The neutrophil percentage-to-albumin ratio is associated with all-cause mortality in patients with chronic heart failure.

BACKGROUND: In this study, we evaluated the predictive utility of neutrophil percentage-to-albumin ratio (NPAR) for all-cause mortality in patients with chronic heart failure (CHF). METHODS: Patients diagnosed as CHF enrolled in this retrospective cohort study were from Beijing Chaoyang Hospital, capital medical university. Admission NPAR was calculated as neutrophil percentage divided by serum albumin. The endpoints of this study were defined as 90-day, 1-year and 2-year all-cause mortality. Multivariable Cox proportional hazard regression model was performed to confirm the association between NPAR and all-cause mortality. Receiver operating characteristics (ROC) curves were used to evaluate the ability for NPAR to predict all-cause mortality. RESULTS: The 90-day (P = 0.009), 1-year (P < 0.001) and 2-year (P < 0.001) all-cause mortality in 622 patients with CHF were increased as admission NPAR increased. Multivariable Cox regression analysis found the higher NPAR value was still independently associated with increased risk of 90-day (Group III versus Group I: HR, 95% CI: 2.21, 1.01-4.86, P trend = 0.038), 1-year (Group III versus Group I: HR, 95% CI:2.13, 1.30-3.49, P trend = 0.003), and 2-year all-cause mortality (Group III versus Group I: HR, 95% CI:2.06, 1.37-3.09, P trend = 0.001), after adjustments for several confounders. ROC curves revealed that NPAR had a better ability to predict all-cause mortality in patients with CHF, than either albumin or the neutrophil percentage alone. CONCLUSIONS: NPAR was independently correlated with 90-day, 1-year, and 2-year all-cause mortality in patients with CHF.

Influence of baseline arterial stiffness on effects of intensive compared with standard blood pressure control: a post hoc analysis of the STEP trial.

BACKGROUND: The benefits and risks of intensive versus standard systolic blood pressure (SBP) treatment in older patients with arterial stiffness (AS) remains unclear. This study aims to investigate the interaction between the baseline AS and SBP treatments on cardiovascular outcomes. METHODS: In this post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, we involved 6865 participants with complete data regarding baseline brachial-ankle pulse wave velocity (baPWV). Patients were categorized by baseline AS status (AS, baPWV ≥ 1800 cm/s; non-AS, baPWV < 1800 cm/s). The primary outcome was a composite of cardiovascular events. The secondary outcomes were stroke, acute coronary syndrome (ACS), major cardiovascular events (MACE), and all-cause death. Cox regression was used to calculate hazard ratios for the outcomes. RESULTS: During a mean follow-up of 2.69 years, a total of 248 primary outcome events and 81 all-cause deaths occurred. The hazard ratios for the primary outcome were 0.76 (95% confidence interval (CI), 0.54-1.09) and 0.63 (95% CI, 0.43-0.92) in the AS and non-AS groups, respectively (P for interaction = 0.43), and that for stroke was 0.58 (95% CI, 0.33-1.02) and 0.48 (95% CI, 0.23-0.99) in the AS and non-AS groups, respectively (P for interaction = 0.68). Effects of intensive SBP treatment on safety outcomes and all-cause death were also similar in the two groups (P for interaction > 0.05 for all). CONCLUSIONS: In the STEP trial, the beneficial effects of intensive SBP treatment were similar among those in the AS group and the non-AS group at baseline. TRIAL REGISTRATION: STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

The common characteristics and mutual effects of heart failure and atrial fibrillation: initiation, progression, and outcome of the two aging-related heart diseases.

Atrial fibrillation (AF) and heart failure (HF) are common chronic diseases noted in humans. AF and HF share several risk factors, such as age, hypertension, obesity, diabetes, and dyslipidemia. They can interact with each other, while both their morbidity and mortality have been considerably increased. And AF and HF often occur together, suggesting a strong association between the two. However, the underlying mechanism behind this association is not well understood. Among them, aging is the most significant common risk factor, which represents an aging heart and is characterized by fibrosis and decreased number of cardiomyocytes, known as senescence-related cardiac remodeling for both atria and ventricles. Finally, it is proposed that cardiac remodeling is the key link between AF and HF.

