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PURPOSE In aortic stenosis (AS), the discrepancy between moderately accelerated flow and effective orifice area (EOA) continues to pose a challenge. We developed a method of measuring the vena contracta area as hemodynamic EOA using cardiac MRI focusing on AS patients with a moderately accelerated flow to solve the problem that AS severity can currently be determined only by echocardiography. METHODS We investigated 40 patients with a peak transvalvular velocity > 3.0 m/s on transthoracic echocardiography (TTE). The patients were divided into highly accelerated and moderately accelerated AS groups according to whether or not the peak transvalvular velocity was ≥ 4.0 m/s. From the multislice 2D cine phase-contrast MRI data, the cross-sectional area of the vena contracta of the reconstructed streamline in the Valsalva sinus was defined as MRI-EOAs. Patient symptoms and echocardiography data, including EOA (defined as TTE-EOA), were derived from the continuity equation using TTE. RESULTS All participants in the highly accelerated AS group (n = 19) showed a peak velocity ≥ 4.0 m/s in MRI. Eleven patients in the moderately accelerated AS group (n = 21) had a TTE-EOA < 1.00 cm2. In the moderately accelerated AS group, MRI-EOAs demonstrated a strong correlation with TTE-EOAs (r = 0.76, P < 0.01). Meanwhile, in the highly accelerated AS group, MRI-EOAs demonstrated positivity but a moderate correlation with TTE-EOAs (r = 0.63, P = 0.004). MRI-EOAs were overestimated compared to TTE-EOAs. In terms of the moderately accelerated AS group, the best cut-off value for MRI-EOAs was < 1.23 cm2, compatible with TTE-EOAs < 1.00 cm2, with an excellent prediction of the New York Heart Association classification ≥ III (sensitivity 87.5%, specificity 76.9%). CONCLUSION MRI-EOAs may be an alternative to conventional echocardiography for patients with moderately accelerated AS, especially those with discordant echocardiographic parameters.

Abstract Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial. Clinical trial registration NCT02918305 (http://www.clinicaltrials.gov).

Background: In the resting conditions, narrowing the window of coronary pressure measurements from the whole cardiac cycle to diastole improves diagnostic performance of coronary pressure–derived physiological index. However, whether this also applies to the hyperemic conditions has not yet been thoroughly evaluated. Objectives: The purpose of this study was to assess whether diastolic fractional flow reserve (diastolic FFR) has better diagnostic performance in identifying ischemia-causing coronary lesions than conventional FFR in a prospective, multicenter, and independent core laboratory–based environment. Methods: In this prospective multicenter registry at 29 Japanese centers, we compared the diagnostic performance of FFR, diastolic FFR, resting distal to aortic coronary pressure (Pd/Pa), and diastolic pressure ratio (dPR) using myocardial perfusion scintigraphy (MPS) as the reference standard in 378 patients with single-vessel coronary disease. Results: Inducible myocardial ischemia was found on MPS in the relevant myocardial territory of the target vessel in 85 patients (22%). In the receiver-operating curve analyses, diastolic FFR had comparable area under the curve (AUC) compared with FFR (AUCdiastolic FFR: 0.66; 95% confidence interval [CI]: 0.58-0.73, vs AUCFFR: 0.66; 95% CI: 0.58-0.74, P = 0.624). FFR and diastolic FFR showed significantly larger AUCs than resting Pd/Pa (0.62; 95% CI: 0.54-0.70; P = 0.033 and P = 0.046) but did not show significantly larger AUCs than dPR (0.62; 95% CI: 0.55-0.70; P = 0.102 and P = 0.113). Conclusions: Diastolic FFR showed a similar diagnostic performance to FFR as compared with MPS. This result reaffirms the use of FFR as the most accurate invasive physiological lesion assessment. (Diagnostic accuracy of diastolic fractional flow reserve (d-FFR) for functional evaluation of coronary stenosis; UMIN000015906)

Aims: This study aimed to assess the clinical efficacy of intravascular ultrasound (IVUS)-guided intraplaque wiring for femoropopliteal (FP) chronic total occlusion (CTO). Methods: This single-center, retrospective, observational study was performed at the Japanese Red Cross Kyoto Daini Hospital. From March 2013 to June 2017, a total of 75 consecutive patients (mean age: 75.4 ± 8.5 years; 59 males), who underwent endovascular treatment (EVT), having 82 de novo FP-CTO lesions, were enrolled in this study. Eleven of the lesions that met the exclusion criteria were excluded, and the remaining 71 lesions were divided into the IVUS-guided wiring group (n = 34) and non-IVUS-guided wiring group (n = 37). Primary patency, defined as a peak systolic velocity ratio of < 2.4 on duplex ultrasonography, and freedom from clinically driven target lesion revascularization (CD-TLR) at 12 months were the primary outcomes. Results: The mean lesion length was 21.6 ± 8.9 cm. The frequencies of primary patency and freedom from CD-TLR were significantly higher in the IVUS-guided wiring group than in the non-IVUS-guided wiring group (70.0% vs. 52.2%, p = 0.045; 83.9% vs. 62.8%, p = 0.036, respectively). The complete clinically true lumen angioplasty rate was also higher in the IVUS-guided wiring group than in the non-IVUS-guided wiring group (91.1% vs. 51.3%, p < 0.001, respectively). The clinically true and false wire passage rates were respectively 97.3% and 2.7% in the IVUS-guided wiring group. Conclusion: IVUS-guided wiring improves the clinical outcomes of EVT for FP-CTO by achieving a high clinically true lumen wire passage rate.

