Aortic Valve Disease Patients Research Articles

TAVI for treating severe aortic valve disease in cardiogenic shock: a single centre experience

Abstract Introduction Recent evidence shows the safety and efficacy of TAVI in patients with aortic valve disease (AVD) presenting in cardiogenic shock (CS). However, there is limited data regarding CS management in the cardiac intensive care unit (CICU) and its outcomes. We aimed to describe the CS features, pre-TAVI management and short-term clinical outcomes of a cohort of CS patients (pts) submitted to TAVI. Methods Single-centre retrospective registry of consecutive pts with AVD undergoing TAVI in CS, from January 2020 to October 2023. CS was defined as pre-procedural hypotension/hypoperfusion requiring vasoactive drugs or mechanical circulatory support (MCS) devices. The severity of CS was defined according to the SCAI classification. Procedural related outcomes according to the VARC-3 criteria and 30-day mortality were assessed. Results A total of 16 pts (1% of our global TAVI cohort, 62% male, mean age 79±5 years) meet the inclusion criteria. The majority (n=13) presented severe aortic stenosis, two had degenerated aortic bioprosthesis with severe regurgitation and one had native valve severe regurgitation. 6 pts (38%) had isolated left ventricle (LV) dysfunction and 10 (62%) had biventricular dysfunction. The admission LVEF was 33±8% and the mean transaortic gradient for those with aortic stenosis was 46±13mmHg. The EuroSCORE II estimated for a single non-CABG emergency procedure was 37±15%. All patients were refused for surgical treatment upon Heart Team discussion. At admission, 12 (75%) patients presented in CS SCAI-C, 1 (6%) in SCAI-D and 3 (19%) in SCAI-E. These last 3 patients presented in cardiac arrest upon admission to the CICU (time to ROSC from 2 to 15 minutes). The peak lactate level at 48 hours was 3.4 mmol/L [2.1-5.1] and the highest Vasoactive-Inotropic Score (VIS) during admission was 21 [11-45]. None of the patients needed MCS pre-TAVI. 5 (31%) patients required invasive mechanical ventilation and 5 (31%) renal replacement therapy. Median time between CICU admission and transfemoral TAVI was 2.5 days [IQR 1-7]. Procedural success was 100%, with 57% receiving a balloon-expandable and 43% a self-expandable valve. Post-TAVI CICU length of stay was 6 days [IQR 5-9]. Most common procedural complication were the need for permanent pacemaker implantation (n=2, 12%) and access-related bleeding (n=2, 12%). Hospital length-of-stay was 20±15 days. Thirty-day mortality was 12% (n=2). Conclusion In this cohort of CS patients selected for TAVI treatment, procedural success was achieved in all cases. While complications were similar to the general TAVI population, in-hospital mortality remained high but very acceptable. These results suggest that, if correctly selected, aortic valve disease patients in CS represent a niche for whom brief stabilization and urgent percutaneous valve treatment might impact their dismal prognosis.

Better prognosis in surgical aortic valve replacement patients with lower red cell distribution width: A MIMIC-IV database study.

Surgical aortic valve replacement (SAVR) currently stands as a primary surgical intervention for addressing aortic valve disease in patients. This retrospective study focused on the role of the red blood cell distribution width (RDW) in predicting adverse outcomes among SAVR patients. The subjects for this study were exclusively derived from the Medical Information Mart for Intensive Care database (MIMIC IV 2.0). Kaplan‒Meier (K-M) curves and Cox proportional hazards regression models were employed to assess the correlation between RDW, one-year mortality, and postoperative atrial fibrillation (POAF). The smooth-fitting curves were used to observe the relative risk (RR) of RDW in one-year mortality and POAF. Furthermore, time-dependent receiver operating characteristic (ROC) curves, the continuous-net reclassification index (NRI), and integrated discrimination improvement (IDI) were employed for comprehensive assessment of the prognostic value of RDW. Analysis of RDW revealed a distinctive inverted U-shaped relationship with one-year mortality, while its association with POAF appeared nearly linear. Cox multiple regression models showed that RDW > 14.35%, along with preoperative potassium concentration and perioperative red blood cell transfusion, were significantly linked to one-year mortality (K-M curves, log-rank P < 0.01). Additionally, RDW was associated with both POAF and prolonged hospital stays (P < 0.05). There was no significant difference in length of stay in ICU. Notably, the inclusion of RDW in the predictive models substantially enhanced its performance. This was evidenced by the time-dependent ROC curve (AUC = 0.829), NRI (P< 0.05), IDI (P< 0.05), and K-M curves (log-rank P< 0.01). RDW serves as a robust prognostic indicator for SAVR patients, offering a novel means of anticipating adverse postoperative events.

Association of TyG index with aortic valve calcification in valvular heart disease patients.