First post-discharge heart rate and long-term prognosis in patients with acute myocardial infarction.

BACKGROUND: Elevated heart rate (HR) is associated with cardiovascular mortality and other events associated with acute myocardial infarction (AMI). The heart rate after discharge is likely superior to reflect the deteriorating heart function, which negatively responds to normal physical activity. This study aimed to explore the effect of HR at the first outpatient visit on clinical outcomes. METHODS: We retrospectively identified 605 patients with AMI. HRs at admission, discharge, and first outpatient visits were measured. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including cardiovascular (CV) death, readmission for worsening heart failure, recurrent nonfatal myocardial infarction (MI), repeated coronary revascularization, and ischemic stroke. RESULTS: During the follow-up period, 145 cases of MACE occurred, including 34 CV deaths, 31 recurrent MI, 89 revascularizations, 41 heart failures, and 4 strokes. The event group displayed an elevated HR at the first outpatient visit compared to the event-free group (p < 0.001). After adjustment for confounding risk factors, Cox models showed that the outpatient HR had the best correlation with MACE [Hazard ratio (HR) = 1.33, 95% confidence interval (CI) = 10.8-59.3, p < 0.01 for increments of 1 standard deviation (SD) in the outpatient HR) and CV mortality (HR = 1.18, 95% CI = 1.052-1.325, p < 0.01) compared with the other two HRs. The restricted spline model indicated that HR at the first post-discharge above 71 bpm was associated with CV mortality. CONCLUSIONS: Elevated HR at the first outpatient visit over a period of 2-4 weeks is related to the adverse outcomes of AMI and may identify AMI patients at higher risk of CV mortality.

Fibroblast activation protein imaging in reperfused ST-elevation myocardial infarction: comparison with cardiac magnetic resonance imaging.

PURPOSE: The aim of this study was to explore the correlation of 18F-labeled fibroblast activation protein inhibitor (FAPI) and cardiovascular magnetic resonance (CMR) parameters in ST-elevation myocardial infarction (STEMI) patients with successful primary percutaneous coronary intervention (PPCI) and to investigate the value of FAPI imaging in predicting cardiac functional recovery, as well as the correlation between FAPI activity and circulating fibroblast activation protein (FAP) and inflammatory biomarkers. METHODS: Fourteen first-time STEMI patients (11 men, mean age: 62 ± 11 years) after PPCI and 14 gender-matched healthy volunteers (10 men, mean age: 50 ± 14 years) who had completed FAPI imaging and blood sample collection were prospectively recruited. All patients underwent baseline FAPI imaging (6 ± 2 days post-MI) and CMR (8 ± 2 days post-MI). Ten patients had follow-up CMR (84 ± 4 days post-MI). Myocardial FAPI activity was analyzed for extent (the percentage of FAPI uptake volume over the left ventricular volume, FAPI%), intensity (target-to-background uptake ratio, TBRmax), and amount (FAPI% × TBRmax). Late gadolinium enhancement (LGE), T2-weighted imaging (T2WI), extracellular volume (ECV), microvascular obstruction (MVO), and cardiac function from CMR imaging were analyzed. Blood samples obtained on the day of FAPI imaging were used to assess circulating FAP, TGF-ß1, TNF-α, IL-6, and hsCRP in STEMI patients and controls. RESULTS: Localized but inhomogeneous FAPI uptake was observed in STEMI patients, which was larger than the edematous and infarcted myocardium, whereas no uptake was detected in controls. The MVO area showed lower FAPI uptake compared with the surrounding myocardium. FAPI activity was associated with the myocardial injury biomarkers T2WI, LGE, and ECV at both per-patient and per-segment levels (all p < 0.05), but was not associated with circulating FAP, TGF-ß1, TNF-α, IL-6, or hsCRP. Among the CMR parameters, T2WI had the greatest correlation coefficient with both FAPI% and FAPI% × TBRmax. Baseline TBRmax was inversely correlated with the follow-up left ventricular ejection fraction (LVEF) (r = - 0.73, p = 0.02). CONCLUSION: FAPI imaging detects more involved myocardium than CMR in reperfused STEMI, and is associated with myocardial damage and follow-up LVEF.

