A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Association of time-varying changes in physical activity with cardiac death and all-cause mortality after ICD or CRT-D implantation.

OBJECTIVE: To evaluate the association of longitudinal changes in physical activity (PA) with long-term outcomes after implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) implantation. METHODS: Patients with ICD/CRT-D implantation from SUMMIT registry were retrospectively analyzed. Accelerometer-derived PA changes over 12 months post implantation were obtained from the archived home monitoring data. The primary endpoints were cardiac death and all-cause mortality. The secondary endpoints were the first ventricular arrthymia (VA) and first appropriate ICD shock. RESULTS: In 705 patients, 446 (63.3%) patients showed improved PA over 12 months after implantation. During a mean 61.5-month follow-up duration, 99 cardiac deaths (14.0%) and 153 all-cause deaths (21.7%) occurred. Compared to reduced/unchanged PA, improved PA over 12 months could result in significantly reduced risks of cardiac death (improved PA ≤ 30 min: hazard ratio (HR) = 0.494, 95% CI: 0.288-0.848; > 30 min: HR = 0.390, 95% CI: 0.235-0.648) and all-cause mortality (improved PA ≤ 30 min: HR = 0.467, 95%CI: 0.299-0.728; > 30 min: HR = 0.451, 95% CI: 0.304-0.669). No differences in the VAs or ICD shocks were observed across different groups of PA changes. PA changes can predict the risks of cardiac death only in the low baseline PA group, but improved PA was associated with 56.7%, 57.4%, and 62.3% reduced risks of all-cause mortality in the low, moderate, and high baseline PA groups, respectively, than reduced/unchanged PA. CONCLUSIONS: Improved PA could protect aganist cardiac death and all-cause mortality, probably reflecting better clinical efficacy after ICD/CRT-D implantation. Low-intensity exercise training might be encouraged among patients with different baseline PA levels.

Beneficial effects of endoscopic screening on gastric cancer and optimal screening interval: a population-based study.

BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95 % confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95 %CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95 %CI 0.13-0.25) and disease-specific survival (RR 0.18, 95 %CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of < 2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (P-trend = 0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric lesion severity.

Genetic variants in Chinese patients with sporadic Stanford type A aortic dissection.

BACKGROUND: Genetic disorders are strongly associated with aortic disease. However, the identities of genetic mutations in sporadic Stanford type A aortic dissection (STAAD) are not clear. The present study analysed the possible genetic mutations of the known pathogenic genes of aortic disease and the clinical characteristics in patients with sporadic STAAD. METHODS: We analysed genetic mutations in 26 genes that underlie aortic aneurysms and dissections in 100 sporadic STAAD patients and 568 healthy controls after whole-genome sequencing (WGS). Clinical features and in-hospital death were determined in all STAAD patients. RESULTS: In total, 60 suspicious pathogenic mutations (56 novel and 4 previously reported) in 19 genes were identified in 50% (50/100) of patients, and 14 patients had more than 1 mutation. The ascending aortic diameter was extended in patients with mutations (49.1±12.3 vs. 43.7±11.2 mm, P=0.023), and the DeBakey type I phenotype was more common in patients with mutations in genes that coded extracellular matrix (ECM) components than in patients with mutations in other genes (96.6% vs. 66.7%, P=0.007). Patients with fibrillin-1 (FBN1) mutations were younger than patients without FBN1 mutations (44.7±11.0 vs. 53.5±12.1, P=0.030). Subgroup analyses revealed an increased risk of in-hospital mortality in mutation carriers (44.4% vs. 10.5%, P=0.029) but only in patients who received conservative treatment. CONCLUSIONS: Half of Chinese patients with a sporadic form of STAAD may carry mutations in known pathogenic genes of aortic disease, and these patients may exhibit distinct clinical features and poor clinical outcomes with the use of conservative treatment.

Plasma big endothelin-1 is an effective predictor for ventricular arrythmias and end-stage events in primary prevention implantable cardioverter- defibrillator indication patients.

