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Journal of the American College of... Nov 2023The American College of Cardiology/American Heart Association guidelines recommend the assessment and grading of severity of aortic stenosis (AS) as mild, moderate, or...
BACKGROUND
The American College of Cardiology/American Heart Association guidelines recommend the assessment and grading of severity of aortic stenosis (AS) as mild, moderate, or severe, per echocardiogram, and recommend aortic valve replacement (AVR) when the AS is severe.
OBJECTIVES
The authors sought to describe mortality rates across the entire spectrum of untreated AS from a contemporary, large, real-world database.
METHODS
We analyzed a deidentified real-world data set including 1,669,536 echocardiographic reports (1,085,850 patients) from 24 U.S. hospitals (egnite Database, egnite). Patients >18 years of age were classified by diagnosed AS severity. Untreated mortality and treatment rates were examined with Kaplan-Meier (KM) estimates, with results compared using the log-rank test. Multivariate hazards analysis was performed to assess associations with all-cause mortality.
RESULTS
Among 595,120 patients with available AS severity assessment, the KM-estimated 4-year unadjusted, untreated, all-cause mortality associated with AS diagnosis of none, mild, mild-to-moderate, moderate, moderate-to-severe, or severe was 13.5% (95% CI: 13.3%-13.7%), 25.0% (95% CI: 23.8%-26.1%), 29.7% (95% CI: 26.8%-32.5%), 33.5% (95% CI: 31.0%-35.8%), 45.7% (95% CI: 37.4%-52.8%), and 44.9% (95% CI: 39.9%-49.6%), respectively. Results were similar when adjusted for informative censoring caused by treatment. KM-estimated 4-year observed treatment rates were 0.2% (95% CI: 0.2%-0.2%), 1.0% (95% CI: 0.7%-1.3%), 4.2% (95% CI: 2.0%-6.3%), 11.4% (95% CI: 9.5%-13.3%), 36.7% (95% CI: 31.8%-41.2%), and 60.7% (95% CI: 58.0%-63.3%), respectively. After adjustment, all degrees of AS severity were associated with increased mortality.
CONCLUSIONS
Patients with AS have high mortality risk across all levels of untreated AS severity. Aortic valve replacement rates remain low for patients with severe AS, suggesting that more research is needed to understand barriers to diagnosis and appropriate approach and timing for aortic valve replacement.
Topics: Humans; Treatment Outcome; Heart Valve Prosthesis Implantation; Aortic Valve Stenosis; Aortic Valve; Echocardiography; Severity of Illness Index; Risk Factors; Transcatheter Aortic Valve Replacement
PubMed: 37877909
DOI: 10.1016/j.jacc.2023.09.796 -
Cells Oct 2023Lipoprotein(a) (Lp(a)) molecule includes two protein components: apolipoprotein(a) and apoB100. The molecule is the main transporter of oxidized phospholipids (OxPL) in... (Review)
Review
Lipoprotein(a) (Lp(a)) molecule includes two protein components: apolipoprotein(a) and apoB100. The molecule is the main transporter of oxidized phospholipids (OxPL) in plasma. The concentration of this strongly atherogenic lipoprotein is predominantly regulated by the LPA gene expression. Lp(a) is regarded as a risk factor for several cardiovascular diseases. Numerous epidemiological, clinical and in vitro studies showed a strong association between increased Lp(a) and atherosclerotic cardiovascular disease (ASCVD), calcific aortic valve disease/aortic stenosis (CAVD/AS), stroke, heart failure or peripheral arterial disease (PAD). Although there are acknowledged contributions of Lp(a) to the mentioned diseases, clinicians struggle with many inconveniences such as a lack of well-established treatment lowering Lp(a), and common guidelines for diagnosing or assessing cardiovascular risk among both adult and pediatric patients. Lp(a) levels are different with regard to a particular race or ethnicity and might fluctuate during childhood. Furthermore, the lack of standardization of assays is an additional impediment. The review presents the recent knowledge on Lp(a) based on clinical and scientific research, but also highlights relevant aspects of future study directions that would approach more suitable and effective managing risk associated with increased Lp(a), as well as control the Lp(a) levels.
Topics: Humans; Aortic Valve; Aortic Valve Stenosis; Atherosclerosis; Lipoprotein(a); Risk Factors
PubMed: 37887316
DOI: 10.3390/cells12202472 -
Circulation Aug 2023Fewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating...
BACKGROUND
Fewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases, tissue-entrapped EVs are associated with early mineralization, but their cargoes, functions, and contributions to disease remain unknown.