Prediction of SYNTAX score II improvement by adding temporal heart rate changes between discharge and first outpatient visit in patients with acute myocardial infarction.

BACKGROUND: The prognostic ability of the temporal changes in resting heart rate (ΔHR) in patients with acute myocardial infarction (AMI) for cardiovascular (CV) mortality and clinical outcomes is rarely examined. This study investigated the predictive value of ΔHR using models with SYNTAX score II (SxS-II) for the long-term prognosis of patients with AMI. METHODS: Six hundred five AMI patients with vital signs recorded at the first outpatient visit (2-4 weeks after discharge) were retrospectively recruited into this study. The changes between discharge and outpatient resting heart rate (D-O ΔHR) were calculated by subtracting the HR at the first post-discharge visit from the value recorded at discharge. The major adverse cardiovascular and cerebrovascular events (MACCE) include cardiovascular death, recurrent myocardial infarction, revascularization, and nonfatal stroke. The predictive values and reclassification ability of the different models were assessed using a likelihood ratio test, Akaike's information criteria (AIC), receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: During the follow-up period, a drop-in resting heart rate (RHR) from discharge to first outpatient visit was independently associated with less risk of CV mortality [D-O ΔHR: hazards ratio (HR) = 0.97, 95% CI = 0.96-0.99, P < 0.001] and MACCE (HR = 0.98, 95% CI = 0.97-0.99, p = 0.001). The likelihood test indicated that the combined model of SxS-II and D-O ΔHR yielded the lowest AIC for CV mortality and MACCE (P < 0.001). Moreover, D-O ΔHR alone significantly improved the net reclassification and integrated discrimination of the models containing SxS-II for CV mortality and MACCE (CV mortality: NRI = 0.5600, P = 0.001 and IDI = 0.0759, P = 0.03; MACCE: NRI = 0.2231, P < 0.05 and IDI = 0.0107, P < 0.05). CONCLUSIONS: The change in D-O ΔHR was an independent predictor of long-term CV mortality and MACCE. The D-O ΔHR combined with SxS-II could significantly improve its predictive probability.

Circulating plasma galectin-3 predicts new-onset atrial fibrillation in patients after acute myocardial infarction during hospitalization.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear. OBJECTIVE: The present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF. METHODS: A total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured. RESULTS: Post-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p < 0.001) than those without. A higher level of the peak brain natriuretic peptide (BNP) (p < 0.001) and Gal-3 (p < 0.001) and a lower low-density lipoprotein cholesterol level (LDL-C) (p = 0.030), and an estimated glomerular filtration rate (e-GFR) (p = 0.030) were recorded in patients with post-AMI NOAF. Echocardiographic information revealed that patients with NOAF had a significantly decreased left ventricular eject fraction (LVEF) (p < 0.001) and an increased left atrial diameter (LAD) (p = 0.004) than those without NOAF. The receiver operating characteristic (ROC) curve analysis revealed a significantly higher value of plasma Gal-3 in the diagnosis of NOAF for patients with AMI during hospitalization (area under the curve (p < 0.001), with a sensitivity of 72.22% and a specificity of 72.22%, respectively. Multivariate logistic regression model analysis indicated that age (p = 0.045), plasma Gal-3 (p = 0.018), and LAD (p = 0.014) were independent predictors of post-MI NOAF. CONCLUSIONS: Plasma Gal-3 concentration is an independent predictor of post-MI NOAF.

The association between visceral adiposity index and leukocyte telomere length in adults: results from National Health and Nutrition Examination Survey.

