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.

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.

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.

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.

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.

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.

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.

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).

Transcatheter versus surgical aortic valve replacement in severe, symptomatic aortic stenosis

Aortic stenosis （AS） is the most common type of valvular heart disease in the elderly. Surgical aortic valve replacement （SAVR） has been the standard practice for treating severe, symptomatic AS, but recently new treatment options have emerged, Transcatheter aortic valve replacement （TAVR） is now an established treatment option in patients at high surgical risk. In this review, we focus on recent developments and compare the two treatment methods in specific populations in terms of efficacy and safety （e.g., in patients with history of prior thoracic surgery, type of anesthesia employed, access site used or need for permanent pacing）. The impact of comorbidities （pulmonary hypertension, arterial hypertension and obesity paradox）, the cost-effectiveness of TAVR vs. SAVR and advances in transcatheter valve technology as well as issues that merit further investigation are further discussed. Moreover, outcomes and complications of TAVR in patients of different risk category （extremely high, high, intermediate and low risk） are analyzed. We strongly believe that during the following years, TAVR may evolve as the treatment of choice in a broader group of patients with symptomatic AS and beyond those with intermediate and high-risk features.

Feasibility and clinical outcomes in nonagenarians undergoing transcatheter aortic valve replacement with the LOTUSTM valve

Surgical aortic valve replacement （AVR） is associated with very high peri-operative risk in the nonagenarian populationflI Patients with severe aortic stenosis treated conservatively have high rates of mortality with poor quality of life and loss of independence. Transcatheter aortic valve replacement （TAVR） has been validated in the high risk elderly population as a viable alternative to surgery with comparable outcomes.

Transcatheter aortic valve replacement and stroke： a comprehensive review

Transcatheter aortic valve implantation （TAVR） has emerged as an alternative, rapidly evolving treatment option for patients with se- vere aortic stenosis and high surgical risk. Stroke is a devastating complication being confined mainly in the periprocedural and 30-day pe- riod following TAVR, with a lower and relatively constant frequency thereafter. Early stroke is mainly due to debris embolization during the procedure, whereas later events are associated with patient specific factors. Despite the fact that the rate of clinical stroke has been constantly decreasing compared to initial TAVR experience, modern neuro-imaging with MRI suggests that new ischemic lesions post-TAVR are almost universal. The impact of the latter is largely unknown. However, they seem to correlate with a reduction in neurocognitive function. Because TAVR is set to expand its indication to lower surgical-risk patients, stroke prophylaxis during and after TAVR becomes of paramount importance. Based on clinical and pathophysiological evidence, three lines of research are actively employed towards this direction： improvement in valve and delivery system technology with an aim to reduce manipulations and contact with the calcified aortic arch and native valve, antithrombotic therapy, and embolic protection devices. Careful patient selection, design of the procedure, and tailored antithrombotic strategies respecting the bleeding risks of this fragile population constitute the main defense against stroke following TAVR.

Bioprosthetic Valve Size Selection to Optimize Aortic Valve ReplacementSurgical Outcome: A Fluid-Structure Interaction Modeling Study

Aortic valve replacement(AVR)remains a major treatment option for patients with severe aortic valve disease.Clinical outcome of AVR is strongly dependent on implanted prosthetic valve size.Fluid-structure interaction(FSI)aortic root models were constructed to investigate the effect of valve size on hemodynamics of the implanted bioprosthetic valve and optimize the outcome of AVR surgery.FSI models with 4 sizes of bioprosthetic valves(19(No.19),21(No.21),23(No.23)and 25 mm(No.25))were constructed.Left ventricle outflow track flow data from one patient was collected and used as model flow conditions.Anisotropic Mooney–Rivlin models were used to describe mechanical properties of aortic valve leaflets.Blood flow pressure,velocity,systolic valve orifice pressure gradient(SVOPG),systolic cross-valve pressure difference(SCVPD),geometric orifice area,and flow shear stresses from the four valve models were compared.Our results indicated that larger valves led to lower transvalvular pressure gradient,which is linked to better post AVR outcome.Peak SVOPG,mean SCVPD and maximum velocity for Valve No.25 were 48.17%,49.3%,and 44.60%lower than that from Valve No.19,respectively.Geometric orifice area from Valve No.25 was 52.03%higher than that from Valve No.19(1.87 cm2 vs.1.23 cm2).Implantation of larger valves can significantly reduce mean flow shear stress on valve leaflets.Our initial results suggested that larger valve size may lead to improved hemodynamic performance and valve cardiac function post AVR.More patient studies are needed to validate our findings.