OBJECTIVE: To investigate whether plasma big endothelin-1 (ET-1) predicts ventricular arrythmias (VAs) and end-stage events in primary prevention implantable cardioverter-defibrillator (ICD) indication patigents. METHODS: In total, 207 patients fulfilling the inclusion criteria from Fuwai Hospital between January 2013 and December 2015 were retrospectively analyzed. The cohort was divided into three groups according to baseline plasma big ET-1 tertiles: tertile 1 (< 0.38 pmol/L, n = 68), tertile 2 (0.38-0.7 pmol/L, n = 69), and tertile 3 (> 0.7 pmol/L, n = 70). The primary endpoints were VAs. The secondary endpoints were end-stage events comprising all-cause mortality and heart transplantation. RESULTS: During a mean follow-up period of 25.6 ± 13.9 months, 38 (18.4%) VAs and 78 (37.7%) end-stage events occurred. Big ET-1 was positively correlated with NYHA class (r = 0.165, P = 0.018), serum creatinine concentration (Scr; r = 0.147, P = 0.034), high-sensitivity C-reactive protein (hs-CRP; r = 0.217, P = 0.002), Lg NT-pro BNP (r = 0.463, P < 0.001), left ventricular end diastolic diameter (LVEDD; r = 0.234, P = 0.039) and negatively correlated with left ventricular ejection fraction (LVEF; r = -0.181, P = 0.032). Kaplan-Meier analysis showed that elevated big ET-1 was associated with increased risk of VAs and end-stage events (P < 0.05). In multivariate Cox regression models, big ET-1 was an independent risk factor for VAs (hazard ratio (HR) = 3.477, 95% confidence interval (CI): 1.352-8.940, P = 0.010, tertile 2 vs. tertile 1; HR = 4.112, 95% CI: 1.604-10.540, P = 0.003, tertile 3 vs. tertile 1) and end-stage events (HR = 2.804, 95% CI: 1.354-5.806, P = 0.005, tertile 2 vs. tertile 1; HR = 4.652, 95% CI: 2.288-9.459, P < 0.001, tertile 3 vs. tertile 1). CONCLUSIONS: In primary prevention ICD indication patients, plasma big ET-1 levels can predict VAs and end-stage events and may facilitate ICD-implantation risk stratification.

Correlations between low thyroid function and incidence of atrial fibrillation in hypertrophic obstructive cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic obstructive cardiomyopathy (HOCM). Data regarding the correlations of thyroid dysfunction and the incidence of AF in HOCM are quite limited. This study aimed to reveal the correlations between different thyroid status and the corresponding incidence of AF in a large HOCM cohort. METHODS: A total of 806 HOCM patients with complete information on thyroid function tests and comprehensive cardiac evaluations were recruited. The participants were divided into the AF group (n = 159) and non-AF group (n = 647) according to established medical history and results of Holter monitoring. The thyroid status of the study population and the corresponding incidence of AF were assessed and analyzed. RESULTS: Hypothyroidism accounted for the greatest proportion of thyroid dysfunction in HOCM patients. The incidence of AF significantly increased in individuals with both overt (P = 0.022) and subclinical (P = 0.007) hypothyroidism. Compared with participants in the non-AF group, those with positive AF episodes presented with lower free triiodothyronine (FT3) (2.86 ± 0.52 pg/mL vs. 3.01 ± 0.42 pg/mL, P = 0.001), higher free thyroxine (FT4) (1.24 ± 0.25 ng/dL vs. 1.15 ± 0.16 ng/dL, P < 0.001), and remarkably increased levels of thyrotropin (TSH) (12.6% vs. 5.3%, P = 0.001). Multivariable analyses demonstrated that the concentrations of FT3 (odds ratio [OR] = 0.470, 95% confidence interval [CI]: 0.272-0.813, P = 0.007) and FT4 (OR = 17.992, 95% CI: 5.750-56.296, P < 0.001), as well as TSH levels above normal ranges (OR = 2.276, 95% CI: 1.113-4.652, P = 0.024) were independently associated with the occurrence of AF in the large HOCM cohort. CONCLUSIONS: This study indicated a strong link between low thyroid function and the presence of AF in HOCM. Hypothyroidism (both overt and subclinical states) seems to be valuable for assessing the incidence of AF in patients with HOCM.