BACKGROUND: Leukocyte telomere length (LTL) is a robust marker of biological aging, which is associated with obesity. Recently, the visceral adiposity index (VAI) has been proposed as an indicator of adipose distribution and function. OBJECTIVE: To evaluated the association between VAI and LTL in adult Americans. METHODS: There were 3193 participants in U.S. National Health and Nutrition Examination Surveys (1999-2002) included in this analysis. LTL was measured using quantitative PCR (qPCR) and expressed as telomere to single-gene copy ratio (T/S ratio). We performed multiple logistic regression models to explore the association between VAI and LTL by adjusting for potential confounders. RESULTS: Among all participants, VAI was associated with the shorter LTL (ß: - 14.81, 95% CI - 22.28 to - 7.34, p < 0.001). There were significant differences of LTL in VAI tertiles (p < 0.001). Participants in the higher VAI tertile had the shorter LTL (1.26 ≤ VAI < 2.46: ß = - 130.16, 95% CI [ - 183.44, - 76.87]; VAI ≥ 2.46: ß = - 216.12, 95% CI [ - 216.12, - 81.42], p for trend: < 0.001) comparing with the lower VAI tertile. We also found a non-linear relationship between VAI and LTL. VAI was negatively correlated with LTL when VAI was less than 2.84. CONCLUSIONS: The present study demonstrates that VAI is independently associated with telomere length. A higher VAI is associated with shorter LTL. The results suggest that VAI may provide prediction for LTL and account for accelerating the biological aging.

Predictive value of CHA2DS2-VASc score combined with hs-CRP for new-onset atrial fibrillation in elderly patients with acute myocardial infarction.

BACKGROUND: New-onset atrial fibrillation (NOAF) is common during acute myocardial infarction (AMI) and independently associated with worse prognosis. We aimed to validate the discrimination performance of CHA2DS2-VASc score combined with hs-CRP in the prediction of NOAF after AMI in elderly Chinese population. METHODS: 311 consecutive elderly patients (age ≥ 65 years old) with AMI from 1 January 2018 to 1 January 2019 without atrial fibrillation history were enrolled in our study. Univariable and multivariable logistic regression analyses were used to identify risk factors of NOAF. The discrimination performance of different score models were evaluated using ROC curve analysis and AUCs were compared using the Z test. RESULTS: 30 (9.65%) patients developed NOAF during hospitalization. The NOAF group were older and had higher hs-CRP, initial Killip class, BNP, LAD, CHADS2 score, CHA2DS2-VASc score, in-hospital mortality and lower LVEF and ACEI/ARB use (P < 0.05 vs group without NOAF for all measures). In multivariate regression analyses, age (OR = 1.127, 95% CI 1.063-1.196, P < 0.001) and hs-CRP (OR = 1.034, 95% CI 1.018-1.05, P < 0.001) were independent predictors of NOAF. In ROC curve analyses, both CHADS2 score (AUC = 0.624, 95% CI 0.516-0.733, P = 0.026) and CHA2DS2-VASc score (AUC = 0.687, 95% CI 0.584-0.79, P = 0.001) had acceptable but unsatisfactory discrimination performance in predicting NOAF after AMI. The combined model with CHA2DS2-VASc score and hs-CRP showed a significant better predictive value (AUC = 0.791, 95% CI 0.692-0.891, P < 0.001) compared to that of the CHA2DS2-VASc score alone (Z test, P = 0.008). CONCLUSION: The combined model with CHA2DS2-VASc score and hs-CRP had high accuracy in predicting post-AMI NOAF.

The potential regulatory role of hsa_circ_0004104 in the persistency of atrial fibrillation by promoting cardiac fibrosis via TGF-ß pathway.

INTRODUCTION: The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. MATERIALS AND METHODS: 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-ß, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. RESULTS: PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-ß1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-ß1 level (r = - 0.797, p < 0.001). CONCLUSION: CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.

Association of atrial arrhythmias with thrombospondin-1 in patients with acute myocardial infarction.

