Healthy lifestyle, lipoprotein (a) levels and the risk of coronary artery disease.

BACKGROUND: Lipoprotein (a) [Lp(a)] is associated with coronary artery disease (CAD). However, the role of healthy lifestyle against the risk of CAD with consideration of high Lp(a) levels remains unclear. METHODS: This study examined 4512 participants who underwent serum Lp(a) level assessment at Kanazawa University Hospital from 2008 to March 2016. Their lifestyle habits were examined based on four questionnaires regarding dietary pattern, exercise habits, smoking status and body weight. Logistic regression analyses were performed to identify the association between healthy lifestyle and CAD independent of Lp(a) levels. RESULTS: The Lp(a) levels were significantly associated with CAD (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.08-1.17, p = 1.3 × 10-7 per 10 mg/dL). Under these circumstances, the lifestyle risk score was also significantly associated with CAD (OR: 1.24, 95% CI: 1.12-1.36, p = 2.4 × 10-8 ). Compared with patients with a favourable lifestyle who have Lp(a) levels of <30 mg/dL, those with an intermediate or unfavourable lifestyle were at higher risk for CAD (OR: 1.11, 95% CI: 1.02-1.20, p = 0.003 and OR: 1.40, 95% CI: 1.16-1.54, p = 3.6 × 10-5 , respectively). Further, patients with a favourable, intermediate or unfavourable lifestyle who have Lp(a) levels of ≥30 mg/dL were at high risk for CAD (OR: 1.21, 95% CI: 1.08-1.34, p = 0.0014; OR: 1.31, 95% CI: 1.14-1.48, p = 1.2 × 10-4 ; and OR: 1.81, 95% CI: 1.44-2.18, p = 2.2 × 10-7 , respectively). CONCLUSIONS: Healthy lifestyle was associated with a lower risk of CAD regardless of Lp(a) levels.

The utility of zebrafish cardiac arrhythmia model to predict the pathogenicity of KCNQ1 variants.

Genetic testing for inherited arrhythmias and discriminating pathogenic or benign variants from variants of unknown significance (VUS) is essential for gene-based medicine. KCNQ1 is a causative gene of type 1 long QT syndrome (LQTS), and approximately 30% of the variants found in type 1 LQTS are classified as VUS. We studied the role of zebrafish cardiac arrhythmia model in determining the clinical significance of KCNQ1 variants. We generated homozygous kcnq1 deletion zebrafish (kcnq1del/del) using the CRISPR/Cas9 and expressed human Kv7.1/MinK channels in kcnq1del/del embryos. We dissected the hearts from the thorax at 48 h post-fertilization and measured the transmembrane potential of the ventricle in the zebrafish heart. Action potential duration was calculated as the time interval between peak maximum upstroke velocity and 90% repolarization (APD90). The APD90 of kcnq1del/del embryos was 280 ± 47 ms, which was significantly shortened by injecting KCNQ1 wild-type (WT) cRNA and KCNE1 cRNA (168 ± 26 ms, P < 0.01 vs. kcnq1del/del). A study of two pathogenic variants (S277L and T587M) and one VUS (R451Q) associated with clinically definite LQTS showed that the APD90 of kcnq1del/del embryos with these mutant Kv7.1/MinK channels was significantly longer than that of Kv7.1 WT/MinK channels. Given the functional results of the zebrafish model, R451Q could be reevaluated physiologically from VUS to likely pathogenic. In conclusion, functional analysis using in vivo zebrafish cardiac arrhythmia model can be useful for determining the pathogenicity of loss-of-function variants in patients with LQTS.

Mechanisms of fever-induced QT prolongation and torsades de pointes in patients with KCNH2 mutation.

