Evaluating convolutional neural network-enhanced electrocardiography for hypertrophic cardiomyopathy detection in a specialized cardiovascular setting.

The efficacy of convolutional neural network (CNN)-enhanced electrocardiography (ECG) in detecting hypertrophic cardiomyopathy (HCM) and dilated HCM (dHCM) remains uncertain in real-world applications. This retrospective study analyzed data from 19,170 patients (including 140 HCM or dHCM) in the Shinken Database (2010-2017). We evaluated the sensitivity, positive predictive rate (PPR), and F1 score of CNN-enhanced ECG in a ''basic diagnosis'' model (total disease label) and a ''comprehensive diagnosis'' model (including disease subtypes). Using all-lead ECG in the "basic diagnosis" model, we observed a sensitivity of 76%, PPR of 2.9%, and F1 score of 0.056. These metrics improved in cases with a diagnostic probability of ≥ 0.9 and left ventricular hypertrophy (LVH) on ECG: 100% sensitivity, 8.6% PPR, and 0.158 F1 score. The ''comprehensive diagnosis'' model further enhanced these figures to 100%, 13.0%, and 0.230, respectively. Performance was broadly consistent across CNN models using different lead configurations, particularly when including leads viewing the lateral walls. While the precision of CNN models in detecting HCM or dHCM in real-world settings is initially low, it improves by targeting specific patient groups and integrating disease subtype models. The use of ECGs with fewer leads, especially those involving the lateral walls, appears comparably effective.

Descriptions of Etiology, Clinical Course, and Prognosis of Patients Presenting with Pericardial Effusion.

Pericardial effusion (PE) presentation varies from an incidental finding to a life-threatening situation; thus, its etiology and clinical course remain unknown. The aim of the present study was to retrospectively investigate these factors.We analyzed 171 patients (0.4%) who presented with PE among 34,873 patients who underwent echocardiography between 2011 and 2021 at our hospital. Clinical and prognostic information was retrieved from electronic medical records. The primary endpoints were all-cause death, hospitalization due to heart failure (HF), and other cardiovascular events such as cardiovascular death, acute coronary syndrome, elective percutaneous coronary intervention, and stroke.The etiologies of PE were as follows: idiopathic (32%), HF-related (18%), iatrogenic (11%), cardiac surgery-related (10%), radiation therapy-related (9%), malignancy (8%), pericarditis/myocarditis (8%), myocardial infarction-related (2%), and acute aortic dissection (2%). Patients with idiopathic/HF etiology were more likely to be older than the others.During a mean follow-up period of 2.5 years, all-cause death occurred in 21 patients (12.3%), cardiovascular events in 10 patients (5.8%), and hospitalization for HF in 24 patients (14.0%). All-cause death was frequently observed in patients with malignancy (44% per person-year). Cardiovascular events were mostly observed in patients with radiation therapy-related and malignancy (8.6% and 7.3% per person-year, respectively).The annual incidence of hospitalization for HF was the highest in patients with HF-related (25.1% per person-year), followed by radiation therapy-related (10.4% per person-year).This retrospective study is the first, to the best of our knowledge, to reveal the contemporary prevalence of PE, its cause, and outcome in patients who visited a cardiovascular hospital in an urban area of Japan.

Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Association between serum alkaline phosphatase and cardiovascular events in patients with atrial fibrillation.

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.

Different Determinants of the Recurrence of Atrial Fibrillation and Adverse Clinical Events in the Mid-Term Period After Atrial Fibrillation Ablation.

