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Glasgow prognostic score (GPS) has been used to evaluate inflammatory response and nutritional status. This study aimed to investigate the impact of nutritional status on cardiac prognosis by using GPS in patients after undergoing percutaneous coronary intervention (PCI). We included 862 patients who underwent PCI for stable angina pectoris between 2015 and 2018. We used the original cutoff values, which were an albumin (Alb) level of 3.5 g/dl and a C-reactive protein (CRP) level of 0.3 mg/dl. We categorized them into the three groups: originally defined GPS (od-GPS) 0 (high Alb and low CRP), 1 (low Alb or high CRP), and 2 (low Alb and high CRP). Major adverse clinical events (MACEs) included all-cause death, nonfatal myocardial infarction, revascularization, and hospitalization for heart failure. The median follow-up period was 398.5 days. During the follow-up, MACEs occurred in 136 patients. Od-GPS 2 had higher prevalence rates in terms of chronic kidney disease (CKD; 31.7% [229/722] vs. 44.9% [53/118] vs. 63.6% [14/22], p

Catheter ablation for atrial fibrillation (AF) has been an established and frequently utilized approach in a variety of clinical settings. Nevertheless, real-world data about the clinical course of AF patients after initial catheter ablation remain limited, and these are mainly derived from particular registries or selected high-volume centers.In this study, we used health check-ups and insurance claims database from a Japanese insurance organization. The study population was comprised of 1777 patients who underwent catheter ablation for AF before June 2016. During the 3-year follow-up period, 396 (22.3%) patients underwent at least one repeated AF ablation, while 74 (4.2%) underwent two or more repeated ablations. In multivariate Cox regression analysis, longer time after AF diagnosis (7-11 months and ≥12 months versus 1-6 months) (HR, 1.05; 95% CI, 1.01-1.08 and HR, 1.04; 95% CI 1.02-1.07) was independently associated with repeated ablation. The discontinuation rates of OACs and AADs after the first ablation were 26.7% and 63.0% at 3 months and 75.2% and 89.1% at 1 year after the initial ablation, respectively. The former was independently associated with shorter time after AF diagnosis and lower diastolic blood pressure, whereas the latter was independently associated with older age, smaller CHADS2 score, and shorter time after AF diagnosis.We presented real-world data regarding the clinical course of young Japanese AF patients after initial catheter ablation based on a claims database in Japan.

Background Direct oral anticoagulants (DOACs) are widely used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). We investigated the adherence of DOACs for years known to be associated with the effectiveness in Japanese NVAF patients, using a claim database. Method We performed a retrospective evaluation of NVAF patients in a claims database in Japan, who initiated dabigatran, rivaroxaban, and apixaban between April 2011 and June 2016. Drug persistence was assessed by Kaplan-Meier method for the initially-prescribed DOAC and all DOACs including switched ones. Proportion of days covered (PDC) was also evaluated in patients with persistent prescription and compared among DOACs. Results In the total of 671 patients, rivaroxaban (47%) was more prescribed than dabigatran (28%) and apixaban (25%). Drug persistence at 3 years was higher in rivaroxaban (69%) than dabigatran (57%) and apixaban (67%). Including switching to other DOACs, persistence of DOACs was 72% at 3 years without significant differences between index-DOACs. In multivariate Cox regression analysis, absence of hypertension, and prior history of cancer were significantly associated with the drug discontinuation of all DOACs. The mean PDC was ~ 95% and the frequency of high-adherent patients (PDC ≥0.80) was more than 90%, which similarly persisted at 3 years and showed no significant differences between index DOACs. Conclusion In a real-world Japanese claim data analysis, about 70% of patients under DOAC showed persistence with anticoagulation therapy at 3 years. High adherence to DOACs assessed by PDC (over 90%) persisted to 3 years regardless of the types of DOACs.

It has been reported that a large decline in estimated glomerular filtration rate (eGFR) over time is associated with increased incidence of cardiovascular disease. We investigated whether this association differs according to the baseline eGFR.A total of 4666 patients (male 71%) with measurements of eGFR at both baseline and 1 year and that had no cardiovascular events at 1-year follow-up were retrieved from the Shinken Database between June 2004 and March 2015. The study population was divided into three groups by baseline eGFR (mL/min/1.73 mA total of 187 cardiovascular events occurred during the mean follow-up of 2.8 ± 0.6 years. The adjusted hazard ratios of eGFR slope (-10 with reference to ≥-10) were 2.37 (95% CI, 1.28-4.40), 3.10 (95% CI, 1.78-5.40), and 2.66 (95% CI, 1.15-6.13) in the high, middle, and low eGFR groups, respectively. Similar results were found in patients with structural heart disease, but not in those without.Decline in eGFR was associated with an increase in cardiovascular events, and this effect was consistent regardless of the baseline eGFR.

