The effect of off-label use of reduced-dose direct oral anticoagulants therapy in the treatment of pulmonary embolism comparable to standard-dose therapy.

Direct oral anticoagulants (DOACs) have been shown to be effective and safe in preventing pulmonary embolism recurrence. In this single-center retrospective observational study, we aimed to evaluate the efficacy and safety of reduced-dose DOACs in 86 consecutive patients with acute pulmonary embolism. Patients were divided into standard-dose and reduced-dose DOACs groups. Initial clot volume did not significantly differ between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 18.8 [Q1-Q3 7.3-30.8] mL vs. 10.0 [Q1-Q3 3.2-27.9] mL, p = 0.1). Follow-up computed tomography (CT) within 30 days showed a higher rate of clot volume reduction or disappearance in the standard-dose group compared to the reduced-dose group (standard-dose DOACs vs. reduced-dose DOACs, 81.6% vs. 53.9%, p = 0.02). However, at the final follow-up CT, there was no significant difference in clot volume change between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 91.5% vs. 82.0%, p = 0.19). Major bleeding occurred in two patients in the standard-dose group (4.3%) and three patients in the reduced-dose DOACs group (7.7%) (p = 0.5). In conclusion, while standard-dose DOACs demonstrated superior efficacy in early clot reduction, reduced doses of apixaban and edoxaban showed comparable efficacy and safety profiles in long-term treatment of acute pulmonary embolism in certain patients.

Radiofrequency Ablation of Re-entrant Atrial Tachycardia Originating from the Superior Vena Cava with a High-resolution, 3-dimensional Mapping System.

An 80-year-old man with no previous history of catheter ablation or cardiac surgery underwent catheter ablation for atrial tachycardia (AT). We suspected that the mechanism causing AT was re-entry indicated by the entrainment phenomenon during AT and through activation mapping with a 3-dimensional mapping system (EnSite™ X EP system; Abbott, Chicago, IL, USA). We used a multipolar catheter (Advisor™ HD Grid Mapping Catheter; Abbott) inserted into the superior vena cava (SVC) to accomplish activation mapping. The AT circuit was localized inside the SVC with a fractionated potential recorded on its right lateral wall. A similar fractionated potential was observed in the surrounding area. These areas functioned as the critical isthmus of the AT. Radiofrequency (RF) catheter ablation at these sites eliminated the tachycardia. After RF delivery, no tachycardia was induced by programmed stimulation, even during isoproterenol infusion. Consequently, there was no recurrence of tachycardia even after catheter ablation.

Histopathological characteristics of the arrhythmogenic right ventricular cardiomyopathy presenting the electrocardiographic characteristics with Brugada syndrome.

INTRODUCTION: The histopathological characteristics of the overlapping disease states of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been fully elucidated. METHODS: A 71-year-old man showed coved-type ST-segment elevation with the right precordial leads, and the echocardiography demonstrated right ventricular (RV) dilatation. After 11 months, he died of a polymorphic VT storm. RESULTS: The pathological tissue demonstrated fibrofatty degeneration in the free wall of the RV outflow tract based on the heart autopsy. CONCLUSION: The overlapping disease states of BrS and ARVC showed histopathological characteristics consistent with ARVC.

Efficacy and feasibility of cryoballoon ablation for atrial fibrillation in patients with heart failure: A large-scale multicenter study.