METHODS
Disease stage-specific proteomics was performed on human carotid endarterectomy specimens (n=16) and stenotic aortic valves (n=18). Tissue EVs were isolated from human carotid arteries (normal, n=6; diseased, n=4) and aortic valves (normal, n=6; diseased, n=4) by enzymatic digestion, (ultra)centrifugation, and a 15-fraction density gradient validated by proteomics, CD63-immunogold electron microscopy, and nanoparticle tracking analysis. Vesiculomics, comprising vesicular proteomics and small RNA-sequencing, was conducted on tissue EVs. TargetScan identified microRNA targets. Pathway network analyses prioritized genes for validation in primary human carotid artery smooth muscle cells and aortic valvular interstitial cells.
RESULTS
Disease progression drove significant convergence (<0.0001) of carotid artery plaque and calcified aortic valve proteomes (2318 proteins). Each tissue also retained a unique subset of differentially enriched proteins (381 in plaques; 226 in valves; q<0.05). Vesicular gene ontology terms increased 2.9-fold (<0.0001) among proteins modulated by disease in both tissues. Proteomics identified 22 EV markers in tissue digest fractions. Networks of proteins and microRNA targets changed by disease progression in both artery and valve EVs revealed shared involvement in intracellular signaling and cell cycle regulation. Vesiculomics identified 773 proteins and 80 microRNAs differentially enriched by disease exclusively in artery or valve EVs (q<0.05); multiomics integration found tissue-specific EV cargoes associated with procalcific Notch and Wnt signaling in carotid arteries and aortic valves, respectively. Knockdown of tissue-specific EV-derived molecules , , and in human carotid artery smooth muscle cells and , , and in human aortic valvular interstitial cells significantly modulated calcification.
CONCLUSIONS
The first comparative proteomics study of human carotid artery plaques and calcified aortic valves identifies unique drivers of atherosclerosis versus aortic valve stenosis and implicates EVs in advanced cardiovascular calcification. We delineate a vesiculomics strategy to isolate, purify, and study protein and RNA cargoes from EVs entrapped in fibrocalcific tissues. Integration of vesicular proteomics and transcriptomics by network approaches revealed novel roles for tissue EVs in modulating cardiovascular disease.
Topics: Humans; Aortic Valve; Aortic Valve Stenosis; Multiomics; Calcinosis; Cells, Cultured; MicroRNAs; Atherosclerosis; Wnt Signaling Pathway; Extracellular Vesicles
PubMed: 37427430
DOI: 10.1161/CIRCULATIONAHA.122.063402 -
European Heart Journal. Cardiovascular... Oct 2023In this EACVI clinical scientific update, we will explore the current use of multi-modality imaging in the diagnosis, risk stratification, and follow-up of patients with...
In this EACVI clinical scientific update, we will explore the current use of multi-modality imaging in the diagnosis, risk stratification, and follow-up of patients with aortic stenosis, with a particular focus on recent developments and future directions. Echocardiography is and will likely remain the key method of diagnosis and surveillance of aortic stenosis providing detailed assessments of valve haemodynamics and the cardiac remodelling response. Computed tomography (CT) is already widely used in the planning of transcutaneous aortic valve implantation. We anticipate its increased use as an anatomical adjudicator to clarify disease severity in patients with discordant echocardiographic measurements. CT calcium scoring is currently used for this purpose; however, contrast CT techniques are emerging that allow identification of both calcific and fibrotic valve thickening. Additionally, improved assessments of myocardial decompensation with echocardiography, cardiac magnetic resonance, and CT will become more commonplace in our routine assessment of aortic stenosis. Underpinning all of this will be widespread application of artificial intelligence. In combination, we believe this new era of multi-modality imaging in aortic stenosis will improve the diagnosis, follow-up, and timing of intervention in aortic stenosis as well as potentially accelerate the development of the novel pharmacological treatments required for this disease.
Topics: Humans; Consensus; Artificial Intelligence; Aortic Valve Stenosis; Aortic Valve; Multimodal Imaging
PubMed: 37395329
DOI: 10.1093/ehjci/jead153 -
Circulation Feb 2024The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The optimal treatment in patients with severe aortic stenosis and small aortic annulus (SAA) remains to be determined. This study aimed to compare the hemodynamic and clinical outcomes between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with a SAA.
METHODS
This prospective multicenter international randomized trial was performed in 15 university hospitals. Participants were 151 patients with severe aortic stenosis and SAA (mean diameter <23 mm) randomized (1:1) to TAVR (n=77) versus SAVR (n=74). The primary outcome was impaired valve hemodynamics (ie, severe prosthesis patient mismatch or moderate-severe aortic regurgitation) at 60 days as evaluated by Doppler echocardiography and analyzed in a central echocardiography core laboratory. Clinical events were secondary outcomes.
