Bioengineered cardiac tissue is expected to be applied to regenerative medicine and tissue models for disease research and drug screening. Recent and rapid progress in technologies for tissue engineering approaches, including cell sheet technology, vascularization of thickened tissues, and large-scale expansion and differentiation of pluripotent stem cells, is about to realize the fabrication of human three-dimensional cardiac tissue. However, a remaining challenge is to make these fabricated tissues closely resemble the phenotypes, and to perform the functions of human cardiac tissue.

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Animal studies have reported a cardioprotective effect for atrial natriuretic peptide (ANP) or brain natriuretic peptide (BNP) administration in the setting of acute myocardial infarction (AMI). However, previous trials performed on AMI patients have reported differences in the cardiac function protection for ANP/BNP infusion, making it diffi cult to confirm the beneficial effect of natriuretic peptides. We performed a meta-analysis of all available trials to determine whether ANP/BNP infusion was effective in improving cardiac function. Methods: We searched various databases including PubMed, EMBASE, Web of Knowledge, the Cochrane Library, and CKNI for studies related to ANP/BNP infusion in AMI. The major outcome was left ventricular ejection fraction (LVEF). Results: Twenty trials (4 for ANP, 16 for BNP) with 1389 patients were included. There were no significant differences in patient characteristics between the ANP/BNP infusion and control groups at baseline. Pooled analysis showed that patients in the ANP/BNP infusion group had significantly higher LVEF than in the control during follow-up [Studies on ANP: weighted mean differences (WMD) 2.94%, 95% confidence interval (CI): 1.39%-4.50%, P = 0.0002; Studies on BNP: WMD 4.45%, 95%CI: 2.25%-6.65%, P < 0.0001]. Conclusions: The present meta-analysis suggested that ANP/BNP infusion might be effective in protecting left ventricular function in patients with AMI. ANP/BNP infusion may be an effective adjunctive therapy for cardiac function protection in AMI patients.

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Some patients with acute myocardial infarction (AMI) have a poor prognosis due to left ventricular remodeling (LVR), resulting in the recurrence of congestive heart failure even when therapy with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II type 1 receptor blockers (ARBs) has been initiated. We investigated the effect of early administration of the direct renin inhibitor (DRI) aliskiren in combination with an ACEI or an ARB on LVR using cardiac magnetic resonance (CMR) imaging in patients with AMI.
Twenty-one consecutive patients were treated with an ACEI or an ARB (non-DRI group), and another 21 consecutive patients received aliskiren 150 mg/day combined with an ACEI or an ARB (DRI group). CMR imaging was performed 7 days after AMI and 10 months later.
CMR imaging revealed no significant changes in LV end-systolic volume, LV end-diastolic volume, or LV ejection fraction between the patients with and without DRI aliskiren. In the DRI group, plasma renin activity was signifi cantly lower in both the acute and chronic phases; however, aldosterone levels were significantly lower in the acute but not the chronic phase.
A low dose of aliskiren may be insufficient to maintain suppression of aldosterone under current standard therapies with an ACEI or an ARB and β-blocker in patients with primary AMI, and results in no attenuation of LVR.

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The purpose of this study was to demonstrate the relationship between the presence and amount of a low-density core (LDC) with a CT density < 30 Hounsfield units (HU) by coronary computed tomography angiography (CCTA) and IVUS-derived markers of vulnerability in the culprit lesions (CL) of patients with acute coronary syndromes (ACS).
In 43 patients with ACS, 105 coronary plaques were scanned using CCTA and IVUS for the quantitative and qualitative assessment of vulnerability markers.
The presence of a low attenuation plaque (LAP) was identified in 67.4% of the CL and 29.03% of the non-CL (P = 0.0001). The presence of a LDC > 6.0 mm³ was significantly correlated with the percentage of the necrotic core (NC) (22.08% versus 7.97%, P = 0.001) and the fibro-fatty tissue by IVUS (18.68% versus 15.87%, P = 0.02). LDC volumes showed a good correlation with the percentage of the NC (r = 0.7303, P < 0.0001) and the fibro-fatty tissue in the CL (r = 0.4928, P < 0.0008). Quantitative plaque analysis revealed a significant difference in plaque composition between CL and non-CL in regards to the LDC (18.45 versus 6.5, P < 0.001), the percentage of NC (20.74 versus 18.74, P = 0.02), fibro-fatty tissue (17.77 versus 15.48, P = 0.002), and fibrotic tissue (51.68 versus 54.8, P = 0.01).
VH-IVUS and CCTA plaque quantification showed that the presence of a low-density (< 30 HU) core within the CL of patients with ACS represents a marker of vulnerability and correlates well with other CCTA and IVUS-derived features of vulnerability, particularly the NC of the plaque.

