronary imaging strategies at different medical facilities in Japanese patients with coronary artery disease: the SAKURA imaging PCI Registry.

The relationships between intracoronary imaging modalities and outcomes among Japanese patients with coronary artery disease (CAD) based on the type of medical facility providing outpatient care remain unclear. In this multicenter prospective study (SAKURA PCI Registry), we aimed to investigate the clinical outcomes of patients with CAD who underwent percutaneous coronary intervention (PCI) between April 2015 and December 2018. In this registry, we investigated differences in patient characteristics, intracoronary imaging modalities, and clinical outcomes between two types of medical facilities. Of the 414 patients enrolled in this registry, 196 were treated at two university hospitals, and 218 were treated at five community hospitals (median follow-up 11.0 months). The primary endpoint was clinically relevant events (CREs), including a composite of all-cause death, non-fatal myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, stroke, and major bleeding. Patients treated at university hospitals had higher rates of diabetes (50% vs. 38%, p = 0.015) and malignant tumors (12% vs. 6%, p = 0.015) and more frequent use of multiple intracoronary imaging modalities than patients treated at community hospitals (21% vs. 0.5%, p < 0.001). The Kaplan-Meier incidence of CREs at 1 year was comparable between university hospitals and community hospitals (8.8% vs. 7.3%, p = 0.527, log-rank test). Despite the relatively higher risk among patients in university hospitals with frequent use of multi-intracoronary imaging modalities, adverse clinical events appeared to be comparable between patients with CAD treated at university and community hospitals in Japan.

Effect of Atorvastatin on Microcirculation Evaluated by Vascular Occlusion Test with Peripheral Near-Infrared Spectroscopy.

The vascular occlusion test (VOT) with peripheral near-infrared spectroscopy (NIRS) is a non-invasive method to evaluate peripheral microcirculation. Statin therapy is widely used for patients with dyslipidaemia and contributes to reducing low-density lipoprotein cholesterol (LDL-C) levels and adverse cardiovascular events. However, it is not yet clear whether statin treatment improves peripheral microcirculation assessed by VOT with NIRS. In the present study, using VOT with NIRS, we evaluated the effect of statin therapy on peripheral microcirculation in patients with dyslipidaemia before and after statin therapy. METHODS: A total of six consecutive patients with dyslipidaemia who had not received statin therapy (6 males, mean age 71.8 ± 7.4 years) were enrolled. All patients were administered atorvastatin and their peripheral microcirculation assessed using VOT with NIRS (NIRO-200NX, Hamamatsu Photonics K.K., Japan) before and after statin therapy. The NIRS probe was attached to the right thenar eminence and brachial artery blood flow was blocked for 3 min at 50 mmHg above the resting systolic blood pressure. Maximum and minimum values of NIRS parameters after the VOT were used to determine concentration changes for total haemoglobin (ΔcHb), oxyhaemoglobin (ΔO2Hb), deoxyhaemoglobin (ΔHHb), and tissue oxygenation index (ΔTOI). RESULTS: During the follow-up period (mean 30.3 ± 6.5 days), LDL-C level decreased from 129.7 ± 26.3 to 67.5 ± 20.2 mg/dL (p-value = 0.031), ΔTOI increased from 24.0 ± 5.3 to 33.7 ± 6.3% (p-value = 0.023), and ΔO2Hb increased from 16.4 ± 5.3 to 20.0 ± 6.6 µmol/L (p-value = 0.007). ΔcHb and ΔHHb did not change significantly. CONCLUSION: ΔO2Hb and ΔTOI were significantly increased during the follow-up period. These findings suggest that ΔO2Hb and ΔTOI could assess the improvement of peripheral microcirculation by statin therapy. Compared to ΔTOI, ΔO2Hb seems to be a more useful parameter to evaluate peripheral microcirculation.

Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome due to an acute type B aortic dissection: a case report.