In recent years, triglyceride glucose (TyG) index, as a popular metabolic index, has been proposed as an alternative index of insulin resistance, and it has been proved to be associated with many cardiovascular diseases, but the relationship between it and aortic valve calcification is still unknown. A total of 450 aortic valve disease patients were enrolled in this study, including 361 patients with aortic valve calcification (AVC) (calcification group) and 89 patients without (control group). According to the severity of AVC, patients with AVC included severe calcification, moderate calcification and low calcification. The TyG index was calculated based on fasting triglyceride and fasting blood glucose levels. The TyG index in the calcification group was significantly higher than that in the control group (P < .05), and with the increase of the degree of calcification, the TyG index showed an increasing trend. The univariate and multivariate logistic regression analysis showed TyG index has a high predictive value for the presence of AVC (OR (95% CI): 1.743 (1.036-2.933)) and severe AVC (OR (95% CI): 1.608 (1.143-2.262)). In assessing the predictive value of the TyG index distribution width for AVC, with the first quartile as a reference, the last quartile of the TyG index had significant predictive value for the presence of AVC and severe AVC. TyG index was significantly associated with the presence and severity of AVC, suggesting that TyG index may be a valid predictor of AVC.

The Specific Molecular Changes Induced by Diabetic Conditions in Valvular Endothelial Cells and upon Their Interactions with Monocytes Contribute to Endothelial Dysfunction.

Aortic valve disease (AVD) represents a global public health challenge. Research indicates a higher prevalence of diabetes in AVD patients, accelerating disease advancement. Although the specific mechanisms linking diabetes to valve dysfunction remain unclear, alterations of valvular endothelial cells (VECs) homeostasis due to high glucose (HG) or their crosstalk with monocytes play pivotal roles. The aim of this study was to determine the molecular signatures of VECs in HG and upon their interaction with monocytes in normal (NG) or high glucose conditions and to propose novel mechanisms underlying valvular dysfunction in diabetes. VECs and THP-1 monocytes cultured in NG/HG conditions were used. The RNAseq analysis revealed transcriptomic changes in VECs, in processes related to cytoskeleton regulation, focal adhesions, cellular junctions, and cell adhesion. Key molecules were validated by qPCR, Western blot, and immunofluorescence assays. The alterations in cytoskeleton and intercellular junctions impacted VEC function, leading to changes in VECs adherence to extracellular matrix, endothelial permeability, monocyte adhesion, and transmigration. The findings uncover new molecular mechanisms of VEC dysfunction in HG conditions and upon their interaction with monocytes in NG/HG conditions and may help to understand mechanisms of valvular dysfunction in diabetes and to develop novel therapeutic strategies in AVD.

Echocardiographic Progression of Calcific Aortic Valve Disease in Patients with Preexisting Aortic Valve Sclerosis.

We aimed to evaluate echocardiographic parameters to predict calcific aortic valve disease (CAVD) progression. CAVD ranges from aortic valve sclerosis (ASc) with no functional impairment of the aortic valve to severe aortic stenosis (AS). It remains uncertain, which patients with ASc have a particularly high risk of developing AS. We included a total of 153 patients with visual signs of ASc and peak flow velocity (Vmax) below 2.5 m/s at baseline echocardiography. Progression of CAVD to AS was defined as an increase in Vmax 2.5 m/s with a delta of 0.1 m/s; stable ASc was defined as Vmax below 2.5 m/s and a delta 0.1 m/s. Finally, we compared clinical and echocardiographic parameters between these two groups. The mean age at baseline was 73.5 ( 8.2) years and 66.7% were of male sex. After a mean follow-up of 1463 days, 57 patients developed AS, while 96 patients remained in the ASc group. The AS group showed significantly more calcification (p 0.001) and thickening (p 0.001) of the aortic valve cusps at baseline, although hemodynamics showed no evidence of AS in both groups (ASc group: Vmax 1.6 0.3 m/s versus AS group: Vmax 1.9 0.3 m/s; p 0.001). Advanced calcification (odds ratio [OR]: 4.8, 95% confidence interval [CI]: 1.5-15.9; p = 0.009) and a cusp thickness 0.26 cm (OR: 16.6, 95% CI: 5.4-50.7; p 0.001) were independent predictors for the development of AS. The acquisition of simple echocardiographic parameter may help to identify patients with particularly high risk of developing AS.

Transcatheter heart valve interventions for patients with rheumatic heart disease.

