The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.

Excimer laser coronary atherectomy (ELCA) has been used for the treatment of complex percutaneous coronary intervention (PCI) such as in-stent restenosis (ISR). However, little information was provided about the clinical outcomes after treatment with ELCA for ISR of drug-eluting stents (DES). This study aimed to investigate the long-term clinical outcomes after PCI with ELCA for ISR of DES.A total of 81 consecutive patients with 87 lesions who underwent PCI for ISR of DES were included. Patients were classified into a PCI with ELCA group (23 patients with 24 lesions) and a PCI without ELCA group (58 patients with 63 lesions). The major adverse cardiac events (MACE) were evaluated. The mean duration of clinical follow-up was 29.8 ± 11.6 months. The incidences of diffuse restenosis and AHA/ACC type B2 or C lesion in the PCI with ELCA group were higher than in the PCI without ELCA group. Quantitative coronary angiography showed the acute luminal gain in the PCI with ELCA group was greater than in the PCI without ELCA group (1.64 ± 0.48 mm versus 1.26 ± 0.42 mm, P < 0.001). There were no significant differences in all-cause death, myocardial infarction, or target lesion revascularization between the 2 groups. Multivariate analysis due to a Cox proportional-hazards model showed that multivessel disease was an independent predictor of MACE (hazard ratio 3.05, 95% confidence interval 1.22 to 7.61, P = 0.02). ELCA was effective as an atherectomy device for lumen enlargement and optimal lesion preparation. Even though ELCA was used for ISR of DES in significantly more complex lesions, the long-term clinical outcomes were favorable and similar.

Prasugrel, a novel P2Y12 receptor inhibitor, is administered to patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI), but it can increase the risk of bleeding. The Japanese exhibit weaker responses to clopidogrel than other races because of CYP2C19 polymorphisms; thus, it is unclear whether these patients should continue dual antiplatelet therapy (DAPT) using prasugrel or switch to clopidogrel in the chronic phase. Here we evaluated the clinical outcomes of DAPT guided by CYP2C19 polymorphisms after implantation of second-generation drug-eluting stents (DESs) for ACS management. Patients with ACS receiving PCI via DES from November 2011 to March 2015 were divided into two groups: conventional DAPT with clopidogrel (n = 41) and gene-guided DAPT (n = 24). In the gene-guided DAPT group, all patients with ACS were given DAPT using prasugrel as soon as possible; extensive and intermediate metabolizers receiving PCI for the first time were switched to clopidogrel at least 2 weeks after discharge, and intermediate metabolizers with repeated ACS and poor metabolizers continued on DAPT using prasugrel. Notably, gene-guided DAPT significantly reduced major adverse cardiovascular/cerebrovascular events (MACCEs; 22.0% versus 4.2%, hazard ratio [HR]: 0.15, 95% confidence interval [CI]: 0.01-0.81; P = 0.0247). Hemorrhagic complications were observed in 3.1% of patients receiving conventional DAPT and absent in the gene-guided group. Moreover, multivariate analysis showed that gene-guided DAPT significantly decreased MACCE incidence (HR: 0.15, 95% CI: 0.01-0.81; P = 0.033). Collectively, these data suggest that CYP2C19 polymorphism analysis may improve treatment decisions in patients with ACS receiving DES-PCI.

Statins can be differentiated into two types, based on their solubility, which have potentially differing effects on the coronary artery wall. However, suspected differences in statins' effects on plaque composition have not been systemically investigated.

Sixty-seven patients with acute coronary syndrome (ACS) were randomly assigned to either atorvastatin (10 mg/day) or rosuvastatin (2.5 mg/day). Intravascular ultrasound (IVUS) and integrated backscatter (IB)-IVUS, an established tool to quantify each plaque's components, were performed immediately after emergent percutaneous coronary intervention (PCI). Follow-up IVUS was performed between 6 and 12 months after PCI. Serial changes in serum lipid profiles and plaque composition volumes were compared between the two groups.

Thirty-five patients were eligible for serial IB-IVUS analyses. The mean low-density lipoprotein-cholesterol level significantly decreased in the atorvastatin and rosuvastatin groups (P < 0.001); plaque volumes were also significantly reduced from 82.0 ± 46.2 to 74.9 ± 41.3 mm³ (P = 0.01) and from 74.7 ± 35.3 to 67.7 ± 27.0 mm³ (P = 0.02), respectively. IB-IVUS revealed a significant reduction in fibrous volume from 33.8 ± 20.0 to 27.5 ± 14.9 mm³ (P < 0.01) and from 29.6 ± 13.6 to 24.8 ± 7.6 mm³ (P < 0.05), respectively; however, significant changes were not noted in the volume of the lipid pool for the atorvastatin group and the rosuvastatin group, respectively.

Water- and lipid-soluble statins may be similarly effective in reducing coronary plaques in patients with ACS as judged qualitatively and quantitatively. Further study is needed to determine whether differences between water- and lipid-soluble statins affect plaque components.

This study aimed to evaluate the feasibility and the mid-term efficacy of an in situ skeletonized right internal mammary artery (IMA) bypass grafting to a left anterior descending artery (LAD), and to determine risk factors for IMA graft failure in a single-center study.

From January 2012 to December 2015, 189 patients (173 males, 50.6 ± 6.0 years old) undergoing first isolated coronary artery bypass grafting surgery with the in situ skeletonized right IMA grafting to the LAD were included in this study. Baseline characteristics, peroperative data, and follow-up outcomes were investigated and analyzed.

