Current knowledge for the risk factors of early permanent pacemaker implantation following transcatheter aortic valve replacement and what is next for the primary prevention?

In this editorial,we comprehensively summarized the preoperative risk factors of early permanent pacemaker implantation after transcatheter aortic valve replacement(TAVR)among patients with severe aortic stenosis from several renowned clinical studies and focused on the primary prevention of managing the modifiable factors,e.g.,paroxysmal atrial fibrillation before the TAVR.

Beyond the Usual Suspects (Aortic Dissection in Patients with Chronic Kidney Disease)

A comprehensive differential diagnosis is essential in the emergency department, even when patient presentations are atypical. Timely recognition of life-threatening conditions, such as aortic dissection, hinges on this critical diagnostic approach.

Is primary transcatheter aortic valve implantation the new normal?

Degenerative calcific aortic valve stenosis(AS)is the most common valvular heart disease in elderly.^[1] It is well documented that symptomatic severe AS follows a malignant course leading to cardiogenic shock(CS).

Animal Model of Aortic Valve Calcification: Their Methodology Helps Us Understand Aortic Valve Calcification

Aortic valve calcification disease (CAVD) is the most prevalent degenerative valve disease in humans, leading to significant morbidity and mortality. Despite its common occurrence, our understanding of the underlying mechanisms remains incomplete, and available treatment options are limited and risky. A more comprehensive understanding of the biology of CAVD is essential to identify new therapeutic strategies. Animal models have played a crucial role in advancing our knowledge of CAVD and exploring potential treatments. However, these models have inherent limitations as they cannot fully replicate the complex physiological mechanisms of human CAVD. In this review, we examine various CAVD models ranging from pigs to mice, highlighting the unique characteristics of each model to enhance our understanding of CAVD. While these models offer valuable insights, they also have limitations and shortcomings. We propose that the guide wire model shows promise for future CAVD research, and streamlining the methodology could enhance our understanding and expand the research scope in this field.

Trans-Frame Aortic Regurgitation of New-Generation Aortic Bioprosthesis

A widely used aortic valve bioprosthesis is susceptible to regurgitation between the sewing ring and the frame of the valve due to its relatively thin fabric coverage. In some cases this leak has been shown to resolve with administration of protamine, however, tension on this area from annular sutures placed in an asymmetric bicuspid valve annulus may exacerbate the defect.

Transcatheter aortic valve replacement in low-risk young population:A double edge sword?

Since the advent of transcatheter aortic valve replacement(TAVR)in 2002,it has now become the default interventional strategy for symptomatic patients presenting with severe aortic stenosis,particularly in intermediate to highsurgical risk patients.In 2019,the United States Food and Drug Administration approved TAVR in low-risk patients based on two randomized trials.However,these breakthrough trials excluded patients with certain unfavorable anatomies and odd profiles.While currently there is no randomized study of TAVR in young patients,it may be preferred by the young population given the benefits of early discharge,shorter hospital stay,and expedite recovery.Nonetheless,it is important to ruminate various factors including lifetime expectancy,risk of pacemaker implantation,and the need for future valve or coronary interventions in young cohorts before considering TAVR in these patients.Furthermore,the data on long-term durability(>10 years)of TAVR is still unknown given most of the procedures were initially performed in the high or prohibitive surgical risk population.Thus,this editorial aims to highlight the importance of considering an individualized approach in young patients with consideration of various factors including lifetime expectancy while choosing TAVR against surgical aortic valve replacement.

Carotid versus axillary artery cannulation for descending aorta remodeling in type A acute aortic dissection

BACKGROUND Arterial cannulation sites for the surgical repair of type A aortic dissection(AAD)have evolved from right axillary artery(AA)cannulation to bilateral carotid artery(CA)based of femoral artery(FA)cannulation.Postoperative descending aorta remodeling is closely linked to the false lumen area ratio(FLAR),defined as false lumen area/aortic area,as well as to the incidence of renal replacement therapy(RRT).AIM To investigate the effect of the updated arterial cannulation strategy on descending aortic remodeling.METHODS A total of 443 AAD patients who received FA combined cannulation between March 2015 and March 2023 were included in the study.Of these,209 received right AA cannulation and 234 received bilateral CA cannulation.The primary outcome was the change in FLAR,as calculated from computed tomography angiography in three segments of the descending aorta:Thoracic(S1),upper abdominal(S2),and lower abdominal(S3).Secondary outcomes were the incidence of RRT and the serum inflammation response,as observed by the levels of high sensitivity C reaction protein(hs-CRP)and Interleukin-6(IL-6).RESULTS The postoperative/preoperative ratio of FLAR in S2 and S3 was higher in the AA group compared to the CA group(S2:0.80±0.08 vs 0.75±0.07,P<0.001;S3:0.57±0.12 vs 0.50±0.12,P<0.001,respectively).The AA group also had a significantly higher incidence of RRT(19.1%vs 8.5%,P=0.001;odds ratio:2.533,95%CI:1.427-4.493)and higher levels of inflammation cytokines 24 h after the procedure[hr-CRP:117±17 vs 104±15 mg/L;IL-6:129(103,166)vs 83(69,101)pg/mL;both P<0.001]compared to the CA group.CONCLUSION The CA cannulation strategy was associated with better abdominal aorta remodeling after AAD repair compared to AA cannulation,as observed by a greater change in FLAR and lower incidence of RRT.

