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.

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.

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.

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.

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.

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.

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.

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.

Pacemaker post transcatheter aortic valve replacement:A multifactorial risk?

Pacemaker post-transcatheter aortic valve replacement is related to multifactorial risk.Nwaedozie et al brought to the body of evidence electrocardiogram and clinical findings.However,procedural characteristics have at least as much impact on the final need for a permanent pacemaker and potentially on the pacing rate.In this regard,long-term follow-up and understanding of the impact of long-term stimulation is of utmost importance.

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.

A Rare Case of Aortic Valve Endocarditis and Acute Meningitis Due to Haemophilus influenzae

HACEK organisms represent a rare but important group of causative pathogens in endocarditis. These bacteria have historically been associated with culture-negative endocarditis;however, modern laboratory techniques have made this less common. In this case, we present a 74-year-old man who presented with acute onset altered mentation, fever, and sepsis. He was ultimately found to have Haemophilus influenzae meningitis, cerebral empyema, aortic valve endocarditis, psoas myositis, and L2 - L3 diskitis with osteomyelitis. Although HACEK organisms are commonly found in the oropharynx and upper respiratory tract in humans, our patient did not report recent preceding dental or ENT procedures. H. influenzae is responsible for approximately 0.16% of all cases of bacterial endocarditis, representing a very limited subset. Although generally considered low virulent pathogens, this case demonstrates the unusual extent of infection from a HACEK organism, H. influenzae, causing aortic valve endocarditis as well as atypical non-cardiac sequelae, including acute meningitis.

Novel predictors of permanent pacemaker implantation following transcatheter aortic valve replacement

BACKGROUND Conduction and rhythm abnormalities requiring permanent pacemakers(PPM)are short-term complications following transcatheter aortic valve replacement(TAVR),and their clinical outcomes remain conflicting.Potential novel predictors of post-TAVR PPM,like QRS duration,QTc prolongation,and supraventricular arrhythmias,have been poorly studied.AIM To evaluate the effects of baseline nonspecific interventricular conduction delay and supraventricular arrhythmia on post-TAVR PPM requirement and determine the impact of PPM implantation on clinical outcomes.METHODS RESULTS Out of the 357 patients that met inclusion criteria,the mean age was 80 years,188(52.7%)were male,and 57(16%)had a PPM implantation.Baseline demographics,valve type,and cardiovascular risk factors were similar except for type II diabetes mellitus(DM),which was more prevalent in the PPM cohort(59.6%vs 40.7%;P=0.009).The PPM cohort had a significantly higher rate of pre-procedure right bundle branch block,prolonged QRS>120 ms,prolonged QTc>470 ms,and supraventricular arrhythmias.There was a consistently significant increase in the odds ratio(OR)of PPM implantation for every 20 ms increase in the QRS duration above 100 ms:QRS 101-120[OR:2.44;confidence intervals(CI):1.14-5.25;P=0.022],QRS 121-140(OR:3.25;CI:1.32-7.98;P=0.010),QRS 141-160(OR:6.98;CI:3.10-15.61;P<0.001).After model adjustment for baseline risk factors,the OR remained significant for type II DM(aOR:2.16;CI:1.18-3.94;P=0.012),QRS>120(aOR:2.18;CI:1.02-4.66;P=0.045)and marginally significant for supraventricular arrhythmias(aOR:1.82;CI:0.97-3.42;P=0.062).The PPM cohort had a higher adjusted OR of heart failure(HF)hospitalization(aOR:2.2;CI:1.1-4.3;P=0.022)and nonfatal myocardial infarction(MI)(aOR:3.9;CI:1.1-14;P=0.031)without any difference in mortality(aOR:1.1;CI:0.5-2.7;P=0.796)at one year.CONCLUSION Pre-TAVR type II DM and QRS duration>120,regardless of the presence of bundle branch blocks,are predictors of post-TAVR PPM.At 1-year post-TAVR,patients with PPM have higher odds of HF hospitalization and MI.

