Degenerative Aortic Valve Research Articles

Cost-effectiveness analysis of valvular surgery in high- and low- to middle-income countries: A scoping review.

Global disparities in valvular surgery services exist. Cost-effectiveness analysis (CEA) and cost-utility analysis can be used to guide national investment decisions. This scoping review aims to synthesize economic evaluations for valvular surgery by income settings and provide recommendations. A systematic literature review identified primary CEAs or CUAs in English comparing surgical management strategies for valvular heart disease. MEDLINE, Embase, CINAHL, Web of Science, and Business Source Complete were searched using keywords "valvular surgery," "valve disease," "cost-effectiveness," and "cost-benefit analysis". Articles comparing outcomes or costs only were excluded. Search results were uploaded and screened on COVIDENCE. Variables from eligible articles were charted in a spreadsheet. Twenty articles were eligible, six from low- and middle-income countries (LMICs) and 14 from high-income countries (HICs). In HICs, the top conditions were degenerative aortic valve disease (7/14) and mitral valve disease (4/14) compared to congenital (2/6) and rheumatic heart diseases (2/6) in LMICs. HICs evaluated new technologies and techniques, whereas LMICs compared different valve types or surgery versus no intervention. Most articles used published studies (12/20) or databases (7/20) to conduct their CEA and quality-adjusted life years was the most common effectiveness measure (12/20). Comparator interventions were cost-effective in all LMIC articles and in 8/14 for HICs. Economic evaluations are mostly conducted in HICs and for adult conditions. More analyses in LMICs are needed. This can be facilitated by maintaining databases, documenting costs, and implementing quality of life assessments.

Successful management of acute left main coronary occlusion following transcatheter aortic valve implantation: a case report

BackgroundTranscatheter aortic valve implantation is an established, highly effective procedure in selected patients with severe degenerative aortic valve stenosis at high risk for conventional surgery.Case presentationWe report a case of a 74-year-old Caucasian man who had an acute left main occlusion after transcatheter implantation of balloon-expandable valve prosthesis, followed by coronary intervention with successful recanalization.ConclusionsAcute coronary occlusion is a rare life-threatening complication of transcatheter aortic valve implantation that is poorly predictable and requires immediate diagnosis and treatment.

Lipoprotein (a) as a Cardiovascular Risk Factor in Controversial Clinical Scenarios: A Narrative Review

Lipoprotein (a) is a complex lipid molecule that has sparked immense interest in recent years, after studies demonstrated its significant association with several cardiovascular conditions. Lp(a) promotes cardiovascular disease through its combined proatherogenic, pro-inflammatory, and prothrombotic effects. While the measurement of Lp(a) has become widely available, effective methods to reduce its concentration are currently limited. However, emerging data from ongoing clinical trials involving antisense oligonucleotides have indicated promising outcomes in effectively reducing Lp(a) concentrations. This may serve as a potential therapeutic target in the management and prevention of myocardial infarction, calcific aortic stenosis, and cerebrovascular accidents. In contrast, the role of Lp(a) in atrial fibrillation, in-stent restenosis, cardiac allograft vasculopathy, and bioprosthetic aortic valve degeneration remains unclear. This review article aims to thoroughly review the existing literature and provide an updated overview of the evidence surrounding the association of Lp(a) and these cardiovascular diseases. We seek to highlight controversies in the existing literature and offer directions for future investigations to better understand Lp(a)’s precise role in these conditions, while providing a summary of its unique molecular characteristics.

