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 poten- tial 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. Con- clusions 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.

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 （WI3Cc） on admission with both in-hospital and long-term all-cause mortality in patients with uncom- plicated 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.

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 resynchro- nization 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） fimctional 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 independ- ent 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： 0.13~3.82） and BiV pacing percentage greater than 98% （OR： 0.29; CI： 0.16~.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.

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%.

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.

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 β-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.

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.

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-is- chemic 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 defmed 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.

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 im-plantable 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-de-rived PA changes over 12 months post implantation were obtained from the archived home monitoring data.The primary end-points were cardiac death and all-cause mortality.The secondary endpoints were the first ventricular arrthymia(VA)and first ap-propriate 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/un-changed 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.

nitial Experience with MultiPoint Pacing Cardiac Resynchronization Therapy in China

Recently, cardiac resynchronization therapy （CRT） with multipoint left ventricular （LV） pacing in a single coronary sinus branch （MultiPointTM Pacing [MPP], St. Jude Medical, Inc., Sylmar, CA, USA） has been introduced commercially. The CRT system with MPP feature offers a new strategy for physicians to further enhance CRT in patients with heart failure. Early clinical studies have shown that MPP, compared with conventional biventricular （BiV） pacing, provides acute benefits to LV dP/dtmax, LV dyssynchrony, LV peak radial strain, and LV electrical activation, and improves CRT response at 12 months. In this report, we presented two MPP CRT cases in China with acute hemodynamic assessment under various MPP and conventional BiV pacing configurations, demonstrating that MPP can offer further benefits to patients.