The length of the in situ skeletonized right IMA grafts was 18.6 ± 1.2 cm (17.0-22.0 cm). Intraoperative graft flow of the in situ skeletonized right IMA grafting to LAD was 42 ± 9 mL/minute (18-72 mL/minute) associated with measured pulsatility index of 0.8-4.3. In-hospital mortality was 0.5%. Postoperative morbidity included acute myocardial infarction (0.5%), stroke (0.5%), and deep sternal wound infections (1.1%). The mid-term survival was 97.2% and the incidence of repeat revascularization was 0.6%. The patency rate of the in situ skeletonized right IMA grafting to the LAD was 97.1% by computed tomography angiography examination during the follow-up period of 23.2 ± 9.7 months. Additionally, logistic regression analysis showed that intraoperative graft flow had an independent influence on the risk of the mid-term right IMA graft failure.

The strategy of the in situ skeletonized right IMA grafting to the LAD is feasible and effective. Intraoperative graft flow was an independent risk factor for the mid-term right IMA graft failure.

We aimed to investigate the distinctive miRNA profiles in the plasma of elderly patients with unstable angina (UA) and stable angina (SA), and to find more effective markers of UA in elderly people. We compared miRNA expression levels in plasma samples from 10 elderly patients with UA and 10 elderly patients with SA by using microarray-based miRNA chip, and then performed validation with Real-time PCR. Mir-1202, mir-1207-5p, and mir-1225-5p showed a statistically significant down-regulation (P < 0.05), while mir-3162-3p showed an up-regulation (P < 0.05) during validation. Among all single miRNAs, miR-3162-3p showed the highest discriminatory power in the diagnosis of elderly patients with UA (AUC: 0.79, 95% CI: 0.675-0.905). The discriminatory power of a panel of three miRNAs (mir-3162-3p/mir-1225-5p/mir-1207-5p) was highest with an AUC of 0.91 (95% CI: 0.84-0.98), followed by mir-3162-3p/mir-1225-5p (AUC: 0.833, 95% CI: 0.732-0.934) and mir-3162-3p/mir-1207-5p (AUC: 0.817, 95% CI: 0.712-0.922). In conclusion, multi-miRNA panel could provide higher diagnostic value for the diagnosis of elderly patients with UA.

Hyper-coagulation after off-pump coronary artery bypass grafting (OPCAB) is one of the main reasons for graft thrombosis. D-dimer is closely linked to the activation of coagulation. Few studies have reported the variation range and long-term abnormal coagulation after OPCAB in the Chinese population. Our study aimed to determine the characteristics and value of D-dimer after OPCAB.

In this prospective study, 265 patients who underwent OPCAB for the first time were recruited from 2011 to 2012. The D-dimer level of the patients was tested before surgery and on the 1st, 4th, and 14th day, and 1st, 2nd, and 3rd month after surgery. Clinical data in the perioperative period and during the one-year follow-up period were recorded.

D-dimer level increased from day 4 after OPCAB ([1321.9 ± 36.4] μg/L), peaked at 1 month ([2839.7 ± 101.4] μg/L), and decreased to the baseline ([370.3 ± 260.2] μg/L) 3 months after surgery. No death occurred, but 25 (10%) patients suffered recurrent angina in the one-year follow-up. They had significantly higher D-dimer level at one month after OPCAB than those of patients who did not suffer from angina. Preoperative ejection fraction <50% and D-dimer level >2915 μg/L at one month after surgery were significantly associated the recurrent angina.

After OPCAB, patients have a higher level of D-dimer. And this lasts for a long period (about 3 months). It may reflect a certain degree of hypercoagulable and hyperfibrinolytic state after OPCAB.

Atrial fibrillation (AF) is the most common clinically relevant arrhythmia. AF is a strong independent risk factor for the subsequent development of heart failure (HF). HF and AF can interact to perpetuate and exacerbate each other. Soluble ST2 (sST2) is a biomarker of cardiomyocyte stretch that is useful in the diagnosis and prognosis of HF. Its role in the field of AF has not yet been well investigated. We studied the concentration of sST2 in a cohort of 174 subjects (62.1% men; mean age, 65.6 ± 10.3 years [± standard deviation (SD) ]) with nonvalvular AF and 116 age-matched patients with sinus rhythm (SR). Subjects were subdivided into 3 groups: paroxysmal AF, persistent AF, and SR. Plasma sST2 concentrations were measured using an electrochemiluminescence-based immunoassay. The sST2 level was higher in persistent AF patients (P < 0.05) and paroxysmal AF patients (P < 0.05) than in SR patients. No significant difference was found between persistent AF and paroxysmal AF. sST2 was correlated with left atrial diameter (LAD) (r = 0.21; P < 0.01). During a median follow-up time of 6 months, 43 subjects with non-valvular AF in the study had HF. Cox proportional hazard analysis revealed both sST2 and LAD were independent predictors of HF. sST2 concentrations are higher in AF than SR. Plasma sST2 may be a useful biomarker in predicting HF in patients with AF.

Myocardial infarction (MI) can cause new-onset atrial fibrillation (AF) due to cardiac remodeling. As a recent study has shown, inflammatory factors are closely tied to cell death and survival in myocardial ischemia injury. Toll-like receptors (TLRs) have been shown to participate in the process of myocardial infarction as innate immune factors.

