Search

Kawasaki disease (KD) is an acute self-limited syndrome that predominantly affects children. Coronary sequelae have been identified to be responsible for a small, but significant percentage of young adults who present with myocardial ischemia. In this study, we present a case of an elderly patient with possible coronary sequelae of KD. A 76-year-old man was referred to our outpatient department for silent myocardial ischemia. Axial images of coronary computed tomography showed multiple lumens in the proximal left anterior descending (LAD) artery. Coronary angiography demonstrated braid-like appearance in the proximal and distal segment of the LAD. Coronary intervention was successfully performed for the proximal LAD lesion using directional atherectomy (DCA) catheter. Microscopic examination of the DCA specimens showed the following histological features: tissues in densely hyalinized fibrosis with occasional microcalcification, or those containing a number of smooth muscle cells (SMCs) with myxoid extracellular matrix. There was paucity of cholesterin crystals and aggregation of foamy cells. In addition, scarcely any inflammatory cell filtration was identified. In the section of SMC-containing samples, formation of multiple re-canalized vessels embracing endothelial cells was confirmed. These histopathologic findings indicated that the present coronary artery lesion has a high possibility of very late cardiovascular sequelae caused by arteritis due to KD, rather than arteriosclerosis. This is the oldest adult case with coronary artery disease possibly resulting from KD sequelae. This case highlights that KD sequelae must be considered as a cause of coronary artery lesion even in older patients.

After taking an estrogen-containing supplement derived from a tropical plant Pueraria mirifica, a 24-year-old woman presented marked QT prolongation and repetitive torsade de pointes. The patient was found to carry a heterozygous KCNQ1-T587M mutation. This is the first report on Pueraria mirifica-related acquired long QT syndrome.

Practical management guidelines for impaired glucose tolerance (IGT) have not been established. Although IGT is a potent marker of cardiovascular disease (CVD), it is still controversial whether its magnitude of CVD risk is comparable to that of frank diabetes. Moreover, information on long-term clinical outcomes of IGT patients undergoing coronary revascularization is limited. The aim of the present work was to investigate the 10-year prognostic impact of IGT in comparison with diabetes in patients with CAD undergoing coronary revascularization. This cohort recruited from two Japanese clinical sites included patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) between 2004 and 2008. Patients were categorized into previously known diabetes (PKD, n = 197), newly diagnosed diabetes (NDD, n = 51), and IGT (n = 50) groups according to oral glucose tolerance test results except for PKD. The primary end point was defined as a composite of cardiovascular death, myocardial infarction, stroke, repeat revascularization, and heart failure hospitalization. The cumulative risk of the primary outcome was significantly higher in the PKD and IGT than in the NDD (log-rank test p = 0.017). A Cox proportional hazards model demonstrated that IGT (hazard ratio [HR], 7.91; 95% confidence interval [CI], 1.84–27.58) and creatinine clearance (HR, 7.89, 95% CI, 2.73–19.10) were predictors of long-term CVD risk, while NDD and PKD were not. IGT significantly increased the long-term risk of developing CVD in patients with CAD after PCI compared with diabetes.

Glycemic variability (GV) is relevant to impaired myocardial salvage in acute ST-elevation myocardial infarction (STEMI). Severity of hypokinesis at the infarct site as assessed from contrast left ventriculography can reportedly predict infarct size in STEMI. We prospectively studied 58 consecutive patients (mean age, 63 ± 11 years) with anterior or inferior STEMI who underwent successful reperfusion therapy. Mean amplitude of glucose excursion (MAGE) was obtained from continuous glucose monitoring system. Patients were divided into the upper tertile of MAGE as Group H, and the other two-thirds as Group L. Serial regional wall motion severity at the infarct site was computed postprocedure and at follow-up using a quantitative left ventricular analysis system. Impaired myocardial salvage was defined as severity recovery ratio

In patients with chronic heart failure (HF), the clinical importance of sarcopenia has been recognized in relation to disease severity, reduced exercise capacity, and adverse clinical outcome. Nevertheless, its impact on acute decompensated heart failure (ADHF) is still poorly understood. Dual-energy X-ray absorptiometry (DXA) is a technique for quantitatively analyzing muscle mass and the degree of sarcopenia. Fat-free mass index (FFMI) is a noninvasive and easily applicable marker of muscle mass.This was a prospective observational cohort study comprising 38 consecutive patients hospitalized for ADHF. Sarcopenia, derived from DXA, was defined as a skeletal muscle mass index (SMI) two standard deviations below the mean for healthy young subjects. FFMI (kg/m2) was calculated as 7.38 + 0.02908 × urinary creatinine (mg/day) divided by the square of height (m2).Sarcopenia was present in 52.6% of study patients. B-type natriuretic peptide (BNP) levels were significantly higher in ADHF patients with sarcopenia than in those without sarcopenia (1666 versus 429 pg/mL, P < 0.0001). Receiver operator curves were used to compare the predictive accuracy of SMI and FFMI for higher BNP levels. Areas under the curve for SMI and FFMI were 0.743 and 0.717, respectively. Multiple logistic regression analysis showed sarcopenia as a predictor of higher BNP level (OR = 18.4; 95% CI, 1.86-181.27; P = 0.013).Sarcopenia is associated with increased disease severity in ADHF. SMI based on DXA is potentially superior to FFMI in terms of predicting the degree of severity, but FFMI is also associated with ADHF severity.