OBJECTIVES: Atrial remodeling is the main developmental cause of atrial arrhythmias (AA), which may induce atrial fibrillation, atrial flutter, atrial tachycardia, and frequent premature atrial beats in acute myocardial infarction (AMI) patients. Thrombospondin-1 (TSP-1) has been shown to play an important role in inflammatory and fibrotic processes, but its role in atrial arrhythmias is not well described. The purpose of this study was to investigate the role of TSP-1 in AMI patients with atrial arrhythmias. METHODS: A total of 219 patients with AMI who underwent percutaneous coronary intervention and with no previous arrhythmias were included. TSP-1 were analyzed in plasma samples. Patients were classified into 2 groups, namely, with and without AA during the acute phase of MI. Continuous electrocardiographic monitoring was used for AA diagnosis in hospital. RESULTS: Twenty-four patients developed AA. Patients with AA had higher TSP-1 levels (29.01 ± 25.87 µg/mL vs 18.36 ± 10.89 µg/mL, p < 0.001) than those without AA. AA patients also tended to be elderly (65.25 ± 9.98 years vs 57.47 ± 10.78 years, p < 0.001), had higher Hs-CRP (39.74 ± 43.50 mg/L vs 12.22 ± 19.25 mg/L, p < 0.001) and worse heart function. TSP-1 (OR 1.033; 95% CI 1.003-1.065, p = 0.034), Hs-CRP (OR 1.023; 95% CI 1.006-1.041, p = 0.008), age (OR 1.067; 95% CI 1.004-1.135, p = 0.038) and LVDd (OR 1.142; 95% CI 1.018-1.282, p = 0.024) emerged as independent risk factors for AA in AMI patients. CONCLUSION: TSP-1 is a potential novel indicator of atrial arrhythmias during AMI.

Plasma Galectin-3 is associated with progression from paroxysmal to persistent atrial fibrillation.

BACKGROUND: Galectin-3 (Gal-3) is currently recognized as a promising biomarker for myocardial fibrosis. This study aimed to explore the potential association between plasma Gal-3 concentrations and atrial fibrillation (AF) progression in paroxysmal AF (PAF) patients METHODS: A total of 213 PAF patients were included for analysis in this study. All peripheral blood samples were prospectively collected and stored at -80℃ for subsequent Gal-3 quantification. The AF progression was defined as transformation from PAF to persistent AF (PsAF). RESULTS: A total of 51 PAF patients progressed to PsAF during a mean follow-up period of 674.44 ± 19.48 days. Patients with AF progression had significantly higher baseline plasma Gal-3 concentrations than those stayed in PAF status (13.52 ± 0.94 vs. 7.93 ± 0.37, p < 0.001). All PAF patients were divided into two subgroups based on the median value of plasma Gal-3 concentrations. Kaplan-Meier curve analysis showed a significantly higher AF progression rate in the higher plasma Gal-3 concentration group (log-rank test p < 0.001). In the Cox regression analysis, plasma Gal-3 concentration and left atrial diameter (LAD) were showed significantly associated with AF progression, even after adjustment of other potential confounding risk factors. Discrimination for AF progression with a simple model which consists of plasma Gal-3 concentration and LAD was modest with a C-statistic 0.72 (95%CI 0.64-0.80). Plasma Gal-3 concentration significantly improved the predictability by appropriately reclassifying several patients with progression (NRI = 28.3%, p = 0.003). CONCLUSION: Elevated plasma Gal-3 concentration is significantly associated with AF progression from PAF to PsAF. Plasma Gal-3 concentration could be used for PAF progression risk stratification and guiding management for PAF patients.

The long-term impact of a chronic total occlusion in a non-infarct-related artery on acute ST-segment elevation myocardial infarction after primary coronary intervention.

OBJECTIVES: To investigate the long-term outcome of patients with acute ST-segment elevation myocardial infarction (STEMI) and a chronic total occlusion (CTO) in a non-infarct-related artery (IRA) and the risk factors for mortality. METHODS: The enrolled cohort comprised 323 patients with STEMI and multivessel diseases (MVD) that received a primary percutaneous coronary intervention between January 2008 and November 2013. The patients were divided into two groups: the CTO group (n = 97) and the non-CTO group (n = 236). The long-term major adverse cardiovascular and cerebrovascular events (MACCE) experienced by each group were compared. RESULTS: The rates of all-cause mortality and MACCE were significantly higher in the CTO group than they were in the non-CTO group. Cox regression analysis showed that an age ≥ 65 years (OR = 3.94, 95% CI: 1.47-10.56, P = 0.01), a CTO in a non-IRA(OR = 5.09, 95% CI: 1.79 ~ 14.54, P < 0.01), an in-hospital Killip class ≥ 3 (OR = 4.32, 95% CI: 1.71 ~ 10.95, P < 0.01), and the presence of renal insufficiency (OR = 5.32, 95% CI: 1.49 ~ 19.01, P = 0.01), stress ulcer with gastraintestinal bleeding (SUB) (OR = 6.36, 95% CI: (1.45 ~ 28.01, P = 0.01) were significantly related the 10-year mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 (OR = 2.97,95% CI:1.46 ~ 6.03, P < 0.01) and the presence of renal insufficiency (OR = 5.61, 95% CI: 1.19 ~ 26.39, P = 0.03) were significantly related to the 10-year mortality of patients with STEMI and a CTO. CONCLUSIONS: The presence of a CTO in a non-IRA, an age ≥ 65 years, an in-hospital Killip class ≥ 3, and the presence of renal insufficiency, and SUB were independent risk predictors for the long-term mortality of patients with STEMI and MVD; an in-hospital Killip class ≥ 3 and renal insufficiency were independent risk predictors for the long-term mortality of patients with STEMI and a CTO.