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In this study, we examined the early results for patients who underwent beating heart coronary bypass surgery and compared these results with those of conventional coronary bypass surgery.
A total of 1094 patients who underwent isolated coronary artery bypass surgery between January 2009 and December 2011 in our clinic were included in this study. Seventy-three patients in whom cardiopulmonary bypass was not used (group 1) were compared to 1021 patients in whom cardiopulmonary bypass was used (group 2).
The mean age was 60.7 ± 9.3 in group 1 and 58.9 ± 9.7 in group 2 (P > 0.05). There was no signifi cant difference between the two groups in terms of gender, or the coexistence of diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), and hypertension (P > 0.05). There was no significant difference between group 1 and group 2 in terms of development of postoperative atrial fibrillation (AF), use of an intra-aortic balloon pump, need for re-operation for bleeding, or duration of hospital stay and intensive care unit stay (P > 0.05). The need for inotropic support and the amount of mediastinal drainage were less in group 1 than in group 2 (P = 0.002, P < 0.001). The incidences of postoperative cerebrovascular accident, development of chronic renal failure, and sternal wound infection did not signifi cantly differ between the groups (P > 0.05). There was no mortality in group 1, whereas it was calculated as 1.8% in group 2 (P = 0.63).
Beating heart coronary artery bypass surgery decreases the need for inotropic support and transfusion.

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Subclinical hypothyroidism and hyperthyroidism have been recognized as clinical entities with negative effects on the cardiovascular system. Moreover, the effect of treated thyroid dysfunction on parameters associated with the cardiovascular control system has been poorly investigated. In the present study we analyzed time-domain heart rate variability in coronary artery disease (CAD) patients with known thyroid diseases. Twenty-four hour ECG monitoring was performed in 344 patients with coronary artery disease (174 with thyroid dysfunction and 170 without thyroid dysfunction used as a control group), using a 3-channel tape recorder. Time domain parameters of heart rate variability (HRV) were definitely lower both in patients with subclinical hypothyroidism and subclinical hyperthyroidism than in the control group, with statistically significant differences in SDNN, RMSSD, TINN, and mean RR for both subgroups. Furthermore, patients on L-thyroxine treatment and restored euthyroidism had generally higher HRV values than patients with subclinical hypothyroidism, nevertheless SDNN, RMSSD, SDNN index, TINN, and mean RR were signifi cantly lower when compared to those of the control group. Significant differences in HRV were also found between hyperthyroid patients under treatment and control group subjects with respect to RMSSD, TINN, and mean RR values. In conclusion, patients with cardiac disease and known thyroid disease, even when the disease is in the subclinical range or despite treatment, should be regarded as patients at additional risk conveyed by thyroid hormone disturbances.

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This study aimed to evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular disease (CVD) in high-risk patients with hypercholesterolemia without a history of CVD. Patients who were receiving or started treatment with pravastatin, were followed-up for 2 years. Patients were divided into quartiles according to on-treatment LDL-C. The maximum contrast method based on the Cox proportional hazards model was used to evaluate the relationship between achieved LDL-C and the incidence of CVD. Incidence of CVD was also compared according to whether a number of risk factor targets were achieved. A total 6,229 patients were enrolled, with 4,916 having reported LDL-C values. During the 2 years, 69 cases of CVD (6.7/1000 patient years), including 36 coronary artery disease (CAD) (3.5/1000 patient years) and 28 strokes (2.7/1000 patient years), occurred. The comparison of on-treatment LDL-C level quartiles suggested that the incidence of all CVD decreased linearly as the LDL-C levels decreased. Incidence of CAD showed a curvilinear relationship to LDL-C levels, suggesting some attenuation of risk below LDL-C of 119 mg/dL. The incidence of all CVD and CAD tended to be decreased as the number of achieved risk factor targets increased. In conclusion, through our observational study, it was shown that a linear relationship between the incidence of CVD and LDL-C was observed in high-risk hypercholesterolemic patients. The low incidence of CVD in the present study may be associated with multifactorial management of conventional risk factors including high LDL-C levels. However, prospective, randomized studies are needed to confirm these findings.