BACKGROUND: It is unclear whether there are differences in the clinical factors between atrial fibrillation (AF) recurrence and adverse clinical events (AEs), including stroke/transient ischemic attack (TIA), major bleeding, and death, after AF ablation.Methods and Results:We examined the data from a retrospective multicenter Japanese registry conducted at 24 cardiovascular centers between 2011 and 2017. Of the 3,451 patients (74.1% men; 63.3±10.3 years) who underwent AF ablation, 1,046 (30.3%) had AF recurrence and 224 (6.5%) suffered AEs (51 strokes/TIAs, 71 major bleeding events, and 36 deaths) over a median follow-up of 20.7 months. After multivariate adjustment, female sex, persistent and long-lasting persistent AF (vs. paroxysmal AF), and stepwise increased left atrial diameter (LAd) quartiles were significantly associated with post-ablation recurrences. A multivariate analysis revealed that an age ≥75 years (vs. <65 years), body weight <50 kg, diabetes, vascular disease, left ventricular (LV) ejection fraction <40% (vs. ≥50%), Lad ≥44 mm (vs. <36 mm), and creatinine clearance <50 mL/min were independently associated with AE incidences, but not with recurrences. CONCLUSIONS: This study disclosed different determinants of post-ablation recurrence and AEs. Female sex, persistent AF, and enlarged LAd were determinants of post-ablation recurrence, whereas an old age, comorbidities, and LV and renal dysfunction rather than post-ablation recurrence were AEs determinants. These findings will help determine ablation indications and post-ablation management.

Glasgow prognostic score can be a prognostic indicator after percutaneous coronary intervention: a two-center study in Japan.

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 < 0.001), hemodialysis (6.4% [46/722] vs. 14.4% [17/118] vs. 31.8% [7/22], p < 0.001), and heart failure cases (HF; 9.1% [66/722] vs. 14.4% [17/118] vs. 27.3% [6/22], p = 0.007), with higher creatinine (1.17 ± 1.37 mg/dl vs. 1.89 ± 2.60 mg/dl vs. 3.49 ± 4.01 mg/dl, p < 0.001) and brain natriuretic peptide levels (104.1 ± 304.6 pg/ml vs. 242.4 ± 565.9 pg/ml vs. 668.1 ± 872.2 pg/ml, p < 0.001) and lower low-density lipoprotein cholesterol (101.5 ± 32.9 mg/dl vs. 98.2 ± 28.8 mg/dl vs. 77.1 ± 24.3 mg/dl, p = 0.002) than od-GPS 0 and 1.Od-GPS 2 (HR 2.42; 95% CI 1.16-5.02; p = 0.018), od-GPS 1 (HR 2.09; 95% CI 1.40-3.13; p < 0.001), diabetes (HR 1.41; 95% CI 1.00-1.99; p = 0.048), CKD (HR 2.10; 95% CI 1.49-2.96; p < 0.001), and HF (HR 1.64; 95% CI 1.05-2.56; p = 0.029) were independent predictors of MACEs. A scoring system using CRP and Alb levels with a milder definition than GPS suitably predicted the risk of MACEs in the patients who underwent PCI.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Relationship between resting 12-lead electrocardiogram and all-cause death in patients without structural heart disease: Shinken Database analysis.

BACKGROUND: Resting 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. METHODS: A 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. RESULTS: During 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. CONCLUSIONS: Parameters 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.

Left atrial dimension and ischemic stroke in patients with and without atrial fibrillation.

The incidence of ischemic stroke (IS) increases in patients with enlarged left atrium (LA) irrespective of whether or not the existence of atrial fibrillation (AF). In such situation, it is unclear whether the impact of LA on incidence of IS still significant in young, non-AF patients with enlarged LA who are primarily unconcerned on anticoagulation therapy. The study population consisted of 18,511 consecutive patients not receiving oral anticoagulants and undergoing echocardiography with measurement of LAD at baseline. The incidence rate of ischemic stroke was calculated in 3 groups according to left atrial dimension (LAD; < 30, 30-45 and ≥ 45 mm) in AF and non-AF patients. Further subgroup analysis was performed in stratification by elderly and young (aged ≥ 65 and < 65 years, respectively). The incidences of IS (per 100 patient-years) were 0.11 and 0.71 in non-AF and AF patients with LAD < 30 mm, respectively, which increased to 0.58 and 1.35 in LAD ≥ 45 mm (adjusted hazard ratios [HRs]; 1.95 [95% confidence intervals, CIs: 0.76-5.01] and 1.22 [95% CIs: 0.27-5.58], interaction P was 0.246). In non-AF patients, the incidences of IS were 0.30 and 0.04 in elderly and young patients with LAD < 30 mm, which increased to 0.67 and 0.48 in LAD ≥ 45 mm (adjusted HRs; 1.34 [95% CIs: 0.43-4.15] and 4.21 [95% CIs: 0.77-23.12], interaction P was 0.158). The incidence of IS significantly increased with increase of LAD in non-AF, especially in non-AF and young patients, although the difference was not independent of other clinical factors. The impact of LAD on IS was numerically larger in non-AF than in AF, and larger in young and non-AF than in elderly counterpart, although a significant interaction was not observed in this small population. Further studies with large population are necessary to judge whether these population with enlarged LA need antithrombotic therapy.