The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

Intimal hyperplasia(IH)is a negative vascular remodeling after arterial injury.IH occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse models.This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA models.The IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were analyzed.Among 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant difference.Both mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH lesions.There was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe IH.However,only a lower numbers of T cells and B cells were found in the IH lesion.Local cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe lesions.In conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA model.This will help researchers better understand this model,and optimize it for use in AAA-related research.

Application of multi-planar reconstruction technique in endovascular repair of aortic dissection

BACKGROUND Endovascular repair of aortic dissection is an effective method commonly used in the treatment of Stanford type B aortic dissection.Stent placement during the operation was one-time and could not be repeatedly adjusted during the operation.Therefore,it is of great significance for cardiovascular physicians to fully understand the branch status,position,angle,and other information regarding aortic arch dissection before surgery.AIM To provide more references for clinical cardiovascular physicians to develop treatment plans.METHODS Data from 153 patients who underwent endovascular repair of aortic dissection at our hospital between January 2021 and December 2022 were retrospectively collected.All patients underwent multi-slice spiral computed tomography angiography.Based on distinct post-image processing techniques,the patients were categorized into three groups:Multiplanar reconstruction(MPR)(n=55),volume reconstruction(VR)(n=46),and maximum intensity projection(MIP)(n=52).The detection rate of aortic rupture,accuracy of the DeBakey classification,rotation,and tilt angles of the C-arm during the procedure,dispersion after stent release,and the incidence of late complications were recorded and compared.RESULTS The detection rates of interlayer rupture in the MPR and VR groups were significantly higher than that in the MIP group(P<0.05).The detection rates of De-Bakey subtypesⅠ,Ⅱ,andⅢin the MPR group were higher than those in the MIP group,and the detection rate of typeⅢin the MPR group was significantly higher than that in the VR group(P<0.05).There was no statistically significant difference in the detection rates of typesⅠandⅡcompared to the VR group(P>0.05).The scatter rate of markers and the incidence of complications in the MPR group were significantly lower than those in the VR and MIP groups(P<0.05).CONCLUSION The application of MPR in the endovascular repair of aortic dissection has improved the detection rate of dissection rupture,the accuracy of anatomical classification,and safety.

Cases Report of Atypical Aortic Dissection

Background: Aortic dissection (AD) is one of the common causes of fatal chest pain in emergency medicine. The main and most common clinical manifestation is pain, with about 90% of patients experiencing sudden persistent, tearing or cutting-like pain in the chest or back. However, there have also been reports of myocardial infarction, heart failure, renal failure, syncope, shock, stroke, paraplegia and other cases. Clinical misdiagnosis is common. Aim: Alert clinicians to aortic dissection with shock and chest tightness as the main clinical presentations. Case Presentation: Report on two cases of aortic dissection with syncope and shock as the main manifestations. Conclusion: Aortic dissection is a highly dangerous cardiovascular emergency with a high mortality rate. In clinical practice, awareness of the clinical manifestations of aortic dissection should be increased. Careful inquiry about medical history, attention to atypical clinical presentations of aortic dissection, thorough physical examination, and comprehensive diagnostic evaluation can improve the success rate of diagnosing aortic dissection.

