N-Terminal Pro-B-Type Natriuretic Peptide in Risk Stratification of Heart Failure Patients With Implantable Cardioverter-Defibrillator.

Background: The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) is well-established. However, whether it could facilitate the risk stratification of HF patients with implantable cardioverter-defibrillator (ICD) is still unclear. Objective: To determine the associations between baseline NT-proBNP and outcomes of all-cause mortality and first appropriate shock due to sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in ICD recipients. Methods and results: N-terminal pro-B-type natriuretic peptide was measured before ICD implant in 500 patients (mean age 60.2 ± 12.0 years; 415 (83.0%) men; 231 (46.2%) Non-ischemic dilated cardiomyopathy (DCM); 136 (27.2%) primary prevention). The median NT-proBNP was 854.3 pg/ml (interquartile range [IQR]: 402.0 to 1,817.8 pg/ml). We categorized NT-proBNP levels into quartiles and used a restricted cubic spline to evaluate its nonlinear association with outcomes. The incidence rates of mortality and first appropriate shock were 5.6 and 9.1%, respectively. After adjusting for confounding factors, multivariable Cox regression showed a rise in NT-proBNP was associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the hazard ratios (HRs) with 95% CI across increasing quartiles were 1.77 (0.71, 4.43), 3.98 (1.71, 9.25), and 5.90 (2.43, 14.30) for NT-proBNP (p for trend < 0.001). A restricted cubic spline demonstrated a similar pattern with an inflection point found at 3,231.4 pg/ml, beyond which the increase in NT-proBNP was not associated with increased mortality (p for nonlinearity < 0.001). Fine-Gray regression was used to evaluate the association between NT-proBNP and first appropriate shock accounting for the competing risk of death. In the unadjusted, partial, and fully adjusted analysis, however, no significant association could be found regardless of NT-proBNP as a categorical variable or log-transformed continuous variable (all p > 0.05). No nonlinearity was found, either (p = 0.666). Interactions between NT-proBNP and predefined factors were not found (all p > 0.1). Conclusion: In HF patients with ICD, the rise in NT-proBNP is independently associated with increased mortality until it reaches the inflection point. However, its association with the first appropriate shock was not found. Patients with higher NT-proBNP levels might derive less benefit from ICD implant.

MicroRNA-144 Suppresses Prostate Cancer Growth and Metastasis by Targeting EZH2.

BACKGROUND: Prostate cancer is a common malignant tumor with a high incidence. MicroRNAs (miRNAs) have been shown to be important post-transcriptional regulators during tumorigenesis. This study aimed to explore the effect of miR-144 on PCa proliferation and apoptosis. MATERIAL AND METHODS: The expression of miR-144 and EZH2 were examined in clinical PCa tissues. PCa cell line LNCAP and DU-145 was employed and transfected with miR-144 mimics or inhibitors. The correlation between miR-144 and EZH2 was verified by luciferase reporter assay. Cell viability, apoptosis and migratory capacity were detected by CCK-8, flow cytometry assay and wound healing assay. The protein level of EZH2, E-Cadherin, N-Cadherin and vimentin were analyzed by western blotting. RESULTS: miR-144 was found to be negatively correlated to the expression of EZH2 in PCa tissues. Further studies identified EZH2 as a direct target of miR-144. Moreover, overexpression of miR-144 downregulated expression of EZH2, reduced cell viability and promoted cell apoptosis, while knockdown of miR-144 led to an inverse result. miR-144 also suppressed epithelial-mesenchymal transition level of PCa cells. CONCLUSION: Our study indicated that miR-144 negatively regulate the expression of EZH2 in clinical specimens and in vitro. miR-144 can inhibit cell proliferation and induce cell apoptosis in PCa cells. Therefore, miR-144 has the potential to be used as a biomarker for predicting the progression of PCa.

The Efficacy and Safety of Wenxin Keli in Patients with Frequent Premature Ventricular Contractions: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial.

BACKGROUND: Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort. METHODS: We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis. RESULTS: At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantli greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%,P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%,P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported. CONCLUSIONS: Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC-related symptoms in patients without structural heart diseases and had no severe side effects.

[The predictive value of mild renal insufficiency on the prognosis of patients with acute coronary syndrome].

OBJECTIVE: To investigate the predictive value of mild renal insufficiency on the endpoint events in patients with acute coronary syndrome (ACS). METHODS: A total of 552 patients with ACS were enrolled in the present study. According to the levels of estimated glomerular filtration rate (eGFR), patients were divided into two groups, normal renal function (eGFR ≥ 90 ml×min(-1)×1.73 m(-2)) and mild renal insufficiency (60 ≤ eGFR<90 ml×min(-1)×1.73 m(-2)). The primary and secondary events were collected and analyzed through the present prospective follow-up study. RESULTS: The patients in mild renal insufficiency group had a higher incidence of the primary endpoint events than normal renal function group [31 cases (12.6%) vs 15 cases (4.9%), P = 0.001]. There was no difference of the secondary endpoint events incidence in the two groups. The incidence rate of all-cause mortality [8.9% (22 cases) vs 2.2% (7 cases), P < 0.001] and cardiac death [6.5% (16 cases) vs 1.3% (4 cases), P = 0.001] was higher in mild renal insufficiency group, but there was no statistical difference of incidence rate of no fatal stroke and myocardial infarction in the two groups. The results of COX regression analysis showed that the incidence of primary endpoint events in patients with mild renal dysfunction was 2.265 folds (95%CI 1.076-4.771, P = 0.031) of patients with normal renal function. Further analysis indicated that the predictive value of mild renal insufficiency was only for all-cause mortality (HR 3.118, 95%CI 1.197-8.125, P = 0.020), not for heart failure and revascularization. According to the Kaplan-Meier curves results, the incidences of the primary endpoint events (P = 0.004) and all-cause mortality (P = 0.001) were higher in mild renal insufficiency group than in normal renal function group. CONCLUSION: Mild renal insufficiency has important predictive value for primary endpoint events in patients with ACS.