Rheumatic heart disease [RHD] is the most prevalent cause of valvular heart disease in the world, outstripping degenerative aortic stenosis numbers fourfold. Despite this, global resources are firmly aimed at improving the management of degenerative disease. Reasons remain complex and include lack of resources, expertise, and overall access to valve interventions in developing nations, where RHD is most prevalent. Is it time to consider less invasive alternatives to conventional valve surgery? Several anatomical and pathological differences exist between degenerative and rheumatic valves, including percutaneous valve landing zones. These are poorly documented and may require dedicated solutions when considering percutaneous intervention. Percutaneous balloon mitral valvuloplasty (PBMV) is the treatment of choice for severe mitral stenosis (MS) but is reserved for patients with suitable valve anatomy without significant mitral regurgitation (MR), the commonest lesion in RHD. Valvuloplasty also rarely offers a durable solution for patients with rheumatic aortic stenosis (AS) or aortic regurgitation (AR). MR and AR pose unique challenges to successful transcatheter valve implantation as landing zone calcification, so central in docking transcatheter aortic valves in degenerative AS, is often lacking. Surgery in young RHD patients requires mechanical prostheses for durability but morbidity and mortality from both thrombotic complications and bleeding on Warfarin remains excessively high. Also, redo surgery rates are high for progression of aortic valve disease in patients with prior mitral valve replacement (MVR). Transcatheter treatments may offer a solution to anticoagulation problems and address reoperation in patients with prior MVR or failing ventricles, but would have to be tailored to the rheumatic environment. The high prevalence of MR and AR, lack of calcification and other unique anatomical challenges remain. Improvements in tissue durability, the development of novel synthetic valve leaflet materials, dedicated delivery systems and docking stations or anchoring systems to securely land the transcatheter devices, would all require attention. We review the epidemiology of RHD and discuss anatomical differences between rheumatic valves and other pathologies with a view to transcatheter solutions. The shortcomings of current RHD management, including current transcatheter treatments, will be discussed and finally we look at future developments in the field.

The Prognostic Nutritional Index in prediction of two-year mortality in patients undergoing Transcatheter Aortic Valve Replacement

Objective: Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure employed to treat aortic valve disease in patients who are ineligible for open-heart surgery. Undergoing TAVR patients generally include the elderly and frail. Malnutrition is associated with high morbidity and mortality in patients with undergoing TAVR. The aim of this study was to investigate the prognostic value of the prognostic nutritional index (PNI) for two-year survival after TAVR. Material and Methods: A cohort of 213 consecutive patients with severe aortic stenosis who underwent transcatheter aortic valve replacement between March 2019 and July 2021. The study population was divided into two groups according to the cut-off PNI level in a receiver operator characteristic (ROC) curve analysis. The two-year follow-up results of the patients were recorded retrospectively. PNI was defined according to the following formula: PNI = (10 x serum albumin [g/dl]) + (0.005 x total lymphocyte counts [1000/mcL]). Results: Mean age of the patients was 76.15, and 93 (43.7%) of them were males. Patients with low PNI (group 1) were significantly older. The mean PNI of group 1 was 43.17 ± 4.04 and the mean PNI of group 2 was 54.23 ± 4.30. Mortality at two-year was 32.6% in low PNI group and 10.7% in high PNI group. Hypertension and PNI were independent predictors of mortality after TAVR. In ROC curve analysis, PNI at a cut off value of 48.325 predicted the mortality after TAVR with 63.5% sensitivity and 70.1% specificity. Kaplan-Meier curves for two-year mortality between low and high PNI groups showed worse outcomes in patients with low PNI. Conclusion: PNI is a practical and useful nutritional index that predicts two-year mortality after TAVR.

Optimizing aortic valve prosthesis selection in patients with obesity: Institutional experience with multidisciplinary perspective.

Aortic valve diseases are life-threatening conditions with increasing prevalence worldwide. Risk factors include gender, age, hypertension, dyslipidemia, and type 2 diabetes. Obesity is closely related to these risk factors and has been linked to a higher risk of developing aortic valve diseases. However, there is no specific guideline for managing aortic valve disease in patients with obesity, and the choice of valve type remains uncertain. A total of 130 patients with obesity who met the inclusion criteria underwent surgical aortic valve replacement. The patients were divided into two groups based on the type of prosthesis used. Among the study cohort, 50 patients received a bioprosthetic valve, while 80 patients received a mechanical valve. We compared these groups in terms of perioperative characteristics and follow-up results. Statistical significance was determined using a p-value threshold of 0.05. There were no significant differences in age, gender, body mass index, or cardiac comorbidities between the two groups. Preoperative blood results and echo findings also showed no significant differences. Intraoperative characteristics and postoperative outcomes, including mortality and acute kidney injury, did not differ significantly between the groups. In addition, BHVG patients had shorter ICU stays compared to MHVG patients without significance. Deliberate consideration is crucial when selecting valves for obese patients, particularly those with class II obesity. This is due to the potential influence of obesity on valve types, as well as the need to account for the possibility of bariatric surgery and its potential effects.

