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Objectives: Direct oral anticoagulants (DOAC) have been approved for oral anticoagulation in patients with non-valvular atrial fibrillation (AF). On the other hand, DOAC are sometimes prescribed off-label under-doses for patients with AF. This study aimed to compare the effects of different DOAC doses on coagulation and fibrinolytic markers. Methods:A total of 88 patients with AF (age, 68 ± 11 years; male sex, 45%; persistent AF, 43%) were analyzed. All patients received edoxaban (60 or 30 mg) once daily. For this study, patients were divided into three groups according to whether they had been treated before the ablation procedure under an appropriate standard-dose group (n = 30 [34.1%]), appropriate low-dose group (n = 35 [39.8%]), or off-label under-dose group (n = 23 [26.1%]). Coagulation and fibrinolytic markers and echocardiographic parameters were examined before ablation. Results:There were no significant baseline differences in AF type, plasma B-type natriuretic peptide, protein C, fibrinogen, D-dimer level, left ventricular ejection fraction, or left atrial dimension among the three groups. The prothrombin fragment 1+2 (F1+2) level was significantly different among the appropriate standard-dose, appropriate low-dose, and off-label under-dose groups (105.9 ± 29.4, 142.6 ± 41.3, and 142.8 ± 84.9 pmol/L, respectively; P = 0.011). After multivariate analysis, the F1+2 was significantly higher in the off-label low-dose group than in the standard-dose group when compared among the three groups (P = 0.034, Bonferroni test). Conclusion:Our results suggest that an appropriate standard dose of edoxaban is required to suppress hypercoagulability in patients with AF.

Background Atrial fibrillation (AF) may cause cerebral and systemic embolism. An increased D-dimer level indicates hyperactivation of secondary fibrinolysis, resulting in predilection for thrombosis. To clarify the differential effects of anticoagulation therapy, we compared the D-dimer levels in peripheral and left atrial (LA) blood of atrial fibrillation patients scheduled for ablation. Methods We analyzed 141 patients with non-valvular AF (dabigatran, n = 30; apixaban, n = 47; edoxaban, n = 64; mean age: 68 years, male: 60%). Peripheral venous blood and LA blood was collected before pulmonary vein isolation. We examined the laboratory and echocardiographic parameters. Results After adjusting for baseline characteristics, D-dimer level in the LA was significantly higher in patients treated with edoxaban than that in those on apixaban (0.77 ± 0.05 vs. 0.60 ± 0.05 μg/mL, P = 0.047), although there were no significant differences in peripheral D-dimer levels. We classified the D-dimer value of the LA into a normal group (P = 0.008) and left ventricular ejection fraction (LVEF) (OR, 0.947; 95% CI, 0.910–0.986; P = 0.008) were potential predictors of high LA D-dimer levels. Conclusions In apixaban-treated patients, the D-dimer level in the left atrium was lower than in edoxaban-treated patients on the day of ablation, suggesting that the anticoagulant effect of apixaban on the left atrium is better than that of edoxaban in patients with AF.

An 80-year-old woman presented with general fatigue and leg edema for several months. Ultrasonography and contrast-enhanced computed tomographic angiography revealed inferior vena cava thrombosis, ilio-iliac arteriovenous fistula (AVF), and iliac artery pseudoaneurysm. Furthermore, malignant cells were observed in the aspirated thrombus. Although thrombus aspiration and anticoagulant therapy were unsuccessful in reducing the thrombotic mass and alleviating her symptoms, endovascular therapy for AVF and pseudoaneurysm improved her leg edema without recurrence or any endoleak. These findings highlight that endovascular therapy can be effective in older adults with cancer because of its low invasiveness.

Background: In superficial femoral artery (SFA) stenosis, stenosis resistance may increase, but the relationship between stenosis resistance and stenotic severity remains to be seen. This study aimed to investigate the physiological response, through a hyperemic condition, and the pathophysiological significance of Doppler flow and stenosis resistance in SFA. Methods: Twenty-four limbs with focal stenosis of the SFA were analyzed. We assessed the fractional flow reserve (FFR), hyperemic stenosis resistance (h-SR), and vascular flow reserve (VFR) of the SFA with a pressure/Doppler flow sensor-tipped combination guidewire before and after endovascular therapy (EVT). Results: FFR, h-SR, and VFR changed significantly after EVT. h-SR was more strongly correlated with % area stenosis, measured by intravascular ultrasound than FFR (FFR: r=−0.716, h-SR: r=0.741, p0.36 mmHg·sec/cm, and FFR 75% area stenosis with area under curves of 0.883 and 0.828, respectively. Conclusion: h-SR can indicate stenotic severity in an SFA focal lesion more prominently than FFR and may be a new physiological index to determine indication for EVT. VFR was not feasible for assessment in SFA focal stenosis.