Background Diagnosis of atrial fibrillation (AF) based on electrocardiogram (ECG) with sinus rhythm remains a major challenge. Obtaining a panoramic view with hundreds of automatically measured ECG parameters at sinus rhythm on the predictive capability for AF would be informative. Methods We used a single-center database of a specialist cardiovascular hospital (Shinken Database 2010–2017; n = 19,170). We analyzed 12,863 index ECGs with sinus rhythm after excluding those showing AF rhythm, other atrial tachyarrhythmia, pacing beat, or indeterminate axis, and those of patients with structural heart diseases. We used 438 automatically measured ECG parameters in the MUSE data management system. The predictive models were developed using random forest algorithm with the 10-fold cross-validation method. Results In 12,863 index ECGs with sinus rhythm, a predictive capability for current paroxysmal AF (n = 1131) by c-statistics was 0.99981 ± 0.00037 for training dataset and 0.91337 ± 0.00087 for testing dataset, respectively. Excluding AF at baseline (n = 11,732), a predictive capability for newly developed AF (n = 98) by c-statistics was 0.99973 ± 0.00086 for training dataset and 0.99160 ± 0.00038 for testing dataset, respectively. The distribution of parameter importance was mostly similar among P, QRS, and ST-T segment for both current and newly developed AF. Conclusions This study intended to provide panoramic information in relation between ECG parameters and AF. The parameter importance of ECG parameters for predicting AF was mostly similar in P, QRS, and ST-T segment in models for both current and future AF.

Background Ischemic stroke (IS) and major bleeding, which are serious adverse events in patients with atrial fibrillation (AF), could have seasonal variations, but there are few reports.Methods and Results:In the Shinken Database 2004-2016 (n=22,018), 3,581 AF patients (average age, 63.5 years; 2,656 men, 74.2%; 1,388 persistent AF, 38.8%) were identified. Median CHADS2and HAS-BLED scores were both 1 point. Oral anticoagulants were prescribed for 2,082 (58.1%) patients (warfarin, 1,214; direct oral anticoagulants [DOACs], 868). Incidence and observation period (maximum 3 years) of IS, extracranial hemorrhage (ECH), and intracranial hemorrhage (ICH) were counted separately for the northern hemisphere seasons. During the mean follow-up period of 2.4 years, there were totals of 90 IS, 73 ECH, and 33 ICH cases. The respective incidence rates per 1,000 patient-years in spring, summer, autumn, and winter were 8.5, 8.8, 7.5, and 16.8 for IS, 7.2, 9.7, 3.8, and 13.1 for ECH, and 2.7, 1.9, 3.8, and 7.0 for ICH. The number of patients with DOACs relatively increased among those with ECH in summer. Conclusions Significant seasonal variations were observed for IS, ECH, and ICH events in AF patients, and were consistently the highest in winter. A small peak of ECH was observed in summer, which seemed, in part, to be related to increased DOAC use.

Although bisoprolol is used widely to treat patients with heart failure (HF), little information is available regarding the association between the dose of bisoprolol administered and the bisoprolol plasma concentration (Bis-PC) in real-world clinical practice.This was a single-center, observational study in 114 patients with HF receiving once-daily bisoprolol. After determination of trough Bis-PC, the relationship between the dose of bisoprolol and Bis-PC was analyzed. In a multiple linear regression model, the dose of bisoprolol and estimated creatinine clearance (reciprocal number) were identified as independent predictors. HF severity and hepatic function were not associated with Bis-PC.Bis-PC was increased by renal dysfunction, which explained most of the discrepancy between the dose of bisoprolol administered and Bis-PC.

Initial screening for proteinuria by urine dipstick test (UDT) may be useful for predicting clinical outcomes. The Shinken Database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. Patients for whom UDT was performed at their initial visit between 2004 and 2010 (n = 7131) were divided into three groups according to the test results: negative, trace, and positive (1+ to 4+) proteinuria. During the mean follow-up period of 3.4 years, 233 (3.1%) deaths, 255 (3.6%) heart failure (HF) events, and 106 (1.5%) ischemic stroke (IS) events occurred. Prevalence of atherothrombotic risks increased with an increase in the amounts of proteinuria. The incidence of all-cause death, HF and IS events increased significantly from negative to trace to positive proteinuria groups (log rank test, P for trend

Background Although bisoprolol has been established to prevent heart failure (HF), finding the optimal dose remains a challenge. It is crucial to understand the distribution of bisoprolol plasma concentration (Bis-PC) and association with outcomes. Methods This was a single-center observational study in 114 HF patients under once-daily bisoprolol. After obtaining trough Bis-PC, patients were followed-up for 1 year. The primary endpoint was worsening of HF. Patients were divided according to the tertiles of Bis-PC. Results In multivariate logistic regression analysis, independent predictors of high Bis-PC (1st tertile: ≥ 5.38 ng/mL) were age, eGFR, and bisoprolol dose. The cumulative incidence rates of the primary endpoint were 10.5%/13.2%/26.3% in low/middle/high Bis-PC categories, respectively (log rank test, p = 0.087). Bis-PC was independently associated with the primary endpoint (hazard ratio [HR], 1.19 [per ng/mL], 95% CI 1.03–1.36). In subgroups, high Bis-PC was independently associated with the primary endpoint in elderly (HR 6.32, 95% CI 1.34–29.83) and HF with preserved ejection fraction (HFpEF) (HR 3.52, 95% CI 1.06–11.70). Conclusions Bis-PC was increased by age and renal dysfunction, and high Bis-PC was associated with worsening of HF in elderly and HFpEF patients. Care should be taken to avoid overdose.