Clinical profile, microbiology and outcomes in infective endocarditis treated with aortic valve replacement: a multicenter case-control study

BackgroundAortic valve infective endocarditis (IE) is associated with significant morbidity and mortality. We aimed to describe the clinical profile, risk factors and predictors of short- and long-term mortality in patients with aortic valve IE treated with aortic valve replacement (AVR) compared with a control group undergoing AVR for non-infectious valvular heart disease.MethodsBetween January 2008 and December 2013, a total of 170 cases with IE treated with AVR (exposed cohort) and 677 randomly selected non-infectious AVR-treated patients with degenerative aortic valve disease (controls) were recruited from three tertiary hospitals with cardiothoracic facilities across Scandinavia. Crude and adjusted hazard ratios (HR) were estimated using Cox regression models.ResultsThe mean age of the IE cohort was 58.5 ± 15.1 years (80.0% men). During a mean follow-up of 7.8 years (IQR 5.1-10.8 years), 373 (44.0%) deaths occurred: 81 (47.6%) in the IE group and 292 (43.1%) among controls. Independent risk factors associated with IE were male gender, previous heart surgery, underweight, positive hepatitis C serology, renal failure, previous wound infection and dental treatment (all p < 0.05). IE was associated with an increased risk of both short-term (≤ 30 days) (HR 2.86, [1.36–5.98], p = 0.005) and long-term mortality (HR 2.03, [1.43–2.88], p < 0.001). In patients with IE, chronic obstructive pulmonary disease (HR 2.13), underweight (HR 4.47), renal failure (HR 2.05), concomitant mitral valve involvement (HR 2.37) and mediastinitis (HR 3.98) were independent predictors of long-term mortality. Staphylococcus aureus was the most prevalent microbe (21.8%) and associated with a 5.2-fold increased risk of early mortality, while enterococci were associated with the risk of long-term mortality (HR 1.78).ConclusionsIn this multicenter case-control study, IE was associated with an increased risk of both short- and long-term mortality compared to controls. Efforts should be made to identify, and timely treat modifiable risk factors associated with contracting IE, and mitigate the predictors of poor survival in IE.

Clinical implications of Sokolow-Lyon voltage less than 3.5 mV in patients who have undergone transcatheter aortic valve replacement.

Degenerative severe aortic valve stenosis (AS) is increasingly prevalent in the aging population, leading to the adoption of transcatheter aortic valve replacement (TAVR) as a less invasive alternative. While TAVR indications have expanded, the procedure is associated with a substantial incidence of major adverse cardiac events (MACE). The study aims to establish a preoperative risk-stratification system for TAVR candidates based on Sokolow-Lyon voltage (SLV) and other relevant factors. A total of 181 consecutive patients who underwent TAVR were retrospectively reviewed. Baseline characteristics, preoperative electrocardiogram (ECG) and echocardiography findings, and TAVR procedures were assessed. Low SLV (<3.5 mV) was defined based on ECG measurements. Baseline characteristics revealed a mean age of 84 years, with 71.8% females. The two-year incidence of MACE defined as a composite of cardiac death and hospitalization due to heart failure, was 11.6%, significantly higher in the low SLV group. Low SLV emerged as an independent prognostic factor. The Tokyo Bay Risk (TBR) Score, including low SLV, Body Mass Index <18.5 kg/m2, and previous coronary artery disease, effectively stratified MACE risk. Higher TBR scores (2 or 3) correlated with increased MACE risk. Patients with low SLV in pre-procedural ECG demonstrated a heightened risk of two-year MACE. The TBR score, incorporating low SLV, proved valuable for preoperative risk assessment. Careful consideration of TAVR indications, along with TBR score integration, is crucial for optimizing outcomes.

Laser ablation for preventing coronary obstruction and maintaining coronary access in redo-TAVR: A proof of concept.

