Sanemasa Ishida

STEVENS-JOHNSON SYNDROME CAUSED BY A HEALTH DRINK (EBERU) CONTAINING OPHIOPOGONIS TUBER

Stevens‐Johnson syndrome is considered to be a severe type of erythema exsudativum multiforme. It is characterized by erythema with bullous and eroded lesions of skin and mucous membranes. We report a case of Stevenjohnson syndrome following consumption of a health drink containing ophiopogonis tuber. A 66‐year‐old female took an O.T.C. health drink for fever. The next morning, she noted erythema and swelling of her face, neck, and chest. She started to develop bullous and eroded lesions on the skin of her entire body and the mucous membranes of her oral cavity, conjunctiva, and cornea, and she became feverish. She had high degrees of corneal erosion and liver dysfunction. Skin biopsy showed diffuse necrosis of the epidermis. After admission to the hospital, steroid pulse therapy (1000 mg/day of methylprednisolone sodium succinate) was continued for 5 days. The health drink induced a positive drug lymphocyte stimulation test (DLST) and patch test. A challenge test was done with a one hundredth dose, and it was positive. We did patch tests with all components of the drink and found that Mai‐Meu‐Dong‐Tang (ophiopogonis) alone was positive at 72 hours. There is no previous report of Stevens‐Johnson syndrome caused by a health drink or Mai‐Meu‐Dong‐Tang. Even though it is a health drink, we should be aware of the possibility of a severe reaction.

Effect of Right Ventricular Apex Pacing on the Tei Index and Brain Natriuretic Peptide in Patients with a Dual‐Chamber Pacemaker

Background: Asynchronous electrical activation induced by right ventricular apex (RVA) pacing can cause various abnormalities in left ventricular (LV) function, particularly in the context of severe LV dysfunction or structural heart disease. However, the effect of RVA pacing in patients with normal LV and right ventricular (RV) function has not been fully elucidated. The aim of this study was to characterize the effects of RVA pacing on LV and RV function by assessing isovolumic contraction time and isovolumic relaxation time divided by ejection time (Tei index) and by assessing changes in plasma brain natriuretic peptide (BNP).

Relationship between clinical outcomes and unintentional pulmonary vein isolation during substrate ablation of atrial fibrillation guided solely by complex fractionated atrial electrogram mapping

BACKGROUND Controversy exists as to whether atrial fibrillation (AF) ablation guided solely by complex fractionated atrial electrogram (CFAE) has a good outcome despite not requiring pulmonary vein isolation (PVI). OBJECTIVES The purpose of this study was to evaluate the effectiveness of AF ablation guided solely by targeting CFAE areas, and to determine whether its clinical efficacy has any relationship with unintentionally isolating the PV. METHODS We studied 100 consecutive patients (ages 59 ± 11 years; 54 with paroxysmal, 35 persistent, and 11 long-standing persistent AF), who underwent CFAE-ablation. PV potential (PVP) was recorded before and after ablation. After excluding 39 patients in whom sinus rhythm could not be maintained before ablation by internal cardioversion and/or who had a history of PVI(s), PVPs were analyzed. RESULTS AF was terminated during ablation in 98% of paroxysmal, 80% of persistent, and 55% of long-standing persistent AF patients. Nifekalant (0.3-0.6 mg/kg) was administered in 30%, 57%, and 83%, respectively. The common areas of CFAE around the PVs were anterior to the right PVs, posterior to the left PVs, and at the ridge of the left atrial appendage. Among 215 PVs in 61 patients (42 paroxysmal, 19 persistent), only 17 PVs (8%) were unintentionally isolated. The atrial potential to PVP was prolonged (>30 ms) in 13% of PVs. After at least 12 months of follow-up (23 ± 5 months), 65% of paroxysmal (11% with drug), 54% of persistent (37% with drug), and 45% of long-standing (60% with drug) AF patients were free from atrial arrhythmia after one session. CONCLUSIONS CFAE-ablation terminates AF without isolating PVs in a high percentage of patients, and yields excellent clinical outcomes.