Predictive value of Tpeak-Tend interval for ventricular arrhythmia and mortality in heart failure patients with an implantable cardioverter-defibrillator: A cohort study.

BACKGROUND: Tpeak-Tend interval (TpTe), a measurement of transmural dispersion of repolarization (TDR), has been shown to predict ventricular tachyarrhythmia in cardiac resynchronization therapy with defibrillator (CRT-D) patients. However, the ability of TpTe to predict ventricular tachyarrhythmia and mortality for heart failure patients with a cardioverter-defibrillator (ICD) is not clear. The purpose of this study was to assess the predictive ability of TpTe in heart failure patients with ICD. METHODS AND RESULTS: We enrolled 318 heart failure patients treated after ICD. Patients were divided into 3 groups according to their post-implantation TpTe values and were evaluated every 6 months. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality. During long-term follow-up, the TpTe > 110 ms group (n = 111) experienced more VT/VF episodes (45%) and all-cause mortality (25.2%) than the TpTe 90-110 ms group (n = 109) (26.4%, 14.5%) and TpTe < 90 ms group (n = 98) (11.3%, 11.3%) (overall P < .05, respectively). In Cox regression, longer post-implantation TpTe was associated with an increased number of VT/VF episodes [HR: 1.017; 95% CI: 1.008-1.026; P < .001], all-cause mortality [HR: 1.015; 95% CI: 1.004-1.027; P = .010] and the combined endpoint [HR: 1.018; 95%CI: 1.010-1.026; P < .001]. CONCLUSIONS: Post-implantation TpTe was an independent predictor of both ventricular arrhythmias and all-cause mortality in heart failure patients with an implanted ICD.

Predictors of non-response to cardiac resynchronization therapy implantation in patients with class I indications: the markedly dilated left ventricular end-diastolic dimension and the presence of fragmented QRS.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a highly effective treatment in patients with a class I recommendation. However, a small proportion of the strictly selected patients still fail to respond. This study was designed to identify predictors of non-response in patients with class I indications for CRT and determine the non-response probability of the patients. METHODS: A total of 296 consecutive patients with a class I recommendation received CRT from January 2009 to January 2017 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify predictors for non-response (defined as cardiac death, heart transplantation, or HF hospitalization during 1-year follow-up). RESULTS: Among 296 patients, 30 (10.1%) met non-response. Multivariate analysis demonstrated that non-response to CRT was associated with a fragmented QRS (odd ratio (OR) = 2.86, 95% CI: 1.14-7.12; P = 0.025) and left ventricular end-diastolic dimension (LVEDD) ≥ 77 mm (OR = 3.02, 95% CI: 1.17-7.82; P = 0.022). Patients with both of the predictors had a non-response probability of 46.2% (95% CI: 19.1%-73.3%). CONCLUSION: In patients with left bundle branch block and wider QRS duration, the proportion of non-response to CRT is not low in real world. The presence of the dilated LVEDD or fragmented QRS is a strong predictor of non-response to CRT. The probability of non-response in the patients with the two predictors was 46.2%.

Does 'super-responder' patients to cardiac resynchronization therapy still have indications for neuro-hormonal antagonists? Evidence from long-term follow-up in a single center.

