Impact of high frequency stimulation to confirm a complete box isolation in catheter ablation of non-paroxysmal atrial fibrillation.

INTRODUCTION: Pulmonary vein (PV) isolation (PVI) including the left atrial posterior wall (LAPW) (Box-PVI) is proposed as an additional strategy for non-paroxysmal atrial fibrillation (NPAF), however, the efficacy remains controversial. The more reliable and durable the Box-PVI we can create, the better the rhythm outcomes might be than with a conventional PVI alone. This study focused on the potential exit conduction of the box lesion and investigated whether the conventional Box-PVI would be sufficient. METHODS AND RESULTS: We enrolled 350 consecutive patients with NPAF that underwent a conventional encircling Box-PVI and examined whether latent exit conduction and dormant "exit" conduction independently remained on the LAPW and in the PVs using high frequency stimulation (HFS) and an adenosine triphosphate (ATP) injection. All electrograms inside the box lesion were eliminated in all cases, however, HFS inside the box propagated outward in 23 cases (6.6%) without any exit conduction by conventional burst stimulation, and 24 cases (6.9%) exhibited only dormant "exit" conduction of the LAPW. Additional ablation where positive HFSs were observed created a complete bidirectional Box-PVI in 43 (41.3%) of the cases without a first pass Box-PVI. The recurrence rates depended on the groups classified according to the HFS response. CONCLUSION: HFS delivered with an ATP injection on the LAPW and in the PVs following a Box-PVI could not only elucidate true exit block but also identified possible incomplete lesions or connections outside the ablation line, whose elimination could achieve a complete Box-PVI leading to a better rhythm outcome.

Novel TSURECOMI Bailout Technique for Transcatheter Heart Valve Implantation After Accidental Wire Withdrawal During TAVR.

This study introduces a case in which our novel "Transarterial Snare-Upholding REcovery technique for COMpletely pulled out LV wire for TAVR valve Insert system (TSURECOMI) technique" with snares was successfully performed for bailout of a transcatheter heart valve during transcatheter aortic valve replacement. (Level of Difficulty: Advanced.).

Potential complications in patients undergoing an ethanol injection into the vein of Marshall.

BACKGROUND: Ethanol injections into the vein of Marshall (VOM) (EIM) are considered to be a good therapeutic option for atrial tachyarrhythmias, however, the safety remains to be determined. To elucidate what would affect the safety and potential complications of an EIM, we investigated the anatomical features of the VOM and patient background. METHODS: We performed the EIM before the conventional pulmonary vein isolation for drug-resistant atrial fibrillation in 88 patients and evaluated the anatomical features of the VOM and their background. RESULTS: All procedures were completed, however, other than myocardial staining, trivial contrast medium leaked out of the VOM into the pericardial space, that is, extravasation of contrast medium with capillary rupture, during the EIM in 20 patients (22.7%) regardless of the features of the VOM. No pericardial effusions requiring further intervention developed after the extravasation, which resolved by the next day on echocardiography in 18 of those patients. However, two patients who had extravasation other than during the initial contrast injection required additional therapeutic intervention for nonnegligible pericardial effusions. Their body weights were significantly lower and the latter two patients were also small lean women with heart failure and a preserved ejection fraction. CONCLUSIONS: The physical constitution, regardless of the characteristics of the VOM, could be strongly associated with adverse events during the EIM. We must take extreme care in smaller patients with poor compliant hearts during the EIM.

Fistula between the Thoracic Duct and an Unusual Vessel Aneurysm Branching Off the Abdominal Aorta Revealed by Aneurysm Rupture: A Case Report.

Fistulas between an aneurysm branching off the abdominal aorta and the thoracic duct are rare. We report a case of aneurysmal-thoracic duct fistula diagnosed by angiography when aneurysm ruptured, and we successfully treated by catheter embolization. A 42-year-old man was referred to our hospital with a chief complaint of sudden back and chest pain. Computed tomography showed both post-mediastinal and retroperitoneal hematomas, with the aneurysm from the aorta being connected to the thoracic duct. After confirming the aneurysmal-thoracic duct fistula by angiography, we performed embolization of the aneurysm. The patient has remained well for 3 postoperative months, to date.

Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06). CONCLUSION: Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI. TRIAL REGISTRATION: CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

Ethanol injection into the Marshall vein provoking a pericardial effusion resulting in a fatal complication in a patient with persistent atrial fibrillation.

An EIM (ethanol infusion into the vein of Marshall [VOM]) provoked a fatal complication in a chronic hemodialysis patient. Autopsy revealed a lacerated VOM covered with thrombi as the only potential cause. The EIM caused vascular damage and clots resulting in myocardial necrosis and interstitial bleeding around the lacerated VOM.

