Risk Factors and Heart Rate Variability Associated with Left Ventricular Enlargement in Patients with Frequent Premature Ventricular Contractions.

INTRODUCTION: Premature ventricular contractions (PVCs) were now well recognized to carry the risk of inducing left ventricular (LV) enlargement and were closely related to the cardiac autonomic nervous activity quantified by heart rate variability (HRV) analysis. However, the relationship between LV enlargement and HRV in patients with frequent PVCs is still unclear. This study aimed to investigate the risk factors and HRV for LV enlargement in patients with frequent PVCs. METHODS: Patients with frequent PVCs (n = 571), whose PVC burden counts >10,000/24 h or PVC burden >10%, were recruited. Patients were divided into LV enlargement group (n = 161), defined as female left ventricular end-diastolic diameter (LVEDD) >49.8 mm or male LVEDD >54.2 mm, and LV normal group (n = 410). Two groups were compared on their clinical, electrocardiographic, and HRV parameters. Logistic regression analysis was used to predict the risk factors of LV enlargement in patients with frequent PVCs. The parameters of echocardiography, Holter monitoring, and HRV were collected after ablation. RESULTS: There were significant differences between the patients with left enlargement and with normal LV structure, in terms of sex, left ventricular ejection fraction (LVEF), level of N-terminal pro-brain natriuretic peptide (NT-proBNP), 24-h PVC burden, with nonsustained ventricular tachycardia, multifocal PVCs, QRS duration of PVC, and values of very low-frequency power of HRV parameter (all p < 0.05). Multivariate analysis showed that female gender (odds ratio [OR] = 2.753, p < 0.001), increased NT-proBNP (OR = 1.011, p = 0.022), increased LVEF (OR = 0.292, p < 0.001), increased 24-h PVC burden (OR = 1.594, p < 0.001), increased standard deviation of all NN intervals (SDNN) (OR = 1.100, p = 0.003), increased the proportion of consecutive NN intervals that differ by more than 50 ms (pNN50) (OR = 0.844, p = 0.026) were predictors for LV enlargement in patients with frequent PVCs. 84.4% (54/64) of patients with LV enlargement at baseline had normalized their LV structure after ablation. The values of SDNN, standard deviation of the averages of NN intervals in all 5-min segments, the square root of the mean of the sum of the squares of differences between adjacent NN intervals, pNN50, low-frequency power (LF), LF/high-frequency power ratio of patients were significantly decreased after ablation (all p < 0.05). CONCLUSION: Female gender, increased level of NT-proBNP, lower LVEF, higher PVC burden, increased sympathetic parameters SDNN, and reduced parasympathetic parameters pNN50 were the independent risk factors of LV enlargement in patients with frequent PVCs. LV enlargement induced by PVCs can be reversible after PVC elimination by ablation. The activities of sympathetic and parasympathetic were reduced after ablation.

Zero-fluoroscopy approach for ablation of supraventricular tachycardia using the Ensite NavX system: a multicenter experience.

BACKGROUND: Three-dimensional electroanatomic mapping systems have demonstrated a significant reduction in radiation exposure during radiofrequency catheter ablation procedures. We aimed to investigate the safety, feasibility and efficacy of a completely zero-fluoroscopy approach for catheter ablation of supraventricular tachycardia using the Ensite NavX navigation system compared with a conventional fluoroscopy approach. METHODS: A multicenter prospective non-randomized registry study was performed in seven centers from January 2013 to February 2018. Consecutive patients referred for catheter ablation of supraventricular tachycardia were assigned either to a completely zero-fluoroscopic approach (ZF) or conventional fluoroscopy approach (CF) according to the operator's preference. Patients with atrial tachycardia were excluded. RESULTS: Totally, 1020 patients were enrolled in ZF group; 2040 patients ablated by CF approach were selected for controls. There was no significant difference between the zero-fluoroscopy group and conventional fluoroscopy group as to procedure time (60.3 ± 20.3 vs. 59.7 ± 22.6 min, P = 0.90), immediate success rate of procedure (98.8% vs. 99.2%, P = 0.22), arrhythmia recurrence (0.4% vs. 0.5%, P = 0.85), total success rate of procedure (98.4% vs. 98.8%, P = 0.39) or complications (1.1% vs. 1.5%, P = 0.41). Compared with the conventional fluoroscopy approach, the zero-fluoroscopy approach provided similar outcomes without compromising the safety or efficacy of the procedure. CONCLUSION: The completely zero-fluoroscopy approach demonstrated safety and efficacy comparable to a conventional fluoroscopy approach for catheter ablation of supraventricular tachycardia, and mitigated radiation exposure to both patients and operators. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03042078; first registered February 3, 2017; retrospectively registered.

