Cardiopulmonary exercise responses in patients with non-ischemic heart failure and a mildly reduced ejection fraction.

Background: The cardiopulmonary response to exercise in patients with heart failure exhibiting a mildly reduced ejection fraction (41% ≤ EF ≤ 49%) remains unclear. Materials & methods: A total of 193 consecutive patients with heart failure (excluding those with coronary artery disease) who underwent cardiopulmonary exercise (CPX) tests were examined. CPX variables were compared among patients with reduced, mildly reduced, and preserved EF. Results: The CPX test responses of patients with mildly reduced EF were similar to those of patients with reduced or preserved EF; however, increases in systolic blood pressure during exercise differed significantly (32 ± 26, 50 ± 24, and 41 ± 31 mmHg, respectively; p = 0.016). Grip strength and an increase in systolic blood pressure during exercise were independently associated with peak oxygen uptake in patients with mildly reduced EF (ß = 0.41, 0.35, respectively; p < 0.05). Conclusion: Measurements of grip strength and blood pressure during exercise are useful predictors of prognoses in patients with non-ischemic and mildly reduced EF.

Cardiopulmonary exercise (CPX) test is widely used to evaluate the function related to heart in heart failure patients. The heart failure patients are divided into three groups: with reduced wall motion (HFrEF), with mildly reduced wall motion (HFmrEF) and with preserved wall motion (HFpEF). We compared the cardiopulmonary reaction to exercise among the three groups. The CPX test responses of patients with HFmrEF were similar to those of patients with HFrEF or HFpEF. However, increases in systolic blood pressure during exercise differed (32 ± 26, 50 ± 24, and 41 ± 31 mmHg, respectively; p = 0.016). Grip strength and an increase in systolic blood pressure during exercise were independently associated with peak oxygen uptake, which is an important predictor of rate of death in patients with HFmrEF. Measurements of grip strength and blood pressure during exercise are useful predictors of progress in patients with enough blood supply to the heart and HFmrEF.

Relationship between epicardial adipose tissue volume and coronary artery spasm.

BACKGROUND: Epicardial adipose tissue (EAT) is considered to play a critical role in vascular endothelial function. Coronary artery spasm has been postulated to be a causal factor in vascular endothelial abnormalities and atherosclerosis. This study aimed to investigate the relationship between coronary artery spasm and EAT volume, total abdominal adipose tissue (AAT) area, and abdominal visceral adipose tissue (AVAT) area. METHOD: Among patients undergoing coronary computed tomography (CT) to evaluate coronary artery disease, we identified 110 patients who did not have significant coronary artery stenosis and underwent a coronary spasm provocation test with cardiac catheterization. They were divided into two groups according to the results of the spasm provocation test: spasm-positive and spasm-negative. EAT volume, total AAT area, and AVAT area were evaluated using CT images. RESULTS: Seventy-seven patients were included in the spasm-positive group and 33 patients in the spasm-negative group. There were no significant differences in baseline clinical characteristics between the two groups, except for the prevalence of current smoking (48% vs. 27%, p = 0.04). EAT volume was significantly higher in the spasm-positive group (108 ±â€¯38 mL vs. 87 ±â€¯34 mL, p = 0.007), while no significant difference was seen in total AAT area (280 ±â€¯113 cm2 vs. 254 ±â€¯128 cm2, p = 0.32) or AVAT area (112 ±â€¯54 cm2 vs. 98 ±â€¯55 cm2, p = 0.27). Multivariate logistic analysis indicated that EAT volume (per 10 cm3) (odds ratio, 1.198; 95% confidence interval, 1.035-1.388; p = 0.016) was a significant predictor of coronary artery spasm. CONCLUSION: Our results suggest that EAT has a strong association with coronary artery spasm, while AAT may not.

Periprocedural Management of Cardiac Tamponade During Catheter Ablation for AF Under Uninterrupted DOAC and Warfarin.