Transcatheter aortic valve replacement in elderly patients

Aortic stenosis is the most common native valve disease, affecting up to 5% of the elderly population. Surgical aortic valve replacement reduces symptoms and improves survival, and is the definitive therapy in patients with symptomatic severe aortic stenosis. However, despite the good results of classic surgery, risk is markedly increased in elderly patients with co-morbidities. Transcatheter aortic valve replacement （TAVR） allows implantation of a prosthetic heart valve within the diseased native aortic valve without the need for open heart surgery and cardiopulmonary bypass, offering a new therapeutic option to elderly patients considered at high surgical risk or with contraindications to surgery. To date, several multicenter registries and a randomized trial have confirmed the safety and efficacy of TAVR in those patients. In this chapter, we review the background and clinical applications of TAVR in elderly patients.

Comparison of in-hospital outcomes between octogenarians and nonagenarians undergoing transcatheter aortic valve replacement： a propensity matched analysis

Background Aortic valve stenosis （AS） is very common in the elderly patients above 80 years. Transcatheter aortic valve replacement （TAVR） in such patients is being increasingly performed. This study sought to assess in-hospital outcome differences between octogenarians and nonagenarians and predictors of mortality in nonagenarians undergoing TAVR with severe AS. Method The study population was derived from the National Inpatient Sample （MS） for the years 2012-2014 using ICD-9 CM procedure codes 35.05 and 35.06 for TAVR. Hospitalizations below 80 years of age were excluded. After performing propensity score matching （1： 2）, in-hospital outcomes were compared in matched cohorts. Then, multivariate model was developed to analyze predictors of in-hospital mortality in nonagenarians. Results There were 11,630 hospitalizations in the octogenarian and 5815 hospitalizations in the nonagenarian group. Primary outcome of in-hospital mortality （6% vs. 4.1%, P ≤ 0.001） was higher in nonagenarians compared to octogenarians. Secondary outcomes including stroke （3.4% vs. 2.8%, P ≤ 0.001）, renal failure （18.9% vs. 17.3%, P ≤0.001）, blood transfusion （35% vs. 32.6%, P ≤ 0.001）, vascular complications （4.5% vs. 3.5%, P ≤ 0.001）, and pacemaker implantation （27.8% vs. 24.8%, P ≤ 0.001） were higher in nonagenarians. There was no difference in their length of stay. Median cost （70,3745 vs. 65,3815, P ≤ 0.001） was slightly higher with nonagenarian. Conclusions Although in-hospital mortality is slightly higher in nonagenarians, it is acceptable. This difference in mortality is at least partly explained by higher complications in nonagenarians. Efforts should be made to decrease the complications which can further narrow the difference in in-hospital mortality between the groups.

Effect of transcatheter aortic valve replacement on P-wave duration, P-wave dispersion and left atrial size

Background P-wave dispersion （PWD）, a measure of heterogeneity of atrial refractoriness, is defined as the difference between the maximum and minimum P-wave duration. In patients with severe aortic stenosis （AS）, P-wave duration and PWD were shown to be increased, indicating atrial electrical remodeling. However, the effect of transcatheter aortic valve replacement （TAVR） on P-wave morphology has not been established yet. The aim of this study is to assess the short and long-term effects of TAVR with two types of bioprosthetic valves on P-wave duration and PWD in association with left atrial （LA） size. Methods Fifty-two （36 female） eligible patients in sinus rhythm who underwent transfemoral TAVR between June 01, 2012 and July 31, 2014 with either a Medtronic CoreValve （MCV） （n = 32） or an Edwards SAPIEN XT Valve （n = 20） were enrolled. Standard 12-lead electrocardiogram and echocardiographic evaluations were per- formed pre-procedurally, post-TAVR day one and 6 months post-TAVR. P-wave duration and PWD were measured and correlation analyses with echocardiographic variables were performed. Results P-wave duration and PWD were significantly decreased on post-TAVR day one （P 〈 0.05）. They continued to decrease during the six month follow-up period, but were not significantly different from short-term values （P 〉 0.05）. The decrease of LA diameter was found significant at the sixth-months of follow-up （P 〈 0.05）. These changes were independent from the types of bioprosthetic valves implanted （P 〉 0.05）. A positive correlation was detected between minimum P-wave duration and maximum aortic valve gradients at post-TAVR day one （r = 0.297, P = 0.032）. Conclusions P-wave duration and PWD were significantly reduced early after TAVR indicating early reverse atrial electrical remodeling. Moreover, structural reverse remodeling of atrium was detected at the 6-months of follow-up. The effects of two types of bioprosthetic valves on atrial remodeling were similar.