Background: The effect of symptoms on clinical outcomes after deferral of revascularization based on fractional flow reserve (FFR) remains poorly understood. Methods and Results: From the J-CONFIRM (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter) Registry, this study evaluated 1,215 patients with stable coronary artery disease, including symptomatic and asymptomatic patients (n=571 and 644, respectively). The primary endpoint was the cumulative 2-year incidence of target vessel failure (TVF), including cardiac death, target vessel-related myocardial infarction (TVMI), and clinically driven target vessel revascularization (CDTVR). An inverse probability weighted analysis was performed to adjust for the differences in baseline clinical characteristics between the 2 groups. At 2 years, the TVF rate did not differ significantly between symptomatic and asymptomatic patients (6.5% vs. 4.9%, respectively; P=0.15) or between symptomatic and asymptomatic patients with lesions with an FFR ≤0.80 (8.0% vs. 12.3%, respectively; P=0.20). Conversely, symptomatic patients showed significantly higher rates of TVF (6.2% vs. 3.3%; P=0.01) and CDTVR (6.2% vs. 3.1%; P=0.009) than asymptomatic patients, regardless of negative FFR values (>0.80). Conclusions: Despite negative FFR values, symptomatic patients were at higher risk of TVF than asymptomatic patients, driven primarily by a higher rate of CDTVR. Conversely, those with a positive FFR were likely to develop TVF regardless of their symptoms.

Left ventricular mechanical dyssynchrony (LVMD) induced by exercise stress was reported to be clinically useful in detecting multivessel coronary artery diseases. The aim of this study was to compare the prognostic value of LVMD induced by pharmacological stress with that induced by exercise stress. We retrospectively examined 918 consecutive patients who underwent exercise (N = 310) or pharmacological stress (N = 608) 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) with normal myocardial perfusion. LVMD was evaluated by phase analysis as the indices of phase bandwidth and phase standard deviation (PSD). During the follow-up period (2.2 ± 1.9 years), 74 major cardiac events (MCEs) occurred (7 cases of cardiac death, 17 cases of heart failure, and 50 cases of coronary intervention). In global patients, the indices of LVMD on rest images were significantly greater in patients with MCEs (bandwidth (°): 51 ± 31 vs 37 ± 21, P = .001, PSD: 14 ± 9 vs 10 ± 6, P = .001). The exercise stress bandwidth was significantly higher in patients with MCEs (62 ± 37° vs 42 ± 21°, P = .026), as was the pharmacological stress bandwidth (57 ± 35° vs 43 ± 24°, P = .006). Multivariate analysis demonstrated the exercise stress bandwidth to be an independent predictor of MCEs (HR 1.017, CI 1.003 to 1.032, P = .019), but the pharmacological stress bandwidth had no influence on MCEs. LVMD induced by exercise stress was an independent predictor of MCEs in patients with normal perfusion SPECT, whereas that induced by pharmacological stress had no association with further events.

This study aimed to evaluate the utility and feasibility of physiological maps coregistered with angiograms using the pullback of a pressure guidewire with continuous instantaneous wave-free ratio (iFR) measurements. iFR pullback was obtained for 70 lesions from 70 patients with stable angina pectoris using SyncVision (Philips Corp.). Physiological maps were created, whereby the post-intervention iFR (post-iFR) was predicted as iFRpred. The iFR gap was defined if the difference between the iFRpred and post-iFR was ≥ 0.3. The lesion morphology changed from that during the physiological assessment to that during the angiographic assessment in 26 lesions (37.1%). In particular, 22.6% of angiographic tandem lesions changed to physiological focal lesions. The mean pre-intervention iFR, post-iFR, and iFRpred were 0.73 ± 0.17, 0.90 ± 0.06, and 0.93 ± 0.05, respectively. The mean difference between the iFRpred and post-iFR was 0.029 ± 0.099, with 95% limits of agreement of -0.070–0.128. iFR gaps occurred in 28 patients (40%). Notably, a new iFR gradient causing a ≥ 0.03 iFR drop after stenting occurred in 11 (15.7%) cases. The study patients were divided into two groups according to biases between post-iFR and iFRpred p = 0.027). Physiological maps under resting conditions may contribute to a reduction in unnecessary stent placements without missing lesions requiring treatment. However, the predictive accuracy of post-iFR performance in the present study was slightly lower than that in the previous reports.

The purpose of this study was to evaluated the clinical characteristics of calcified nodule-like in-stent restenosis (ISR) lesions using optical coherence tomography (OCT) in vivo. A total of 124 ISR lesions that were treated with a repeat coronary intervention under OCT guidance were included in this analysis. ISR neointimal morphology was classified as “calcified nodule-like ISR”, that appeared as a high-backscattering protruding mass with an irregular surface covered by signal-rich bands, or “non-calcified nodule-like ISR”. The maximum arc and thickness of calcium behind the stent struts was also measured. Of the 124 ISR lesions, calcified nodule-like ISR was observed in 11 lesions (9%). OCT analysis data showed that the maximum arc of calcium and the maximum calcium thickness behind the stent were significantly larger in the calcified nodule-like ISR lesions than in the non-calcified nodule-like ISR lesions (269 ± 51 vs. 179 ± 92°, p