OBJECTIVES: This was a retrospective analysis of a registry of patients who underwent catheter ablation for atrial fibrillation (AF) under uninterrupted direct oral anticoagulant (DOAC) and warfarin administration. BACKGROUND: Uninterrupted DOAC used during catheter ablation for AF causes a life-threatening bleeding risk of cardiac tamponade. METHODS: Of 3,149 catheter ablation procedures for AF with uninterrupted oral anticoagulants used in 2,406 patients in 3 institutions, DOAC and warfarin were administered in 1,896 and 1,253 procedures, respectively. Among them, cardiac tamponade requiring pericardiocentesis and surgical intervention occurred in 13 (0.7%) and 11 (0.9%) procedures in the DOAC and warfarin groups, respectively. In this study, the outcomes between these 2 groups were compared. RESULTS: The total blood volumes drained after pericardiocentesis was 300 (190 to 715) ml and 300 (200 to 380) ml in the DOAC and warfarin groups, respectively (p = 0.697). Approximately two-thirds of patients (9 in the DOAC group and 7 in the warfarin group) recovered with only pericardiocentesis and protamine infusion (including vitamin K in the warfarin group) in both groups. Two patients in the DOAC group underwent surgical intervention but recovered uneventfully, whereas none of the patients taking warfarin required surgical intervention. DOAC and warfarin were successfully resumed 2.0 (2.0 to 5.0) days and 4.0 (2.0 to 5.5) days after tamponade in all patients without an increase in effusion (p = 0.102). CONCLUSIONS: Managing cardiac tamponade under uninterrupted DOAC administration was feasible. Early intensive treatment resulted in hemostasis in most patients. However, surgical intervention was required in some cases refractory to the initial treatment.

Prospective comparison of periprocedural coagulation markers among uninterrupted anticoagulants for atrial fibrillation ablation.

BACKGROUND: The difference in coagulation state during the periprocedural period of atrial fibrillation (AF) ablation among patients with uninterrupted anticoagulation has not been fully elucidated. OBJECTIVE: The purpose of this study was to compare periprocedural trends in coagulation markers among patients on uninterrupted anticoagulation for AF ablation. METHODS: In total, 275 consecutive patients who underwent AF ablation were evaluated. These patients were divided according to the anticoagulant they received into the dabigatran group (DG) (n = 64); rivaroxaban group (RG) (n = 62); apixaban group (AG) (n = 60); edoxaban group (EG) (n = 59); and warfarin group (WG) (n = 30). The trends in coagulation markers and the rate of silent stroke (SS) confirmed by postoperative magnetic resonance imaging were evaluated. RESULTS: The fibrin monomer complex (FMC) level on postoperative day 1 and the prothrombin fragment 1+2 (PF1+2) levels on the operative day and postoperative day 1 were higher in DG than in the other groups (P <.05, <.001, and <.001, respectively). The incidence of SS in DG (17%) was significantly higher than in RG (6%), AG (3%, EG (7%), or WG (4%) (P <.05). Dabigatran use independently predicted the occurrence of SS (odds ratio 4.12; 95% confidence interval 1.37-12.7; P <.05). CONCLUSION: FMC and PF1+2 levels during the periprocedural period of AF ablation were higher in DG than in the other groups. Dabigatran use independently predicted the occurrence of SS.

Impact of periprocedural anticoagulation therapy on the incidence of silent stroke after atrial fibrillation ablation in patients receiving direct oral anticoagulants: uninterrupted vs. interrupted by one dose strategy.

AIMS: Data on the comparison between uninterrupted and interrupted by one dose strategies for direct oral anticoagulant (DOAC) use during the periprocedural period of atrial fibrillation (AF) ablation are scarce. The purpose of this study is to investigate the feasibility of uninterrupted DOAC strategy by evaluating the incidence of silent stroke (SS) and perioperative trends in coagulation markers compared with the interrupted strategy. METHODS AND RESULTS: We randomly divided 200 consecutive patients receiving DOACs, who underwent AF ablation into uninterrupted group (UG = 100) and interrupted by one dose group (IG = 100). The rate of SS confirmed by post-operative magnetic resonance imaging and periprocedural trends in coagulation markers was investigated. A significant difference in SS incidence was found between the UG and IG (UG 4%, IG 17%, P < 0.005), although there were no differences in the rate of complications including bleeding and symptomatic thrombo-embolic events between the two groups. Intraoperative cardioversion [odds ratio (OR) 7.27, 95% confidence interval (CI) 1.76-30.0; P < 0.01] and the length of procedure time (OR 1.03, 95% CI 1.01-1.05; P < 0.05) independently predicted the occurrence of SS in the IG. A significant increase in prothrombin fragment 1 + 2 (PF1 + 2) values was observed in the IG compared with the UG on the operative and first post-operative days. CONCLUSION: Silent stroke incidence in the IG was significantly higher than that in the UG; this seems to be supported by the difference in PF1 + 2 values between the UG and IG. Intraoperative cardioversion and procedure time predicted the occurrence of SS in the IG.