Early mortality and safety after transcatheter aortic valve replacement using the SAPIEN 3 in nonagenarians

Background Transcatheter aortic valve replacement （TAVR） has been performed for many elderly patients with severe aortic stenosis （AS）. The SAPIEN 3 is one of the latest balloon-expandable prosthesis. This study aimed to investigate the early clinical outcomes after TAVR using the SAPIEN 3 in nonagenarians. Methods A total of 97 consecutive patients underwent TAVR for severe AS between De- cember 2015 and December 2016. Of these, 85 consecutive patients who underwent TAVR using the SAPIEN 3 were included. According to the age, patients were classified into age 〉 90 years group （17 patients） or age 〈 90 years group （68 patients）. The clinical outcomes in- cluding all-cause mortality and composite endpoint of early safety at 30 days were evaluated. Results The Society of Thoracic Surgeons score in age 〉 90 years group was higher than age 〈 90 years group （12.3 ±6.1% vs. 8.5 ± 5.1%, P 〈 0.01）. There was no significant difference in 30-day mortality between the two groups. However, the life-threatening bleeding and major vascular complications in age 〉 90 years group were greater than age 〈 90 years group （11.8% vs. 1.5%, P = 0.04 and 11.8% vs. 1.5%, P = 0.04, respectively）. The composite endpoint of early safety at 30 days was similar between the two groups. Multivariate logistic regression analysis showed that prior myocardial infarction was an independent predictor of the composite endpoint of early safety （odds ratio： 4.76, 95% confidence interval： 1.02-22.21, P = 0.047）. Conclusions The early mortality and safety after TAVR using the SAPIEN 3 in nonagenarians were similar and acceptable despite of higher operative risk.

Risk scoring model for prediction of non-home discharge after transcatheter aortic valve replacement

Background Patients undergoing transcatheter aortic valve replacement(TAVR) are likely to be discharged to a location other than home. We aimed to determine the association between preoperative risk factors and non-home discharge after TAVR. Methods Patients discharged alive after TAVR at three centers were identified from a prospectively maintained database randomly divided into 80% derivation and 20% validation cohorts. Logistic regression models were fit to identify preoperative factors associated with non-home discharge in the derivation cohort. Multivariable models were developed and a nomogram based risk-scoring system was developed for use in preoperative counseling. Results Between June 2012 and December 2018, a total of 1,163 patients had TAVR at three centers. Thirty-seven patients who died before discharge were excluded. Of the remaining 1,126 patients(97%) who were discharged alive, the incidence of non-home discharge was 25.6%(n = 289). The patient population was randomly divided into the 80%(n = 900) derivation cohort and 20%(n = 226) validation cohort. Mean ± SD age of the study population was 83 ± 8 years. In multivariable analysis, factors that were significantly associated with non-home discharge were extreme age, female sex, higher STS scores, use of general anesthesia, elective procedures, chronic liver disease, non-transfemoral approach and postoperative complications. The unbiased estimate of the C-index was 0.81 and the model had excellent calibration. Conclusions One out of every four patients undergoing TAVR is discharged to a location other than home. Identification of preoperative factors associated with non-home discharge can assist patient counseling and postoperative disposition planning.

Patient selection for transcatheter aortic valve replacement:A combined clinical and multimodality imaging approach

Transcatheter aortic valve replacement(TAVR) has been validated as a new therapy for patients affected by severe symptomatic aortic stenosis who are not eligible for surgical intervention because of major contraindication or high operative risk. Patient selection for TAVR should be based not only on accurate assessment of aortic stenosis morphology, but also on several clinical and functional data. Multi-Imaging modalities should be preferred for assessing the anatomy and the dimensions of the aortic valve and annulus before TAVR. Ultrasounds represent the first line tool in evaluation of this patients giving detailed anatomic description of aortic valve complex and allowing estimating with enough reliability the hemodynamic entity of valvular stenosis. Angiography should be used to assess coronary involvement and plan a revascularization strategy before the implant. Multislice computed tomography play a central role as it can give anatomical details in order to choice the best fitting prosthesis, evaluate the morphology of the access path and detect other relevant comorbidities. Cardiovascular magnetic resonance and positron emission tomography are emergent modality helpful in aortic stenosis evaluation. The aim of this review is to give an overview onTAVR clinical and technical aspects essential for adequate selection.