Clinical features and outcomes of acute myocardial infarction (AMI) in the young have been poorly investigated. The aim of this study was to investigate the clinical features and hospital outcomes of AMI in young Japanese. We conducted a case-control study. A total of 53 consecutive AMI patients whose age was ≤ 45 years old were assigned to the young group and 106 AMI patients whose age was > 45 years old were assigned to the non-young group. We compared the clinical features and hospital outcomes between the two groups. Compared with the non-young group, the young group was associated with male sex, hyperlipidemia, current smoking, being overweight, single vessel disease, and Killip class I on admission. There were no differences in the length of hospital stay or major adverse cardiac events between the groups. However, mortality and ventricular rupture were slightly lower in the young. In conclusion, young AMI patients had clinical characteristics different to those of the non-young patients. Compared to non-young patients, modifiable risk factors such as smoking, hyperlipidemia, and being overweight were associated with young AMI patients.

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Extrathoracic subclavian/axillar venipuncture is an accepted method for implanting pacemaker leads. Although several procedures have been reported, no standard method has been established yet. We evaluated the usefulness of a method in which only J-type guidewires are used. Between August 2011 and November 2012, 33 patients (20 men and 13 women; age, 77.5 ± 10.3 years) underwent permanent pacemaker lead insertion by extrathoracic subclavian venipuncture at our hospital. Thirty-two of the patients underwent primary implantation, whereas 1 patient required an additional lead because of lead fracture. The guidewires were inserted from the cubital vein to the subclavian vein. After the pacemaker pockets were created, we set the X-ray projection in the ipsilateral anterior oblique view. The distal edge of the guidewire was positioned on the ventral side of the first rib on fluoroscopy. The needle tip was positioned within the Ushaped distal tip of the J-type guidewire. The needle was held parallel to the X-ray angle and advanced towards the first rib until the tip entered the subclavian vein. The guidewire was inserted through the cubital vein in 31 patients, and through the femoral vein in 2 patients. Using this method, we successfully performed subclavian venipunctures in all 33 patients (total, 60 punctures) without any complications. Extrathoracic subclavian venipuncture using only a J-type guidewire is an easy, safe, and economical method for pacemaker lead implantation.

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Soluble fms-like tyrosine kinase 1 (sFlt-1) is an endogenous inhibitor of vascular endothelial growth factor, which is involved in cardiovascular remodeling and atherosclerosis development. To examine the predictive role of sFlt-1 levels in patients with asymptomatic heart failure, we measured circulating sFlt-1 in patients with or without coronary artery disease (CAD). We analyzed 88 Japanese patients with CAD or patients at high risk for atherosclerosis and who were undergoing total risk management for cardiovascular disease prevention. Circulating sFlt-1 levels correlated with the increase in plasma brain natriuretic peptide levels (ΔBNP) from baseline to the observed levels 5 years later in CAD patients, patients with previous myocardial infarction, and men. ΔBNP levels correlated with sFlt-1 levels in the high-sFlt-1 patients with CAD (r = 0.511, P < 0.01). In all patients, end-systolic volume index (ΔESVI) increased in correlation with a decrease in left ventricular ejection fraction (ΔEF) in the long-term observation, independent of their history of myocardial infarction (ΔESVI = 2.5 mL/m² increase/year). Baseline level of sFlt-1 was independent of ΔESVI or ΔEF. The present 5-year observational study demonstrated that high sFlt-1 levels predicted moderate increases in BNP levels in CAD patients. Moreover, ΔBNP was correlated with ΔESVI/year in CAD patients with high-sFlt-1 levels. These data suggest that high sFlt-1 levels may be an effective biomarker to predict the progression of heart failure in patients with CAD.