The subjects were divided into 3 groups: healthy controls (n = 82), MI patients (n = 84), and AFMI (new-onset atrial fibrillation after myocardial infarction) patients (n = 85). Peripheral blood mononuclear cell (PBMC) TLR mRNA expression was detected by rt-PCR. Western blot was used to analyze PBMC TLRs and their downstream signal protein expression. PBMCs were presented as TLR2 expression or TLR4 expression using flow cytometry.

From mRNA to protein detection, PBMC TLR2 and TLR4 were significantly higher in the AFMI group than in the control group and MI group. A similar tendency was also observed in the expression of downstream signaling proteins. When further analyzed with TLR2 and TLR4 antibodies by flow cytometry, PBMC levels also appeared to be higher in AFMI patients than those in MI patients and the healthy control group.

In our study, PBMC TLRs and their downstream signaling proteins were significantly higher in the acute myocardial infarction patients with new-onset atrial fibrillation compared with healthy people and acute myocardial infarction patients without new-onset atrial fibrillation. They have the potential to be novel biomarkers for new-onset atrial fibrillation after acute myocardial infarction.

Discrimination between atrioventricular node reentry tachycardia (AVNRT) and orthodromic reciprocating tachycardia (ORT) during an electrophysiological study is sometimes challenging. This study aimed to investigate if the difference in the local VA (ventricle-atrium) interval during ventricular entrainment pacing and during tachycardia (DVA, defined as the shortest local VA interval of coronary sinus [CS] during entrainment minus the shortest local VA interval of CS during tachycardia) was different in patients with AVNRT and patients with ORT.

Diagnoses of AVNRT or ORT through a concealed accessory pathway (AP) were made according to conventional electrophysiological criteria and ablation results. Entrainment by right ventricular (RV) pacing was performed in each patient before ablation and patients with successful entrainment were included in the study. The DVA was compared between patients with AVNRT and patients with ORT. The DVA in patients with AVNRT was significantly longer than that in patients with ORT (120 ± 20 versus 5.7 ± 9; P < 0.001). In each patient with AVNRT of slow-fast type, fast-slow type, and slow-slow type, the DVA was more than 48 ms. In each patient with ORT using a left free wall accessory pathway (AP), right free wall AP, and septal AP, the DVA was less than 20 ms.

DVA was found to be a rapid, useful test in distinguishing patients with AVNRT from those with ORT.

Manual planimetry is a well-established method using transesophageal echocardiography (TEE) to assess the severity of aortic stenosis (AS). TEE, however, is a less than optimal approach in patients with calcified valves. Even when using cine-cardiac magnetic resonance (CMR), it is often difficult to evaluate the true border of the aortic orifice because of jet turbulence. With phase-contrast sequences of CMR, high flow signals at the aortic orifice can be clearly visualized, even in cases with severe calcification and jet turbulence. Therefore, the aims of the present study were to compare the utility of CMR using phase-contrast imaging with TEE and cine-CMR for the performance of planimetry of the aortic valve. The study cohort consisted of 30 consecutive patients with moderate or severe aortic valve stenosis documented by TEE who had undergone phase-contrast and cine-CMR for the evaluation of AS. Manual planimetry of the area of high flow signal was traced over the phase-contrast images at systolic peak, when the aortic valve is maximally opened. The results showed that the aortic valvular area (AVA) value derived from TEE correlated better with phase-contrast planimetry (r² = 0.84, P < 0.05) than cine-mode planimetry (r² = 0.57, P < 0.05). Bland-Altman plots indicated that the variation of measuring AVA was greater using the cine-mode method than the phase-contrast method. In conclusion, phase-contrast CMR offers a tool for evaluating the severity of aortic valve stenosis noninvasively. Phase-contrast CMR has the potential to become a routine clinical option as an alternative to TEE, at least in selected cases.

Hyperlactatemia (HL) is associated with tissue hypoperfusion during cardiac surgery, which results in postoperative morbidity and mortality among patients undergoing cardiopulmonary bypass surgery. The aim of this study was to determine the incidence, risk factors, and outcome of HL after heart transplantation (HTx) in one of the largest Japanese single-center cohorts. We retrospectively studied the lactate levels in 49 patients who underwent HTx at the University of Tokyo Hospital from August 1, 2010 to November 30, 2015. All of the patients were over 20 years of age. Arterial blood samples were analyzed during the operation and until 24 hours after surgery. Twenty-nine patients (59.2%) had HL after intensive-care unit admission. At 24 hours after surgery, the lactate levels of all patients had recovered to the normal range. A multivariate analysis showed that the total ischemic time of the donor heart (odds ratio [OR], 1.0176; 95% confidence interval [CI], 1.0004-1.0375; P = 0.0444) and the duration of preoperative left ventricular assist device (LVAD) support (OR, 0.9977; 95% CI, 0.9952-0.9997; P = 0.0218) were risk factors for HL. Pulmonary complications were noted in 24.1% of the patients with high lactate values but in none of the patients without HL (P = 0.0182); however, there were no cases of hospital death, and the length of hospital stay did not differ to a statistically significant degree between HL groups (P = 0.719). Although HL after HTx was common, it appeared to be transient and benign. Donor heart ischemia and the duration of preoperative LVAD support were associated with HL after transplantation.

