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.

Aortic valve replacement reduces mortality in moderate aortic stenosis:a systematic review and meta-analysis

BACKGROUND With the introduction of transcatheter aortic valve replacement and an evolving understanding of the natural progression and history of aortic stenosis,the potential for earlier intervention in appropriate patients is promising;however,the benefit of aortic valve replacement in moderate aortic stenosis remains unclear.METHODS Pubmed,Embase,and the Cochrane Library databases were searched up until 30th of December 2021 using keywords including moderate aortic stenosis and aortic valve replacement.Studies reporting all-cause mortality and outcomes in early aortic valve replacement(AVR)compared to conservative management in patients with moderate aortic stenosis were included.Hazard ratios were generated using random-effects meta-analysis to determine effect estimates.RESULTS 3470 publications were screened with title and abstract review,which left 169 articles for full-text review.Of these studies,7 met inclusion criteria and were included,totalling 4,827 patients.All studies treated AVR as a time-dependent co-variable in cox-regression multivariate analysis of all-cause mortality.Intervention with surgical or transcatheter AVR was associated with a 45% decreased risk of all-cause mortality(HR=0.55[0.42-0.68],I2=51.5%,P<0.001).All studies were representative of the overall cohort with appropriate sample sizes,with no evidence of publication,detection,or information biases in any of the studies.CONCLUSION In this systematic review and meta-analysis,we report a 45% reduction in all-cause mortality in patients with moderate aortic stenosis who were treated with early aortic valve replacement compared to a strategy of conservative management.Randomised control trials are awaited to determine the utility of AVR in moderate aortic stenosis.

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).

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.

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.

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.

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.

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.

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.

Association of serum lipoprotein(a) level with the severity and prognosis of calcific aortic valve stenosis: a Chinese cohort study

Background There was a causal relationship between elevated lipoprotein(a)[Lp(a)]levels and increased risk of calcific aortic valve stenosis(CAVS)in whites and blacks.The present study aimed to investigate whether Lp(a)levels were associated with aortic stenosis(AS)severity and clinical events in Chinese patients.Methods Levels of serum Lp(a)were measured in 652 patients with CAVS,whom all underwent baseline echocardiographic examination.The clinical endpoint was defined as a composite of aortic valve replacement(AVR)and cardiac death.Results Patients in the tertile 3 of Lp(a)had a higher percentage of severe AS compared with those in the tertile 1 and 2 of Lp(a)(46.2%vs.33.9%,P=0.005).Moreover,the top tertile of Lp(a)was an independent predictor of severe AS(OR=1.78,95%CI:1.18-2.66,P=0.006).However,there was no significant association between tertile 3 of Lp(a)and clinical events(hazard ratio:0.73;95%CI:0.43-1.24;P=0.239)in the multivariate Cox regression analysis during a mean follow-up time of 3.16±2.74 years.Conclusions Elevated Lp(a)level was an independent predictor of severe AS by echocardiography in the Chinese population,but was not associated with the increased risk of AVR and cardiac death,suggesting that Lp(a)levels might be helpful in the risk stratification of patients with CAVS.

Aortic valve stenosis provides complementary information to bleeding risk scores in non-valvular atrial fibrillation patients initiating anticoagulation

Background The identification of modifiable bleeding risk factors may be of relevance.The aim is to evaluate if aortic stenosis(AS)provides additional information to bleeding risk scores for predicting major bleeding(MB)in non-valvular atrial fibrillation(AF).Methods We designed a retrospective multi-center study including 2880 consecutive non-valvular AF patients initiating oral anticoagulation between January 2013 and December 2016.AS was defined as moderate or severe according to European echocardiography guidelines criteria.HASBLED,ATRIA and ORBIT scores were used to evaluate the bleeding risk.MB was defined according to the International Society on Thrombosis and Haemostasia criteria and registered at 18 months of follow-up.Results 168(5.8%)patients had AS.Patients with AS had higher risk for MB compared to those without AS(HR=2.13,95%CI:1.40-3.23,P<0.001).Patients without AS and low-intermediate bleeding risk(0 points)showed the lowest MB rate,whereas the MB rate observed among patients with AS and high bleeding risk(2 points)was the highest one.Discrimination and reclassification analyses showed that AS provided additional information to bleeding risk scores for predicting MB at 18 months of follow-up.Conclusions In this population,AS was associated with an increased risk for MB at midterm follow-up.The three scoring systems showed a moderate discriminatory ability for MB.Moreover,the addition of AS was associated with a significant improvement in their predictive accuracy.We suggest that the presence of this valvulopathy should be taken into account for bleeding risk assessment.

Transcatheter aortic valve implantation： a revolution in the therapy of elderly and high-risk patients with severe aortic stenosis

Transcatheter aortic valve implantation （TAV1） represents a real revolution in the field of interventional cardiology for the treatment of elderly or high-risk surgical patients with severe symptomatic aortic valve stenosis. Today, TAVI seems to play a key and a reliable role in the treatment of intermediate and maybe low-risk patients with severe aortic stenosis. TAVI has also evolved from a complex and hazardous procedure into an effective and safe therapy by the development of new generation devices. This article aims to review the background and future of TAVI, elinieal trials and registries with old and new generation TAVI devices and to focus on some open issues related to post-procedural outcomes.

Long-term follow-up of quality of life in high-risk patients undergoing transcatheter aortic valve implantation for symptomatic aortic valve stenosis

Background Transcatheter aortic valve implantation （TAVI） has become the standard treatment for patients with severe symptomatic aortic stenosis （AS） considered at very high risk for surgical aortic valve replacement. The purpose of this sub-study was to evaluate long-term （〉 4 years） health-related quality of life （QoL） in octogenarians who underwent TAVI. Methods A single center observational registry in twenty patients who underwent frame analysis assessment ≥ 4 years after TAVI. Health-related QoL was evaluated, using the Short Form-36 （SF-36）, the EuroQoL-5D （EQ-5D） and the visual analogue score （EQ-VAS） questionnaires. Results The mean SF-36 subscale scores at follow-up were physical functioning 40.8 ± 26.3, role physical functioning 67.7 ± 34.9, vitality 54.6 ± 21.6, general health 52.1 ± 20.4, social functioning 63.8 ± 37.7, role emotional functioning 70.2 ± 36.0, mental health 73.2 ± 23.3 and bodily pain 80.9 ± 22.9. The mean EQ-VAS score 〉 4 years after TAVI was 64.7 ± 15.1. With respect to functional class, 80% of the patients were in NYHA class I/II at follow-up compared to 15% prior to TAVI. Conclusions This sub-study reports a significant improvement in functional class （NYHA） in a selected group of very elderly patients 〉 4 years after TAVI. Furthermore, all patients showed a satisfactory QoL despite their age and multiple comorbidities. In addition, our study reveals a lower QoL when compared with the general age matched Dutch population.