The evaluation of baroreflex sensitivity (BRS), which maintains systemic circulatory homeostasis, is an established tool to assess cardiovascular autonomic neuropathy in type 2 diabetes mellitus (T2DM). As BRS plays an important function in blood pressure regulation, reduced BRS leads to an increase in blood pressure variability, which further leads to reduced BRS. This sequence of events becomes a vicious cycle. The major risk factors for reduced BRS are T2DM and essential hypertension, but many other risk factors have been reported to influence BRS. In recent years, reports have indicated that glycemic variability (GV), such as short- and long-term GV that are considered important risk factors for macrovascular and microvascular complications, is involved in reductions in BRS independently of blood glucose levels. In this review, we discuss reduced BRS in T2DM, its features, and the potential for its reversal.

An optimal hydration volume (HV) that prevents contrast-induced acute kidney injury (CI-AKI) in patients with renal insufficiency and heart failure (HF) at a high risk of worsening HF (WHF) has not been determined. We aimed to determine a safe HV that prevents CI-AKI and WHF following coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with renal insufficiency and HF. We recruited 1,307 patients with renal insufficiency and HF and investigated the relationships between the peri-procedural HV/weight (HV/W) ratio, and the risks of CI-AKI and WHF following CAG or PCI. Higher HV/W quartiles were associated with higher CI-AKI rates (Q1: 6.2%, Q2: 9.1%, Q3: 12.5%, and Q4: 18.7%; P < 0.001) and a greater likelihood of WHF (Q1: 2.2%, Q2: 2.7%, Q3: 4.9%, and Q4: 11.7%; P < 0.001). The multivariate analyses indicated that excessively high HV/W ratios were associated with moderately increased risks of CI-AKI (Q4 versus Q1: adjusted odds ratio [OR] 2.16, 95% confidence interval [CI] 1.17-4.00) and WHF (Q4 versus Q1: adjusted OR 3.09, 95% CI 1.21-7.88). The multivariate Cox regression analysis indicated that a higher HV/W ratio was associated with significantly increased long-term mortality (Q2 versus Q1: adjusted hazard ratio [HR] 2.36; Q3 versus Q1: adjusted HR 2.85; Q4 versus Q1: adjusted HR 2.94; all P < 0.05). In conclusion, an excessively high HV/W might be associated with a moderately increased risk of CI-AKI, WHF, and long-term mortality in patients with renal insufficiency and HF.

Previous clinical studies have shown inconsistent results regarding the effect of erythropoietin in ST-segment elevation myocardial infarction (STEMI). This study investigated whether directed intracoronary infusion of darbepoetin-α into ischemic myocardium before reperfusion would reduce infarct size or post-infarct remodeling in STEMI patients.

Eighty STEMI patients received one of the following treatments simultaneously with the first balloon inflation: intracoronary darbepoetin-α 300 μg (n = 40) or saline (n = 40), administered via the over-the-wire balloon system. The primary endpoint was infarct size estimated by serial cardiac enzyme levels after procedure. The secondary endpoints were (1) infarct size and proportion of salvaged myocardium measured with cardiac magnetic resonance (CMR) at baseline; (2) post-infarct remodeling (PIR), defined as an increase in left ventricular end-diastolic volume more than 20% at 4 months compared to the baseline on CMR; and (3) composite cardiovascular endpoints assessed at 4 months.

The peak CK-MB [median 270.0 (interquartile range 139.8-356.3) versus 231.5 (131.0-408.5) ng/mL, P = 0.55] and troponin-I [128.5 (63.5-227.8) versus 109.0 (43.8-220.0) ng/mL, P = 0.52) ] did not differ between the darbepoetin-α and control group. Fifty-seven patients completed the baseline and 4-month follow-up CMR. There were no differences in infarct size [30.6 (18.1-49.8) versus 31.5 (22.5-47.3) cm³, P = 0.91), proportion of salvaged myocardium [26.7% (15.9-42.6%) versus 35.8% (22.4-48.8%), P = 0.12) or PIR (8.0% versus 6.7%, P = 0.62) between the two groups. Composite cardiovascular outcomes did not differ between the two groups.

In conclusion, administration of intracoronary darbepoetin-α before reperfusion did not reduce infarct size or post-infarct remodeling in STEMI patients.

The utilization of electronic medical records and multimodal medical data is an ideal approach to build a real-time and precision registry type study with a smaller effort and cost, which may fill a gap between evidence-based medicine and the real-world clinical practice. The Japan Ischemic heart disease Multimodal Prospective data Acquisition for preCision Treatment (J-IMPACT) project aimed to build an clinical data registry system that electronically collects not only medical records, but also multimodal data, including coronary angiography and percutaneous coronary intervention (PCI) report, in standardized data formats for clinical studies.

The J-IMPACT system comprises the standardized structured medical information exchange (SS-MIX), coronary angiography and intervention reporting system (CAIRS), and multi-purpose clinical data repository system (MCDRS) interconnected within the institutional network. In order to prove the concept, we acquired multimodal medical data of 6 consecutive cases that underwent PCI through the J-IMPACT system in a single center. Data items regarding patient background, laboratory data, prescriptions, and PCI/cardiac catheterization report were correctly acquired through the J-IMPACT system, and the accuracy of the multimodal data of the 4 categories was 100% in all 6 cases.

The application of J-IMPACT system to clinical studies not only fills the gaps between randomized clinical trials and real-world medicine, but may also provide real-time big data that reinforces precision treatment for each patient.