Redo-transcatheter aortic valve replacement (TAVR) is a promising treatment for transcatheter aortic valve degeneration, becoming increasingly relevant with an aging population. In redo-TAVR, the leaflets of the initial (index) transcatheter aortic valve (TAV) are displaced vertically when the second TAV is implanted, creating a cylindrical cage that can impair coronary cannulation and flow. Preventing coronary obstruction and maintaining coronary access is essential, especially in young and low-risk patients undergoing TAVR. This study aimed to develop a new leaflet modification strategy using laser ablation to prevent coronary obstruction and facilitate coronary access after repeat TAVR. To evaluate the feasibility of the leaflet modification technique using laser ablation, the initial phase of this study involved applying a medical-grade ultraviolet laser for ablation through pericardial tissue. Following this intervention, computational fluid dynamics simulations were utilized to assess the efficacy of the resulting perforations in promoting coronary flow. These simulations played a crucial role in understanding the impact of the modifications on blood flow patterns, ensuring these changes would facilitate the restoration of coronary circulation. Laser ablation of pericardium leaflets was successful, demonstrating the feasibility of creating openings in the TAV leaflets. Flow simulation results show that ablation of index valve leaflets can effectively mitigate the flow obstruction caused by sinus sequestration in redo-TAVR, with the extent of restoration dependent on the number and location of the ablated openings. Laser ablation could be a viable method for leaflet modification in redo-TAVR, serving as a new tool in interventional procedures.

Treating Aortic Valve Stenosis for Vitality Improvement: The TAVI Study.

Degenerative aortic valve stenosis (AS) is the most common valvular heart disease among the elderly. Once cardiac symptoms occur, current guidelines recommend aortic valve replacement. Progressive degeneration/calcification reduces leaflet mobility with gradual cardiac output (CO) impairment. Low CO might induce abnormal brain-aging with cognitive impairment and increased risk of dementia, such as Alzheimer's disease or vascular dementia. On the contrary, cognitive improvement has been reported in patients in whom CO was restored. Transcatheter aortic valve implantation (TAVI) has proven to be a safe alternative to conventional surgery, with a similar mid-term survival and stroke risk even in low-risk patients. TAVI is associated with an immediate CO improvement, also effecting the cerebrovascular system, leading to an increased cerebral blood flow. The correlation between TAVI and cognitive improvement is still debated. The present study aims at evaluating this relationship in a cohort of AS patients where cognitive assessment before and after TAVI was available. a total of 47 patients were retrospectively selected. A transcranial Doppler ultrasound (TCD) before and after TAVI, a quality of life (QoL) score, as well as a mini-mental state examination (MMSE) at baseline and up to 36 months, were available. TAVI was associated with immediate increase in mean cerebral flow at TCD. MMSE slowly increase at 36-months follow-up with improved QoL mainly for symptoms, emotions and social interactions. this proof-of-concept study indicates that TAVI might induce cognitive improvement in the long-term as a result of multiple factors, such as cerebral flow restoration and a better QoL.

Precise reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in new formula: a case report

BackgroundThe current study presents a novel and precise surgical technique for complete reconstruction of the aortic valve using glutaraldehyde-treated autologous pericardium in a patient with aortic valve disease and endocarditis. The technique aims to provide a more effective and reproducible method for aortic valve repair, with the goal of improving outcomes and quality of life for patients with aortic valve disease.Case presentationA 35-year-old Iranian male with aortic valve disease and endocarditis underwent aortic valve reconstruction surgery. Preoperative echocardiography showed a degenerative aortic valve with severe regurgitation, reduced left ventricular ejection fraction, and specific aortic root dimensions. The surgical technique involved precise measurements and calculations to design the size and shape of the new aortic valve cusps using autologous pericardium, with the goal of optimizing coaptation and function. The surgeon calculated the intercommissural distance based on the aortic annulus diameter to determine cusp size and shape. He tailored the pericardial cusps to have a height equal to 80% of the coaptation margin length. Detailed suturing techniques were used to ensure proper alignment and coaptation of the new cusps. Intraoperative evaluation of the valve function using suction and transesophageal echocardiography showed good coaptation and minimal residual regurgitation. At the 3-year follow-up, the patient had a well-functioning aortic valve with only trivial leak and was in satisfactory clinical condition.ConclusionsGlutaraldehyde-treated autologous pericardium is a validated leaflet alternative, and the causes of its failure are late annular dilatation and other technique breakdowns. Current evidence reveals that aortic valve reconstruction with glutaraldehyde-treated autologous pericardium is associated with many advantages with the potential to improve patient outcomes and quality of life. Further clinical studies are warranted to evaluate the long-term durability and efficacy of this approach.