Introduction: Atrial fibrillation causes cerebral infarction and systemic embolism. Increased D-dimer level indicates the hyperactivation of secondary fibrinolysis, showing thrombosis tendency in the vessel. Hypothesis: To clarify the effects of anticoagulation therapy, we planned to compare the D-dimer levels of peripheral and left atrial (LA) blood in patients scheduled for atrial fibrillation ablation during administration of dabigatran (D), apixaban (A) and edoxaban (E). Methods and Results: We analyzed 141 patients with non-valvular atrial fibrillation (D, n=30; A, n= 47; E, n=64; median age: 68[38-84] years, male: 60%) after exclusion of patients on dialysis. Peripheral venous blood was collected immediately before ablation and LA blood was collected immediately after the Brockenbrough method. We examined laboratory and echocardiographic parameters such as D-dimer and protein C levels, and LA diameter. Anticoagulation therapy was discontinued on the day of ablation. There were no significant differences in ejection fraction, LA diameter and peripheral C-reactive protein levels among the three groups treated with D, A and E. After adjusting for baseline characteristics, D-dimer level in the left atrium treated with E was significantly higher among the three groups (D, 0.550±0.078 vs. A, 0.603±0.052 vs. E, 0.774±0.046), although there were no significant differences in peripheral D-dimer levels (Table). Protein C levels of peripheral blood in group E were significantly suppressed among the three groups (D, 130.17±4.84 vs. A, 102.13±3.59 vs. E, 91.92±2.11, p Conclusions: In the edoxaban group, the D-dimer level in the left atrium was higher than that in the apixaban group, suggesting that the anticoagulatory effect of left atrium is better in apixaban as compared to edoxaban in patient with non-valvular atrial fibrillation.

Backgrounds Tolvaptan significantly increases urine volume in acute decompensated heart failure (ADHF); serum sodium level increases due to aquaresis in almost all cases. We aimed to elucidate clinical factors associated with hypernatremia in ADHF patients treated with tolvaptan. Methods We enrolled 117 ADHF patients treated with tolvaptan in addition to standard therapy. We examined differences in clinical factors at baseline between patients with and without hypernatremia in the initial three days of hospitalization. Results Systolic (p = 0.045) and diastolic (p = 0.004) blood pressure, serum sodium level (p = 0.002), and negative water balance (p = 0.036) were significantly higher and serum potassium level (p = 0.026) was significantly lower on admission day in patients with hypernatremia (n = 22). In multivariate regression analysis, hypernatremia was associated with low serum potassium level (p = 0.034). Among patients with serum potassium level ≤ 3.8 mEq/L, the cutoff value obtained using receiver operating characteristic curve analysis, those with hypernatremia related to tolvaptan treatment showed significantly higher diastolic blood pressure on admission day (p = 0.004). Conclusion In tolvaptan treatment combined with standard therapy in ADHF patients, serum potassium level ≤ 3.8 mEq/L may be a determinant factor for hypernatremia development. Among hypokalemic patients, those with higher diastolic blood pressure on admission may be carefully managed to prevent hypernatremia.