Objective The pharmacodynamic effect of warfarin varies among individuals, and its maintenance dose is widely distributed. Although many formulae for predicting the maintenance dose of warfarin have been developed, most of them are complex and not in practical use. Methods and Materials Among 12,738 new patients visiting the Cardiovascular Institute between 2004 and 2009, we identified 127 patients (66.6±8.8 years, 89 men) with atrial fibrillation for whom warfarin was newly started with an initial dose of 2 mg/day and the international normalized ratio (INR) at 1 year after warfarin was started was within the therapeutic range. The prediction models for the maintenance dose were developed by an exponential equation and a first-order equation. Results The initial response of the INR to the dose of 2 mg/day (initial INR) ranged from 1.00-3.24 (mean 1.43), while the maintenance dose of warfarin ranged from 0.5-14 mg (mean 3.8 mg). The maintenance dose showed an exponential correlation to the initial INR: (predicted maintenance dose) =5.522× (initial INR) -1.556 (R2=0.795, p

High alkaline phosphatase (ALP) levels are reported to be associated with an increased risk of cardiovascular events in patients with chronic kidney disease (CKD). Given the pathological link with CKD, a similar relationship may exist in patients with atrial fibrillation (AF). We retrospectively evaluated 1,719 patients with AF and normal hepatic function who were registered in the Shinken Database between November 2011 and March 2017. Study patients were divided into three groups according to ALP value tertiles with cut-offs of 175 and 227 IU/L (normal range: 95-350 IU/L). Each group's incidence rate was recorded, and the risks of cardiovascular events and each component for patients in the middle and high ALP tertiles were compared with those in the low tertile and evaluated using Cox regression models. The additional predictive value of the high ALP tertile over the existing risk scores for the components of cardiovascular events was evaluated via receiver operating characteristic (ROC) curve analysis. During the median follow-up of 731 days (IQR: 444-1095 days), 137 cardiovascular events occurred, with incidence rates of 2.94%, 3.44%, and 6.19%/person-year for the low, middle, and high ALP tertiles, respectively. Of these cardiovascular events, heart failure had the highest incidence rates (1.34%, 1.89%, and 4.29%/person-year for the low, middle, and high ALP tertiles, respectively) and the incidence rates of the other components of cardiovascular event were similar in each ALP groups. Multivariate Cox regression analysis yielded hazard ratios of 1.22 (95% confidence interval [CI] 0.70-1.96) and 1.62 (95% CI 1.06-2.48) for cardiovascular events and 1.66 (95% CI 0.87-3.15) and 2.50 (95% CI 1.39-4.48) for heart failure admission in the middle and high ALP tertiles, respectively. By ROC curve analysis for heart failure admission showed that the high ALP tertile lacked significant additive predictive value over the existing risk scores. High serum ALP levels, even those in the normal range, were significantly associated with an increased risk of cardiovascular events, especially heart failure admission in patients with AF.

Background Detection of atrial fibrillation (AF) out of electrocardiograph (ECG) on sinus rhythm (SR) using artificial intelligence (AI) algorithm has been widely studied within recent couple of years. Generally, it is believed that a huge number of ECGs are necessary for developing an AI-enabled ECG to be adequate to correspond to a lot of minor variations of ECGs. For example, structural heart diseases have typical ECG characteristics, but they could be a noise for the purpose of detecting the small signs of electrocardiographic signature of AF. We hypothesized that when patients with structural heart diseases are excluded, AI-enabled ECG for identifying patients with AF can be developed with a small number of ECGs. Methods We developed an AI-enabled ECG using a convolutional neural network to detect the electrocardiographic signature of AF present during normal sinus rhythm (NSR) using a digital, standard 10-second, 12-lead ECGs. We included all patients who newly visited the Cardiovascular Institute with at least one NSR ECG between Feb 1, 2010, and March 31, 2018. We classified patients with at least one ECG with a rhythm of AF as positive for AF (AF label) and others as negative for AF (SR label). We allocated ECGs to the training, internal validation, and testing datasets in a 7:1:2 ratio. We calculated the area under the curve (AUC) of the receiver operating characteristic curve for the internal validation dataset to select a probability threshold, which we applied to the testing dataset. We evaluated model performance on the testing dataset by calculating the AUC and the sensitivity, specificity, F1 score, and accuracy with two-sided 95% confidence intervals (CIs). Results We totally included 19170 patients with 12-lead ECG. After excluding patients with structural heart diseases, 12825 patients with NSR ECGs at the initial visit were identified (1262 were clinically diagnosed as AF anytime during the time course and 11563 were never diagnosed as AF). Of 11563 non-AF patients, 1818 patients who were followed over 1095 days were selected for the analysis with the SR label, to secure the robustness for maintaining SR. Of 1262 AF patients, 251 patients were selected for the analysis with the AF label, of whom a NSR ECG within 31 days before or after the index AF ECG (the first AF ECG during the time course) could be obtained. In the patients with AF label, the NSR ECG of which the date was the nearest to the index AF ECG was selected for the analysis. The AI-enabled ECG showed an AUC of 0.88 (0.84–0.92) with sensitivity 81% (72–88), specificity 80% (77–83), F1 score 50% (43–57), and overall accuracy 80% (78–83). Conclusion An AI-enabled ECG acquired during NSR allowed identification of patients with AF in a small population without structural heart diseases. Funding Acknowledgement Type of funding sources: None.