Causal Relationship between Chronic Obstructive Pulmonary Disease and Abdominal Aortic Aneurysm: A Mendelian Randomization Study

Background: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory lung condition associated with significant morbidity and mortality. Observational studies indicate a positive correlation between COPD and the risk of abdominal aortic aneurysm (AAA), suggesting individuals with COPD are more likely to develop AAA. However, the causal relationship between COPD and AAA remains unclear. Method: This study employed a bidirectional Mendelian Randomization (MR) approach to assess the causal relationship between COPD and AAA. A two-step MR analysis was conducted to evaluate the mediating effect of 1400 circulating metabolites between COPD and AAA. Expression quantitative trait loci (eQTL) were sourced from the MRC Integrative Epidemiology Unit (MRC-IEU) database, and MR analysis was performed using the TwoSampleMR R package. The results were filtered using the Inverse Variance Weighted (IVW) method to identify genes strongly associated with both COPD and AAA. Furthermore, the Super Exact Test R package was utilized to determine the overlapping genes between COPD and AAA. Enrichment analysis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was conducted using the clusterProfiler R package. Protein-protein interaction (PPI) analysis was carried out using STRING v12.0. Results: The IVW method indicated a causal relationship between the risk increase of COPD and AAA (OR: 1.47, 95% CI: 1.16 - 1.86, p = 0.001). Among 1400 circulating metabolites, plasma-free proline was identified as mediating the relationship between COPD and AAA, with a mediation effect proportion of −4.6% (95% CI: −9.032%, −0.164%, p = 0.042). Additionally, PPI analysis revealed 20 functionally interrelated genes mediating the linkage between COPD and AAA. KEGG enrichment analysis showed functional enrichment of these genes in the pathway of aldosterone synthesis and secretion. Conclusion: Our study supports a causal relationship between COPD and an increased risk of AAA. Specifically, plasma-free proline and pathways related to aldosterone synthesis and secretion may play key roles in the connection between COPD and AAA.

Bicuspidization Using the Open-Sleeve Technique for Congenital Aortic Stenosis during Infancy

Congenital aortic stenosis(cAS)frequently requires intervention during the neonatal or infantile period.However,surgical repair is challenging because of the narrow surgical space.We performed bicuspidization using the open-sleeve technique for cAS with a unicuspid aortic valve in two patients.Postoperatively,the patients were doing well without reintervention for the aortic valve for 8 and 6 years,respectively.Their aortic annular diameter increased along with somatic growth.Bicuspidization for neonates or infancy can be performed safely using the open-sleeve technique as its midterm results have been satisfactory.

A novel mouse model of calcific aortic valve stenosis

Background:Calcific aortic valve stenosis(CAVS)is one of the most challenging heart diseases in clinical with rapidly increasing prevalence.However,study of the mecha-nism and treatment of CAVS is hampered by the lack of suitable,robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposi-tion.Here,we aim to establish a mouse model to mimic the development and features of CAVS.Methods:The model was established via aortic valve wire injury(AVWI)combined with vitamin D subcutaneous injected in wild type C57/BL6 mice.Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradi-ent.Histopathological specimens were collected and examined in respect of valve thickening,calcium deposition,collagen accumulation,osteogenic differentiation and inflammation.Results:Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time depend-ent manner and tended to be stable at 28 days.Compared with the sham group,sim-ple AVWI or the vitamin D group,the hybrid model group showed typical pathological features of CAVS,including hemodynamic alterations,increased aortic valve thicken-ing,calcium deposition,collagen accumulation at 28 days.In addition,osteogenic dif-ferentiation,fibrosis and inflammation,which play critical roles in the development of CAVS,were observed in the hybrid model.Conclusions:We established a novel mouse model of CAVS that could be induced efficiently,robustly and economically,and without genetic intervention.It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effec-tive pharmacological targets.

Impact of D-dimer on in-hospital mortality following aortic dissection:A systematic review and meta-analysis

BACKGROUND The utility of D-dimer(DD)as a biomarker for acute aortic dissection(AD)is recognized.Yet,its predictive value for in-hospital mortality remains uncertain and subject to conflicting evidence.AIM To conduct a meta-analysis of AD-related in-hospital mortality(ADIM)with elevated DD levels.METHODS We searched PubMed,Scopus,Embase,and Google Scholar for AD and ADIM literature through May 2022.Heterogeneity was assessed using I2 statistics and effect size(hazard or odds ratio)analysis with random-effects models.Sample size,study type,and patients’mean age were used for subgroup analysis.The significance threshold was P<0.05.RESULTS Thirteen studies(3628 patients)were included in our study.The pooled prevalence of ADIM was 20%(95%CI:15%-25%).Despite comparable demographic characteristics and comorbidities,elevated DD values were associated with higher ADIM risk(unadjusted effect size:1.94,95%CI:1.34-2.8;adjusted effect size:1.12,95%CI:1.05-1.19,P<0.01).Studies involving patients with a mean age of<60 years exhibited an increased mortality risk(effect size:1.43,95%CI:1.23-1.67,P<0.01),whereas no significant difference was observed in studies with a mean age>60 years.Prospective and larger sample size studies(n>250)demonstrated a heightened likelihood of ADIM associated with elevated DD levels(effect size:2.57,95%CI:1.30-5.08,P<0.01 vs effect size:1.05,95%CI:1.00-1.11,P=0.05,respectively).CONCLUSION Our meta-analysis shows elevated DD increases in-hospital mortality risk in AD patients,highlighting the need for larger,prospective studies to improve risk prediction models.

