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.

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.

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.

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.

Aortic valve stenosis： treatments options in elderly high-risk patients

In the last decades, a trend towards a worldwide aging has been reported and diseases which are common in the elderly people would have important implications in clinical practice. Aortic stenosis （AS） is perhaps the most common and most often cause of sudden death among valvular heart diseases. Its prevalence is low among adults aged 〈 60 years, but increases to almost 10% in adults ≥ 80 years.[2] Since the degenerative calcific disease represents the lead- ing cause of AS in developed countries, the improved understanding on its pathogenesis （atherosclerotic processes and/or skeleton key） may offer potentially new targets for preventing and inhibiting AS development and progres- sion.[3] Patients with AS are generally asymptomatic for a prolonged period and the development of symptoms is a critical point in the natural history. Indeed, the prognosis changes dramatically with the onset of symptoms of angina,

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.

Effect of transcatheter aortic valve implantation on QT dispersion in patients with aortic stenosis

Background QT dispersion （QTd） is a predictor of ventricular arrhythmia. Ventricular arrhythmia is an important factor influencing morbidity and mortality in patients with aortic stenosis. Surgical aortic valve replacement reduced the QTd in this patients group. However, the effect of transcatheter aortic valve implantation （TAVI） on QTd in patients with aortic stenosis is unknown. The aim of this study was to investigate the effect of TAVI on QTd in patients with aortic stenosis. Methods Patients with severe aortic stenosis, who were not candi-dates for surgical aortic valve replacement due to contraindications or high surgical risk, were included in the study. All patients underwent electrocardiographic and echocardiographic evaluation before, and at the 6th month after TAVI, computed QTd and left ventricular mass index （LVMI）. Results A total 30 patients were admitted to the study （mean age 83.2 ± 1.0 years, female 21 and male 9, mean valve area 0.7 ± 3 mm2）. Edwards SAPIEN heart valves, 23 mm （21 patients） and 26 mm （9 patients）, by the transfemoral approach were used in the TAVI procedures. All TAVI procedures were successful. Both QTd and LVMI at the 6th month after TAVI were significantly reduced com-pared with baseline values of QTd and LVMI before TAVI （73.8 ± 4 ms vs. 68 ± 2 ms, P=0.001 and 198 ± 51 g/m2 vs. 184 ± 40 g/m2, P=0.04, respectively）. There was a significant correlation between QTd and LVMI （r=0.646, P〈0.001）. Conclusions QTd, which malign ventricular arrhythmia marker, and LVMI were significantly reduced after TAVI procedure. TAVI may decrease the possibility of ventricu-lar arrhythmia in patients with aortic stenosis.

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.

Will Transcatheter Aortic Valve Replacement(TAVR)be the Primary Therapy for Aortic Stenosis?

Transcatheter aortic valve replacement(TAVR)is increasingly used for the treatment of high or very high surgical risk patients with severe aortic stenosis(AS)or failing surgical bioprosthesis(valve-in-valve,VIV-TAVR).In TAVR,the collapsed transcatheter heart valve(THV)is introduced using the delivery system inserted from the femoral artery(preferred)or other alternative accesses(transapical,transaortic,transcarotid,subclavian/transinnominate or transcaval).The delivery system is then advanced until coaxially aligned with the aortic annulus,where the THV is deployed.This procedure can be associated with complications such as access site injury(vascular complication),paravalvar leak,cerebrovascular events and conduction disturbances.However,the rapid acceptance and successes observed with TAVR have been made possible through careful patient selection,preprocedural planning(i.e.MDCT annular sizing),THV technology(i.e.new generation valves),and procedural techniques(i.e.minimalist TF-TAVR and alternative percutaneous access options),as well as a decrease in complications as TAVR experience grows.Though the results or ongoing clinical trials evaluating TAVR in intermediate surgical risk patients are pending,it is likely that TAVR will soon be approved for lower risk patients as well.

Medical management of symptomatic severe aortic stenosis in patients non-eligible for transcatheter aortic valve implantation

1 Transcatheter aortic valve implantation in symptomatic severe aortic stenosis: where do we stand? Aortic stenosis occurs in 2%-9% of patients over the age of 65, the most common cause being degenerative.^([1,2]) The preferred treatment in symptomatic severe aortic stenosis(SAS) is surgical aortic valve replacement(SAVR), but in the elderly, the surgical risk can be greater than the benefit.([3]).

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.