Catheter ablation for atrial fibrillation (AF) has been an established and frequently utilized approach in a variety of clinical settings. Nevertheless, real-world data about the clinical course of AF patients after initial catheter ablation remain limited, and these are mainly derived from particular registries or selected high-volume centers.In this study, we used health check-ups and insurance claims database from a Japanese insurance organization. The study population was comprised of 1777 patients who underwent catheter ablation for AF before June 2016. During the 3-year follow-up period, 396 (22.3%) patients underwent at least one repeated AF ablation, while 74 (4.2%) underwent two or more repeated ablations. In multivariate Cox regression analysis, longer time after AF diagnosis (7-11 months and ≥12 months versus 1-6 months) (HR, 1.05; 95% CI, 1.01-1.08 and HR, 1.04; 95% CI 1.02-1.07) was independently associated with repeated ablation. The discontinuation rates of OACs and AADs after the first ablation were 26.7% and 63.0% at 3 months and 75.2% and 89.1% at 1 year after the initial ablation, respectively. The former was independently associated with shorter time after AF diagnosis and lower diastolic blood pressure, whereas the latter was independently associated with older age, smaller CHADS

AIM Although polypharmacy has been associated with poor clinical outcomes, whether taking an increased number of medications is harmful or beneficial for older adult patients treated for cardiovascular diseases might require further discussion. METHODS We analyzed data of 2089 patients aged ≥75 years in a single hospital-based cohort. The study population was divided into three groups according to the tertiles of the number of medications at baseline

Aim Polypharmacy is known to be a risk factor for falls or bone fracture (F/F) in elderly patients. However, this relationship is not fully described in patients with non-valvular atrial fibrillation (NVAF), for which F/F may lead to serious clinical outcomes, including major bleeding. Methods We analyzed 509 elderly (aged ≥75 years) patients with NVAF who had recently visited a hospital specializing in cardiology, of which 272 patients had paroxysmal atrial fibrillation (PAF) and 237 had persistent/permanent atrial fibrillation (PeAF). Patients were divided into four groups according to the number of medications: ≤3, 4-6, 7-9, and ≥10. The relationship between the number of medications and incidence rate of F/F in AF patients was analyzed. In addition, this relationship was analyzed in patients with each AF type. Results Cumulative incidence of F/F at 3 years in the respective categories was 3.7%, 5.4%, 4.3% and 5.7% for PAF, and 5.2%, 7.5%, 7.8% and 25.0% for PeAF (log-rank test, P = 0.930 and 0.003, respectively). In a multivariable model, patients with ≥10 medications showed a significantly higher risk for F/F compared with those with ≤3 medications as reference only in PeAF (adjusted hazard ratio 4.82, 95%CI 1.42-16.33), without significant interaction (P = 0.081). Conclusions Elderly NVAF patients using ≥10 medications showed a higher risk for F/F. In subgroup analysis, this association was observed only in patients with PeAF, although there was no significant interaction between number of medications and AF type. Geriatr Gerontol Int 2021; ••: ••-••.

The relationship between myocardial bridging (MB) and coronary spasms during spasm provocation testing (SPT) remains unclear. We aimed to investigate whether MB was correlated with the SPT by ergonovine (ER) injections in a retrospective observational study. Of the 3340 patients who underwent a first coronary angiography, 166 underwent SPT using ER injections and were divided into 2 groups: MB(+) (n = 23), and MB(−) (n = 143). MB was defined as an angiographic reduction in the diameter of the coronary artery during systole. The patients who had severe organic stenosis in the left anterior descending coronary artery were excluded. The MB(+) group more frequently had diabetes mellitus and chronic kidney disease, and a thicker interventricular septum thickness. The rate of SPT-positivity was higher in the MB(+) group than MB(−) group (56.5% vs. 22.4%, P = 0.001). A multivariate regression analysis showed that the presence of MB was independently associated with SPT-positivity (odds ratio 5.587, 95% confidence interval 2.061–15.149, P = 0.001). In conclusion, coronary spasms during provocation tests with ER independently correlated with the MB. MB may predict coronary spasms.

Several studies have suggested a possible relationship between atrial fibrillation (AF) and falls. However, whether the relationship depends on AF types is unclear. We investigated the relationship between sustaining AF and falls.Single hospital-based cohort study with a follow-up of falls within 3 years after baseline.A total of 14,056 patients from our cohort between February 2010 and March 2016.Incidence of falls within 3 years by baseline cardiac rhythm was measured, and we investigated the effects of AF types on incidence of falls.The study population was divided into younger (75 years old; n = 11,808) and older (≥75 years old; n = 2248) groups, and then divided into 3 groups according to the baseline cardiac rhythm: sinus rhythm (SR), paroxysmal AF (PAF), and persistent AF (PeAF). There were more male patients in the PeAF group; these patients had more comorbidities both in the younger and older groups. The cumulative incidence rates of falls at 1 year in patients with SR, PAF, and PeAF were similar in the younger group (0.4%, 0.4%, and 0.6%, respectively; P = .496), whereas those were significantly different in the older group (2.3%, 2.7%, and 5.0%, respectively; P = .024). In multivariate analysis, both PAF [hazard ratio (HR) 1.179; 95% confidence interval (CI) 0.553-2.511, reference SR] and PeAF (HR 1.502; 95% CI 0.635-3.556) were not associated with falls in the younger group. In the older group, PeAF was independently associated with incidence of falls (HR 2.257; 95% CI 1.262-4.037), but PAF was not (HR 1.317; 95% CI 0.673-2.574).PeAF, not PAF, was associated independently with falls in older patients, suggesting the possible effect of irregular beats on physical frailty in the older population.