Prevalence, characteristics and prognostic impact of aortic valve disease in patients with heart failure and reduced, mildly reduced, and preserved ejection fraction: An analysis of the ESC Heart Failure Long-Term Registry.

To assess the prevalence, clinical characteristics, and outcomes of patients with heart failure (HF) with or without moderate to severe aortic valve disease (AVD) (aortic stenosis [AS], aortic regurgitation [AR], mixed AVD [MAVD]). Data from the prospective ESC HFA EORP HF Long-Term Registry including both chronic and acute HF were analysed. Of 15 216 patients with HF (62.5% with reduced ejection fraction, HFrEF; 14.0% with mildly reduced ejection fraction, HFmrEF; 23.5% with preserved ejection fraction, HFpEF), 706 patients (4.6%) had AR, 648 (4.3%) AS and 234 (1.5%) MAVD. The prevalence of AS, AR and MAVD was 6%, 8%, and 3% in HFpEF, 6%, 3%, and 2% in HFmrEF and 4%, 3%, and 1% in HFrEF. The strongest associations were observed for age and HFpEF with AS, and for left ventricular end-diastolic diameter with AR. AS (adjusted hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.23-1.67), and MAVD (adjusted HR 1.37, 95% CI 1.07-1.74) but not AR (adjusted HR 1.13, 95% CI 0.96-1.33) were independently associated with the 12-month composite outcome of cardiovascular death and HF hospitalization. The associations between AS and the composite outcome were observed regardless of ejection fraction category. In the ESC HFA EORP HF Long-Term Registry, one in 10 patients with HF had AVD, with AS and MAVD being especially common in HFpEF and AR being similarly distributed across all ejection fraction categories. AS and MAVD, but not AR, were independently associated with increased risk of in-hospital mortality and 12-month composite outcome, regardless of ejection fraction category.

A comparative study of minimally invasive aortic valve replacement with sutureless biological versus mechanical prostheses.

The ministernotomy approach with sutureless aortic bioprosthesis may provide an attractive and safe option for aortic valve disease patients. To assess the early and mid-term outcomes of minimally invasive aortic valve replacement (miniAVR) with sutureless vs. standard prostheses. The study involved 76 consecutive patients (51 males and 25 females) with mean age of 63.2 years who were treated with miniAVR between 2015 and 2022. They were divided into 2 subgroups: group I (n = 40) subjects with sutureless bioprostheses and group II (n = 36) with standard prostheses implanted. Early and mid-term outcomes were evaluated. A probability of survival was estimated by means of the Kaplan-Meier method. No conversion to complete sternotomy was necessary. The median (minimum; maximum) aorta cross clamping and cardio-pulmonary bypass times were 49 (27; 84) and 70 (40; 188) minutes in group I whereas 69 (50; 103) and 95 (69; 170) minutes in group II, respectively (p < 0.001). In-hospital mortality was 5.0% (n = 2) and 2.8% (n = 1) in group I vs. II, respectively (ns). Permanent ICD implantation was performed in 8 (20.0%) in group I and in 3 (8.3%) subjects in group II. In the discharge echocardiography, the function of all prostheses was correct. Five-year probability of survival was much lower in group I (0.75 ±0.10) than in group II (0.94 ±0.04). No wound infection or sternum instability was noted. Intraoperative advantages of miniAVR procedures for aortic valve patients with sutureless bioprostheses do not translate directly into improved early and middle-term outcomes.

Abstract 11504: Elevated Seismocardiography-Derived Chest Energy is Associated With Aortic Flow Abnormalities in Patients With Aortic Valve Disease

Introduction: Aortic valve disease (AVD) can induce abnormal flow and elevated peak velocity (Vmax), which has known association with aortopathy and implications for intervention, and thus is a key metric in AVD management. Seismocardiogram (SCG) chest acceleration measurements have been shown indicative of AVD. This study investigated relations between SCG energy and established aortic flow measures. Hypothesis: We hypothesize that standard of care clinical Vmax measurements from echocardiography or MRI correlate with SCG chest acceleration energy metrics. Methods: Healthy controls and AVD patients received standard of care echo or MRI and a same day SCG measurement (image, A). Patients had tricuspid or bicuspid aortic valve (TAV, BAV) and were presenting for routine imaging to assess valve/flow function (image, B). Controls (no known cardiovascular disease) were prospectively recruited. Subjects gave informed consent with IRB approval. MRI included 4D flow (1.5T, 1-3mm³/30-40ms); echo included 2D Doppler imaging (1.7-3.3MHz, 12-40 FPS). Standardized ascending aorta (AAo) Vmax measurements were taken from MR or echo images. SCG energy was calculated by spectral decomposition. Results: Enrolment was 76 subjects: 52 controls (48±17.4y, 23 F), 24 patients (18 BAV, 6 TAV, 31±20.9y, 5 F). Patients had elevated peak velocities (227±103cm/s vs. 106±21cm/s, p&lt;0.01) and elevated SCG energy (10.4±2.6dB vs. 8.3±1.4dB, p&lt;0.01). A significant relationship between elevated AAo Vmax and increased SCG energy was observed (R=0.63, p&lt;0.01) (image, C). Conclusions: Evaluation of SCG in context of AVD shows its potential utility to screen for valve mediated aortic flow changes. Correlation observed between SCG energy and peak velocities, a key metric for management of valve disease and aortopathy, indicates the relevance of SCG measurements in this context. These results show potential for use of SCG as simple, cost-effective front-line screening tool for AVD patients.