It is unknown whether a response to tolvaptan (TLV) is related to prognosis in patients with acute decompensated heart failure (ADHF). We selected 25 patients as responders by their urinary response to TLV and by reduction of loop diuretics from 37 consecutive ADHF patients treated with TLV. As a control group, we selected 25 patients from 100 consecutive ADHF patients who were not treated with TLV by propensity score matching for age, serum sodium level, serum creatinine level, plasma B-type natriuretic peptide (BNP) level, systolic blood pressure, heart rate, and dose of loop diuretics. The primary outcome was defined as a composite endpoint of mortality and/or hemodialysis. The amount of loop diuretics administered to responders was reduced by TLV from 68.8 ± 26.2 mg to 30.4 ± 18.6 mg of furosemide equivalents per day, whereas the loop diuretic dose administered to non-responders was increased. The event-free survival of the TLV responders during 20 months was significantly better than that of the control group (95.8% versus 68.4%, P = 0.0406). The TLV responders, plasma BNP level, and estimated glomerular filtration rate were significantly related to the events in the Cox proportional hazard analysis. Patients with ADHF who respond to TLV may have a better prognosis than propensity-matched patients not receiving TLV treatment. In TLV responders, it may be possible to improve the patient's prognosis if the dose of loop diuretics can be reduced with TLV therapy.

Early extubation in the operating room after congenital open-heart surgery is feasible, but extubation in the intensive care unit after the operation remains common practice at many institutions. The purpose of this study was to evaluate retrospectively the adequacy of our early-extubation strategy and exclusion criteria through analysis based on the Risk Adjustment in Congenital Heart Surgery method (RACHS-1).

This retrospective analysis included 359 cases requiring cardiopulmonary bypass (male, 195; female, 164; weight > 3.0 kg; aged 1 month to 18 years). Neonates and preoperatively intubated patients were excluded. Other exclusion criteria included severe preoperative pulmonary hypertension, high-dose catecholamine requirement after cardiopulmonary bypass, delayed sternal closure, laryngomalacia, serious bleeding, and delayed awakening. The early-extubation rates were compared between age groups and RACHS-1 classes.

Overall, 83% of cases (298/359) were extubated in the operating room, classified by RACHS-1 categories as follows: 1, 59/59 (100%); 2, 164/200 (84%); 3, 61/78 (78%); and 4-6, 10/22 (45%). The early extubation rate in categories 1-3 (86%, 288/337) was significantly higher than for categories 4-6 (45.5%, 10/22) (P < 0.001). Because they met one of the exclusion criteria, 61 patients (17%) were not extubated in the operating room. Eight patients (2.7%) required re-intubation after early extubation in the operating room, and longer operation time was significantly associated with re-intubation (P < 0.001).

Extubation in the operating room after congenital open-heart surgery was feasible based on our criteria, especially for patients in the low RACHS-1 categories, and involves a very low rate of re-intubation.

Renal sympathetic denervation (RDN) is currently being investigated in multiple studies of heart failure (HF). Our aim was to assess the safety and effectiveness of RDN in patients with HF, and determine which patients could achieve more beneficial effects of RDN. A total of 17 consecutive patients with HF were enrolled in the study. Clinical symptoms, office blood pressure, and laboratory results were obtained and echocardiography was performed before and 12 months after RDN. Changes from baseline to 12 months were analyzed for all patients and for two subgroups based on HF duration (group 1: HF duration ≤ 3 years, n = 9; group 2: HF duration > 3 years, n = 8). The RDN procedure was successful in all patients and no procedure-related complications were documented. In comparison to baseline, there was a significant increase in left ventricular ejection fraction (LVEF) in all patients and group 1 (P < 0.05 for both), which did not happen in group 2. LAD, LVDs, and RVD also showed a significant reduction in group 1 (P < 0.05 for both). At 12 months, the reductions in TNF-α and CRP were significant for all patients and for patients in group 1 separately. No obvious changes in echocardiographic parameters, 6-minute walking distance, TNF-α, or CRP were recorded in group 2. No changes in BNP in either group were observed at the 12th month of follow-up. RDN could improve cardiac function and led to a significant drop in inflammatory markers in patients with HF. We also found that patients in early-stage HF could benefit more from RDN.

Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in acute decompensated heart failure (HF) patients. However, there are limited data regarding the effect of continuous TLV administration on medium-term WRF.

This was a retrospective observational study in hospitalized HF patients with chronic kidney disease (CKD). TLV was administered to those patients with fluid retention despite standard HF therapy. We compared 34 patients treated with TLV (TLV group) to 33 patients treated with conventional HF therapy with high-dose loop diuretics (furosemide ≥ 40 mg) (Loop group). Clinical outcomes, including the incidence of medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months after discharge and adverse events rate, were evaluated.

Baseline patient characteristics were not different between the TLV and Loop group. The TLV group consisted of less frequent use of loop diuretics and carperitide compared with the Loop group. The incidence of medium-term WRF was significantly lower in the TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate logistic analysis showed that the TLV non-user was an independent predictor of medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free survival was significantly higher in the TLV group (log-rank P = 0.01).

Continuous administration of TLV may reduce the risk of medium-term WRF, resulting possibility in improvement of long-term adverse outcomes in HF patients with CKD.