Acute type B aortic dissection is sometimes complicated by acute respiratory failure requiring mechanical ventilation. Herein, we describe our experience in a rare acute type B aortic dissection-associated respiratory failure case culminating in acute respiratory distress syndrome. The patient was a 45-year-old man admitted with a complaint of sudden chest pain radiating to his back. On computed tomography, an acute type B aortic dissection was diagnosed. He had no dyspnea on admission, but his respiratory function subsequently deteriorated, and severe acute respiratory distress syndrome was diagnosed on Day 4. Venovenous extracorporeal membrane oxygenation with anticoagulation plus continuous renal replacement therapy for oliguria improved the oxygenation, and the patient was weaned from the extracorporeal membrane oxygenation on Day 8. This patient fully recovered without worsening the aortic dissection, using venovenous extracorporeal membrane oxygenation with anticoagulation plus a continuous renal replacement therapy.

Institutional Characteristics and Prognosis of Acute Myocardial Infarction With Cardiogenic Shock in Japan　- Analysis From the JROAD/JROAD-DPC Database.

BACKGROUND: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients.Methods and Results:In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%. CONCLUSIONS: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

Prognostic benefits of prior amiodarone or ß-blocker use before the onset of ventricular arrhythmia with hemodynamic collapse.

Although antiarrhythmic drugs have long been used for the suppression of various types of arrhythmias, their prior use before the onset of ventricular arrhythmia with hemodynamic collapse and the effect on prognosis is not well known. Data from 1004 consecutive patients with cardiovascular shock in the Japanese Circulation Society's Shock Registry were analyzed. Eighty-four cases of ventricular arrhythmia-induced shock and ROSC (return of spontaneous circulation) were divided into the prior amiodarone or ß-blockers use group (Aß group, n = 27) and the non-amiodarone and non-ß-blockers use group (non-Aß group; n = 57) based on treatment before the onset of those arrhythmias. Clinical outcomes related to hemodynamic collapse such as OHCA (out-of-hospital cardiovascular arrest) was less in the Aß group [Aß group, 11/26 (42%) vs. non-Aß group, 41/56 (73%); p = 0.007]. Similarly, syncope was less common in the Aß group than in the non-Aß group [Aß group 4/27 (15%) vs. non-Aß group 27/57 (47%); p = 0.004]. Furthermore, prior amiodarone or ß-blockers use before the onset of ventricular arrhythmias was strongly associated with both survival at discharge (odds ratio 3.19; 95% confidence interval 1.06-9.67; p = 0.040) and neurological outcomes at discharge (odds ratio 3.96; 95% confidence interval 1.32-11.85; p = 0.014) based on multivariate logistic regression analysis. Prior amiodarone or ß-blockers use before the onset of malignant ventricular arrhythmia and maintaining appropriate blood concentrations in advance is associated with a good survival rate and better neurological outcomes after recovery from ventricular arrhythmia with hemodynamic collapse.

Gastrointestinal Bleeding From Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA Atrial Fibrillation Registry.

BACKGROUND: In the Japanese clinical setting, the prevalence, potential cofounders of gastrointestinal (GI) bleeding from anticoagulant therapy, including direct oral anticoagulants (DOACs) and warfarin, and prognosis after GI bleeding are unclear.Methods and Results:We examined about GI bleeding from anticoagulant therapy using data from the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 48.8% (n=1,561) were warfarin users and 51.2% (n=1,676) DOAC users. GI bleeding was identified in 68 patients (2.1%). No incidental differences in GI bleeding were observed between the DOAC and warfarin users (32 [1.9%] patients [0.67 events per 100 person-years] vs. 36 [2.3%] patients [0.75 events per 100 person-years], respectively; P=0.43). Multivariate Cox proportional hazard model analysis revealed that creatinine (hazard ratio [HR] 1.379, 95% confidence interval [CI] 1.091-1.743 P=0.007) and hemoglobin (HR 0.814, 95% CI 0.705-0.941, P=0.005) remained independent determinants of GI bleeding. Patients experiencing GI bleeding events had a higher risk of all-cause death (18%) than those without GI bleeding (6%) (P=0.045). CONCLUSIONS: GI bleeding was strongly associated with anemia and renal impairment. Patients experiencing GI bleeding had higher risk for all-cause death than those without GI bleeding.