BACKGROUND: Whether cardiac resynchronization therapy super-responders (CRT-SRs) still have indications for neuro-hormonal antagonists or not remains uninvestigated. METHODS: We reviewed clinical data from 376 patients who underwent CRT implantation in Fuwai Hospital from 2009 to 2015 and followed up to 2017. CRT-SRs were defined by an improvement of the New York Heart Association functional class and left ventricular ejection fraction to ≥ 50% in absolute values at 6-month follow-up. All CRT-SRs were assigned into two groups on the basis of whether persistently receiving neuro-hormonal antagonists (NHA) (defined as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and ß-blockers) after 6-month follow-up and then we compared long-term outcome. RESULTS: A total of 60 patients met criteria for super-response. One of thirteen (7.7%) CRT-SRs without NHA had all-cause death, which also occurred in 2 of 47 (4.3%) in CRT-SRs with NHA (P = 0.526). However, 3 of 13 (23.1%) CRT-SRs without NHA had heart failure (HF) hospitalization, 1 of 47 (2.1%) CRT-SRs with NHA had this endpoint (P = 0.040). Besides, subgroup analysis indicated that, for ischemic etiology group, CRT-SRs receiving NHA had considerably lower incidence of HF hospitalization than those without NHA (0 vs. 75%, P = 0.014), which was not observed in non-ischemic etiology group (2.6% vs. 0, P = 1.000) during long-term follow-up. CONCLUSIONS: Our study found that for ischemic etiology, compared with CRT-SRs with NHA, CRT-SRs without NHA were associated with a higher risk of HF hospitalization. However, for non-ischemic etiology, we found that CRT-SRs with NHA or without NHA at follow-up were associated with similar outcomes, which needed further investigation by prospective trials.

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.

Repetitive optimizing left ventricular pacing configurations with quadripolar leads improves response to cardiac resynchronization therapy: A single-center randomized clinical trial.

BACKGROUND: This study aimed to investigate whether repetitive optimizing left ventricular pacing configurations (LVPCs) with quadripolar leads (QUAD) can improve response to cardiac resynchronization therapy (CRT). METHODS: Fifty-two eligible patients were enrolled and 1:1 randomized to either the quadripolar LV leads (QUAD) group or the conventional bipolar leads (CONV) group. In the QUAD group, optimization of LVPC was performed for all patients before discharge and for nonresponders at 3 months follow-up. Clinical evaluations and transthoracic echocardiograms were performed before, 3, and 6 months after CRT implantation. RESULTS: At 3 months follow-up, 16 of 25 (64%) patients in the CONV group (1 patient was lost to follow-up) and 18 of 26 (69%) patients in the QUAD group were classified as responders. After optimizing the LVPCs in 3-month nonresponders in the QUAD group, 21 of 26 (80.8%) patients in the QUAD group were classified as responders at 6 months as compared with 17 of 25 (68%) patients in the CONV group. Left ventricular end-systolic volume (LVESV) reduction, left ventricular ejection fraction (LVEF) increase, and New York Heart Association (NYHA) functional class reduction at 6 months were significantly greater in the QUAD group than in the CONV group (LVESV: -26.9 ±â€Š13.8 vs -17.2 ±â€Š13.3%; P = .013; LVEF: +12.7 ±â€Š8.0 vs +7.8 ±â€Š6.3 percentage points; P = .017; NYHA: -1.27 ±â€Š0.67 vs -0.72 ±â€Š0.54 functional classes; P = .002). CONCLUSIONS: Compared with conventional bipolar leads, CRT using quadripolar leads with repetitive optimized LVPCs resulted in an additional increase in LVEF and reduction in LVESV and NYHA functional class at 6-month follow-up.

Clinical outcome of cardiac resynchronization therapy in dilated-phase hypertrophic cardiomyopathy.