Prognostic value of elevated cardiac troponin I in patients with intracerebral hemorrhage.

BACKGROUND: Although cardiac troponin has been well established as diagnostic and prognostic makers for acute coronary heart disease, the prognostic value of elevated cardiac troponin in patients with intracerebral hemorrhage (ICH) was inconsistent and not systematically evaluated. HYPOTHESIS: We proposed the hypothesis that the practical utility of cardiac troponin levels for prediction of mortality and poor outcome in ICH patients. METHODS: A total of 1004 patients with ICH were retrospectively reviewed and qualified for further analysis from June 2012 to December 2015. The patients were divided into different groups based on measurements of cardiac troponin I (cTnI) at the time of admission and the following day. Multivariate Cox proportional hazards analysis were performed to determine the independent prognostic value of the cTnI for patients in-hospital mortality and poor outcomes, the receiver operator characteristic (ROC) analysis was performed to assess the predictive value of cTnI, ICH score, and combination of them. RESULTS: Serum cTnI level was an independent predictor in-hospital mortality (positive vs negative, HR (hazard ratios) = 3.44, 95% CI (confidence interval) 1.66-7.13, P < .001) and poor outcomes in patients with ICH (positive vs negative, HR = 6.69, 95% CI 4.25-10.52, P < .001). Addition of cTnI to ICH score significantly improved the prognostic discrimination for both in-hospital mortality and poor outcomes. CONCLUSION: Serum cTnI levels may be valuable as predictor for in hospital mortality and poor outcomes and may be useful in the risk stratification of ICH during hospitalization.

Carotid artery plaque intervention with Tongxinluo capsule (CAPITAL): A multicenter randomized double-blind parallel-group placebo-controlled study.

To determine whether the traditional Chinese medicine Tongxinluo (TXL) is efficacious at retarding the progression of carotid atherosclerotic lesions, a total of 1,212 patients with a focal intima-media thickness (IMT) of ≥1.2 mm of the carotid arteries received TXL or placebo capsules in addition to current routine therapy. The primary outcome was between-group differences in annualized change in mean IMT of 12 sites of bilateral carotid arteries over 24 months. The secondary outcomes were between-group differences in plaque area, vascular remodeling index (RI), serum levels of lipids and high-sensitivity C-reactive protein, and a composite of first major cardiovascular events. The results showed that the annualized change in mean IMT in the TXL and placebo groups was -0.00095 (95% CI, -0.00330 to 0.00141) mm and 0.01312 (95% CI, 0.01076 to 0.01548) mm, respectively, with a difference between the two groups of -0.01407 (95% CI, -0.01740 to -0.01073) mm (P < 0.001). Compared with placebo, TXL treatment significantly reduced the change from baseline in the plaque area and RI, as well as the first major cardiovascular events. In conclusion, TXL retarded the progression of mean IMT, plaque area and vascular remodeling of the carotid artery with a good safety profile.

Global Longitudinal Strain at Rest for Detection of Coronary Artery Disease in Patients without Diabetes Mellitus.

