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European Journal of Cardio-thoracic... Sep 2021This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type...
International consensus statement on nomenclature and classification of the congenital bicuspid aortic valve and its aortopathy, for clinical, surgical, interventional and research purposes.
This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes.
Topics: Aortic Valve; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Consensus; Humans; Phenotype
PubMed: 34293102
DOI: 10.1093/ejcts/ezab038 -
JACC. Cardiovascular Imaging Sep 2019The first-line evaluation of aortic stenosis severity is Doppler echocardiography. However, in up to 40% of patients, resting echocardiographic assessment of aortic... (Review)
Review
The first-line evaluation of aortic stenosis severity is Doppler echocardiography. However, in up to 40% of patients, resting echocardiographic assessment of aortic stenosis severity is discordant, leading to clinical uncertainty. Interest has therefore grown in aortic valve calcium scoring by multidetector computed tomography (CT-AVC) as an alternative load independent assessment of aortic stenosis severity. This paper will briefly review the pathophysiology of aortic stenosis and the crucial role that calcification plays in driving progressive obstruction of the valve. Subsequently, it will describe published reports that have investigated CT-AVC, validating this parameter against histology, and establishing its diagnostic accuracy versus echocardiography as well as its powerful independent prognostic capability. Finally, this review seeks to provide a practical guide about how best to acquire and interpret CT-AVC with a close focus on potential pitfalls and how these might be best avoided as this technique becomes more widely adopted in to clinical practice.
Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Echocardiography, Doppler, Color; Echocardiography, Transesophageal; Female; Hemodynamics; Humans; Male; Multidetector Computed Tomography; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index
PubMed: 31488252
DOI: 10.1016/j.jcmg.2019.01.045 -
Circulation Research Apr 2021Calcific aortic valve disease sits at the confluence of multiple world-wide epidemics of aging, obesity, diabetes, and renal dysfunction, and its prevalence is expected... (Review)
Review
Calcific aortic valve disease sits at the confluence of multiple world-wide epidemics of aging, obesity, diabetes, and renal dysfunction, and its prevalence is expected to nearly triple over the next 3 decades. This is of particularly dire clinical relevance, as calcific aortic valve disease can progress rapidly to aortic stenosis, heart failure, and eventually premature death. Unlike in atherosclerosis, and despite the heavy clinical toll, to date, no pharmacotherapy has proven effective to halt calcific aortic valve disease progression, with invasive and costly aortic valve replacement representing the only treatment option currently available. This substantial gap in care is largely because of our still-limited understanding of both normal aortic valve biology and the key regulatory mechanisms that drive disease initiation and progression. Drug discovery is further hampered by the inherent intricacy of the valvular microenvironment: a unique anatomic structure, a complex mixture of dynamic biomechanical forces, and diverse and multipotent cell populations collectively contributing to this currently intractable problem. One promising and rapidly evolving tactic is the application of multiomics approaches to fully define disease pathogenesis. Herein, we summarize the application of (epi)genomics, transcriptomics, proteomics, and metabolomics to the study of valvular heart disease. We also discuss recent forays toward the omics-based characterization of valvular (patho)biology at single-cell resolution; these efforts promise to shed new light on cellular heterogeneity in healthy and diseased valvular tissues and represent the potential to efficaciously target and treat key cell subpopulations. Last, we discuss systems biology- and network medicine-based strategies to extract meaning, mechanisms, and prioritized drug targets from multiomics datasets.
Topics: Aortic Valve; Aortic Valve Stenosis; Biomechanical Phenomena; Calcinosis; Computational Biology; Disease Progression; Drug Discovery; Epigenesis, Genetic; Gene Expression; Genomics; Heart Failure; Humans; Mass Spectrometry; Medical Illustration; Metabolomics; Phenotype; Proteomics; Transcatheter Aortic Valve Replacement; Transcriptome
PubMed: 33914608
DOI: 10.1161/CIRCRESAHA.120.317979 -
Science Advances Jun 2023Hemodynamic overload and dysregulation of cellular metabolism are involved in development of calcific aortic valve disease (CAVD). However, how mechanical stress relates...