Comparison of continuous 24-h and 14-day monitoring for detection of otherwise unknown atrial fibrillation: a registry to identify Japanese concealed atrial fibrillation (REAL-AF)-based study.

Early detection of atrial fibrillation (AF) is desirable for preventing strokes. Not only does AF often go undetected in patients being followed up for various disease conditions, but the optimal detection method also remains to be elucidated. In a prospective observational study of 24-h Holter monitoring versus 14-day external loop recording performed for detection of previously undiagnosed AF in 868 Japanese outpatients (aged 75 ± 6 years), with a CHA2DS2-vasc score ≥ 1, but no prior AF episodes, AF was detected during the initial monitoring period in 16 (1.8%) patients, in 7 (1.1% [7/645]) by 24-h monitoring and 9 (4.0% [9/223]) by 14-day monitoring (P = 0.005), and overall in 32 (3.7%) during the 1-year study period. Absence of a beta-blocker therapy and the serum N-terminal pro-brain natriuretic peptide level were independent predictors of a new detection of AF. Oral anticoagulation (OAC) therapy was given to 22 (69%) of the 32 patients in whom AF was detected, and no difference in the incidence of subsequent major adverse events was found between the patients managed with and without oral OAC therapy. Previously unknown AF was documented at a prevalence of 3.7% per year among Japanese with a notable CHA2DS2-VASc score, and 14-day external loop monitoring was significantly more effective for detection of the disorder. A large-scale prospective AF screening study conducted to clarify the type or types of patients who would benefit from "early" OAC therapy for primary stroke prevention is warranted.

Usefulness of a New Device to Monitor Cerebral Blood Oxygenation Using NIRS During Cardiopulmonary Resuscitation in Patients with Cardiac Arrest: A Pilot Study.

Recent guidelines on cardiopulmonary resuscitation (CPR) have stressed the necessity to improve the quality of CPR. Our previous studies demonstrated the usefulness of monitoring cerebral blood oxygenation (CBO) during CPR by near-infrared spectroscopy (NIRS). The present study evaluates whether the NIRO-CCR1, a new NIRS device, is as useful in the clinical setting as the NIRO-200NX. We monitored CBO in 20 patients with cardiac arrest by NIRS. On the arrival of patients at the emergency department, the attending physician immediately assessed whether the patient was eligible for this study after conventional advanced life support and, if eligible, measured CBO in the frontal lobe by NIRS. We found that in all patients, the cerebral blood flow waveform was in synchrony with the chest compressions. Moreover, the tissue oxygenation index increased following cardiopulmonary bypass (CPB) in patients undergoing CPB, including one patient in whom CBO was monitored using the NIRO-CCR1. In addition, although the NIRO-CCR1 could display the pulse rate (Tempo) in real time, Tempo was not always detected, despite detection of the cerebral blood flow waveform. This suggested that chest compressions may not have been effective, indicating that the NIRO-CCR1 also seems useful to assess the quality of CPR. This study suggests that the NIRO-CCR1 can measure CBO during CPR in patients with cardiac arrest as effectively as the NIRO-200NX; in addition, the new NIRO-CCR1 may be even more useful, especially in prehospital fields (e.g. in an ambulance), since it is easy to carry.

Application of Peripheral Near Infrared Spectroscopy to Assess Risk Factors in Patient with Coronary Artery Disease: Part 1.

