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JACC. Cardiovascular Interventions Mar 2023
Topics: Humans; Transcatheter Aortic Valve Replacement; Goals; Treatment Outcome; Aortic Valve; Aortic Valve Stenosis
PubMed: 36990557
DOI: 10.1016/j.jcin.2023.02.018 -
The Canadian Journal of Cardiology Feb 2024In this narrative review, we aim to summarize the literature surrounding the assessment and management of the common, yet understudied combination of aortic stenosis... (Review)
Review
In this narrative review, we aim to summarize the literature surrounding the assessment and management of the common, yet understudied combination of aortic stenosis (AS) and mitral regurgitation (MR), the components of which are complexly inter-related and interdependent from diagnostic, prognostic, and therapeutic perspectives. The hemodynamic interdependency of AS and MR confounds the assessment of the severity of each valve disease, thus underscoring the importance of a multimodal approach integrating valvular and extravalvular indicators of severity. A large body of literature suggests that baseline MR is associated with reduced survival post aortic valve (AV) intervention and that regression of MR post-AV intervention confers a mortality benefit. Functional MR is more likely to regress after AV intervention than primary MR. The respective natural courses of the 2 valve diseases are not synchronized; therefore, significant AS and MR at or above the respective threshold for intervention might not coincide. Surgery is primarily a 1-stop-shop procedure because of a considerable perioperative risk of repeat interventions, whereas transcatheter treatment modalities allow for a more tailored timing of intervention with reassessment of concomitant MR after AV replacement and a potential staged intervention in the absence of MR regression. In summary, AS and MR, when combined, are interlaced into a complex hemodynamic, diagnostic, and prognostic synergy, with important therapeutic implications. Contemporary approaches should consider stepwise intervention by exploiting the advantage of transcatheter options. However, evidence is needed to demonstrate the efficacy of different timing and therapeutic options.
Topics: Humans; Mitral Valve Insufficiency; Treatment Outcome; Aortic Valve Stenosis; Aortic Valve; Transcatheter Aortic Valve Replacement; Severity of Illness Index
PubMed: 37931671
DOI: 10.1016/j.cjca.2023.11.003 -
ESC Heart Failure Oct 2022Aortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve... (Meta-Analysis)
Meta-Analysis
AIMS
Aortic stenosis (AS) and cardiac amyloidosis (CA) are typical diseases of the elderly. Up to 16% of older adults with severe AS referred to transcatheter aortic valve replacement (TAVR) have a concomitant diagnosis of CA. CA-AS population suffers from reduced functional capacity and worse prognosis than AS patients. As the prognostic impact of TAVR in patients with CA-AS has been historically questioned and in light of recently published evidence, we aim to provide a comprehensive synthesis of the efficacy and safety of TAVR in CA-AS patients.
METHODS AND RESULTS
We performed a systematic review and meta-analysis of studies: (i) evaluating mortality with TAVR as compared with medical therapy in CA-AS patients and (ii) reporting complications and clinical outcomes of TAVR in CA-AS patients as compared with patients with AS alone. A total of seven observational studies were identified: four reported mortality with TAVR, and four reported complications and clinical outcomes after TAVR of patients with CA-AS compared with AS alone patients. In patients with CA-AS, the risk of mortality was lower with TAVR (n = 44) as compared with medical therapy (n = 36) [odds ratio (OR) 0.23, 95% confidence interval (CI) 0.07-0.73, I = 0%, P = 0.001, number needed to treat = 3]. The safety profile of TAVR seems to be similar in patients with CA-AS (n = 75) as compared with those with AS alone (n = 536), with comparable risks of stroke, vascular complications, life-threatening bleeding, acute kidney injury, and 30 day mortality, although CA-AS was associated with a trend towards an increased risk of permanent pacemaker implantation (OR 1.76, 95% CI 0.91-4.09, I = 0%, P = 0.085). CA is associated with a numerically higher rate of long-term mortality and rehospitalizations following TAVR in patients with CA-AS as compared with those with AS alone.
CONCLUSIONS
TAVR is an effective and safe procedure in CA-AS patients, with a substantial survival benefit as compared with medical therapy, and a safety profile comparable with patients with AS alone except for a trend towards higher risk of permanent pacemaker implantation.
Topics: Humans; Aged; Transcatheter Aortic Valve Replacement; Aortic Valve; Heart Valve Prosthesis Implantation; Risk Factors; Aortic Valve Stenosis; Amyloidosis
PubMed: 35770333
DOI: 10.1002/ehf2.13876 -
Frontiers in Immunology 2022Aortic stenosis (AS) is the most common valve disorder characterized by fibro-calcific remodeling of leaflets. Recent evidence indicated that there is a sex-related...