BACKGROUNDS: Clinical trials have demonstrated that cardiac resynchronization therapy (CRT) is effective in patients with "non-ischemic cardiomyopathy". However, patients with dilated-phase hypertrophic cardiomyopathy (DHCM) have been generally excluded from such trials. We aimed to compare the clinical outcome of CRT in patients with DHCM, idiopathic dilated cardiomyopathy (IDCM), or ischemic cardiomyopathy (ICM). METHODS: A total of 312 consecutive patients (DHCM: n = 16; IDCM: n = 231; ICM: n = 65) undergoing CRT in Fuwai hospital were studied respectively. Response to CRT was defined as reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-month follow-up. RESULTS: Compared with DHCM, IDCM was associated with a lower total mortality (HR: 0.35, 95% CI: 0.13-0.90), cardiac mortality (HR: 0.29; 95% CI: 0.11-0.77), and total mortality or heart failure (HF) hospitalizations (HR: 0.34, 95% CI: 0.17-0.69), independent of known confounders. Compared with DHCM, the total mortality, cardiac mortality and total mortality or HF hospitalizations favored ICM but were not statistically significant (HR: 0.59, 95% CI: 0.22-1.61; HR: 0.59, 95% CI: 0.21-1.63; HR: 0.54, 95% CI: 0.26-1.15; respectively). Response rate to CRT was lower in the DHCM group than the other two groups although the differences didn't reach statistical significance. CONCLUSIONS: Compared with IDCM, DHCM was associated with a worse outcome after CRT. The clinical outcome of DHCM patients receiving CRT was similar to or even worse than that of ICM patients. These indicate that DHCM behaves very differently after CRT.

Admission white blood cell count predicts short-term clinical outcomes in patients with uncomplicated Stanford type B acute aortic dissection.

OBJECTIVES: Inflammation has been shown to be related with acute aortic dissection (AAD). The present study aimed to evaluate the association of white blood cell counts (WBCc) on admission with both in-hospital and long-term all-cause mortality in patients with uncomplicated Stanford type B AAD. METHODS: From 2008 to 2010, a total of 377 consecutive patients with uncomplicated type B AAD were enrolled and then followed up. Clinical data and WBCc on admission were collected. The primary end points were in-hospital death and long-term all-cause death. RESULTS: The in-hospital death rate was 4.2%, and the long-term all-cause mortality rate was 6.9% during a median follow-up of 18.9 months. WBCc on admission was identified as a risk factor for in-hospital death by univariate Cox regression analysis as both a continuous variable and a categorical variable using a cut off of 11.0 × 109 cell/L (all P < 0.05). After adjusting for age, sex and other risk factors, elevated admission WBCc was still a significant predictor for in-hospital death as both a continuous variable [hazard ratio (HR): 1.052, 95% CI: 1.024-1.336, P = 0.002] and a categorical variable using a cut off of 11.0 × 109 cell/L (HR: 2.056, 95% CI: 1.673-5.253, P = 0.034). No relationship was observed between WBCc on admission and long-term all-cause death. CONCLUSIONS: Our results indicate that elevated WBCc upon admission might be used as a predictor for increased risk of in-hospital death in uncomplicated type B AAD. There might be no predictive value of WBCc for the long-term survival of type B AAD.

Short-Term Availability of Viable Left Ventricular Pacing Sites with Quartet™ Quadripolar Leads.

BACKGROUND Whether quadripolar leads can provide sufficient viable left ventricular pacing sites (LVPSs) for device optimization and multipoint pacing remains unclear. This study aimed to evaluate the acute and 3-month availability of viable LVPSs provided by a quadripolar LV pacing lead. MATERIAL AND METHODS A single-center cohort study evaluated consecutive patients who underwent a CRT implant with the QuartetTM LV lead under local guidelines. The availability of viable LVPSs was assessed at the pre-discharge and 3-month follow-up visit. Bipolar lead configurations, which served as the control group, were modeled by eliminating the 2 proximal electrodes on the Quartet™ LV lead. RESULTS A total of 24 patients were enrolled and finished 3-month follow-up. The mean follow-up period was 93±3 days. At pre-discharge, the Quartet™ LV lead provided more viable LVPSs compared with the bipolar equivalents (median 3 [IQR 2-4] vs. median 2 [IQR 1-2], P<0.001). The percentage of patients with at least 1, 2, 3, and 4 viable LVPSs were 100% (24/24), 91.7% (22/24), 58.3% (14/24), and 33.3% (8/24) for Quartet™ leads and 91.7% (22/24), 70.8% (17/24), 0% (0/24), and 0% (0/24) for bipolar lead configurations, respectively. The median and IQR values of viable LVPSs provided by the Quartet™ LV lead remained the same (3 [IQR 2-4]) between pre-discharge and 3-month follow-up (P=0.45). CONCLUSIONS Compared with the bipolar equivalent, QuartetTM LV lead provides more viable LVPSs and opportunities for CRT optimization and multipoint LV pacing. The number of LVPSs provided by Quartet™ leads remained unchanged between pre-discharge and 3-month follow-up.