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The majority of cardiovascular events in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (PPCI) arise from the progression of nonculprit lesions (NCL) during the long-term follow-up period. However, the clinical and angiographic factors related to the progression of nonculprit lesions are unknown.
The purpose of the study was to investigate the clinical and angiographic factors related to the progression of nonculprit lesions of patients with STEMI undergoing PPCI.
A total of 492 patients with STEMI who underwent PPCI from January 2006 to December 2009 were enrolled. All patients underwent PPCI as a treatment for the culprit lesion. The clinical and angiographic follow-up was performed at 12 months. Primary endpoint: Clinically driven nonculprit lesion PCI. The levels of serum catecholamines [epinephrine (E), norepinephrine (NE)] and C-reactive protein (CRP) were assayed, and the clinical and angiographic features were also analyzed.
The clinical and angiographic follow-up was performed in 492 patients, and 45 patients underwent clinically driven nonculprit lesions PCI (study group). A total of 447 patients were free of additional PCI (control group). There were significant differences in the level of catecholamines (E (621.48 ± 79.31) pg/mL versus (268.14 ± 73.26) pg/mL, P < 0.0001), NE (6212.43 ± 822.41) pg/mL versus (3218.34 ± 614.16) pg/mL, P < 0.0001), CRP (3.29 ± 1.31) mg/dL versus (2.51 ± 1.14) mg/dL, P < 0.0001, cTnI peak value (27.27 ± 4.02) ng/mL versus (16.12 ± 3.23) ng/mL, P < 0.0001), thrombotic lesion rate ((62.22% versus 23.04%), P < 0.0001), ≥ 2 vessel lesions rate (80.00% versus 46.09%), P < 0.0001), culprit lesion length ((33.2 ± 2.9 versus 28.1 ± 3.1), P = 0.013), and complex lesion rate ((57.78% versus 36.02%), P = 0.006) between the two groups. Correlation analysis between nonculprit lesion stenosis degree and serum E, serum NE, serum CRP, cTnI peak value, thrombotic lesion rate, ≥ 2 vessel lesions rate, culprit lesion length, and complex lesion rate showed that there were significant correlations between serum E, serum NE, serum CRP, cTnI peak value, thrombotic lesion rate, ≥ 2 vessel lesions rate, culprit lesion length, complex lesion rate, and nonculprit lesion stenosis degree. The correlation coefficients were 0.95, 0.97, 0.83, 0.90, 0.81, 0.84, 0.95, and 0.96, respectively, and P < 0.0001, P < 0.0001, P = 0.01, P = 0.01, P = 0.01, P = 0.01, P < 0.0001, and P < 0.0001, respectively.
Recurrent PCI was mainly due to nonculprit lesion progression in patients with STEMI after primary PCI. Complex nonculprit lesions may be prone to for additional PCI. Chronic inflammation and sustained stress may be involved in the progression of nonculprit lesions in patients with STEMI.

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Several studies have revealed that stress after catastrophic disasters can trigger cardiovascular events, however, little is known about its association with the occurrence of heart failure in past earthquakes. The objective of the present study was to determine whether the Great East Japan Earthquake on March 11, 2011, increased the incidence of worsening heart failure in chronic heart failure (CHF) patients with implantable devices. Furthermore, we examined whether intrathoracic impedance using remote monitoring was effective for the management of CHF.
We enrolled 44 CHF patients (32 males, mean age 63 ± 12 years) with implantable devices that can check intrathoracic impedance using remote monitoring. We defined the worsening heart failure as accumulated impedance under reference impedance exceeding 60 ohms-days (fluid index threshold), and compared the incidence of worsening heart failure and arrhythmic events 30 days before and after March 11.
Within the 30 days after March 11, 10 patients exceeded the threshold compared with only 2 patients in the preceding 30 days (P < 0.05). Although 9 patients using remote monitoring among the 10 patients with threshold crossings were not hospitalized, one patient without the system was hospitalized due to acute decompensated heart failure. On the contrary, arrhythmic events did not change between before and after March 11.
Our results suggest that earthquake-induced stress causes an increased risk of worsening heart failure without changes in arrhythmia. Furthermore, intrathoracic impedance using remote monitoring may be a useful tool for the management of CHF in catastrophic disasters.

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Comparison of the prognostic value of red cell distribution width (RDW) and N-terminal pro B-type natriuretic peptide (NT-proBNP) for short-term clinical outcomes in acute heart failure (AHF) patients has not been fully investigated.
A total of 128 patients with AHF were enrolled and followed for 3 months. Primary endpoints were cardiovascular (CV) events, defined as cardiac death and/or readmission for HF. Baseline RDW and NT-proBNP were measured at admission.
The 30-day and 90-day CV event rates were 16.4% and 35.9%, respectively. NT-proBNP was higher in people with cardiovascular events at both time points, while RDW was significantly higher only at the 90-day time point. The area under the ROC curve of RDW (area under the ROC curve = 0.695) for the prediction of CV events was higher than that of NT-proBNP (area under the ROC curve = 0.610) at the 90-day time point, but lower at the 30-day time point. Cox hazard analysis revealed RDW and NT-proBNP were independent predictive factors of a 90-day CV event (RDW, hazard ratio, 4.610, 95% confidence interval 1.935-10.981, P = 0.001; NT-proBNP, hazard ratio, 3.661, 95% confi dence interval 1.125-11.907, P = 0.031). Kaplan-Meier survival analysis revealed that patients with an RDW level > 14.5% and NT-proBNP > 1471.5 pg/mL were at highest risk for a CV event (P < 0.001).
RDW and NT-proBNP are strong independent predictors of 90-day cardiovascular events in patients hospitalized with AHF. RDW can add prognostic value to NT-proBNP for predicting early cardiovascular events.