Background During bipolar (BIP) radiofrequency (RF) ablation using two catheters in humans, each catheter is placed in separate cardiac chambers or spaces. We developed a contact force-controlled experimental preparation, and compared measurements made with two catheters placed in a single bath (SB), versus each catheter placed in separate baths, in order to assess the preparation-dependent differences in the results of BIP-RF ablation. Methods In the SB experiments, a porcine heart was placed in the center of the bath, while in the dual-bath (DB) experiments, it was placed between two half baths communicating through windows. Results The initial impedance was greatest (110.5 ± 7.2 Ω) with the BIP-DB, followed by the BIP-SB (92.0 ± 5.6 Ω) and the unipolar (UNIP) DB (84.9 ± 4.7 Ω) configurations. During 50-W ablation for 60 seconds at a 20-g contact force, the root mean square voltage was 75.7 ± 2.5 V in the BIP-DB, 68.0 ± 2.1 V in the BIP-SB, and 66.8 ± 2.0 V in the UNIP-DB. The mean surface lesion diameters were similar among the three configurations. However, the endocardial lesion depth was 5.60 ± 0.56 mm with the BIP-DB, 4.71 ± 0.64 mm with the BIP-SB, and 4.24 ± 0.58 mm with the UNIP-DB configuration. On average, the endocardial lesions were significantly deeper than the epicardial ones. Conclusions BIP ablation created much deeper lesions as compared to UNIP ablation. Lesion depth could be different depending on experimental preparation, and contact force-controlled DB preparation may be a much more appropriate model for studying the effects of BIP ablation.

Objective Left ventricular outflow tract (LVOT) obstruction is a complication in 15-25% of patients with Takotsubo cardiomyopathy and sometimes leads to catastrophic outcomes, such as cardiogenic shock or cardiac rupture. However, the underlying mechanisms have not been clarified. Methods and Results We experienced 22 cases of Takotsubo cardiomyopathy during 3 years, and 4 of these 22 cases were complicated with LVOT obstruction in the acute phase (mean age 79±5 years, 1 man, 21 women). The LVOT pressure gradient in the acute phase was 100±17 mmHg. Transthoracic echocardiogram (TTE) revealed left ventricular hypertrophy (LVH) in one case and sigmoid-shaped septum without LVH in three cases. The complete resolution of the LVOT obstruction was achieved in a few days with normalization of the left ventricular wall motion following administration of beta-blockers. A dobutamine provocation test after normalization of the left ventricular wall motion reproduced the LVOT obstruction in all cases and revealed the presence of latent LVOT obstruction. Conclusion The manifestation of latent LVOT obstruction in the acute phase of Takotsubo cardiomyopathy is one potential reason for the complication of LVOT obstruction with Takotsubo cardiomyopathy.

Background J waves develop during hypothermia, but the dynamicity of hypothermia-induced J waves is poorly understood. Objective The purpose of this study was to investigate the mechanism of the rate-dependent change in the amplitude of hypothermia-induced J waves. Methods Nineteen patients with severe hypothermia were included (mean age 70 ± 12 years; 16 men [84.2%]). The rectal temperature at the time of admission was 27.8° ± 2.5°C. In addition to prolonged PR, QRS complex, and corrected QT intervals, the distribution of prominent J waves was widespread in all 19 patients. Results Nine patients showed changes in RR intervals. When the RR interval shortened from 1353 ± 472 to 740 ± 391 ms (P = .0002), the J-wave amplitude increased from 0.50 ± 0.29 to 0.61 ±0.27 mV (P = .0075). The J-wave amplitude increased in 7 patients (77.8%) and decreased in 2 patients (22.2%) after short RR intervals. The augmentation of J waves at short RR intervals was associated with a significant prolongation of ventricular activation time (35 ± 5 ms vs 46 ± 5 ms; P = .0020), suggesting accentuated conduction delay. Increased conduction delay at short RR intervals was suggested to accentuate the phase 1 notch of the action potential and J waves in hypothermia. None developed ventricular fibrillation, and in 2 of 9 patients with atrial fibrillation, atrial fibrillation persisted after rewarming to normothermia. Conclusion J waves in severe hypothermia were augmented after short RR intervals in 7 patients as expected for depolarization abnormality, whereas 2 patients showed a bradycardia-dependent augmentation as expected for transient outward current–mediated J waves. Increased conduction delay at short RR intervals can be responsible for the accentuation of the transient outward current and J waves during severe hypothermia.