Urinary excretion of 8-iso-prostaglandin F_2α (8-iso-PGF_2α), a reliable biomarker for enhanced oxidant stress in vivo, has been described in association with diabetes and coronary heart disease. The aim of this study was to evaluate the relationship between urinary 8-iso-PGF_2α levels and the characteristics of coronary culprit lesion in diabetic patients with acute coronary syndrome (ACS). A total of 79 diabetic patients with ACS were included. iMAP intravascular ultrasound (iMAP-IVUS) was performed to evaluate the characteristics of culprit plaques. Fasting urinary 8-iso-PGF_2α level was measured and corrected by creatinine clearance. iMAP-IVUS data showed culprit plaques in high urinary 8-iso-PGF_2α level patients had a greater percentage of necrotic core and less fibrous components. High urinary 8-iso-PGF_2α levels were correlated with increased necrotic plaque components (r = 0.325, P = 0.003). Meanwhile, the presence of thin-capped fibroatheroma (50.0% versus 11.5%, P = 0.003), ruptured plaques (30.8% versus 7.7%, P = 0.035), and thrombus (38.5% versus 7.7%, P = 0.008) were significantly more frequent in the upper tertile of urinary 8-iso-PGF_2α levels than in the low tertile. Multivariate analysis showed high levels of urinary 8-iso-PGF_2α (OR 4.240, P = 0.007) was independently associated with the presence of vulnerable culprit plaque in diabetic ACS patients. Urinary 8-iso-PGF_2α also displayed a significant value in predicting vulnerable plaques in diabetic patients with ACS by constructing the receiver-operating characteristic (ROC) curve (Area under the ROC curve: 0.713, P = 0.001). Urinary 8-iso-PGF_2α levels are associated with the vulnerability of the coronary culprit lesion in diabetic patients with ACS and may provide additional information for risk assessment in suspected vulnerable patients.

Patients with ischemic heart disease are associated with poor prognosis, and their number has increased globally. Therefore, biomarkers that could predict post-acute myocardial infarction (AMI) heart failure (HF) would be helpful to guide appropriate treatment. Based on the diagnosis on admission and results of echocardiogram performed on admission and 1 year after discharge, the current study recruited 54 patients with post-AMI HF, 59 patients with post-AMI non-HF, and 59 healthy controls. Eight candidate microRNAs (miRs) were screened through real-time quantitative PCR. Serum circulating miR-150 level in the post-AMI HF group was significantly lower than the post-AMI non-HF group (0.4 ± 0.3 versus 0.7 ± 0.3, P < 0.001). Further analysis showed that serum circulating miR-150 level was associated with ejection fraction (EF) 1 year after discharge (P < 0.001). Receiver operating characteristic curve (ROC) analysis found that area under the ROC (AUC) was 0.616 (95%CI = 0.511-0.721, P = 0.034) when BNP was used to predict post-AMI HF, whereas AUC improved to 0.764 (95%CI = 0.674-0.855, P < 0.001) when miR-150 was used. The combination of BNP and miR-150 significantly improved the AUC to 0.807 (95%CI = 0.727-0.886, P < 0.001). Finally, multivariate logistic regression analysis revealed that either LVEF on admission or serum circulating miR-150 level was independently associated with post-AMI HF. Serum circulating miR-150 is a novel biomarker to predict post-AMI HF. Further large sample prospective clinical research is needed to validate its role in the future.

The late consequences of acute coronary syndrome (ACS) have been underestimated. We hypothesized that the temporal distribution of the clinically silent coronary artery disease progression (CP) is associated with the subsequent consequences of ACS.

We studied 243 patients (202 men, 64 ± 10 years) with ACS undergoing percutaneous coronary intervention (PCI) during initial hospitalization. All patients underwent serial coronary angiograms (CAGs) immediately before PCI and at 7 ± 3 and 60 ± 10 months after presentation. CP was defined as an increase ≥ 15% in stenosis severity of the lesion between 2 serial CAGs. The impact of CP between each 2 serial CAGs on subsequent major adverse cardiovascular and cerebrovascular events (MACCEs) after the final CAG was examined using multivariate Cox and propensity-matched analyses.

During the median follow-up duration after the final CAG of 67 months, 76 MACCEs (31.3%) were observed. Multivariate Cox proportional hazards analysis revealed that CP between the first and second CAGs (hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.32-3.94; P = 0.003) and CP between the second and final CAGs (HR, 1.96; 95% CI, 1.20-3.21; P = 0.008) were independently associated with a higher rate of MACCEs beyond the final CAG. Consistent results were obtained in the propensity score-matched analyses.

CP in both the early (0-7 months) and late phases (7-60 months) were independently associated with subsequent clinical events. This may indicate the prognostic significance of persistent widespread coronary disease activity following presentation in patients with ACS undergoing PCI.

Recent reports show that an early repolarization pattern (ERP) is associated with a higher incidence of sudden cardiac death in patients with obstructive coronary artery disease (CAD). Sporadic case studies have pointed out that ERP might be related to obstructive CAD.

In consecutive patients who had undergone coronary angiography, we investigated the relationship between ERP and obstructive CAD by evaluating its association with coronary artery stenosis.

The study population consisted of 3785 patients (59.9% men; mean age 63.1 years) with or without obstructive CAD. Adjusting for major cardiovascular risk factors, ERP was significantly associated with obstructive CAD (adjusted odds ratio (OR): 2.24 [95% CI 1.70-2.95]) with an incremental predictive value (ROC AUC 0.76 versus 0.71, P = 0.02; NRI 55.3%, P < 0.001; IDI = 0.05, P = 0.008), specifically in subjects with low risk and intermediate risk. ERP also significantly improved the predictive value for multi-vessel disease (AUC: 0.77 versus 0.72, P = 0.02 for two-vessel disease; 0.79 versus 0.73, P = 0.04 for three-vessel disease). ERP was consistently associated with stenoses of 3 main coronary arteries.