Successful minimal approach transcatheter aortic valve replacement in an allograft heart recipient 19 years post transplantation for severe aortic stenosis: A case report

BACKGROUND Aortic stenosis is one of the rare valvular complications in a transplanted heart.Over the past 8 years,transcatheter approach for aortic valve replacement(TAVR)has been slowly evolving to be the preferred approach in these patient population when compared to the surgical approach.We report a second case in the United States with successful transfemoral minimal approach with minimal sedation for TAVR in a heart transplant recipient 19 years post transplantation for severe symptomatic calcified aortic stenosis.CASE SUMMARY We present a case of 73-year-old male who has undergone successful minimal approach transcatheter aortic valve replacement in an allograft heart.Patient had received orthotopic heart transplantation 19 years ago for non-ischemic cardiomyopathy.Follow up transthoracic echocardiograms as per routine protocol did not show any aortic valve disease until 15 years post transplantation.Aortic valve was noted to be mildly sclerotic at that time and gradually progressed to severe symptomatic aortic stenosis over the next 4 years.Patient had complaints of worsening shortness of breath that limited his functional capacity.Overall his post heart transplantation period has been mostly uneventful except for allograft non occlusive vasculopathy and aortic stenosis.His Society of Thoracic Surgery risk score was 12.205%and he was considered to be a high-risk surgical candidate by surgeon.Decision was made to undergo transcatheter aortic valve replacement.CONCLUSION With the improved survival of these patients,we think it is time to look intopathophysiology of valvular disease in transplant heart recipients.Some other unanswered questions include,underlying donor and recipient risk factors for valvular diseases in heart transplant recipients.

Inoperable severe aortic valve stenosis in geriatric patients: treatment options and mortality rates

Among geriatric patients suffering from severe but inoperable aortic valve stenosis because of high surgical risk and severe co-morbidities,[1] some benefit from trans-aortic valve implantation (TAVI) while others are deemed too frail for TAVI and received medical treatment (MT). This study conducted in frail geriatric patients aimed at describing the patienfs characteristics and the mortality rate associated with the treatment option (MT vs. TAVI) as well as the patient's characteristics associated with one-year mortality.

Is there evidence for statins in the treatment of aortic valve stenosis?

Research revealed that the pathogenesis of aortic stenosis(AS) not merely comprises of a mechanical wear and tear process yet that active biological processes, similar to those of coronary artery disease are involved, a promising role for statins in disease-modifying therapy was suggested. However, recently, many prospective studies could not observe decreased progression nor regression of the disease. Here, we review the current knowledge on the pathomechanisms of AS and its similarities and differences with atherosclerosis. Moreover, we discuss whether there is still a place for statins in the treatment of particular AS patient subgroups.

Combined Surgical Treatment of Atherosclerotic Coronary Artery Disease and Moderate Aortic Valve Stenosis in Patient with Concomitant Lipton’s R-III Type of Single Coronary Artery Anomaly

A single coronary artery is a very rare condition,commonly associated with other congenital anomalies.It could be generally considered as neither benign nor malignant form of congenital coronary artery anomalies since its pathophysiological and clinical implications grossly depend on different anatomical patterns defined by the site of origin and distribution of the branches.By presenting the patient who underwent successful coronary artery bypass grafting and aortic valve replacement surgery in a presence of isolated single coronary artery,we intend to emphasize natural and procedural risks and distinguish casual from causal in this extremely rare clinical and surgical scenario.

Assessment of Left Ventricular Function after Transcatheter Aortic Valve Implantation in Sever Aortic Stenosis: A Speckle Tracking Imaging Study

