Severity by National Institute of Health Stroke Scale Score and Clinical Features of Stroke Patients with Patent Foramen Ovale Stroke and Atrial Fibrillation.

The comparative severity of patent foramen ovale (PFO)-related stroke in patients without atrial fibrillation (AF) and AF-related stroke in patients without PFO is unknown. Therefore, we compared the severity of PFO-related stroke and AF-related stroke. Twenty-six patients who underwent transesophageal echocardiography (TEE) were diagnosed with cardioembolic stroke from July 2018 to March 2020. Cases with AF detected by electrocardiograms or thrombus in the left atrium or left atrial appendage on TEE were included in the AF-related stroke group. Cases with a positive microbubble test on the Valsalva maneuver during TEE, and with no other factors that could cause stroke, were included in the PFO-related stroke group. This study was designed as a single-center, small population pilot study. The stroke severity of the two groups by the National Institute of Health Stroke Scale (NIHSS) score was compared by statistical analysis. Of the 26 cases, five PFO-related stroke patients and 21 AF-related stroke patients were analyzed. The NIHSS score was 2.2 ± 2.8 and 11.5 ± 9.2 (p-value < 0.01), the rate of hypertension was 20.0% and 85.7% (p-value = 0.01), and the HbA1c value was 5.5 ± 0.2% and 6.3 ± 1.3% (p-value = 0.02) in the PFO-related and AF-related stroke groups, respectively. Compared with AF-related stroke patients, stroke severity was low in PFO-related stroke patients.

Comparison of anti-inflammatory effects of rivaroxaban vs. dabigatran in patients with non-valvular atrial fibrillation (RIVAL-AF study): multicenter randomized study.

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1ß, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.

Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease.

OBJECTIVE: To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin. METHODS: Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks. RESULTS: Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks. CONCLUSION: Although the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.

Clinical usefulness of additional treatment with ezetimibe in patients with coronary artery disease on statin therapy. - From the viewpoint of cholesterol metabolism.-.

BACKGROUND: Ezetimibe-plus-statin therapy has been reported to provide greater reduction in low-density lipoprotein cholesterol (LDL-C) level than statin monotherapy. The aim of the present study was to evaluate the relationship between LDL-C lowering effect and baseline cholesterol absorption and synthesis markers in patients with coronary artery disease (CAD). METHODS AND RESULTS: A total of 171 patients with CAD whose LDL-C level was ≥ 100 mg/dl after treatment with atorvastatin (10mg/day) or rosuvastatin (2.5 mg/day) for 4 weeks were assigned to additionally receive ezetimibe (10mg/day) plus a statin or a double dose of statin for 12 weeks. The decreases in LDL-C (-30.0 ± 15.6 mg/dl vs. -19.2 ± 14.2 mg/dl) and the ratio of campesterol, an absorption marker, to total cholesterol levels (-1.35 ± 0.90 µg/mg vs. 0.33 ± 0.74 µg/mg) were greater in the ezetimibe-plus-statin group (P<0.05, respectively). The decrease in LDL-C level in the ezetimibe-plus-statin group was greatest in patients with baseline levels of higher absorption and lower synthesis markers and smallest in patients with baseline levels of lower absorption and higher synthesis markers (-34.3 ± 15.6 mg/dl vs. -21.5 ± 16.7 mg/dl, P<0.05). The decrease in LDL-C did not differ, irrespective of baseline levels of cholesterol absorption and synthesis markers, in the double-dose statin group, and was similar to that in patients with lower absorption and higher synthesis markers in the ezetimibe-plus-statin group. CONCLUSIONS: Ezetimibe-plus-statin therapy may be useful for lowering LDL-C level, irrespective of baseline levels of cholesterol absorption and synthesis markers.

Sustained inhibition of oxidized low-density lipoprotein is involved in the long-term therapeutic effects of apheresis in dialysis patients.