Clinical outcomes of ablation versus non-ablation therapy for atrial fibrillation in Japan: analysis of pooled data from the AF Frontier Ablation Registry and SAKURA AF Registry.

Whether ablation for atrial fibrillation (AF) is, in terms of clinical outcomes, beneficial for Japanese patients has not been clarified. Drawing data from 2 Japanese AF registries (AF Frontier Ablation Registry and SAKURA AF Registry), we compared the incidence of clinically relevant events (CREs), including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular events, and death, between patients who underwent ablation (n = 3451) and those who did not (n = 2930). We also compared propensity-score matched patients (n = 1414 in each group). In propensity-scored patients who underwent ablation and those who did not, mean follow-up times were 27.2 and 35.8 months, respectively. Annualized rates for stroke/TIA (1.04 vs. 1.06%), major bleeding (1.44 vs. 1.20%), cardiovascular events (2.15 vs. 2.49%) were similar (P = 0.96, 0.39, and 0.35, respectively), but annualized death rates were lower in the ablation group than in the non-ablation group (0.75 vs.1.28%, P = 0.028). After multivariate adjustment, the risk of CREs was statistically equivalent between the ablation and non-ablation groups (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.71-1.11), but it was significantly low among patients who underwent ablation for paroxysmal AF (HR 0.68 [vs. persistent AF], 95% CI 0.49-0.94) and had a CHA2DS2-VASc score < 3 (HR 0.66 [vs. CHA2DS2-VASc score ≥ 3], 95% CI 0.43-0.98]). The 2-year risk reduction achieved by ablation may be small among Japanese patients, but AF ablation may benefit those with paroxysmal AF and a CHA2DS2-VASc score < 3.

Prediction of biological age and all-cause mortality by 12-lead electrocardiogram in patients without structural heart disease.

BACKGROUND: There is a well-established relationship between 12-lead electrocardiogram (ECG) and age and mortality. Furthermore, there is increasing evidence that ECG can be used to predict biological age. However, the utility of biological age from ECG for predicting mortality remains unclear. METHODS: This was a single-center cohort study from a cardiology specialized hospital. A total of 19,170 patients registered in this study from February 2010 to March 2018. ECG was analyzed in a final 12,837 patients after excluding those with structural heart disease or with pacing beats, atrial or ventricular tachyarrhythmia, or an indeterminate axis (R axis > 180°) on index ECG. The models for biological age were developed by principal component analysis (BA) and the Klemera and Doubal's method (not adjusted for age [BAE] and adjusted for age [BAEC]) using 438 ECG parameters. The predictive capability for all-cause death and cardiovascular death by chronological age (CA) and biological age using the three algorithms were evaluated by receiver operating characteristic analysis. RESULTS: During the mean follow-up period of 320.4 days, there were 55 all-cause deaths and 23 cardiovascular deaths. The predictive capabilities for all-cause death by BA, BAE, and BAEC using area under the curves were 0.731, 0.657, and 0.685, respectively, which were comparable to 0.725 for CA (p = 0.760, 0.141, and 0.308, respectively). The predictive capabilities for cardiovascular death by BA, BAE, and BAEC were 0.682, 0.685, and 0.692, respectively, which were also comparable to 0.674 for CA (p = 0.775, 0.839, and 0.706, respectively). In patients aged 60-74 years old, the area under the curves for all-cause death by BA, BAE, and BAEC were 0.619, 0.702, and 0.697, respectively, which tended to be or were significantly higher than 0.482 for CA (p = 0.064, 0.006, and 0.005, respectively). CONCLUSION: Biological age by 12-lead ECG showed a similar predictive capability for mortality compared to CA among total patients, but partially showed a significant increase in predictive capability among patients aged 60-74 years old.

Current Status of Catheter Ablation for Atrial Fibrillation in Japan.

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.

Seasonal Variations in the Incidence of Ischemic Stroke, Extracranial and Intracranial Hemorrhage in Atrial Fibrillation Patients.