The study sought to investigate the prognostic implications of relative increase of fractional flow reserve (FFR) with PCI in combination with post-percutaneous coronary intervention (PCI) FFR.FFR, measured after PCI has been shown to possess prognostic implications. The relative increase of FFR with PCI can be determined by the interaction of baseline disease pattern, adequacy of PCI, and residual disease burden in a target vessel. However, the role of relative increase of FFR with PCI has not yet been evaluated.A total of 621 patients who underwent PCI using second-generation drug-eluting stents based on low pre-PCI FFR (≤0.80) and available post-PCI FFR were analyzed. The relative increase of FFR was calculated by %FFR increase with PCI ([post-PCI FFR - pre-PCI FFR]/pre-PCI FFR × 100). Patients were divided according to the optimal cutoff values of post-PCI FFR (0.84) and %FFR increase (≤15%). The primary outcome was target vessel failure (TVF) (a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years.Among the total population, 66.0% showed high post-PCI FFR (≥0.84) and 69.2% showed high %FFR increase (15%). Patients with low post-PCI FFR showed a higher risk of 2-year TVF than did those with high post-PCI FFR (9.1% vs. 2.6%; hazard ratio [HR]: 3.367; 95% confidence interval [CI]: 1.412 to 8.025; p = 0.006). Patients with low %FFR increase also showed a higher risk of 2-year TVF compared with those with high %FFR increase (9.2% vs. 3.0%; HR: 3.613; 95% CI: 1.543 to 8.458; p = 0.003). Among the high post-PCI FFR group, there were no significant differences in clinical outcomes according to %FFR increase. Conversely, among the low post-PCI FFR group, those with low %FFR increase showed a significantly higher risk of TVF than did those with high %FFR increase (14.3% vs. 4.1%; HR: 4.334; 95% CI: 1.205 to 15.594; p = 0.025). Percent FFR increase significantly increased discriminant and reclassification ability for the occurrence of TVF when added to a model with clinical risk factors and post-PCI FFR (C-index 0.783 vs. 0.734; relative integrated discrimination improvement 0.702; p = 0.009; category-free net reclassification index 0.479; p = 0.031).Percent FFR increase with PCI showed similar prognostic implications with post-PCI FFR. Adding the relative increase of FFR to post-PCI FFR would enable better discrimination of high-risk patients after stent implantation. (Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE]; NCT01873560).

The most important factor for preventing contrast-induced nephropathy (CIN) during percutaneous coronary intervention (PCI) in patients with severe renal dysfunction is to minimize the contrast volume. Herein, we report a successful case of complete revascularization after 3 separate PCI procedures using a super-low volume of contrast medium in a patient with 3-vessel disease, including two chronic total occlusions (CTOs). A 70-year-old man having exertional angina despite maximal medical therapy was referred to our hospital. He had severe renal dysfunction (estimated glomerular filtration rate 19 mL/minute/1.73 m2). Coronary angiography, in which a total volume of 15 mL (over 3 injections) of contrast medium was used after hydration with normal saline, demonstrated 2 CTOs in the proximal left circumflex artery (LCX) and the proximal right coronary artery (RCA) as well as focal stenosis in the mid left descending artery (LAD). Because the patient refused coronary artery bypass grafting, we opted for revascularization with PCI, divided into 3 procedures. We made full use of microcatheter tip injection and evaluation with intravascular ultrasound and achieved complete revascularization with a total of 31 mL of contrast medium: 9 mL for RCA, 6 mL for LAD, and 16 mL for LCX, without the occurrence of CIN. Additionally, we present tips for performing PCI using super-low contrast medium.

This study aimed to evaluate the feasibility and utility of using motorized pullback of the pressure guidewire to provide a graphic assessment and prediction of the benefits of coronary intervention. Fractional flow reserve (FFR) measurements were performed with motorized pullback imaging in 20 patients who underwent successful percutaneous coronary intervention (PCI) of the left anterior descending artery. Physiological lesion length (PLL) was calculated using frame counts to determine stent length. FFR area was calculated by integrating the FFR values recorded during pullback tracing (FFRarea). The percentage increase in FFR area (%FFRarea) was defined as the ratio of the difference between the pre- and post-intervention FFRarea to the total frame count. The average FFR values were enhanced following PCI, from 0.64 to 0.82, and the median value of the difference between pre- and post-interventional FFR values (D-FFR) and %FFRarea were 0.13 and 10.6%, respectively. The %FFRarea demonstrated a significant positive correlation with D-FFR (R 2, 0.61; p

We herein report a case involving the systemic presentation of angiolymphoid hyperplasia with eosinophilia (ALHE) in association with membranous nephropathy (MN). A 34-year-old Japanese man presented with leg edema and bilateral temporal nodules. He had a history of Buerger's disease and recurrent coronary stenosis. A renal biopsy performed to assess nephrotic syndrome revealed MN. Furthermore, a temporal nodule was excised, and ALHE was diagnosed. We reevaluated the coronary and posterior tibial artery specimens obtained in his twenties and presumed that these lesions were also vascular tumors arising from ALHE. The association of ALHE and MN is quite rare.

Background The involvement of cholesterol crystals (CCs) in plaque progression and destabilization of atherosclerotic plaques has been recently recognized. This study aimed to evaluate the association between the intraplaque localization of CCs and plaque vulnerability. Methods We investigated 55 acute coronary syndrome (ACS) and 80 stable angina pectoris (stable AP) lesions using optical frequency domain imaging (OFDI) prior to percutaneous coronary intervention. The distance between CCs and the luminal surface of coronary plaques was defined as CC depth. Results Although the incidence of CCs had similar frequencies in the ACS and stable AP groups (95% vs. 89%, p = 0.25), CC depth was significantly less in patients with ACS than in those with stable AP (median [25th to 75th percentile]: 68 μm [58 to 92 μm] vs. 152 μm [115 to 218 μm]; p < 0.001). The incidences of plaque rupture, thrombus, lipid-rich plaques, and thin-cap fibroatheroma were significantly greater in patients with ACS than in those with stable AP (62% vs. 18%, p < 0.001; 67% vs. 16%, p < 0.001; 84% vs. 57%, p < 0.01; and 56% vs. 19%, p < 0.001, respectively). Conclusion OFDI analysis revealed that CCs were found in the more superficial layers within the coronary atherosclerotic plaques in patients with ACS than in those with stable AP, suggesting that CC depth is associated with plaque vulnerability. CC depth, a novel OFDI-derived parameter, could be potentially used as an alternative means of evaluating plaque vulnerability in coronary arteries.