Prediction of permanent pacemaker implantation after transcatheter aortic valve replacement:The role of machine learning

BACKGROUND Atrioventricular block requiring permanent pacemaker(PPM)implantation is an important complication of transcatheter aortic valve replacement(TAVR).Application of machine learning could potentially be used to predict preprocedural risk for PPM.AIM To apply machine learning to be used to predict pre-procedural risk for PPM.METHODS A retrospective study of 1200 patients who underwent TAVR(January 2014-December 2017)was performed.964 patients without prior PPM were included for a 30-d analysis and 657 patients without PPM requirement through 30 d were included for a 1-year analysis.After the exclusion of variables with near-zero variance or≥50%missing data,167 variables were included in the random forest gradient boosting algorithm(GBM)optimized using 5-fold cross-validations repeated 10 times.The receiver operator curve(ROC)for the GBM model and PPM risk score models were calculated to predict the risk of PPM at 30 d and 1 year.RESULTS Of 964 patients included in the 30-d analysis without prior PPM,19.6%required PPM post-TAVR.The mean age of patients was 80.9±8.7 years.42.1%were female.Of 657 patients included in the 1-year analysis,the mean age of the patients was 80.7±8.2.Of those,42.6%of patients were female and 26.7%required PPM at 1-year post-TAVR.The area under ROC to predict 30-d and 1-year risk of PPM for the GBM model(0.66 and 0.72)was superior to that of the PPM risk score(0.55 and 0.54)with a P value<0.001.CONCLUSION The GBM model has good discrimination and calibration in identifying patients at high risk of PPM post-TAVR.

Bicuspid aortic valve with associated aortopathy, significant left ventricular hypertrophy or concomitant hypertrophic cardiomyopathy: A diagnostic and therapeutic challenge

Due to its prevalence of 0.5%to 2%in the general population,with a 75%predominance among men,bicuspid aortic valve is the most common congenital heart defect.It is frequently accompanied by other cardiac congenital anomalies,and clinical presentation can vary significantly,with stenosis being the most common manifestation,often resulting in mild to moderate concentric hypertrophy of the left ventricle.Echocardiography is the primary diagnostic modality utilized for establishing the diagnosis,and it is often the sole diagnostic tool relied upon by clinicians.However,due to the heterogeneous clinical presentation and possible associated anomalies(which are often overlooked in clinical practice),it is necessary to employ various diagnostic methods and persist in finding the accurate diagnosis if multiple inconsistencies exist.By employing this approach,we can effectively manage these patients and provide them with appropriate treatment.Through a clinical case from our practice,we provide an overview of the literature on bicuspid aortic valve with aortophaty and the possible association with hypertrophic cardiomyopathy,diagnostic methods,and treatment options.This review article highlights the critical significance of achieving an accurate diagnosis in patients with bicuspid aortic valve and significant left ventricular hypertrophy.It is crucial to exclude other possible causes of left ventricular outflow tract obstruction,such as sub-or supra-aortic obstructions,and hypertrophic cardiomyopathy.

Importance of concomitant functional mitral regurgitation on survival in severe aortic stenosis patients undergoing aortic valve replacement

BACKGROUND Mitral regurgitation(MR)is commonly seen in patients with severe aortic stenosis(AS)undergoing aortic valve replacement(AVR).But the long-term implications of MR in AS are unknown.AIM To investigate MR’s impact on survival of patients undergoing surgical AVR for severe AS.METHODS Of the 740 consecutive patients with severe AS evaluated between 1993 and 2003,287 underwent AVR forming the study cohort.They were followed up to death or till the end of 2019.Chart reviews were performed for clinical,echocardiographic,and therapeutic data.MR was graded on a 1-4 scale.Mortality data was obtained from chart review and the Social Security Death Index.Survival was analyzed as a function of degree of MR.RESULTS The mean age of the severe AS patients who had AVR(n=287)was 72±13 years,46%women.Over up to 26 years of follow up,there were 201(70%)deaths,giving deep insights into the determinants of survival of severe AS who had AVR.The 5,10 and 20 years survival rates were 75%,45%and 25%respectively.Presence of MR was associated with higher mortality in a graded fashion(P=0.0003).MR was significantly associated with lower left ventricular(LV)ejection fraction and larger LV size.Impact of MR on mortality was partially mediated through lower LV ejection fraction and larger LV size.By Cox regression,MR,lower ejection fraction(EF)and larger LV end-systolic dimension were independent predictors of higher mortality(χ^(2)=33.2).CONCLUSION Presence of greater than 2+MR in patients with severe AS is independently associated with reduced survival in surgically managed patients,an effect incremental to reduced EF and larger LV size.We suggest that aortic valve intervention should be considered in severe AS patients when>2+MR occurs irrespective of EF or symptoms.

