Impact of left atrial size on isolation area in the acute phase of pulmonary vein isolation using 28 mm cryoballoon.

BACKGROUND: The impact of left atrial (LA) size on isolation area (ISA) using a 28-mm second-generation cryoballoon (CB) in the acute phase after pulmonary vein isolation (PVI) and the differences of CB from contact force-guided radiofrequency (RF) ablation have not been fully investigated. METHODS: We examined 85 consecutive patients (CB group, 35; RF group, 50) with drug-refractory paroxysmal atrial fibrillation who underwent their first PVI procedure at two institutions. We evaluated ISA after PVI using 3D-Merge computed tomography images (GE Healthcare, Little Chalfont, UK) and high-resolution electroanatomical mapping. RESULTS: Total ISA was significantly smaller in the CB group (20.6 ± 6.0 cm2 ) than in the RF group (29.0 ± 7.1 cm2 ; P < 0.0001). In the CB group, ISA of the left pulmonary vein (LPV), right pulmonary vein (RPV), and total ISA were not correlated with the left atrial surface area (LASA). The ratios of ISA to LASA (%ISA) of LPV and total ISA negatively correlated with LASA in the CB group (LPV: r = -0.4001, P = 0.0173; total ISA: r = -0.4733, P = 0.0041). In contrast, in the RF group, ISA of LPV, RPV, and total ISA positively correlated with LASA; (LPV: r = 0.5155, P = 0.001; RPV: r = 0.6398, P < 0.0001; total ISA: r = 0.7299, P < 0.0001). CONCLUSION: ISA created using CB was significantly smaller than that using RF and did not change regardless of LASA increment. Differences in ISA between the two groups became more prominent in the large atrium.

Catecholaminergic polymorphic ventricular tachycardia managed as orthostatic dysregulation and epilepsy in 11- and 15-year-old sisters.

BACKGROUND: In pediatric patients, syncope commonly occurs as vasovagal syncope, or in epilepsy or orthostatic dysregulation. Cardiogenic syncope is rare but it is lethal, and needs to be promptly diagnosed and treated. METHODS AND RESULTS: We describe the cases of 11- and 15-year-old sisters with frequent syncope during exercise and emotional stress since the age of 10 and 12, respectively. There were no abnormalities on 12-lead electrocardiogram (ECG) at rest. They were first diagnosed with orthostatic dysregulation and epilepsy. Because of recurrent exercise-induced syncope, cardiac examinations were performed. On treadmill exercise stress test, bidirectional ventricular tachycardia was induced in the 11-year-old girl, which degenerated into ventricular fibrillation; frequent polymorphic premature ventricular contractions were induced in her elder sister. They were diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT) and started on oral beta-blockers and exercise restriction. CONCLUSIONS: It is important to suspect CPVT in pediatric exercise-induced syncope, and to recognize that CPVT does not show ECG abnormalities at rest.

Risk factor profile for newly diagnosed atrial fibrillation: 4-year follow-up of annual health examinations in a Japanese Adult Cohort.

Background: Detecting unknown atrial fibrillation (AF) would provide an opportunity to prevent ischemic stroke by instituting appropriate anticoagulation. Although opportunistic screening of older patients is recommended in current guidelines, which patients may benefit from intensive AF screening remains unclear. We sought to clarify the risk factor profile for newly diagnosed AF in annual health examinations of a Japanese adult cohort. Methods: Among 141 441 Japanese patients who underwent annual health examinations in 2014, 87 872 patients aged ≥20 years without known AF who had undergone electrocardiography were analyzed (mean age: 47 ± 12 years; 64% men). The absence of known AF was confirmed by prior electrocardiography in 2012 and/or 2013. Newly diagnosed AF was observed in 244 patients in 2014-2017 (mean age: 62 ± 12 years; 83% men). Results: In the multivariable analysis, waist circumference obesity (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.13-1.99; p = .005) high blood pressure (HR, 1.9; 95% CI, 1.01-3.59; p = .047), on-treatment hypertension (HR, 1.53; 95% CI, 1.01-2.31; p = .046), and daily alcohol drinking (HR, 2.18; 95% CI, 1.52-3.12; p < .001) were significantly associated with newly diagnosed AF. Conclusions: In this Japanese cohort, waist circumference obesity, hypertension, and alcohol drinking were independent predictors of newly diagnosed AF in annual medical examinations. This finding encourages further evaluation of systematic AF screening programs in at-risk populations.