Obesity, a risk factor of coronary artery disease, is known to cause peripheral microcirculatory disturbances. This study evaluated the relationship between the degree of obesity and peripheral microcirculatory disturbances, using peripheral near infrared spectroscopy (NIRS) with a vascular occlusion test (VOT). We compared correlations between the NIRS parameter changes induced by VOT and body mass index (BMI) in patients with and without statin therapy. A NIRS probe was set on the right thenar eminence, brachial artery blood flow was blocked for 3 min, and then released. Although total hemoglobin (ΔcHb), deoxyhemoglobin (ΔHHb) and tissue oxygenation index (ΔTOI) were not correlated with BMI, a significant negative correlation was found between oxyhemoglobin (ΔO2Hb) and BMI in the overall study population (r = -0.255, p-value 0.02). In addition, a significant negative correlation was found between ΔO2Hb and BMI in patients without statin therapy (r = -0.353, p-value 0.02) but not in patients with statin therapy (r = -0.181, p-value 0.27). These findings suggest that ΔO2Hb may be a useful indicator to assess peripheral microcirculation.

Application of Peripheral Near Infrared Spectroscopy to Assess Risk Factors in Patient with Coronary Artery Disease: Part 2.

Epicardial adipose tissue (EAT) is associated with visceral fat and various cardiac disorders, such as atrial fibrillation and adverse cardiovascular events. Therefore, it is important to develop a simple and non-invasive inspection method to assess EAT, to prevent unfavorable cardiac events. This study assessed correlations between near-infrared spectroscopy (NIRS) changes induced by a vascular occlusion test (VOT) and EAT volume measured by cardiac computed tomography (CCT) in patients with suspected coronary artery disease. We also assessed correlations between body mass index (BMI) and EAT volume in the same population. In addition, these correlations were compared in patients treated with statin therapy and in those without statin therapy. A NIRS probe was set on the right thenar eminence, and brachial artery blood flow was blocked for 3 min before being released. A negative correlation was found between oxyhemoglobin (ΔO2Hb) and EAT volume in the overall study population (r = -0.236, p = 0.03). Interestingly, although a strong correlation was observed in patients without statin therapy (r = -0.488, p < 0.001), this correlation was not observed in patients with statin therapy (r = 0.157, p = 0.34). These findings suggest that NIRS measurements with VOT may be a useful method to identify patients with high EAT volume and high cardiovascular risks.

Prognostic Value of Serum N-Terminal Pro-Brain Natriuretic Peptide Level over Heart Failure for Stroke Events and Deaths in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) and heart failure (HF) often coexist. The aims of this study were to explore the factors associated with the serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the association between prognosis and a history of HF or the serum NT-proBNP level in Japanese patients with AF.The present sub-study was based on the SAKURA AF Registry, a Japanese multicenter observational registry that included 3267 AF patients (median follow-up period: 39 months). All the patients were receiving warfarin or any of four direct oral anticoagulants. Serum NT-proBNP levels were available for 2417 patients, and the median value was 508 (interquartile range 202-1095) pg/mL at the time of enrollment. Log NT-proBNP was associated with non-paroxysmal AF, creatinine clearance > 60 mL/minute, history of HF and ischemic heart disease, antiarrhythmic drug use, anemia, being elderly female, and history of AF ablation. The relative risk of adverse clinical events, except major bleeding, was significantly higher in the highest NT-proBNP quartile as compared to the lowest quartile (adjusted hazard ratios: 2.87 for death, 2.39 for stroke), but a history of HF was associated only with a higher incidence of all-cause death.Concomitant HF was associated with a higher mortality, but the high NT-proBNP was associated with higher mortality and stroke events. In Japanese AF patients receiving anticoagulant treatment, high serum NT-proBNP levels predict the risk for both stroke events and deaths, and intensive follow-up is needed in such patients.

Prognostic Value of Neurological Status on Hospital Arrival for Short-Term Outcome in Patients With Cardiovascular Shock　- Sub-analysis of the Japanese Circulation Society Cardiovascular Shock Registry.