OBJECTIVE: Low-density lipoprotein (LDL) apheresis is a potential therapy for conventional therapy-resistant peripheral artery disease. In the present study, we examined the chronic effects of LDL apheresis on clinical parameters in vivo and endothelial cell functions in vitro in hemodialysis patients who had the complication of peripheral artery disease. METHODS AND RESULTS: Twenty-five patients were enrolled, and the responses of 19 patients to LDL apheresis were analyzed. Patients were classified into 2 groups according to change in ankle-brachial pressure index (ABI) after treatment: patients with improved ABI (responders, n=10) and patients with worsened ABI (nonresponders, n=9). In the responders, apheresis resulted in a long-term reduction of circulating levels of oxidized LDL, C-reactive protein, and fibrinogen. In human umbilical vein endothelial cells (HUVECs), the serum from the responders increased expression of activated endothelial nitric oxide synthase protein and proliferative activity. Furthermore, there was a significant correlation between ABI and activated endothelial nitric oxide synthase protein level in HUVECs treated with responder serum (R=0.427, P<0.05). CONCLUSION: These results demonstrate that LDL apheresis decreases oxidized LDL and inflammation and improves endothelial cell function in the responders. This may be one of the mechanisms involved in the long-term therapeutic effect of LDL apheresis on peripheral circulation in hemodialysis patients.

A case of giant coronary artery aneurysm and literature review.

A 40-year-old man was referred to our hospital because of an abnormal shadow on the left cardiac border on the chest roentgenogram at the regular medical health examination without any symptoms. A giant coronary artery aneurysm of left anterior descending artery with a maximum diameter of approximately 50 mm was detected with computed tomography and coronary angiography. The patient was treated and followed up medically. Four years later, the size of the coronary artery aneurysm became larger. Then resection of the coronary artery aneurysm and coronary artery bypass grafting were successfully performed. Coronary artery aneurysms are rare in adults and are usually found in association with Kawasaki disease, coronary atherosclerosis, and so on. We also review the literature of giant coronary artery aneurysms exceeding 50 mm in diameter.

Current status of emergency care for ST-elevation myocardial infarction in an urban setting in Japan.

BACKGROUND: The door-to-balloon time (DTB) is an important predictor of the outcome for patients with ST-elevation myocardial infarction (STEMI). In Japan, percutaneous coronary intervention (PCI) can be performed at many hospitals, and the predominant strategy for reperfusion therapy is primary PCI. However, it remains unclear how rapidly reperfusion is achieved at these hospitals. METHODS AND RESULTS: The study group comprised 369 patients with STEMI who presented within 12 h of symptom onset to a tertiary emergency center (TEC) or at 11 community hospitals (CHs) in 2006 and underwent emergency coronary angiography. Median DTB was shorter in the TEC (63 vs 104 min, P<0.001), and the rate of DTB within 90 min was higher in the TEC (96% vs 39%, P<0.001). Lateral myocardial infarction, presentation during off-hours, and non-cardiologist as the first-contact physician were significantly associated with a prolonged DTB in CHs. There was a trend toward lower 30-day mortality from all causes in the TEC (2.0% vs 4.8%, P=0.08). Multiple logistic regression analysis demonstrated that prolonged DTB (>90 min) was an independent predictor of 30-day mortality (odds ratio 12.6; 95% confidence interval 1.85-86.2, P=0.01). CONCLUSIONS: Establishment of emergency cardiac care systems with the goal of DTB within 90 min is required in PCI-capable hospitals to improve clinical outcomes.

Diagnostic use of T2-weighted inversion-recovery magnetic resonance imaging in acute coronary syndromes compared with 99mTc-Pyrophosphate, 123I-BMIPP and 201TlCl single photon emission computed tomography.