Global longitudinal strain (GLS) at rest on two-dimensional speckle tracking echocardiography (2D STE) was demonstrated to help detect coronary artery disease (CAD). However, the optimal cut-off point of GLS and its diagnostic power for detecting critical CAD in non-diabetes mellitus (DM) patients are unknown. In the present study, 211 patients with suspected CAD were prospectively included, with DM patients excluded. All patients underwent echocardiography and subsequently coronary angiography within 3 days. Left ventricular (LV) GLSs were quantified by 2D STE. Territorial peak systolic longitudinal strains (TLSs) were calculated based on the perfusion territories of the 3-epicardial coronary arteries in a 17-segment LV model. Critical CAD was defined as an area stenosis ≥70% in ≥1 epicardial coronary artery (≥50% in left main coronary artery). Totally 145 patients were diagnosed as having critical CAD by coronary angiography. Significant differences were observed in all strain parameters between patients with and without critical CAD. The area under the receiver operating charcteristic (ROC) curve (AUC) for GLS in the detection of left main (LM) or threevessel CAD was 0.875 at a cut-off value of -19.05% with sensitivity of 78.1% and specificity of 72.7%, which increased to 0.926 after exclusion of apical segments (cut-off value -18.66%; sensitivity 84.4% and specificity 81.8%). The values of TLSs were significantly lower in regions supplied by stenotic arteries than in those by non-stenotic arteries. The AUC for the TLSs to identify critical stenosis of left circumflex (LCX) artery, left anterior descending (LAD) artery and right coronary artery (RCA), in order of diagnostic accuracy, was 0.818 for LCX, 0.764 for LAD and 0.723 for RCA, respectively. In conclusion, in non-DM patients with suspected CAD, GLS assessed by 2D STE is an excellent predictor for LM or three-vessel CAD with high diagnostic accuracy, and a higher cut-off point than reported before should be used. Excluding apical segments in the calculation of GLS can further improve the predictive accuracy of GLS. It is unsatisfactory for TLSs to be used to identify stenotic coronary arteries.

Crosstalk between lysine methylation and phosphorylation of ATG16L1 dictates the apoptosis of hypoxia/reoxygenation-induced cardiomyocytes.

Post-translational modifications of autophagy-related (ATG) genes are necessary to modulate their functions. However, ATG protein methylation and its physiological role have not yet been elucidated. The methylation of non-histone proteins by SETD7, a SET domain-containing lysine methyltransferase, is a novel regulatory mechanism to control cell protein function in response to various cellular stresses. Here we present evidence that the precise activity of ATG16L1 protein in hypoxia/reoxygenation (H/R)-treated cardiomyocytes is regulated by a balanced methylation and phosphorylation switch. We first show that H/R promotes autophagy and decreases SETD7 expression, whereas autophagy inhibition by 3-MA increases SETD7 level in cardiomyocytes, implying a tight correlation between autophagy and SETD7. Then we demonstrate that SETD7 methylates ATG16L1 at lysine 151 while KDM1A/LSD1 (lysine demethylase 1A) removes this methyl mark. Furthermore, we validate that this methylation at lysine 151 impairs the binding of ATG16L1 to the ATG12-ATG5 conjugate, leading to inhibition of autophagy and increased apoptosis in H/R-treated cardiomyocytes. However, the cardiomyocytes with shRNA-knocked down SETD7 or inhibition of SETD7 activity by a small molecule chemical, display increased autophagy and decreased apoptosis following H/R treatment. Additionally, methylation at lysine 151 inhibits phosphorylation of ATG16L1 at S139 by CSNK2 which was previously shown to be critical for autophagy maintenance, and vice versa. Together, our findings define a novel modification of ATG16L1 and highlight the importance of an ATG16L1 phosphorylation-methylation switch in determining the fate of H/R-treated cardiomyocytes.

The positive therapeutic effect in a patient of Evans syndrome combined with acute myocardial infarction.

