Heart rate-adjusted PR as a prognostic marker of long-term ventricular arrhythmias and cardiac death in ICD/CRT-D recipients.

OBJECTIVE: To evaluate the PR to RR interval ratio (PR/RR, heart rate-adjusted PR) as a prognostic marker for long-term ventricular arrhythmias and cardiac death in patients with implantable cardioverter defibrillator (ICDs) and cardiac resynchronization therapy with defibrillators (CRT-D). METHODS: We retrospectively analyzed data from 428 patients who had an ICD/CRT-D equipped with home monitoring. Baseline PR and RR interval data prior to ICD/CRT-D implantation were collected from standard 12-lead electrocardiograph, and the PR/RR was calculated. The primary endpoint was appropriate ICD/CRT-D treatment of ventricular arrhythmias (VAs), and the secondary endpoint was cardiac death. RESULTS: During a mean follow-up period of 38.8 ± 10.6 months, 197 patients (46%) experienced VAs, and 47 patients (11%) experienced cardiac death. The overall PR interval was 160 ± 40 ms, and the RR interval was 866 ± 124 ms. Based on the receiver operating characteristic curve, a cut-off value of 18.5% for the PR/RR was identified to predict VAs. A PR/RR ≥ 18.5% was associated with an increased risk of VAs [hazard ratio (HR) = 2.243, 95% confidence interval (CI) = 1.665-3.022, P < 0.001) and cardiac death (HR = 2.358, 95%CI = 1.240-4.483, P = 0.009) in an unadjusted analysis. After adjustment in a multivariate Cox model, the relationship remained significant among PR/RR ≥ 18.5%, VAs (HR = 2.230, 95%CI = 1.555-2.825, P < 0.001) and cardiac death (HR = 2.105, 95%CI = 1.101-4.025, P = 0.024. CONCLUSIONS: A PR/RR ≥ 18.5% at baseline can serve as a predictor of future VAs and cardiac death in ICD/CRT-D recipients.

MicroRNA­20b­5p promotes ventricular remodeling by targeting the TGF­ß/Smad signaling pathway in a rat model of ischemia­reperfusion injury.

Myocardial ischemic injury results from severe impairment of the coronary blood supply and may lead to metabolic and ultrastructural changes, thereby causing irreversible damage. MicroRNA (miR)­20b­5p has been demonstrated to be involved in malignancies of the breast, colorectum, stomach, blood and oropharynx. The present study aimed to investigate the effects of miR­20b­5p on ventricular remodeling following myocardial ischemia­reperfusion (IR) injury in rats by targeting small mothers against decapentaplegic homolog 7 (Smad7) via the transforming growth factor­ß (TGF­ß)/Smad signaling pathway. A total of 70 adult male Sprague­Dawley rats were divided into seven groups: Sham group, IR group, negative control group, miR­20b­5p mimics group, miR­20b­5p inhibitors group, small interfering RNA (siRNA)­Smad7 group, and miR­20b­5p inhibitors + siRNA­Smad7 group. Dual luciferase reporter gene assays were used to verify the association between miR­20b­5p and Smad7. Myocardial infarction size, myocardial collagen volume fraction and perivascular collagen area were detected separately using triphenyltetrazolium chloride and Masson's staining. The rate of positive expression of Smad7 was detected using immunohistochemistry, and the expression levels of miR­20b­5p, TGF­ß1, Smad3 and Smad7 were detected using reverse transcription­quantitative polymerase chain reaction and western blot analyses. The findings revealed that miR­20b­5p inhibited Smad7. Compared with the sham group, the other six groups had increased myocardial infarction size, myocardial collagen, and expression of miR­20b­5p, TGF­ß1 and Smad3, and decreased expression of Smad7. Compared with the IR group, the miR­20b­5p mimics group and the siRNA­Smad7 group had increased myocardial infarction size and myocardial collagen, increased expression of TGF­ß1 and Smad3, and decreased expression of Smad7. The expression of miR­20b­5p was markedly increased in the miR­20b­5p mimics group, but did not differ significantly from that in the siRNA­Smad7 group. The results demonstrated that miR­20b­5p promoted ventricular remodeling following myocardial IR injury in rats by inhibiting the expression of Smad7 through activating the TGF­ß/Smad signaling pathway.