The aims of this study were to determine the distribution of plasma concentration of edoxaban (PC-Ed) with their 90% interval (on therapy range) and its correlation with anticoagulation markers in patients with non-valvular atrial fibrillation (NVAF). Consecutive 97 NVAF patients under edoxaban therapy were evaluated (60/30 mg dose, n = 48/49; men/women, n = 71/26; age, 69 years). CHADS2 score 0, 1, and ≥ 2 were 27%, 44%, and 29%, respectively. The mean (90% interval) of PC-Ed by LC–MS/MS was 194.3 (49.4–345.3) and 17.0 (4.8–40.7) ng/mL at peak (2–4 h post-dose) and trough (pre-dose), respectively. Correlation of prothrombin time (PT) with PC-Ed was higher than that of activated partial thromboplastin time (aPTT). Among 6 PT reagents, Coagupia PT–N and Simplastin Excel S (both PT reagents) showed the highest predictive capability for the upper outlier of PC-Ed at peak and trough. Among 4 aPTT reagents, only Thrombocheck APTT measured at peak had a significant predictive capability. When using PT reagents, both peak and trough sampling showed a similar predictive capability for the upper outliers of PC-Ed with a high sensitivity, but a relatively low specificity. We demonstrated the distributions of plasma concentration, PT with 6 reagents, and aPTT with 4 reagents under edoxaban therapy in Japanese patients with NVAF, showing their 90% intervals. For predicting the upper outlier of PC-Ed, PT was more sensitive compared with aPTT, whereas predicting capability for the outliers of PC-Ed was mostly similar between peak and trough samplings among PT reagents (UMIN 000032492).

BackgroundResting 12-lead electrocardiography is widely used for the detection of cardiac diseases. Electrocardiogram readings have been reported to be affected by aging and, therefore, can predict patient mortality.MethodsA total of 12,837 patients without structural heart disease who underwent electrocardiography at baseline were identified in the Shinken Database among those registered between 2010 and 2017 (n = 19,170). Using 438 electrocardiography parameters, predictive models for all-cause death and cardiovascular (CV) death were developed by a support vector machine (SVM) algorithm.ResultsDuring the observation period of 320.4 days, 55 all-cause deaths and 23 CV deaths were observed. In the SVM prediction model, the mean c-statistics of 10 cross-validation models with training and testing datasets were 0.881 ± 0.027 and 0.927 ± 0.101, respectively, for all-cause death and 0.862 ± 0.029 and 0.897 ± 0.069, respectively for CV death. For both all-cause and CV death, high values of permutation importance in the ECG parameters were concentrated in the QRS complex and ST-T segment.ConclusionsParameters acquired from 12-lead resting electrocardiography could be applied to predict the all-cause and CV deaths of patients without structural heart disease. The ECG parameters that greatly contributed to the prediction were concentrated in the QRS complex and ST-T segment.

Additional file 1: Table S1. The full list of 438 ECG parameters analyzed by univariate logistic regression analysis. Table S2. The permutation importance of the 109 ECG parameters for all-cause death. Table S3. The permutation importance of the 109 ECG parameters for cardiovascular death. Table S4. The c-statistics of the predictive models for all-cause and cardiovascular death by support vector machine.

Background Recently, the analysis of electrocardiogram (ECG) waveform by artificial intelligence has been reported to pick out those who have atrial fibrillation (AF) or have a high potential of developing AF, which, however, cannot explain the mechanisms or algorisms for the prediction from its nature. Purpose The purpose of this study is to conduct a comprehensive analysis to investigate the difference of weighting in predicting capability for AF among hundreds of automatically-measured ECG parameters using a single ECG at sinus rhythm. Methods and results Out of Shinken Database 2010–2017 (n=19170), 12825 patients were extracted, where those with ECG showing AF rhythm at the initial visit (including all persistent/permanent AF and a part of paroxysmal AF) and those with structural heart diseases were excluded. Out of 639 automatically-measured ECG parameters in MUSE data management system (GE Healthcare, USA), 438 were used. [Analysis 1] A predicting model for paroxysmal AF were determined by logistic regression analysis (Total, n=12825; paroxysmal AF, n=1138), showing a high predictive capability (AUC = 0.780, p Conclusions We determined ECG parameters that potentially contribute to picking up existing AF or predicting future development of AF, where the measurement of P wave strongly contributed in the former whereas all time phases were similarly important in the latter. Weighting of parameters to predict AF Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Self funding of the institute

Background A delayed heart rate recovery (HRR) after exercise is related to mortality in sinus rhythm. This study aimed to investigate this concept can be applied to patients with atrial fibrillation (AF). Methods We analyzed 483 patients with AF (mean 65 years, male 74%). HRR integral was calculated by integrating the difference in HR in every 3 second between the end of exercise and the specified time after the exercise (30, 60, 120 and 180 seconds). After evaluating the prognostic power of each HRR integral, we selected HRR integral of 180 seconds (180HRR-integral). Results We divided the patients into two groups using median value of 180HRR-integral. All-cause mortality, the incidence of cardiovascular events and heart failure events were higher in the poor 180HRR-integral. After adjustment for covariates, the impact of the high 180HRR-integral for all-cause mortality was 3.15 (p=0.057), 1.77 for cardiovascular events (p=0.067) and 1.28 for heart failure events (p=0.519). Conclusion Poor HRR was associated with worse prognosis in patients with AF. Funding Acknowledgement Type of funding source: None

Background: The 12-lead electrocardiogram (ECG) is affected by not only the cardiovascular but also the non-cardiovascular status. Whether ECG can be the determinant of biological age (BA) and the gap between chronological age (CA) and ECG-predicted BA reflect differences in prognosis are unclear. Methods: In the Shinken Database 2010 – 2017 (n = 19170), 12-lead ECG was analyzed in 13005 patients excluding those with structural heart disease or having pacing beats, atrial or ventricular tachyarrhythmia, and indeterminate axis (R axis > 180˚) on index ECG. The prediction model of BA was developed by principal component analysis with 438 ECG parameters. The gap between ECG-predicted BA and CA was calculated (AgeDiff = ECG-predicted BA − CA). Results: The ECG-predicted BA was significantly correlated with CA (r = 0.967). Patients with a positively wide AgeDiff had a higher incidence of all-cause mortality compared to those with a narrow AgeDiff or those with negative AgeDiff. The risk of AgeDiff > 0 for all-cause mortality compared with AgeDiff ≤ 0 was 1.78 (95%CI: 1.00 − 3.16), which increased according to the aging and became the highest in patients with CA of 71 − 80 years. Conclusion: Our data suggested that 12-lead ECG can be a tool to estimate BA. The gap between ECG-predicted BA and CA allowed estimation of increased risk of all-cause mortality in patients without structural heart disease.