According to recent studies, lung uptake of iodine-123-metaiodobenzylguanidine (¹²³I-MIBG) is impaired in many lung diseases and low lung uptake of ¹²³I-MIBG suggests endothelial dysfunction of the pulmonary artery. ¹²³I-MIBG scintigraphy in patients with pulmonary hypertension (PH) has not yet been clinically evaluated. We hypothesized that the lung uptake of ¹²³I-MIBG is reduced in patients with PH and differs among PH subtypes. The purpose of the present study was to analyze the lung uptake of ¹²³I-MIBG in patients with PH and compare it with the data obtained by echocardiography or right heart catheterization. ¹²³I-MIBG scintigraphy was performed in 286 consecutive patients from 2003 to 2014. We enrolled 21 patients with PH and 8 control patients. The 21 patients with PH were categorized into those with pulmonary artery hypertension (PAH, n = 12) and those with chronic thromboembolic pulmonary hypertension (CTEPH, n = 9). The mean pulmonary artery pressure was not significantly different between patients with CTEPH and PAH (37.7 ± 6.8 versus 32.3 ± 5.3 mmHg respectively; P = 0.054). There were no significant differences in any other hemodynamic parameters between the two groups. The lung uptake of ¹²³I-MIBG in PAH patients (early image: 1.54 ± 0.18, delayed image: 1.41 ± 0.16) was significantly lower than that of CTEPH patients (early image: 2.17 ± 0.25, P < 0.0001; delayed image: 1.99 ± 0.20, P = 0.0001, adjusted for age and World Health Organization classification) and controls (early image: 2.32 ± 0.27, P = 0.0007; delayed image: 1.92 ± 0.19, P = 0.0007). In conclusion, we found for the first time that the lung uptake of ¹²³I-MIBG in patients with PAH is lower than that in patients with CTEPH and controls.

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and ¹²³I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

We assessed the efficacy and safety of direct oral anticoagulants (DOACs) for the treatment of deep venous thrombosis (DVT) in the chronic phase through comparison with conventional warfarin therapy.

A total of 807 consecutive patients who were diagnosed with having DVT in the chronic phase were included (484 patients to warfarin therapy and 323 patients to DOAC therapy). The condition of leg veins was assessed 3 to 6 months after starting the therapies by ultrasound examination. Major bleeding and mortality during the therapies were followed-up.

There was no significant difference between the two groups in the thrombosis improvement rate (DOAC group: 91.2% versus warfarin group: 88.9%). There was no significant difference between the two groups in major bleeding (DOAC group: 1.8% versus warfarin group: 1.8%). In patients with active cancer, the DOAC group had a borderline higher thrombosis improvement rate than the warfarin group (92.1% versus 80.0%, P = 0.05). The proportion of major bleeding in the patients with active cancer was slightly higher in the warfarin group than in the DOAC group (4.3% versus 2.8%; P = 0.71). Active cancer was not an independent risk factor for major bleeding and recurrence in the DOAC group (OR 2.68, 95% CI 0.51-14.1; P = 0.24 and OR 0.65, 95% CI 0.20-2.07; P = 0.47).

In treatment using oral anticoagulants for DVT in the chronic phase, DOACs exhibited equal efficacy and safety as warfarin did. Particularly DOACs appear to be an attractive therapeutic option for cancer-associated DVT in chronic phase, with relatively low anticipated rates of recurrence and major bleeding.

Electrocardiography (ECG) is used to screen for pulmonary hypertension (PH). However, it is unclear which parameters of ECG are the most useful for screening.

ECG parameters related to right ventricular hypertrophy criteria were examined in 145 ECGs of subjects who were suspected to have PH and underwent right heart catheterization (RHC) (age 58.4 ± 17.5 years, 112 women, mean pulmonary arterial pressure [MPAP] 35.4 ± 13.3 mmHg). Based on the results of RHC, 108 subjects had PH (56 pulmonary arterial hypertension [PAH] and 52 chronic thromboembolic pulmonary hypertension [CTEPH]).

Fourteen of 17 ECG parameters in the present study were significantly associated with PH on univariate analysis. On multivariable logistic regression analysis, S wave depth in lead V5 (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.10-1.47) and depth of T wave inversion in lead V4 (OR 1.21, 95% CI 1.03-1.46) were independent predictors of MPAP ≥ 25 mmHg, and the cut-off values determined by receiver operating characteristic curve analyses were 0.42 mV and -0.28 mV, respectively.

In conclusion, a deeper S wave in lead V5 and the presence of a wider extent of negative T waves in the precordial leads may be clinically simple and useful ECG parameters for screening for PH.

In patients with chronic heart failure (HF), the clinical importance of sarcopenia has been recognized in relation to disease severity, reduced exercise capacity, and adverse clinical outcome. Nevertheless, its impact on acute decompensated heart failure (ADHF) is still poorly understood. Dual-energy X-ray absorptiometry (DXA) is a technique for quantitatively analyzing muscle mass and the degree of sarcopenia. Fat-free mass index (FFMI) is a noninvasive and easily applicable marker of muscle mass.

This was a prospective observational cohort study comprising 38 consecutive patients hospitalized for ADHF. Sarcopenia, derived from DXA, was defined as a skeletal muscle mass index (SMI) two standard deviations below the mean for healthy young subjects. FFMI (kg/m²) was calculated as 7.38 + 0.02908 × urinary creatinine (mg/day) divided by the square of height (m²).

Sarcopenia was present in 52.6% of study patients. B-type natriuretic peptide (BNP) levels were significantly higher in ADHF patients with sarcopenia than in those without sarcopenia (1666 versus 429 pg/mL, P < 0.0001). Receiver operator curves were used to compare the predictive accuracy of SMI and FFMI for higher BNP levels. Areas under the curve for SMI and FFMI were 0.743 and 0.717, respectively. Multiple logistic regression analysis showed sarcopenia as a predictor of higher BNP level (OR = 18.4; 95% CI, 1.86-181.27; P = 0.013).

Sarcopenia is associated with increased disease severity in ADHF. SMI based on DXA is potentially superior to FFMI in terms of predicting the degree of severity, but FFMI is also associated with ADHF severity.