ERP is associated with significant increased risk for obstructive CAD.Further studies are warranted to confirm our results and to elucidate the specific pathogenic mechanisms.

In clinical practice, some atrial fibrillation (AF) patients were classified as having low and moderate stroke risk by the CHADS₂ score (≤ 1) in 2001 but in 2012 they were not truly classified as low risk of stroke according to the CHA₂DS₂-VASc score (≥ 2) (defined gray zone). Therefore, a treatment gap exists in gray zone AF patients. This study aimed to evaluate whether gray zone AF patients could benefit from reduced all-cause mortality under antithrombotic treatment. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance from January 2000 to December 2011. The new-onset AF patients consisted of a gray zone cohort with a total of 1237 patients being enrolled. The primary outcome was all-cause mortality between 2001 and 2011. Patients in the gray zone receiving antithrombotic treatment had a significant reduction in all-cause mortality [hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.16-0.28] compared with the no treatment group [warfarin only: HR, 0.28 (95% CI, 0.15-0.52); warfarin + Aspirin: HR, 0.21 (95% CI, 0.15-0.30); and Aspirin only: HR, 0.22 (95% CI, 0.16-0.29) ]. All-cause mortality was notably increased when any of the following risk factors were present: age 65-74 years, age ≥ 75 years, chronic kidney disease, and vascular disease. We concluded that AF patients in the gray zone must receive either anticoagulant and/or antiplatelet treatment and there is a lower mortality in these groups during long-term follow-up. Further investigation is needed to observe whether the antithrombotic drugs have benefits for patients with AF with a CHA₂DS₂-VASc score < 2.

Serum thrombospondin-2 (TSP-2) is a glycoprotein expressed in the extracellular matrix (ECM), which increases during tissue remodeling. It has been shown in recent studies that TSP-2 is a useful predictor of cardiovascular death in patients with heart failure (HF). However, the clinical importance of serum TSP-2 levels in a general population is still unknown. Therefore, we aimed to clarify the association between TSP-2 and clinical risk factors. A periodic epidemiological survey was performed in a community dwelling in the town of Uku, Nagasaki, Japan. A total of 445 residents received a health checkup examination including blood tests such as fasting serum levels of TSP-2. Uni- and multivariate analyses were performed to examine the relationship between TSP-2 and clinical risk factors. All statistical analyses were performed using SAS v9.4 program. The mean ± standard deviation of age was 67.0 ± 9.4 years old. Although serum TSP-2 levels (mean: 20.9 ± 8.5 ng/mL) showed no significant sex difference, they were significantly correlated with the levels of plasma glucose (P < 0.001), insulin (P < 0.01), homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001), estimated glomerular filtration rate (eGFR) (P < 0.01, inversely), high-sensitivity C-reactive protein (hs-CRP) (P < 0.001), history of atrial fibrillation (P < 0.001), history of cardiovascular diseases (P < 0.001), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (P < 0.001). Moreover, in the multiple stepwise linear regression analysis, the levels of TSP-2 were independently and significantly associated with the history of atrial fibrillation (P < 0.0001), HOMA-IR (P < 0.001), high-sensitivity CRP (P = 0.011), and NT-proBNP (P = 0.043). These results indicated the significant relationship between TSP-2 and clinical risk factors in a general population, suggesting its role as a predictor of heart disease morbidity and mortality.

Implantable cardioverter-defibrillators (ICDs) improve survival in patients who are at risk of sudden death. However, inappropriate therapy is commonly given to ICD recipients, and this situation may be associated with an increased risk of death. This study aimed to construct a risk stratification scheme by using decision tree analysis in patients who received inappropriate ICD therapy.

Mortality was calculated from a retrospective data analysis of a multicenter cohort involving 417 ICD recipients. Inappropriate therapy was defined as therapy for nonventricular arrhythmias, including sinus tachycardia, supraventricular tachycardia, atrial fibrillation/flutter, oversensing, and lead failure. Inappropriate therapy included antitachycardia pacing, cardioversion, and defibrillation. The prognostic factors were identified by a Cox proportional hazards regression analysis, and we constructed a decision tree.

During an average follow-up of 5.2 years, 48 patients (12%) had all-cause death. A multivariate Cox hazard model revealed that the age (hazard ratio [HR] 1.06, P < 0.001), ln B-type natriuretic peptide (BNP) (HR 1.47, P = 0.02), nonsinus rhythm at implantation (HR 2.70, P < 0.05), and inappropriate therapy occurring during sedentary/awake conditions (HR 3.51, P = 0.001) correlated with an increased risk of mortality. An inappropriate therapy due to abnormal sensing (HR 0.16, P = 0.04) decreased the risk of mortality. Furthermore, a decision tree analysis stratified the patients well by using 4 covariates: BNP, activity at the time of inappropriate therapy, mechanism of inappropriate therapy, and baseline rhythm at ICD implantation (log-rank test, P < 0.0001).

We identified the predictors of mortality in inappropriate ICD therapy recipients and constructed a risk stratification scheme by using decision tree analysis.

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Data regarding the correlations of biomarkers and AF in HCM patients are rather limited. We sought to explore the associations between the presence of AF and circulating biomarkers reflecting cardiovascular function (N-terminal pro-brain natriuretic peptide, NT-pro BNP), endothelial function (big endothelin-1, big ET-1), inflammation (high-sensitivity C-reactive protein), and myocardial damage (cardiac troponin I, cTnI) in HCM patients with and without left ventricular outflow tract obstruction (LVOTO).

In all, 375 consecutive HCM in-hospital patients were divided into an AF group (n = 90) and a sinus rhythm (SR) group (n = 285) according to their medical history and electrocardiogram results.