BACKGROUND: The incidence of missed diagnoses of acute cardiac ischemia in the emergency department could be reduced by a new imaging modality. In the present study, the clinical significance of (99m)Tc-pyrophosphate (PYP), (123)I-beta-methyl-p-iodephenyl-pentadecanoic acid (BMIPP), (201)TlCl scintigraphy (imaging) and T2-weighted inversion-recovery magnetic resonance imaging (MRI) for the detection of culprit lesion in patients with acute coronary syndromes (ACS) was compared. METHODS AND RESULTS: The study group comprised 18 patients with ACS: 12 patients with acute myocardial infarction (AMI) (11 males; mean age, 63+/-11 years) and 6 patients with unstable angina (UA) (3 males, mean age, 67+/-5 years). Of the 12 patients with AMI, 10 underwent (201)TlCl and PYP single photon emission computed tomography (SPECT) studies as a dual-energy acquisition ((201)TlCl/PYP) and 8 underwent (201)TlCl SPECT within 1 week of the BMIPP study. All 18 patients underwent BMIPP SPECT and MRI. The MRI pulse sequence was black blood turbo short-inversion-time inversion recovery (STIR) (breath-hold T2-weighted studies). The T2-weighted inversion-recovery MRI showed higher sensitivity and negative predictive value than PYP and (201)TlCl, and higher specificity and positive predictive value than BMIPP and (201)TlCl. The area under the receiver-operating characteristic curve for PYP, BMIPP, (201)TlCl and MRI was 0.787, 0.725, 0.731 and 0.878, respectively. The difference between the areas of MRI and BMIPP was significant (p<0.05). CONCLUSION: Accurate detection of culprit lesion is improved by using MRI rather than BMIPP, particularly for patients with ACS.

Clinical usefulness of ECG-gated 18F-FDG PET combined with 99mTC-MIBI gated SPECT for evaluating myocardial viability and function.

OBJECTIVES: This study sought to evaluate an imaging approach using gated 99mTc-MIBI (MIBI) SPECT and gated 18F-FDG (FDG) PET for assessment of myocardial viability and cardiac function. METHODS: Forty-eight patients (38 men, mean age 68.1 +/- 9.6 years) underwent ECG-gated FDG PET and MIBI SPECT within a week. The baseline diagnoses were coronary artery disease (31), mitral regurgitation (1), paroxysmal arrhythmia (10), and dilated cardiomyopathy (6). The gated FDG PET data were analyzed using pFAST software, and the gated MIBI SPECT data were analyzed using QGS software. Fifteen patients were diagnosed with myocardial infarction, and follow-up study was performed to assess the functional outcome four months later. An improvement in LVEF of >5% was defined as significant. The LV myocardium was divided into 17 segments, and regional defect scores were visually assessed using a 4-point scale for each segment (0 = normal, 1 = mildly reduced, 2 = moderately reduced, 3 = absent). A segment with a greater defect score on MIBI SPECT than on FDG PET was defined as a mismatch. The patients were divided into two groups: those with at least two mismatched segments (MM-group), and those with none or one (M-group). RESULTS: LVEF, EDV and ESV measured by gated FDG PET were highly correlated with those obtained by gated MIBI SPECT (r = 0.848, 0.855 and 0.911, p < 0.0001, respectively). The mean values of LVEF did not differ significantly, but EDV and ESV obtained by gated FDG PET were significantly grater than those obtained by gated MIBI SPECT (p < 0.0001). In 15 patients diagnosed with myocardial infarction, a significant association (p < 0.05) was found between the relative uptake of FDG PET and MIBI SPECT and the functional outcome 4 months later. Global LV function improved in 6 of the 8 patients showing mismatch but in only 1 of the 7 patients with matched defects, resulting in a sensitivity of 86% and specificity of 75%. The overall accuracy to predict global functional outcome was high (80%). CONCLUSION: This imaging approach allows accurate evaluation of myocardial viability. Furthermore, the high correlations of gated FDG PET and gated MIBI SPECT measurements hold promise for the assessment of left ventricular function using gated FDG PET.

Prevalence of right bundle-branch block and right precordial ST-segment elevation (Brugada-type electrocardiogram) in Japanese children.