The Moral Foundations Dictionary (MFD) is a useful tool for applying the conceptual framework developed in Moral Foundations Theory and quantifying the moral meanings implicated in the linguistic information people convey. However, the applicability of the MFD is limited because it is available only in English. Translated versions of the MFD are therefore needed to study morality across various cultures, including non-Western cultures. The contribution of this paper is two-fold. We developed the first Japanese version of the MFD (referred to as the J-MFD) by introducing a semi-automated method---this serves as a reference when translating the MFD into other languages. We next tested the validity of the J-MFD by analyzing open-ended written texts about the situations that Japanese participants thought followed and violated the five moral foundations. We found that the J-MFD correctly categorized the Japanese participants' descriptions into the corresponding moral foundations, and that the Moral Foundations Questionnaire (MFQ) scores were correlated with the frequency of situations, of total words, and of J-MFD words in the participants' descriptions for the Harm and Fairness foundations. The J-MFD can be used to study morality unique to the Japanese and cultural differences in moral behavior., Comment: 14 pages, 2 figures, 2 tables

Background: Dilated cardiomyopathy (DCM) is characterized by a dilated left ventricular cavity with systolic dysfunction manifested by heart failure. It has been revealed that mutations in genes for cytoskeleton or sarcomere proteins cause DCM. However, the disease-causing mutations can be found only in far less than half of patients with a family history, indicating that there should be other disease genes for DCM. Formin homology 2 domain containing 3 (FHOD3) is a sarcomeric protein expressed in the heart that plays an essential role in sarcomere organization during myofibrillogenesis. The purpose of this study was to explore a possible novel disease gene for DCM. Methods and Results: We analyzed 48 Japanese familial DCM patients for mutations in FHOD3, and a missense variant, Tyr1249Asn, which was predicted to modify the 3D structure and damage protein function, was found in a case with adult-onset DCM. Functional studies revealed that the DCM-associated mutation significantly reduced the ability to induce actin dynamics-dependent activation of serum response factor, although no remarkable change in the cellular localization was induced in neonatal rat cardiomyocytes transfected with a mutant construct of FHOD3. Conclusions: The DCM-associated FHOD3 variant may cause DCM by interfering with actin filament assembly. (Circ J 2013; 77: 2990–2996)

This study investigated the effect of fractional flow reserve (FFR) after stent implantation on clinical outcomes. Pressurewire measurements and follow-up data were obtained after stent implantation. Regarding the end point, target lesion revascularization (TLR) occurred in 11 patients (15.9 %). Patients with TLR had higher frequencies of multiple stenting (54.5 vs. 19.0 %, p = 0.01), lower post-interventional FFRs (0.84 vs. 0.88, p = 0.01), and longer stent lengths (42.20 vs. 27.69 mm, p = 0.01) than patients without TLR. The post-interventional FFR cutoff for TLR was 0.79, although this value had a weak discriminatory ability. However, multivariate analysis did not show any significant independent predictors of TLR (odds ratio 6.33; confidence interval 0.75–53.4, p = 0.09). Post-interventional FFR values were not significantly associated with TLR when a sub-analysis was performed in patients who underwent only drug-eluting stent (DES) implantation. It was difficult to achieve post-interventional FFRs of 0.9 or greater. DES implantation eliminated the effect of post-interventional FFR on TLR. Post-interventional FFR was not able to predict TLR in the present study.

Myocardial perfusion single-photon emission-computed tomography (SPECT) can predict cardiac events in patients with coronary artery disease with high accuracy; however, pseudo-negative cases sometimes occur. Heart Risk View, which is based on the prospective cohort study (J-ACCESS), is a software for evaluating cardiac event probability. We examined whether Heart Risk View was useful to evaluate the cardiac risk in patients with normal myocardial perfusion SPECT (MPS). We studied 3461 consecutive patients who underwent MPS to detect myocardial ischemia and those who had normal MPS were enrolled in this study (n = 698). We calculated cardiac event probability by Heart Risk View and followed-up for 3.8 ± 2.4 years. The cardiac events were defined as cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization. During the follow-up period, 21 patients (3.0 %) had cardiac events. The event probability calculated by Heart Risk View was higher in the event group (5.5 ± 2.6 vs. 2.9 ± 2.6 %, p

Although narcissism has long been researched in relation to anger, previous research examined narcissistic anger toward negative feedback that had already occurred. In this study, we investigated the effects of anticipation of evaluation (present vs. absent) and negative feedback (present vs. absent), using a creativity task paradigm, on state anger scores among 231 U.S. undergraduates (76% White, 60% women). We also measured undergraduates’ narcissistic tendencies and impressions of the creativity task. Multiple regression analyses revealed a significant interaction between narcissism and negative feedback on total anger scores, with narcissists responding with more anger than non-narcissists in the condition of negative feedback. We also found a significant two-way interaction between narcissism and anticipation of evaluation on total enjoyment scores. Anticipation of feedback inhibited narcissist-prone individuals from enjoying the task in the anticipation condition, but this pattern was not present in the no-anticipation condition. Implications and recommendations to better understand the nature of narcissism are discussed.