In comparison with the SR group, peripheral concentrations of big ET-1, NT-pro BNP, and cTnI were significantly higher in patients with AF. Only the biomarker of big ET-1, together with palpitation and left atrial diameter (LAD), was independently associated with AF in HCM patients. Ln big ET-1 was positively related to Ln NT-pro BNP, LAD, and heart rate, but negatively related to left ventricular ejection fraction. Combined measurements of big ET-1 ≥ 0.285 pmol/L and LAD ≥ 44.5 mm indicated good predictive values in the presence of AF, with a specificity of 94% and a sensitivity of 85% in HCM patients.

Big ET-1 has been identified as an independent determinant of AF, regardless of LVOTO, and is significantly related to parameters representing cardiac function and remodeling in HCM. Big ET-1 might be a valuable index to evaluate the clinical status of AF in HCM patients.

Data involving combined mitral and aortic valve procedure via the right mini-thoracotomy approach are very limited. This single-center propensity-matching study aimed to evaluate early clinical outcomes of patients who underwent combined mitral and aortic valve procedure via right mini-thoracotomy versus full median sternotomy.

From January 2013 to December 2016, 926 eligible patients in our center were identified for this study. After propensity score-matching, 91 pairs of patients were entered into a RT group (right mini-thoracotomy surgery) or a FS group (full median sternotomy surgery). In-hospital and follow-up clinical outcomes were investigated and analyzed.

Patients in the RT group received similar surgical mortality as patients in the FS group (1.1% versus 2.2%, P > 0.05). Patients in the RT group as compared with the FS group were less likely to receive postoperative new onset of atrial fibrillation and red cell transfusion (11.0% versus 25.3%, P = 0.012; 17.6% versus 37.4%, P = 0.003, respectively), but they shared similar incidences of other major postoperative morbidity. Patients in the RT group as compared with the FS group experienced 6-minute longer aortic cross-clamping times and 9-minute longer cardiopulmonary bypass times, but received shorter intensive care unit stay and postoperative hospitalization time. No repeat valve operation, peri-prosthetic leak, or moderate or severe mitral valve regurgitation following valvuloplasty were observed in either group before discharge and also within one year of surgery.

In primary, isolated, combined mitral and aortic valve procedure, a right mini-thoracotomy approach may be utilized with accepted early clinical outcomes, and may be considered as a feasible alternative to the approach of full median sternotomy.

The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) are emerging indirect blood markers to roughly reflect the inflammation level in our body while some pathological changes occurring in aortic valve tissue. Few recent studies demonstrated that NLR is related to calcific aortic valve disease (CAVD). However, the extent of the relationship between them and the impact of CRP on CAVD are not clear. This study aimed to investigate the diagnostic influence and surgical predictive effect of NLR and CRP on CAVD.

A total of 278 consecutive patients with CAVD (123 patients with bicuspid aortic valve and others with tricuspid aortic valve) and 108 healthy individuals who were included in the control group were enrolled in the study. The NLR was calculated from the complete blood count, and the CRP was measured from peripheral blood samples. Echocardiography was used to evaluate the severity of aortic stenosis. Intraoperation/postoperation indicators were collected in 166 patients from the total consecutive patients who underwent aortic valve replacement (AVR) alone.

Significantly higher NLR was measured in both the BAV group (1.96 ± 0.78 versus 0.97 ± 0.15, P < 0.001) and the TAV group (2.51 ± 2.03 versus 0.97 ± 0.15, P < 0.001) compared with the control group. Moreover, the NLR level was significantly higher (P < 0.001) and the CRP level was significantly lower (P = 0.007) of the TAV group than that of the BAV group; a significant positive correlation between the NLR and the maximum gradient of aortic valve was detected. Furthermore, there was a moderate correlation between the NLR and the postoperative mechanical ventilation time.

Our results indicated that the NLR and CRP were novel and useful predictive factors in patients with CAVD, and these two potential factors have guiding significance for the prediction of different pathological typing (BAV or TAV). Higher NLR level will not extend the cardiopulmonary bypass time (CPB); however, it will prolong the operation time and the postoperative mechanical ventilation time.

Cirrhosis is a significant adverse factor of cardiac surgeries. Transcatheter aortic valve implantation (TAVI) has evolved as a less invasive therapy for aortic stenosis, whereas detailed case analysis of TAVI in cirrhotic patients is limited.

Among 444 consecutive patients who underwent TAVI in the Sakakibara Heart Institute between October 2013 and January 2018, we retrospectively reviewed 11 patients (2.5%) with cirrhosis. All outcomes were defined according to the Valve Academic Research Consortium-2 criteria.

The median age of the patients was 82 years, and eight (73%) were female. Seven patients (64%) were Child-Turcotte-Pugh class A, and four patients (36%) were class B. The Model for End-Stage Liver Disease score was 10 (7.0-13). TAVI was performed using Edwards SAPIEN XT/SAPIEN3 in nine patients (82%), and Medtronic CoreValve/Evolut R in two patients (18%), via transfemoral (n = 8, 73%) or transapical (n = 3, 27%) approach. The device success rate was 100% and no extracorporeal circulation had been inducted. No death, stroke, life-threatening bleeding, and acute kidney injury stage 2 or 3 occurred within 30 days, but three major bleeding events (27%) were documented (two access-site bleeding in transapical approach, and one pulmonary hemorrhage caused by transient mitral regurgitation). During a median follow-up of 493 days, four deaths had occurred, and the mid-term survival rate was 81% and 65% at one and two years each.

TAVI is a promising therapeutic option for patients with cirrhosis. Further study should be needed regarding optimal patient selection and procedures in patients with cirrhosis.

The efficacy of intravenous immunoglobulin (IVIG) in the treatment of acute myocarditis remains controversial. The aim of this study was to conduct a meta-analysis to assess the efficacy of IVIG in children and adults with acute myocarditis.