INTRODUCTION: Data are limited regarding outcomes of cryoballoon ablation for atrial fibrillation (AF) in patients with heart failure (HF). This large-scale multicenter study aimed to evaluate the prognosis of patients with HF after cryoballoon ablation for AF. METHODS: Among 3655 patients undergoing cryoballoon ablation at 17 institutions, 549 patients (15%) (391 with paroxysmal AF and 158 with persistent AF) diagnosed with HF preoperatively were analyzed. Clinical endpoints were recurrence, mortality, and HF hospitalization after ablation. RESULTS: Most patients had a preserved left ventricular ejection fraction (LVEF) ≥ 50%. During a mean follow-up period of 25.7 months, recurrence, all-cause death, and HF hospitalization occurred in 29%, 4.0%, and 4.8%, respectively. Cardiac function on echocardiography and B-type natriuretic peptide (BNP) levels significantly improved postoperatively, and the effect was more pronounced in the nonrecurrence group. Major complications occurred in 33 patients (6.0%), but most complications were phrenic nerve palsy (3.6%). Although death and HF hospitalization occurred more frequently in patients with LVEF ≤ 40% (n = 73) and New York Heart Association (NYHA) class III-IV (n = 19) than other subgroups, the BNP levels, and LVEF significantly improved after ablation in all LVEF and NYHA class subgroups. High BNP levels, NHYA class, CHADS2 score, and structural heart disease, but not postablation recurrence, independently predicted death, and HF hospitalization on multivariate analysis. The patients with tachycardia-induced cardiomyopathy had better recovery of BNP levels and LVEF after ablation than those with structural heart disease. CONCLUSIONS: Cryoballoon ablation for AF in HF patients is feasible and leads to significantly improved cardiac function.

Short coupling interval with high burden of atrial ectopy predicts recurrence after atrial fibrillation ablation.

Atrial ectopy (AE) with a short coupling interval (S-AE) causes atrial fibrillation (AF). A higher burden of AE is associated with recurrence after AF ablation. However, a few reports have evaluated the prognostic impact of both AE burden and S-AE after the acute phase of ablation. This study aimed to assess the characteristics of AE beyond the blanking period in predicting the recurrence. We retrospectively analyzed 173 patients who underwent first catheter ablation for AF and 24-h Holter recording following a 3-month blanking period. AE was defined as a narrow QRS complex occurring < 75% earlier than the prior reference R-R interval. We investigated the relationship between the AE's characteristics in Holter recordings and atrial arrhythmia recurrence. Forty-two patients (24%) had a recurrence during a median 488-day follow-up. Patients with S-AE (minimum coupling interval ratio of AE ≤ 45%) had a higher recurrence rate than those without S-AE (44.9% vs. 16.1%, p < 0.001). Moreover, patients with AE ≥ 241/day exhibited a significantly higher recurrence rate than those with AE < 241/day (44.3% vs. 10.7%, p < 0.001). In multivariate analysis, S-AE with a higher AE burden was an independent predictor of recurrence (hazard ratio 5.82, 95% confidence interval: 2.64-12.82, p < 0.001). Kaplan-Meier analysis showed that patients with S-AE and a higher AE burden had the worst prognosis for recurrence (p < 0.001). The combination of a higher AE burden with S-AE could be an efficient predictor of recurrence. These results can help to develop follow-up strategies after AF ablation.

Usefulness of P-wave duration in patients with sick sinus syndrome as a predictor of atrial fibrillation.

BACKGROUND: This study aimed to clarify P-wave duration (PWD) ability before pacemaker implantation to predict worsening atrial fibrillation (AF) burden after the procedure. METHODS: We retrospectively investigated 75 patients who underwent permanent pacemaker implantation due to sick sinus syndrome (SSS) at Komaki City Hospital between January 2006 and May 2019. Worsening AF burden was defined as an increase in the number of AF episodes, each lasting ≥5.5 hours a day. RESULTS: In the study population, 17 patients (23%) had worsening AF burden during the follow-up period. These patients had significantly longer PWD in lead Ⅱ (117.9 ± 19.9 ms vs 101.3 ± 20.0 ms, P = .002) than the patients without worsening AF burden. The best discriminative cutoff value for PWD in lead Ⅱ was 108 ms (sensitivity, 77%; specificity, 67%). In multivariate analysis, PWD in lead II ≥108 ms (hazard ratio, 5.395; 95% confidence interval, 1.352-21.523; P = .017) was an independent predictor of worsening AF burden. Patients with PWD in lead II <108 ms showed a significantly higher event-free rate against worsening AF burden than those with PWD in lead II ≥108 ms (81% vs 9%, P = .005). CONCLUSIONS: Prolonged PWD before pacemaker implantation was the most important independent predictor of worsening AF burden after the procedure. In patients with SSS, prolonged PWD can be a useful marker for predicting worsening of AF burden after pacemaker implantation.