High prevalence of fragmented QRS on electrocardiography in Japanese patients with diabetes irrespective of metabolic syndrome.

AIMS/INTRODUCTION: Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and myocardial scar formation. This study aimed to clarify the relationship of fQRS with diabetes mellitus and metabolic syndrome (MetS) in Japanese patients. MATERIALS AND METHODS: Approximately 702 individuals who had a routine health checkup at the Hokuriku Health Service Association (Toyama, Japan) in October 2014 were enrolled and categorized into one of the following four groups based on MetS and diabetes mellitus status: with diabetes mellitus (+) MetS+ (164 participants); diabetes mellitus+ without MetS (Mets-; 103 participants); diabetes mellitus- MetS+ (133 participants); and diabetes mellitus- MetS- (302 participants). fQRS was assessed using the results of electrocardiography. RESULTS: The prevalence of fQRS was statistically higher in patients with diabetes mellitus+ MetS+ (37%) and diabetes mellitus+ MetS- (35%), than those with diabetes mellitus- MetS+ (14%) or diabetes mellitus- MetS- (10%; P < 0.0001). Significant differences were observed between the fQRS(+) and fQRS(-) groups for age, sex, waist circumference, heart rate, hypertension, hemoglobin A1c, total cholesterol, MetS and diabetes mellitus. The area under the receiver operating characteristic curve for traditional risk factors and diabetes mellitus was 0.72 (P = 0.0007, 95% confidence interval 0.67-0.76), and for traditional risk factors and MetS it was 0.67 (P = 0.28, 95% confidence interval 0.62-0.72). Patients with diabetes mellitus had more than threefold higher likelihood of showing fQRS (odds ratio 3.41; 95% confidence interval 2.25-5.22; P < 0.0001) compared with the reference group without diabetes mellitus, after adjusting for age, sex, dyslipidemia, hypertension and waist circumference. CONCLUSIONS: fQRS was observed more frequently in diabetes mellitus patients than in MetS and control individuals. Diabetes mellitus was the most significant determinant for fQRS among MetS and other traditional metabolic risk factors.

Incremental yield of ECG screening repeated annually over 4 years in an adult Japanese population without prior atrial fibrillation: a retrospective cohort study.

OBJECTIVES: International guidelines recommend opportunistic screening for atrial fibrillation (AF); however, there is no current data to inform how often to repeat screening. We aimed to investigate the incremental annual yield and stroke risk of new AF cases in individuals screened annually over 4 years. DESIGN: A retrospective cohort study. SETTING: Hokuriku Health Service Association, Toyama prefecture, Japan. PARTICIPANTS: Employees and their families receiving annual health examinations from Hokuriku Health Service Association. INTERVENTION: Each subject received an annual health examination (including 12-lead ECG) from 2014 to 2017. Only subjects with baseline ECGs in 2012 and/or 2013 were included. MAIN OUTCOME MEASURES: Rates (cases/100 person-years) of new AF identified each year for 4 consecutive years of screening (stratified according to gender and age groups). Calculated stroke risk of new AF cases using modified CHA2DS2-VASc scores (without heart failure data) (CHA2DS2VASc = C: congestive heart failure [1 point]; H: hypertension [1 point]; A2: age 65-74 years [1 point] or age ≥75 years [2 points]; D: diabetes mellitus [1 point]; S: prior stroke or transient ischemic attack [2 points]; VA: vascular disease [1 point]; and Sc: sex category [female] [1 point]) RESULTS: In 2014, 88 218 subjects had an ECG (46.8±12.5 years; 64% men): identifying 346 (0.39%) known AF and 69 (0.08%) new AF. The incidence rate of new AF increased with age from 0.01% (<50 years) to 0.98% (≥75 years) and was higher in men (0.1%) than women (0.05%). Repeated annual screening over 4 years identified a consistent new AF yield 0.06%-0.10% per year (0.33%-0.55% ≥65 years). Forty-two per cent of all new AF cases, and 76% of cases aged ≥65 years, had a class-1 oral anticoagulation (OAC) recommendation (modified CHA2DS2-VASc score ≥2 men, ≥3 women). CONCLUSIONS: Repeated annual ECG screening of the same population provides a consistent yield of new AF each year. The majority of new AF (≥65 years) are eligible for anticoagulation for stroke prevention. Although AF prevalence and incidence are lower in Japan than Western countries, 2318 new cases would be identified in Toyama prefecture each year with annual screening, of whom ~927 would have a high stroke risk with a recommendation for OAC therapy.