RESULTS
The mean age of the participants was 75.5±5.1 years, with 140 (93%) women, a median Society of Thoracic Surgeons predicted risk of mortality of 2.50% (interquartile range, 1.67%-3.28%), and a median annulus diameter of 21.1 mm (interquartile range, 20.4-22.0 mm). There were no differences between groups in the rate of severe prosthesis patient mismatch (TAVR, 4 [5.6%]; SAVR, 7 [10.3%]; =0.30) and moderate-severe aortic regurgitation (none in both groups). No differences were found between groups in mortality rate (TAVR, 1 [1.3%]; SAVR, 1 [1.4%]; =1.00) and stroke (TAVR, 0; SAVR, 2 [2.7%]; =0.24) at 30 days. After a median follow-up of 2 (interquartile range, 1-4) years, there were no differences between groups in mortality rate (TAVR, 7 [9.1%]; SAVR, 6 [8.1%]; =0.89), stroke (TAVR, 3 [3.9%]; SAVR, 3 [4.1%]; =0.95), and cardiac hospitalization (TAVR, 15 [19.5%]; SAVR, 15 [20.3%]; =0.80).
CONCLUSIONS
In patients with severe aortic stenosis and SAA (women in the majority), there was no evidence of superiority of contemporary TAVR versus SAVR in valve hemodynamic results. After a median follow-up of 2 years, there were no differences in clinical outcomes between groups. These findings suggest that the 2 therapies represent a valid alternative for treating patients with severe aortic stenosis and SAA, and treatment selection should likely be individualized according to baseline characteristics, additional anatomical risk factors, and patient preference. However, the results of this study should be interpreted with caution because of the limited sample size leading to an underpowered study, and need to be confirmed in future larger studies.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03383445.
Topics: Humans; Female; Aged; Aged, 80 and over; Male; Aortic Valve; Heart Valve Prosthesis Implantation; Aortic Valve Insufficiency; Prospective Studies; Aortic Valve Stenosis; Treatment Outcome; Heart Valve Prosthesis; Transcatheter Aortic Valve Replacement; Risk Factors; Stroke
PubMed: 37883682
DOI: 10.1161/CIRCULATIONAHA.123.067326 -
Heart Failure Reviews Sep 2023Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the... (Review)
Review
Acute decompensation often represents the onset of symptoms associated with severe degenerative aortic stenosis (AS) and usually complicates the clinical course of the disease with a dismal impact on survival and quality of life. Several factors may derange the faint balance between left ventricular preload and afterload and precipitate the occurrence of symptoms and signs of acute heart failure (HF). A standardized approach for the management of this condition is currently lacking. Medical therapy finds very limited application in this setting, as drugs usually indicated for the control of acute HF might worsen hemodynamics in the presence of AS. Urgent aortic valve replacement is usually performed by transcatheter than surgical approach whereas, over the last decades, percutaneous balloon valvuloplasty gained renewed space as bridge to definitive therapy. This review focuses on the pathophysiological aspects of acute advanced AS and summarizes current evidence on its management.
Topics: Humans; Quality of Life; Balloon Valvuloplasty; Aortic Valve Stenosis; Aortic Valve; Heart Valve Prosthesis; Heart Failure; Treatment Outcome
PubMed: 37083966
DOI: 10.1007/s10741-023-10312-7 -
Cardiovascular Research Jul 2023Although evidence indicates the association of lipoprotein(a) [Lp(a)] with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This... (Meta-Analysis)
Meta-Analysis
Although evidence indicates the association of lipoprotein(a) [Lp(a)] with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This systematic review and meta-analysis explores the connection between Lp(a) and aortic valve calcification and stenosis (AVS). We included all relevant studies, indexed in eight databases, up to February 2023. A total of 44 studies (163 139 subjects) were included, with 16 of them being further meta-analysed. Despite considerable heterogeneity, most studies support the relationship between Lp(a) and CAVD, especially in younger populations, with evidence of early aortic valve micro-calcification in elevated-Lp(a) populations. The quantitative synthesis showed higher Lp(a) levels, by 22.63 nmol/L (95% CI: 9.98-35.27), for patients with AVS, while meta-regressing the data revealed smaller Lp(a) differences for older populations with a higher proportion of females. The meta-analysis of eight studies providing genetic data, revealed that the minor alleles of both rs10455872 and rs3798220 LPA gene loci were associated with higher risk for AVS (pooled odds ratio 1.42; 95% CI: 1.34-1.50 and 1.27; 95% CI: 1.09-1.48, respectively). Importantly, high-Lp(a) individuals displayed not only faster AVS progression, by a mean difference of 0.09 m/s/year (95% CI: 0.09-0.09), but also a higher risk of serious adverse outcomes, including death (pooled hazard ratio 1.39; 95% CI: 1.01-1.90). These summary findings highlight the effect of Lp(a) on CAVD initiation, progression and outcomes, and support the early onset of Lp(a)-related subclinical lesions before clinical evidence.