Evans syndrome (ES) is a rare combination of autoimmune hemolytic anemia and thrombocytopenia. This case report details an old male ES patient with acute myocardial infarction. He was successfully treated by primary percutaneous coronary intervention in the case of low hemoglobin level (60 g/L). Considering ES recurrence after surgery, he was given human immunoglobulin, methyl prednisolone and TPO treatment. On the basis of his platelet count, the patient was required to take only one anti-platelet drug or stop all anti-platelet drugs. To the best of our knowledge, this is the first report of ES with AMI. This case suggests that primary PCI can be a useful therapeutic strategy even if patient has low hemoglobin level, but careful balance between anti-platelet therapy and efforts to raise platelet count are needed after surgery.

ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation.

Recent studies have shown that the phosphorylation and dephosphorylation of ULK1 and ATG13 are related to autophagy activity. Although ATG16L1 is absolutely required for autophagy induction by affecting the formation of autophagosomes, the post-translational modification of ATG16L1 remains elusive. Here, we explored the regulatory mechanism and role of ATG16L1 phosphorylation for autophagy induction in cardiomyocytes. We showed that ATG16L1 was a phosphoprotein, because phosphorylation of ATG16L1 was detected in rat cardiomyocytes during hypoxia/reoxygenation (H/R). We not only demonstrated that CSNK2 (casein kinase 2) phosphorylated ATG16L1, but also identified the highly conserved Ser139 as the critical phosphorylation residue for CSNK2. We further established that ATG16L1 associated with the ATG12-ATG5 complex in a Ser139 phosphorylation-dependent manner. In agreement with this finding, CSNK2 inhibitor disrupted the ATG12-ATG5-ATG16L1 complex. Importantly, phosphorylation of ATG16L1 on Ser139 was responsible for H/R-induced autophagy in cardiomyocytes, which protects cardiomyocytes from apoptosis. Conversely, we determined that wild-type PPP1 (protein phosphatase 1), but not the inactive mutant, associated with ATG16L1 and antagonized CSNK2-mediated phosphorylation of ATG16L1. Interestingly, one RVxF consensus site for PPP1 binding in the C-terminal tail of ATG16L1 was identified; mutation of this site disrupted its association with ATG16L1. Notably, CSNK2 also associated with PPP1, but ATG16L1 depletion impaired the interaction between CSNK2 and PPP1. Collectively, these data identify ATG16L1 as a bona fide physiological CSNK2 and PPP1 substrate, which reveals a novel molecular link from CSNK2 to activation of the autophagy-specific ATG12-ATG5-ATG16L1 complex and autophagy induction.

Incidence and clinical characteristics of postcardiac injury syndrome complicating cardiac perforation caused by radiofrequency catheter ablation for cardiac arrhythmias.

BACKGROUND: Postcardiac injury syndrome (PCIS) is a complication of a variety of cardiac injuries, of which small heart perforation is the etiology that is often unrecognized. We reported a series of patients with PCIS secondary to cardiac perforation during catheter ablation procedures. METHODS AND RESULTS: Out of 1728 radiofrequency catheter ablation procedures, 21 patients (1.2%) were complicated by echo-defined cardiac perforation not requiring surgical intervention. Among them, 6 patients (6/21, 28.6%) were diagnosed with PCIS secondary to cardiac perforation because they also developed pleural effusions (6/6, 100%) and fever (4/6, 66.7%) in addition to pericardial effusion/tamponade. Four patients with PCIS (4/6, 66.7%) and four patients without PCIS (4/15, 26.7%) underwent pericardial drainage but the drainage volume during the first 24 h was not significantly different (441.3±343.9 mL vs. 182.5±151.3 mL, P=0.248). In the 6 PCIS patients, pleural effusion was detected from 3 h to 4 days (median: 2 days) after ablation procedure, predominantly bilateral (66.7%) or left-sided if unilateral. Patients with PCIS were older (64.8±7.3 years vs. 45.9±14.8 years, P=0.0078), were more likely accompanied by hypertension (66.7% vs. 6.7%, P=0.0114) and had a prolonged hospital stay (34.2±15.8 days). CONCLUSIONS: More than 25% of patients with small cardiac perforation during catheter ablation may develop PCIS which can be masked by pericardial effusion/tamponade. This kind of PCIS is more likely associated with elder or hypertensive patients and is usually characterized by early onset of pleural effusion.

