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.

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.

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.

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.

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.

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).

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.

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.

A meta-analysis of 1-year outcomes of transcatheter versus surgical aortic valve replacement in low-risk patients with severe aortic stenosis

Background Transcatheter aortic valve replacement(TAVR)for the treatment symptomatic severe aortic stenosis(AS)is indicated in patients with intermediate or higher surgical risk.Latest trials showed TAVR,and surgical aortic valve replacement(SAVR)perform similarly at 1-year for the composite outcomes of mortality,stroke and rehospitalization.We performed a comprehensive meta-analysis to compare individual outcomes at 1-year for TAVR compared to SAVR in low-risk patients.Methods Pub Med,Embase,and Cochrane central were searched for all the randomized controlled trials(RCTs)that reported 1-year comparative outcomes of TAVR and surgical aortic valve replacement(SAVR).Our conclusions are based upon the random-effects model using Der Simonian-Laird estimator.Results Data from 4 trials and 2887 randomized patients showed that TAVR had lower rates of all-cause mortality,cardiovascular mortality,and atrial fibrillation compared to SAVR at 1-year follow-up(P<0.05 for all).Also,TAVR was also associated with a significantly higher risk of permanent pacemaker implantation and moderate-severe paravalvular leak(P<0.05).Conclusions The latest randomised trial data demonstrates that in short-term,TAVR is safe and effective in reducing all-cause mortality or stroke.Longer follow-up of RCTs is needed to determine the durability of clinical benefits in TAVR over SAVR in low-risk patients.

Measuring frailty in patients with severe aortic stenosis:a comparison of the edmonton frail scale with modified fried frailty assessment in patients undergoing transcatheter aortic valve replacement

Frailty is generally defined as a clinical syndrome of decreased physiologic reserve which drives to increased vulnerability and susceptibility to different stressors together with poor recovery to homeostasis.[1]The relevance of frailty status in a wide range of prospective cohorts is mostly related to an increasing burden in both mortality,hospital readmissions,disability,and falls.

Early Postoperative Anticoagulation by Enoxaparin after Mechanical Aortic Valve Replacement

Background: The use of low molecular weight heparin for early anticoagulation after mechanical aortic valve replacement is still a matter of debate even more that the early postoperative phase is associated with maximum of thrombo-embolic and bleeding risks. The objective of this study is to verify the efficacy and the safety of low molecular weight heparin for the early anticoagulation after mechanical aortic valve replacement. Methods and Results: It is a prospective study conducted over 6 months and interested 40 consecutive patients (32 male and 8 female) with a mean age 53.83 ± 16.93 years (19-75 years) who underwent a mechanical aortic valve replacement and received enoxaparin as bridging therapy between continuous unfractionated heparin and fully effective vitamin K antagonist therapy. There was no in-hospital death and no in-hospital thromboembolic events. We report 2 major bleeding events (5%). Conclusion: The use of low molecular weight heparin should be an alternative to explore for early anticoagulation after valve heart surgery and the results of our study must be verified by large randomized studies before drawing any hasty conclusions.

Anemia and risk of periprocedural cerebral injury detected by diffusion-weighted magnetic resonance imaging in patients undergoing transcatheter aortic valve replacement

BACKGROUND: Anemia is prevalent in patients undergoing transcatheter aortic valve replacement(TAVR) and has been linked to impaired outcomes after the procedure. Few studies have evaluated the impact of anemia and new ischemic lesions post TAVR.METHODS: We prospectively enrolled 158 patients who received TAVR in our center. Anemia was defined according to the World Health Organization criteria as hemoglobin <12 g/dL in women and <13 g/dL in men. All patients underwent diffusion-weighted magnetic resonance imaging(DW-MRI) procedure before and within 4–7 days after TAVR. RESULTS: Anemia was present in 85(53.8%) patients who underwent TAVR, and 126(79.7%) patients had 718 new DW-MRI positive lesions with a mean of 4.54±5.26 lesions per patient. The incidence of new ischemic lesions was 81.2% in patients with anemia versus 78.1% in patients without anemia(P=0.629). Moreover, anemic patients had bigger total volume/lesions in the anterior cerebral artery/middle cerebral artery(ACA/MCA) and MCA regions compared to the non-anemic patients(31.89±55.78 mm^(3) vs. 17.08±37.39 mm^(3), P=0.049;and 54.54±74.72 mm^(3) vs. 33.75±46.03 mm^(3), P=0.034). Anemia was independently associated with the volume/lesion in the ACA/MCA(β=16.796, 95% confidence interval [95% CI] 2.001 to 31.591, P=0.026) and in the MCA zone(β=0.020, 95% CI 0.001 to 0.040, P=0.041). CONCLUSIONS: Patients with pre-procedural anemia may have bigger total volume/lesions in the ACA/MCA and MCA regions compared to the non-anemic patients. Whether the consequences of bigger total volume/lesions impact neurological and cognitive outcomes remains to be investigated.

