Long-term Efficacy of Pulmonary Artery Desnervation Treatment in Heart Failure With Preserved Ejection Fraction:A Subgroup Analysis of 3-year Results From the PADN-5 Study

Objective:The Pulmonary Arterial Denervation in Patients With Pulmonary Hypertension Associated With the Left Heart Failure(PADN-5)study proved that pulmonary artery denervation(PADN)is associated with significant improvements in hemodynamic and clinical outcomes in patients with combined pre-and post-capillary pulmonary hypertension(CpcPH).This study aimed to assess the 3-year clinical results of PADN in patients who had heart failure with preserved ejection fraction(HFpEF)developing into CpcPH(HFpEF-CpcPH).Methods:In this post hoc analysis of the PADN-5 trial,38 patients with HFpEF were included in screening out of 98 patients with CpcPH who were randomly assigned to treatment with sildenafil and sham PADN(sham PADN(plus sildenafil)group,abbreviated as sham group)or PADN(PADN group).HFpEF in the PADN-5 trial was defined as a left ventricular ejection fraction≥50%,and CpcPH was defined as a mean pulmonary arterial pressure≥25 mmHg,a pulmonary arterial wedge pressure>15 mmHg,and a pulmonary vascular resistance>3.0 WU.The changes in the 6-minute walk distance(6-MWD)and the plasma concentration of N-terminal pro-brain natriuretic peptide(NT-proBNP)at 6-month and 3-year follow-up,as well as the clinical endpoint of the occurrence of clinical worsening,defined as cardiopulmonary-related death,rehospitalization,or heart or lung transplantation at 3-year follow-up were examined.Results:Thirty-eight patients with HFpEF-CpcPH were assigned to the PADN group(n=19)or the sham group(n=19).At the 6-month follow-up,6-MWD(433(275,580)m vs.342(161,552)m),and reductions in NT-proBNP(−47%(−99%,331%)vs.−12%(−82%,54%))were significantly improved in the PADN group(all P<0.05).Over the 3-year follow-up period,PADN treatment resulted in marked increases in 6-MWD(450(186,510)m vs.348(135,435)m)and reductions in NT-proBNP(−55%(−99%,38%)vs.−10%(−80%,95%))(all P<0.05).Clinical worsening was experienced by 12 patients(63%)in the sham group,but by only 5 patients(26%)in the PADN group(hazard ratio=0.149,95%confidence interval:0.038–0.584,P=0.006).The 6-MWD and PADN treatments were independent predictors of clinical deterioration in patients with HFpEF-CpcPH.Conclusions:PADN therapy is associated with improvements in exercise capacity and clinical outcomes.PADN therapy may have a potential role in patients with HFpEF-CpcPH for whom current treatment options are limited.

Obstructive Sleep Apnea Affecting Platelet Reactivity in Patients Undergoing Percutaneous Coronary Intervention

Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.Methods：A total of 242 patients were finally included in the study.OSA was screened overnight by polysomnography.Platelet reactivity was assessed with a sequential platelet counting method,and the platelet maximum aggregation ratio （MAR） and average aggregation ratio were calculated.All patients were assigned per apnea-hypopnea index （AHI） to non-OSA （n =128） and OSA （n =l 14） groups.The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity （HPR） on aspirin and clopidogrel,and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.Results：Median AHI was significantly higher in the OSA group than in the non-OSA group （34.5 events/h vs.8.1 events/h,Z =-13.422,P 〈 0.001）.Likewise,median arachidonic acid-and adenosine diphosphate-induced maximum aggregation rate （MAR） in the OSA group was significantly higher than those in the non-OSA group （21.1% vs.17.7%,Z=-3.525,P 〈 0.001 and 45.8% vs.32.2%,Z =-5.708,P 〈 0.001,respectively）.Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin （odds ratio [OR]：1.055,95% confidence interval [CI]：1.033-1.077,P 〈 0.001） and clopidogrel （OR：1.036,95% CI：1.017-1.056,P 〈 0.001）.The cutoffvalue of AHI for HPR on aspirin was 45.2 events/h （sensitivity 47.1% and specificity 91.3%）,whereas cutoffvalue of AHI for HPR on clopidogrel was 21.3 events/h （sensitivity 68.3% and specificity 67.7%）.