Hemodynamic overload and dysregulation of cellular metabolism are involved in development of calcific aortic valve disease (CAVD). However, how mechanical stress relates to metabolic changes in CAVD remains unclear. Here, we show that Piezo1, a mechanosensitive ion channel, regulated glutaminase 1 (GLS1)-mediated glutaminolysis to promote osteogenic differentiation of valve interstitial cells (VICs). In vivo, two models of aortic valve stenosis were constructed by ascending aortic constriction (AAC) and direct wire injury (DWI). Inhibition of Piezo1 and GLS1 in these models respectively mitigated aortic valve lesion. In vitro, Piezo1 activation induced by Yoda1 and oscillatory stress triggered osteogenic responses in VICs, which were prevented by Piezo1 inhibition or knockdown. Mechanistically, Piezo1 activation promoted calcium-dependent Yes-associated protein (YAP) activation. YAP modulated GLS1-mediated glutaminolysis, which enhanced osteogenic differentiation through histone acetylation of runt-related transcription factor 2 (RUNX2) promoters. Together, our work provided a cross-talk between mechanotransduction and metabolism in the context of CAVD.
Topics: Aortic Valve; Osteogenesis; Mechanotransduction, Cellular; Cells, Cultured; Cell Differentiation
PubMed: 37267365
DOI: 10.1126/sciadv.adg0478 -
Circulation May 2022Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis.
METHODS
In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events.
RESULTS
From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225-326 AU) and 292 AU (95% CI, 246-338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, -86 to 53 AU; =0.64). The mean change in aortic valve area was 0.02 cm (95% CI, -0.09 to 0.12 cm; =0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, -0.11 to 0.02 m/s; =0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; =0.99), all-cause death (1 versus 4 patients; =0.37), or cardiovascular events (10 versus 10 patients; =0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (-212 pmol/L versus 45 pmol/L; <0.001).
CONCLUSIONS
In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT03243890.
Topics: Aged; Aortic Valve; Aortic Valve Stenosis; Calcinosis; Female; Humans; Male; Vitamin D; Vitamin K 2
PubMed: 35465686
DOI: 10.1161/CIRCULATIONAHA.121.057008 -
JACC. Cardiovascular Interventions Nov 2021
Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34756540
DOI: 10.1016/j.jcin.2021.09.005 -
JACC. Cardiovascular Interventions Nov 2021
Topics: Aortic Valve; Aortic Valve Stenosis; Heart Valve Prosthesis; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34794657
DOI: 10.1016/j.jcin.2021.09.030 -
Circulation. Cardiovascular... Jul 2021The bicuspid aortic valve (BAV) represents a complex anatomic scenario for transcatheter aortic valve replacement (TAVR) because of its unique technical challenges. As... (Review)
Review
The bicuspid aortic valve (BAV) represents a complex anatomic scenario for transcatheter aortic valve replacement (TAVR) because of its unique technical challenges. As TAVR is moving towards younger and lower-risk populations, the proportion of BAV patients undergoing TAVR is expected to rise. Initial experiences of TAVR with first-generation transcatheter heart valves in high surgical risk patients with BAV stenosis showed higher rates of device failure and periprocedural complications as compared to tricuspid anatomy. The subsequent advances in imaging techniques and understanding of BAV anatomy, new iterations of transcatheter heart valves, and growing operators' experience yielded better outcomes. However, in the lack of randomized trials and rigorous evidence, the field of TAVR in BAV has been driven by empirical observations, with wide variability in transcatheter heart valve sizing and implantation techniques across different centers and operators. Thus, in this review article, we provide a fully illustrated overview of operative periprocedural steps for TAVR in BAV stenosis, though recognizing that it still remains anecdotal.
Topics: Aortic Valve; Aortic Valve Stenosis; Bicuspid Aortic Valve Disease; Constriction, Pathologic; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 34130478
DOI: 10.1161/CIRCINTERVENTIONS.120.009827 -
JACC. Cardiovascular Interventions Nov 2020
Topics: Aortic Valve; Aortic Valve Stenosis; Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome
PubMed: 33153564
DOI: 10.1016/j.jcin.2020.07.042 -
The Journal of Thoracic and... May 2021
Topics: Aortic Valve; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Robotic Surgical Procedures
PubMed: 33461816
DOI: 10.1016/j.jtcvs.2020.11.122