Clinical Characteristics of Nonobese Patients with Acute Coronary Syndrome and Increased Epicardial Fat Volume.

AIM: Increased epicardial fat volume (EFV) is an independent risk factor for acute coronary syndrome (ACS). Although EFV increases with body mass index (BMI), some ACS patients have an increased EFV but normal BMI. We here investigated the clinical characteristics of nonobese ACS patients with an increased EFV. METHODS: A total of 197 Japanese patients hospitalized for ACS was evaluated for EFV, abdominal visceral fat area (VFA), and lipid and glucose profiles. Control subjects comprised 141 individuals who were suspected of having ACS but whose coronary computed tomography findings were normal. RESULTS: EFV was increased in ACS patients compared with control subjects (120±47 versus 95±45 mL, P＜0.01). ACS patients were divided into four groups based on average EFV (120 mL) and a BMI obesity cutoff of 25 kg/m2. For the 30 nonobese ACS patients with an above-average EFV, EFV was positively correlated with VFA (r=0.23, P=0.031). These individuals were significantly older (74±10 years) and tended to have a higher homeostasis model assessment-insulin resistance value (5.5±3.8) compared with other ACS patients. Among nonobese study subjects, EFV was independently associated with ACS (odds ratio=2.01, P=0.021) and correlated with abdominal circumference (r=0.26, P=0.017). CONCLUSION: Nonobese ACS patients with an increased EFV were elderly and tended to manifest insulin resistance. Measurement of EFV may prove informative for evaluation of ACS risk among elderly nonobese individuals with an increased abdominal girth.

Trends in physiological coagulation factors in Japanese patients receiving novel oral anticoagulants.

BACKGROUND: Little is known about physiological anticoagulation effects via antithrombin III (AT III) and protein C/S (PC/PS) in patients using new oral anticoagulants (NOACs). METHODS: We evaluated 120 consecutive patients with non-valvular atrial fibrillation (AF) receiving NOACs. Patients were randomly divided into three groups: a dabigatran group (DG, N=40), a rivaroxaban group (RG, N=40) or an apixaban group (AG, N=40). A warfarin group (WG, N=40) was matched with NOAC groups for age, sex and type of AF during the same time period. Blood samples were obtained in pretreatment, trough and peak phases to measure the activity of physiological coagulation inhibitors, including AT III and PC/PS or thrombus formation markers such as D-dimer and thrombin-antithrombin complex (TAT). RESULTS: D-dimer, TAT and AT III values for the NOAC groups were equivalent in the peak and trough phases. PC/PS activity in both phases was equally maintained in the pretreatment phase in the NOAC groups, while the activity in the WG was significantly suppressed in steady state. Moreover, no differences in trends for PC/PS activity were observed among NOAC groups. CONCLUSIONS: PC/PS activity was constant in both peak and trough phases in the patients on NOACs compared with activity of those on warfarin. In addition, there was no difference in the findings among NOACs.

Increased expression of the adipocytokine omentin in the epicardial adipose tissue of coronary artery disease patients.