Atrial fibrillation-induced endothelial dysfunction improves after restoration of sinus rhythm

BACKGROUND Recent evidence suggests that atrial fibrillation (AF) adversely affects endothelial function. The goal of this study was to assess endothelial function in patients with AF before and after restoration of sinus rhythm by catheter ablation (ABL). METHODS Reactive hyperemia peripheral arterial tonometry (RH-PAT) measurements reflecting endothelial function were conducted with Endo-PAT2000 (Itamar Medical, Caesarea, Israel) in 27 patients with persistent AF before ABL and in 21 control subjects with sinus rhythm (SR). According to cardiac rhythm on the morning after ABL, patients were divided into two groups: day 1-restored SR group (n=19) and day 1-recurred AF group (n=8). Based on the cardiac rhythm at 6 months after ABL, the restored SR group was further subdivided into the month 6-maintained SR group (n=11) and the month 6-recurred AF group (n=6). RESULTS Loge RH-PAT index (RHI) was significantly lower in the persistent AF group than in the control (SR) group (0.52 ± 0.20; 0.69 ± 0.24, p<0.01). Multivariate logistic regression analysis revealed that persistent AF was the only independent predictor of impaired endothelial function defined as loge RHI<0.6 (odds ratio, 4.96; 95% CI, 1.2 to 21.3; p<0.05). Loge RHI was significantly higher after ABL than before ABL (0.53±0.20; 0.73 ± 0.25; p<0.01) in the day 1-restored SR group. Loge RHI of the month 6-maintained SR group was comparable to that of the day 1-restored SR group. CONCLUSIONS These results suggest that AF is associated with impairment of endothelial dysfunction and that this impairment is reversed by restoration of sinus rhythm.

The role of infection in the development of non-valvular atrial fibrillation: Up-regulation of Toll-like receptor 2 expression levels on monocytes

Many studies have suggested that inflammation may participate in the pathogenesis of non-valvular atrial fibrillation (AF). However, it has been unknown by exposure to what the inflammation is caused. Recently, we reported that Toll-like receptor 2 (TLR2) level on monocytes was significantly up-regulated in viral and bacterial infections, but not in non-infectious inflammatory states. Our purpose was to test the hypothesis that expression of TLR2 levels may be up-regulated in patients with non-valvular AF. A total of 48 consecutive patients with non-valvular AF who were hospitalized for catheter ablation were enrolled in this study. TLR2 levels were assayed by using flow-cytometric analysis and compared with volunteers in sinus rhythm (control group, n = 24). Additionally, C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assayed, and the left atrial volume indexes (LAVI) in the non-valvular AF group were measured. The results demonstrated that TLR2 levels in the non-valvular AF group were significantly higher than in the control group (median, 4682 vs. 3866 sites/cell; P < 0.01). Moreover, non-valvular AF patients had significantly higher IL-6 levels than controls. However, there was no significant difference in CRP levels between the two groups. It was observed in 44 AF patients, in whom pulmonary vein isolation was confirmed to be successful, that the LAVI significantly diminished 1 month after ablation (median, 33.6 vs. 29.5 ml/m²; P < 0.001), but not the TLR2 and IL-6 levels. Our results implied that an infectious inflammation may participate in the pathogenesis of non-valvular AF.

Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol

Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = −0.24, P < 0.05; r = −0.17, P < 0.05, r = −0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.

Time-course of Toll-like receptor 2 expression, as a predictor of recurrence in patients with bacterial infectious diseases

The clinical course of bacterial infectious diseases is often variable, especially in elderly patients. Thus, new biological markers have been sought to predict the disease outcome. Recent studies have revealed that Toll‐like receptor (TLR) 2 and/or TLR4 on circulating monocytes are significantly up‐regulated in bacterial infections. However, the lack of reliable quantification methods hampers extensive study on the modulation of these molecules in response to the patients clinical condition. In this study, we developed a new quantitative flow cytometric analysis system for TLR2. We then carried out a longitudinal study on TLR2 expression levels on monocytes from patients suffering from bacterial infectious diseases during and after antibiotic treatment. The clinical outcome divided 37 patients into ‘cure’ (n = 24) and ‘recurrence’ (n = 13) groups. A significant difference between the two groups was recognized in the TLR2 levels just after antibiotic treatment (antibody‐binding sites/cell, 4395 ± 784 versus 5794 ± 1484, P < 0·001). The risk of recurrence was associated significantly with TLR2 (P < 0·001), but not C‐reactive protein (P = 0·351) levels assayed during the first remission. Furthermore, antibiotic effectiveness was associated inversely with TLR2 levels during antibiotic administration (P < 0·001). Taken together, TLR2 expression levels on monocytes provide critical information for planning treatment against bacterial infectious diseases.