The impact of the dominant frequency of body surface electrocardiography in patients with persistent atrial fibrillation.

The dominant frequency (DF) of atrial fibrillation (AF) reflects atrial electrical activity. However, the relationship between DF measured using surface electrocardiography (ECG) and AF ablation success remains unclear. This study aimed to clarify whether the DF of surface ECG in patients with persistent AF could predict arrhythmia recurrence after catheter ablation. We investigated 125 patients with persistent AF who underwent catheter ablation between January 2009 and December 2016. Thirty-four patients (27%) had arrhythmia recurrence after catheter ablation. These patients showed a significantly high DF value in leads aVL (7.2 ± 0.7 Hz vs 6.6 ± 0.9 Hz, p < 0.001) and V1 (7.4 ± 0.8 Hz vs 6.7 ± 0.7 Hz, p < 0.001). We set the cutoff value of DF as 6.9 Hz in lead aVL (sensitivity, 80%; specificity, 63%) and as 7.1 Hz in lead V1 (sensitivity, 72%; specificity, 67%). Patients with DF < 6.9 Hz in lead aVL showed a significantly higher recurrence-free rate than those with DF ≥ 6.9 Hz (88% vs 45%; p < 0.001). Patients with DF of < 7.1 Hz in lead V1 showed a significantly higher recurrence-free rate than those with DF of ≥ 7.1 (87% vs 47%; p < 0.001). Patients with a high DF in leads aVL and V1 showed a lower success rate of persistent AF ablation. The DF measured from surface ECG can be a useful marker to predict ablation success.

Study design and protocol for evaluating the long-term prognosis of patients receiving his bundle pacing: A multicenter observational study.

BACKGROUND: His bundle pacing (HBP) is a recently developed pacing technique that can achieve an ideal physiological pattern of ventricular activation via stimulation of the native His-Purkinje system. Despite the widespread introduction of HBP in clinical practice, its appropriate indications are yet to be determined clearly. Moreover, the efficacy and safety of HBP and long-term prognosis of patients undergoing such are unknown. METHODS: We conducted a multicenter observational prospective study in patients undergoing HBP in Japan. Patients with atrioventricular block or conduction delay and estimated ventricular pacing of ≥ 40% scheduled for HBP implantation are included. All patients are followed up until 3 years after the implantation. The primary endpoints are all-cause death, heart failure-related hospitalization, and upgrade to cardiac resynchronization therapy. The secondary endpoint is changes in cardiac function based on echocardiographic findings and laboratory data after the implantation. RESULTS: The results are currently under investigation. CONCLUSIONS: This multicenter observational study evaluates the long-term prognosis and changes in cardiac function of patients undergoing HBP implantation in a clinical setting. Considering the large number of patients included, the cumulative results would be helpful in establishing evidence on HBP application in this area and consequently allow accurate management and treatment of patients undergoing HBP.

Effects of Repetitive Altitude Training on Salivary Immunoglobulin A Secretion in Collegiate Swimmers.

BACKGROUND: Altitude training has often been conducted just before main competition games in many sports. An increase in the frequency of upper respiratory tract infections and gastrointestinal infections due to an altitude-induced suppression of the immune system has been reported after altitude training. Salivary secretory immunoglobulin A (SIgA) is the major immunoglobulin of the mucosal immune system. A suppressive effect of heavy training on SIgA has been reported. However, little is known regarding the effects of repetitive altitude training and hypoxic exposure on SIgA. The objective of this study was to evaluate the changes in SIgA in swimmers undergoing repetitive altitude training at 1,900 m. METHODS: Nine collegiate swimmers who experienced their first altitude training experience (FT group) were compared to nine swimmers who experienced repetitive training (RT group) and non-training subjects (Con group). Saliva was collected before ascent and eight times every 2 days during altitude training. SIgA levels were measured by enzyme-linked immunosorbent assays. RESULTS: Compared to the Con group, SIgA levels and the secretion velocity were decreased after ascent and were slowly restored in both the FT and RT groups. The chronological trends in SIgA levels were similar, even though the decline in SIgA levels in the FT group was larger than that in the RT group. CONCLUSION: Altitude training and experience with altitude training may be one of the factors influencing SIgA.