Background: Long standing aortic stenosis leads to elevated left ventricular (LV) pressure and as a result LV hypertrophy and myocardial fibrosis shall increase. The left ventricular ejection fraction (EF) usually remains adequately-preserved until advanced and late stages of aortic stenosis. But the preserved muscle of the LV is only limited to a portion of the entire myocardium. Speckle tracking echocardiography has proved its superiority to the standard two-dimensional echocardiography method in the detection of Left Ventricular (LV) function. Global Longitudinal strain (GLS) is considered as the most robust myocardial strain component.?Objective: The aim of the study is to assess the early course of left ventricular reverse remodelling after Transcutaneous Aortic Valve Implantation (TAVI) in patients with symptomatic severe aortic valve stenosis.?Methods: 50 patients with severe symptomatic valvular aortic stenosis undergoing TAVI as decided by the heart team after comprehensive discussion.?Standard transthoracic echocardiography including Doppler analysis was performed. 2D speckle-tracking strain assessment of Global radial, circumferential and longitudinal strain at parasternal mid-ventricular short-axis view (at the level of papillary muscle) and from the apical long-axis, two-chamber and four-chamber views with a frame rate between 40 and 80 frames per second. Tracing of endocardial borders was done. Patients with significant coronary artery disease were fully revascularized by percutaneous coronary intervention prior to the study and the procedure. Results: 23 (46%) patients were males, while 27 (54%) were females. The patients’ stratification according to comorbidities/associated risk factors revealed that 54% of the patients had DM, 86% were hypertensive, 38% had chronic kidney disease (CKD), and 32% had a previous percutaneous coronary intervention (PCI).?The mean age for our study participants ranged?from 60 to 92 years (Mean ± SD = 76.60 ± 5.96). Left ventricular diastolic diameter (LVDd) was 44.24?±?2.8?mm before TAVI that became 45.5?±?2.6?mm after TAVI, and ejection fraction (EF) increased from 52.82?±?6.3?before TAVI to 56.70?±?5.4?after TAVI, both with highly significant difference (P P value less than 0.001. Global circumferential strain (GCS) also improved significantly from -20.14?±?1.8 before TAVI to -21.72?±?1.7 after TAVI with a P value less than 0.001. Global radial strain (GRS) also increased significantly from 37.38?±?8 before TAVI to 41.68?± 6.3 after TAVI with a P value less than 0.001. Conclusion: TAVI is effective in improving left ventricular function presented not only by ejection fraction (EF%), but also in global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS).

Rheumatic Aortic Valve Disease with Mitral Stenosis—A Case Report

Congenitally malformed aortic valves are more susceptible to valve injury due to rheumatic fever, mechanical stress of altered flow patterns, atherosclerotic risk factors and degenerative changes. Rheumatic involvement usually occurs in childhood and it is progressive leading to diffuse thickening and fibrosis at leaflet edges and thus differentiated from other patterns of valve damage. Background of this case report revealed the bicuspid nature of the aortic valve due to rheumatic commissural fusion and analysis of echocardiographic parameters in combined lesions of both aortic and mitral valves with severe LV (left ventricular) dysfunction. Left ventricular (LV) and left atrial (LA) dilations predisposing to the formation of smoke (SEC-spontaneous echo contrast) in LV and LA as a consequence of mitral and aortic valve disease are illustrated by 2D echocardiographic imaging in this 41-year-old male.

Simultaneous Endovascular Approach for Aortic Arch Aneurysm Associated with Aortic Valve Stenosis. What Have We Learned?

Aortic arch aneurysms are rarely isolated entities, and most frequently associated with either ascending or descending aorta pathologies. Association with aortic valve stenosis is uncommon and traditional surgical treatment is always challenging. Here we report a minimally invasive and endovascular management of these two pathologies in a 89-year-old man with LAD-stented ischemic cardiomyopathy. We describe our initial therapeutic strategy, per procedure difficulties and final management of this challenging case. Finally, we discuss the different therapeutic options for the endovascular treatment of aortic arch aneurysm associated with aortic valve stenosis.

The effects of severe aortic stenosis and high pulmonary artery pressure on aortic valve replacement

Background: Pulmonary hypertension development in pure severe aortic stenosis is a situation that affects mortality and morbidity. Material and Methods: Data from files of 31 patients with systolic pulmonary artery pressure over 50 mm Hg and with pure severe aortic stenosis, and underwent aortic valve replacement in our clinic were examined retrospectively. Results: Preoperative effort capacities of the patients were evaluated as follows according to NYHA;4 patients class 1-2, 16 patients class 3, and 11 patients class 4. Twenty-five metal, and 6 biologic aortic valves were used. Postoperative hospital mortality was recorded as 12% with 4 patients. Patients were reevaluated on the postoperative 2nd and 12th months. Pulmonary arterial pressure of the patients was measured using echocardiography. Preoperative average pulmonary artery systolic pressure was measured as 55 ± 3 mmHg. The average pressure was measured as 41 ± 3 mmHg on the 2nd, and as 37.8 ± 4 mmHg on the 12th month. The effort capacity evaluation in the postoperative 2nd month was as follows: 11 patients class 1-2, 12 patients class 3, and 4 patients class 4. The effort capacity evaluation conducted in the 12th month was: 14 patients were class 1-2, 10 patients were class 3, and 2 patients were class 4. During the follow-up 1 year, survival rate of the patients was determined as 83.8% average, 5 year survival rate was determined as 61.5%. Conclusion: We believe that AVR may be performed in severe aortic stenosis cases with high pulmonary pressure with acceptable ortality, leading to a better quality and longer life.

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.