Background: Myocardial perfusion single-photon emission computed tomography (SPECT) imaging with stress is a useful examination for detecting coronary artery disease. Since the presence of artifacts is remaining challenges, we aimed to define the minimum intensity of low-grade exercise stress levels combined with drug stress to reduce undesired artifacts and their related factors.Methods: We divided patients with suspicious coronary artery disease into 4 groups as follows: group A, adenosine triphosphate (ATP) for 6 min; group A+25 W, ATP+25 W exercise for 6 min; group A+35 W, ATP+35 W exercise for 6 min; group A+45 W, ATP+45 W exercise for 6 min) and enrolled only those whose summed stress scores were H/L) ratio and heart-to-10 pixels below the heart (H/below the H) ratio. Results: The logarithmic values of H/L and H/below the H ratios were significantly higher in groups A+35 W and A+45 W than in group A (pH/L and H/below the H ratios positively correlated with the increment of rate pressure product (RPP, p=0.002 and p=0.005, respectively) after stress in the univariate analysis. The left ventricular end-diastolic volume (LVEDV) after stress (p=0.002) negatively correlated with the logarithmic value of H/below the H ratio, but not H/L ratio. Although the increment of RPP was independently associated with the logarithmic values of both H/L (p=0.001) and H/below the H ratios (p=0.005), LVEDV was also independently associated with the logarithmic value of H/below the H ratio (pConclusion: ATP plus ≥35 W exercise stress for 6 min was useful for reducing undesired artifacts after stress in myocardial perfusion SPECT. LVEDV after stress in addition to the increment of RPP was independently associated with the H/below the H ratio, but not the H/L ratio.

The relationship between alterations in left ventricular (LV) diastolic function and the incidence of recurrence, as well as the associated factors after cryoballoon (CB) and radiofrequency (RF) catheter ablation in patients with paroxysmal atrial fibrillation (Paf), require clarification. We enrolled 138 patients with Paf (RF/CB 69/69) who underwent the first catheter ablation and follow-up for 12 months. Transthoracic echocardiography was performed before and after ablation. An afterload-integrated index of LV diastolic function was calculated as diastolic elastance (Ed)/arterial elastance (Ea), Ed/Ea. No significant increases were observed in Ed/Ea 3 days after RF ablation in patients with (n=12) and without (n=57) recurrence. However, a significant increase was observed in recurrence-free patients with CB ablation (n=59; P

Purpose: To identify lower limb 2-dimensional (2D) perfusion angiographic parameters that are related to skin perfusion pressure (SPP), a predictor of wound healing in patients with chronic limb-threatening ischemia (CLTI) undergoing below-the-knee (BTK) endovascular treatment (EVT). Materials and Methods: Thirty-three consecutive patients (mean age 74.5 years; 18 men) with 47 isolated BTK lesions in 33 limbs (Rutherford category 3–5) underwent EVT. Dorsal and plantar SPPs were measured before EVT and the day after. The indexed blood flow below the ankle was measured using 2D perfusion angiography before and after EVT to determine changes in perfusion parameters [arrival time (AT), time to peak, wash-in rate, mean transit time, and width and area under the time-density curve] at rest vs during hyperemia induced with a 20-mg intra-arterial papaverine infusion. Correlations between the 2D perfusion parameters and SPPs were assessed using the Pearson coefficient. The cutoff points to predict mean SPPs >40 mm Hg were analyzed using a receiver operating characteristic curve; outcomes are reported as the area under the curve (AUC) with 95% confidence interval (CI). Results: After EVT at rest and during hyperemia, only AT was significantly changed, although hyperemia produced significant changes in all the pre-/post-EVT 2D perfusion parameters except the wash-in rate. Dorsal and plantar SPPs after EVT were significantly increased and correlated with hyperemic AT and the AT ratio (hyperemia/at rest values) below the ankle. Hyperemic ATs 40 mm Hg, with AUCs of 0.83 (95% CI 0.67 to 0.99) and 0.78 (95% CI 0.61 to 0.95), respectively. Conclusion: Hyperemic ATs

The index for a target that can lead to improved prognoses and more reliable therapy in each heterogeneous patient with heart failure with preserved ejection fraction (HFpEF) remains to be defined. We examined the heterogeneity in the cardiac performance of patients with HFpEF by clarifying the relationship between the indices of left atrial (LA) volume (LAV) overload and pressure overload with echocardiography. We enrolled patients with HFpEF (N = 105) who underwent transthoracic echocardiography during stable sinus rhythm. Relative LAV overload was evaluated using the LAV index or stroke volume (SV)/LAV ratio. Relative LA pressure overload was estimated using E/e’ or the afterload-integrated index of left ventricular (LV) diastolic function: diastolic elastance (Ed)/arterial elastance (Ea) ratio = (E/e’)/(0.9 × systolic blood pressure). The logarithmic value of the N-terminal pro-brain natriuretic peptide was associated with SV/LAV (r = −0.214, p = 0.033). The pulmonary capillary wedge pressure was positively correlated to Ed/Ea (r = 0.403, p = 0.005). SV/LAV was negatively correlated to Ed/Ea (r = −0.292, p = 0.002), with no observed between-sex differences. The correlations between the LAV index and E/e’ and Ed/Ea and between SV/LAV and E/e’ were less prominent than the abovementioned relationships. SV/LAV and Ed/Ea, showing relative LAV and LA pressure respectively, were significantly but modestly correlated in patients with HFpEF. There may be considerable scatter in the relationships between these indices, which could possibly affect the selection of medications or efforts to improve the prognoses of patients with HFpEF.