Combined myocardial deformation to predict cardiac resynchronization therapy response in nonischemic cardiomyopathy.

BACKGROUND: 20-30% of patients do not benefit from cardiac resynchronization therapy (CRT) when the established selection criteria were applied. We hypothesized that a combined assessment of mechanical dyssynchrony, myocardial deformation, and diastolic function would identify patients who would benefit most from CRT. METHOD: In 36 CRT patients, clinical evaluation and echocardiography were performed before and after CRT. Patients were classified into three subgroups according to their amount of response: echocardiographic responders, clinical responders, and nonresponders. Radial dyssynchrony and left ventricular (LV) global longitudinal, radial, and circumferential peak strain was assessed by speckle-tracking image. Diastolic function was quantified by conventional echocardiography. RESULT: In addition to left bundle branch block, nonspecific intraventricular conduction disturbance with intraventricular dyssynchrony could also improve LV remodeling. Echocardiographic responders had better global longitudinal strain, global circumferential peak strain, and global radial strain at baseline which significantly increased at 12-month follow-up. An improvement in estimates of LV filling pressure and a decrease in mitral regurgitation and left atrial dimensions were observed only in echocardiographic responders to CRT. Patients with clinical but without echocardiographic response showed a significant improvement in atrioventricular (AV) synchrony and a nonsignificant improvement in other parameters. The nonresponder group did not improve the AV and intraventricular dyssynchrony. CRT could not improve restrictive filling pattern with normal filling time. Overall, those patients with AV and intraventricular dyssynchrony and those with best contractile function and short diastolic filling time of restrictive filling pattern at baseline demonstrated the greatest benefit from CRT. CONCLUSIONS: Mechanical dyssynchrony, contractile function, and filling pattern are important determinants of the benefits in CRT.

Postoperative Assessment of Myocardial Function and Microcirculation in Patients with Acute Coronary Syndrome by Myocardial Contrast Echocardiography.

BACKGROUND Postoperative myocardial function and microcirculation of acute coronary syndrome (ACS) was assessed by myocardial contrast echocardiography (MCE). MATERIAL AND METHODS Eighty-nine ACS patients treated with percutaneous coronary intervention (PCI) were detected by MCE and two-dimensional ultrasonography before and a month later after PCI respectively. Their myocardial perfusion was evaluated by myocardial contrast score (MSC) and contrast score index (CSI); cross-sectional area of microvessel (A), average myocardial microvascular impairment (ß), and myocardial blood flow (MBF) were analyzed by cardiac ultrasound quantitative analysis (CUSQ), and fractional flow reserve (FFR) change was observed. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), and left ventricular end-systolic dimension (LVESD) were observed; the index of microcirculatory resistance (IMR), FFR, and coronary flow reserve (CFR) were detected to evaluate coronary microcirculation. RESULTS None of the 89 patients experienced no-reflow. Patients with normal myocardial perfusion mostly had normal or slightly decreased ventricular wall motion after PCI. A month after the operation, there was an increase in A, ß, MBF, LVEF, E/A, IMR, FFR, and CFR (all P<0.05), while LVEDD, LVESD, diastolic gallop A peak, E/Ea, E/Ea×S, and Tei decreased (all P<0.05). LVEF and IMR were in positive correlations with A. LVEF, IMR, FFR and CFR were positively correlated with b and MBF (both r>0, P<0.05), while E/Ea×Sa and Tei were negatively correlated with b and MBF (r<0, P<0.05). CONCLUSIONS MCE can safely assess post-PCI myocardial function and microcirculation of ASC.

Value of Low-Dose Dobutamine Stress Real-Time Myocardial Contrast Echocardiography in the Diagnosis of Coronary Heart Disease.