Highlights • High performance of AI algorithm to detect AF using SR-ECG was confirmed in patients without structural heart disease. • The performance of AI-enabled ECG to detect AF was high especially when the algorithm included SR-ECG taken after the index AF-ECG. • A similar tendency was observed when the performance was tested in patients with structural heart diseases., Background This study aimed to increase the knowledge on how to enhance the performance of artificial intelligence (AI)-enabled electrocardiography (ECG) to detect atrial fibrillation (AF) on sinus rhythm ECG (SR-ECG). Methods It is a retrospective analysis of a single-center, prospective cohort study (Shinken Database). We developed AI-enabled ECG using SR-ECG to predict AF with a convolutional neural network (CNN). Among new patients in our hospital (n = 19,170), 276 AF label (having ECG on AF [AF-ECG] in the ECG database) and 1896 SR label with following three conditions were identified in the derivation dataset: (1) without structural heart disease, (2) in AF label, SR-ECG was taken within 31 days from AF-ECG, and (3) in SR label, follow-up ≥ 1,095 days. Three patterns of AF label were analyzed by timing of SR-ECG to AF-ECG (before/after/before-or-after, CNN algorithm 1 to 3). The outcome measurement was area under the curve (AUC), sensitivity, specificity, accuracy, and F1 score. As an extra-testing dataset, the performance of AI-enabled ECG was tested in patients with structural heart disease. Results The AUC of AI-enabled ECG with CNN algorithm 1, 2, and 3 in the derivation dataset was 0.83, 0.88, and 0.86, respectively; when tested in patients with structural heart disease, 0.75, 0.81, and 0.78, respectively. Conclusion We confirmed high performance of AI-enabled ECG to detect AF on SR-ECG in patients without structural heart disease. The performance enhanced especially when SR-ECG after index AF-ECG was included in the algorithm, which was consistent in patients with structural heart disease.

Aims This study aimed to investigate the correlation of heart rate profile during exercise with exercise capacity and heart failure occurrence in patients with atrial fibrillation compared with patients with sinus rhythm. Methods We analyzed 2231 patients (atrial fibrillation: n = 321, sinus rhythm: n = 1910) who underwent a symptom-limited maximal cardiopulmonary exercise test at our institute. Their heart rate profile during exercise was assessed using peak heart rate and chronotropic response; (peak heart rate−resting heart rate)/(220−age−resting heart rate). The endpoint was the occurrence of heart failure events, defined as hospitalization for heart failure or heart failure-related death. Results There were significant positive correlations of peak heart rate and chronotropic response to peak oxygen consumption, both in atrial fibrillation and sinus rhythm. During a median follow-up period of 1262 (interquartile range 974–2921) days, 117 (5.2%) heart failure events were observed. Multivariate analyses showed that peak heart rate and chronotropic response were statistically significant predictors of heart failure events both in atrial fibrillation (peak heart rate: heart rate 0.975, p = 0.002, chronotropic response: heart rate 0.196, p = 0.003) and in sinus rhythm (peak heart rate: heart rate 0.988, p = 0.036, chronotropic response: heart rate 0.347, p = 0.020). Bivariate models showed that compared with chronotropic response, peak heart rate was a stronger predictor of heart failure in atrial fibrillation, whereas the finding was reversed in sinus rhythm. Conclusion The exercise- heart rate profile was significantly related to exercise capacity and future heart failure events, regardless of rhythm. However, the impacts of peak heart rate and chronotropic response on the endpoint varied according to the cardiac rhythm.

Despite the increasing incidence of acute coronary syndrome (ACS) in Japan, its prognosis has improved. However, there is a paucity of longitudinal registry data providing trends of in-hospital care and prognosis of ACS in Japan. ACS patients undergoing percutaneous coronary intervention (PCI) included in the Shinken Database 2004-2014 were divided into two groups according to admission year (2004-2009, n = 390; 2010-2014, n = 328). Patient characteristics, lesion/procedure characteristics, medications at discharge, all-cause mortality, cardiovascular death, acute myocardial infarction (AMI), target lesion revascularization (TLR), re-PCI to new lesion, and coronary artery bypass graft (CABG) within 2 years after discharge were compared between the groups. Prevalence of hypertension, dyslipidemia, and dual antiplatelet/statin prescription increased significantly between periods. Usage of second-generation drug-eluting stents (DES) increased markedly between the two periods (2.6, 66.8%), while those of bare metal stents (64.4, 26.5%) and first-generation DES (25.6, 1.5%) decreased (all, p