AIMS: Patients with particular mutations of type-2 long QT syndrome (LQT2) are at an increased risk for malignant arrhythmia during fever. This study aimed to determine the mechanism by which KCNH2 mutations cause fever-induced QT prolongation and torsades de pointes (TdP). METHODS AND RESULTS: We evaluated three KCNH2 mutations, G584S, D609G, and T613M, in the Kv11.1 S5-pore region, identified in patients with marked QT prolongation and TdP during fever. We also evaluated KCNH2 M124T and R269W, which are not associated with fever-induced QT prolongation. We characterized the temperature-dependent changes in the electrophysiological properties of the mutant Kv11.1 channels by patch-clamp recording and computer simulation. The average tail current densities (TCDs) at 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller and less increased with rising temperature from 35°C to 40°C than those for WT, M124T, and R269W. The ratios of the TCDs at 40°C to 35°C for G584S, WT+D609G, and WT+T613M were significantly smaller than for WT, M124T, and R269W. The voltage dependence of the steady-state inactivation curve for WT, M124T, and R269W showed a significant positive shift with increasing temperature; however, that for G584S, WT+D609G, and WT+T613M showed no significant change. Computer simulation demonstrated that G584S, WT+D609G, and WT+T613M caused prolonged action potential durations and early afterdepolarization formation at 40°C. CONCLUSION: These findings indicate that KCNH2 G584S, D609G, and T613M in the S5-pore region reduce the temperature-dependent increase in TCDs through an enhanced inactivation, resulting in QT prolongation and TdP at a febrile state in patients with LQT2.

Hypertrophic Cardiomyopathy Predicts Thromboembolism and Heart Failure in Patients With Nonvalvular Atrial Fibrillation　- A Prospective Analysis From the Hokuriku-Plus AF Registry.

BACKGROUND: The prognostic effect of concomitant hypertrophic cardiomyopathy (HCM) on adverse events in patients with atrial fibrillation (AF) has not been evaluated in a multicenter prospective cohort study in Japan.Methods and Results: Using the Hokuriku-Plus AF Registry, 1,396 patients with nonvalvular AF (1,018 men, 72.3±9.7 years old) were assessed prospectively; 72 (5.2%) had concomitant HCM. During a median follow-up of 5.0 years (interquartile range 3.5-5.3 years), 79 cases of thromboembolism (1.3 per 100 person-years) and 192 of heart failure (HF) (3.2 per 100 person-years) occurred. Kaplan-Meier analysis revealed that the HCM group had a significantly greater incidence of thromboembolism (P=0.002 by log-rank test) and HF (P<0.0001 by a log-rank test) than the non-HCM group. The Cox proportional hazards model demonstrated that persistent AF (adjusted hazard ratio 2.98, 95% confidence interval 1.56-6.21), the CHA2DS2-VASc score (1.35, 1.18-1.54), and concomitant HCM (2.48, 1.16-4.79) were significantly associated with thromboembolism. Conversely, concomitant HCM (2.81, 1.72-4.43), older age (1.07, 1.05-1.10), lower body mass index (0.95, 0.91-0.99), a history of HF (2.49, 1.77-3.52), and lower left ventricular ejection fraction (0.98, 0.97-0.99) were significantly associated with the development of HF. CONCLUSIONS: Concomitant HCM predicts the incidence of thromboembolism and HF in AF patients.

Effect of Catheter Ablation for Atrial Fibrillation in Heart Failure With Mid-Range or Preserved Ejection Fraction　- Pooled Analysis of the AF Frontier Ablation Registry and Hokuriku-Plus AF Registry.

BACKGROUND: A recent randomized trial demonstrated that catheter ablation for atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (EF) is associated with a reduction in death or heart failure. However, the effect of catheter ablation for AF in patients with heart failure with mid-range or preserved EF is unclear.Methods and Results: We screened 899 AF patients (72.4% male, mean age 68.4 years) with heart failure and left ventricular EF ≥40% from 2 Japanese multicenter AF registries: the Atrial Fibrillation registry to Follow the long-teRm Outcomes and use of aNTIcoagulants aftER Ablation (AF Frontier Ablation Registry) as the ablation group (525 patients who underwent ablation) and the Hokuriku-Plus AF Registry as the medical therapy group (374 patients who did not undergo ablation). Propensity score matching was performed in these 2 registries to yield 106 matched patient pairs. The primary endpoint was a composite of cardiovascular death and hospitalization for heart failure. At 24.6 months, the ablation group had a significantly lower incidence of the primary endpoint (hazard ratio 0.32; 95% confidence interval 0.13-0.70; P=0.004) than the medical therapy group. CONCLUSIONS: Compared with medical therapy, catheter ablation for AF in patients with heart failure and mid-range or preserved EF was associated with a significantly lower incidence of cardiovascular death or hospitalization for heart failure.