Preliminary investigation of the clinical value of vascular endothelial growth factor and hypoxia-inducible factor-1alpha in pericardial fluid in diagnosing malignant and tuberculous pericardial effusion.

OBJECTIVES: To investigate the clinical value of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1alpha) in diagnosing malignant and tuberculous pericardial effusion. METHODS: Eighty patients with exudative pericardial effusion undergoing pericardiocentesis and drainage were divided into 2 groups, namely those with malignancy and those with tuberculosis. The levels of HIF-1alpha, VEGF, lactate dehydrogenase (LDH) and adenosine deaminase (ADA) in pericardial fluid and serum were measured. Routine and cytological examination of pericardial fluid, clinical characteristics and some blood parameters were compared between the 2 groups. RESULTS: There were 33 patients with tuberculous pericardial effusion and 47 with malignant pericardial effusion. The levels of VEGF and HIF-1alpha in pericardial fluid in the malignancy group were significantly higher than those in the tuberculosis group (p < 0.01), and there was a moderate positive correlation between the levels of VEGF and HIF-1alpha (r = 0.79, p < 0.01). The sensitivity and specificity of combining VEGF and HIF-1alpha were 90.8 and 88.3%, respectively. The 2 groups showed no differences with regard to gender distribution, occurrence of fever, erythrocyte sedimentation rate or the levels of hemoglobin, LDH, ADA, serum HIF-1alpha and VEGF. CONCLUSIONS: Both VEGF and HIF-1alpha in pericardial fluid have determinative value in the differential diagnosis of malignant and tuberculous pericardial effusion.

Comparative study of clinical characteristics between Chinese Han and German Caucasian patients with coronary heart disease.

BACKGROUND: The differences of the clinical characteristics, risk factors, treatment and prognosis in coronary heart disease (CHD) patients from different races, area and countries are rarely reported. METHODS: Collecting, comparing and analyzing the clinical data and blood examination results of 650 Chinese Han and 640 German Caucasian patients with CHD. RESULTS: The ratio of the first hospitalization because of CHD in Chinese patients was higher than that in Germans (95.1 vs. 38.1% P < 0.01). CHD occurred most frequently in elder men of both nations. The German CHD patients combined with hypertension, dyslipidemia and abnormal glucose metabolism were clearly more often than Chinese patients. Other risk factors such as fibrinogen, homocysteine and the proportion of positive family history of premature CHD, obesity, hyperuricemia were higher in German patients than that in Chinese patients. However, the ratio of smoking, acute myocardial infarction and the levels of high-sensitivity C-reactive protein in Chinese patients were obviously higher than that in Germans (P < 0.01, P < 0.05). The use of aspirin in both groups was the same, but the use of statins, beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers were distinctly lower in Chinese patients compared to Germans (P < 0.01, P < 0.05). The proportion of percutaneous coronary intervention and coronary artery bypass grafting in Chinese patients was lower than that in Germans (P < 0.01). The usage of drug-eluting stents to bare-metal stents was slightly higher in German patients, whereas it was obviously higher in Chinese patients (P < 0.01). CONCLUSION: There were significant differences in clinical characteristics, risk factors and treatment of Chinese Han and German Caucasian patients with CHD.

Influence of osteopontin short hairpin RNA on the proliferation and activity of rat vascular smooth muscle cells.