ß1-Adrenoceptor antibodies induce PPCM via inhibition of PGC-1α related pathway.

OBJECTIVES: Peripartum cardiomyopathy (PPCM) is a pregnancy-associated and life-threatening cardiac disease. However, the causes and pathogenesis are not fully understood. Accumulating studies show that cardiomyopathy often appears to be associated with elevated levels of ß1-adrenoceptor (ß1AR) antibodies, indicating a possible involvement of ß1AR antibodies in the development of PPCM. DESIGN: We injected the antigen peptide segment of the ß1AR into the postpartum Wistar rats to make the immune models and their cardiac function was detected by echocardiography. Also, the concentration of ß1AR antibodies and apoptosis rate of left ventricular myocytes was tested by SA-ELISA, TUNEL, HE staining, qRT-PCR and western blot methods. Finally, the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and its related proteins were examined by qRT-PCR and western blot methods. RESULTS: We found that the level of ß1AR antibodies in the serum was significantly increased and the postpartum rats exhibited symptoms of PPCM after autoimmunity. Moreover, the expression of peroxisome PGC-1α, which was a master regulator of mitochondrial metabolism, and its downstream transcript vascular endothelial growth factor (VEGF), was decreased in autoimmune perinatal rats. In addition, the expression of the apoptosis factor caspase 3 as well as the apoptosis rate of left ventricular myocytes was significantly increased. CONCLUSIONS: The results suggested that the symptoms of PPCM that appeared in autoimmune perinatal rats may be due to the increase of ß1AR antibodies, which inhibited the pathway associated with peroxisome PGC-1α.

Comparison of Safety between Different Kinds of Heparins in Patients Receiving Intra-Aortic Balloon Counterpulsation.

BACKGROUND: The present study aimed to compare the effectiveness and safety of low molecular-weight-heparin (LMWH) and unfractionated heparin (UFH) in acute myocardial infarction (AMI) patients receiving intra-aortic balloon counterpulsation (IABP). MATERIALS AND METHODS: We retrospectively analyzed a total of 344 patients receiving IABP for cardiogenic shock, severe heart failure, ventricular septal rupture, or mitral valve prolapse due to AMI. A total of 161 patients received UFH (a bolus injection 70 U/kg immediately after IABP, followed by infusion at a rate of 15 U/kg/hour and titration to for 50 to 70 seconds of activated partial thromboplastin time. A total of 183 patients received LMWH (subcutaneous injection of 1.0 mg/kg every 12 hours for 5 to 7 days and 1.0 mg/kg every 24 hours thereafter). Events of ischemia, arterial thrombosis or embolism, and bleeding during IABP were evaluated. Major bleeding was defined as a hemoglobin decrease by >50 g/L (vs. prior to IABP) or bleeding that caused hemodynamic shock or life-threatening or requiring blood transfusion. RESULTS: Subjects receiving UFH and LMWH did not differ in baseline characteristics. Ischemia was noted in five (3.1%) and two (1.1%) subjects in UFH and LMWH groups, respectively. Arterial thromboembolism occurred in three (1.9%) subjects in the UFH group, but not in the LMWH group. Logistic regression analysis failed to reveal an association between ischemia or bleeding with heparin type. Major bleeding occurred in 16 (9.9%) and six (3.3%) patients in the UFH and LWMH groups, respectively (p = 0.014). Regression analysis indicated that LMWH is associated with less major bleeding. CONCLUSION: LMWH could reduce the risk of major bleeding in patients receiving IABP. Whether LMWH could reduce arterial thromboembolism needs further investigation.