To investigate the value of low-dose dobutamine stress real-time myocardial contrast echocardiography (RT-MCE) in the diagnosis of coronary heart disease (CHD). A total of 65 hospitalized patients with suspected or confirmed CHD were detected by RT-MCE combined with low-dose dobutamine stress (0.84 mg/kg). Perfusion curves were quantitatively analyzed using QLAB software. Peak intensity (A), slope of curves (ß), and perfusion (A × ß) were also calculated. Based on the results of coronary angiography, patients were divided into no obvious stenosis group (<50%), mild stenosis group (50%-74%), moderate stenosis group (75%-89%), and severe stenosis group (≥90%). The A, ß, and A × ß values before and after low-dose dobutamine stress of each group were compared. In the basal state and after low-dose dobutamine stress, the A, ß, and A × ß values significantly decreased as the stenosis degree of the myocardial segments increased. The same variation tendency was also found in the A, ß, and A × ß reserve values, and there was significant difference in these reserve values between moderate and severe stenosis groups and no obvious stenosis and mild stenosis groups. Collateral circulation had marked effects on the values of myocardial perfusion parameters and their reserve values, especially in the segments with severe stenosis. Low-dose dobutamine stress RT-MCE can be a sensitive method for clinical diagnosis and risk assessment of CHD and may provide a basis for further treatment of CHD.

Fluvastatin combined with benazepril may contribute to the favorable prognosis of patients with atrial fibrillation.

The aim of this study was to observe the clinical efficacy of fluvastatin combined with benazepril in the treatment of patients with atrial fibrillation (AF). A total of 92 patients with AF were randomly assigned to the case group (n=46), in which the patients were treated with fluvastatin (80mg) plus benazepril (10mg), or to the control group (n=46), in which the patients were treated with fluvastatin (80mg). The conversion rate of sinus rhythm was higher in the case group than in the control group (P<0.05). The case group had more treatment-effective patients than the control group, with fewer treatment-ineffective patients (P<0.05). The LVEDd, LVESd, LAD, and LVEF indexes in the case group were lower than in the control group after 6 months of treatment (all P<0.05). Levels of hs-CRP were also lower in patients in the case group than in patients in the control group after 1 month of treatment (P<0.05). After 12 months, renin and Ang II concentrations were lower in patients in the case group than in the control group (both P<0.05). Significant differences in IL-6 and TNF-α expression were found between the two groups after 1 month, 6 months, and 12 months of treatment (all P<0.05). Compared to patients in the control group, the levels of total cholesterol (TC), triglycerides, and LDL-C in the case group were lower after 6 and 12 months of treatment (all P<0.05), while the HDL level was higher (P<0.05). Treatment with fluvastatin combined with benazepril further increased the conversion rate of sinus rhythm and significantly improved the quality of life and prognosis of AF patients.

Roles of MicroRNA-195 in cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion injury.

This study aims to investigate microRNA-195 (miR-195) expression in myocardial ischaemia-reperfusion (I/R) injury and the roles of miR-195 in cardiomyocyte apoptosis though targeting Bcl-2. A mouse model of I/R injury was established. MiR- 195 expression levels were detected by real-time quantitative PCR (qPCR), and the cardiomyocyte apoptosis was detected by TUNEL assay. After cardiomyocytes isolated from neonatal rats and transfected with miR-195 mimic or inhibitor, the hypoxia/reoxygenation (H/R) injury model was established. Cardiomyocyte apoptosis and mitochondrial membrane potential were evaluated using flow cytometry. Bcl-2 and Bax mRNA expressions were detected by RT-PCR. Bcl-2, Bax and cytochrome c (Cyt-c) protein levels were determined by Western blot. Caspase-3 and caspase-9 activities were assessed by luciferase assay. Compared with the sham group, miR-195 expression levels and rate of cardiomyocyte apoptosis increased significantly in I/R group (both P < 0.05). Compared to H/R + negative control (NC) group, rate of cardiomyocyte apoptosis increased in H/R + miR-195 mimic group while decreased in H/R + miR-195 inhibitor group (both P <0.05). MiR-195 knockdown alleviated the loss of mitochondrial membrane potential (P <0.05). MiR-195 overexpression decreased Bcl-2 mRNA and protein expression, increased BaxmRNA and protein expression, Cyt-c protein expression and caspase-3 and caspase-9 activities (all P <0.05).While, downregulated MiR-195 increased Bcl-2 mRNA and protein expression, decreased Bax mRNA and protein expression, Cyt-c protein expression and caspase-3 and caspase-9 activities (all P < 0.05). Our study identified that miR-195 expression was upregulated in myocardial I/R injury, and miR-195 overexpression may promote cardiomyocyte apoptosis by targeting Bcl-2 and inducing mitochondrial apoptotic pathway.