We searched PubMed, Scopus, Embase, Medline, the Cochrane Library, Google Scholar, and the ClinicalTrials.gov website. Eligible studies were clinical trials of patients with acute myocarditis who received IVIG therapy. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes.

Thirteen studies with 1534 cases were incorporated into our meta-analysis. Pooled results showed that IVIG therapy significantly reduced in-hospital mortality (OR: 0.44, 95% CI 0.17 to 0.71, P < 0.001) and improved the left ventricular ejection fraction (LVEF) (OR: 1.73, 95% CI 1.34 to 2.13, P < 0.001) in acute myocarditis patients. Furthermore, patients with acute fulminant myocarditis (AFM) exhibited a significantly higher survival rate (OR: 2.80, 95% CI 1.16 to 6.77, P = 0.022) in the IVIG group.

IVIG therapy can not only result in lower in-hospital mortality and superior recovery of left ventricular function in patients with acute myocarditis, but also increase the survival rate of AFM patients. The present study provides some supportive evidence for IVIG therapy in acute myocarditis patients.

The diffusing capacity of the lung for carbon monoxide (DLCO) is indicative of the alveolar-capillary membrane function. A reduced DLCO is associated with poor prognosis in chronic heart failure (HF). However, the significance of DLCO as an independent prognostic predictor has not been established. Here, we aimed to determine the prognostic value of DLCO in patients with chronic HF.

We enrolled 214 patients (139 females, mean age: 63 ± 16 years, left ventricular ejection fraction [LVEF]: 45 ± 21%) with stable chronic HF who underwent pulmonary function tests. Only never smokers were included in the analysis because smoking can decrease DLCO.

During a median follow-up period of 2.1 years, 52 patients (24.3%) experienced cardiac events, including unplanned HF admissions, left ventricular assist device (LVAD) implantations, all-cause deaths, and cardiopulmonary arrests (CPAs). The median percent predicted DLCO (%DLCO) was 87.3%. In a Cox regression analysis, a %DLCO of ≤87.3% was independently associated with the cardiac events, even after adjusting for age, sex, systolic blood pressure (SBP), LVEF, anemia, brain natriuretic peptide, estimated glomerular filtration rate (eGFR), and prior HF admission (hazard ratio [HR]: 1.87, 95% confidence interval: 1.03-3.53, P = 0.030).

A reduced DLCO is an independent predictor of poor prognosis in nonsmoking patients with chronic HF.

Atrial fibrillation has caused severe burden for people worldwide. Differentiation of fibroblasts into myofibroblasts, and consequent progress in atrial structural remodeling have been considered the basis for persistent atrial fibrillation, yet little is known about the molecular mechanisms underlying the process. Here, we show that cyclin-dependent kinase 1 (CDK1) is activated in atrial fibroblasts from patients with atrial fibrillation (AFPAF) and in platelet derived growth factor BB (PDGF-BB)-treated atrial fibroblasts from patients with sinus rhythm (AFPSR). We also demonstrate that inhibition of CDK1 suppresses fibroblast differentiation and focal adhesion (FA) complex formation. The FA protein paxillin is phosphorylated directly at Ser244 by CDK1. Importantly, transfection of a paxillin construct harboring a Ser to Ala mutation causes FA complex disassembly and greatly inhibits fibroblast activation. AFPSRs applied with a lentiviral vector carrying the shRNA sequence of paxillin dramatically prevents PDGF-BB induced functional activation. Taken together, all these results suggest that phosphorylation of paxillin at Ser244 by CDK1 is a key mechanism in fibroblast differentiation and could eventually assist atrial fibrosis.

The physiological control of appetite regulation involves circulating hormones with orexigenic (ghrelin) and anorexigenic (cholecystokinin) properties that induce alterations in energy intake via perceptions of hunger and satiety. We sought to investigate the relationship between appetite-regulating hormones and the cachexia associated with chronic heart failure.

We randomized male Sprague-Dawley rats into myocardial infarction (MI) or sham operation (SO) groups. The levels of brain natriuretic peptide (BNP), cholecystokinin (CCK) and ghrelin in the plasma of all rats were detected by enzyme-linked immunosorbent assay (ELISA); the expression of BNP, CCK, and ghrelin in the myocardial tissue of all rats were detected by western blotting, immunohistochemistry, real-time polymerase chain reaction (PCR); myocardial morphology was assessed by microscopy.

Plasma BNP and CCK levels in the cardiac cachexia (CC) groups and the heart failure non-cachexia (HF-nc) groups were significantly higher than those in the control groups (P < 0.01), and the expression of BNP and CCK in the myocardial tissue of rats: in CC groups and HF-nc groups were increased compared with the corresponding control groups (P < 0.01). In contrast, Plasma and cardiac expression of ghrelin decreased compared with the sham group (P < 0.01). Furthermore, plasma CCK levels were positively correlated with BNP concentrations (P < 0.001) and significantly negatively correlated with the ejection fraction (P < 0.001) in model animals; plasma ghrelin levels were negatively associated with BNP levels (P = 0.0023) and positively associated with ejection fraction (P = 0.0042).

The appetite-regulating hormones (ghrelin and CCK) may present as a potential significant biomarker for cachexia associated with chronic heart failure.