Wearable device-measured moderate to vigorous physical activity and risk of degenerative aortic valve stenosis.

Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

Aortic valve degeneration after valve-sparing root replacement in patients with bicuspid aortopathy or connective tissue disorder

ObjectiveWe sought to evaluate outcomes of valve-sparing root replacement (VSRR) in patients with bicuspid aortopathy (BAV) versus other connective tissue disorder (CTD). MethodsThis was a single-center cohort study of consecutive patients undergoing VSRR via reimplantation from 2000 to 2023 with BAV or CTD. Operative outcomes, Kaplan-Meier survival estimates, and cumulative risk of reoperation and recurrent aortic insufficiency (AI) with the competing risk of death were assessed. ResultsOf 516 patients who underwent VSRR, 109 (51.9%) had BAV and 101 (48.1%) had CTD. Patients with BAV were older (46.9 ± 10.4 vs 38.4 ± 14 years, P < .001) and more likely male (89.0% vs 56.4%, P < .001) and hypertensive (66.1% vs 28.7%, P < .001). Preoperative AI was similar (P = .57) between groups (30.3% mild, 18.3% moderate, 11.1% severe). Most patients had no/trivial immediate postoperative residual AI (96.3% vs 93.1%). Operative mortality was zero; postoperative adverse events were minimal. Mean clinical follow-up was 5.2 ± 4.4 years; 10-year survival was 95.6% versus 95.7% (P = .70). Echocardiographic follow-up was 3.9 ± 4.1 years; incidence of >2+ AI (9.7% vs 10.1%, P = 1.0) was similar between groups, whereas the incidence of moderate or greater aortic stenosis was greater with BAV (7.5% vs 0%, P = .02). Reoperation was low in both groups (3.7% vs 5.9%, P = .65). Competing risk analysis found no difference in reoperation hazard between BAV and CTD groups (hazard ratio, 0.36; 95% confidence interval, 0.07-1.81, P = .21). ConclusionsPatients with BAV and CTD have excellent operative outcomes, no mortality, and minimal residual AI after VSRR. Although the incidence of recurrent AI was similar, patients with BAV are at risk for AS.

Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Relationship Between Clinical Parameters and Histological Features of Epicardial Adipose Tissue and Aortic Valve Calcification Assessed on Computed Tomography.

The relationships of the clinical and biological attributes of epicardial adipose tissue (EAT) with aortic valve calcification (AVC) have not been characterized. We evaluated the relationships of the clinical and histological features of EAT with AVC assessed using computed tomography (CT).Methods and Results: We enrolled 43 patients undergoing cardiac CT examination prior to elective cardiac surgery in whom AVC was identified on CT. EAT volume and density, coronary calcium score (CCS), AVC score (AVCS), and coronary atherosclerosis on CT angiography were evaluated in each patient. During cardiac surgery, 2 EAT samples were obtained for immunohistochemistry. The number of CD68- and CD11c-positive macrophages and osteocalcin-positive cells was counted in 6 random high-power fields of EAT sections. EAT density, but not EAT volume normalized to body surface area, was positively correlated with the number of macrophages and osteocalcin-positive cells in EAT. There was a positive correlation between ln(AVCS), but not ln(CCS+1), and the number of macrophages and osteocalcin-positive cells in EAT. Multivariate analysis revealed significant positive correlations for ln(AVCS) with EAT density (β=0.42; P=0.0072) and the number of CD68-positive macrophages (β=0.57; P=0.0022), CD11c-positive macrophages (β=0.62; P=0.0003), and osteocalcin-positive cells (β=0.52; P=0.0021) in EAT. Inflammation and osteogenesis in EAT, reflected by high CT density, are associated with the severity of AVC representing aortic valve degeneration.