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The association of serum uric acid (UA) with left ventricular hypertrophy (LVH) remains controversial. We investigated this issue in a general population. Participants consisted of 1,943 subjects (774 males and 1,169 females) aged over 40 years, living in Tanushimaru (a Japanese cohort of the Seven Countries Study). Serum UA and other biochemistry parameters were determined by a standard analytical technique. All individuals underwent anthropometric measurements and 2-dimensional echocardiography. Because serum UA levels are much higher in males than in females, they were analyzed separately. When LV mass index (LVMI) levels were stratified according to tertile as low (≤ 80 cm²: n = 261), middle (81-103 cm²: n = 261), and high (≥ 104 cm²: n = 252) in males, there were significant relationships between LVMI and UA, in addition to age, body mass index, systolic blood pressure, medication for hypertension, triglycerides, and alcohol intake. Multiple stepwise regression analysis revealed LVMI was significantly associated with systolic BP (P < 0.0001), medication for hypertension (P < 0.0001), UA (P = 0.003), BMI (P = 0.019), and alcohol intake (P = 0.038) in males. In females, LVMI was not associated with UA. In a multiple logistic regression analysis, a signifi cantly higher odds ratio of LVH (odds ratio: 1.77, 95%CI: 1.01-3.09, P < 0.05) was observed for males in the highest UA tertile versus the lowest UA tertile after adjustments for confounding factors, but not for females. In this cross-sectional study, there was a clear difference in the relation of UA and LVH between males and females. High serum UA was signifi cantly and independently associated with LVH evaluated by echocardiography in only males of a general population.

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with increased risks of stroke and heart failure. However, the exact mechanisms of left atrium remodeling and AF-related biological behaviors are not completely understood.
The transcripts of left atrium in permanent atrium fibrillation patients (n = 7) were compared with those of healthy heart donors (n = 4) in sinus rhythm using Agilent 4x44K microarrays. Differently expressed genes were analyzed based on Gene Ontology and KEGG and Biocarta pathway analysis databases.
We identified 567 down- and 420 up-regulated genes in atrial fibrillation. The majority of the down-regulated genes participated in metabolic processes, particularly that for fatty acids. The most remarkable up-regulating effects were immune and platelet activation. In addition, atrial remodeling including structural, contractile, electrophysiological, neurohormone, and oxidant stress was also observed, suggesting various pathophysiology changes in fi brillating atrium. Nine AF closely related genes were validated by real-time RT-PCR.
Some AF specific genes were determined which may be a complement to the mechanism of left atrium remodeling. Metabolic changes and inflammation could promote or aggravate atrial fibrillation.

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We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

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An 81-year-old man with long RP narrow QRS tachycardia underwent catheter ablation. Ventricular pacing reset the atrial cycle over a retrograde slow pathway, followed by termination of the tachycardia without atrial capture, confirming the diagnosis of fast-slow atrioventricular nodal reentrant tachycardia (AVNRT). The earliest atrial activation during tachycardia was found in the noncoronary sinus of Valsalva, where the first delivery of radiofrequency energy terminated and eliminated the inducibility of the tachycardia, by retrograde conduction block over the slow pathway. This is the first report of a fast-slow AVNRT, with successful ablation of the slow pathway from a noncoronary sinus of Valsalva.

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According to several previous reports on persistent fifth aortic arch (PFAA), the presentation of the patients was usually either very mild when diagnosed by physical examination including upper body systemic hypertension and systolic murmur, or severe with ductal shock in the neonatal period. In our case, the clinical course was unique with relatively mild narrowing at the distal PFAA and an interrupted fourth aortic arch. It can be classified as medium severity based on the timing of presentation to the hospital. In the present case, severe LV dysfunction suggested sustained narrowing at the junction between the PFAA and the descending aorta and insufficient development of collateral arteries.
We experienced a case with PFAA with severe LV dysfunction. These findings suggest another differential diagnosis for severe LV dysfunction in infancy.

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Late-onset residual shunt after surgical repair of aortopulmonary septal defect (APSD) is a rare event complicating the management strategy. Surgical reoperation was the treatment of choice traditionally, while associated with increased risk and suffering. We report a case of successful treatment of this type of residual shunt using a transcatheter closure technique with an infrequently used muscular ventricular septal device.

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