Direct addition of a food additive-grade Aspergillus niger phytase preparation to 30% brown rice flour-added bread ingredients reduced the bread myo-inositol hexaphosphate (IP 6 ) content. The phytase preparation had protease and amylase activities. Addition of the crude phytase preparation induced bread crust collapse. Protease-free high- and low-amylase phytase fractions were prepared using preparative ampholyte-free isoelectric focusing (autofocusing). Addition of the protease-free low-amylase phytase fraction did not significantly affect loaf volume and did not collapse the crust. Addition of the protease-free high-amylase phytase fraction significantly increased loaf volume approximately 1.5× in the presence of amylase at 193–1029 U. However, addition of 1029 and 2058 U of amylase induced partial and whole bread crust collapse, respectively. Therefore, removal of protease and control of amylase activities in the phytase preparation are crucial in the preparation of brown rice flour-added bread with a low myo-inositol phosphate (IP 6 ) and good swelling property.

Previous reports have suggested that right ventricular apical pacing may lead to cardiac dysfunction. Septal pacing is thought to be superior to apical pacing in the prevention of cardiac dyssynchrony, however, there have been no reports on the contribution of septal pacing to improving clinical outcome.We retrospectively evaluated factors associated with cardiac events in patients with right ventricular pacing.The study population consisted of 256 consecutive patients newly implanted with permanent pacemakers and followed-up for 29 ± 18 months. Cardiac events, consisting of cardiac death or heart failure requiring hospitalization, occurred in 22 patients. Kaplan-Meier curves revealed that patients with a high percentage of ventricular pacing (> 90%, n = 101, group H) had a higher incidence of cardiac events than patients with a low percentage of ventricular pacing (< 10%, n = 83, group L) (P = 0.002). In group H, multivariate analysis showed that age (HR: 1.174, 95%CI: 1.066-1.291, P = 0.001), ejection fraction (EF) (HR: 0.898, 95%CI: 0.836-0.964, P = 0.003), QRS duration during cardiac pacing (HR: 1.059, 95%CI: 1.017-1.103, P = 0.006), and existing basal cardiac diseases (HR: 13.080, 95%CI: 2.463-69.479, P = 0.003) were significant predictors of cardiac events, although pacing site had no significant association with prognosis (P = 0.56).Higher age, lower EF, longer QRS duration during cardiac pacing, and existing basal cardiac diseases are associated with poor prognosis in patients with a high percentage of ventricular pacing.

Angiography is not always an accurate indicator of physiologically significant stenosis. We examined the usefulness of functional evaluation of coronary stenosis severity by determining the fractional flow reserve (FFR) using a pressure wire in patients who received hemodialysis with angiographically intermediate lesions. We recruited 44 patients with intermediate lesions; of these, 22 were undergoing hemodialysis while 22 were not. Quantitative coronary angiography (QCA) was performed to measure the minimal lumen diameter (MLD) and calculate the percent diameter stenosis (%DS). The FFR was calculated as the ratio of the coronary pressure at the distal stenotic site to the mean aortic pressure during maximum hyperemia. In each group, we investigated the relationship between the FFR and %DS and FFR and MLD. The patients in the hemodialysis group were significantly younger and had more calcified and type B2/C lesions than those in the non-dialysis group. Although the FFR was correlated with both %DS (r = 0.71, p

66歳，男性。コントロール不良な1型糖尿病・腎症で治療中の患者。初診の2ヵ月前から頭部，顔面，躯幹，四肢に痂皮を付す紅斑，びらん，膿疱が出現した。膿疱部は組織学的に角層下に棘融解と好中球の集積を認め，蛍光抗体直接法で表皮細胞間にIgGの沈着がみられ，抗Dsg1 IgG 1480，抗Dsg3 IgG

SummaryThe patient was a 74-year-old woman with angina pectoris, who had undergone percutaneous coronary intervention with stent placement in the right coronary artery on October 2, 2007. On November 12 of the same year, she suffered from paroxysmal atrial fibrillation. She was treated with pilsicainide hydrochloride administered by intravenous injection, which was followed by a sudden sinus standstill, with marked bradycardia and a shock state. The patient was then treated with a catecholamine, however, the shock state persisted for about an hour. An electrocardiogram revealed persistent ST depression in leads V4–6 along with elevation of the serum creatinine kinase. A coronary angiography performed on the admission day revealed no abnormality. On the third hospital day, a dual-isotope myocardial SPECT using 201Tl and 99mTc-pyrophosphate demonstrated an annular accumulation of 99mTc-pyrophosphate concordant with the endocardium from apex to the mid-portion of the left ventricle, suggestive of subendocardial infarction. The case is reported here, as there are few reports of subendocardial infarction developing due to ischemia arising from a shock state.