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There is no reliable method of screening for pregnant women at high risk of developing severe myocardial disorders. In this study, we used vector-projected 187 channel electrocardiography (DREAM-ECG) and serum biochemical markers to evaluate peripartum myocardial burden in pregnant women. Forty-one pregnant women were examined at 36-37 weeks gestation (GW36), 7 days postpartum (PPD7), and 1 month postpartum (PPM1). Ten non-pregnant control women were assessed at a single time point. Heart rate, sympathetic index, and repolarization index (RTc dispersion) were quantified using the DREAM-ECG system, and serum levels of NT-proBNP, cardiac troponin T, estrogen, and progesterone were determined. Heart rate and the sympathetic index decreased from GW36 to PPM1 (P = 0.0031). The repolarization index decreased over time and was greater than in non-pregnant controls (31 ± 13 ms). Estrogen and progesterone at PPD7 and PPM1 were significantly lower than those at GW36 (P < 0.0001, P < 0.001). NT-proBNP at PPD7 was greater than at GW36 (median 29 pg/mL at GW36, 86 pg/mL at PPD7), and decreased at PPM1 in comparison to PPD7 (median 18.5 pg/mL). Troponin T was in the normal range during the whole period (< 0.003 ng/mL). In conclusion, these results indicate that the peripartum myocardial burden in pregnant women does not return to normal nonpregnant levels by PPM1. We propose that both repolarization indexes such as RTc dispersion by DREAM-ECG and serum biochemical markers may identify pregnant women at high risk of developing severe myocardial damage in the peripartum period.

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Eosinophilic infiltration of the myocardium is occasionally observed as an incidental histological finding in endomyocardial biopsy specimens before heart transplantation (HTx) as well as in explanted heart obtained at the time of HTx. However, the indications for HTx in these patients have not yet been fully established. We investigated the pre-HTx characteristics of the recipients with myocardial eosinophilic infiltration in the explanted heart and diagnosed as hypersensitivity myocarditis (HSM) (21 among 761 recipients, 2.8%). Dobutamine, a common cause of HSM, was administered to 12 patients (57%). Ten patients (47.6%) were on milrinone and 4 (19.0%) were on ventricular assist devices. Post-transplant survival of HSM patients was comparable to that of patients transplanted for active myocarditis or other cause of heart failure. In conclusion, myocardial eosinophilic infiltration is associated with multiple medications in patients with advanced heart failure; however, it does not affect the post-transplant prognosis.

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Cardiopulmonary bypass (CPB) evokes activation of a systemic inflammatory response. Sivelestat has been used clinically to treat acute lung injury associated with systemic inflammatory response syndrome. This prospective, doubleblind, randomized study was designed to evaluate the effects of sivelestat in the perioperative period of elective pediatric open-heart surgery with CPB. Twenty-six consecutive pediatric patients weighing between 5 and 10 kg and undergoing open-heart surgery with CPB were divided into a sivelestat group (n = 13) and a control group (n = 13). The patients in the sivelestat group were administered a continuous intravenous infusion of 0.2 mg/kg/hour of sivelestat, and the patients in the control group were administered the same volume of 0.9% saline from the initiation of CPB to 24 hours after surgery. Blood samples were drawn for the measurement of cytokines, polymorphonuclear elastase (PMN-E), white blood cell count (WBC), neutrophil count (NC), and C-reactive protein (CRP). There were no significant differences in cytokine data between the two groups. The peak PMN-E and WBC levels were significantly increased in the control group (P = 0.049, P = 0.039). The WBC and NC levels immediately after surgery in the control group were significantly greater than those in the sivelestat group (P = 0.049, P = 0.044). The peak CRP level in the control group was significantly greater than the sivelestat group (P = 0.04), and the CRP level on postoperative day 4 in the control group was significantly greater than in the sivelestat group (P = 0.014). This study showed that sivelestat attenuates the perioperative inflammatory response in pediatric heart surgery with CPB.