In patients with chronic heart failure (HF), the clinical importance of sarcopenia has been recognized in relation to disease severity, reduced exercise capacity, and adverse clinical outcome. Nevertheless, its impact on acute decompensated heart failure (ADHF) is still poorly understood. Dual-energy X-ray absorptiometry (DXA) is a technique for quantitatively analyzing muscle mass and the degree of sarcopenia. Fat-free mass index (FFMI) is a noninvasive and easily applicable marker of muscle mass.This was a prospective observational cohort study comprising 38 consecutive patients hospitalized for ADHF. Sarcopenia, derived from DXA, was defined as a skeletal muscle mass index (SMI) two standard deviations below the mean for healthy young subjects. FFMI (kg/m

Background The circadian pattern of ventricular fibrillation (VF) episodes in patients with idiopathic ventricular fibrillation (IVF) is poorly understood. Objective The purpose of this study was to assess the circadian pattern of VF occurrence in patients with IVF. Methods Excluding Brugada syndrome and other primary electrical diseases, the circadian pattern of VF occurrence was determined in 64 patients with IVF. The clinical and electrocardiographic characteristics were compared among patients with nocturnal (midnight to 6:00 AM) VF and nonnocturnal VF in relation to J waves. A J wave was defined as either notching or a slur at the QRS terminal >0.1 mV above the isoelectric line in contiguous leads. Results The overall distribution pattern of VF occurrence showed 2 peaks at approximately 6:00 AM and around 8:00 PM. Nocturnal VF was observed in 20 patients (31.3%), and J waves were present in 14 of these 20 individuals (70.0%), whereas J waves were less frequent in the 44 nonnocturnal patients with VF: 16 (36.4%) (P = .0117). Among patients with J waves, nocturnal VF was observed in 46.7% with a peak at approximately 4:00 AM. Nocturnal VF was less common in patients without J waves, occurring in only 17.6% (P = .0124). Both the type and location of J waves and the pattern of the ST segment were similar between the nocturnal and nonnocturnal VF groups. J waves were associated with a VF storm and long-term arrhythmia recurrence. Conclusion In IVF, the presence of J waves may characterize a higher nocturnal incidence of VF and a higher acute and chronic risk of recurrence.

This study was conducted to assess whether any relationships exist between glucose fluctuations and electrocardiographic surrogate markers of reperfusion injury in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).We prospectively studied 63 consecutive patients with STEMI undergoing primary PCI. Patients had either diabetes (n = 30), impaired glucose tolerance (n = 26), impaired fasting glucose (n = 1), or normal glucose tolerance (n = 6). STsegment resolution (STR, %) was measured using electrocardiograms recorded 60 minutes after PCI. STR was categorized as ≥ 30% and < 30%. Glucose fluctuations were assessed by the following parameters obtained from a continuous glucose monitoring system: mean amplitude of glucose excursion (MAGE, mg/dL); and area under curve with reference to mean blood glucose (AUCMBG, mg/ dL/day).Both MAGE and AUCMBG were significantly higher in STR < 30%. In univariate analysis, MAGE ≥ 70 mg/dL (OR = 17.0; 95%CI, 1.93-150.12; P < 0.01), AUCMBG ≥ 20 mg/dL/day (OR = 10.9; 95%CI, 1.92-61.77; P < 0.01), and reperfusion arrhythmias (OR = 7.6; 95%CI, 1.32-44.29; P < 0.05) were significantly associated with suboptimal STR. Multiple logistic regression analysis showed only MAGE ≥ 70 mg/dL was predictive of suboptimal STR (OR = 22.5; 95%CI, 2.43-208.66, P < 0.01).Parameters of glucose fluctuations correlated with electrocardiographic surrogate markers of impaired myocardial salvage in STEMI after reperfusion therapy. Our results suggest that glucose fluctuations may represent a potential therapeutic target to reduce myocardial reperfusion injury in STEMI.

Trunk muscle size decrease is reportedly an increased risk of multiple adverse clinical outcomes. Acute aortic dissection (AAD) involves a systemic inflammatory response which is associated with exaggerated muscle protein catabolism. AAD requires prolonged hospitalization and potentially exacerbates

ObjectivesThis study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms.BackgroundSome IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known.MethodsNinety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves >0.1 mV above the isoelectric line in contiguous leads.ResultsFourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs.ConclusionsThe VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents.

A 70-year-old man with severe symptomatic functional mitral valve regurgitation underwent successful mitral valve repair combined with tricuspid valve ring annuloplasty. Pre-operative coronary angiography (CAG) showed no significant stenosis. One-and-a-half years later, the patient presented with an acute exacerbation of heart failure. Repeat CAG demonstrated tight stenosis in the right coronary artery (RCA) with arterial kinking that corresponded to the same point as the stenosis where the RCA is the closest to the tricuspid valve ring. The new lesion probably occurred as a consequence of the tricuspid valve ring annuloplasty.

The patient was a 62-year-old woman with a chest X-ray abnormality. Transthoracic echocardiography (TTE) showed a dilated right ventricle and right atrium and an enlarged coronary sinus (CS), but definite diagnosis was not possible. Using contrast-enhanced 64-slice multidetector computed tomography (MDCT), curved planar reconstruction along the CS showed a direct connection of the left atrium and CS, in addition to the CS to right atrium connection. Unroofed CS is a rare congenital cardiac anomaly that is difficult to diagnose with TTE alone. Our case indicates that MDCT is useful for determining structural information that cannot be obtained from TTE. .