Brown rice-added breads were prepared with and without crude and purified Aspergillus niger phytase preparations. By adding 30% (w/w) brown rice flour and no phytase preparation, the phytate (myo-inositol hexaphosphate; IP6) content of the bread was increased and the loaf volume was reduced. The direct addition of a food-additive grade phytase preparation (3,000 U) resulted in a significant decrease in the IP6 content. However, it collapsed the bread crust. The crude phytase preparation had significant protease and amylase activities. A simple chromatographic method for the separation of phytase activity from the protease and amylase activities was developed. By using purified phytase, the IP6 content was reduced without any adverse effects on the rising of the bread, which indicates that protease and amylase may be responsible for the collapse of the crust by the commercial phytase preparation. PRACTICAL APPLICATIONS Phytate in unrefined cereals and beans lowers bioavailability of minerals. On the other hand, these materials are rich in health-promoting components. To reduce the phytate in them during processing, some commercially available phytase preparations are now used. However, we found that such preparation contains significant amylase and protease activities, which may cause adverse effect on the appearance and textural properties of final products. To solve these problems, a simple and inexpensive procedure for separation of phyatase from amylase and protease was developed in the present study. The purified phytase can reduce phytate in brown rice-added bread without adverse effect on rising of bread. These results would encourage prepare the phytase preparation in high purity in an industrial scale to improve nutritional value of unrefined cereal- and bean-based functional foods.

Patients with apical hypertrophic cardiomyopathy (APH) associated with paradoxic jet flow (ie, diastolic flow away from the apex) may gradually develop an apical aneurysm, which often leads to arrhythmia and mural thrombus formation. We observed systolic outward motion of the left ventricular apical myocardium in patients with APH using a magnetic resonance tagging procedure and examined the relationship of the outward motion to echocardiographic and scintigraphic findings and to cardiac events. Systolic displacement of the myocardial tags of the apical region perpendicular to the long axis in the 4-chamber view was recorded in 31 patients with APH. Of these patients, 14 showed no outward movement of tags (group A), and 17 showed outward movement (group B). In group B, apical hypertrophy was more severe (35 +/- 7 mm vs. 29 +/- 6 mm, p < 0.05), paradoxic jet flow was more frequent (64% vs. 14%, p < 0.05) and the defect score in I-123-beta-methyliodophenylpentadecanoic acid scintigraphy was higher (2.1 +/- 0.7 vs. 1.3 +/- 0.7, p < 0.01). During a mean follow-up period of 55 months, only 1 patient experienced paroxysmal atrial fibrillation in group A. In group B, 1 patient died suddenly, 1 was admitted to hospital because of congestive heart failure, 2 developed angina pectoris, 2 exhibited non-sustained ventricular tachycardia, and 1 showed multifocal premature ventricular contraction; in these 7 patients the outward movement was greater than in the 10 patients in Group B who had no cardiac events (1.00 +/- 0.59 vs. 0.52 +/- 0.40, p < 0.05). Hence, our results show that outward tag displacement is frequently associated with severe apical hypertrophy, paradoxic jet flow, apical ischemia, and cardiac events. The tagging method may be useful in assessing the severity of APH and predicting the occurrence of cardiac events at an early stage.

Objective The thiazide-sensitive Na-Cl cotransporter (TSC) is located in the distal renal tubules. Several mutations of the TSC gene cause Gitelman's syndrome, which is an autosomal recessive disease characterized by low blood pressure and hypokalemia. Recently, an association between TSC gene polymorphisms (Arg904Gln, G2736A; Thr465Thr, C1420T; Gly264Ala, G816C) and essential hypertension has been reported in Sweden. We examined the genetic involvement of the TSC gene in essential hypertension in Japanese. Design Participants were recruited from outpatients of Osaka University Hospital. We investigated 386 hypertensive and 371 normotensive subjects. Methods Genotypes of TSC polymorphisms (G2736A, C1420T, G816C) were determined by the TaqMan polymerase chain reaction (PCR) method, and statistical significance was examined using JMP 5.0.1 J (SAS Institute Inc., Cary, North Carolina, USA). The allele frequency of A2736 and T1420 was 6.0 and 3.0%, respectively, whereas we could not detect the G816C polymorphism in this study. Only the G2736A polymorphism was significantly associated with the prevalence of hypertension (P < 0.04), and the estimated odds ratio was 1.8 (95% confidence interval, 1.1-3.0) in A2736 allele carriers. The odds ratio for hypertension in A2736 carriers was increased to 2.2 (1.1-4.9) in women (n = 413), and further to 3.3 (1.4-8.0) in women with early onset of hypertension (≤ 50 years old). In addition, all subjects with the homozygous A2736 allele in this study (n = 2) and the Swedish study (n = 5) were hypertensive. Conclusion G2736A polymorphism of the TSC gene is a genetic predisposing factor for essential hypertension in Japanese women.

The bradykinin B2 receptor shows a protective role in the development of hypertension and renal and cardiovascular complications. It was recently reported that a polymorphism of the bradykinin B2 receptor gene (BDKRB2) is a genetic predisposing factor for hypertension and cardiovascular disease. The aim of this study was to examine the relationship of a polymorphism (-58 T/C and exon 1 +9/-9) of BDKRB2, and an insertion/deletion polymorphism (I/D) of the angiotensin converting enzyme gene (ACE) with essential hypertension and cardiovascular mortality in the Japanese population. Genotyping was carried out in 275 hypertensive and 441 normotensive subjects. Left ventricular hypertrophy (LVH) was detected by ECG in 242 untreated patients with hypertension. All participants were Japanese and gave their written informed consent. The polymorphism (-58 T/C) in the promoter region of the BDKRB2 was determined using the TaqMan-polymerase chain reaction (PCR) method, the exon 1 +9/-9 polymorphism of the BDKRB2 and I/D polymorphism of the ACE were monitored by PCR and gel electrophoresis. The genotypes and allelic frequencies were in Hardy-Weinberg equilibrium. The polymorphism (-58 T/C) in the promoter of the BDKRB2 was associated with LVH in the hypertensive group (n =242) (p =0.048; χ2 =3.9; odds ratio: 1.8; 95% confidence interval (CI): 1.0-3.3). Furthermore, the frequency of LVH in hypertensives was significantly higher in the subjects with both the BDKRB2 CC and ACE D allele than those with other genotypes (p =0.002, χ2 =9.4). However, no relationship could be found between polymorphism of the BDKRB2 (p =0.86, χ2 =0.3) or the ACE (p =0.21, χ2 =3.1) and hypertension in this group of subjects. These results suggest that the polymorphism (-58 T/C) in the promoter region of BDKRB might be a risk factor and might have a synergetic effect with the ACE for LVH in hypertensives, but it is not associated with hypertension in the Japanese population. (Hypertens Res 2004; 27: 933-938)