Myocardial viability as shown by left ventricular lead pacing threshold and improved dyssynchrony by QRS narrowing predicts the response to cardiac resynchronization therapy.

INTRODUCTION: Patients with advanced heart failure and dyssynchrony can benefit from cardiac resynchronization therapy (CRT). To predict the response to CRT, myocardial viability and improved dyssynchrony are suggested to be important. METHODS: We retrospectively investigated 93 patients who underwent CRT implantation in Nagoya University Hospital. We assessed QRS narrowing the day after implantation to measure the improvement in dyssynchrony and measured the left ventricular pacing threshold (LVPT) to determine the local myocardial viability in all patients. Responders to CRT were defined as those having a greater than or equal to 15% decrease in left ventricular end-systolic volume by echocardiography at their 6-month follow-up. RESULTS: Sixty-two patients (67%) were classified as responders. The QRS width before CRT implantation, QRS narrowing after implantation, left atrial diameter, septal-to-posterior wall motion delay, left ventricular end-diastolic diameter, radial strain, and LVPT were significantly different between the responder and nonresponder groups. On multivariate analysis, QRS narrowing (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = 0.005) and LVPT (OR, 0.42; 95% CI, 0.22-0.82; P = 0.011) were independent predictors of a response to CRT. We calculated the cutoff values from the receiver operating characteristic curves as 22.5 milliseconds of QRS narrowing and 1.55 V of LVPT. The response rates in patients with both predictive factors (QRS narrowing ≥ 22.5 milliseconds and LVPT ≤ 1.55 V), one factor, and no factors were 91%, 61%, and 25%, respectively (P < 0.001). CONCLUSION: Both myocardial viability and improved electrical dyssynchrony may be essential to predict a good response to CRT.

Clinical significance of the timing of early recurrence of atrial arrhythmia after pulmonary vein isolation: a two-institution clinical study.

Early recurrence of atrial arrhythmia (ERAA) after ablation frequently occurs, but there is limited evidence about ERAA-timing. This study aimed to investigate the association between ERAA-timing and late recurrence. We retrospectively investigated 332 patients who underwent PVI for paroxysmal atrial fibrillation at Nagoya University Hospital and Komaki City Hospital. Seventy-six patients (23%) had ERAA. The cutoff value of the first ERAA for late recurrence was set as 3 days, with a specificity of 77% and sensitivity of 43%. On multivariate analysis, first ERAA beyond 3 days (hazard ratio, 2.477; 95% confidence interval, 1.168-5.25; p = 0.018) and large left atrial diameter (LAD) (hazard ratio, 1.101; 95% confidence interval, 1.024-1.184; p = 0.009) were independent predictors for late recurrence. Patients who had first ERAA within 3 days and no ERAA beyond 3 days showed a significantly higher recurrence-free rate than those who had first ERAA beyond 3 days and those who had ERAA both within 3 days and beyond 3 days (89% versus 39%, 44%; p < 0.001). Moreover, the patients with ERAA within 3 days and LAD ≤ 37.7 mm showed a significantly higher recurrence-free rate than those with ERAA beyond 3 days and LAD > 37.7 mm, and as compared with the other patients (100% versus 26% and 60%, respectively; p < 0.001). ERAA beyond 3 days after ablation was a predictor for late recurrence. Among patients with ERAA, those with ERAA within 3 days and smaller LAD showed favorable prognosis after ablation.

Uninterrupted Direct Oral Anticoagulant and Warfarin Administration in Elderly Patients Undergoing Catheter Ablation for Atrial Fibrillation: A Comparison With Younger Patients.