Machine Learning Prediction Models of Optimal Time for Aortic Valve Replacement in Asymptomatic Patients

Currently,the decision of aortic valve replacement surgery time for asymptomatic patients with moderate-to-severe aortic stenosis(AS)is made by healthcare professionals based on the patient’s clinical biometric records.A delay in surgical aortic valve replacement(SAVR)can potentially affect patients’quality of life.By using ML algorithms,this study aims to predict the optimal SAVR timing and determine the enhancement in moderate-to-severe AS patient survival following surgery.This study represents a novel approach that has the potential to improve decision-making and,ultimately,improve patient outcomes.We analyze data from 176 patients with moderate-to-severe aortic stenosis who had undergone or were indicated for SAVR.We divide the data into two groups:those who died within the first year after SAVR and those who survived for more than one year or were still alive at the last follow-up.We then use six different ML algorithms,Support Vector Machine(SVM),Classification and Regression Tree(C and R tree),Generalized Linear(GL),Chi-Square Automatic Interaction Detector(CHAID),Artificial Neural Net-work(ANN),and Linear Regression(LR),to generate predictions for the best timing for SAVR.The results showed that the SVM algorithm is the best model for predicting the optimal timing for SAVR and for predicting the post-surgery survival period.By optimizing the timing of SAVR surgery using the SVM algorithm,we observed a significant improvement in the survival period after SAVR.Our study demonstrates that ML algorithms generate reliable models for predicting the optimal timing of SAVR in asymptomatic patients with moderate-to-severe AS.

Emergency Hybrid Correction in a Newborn with Critical Aortic Valve Stenosis with Acute Pulmonary Edema in the First Hour after Birth

Critical aortic valve stenosis in newborns is the cause of a severe clinical condition with the onset of symptoms during first hours after birth.We present a clinical case of a successful surgical correction of a critical aortic stenosis using a hybrid method applied in a newborn during the first day of life.The infant was diagnosed with a hypoplastic left heart complex with an intact atrial septum(aortic and mitral valves stenosis variant),that led to the cardiogenic shock and acute pulmonary edema.The procedure included bilateral banding of the pulmonary artery branches and atrioseptostomy with stenting of the interatrial septum.The surgery was performed through a median sternotomy.

Unicuspid Aortic Valve, an Extremely Rare Congenital Anomaly in Adults: A Systemic Review

The most common congenital heart defect is the bicuspid aortic valve (BAV) occurring with fusion of one of the three-valve commissures. A rarer valvular phenomenon is the unicuspid aortic valve (UAV) which has an estimated prevalence of 0.02% in the adult population. Two morphologic subtypes of UAV exist: the earlier presenting, acommissural UAV and the later appearing unicommissural. To better characterize and manage patients with UAVs, a systematic review of this rare phenomenon was performed. The objective of our study was to conduct a systematic review of adequate case studies involving UAV patients to describe patient characteristics, clinical presentation, management, and common sequela featured there within. The mean age of presentation in this review was 35.6 years. When diagnosing UAV, TEE was the most utilized diagnostic modality (65%) followed by intraoperative diagnosis (17%) discovered with valve repair or incidentally during another procedure. TTE was utilized to diagnose only 7% of the cases reviewed likely owing to the difficulty and inaccuracies in identifying UAV with this method that were previously established by multiple series. Interventional options for UAV are balloon versus surgical valvotomy, aortic valve replacement, Ross procedure and aortic root replacement. They are performed on an individual basis and all cases ultimately require aortic valve replacement (AVR) or Ross procedure (to avoid anticoagulation). Aortic root replacement is additionally required if aortic root/ascending aorta diameter exceeds 4.5 cm. In this review, Aortic aneurysm (16%) cases resulted in surgical interventions. There may be a need to implant permanent pacemaker (in 3% - 8%) during AVR when calcified UAV has calcification extending into interventricular septum.

Delayed Coronary Ostial Stenosis after Surgical Aortic Valve Replacement and Root Enlargement Treated with Beating Heart On-Pump CABG

Coronary ostial stenosis after surgical aortic valve replacement (SAVR) is a rare but potentially fatal complication. Surgeons must have a high level of vigilance regarding the presentation of acute myocardial ischemia, arrhythmia, and heart failure after AVR. According to most reports, this event can be time-dependent divided into two groups;early acute phase that mostly happens intraoperative during weaning of CPB or in early ICU stay, and late presentation usually appears 1 - 6 months post surgery. Here, we describe an unusual subacute presentation of right coronary ostial stenosis 12 days after SAVR, which was treated successfully with redo beating heart coronary artery bypass grafting (CABG).