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.

Association between plasma concentration of edoxaban determined by direct and indirect methods in Japanese patients with non-valvular atrial fibrillation (CVI ARO 7).

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 < 0.0001), respectively. By a Bland-Altman plot, mean differences between the direct and indirect PC-Ed [lower to upper percent limit of agreement] were - 4.87 [- 46.71 to 36.98] and 4.66 [- 1.37 to 10.69] ng/mL at peak and trough, respectively. Moreover, mean % error for difference between the direct and indirect PC-Ed [lower to upper percent limit of agreement] was - 1.22 [- 20.59 to 18.14] and 31.75 [- 14.03 to 77.53] % at peak and trough, respectively, where the % error extremely increased around the lower limit of detection (LLOD) in the anti-Xa assay. Strong similarity was observed between the direct and indirect PC-Ed, especially at peak. The indirect PC-Ed was higher than the direct PC-Ed, especially around the LLOD, suggesting the need for caution when we use the anti-Xa assay for measurement of trough PC-Ed (UMIN 000032492).

Role of dipstick proteinuria for predicting cardiovascular events: a Japanese cardiovascular hospital database analysis.

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 < 0.001). Multivariate analysis revealed independent association between proteinuria and all-cause death [hazard ratio (HR): 1.50, 95% confidence interval (CI) 1.07-2.10], HF (HR: 1.55, 95% CI 1.14-2.12), and IS (HR: 2.08, 95% CI 1.26-3.45). Even trace proteinuria was independently associated with HF (HR: 1.64, 95% CI 1.07-2.53) and IS (HR: 2.17, 95% CI 1.14-4.11) and with all-cause death (HR: 1.56, 95% CI 0.99-2.47). In conclusions, dipstick proteinuria was independently associated with cardiovascular events and death, suggesting that the UDT is a useful tool for evaluating patients' risk for such adverse events.

Creatinine clearance and inappropriate dose of rivaroxaban in Japanese patients with non-valvular atrial fibrillation.

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 < 50 mL/min (n = 98), inappropriate underdose and overdose were used in 123 (23%) and 8 (8%), respectively. The predictors of inappropriate underdose (in patients with CCr ≥ 50 mL/min) were CCr [50-63 mL/min (the lowest tertile) compared to ≥ 64 mL/min], age ( ≥ 75 years), female gender, prescription of antiplatelet, and coexistence of heart failure. Although PT under rivaroxaban was lower in patients with inappropriate underdose than in those with an appropriate dose, no significant increase in the incidence of thromboembolism or major bleeding was observed within the mean follow-up of 683 days. Inappropriate underdose of rivaroxaban was frequently observed for NVAF patents even in a cardiovascular hospital, particularly in patients with CCr adjacent to the dose reduction criteria. The responses of PT and the incidence of adverse outcomes under an inappropriate dose of rivaroxaban should be further investigated.

Myocardial bridging is an independent predictor of positive spasm provocation testing by intracoronary ergonovine injections: a retrospective observational study.

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.

Differences in treatment and prognosis by the experience of falls or bone fracture in elderly patients with atrial fibrillation.

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 < 0.001) and had more comorbidities compared with those in the non-F/F group. The prescription rate of oral anticoagulant was similar between the two groups (77.6% vs 68.2%, P = 0.201), where warfarin was predominant. The F/F group was not associated with higher incidence of ischemic stroke. The F/F group was associated with a higher incidence of heart failure events (adjusted odds ratio (OR) 3.88; 95% confidence intervals (Cl) 1.70-8.85; P = 0.001), and cardiovascular events (OR 3.43; 95% Cl 1.71-6.85; P < 0.001). In elderly AF patients in a cardiovascular hospital, the experience of fall or fracture did not affect the prescription of oral anticoagulants and the incidence of ischemic stroke, but it was significantly associated with increase of heart failure.

Exploratory Analysis of Circulating miRNA Signatures in Atrial Fibrillation Patients Determining Potential Biomarkers to Support Decision-Making in Anticoagulation and Catheter Ablation.

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-ß 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.

Association Between Dose and Plasma Concentration of Bisoprolol in Patients with Heart Failure (CVI ARO 6).

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.