OBJECTIVES: The goal of this study was to evaluate the efficacy and safety of uninterrupted direct oral anticoagulant (DOAC) use and uninterrupted warfarin administration in elderly patients undergoing catheter ablation for atrial fibrillation (AF). BACKGROUND: There is limited knowledge regarding the uninterrupted use of oral anticoagulant agents in elderly patients undergoing catheter ablation for AF. METHODS: This retrospective study included 2,164 patients (n = 325 ≥75 years of age and n = 1,839 <75 years of age) who underwent catheter ablation for AF. All the patients received uninterrupted oral anticoagulant agents during the procedure. We investigated the occurrences of periprocedural events and compared these between the DOAC and warfarin groups of the elderly and younger groups. RESULTS: Major bleeding events (3.1% vs. 1.3%; p = 0.023) and minor bleeding events (9.2% vs. 5.0%; p = 0.002), except for thromboembolic events (0% vs. 0.8%; p = 0.248), were significantly higher in the elderly group than in the younger group. No significant differences in thromboembolic and bleeding events were found between the DOAC and warfarin groups of both the elderly and younger groups. Adverse complications did not differ between the groups after adjustment using propensity score matching analysis. Multivariate analysis revealed that lower body weight (odds ratio: 0.96; p = 0.010) and antiplatelet drug use (odds ratio: 2.21; p = 0.039) were independent predictors of adverse events in the elderly group. CONCLUSIONS: The periprocedural bleeding risk during the use of uninterrupted oral anticoagulants was higher in the elderly group than in the younger group. This area needs more attention for these patients in whom caution is required.

Assessment of autonomic nervous system modulation after novel catheter ablation techniques for atrial fibrillation using multiple short-term electrocardiogram recordings.

PURPOSE: The effect of novel catheter ablation techniques for atrial fibrillation (AF) on the autonomic nervous system (ANS) is unclear. This study aimed to assess the ANS after three novel catheter ablation techniques for paroxysmal AF by evaluating heart rate variability (HRV) parameters using a 3-min electrocardiogram recording. METHODS: Two hundred and thirty-five patients who underwent catheter ablation for paroxysmal AF (119 in irrigated-tip, 51 in contact-force sensing-guided, and 65 patients in second-generation cryoballoon ablation) were included. HRV analysis was performed at baseline and 1, 3, 6, and 12 months after the ablation. RESULTS: The three ablation groups had similarly decreased HRV parameters after the ablation, and this change was maintained > 1 year. A reduction in parasympathetic nervous function was more apparent after the ablation, compared to changes in the sympathetic nervous function. Of the total population, 45 patients had recurrence. Ln high frequency (HF) 12 months after the ablation was significantly higher in the recurrence group than in the non-recurrence group (1.52 ± 0.47 vs. 1.26 ± 0.57 ms2, p = 0.007). Multivariate analysis demonstrated that AF duration (hazards ratio 1.09, 95% confidence interval 1.04-1.15, p = 0.001) and ln HF 12 months after ablation (hazards ratio 1.91, 95% confidence interval 1.12-3.25, p = 0.017) were independent predictors of AF recurrence after the ablation. CONCLUSIONS: ANS modulation after the three catheter ablation methods was similar and maintained > 1 year after the procedure. Higher parasympathetic nervous function at 1 year after ablation was associated with AF recurrence after the ablation.

Renal function and risk of stroke and bleeding in patients undergoing catheter ablation for atrial fibrillation: Comparison between uninterrupted direct oral anticoagulants and warfarin administration.