Characterization of baseline clinical factors associated with incident worsening kidney function in patients with non-valvular atrial fibrillation: the Hokuriku-Plus AF Registry.

Evidence suggests that atrial fibrillation (AF) could increase the risk of worsening kidney function (WKF) which is linked to an increased risk of stroke, bleeding, and death in AF patients. However, limited data exist regarding the factors that could lead to WKF in these patients. Therefore, we sought to identify the potential factors associated with the development of WKF in patients with non-valvular AF (NVAF). We analyzed prospectively recruited 1122 NVAF patients [men 71.9%, median age 73.0 years (interquartile range: 66.0-79.0)] with a baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 from the Hokuriku-Plus AF Registry. The primary outcome was incident WKF, defined as the %eGFR change from the baseline ≥ 30% during the follow-up period. We evaluated the association between baseline variables and incident WKF using univariate and multivariate Cox proportional hazard models. We also evaluated the non-linear association between the identified factors and incident WKF. During a median follow-up period of 3.0 years (interquartile range: 2.7-3.3), incident WKF was observed in 108 patients (32.6 per 1000 person-years). Compared to the patients without incident WKF, the patients with incident WKF were older and had a higher prevalence of heart failure (HF), diabetes mellitus (DM), and vascular disease at baseline. Those who experienced incident WKF also had higher diastolic blood pressure, lower hemoglobin, lower eGFR, higher B-type natriuretic peptide (BNP) and used warfarin more frequently. Upon multivariate analysis, age ≥ 75 years, HF, DM, and anemia were independently associated with incident WKF. Additionally, age and hemoglobin were linearly associated with the risk of incident WKF, whereas a J- or U-shaped association was observed for HbA1c and BNP. Age ≥ 75 years, HF, DM, and anemia were associated with the development of WKF in Japanese patients with NVAF. In patients with these risk factors, a careful monitoring of the kidney function and appropriate interventions may be important when possible.

Important Role of Endogenous Nerve Growth Factor Receptor in the Pathogenesis of Hypoxia-Induced Pulmonary Hypertension in Mice.

Pulmonary arterial hypertension (PAH) remains a disease with poor prognosis; thus, a new mechanism for PAH treatment is necessary. Circulating nerve growth factor receptor (Ngfr)-positive cells in peripheral blood mononuclear cells are associated with disease severity and the prognosis of PAH patients; however, the role of Ngfr in PAH is unknown. In this study, we evaluated the function of Ngfr using Ngfr gene-deletion (Ngfr-/-) mice. To elucidate the role of Ngfr in pulmonary hypertension (PH), we used Ngfr-/- mice that were exposed to chronic hypoxic conditions (10% O2) for 3 weeks. The development of hypoxia-induced PH was accelerated in Ngfr-/- mice compared to littermate controls. In contrast, the reconstitution of bone marrow (BM) in Ngfr-/- mice transplanted with wild-type BM cells improved PH. Notably, the exacerbation of PH in Ngfr-/- mice was accompanied by the upregulation of pulmonary vascular remodeling-related genes in lung tissue. In a hypoxia-induced PH model, Ngfr gene deletion resulted in PH exacerbation. This suggests that Ngfr may be a key molecule involved in the pathogenesis of PAH.

Effect of pulmonary vein isolation on the relationship between left atrial reverse remodeling and sympathetic nerve activity in patients with atrial fibrillation.

PURPOSE: Catheter ablation (CA) to isolate the pulmonary vein, which is an established treatment for atrial fibrillation (AF), is associated with left atrium reverse remodeling (LARR). The intrinsic cardiac autonomic nervous system includes the ganglion plexi adjacent to the pulmonary vein in the left atrium (LA). However, little is known about the effect of CA on the relationship between LARR and sympathetic nerve activity in patients with AF. METHODS: This study enrolled 22 AF patients with a normal left ventricular ejection fraction (LVEF) aged 64.6 ± 12.9 years who were scheduled for CA. Sympathetic nerve activity was evaluated by direct recording of muscle sympathetic nerve activity (MSNA) before and 12 weeks after CA. Blood pressure, heart rate (HR), HR variability, and echocardiography were also measured. RESULTS: The heart rate increased significantly after CA (63 ± 10.9 vs. 70.6 ± 7.7 beats/min, p < 0.01), but blood pressure did not change. A high frequency (HF) and low frequency (LF) of HR variability decreased significantly after ablation, but no significant change in LF/HF was observed. CA significantly decreased MSNA (38.9 ± 9.9 vs. 28 ± 9.1 bursts/min, p < 0.01). Moreover, regression analysis revealed a positive correlation between the percentage change in MSNA and the LA volume index (r = 0.442, p < 0.05). CONCLUSIONS: Our results show that CA for AF reduced MSNA and the decrease was associated with the LA volume index in AF patients with a normal LVEF. These findings suggest that LARR induced by CA for AF decrease sympathetic nerve activity.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