Predictors of super-response to cardiac resynchronization therapy: the significance of heart failure medication, pre-implant left ventricular geometry and high percentage of biventricular pacing.

BACKGROUND: Super-responders (SRs) are defined as patients who show crucial cardiac function improvement after cardiac resynchronization therapy (CRT). The purpose of this study is to identify and validate predictors of SRs after CRT. METHODS: This study enrolled 201 patients who underwent CRT during the period from 2010 to 2014. Clinical and echocardiographic evaluations were conducted before CRT and 6 months after. Patients with a decrease in New York Heart Association (NYHA) functional class ≥ 1, a decrease in left ventricular end-systolic volume (LVESV) ≥ 15%, and a final left ventricular ejection fraction (LVEF) ≥ 45% were classified as SRs. RESULTS: 29% of the 201 patients who underwent CRT were identified as SRs. At baseline, SRs had significantly smaller left atrial diameter (LAD), LVESV, left ventricular end-diastolic volume (LVEDV) and higher LVEF than the non-super-responders (non-SRs). The percentage of patients using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) was higher in SRs than non-SRs. Most SRs had Biventricular (BiV) pacing percentage greater than 98% six months after CRT. In the multivariate logistic regression analysis, the independent predictors of SRs were lower LVEDV [odd ratios (OR): 0.93; confidence intervals (CI): 0.90-0.97], use of ACEI/ARB (OR: 0.33; CI: 0.13-0.82) and BiV pacing percentage greater than 98% (OR: 0.29; CI: 0.16-0.87). CONCLUSION: Patients with a better compliance of ACEI/ARB and a less ectatic ventricular geometry before CRT tends to have a greater probability of becoming SRs. Higher percentage of BiV pacing is essential for becoming SRs.

Acute and Chronic Changes and Predictive Value of Tpeak-Tend for Ventricular Arrhythmia Risk in Cardiac Resynchronization Therapy Patients.

BACKGROUND: Prolongation of the Tpeak-Tend (TpTe) interval as a measurement of transmural dispersion of repolarization (TDR) is an independent risk factor for chronic heart failure mortality. However, the cardiac resynchronization therapy's (CRT) effect on TDR is controversial. Therefore, this study aimed to evaluate CRTs acute and chronic effects on repolarization dispersion. Furthermore, we aimed to investigate the relationship between TpTe changes and ventricular arrhythmia. METHODS: The study group consisted of 101 patients treated with CRT-defibrillator (CRT-D). According to whether TpTe was shortened, patients were grouped at immediate and 1-year follow-up after CRT, respectively. The echocardiogram index and ventricular arrhythmia were observed and compared in these subgroups. RESULTS: For all patients, TpTe slightly increased immediately after CRT-D implantation, and then decreased at the 1-year follow-up (from 107 ± 23 to 110 ± 21 ms within 24 h, to 94 ± 24 ms at 1-year follow-up, F = 19.366,P< 0.001). No significant difference in the left ventricular reverse remodeling and ventricular tachycardia/ventricular fibrillation (VT/VF) episodes between the TpTe immediately shortened and TpTe immediately nonshortened groups. However, patients in the TpTe at 1-year shorten had a higher rate of the left ventricular (LV) reverse remodeling (65% vs. 44%, χ2 = 4.495, P = 0.038) and less VT/VF episodes (log-rank test, χ2 = 10.207, P = 0.001) compared with TpTe 1-year nonshortened group. TpTe immediately after CRT-D independently predicted VT/VF episodes at 1-year follow-up (hazard ratio [HR], 1.030; P = 0.001). CONCLUSIONS: Patients with TpTe shortened at 1-year after CRT had a higher rate of LV reverse remodeling and less VT/VF episodes. The acute changes of TpTe after CRT have minimal value on mechanical reverse remodeling and ventricular arrhythmia.