BACKGROUND AND AIMS: Omentin, an adipocytokine secreted by visceral adipose tissue, protects against obesity-linked cardiovascular complications. However, little is known about its role in epicardial adipose tissue (EAT) and coronary artery disease (CAD). We investigated the expression of omentin in EAT from CAD subjects. METHODS: EAT, subcutaneous adipose tissue (SCAT), and plasma samples were collected from CAD (n = 15; 23.3 ± 3.1 kg/m(2)) and non-CAD patients (n = 10; 20.8 ± 3.9 kg/m(2)). Omentin mRNA expression was measured using real-time PCR, while plasma concentrations were measured using an ELISA. EAT volume was determined with 64-slice computed tomography. RESULTS: Omentin expression in EAT and EAT volume were higher in CAD patients compared with controls (2.49 ± 2.6 vs. 0.85 ± 0.3, p = 0.002 and 113 ± 58 ml vs. 92.4 ± 30 ml, p = 0.045, respectively). Omentin expression in SCAT was similar between CAD and control patients (1.37 ± 0.84 vs. 1.07 ± 0.55, p = 0.267). Plasma omentin levels were lower in CAD patients compared with controls (343 ± 158 ng/ml vs. 751 ± 579 ng/ml, p = 0.025), and were negatively associated with the expression of omentin in EAT, in patients with CAD (ß = -0.78, p = 0.049). On the other hand, there was no association between omentin in EAT and clinical variables in patients with non-CAD. CONCLUSIONS: Omentin expression increases in the EAT of non-obese CAD patients, despite a decrease in plasma levels, suggesting that omentin may play a role in the pathogenesis of CAD.

Feasibility and safety of uninterrupted dabigatran therapy in patients undergoing ablation for atrial fibrillation.

OBJECTIVE: Uninterrupted oral warfarin strategy has become the standard protocol to prevent complications during catheter ablation (CA) for the treatment of atrial fibrillation (AF). However, little is known about the safety and efficacy of uninterrupted dabigatran therapy in patients undergoing CA for AF. Therefore, this study investigated the safety and efficacy of uninterrupted dabigatran therapy and compared the findings with those for uninterrupted warfarin therapy. METHODS: Bleeding and thromboembolic events during the periprocedural period were evaluated in 363 consecutive patients who underwent CA for AF at Nagoya University Hospital, and received uninterrupted dabigatran (n=173) or uninterrupted warfarin (n=190) for periprocedural anticoagulation. RESULTS: A total of 27 (7%) patients experienced either bleeding or thromboembolic complications. Major bleeding complications occurred in 2 (1%) patients in the dabigatran group (DG) and 2 (1%) patients in the warfarin group (WG). Eight (5%) patients in the DG and 9 (5%) patients in the WG experienced groin hematoma, a type of minor bleeding complication. Meanwhile, no patient in the DG and 1 (1%) in the WG developed cerebral ischemic stroke. Overall, there was no significant difference between the groups for any category. The activated partial thromboplastin time (APTT) independently predicted periprocedural complications in the DG. CONCLUSION: Uninterrupted dabigatran therapy in CA for AF thus may be a safe and effective anticoagulant therapy, and appears to be closely similar to continuous warfarin; however, it is essential to pay close attention to the APTT values when using dabigatran during CA.

Impact of cardiac resynchronization therapy-defibrillator implantation on the association between body mass index and prognosis in patients with heart failure.

PURPOSE: This study aimed to examine the association between body mass index (BMI) and prognosis in heart failure patients after cardiac resynchronization therapy-defibrillator (CRT-D) implantation. METHODS: We retrospectively investigated 125 patients (33 overweight [BMI ≥25 kg/m(2)], 75 normal weight [BMI 18.5-24.9 kg/m(2)], and 17 underweight patients [BMI <18.5 kg/m(2)]) who underwent CRT-D implantation. The clinical outcome endpoints were all-cause death and appropriate shock therapy. RESULTS: During the follow-up period (mean 3.1 ± 1.8 years), 23 patients died (1 [3.0 %] overweight, 17 [22.7 %] normal weight, and 5 [29.4 %] underweight patients), and appropriate shock events were observed in 14 patients (2 [6.1 %] overweight, 10 [13.3 %] normal weight, and 2 [11.8 %] underweight patients). All patients survived shock therapy. After adjusting for confounding factors, overweight patients had significantly fewer outcomes relating to all-cause death and appropriate shock events (hazard ratio 0.27, 95 % confidence interval 0.08-0.91, p = 0.034) than normal weight patients. However, the prognostic difference between overweight and normal weight patients could be diminished as a result of the successful shock therapies (p = 0.067). Additionally, prognosis did not differ between overweight and normal weight patients among the responders, but did differ among the non-responders. The underweight patients had a poorer prognosis after CRT-D implantation compared with the other groups. CONCLUSIONS: Although high BMI was associated with better outcomes among heart failure patients with CRT-D implantations, the difference in the prognosis between overweight and normal weight patients was reduced because of defibrillator therapy and the improvement in cardiac function provided by CRT-D implantation.