In-hospital outcomes of transapical versus surgical aortic valve replacement: from the U.S. national inpatient sample

OBJECTIVE To compare the outcomes of transapical transcatheter aortic valve replacement(TA-TAVR)and surgical aortic valve replacement(SAVR)using a large US population sample.METHODS The U.S.National Inpatient Sample was queried for all patients who underwent TA-TAVR or SAVR during the years2016-2017.The primary outcome was all-cause in-hospital mortality.Secondary outcomes were in-hospital stroke,pericardiocentesis,pacemaker insertion,mechanical ventilation,vascular complications,major bleeding,acute kidney injury,length of stay,and cost of hospitalization.Outcomes were modeled using multi-variable logistic regression for binary outcomes and generalized linear models for continuous outcomes.RESULTS A total of 1560 TA-TAVR and 44,280 SAVR patients were included.Patients who underwent TA-TAVR were older and frailer.Compared to SAVR,TA-TAVR correlated with a higher mortality(4.5%vs.2.7%,effect size(SMD)=0.1)and higher periprocedural complications.Following multivariable analysis,both TA-TAVR and SAVR had a similar adjusted risk for in-hospital mortality.TA-TAVR correlated with lower odds of bleeding with(adjusted OR(aOR)=0.26;95%CI:0.18-0.38;P<0.001),and a shorter length of stay(adjusted mean ratio(aMR)=0.77;95%CI:0.69-0.84;P<0.001),but higher cost(aMR=1.18;95%CI:1.10-1.28;P<0.001).No significant differences in other study outcomes.In subgroup analysis,TA-TAVR in patients with chronic lung disease had higher odds for mortality(aOR=3.11;95%CI:1.37-7.08;P=0.007).CONCLUSION The risk-adjusted analysis showed that TA-TAVR has no advantage over SAVR except for patients with chronic lung disease where TA-TAVR has higher mortality.

Asia's first combined liver transplant and aortic valve replacement

To the editor:Liver transplantation is the only cure for patients with endstage liver disease.It is however an ultra-major surgery which is physiologically challenging to the cardiopulmonary function of the patients.Hence,in patients who also have valvular heart disease or coronary artery disease,liver transplantation would be con-

Aorto-Pulmonary Artery Fistula Following Aortic Valve Replacement: A Diagnostic Dilemma

Aorto-pulmonary artery fistula is a rare and lethal occurrence after thoracic surgery and aortic aneurysms. Here we present a rare occurrence of acute aorto-pulmonary artery fistula in outpatient department in a follow up patient of aortic valve replacement and discuss challenges faced in diagnosis, etiopathogenesis and management.

Iatrogenic Disruption of Left Main Coronary Artery during Aortic Valve Replacement

This aortic valve replacement (AVR) remains the gold standard for symptomatic aortic stenosis. Peri-operative complications like dissection, stenosis involving coronary artery are well described in many series. We present a rare iatrogenic complication of disrupted left main coronary artery during the delivery of cardioplegia while performing AVR in a 54 year male patient for severe calcific aortic stenosis. The inadvertent injury to the artery was timely noticed and managed successfully with long saphenous vein graft.

Effect of aortic valve replacement on ventricular recovery and functional class in patients with reduced left ventricular function

Objective: The aim of the study was to assess the effects of aortic valve replacement (AVR) in patients with aortic stenosis (AS) or regurgitation (AR) and left ventricular (LV) dysfunction. Patients and methods: Retrospective analysis identified 75 consecutive patients with left ventricular ejection fraction (LVEF) assessed by echocardiography < 40% who underwent AVR for AS (n = 40) or AR (n = 35) between 1994 and 2011. Exclusion criteria were previous myocardial infarction or concomitant valvular disorders other than aortic disease. Follow-up evaluated the New York Heart Association (NYHA) functional class, LVEF and survival rate. Results: Mean ages were respectively 56.5 ± 9.3 and 47.9 ± 11.7 years in AS and AR groups, p = 0.001. Before surgery, 88% and 75% of patients were in NYHA III-IV respectively in AS and AR. In the AS group, the mean LVEF and aortic valve area (AVA) were respectively 32.2% ± 8% and 0.65 ± 0.15 cm2. AR group had a mean LVEF of 33.8 ± 6.7% and a mean LV systolic diameter of 62 ± 8.8 mm. All patients underwent AVR under cardiopulmonary bypass. There were 5 operative deaths (12.5%) in AS group and 6 (17.6%) in AR group, p = 0.57. LVEF increased to 49% ± 14.7% and 51.2% ± 10.9% in the AS and AR groups after echocardiography control. The survival rates at 1, 5 and 10 years were respectively 94.4%, 87% and 80% in AS group and 95.2%, 93% and 89% in AR group. Conclusion: Despite higher perioperative mortality in patients with aortic valve disease (AS or AR) and LV dysfunction, long-term outcome is excellent. We, therefore, conclude that AVR can be performed and it should not be denied to patients on the basis of low EF alone.