Abstract 10343: Prospective Multi-Modality Imaging Comparisons of Left Ventricular Quantification in Aortic Valve Regurgitation and Stenosis

Background: Cardiac magnetic resonance (CMR) has become reference standard for chamber quantification, with complimentary utility of valvular heart disease CMR may provide additional insights to transthoracic echocardiography (TTE) into chamber remodeling in aortic valve disease. We prospectively compared chamber quantification measured by TTE and CMR between AR and AS patients. Methods: In this study, we prospectively recruited moderate-to-severe AR (n=101) or AS (n=44) patients undergoing clinically-indicated TTE and CMR within 3-months of each other. TTE and CMR measurements were compared using Pearson correlation coefficient and Bland-Altman plots. Results: AR patients were significantly younger (57±15 versus 69±15 years, P&lt;0.001), with lower proportion of females (26% versus 43%, P=0.050), being symptomatic (42% versus 68%, P=0.004), and higher proportion having bicuspid aortic valve (45% versus 27%, P=0.064) and dilated thoracic aorta (52% versus 23%, P=0.002) than AS patients. Moderate-to-high correlations were observed by TTE- and CMR-left ventricular parameters in both valve groups (r=0.50-0.80). The Figure shows that eft ventricular volumes were significantly higher by CMR than TTE, while ejection fraction (LVEF) were similar, and left ventricular global longitudinal strain (LVGLS) was more negative by CMR-SENC technique than TTE-velocity vector imaging technique. By CMR, AR patients had significantly higher left ventricular volumes (P&lt;0.001), lower LVEF (P=0.033) and similar LVGLS (P=0.593) than AS patients. Conclusion: CMR left ventricular parameters had moderate-to-high correlations but systematic differences in measurements compared in aortic valve disease patients. Expected differences were observed between CMR-derived left ventricular remodeling of AR and AS.

Abstract 11499: Management of Mixed Aortic Valve Disease Patients: Can N-terminal Pro-Brain Natriuretic Peptide Ratio Improve Risk Assessment?

Introduction: Risk assessment of mixed aortic valve disease (MAVD: concomitant aortic stenosis [AS] and regurgitation [AR]) patients is challenging, especially in non-severe lesions. In fact, these patients often present LV dysfunction after aortic valve replacement (AVR), and concomitant non-severe lesions appear to have similar outcomes than severe AS. Objective: We aimed to evaluate the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) ratio in risk stratification of MAVD patients. Methods: A total of 582 consecutive MAVD patients (mean age 73±11 years, 63% men) with at least concomitant mild AS and AR in whom a measurement of NT-proBNP during the same episode of care was available were included. NT-proBNP ratio (i.e., plasma level divided by maximal normal values for age and sex derived from Mayo Clinic laboratory) was calculated. In subgroups analyses, patients were divided according to MAVD pattern (severe AS or AR [n=364] and non-severe AS/AR [n=218]) and according to treatment strategy (early AVR [i.e., ≤3 months, n=429] or initial medical treatment [MT; n=153]). Results: Baseline median NT-proBNP ratio was 3.5 (IQR: 1.2-10.0). A total of 105 patients died during a median follow-up of 5.6 (2.8-6.1) years. Overall, NT-proBNP ratio ≥3 was significantly associated with long-term all-cause mortality in multivariable analyses adjusted for clinical and echocardiographic parameters as well as AVR as a time-dependent variable . NT-proBNP-ratio also showed incremental prognostic value at 1, 2 and 5 years over EuroSCORE II and echocardiographic parameters (all, net reclassification index &gt;0.45; p≤0.005). In all subgroups, NT-proBNP-ratio ≥3 remained independently associated with excess mortality ( severe AS or AR - HR[95CI]: 3.30[1.54-7.05], non-severe AS/AR : 2.14[1.03-4.43], early AVR : 2.48[1.16-5.39], initial MT : 2.72[1.02-7.22]; all p≤0.04). In patients who underwent early AVR, NT-proBNP-ratio ≥3 was also associated with higher 30-days mortality (9[4%] vs. 1[0.5%], p=0.02). Conclusions: In this series of MAVD patients, NT-proBNP-ratio was a powerful predictor of mortality, even in non-severe lesions, early AVR and medically treated patients. AVR may be reasonable before reaching an NT-proBNP-ratio ≥3.