Tissue Doppler velocity during early diastole (e') is one of the most feasible and reproducible echocardiographic assessments to reflect active relaxation of the left ventricle. Although several reports have described the mechanisms of temporal diastolic dysfunction in the early neonatal period, factors influencing diastolic function have not been determined. The purpose of this study was to elucidate factors significantly influencing e' in the early neonatal period.

A total of 179 consecutive normal neonates underwent echocardiographic studies performed at 0 days and 5-10 days after birth. The statistical relationships between e' and age, body weight, mean blood pressure, heart rate, shortening fraction of the left ventricle, peak systolic motion velocity (s'), early diastolic transmitral flow velocity over annulus velocity, Tei index, and diastolic wall strain (DWS) were analyzed.

Between the 0 days and 5-10-days-after birth groups, significant differences were shown in mean blood pressure, shortening fraction of left ventricle, e', and Tei index. Age, body weight, mean blood pressure, s', and DWS showed significant correlations with e'. In multivariate regression analysis within these parameters, s' (β = 0.6119, P < 0.0001) and DWS (β = 0.1216, P = 0.0321) showed positive correlations with e'.

Longitudinal systolic motion velocity and ventricular wall stiffness of the left ventricle influence diastolic relaxation in normal neonates. Age, body weight, and circumferential systolic function are not significant factors.

Our previous study showed that pravastatin prevents ischemia and reperfusion-induced lethal ventricular fibrillation in rats. This study explored whether pravastatin decreases myocardial infarct size and this effect is associated with endothelial nitric oxide synthase (eNOS) expression in myocardium. Rats were treated with ischemia (30 minutes) and reperfusion (60 minutes) after chronic oral administration of pravastatin, fluvastatin, or vehicle once daily for 22 days. Electrocardiograms and blood pressure were continuously recorded, myocardial infarct size was measured by TTC-staining, and eNOS expression was measured by western blot. The results showed that pravastatin and fluvastatin significantly reduced myocardial infarct size. No statistical differences were found in the areas at risk among all groups. However, a significant reduction in infarct size was observed in three pravastatin groups and one fluvastatin group compared to control. Both pravastatin and fluvastatin significantly increased eNOS protein expression in ischemic and non-ischemic tissues compared to control. Our results suggest that pravastatin decreases cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in reducing infarct size. These effects may be associated with elevation of eNOS expression.

Transforming growth factor (TGF)-β1 has been implicated in the pathogenesis of restenosis. However, the role of TGF-β1 polymorphisms in development of in-stent restenosis (ISR) after coronary bare metal stent (BMS) implantation in Chinese Han population has not been reported to date. The aim of this study was to explore the association between TGF-β1 gene polymorphisms (-509C/T and 869T/C) and its plasma level in Chinese Han patients with BMS-ISR.

We investigated 419 patients after successful coronary stent placement. All patients were reexamined by angiography. Genotyping for the two TGF-β1 gene polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism analysis. Plasma TGF-β1 levels were measured by enzyme-linked immunosorbent assay.

Ninety-two patients (21.96%) developed ISR during the follow-up period. The multivariable analysis adjusted for potential confounders and it revealed that the C allele of TGF-β1 869T/C polymorphism was linked to an increased risk of ISR in both additive (Per each C allele) and dominant (TC+CC versus TT) models with odds ratios (ORs) of 1.88 (95% confidence interval [CI]: 1.21-2.84, P = 0.008) and 2.52 (95% CI: 1.40-4.80, P = 0.005), respectively. In accord with this, C-dominant CC/CT genotype was linked to higher plasma TGF-β1 level compared to TT genotype. One haplotype (TC) (-509T, +869C) was associated with an increased risk for ISR (OR = 1.48, 95% CI: 1.06-2.06, P = 0.010).

The C allele of TGF-β1 869T/C polymorphism, correlated with high plasma TGF-β1 level, represented an independent risk factor for BMS-ISR in Chinese Han patients with coronary artery disease.

It has been shown that microRNAs (miRNAs) greatly affect the functions of vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic conditions remain unclear.

Using a model of diabetic db/db mice, we studied the functions of microRNA-135a (miR-135a) during VSMC dysfunction.

Compared to control WT mice, miR-135a expression in VSMC was significantly increased while the level of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1) expression levels were increased, thus promoting the interaction between monocytes and WT VSMC. On the other hand, transfection of an miR-135a inhibitor reversed the activated interaction between monocytes and db/db VSMC. The pro-inflammatory responses could also be enhanced by using siRNAs to silence the FOXO1 gene in WT VSMC, suggesting a negative regulatory role of FOXO1. FOXO1 siRNAs and miR-135a mimics could both enhance the transcriptional activity of COX-2 promoter. Using chromatin immunoprecipitation, we found that in db/db VSMC, the occupancy in promoter regions of inflammatory genes by FOXO1 was reduced.

miR-135a increased the inflammatory responses of VSMC involved in complications of vascular diseases by downregulating the expression of FOXO1.