Differences in activated clotting time among uninterrupted anticoagulants during the periprocedural period of atrial fibrillation ablation.

BACKGROUND: Close monitoring of intraoperative activated clotting time (ACT) is crucial to prevent complications during the periprocedural period of atrial fibrillation (AF) ablation. However, little is known about the ACT in patients receiving new oral anticoagulant agents (NOACs). OBJECTIVE: The purpose of this study was to evaluate change in the ACT among anticoagulant agents used during the periprocedural period of AF ablation. METHODS: We examined 869 consecutive patients who underwent AF ablation between April 2012 and August 2014 and received NOACs (n = 499), including dabigatran, rivaroxaban, and apixaban, or warfarin (n = 370) for uninterrupted periprocedural anticoagulation. Changes in intraprocedural ACT were investigated among the anticoagulant agents. Furthermore, the incidence of periprocedural events was estimated. RESULTS: The average time in minutes required for achieving a target ACT >300 seconds was significantly longer in the dabigatran group (DG) and apixaban group (AG) than in the warfarin group (WG) and rivaroxaban group (RG) (60 and 70 minutes vs 8 and 9 minutes, respectively; P < .001). In addition, the proportion of patients who achieved the target ACT after initial heparin bolus was significantly lower in the DG and AG than in the WG and RG (36% and 26% vs 84% and 78%, respectively; P < .001). Furthermore, the incidence of periprocedural complications was equivalent among the groups. CONCLUSION: The average time required to reach the target ACT was longer in the DG and AG than in the WG and RG.

Efficacy and safety of apixaban in the patients undergoing the ablation of atrial fibrillation.

INTRODUCTION: Apixaban, a factor Xa (FXa) inhibitor, is a new oral anticoagulant for stroke prevention in atrial fibrillation (AF). However, little is known about its efficacy and safety as a periprocedural anticoagulant therapy for patients who had undergone catheter ablation (CA) for AF. METHODS AND RESULTS: We evaluated 342 consecutive patients who underwent CA for AF between April 2013 and March 2014 and received apixaban (n = 105) and warfarin (n = 237) for uninterrupted periprocedural anticoagulation. We retrospectively investigated the occurrence of bleeding and thromboembolic complications during the procedural period and compared them between the apixaban group (AG) and warfarin group (WG). Thromboembolic complications occurred in one (0.4%) patient in the WG. Major and minor bleeding complications occurred in one (1%) and four (4%) patients in the AG, and three (1%) and 12 (5%) patients in the WG. No significant difference in complications was observed between the AG and WG. Of importance, adverse event rates did not differ between the two groups after adjusting by a propensity score analysis. In preoperative tests of blood coagulation, there were significant differences in the prothrombin time, activated partial thromboplastin time, FXa activity, and prothrombin fragment 1 + 2 (F1+2) levels between the AG and WG. CONCLUSION: The use of apixaban during the periprocedural period of AF ablation seemed as efficacious and safe as warfarin.

Clinical characteristics and predictors of super-response to cardiac resynchronization therapy: a combination of predictive factors.