Background: Vasospastic angina (VSA) is reported to cause sudden cardiac death (SCD) due to lethal ventricular arrhythmias, even while a patient is undergoing drug therapy with calcium channel blockers (CCB). The prognostic factors are not fully assessed and the indication of implantable cardioverter-defibrillator (ICD) for patients with VSA is still controversial. We assessed the prognostic factors and outcomes of patients with VSA surviving out-of-hospital cardiopulmonary arrest (OHCA). Methods: Between November 2007 and February 2014, 129 VSA patients were diagnosed by provocative tests using ergonovine during coronary angiographies. The patients were divided into two groups: OHCA group consisted of patients with VSA surviving OHCA (n=15, median age: 58.2 ± 12.2 years) and non-OHCA group (n=114, median age: 60.3 ± 0.9 years). We analyzed the appearance of J wave in the resting ECG and T wave augmentation (more than two times compared to resting) during treadmill exercise tests in three groups (OHCA group, non-OHCA group and Control group consisting of healthy subjects (n=25, median age: 57.9 ± 1.8years)). Results: In resting ECG analysis, J wave was found in 9/15 (60%) of OHCA group, 42/114 (37%) of non-OHCA group and 3/25 (12%) of Control group. There was no significant difference in the appearance of J wave among the three groups. In ECG analysis of treadmill exercise tests, T wave augmentation in non-OHCA group (15/38, 39%) was significantly more frequent than that of Control group (3/25, 12%) (p=0.04). Furthermore T wave augmentation in OHCA group (10/12, 83%) was significantly more frequent than that of non-OHCA group (p=0.008). In OHCA group, all patients began treatment with CCB. Twelve of 15 patients (87%) underwent ICD therapy. During a follow up of 38.7 ± 18.4 months, three of 15 patients (20%) in OHCA group had appropriate ICD therapy or died: one patient received an appropriate ICD therapy for VF and successfully resuscitated, and two patients died suddenly among 3 patients without ICD implantations. Conclusions: In the risk stratification of SCD in VSA patients, T wave augmentation during treadmill exercise tests might be a new prognostic factor. ICD might result in favorable clinical outcomes for high-risk VSA patients.

To assess the electrophysiological characteristics of the breakout site of ventricular activation using electroanatomical voltage mapping (EVM) and its relation to the optimal ablation site in idiopathic ventricular tachyarrhythmias originating from the outflow tract of the (RVOT) septum.Twenty-eight patients with symptomatic drug-refractory premature ventricular complexes (PVCs) and/or ventricular tachycardia (VT) originating from the RVOT septum and 5 control subjects with WPW syndrome were included. Low-voltage areas (LVAs) were defined as signal amplitudes between 0.1 and 1.5 mV. The borderline between the normal area and the LVA was defined as "border," and the distance from the LVA to the border (length of LVA) was measured.In all 28 patients and control subjects, there was an LVA below the pulmonary valve. There was no significant difference in length of LVA between patients with idiopathic ventricular arrhythmias and control subjects (2.0 ± 0.6 vs. 1.9 ± 0.1 cm). In 19 of the 28 patients, the optimal ablation site was identical to the border area. In all 11 patients who had pre-potentials at the successful ablation site, there were two cases with polymorphic VT and/or ventricular fibrillation associated with PVCs. In these two cases, length of LVA was longer than in other patients (4.0 and 3.9 cm vs. 1.8 ± 0.5 cm (n = 26)), and the optimal ablation site was located at the border area.The border area, including the LVA, tends to be the breakout site and/or origin of ventricular arrhythmias in idiopathic ventricular tachyarrhythmia originating from the RVOT septum.

Premature ventricular complexes (PVC) falling after the end of the T wave triggered ventricular fibrillation (VF) at night and monomorphic ventricular tachycardia (MVT) during daytime, in a recipient of implantable cardioverter defibrillator with Brugada syndrome. Treatment with bepridil (1) decreased the height of ST segment elevation in leads V1-V3, (2) completely eliminated VF, and (3) markedly decreased the incidence of PVC and MVT. Albeit rare, VF can be triggered by late-coupled PVC, due to a mechanism other than phase 2 reentry in some patients with Brugada syndrome.

Inappropriate inhibition of atrial pacing due to T-wave oversensing (TWOS) was observed in a patient presenting with congenital long QT syndrome, treated with an implantable cardioverter defibrillator (ICD) and beta-adrenergic blocker. Development of TWOS was associated with further QT interval prolongation in the absence of amplitude changes in the intracardiac T and R waves. Replacement of the ICD generator with a sensing filter designed to attenuate the intracardiac T wave suppressed TWOS and normalized the pacing functions.

More than 20% of out-of-hospital cardiopulmonary arrest (OHCA) from malignant ventricular tachyarrhythmias develops in the acute phase of myocardial infarction (MI). There are not enough data about ventricular fibrillation (VF) during the acute MI. In this study, we assumed that electrocardiographic

Background: Because bepridil blocks multiple myocardial ionic channels, including the muscarinic acetylcholine receptor-operated potassium current (IKAch), bepridil is expected to suppress atrial fibrillation (AF) mediated by vagal nerve stimulation (VNS). Methods and Results: The therapeutic effects of bepridil were studied with a special focus on heart rate variability (HRV) in a canine model of AF. During VNS, AF was induced in 9 of 9 experiments before, vs 3 of 9 experiments after administration of bepridil (P

A delayed pericardial effusion developed in a recipient of a cardioverter defibrillator (ICD). After an uneventful implant procedure and postoperative recovery, the patient suffered loss of appetite and fatigue, and was re-admitted to the hospital 48 days later. Her vital signs were stable and cardiac silhouette on chest roentgenogram was normal. However, blood cell counts and chemistry revealed the presence of anemia and liver dysfunction, an echocardiogram showed a diffuse pericardial effusion, and computed tomography suggested that the ICD lead, screwed in the right ventricular outflow tract, had perforated the wall. In order to make a prompt diagnosis and initiate timely corrective treatment, the physician in charge of long-term follow-up should remember that a pericardial effusion can be delayed and accumulate in the absence of typical signs of cardiac tamponade after ICD lead implantation.