Background The predictive role of E / e ′ on ischemic stroke (IS) and atrial fibrillation (AF) in Japanese patients without AF are unclear. Methods and results Shinken database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. E / e ′ has been routinely measured since 2007. Patients without AF for whom E / e ′ was measured at the initial visit between 2007 and 2014 ( n = 11 477, mean age 57.2 years old, men 59.5%) were divided into E / e ′ tertiles ( 11.00). During the mean follow-up period of 1.8 years, 58 IS and 140 new appearances of AF were observed. High E / e ′ tertile was associated with more prevalence of atherothrombotic risks. The cumulative incidence of IS events and new appearance of AF at 6 years in low, middle, and high E / e ′ tertiles were 0.5%, 1.4%, and 3.0%/year (log-rank test, p p = 0.007), respectively. In multivariate analysis, high E / e ′ tertile was independently associated with IS (HR, 2.857, 95%CI 1.257–6.495, p = 0.012). Although high E / e ′ tertile was independently associated with new appearance of AF when adjusted for coexistence of atherothrombotic risk factors (HR, 1.694, 95%CI, 1.097–2.616, p = 0.017), the association was attenuated after adjustment for left atrial dimension. Conclusions E / e ′ was significantly associated with incidence of IS and new appearance of AF in non-AF patients.

Treatment and prognosis of elderly patients with atrial fibrillation (AF) may differ by the experience of fall or bone fracture. However, their current status is still unclear. From our institute database between 2010 and 2015, 674 AF patients with age ≥ 70 years were selected and were divided into those who experienced fall or fracture during the observation period (F/F group; n = 49) and those who did not (non-F/F group; n = 625). We compared the treatment and prognosis between the 2 groups. Patients in the F/F group were older (79 vs 76 years, P

Direct oral anticoagulants, including edoxaban, primarily do not need routine monitoring of the anticoagulant effect. However, extremely high/low plasma concentrations of edoxaban (PC-Ed) should be properly evaluated, especially when patients under anticoagulation therapy are at an emergency state. For this purpose, PC-Ed determined by an anti-Xa assay (indirect PC-Ed) is more convenient and, therefore, more useful compared with PC-Ed determined by an LC–MS/MS (direct PC-Ed) in daily clinical practice. Consecutive 97 patients with non-valvular atrial fibrillation (NVAF) under edoxaban therapy were evaluated, in whom edoxaban 60/30 mg doses were prescribed for 48/49 patients, 71 (73.2%) were men, and the average age was 69 years. CHADS2 score 0, 1, and ≥ 2 were 26.8%, 44.3%, and 28.9%, while CHA2DS2-VASc score 0, 1, and ≥ 2 were 14.4%, 16.5%, and 69.1%, respectively. Median values of direct and indirect PC-Ed by LC–MS/MS and anti-Xa assay were 187.1 and 176.1 ng/mL at peak (2–4 h post-dose) and 14.4 and 17.5 ng/mL at trough (pre-dose), respectively. The PC-Ed at peak and trough by two methods were significantly correlated, and the correlation coefficients were r = 0.973 and 0.963 (both, p

In Japanese surveillance in an early phase after the approval of rivaroxaban, inappropriate underdose was frequently utilized. The aim of this study was to describe the prevalence and predictors of the inappropriate usage of rivaroxaban in a single-center, cardiovascular-specialized hospital. Consecutive 661 non-valvular atrial fibrillation (NVAF) patients treated with rivaroxaban between 2012 and 2017 were recruited. After excluding 30 patients without assessment of creatinine clearance (CCr), the proportion and predictors of inappropriate underdose were analyzed. Additionally, patient outcomes, including thromboembolism (ischemic stroke or systemic embolism) and major bleeding, were determined. In patients with CCr ≥ 50 mL/min (n = 532) and

Novel biomarkers are desired to improve risk management for patients with atrial fibrillation (AF). We measured 179 plasma miRNAs in 83 AF patients using multiplex qRT-PCR. Plasma levels of eight (i.e., hsa-miR-22-3p, hsa-miR-128-3p, hsa-miR-130a-3p, hsa-miR-140-5p, hsa-miR-143-3p, hsa-miR-148b-3p, hsa-miR-497-5p, hsa-miR-652-3p) and three (i.e., hsa-miR-144-5p, hsa-miR-192-5p, hsa-miR-194-5p) miRNAs showed positive and negative correlations with CHA2DS2-VASc scores, respectively, which also showed negative and positive correlations with catheter ablation (CA) procedure, respectively, within the follow-up observation period up to 6-month after enrollment. These 11 miRNAs were functionally associated with TGF-&beta, signaling and androgen signaling based on pathway enrichment analysis. Seven of possible target genes of these miRNAs, namely TGFBR1, PDGFRA, ZEB1, IGFR1, BCL2, MAPK1 and DICER1 were found to be modulated by more than four miRNAs of the eleven. Of them, TGFBR1, PDGFRA, ZEB1 and BCL2 are reported to exert pro-fibrotic functions, suggesting that dysregulations of these eleven miRNAs may reflect pro-fibrotic condition in the high-risk patients. Although highly speculative, these miRNAs may potentially serve as potential biomarkers, providing mechanistic and quantitative information for pathophysiology in daily clinical practice with AF such as possible pro-fibrotic state in left atrium, which would enhance the risk of stroke and reduce the preference for performing CA.