Abstract 9903: Artificial Intelligence Driven Wearable 2-minute Seismocardiography Test for Detection of Aortic Valve Stenosis Severity

Introduction: Standard diagnosis of aortic valve stenosis (AS) requires clinical imaging by echocardiography or cardiac MRI. The purpose of this study was to test the performance of easy to use, artificial intelligent (AI) driven seismocardiogram (SCG) chest acceleration recordings for point of care screening and identification of AS. Hypothesis: SCG measurements can be used by a low dimensional convolutional neural network (CNN) to accurately predict presence or absence of aortic valve stenosis (AS) and severity of dysfunction. Methods: This IRB approved study included 45 controls (age 46±17y, 20 F, no known cardiovascular disease) and 30 aortic valve disease (AVD) patients (age 30±20y, 7 F, 21 bicuspid). A wearable SCG device (integrated ECG/accelerometer microelectronics) was placed for 2min chest acceleration recordings on the same day as standard of care echocardiography or cardiac MRI, which was used as ground truth data to classify valve function (normal: AS-, mild AS: AS+, moderate/severe AS: AS++). A deep learning CNN (2х2 kernel, softmax/cross entropy classification) was configured to predict/detect degree of AS from spectrally decomposed SCG measurements. Randomized 50% split of subjects was used for CNN training/testing. Performance detecting AS was evaluated for classification accuracy. Results: AI driven SCG detection of valve function abnormality had high sensitivity/specificity (90%, 67%) with a net area under curve (AUC) 0.86. Correct classification of the degree of AS was achieved in 76% of subjects. Normal (AS-) vs abnormal function (AS+ or AS++) was accurately identified by AI driven SCG for 86% of subjects. Conclusions: This feasibility study demonstrates that the combination of easily measured 2 minute SCG with a deep processing pipeline could successfully detect the presence and severity of AS, supporting clinical promise for potential use as a low cost, front line screening tool to identify patients with aortic valve dysfunction.

Deslocamento Linear Longitudinal do Ventrículo Esquerdo Comparado ao Strain Longitudinal Global por Ressonância Magnética Cardiovascular

Background: Left ventricular (LV) systolic diastolic function is prognostic in cardiovascular diseases and can be assessed via global longitudinal strain (GLS) on echocardiography and cardiac magnetic resonance (CMR). However, GLS by CMR requires the use of expensive software. Longitudinal linear displacement (LLD) may be a simple and inexpensive alternative to GLS, but the two have not been systematically compared. Objective: To compare LLD with GLS and LV ejection fraction (LVEF) in aortic valve disease patients and controls. Methods: We included 44 participants (26 with aortic valve disease, 19 controls). GLS was determined using CVI42 software (Circle Cardiovascular Imaging), while the LLD linear measurements of the distance between the base/apex of the LV included maximum displacement (MD), maximum velocity in early diastole (MVED), atrioventricular junction velocity in diastasis (VDS), and VDS/MVED ratio. Results: DM and MVED were correlated with GLS (r=0.69 and r=0.65, respectively) and LVEF (r=0.47 and r=0.57, p&lt;0.001 for both). DM and MVED showed areas under the receiver operating characteristic curve (AUC) of 0.88 and 0.91, and at the best cut-off point (-0.13 and 0.66), sensitivities of 72.43% and 57.14% and specificities of 80.65% and 87.10%, respectively, compared to GLS. Using LVEF as a reference, we obtained AUC of 0.70 and 0.82, and at the best cut-off point (-0.11 and 0.61), sensitivities of 75.00% and 50.00% and specificities of 72.97% and 78.38%, respectively. Conclusion: LLD demonstrated similar performance to that of GLS. MD derived from LLD was the best parameter during systole, while MVED was the best during diastole. Our findings demonstrate the routine, quick, and inexpensive assessment of diastolic function on CMR.

Ascending aortic perivascular adipose tissue inflammation associates with aortic valve disease