Congenital left main coronary artery atresia presenting as syncope and generalized seizure during exercise in a 13-year-old boy.

We report the case of a 13-year-old boy who, while running in a school gymnasium, experienced sudden syncope and seizure. CPR was started immediately, and an automated external defibrillator (AED) was attached, but shock was not induced. He was referred to our hospital for loss of consciousness and intermittent general tonic-clonic seizure. A 12-lead electrocardiogram showed normal sinus rhythm and no ST-T wave abnormalities. Echocardiography showed normal structural heart and normal cardiac function. On the second day of hospitalization, AED electrocardiogram showed complete atrioventricular (AV) block at syncope and seizure. After the patient recovered from this neurological state, we performed the treadmill exercise test, and it did not show ST-T wave abnormalities or AV block, and he did not complain of chest pain. Coronary angiography showed atresia of the left main trunk and the collateral vessel from the right coronary artery connected to the left coronary artery. He was diagnosed with congenital left main coronary artery atresia. We began administration of calcium antagonist and aspirin to prevent a coronary artery spasm and then performed a coronary artery bypass graft (CABG) to prevent sudden cardiac death. After CABG, he has had no syncope episodes at rest or during light exercise. .

Adaptive cardiac resynchronization therapy for dilated cardiomyopathy with functional mitral regurgitation.

We report the case of a man in his 60s who had dilated cardiomyopathy with severe functional mitral regurgitation. Four years after a cardiac resynchronization therapy (CRT) device with an implantable cardioverter defibrillator was implanted, this device was replaced with an adaptive CRT device because of battery consumption. Seven months after replacement of this device, the left ventricular pacing to right ventricular activation and the atrioventricular delay from automatic adjustments contributed to less functional mitral regurgitation. The findings from our case suggest that optimal CRT, by measuring intracardiac conduction parameters, is effective for functional mitral regurgitation.

Altered gene expression in T-cell receptor signalling in peripheral blood leucocytes in acute coronary syndrome predicts secondary coronary events.

OBJECTIVE: Comprehensive profiling of gene expression in peripheral blood leucocytes (PBLs) in patients with acute coronary syndrome (ACS) as a prognosticator is needed. We explored the specific profile of gene expression in PBLs in ACS for long-term risk stratification. METHODS: 30 patients with ACS who underwent primary percutaneous coronary intervention (PCI) and 15 age-matched adults who participated in medical check-ups were enrolled from three centres. Peripheral blood samples were collected to extract RNA for microarray analyses. RESULTS: During the 5-year follow-up, 36% of this cohort developed the expected non-fatal coronary events (NFEs) of target lesion revascularisation (TLR) and PCI for a de novo lesion. Class comparison analysis (p<0.005) demonstrated that 83 genes among 7785 prefiltered genes (41 upregulated vs 42 downregulated genes) were extracted to classify the patients according to the occurrence of NFE. Pathway analysis based on gene ontology revealed that the NFEs were associated with altered gene expression regarding the T-cell receptor signalling pathway in ACS. Univariate t test showed that the expression level of death-associated protein kinase1 (DAPK1), known to regulate inflammation, was the most significantly negatively regulated gene in the event group (0.61-fold, p<0.0005). Kaplan-Meier curve analysis and multivariate analysis adjusted for baseline characteristics or clinical biomarkers demonstrated that lower DAPK1 expression in PBL emerged as an independent risk factor for the NFEs (HR: 8.73; CI 1.05 to 72.8, p=0.045). CONCLUSIONS: Altered gene expression in T-cell receptor signalling in PBL in ACS could be a prognosticator for secondary coronary events. TRIAL REGISTRATION NUMBER: UMIN000001932; Results.

A case of delayed occlusive dissection of the right coronary artery during coronary intervention of the left anterior descending artery.