Patient-specific bicuspid aortic valve hemodynamics study based on computer simulation and in vitro experiment

Bicuspid aortic valve(BAV)is a common congenital malformation of the aortic valve with various structural characteristics.Different types of BAV can cause secondary aortic diseases,including calcific aortic valve stenosis and aortic dilation,although their pathogenesis remains unclear.In this study,we first established patient-specific BAV simulation models and silicone models(Type 0 A-P,Type 1 R-N,and Type 1 L-R)based on clinical computed tomography angiography(CTA)and pressure data.Next,we applied a research method combining fluid-structure interaction(FSI)simulation and digital particle image velocimetry(DPIV)experiment to quantitatively analyze the hemodynamic,structural mechanical,and flow field characteristics of patients with different BAV types.Simulation-based hemodynamic parameters and experimental results were consistent with clinical data,affirming the accuracy of the model.The location of the maximum principal strain in the patientspecific model was associated with the calcification site,which characterized the mechanism of secondary aortic valve stenosis.The maximum wall shear stress(WSS)of the patient-specific model(>67.1 Pa)exceeded 37.9 Pa and could cause endothelial surface injury as well as remodeling under long-term exposure,thus increasing the risk of aortic dilation.The distribution of WSS was mainly caused by BAV type,resulting in different degrees of dilation in different parts guided by the type.The patient-specific model revealed a maximum viscous shear stress(VSS)value of 5.23 Pa,which was smaller than the threshold for shear-induced hemolysis of red blood cells(150 Pa)and platelet activation(10 Pa),but close to the threshold for platelet sensitization(6 Pa).The results of flow field characteristics revealed a low risk of hemolysis but a relative high risk of thrombus formation in the patient-specific model.This study not only provides a basis for future comprehensive research on BAV diseases,but also generates relevant insights for theoretical guidance for calcific aortic valve stenosis and aortic dilation caused by different types of BAV,as well as biomechanical evidence for the potential risk of hemolysis and thrombus formation in BAV,which is of great value for clinical diagnosis and treatment of BAV.

Prospective Cohort Research of Aortic Root Dilatation after Surgical Repair in Adults with Tetralogy of Fallot(TRANSIT)

Background:Aortic root dilatation occurs in adults with tetralogy of Fallot(TOF)after surgical repair,but the longitudinal changes are unclear.The main research aim is to determine the annual dilatation rate of aorta in adults with repaired TOF.Methods:The present,multicentric,prospective cohort study assessed the rate of aortic diameter change in adults aged 20 years or older with TOF,including pulmonary artery atresia,who underwent surgical repair.Clinical data,focusing on echocardiograms,were collected at three-year intervals from seven hos-pitals.Results:In total,104 patients(58 males;median age:29 years)were enrolled.The actual Valsalva sinus(VS)diameter was 34.3±5.8(mean±standard deviation)and 36.1±6.0 mm at the initial andfinal examinations,respectively,and the annual dilatation rate was 0.64(0.07,1.33)(median,interquartile)mm/year.The corrected diameter at the respective examination was 21.3±3.8 and 22.2±3.7 mm/m^(2),and the annual dilation rate was 0.28(-0.21,0.76)mm/m^(2)/year.Multiple regression analysis showed that factors significant associated with dila-tation rate of actual VS diameter were the diastolic blood pressure(standardized coefficient-0.22;p=0.04),cardiothoracic ratio(0.28;0.02),and the ratio of early mitral valve inflow velocity to early diastolic annular velocity(E/e′)ratio(0.31;0.004).Factors significantly associated with corrected VS diameter were diastolic blood pressure(-0.25;0.02)and the E/e′ratio(0.34;0.001).Conclusions:In adults with repaired TOF,the rate of dilatation of the aortic diameter was associated with decreased diastolic blood pressure and left ventricular diastolic dysfunction,possibly reflecting decreased aortic wall elasticity.