BACKGROUND
Aortic stenosis (AS) is the most common valve disorder characterized by fibro-calcific remodeling of leaflets. Recent evidence indicated that there is a sex-related difference in AS development and progression. Fibrotic remodeling is peculiar in women's aortic valves, while men's leaflets are more calcified. Our study aimed to assess aortic valve fibrosis (AVF) in a severe AS cohort using non-invasive diagnostic tools and determine whether sex-specific pathological pathways and cell types are associated with severe AS.
MATERIALS AND METHODS
We have included 28 men and 28 women matched for age with severe AS who underwent echocardiography and cardiac contrast-enhanced computed tomography (CT) before intervention. The calcium and fibrosis volumes were assessed and quantified using the ImageJ thresholding method, indexed calcium and fibrosis volume were calculated by dividing the volume by the aortic annular area. For a deeper understanding of molecular mechanisms characterizing AS disorder, differentially expressed genes and functional inferences between women and men's aortic valves were carried out on a publicly available microarray-based gene expression dataset (GSE102249). Cell types enrichment analysis in stenotic aortic valve tissues was used to reconstruct the sex-specific cellular composition of stenotic aortic valves.
RESULTS
In agreement with the literature, our CT quantifications showed that women had significantly lower aortic valve calcium content compared to men, while fibrotic tissue composition was significantly higher in women than men. The expression profiles of human stenotic aortic valves confirm sex-dependent processes. Pro-fibrotic processes were prevalent in women, while pro-inflammatory ones, linked to the immune response system, were enhanced in men. Cell-type enrichment analysis showed that mesenchymal cells were over-represented in AS valves of women, whereas signatures for monocytes, macrophages, T and B cells were enriched men ones.
CONCLUSIONS
Our data provide the basis that the fibro-calcific process of the aortic valve is sex-specific, both at gene expression and cell type level. The quantification of aortic valve fibrosis by CT could make it possible to perform population-based studies and non-invasive assessment of novel therapies to reduce or halt sex-related calcific aortic valve stenosis (CAVS) progression, acting in an optimal window of opportunity early in the course of the disease.
Topics: Aortic Valve; Aortic Valve Stenosis; Calcinosis; Calcium; Female; Fibromyalgia; Fibrosis; Humans; Male
PubMed: 35280999
DOI: 10.3389/fimmu.2022.747714 -
The Journal of Thoracic and... Dec 2021
Topics: Aortic Valve; Aortic Valve Stenosis; Heart Valve Prosthesis; Humans
PubMed: 32387158
DOI: 10.1016/j.jtcvs.2020.03.120 -
Open Heart Mar 2023Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the... (Review)
Review
Our perspectives on aortic stenosis (AS) are changing. Evolving from the traditional thought of a passive degenerative disease, developing a greater understanding of the condition's mechanistic underpinning has shifted the paradigm to an active disease process. This advancement from the 'wear and tear' model is a result of the growing economic and health burden of AS, particularly within industrialised countries, prompting further research. The pathophysiology of calcific AS (CAS) is complex, yet can be characterised similarly to that of atherosclerosis. Progressive remodelling involves lipid-protein complexes, with lipoprotein(a) being of particular interest for diagnostics and potential future treatment options.There is an unmet clinical need for asymptomatic patient management; no pharmacotherapies are proven to slow progression and intervention timing varies. Novel approaches are developing to address this through: (1) screening with circulating biomarkers; (2) development of drugs to slow disease progression and (3) early valve intervention guided by medical imaging. Existing biomarkers (troponin and brain natriuretic peptide) are non-specific, but cost-effective predictors of ventricular dysfunction. In addition, their integration with cardiovascular MRI can provide accurate risk stratification, aiding aortic valve replacement decision making. Currently, invasive intervention is the only treatment for AS. In comparison, the development of lipoprotein(a) lowering therapies could provide an alternative; slowing progression of CAS, preventing left ventricular dysfunction and reducing reliance on surgical intervention.The landscape of AS management is rapidly evolving. This review outlines current understanding of the pathophysiology of AS, its management and future perspectives for the condition's assessment and treatment.
Topics: Humans; Aortic Valve Stenosis; Aortic Valve; Biomarkers; Heart Valve Prosthesis Implantation; Lipoprotein(a)
PubMed: 36963766
DOI: 10.1136/openhrt-2022-002244 -
International Journal of Molecular... Nov 2020Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets,... (Review)
Review
Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets, leading to progressive obstruction to the blood flow. CAVS is an increasing health care burden and the development of an effective medical treatment is a major medical need. To date, no effective pharmacological therapies have proven to halt or delay its progression to the severe symptomatic stage and aortic valve replacement represents the only available option to improve clinical outcomes and to increase survival. In the present report, the current knowledge and latest advances in the medical management of patients with CAVS are summarized, placing emphasis on lipid-lowering agents, vasoactive drugs, and anti-calcific treatments. In addition, novel potential therapeutic targets recently identified and currently under investigation are reported.