Catheter-induced coronary artery dissection occurs rarely during selective coronary angiography but generally progresses to complete coronary occlusion. We present a case of delayed occlusive dissection of the right coronary artery during coronary intervention of the left anterior descending artery. Bailout stenting was employed to treat the giant hematoma quickly using a unique technique. The use of two guidewires created a high probability that the true lumen was selected, and aspiration of the hematoma with the microcatheter and indeflator effectively repaired a catheter-induced coronary artery dissection.

Detection of WIPI1 mRNA as an indicator of autophagosome formation.

Autophagy is a cellular bulk degradation system for long-lived proteins and organelles that operates during nutrient starvation and is thus a type of recycling system. In recent years, a series of mammalian orthologs of yeast autophagy-related (ATG) genes have been identified; however, the importance of the transcriptional regulation of ATG genes underlying autophagosome formation is poorly understood. In this study, we identified several ATG genes, including the genes ULK1, MAP1LC3B, GABARAPL1, ATG13, WIPI1, and WDR45/WIPI4, with elevated mRNA levels in thapsigargin-, C2-ceramide-, and rapamycin-treated as well as amino acid-depleted HeLa cells except for MAP1LC3B mRNA in rapamycin-treated HeLa cells. Rapamycin had a weaker effect on the expressions of ATG genes. The increase in WIPI1 and MAP1LC3B mRNA was induced prior to the accumulation of the autophagy marker protein MAP1LC3 in the thapsigargin- and C2-ceramide-treated A549 cells. By counting the puncta marked with MAP1LC3B in HeLa cells treated with different autophagy inducers, we revealed that the time-dependent mRNA elevation of a specific set of ATG genes was similar to that of autophagosome accumulation. The transcriptional attenuation of WIPI1 mRNA using RNA interference inhibited the puncta number in thapsigargin-treated HeLa cells. Remarkably, increases in the abundance of WIPI1 mRNA were also manifested in thapsigargin- and C2-ceramide-treated human fibroblasts (WI-38 and TIG-1), human cancer cells (U-2 OS, Saos-2, and MCF7), and rodent fibroblasts (Rat-1). Taken together, these results suggest that the detection of WIPI1 mRNA is likely to be a convenient method of monitoring autophagosome formation in a wide range of cell types.

Impact of proton pump inhibitors or famotidine on the antiplatelet actions during dual-antiplatelet therapy in Japanese patients.

BACKGROUND: It has been reported that the antiplatelet action becomes attenuated when a proton pump inhibitor is used in combination with clopidogrel. PURPOSE: The effect of an antacid causing platelet aggregation during the administration of clopidogrel was investigated. SUBJECTS AND METHODS: The subjects consisted of 265 patients with coronary artery disease. Platelet aggregation function testing (light transmittance aggregometry) was conducted while aspirin and clopidogrel 75 mg were taken orally and the minimum concentration of aggregation induction platelet aggregation threshold index was measured. The ADP-PATI, measured with ADP as the inducing substance, was compared and investigated according to the type of concomitantly used antacid. RESULT: The results of the ADP-PATI were: control group: 3.47 ± 0.95 µM (N = 67), famotidine group: 3.80 ± 0.52 µM (N = 32), rabeprazole group: 3.43 ± 0.93 µM (N = 87), lansoprazole group: 3.28 ± 1.04 µM (N = 63) and omeprazole group: 3.33 ± 0.81 µM (N = 16). No statistically significant difference was observed regarding the ADP-PATI of respective groups compared to the control group. CONCLUSION: The concomitant use of famotidine, rabeprazole, lansoprazole, and omeprazole did not affect the antiplatelet action of clopidogrel in Japanese patients.

Successful percutaneous revascularization in a patient with a chronic totally occluded renal artery in an atrophied kidney.

A 57-year-old man presented with renovascular hypertension with chronic kidney disease. 16-Multi-detector row computed tomography (MDCT) showed that the left renal artery was totally occluded and the left kidney was atrophied. The left atrophied kidney was hormonally active despite the desolation of glomerular filtration function. Percutaneous renal revascularization was successful for stenting this lesion. The renin activity in the left renal vein was decreased immediately after the procedure. He remained healthy with adequate blood pressure for three years. In this case, MDCT and renal vein renin measurement provided useful information for the decision to perform percutaneous renal revascularization.