BACKGROUND: Patients with greater improvement of cardiac function after cardiac resynchronization therapy (CRT) implantation are identified as "super-responders." However, it remains unclear which kind of preimplant assessments could accurately predict outcomes after CRT. Thus, we aimed to examine the essential predicting factors for super-response to CRT, and to construct an accurate predictable model. METHODS: We retrospectively analyzed the CRT patients who underwent implantation at Nagoya University Hospital. Super-responders are defined as those who show a relative reduction in left ventricular end-systolic volume ≥30% after 6 months of CRT. RESULTS: Eighty patients (mean age, 67.8 ± 10.2 years) were included. Twenty-two patients received upgrading procedure to CRT implantation. Six months after the implantation, 29 patients (36%) were super-responders. Multiple logistic regression analysis shows that consistent right ventricular pacing with a previous device (odds ratio [OR] 7.28, 95% confidence interval [CI] 1.52-34.9; P = 0.013), lack of prior history of ventricular arrhythmia (OR 5.32, 95% CI 1.52-18.6; P = 0.009), and smaller left atrial diameter (LAD) (OR 0.92, 95% CI 0.86-0.98; P = 0.014) are independent predictors for CRT super-responders. The use of a combination of these predictive factors could increase the certainty with which a greater response to CRT is predicted and the presence of such a combination could improve prognosis. CONCLUSION: Greater response to biventricular pacing occurs more frequently in patients with consistent right ventricular pacing, lack of prior history of ventricular arrhythmia, and smaller LAD. An association between patient background characteristics and a super-response to CRT was also identified.

Clinical outcome of implantable cardioverter defibrillators with recalled and non-recalled leads in Japanese patients. Increased failure rate of the Sprint Fidelis lead.

BACKGROUND: In recent years, there has been a series of recalls of popular implantable cardioverter defibrillators leads, and several reports have demonstrated an increasing rate of failure of such leads over time in Caucasian patients. However, little is known about the performance of these leads in Asian patients. The aim of this study was to investigate the rate of failure of the recalled leads and the characteristics as compared with non-recalled leads in Japanese patients. METHODS AND RESULTS: A retrospective chart review was conducted in 214 patients (75 Sprint Fidelis, 8 Riata, and 131 Sprint Quattro leads) who underwent implantation and follow-up at Nagoya University Hospital. During the follow-up period, 14 Sprint Fidelis leads (19%) and 1 Riata lead (13%) failed, but no abnormality was found in the Sprint Quattro, non-recalled leads. Five patients (4 Sprint Fidelis and 1 Riata, 33% of lead failure patients) received inappropriate shocks. The 3-, 4-, and 5-year lead survival rates in Sprint Fidelis leads were 95.1% (95% confidence interval [CI]: 89.6%-100%), 89.8% (95% CI: 82.1%-97.6%), and 88.0% (95% CI: 79.6%-96.4%), respectively. A previous device implantation before Sprint Fidelis lead was the only significant predictor for lead fracture (hazard ratio, 5.33; 95% CI: 1.55-18.4; P=0.008). CONCLUSIONS: The rate of Sprint Fidelis lead failure continues to increase over time in Japanese patients.

Effects of bag-mask versus advanced airway ventilation for patients undergoing prolonged cardiopulmonary resuscitation in pre-hospital setting.

BACKGROUND: There is no evidence that the advanced airway ventilation (AAV) method improves patient outcome in the pre-hospital cardiac arrest setting. OBJECTIVE: The aim of this study was to estimate the effectiveness of AAV vs. bag-mask ventilation (BMV) for cardiopulmonary arrest (CPA) patients, when administered by a licensed emergency medical technician in the pre-hospital setting. METHODS: The study used the database of patients who suffered out-of-hospital cardiogenic CPA from 2006 to 2007 in our hospital. Patient records were searched for the method of pre-hospital airway management (BMV or AAV) and the patient's outcomes were compared between groups. The primary endpoint was a favorable neurological outcome; the secondary endpoints were rate of return of spontaneous circulation (ROSC) and rate of admission to the intensive care unit (ICU). RESULTS: A total of 355 CPA patients (156 BMV and 199 AAV) were retrospectively enrolled. There was no significant difference in demographics between the two groups. The transportation time exceeded 30 min in both groups. The overall ROSC rate and ICU admission rate were significantly higher in the AAV group (p = 0.0352 and p = 0.0089, respectively). The data showed that AAV (odds ratio 1.960; 95% confidence interval 1.015-3.785) resulted in a higher overall ROSC rate than BMV, but there were no significant differences in either the rate of pre-hospital ROSC or in favorable neurological outcome. CONCLUSION: AAV may yield advantages over BMV in the overall rate of ROSC in CPA patients, but both approaches for airway management in this study resulted in a comparably favorable neurological outcome. Earlier ROSC would be required for improved overall outcome.