Endogenous cardiac regeneration has been focused for decades as a potential therapy for heart diseases with cell loss, and dimethyl sulfoxide (DMSO) has been proposed as a treatment for many diseases. In this study, we aimed to investigate the function of DMSO on fetal cardiomyocyte proliferation. By tracing BrdU⁺/α actinin⁺ cells or Ki67⁺/α actinin⁺ cells with immunohistochemical staining, we found that DMSO remarkably promoted fetal cardiomyocytes proliferation, and at the late developmental stage (LDS), such effects were more efficient than that at early developmental stage (EDS). Western blot data revealed a significant increase in STAT3 phosphorylation under DMSO treatments at LDS, while not at EDS. Consistently, STAT3 phosphorylation blocker STA21 could greatly reverse DMSO's function at LDS whereas hardly at EDS. Moreover, hearts at the EDS had less total STAT3 protein, but relatively much higher level of phosphorylated STAT3. This suggests that DMSO promote fetal cardiomyocytes proliferation, and STAT3 phosphorylation play a pivotal role in DMSO's function. With maturation, DMSO exerted a better ability to favor cardiomyocyte proliferation depending on STAT3 phosphorylation. Therefore, DMSO could serve as an effective, economic, and safe therapy for heart diseases with cell loss.

Flexible, in vivo maneuverable electrophysiology mapping techniques are not available in rat models. A novel cardiac stereotactic electrophysiology epicardial mapping system (CREAMS) allows for various measurements, including: (1) recording unipolar electrograms at multiple sites; (2) positioning of mapped sites and precision testing (Distance between the two "centers" = 297 ± 54 μm, n = 15); (3) evaluation of electrophysiology in an in vivo Sprague-Dawley rat model with high-frequency stimulation (HFS)-induced Atrial fibrillation (AF) at high right atrium (HRA) sites. We found that of the right atrium dispersion of effective refractory period (P < 0.05) and the window of vulnerability (P < 0.01) were significantly increased (P < 0.05) after HRA HFS. CREAMS has the potential for convenient electrophysiology assessment in a rat AF model through stereo-positioning, and flexible operating manipulation.

The effect of DPP-4 inhibitor on the electrical and structural remodeling in myocardial injury has not been evaluated. We hypothesized that linagliptin, DPP-4 inhibitor, suppresses myocardial remodeling in the isoproterenol (ISP)-induced myocardial injury model.

Sprague-Dawley rats were assigned to 3 groups: 1) sham group, 2) ISP group (subcutaneous ISP injection of 70 mg/kg), and 3) ISP + linagliptin (ISP + Lin) (5 mg/kg/day, p.o.) group. Serum was sampled on day 1 (acute phase) and day 7 (sub-acute phase) to evaluate derivatives of reactive oxidative metabolites (d-ROMs). The electrophysiological study was performed in sub-acute phase for the evaluation of the ventricular effective refractory period (VERP) and monophasic action potential duration (MAPD). The VERP and MAPD were markedly prolonged in the ISP group in comparison with the sham (MAPD20: 14 ± 6 versus 11 ± 3 ms, MAPD90: 57 ± 8 versus 44 ± 7 ms, VERP: 74 ± 22 versus 38 ± 10 ms, P < 0.05). In contrast in the ISP + Lin group, such prolongations were suppressed, and the parameters were shorter than the ISP group (MAPD20: 9 ± 2 ms, MAPD90: 35 ± 6 ms, VERP: 52 ± 13 ms, P < 0.05). ISP treatment induced myocardial injury. The injured area was reduced in the ISP + Lin group in comparison with the ISP group (P < 0.05). Serum d-ROMs level in acute phase was higher in ISP group than the other 2 groups (sham: 214 ± 55 versus ISP: 404 ± 45 versus ISP + Lin: 337 ± 20 U.CARR, P < 0.05).

Linagliptin suppressed structural and electrical changes, possibly through the antioxidative effect, in this myocardial injury model.

The role of autophagy in the cardioprotection conferred by ischemic preconditioning (IPC) has been well described. This study aimed to investigate the changes in autophagy levels during the cardioprotective effects initiated by exercise preconditioning (EP).

Rats were randomly divided into 4 groups: group C (control), group EP, group EE (exhaustive exercise), and group EP + EE (EP pretreatment at 0.5 hours before EE). The EP protocol included 4 periods of 10 minutes of treadmill running each at 30 m/minute with intervening 10 minute periods of rest. Hematoxylin-basic fuchsin-picric acid (HBFP) staining and plasma levels of cardiac troponin I (cTnI) were used to evaluate the ischemia-hypoxia injury in rat myocardium. Alteration levels in several autophagy proteins in the left ventricular myocardium were analyzed by Western blot. The phasic alterations of autophagy levels during EP-initiated cardioprotective phase were also examined.

Compared with group C, the ischemia-hypoxia positive areas and IOD value in HBFP-staining and cTnI plasma levels increased significantly in group EE. Compared with group EE, the ischemia-hypoxia injury was markedly attenuated in group EP + EE. Compared with group C, the LC3-II/LC3-I ratio, a marker of autophagosome formation, was reduced in group EE, but the LC3-II/LC3-I ratio remained unaltered in group EP + EE. Furthermore, the LC3-II/LC3-I ratio increased significantly at 2 hours during the cardioprotective phase after EP.

These results suggest that the activated autophagy level during the EP-initiated cardioprotective phase may be partly involved in the cardioprotective effects by maintaining a normal autophagy basal level during the subsequent exhaustive exercise in rat myocardium.