Proteomics of epicardial adipose tissue in patients with heart failure.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot closely linked to the pathogenesis of heart failure (HF). But the molecular signatures related to the mechanism of HF have not been systematically explored. Here, we present comprehensive proteomic analysis of EAT in HF patients and non-HF patients as controls. A total of 771 proteins were identified in liquid chromatography-tandem mass spectrometry experiments. Amongst them, 17 increased in abundance in HF and seven decreased. They were involved in HF-related processes including inflammation and oxidative stress response and lipid metabolism. Of these proteins, serine proteinase inhibitor A3 (Serpina3) levels in EAT were highly up-regulated in HF, with HF/non-HF ratio of 4.63 (P = .0047). Gene expression of Serpina3 via quantitative polymerase chain reaction was significantly increased in the HF group. ELISA analysis confirmed a significant increase in circulating plasma Serpina3 levels in the HF group (P = .004). In summary, for the first time, we describe that parts of EAT proteome may be reactive and work as modulators of HF. Our profiling provides a comprehensive basis for linking EAT with pathogenesis of HF. Understanding the role of EAT may offer new insights into the treatment of HF.

Myofibroblast-Derived Exosomes Contribute to Development of a Susceptible Substrate for Atrial Fibrillation.

OBJECTIVE: Atrial fibrosis plays a critical role in atrial fibrillation (AF). A key event in the pathogenesis of fibrosis is the activation of fibroblasts (FBs) into myofibroblasts (MFBs). Paracrine factors released from MFBs lead to ion channel expression changes in cardiomyocytes (CMs). Downregulation of L-type calcium channel Cav1.2 expression is a hallmark of AF-associated ionic remodeling. However, whether exosome (Exo)-mediated crosstalk between MFBs and CMs regulates Cav1.2 expression remains unknown. METHODS: Atrial FBs and CMs were isolated and cultured from neonatal rats by enzymatic digestion. The activation of FBs into MFBs was induced by angiotensin II. Co-culture assay and in vitro Exo treatment were used to determine the effect of MFB-derived Exos on Cav1.2 expression. Confocal Ca2+ imaging was performed to examine the adrenergic stimulation-elicited Ca2+ influx signals. The levels of potential Cav1.2-inhibitory microRNAs (miRNAs) were measured by qRT-PCR. RESULTS: Untreated FBs expressed limited amounts of alpha smooth muscle actin (α-SMA), while angiotensin II induced a significant upregulation of α-SMA-expressing MFBs. Co-cultures of MFBs and CMs resulted in downregulation of Cav1.2 expression in CMs, which was largely abolished by pretreatment of MFBs with exosomal inhibitor GW4869. More importantly, treatment with MFB-derived Exos caused repression of Cav1.2 expression in CMs. Additionally, the adrenergic receptor agonist-elicited Ca2+ influx signals in CMs were remarkably attenuated by pretreatment with MFB-derived Exos, corresponding to the paralleled change in Cav1.2 expression. Finally, miR-21-3p, a potential Cav1.2-inhibitory miRNA, was enriched in MFB-derived Exos and upregulated in CMs in response to MFB-derived Exos. CONCLUSION: We uncover an Exo-mediated crosstalk between MFBs and CMs, contributing to increased vulnerability to AF by reducing the expression of Cav1.2 in CMs.