The Response Difference of Mitochondria in Recalcitrant Antiaris toxicaria Axes and Orthodox Zea mays Embryos to Dehydration Injury

Long-term preservation of recalcitrant seeds is very difficult because the physiological basis on their desiccation sensitivity is poorly understood. Survival of Antiaris toxicaria axes rapidly decreased and that of immature maize embryos very slowly decreased with dehydration. To understand their different responses to dehydration, we examined the changes in mitochondria activity during dehydration. Although activities of cytochrome （Cyt） c oxidase and malate dehydrogenase of the A. toxicaria axis and maize embryo mitochondria decreased with dehydration, the parameters of maize embryo mitochondria were much higher than those of A. toxicaria, showing that the damage was more severe for the A. toxicaria axis mitochondria than for those of maize embryo. The state I and III respiration of the A. toxicaria axis mitochondria were higher than those of maize embryo, the former rapidly decreased, and the latter slowly decreased with dehydration. The proportion of Cyt c pathway to state III respiration for the A. toxicaria axis mitochondria was low and rapidly decreased with dehydration, and the proportion of alternative oxidase pathway was high and slightly increased with dehydration. In contrast, the proportion of Cyt c pathway for maize embryo mitochondria was high, and that of alternative oxidase pathway was low. Both pathways decreased slowly with dehydration.

Impact of Side Branch Lesion Length on Clinical Outcome after Coronary Stenting Techniques in Patients with Coronary Artery Bifurcation Disease:A Meta-Analysis

Objective:The optimal percutaneous coronary intervention(PCI)technique for bifurcation lesions remains controversial,especially considering the variability of the side branch(SB).A provisional stenting technique is currently recommended in most cases.This meta-analysis aimed to compare outcomes of different bifurcation PCI strategies,clarifying their scope of application.Methods:Randomized controlled trials comparing PCI strategies for coronary bifurcation lesions were systematically retrieved from PubMed,Cochrane,Web of Science,and EBSCO literature databases without limitations on published date or language.Major adverse cardiovascular events(MACEs)were stipulated as main outcomes.Secondary outcomes of interest were all-cause mortality,cardiovascular mortality,target lesion revascularization(TLR),target vessel revascularization,myocardial infarction(MI),and stent thrombosis.Both pooled analysis and sub-group analysis were performed.Results:Twenty-three randomized controlled trials with 6380 participants were included.Eighteen studies compared the provisional strategy with 2-stent approaches.No significant difference in MACEs(relative risk(RR),1.16;95%confidence interval(CI),0.90-1.48;I2=62%)was found between 1-stent and 2-stent techniques.However,when SB lesion length was used as the separation condition,the 2-stent strategy was associated with fewer MACEs(RR,1.87;95%CI,1.46-2.41;I2=70%),TLRs(RR,2.13;95%CI,1.50-3.02;I2=59%),and MIs(RR,2.17;95%CI,1.19-3.95;I2=52%)than the provisional strategy in those where SB lesions measured>10 mm long.Conclusions:In the current work,there was no significant difference between 1-stent and 2-stent techniques in terms of MACEs or secondary outcomes.However,2-stent approaches have clinical advantages over the provisional strategy in bifurcation when the SB lesion length is>10 mm due to fewer cases of TLR and MI.

A novel angiography-based computational modelling for assessing the dynamic stress and quantitative fatigue fracture risk of the coronary stents immediately after implantation: Effects of stent materials, designs and target vessel motions