Flecainide augments muscle sympathetic nerve activity in humans.

The Cardiac Arrhythmia Suppression Trial has shown that treatment with flecainide is associated with an increased incidence of cardiac death in patients following myocardial infarction. It is believed that there is a complex mechanism involving an interaction between flecainide, sympathetic activation, and acute ischemia that is responsible for the increased risk of sudden death. The purpose of this study was to determine the effects of flecainide on muscle sympathetic nerve activity (MSNA) in humans. We measured MSNA using microneurography and cardiac output using the dye dilution method in 30 healthy individuals. Measurements were made at rest and after the oral administration of flecainide (200mg, n=12) or placebo (n=9), or intravenous administration of propranolol (0.2 mg/kg, n=9). Flecainide significantly increased heart rate and decreased the cardiac index (both p<0.01). Flecainide increased the burst rate from 16.7 +/- 3.5 to 23.3 +/- 4.1 bursts/min and the burst incidence from 26.6 +/- 5.1 to 34.7 +/ -5.6bursts/100 heartbeats (both p<0.01). For all of the hemodynamic parameters except heart rate, the effects of propranolol were similar to those of flecainide. Propranolol also increased the burst rate by 52 +/- 34% and the burst incidence by 106 +/- 39%. These results suggest that flecainide suppresses myocardial contractility and produces reflex-mediated increases in sympathetic nerve firing in humans.

Characteristics of the pathological images of coronary artery thrombi according to the infarct-related coronary artery in acute myocardial infarction.

BACKGROUND: Unstable plaque and coronary arterial thrombi sometimes induce a no-reflow phenomenon after intervention whereby there is sufficient reperfusion. The greater susceptibility of the right coronary artery to development of large thrombi makes successful reperfusion more difficult, therefore the characteristics of the pathological images of coronary arterial thrombi according to the infarct-related coronary artery were investigated. METHODS AND RESULTS: Coronary arterial thrombi were extracted from 77 patients with acute myocardial infarction (AMI) using a thrombectomy catheter. The 36 patients had a thrombus containing atherosclerotic cells. Platelets, fibrin, and neutrophils were seen in all cases. The mean ratios of structural components of thrombi were 51.0 +/- 29.5% (mean +/- SD) of the platelet component, 19.9 +/- 25.7% of the erythrocyte component and 11.9 +/- 22.5% of atherosclerosis component. Erythrocyte-rich thrombi and mixed thrombi mainly composed of erythrocytes were seen in 14 of the 30 cases involving the right coronary artery, 6 of the 35 cases in the left anterior descending artery, 2 of the 11 cases of the left circumflex artery, and in the 1 case of saphenous vein bypass graft. There was significantly more erythrocyte component in the thrombi from the right coronary artery (28.7 +/- 30.1%) than in those from the left coronary artery (12.1 +/- 18.4%). CONCLUSION: Coronary artery thrombi in AMI are composed principally of platelets. Atherosclerotic cells were identified within thrombi from some patients. In the right coronary artery there were many more thrombi that were rich in erythrocytes than in thrombi from the left coronary artery.

Effects of endoscopic transthoracic sympathicotomy on hemodynamic and neurohumoral responses to exercise in humans.

Endoscopic transthoracic sympathicotomy (ETS) is a minimal invasive procedure of thoracic sympathetic block and has been used successfully in the treatment of primary palmar hyperhidrosis. To examine the effect of Th 2-3 ETS on hemodynamic responses to submaximal upright treadmill exercise in humans, cardiac output, plasma noradrenaline and adrenaline at rest and during the last 40s of stage 2 in a modified Bruce protocol were measured before and after ETS in 21 patients with primary palmar hyperhidrosis. Heart rate, mean arterial pressure, rate-pressure product, and noradrenaline decreased at rest and at submaximal exercise after ETS. Cardiac index at rest did not change either before or after ETS, but decreased (8.9 +/- 0.6 vs 6.8 +/- 0.4L x min(-1) m-2; p<0.01, mean +/- SEM) at submaximal exercise after ETS. Stroke index and systemic vascular resistance were similar both at rest and at submaximal exercise before and after ETS. Thus, ETS reduces myocardial oxygen demand and plasma noradrenaline levels both at rest and during exercise without significantly depressing cardiac function in terms of stroke volume.