Topics: Aortic Valve; Aortic Valve Stenosis; Calcinosis; Calcium-Regulating Hormones and Agents; Disease Progression; Drug Discovery; Heart Valve Prosthesis; Humans; Hypolipidemic Agents; Lipid Metabolism; Vasoconstrictor Agents
PubMed: 33158204
DOI: 10.3390/ijms21218263 -
Journal of the American Heart... Sep 2020Aortic stenosis (AS) is a common valvular heart disease in the aging population that is characterized by a variable period of asymptomatic phase before development of... (Review)
Review
Aortic stenosis (AS) is a common valvular heart disease in the aging population that is characterized by a variable period of asymptomatic phase before development of symptoms and severe AS. Mortality and morbidity is substantial even after aortic valve replacement, in part related to persistent left ventricular hypertrophy, diastolic dysfunction, and heart failure. Renin-angiotensin system (RAS) blockade therapy is associated with modulation of adverse left ventricular remodeling, reduction in myocardial hypertrophy, and fibrosis, resulting in clinical improvements in patients with congestive heart failure There are emerging data to suggest benefit of RAS blockade in patients with AS before and after AVR with regard to potentially slower progression of aortic valve calcification, left ventricular mass and survival benefit in favor of RAS blockade group before AVR, and also survival benefit in patients after AVR. We review the available data to understand the role of RAS blockade before AVR and in patients undergoing surgical AVR and transcatheter AVR. There are significant survival advantages of RAS inhibition in patients with AS undergoing surgical AVR or transcatheter AVR. On the basis of existing literature, adequately powered randomized trials are needed to evaluate the role of RAS inhibition in patients with AS.
Topics: Aortic Valve Stenosis; Heart Valve Prosthesis Implantation; Humans; Renin-Angiotensin System; Transcatheter Aortic Valve Replacement; Ventricular Remodeling
PubMed: 32893727
DOI: 10.1161/JAHA.120.016911 -
International Journal of Cardiology Jul 2022Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of...
BACKGROUND
Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of CAVS and the prevalence of bicuspid aortic valve among CAVS families.
METHODS
Probands were recruited following aortic valve replacement (AVR) for severe CAVS on either tricuspid (TAV) or bicuspid aortic valve (BAV). After screening, relatives underwent a Doppler-echocardiography to assess the aortic valve morphology as well as the presence and severity of CAVS. Families were classified in two types according to proband's aortic valve phenotype: TAV or BAV families. Control families were recruited and screened for the presence of BAV.
RESULTS
Among the 2371 relatives from 138 CAVS families (pedigree cohort), heritability of CAVS was significant (h = 0.47, p < 0.0001), in TAV (h = 0.49, p < 0.0001) and BAV families (h = 0.50, p < 0.0001). The prevalence of BAV in 790 relatives (phenotype cohort) was significantly increased in both TAV and BAV families compared to control families with a prevalence ratio of 2.6 ([95%CI:1.4-5.9]; p = 0.005) and 4.6 ([95%CI:2.4-13.4]; p < 0.0001), respectively. At least one relative had a BAV in 22.2% of tricuspid CAVS families.
CONCLUSIONS
Our study confirms the heritability of CAVS in both TAV and BAV families, suggesting a genetic background of this frequent valvular disease. In addition, BAV enrichment in TAV families suggests an interplay between tricuspid CAVS and BAV. Overall results support the need to improve phenotyping (i.e. BAV, TAV, risk factors) in CAVS families in order to enhance the identification of rare and causal genetic variants of CAVS.
CLINICAL TRIALS IDENTIFIER
NCT02890407.
Topics: Aortic Valve; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Calcinosis; Heart Valve Diseases; Humans
PubMed: 35427703
DOI: 10.1016/j.ijcard.2022.04.022 -
EuroIntervention : Journal of EuroPCR... Apr 2020The ACURATE neo aortic valve system is a self-expanding transcatheter device that was granted CE mark in 2014 and has since been widely adopted in the treatment of... (Review)
Review
The ACURATE neo aortic valve system is a self-expanding transcatheter device that was granted CE mark in 2014 and has since been widely adopted in the treatment of patients with severe aortic stenosis. The ACURATE neo can be used in a wide clinical spectrum, but there are some specific indications and anatomies where this device is particularly suitable. Recently, it was shown that, with appropriate patient screening, size selection, and optimised positioning, results can be improved substantially. This review provides an overview of existing data and compiles a standardised manual of best practice for the implantation of this device based on both evidence and individual experience.
Topics: Aortic Valve; Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Prosthesis Design; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 31911402
DOI: 10.4244/EIJ-D-19-00908