Dilated cardiomyopathy (DCM), as one of the common cardiomyopathies, is a disease of the heart muscle; however, the etiology and pathogenesis of DCM were still poorly understood. Nestin has been reported a special marker of stem/progenitor cells in various tissues, and the tissue resident Nestin⁺ cells could promote the wound healing and tissue remodeling. However, it remains unclear whether Nestin⁺ cells participate in the protection of cardiomyocytes during the pathogenesis of DCM. Here the model of mice DCM was induced by doxorubicin (DOX) intraperitoneal injection and observed heart failure and ventricular enlargement via echocardiography and histologic analysis, respectively. During DCM pathogenesis, the number of Nestin⁺ cells showed a significant peak on day 6 after DOX treatment, which then gradually decreases to lower than normal levels after day 30 in the total population of the heart. Furthermore, we found that the isolated increased heart-derived Nestin⁺ cells are mesenchymal property and could protect DOX-induced HL-1 cells toxicity in vitro by promoting their proliferation and inhibiting their apoptosis. Collectively, our results showed that Nestin⁺ cells increased during DCM pathogenesis and played an important role in protecting against the DOX-induced HL-1 cells loss via regulating proliferation and apoptosis. Thus, the loss of Nestin⁺ cells might be an etiology to DCM pathogenesis, and these cells could be a promising candidate cell source for study and treatment of DCM patients.

The aim of this study was to investigate the effects of taurine (Tau) on primary cultured neonatal myocardial cells treated with hydrogen peroxide (H₂O₂) and the underlying mechanism. Primary cardiac myocytes from neonatal Wistar rats were pre-incubated with Tau, and its effects on cell viability and expression of CaM, CaMKII, p53, Bcl-2, and Bax were examined. Tau enhanced the viability of myocardial cells, decreased apoptosis, and alleviated the intracellular calcium overload, especially at dosages of 40 or 80 mM (P < 0.01 or P < 0.001, respectively). Moreover, Tau could inhibit the H₂O₂-induced decrease in CamKII and CaM expression at both the mRNA and protein levels. The pattern of CaMKII expression was consistent with that of the anti-apoptotic protein Bcl-2, but contrasted the pattern of the pro-apoptotic proteins p53 and Bax. Thus, our results show that Tau protects myocardial cells against damage caused by H₂O₂ exposure, suggesting that it might play a role in the mitochondrial apoptotic pathway by upregulating the expression of CaMKII to rescue myocardial cells. However, the underlying mechanism still needs to be investigated. In addition, we tested the protective effect of taurine on cardiac myocytes, and the effect of taurine on another model, specifically an animal model.

The aim of this study was to explore how atrial natriuretic polypeptide (ANP) affects the properties and function of endothelial cells. Gene expression data GSE56976 generated at 0, 1, and 6 hours after ANP incubation in human umbilical vein endothelial cells (HUVEC) was used. Microarray data were preprocessed for differentially expressed genes (DEGs) in each time-dependent group. Next, gene ontology (GO), pathway analysis, and transcriptional regulation were performed. Co-expression clustering analysis of DEGs and functional enrichment analysis of co-expression modules were processed. RT-PCR analysis was performed to validate gene expression. DEGs were obtained and their counts were increased from 0 hours to 6 hours. No overlapping DEGs were obtained among the 3 groups. The DEGs of ANP_6hours, including TGFB2 (transforming growth factor, beta 2), LTF (lactotransferrin/lactoferrin), and ETV7 (Ets variant 7) were mainly related with cell apoptosis and immune responses. The DEGs in the network of ANP_0hour were mainly associated with epithelial ion transport processes. In addition, 3 co-expressed modules were detected. CSF2 (colony stimulating factor 2) and PF4 (platelet factor 4) of the blue module were related with cytolysis, while FXYD1 (FXYD domain containing ion transport regulator 1) and TGFB2 of the yellow module were mainly enriched in ion transport and the ovulation cycle. The expression of TGFB2 obtained by microarray analysis was consistent with that of RT-PCR. Ion transport could be affected promptly after ANP treatment, and subsequently, the cytolysis of vein endothelial cells may be promoted and endothelial permeability would be enhanced, followed by activated immune responses.

Coronary stent fracture (SF) is rare as a complication of percutaneous coronary intervention (PCI), and its adverse events are increasingly being recognized with the development in devices of PCI. The major adverse events caused by SFs are in-stent restenosis due to neointimal overgrowth caused by poor drug delivery.^1,2) A coronary artery aneurysm (CAA) is a rare complication of SF, but may lead to lethal events such as acute coronary syndrome or rupture of the CAA further leading to cardiac tamponade.^3-5) However, the management of CAAs is controversial with or without SF.⁶⁾ Herein, we report a case of a CAA caused by an SF and discuss the management of CAA complicated with SF, along with a literature review. We suggest that surgical treatment should be considered the higher-priority strategy in the cases of CAA with SF as compared to CAA without SF.

A 43-year-old man was admitted to our hospital with ST-segment elevation acute coronary syndrome. He had experienced myocardial infarction 19 months previously, and a bare-metal stent (BMS) had been implanted in the culprit distal right coronary artery at another hospital. Emergency coronary angiography showed thrombotic in-stent occlusion of the BMS. Intravascular ultrasound revealed an undersized stent compared with the size of the vessel and late stent malapposition (LSM) with abundant thrombi. The lesion was successfully recanalized via thrombectomy and plain old balloon angioplasty. Optical frequency domain imaging performed at follow-up coronary angiography confirmed the improvement of the LSM and incomplete neointimal stent coverage. This report illustrates the importance of imaging modalities in elucidating the mechanism of BMS-related very late stent thrombosis.

Congenital double-orifice mitral valve (DOMV) is a rare malformation that may affect both mitral valve and apparatus, and it is usually associated with other cardiac disorders. Asymptomatic DOMV is extremely rare. We present two similar cases of asymptomatic congenital double-orifice mitral valve. Both cases presented functionally normal mitral valve apparatus with two equally sized orifices, which were formed by a central fibrosis. In addition, final confirmatory diagnosis was made using three-dimensional (3D) echocardiography in both cases.