BACKGROUND: The effect of uninterrupted oral anticoagulant use in patients with chronic kidney disease (CKD) during catheter ablation for atrial fibrillation (AF) is not fully understood. OBJECTIVE: The present study aimed to evaluate the safety and efficacy of periprocedural uninterrupted direct oral anticoagulant (DOAC) use compared with those of uninterrupted warfarin use in patients undergoing catheter ablation for AF stratified by various renal function groups. METHODS: A total of 2091 patients were retrospectively included in this study. The study population was divided into 4 groups: creatinine clearance level ≥80 mL/min (n = 1086), 50-79 mL/min (n = 774), 15-49 mL/min (n = 209), and <15 mL/min (n = 22). We investigated periprocedural complications and compared them between uninterrupted DOAC and warfarin groups. RESULTS: There was no significant difference in thromboembolic events among the 4 groups (0.6%, 0.6%, 1.0%, and 0%, respectively; P = .792). However, major bleeding events (0.9%, 1.4%, 4.8%, and 4.5%; P < .001) and minor bleeding events (4.1%, 6.1%, 11.5%, and 13.6%; P < .001) primarily occurred in patients with CKD. The rate of periprocedural complications in the DOAC group was similar to that in the warfarin group for each renal function category. Adverse events did not differ after adjustment using propensity score-matched analysis. Multivariate analysis showed that lower body weight, antiplatelet drug use, initial ablation session, and CKD were independent predictors of adverse events. CONCLUSION: The periprocedural bleeding risk was increased in patients with CKD. Uninterrupted DOAC and warfarin administration during catheter ablation for AF in patients with CKD is feasible and effective.

Vagal response in cryoballoon ablation of atrial fibrillation and autonomic nervous system: Utility of epicardial adipose tissue location.

BACKGROUND: Mechanism and effects of vagal response (VR) during cryoballoon ablation procedure on the cardiac autonomic nervous system (ANS) are unclear. The present study aimed to evaluate the relationship between VR during cryoballoon catheter ablation for atrial fibrillation and ANS modulation by evaluating epicardial adipose tissue (EAT) locations and heart rate variability (HRV) analysis. METHODS: Forty-one patients with paroxysmal atrial fibrillation (11 with VR during the procedure and 30 without VR) who underwent second-generation cryoballoon ablation were included. EAT locations and changes in HRV parameters were compared between the VR and non-VR groups, using Holter monitoring before ablation, immediately after ablation and one month after ablation. RESULTS: The total EAT volume surrounding the left atrium (LA) in the VR and non-VR groups was 29.0±18.4 cm3 vs 27.7±19.7 cm3, respectively (p=0.847). The VR group exhibited greater EAT volume overlaying the LA-left superior pulmonary vein (PV) junction (6.1±3.6 cm3 vs 3.6±3.3 cm3, p=0.039) than the non-VR group. HRV parameters similarly changed following ablation in both the groups. EAT volume overlaying LA-right superior PV junction was significantly correlated with the relative changes in root-mean-square successive differences (r=-0.317, p=0.043) and high frequency (r=-0.331, p=0.034), immediately after the ablation. CONCLUSIONS: Changes in HRV parameters following ablation were similarly observed in both the groups. EAT volume on the LA-PV junction is helpful for interpretation of VR occurrence and ANS modulation.

Monitoring of anti-Xa activity and factors related to bleeding events: A study in Japanese patients with nonvalvular atrial fibrillation receiving rivaroxaban.

BACKGROUND: Anti-Xa activity (AXA) in patients with nonvalvular atrial fibrillation (NVAF) and relationship to bleeding events remains unclear. METHODS: We evaluated AXA in 94 patients at both trough and peak rivaroxaban concentrations. Rivaroxaban dosage was determined according to creatinine clearance (CrCl): 10 and 15mg once daily for patients with CrCl 15-49 and CrCl ≥50mL/min, respectively. AXA value distribution and its association with bleeding events were examined in enrolled subjects. RESULTS: The mean peak AXA level was significantly higher than the mean trough level (1.98±0.81 vs. 0.16±0.15IU/mL; p<0.001). The peak AXA level significantly differed among patients with CrCl 15-29, 30-49, 50-79, and ≥80mL/min (2.51±0.83, 1.72±0.76, 2.05±0.82, and 1.66±0.51IU/mL, respectively; p=0.004). Major and non-major clinically relevant bleeding events occurred in 22 patients (23.4% and 14.6% per year, respectively). The mean peak AXA level was significantly higher in patients who experienced bleeding events than in those who did not (2.40±0.70 vs. 1.84±0.80IU/mL; p=0.001). A Cox multivariate analysis showed that the peak AXA level was independently related to the incidence of major and non-major clinically relevant bleeding events (p=0.012). Cumulative bleeding rates were significantly higher in patients with high peak AXA levels (p<0.001). CONCLUSION: Peak AXA level was an independent predictor for bleeding events in Japanese NVAF patients receiving rivaroxaban.