The Association Between Serum Uric Acid and Mortality in Patients with Acute Coronary Syndrome After Percutaneous Coronary Intervention.

This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P < 0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P < 0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m2; P < 0.001) and lower left ventricular ejection fractions (58 ± 14 versus 57 ± 14 versus 53 ± 15%; P < 0.001). During the median 4-year follow-up, there were 158 incidents of all-cause death. Patients in the top quintile, followed by patients in the bottom quintile, had greater all-cause mortality compared with patients in the middle quintile (16.5 versus 11.4 versus 23.8%; P < 0.001). When the middle of the 3 quintiles was assigned as the reference group, the adjusted hazard ratios for all-cause mortality for the top and bottom quintiles were 1.72 (95% confidence interval [CI] 1.16-2.53, P < 0.05) and 1.57 (95% CI 1.03-2.36, P < 0.05), respectively. These results demonstrate that UA levels upon admission in patients with ACS who underwent PCI exhibited a 'J-shaped' association with all-cause mortality.

[A Case of Solitary Liver Metastasis of Low-Grade Endometrial Stromal Sarcoma 31 Years after Resection of Primary Lesion].

A 73-year-old woman was referred to our hospital after a liver tumor was discovered during an abdominal ultrasonography. Thirty-one years ago, she underwent a total hysterectomy for uterine myoma and was diagnosed with a leiomyoma. Twenty years ago, she underwent a bilateral oophorectomy for an ovarian tumor and was diagnosed with a luteinized theca cell tumor accompanied by sclerosing peritonitis. A CT scan and MRI revealed a 65-mm tumor in the S6-7 of the liver. There was no sign of any lesions other than in the liver, and TACE was performed for suspected hepatocellular carcinoma. However, a favorable treatment outcome was unable to be obtained and a posthepatic segmental resection was performed. Histopathological morphology suggested a similarity to endometrial stromal cells and, considering the history of myoma of the uterus and ovarian tumor, immunohistological staining was carried out. The myoma of the uterus and the ovarian and liver tumors were all CD10(+), α⊖SMA(-), MIB-1 index 3%. The uterine myoma, which was initially operated on, was rediagnosed as a low-grade endometrial stromal sarcoma. After 11 years, ovarian metastasis was observed, and after 31 years liver metastasis occurred. Examples of resection of liver metastasis of endometrial stromal sarcoma are extremely rare and, we will include a review of the literature in this report.

Clinical Diagnostic Criteria of Familial Hypercholesterolemia　- A Comparison of the Japan Atherosclerosis Society and Dutch Lipid Clinic Network Criteria.

BACKGROUND: This study is aimed to compare the efficacy of the 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria, which focuses on only 3 essential clinical manifestations, with that of Dutch Lipid Clinic Network (DLCN) FH criteria, which adopts a scoring system of multiple elements.Methods and Results:A total of 680 Japanese dyslipidemic participants (51% men) were enrolled between 2006 and 2018, all of whom had full evaluations of low-density lipoprotein (LDL) cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes (LDLR,APOB, andPCSK9). Predictive values for the existence of FH mutations by both clinical criteria were evaluated. Overall, 173 FH patients were clinically diagnosed by using the 2017 JAS criteria and 100, 57, 156, and 367 subjects were also diagnosed as having definite, probable, possible, and unlikely FH by the DLCN FH criteria, respectively. The positive and negative likelihood ratio predicting the presence of FH mutations by using the 2017 JAS FH criteria were 19.8 and 0.143, respectively; whereas, using the DLCN criteria of definite, probable, and possible FH, the ratios were 29.2 and 0.489, 9.70 and 0.332, and 3.43 and 0.040, respectively. CONCLUSIONS: Among Japanese patients, the JAS 2017 FH criteria is considered superior to diagnose FH mutation-positive patients and simultaneously rule out FH mutation-negative patients compared with the DLCN FH criteria.