BackgroundAscending aortic perivascular adipose tissue (AA-PVAT) mainly comprises brown adipose tissue (BAT), originates from neural crest cells that derive from ectoderm, and plays important role in angiotensin II-induced vascular inflammation and remodeling in mice. However, the characterization and function of human AA-PVAT remains highly unclear. MethodsPatients with coronary artery disease (CAD) (n = 20) and aortic valve disease (AVD) (n = 23) who underwent cardiac surgery consented to take part in transcriptome and histological studies. Paired samples of AA-PVAT, epicardial adipose tissue (EAT), and subcutaneous adipose tissue (SAT) were obtained. RNA sequencing, histological analysis, quantitative reverse transcription polymerase chain reaction and western blot studies were performed on those samples. ResultsHuman AA-PVAT exhibited smaller adipocyte morphology and high expression of brown adipocyte marker. Transcriptome analysis revealed that AA-PVAT showed unique transcriptome characteristics compared with EAT and SAT. While comparing CAD and AVD patients, AA-PVAT exhibited a decreasing brown phenotype and higher inflammatory response in AVD patients. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the differentially expressed genes in AA-PVAT between CAD and AVD patients were involved mainly in the processes of inflammation and metabolism regulation. ConclusionsHuman AA-PVAT is a BAT-like adipose tissue with unique transcriptome characteristics, and exhibits a weakened brown phenotype and an enhanced inflammation response in AVD patients.

Endothelial cell-derived tetrahydrobiopterin prevents aortic valve calcification.

Tetrahydrobiopterin (BH4) is a critical determinant of the biological function of endothelial nitric oxide synthase. The present study was to investigate the role of valvular endothelial cell (VEC)-derived BH4 in aortic valve calcification. Plasma and aortic valve BH4 concentrations and the BH4:BH2 ratio were significantly lower in calcific aortic valve disease patients than in controls. There was a significant decrease of the two key enzymes of BH4 biosynthesis, guanosine 5'-triphosphate cyclohydrolase I (GCH1) and dihydrofolate reductase (DHFR), in calcified aortic valves compared with the normal ones. Endothelial cell-specific deficiency of Gch1 in Apoe-/- (Apoe-/-Gch1fl/flTie2Cre) mice showed a marked increase in transvalvular peak jet velocity, calcium deposition, runt-related transcription factor 2 (Runx2), dihydroethidium (DHE), and 3-nitrotyrosine (3-NT) levels in aortic valve leaflets compared with Apoe-/-Gch1fl/fl mice after a 24-week western diet (WD) challenge. Oxidized LDL (ox-LDL) induced osteoblastic differentiation of valvular interstitial cells (VICs) co-cultured with either si-GCH1- or si-DHFR-transfected VECs, while the effects could be abolished by BH4 supplementation. Deficiency of BH4 in VECs caused peroxynitrite formation increase and 3-NT protein increase under ox-LDL stimulation in VICs. SIN-1, the peroxynitrite generator, significantly up-regulated alkaline phosphatase (ALP) and Runx2 expression in VICs via tyrosine nitration of dynamin-related protein 1 (DRP1) at Y628. Finally, folic acid (FA) significantly attenuated aortic valve calcification in WD-fed Apoe-/- mice through increasing DHFR and salvaging BH4 biosynthesis. The reduction in endothelial-dependent BH4 levels promoted peroxynitrite formation, which subsequently resulted in DRP1 tyrosine nitration and osteoblastic differentiation of VICs, thereby leading to aortic valve calcification. Supplementation of FA in diet attenuated hypercholesterolaemia-induced aortic valve calcification by salvaging BH4 bioavailability.

Characteristics and outcomes following transcatheter aortic valve replacement in China: a report from China aortic valve transcatheter replacement registry (CARRY).

Background:The past decade has witnessed an ever-increasing momentum of transcatheter aortic valve replacement (TAVR) and a subsequent paradigm shift in the contemporary management of severe aortic stenosis (AS). We conducted a multi-centric TAVR registry based on Chinese patients (the China Aortic valve tRanscatheter Replacement registrY [CARRY]) to delineate the clinical characteristics and outcomes of Chinese patients who underwent TAVR and compare the results between different valve types in different Chinese regions.Methods:CARRY is an all-comer registry of aortic valve disease patients undergoing TAVR across China and was designed as an observational study that retrospectively included all TAVR patients at each participating site. Seven hospitals in China participated in the CARRY, and 1204 patients from April 2012 to November 2020 were included. Categorical variables were compared using the chi-squared test, and continuous variables were analyzed using a t test or analysis of variance (ANOVA) test. The Kaplan–Meier curve was used to estimate the risk of adverse events during follow-up.Results:The mean age of the patients was 73.8 ± 6.5 years and 57.2% were male. The median Society of Thoracic Surgeon-Predicted Risk of Mortality score was 6.0 (3.7–8.9). Regarding the aortic valve, the proportion of bicuspid aortic valve (BAV) was 48.5%. During the hospital stay, the stroke rate was 0.7%, and the incidence of high-degree atrioventricular block indicating permanent pacemaker implantation was 11.0%. The in-hospital all-cause mortality rate was 2.2%. After 1 year, the overall mortality rate was 4.5%. Compared to patients with tricuspid aortic valve (TAV), those with BAV had similar in-hospital complication rates, but a lower incidence of in-hospital mortality (1.4% vs. 3.3%) and 1 year mortality (2.3% vs. 5.8%).Conclusions:TAVR candidates in China were younger, higher proportion of BAV, and had lower rates of post-procedural complications and mortality than other international all-comer registries. Given the use of early generation valves in the majority of the population, patients with BAV had similar rates of complications, but lower mortality than those with TAV. These findings further propel the extension of TAVR in low-risk patients.Trial Registration:https://www.chictr.org.cn/ (No. ChiCTR2000038526).