The pathogenesis of aortic dissection (AD) is unclear. The aim of this study was to explore the relationship between osteopontin (OPN) and AD. Fifty AD patients were enrolled; 29 had hypertension with AD (H-AD) and 21 no hypertension with HD (NH-AD). Twenty-five healthy controls (NH-C) and 14 patients with hypertension (H-C) were also enrolled. Serum and aortic wall OPN levels were determined. Human vascular muscle cells (HVSMC) were stimulated by both low (1 μg/mL) and high (5 μg/mL) concentrations of OPN and cell proliferation as well as apoptosis was measured. Transforming growth factor-β (TGF-β), matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-9, TIMP-1, and TIMP-2 gene expressions by HVSMC were measured and Akt, IκB, Smad1/5/8 and Erk1/2 signaling pathways were detected. Our results showed that AD patients demonstrated significantly higher levels of serum and local OPN expressions compared to healthy controls. In those with hypertension, the serum concentrations of OPN were increased compared to those without hypertension. In in vitro culture, a high dose of OPN stimulation promoted the proliferation of HVSMC but did not affect cell apoptosis. Both concentrations of OPN enhanced MMP-2 gene expression and its activity in HVSMC. Moreover, Akt and IκB signaling pathways were significantly activated after OPN stimulation while the Smad1/5/8 and Erk1/2 signaling pathways were not changed. The addition of an IκB inhibitor significantly abrogated MMP-2 gene expression. Our data show that OPN may participate in the pathogenesis of AD by the enhancement of MMP-2 expression.

Emodin is a natural product extracted from Rheum palmatum. There are few recent studies on emodin in the treatment of myocarditis. This study aimed to investigate the effect of emodin on lipopolysaccharide (LPS)-induced inflammatory injury in cardiomyocytes. H9c2 cells were treated with 10 μM of LPS and different concentrations (0, 1, 5, 10, 15, and 20 μM) of emodin. The expression of miR-223 was changed by transient transfection. Thereafter, cell viability, apoptosis, the expression of CyclinD1 and Jnk-associated proteins, and the release of pro-inflammatory factors were assessed by cell Counting Kit-8, flow cytometry analysis, quantitative real-time polymerase chain reaction Western blot, and enzyme-linked immunosorbent assay respectively. The results showed that 20 μM of emodin significantly decreased H9c2 cells viability. LPS significantly damaged H9c2 cells, as cell viability was reduced, CyclinD1 was down-regulated, apoptosis was induced, the release of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha were increased, and the phosphorylation of Jnk and c-Jun were promoted. Emodin protected H9c2 cells against LPS-induced inflammatory injury. miR-223 expression was significantly up-regulated by LPS exposure, while emodin lessened this up-regulation. LPS-injured H9c2 cells were attenuated by the overexpression of miR-223; emodin has protective actions on LPS-injured H9c2 cells and targets. Besides, SP600125 (an inhibitor of Jnk) eliminated miR-223-modulated inflammatory injury in H9c2 cells. These data demonstrated that emodin could attenuate LPS-induced inflammatory injury and deactivate Jnk signaling pathway through down-regulation of miR-223.

The balance between proliferation and apoptosis of vascular smooth muscle cells (VSMCs) plays a critical role in the initiation of atherosclerosis. LncRNA-MEG3 is involved in the pathophysiology of atherosclerosis through regulation of endothelial cell proliferation and migration. Its effect on the dysfunction of VSMCs and the corresponding mechanisms are actively researched. In this study, we observed that downregulated lncRNA-MEG3 expression was inversely correlated with the microRNA-26a level in coronary artery disease tissues. The overexpression of lncRNA-MEG3 could inhibit VSMCs proliferation while facilitating apoptosis. Moreover, alteration in the miR-26a/Smad1 axis could antagonize this effect. Bioinformatic analysis indicated that lncRNA-MEG3 could interact with miR-26a via complementary binding sites. The enforced expression of lncRNA-MEG3 could reduce the level of miR-26a in VSMCs, while the expression of Smad1 increases. Further, the direct binding between lncRNA-MEG3 and miR-26a was confirmed via dual-luciferase reporter assay, which indicated that lnc-MEG3 could sponge miR-26a as a competing endogenous RNA. In summary, we propose that lncRNA-MEG3 modulates the proliferation/apoptosis balance of VSMCs in atherosclerosis by regulating the miR-26a/Smad1 axis.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops as a consequence of unresolved pulmonary embolism or clots in the pulmonary arteries. The obstruction not only reduces the area of the pulmonary vascular bed, but also elicits high pressure and high shear stress in the spared unobstructed arteries. Subsequent overflow of the small pulmonary arteries induces vascular remodeling, termed as overflow vasculopathy (OV). While the development of OV significantly contributes to the occurrence of pulmonary hypertension, its precise molecular mechanisms are yet to be determined.

We established a novel murine pulmonary artery OV (PAOV) model, in which we resected left lung and induced redistribution of the cardiac output to the remaining pulmonary artery of the right lung. At 21 days after operation, mice showed an increase in the vascular media area, indicating the development of pulmonary arterial remodeling. In addition, right ventricular hypertrophy was detected in the PAOV model. Intriguingly, marked accumulation of F4/80-positive monocytes/macrophages was visualized in high-flow arteries, implying the role of an inflammatory process in the pathogenesis of overflow-induced vascular remodeling.

Delayed complete atrioventricular (AV) block associated with an occluded septal perforator branch (SPB) is an uncommon complication after performing percutaneous coronary intervention (PCI) for the left anterior descending coronary artery (LAD). Here we report the case of a 74-year-old man who underwent elective PCI for proximal LAD complicated with occlusion of the first major SPB and developed a complete AV block 78 hours after PCI was performed. The patient received a temporary transvenous pacemaker via the jugular vein and successfully underwent balloon angioplasty of the lethal "jailed" SPB, resulting in recovery from the complete AV block. Permanent pacemaker implantation was avoided. Our findings indicate the importance of postprocedural monitoring and consideration of rescue PCI for an occluded SPB in cases of complicated AV conduction disturbances.

Implantable cardioverter-defibrillators (ICDs) are an effective treatment to prevent sudden cardiac death; however, lead dysfunction is an important complication during the long-term follow-up period in ICD recipients. Careful device programming is required in accordance with the individual situation in patients with lead dysfunction. We herein present a patient in whom programming to AAI triggered palpitations during exercise.