Key Clinical Message In Japan and worldwide, the increase in educational interventions about resuscitation training significantly increases favorable neurological survival in out‐of‐hospital cardiopulmonary arrest cases treated with bystander cardiopulmonary resuscitation (BCPR) each year. This case with Bland‐White‐Garland syndrome having high‐quality BCPR by nurses demonstrates the importance of education about BCPR.

BACKGROUND: We previously reported that an index of afterload‐related left ventricular diastolic function, operant diastolic elastance (Ed)/effective arterial elastance (Ea) = E/e’/(0.9 × systolic blood pressure), was significantly higher in elderly hypertensive women. We aimed to determine sex‐related differences in the E/e’‐related indices for left ventricular diastolic function and their related factors during admission in patients with heart failure with preserved ejection fraction (HFpEF). HYPOTHESIS: Elderly HFpEF women exhibit severe left ventricular diastolic dysfunction associated with different left atrioventricular volume ratio. METHODS: We divided 267 patients with HFpEF (men/women, 116/151) into two groups by age (≥75 years, n = 212

BACKGROUND: In patients with atrial fibrillation, ablation decreases left atrial (LA) compliance, which may lead to left ventricular (LV) diastolic dysfunction. We aimed to examine serial changes in LV diastolic function after 2 ablation procedures and their related factors in patients with paroxysmal atrial fibrillation (PAF). HYPOTHESIS: LV diastolic function is different after 2 ablation procedures. METHODS: We enrolled 132 patients with PAF (76 males, mean age 67 years; cryoballoon [CB] ablation/radiofrequency [RF] ablation 60/72) who underwent a single ablation procedure. The transthoracic echocardiographic parameters were obtained before, 3 days after, and 6 months after ablation. RESULTS: The afterload‐related index of LV diastolic function, Ed/Ea = E/e' / (0.9 × systolic blood pressure), increased significantly at 3 days after ablation, especially after CB ablation (P

Aim: Maximal hyperemic response, leading to examination of microvascular resistance in lower-limb lesions is not well understood. This study aimed to investigate the infrainguinal arterial physiological response through a hyperemic condition and the pathophysiological significance of microvascular resistance in peripheral artery disease. Methods: Sixteen limbs with focal stenosis of the superficial femoral artery (SFA) and 16 control limbs were analyzed. We assessed the fractional flow reserve (FFR), vascular flow reserve (VFR), and hyperemic microvascular resistance (h-MR) of the SFA with a pressure/Doppler flow sensor-tipped combination guidewire before and after endovascular therapy (EVT). Skin perfusion pressure (SPP) on both the dorsal and the plantar sides of the foot was measured at baseline before and after the endovascular procedures. Results: FFR (p < 0.05) and VFR (p < 0.05), but not h-MR, improved after EVT. There was no association between h-MR and FFR or VFR before EVT. h-MR was negatively correlated with the dorsal SPP before EVT (r = −0.589, p < 0.05). h-MR in patients with high h-MR before EVT significantly decreased after EVT (p < 0.05). Patients with high, but not those with low, h-MR before EVT exhibited a significant increase in dorsal and plantar SPP after EVT (p < 0.05, each). Conclusion: EVT for SFA stenosis improved FFR and VFR comprehensively, with no apparent change in h-MR. However, high h-MR before EVT may play a predictive role for limb perfusion improvement associated with h-MR reduction after EVT.

