Masako Misaki

Triple Antithrombotic Therapy Is the Independent Predictor for the Occurrence of Major Bleeding Complications Analysis of Percent Time in Therapeutic Range

Background—Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention. However, it remains unclear whether good control of percent time in therapeutic range is associated with reduced occurrence of bleeding complications in patients undergoing triple antithrombotic therapy. Methods and Results—This study included 2648 patients (70±11 years; 2037 men) who underwent percutaneous coronary intervention with stent in the Ibaraki Cardiovascular Assessment Study registry and received dual antiplatelet therapy with or without warfarin. Clinical end points were defined as the occurrence of major bleeding complications (MBC), major adverse cardiac and cerebrovascular event, and all-cause death. Among these 2648 patients, 182 (7%) patients received warfarin. After a median follow-up period of 25 months (interquartile range, 15–35 months), MBC had occurred in 48 (2%) patients, major adverse cardiac and cerebrovascular event in 484 (18%) patients, and all-cause death in 206 (8%) patients. Multivariable Cox regression analysis revealed that triple antithrombotic therapy was the independent predictor for the occurrence of MBC (hazard ratio, 7.25; 95% confidence interval, 3.05–17.21; P<0.001). The time in therapeutic range value did not differ between the patients with and without MBC occurrence (83% [interquartile range, 50%–90%] versus 75% [interquartile range, 58%–87%]; P=0.7). However, the mean international normalized ratio of prothrombin time at the time of MBC occurrence was 3.3±2.1. Triple antithrombotic therapy did not have a predictive value for the occurrence of all-cause death (P=0.1) and stroke (P=0.2). Conclusions—Triple antithrombotic therapy predisposes patients to an increased risk of MBC regardless of the time in therapeutic range.

Elevated plasma norepinephrine level and sick sinus syndrome in patients with lone atrial fibrillation

Objective Plasma norepinephrine (NE) level can be a guide to mortality in patients with heart failure. This study aimed to evaluate the significance of plasma NE level compared with plasma natriuretic peptides (atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) levels in patients with atrial fibrillation (AF). Methods Included in this study were 137 consecutive patients referred for catheter ablation of lone AF (paroxysmal in 90 and persistent in 47 patients). Blood samples for measurements of ANP, BNP and NE were drawn in the supine position before the procedure. Results ANP, BNP and NE levels were greater in patients with persistent AF than in patients with paroxysmal AF (median (25th–75th centile)=28 (18–49) vs 69 (36–106), p<0.0001; 28 (15–50) vs 94 (39–156), p<0.0001; and 315 (223–502) vs 382 (299–517) pg/mL, p=0.04, respectively). NE level correlated weakly with ANP and BNP levels (r=0.28 and r=0.23, respectively, p<0.01 for both). BNP and NE levels differed between patients with and without recurrence of AF (55 (26–135) vs 35 (18–64), p=0.005 and 431 (323–560) vs 302 (225–436) pg/mL, p<0.001, respectively). Of note, only NE level was significantly greater in patients with symptomatic sick sinus syndrome (SSS) (n=21) than in those without SSS (560 (466–632) vs 321 (242–437) pg/mL, p<0.0001). Logistic regression analysis showed NE level to be the only independent discriminator for SSS (OR 1.006, 95% CI 1.002 to 1.010, p=0.001). Conclusions An increase in plasma NE level was observed in patients with AF and SSS. Although this implies a pathophysiological link between clinical manifestation of SSS and the autonomic nervous dysfunction, further studies are needed to clarify the mechanisms for this novel finding.

Drug-eluting versus bare-metal stents in large coronary arteries of patients with ST-segment elevation myocardial infarction: Findings from the ICAS registry