A 28-year-old female presented with fulminant lymphocytic myocarditis. She developed cardiogenic shock, frequent sustained ventricular tachycardia, and fibrillation (VT and VF). The left ventricular ejection fraction improved from 5% to 40% after medical therapy, but the right ventricular systolic dysfunction and enlargement persisted. In addition, sustained VTs, requiring direct current cardioversion, occurred during oral administration of amiodarone following intravenous amiodarone, even after percutaneous stellate ganglion block. Standard body surface electrocardiogram (ECG) screening for an implantation of a subcutaneous implantable cardioverter-defibrillator (S-ICD) (EMBLEM™ S-ICD, Boston Scientific, Marlborough, MA, USA) demonstrated that two of the three sensing vectors were eligible in spite of very low-amplitude QRS complexes in the body surface ECGs. After implantation of the S-ICD, the patient experienced repetitive, inappropriate shocks due to pectoral myopotential oversensing, which could not be resolved by reprogramming the device settings. Thus, the S-ICD lead was changed from the standard left parasternal position to the midline of the sternum to reduce muscular noise due to myopotentials. Thereafter, the patient experienced appropriate ICD shocks for sustained VT and VF but no inappropriate ICD sensing or shocks. Lead repositioning may be one of the feasible solutions in S-ICD patients with low-amplitude QRS complexes and inappropriate shocks due to myopotential oversensing which cannot be resolved by reprogramming the device settings.

A 41-year-old man developed cardiac arrest. A resting 12-lead electrocardiogram showed a delta wave, suggestive of preexcitation syndrome. An electrophysiological test revealed the existence of inducible atrial fibrillation and a fasciculoventricular accessory pathway (FVAP). After these examinations, idiopathic ventricular arrhythmia was suspected. For evaluating concealed Brugada syndrome, pilsicainide was administered, which diminished the delta wave and no Brugada-like electrocardiogram was observed. Ventricular double extra-stimulation from the RV apex easily induced VF, which could not be defibrillated by an external defibrillator, and later stopped spontaneously. These results established the diagnosis of FVAP and idiopathic VF, and not pre-excited atrial fibrillation or Brugada syndrome.

Simultaneous left and right-sided native valve infective endocarditis (IE) is rare. Staphylococcus aureus was the predominant organism for bilateral IE. Shunt diseases are common risk factors of both-sided IE. Streptococcus anginosus (S. anginosus) is usually associated with pyogenic infections, but rarely a cause of IE. Here we present an extremely rare case of simultaneous left and right-sided native valve IE affecting the mitral and tricuspid valves caused by S. anginosus in an adult patient that has not been reported in the literature previously, particularly without the most frequent predisposing factors of IE. A 66-year-old man was admitted due to generalized fatigue, chills, malaise, and intermittent fevers for 1 year. A grade III-IV/VI systolic murmur at the mitral area and a III/VI systolic murmur at the tricuspid area were noted on physical examination. Laboratory evaluation revealed an elevated erythrocyte sedimentation rate and C-reactive protein level, and high fasting blood glucose. Blood culture was positive for S. anginosus. Echocardiography revealed vegetations in both sides of the heart: a large mitral valve vegetation with severe mitral regurgitation, as well as another vegetation on the tricuspid valve with moderate regurgitation. The case highlights a rare pathogen of both-sided IE, a rare presentation of S. anginosus infection, and several points worthy of note in echocardiography of IE.

This case report demonstrates a pair of monozygotic twins with hypertrophic cardiomyopathy (HCM) carrying the same pathogenic mutation of MYH7 (p.G768R; c.2302G>A), detected by whole exome and Sanger genetic sequencing methods. On multi-modality imaging, they were reported to have similar, but not identical, morphologic expression. Particularly, the clinical presentation and tissue characteristics were not the same. Late gadolinium enhancement (LGE) and T1 mapping of cardiac magnetic resonance showed different extents of myocardial fibrotic characteristics in the twins (twin A: 16.3% LGE and 32.6% extracellular volume [ECV] of the whole left ventricle; twin B: 5.4% LGE and 28.1% ECV of the whole left ventricle). This extraordinary case of HCM provides evidence on the complex pathophysiological mechanisms of HCM and suggests the likely impact of epigenetics and environmental factors on HCM phenotype.

Unicuspid aortic valve (UAV) is an extremely rare form of congenital cardiac malformation, leading to aortic stenosis (AS), aortic regurgitation (AR), or both. We report the case of a 55-year-old man with unicommissural UAV associated with severe AS and mild AR using different multimodality imaging approaches. The excised UAV isolated after aortic valve replacement exhibited an eccentric "teardrop" opening with a slit-shaped unicommissural structure. Raman spectroscopic results indicated that 3 unevenly distributed components were deposited on the surface of the UAV, in which calcium hydroxyapatite and type-B carbonate apatite were the predominate components deposited on the surface, leading to severe AS formation.

The patient was a 101-year-old woman whose chief complaints were difficulty of breathing and high fever. The history of the present illness included paroxysmal atrial flutter which was untreated, but she had not developed heart failure.

At admission, auscultation of the chest revealed moist rales and systolic murmur but did not clearly show the presence of fixed splitting of S2. X-ray examination of the chest showed a cardiothoracic ratio of 61%, moderate bilateral pulmonary congestion, pleural fluid, and enlarged pulmonary arteries. Electrocardiogram showed atrial flutter with a heart rate of approximately 150 beats/minute. Echocardiographic examination revealed an atrial septal defect (ASD) of the ostium secundum type (left to right shunt) and right ventricular pressure 71 mmHg. The diameter of the ASD was approximately 10 mm.

She began receiving an antibiotic and a diuretic immediately after admission, but died on the second day of hospitalization.

This case could be the oldest individual with ASD among those reported to date.