Hepatocyte growth factor (HGF) is a growth factor which contributes to protection and/or repair of vascular endothelial cells. Serum HGF level is elevated in response to hypertensive organ damage, which suggests that blood pressure regulation may be affected by HGF gene polymorphisms via serum HGF. To examine the interaction between a HGF gene polymorphism and hypertension, we carried out a case-control study. The present study was conducted in outpatients of Osaka University Hospital. Subjects (n =654) who gave informed consent to the study protocol and genetic analysis were recruited. A C to A nucleotide substitution in intron 13 of the HGF gene was determined by the TaqMan polymerase chain reaction (PCR) method using an MGB (Minor Groove Binder) probe. The genotype distribution of the C/A polymorphism of the HGF gene in total subjects was as follows: CC, 83%; CA, 16%; and AA 1%. This distribution was not significantly different from the predicted by Hardy-Weinberg’s equilibrium. The prevalence of hypertension was significantly higher in subjects with the CC genotype than in those with an A allele, and the positive association remained after adjustment for confounding factors, with the estimated odds ratio for hypertension (CC vs. CA+AA) being 1.71 (95% confidence interval: 1.02-2.93). A significant association with hypertension was observed in lean or female subjects but not in obese or male subjects. In conclusion, our data suggested that C/A polymorphism in intron 13 of the HGF gene is associated with susceptibility to essential hypertension in lean or female subjects. (Hypertens Res 2004; 27: 247-251)

We experienced an entrapped rotablator burr that could not be retrieved even by deep seating of the guiding catheter. We successfully retrieved the burr by balloon inflation after the tapered tip of a Conquest wire managed to penetrate the quite hard plaque and pass through the outer lumen of the burr.

Background: With the imminent advent of an extremely aged society, there will be an increasing requirement for the prediction, early detection and treatment of cerebral infarction. Involved in the etiological mechanisms of cerebral infarction are a number of complex genetic and environmental factors related to the onset and progression of hypertension and arteriosclerosis. Elucidation of the significance of the various risk factors will require definite identification of phenotypes using large numbers of subjects. Methods: The present study was conducted as part of a cohort study with subjects from the general population of a rural community (the Ohasama Study). Blood pressure (BP) patterns were assessed through random home-based and clinical measurements, as well as 24 h ambulatory BP monitoring. Magnetic resonance imaging of the brain was carried out in some subjects in order to detect asymptomatic cerebral infarcts, the maximum intima–media thickness was determined by carotid high-resolution ultrasonography, and cognitive function was assessed using the mini mental state examination. Correlation analysis of these parameters and the candidate hypertensive genotypes was then performed. Results: Significant associations were seen between (i) gene polymorphisms in the renin–angiotensin system and asymptomatic cerebral infarction and the non-dipper pattern of circadian blood pressure variation; and (ii) endothelial nitric oxide synthase (eNOS) gene polymorphism and arterial pressure, lacunar score and cognitive function. An association was seen between the endothelin-1 polymorphism and hypertension, but only in obese subjects. Conclusion: There are interactions between genes and the environment in the etiology of cerebral infarction.

Background: The purpose of the present paper was to determine clinical risk factors for the development of pressure ulcers in bedridden elderly inpatients. Methods: A case-control study was performed for 117 subjects with pressure ulcers (mean age: 80.6 ± 7.2 years) with a 1-year observation period, and 351 age- and sex-matched controls. Factors examined were subitems of the Braden scale; convenient clinical assessment (continence, sitting, turning, oral intake, and sitting up); underlying chronic conditions (stroke and diabetes mellitus); and circulating levels of albumin, total cholesterol, total lymphocyte count, and hemoglobin. Results: Compared to the controls, test cases showed lower scores of the Braden scale and lower levels of circulating factors, and higher incidences of incapability of the subitems of convenient clinical assessment, and of diabetes mellitus (P < 0.20). Three models of multiple logistic regression analysis revealed that decreased serum level of albumin and impaired self-positioning in bed were significant independent risk factors. The relative risk for the development of pressure ulcers after full adjustment in the group with both hypoalbuminemia (< 35 g/L) and incapability of turning over in bed, the group with the former risk alone, and the group with the latter risk alone, was 14.0 (95% confidence interval (CI): 4.2–46.6), 4.9 (1.6–14.9), and 5.9 (1.8–19.0), respectively, compared to subjects without the two risk factors. Moreover, decreased circulating levels of albumin and hemoglobin were associated with aggravation of pressure ulcers. Conclusion: A combined measure of albumin and incapability of self-positioning may serve as a simple but useful index for the risk of pressure ulcers in bedridden elderly inpatients.