ß1 adrenoceptor antibodies induce myocardial apoptosis via inhibiting PGC-1α-related pathway.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is life-threatening heart disease. However, the causes and pathogenesis of PPCM remain unclear. Previous studies found that ß1 adrenoceptor antibodies (ß1AA) had possible involvement in the development of PPCM. In the present study, we determined the potential relationship between PPCM and ß1AA, including the mechanism of ß1AA leading to PPCM. METHODS: We extracted the ß1AA from the postpartum Wistar rats that were injected by the antigen peptide segment of the ß1 adrenoceptor to produce PPCM. We tested the effects of ß1AA on H9C2 cell line by CCK-8, LDH, TUNEL, SA-ELISA, qRT-PCR, and western blot methods. Furthermore, PGC-1α was overexpressed to rescue the effect of ß1AA on H9C2 cells. RESULTS: We found that the extracted ß1AA induced apoptosis of cardiac myocytes of H9C2 cell line. Moreover, the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is a master regulator of mitochondrial metabolism, and its downstream transcript vascular endothelial growth factor (VEGF) got decreased in H9C2 cells after ß1AA treatment. In addition, the effect of ß1AA could be inhibited by atenolol, the antagonist of ß1 adrenoceptors (ß1AR) and imitated by isoprenaline, the agonist of ß1AR. Furthermore, overexpression of PGC-1α in the H9C2 cells rescued the apoptosis of cells and inhibitory expression of VEGF induced by ß1AA. CONCLUSIONS: Our results suggest that the symptoms of PPCM due to myocardial cell apoptosis induced by ß1AA inhibiting the PGC-1α-related pathway impairs mitochondrial energy metabolism. Therefore, our results uncover a previously unknown role of the ß1AA pathway in the etiology of PPCM and provide a novel potential target for the treatment of PPCM.

Blood group A: a risk factor for heart rupture after acute myocardial infarction.

INTRODUCTION: Studies have been performed to identify the association between ABO blood groups and coronary artery disease. However, data is scarce about the impact of ABO blood groups on heart rupture (HR) after acute myocardial infarction (AMI). METHODS: We conducted a retrospective case-control study that included 61 consecutive patients with HR after AMI during a period from 1 January 2012 to 1 December 2019. The controls included 600 patients who were selected randomly from 8143 AMI patients without HR in a ratio of 1:10. Univariate and multivariate logistic regression analysis were used to identify the association between ABO blood groups and HR. RESULTS: Patients with blood group A had a greater risk of HR after AMI than those with non-A blood groups (12.35% vs 7.42%, P < 0.001). After adjusting for age, gender, heart rate at admission, body mass index (BMI), and systolic blood pressure (SBP), blood group A was independently related to the increased risk of HR after AMI (OR = 2.781, 95% CI 1.174-7.198, P = 0.035), and remained as an independent risk factor of HR after AMI in different multivariate regression models. CONCLUSION: Blood group A is significantly associated with increased HR risk after AMI.

Study on the relationship between telomere length changes and recurrence of atrial fibrillation after radiofrequency catheter ablation.

INTRODUCTION: Advanced age is the foremost risk factor for atrial fibrillation (AF). Telomere length is a surrogate for biological aging, but the association between shortened leukocyte telomere length (LTL) and recurrence of AF (RAF) after ablation remains inconclusive. METHODS: In this prospective analysis, 282 patients underwent an initial catheter ablation for paroxysmal or persistent AF. The association between RAF and LTL was analyzed by univariate and multivariate Cox regression, as well as time-dependent receiver operating characteristic (ROC) analysis and Kaplan-Meier analysis. RESULTS: After a mean follow-up of 14.20 ± 5.04 months, RAF was documented in 78 of the 277 patients who completed the study (28.16%). In Cox proportional hazards models, LTL, age, diagnosis to ablation time (DTAT), N-terminal pronatriuretic peptide, and CHA2DS2-VASc score were significantly associated with RAF. After multivariable adjustment, LTL and DTAT were predicted as independent risk factors for RAF with hazard ratio (HR) of 3.17 (95% confidence interval [CI]: 1.23-8.15, P = 0.017) and 1.43 (95% CI: 1.10-1.86, P = 0.007), respectively. In addition, ROC analysis indicated the potential diagnostic value of LTL with an area under the curve of 0.64 (P < 0.001; sensitivity = 60.3%, specificity = 57.8%), and an optimum cut-off value of 1.040. LTL less than or equal to 1.040 was defined as shortened LTL, while LTL greater than 1.040 nonshortened LTL. Kaplan-Meier analysis showed RAF rate curve was separated significantly between two groups (21.2% vs 35.9%, log-rank test result P = 0.007). Patients with shortened LTL might have a higher risk for RAF with HR = 1.84 (P = 0.008). CONCLUSIONS: Shortened LTL is an independent risk factor for AF recurrence. Shortened LTL could be a potential biomarker in predicting RAF after ablation.