Everolimus-Eluting Biodegradable Abluminal Coating Stent versus Durable Conformal Coating Stent: Termination of the Inflammatory Response Associated with Neointimal Healing in a Porcine Coronary Model.

OBJECTIVES: We evaluated the effect of the different carrier systems on early vascular response through histological analysis and scanning electron microscopy using a porcine model. BACKGROUND: Although Synergy™ and Promus PREMIER™ share an identical stent material and drug elution (everolimus), they use different drug carrier systems: biodegradable abluminal coating polymer or durable conformal coating polymer, respectively. However, data regarding the impact of the different coating systems on vessel healing are currently limited. METHODS: Twelve Synergy™ and Promus PREMIER™ were implanted in 12 swine. Histopathological analysis of the stented segments was performed on the 2nd and 14th days after implantation. Morphometric analysis of the inflammation and intimal fibrin content was also performed. RESULTS: On the 2nd day, neointimal thickness, percentage of neointimal area, and inflammatory and intimal fibrin content scores were not significantly different between the two groups. On the 14th day, the inflammatory and intimal fibrin content scores were significantly lower in Synergy™ versus those observed in Promus PREMIER™. In Synergy™, smooth muscle cells were found and the neointimal layers were smooth. In contrast, inflammatory cells were observed surrounding the struts of Promus PREMIER™. CONCLUSIONS: These results demonstrate that termination of reactive inflammation is accelerated after abluminal coating stent versus implantation of conformal coating stent.

Takotsubo cardiomyopathy complicated by cardiac tamponade due to non-hemorrhagic pericardial effusion: a case report.

BACKGROUND: Cardiac tamponade is a rare but serious complication of Takotsubo cardiomyopathy (TC). Two cases of cardiac tamponade subsequent to TC have been reported. The pericardial effusion in these cases was hemorrhagic and caused by ventricular rupture. Cardiac tamponade induced by an inflammatory effusion complicated with TC has not been reported. This is the first case report of TC, which developed cardiac tamponade during the recovery phase with a large volume non-hemorrhagic inflammatory effusion. CASE PRESENTATION: We describe a case of an 81-year-old woman admitted to our hospital because of severe chest pain. Her symptoms began soon after her son's hospitalization. We diagnosed her with TC based on results of an electrocardiogram, echocardiogram, and emergent coronary angiography. Her symptoms and left ventricular dysfunction improved gradually. She developed newly confirmed chest pain and dyspnea on day 9 after admission. A large pericardial effusion developed, resulting in cardiac tamponade. Her symptoms and hemodynamic status improved immediately after the pericardiocentesis. The effusion was non-hemorrhagic and exudative. No specific signs of infection, collagen disease, or malignant tumors were observed, except for TC. CONCLUSIONS: We experienced a case of circulatory collapse induced by TC-related inflammatory pericardial effusion at recovery phase. This case emphasizes the importance of careful follow-up even after improved left ventricular dysfunction in a patient with TC.

Impact of concomitant peripheral artery disease on contrast-induced acute kidney injury and mortality in patients with acute coronary syndrome after percutaneous coronary intervention.

Subclinical peripheral artery disease (PAD) might be associated with pathophysiology of contrast-induced acute kidney injury (CI-AKI). We hypothesized that concomitant PAD in patients with the acute coronary syndrome (ACS) would represent a high-risk subgroup with a greater incidence of CI-AKI, both of which lead to higher mortality after percutaneous coronary intervention (PCI). Six hundred and seventy-five consecutive patients with ACS who underwent PCI and examination of ankle-brachial index (ABI) were analyzed retrospectively. The presence of PAD was defined as an ABI < 0.9. We investigated whether (1) PAD was an independent predictor of CI-AKI (≥ 0.3 mg/dL or ≥ 50% relative increase in serum creatinine within 48 h after PCI) and (2) PAD and CI-AKI were independently associated with long-term mortality. Of the 675 patients with ACS, 114 (17%) exhibited PAD. The incidence of CI-AKI was significantly higher in PAD patients, compared with the remaining patients (12% vs. 4%, p < 0.001). Multivariate logistic regression analysis revealed that the presence of PAD was an independent predictor for the development of CI-AKI [odds ratio 2.50, 95% confidence interval (CI) 1.07-5.73, p < 0.05]. During the median 4-year follow-up, there were 65 incidents of all-cause death. In the multivariate Cox proportional hazard regression analysis, the presence of PAD [hazard ratio (HR) 2.08, 95% CI 1.17-3.65, p < 0.05] and CI-AKI (HR 2.23, 95% CI 1.08-4.26, p < 0.05) were associated with an increased risk of all-cause mortality. Assessment of ABI provides useful information for predicting CI-AKI and long-term mortality in patients with ACS after PCI.