Summary Background Peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonists are used as anti-diabetic drugs, and their pleiotrophic action has been reported to improve endothelial function leading to cardioprotective effects. In this study we evaluated the long-term effect of pioglitazone on cardiac function in diabetic patients after percutaneous coronary intervention (PCI) by drug-eluting stent (DES). Methods and results We investigated 54 diabetic patients who received PCI using a sirolimus-eluting stent. We excluded cases of acute myocardial infarction. They were divided into two groups: Group C received only conventional therapy (n = 26) and Group P received additionally pioglitazone 15 mg/day (n = 28). The left ventricular ejection fraction (LVEF) was measured by left ventriculography and analyzed before and 8 months after PCI. In Group C, LVEF did not change significantly: 55.6% vs. 56.7%, before and after PCI respectively (p = 0.58). However, pioglitazone significantly improved LVEF: 54.4% vs. 60.0% (p = 0.014). Multiple linear regression analysis showed that ΔLVEF was significantly related to pioglitazone therapy (p = 0.037). In particular, the combination of pioglitazone and statin improved LVEF (ΔLVEF 9.6% with vs. 2.2% without statin). Conclusions Pioglitazone improved cardiac function after PCI using SES in diabetic patients, especially in combination with a statin.

We observed a case of idiopathic ventricular arrhythmias originating from the right ventricular outflow tract (RVOT). The origin of target premature ventricular contraction (PVC) and nonsustained ventricular tachycardia (VT) was within a wide low-voltage area around the RVOT. During radiofrequency (RF) application to the site of arrhythmia origin, polymorphic VT and ventricular fibrillation were repeatedly triggered by new PVC that had developed near the site of ablation. This electrical storm persisted >30 minutes after cessation of RF current delivery, and was suppressed by additional RF applications to the site of origin of the new PVC.

Background Cardiac resynchronization therapy (CRT) has recently been introduced as a new option for patients with severe heart failure, but its effect on renal function remains unclear. Methods and Results Twenty-three patients receiving CRT were studied. Responders were those who showed >0% increase in left ventricular ejection fraction after CRT by echocardiography. Clinical parameters, echocardiographic measurement, renal function, and prescriptions were examined before and 3 months after CRT, and the relationship between the response to CRT and renal function was examined. The responders had a better prognosis than the non-responders (p

Chemicals and toxins are useful tools to elucidate the structure-function relationship of various proteins including ion channels. The HERG channel is blocked by many compounds and this may cause life-threatening cardiac arrhythmia. Besides block, some chemicals such as the class III anti-arrhythmic agent nifekalant stimulate HERG at low potentials by shifting its activation curve towards hyperpolarizing voltages. This is called "facilitation". Here, we report mutations and simulations analyzing the association between nifekalant and channel pore residues for block and facilitation. Alanine-scanning mutagenesis was performed in the pore region of HERG. The mutations at the base of the pore helix (T623A), the selectivity filter (V625A) and the S6 helix (G648A, Y652A and F656A) abolished and S624A attenuated both block and facilitation induced by the drug. On the other hand, the mutation of other residues caused either an increase or a decrease in nifekalant-induced facilitation without affecting block. An open-state homology model of the HERG pore suggested that T623, S624, Y652 and F656 faced the central cavity, and were positioned within geometrical range for the drug to be able to interact with all of them at the same time. Of these, S649 was the only polar residue located within possible interaction distance from the drug held in its blocking position. Further mutations and flexible-docking simulations suggest that the size, but not the polarity, of the side chain at S649 is critical for drug induced facilitation.

Quinidine, a class I antiarrhythmic agent with blocking property of transient outward current, is a possible candidate for the suppression of ventricular fibrillation in patients with Brugada syndrome; although there is a concern that its ability to these effects may be proarrhythmic. Therefore, we evaluated the effect of quinidine sulfate on ST-segment elevation in Brugada syndrome. In 8 patients with Brugada syndrome, the magnitude of ST-elevation at the J-point (ST(J)), and the ST-segment configuration in leads V1-V3, were compared before and on day 2 after the initiation of quinidine administration. In 3 patients, quinidine attenuated ST(J) byor = 0.1 mV. Of these 3 patients, ST-segment elevation was normalized in 2 patients, while the ST-segment configuration was unchanged in another. In another 3 patients, quinidine augmented ST(J) byor = 0.1 mV without any change of ST-segment configuration, and the augmentation was returned to baseline after the discontinuation of quinidine. Quinidine exhibited no effect on the ST-segment in the remaining 2 patients. The favorable effects of quinidine on the ST-segment tended to be more pronounced in patients with prominent ST-elevation at baseline. In 1 patient, quinidine was effective in eliminating both ST-segment elevation and repetitive tachyarrhythmia episodes. In conclusion, the effects of quinidine on ST-segment elevation were variable. Quinidine may potentially augment the ST-segment elevation in some patients with Brugada syndrome.