Background The mechanisms of heart failure with preserved ejection fraction (HFpEF) need to be clarified immediately.Methods and Results:We examined diastolic function relative to arterial elasticity among hypertensive patients with preserved EF. Diastolic elastance (EdI)/effective arterial elastance (EaI), EdI/EaI=E/e'/(0.9×systolic blood pressure [SBP]) was significantly more impaired in women than in men among patients ≥75 years. The higher EdI/EaI value in elderly women implies they are intermittently exposed to higher left ventricular filling pressure relative to SBP during daily life. Conclusions Highly fluctuating impairment of diastolic function relative to arterial elasticity may predispose elderly women to pulmonary edema.

We aimed to elucidate the relationship between echocardiographic data after ablation and atrial fibrillation (AF) recurrence, and to examine the difference in this relationship between paroxysmal and persistent AF. We enrolled 105 patients (72 men, paroxysmal/persistent 56/49, mean age 67 years) who underwent a single radiofrequency catheter ablation procedure. The transthoracic echocardiographic parameters were measured before ablation and at 3 days/6 months after ablation. Recurrence was observed in 30 patients (29%) at 12 months (paroxysmal 18%, persistent 41%). Stroke volume index (SVI) increased significantly in recurrence-free patients only with persistent AF shortly after ablation. Patients with persistent AF showing an increase in tricuspid regurgitation pressure gradient (ΔTRPG>0) exhibited an increase in SVI after ablation and a lower incidence of recurrence at 12 months than those with ΔTRPG

Aims The prevalence of left ventricular diastolic dysfunction increases with age, particularly in hypertensive women. We aimed to determine the age- and sex-related differences in diastolic function, and its relation to alterations of cardiac dimensions in a hypertensive population. Methods and results We enrolled 479 hypertensive patients with a left ventricular ejection fraction (LVEF) ≥50% (men/women, 267/212) and their echocardiographic parameters regarding LV performance and vascular function were measured. Left atrial volume index (LAVI) and operant diastolic elastance (EdI: E/e′/stroke volume index), but not LV mass index (LVMI), correlated weakly with age in both sexes. The arterial elastance index (EaI) and EdI did not differ significantly between sexes in any of the three age groups (A

A 70 year-old woman underwent a dual-chamber pacemaker implantation for episodes of transient block and syncope. The transitional zone of her ECG was observed between V4 and V5, indicating clockwise rotation. An experienced physician performed the Right Ventricular Outflow Tract (RVOT) pacing using an active fixation lead without any immediate complications. For RVOT pacing, the lead was placed approximately two-thirds of the distance from the apex to the pulmonary valve in the postero-anterior view and pointing towards the septum in the left anterior oblique view. The ECG revealed a narrow QRS (120 msec) and the lead I morphology was minus-plus. Six days post-implant, a pacemaker interrogation revealed ventricular undersensing and loss of capture with high output pacing. Chest computed tomography revealed the left ventricle was displaced to the left and the left-sided angle between the interventricular septum and horizontal axis of the body was reduced to 16°. It confirmed an RV lead perforation through the RVOT, with 1 cm of the lead positioned outside the heart. We performed a surgical repair. Though ECG and x-rays showed septal pacing, we experienced an unusual case of a subacute myocardial perforation caused by an active fixation lead possibly due to heart rotation. The present case report described a patient with a subacute lead perforation and no hemodynamic instability. It is important for the general cardiologist to pay attention to heart rotation. After implantation, symptoms that can suggest a lead perforation, as major signs such as pericardial effusion are not necessarily present. A pacemaker interrogation shows lower impedance, as well as undersensing or failure to capture the involved chamber in suspicious findings.

The presence of spontaneous echo contrast (SEC) in the left atrium has been reported to be an independent predictor of thromboembolic risk in patients with atrial fibrillation (AF). Dabigatran was associated with lower rates of stroke and systemic embolism as compared with warfarin when administered at a higher dose. Between July 2011 and October 2015, nonvalvular AF patients treated with warfarin or dabigatran who had transesophageal echocardiography prior to ablation therapy for AF were enrolled. The intensity of SEC was classified into four grades, from 0 to 3. Univariate and multivariate analysis was performed to analyze factors associated with SEC. Sixty-five patients were on dabigatran and 65 were on warfarin, with the prothrombin time in therapeutic range. There were no significant differences in the age, CHADS2 score, left atrial dimension, and left atrial appendage flow between the two groups. However, there were more grade 2 or higher patients with left atrial SEC in the warfarin group (n = 20) than in the dabigatran group (n = 2) (p