Salivary extracellular heat shock protein 70 (eHSP70) levels increase after 59 min of intense exercise and correlate with resting salivary secretory immunoglobulin A (SIgA) levels at rest.

This study aimed to identify the response of a salivary stress protein, extracellular heat shock protein (eHSP70), to intense exercise and to investigate the relationship between salivary eHSP70 and salivary immunoglobulin A (SIgA) levels in response to exercise. Sixteen healthy sedentary young males (means ± SD 23.8 ± 1.5 years, 172.2 ± 6.4 cm, 68.3 ± 7.4 kg) performed 59 min of cycling exercise at 75% VO2max. Saliva and whole blood samples were collected before (Pre), immediately after (Post), and at 1, 2, 3, and 4 h after completion of the exercise (1, 2, 3, and 4 h). The salivary eHSP70 and SIgA levels were measured by enzyme-linked imunosorbent assay (ELISA), and the secretion rates were computed by multiplying the concentration by the saliva flow rate. White blood cells were analyzed using an automated cell counter with a direct-current detection system. The salivary eHSP70 secretion rates were 1.11 ± 0.86, 1.51 ± 1.47, 1.57 ± 1.32, 2.21 ± 2.04, 3.36 ± 2.72, and 6.89 ± 4.02 ng · min(-1) at Pre, Post, and 1, 2, 3, and 4 h, respectively. The salivary eHSP70 secretion rate was significantly higher at 4 h than that at Pre, Post, 1, and 3 h (p < 0.05). The SIgA secretion rates were 26.9 ± 12.6, 20.3 ± 10.4, 19.6 ± 11.0, 21.8 ± 12.8, 21.5 ± 11.9, and 21.9 ± 11.7 µg · min(-1) at Pre, Post, 1, 2, 3, and 4 h, respectively. The salivary SIgA secretion rate was significantly lower between 1 and 4 h than that at Pre (p < 0.05). There was a positive correlation between salivary eHSP70 and SIgA in both concentration and secretion rates before exercise (p < 0.05). The absolute number of white blood cells significantly increased after exercise, with a maximum at 2 h (p < 0.05). The neutrophil/lymphocyte ratio was significantly increased from 1 to 4 h when compared with that in the Pre samples (p < 0.05). The present study revealed that salivary eHSP70 significantly increased at 4 h after the 59 min of intense exercise in sedentary male subjects. Exercise stress can induce elevated salivary eHSP70 level and upregulate oral immune function partially.

Long-term effects of tolvaptan in patients requiring recurrent hospitalization for heart failure.

Although reports suggest that tolvaptan does not reduce survival or subsequent hospitalization rates in heart failure patients, its continuous use has shown good outcomes in some patients who cannot be effectively managed with high doses of loop diuretics. Therefore, we investigated the association of patient characteristics and continued tolvaptan use in heart failure patients with changes in the frequency and annual duration of patient hospitalization due to heart failure. We carefully reviewed the medical records of patients hospitalized due to heart failure who began tolvaptan therapy and continued with outpatient treatment between December 2010 and November 2013 (tolvaptan group); patients hospitalized for heart failure between May 2008 and March 2009 served as controls. We set the reference dates as the start of tolvaptan therapy (tolvaptan group) or as the date of admission (control group). The changes in hospitalization frequency and total hospitalization time due to heart failure, before and after the reference dates, were not significantly different between the tolvaptan and control groups. In the tolvaptan group, a high estimated glomerular filtration rate was a predictor of decreased hospitalization. Continuous tolvaptan use did not decrease hospitalization duration in all heart failure patients, but good renal function was predictive of a good response.