BACKGROUND: The prevalence of Brugada-type electrocardiogram (ECG) in schoolchildren remains unclear. This study aimed to further investigate this condition. METHODS AND RESULTS: We studied the prevalence of Brugada-type ECG in 20,387 children (10,434 males and 9,953 females, 9.7 +/- 3.2 [SD] years old) during a school health examination in Kanagawa Prefecture, Japan, in 2002. We considered right bundle-branch block and ST-segment elevation of the J point of > or =0.1 mV in leads V1 through V3 as Brugada-like ECG, and an ECG was considered to be Brugada-type when the 12-lead ECG fully meet the criteria for the Brugada syndrome as recently published in a consensus report. Only 2 children (0.0098%, 95% confidence interval (CI): 0 to 0.023%) completely conformed to the criteria for Brugada-type ECG. Brugada-like ECG was found in 11 (10 male) of 20,387 children (0.054%, 95% CI: 0.022 to 0.086%). The prevalence in males was significantly higher than that in females, even in children (0.096% vs 0.010%, p=0.012). Stratified according to age, there was tendency for the prevalence of Brugada-like ECG to increase up to puberty (first graders, 0.01%; fourth graders, 0.05%; seventh graders, 0.08%; tenth graders, 0.23%; p=0.068). CONCLUSION: The prevalence of Brugada-type ECG in Japanese children was much lower than that reported in the adult population.

Double-counting of intracardiac electrogram during biatrial pacing.

BACKGROUND: Biatrial pacing has a significant problem with memory function that misinterprets normal sinus rhythm as atrial tachyarrhythmias and in addition estimation of the atrial pacing thresholds (biatrial and uniatrial pacing thresholds) is sometimes difficult because of small P waves. METHODS AND RESULTS: The intracardiac electrograms recorded by a pacemaker in 10 patients (age, 66.7+/-10.7 (SD) years) with implanted biatrial pacemakers were analyzed. Atrial sensing within the atrial refractory period after atrial pacing was counted in 6 of the 10 patients (timing of the double counting was 143+/-64 ms) when pacing failed in the left or right atrium. Atrial sensing within the atrial refractory period after atrial pacing disappeared when biatrial pacing was successfully performed. Atrial double-counts depend on interatrial conduction delay. The memory function of implanted pacemaker devices misinterpreted normal sinus rhythm as atrial tachyarrhythmias because of atrial double-counts. On the other hand, the biatrial pacing threshold was easily recognized using this phenomenon. CONCLUSIONS: The memory function of pacemaker devices is unreliable because of atrial double-counting during sinus rhythm in patients with biatrial pacing. However, the biatrial pacing threshold is easily checked using this phenomenon.

[Brugada syndrome associated with ventricular fibrillation induced by administration of pilsicainide: a case report].

A 56-year-old man with Brugada syndrome presented with ventricular fibrillation induced by administration of pilsicainide. He had syncope at age 46 years, and his uncle suddenly died of unknown cause. He had taken pilsicainide (150 mg/day) for paroxysmal atrial fibrillation, and suffered from syncope due to ventricular fibrillation. Coved type ST elevation was observed in the V1 lead, and saddle back type ST elevation was observed in the V2 lead. The ST elevation gradually recovered after stopping pilsicainide therapy. No structural heart disease was found. After intravenous injection of pilsicainide, the ST segment elevated in the V1 and V2 leads. Ventricular fibrillation was induced by triple extrastimulation at the right ventricular apex. The diagnosis was Brugada syndrome, and a cardioverter-defibrillator was implanted. Brugada syndrome should be considered before administering pilsicainide.

[Factors for successful conversion of atrial fibrillation using intravenous injection of pilsicainide hydrochloride].