The aim of this study was to investigate the long-term efficacy and safety of electrophysiologic study (EPS)-guided sotalol administration combined with implantable cardioverter defibrillators (ICD) for ventricular tachyarrhythmias (VTA). This study enrolled 92 patients with both structural heart disease and sustained VTA. Sotalol was administered to 57 patients, and its efficacy was assessed by EPS. Long-term treatment was continued in combination with ICD in 31 patients (57%) whose VTA was no longer inducible (responder group) and in 16 patients whose VTA remained inducible (nonresponder group). The long-term outcomes were compared among the responder group, the nonresponder group, and 35 ICD recipients untreated with antiarrhythmic drugs (ICD-only group). During a mean follow-up of 44 +/- 33 months, the recurrence of VTA was not significantly different between all patients treated with sotalol (30%) and patients in the ICD-only group (46%). However, the recurrence of VTA was significantly lower in the responder (13%) than in the nonresponder (63%) or the ICD-only groups (46%). There was no significant difference in VTA recurrence between the nonresponder and the ICD-only groups. One patient each in the responder and the ICD-only groups died suddenly, and all-cause mortality was similar in the three groups. The incidence of inappropriate ICD discharges was less in the sotalol than in the ICD-only groups. No patient had to discontinue long-term sotalol treatment because of the adverse effects. In conclusion, sotalol reduced VTA recurrence in the responding patients and inappropriate ICD discharge. EPS may predict the efficacy of sotalol for VTA recurrence.

High Defibrillation Threshold in Brugada Syndrome. Introduction: In patients with Brugada syndrome, implantable cardioverter defibrillator (ICD) is the only reliable treatment to prevent sudden death though, in some cases, internal defibrillation may be unsuccessful. The aim of this study was to examine the determinants of defibrillation failure, with a focus on electrophysiologic characteristics. Methods: The study included 51 patients treated with ICD: 22 with Brugada syndrome and 29 with structural heart disease (SHD). The prevalence of defibrillation energy requirement precluding the programming of a 10-J safety margin, the mean right ventricular effective refractory period (ERP), and mean induced ventricular fibrillation cycle length (VFCL) from the stored ICD electrograms, were compared between the two patient groups. Results: High defibrillation requirements were observed in 18% of patients with Brugada syndrome versus 0% of patients with SHD. However, the patients with SHD had larger heart size than those with Brugada syndrome. Mean VFCL and mean ERP were both significantly shorter in patients with Brugada syndrome than in patients with SHD, and ERP and VFCL were significantly correlated. Conclusion: Patients with Brugada syndrome have a high prevalence of high defibrillation energy requirement, and short ventricular ERP and VFCL.

RGS (regulators of G-protein signalling) are a diverse group of proteins, which accelerate intrinsic GTP hydrolysis on heterotrimeric G-protein α subunits. They are involved in the control of a physiological behaviour known as ‘relaxation’ of G-protein-gated K+ channels in cardiac myocytes. The GTPase-accelerating activity of cardiac RGS proteins, such as RGS4, is inhibited by PtdIns(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate) and this inhibition is cancelled by Ca2+/calmodulin (CaM) formed during membrane depolarization. G-protein-gated K+ channel activity decreases on depolarization owing to the facilitation of GTPase-activating protein activity by RGS proteins and vice versa on hyperpolarization. The molecular mechanism responsible for this reciprocal control of RGS action by PtdIns(3,4,5)P3 and Ca2+/CaM, however, has not been fully elucidated. Using lipid–protein co-sedimentation assay and surface plasmon resonance measurements, we show in the present study that the control of the GTPase-accelerating activity of the RGS4 protein is achieved through the competitive binding of PtdIns(3,4,5)P3 and Ca2+/CaM within its RGS domain. Competitive binding occurs exclusively within the RGS domain and involves a cluster of positively charged residues located on the surface opposite to the Gα interaction site. In the RGS proteins conserving these residues, the reciprocal regulation by PtdIns(3,4,5)P3 and Ca2+/CaM may be important for their physiological regulation of G-protein signalling.

Atrial fibrillation is one of the common arrhythmias associated with hyperthyroidism. This study examined the effects of thyroid hormone (T3) on mRNA expression and currents of major ionic channels determining the action potential duration (APD) in the rat atrium using the RNase protection assay and the whole-cell patch-clamp technique, respectively. T3 increased the Kv1.5 mRNA expression and decreased the L-type calcium channel mRNA expression, while the Kv4.2 mRNA expression did not change. APD was shorter in hyperthyroid than in euthyroid myocytes. The ultrarapid delayed rectifier potassium currents were remarkably increased in hyperthyroid than in euthyroid myocytes, whereas the transient outward potassium currents were unchanged. L-type calcium currents were decreased in hyperthyroid than in euthyroid myocytes. T3 shifted the current-voltage relationship for calcium currents negatively. In conclusion, T3 increased the outward currents and decreased the inward currents. The resultant changes of ionic currents shortened APD, providing a substrate for atrial fibrillation.