TAVI in younger patients: is it a reliable option?

Abstract Funding Acknowledgements None. Background/Introduction Severe aortic stenosis is the most common valve disease requiring intervention. It has very poor prognosis, and early intervention is recommended. Either surgical or percutaneous transcatheter intervention is possible. According to European guidelines, surgical aortic valve replacement (SAVR) is usually indicated for patients younger than 75 years old. However, some patients are refused surgery, and transcatheter aortic valve implantation (TAVI) might be an option of treatment for these patients, however medium-long term results are still uncertain. Purpose This study intends to evaluate the efficacy and safety of TAVI in younger patients with severe symptomatic aortic stenosis. Methods Retrospective cohort of 224 patients were submitted to TAVI in the last 3 years, of which 21 patients were younger than 75 years old. The primary endpoints are mortality, major adverse cardiovascular events (MACE) and rehospitalization (related to the procedure, valve, or heart failure). Efficacy and safety were evaluated during a follow-up of at least 6 months, compared with the traditional group. Results A total of 224 patients underwent TAVI during the last 3 years at our center. Of these, 21 patients (9%) were younger than 75 years. The mean age was 72,1±3 [62-75] years old and 33% were female (n=7). 95% (n=20) of the TAVI procedures were due to degenerative severe aortic stenosis and 5% (n=1) due to degenerative aortic surgical valve prothesis. The mean euroscore risk value was 6,2±1,3%, and 18 patients were refused for surgery (86%) and 3 patients refused surgery (14%). All procedures were performed by transfemoral access, with 2 peripheral access complications (9,5%), 1 hemorrhagic (4%), solved with covered stent, and 1 closure device occlusion solved with wire crossing and balloon inflation (4%). It was necessary to implant 3 temporary pacemakers, however, only 2 patients required a definitive pacemaker implantation (9,5%). There were no cases intraprocedural death, MACE or aortic severe complications. There was a statistically significant reduction of risk of peripheral complications and pacemaker implantation on younger patients comparing with older patients (p=0,04 and p=0,05 respectively). Mean follow-up time was 14±8,3 months [6-39 months]. During follow-up there were no deaths, MACE or episodes of rehospitalization due to heart failure recorded. Regarding echocardiographic evaluation, there were no cases of significant valve degeneration, with mean aortic gradient of 13±4,1mmHg, no significant leakage or other echocardiographic findings. In younger patients, TAVI appears to be also valid therapeutic option, with less risk of peripheral access complication or need of permanent pacemaker implantation. During the follow-up there was no cases of prothesis degeneration, proving to be a reliable option for the medium to long term.

Abstract 3062: Activation Of Adam17-dlk1 Axis Induces Aortic Valve Calcification.

Aortic valve stenosis (AS) is characterized by valve architecture disruption through mineralization and valve cusps fibrosis. Currently, there are no proven pharmacotherapies to prevent or decelerate AS progression. Understanding the molecular mechanisms leading to aortic valve mineralization is of inestimable importance. A balance between calcium deposition and regression may be involved in the pathogenesis of calcified aortic valve disease. Delta-like 1 homolog (Dlk1) is an imprinted gene that can be proteolytically cleaved within the juxta-membrane region by TACE, resulting in the release of an extracellular part of Dlk1 as a soluble fragment known as fetal antigen 1 (FA1). DLK1 is associated with increased adiposity and fibrosis. Objective: extracellular matrix (ECM) remodeling disorder in response to TACE-Dlk1 defect might affect valve structure through ECM-lipid interaction in patients with abdominal obesity. We investigated the potential role of TACE/DLK1 in activating osteoblastic differentiation in mouse valve interstitial cells (VICs) in vitro. Method: We first isolated VICs from WT and DLK1-/- mice and treated them with a calcifying medium for seven days. Mass spectrometry examined extracellular protein expression (ECM) and increased lipid retention. Results: The loss of function of Dlk1 was associated with disrupted ECM expression and the increase of osteogenic genes (RUNX2, SPP1, BMP2, MSX2) expression. Conclusion: Dlk1 affects ECM expression and lipid retention, enhancing aortic valve degeneration.