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Current evidence indicates that abnormalities in physical properties of the cell membranes may be strongly linked to hypertension and other circulatory disorders. Recent studies have shown that chronic kidney disease (CKD) might be a risk factor for cardiovascular and cerebrovascular outcomes. The purpose of the present study was to examine the possible relationship between kidney function and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive subjects using an electron spin resonance (ESR) and spin-labeling method. The order parameter (S) for the ESR spin-label agent (5-nitroxide stearate) in RBC membranes was significantly higher in hypertensive subjects than in normotensive subjects, indicating that membrane fluidity was decreased in hypertension. The order parameter (S) of RBCs was inversely correlated with estimated glomerular filtration rate (eGFR), suggesting that a decreased eGFR value might be associated with reduced membrane fluidity of RBCs. Multivariate regression analysis also demonstrated that, after adjustment for general risk factors, eGFR might be a significant predictor of membrane fluidity of RBCs. The reduced levels of both membrane fluidity of RBCs and eGFR were associated with increased plasma 8-iso-prostaglandin F2α (an index of oxidative stress) and decreased plasma nitric oxide (NO)-metabolites, suggesting that kidney function could be a determinant of membrane microviscosity of RBCs, at least in part, via oxidative stress- and NO-dependent mechanisms. The ESR study suggests that CKD might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory disorders in hypertensive subjects.

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Several recent studies have suggested that arterial stiffness parameters such as peripheral pulse pressure (PPP), central blood pressure (CBP), and pulse wave velocity (PWV) are more accurate markers than brachial blood pressure for prediction of cardiovascular (CV) events. However, it remains unknown which arterial stiffness parameter is the most useful for predicting CV risk in the general population. Participants in the present study were randomly selected from the 40 to 79 year age group in the general population (n = 973; mean age, 59). PPP was determined in the upper arm with an oscillometric device. CBP was estimated noninvasively by radial pulsatile analysis, and brachial-ankle PWV was measured using a validated automatic device. A follow-up survey assessing the incidence of CV events including CV death was carried out after the baseline study. The mean follow-up duration was 7.8 years. Subjects were divided into quartiles according to PPP, CBP, or PWV. Event-free rates among the PWV quartiles were clearly divergent (P < 0.001); however, the rates among quartiles for the other parameters were not significant. In a multivariate Cox regression model, both the 90th percentile level of PWV (HR = 2.51, 95% CI; 1.21 – 5.22: P = 0.014) and the increase in PWV per one standard deviation (HR = 1.42, 95% CI; 1.06 – 1.90: P = 0.019) were significantly associated with risk of CV events. The area under the curves of the receiver operating characteristics analysis for CV event prediction of PWV was significantly larger than the others (P = 0.002 versus PPP; P = 0.043 versus systolic CBP). The measurement of brachial-ankle PWV is more useful than determination of PPP or CBP for identifying subjects at high risk of CV events within the general population.

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Pulmonary thromboembolism (PTE) is a life-threatening disease which always presents in patients with deep vein thrombosis (DVT). There are few statements in guidelines regarding indications for anticoagulation based on the location of DVT. We investigated whether the relative risk of PTE depends on thrombus location and bleeding complications with anticoagulation therapy. Between January 1 and July 10, 2007, 461 patients underwent lower extremity venous ultrasound studies, and 129 patients were diagnosed as DVT (60 males, 66.9 ± 13.3 years). We retrospectively studied the incidence of PTE and bleeding complications associated with anticoagulation therapy. Average follow-up period was 536 ± 324 days. Above and below knee thrombosis was present in 60 and 69 patients, respectively. Warfarin was administered in 60 patients. Nine patients developed PTE. Multivariate analysis showed the absence of anticoagulation therapy and location of DVT (above knee) to be significantly correlated with onset of PTE (anticoagulation; P < 0.01, location; P = 0.02). However, the incidence of bleeding was not significantly different between above knee and below knee vein thrombosis (P = 0.72). In conclusion, below knee vein thrombosis carries a relatively low risk of PTE, but the incidence of bleeding complications does not depend on thrombosis location. This suggests that the indication of anticoagulation therapy should be based on DVT location.