BACKGROUND: Consciousness disturbance is one of the major clinical signs associated with shock state, but its prognostic value has not been previously evaluated in cardiovascular shock patients. We aimed to evaluate the prognostic value of neurological status for 30-day mortality in cardiovascular shock patients without out-of-hospital cardiac arrest (OHCA). Methods and Results: Patients with out-of-hospital onset cardiovascular shock were recruited from the Japanese Circulation Society Shock Registry. Neurological status upon hospital arrival was evaluated using the Japan Coma Scale (JCS). Patients were divided into 4 groups according to the JCS: alert, JCS 0; awake, JCS 1-3 (not fully alert but awake without any stimuli); arousable, JCS 10-30 (arousable with stimulation); and coma JCS 100-300 (unarousable). The primary endpoint was 30-day all-cause death. In total, 700 cardiovascular shock patients without OHCA were assessed. The coma group was associated with a higher incidence of 30-day all-cause death compared with other groups (alert, 15.3%; awake, 24.4%; arousable, 36.8%; coma, 48.5%, P<0.001). Similar trends were observed in etiologically divergent subgroups (acute coronary syndrome, non-ischemic arrhythmia, and aortic disease). On multivariate Cox regression analysis, arousable (hazard ratio [HR], 1.82; 95% CI: 1.16-2.85, P=0.009) and coma (HR, 2.72; 95% CI: 1.76-4.22, P<0.001) (reference: alert) independently predicted 30-day mortality. CONCLUSIONS: Neurological status upon hospital arrival was useful to predict 30-day mortality in cardiovascular shock patients without OHCA.

Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry.

BACKGROUND: Off-label dosing of direct oral anticoagulants (DOACs) is encountered clinically among patients with atrial fibrillation (AF), although data on the clinical outcomes of over- and under-dosing are lacking in Japan. Methods and Results: We examined the clinical outcomes of off-label DOAC dosing using the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 1,676 under any of the 4 DOAC regimens were followed up for a median of 39.3 months: 746 (45.0%), appropriate standard-dose; 477 (28.7%), appropriate low-dose; 66 (4.0%), over-dose; and 369 (22.2%) under-dose. Compared with the standard-dose group, patients in the under- and over-dose groups were significantly older and had a higher stroke risk. After multivariate adjustment, stroke/systemic embolism (SE) and death events were equivalent between the standard- and under-dose groups, but major bleeding events tended to be lower in the under-dose group (hazard ratio [HR] 0.474, P=0.0739). Composite events (stroke/SE, major bleeding, or death) were higher in the over-dose than in the standard-dose group (HR 2.714, P=0.0081). CONCLUSIONS: Clinical outcomes were not worse for under-dose than for standard-dose users among patients with different backgrounds. Over-dose users, however, were at higher risk for all clinical events and required careful follow-up. Further studies are needed to clarify the safety and effectiveness of off-label DOAC dosing in Japan.

Clinical characteristics and prognostic factors in acute coronary syndrome patients complicated with cardiogenic shock in Japan: analysis from the Japanese Circulation Society Cardiovascular Shock Registry.

Cardiogenic shock frequently leads to death even with intensive treatment. Although the leading cause of cardiogenic shock is acute coronary syndrome (ACS), the clinical characteristics and the prognosis of ACS with cardiogenic shock in the present era still remain to be elucidated. We analyzed clinical characteristics and predictors of 30-day mortality in ACS with cardiogenic shock in Japan. The Japanese Circulation Society Cardiovascular Shock registry was a prospective, observational, multicenter, cohort study. Between May 2012 and June 2014, 495 ACS patients with cardiogenic shock were analyzed. The primary endpoint was 30-day all-cause mortality. The median [interquartile range; IQR] age was 71.0 [63.0, 80.0] years. The median [IQR] value of systolic blood pressure (SBP) and heart rate were 75.0 [50.0, 86.5] mm Hg and 65.0 [38.0, 98.0] bpm, respectively. Multivariable analysis showed an odds ratio (OR) of 4.76 (confidence intervals; CI 1.97-11.5, p < 0.001) in the lowest SBP category (< 50 mm Hg) for SBP ≥ 90 mm Hg. Moreover, age per 10 years increase (OR 1.38, CI 1.18-1.61, p = 0.002), deep coma (OR 3.49, CI 1.94-6.34, p < 0.001), congestive heart failure (OR 3.81, CI 2.04-7.59, p < 0.001) and left main trunk disease (LMTD) (OR 2.81, CI 1.55-5.10, p < 0.001) were independent predictors. Severe hypotension, older age, deep coma, congestive heart failure, and LMTD were independent unfavorable factors in ACS complicated by cardiogenic shock in Japan. A prompt assessment of high-risk patients referring to those predictors in emergency room could lead to appropriate treatment without delay.