TRANSCATHETER AORTIC VALVE REPLACEMENT: FROM IDEA TO IMPLEMENTATION

HighlightsTranscatheter aortic valve replacement is an innovative trend in modern cardiovascular surgery. This minimally invasive image-guided endovascular technology is becoming more and more safe, nowadays it can involve a minimalistic approach in which the aortic valve replacement is performed without incisions, anesthesia and cardiopulmonary bypass - patients are conscious and spontaneously breathing. The article describes a paradigm shift in modern cardiology, in which the concept of treating patients with degenerative aortic valve stenosis has changed over the 20 years of existence of the transcatheter replacement, starting as a method used only in small number of extremely high-risk patients unsuitable for cardiac surgery and now being the most prevalent treatment modality in patients at intermediate and even low surgical risk. The main clinical and technical principles of transcatheter aortic valve replacement, as well as the prospects for the development of this technique, are highlighted. Abstract Transcatheter aortic valve replacement technique was first implemented about 20 years ago, in April 2002. A quarter of a century ago, specialists involved in image-guided surgery would have never believed that they would perform transcatheter interventions on heart valves. Transcatheter interventions are an alternative to open-heart surgery for acquired heart disease. Transcatheter heart valve replacement or repeat transcatheter aortic valve replacement, which do not require incisions, cardiopulmonary bypass, and in some cases general anesthesia, to this day continue to be perceived as revolutionary and breakthrough, saving the lives of many patients. The article presents the main milestones in the development of image-guided endovascular surgery and transcatheter aortic valve replacement technique, the number of which in the United States and several European countries increases by 10–15% annually, reaching hundreds of thousands per year. The etiology and pathophysiology of aortic stenosis, the technique of transcatheter aortic valve replacement and the outcome of this promising minimally invasive procedure are presented.

Specific Multiomic Profiling in Aortic Stenosis in Bicuspid Aortic Valve Disease.

Bicuspid aortic valve (BAV) disease is associated with faster aortic valve degeneration and a high incidence of aortic stenosis (AS). In this study, we aimed to identify differences in the pathophysiology of AS between BAV and tricuspid aortic valve (TAV) patients in a multiomics study integrating metabolomics and transcriptomics as well as clinical data. Eighteen patients underwent aortic valve replacement due to severe aortic stenosis: 8 of them had a TAV, while 10 of them had a BAV. RNA sequencing (RNA-seq) and proton nuclear magnetic resonance spectroscopy (1H-NMR) were performed on these tissue samples to obtain the RNA profile and lipid and low-molecular-weight metabolites. These results combined with clinical data were posteriorly compared, and a multiomic profile specific to AS in BAV disease was obtained. H-NMR results showed that BAV patients with AS had different metabolic profiles than TAV patients. RNA-seq also showed differential RNA expression between the groups. Functional analysis helped connect this RNA pattern to mitochondrial dysfunction. Integration of RNA-seq, 1H-NMR and clinical data helped create a multiomic profile that suggested that mitochondrial dysfunction and oxidative stress are key players in the pathophysiology of AS in BAV disease. The pathophysiology of AS in BAV disease differs from patients with a TAV and has a specific RNA and metabolic profile. This profile was associated with mitochondrial dysfunction and increased oxidative stress.