Fluctuating stress on the implanted coronary stents within cardiac cycle is an important mechanism of fatigue fracture,which is associated with in-stent restenosis and stent thrombosis.We developed a novel computational modelling to calculate the dynamic stress of stents based on the time sequence angiography immediately after treatment.Two groups of patient-specific cases(one same stent design treated in 4 different coronary arteries and one same artery actually/virtually implanted one stent with 3 different designs)were performed the dynamic stress analysis by this computational modelling and subsequently assessed the fatigue fracture risk by Goodman method.The motion of target arteries significantly impacts on distribution of the stress and the risk of stent fracture,particularly in the site of hinge motion.Both the location of stent stress concentration in the obtuse marginal artery and the“unsafe”region in the inverse fatigue safety factor contour co-registered with the position of complete transverse fracture 13 months later after implantation.Three stents with different designs had the same location of highest stress concentration at the hinge motion site of the actually/virtually treated artery.Higher strength stent materials are significantly lower the risk of stent fracture rather than stent designs.This new computational modelling might be a useful tool in assessment of fracture risk of the implanted stent and in optimizing new design of dedicated stent treated specific coronary arteries and mechanical properties in vivo of bioresorbable scaffold during degradation process.

A New Coronavirus Estimation Global Score for Predicting Mortality During Hospitalization in Patients with COVID-19

Objective:Coronavirus disease 2019(COVID-19)exists as a pandemic.Mortality during hospitalization is multifactorial,and there is urgent need for a risk stratification model to predict in-hospital death among COVID-19 patients.Here we aimed to construct a risk score system for early identification of COVID-19 patients at high probability of dying during in-hospital treatment.Methods:In this retrospective analysis,a total of 821 confirmed COVID-19 patients from 3 centers were assigned to developmental(n=411,between January 14,2020 and February 11,2020)and validation(n=410,between February 14,2020 and March 13,2020)groups.Based on demographic,symptomatic,and laboratory variables,a new Coronavirus estimation global(CORE-G)score for prediction of in-hospital death was established from the developmental group,and its performance was then evaluated in the validation group.Results:The CORE-G score consisted of 18 variables(5 demographics,2 symptoms,and 11 laboratory measurements)with a sum of 69.5 points.Goodness-of-fit tests indicated that the model performed well in the developmental group(H=3.210,P=0.880),and it was well validated in the validation group(H=6.948,P=0.542).The areas under the receiver operating characteristic curves were 0.955 in the developmental group(sensitivity,94.1%;specificity,83.4%)and 0.937 in the validation group(sensitivity,87.2%;specificity,84.2%).The mortality rate was not significantly different between the developmental(n=85,20.7%)and validation(n=94,22.9%,P=0.608)groups.Conclusions:The CORE-G score provides an estimate of the risk of in-hospital death.This is the first step toward the clinical use of the CORE-G score for predicting outcome in COVID-19 patients.

Antiviral Abidol is Associated with the Reduction of In-Hospital Mortality in COVID-19 Patients

Objective:Coronavirus disease 2019(COVID-19)is a global public health crisis.There are no specific antiviral agents for the treatment of SARS-CoV-2.Information regarding the effect of Abidol on in-hospital mortality is scarce.The present study aimed to evaluate the treatment effect of Abidol for patients with COVID-19 before and after propensity score matching(PSM).Methods:This retrospective cohort study analyzed 1019 patients with confirmed COVID-19 in China from December 22,2019 to March 13,2020.Patients were divided to Abidol(200mg,tid,5-7days,n=788,77.3%)and No-Abidol(n=231,22.7%)groups.The primary outcome was the mortality during hospitalization.Results:Among 1019 COVID-19 patients,the age was(60.4±14.5)years.Abidol-treated patients,compared with No-Abidoltreated patients,had a shorter duration from onset of symptoms to admission,less frequent renal dysfunction,lower white blood cell counts(lymphocytes<0.8)and erythrocyte sending rate,lower interleukin-6,higher platelet counts and plasma IgG and oxygen saturation,and less frequent myocardial injury.The mortality during hospitalization before PSM was 17.9% in Abidol group and 34.6% in No-Abidol(hazard ratio(HR)=2.610,95% confident interval(CI):1.980–3.440),all seen in severe and critical patients.After PSM,the in-hospital death was 13.6% in Abidol and 28.6% in No-Abidol group(HR=2.728,95%CI:1.598–4.659).Conclusions:Abidol-treatment results in less in-hospital death for severe and critical patients with COVID-19.Further randomized study is warranted to confirm the findings from this study.