Andersen’s syndrome, which is characterized by periodic paralysis, cardiac arrhythmias and dysmorphic features, is a hereditary disease, and missense mutations of KCNJ2, which encodes an inward rectifying potassium channel, have been reported recently. We performed clinical and molecular analyses of a patient with Andersen’s syndrome, and found a novel mutation (G215D) of KCNJ2. Twelve lead electrocardiography revealed a long QT interval and frequent premature ventricular contractions, and polymorphic ventricular tachycardia was induced by programmed electrical stimulation. Use of a conventional whole-cell patch-clamp system with COS7 cells demonstrated that the G215D mutant was non functional, and that co-expression of wild type (WT)- and mutant-KCNJ2 shows a dominant negative effect on both inward and outward currents. We performed confocal laser scanning microscopy to assess the cellular trafficking of WT- and mutant-KCNJ2 subunits tagged with yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP), respectively. Tagging with the YFP did not affect the channel function of WT-KCNJ2 and both proteins showed similar plasma membrane fluorescence patterns. Furthermore, the result of fluorescence resonance energy transfer (FRET) studies at the plasma membrane region suggested that both YFP-tagged WT- and CFP-tagged mutant-KCNJ2 combine to construct a hetero-multimer of the potassium channel. In conclusion, the G215D mutant of KCNJ2 is distributed normally in the plasma membrane, but exhibits a dominant negative effect and reduces the Kir2.1 current, presumably due to hetero-multimer construction.

Thyroid hormone has been shown to modulate the gene expression of cardiac potassium channels, however, it is not known if gene expression is different between the atrium and the ventricle. The long-term effects of thyroid hormone on nuclear thyroid hormone receptors are also not known. Triiodothyronine (T3) at 25 μg/100 g of body weight or propylthiouracil (PTU) at 4 mg/100 g of body weight was given to adult rats via a gastric tube for 14 days. The levels of mRNA of Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2, erg, LQT1, and minK were assayed by RNase protection assay. The mRNA of nuclear T3-receptor-α1 and T3-receptor-β1 were also assayed for 15 days. After T3 (or PTU), plasma free T3 and free T4 increased (or decreased) significantly. The mRNA levels of Kv1.2 and Kv1.4 were reduced after T3 in the atrium and the ventricle, while PTU increased the levels in both chambers. Kv1.5 was significantly up-regulated by T3 in the atrium and the ventricle (P

The ventricular tachyarrhythmias associated with the LQT3 syndrome are typically bradycardia-dependent. However, some episodes can be associated with exercise or emotional stress, suggesting a different arrhythmogenic mechanism when sympathetic activity predominates. This study examined the potential arrhythmogenic mechanisms during periods of autonomically mediated transient heart rate acceleration in a canine anthopleurin-A model of LQT3 syndrome. Using plunge needle electrodes, transmural unipolar electrograms of the left ventricle were recorded from endocardial (Endo), mid-myocardial (Mid) and epicardial (Epi) sites. The activation-recovery interval (ARI) was measured to estimate local refractoriness. The cardiac cycle length was gradually shortened by cessation of vagal stimulation (vagal stimulation protocol (VSP)), and intramural electrograms and onset mode of ventricular tachyarrhythmias were analyzed in 7 experiments. The VSP was performed 8 times before and 5 times after administration of mexiletine in each experiment. Before mexiletine, vagal stimulation slowed the heart rate and created large transmural ARI dispersion because of a greater ARI prolongation at Mid rather than Epi/Endo sites. After cessation of vagal stimulation, unipolar electrograms started to show ARI alternans and ventricular premature beats developed sporadically. Sustained ventricular tachyarrhythmias were induced in 12 of the 56 trials of the VSP. Initiation of ventricular tachyarrhythmias was associated with delayed conduction at Mid/Endo sites. Mexiletine attenuated transmural ARI dispersion, and neither ARI alternans nor ventricular tachyarrhythmias was observed during all 35 trials of the VSP after mexiletine administration. Heart rate acceleration induced by an abrupt shift to a state of predominant sympathetic activity enhances arrhythmias in this LQT3 model. Mexiletine homogenizes ventricular repolarization, suppresses premature complexes and was antiarrhythmic during ventricular tachyarrhythmias induced by the VSP.

P experimental studies have reported that the activation-recovery interval (ARI) calculated from the unipolar electrogram was approximate to the local effective refractory period (ERP), but this subject has not been well studied in human intracardiac electrograms. The analysis of intracardiac ARIs in patients with congenital long QT syndrome (LQTS) may be useful and relevant to study, focusing on the arrhythmogenesis and therapeutic effects, so we examined whether the ARI calculated from the intracardiac electrograms of patients with LQTS reasonably corresponded to local refractoriness. The alteration of intracardiac ARI distribution by epinephrine and mexiletine was also studied in some of the patients.