Safety margin of minimized contrast volume during percutaneous coronary intervention in patients with chronic kidney disease.

Maximum allowable contrast dose (MACD) calculated as body weight × 5/serum creatinine has been a standard contrast dye volume (CV) used to decrease contrast-induced acute kidney injury. Recent advances in intravascular ultrasound-guided percutaneous coronary intervention (PCI) can dramatically minimize CV. The safe threshold when using an extremely low-dose CV is unknown. This study was designed as a multicenter, retrospective study of chronic kidney disease (CKD) patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m(2) undergoing elective PCI. We divided the patients into three groups according to following criteria: (1) low dose, CV/eGFR ratio <1.0; (2) medium dose, CV/eGFR ratio ≥1 and

Coexistence of visceral fat and multiple risk factor accumulations is strongly associated with coronary artery disease in Japanese (the VACATION-J study).

AIM: Multiple risk factor syndrome is a target for the prevention of coronary artery disease (CAD). A cluster of multiple risk factors, such as hypertension, glucose intolerance, and/or dyslipidemia, is encountered in Japanese without and with excess visceral fat. The present study investigated the relationship between multiple risk factor accumulation and CAD in Japanese without and with visceral fat accumulation. METHODS: The study subjects comprised 257 Japanese with suspected CAD (males/females= 153/ 104), who underwent 64-row multislice computed tomography (CT) coronary angiography and visceral fat area (VFA) measurement by CT. Based on the Japanese criteria for visceral fat accumulation, they were divided into those with VFA <100 and ≥10 cm(2). RESULTS: In subjects with VFA <100 cm(2), the age- and sex-adjusted odds ratios (ORs) for 2 and 3 risk factors were 5.33 (95% confidence intervals; 1.04-27.38, p=0.0449) and 4.07 (0.72-23.15, p=0.1138), respectively, compared with VFA <100 cm(2) and 0 risk factor set at 1.0 (p=0.0569 for trend). In contrast, the respective ORs for subjects with VFA ≥100 cm(2) were much higher [6.46 (1.25-33.44, p=0.0261) and 20.42 (3.60-115.73, p=0.0007)] (p<0.0001 for trend). The multivariate adjusted model demonstrated a significant relative excess CAD risk of 1.08 (p=0.0484) and 5.01 (p<0.0001) for the interactions of 2 risk factors and VFA ≥100 cm(2), and 3 risk factors and VFA ≥100 cm(2), whereas multiple risk factor accumulation was not related with the increase of CAD risk in subjects with VFA <100 cm(2). CONCLUSIONS: Coexistence of visceral fat and risk factor accumulations is strongly associated with CAD in Japanese.

Spatiotemporal characteristics of rhythmic, stationary basketball bouncing in skilled and unskilled players.

The aim of this study was to investigate the spatiotemporal characteristics of rhythmic, stationary basketball bouncing in skilled and unskilled adult basketball players. Skilled (n=12) and unskilled (n=11) basketball players were asked to bounce a basketball every 700 msec. in as temporally stable and spatially accurate a manner as possible, while keeping their eyes fixed straight ahead. Spatial analyses revealed a lower variability of the ball bouncing point and less deviation from a target point in the performance of skilled players compared to unskilled players. Temporal analyses revealed no significant difference in variability of the interbounce interval in skilled versus unskilled players. However, skilled players had longer and more consistent contact time between hand and ball compared to the unskilled players. These results suggest that longer and more consistent hand contact with the ball play an important role in spatial control of basketball bouncing position.

Pleiotropic effects of the beta-adrenoceptor blocker carvedilol on calcium regulation during oxidative stress-induced apoptosis in cardiomyocytes.

Carvedilol is a nonselective beta-adrenoceptor blocker with multiple pleiotropic actions. A recent clinical study suggested that carvedilol may be superior to other beta-adrenoceptor blockers in the treatment of heart failure. Despite numerous investigations, the underlying mechanisms of carvedilol on improving heart failure are yet to be fully established. The purpose of this study is to clarify the pleiotropic effect of carvedilol on cytosolic and mitochondrial calcium regulation during oxidative stress-induced apoptosis in cardiomyocytes. Carvedilol (10 microM), but not metoprolol (10 microM), reduced H2O2 (100 microM)-induced apoptosis in neonatal rat cardiomyocytes. During the process, changes in cytosolic calcium concentration ([Ca2+]i) and mitochondrial calcium concentration ([Ca2+]m) and mitochondrial membrane potential (DeltaPsim) were measured by fluorescent probes [Fluo-3/acetoxymethyl ester (AM), Rhod-2/AM, and tetramethylrhodamine ethyl ester, respectively] and imaged by laser confocal microscopy. The results showed that H2O2 caused [Ca2]m overload first, followed by [Ca2+]i overload, leading to DeltaPsim dissipation and the induction of apoptosis. Carvedilol (10 microM) significantly delayed these processes and reduced apoptosis. These effects were not observed with other beta-adrenoceptor blockers (metoprolol, atenolol, and propranolol) or with a combination of the alpha (phentolamine)- and the beta-adrenoceptor blocker. The antioxidant N-acetyl-L-cysteine (NAC, 5 mM) and the combination of NAC and propranolol (10 microM) showed an effect similar to that of carvedilol. Therefore, the effect of carvedilol on H2O2-induced changes in [Ca2+]m, [Ca2+]i, and DeltaPsi(m) is independent of alpha- and beta-adrenoceptors but is probably dependent on the antioxidant effect.