BACKGROUND AND PURPOSE There are a few retrospective subgroup analyses or registries of large-vessel (≥ 3.5mm) stenting. We investigated clinical outcomes of patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare-metal stents (BMS) in large coronary vessels. METHODS AND SUBJECTS Of 1100 STEMI patients registered in the Ibaraki Cardiovascular Assessment Study (ICAS) multicenter registry from April 2007 to June 2012 who underwent PCI, we enrolled 454 patients (65.8 ± 12.7 years old, 81% male) with ≥ 3.5-mm stents. We excluded 53 patients with cardiogenic shock or left main trunk lesions. The remaining 401 patients were divided into Group-D, PCI with DES (n = 184), and Group-B, PCI with BMS (n = 217). Propensity score analysis matched 1:1 according to treatment with DES (n = 101) or with BMS (n = 101). We evaluated major adverse cardiac and cerebrovascular events (MACCE) and incidence of stent thrombosis (ST). MACCE was defined as all-cause death, myocardial infarction (MI), target-vessel revascularization (TVR), or cerebrovascular accident (CVA). ESSENTIAL RESULTS During a mean follow-up period of 526 days, all-cause death, MI, CVA, MACCE, and ST were not significantly different in Group-D versus Group-B (all-cause death: 4.35% vs. 4.61%, p = 0.90; MI: 0% vs. 0%; CVA: 2.72% vs. 3.23%, p = 0.76; MACCE: 15.2% vs. 20.3%, p = 0.19; and ST: 0.0% vs. 1.38%, p = 0.11). After adjusting for age, insulin use, multivessel disease, intra-aortic balloon pump use, culprit lesions, and estimated glomerular filtration rate <60 ml/min/1.73 m(2), MACCE was not significantly different between the groups (odds ratio: 0.69; 95% CI: 0.40-1.23; p = 0.21). However, TVR was significantly lower in Group-D than Group-B in Kaplan-Meier analysis (p = 0.048) after propensity score matching. PRINCIPAL CONCLUSION There was no advantage to using a DES in large vessels for preventing a hard endpoint, whereas DES use resulted in a significant reduction in TVR in the patients with STEMI in this registry.

Addition of spironolactone to an angiotensin-converting enzyme inhibitor decreases lung congestion and edema in Dahl hypertensive rats

We investigated the effect of adding spironolactone to treatment with an angiotensin-converting enzyme (ACE) inhibitor, imidapril, in Dahl salt-sensitive (DS) hypertensive heart failure rats with preserved systolic function. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Rats were divided into four groups and treated for 9 weeks with vehicle alone (water; n = 23), the ACE inhibitor imidapril (1 mg kg−1 day−1; n = 16), spironolactone (2 mg kg−1 day−1; n = 15), or a combination of imidapril and spironolactone at the doses above (n = 16). The left ventricular weight to body weight (BW) ratio was significantly lower in the imidapril group (3.28 ± 0.30 mg g−1) and the combination group (3.34 ± 0.38 mg g−1) than in the vehicle group (3.71 ± 0.46 mg g−1). Adding spironolactone to imidapril inhibited an increase in the ratio of lung weight to BW (4.38 ± 0.50 mg g−1) related to high salt intake, while monotherapy (imidapril group, 4.61 ± 0.90 mg g−1; spironolactone group, 5.40 ± 2.50) did not significantly change the ratio from that seen with vehicle treatment (6.32 ± 3.62 mg g−1). All active treatments (imidapril, 0.66% ± 0.67%; spironolactone, 0.51% ± 0.55%; both together, 0.31% ± 0.26%) inhibited a salt-intake related increase in the percentage area representing fibrous tissue compared with vehicle treatment alone (1.81% ± 1.51%). These findings suggest that adding spironolactone to an ACE inhibitor is more effective in improving pulmonary congestion and edema in hypertensive heart failure with preserved systolic function than an ACE inhibitor alone.

Electrophysiological relation between the superior vena cava and right superior pulmonary vein in patients with paroxysmal atrial fibrillation

The superior vena cava (SVC) is a main source of nonpulmonary vein (PV) ectopies initiating atrial fibrillation (AF). Empiric SVC isolation may improve rhythm outcomes after catheter ablation of AF. Because the SVC passes immediately adjacent to the right superior PV (RSPV), an electrophysiological relation could be present between the two structures. The present study aimed to estimate the interrelation between the SVC and RSPV by evaluating arrhythmogenic activities observed during catheter ablation of AF.

TROPONIN ELEVATION AFTER RADIOFREQUENCY CATHETER ABLATION OF ATRIAL FIBRILLATION: RELEVANCE TO AF SUBSTRATE AND REVERSE STRUCTURAL REMODELING

Although radiofrequency ablation energy creates localized lesions and myocardial necrosis leading to troponin T (TnT) release into the systemic circulation, the significance of TnT elevation post atrial fibrillation (AF) ablation is unknown. We aimed to demonstrate a possible mechanism of left