18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography imaging in assessing early stages of aortic valve degeneration after transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is a standard treatment for severe aortic stenosis, primarily in elderly patients. With an increasing number of procedures and younger patients, understanding the valve degeneration and its risk factors becomes crucial. We aimed to utilize 18F‑sodium fluoride (18F‑NaF) and 18F‑fluorodeoxyglucose (18F‑FDG) positron emission tomography/computed tomography (PET/CT) to evaluate early TAVI valve degeneration. In this prospective study with a prespecified follow‑up protocol, 71 TAVI patients underwent baseline transthoracic and transesophageal echocardiography, and PET/CT with 18F‑NaF and 18F‑FDG. Of these, 31 patients completed 24‑month control examinations, while the others were lost to mortality and the COVID‑19 pandemic. We measured PET tracer activity and compared 18F‑NaF and 18F‑FDG PET/CT uptake at baseline and 24‑month follow‑up. PET/CT and echocardiography data were analyzed for 31 of the 71 enrolled TAVI patients at a median age of 84 years (interquartile range, 80-86). After TAVI, an improvement in the valve function was observed. During follow‑up, the valve function remained stable. PET/CT demonstrated an increase in 18F‑FDG maximal uptake in the inner (tissue‑to‑background ratio, P = 0.009) and outer (P = 0.01) sides of the TAVI valve stent, but no difference in 18F‑NaF maximal activity (inner, P = 0.17; outer, P = 0.57). Twenty‑four months post‑TAVI, an increase in 18F‑FDG uptake, indicative of inflammation, was observed in the valve, while the uptake of the calcification marker (18F‑NaF) remained stable. Theseobservations might suggest early stages of TAVI valve degeneration, although further investigation is required to confirm this interpretation.

Elevated lipoprotein a level in heart transplant patients is associated with cardiac allograft vasculopathy

Abstract Introduction Lipoprotein A (LpA) is considered a cardiovascular disease (CVD) risk factor and its interest has grown in recent years. High LpA levels (above 50 mg/dL) are associated with an increase in the occurrence of CVD and degenerative aortic valve disease despite treatment with statins and low LDL levels. The prevalence of elevated LpA levels after heart transplantation (HT) and the implication on the development of cardiac allograft vasculopathy (CAV) is not well known. Objective To assess the prevalence of elevated LpA levels in patients with HT and the relationship between higher LpA levels and CAV at 1 year. Methods Retrospective, unicentric and observational study based on the historical cohort of HT patients. We selected those patients in whom a pre-transplant serum sample was available in the biobank for LpA analysis. CAV was diagnosed with coronary angiography. Results We studied 80 HT patients. Baseline characteristics are in table 1. Median LpA levels were 14.5 (5.0-35.3), and from the 80 HT patients, 16 (20,0%) had LpA≥50 mg/dl (figure 1A). Out of the 80 patients, 68 had a coronary angiography at 1 year follow up (3 died before 1 year and 9 patients did not have angiography at 1 year for diverse reasons). Twenty patients (29.4%) presented CAV in the first year. Patients with elevated LpA levels had more frequency of CAV at 1 year [11/16 (68.8%) vs 9/43 (17.3%); p&amp;lt;0,001]. LpA levels in patients with CAV was higher (62.5+-58.8 vs 23.9+29.8; p&amp;lt;0,001) (figure 1B). LDLc and Total cholesterol were significantly lower in patients with CAV at 1 year in this population. In univariate analysis, smoker donors were associated with CAV development (60.0% vs 33.3%; p 0.042). We did not find differences in other recipient or donor cardiovascular risk factors, rejection episodes or CMV infection in the first year. Conclusion Elevated LpA levels (≥50 mg/dl) are frequent in HT patients (20%) and in our cohort, were associated with CAV at 1-year post-HT. Further studies are needed to verify these results and study the relationship with the development of other cardiovascular events in HT patients.Table 1Figure 1

The senescence-associated secretome for prediction of mortality in patients with aortic valve stenosis undergoing TAVR