Impact of osteogenic activity on degenerative aortic valve disease in patients with osteoporotic hip fracture

BackgroundPrevious studies have proposed that osteogenic and apoptotic processes of valve interstitial cells contribute to the mineralization and then calcification of the aortic valve. Osteoblast-like cells subsequently mediate calcification of the aortic valve as part of a highly regulated process analogous to skeletal bone formation. The objective of this study was to evaluate the pathogenesis of the sclerotic/calcific changes in the aortic valve from histological and biological findings, and investigate the role of osteoblasts in the calcified pathway of aortic stenosis. MethodsPreoperative echocardiography in 550 consecutive patients with osteoporotic hip fracture were retrospectively examined (475 females, mean 25th–75th, 89 [85–93] years). One hundred sixteen patients were under medical treatment with anti-osteoporosis drugs. We evaluated the prevalence and degree of degenerative changes in the aortic valve and examined the associations of bone turnover biomarkers N-terminal pro-peptide of type 1 collagen (P1NP) and serum tartrate-resistant acid phosphatase (TRACP-5b) with degenerative calcific changes in the aortic valve. ResultsOf 550 patients, 112 patients (20.9%) showed no leaflet calcification; 296 (53.8%), 1 leaflet calcification; and 142 (25.8%), 2 ≥ leaflets calcification. Significant (peak velocity ≥ 3.0m/s) Aortic stenosis was found in 43 patients (7.8%). In patients who were not taking anti-osteoporotic drugs, P1NP was higher in the 2 ≥ leaflets calcification group than in the other groups (p < 0.01). TRACP-5b was not significantly different among the three groups (p = 0.15). ConclusionsDegenerative changes in the aortic valve were related to bone biomarker activation in osteoporotic hip fracture patients.

86057 High Screening Efficacy Using Wearable Seismocardiography to Identify Aortic Valve Disease Patients, Potential to Tailor MRI Exams to Patient Needs

ABSTRACT IMPACT: A single seismocardiography (SCG) parameter has been shown to accurately classify aortic valve disease (AVD) status in healthy controls and AVD patients. This could support development of SCG as a quick, inexpensive screening tool to better tailor MRI examination to patients’ needs. OBJECTIVES/GOALS: MRI is used commonly for monitoring of aortic valve disease (AVD), but it has high costs. We hypothesize that energy in seismocardiograms (SCG)’‘ signals from chest surface vibrations’‘ is different between healthy controls and AVD patients, and we evaluate potential efficacy of using SCG to recommend MRI only for patients with flow abnormalities. METHODS/STUDY POPULATION: With IRB approval, 45 healthy control subjects (47 ±18years, 18 female) and 9 patients (63 ±16years, 2 female) with aortic valve disease history and known flow abnormalities were recruited. SCG signals were acquired supine, immediately prior to MRI of thoracic aortic blood flow at 1.5T with a time-resolved phase contrast (4D Flow) sequence.The SCG was processed to calculate late-systole high-frequency (120-240Hz) RMS energy. MR velocity images were analyzed to measure peak velocity and trace pathlines of flow.Screening efficacy of the SCG energy metric was assessed, with hypothesis testing for differences in energy level distributions between controls and patients, and receiver-operator characteristic (ROC) analysis was used to calculate rates of correct/incorrect classification of disease. RESULTS/ANTICIPATED RESULTS: Healthy subjects had coherent flow pathlines through the aortic arch and mid-ascending aorta peak velocities of 106 ±21cm/s (cohort mean ±standard deviation). All valve disease subjects had flow abnormalities, such as jetting flow near the valve or swirling through the arch, as visualized by pathlines. Patients’ peak mid-ascending aorta velocities were 167 ±69cm/s. The SCG energy for healthy controls was significantly different than that of valve patients (-5.6 ±0.3dBmm/s/s vs. -4.0 ±1.2dBmm/s/s respectively; p&lt;0.001). Thresholding SCG energy to distinguish patients from controls correctly classifies subjects with a high true-positive rate and low false-positive rate. The ROC for this classification has area-under-curve 0.956. DISCUSSION/SIGNIFICANCE OF FINDINGS: A high potential screening efficacy was observed using a single, linear SCG metric to identify AVD patients with flow abnormalities. If used to complement MRI surveillance protocols for AVD, this method has potential to serve as a quick, inexpensive tool for better tailoring MRI exams to patient needs.