Large-Scale Evaluation of Major Soluble Macromolecular Components of Fish Muscle from a Conventional 1H-NMR Spectral Database.

Conventional proton nuclear magnetic resonance (1H-NMR) has been widely used for identification and quantification of small molecular components in food. However, identification of major soluble macromolecular components from conventional 1H-NMR spectra is difficult. This is because the baseline appearance is masked by the dense and high-intensity signals from small molecular components present in the sample mixtures. In this study, we introduced an integrated analytical strategy based on the combination of additional measurement using a diffusion filter, covariation peak separation, and matrix decomposition in a small-scale training dataset. This strategy is aimed to extract signal profiles of soluble macromolecular components from conventional 1H-NMR spectral data in a large-scale dataset without the requirement of re-measurement. We applied this method to the conventional 1H-NMR spectra of water-soluble fish muscle extracts and investigated the distribution characteristics of fish diversity and muscle soluble macromolecular components, such as lipids and collagens. We identified a cluster of fish species with low content of lipids and high content of collagens in muscle, which showed great potential for the development of functional foods. Because this mechanical data processing method requires additional measurement of only a small-scale training dataset without special sample pretreatment, it should be immediately applicable to extract macromolecular signals from accumulated conventional 1H-NMR databases of other complex gelatinous mixtures in foods.

Acute myocardial infarction in a patient positive for lupus anticoagulant: a case report.

BACKGROUND: Autoimmune diseases, such as systemic lupus erythematosus (SLE), are associated with thrombosis and atherosclerosis. Presence of lupus anticoagulant is an independent risk factor for atherosclerotic diseases. CASE PRESENTATION: A 56-year-old man with past history of hypertension, and cerebral infarction was admitted to our hospital owing to acute chest pain. He was diagnosed with acute myocardial infarction based on his symptoms and electrocardiogram results, which demonstrated ST elevation in the precordial leads. Coronary angiography images revealed total occlusion at the proximal site of the left anterior descending artery. A drug-eluting stent was deployed, which successfully recovered coronary blood flow. The patient had fever of unknown cause when he was 30 years old; on admission, he presented with a low-grade fever and reddish exanthema affecting both cheeks. Based on his physical signs as well as elevated antinuclear antibodies (anti-double-stranded DNA), decreased lymphocytes, and a positive direct Coombs test, he was diagnosed with SLE. Owing to a positive lupus anticoagulant test, he was also suspected to have antiphospholipid syndrome (APS). Triple antithrombotic therapy, including dual antiplatelet therapy with aspirin and clopidogrel during coronary stenting and single anticoagulation therapy with warfarin, was initiated. CONCLUSIONS: Careful diagnosis of autoimmune diseases should be performed in patients with thrombosis and atherosclerosis. Moreover, risk factors for coronary artery disease should be strictly controlled in patients with APS.

Clinical characteristics of spontaneous isolated visceral artery dissection.