Background Ventilatory efficiency decreases with age. This study aimed to investigate the prognostic significance and cut-off value of the minute ventilation/carbon dioxide production (VE/VCO2) slope according to age in patients with heart failure. Methods and results We analysed 1501 patients with heart failure from our observational cohort who performed maximal symptom-limited cardiopulmonary exercise testing and separated them into three age groups (≤55 years, 56–70 years and ≥71 years) in total and according to the three ejection fraction categories defined by European Society of Cardiology guidelines. The endpoint was set as heart failure events, hospitalisation for heart failure or death from heart failure. The VE/VCO2 slope increased with age. During the median follow-up period of 4 years, 141 heart failure (9%) events occurred. In total, univariate Cox analyses showed that the VE/VCO2 slope (cont.) was significantly related to heart failure events, while on multivariate analysis, the prognostic significance of the VE/VCO2 slope (cont.) was poor, accompanied by a significant interaction with age ( P 2 slope increased with the increase in age in not only the total but also the sub-ejection fraction categories. Multivariate analyses with a stepwise method adjusted for estimated glomerular filtration rate, peak oxygen consumption, atrial fibrillation and brain natriuretic peptide, showed that the predictive value of the binary VE/VCO2 slope separated by the cut-off value varied according to age. There was a tendency for the prognostic significance to increase with age irrespective of ejection fraction. Conclusion The prognostic significance and cut-off value of the VE/VCO2 slope may increase with advancing age.

Background Seasonal variations in cardiovascular disease is well recognized. However, little is known about the presentations and outcomes of Japanese heart failure (HF) patients in the winter season. Methods and results We used a single hospital-based cohort from the Shinken Database 2004–2012, comprising all new patients (n = 19,994) who visited the Cardiovascular Institute Hospital. A total of 375 patients who were admitted owing to acute decompensated HF were included in the analysis. Of these patients, 136 (36%) were admitted in winter. Winter was defined as the period between December and February. The HF patients admitted in winter were older, and had a higher prevalence of hypertension and diabetes mellitus than the patients admitted in other seasons. Patients with conditions categorized as clinical scenario 1 tended to be admitted more commonly in winter. HF with preserved left ventricular ejection fraction (LVEF) was more common in HF patients admitted in winter than in those admitted in other seasons. Beta-blocker use at hospital discharge was more common in the patients admitted in other seasons. Kaplan–Meier curves and log-rank test results indicated that the incidences of all-cause death, cardiovascular death, and HF admission were comparable between the patients admitted in winter and those admitted in other seasons. Conclusions HF admission was frequently observed in the winter season and HF patients admitted in the winter season were older, and had higher prevalence of hypertension and diabetes mellitus, and preserved LVEF suggesting that we might need to pay more attention for elderly patients with hypertension, diabetes mellitus, and HF with preserved LVEF to decrease HF admissions in the winter season.

BACKGROUND Variability in the international normalized ratio (INR) of prothrombin time has been suggested to be related to outcome in patients with atrial fibrillation (AF) under warfarin therapy, but its determinants remain unclear.Methods and Results:The study population consisted of 626 AF patients under warfarin therapy in the Shinken Database (n=22,230). INR variability was calculated by Fihn's method. Determinants of high log INR variability (defined as over mean+standard deviation) were determined by logistic regression analyses. Symptomatic heart failure (odds ratio [OR] 3.974, 95% confidence interval [CI] 2.510-6.292), older age (≥75 years old; OR 2.984, 95% CI 1.844-4.826) and severe renal dysfunction (eGFR

Aims Non-linear models by machine learning may identify different risk factors with different weighting in comparison to conventional linear models. Methods and results The analyses were performed in 15,933 patients included in the Shinken Database (SD) 2004–2014 (n = 22,022) for whom baseline data of blood sampling and ultrasound cardiogram and follow-up data at 2 years were available. Using non-linear models with machine learning software, 118 risk factors and their weighting of risk for all-cause mortality, heart failure (HF), acute coronary syndrome (ACS), ischemic stroke (IS), and intracranial hemorrhage (ICH) were identified, where the top two risk factors were albumin/hemoglobin, left ventricular ejection fraction/history of HF, history of ACS/anti-platelet use, history of IS/deceleration time, and history of ICH/warfarin use. The areas under the curve of the developed models for each event were 0.900, 0.912, 0.879, 0.758, and 0.753, respectively. Conclusion Here, we described our experience with the development of models for predicting cardiovascular prognosis by machine learning. Machine learning could identify risk predicting models with good predictive capability and good discrimination of the risk impact.

Repeated hospitalization due to acute decompensated heart failure (HF) is a pandemic health problem in Japan. However, it is difficult to predict rehospitalization after discharge for acute decompensated HF. We used a single hospital-based cohort from the Shinken Database 2004-2012, comprising all new patients (n = 19,994) who visited the Cardiovascular Institute Hospital. A total of 282 patients discharged after their first acute HF admission were included in the analysis. The median follow-up period was 908 ± 865 days. Of these patients, rehospitalization due to worsening HF occurred in 55 patients. The cumulative rate of rehospitalization was 17.5% at 1 year, 21.4% at 2 years, and 25.5% at 3 years. Patients with rehospitalization were older than those without rehospitalization. Prevalence of diabetes mellitus (DM) was more common in patients with rehospitalization. Average heart rate (HR) tended to be higher in patients with rehospitalization. Loop diuretics were more commonly used at hospital discharge in patients with rehospitalization. Multivariate Cox regression analysis revealed that age ≥ 75 years, DM, HR ≥ 75 bpm at discharge, and use of loop diuretics at discharge were independent predictors for rehospitalization. The number of these independent risk factors could be used to clearly discriminate between the HF rehospitalization low-, middle- and high-risk patients. HF rehospitalization commonly occurred in patients who were discharged after their first acute HF admission. Older age, DM, increased HR, and loop diuretics use at discharge were independently associated with HF rehospitalization. By simply counting these risk factors, we might be able to predict the risk of HF rehospitalization after discharge.