Oral anticoagulant use and clinical outcomes in elderly Japanese patients: findings from the SAKURA AF Registry.

Direct-acting oral anticoagulants (DOACs) are widely used in aged Japanese patients with atrial fibrillation (AF), but outcome data for such patients are limited. We compared outcomes between 1895 (58.5%) patients aged < 75 years (non-elderly), 1078 (33.3%) 75-84 years (elderly) and 264 (8.2%) ≥ 85 years (very elderly) enrolled in a prospective multicenter registry. Kaplan-Meier analysis (median follow-up: 39.3 months) revealed a significantly high incidence of stroke/systemic embolism (SE) among the very elderly relative to that among the non-elderly or elderly (3.2 vs. 1.2 and 1.5 events per 100 patient-years, p < 0.001). Major bleeding in the non-elderly group was significantly infrequent relative to that among the elderly or very elderly group (1.1 vs. 1.6 vs. 1.8 events, p = 0.033). After multivariate adjustment, the stroke/SE incidence was comparable between DOAC and warfarin users, regardless of age, but major bleeding decreased significantly among very elderly DOAC users (adjusted HR 0.220, 95% CI 0.042-0.920). The greater increasing incidence of stroke/SE than major bleeding as patients age suggests that stroke prevention should outweigh the bleeding risk when anticoagulants are being considered for aged patients. Our data indicated that DOACs can be a therapeutic option for stroke prevention in very elderly patients.

Adverse Clinical Events during Long-Term Follow-Up After Catheter Ablation of Atrial Fibrillation.

Pulmonary vein isolation (PVI) of atrial fibrillation (AF) can reduce the AF burden and, potentially, reduce the long-term risk of strokes and death. However, it remains unclear whether anticoagulants can be stopped after PVI because of post-ablation AF recurrence in some patients. This study aimed to investigate the discontinuation rate of anticoagulants and long-term incidence of strokes after PVI.We enrolled 512 consecutive Japanese patients with AF (mean age, 63.4 ± 10.4 years; 123 women; 234 with non-paroxysmal AF; CHADS2 score/CHA2DS2-VASC score, 1.32 ± 1.12/2.21 ± 1.54) who underwent PVI between 2012 and 2015. During a 28.0 ± 17.1 -month follow-up, anticoagulants were terminated in 230 (44.9%) of the 512 patients, AF recurred in 200 (39.1%), and 10 (1.95%) suffered from a stroke. Death occurred in 5 (0.98%) patients. Although the incidence of strokes, by a Kaplan-Meier analysis, was similar, the incidence of death was lower (Hazard ratio 0.37, 95% confidence interval 0.12-0.93, P = 0.041) in the AF ablation group than the control group without ablation after 1:1 propensity score matching (the control data was derived from 2,986 patients in the SAKURA AF Registry, a large-cohort AF registry).Anticoagulants were discontinued in nearly half the patients who underwent AF ablation; of these, 39.1% experienced AF recurrences, 1.95% suffered from strokes, and 0.98% died, but the risk of death after AF ablation appeared to be lower than that in a propensity score-matched control group without ablation during long-term follow-up.