Aerobic training based on anaerobic threshold (AT) is well-known to improve cardiac function, exercise capacity, and long-term outcomes of patients with heart failure. Recent reports suggested that high-intensity interval training (HIIT) for patients with cardiovascular disease may improve cardiopulmonary exercise capacity. We present a 61-year-old male patient of severe left ventricular dysfunction with left ventricular assisted device (LVAD). Following HIIT for 8 weeks, exercise capacity and muscle strength have improved without worsening left ventricular function. Our case showed the possibility that HIIT was feasible and effective even in patients with LVAD.

We encountered a 35-year-old male patient with scimitar syndrome, acute type A aortic dissection, and severe iliac malperfusion. He presented with pain and weakness of the left lower extremity and underwent ascending aorta replacement through sternotomy and right anterior thoracotomy. Left iliac artery flow was recovered after the operation and the patient was discharged on the tenth day without any complication. The purpose of this report is to discuss the considerations in aortic surgery in patients with scimitar syndrome, and the surgical principles for treatment of aortic dissection with critical limb ischemia.

An aorto-cutaneous fistula is a rare complication that occurs after aortic surgery. Due to its rarity, postoperative complications are not normally highlighted in most standard teaching. We report here a case of aorto-cutaneous fistula after surgical treatment of a Stanford type A aortic dissection (AD) in a 67-year-old Chinese male. The patient presented with severe right heart dysfunction and a mass was found in the upper-middle of his chest, which started bleeding in the next years. On admission, preoperative aortic computed tomography angiography (CTA) showed a huge hematoma located in the anterior superior mediastinum and a shunt between the embedding cavity of the aortic root and right atrium. An emergent procedure was performed. Intraoperatively, we found two leaks approximately 2 mm from the anastomosis of the greater curvature of the ascending aortic graft and stented graft after the hematoma was cleared and we confirmed the shunt had a large amount of blood flow after a right atrium incision. After the surgery, the patient was diagnosed with a cerebral hemorrhage, and his family decided to refuse therapy on the third postoperative day (p.o.d.).

This case study describes the successful percutaneous transcatheter retrieval of an embolized Amplatzer occluder device using the "waist capture technique" in a patient with an atrial septal defect. This technique allowed for stability of the Amplatzer device, compression of the atrial discs for easier removal, prevention of further embolization, and minimal injury to vasculature during device retrieval. This novel and effective technique can be used safely for the retrieval of Amplatzer devices in the venous system.

A 69-year-old woman without any past disease history was hospitalized for heart failure. After hospitalization, she showed myocardial infarction, atrioventricular dissociation, and cardiac dysfunction, and finally she passed away despite intensive care. Autopsy revealed that the cardiac abnormalities were due to bacterial myocarditis possibly resulting from urinary tract infection by E. coli. Although bacterial myocarditis is rare in developed countries, we should consider its possibility when patients show various cardiac abnormalities with bacterial infection.

We experienced a 45-year-old Japanese man who was transferred to our hospital complaining of acute onset of pain and pallor in the right lower limb. Two years earlier, he had complained of repetitive pain at rest and pallor in the left third and fourth fingers. The physical exam and angiography demonstrated occlusion of finger arteries, however we could not reach final diagnosis. Acute arterial occlusive disease in the right lower limb was suspected. Transthoracic echocardiography demonstrated a gross tumor in the left atrium, which suggested left atrial myxoma. An emergency tumorectomy was successfully conducted. Pathologically, the fragile tumor and resultant thrombosis could have caused the patient's peripheral circulatory failure at least two years prior to this episode. A rigorous systemic survey is important even when the ischemic symptom is localized in peripheral circulation.

The use of unilateral pulmonary artery occlusion (UPAO) test for the preoperative evaluation of pneumonectomy was reported in adult patients. On the contrary, in infants, no strategies have yet been recommended to predict hemodynamics after pneumonectomy, nor has use of the UPAO test been reported. We describe the first case of infant with abnormal pulmonary circulation in whom successful pneumonectomy was performed after preoperative evaluation using UPAO test. Right pneumonectomy was planned for an 8-month-old girl, because of decreased right pulmonary function, high risk of pneumothorax, and impaired left lung expansion due to overexpansion caused by severe left bronchial stenosis and bronchomalacia. However, she had also prolonged pulmonary hypertension and there was difficulty in accurate echocardiographic evaluation of its severity due to concomitant left pulmonary artery stenosis. Furthermore, contrast-enhanced computer tomography suggested a certain degree of right pulmonary venous flow, discordant with the result showing scarce right pulmonary flow in perfusion scintigraphy. Predicting postoperative hemodynamic changes was therefore considered difficult. To evaluate these concerns, we performed cardiac catheterization and UPAO test to simulate postoperative hemodynamics. Pulmonary arteriography showed decreased but significant right pulmonary arterial and venous flows. Measurements including pulmonary artery pressure and cardiac index showed no marked changes after occlusion. Based on UPAO test results, the operation was successfully performed and hemodynamics remained stable postoperatively. The UPAO test may be useful for infants with cardiopulmonary impairment to evaluate the tolerability of pneumonectomy.

We report the case of a 38-year-old woman who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral annular calcification (MAC). The cardiac mass was removed, and mitral valve replacement surgery was performed. Pathological examination revealed an amorphous accumulation of degenerating material within both lesions, indicating that build-up of calcium along the mitral annulus and subsequent rupture of the fibrotic tissue may be involved in the initiation and progression of CAT.