OBJECTIVE: Spontaneous isolated visceral artery dissection (SIVAD) involving the celiac artery or superior mesenteric artery is rare, but it can be fatal. Given its rare incidence, the clinical characteristics of SIVAD are not fully understood. Therefore, the aim of this study was to investigate the clinical characteristics and prognosis of SIVAD. METHODS: We retrospectively reviewed 39 consecutive patients diagnosed with SIVAD from January 2007 to December 2016. Demographic characteristics, symptoms, vital signs, blood examination results, and computed tomography findings were retrieved through medical record review. RESULTS: The median age of the patients was 52 years; 94.9% were male, and 64.1% were symptomatic. Median follow-up duration was 11 months. Overall, hypertension (48.7%) and smoking (79.5%) were frequently observed. There were significant differences between symptomatic and asymptomatic patients in white blood cell count and creatine kinase level but not in fibrin degradation products or D-dimer level. There was a significant correlation between symptoms and length of dissection on computed tomography (P < .01). Conservative treatment was performed in 32 patients (82.1%), and only 7 patients required open surgery or intravascular intervention. Notably, the diameter of affected vessels decreased spontaneously with no rupture or symptom recurrence during follow-up, and mortality was 0% at both 30 days and 1 year. CONCLUSIONS: The utility of blood examination, especially for fibrin degradation products and D-dimer levels, for diagnosis of SIVAD is limited. A high index of suspicion is warranted in patients presenting with persistent severe abdominal pain. Conservative treatment should be considered first-line therapy in patients without any signs of bowel ischemia or rupture.

Impact of stent deformity induced by the kissing balloon technique for bifurcating lesions on in-stent restenosis after coronary intervention.

OBJECTIVES: To investigate the impact of stent deformity induced by final kissing balloon technique (KBT) for coronary bifurcation lesions on in-stent restenosis (ISR). BACKGROUND: In experimental models, the detrimental effects of KBT have been clearly demonstrated, but few data exists regarding the impact of proximal stent deformity induced by KBT on clinical outcomes. METHODS: We examined 370 coronary lesions where intravascular ultrasound (IVUS)-guided second-generation drug-eluting stent (DES) implantation for coronary bifurcation lesions was performed. Based on IVUS analysis, the stent symmetry index (minimum/maximum stent diameter) and stent overstretch index (the mean of stent diameter/the mean of reference diameter) were calculated in the proximal main vessel. RESULTS: The stent symmetry index was significantly lower (0.75 ± 0.07 vs 0.88 ± 0.06, P < 0.0001) and the stent overstretch index was significantly higher (1.04 ± 0.08 vs 1.01 ± 0.06, P = 0.0007) in lesions with KBT (n = 174) compared to those without KBT (n = 196). The number of two-stent technique in lesions with KBT was 31 (18%). In multivariate analysis, the degree of stent deformity indices was not associated with ISR in lesions with KBT; however, two-stent technique use was the only independent predictor of ISR at 8 months (hazard ratio: 3.96, 95% confidence interval: 1.25-12.5, P = 0.01). CONCLUSIONS: Second-generation DES deformity induced by KBT was not associated with mid-term ISR.

Impact of B-Type Natriuretic Peptide Level on Risk Stratification of Thromboembolism and Death in Patients With Nonvalvular Atrial Fibrillation　- The Hokuriku-Plus AF Registry.

BACKGROUND: B-type natriuretic peptide (BNP) may be a predictor of stroke risk in patients with nonvalvular atrial fibrillation (NVAF); because heart failure is associated with the incidence of stroke in AF patients. However, limited data exist regarding the association between BNP at baseline and risks of thromboembolic events (TE) and death in NVAF patients. Methods and Results: We prospectively studied 1,013 NVAF patients (725 men, 72.8±9.7 years old) from the Hokuriku-plus AF Registry to determine the relationship between BNP at baseline and prognosis among Japanese NVAF patients. During the follow-up period (median, 751 days); 31 patients experienced TE and there were 81 cases of TE/all-cause death. For each endpoint we constructed receiver-operating characteristic curves that gave cutoff points of BNP for TE (170 pg/mL) and TE/all-cause death (147 pg/mL). Multivariate analysis with the Cox-proportional hazards model indicated that high BNP was significantly associated with risks of TE (hazard ratio [HR] 3.86; 95% confidence interval [CI] 1.83-8.67; P=0.0003) and TE/all-cause death (HR 2.27; 95% CI 1.45-3.56; P=0.0003). Based on the C-index and net reclassification improvement, the addition of BNP to CHA2DS2-VASc statistically improved the prediction of TE. CONCLUSIONS: In a real-world cohort of Japanese NVAF patients, high BNP was significantly associated with TE and death. Plasma BNP might be a useful biomarker for these adverse clinical events.