Differential expression of microRNAs in aortic tissue and plasma in patients with acute aortic dissection.

BACKGROUND: Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study is to search for new potentially microRNA (miRNAs) biomarkers in AAD. METHODS: The miRNAs expression profiles in ascending aortic tissue and plasma were examined by microarray analysis in two sets or groups. The tissue group was composed of four patients with AAD and four controls of healthy male organ donors. The plasma group included 20 patients with AAD and 20 controls without cardiovascular disease. Bioinformatics was used to analyze the potential targets of the differentially expressed miRNAs. RESULTS: Our study revealed that in AAD patients, the aortic tissue had 30 differentially expressed miRNAs with 13 up-regulated and 17 down-regulated, and plasma had 93 differentially expressed miRNAs, of which 33 were up-regulated and 60 were down-regulated. Four miRNAs were found to be up-regulated in both aortic tissue and plasma in AAD patients. The predicted miRNA targets indicated the four dysregulated miRNAs mainly targeted genes that were associated with cell-cell adhesion, extracellular matrix metabolism, cytoskeleton organization, inflammation, and multiple signaling pathways related to cellular cycles. CONCLUSIONS: Four miRNAs, which are up-regulated both in aortic tissue and in plasma in AAD patients, have been identified in this study. These miRNAs might be potential diagnostic biomarkers for AAD. Larger sample investigations are needed for further verification.

Screening of pathogenic genes in Chinese patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes. METHODS: A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C. RESULTS: Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers. CONCLUSIONS: Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.

Upregulation of TRPM7 channels by angiotensin II triggers phenotypic switching of vascular smooth muscle cells of ascending aorta.

RATIONALE: Angiotensin II (Ang II) has pleiotropic effects on vascular smooth muscle cells (VSMCs). It has been demonstrated to promote the proliferative phenotype of VSMCs in mouse ascending aorta, but the underlying mechanisms remain incompletely understood. OBJECTIVE: The present study was designed to explore whether the Ca(2+)-permeable transient receptor potential melastatin 7 (TRPM7) channel is involved in Ang II-induced phenotype switching of ascending aortic VSMCs and to dissect the molecular mechanisms by which TRPM7 modulates VSMC phenotype. METHODS AND RESULTS: As revealed by current recording, Ang II infusion increased TRPM7 whole-cell currents in ascending aortic VSMCs. The increase in TRPM7 currents was found to result from enhanced expression of TRPM7 protein rather than elevated single-channel activity (open probability and slope conductance) and/or reduced Mg(2+)-mediated channel block. Mechanistically, Ang II elevated TRPM7 expression via Ang II type 1 receptor-mediated ERK1/2 signaling. As indicated by the expression levels of VSMC differentiation marker genes, phenotypic switching of ascending aorta occurred during Ang II infusion. Meanwhile, ERK1/2-Elk-1 signaling pathway known to suppress VSMC differentiation was activated in Ang II-infused ascending aorta. Knockdown of TRPM7 with small interfering RNA established a causative role of TRPM7 in Ang II-induced phenotypic change and promotion of cell proliferation. Moreover, TRPM7 was shown to be required for Pyk2-ERK1/2-Elk-1 pathway activation by Ang II, which potentiated TRPM7 channel function and thus activated the Ca(2+)-sensitive kinase Pyk2. Finally, TRPM7 knockdown attenuated Ang II-induced displacement of myocardin from SM22 promoter, but the effects could be reversed by expression of constitutively active c-Src. CONCLUSIONS: Our data establish that upregulation of TRPM7 channels by Ang II contributes to the development of the proliferative phenotype of ascending aortic VSMCs, and TRPM7 channel suppresses VSMC gene expression via Ca(2+) influx-mediated activation of Pyk2-ERK1/2-Elk-1 pathway.