Abstract Background Cellular senescence is an essential mechanism in the process of aging. The senescence-associated secretory phenotype (SASP) includes mainly pro-inflammatory cytokines, proteases, soluble signalling factors, and growth modulators. Degenerative aortic valve stenosis (AVS) is the prototypical inflammatory age-related cardiovascular disease. Purpose Our aim was to assess whether circulating concentrations of SASP factors are associated with prognosis in elderly patients with AVS undergoing transcatheter aortic valve replacement (TAVR), the current standard therapy for severe cases. Methods A total of 24 SASPs were measured using the Luminex Multiplex ELISA Assay (Biotechene, GmbH) in 120 AVS patients undergoing TAVR between February 2017 and February 2020 with a prospective follow-up of up to 4 years. Receiver operating characteristic (ROC) curves were created for each SASP protein in order to identify predictive markers. SASPs were considered positive if their baseline value was above the cut-off value derived from ROC-curves. The only 3 independent predictive factors were selected to develop an easy-to-calculate score based on the number of positive SASP proteins (0 to 3). Primary endpoint was long-term all-cause mortality. Results Median (IQR) age of the population was 83.2 (78.9-87.0) years, 56.7% were women. According to ROC curves, 9 out of 24 SASPs showed a significant area under the curve (AUC), with values above 0.623 (see Table). Only 3 of the markers reflecting potentially different underlying mechanisms remained independent predictors, after including all SASP factors in a Cox Regression analysis: GDF-15, ICAM-1 and Osteoprotegerin (all, p&amp;lt;0.03). A score based on the number of baseline factors being above the AUC-derived threshold level showed an excellent discrimination ability to predict survival, with long-term all-cause mortality substantially increasing for each additional positive marker (see Kaplan-Meier curves). Conclusion In conclusion, the presence of elevated baseline levels for 0, 1, 2, or 3 of the independent SASP factors reflecting different underlying pathophysiological mechanisms predicts increased long-term all-cause mortality with profoundly improved discrimination power in AVS patients undergoing TAVR. If confirmed in further prospective studies, a combination of these 3 SASP markers could serve as a highly useful risk stratification tool in the elderly population with AVS.

Left ventricular early diastolic strain rate predicts mortality after transcatheter aortic valve implantation

Abstract Introduction Speckle-tracking echocardiography is an increasingly important tool for assessing degenerative aortic valve stenosis (AS). This study aims to analyse left ventricular early diastolic strain rate (eSR) in patients with severe AS undergoing transcatheter aortic valve implantation (TAVI) and explore its association with mortality during long-term follow-up. Methods From our prospective AS cohort study, 100 patients with severe AS and a comprehensive echocardiographic examination prior to TAVI were identified and eSR was determined using TomTec ImageArena v.4.6 (Figure A). All-cause five-year mortality was defined as the endpoint.± Results Baseline characteristics were comparablebetween non-survivors (14%) and survivors (86%) except for a higher STS-Score among the former (non-survivors: 3.6 [2.7–7.4]%; survivors: 2.6 [1.8–3.7]%; P=0.024). There was no significant difference between non-survivors and survivors with regard to LVEF (54 [50–58]% vs 58 [52–63]%; P=0.069) and LVGLS (-14.8 [-15.8 to -12.7]% vs -15.4 [-15.8 to -14.7]%; P=0.339). In contrast, eSR was significantly lower in non-survivors (0.72 [0.67–0.87]s-1) than survivors (0.88 [0.73–1.22]s-1); P=0.013; Figure B). Patients with an eSR ≤ 0.72 s-1 (ROC AUC 71%; P=0.008) exhibited a lower survival probability as revealed by Kaplan-Meier survival analysis (P=0.001; Figure C). Inclusion of eSR improved the fitness (2) of a multivariable logistic regression model for LV systolic function (LVEF and LVGLS; Figure D). A similar effect was observed when eSR was included in a model for LV diastolic function (E/A and E/e’; Figure D). These improvements in 2 were significant for both models (ANOVA P=0.026, and P=0.037, respectively). Conclusions eSR differentiated non-survivors from survivors and was associated with long-term mortality after TAVI. This association was independent of and improved outcome prediction by LV systolic or diastolic function parameters. These findings highlight the potential value of eSR for assessing long-term mortality after TAVI.Figures