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Partial and generalized seizures often affect autonomic functions during seizures, and interictal and postictal periods. We investigated possible interictal electrocardiographic abnormalities in patients with generalized tonic-clonic seizures (GTCS), together with evaluating any structural heart changes by echocardiography in these patients in comparison with healthy controls. We studied 120 definite GTCS patients (76 males and 44 females) who are neither diabetic nor under any medical treatment, and 60 healthy controls with a mean age of 25.2 ± 9.3 and 27.3 ± 7.5 years; respectively. Resting systolic and diastolic arterial blood pressures were measured, and standard 12-lead electrocardiograms and a 2-dimensional echocardiographic examination were performed. In univariate analysis, GTCS patients (compared to controls) had significantly lower means of PR interval (147.2 ± 18.6 versus 153.8 ± 22.6 msec; P = 0.037), QT interval (362.8 ± 22.9 versus 379.9 ± 29.3 msec; P < 0.001), and QTc interval (425.5 ± 20.7 versus 441.6 ± 19.9 msec; P < 0.001) but significantly higher mean left atrial diameter (3.49 ± 0.64 versus 3.09 ± 0.45 cm; P < 0.001). After adjusting for age, gender, and body mass index in a multivariate adjusted logistic regression model, left atrial diameter (OR = 3.941 [1.739 – 8.932]) and QTc (OR = 0.924 [0.895 – 0.954]) were significantly and independently associated with GTCS. In conclusion, patients with epilepsy may be predisposed to disturbances of autonomic functions with subsequent cardiac arrhythmias due to the effects of recurrent seizures on cardiac microstructure. Further work is needed to stratify the risk of sudden unexplained cardiac death (SUDEP) on the basis of interictal autonomic parameters to improve prognosis.

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Chlorogenic acid (CGA), which is a key component of coffee, has many biological effects such as anti-inflammation activity. However, the effects of CGA on ventricular remodeling after myocardial ischemia have not been well investigated. To test the hypothesis that CGA can attenuate chronic ventricular remodeling after myocardial ischemia, we orally administered CGA to murine myocardial ischemia models. Seven to nine week-old C57BL/6 mice were used. A myocardial infarction (MI) model was produced by permanent ligation of the left anterior descending coronary artery (LAD) using an 8-0 suture passed under the arteries. These mice were randomly assigned into 4 groups in each experimental model. Some MI mice were supplemented orally with CGA (30 mg/kg/day, MI+CGA group, n = 13) as a CGAtreated MI group, and other MI mice received vehicle (MI+vehicle group, n = 11) as a vehicle-treated MI group. Shamoperated mice without MI also received vehicle (Sham+vehicle group, n = 3) as a sham group, and sham-operated mice without MI received CGA (30 mg/kg/day, Sham+CGA group, n = 8) as a Sham+CGA group. Just before sacrifice on day 14, we measured blood pressure and heart rate and performed echocardiography. We obtained 3 transverse sections per heart for histopathologic examination. There were no differences in body weight, heart rate, or blood pressure among the groups on day 14. The vehicle-treated MI group showed significantly impaired left ventricular contraction compared to the sham-operated group. However, the CGA-treated MI group showed significantly improved ventricular contraction compared to the vehicle-treated MI group. Severe myocardial fibrosis with enhanced macrophage infiltration was observed in the vehicle-treated ischemia group on day 14. CGA attenuated these fibrotic changes with suppressed macrophage infiltration without systemic adverse effects. CGA may effectively suppress chronic ventricular remodeling after myocardial ischemia because it is critically involved in the suppression of macrophage infiltration.

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Spontaneous coronary artery dissection (SCAD) is considered to be a rare cause of acute coronary syndrome, especially recurrent or multivessel dissection. We present here the case of 51 year-old man who had recurrent and multivessel SCAD. In the initial event, the distal segment of the right coronary artery was spontaneously dissected, which was confirmed by coronary angiography (CAG), intracoronary ultrasound (IVUS), and multidetector computed tomography (MDCT). In the second event, the left coronary artery was spontaneously dissected. The dissection was confirmed by IVUS and MDCT, although CAG did not show stenosis, occlusion, or dissection in the left coronary artery. These findings suggest the weakness of CAG and the usefulness of IVUS or MDCT for the diagnosis of SCAD.

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