Comparison of effect between nitrates and calcium channel antagonist on vascular function in patients with normal or mildly diseased coronary arteries

The comparative long-term antianginal efficacy of long-acting nitrates versus calcium channel antagonists remains unclear. The goal of the present study was to compare the coronary endothelial cell function and coronary artery vasoconstriction between patients with normal or mildly diseased coronary arteries treated with long-acting nitrates or calcium channel antagonists. Forty-two patients suspected to have angina pectoris and with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. All patients were suspected to have angina pectoris and were receiving either long-acting nitrates (n = 18; Nitrates group) or calcium channel antagonists (n = 24; Ca-antagonists group) for at least 1 year. Vascular reactivity was assessed by intracoronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Segments that showed the greatest constrictive response to Ach were used for assessment of vasoconstriction. The percent increase in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach was significantly smaller in the Nitrates group than in the Ca-antagonists group (33% ± 74% vs 83% ± 77%, P < 0.05; −3% ± 16% vs 11% ± 12%, P < 0.01, respectively). The percent diameter reduction in the region of greatest constrictive response to Ach was significantly greater in the Nitrates group than in the Caantagonists group (44% ± 39% vs 15% ± 32%, P < 0.02). Long-term treatment with long-acting nitrates may produce less favorable effects on coronary endothelial function and the constrictive response to Ach when compared with long-acting calcium channel antagonists in patients with normal or mildly diseased coronary arteries.

Left atrium volume index and pathological features of left atrial appendage as a predictor of failure in postoperative sinus conversion

BACKGROUND Previous studies showed that some parameters, including left atrium diameter and left atrium volume index (LAVI), predicted the success of sinus conversion. However, no previous studies have investigated the association of sinus conversion with LAVI and histopathological findings. This study was designed to investigate the relationship among LAVI, pathological assessment, and failure in sinus conversion after surgery for valvular atrial fibrillation (AF). METHODS AND RESULTS A total of 78 patients with left atrium enlargement and valvular AF who underwent maze procedure concomitantly with various cardiac surgeries were classified into one of two groups: those who successfully underwent sinus conversion (Group 1; n=40) and those who did not achieve sinus conversion (Group 2; n=38). Histopathological assessment was performed in 9 cases using tissues derived from the left atrial appendage (LAA). The degree of histopathological change was classified into 1 of 4 grades. LAVI was significantly less in Group 1 than in Group 2 (81 + or - 22 ml/m(2) vs. 122 + or - 49 ml/m(2), p<0.001). Preoperative LAVI predicted 100% failure of sinus conversion after surgery with a cut-off value of 135 ml/m(2). Histopathological analyses clearly showed that the grades for intercellular fibrosis, fatty infiltration, endocardial thickening, and nuclear enlargement/abnormalities were significantly and positively correlated with LAVI (r=0.75, p<0.05; r=0.74, p<0.05; r=0.69, p<0.05; r=0.77, p<0.05, respectively). CONCLUSIONS LAVI associated with histopathological features of the resected LAA is a predictor of failure in sinus conversion following surgical intervention in patients with valvular AF.

Association of coronary shear stress with endothelial function and vascular remodeling in patients with normal or mildly diseased coronary arteries

BackgroundThe relationship between coronary remodeling, shear stress and endothelial function remains unclear. ObjectiveThe present study investigated the effects of mechanical factors on structure and function of epicardial coronary arteries. MethodsPatients (group 1: %area stenosis<40%, n=55; or group 2: %area stenosis ≥40%, n=17) with a discrete mildly stenotic lesion (%diameter stenosis<30%) underwent intravascular ultrasound examination of the left anterior descending coronary artery for determination of vessel area, lumen area, plaque area, cross-sectional areas at reference segments, and remodeling index (the ratio of vessel area at the culprit lesion to vessel area at the proximal reference site). Further, vascular reactivity was examined using intracoronary administration of acetylcholine, papaverine, and nitroglycerin. ResultsVessel area significantly correlated with plaque area in both groups (r=0.65, P<0.0001 and r=0.85, P<0.0001). Group 1 showed significantly greater acetylcholine-induced percentage changes in coronary blood flow (67±70 vs. 16±75%, P<0.05) and coronary artery diameter (−7±18 vs.−32±31%, P<0.01) and also significantly smaller coronary wall shear stress (65±27 vs. 81±32 dynes/cm2, P<0.05) than group 2. The percentage increase in coronary blood flow induced by acetylcholine was significantly and positively correlated with remodeling index in group 1 (r=0.64, P<0.0001) but not in group 2 (r=−0.03, P=0.90) and was also significantly and positively correlated with coronary wall shear stress in group 1 (r=0.46, P<0.001) but not in group 2 (r=−0.33, P=0.19). ConclusionsEndothelium-dependent vasodilation in the resistance coronary artery correlates with remodeling via increased wall shear stress when target lesions %area stenosis is <40%.