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.

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.

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.

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.

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.

The use of contact lenses during water-polo play: a 20-year study of Japanese college players.

This study investigated the extent of contact-lens use in Japanese college water-polo male players over 20 years (1991-2011, once every five years). Information about the use of contact lenses during play and the types of contact lens was obtained through a self-report questionnaire. The proportion of contact lens use among the players while playing water polo differed from 1991 to 2011 (χ2(4) = 25.28, P < 0.001, Cohen's d = 0.63). Fifty-four per cent of the players used contact lenses while playing in 1991 (P < 0.001); more than 74% in 1996; 89% in 2001; 84% in 2006; and 86% in 2011. While 96% of the contact lenses used by the players in 1991 were the soft type, 74%, 92%, 86%, and 88% of the contact lenses used in 1996, 2001, 2006, and 2011, respectively, were the disposable type. These findings indicated a high percentage of players were using contact lenses while playing water polo between 1996 and 2011. This could be because the majority of players used disposable lenses. The results suggest that increasing use of contact lenses by water-polo players is beneficial.

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.

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.

Effects of extracellular matrix on differentiation of human bone marrow-derived mesenchymal stem cells into smooth muscle cell lineage: utility for cardiovascular tissue engineering.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into various types of cell, and the extracellular matrix (ECM) is acknowledged to be important for the regulation of cell functions. In this study, we demonstrated the effects of ECMs on the differentiation of human bone marrow-derived MSCs into a smooth muscle cell (SMC) lineage. METHODS: Human MSCs (hMSCs) were cultured on dishes coated with 3 types of ECM including laminin (LM), collagen type IV (Col-IV) and fibronectin for 7 days, and simultaneously cultured on a noncoated dish as a control. Cell numbers of these cultured hMSCs were counted, and their expression of SMC-specific genes and proteins was evaluated. hMSCs were then seeded on LM-coated biodegradable sheets and implanted into rat subcutaneous space. After 2 weeks of implantation, these tissues were evaluated. RESULTS: The number of hMSCs was significantly increased by culture on Col-IV-coated dishes. The expression of SMC-specific genes and proteins (alpha-smooth muscle actin, ASMA; h1-calponin, CALP) in hMSC was significantly upregulated from culture on LM-coated dishes. LM-coated sheets showed a significantly increased expression of ASMA and CALP protein in vivo. Moreover, a fully differentiated marker (SM2) was expressed in the in vivo implanted hMSCs in the course of 2 weeks on the LM-coated sheet. CONCLUSION: These results suggest that the signal transduction of the cell-matrix interaction for the differentiation of hMSCs into SMCs was activated when cultured with LM. LM-coated materials may thus be useful for cardiovascular tissue engineering.

Beneficial effects of torasemide on systolic wall stress and sympathetic nervous activity in asymptomatic or mildly symptomatic patients with heart failure: comparison with azosemide.

Loop diuretics could adversely influence prognosis due to activation of neurohumoral mechanism in the long term. Previous study showed torasemide, a loop diuretic with anti-aldosteronergic properties, was associated with lower mortality in patients with chronic heart failure (CHF). We evaluated the effects of torasemide, in comparison with azosemide, in patients with CHF. Patients received oral diuretic therapy with torasemide (8 mg/d, n = 15) or azosemide (60 mg/d, n = 15) for 3 months. Torasemide and azosemide were then switched, and the patients were treated for another 3 months. Torasemide treatment induced significant decreases in left ventricular (LV) systolic wall stress (from 259 +/- 95 to 232 +/- 80 kdyn/cm2) and the plasma level of aldosterone (from 133 +/- 61 to 95 +/- 50 pg/mL) and was not associated with a change in the plasma level of norepinephrine. In contrast, the plasma level of norepinephrine was significantly increased (from 370 +/- 170 to 481 +/- 247 pg/mL), whereas LV systolic wall stress was unchanged after azosemide treatment. This study indicates that torasemide treatment reduced LV systolic wall stress without activation of the sympathetic nervous system in patients with CHF. The anti-aldosteronergic properties of torasemide may contribute to its favorable effects.

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.

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.

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.

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.

Localization of prefoldin interaction sites in the hyperthermophilic group II chaperonin and correlations between binding rate and protein transfer rate.

Prefoldin is a molecular chaperone that captures a protein-folding intermediate and transfers it to a group II chaperonin for correct folding. The manner by which prefoldin interacts with a group II chaperonin is poorly understood. Here, we have examined the prefoldin interaction site in the archaeal group II chaperonin, comparing the interaction of two Thermococcus chaperonins and their mutants with Pyrococcus prefoldin by surface plasmon resonance. We show that the mutations of Lys250 and Lys256 of Thermococcus alpha chaperonin residues to Glu residues increase the affinity to Pyrococcus prefoldin to the level of Thermococcus beta chaperonin and Pyrococcus chaperonin, indicating that their Glu250 and Glu256 residues of the helical protrusion region are responsible for relatively stronger binding to Pyrococcus prefoldin than Thermococcus alpha chaperonin. Since the putative chaperonin binding sites in the distal ends of Pyrococcus prefoldin are rich in basic residues, electrostatic interaction seems to be important for their interaction. The substrate protein transfer rate from prefoldin correlates well with its affinity for chaperonin.

Beneficial effect of bilevel positive airway pressure on left ventricular function in ambulatory patients with idiopathic dilated cardiomyopathy and central sleep apnea-hypopnea: a preliminary study.

BACKGROUND: Sleep-disordered breathing is common in individuals with left ventricular (LV) dysfunction and has been treated with nocturnal positive airway pressure. We investigated whether treatment of central sleep apnea-hypopnea with bilevel positive airway pressure (BPAP) in ambulatory patients with idiopathic dilated cardiomyopathy (IDCM) might improve LV function. METHODS: Fifty-two consecutive patients with IDCM who underwent both cardiac catheterization and standard polysomnography were enrolled in the study; individuals with obstructive sleep apnea syndrome were excluded. Subjects with an apnea-hypopnea index (AHI) >or= 20 episodes per hour were randomized to receive medical therapy either alone (n = 11) or together with BPAP (n = 10). RESULTS: LV end-diastolic pressure, pulmonary capillary wedge pressure, and plasma concentration of brain natriuretic peptide were significantly greater, and LV ejection fraction (LVEF) was significantly lower in patients with an AHI >or= 20/h (n = 21, 40.4%) than in those with an AHI < 20/h (n = 31, 59.6%). LVEF (30.5 +/- 1.6% vs 50.8 +/- 3.5%, p < 0.001) [mean +/- SE] and plasma concentration of brain natriuretic peptide (162.8 +/- 44.5 pg/mL vs 32.7 +/- 17.6 pg/mL, p = 0.02) were significantly increased and decreased, respectively, after treatment with BPAP (daily use, 4.8 +/- 0.3 h) for 3 months, whereas these parameters remained unchanged in the control subjects. CONCLUSIONS: Our findings suggest that treatment of coexisting central sleep apnea-hypopnea with BPAP improves LV function in ambulatory patients with IDCM. BPAP should thus be considered as a nonpharmacologic adjunct to conventional drug therapy in such patients.