OBJECTIVES We sought to identify the triggers of ventricular tachyarrhythmia (VTA) in experimental models of long QT type 2 (LQT2) and long QT type 3 (LQT3) syndromes. BACKGROUND Most adverse cardiac events occurring in the long QT type 1 syndrome are related to sympathetic nerve activity. In contrast, various factors may trigger VTA in patients with LQT2 and LQT3. METHODS The mode of onset of VTA and therapeutic effects of the potassium-adenosine triphosphate channel opener nicorandil were compared in canine models of LQT2 and LQT3, using three induction protocols: 1) bradycardia produced by atrioventricular block (BRADY); 2) programmed ventricular stimulation; and 3) electrical stimulation of the left stellate ganglion (left stellate stimulation [LSS]). Transmural unipolar electrograms were recorded, and the activation-recovery interval (ARI) was measured. RESULTS Ventricular tachyarrhythmias developed during BRADY in all six experiments in the LQT3 model, but in none of the six experiments in LQT2. Programmed ventricular stimulation induced VTA in two experiments of the LQT2 model, but in none of the LQT3 experiments. Stimulation of the left stellate ganglion induced VTA in three experiments in LQT2 and in two experiments in LQT3. Nicorandil caused greater shortening of ARI and greater attenuation of transmural ARI dispersion in the LQT2 model than in the LQT3 model. After treatment with nicorandil, a single VTA was induced in the LQT2 model by LSS, whereas in the LQT3 model, VTA remained inducible by BRADY in four experiments and LSS in one experiment. CONCLUSIONS An abrupt increase in sympathetic activity appeared arrhythmogenic in both models. Nicorandil attenuated the heterogeneity of ventricular repolarization and suppressed the induction of VTA in the LQT2 model, but had a limited therapeutic effect in the LQT3 model.

Data of long-term efficacy and safety including bleeding risk associated with antithrombotic regimens after primary percutaneous coronary intervention (PCI) using first-generation drug-eluting stent (1st DES) are scarce. Consecutive 422 patients with ST-elevation myocardial infarction (STEMI) underwent primary PCI with DES (285 patients), bare metal stent (BMS, 58 patients) or balloon angioplasty (BA 79 patients). At a median follow-up of 44 months, major cardiovascular events were significantly lower for 1st DES compared with BMS and BA (11.9 vs. 25.9 vs. 16.5 %, p = 0.027). Cardiac death, recurrent myocardial infarction and target lesion revascularization (TLR), differed among the groups (DES 8.8 %; BMS 13.8 %; BA 17.7 %; p = 0.019), although the superiority of DES subsided beyond 1 year by increased late TLRs. Major bleedings were not higher in DES than in BMS and BA (4.6 vs. 6.9 vs. 1.5 %, p = 0.252). Multivariate logistic regression analysis revealed that both dual antiplatelet therapy (DAPT) >24 months and indefinite oral anticoagulation (OAC) were associated with a major bleeding. The risk was even greater with triple antithrombotic therapy (odds ratio 19.5; 95 % confidence interval 3.73–102.07; p

In this paper, an estimation system of rice plant nitrogen contents in the whole rice field is discussed for a precision farming by using the remote sensing image. These images are taken at a panicle formation stage and a reduction division stage from a boundary of the rice field. These bird’s-eye view images are transformed to top views of a parallel projection to ease mapping. On parallel projected images, some combinations of two spectral images have significant correlation with the nitrogen contents. On the other hand, Hue and Saturation transformed from RGB color image have correlation with the nitrogen contents.

α1-Syntrophin, a member of dystrophin-associated proteins, is expressed at the sarcolemma and at perivascular astrocytes, and participates in protein-protein interactions through its PDZ domain. Aquaporin-4 (AQP4) is the predominant water channel protein in the brain, and also expressed at the sarcolemma of fast-twitch muscle fibers. AQP4 is concentrated in orthogonal array particles (OAPs), and its expression has been reported to be decreased at the sarcolemma of dystrophin-deficient mdx mice. We examined whether α1-syntrophin targets AQP4 at the sarcolemma. Immunohistochemistry showed that AQP4 is absent at the sarcolemma in α1-syntrophin knockout mice and that its expression is also lost from the perivascular astrocyte endfeet. On the other hand, expression of AQP4 is not decreased at the sarcolemma of the knockout mice in the neonatal stage. Moreover, AQP4 is expressed in lung, stomach, and kidney of wild-type and α1-syntrophin null mice. Our results show that α1-syntrophin is a key molecule to localize AQP4 to the sarcolemma of mature fast myofibers and astrocyte endfeet, but AQP4 is targeted to the plasma membrane by different molecules in lung, stomach, and kidney.

Ventricular fibrillation associated with coronary vasospasm developed 8 h after successful radiofrequency (RF) ablation of the right accessory pathway in an 81-year-old male. A segment of the coronary vasospasm was located close to the accessory pathway, where seven RF ablations had been applied. Although rare, physicians should carefully consider the risk of such events when an RF current is applied near a coronary artery.

A 74-year-old man with a history of partial gastrectomy presented with an electrocardiogram consistent with Brugada syndrome and marked meal related fluctuations in the ST segment. ST-segment elevation was prominently attenuated at 30 minutes and increased at 120 minutes after meals. Analysis of heart rate variability revealed a relationship between postprandial heightened parasympathetic activity and increase in Brugada-type ECG abnormality. A rapid postprandial increase in blood glucose may initially stimulate sympathetic nervous activity and secondarily increase parasympathetic tone. Food intake can be associated with fluctuations in ST-segment elevation in patients with the Brugada syndrome.