OBJECTIVES: The factors affecting successful conversion of atrial fibrillation using intravenous injection of pilsicainide hydrochloride are unclear. The efficacy of intravenous injection of pilsicainide hydrochloride and the factors affecting successful conversion of symptomatic atrial fibrillation were investigated. METHODS: Twenty-six patients[21 men, 5 women, 64 +/- 12 years (mean +/- SD)] with electrocardiographically confirmed, symptomatic atrial fibrillation were treated with intravenous injection 1.0 mg/kg of pilsicainide hydrochloride between October 31, 2000 and February 17, 2003. Successful conversion was defined as termination of atrial fibrillation within 30 min of intravenous injection. Before the injection of pilsicainide hydrochloride, blood pressure, conventional electrocardiography, chest radiography, echocardiography and blood examinations were performed. During and after injection of pilsicainide hydrochloride, blood pressure and conventional electrocardiography were monitored. After injection of pilsicainide hydrochloride, blood examinations were performed. RESULTS: Pharmacological conversion to sinus rhythm was achieved in 7 of 26 patients(27%). The successful conversion group and unsuccessful conversion group showed significant differences in duration of atrial fibrillation(61 +/- 122 vs 12,257 +/- 25,959 hr, p < 0.01), heart rates before injection of pilsicainide (110 +/- 26 vs 87 +/- 26 beats/min, p < 0.05), cardiothoracic ratio(47.8 +/- 2.6% vs 53.5 +/- 5.1%, p < 0.01) and left atrial dimension(38 +/- 7 vs 45 +/- 6 mm, p < 0.05). CONCLUSIONS: Pilsicainide hydrochloride is effective in patients with atrial fibrillation of short duration with small left atrium and rapid ventricular response.

Polymorphism of the type 6 adenylyl cyclase gene and cardiac hypertrophy.

We investigated whether polymorphism of the type 6 adenylyl cyclase gene influences the occurrence of left ventricular hypertrophy in a Japanese population. Type 6 adenylyl cyclase is a major cardiac adenylyl cyclase isoform and plays an important role in regulating cardiac function. We examined the type 6 adenylyl cyclase gene for single nucleotide polymorphism by heteroduplex analysis and found a mutation (T11215A) in intron 17. We genotyped the single nucleotide polymorphism (TT/TA/AA groups) by the mutagenically separated polymerase chain reaction method in 2068 subjects who underwent health screening for cardiovascular disease. Genetic variation was in the Hardy-Weinberg equilibrium. We found no significant association between the frequency of left ventricular hypertrophy and any of the genotype groups. In the TT and the TA genotype group, however, left ventricular hypertrophy was associated with increased blood pressure, while no association with increased blood pressure was found in the AA genotype group. It was concluded that the AA group may be at risk of developing left ventricular hypertrophy independent of increased blood pressure.

Infected left atrial myxoma.

A 47-year-old Japanese woman with a continuing high fever was promptly diagnosed as having infected atrial myxoma one day after admission based on transthoracic echocardiographic findings and positivity for bacteria in blood culture. The mass was removed by an urgent open heart surgery. Histopathological examination confirmed that this mass was a myxoma with gram-positive bacterial colonies. Generally, antemortem diagnosis is difficult and there is a high mortality of patients with infected myxoma; however, this patient completely recovered from the illness because of the prompt diagnosis. This is the 37th case of definite infected myxoma reported in the literature. The cause of infection of this patient might have been the acupuncture therapy she underwent for weight reduction.

[Biventricular pacing using two pacemakers and triggered VVT mode in patients with atrial fibrillation and congestive heart failure: a case report].

A 76-year-old female had undergone implantation of a single chamber pacemaker for sick sinus syndrome 20 years previously. She developed chronic atrial fibrillation and required repeated admission due to congestive heart failure. She had significant mitral and tricuspid regurgitation. Paradoxical movement of the intraventricular septum was severe. Due to right ventricular apical pacing, significant interventricular conduction delay was present with a paced QRS duration of 189 msec. The left ventricular pacing lead was positioned via the coronary sinus. The mode of the previously implanted pacemaker was set at VVT. Biventricular pacing could be achieved even in intrinsic beats by VVT mode. The battery life time was improved. This method is useful in patients with conventional pacemakers.