Isogeometric Analysis of Hyperelastic Material Characteristics for Calcified Aortic Valve

This study explores the implementation of computed tomography(CT)reconstruction and simulation techniques for patient-specific valves,aiming to dissect the mechanical attributes of calcified valves within transcatheter heart valve replacement(TAVR)procedures.In order to facilitate this exploration,it derives pertinent formulas for 3D multi-material isogeometric hyperelastic analysis based on Hounsfield unit(HU)values,thereby unlocking foundational capabilities for isogeometric analysis in calcified aortic valves.A series of uniaxial and biaxial tensile tests is executed to obtain an accurate constitutive model for calcified active valves.To mitigate discretization errors,methodologies for reconstructing volumetric parametric models,integrating both geometric and material attributes,are introduced.Applying these analytical formulas,constitutive models,and precise analytical models to isogeometric analyses of calcified valves,the research ascertains their close alignment with experimental results through the close fit in displacement-stress curves,compellingly validating the accuracy and reliability of the method.This study presents a step-by-step approach to analyzing themechanical characteristics of patient-specific valves obtained fromCT images,holding significant clinical implications and assisting in the selection of treatment strategies and surgical intervention approaches in TAVR procedures.

Rates, predictors, and causes of readmission after transcatheter aortic valve replacement in patients with chronic kidney disease

BACKGROUND Transcatheter aortic valve replacement(TAVR)is a revolutionary procedure for severe aortic stenosis.The coexistence of chronic kidney disease(CKD)and TAVR introduces a challenge that significantly impacts patient outcomes.AIM To define readmission rates,predictors,and causes after TAVR procedure in CKD stage 1-4 patients.METHODS We used the national readmission database 2018 and 2020 to look into readmission rates,causes and predictors after TAVR procedure in patients with CKD stage 1-4.RESULTS Out of 24758 who underwent TAVR and had CKD,7892(32.4%)patients were readmitted within 90 days,and had higher adjusted odds of being females(adjusted odds ratio:1.17,95%CI:1.02-1.31,P=0.02)with longer length of hospital stay>6 days,and more comorbidities including but not limited to diabetes mellitus,anemia,and congestive heart failure(CHF).CONCLUSION Most common causes of readmission included CHF(18.0%),sepsis,and complete atrioventricular block.Controlling readmission predictors with very close followup is warranted to prevent such high rate of readmission.

Risk of permanent pacemaker implantation following transcatheter aortic valve replacement:Which factors are most relevant?

Transcatheter aortic valve replacement(TAVR)has emerged as a formidable treatment option for severe symptomatic aortic stenosis ahead of surgical aortic valve replacement.The encouraging results from large randomized controlled trials has resulted in an exponential rise in the use of TAVR even in the low-risk patients.However,this is not without challenges.Need for permanent pacemaker(PPM)post-TAVR remains the most frequent and clinically relevant challenge.Naturally,identifying risk factors which predispose an individual to develop high grade conduction block post-TAVR is important.Various demographic factors,electrocardiographic features,anatomic factors and procedural characteristics have all been linked to the development of advanced conduction block and need for PPM following TAVR.Amongst these electrophysiological variables,most notably a prolonged QRS>120 ms regardless of the type of conduction block seems to be one of the strongest predictors on logistic regression models.The index study by Nwaedozie et al highlights that patients requiring PPM post-TAVR had higher odds of having a baseline QRS>120 ms and were more likely to be having diabetes mellitus that those who did not require PPM.

Predictors of permanent pacemaker implantation following transcatheter aortic valve replacement-the search is still on!

Several anatomical,demographic,clinical,electrocardiographic,procedural,and valve-related variables can be used to predict the probability of developing con-duction abnormalities after transcatheter aortic valve replacement(TAVR)that necessitate permanent pacemaker(PPM)implantation.These variables include calcifications around the device landing zone and in the mitral annulus;pre-existing electrocardiographic abnormalities such as left and right bundle branch blocks(BBB),first-and second-degree atrioventricular blocks,as well as bifas-cicular and trifascicular blocks;male sex;diabetes mellitus(DM);hypertension;history of atrial fibrillation;renal failure;dementia;and use of self-expanding valves.The current study supports existing literature by demonstrating that type 2 DM and baseline right BBB are significant predictors of PPM implantation post-TAVR.Regardless of the side of the BBB,this study demonstrated,for the first time,a linear association between the incidence of PPM implantation post-TAVR and every 20 ms increase in baseline QRS duration(above 100 ms).After a 1-year follow-up,patients who received PPM post-TAVR had a higher rate of hospital-ization for heart failure and nonfatal myocardial infarction.