Reduction of atrial fibrillation in remotely monitored pacemaker patients: results from a Chinese multicentre registry.

BACKGROUND: Many recipients of implantable cardiac electronic devices have atrial fibrillation (AF) occurrences after device implantation, even if there is no previous history of AF, and some of the episodes are asymptomatic. The purpose of this study was to evaluate trends in AF burden following early AF detection in patients treated with pacemakers equipped with automatic, daily Home Monitoring function. METHODS: Between February 2009 and December 2010, the registry recruited 701 pacemaker patients (628 dual-chamber, 73 biventricular devices) at 97 clinical centers in China. Daily Home Monitoring data transmissions were analyzed to screen for the AF burden. In-office follow-ups were scheduled for 3 and 6 months after implantation. Upon first AF (i.e., mode-switch) detection in a patient, screening of AF burden by Home Monitoring was extended for the next 180 days. RESULTS: At least one episode of AF was observed in 22.9% of patients with dual-chamber pacemakers and in 28.8% of patients with biventricular pacemakers. The first AF detection in a patient occurred, on average, about 2 months before scheduled follow-up visits. In both pacemaker groups, mean AF burden decreased significantly (P < 0.05) over 180 days following first AF detection: from 12.0% to 2.5% in dual-chamber and from 12.2% to 0.5% in biventricular pacemaker recipients. The number of patients with an AF burden >10% per month was significantly reduced over 6 months of implantation in both dual chamber (38 patients in the first month vs. 21 patients in month 6, P < 0.05) and biventricular (7 patients in the first month vs. 0 patient in months 4-6, P < 0.05) pacemaker recipients. CONCLUSIONS: Automatic, daily Home Monitoring of patients treated with cardiac pacemakers allows early detection of AF, and there is a gradual and significant decrease in AF burden.

Ginkgo biloba extract and ginkgolide antiarrhythmic potential by targeting hERG and ICa-L channel.

We investigated the effects of Ginkgo biloba extract (GBE) and ginkgolide (GLD) on human ether-a-go-go-related gene (hERG)-encoded K(+) channels and its underlying mechanisms in the hERG-HEK293 cell line by determining GBE- and GLD-induced changes in action potential duration (APD), L-type calcium currents (ICa-L), and the intracellular calcium concentration ([Ca(2+)]i) in guinea-pig ventricular myocytes. hERG currents, APD and ICa-L were recorded using the whole-cell patch clamp technique, the [Ca(2+)]i was examined by an immunofluorescence experiment. In the present study, we found that a low concentration of GBE (0.005 mg/ml) increased hERG currents, but the high concentration of GBE (from 0.05 to 0.25 mg/ml) reduced hERG currents. GLD reduced hERG currents in a concentration-dependent manner (from 0.005 to 0.25 mg/ml). Both GBE and GLD altered kinetics of the hERG channel. GBE accelerated the activation of hERG channels without changing the inactivation curve, but reduced the time constant of inactivation; GLD did not shift the activation or the inactivation curve, but only reduced the time constant of inactivation. Both GBE and GLD shortened the APD, inhibited the ICa-L currents, and decreased the [Ca(2+)]i in isolated guinea-pig ventricular myocytes. The results indicate that GBE and GLD can prevent ischemic arrhythmias and have an antiarrhythmic effect potential via inhibition of IKr and ICa-L currents.