Carvedilol inhibits mitochondrial oxygen consumption and superoxide production during calcium overload in isolated heart mitochondria.

BACKGROUND: The COMET study suggested the better effect of carvedilol to metoprolol in treating heart failure. However, its underlying mechanisms of action remain unclear. As a result, evaluation of the distinct effects of both drugs on the mitochondrial function and reactive oxygen species (ROS) production during Ca(2+) overload was investigated. METHODS AND RESULTS: The mitochondrial oxygen consumption (mVO(2)) and the mitochondrial ROS production in isolated rat heart mitochondria was measured. Ca(2+) overload from 10 to 100 micromol/L augmented mVO(2) was from 527+/-139 to 671 +/-138 nmol/mg (p<0.05), and this was then completely suppressed by carvedilol (1 micromol/L), but not by metoprolol (100 micromol/L). Ca(2+) overload augmented the ROS production upon complex I injury (9.7+/-1.2 to 11.4+/-1.4 nmol/mg, p<0.05). Carvedilol dose-dependently suppressed this ROS production, whereas metoprolol did not. CONCLUSIONS: Carvedilol, but not metoprolol, was thus found to inhibit the calcium-dependent augmentation of mVO(2) and ROS production upon complex I injury. This new effect of carvedilol might partly explain the beneficial effect of carvedilol for the treatment of heart failure.

NO donor-activated PKC-delta plays a pivotal role in ischemic myocardial protection through accelerated opening of mitochondrial K-ATP channels.

Nitric oxide (NO) can activate protein kinase C (PKC) and the activation of mitochondrial ATP-sensitive potassium (K-ATP) channels is cardioprotective. However, interactions among NO, PKC, and mitochondrial K-ATP channels remain vague. To clarify the cardioprotective mechanism induced by nicorandil, we compared its ability to activate PKC isoforms with that of the mitochondrial K-ATP channel opener, diazoxide. We induced myocardial infarction in rats by 30 minutes of ischemia followed by reperfusion, then assessed the infarct size 3 weeks later. We also examined the translocation of PKC isoforms in the isolated perfused rat heart. Nicorandil and diazoxide reduced infarct size, and the effect of nicorandil, but not of diazoxide attenuated by the PKC inhibitor, chelerythrine, or by the NO quencher, carboxy PTIO. Immunoblotting revealed that nicorandil translocated PKC-delta to the mitochondria, and that this was inhibited by carboxy PTIO. The protective effect of nicorandil against myocardial infarction partly depended on the translocation of PKC-delta to the mitochondria, which we attributed to the NO donor effect of nicorandil. The PKC-delta- dependent activation of mitochondrial K-ATP channel opening might be synergistic with its direct effect, making nicorandil an efficient opener of such channels.

Effect of ischemic preconditioning and mitochondrial KATP channel openers on chronic left ventricular remodeling in the ischemic-reperfused rat heart.

The influence of ischemic preconditioning (IP) and mitochondrial ATP-sensitive potassium (mito-KATP) channel openers on chronic left ventricular (LV) remodeling remains unknown, so the effect of IP and mito-KATP channel openers on the LV pressure-volume curve was assessed in rats subjected to 30 min ischemia followed by a 3-week reperfusion. Infarct size was histologically determined at 3 weeks after reperfusion. The LV pressure-volume curve was significantly shifted left by IP, diazoxide and nicorandil compared with the controls. These effects were blocked by the selective mito-KATP channel blocker 5-hydroxydecanoate. The LV remodeling and the infarct size at 3 weeks after reperfusion correlated well, indicating that the reduction of LV remodeling in the ischemic-reperfused model was strongly influenced by attenuation of the ischemic injury. LV remodeling in the chronic phase is attenuated by IP and mito-KATP channel openers with concomitant reduction of infarct size.