To investigate the influence of osteopontin (OPN) short hairpin RNA (shRNA) on the proliferation and activity of rat vascular smooth muscle cells (VSMCs), the expressing vector of shRNA targeting OPN was constructed and transferred into the rat VSMCs. After amplification and purification, pGenesil-1/OPNshRNA1 (PG1), pGenesil-1/OPNshRNA2 (PG2) and pGenesil-1/OPNshRNAHK (PGH) were transfected into the cultured rat VSMC by Lipofectamine 2000. Transfected cells were visualized by using an inverted fluorescent microscope. VSMCs transfected by optimal recombined plasmid was selected by culturing in G418 48 h later. Nude cells and cells transfected by PGH were used as control. The expression levels of OPN mRNA and protein were assayed by RT-PCR and Western blotting. The OPN of VSMCs was suppressed by transfection of optimal recombined plasmid, and the changes in cell proliferation, adhesion and motility were evaluated by MTT, adhesion test and transwell chamber test. Levels of type I and III collagen were measured with ELISA kit. Our results showed that VSMCs stably transfected by OPN shRNA accounted for over 50% of total cells. OPN mRNA and protein were reduced by 81% and 67% (P<0.01) by PG1, 73% and 52% (P<0.01) by PG2, respectively while no change was found in PGH and non-treated VSMCs. PG1 significantly suppressed the proliferation, adhesion, mobility of VSMCs and reduced the amount of type I and III collagen. It is concluded that recombinant plasmid can be successfully transfected into VSMCs by Lipofectamine 2000 and inhibit the expression of OPN. The proliferation, adhesion and mobility of VSMCs can be inhibited by knocking down OPN expression. Moreover, the transferring capability of cells is attenuated, and the secretion of type I and III collagen is inhibited after knocking-down of OPN expression. The study provides experimental evidence for clinical prevention of restenosis after percutaneous coronary intervention (PCI) by RNA interference (RNAi) technology.

Influence of Osteopontin Short Hairpin RNA on the Proliferation and Activity of Rat Vascular Smooth Muscle Cells / 华中科技大学学报（医学）（英德文版）

To investigate the influence of osteopontin (OPN) short hairpin RNA (shRNA) on the proliferation and activity of rat vascular smooth muscle cells (VSMCs),the expressing vector of shRNA targeting OPN was constructed and transferred into the rat VSMCs.After amplification and purification,pGenesil-1/OPNshRNA1 (PG1),pGenesil-1/OPNshRNA2 (PG2) and pGenesil-1/OPNshRNAHK (PGH) were transfected into the cultured rat VSMC by LipofectamineTM 2000.Transfected cells were visualized by using an inverted fluorescent microscope.VSMCs transfected by optimal recombined plasmid was selected by culturing in G418 48 h later.Nude cells and cells transfected by PGH were used as control.The expression levels of OPN mRNA and protein were assayed by RT-PCR and Western blotting.The OPN of VSMCs was suppressed by transfection of optimal recombined plasmid,and the changes in cell proliferation,adhesion and motility were evaluated by MTT,adhesion test and transwell chamber test.Levels of type Ⅰ and Ⅲ collagen were measured with ELISA kit.Our results showed that VSMCs stably transfected by OPN shRNA accounted for over 50% of total cells.OPN mRNA and protein were reduced by 81% and 67% (P<0.01) by PGI,73% and 52% (P<0.01) by PG2,respectively while no change was found in PGH and non-treated VSMCs.PG1 significantly suppressed the proliferation,adhesion,mobility of VSMCs and reduced the amount of type Ⅰ and Ⅲ collagen.It is concluded that recombinant plasmid can be successfully transfected into VSMCs by LipofectamineTM 2000 and inhibit the expression of OPN.The proliferation,adhesion and mobility of VSMCs can be inhibited by knocking down OPN expression.Moreover,the transferring capability of cells is attenuated,and the secretion of type Ⅰ and Ⅲ collagen is inhibited aftter knocking-down of OPN expression.The study provides experimental evidence for clinical prevention of restenosis after percutaneous coronary intervention (PCI) by RNA interference (RNAi) technology.

Experimental study of adenovirus vector mediated-hVEGF165 gene on prevention of restenosis after angioplasty.

This study evaluated the effects of adenovirus vector mediated human vascular endothelial growth factor-165 (hVEGF165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenoviruses containing hVEGF165 cDNA was directly injected into left side of the injured carotid arteries. On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and immunohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in carotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer. The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF165 gene transfer the VEGF mRNA and antigen expression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima area/media area (I/M), maximal intimal and medial thicknesses (ITmax and MTmax) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of recombinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit thrombokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.