CD36 is homologous with myocardial long-chain fatty acid (LCFA) binding protein and has been suggested to relate to myocardial fatty acid metabolism. Myocardial scintigraphy with iodine-123 15-(p-iodophenyl)-3-(R, S)-methylpentadecanoic acid (BMIPP) revealed an impairment in LCFA metabolism chiefly in the hypertrophic myocardium in hypertrophic cardiomyopathy (HCM). Recently, the incidence of CD36 deficiency has been reported to be high in HCM patients, and CD36 deficiency was proposed as an etiology of hereditary HCM. However, the pathophysiological effect of CD36 deficiency on HCM has not been fully investigated. We analysed the expression of CD36 antigens on both platelets and monocytes obtained from 82 patients with HCM using two-color flow cytometry. Among the study patients, seven patients (8.5%) demonstrated type II CD36 deficiency, whereas type I CD36 deficiency was not detected. Two of 23 patients (8.7%) with a family history of HCM and five of 59 patients (8.5%) without a family history of HCM showed type II CD36 deficiency respectively. Contrary to the previous report, three of 53 patients with asymmetric septal hypertrophy (ASH) (5.7%) and four of 29 patients without ASH (13.8%) showed CD36 deficiency. Moreover, clinical characteristics, scintigraphic findings, echocardiographic data, and hemodynamic findings disclosed no significant differences between the HCM patients showing normal CD36 expression and those with CD36 deficiency. The incidence of CD36 deficiency in HCM patients is not higher than in the general population. Therefore, CD36 deficiency is not a characteristic factor of HCM and has little influence on the pathyphysiology of HCM.

To analyze the recent change in the long-term survival of patients with dilated cardiomyopathy (DCM), the present study comprised consecutive 111 patients with ejection fraction50% and left ventricular end-diastolic diameter58 mm. who were admitted to hospital from January 1983 to December 1994. The patients were divided into 2 groups: group A who were diagnosed before 1989 and group B diagnosed after 1990. Basic characteristics at diagnosis, including age, NYHA functional class, left ventricular end-diastolic diameter and ejection fraction, were similar between these 2 groups. Calculated survival rate at 5 years was 90.0% in group B in contrast to 62.3% in group A. Event-free survival also improved in group B. In group B, beta-blockers and angiotensin converting enzyme inhibitors were more frequently used than in group A (p0.0001) whereas digitalis and other positive inotropic agents were significantly less used. Left ventricular ejection fraction was significantly improved during the follow-up period in patients treated with beta-blockers compared with those not treated with beta-blockers. These data indicate a significant improvement in the survival of patients with dilated cardiomyopathy after 1990, which may be explained by the change of medical treatment, especially the use of beta-blockers.

Triclofos sodium (TCS) is a phosphoric ester of trichlorethanol, the active metabolite of chloral hydrate (CH). TCS is widely used as a hypnotic drug for electroencephalogram (EEG) or electrocardiogram (ECG) recording in children [1, 2]. We here present an 11-year-old boy with a multilocalized, non-pigmenting FDE, following oral intake of TCS for EEG recording.An 11-year-old boy presented with multiple erythematous macules on the limbs and trunk of 12 hours duration. Twelve hours before the eruptions [...]

Background Myocardial remodeling is a crucial step for progression of heart failure (HF). Free radical generation by the failing myocardium has been proposed as linked to myocardial remodeling. The aim of this study was to evaluate the urinary excretion of 8-iso-prostaglandin F2α (8-iso-PGF2α), a reliable marker for oxidant stress in vivo, and collagen turnover in patients with acute worsening of congestive HF. Methods and Results Enrolled were 43 patients with acute worsening of congestive HF of various etiologies. On admission (acute phase) and after approximately 2 weeks of conventional treatment (chronic phase), the following were measured: (1) immunoreactive urinary 8-iso-PGF2α, (2) serum total antioxidant status (TAS); and (3) serum levels of procollagen type I carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide (CITP), biochemical markers for collagen synthesis and degradation, respectively. From the acute to the chronic phase the parameters changed as follows: 335.1±245.4 to 205.3±107.4 pg/mg creatinine for urinary 8-iso-PGF2α (p

Gene targeting approaches have suggested that the angiotensin II type 1 receptor (AT1R) is involved in blood pressure (BP) regulation and modulation of the effect of angiotensin II. The A1166C polymorphism of the AT1 receptor gene (AT1R/A1166C) is associated with hypertension in Caucasians, but not in Japanese. The goal of this study, the Ohasama Study, was to examine the association between AT1R/A1166C and hypertension, especially home BP, in the Japanese general population. The Ohasama Study was a cohort study based on Japanese rural residents of Ohasama Town in the northern part of Japan. Subjects who gave informed consent to the study protocol and genetic analysis were recruited. Home BP was measured twice in the morning within 1 h of waking up and in the evening just before going to bed. The TaqMan polimerase chain reaction (PCR) method clearly determined AT1R/A1166C genotypes (n =1,207). The genotype distribution of AT1R/A1166C was as follows: AA 84%; AC 15%; CC 1%. There was almost no difference in baseline characteristics among the AT1R genotypes (AA, AC, CC). In the subjects not receiving antihypertensive medication (n =817), both casual BP and home BP were not different among the AT1R genotypes after adjusting for confounding factors (age, sex, body mass index, current smoking habit and current alcohol consumption). The frequency of hypertension showed no difference among AT1R genotypes after adjusting for confounding factors, though the AC and CC genotypes were more frequent in hypertensives than in normotensives. Our data suggested that the AT1R/A1166C polymorphism is not a major genetic predisposing factor for hypertension in Japanese. (Hypertens Res 2004; 27: 551-556)