Radiofrequency catheter ablation of idiopathic ventricular tachycardia and symptomatic premature ventricular contraction originating from valve annulus.

BACKGROUND: Radiofrequency catheter ablation (RFCA) has been established as an effective and curative therapy for ventricular tachycardia (VT) and severely symptomatic premature ventricular contraction (PVC) from the outflow tract in structurally normal hearts. This study aimed to investigate electrophysiologic characteristics and effects of RFCA for patients with idiopathic VT and symptomatic PVC originating from the valve annulus. METHODS: Characteristics of body surface electrocardiogram (ECG) and endocardiogram in a successful RFCA target were analyzed in 16 patients with idiopathic VT and symptomatic PVC originating from the valve annulus. Additionally, the ECG characteristics of VT or PVC were compared with those of manifest Wolff-Parkinson-White (WPW) syndrome originating from the same site of origin in 15 patients. RESULTS: Thirteen patients were successful, 2 recurrent and 1 failed. The recurrent cases underwent successful ablation the second time guided by the Ensite 3000 mapping system. In all patients with the WPW syndrome, the characteristics of QRS morphology were well matched with those of the VT and PVC that originated from corresponding sites of origin. CONCLUSIONS: RFCA is an effective curative therapy for VT and symptomatic PVC originating from the valve annulus. There are specific characteristics in ECG and the ablation site could be located by means of the WPW syndrome accessory pathway's algorithm.

[Effects of catheter ablation of ventricular tachycardia and premature ventricular contraction originating from left and right ventricular outflow tracts].

OBJECTIVE: To observe the ECG and electrophysiological characteristic of patients with idiopathic ventricular tachycardia (VT) and premature ventricular contraction (PVC) originating from left (LVOT) and right (RVOT) ventricular outflow tracts and assess the clinical effect of radio frequency catheter ablation (RFCA) on these patients. METHODS: RFCA was performed in 58 patients (10 with VT and 48 with PVC, 5 patients with VT from RVOT under the guidance of non-contact mapping system Ensite3000). VT or PVC originated from LVOT in 15 patients (12 out of 15 from left sinus of Valsalva) and RVOT in 43 patients. RESULTS: (1) R wave in II, III, aVF leads was the common characteristics of VT or PVC originated from LVOT and RVOT and difference in wave duration index and R/S-wave amplitude ratio in V(1) or V(2) could be used to define VT and PVC originated from LVOT or RVOT. (2) Ablation was successful in 55 out of 58 patients (9 patients with the 2nd ablation, evaluated as arrhythmia-free at 3 months post ablation without medication) and failed in 3 patients. One patient developed pericardial tamponade during ablation and recovered without complication after related treatments. CONCLUSIONS: RFCA is an effective, safe and curative therapy for VT or PVC originated from LVOT and RVOT. Non-contact mapping system (Ensite3000) is a safe and reliable tool to guide mapping and ablation in patients with complex VT and unstable hemodynamics.

[Clinical evaluation of catheter ablation for idiopathic ventricular arrhythmia originating from ventricular outflow tract].

OBJECTIVE: To study the ECG and electrophysiological characteristic of idiopathic ventricular tachycardia (VT) and premature ventricular contraction (PVC) originating from ventricular outflow tract and assess the clinical effect of radiofrequency catheter ablation (RFCA) for treatment. METHODS: 105 patients aged from 12 to 73 years old were treated with RFCA. Activation mapping, pace mapping and non-contact mapping system of Ensite 3000 were used during the procedure. RESULTS: (1) VT and PVC were successfully ablated in 97 out of the 105 patients (93.3%), 15 were recurrent but succeed in the second time. (2) 84 patients originated from right ventricle outflow tract (RVOT) and the remaining 21 patients from left ventricle outflow tract (LVOT). (3) 3 patients have the pericardial tamponade during ablation. CONCLUSION: RFCA is an effective and curative therapy for ventricular arrhythmia originating from ventricular outflow tract.