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 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.

Jujuboside a Improved Energy Metabolism in Senescent H9c2 Cells Injured by Ischemia, Hypoxia, and Reperfusion through the CD38/Silent Mating Type Information Regulation 2 Homolog 3 Signaling Pathway

Objective:This study explored the myocardial protection role of Jujuboside A through an ischemia–hypoxia–reperfusion(IHR)model.Materials and Methods:H9c2 cells were induced by D-galactose(D-gal)and IHR to establish an aging and IHR model.There are four groups of experiments:Control,IHR,D-gal+IHR,and D-gal+IHR+Jujuboside A.Cells viability,Adenosine triphosphate(ATP),reactive oxygen species(ROS),nicotinamide adenine dinucleotide(NAD+),nicotinamide adenine dinucleotide hydride(NADH)content,and NAD+/NADH ratio were detected using biochemical methods.Inflammatory cytokines level was detected by enzyme-linked immunosorbent assay.The expression of CD38,Recombinant NLR Family,pyrin domain-containing protein 3(NLRP3),and silent mating type information regulation 2homolog 3(SIRT3)protein was detected by Western blotting.Results:Compared to the IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and SIRT3 protein expression decreased,ROS level and inflammatory cytokines increased,and CD38 and NLRP3 proteins raised in the D-gal+IHR group.Compared to the D-gal+IHR group,cell viability,ATP content,NAD+content,NAD+/NADH ratio,and expression of SIRT3 protein increased,ROS level and inflammatory cytokines level decreased,and expression of the CD38 and NLRP3proteins decreased in the D-gal+IHR+Jujuboside A group.Conclusions:Jujuboside A inhibited the expression of CD38,improved energy metabolism disorder,and mitochondrial function,and decreased inflammation in D-gal-induced H9c2 cells.

Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease

Objective: To investigate the effect and underlying mechanisms of Tiaoxin Recipe(a Chinese herbal formula) treatment on Alzheimer's disease(AD).Methods: Twelve-week-old APPswe/PS1 DE9(APP/PS1) double transgenic mice were used as a model of AD-afflicted mice. One group of mice was treated with Tiaoxin Recipe by gastrogavage for 12 weeks,while two other groups were given intraperitoneal injections of nicotinamide adenine dinucleotide or FK866 for 4 weeks. Morris water maze and thioflavin S staining tests were performed to evaluate cognitive impairment and amyloid plaque deposition, respectively. Serum amyloid-β1-42(Aβ1-42) content was detected using an enzyme-linked immunosorbent assay, and quantitative reverse transcriptionpolymerase chain reaction was performed to examine the expression levels of microRNA-34 a(miR-34 a) in cortex and hippocampus samples of the study mice.Results: Compared with the normal control group, the memory and learning abilities of the APP/PS1 model group were found to be impaired(P < 0.01), as shown by the increased levels of senile plaque deposition in cortex and hippocampus(P < 0.01), miR-34 a expression(P < 0.01) and serum Aβ1-42 content(P < 0.01). Treatment with Tiaoxin Recipe significantly reduced memory impairment(P < 0.01) by reducing amyloid plaque accumulation in cortex and hippocampus(P < 0.01), miR-34 a expression(P < 0.01) and serum Aβ1-42 content(P < 0.01) in APP/PS1 mice.Conclusion: Tiaoxin Recipe is a viable complementary or alternative therapeutic treatment that is capable of delaying the development of early-stage AD by inhibiting the expression of miR-34 a.