Topics: Female; Humans; Aortic Valve; Aortic Valve Stenosis; Hyperlipidemias; Lipoprotein(a); Risk Factors
PubMed: 37078819
DOI: 10.1093/cvr/cvad062 -
European Heart Journal Sep 2023Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated... (Meta-Analysis)
Meta-Analysis
AIMS
Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding.
METHODS AND RESULTS
A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002).
CONCLUSION
Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.
Topics: Humans; Aortic Valve; Angiodysplasia; Aortic Valve Stenosis; von Willebrand Diseases; Gastrointestinal Hemorrhage; Syndrome; von Willebrand Factor
PubMed: 37555393
DOI: 10.1093/eurheartj/ehad340 -
Biomedicine & Pharmacotherapy =... Jul 2023Calcified aortic valve disease (CAVD) is a common cardiovascular disease in elderly individuals. Although it was previously considered a degenerative disease, it is, in... (Review)
Review
Calcified aortic valve disease (CAVD) is a common cardiovascular disease in elderly individuals. Although it was previously considered a degenerative disease, it is, in fact, a progressive disease involving multiple mechanisms. Aortic valve endothelial cells, which cover the outermost layer of the aortic valve and are directly exposed to various pathogenic factors, play a significant role in the onset and progression of CAVD. Hemodynamic changes can directly damage the structure and function of valvular endothelial cells (VECs). This leads to inflammatory infiltration and oxidative stress, which promote the progression of CAVD. VECs can regulate the pathological differentiation of valvular interstitial cells (VICs) through NO and thus affect the process of CAVD. Under the influence of pathological factors, VECs can also be transformed into VICs through EndMT, and then the pathological differentiation of VICs eventually leads to the formation of calcification. This review discusses the role of VECs, especially the role of oxidative stress in VECs, in the process of aortic valve calcification.
Topics: Humans; Aged; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Endothelial Cells; Cells, Cultured; Oxidative Stress
PubMed: 37116353
DOI: 10.1016/j.biopha.2023.114775 -
EuroIntervention : Journal of EuroPCR... Jul 2023A small aortic annulus (SAA) is a risk factor for prosthesis-patient mismatch (PPM) in patients undergoing surgical or transcatheter aortic valve implantation (TAVI)....
BACKGROUND
A small aortic annulus (SAA) is a risk factor for prosthesis-patient mismatch (PPM) in patients undergoing surgical or transcatheter aortic valve implantation (TAVI). Data regarding TAVI in patients with extra-SAA are scarce.
AIMS
The aim of this study was to analyse the safety and efficacy of TAVI in patients with extra-SAA.
METHODS
A multicentre registry study including patients with extra-SAA (defined as an aortic annulus area <280 mm and/or perimeter <60 mm) undergoing TAVI was established. Primary efficacy and safety endpoints were defined as device success and early safety at 30 days, respectively, using the Valve Academic Research Consortium-3 criteria, and were analysed according to valve type: self-expanding (SEV) versus balloon-expandable (BEV).
RESULTS
A total of 150 patients were included, of which 139 (92.7%) were women, and 110 (73.3%) received an SEV. Intraprocedural technical success was 91.3%, with a higher rate in patients receiving an SEV (96.4% vs 77.5% with BEV; p=0.001). Overall, 30-day device success was 81.3%, (85.5% with SEV vs 70.0% with BEV; p=0.032). The primary safety endpoint occurred in 72.0% of patients (with no difference between groups; p=0.118). Severe PPM occurred in 12% (9.0% with SEV and 24.0% with BEV; p=0.039), with no impact on all-cause mortality, cardiovascular mortality, or heart failure readmission at 2-year follow-up.
CONCLUSIONS
TAVI is a safe and feasible treatment in patients with extra-SAA with a high rate of technical success. The use of SEV was associated with a lower rate of intraprocedural complications, higher device success at 30 days and better haemodynamic outcomes compared to BEV.
Topics: Humans; Female; Male; Transcatheter Aortic Valve Replacement; Aortic Valve; Aortic Valve Stenosis; Prosthesis Design; Risk Factors; Heart Valve Prosthesis; Treatment Outcome
PubMed: 37334654
DOI: 10.4244/EIJ-D-23-00011