Idiopathic ventricular fibrillation with fragmented QRS complex and J wave in resting electrocardiogram.

OBJECTIVE: To describe the clinical characteristics of idiopathic ventricular fibrillation (IVF) with fragmented QRS complex (f-QRS) and J wave in resting electrocardiogram. METHODS: We reviewed data from 21 case subjects in our hospital who were resuscitated after cardiac arrest due to IVF and assessed the prevalence of f-QRS and J wave in resting electrocardiogram (ECG). All the case subjects were classified among three groups based on the electrocardiographic morphology: group I, both f-QRS and J wave were observed (n = 6), group II, only J wave was observed (n = 9), group III, neither f-QRS nor J wave was observed (n = 6). Population characteristics, history of syncope or sudden cardiac arrest, incidence of ventricular fibrillation (VF), and circumstance of VF were evaluated among the three groups. RESULTS: The incidence of index events (syncope, survived cardiac arrest and VF episodes recorded in implantable cardioverter defibrillator (ICD) or pacemakers) was 13.4 ± 5.6 per-year in group I, 10.8 ± 3.9 per-year in group II, and 9.8 ± 4.2 per-year in group III. There were significant differences in incidences among the three groups, the most frequent index events were observed in group I. The hazard ratio for incidence was 3.2 (95%CI, 1.1-7.9; P = 0.01). The history and circumstance of the index events were different among the groups. In group I, all the index events occurred during sleep in early morning. In group II, four subjects suffered VF during strenuous physical activities or agitation state, two during sleep in early morning, three in usual activity. In group III, one subject suffered VF during sleep in early morning, one in agitation state, four in usual activity. CONCLUSIONS: This study suggests that the IVF patients with the combined appearance of f-QRS and J wave in the resting ECG suffer an increased risk of VF, this subgroup of IVF patients has a unique clinical feature.

[Association between abnormal electrocardiographic features and disease severity in patients with arrhythmogenic right ventricular cardiomyopathy].

OBJECTIVE: To analyze the relationship between electrocardiographic (ECG) features and disease severity in patients with the arrhythmogenic right ventricular cardiomyopathy (ARVC). METHOD: The study group consisted of 61 subjects with a definite diagnosis of ARVC on the basis of published guideline criteria and patients were divided into 3 subgroups according to the extent of diseased myocardium defined by cardiac magnetic resonance imaging (MRI): Group A: local involvement (n = 19, 31%), Group B: diffuse involvement of whole right ventricle (n = 28, 46%) and Group C: involvement of both right and left ventricles (n = 14, 23%). RESULTS: Normal electrocardiogram was shown in 1 patient in each group. Epsilon wave was detected in 24 (39%) patients, QRS duration was prolonged [≥ 110 ms (V(1)-V(3))] in 21 (34%) patients, S-wave upstroke was prolonged (≥ 55 ms) in 17 (28%) patients, complete right branch bundle block was evidenced in 10 (16%) patients and pathologic Q waves was found in 9 (15%) patients. The incidence of above abnormal ECG changes was increased in proportion to the degree of disease severity (group A < group B < group C). Incidence of Epsilon wave and prolonged QRS duration [ ≥ 110 ms (V(1)-V(3))] were significantly higher in Group C than in Group A. Incidence of prolonged S-wave upstroke (≥ 55 ms) was significantly higher in Group C than in Group A and Group B. T-wave inversion in V(1) leads was often found in Group A. T-wave inversion in inferior leads (V(1)-V(3) leads or beyond V(3)) was often presented in Group B and Group C. CONCLUSIONS: Normal ECG does not exclude the possibility of diagnosis of ARVC. The extent of T-wave inversion in the precordial leads and incidence of Epsilon wave, prolonged QRS duration [ ≥ 110 ms (V(1)-V(3))] and prolonged S-wave upstroke (≥ 55 ms) were related to degree of disease severity in patients with ARVC.

[Association between electrocardiogram characteristics and long-term outcome in patients with idiopathic ventricular fibrillation].

OBJECTIVE: To explore the association between clinical and ECG characteristics and prognoses in patients with idiopathic ventricular fibrillation (VF). METHODS: We reviewed the data from 21 VF patients [male 47.6%, mean age (38.5 ± 19.0) years] with first event of VF, all patients were resuscitated after cardiac arrest and diagnosed as idiopathic VF. The prevalence of J wave was assessed and patients were divided into J wave positive (J+ group) and negative group (J- group). The end point was death or syncope from arrhythmia, and recorded VF recurrence during the follow-up. RESULTS: J wave was frequent in subjects with idiopathic VF (71.4%). Among patients in the J+ group (15 cases), notch on the QRS wave was found in 7 subjects (46.7%), these patients were more likely to suffer from the sudden cardiac arrest during sleep at early morning than those with J wave but without notch on the QRS wave. Two patients dead suddenly in the J+ group and 1 dead from embolism in the J- group during follow-up [mean (42.4 ± 39.9) months]. The mean year-onset of VF or syncope was significantly higher in the J+ group than in the J-group [(1.3 ± 0.5) episodes/year vs. (0.4 ± 0.3) episodes/year, P < 0.01]. J wave positive was also associated with an increased risk of VF recurrence (RR 1.9, 95%CI 1.1 to 2.9, P = 0.03). CONCLUSION: J wave prevalence is high in patients with history of idiopathic VF, and positive J wave is associated with high risk of recurrence of sudden cardiac death.