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European Heart Journal Nov 2023Bicuspid aortic valve (BAV) is the most common congenital heart anomaly. Lifetime morbidity and whether long-term survival varies according to BAV patient-sub-groups are...
BACKGROUND AND AIMS
Bicuspid aortic valve (BAV) is the most common congenital heart anomaly. Lifetime morbidity and whether long-term survival varies according to BAV patient-sub-groups are unknown. This study aimed to assess lifetime morbidity and long-term survival in BAV patients in the community.
METHODS
The authors retrospectively identified all Olmsted County (Minnesota) residents with an echocardiographic diagnosis of BAV from 1 January 1980 to 31 December 2009, including patients with typical valvulo-aortopathy (BAV without accelerated valvulo-aortopathy or associated disorders), and those with complex valvulo-aortopathy (BAV with accelerated valvulo-aortopathy or associated disorders).
RESULTS
652 consecutive diagnosed BAV patients [median (IQR) age 37 (22-53) years; 525 (81%) adult and 127 (19%) paediatric] were followed for a median (IQR) of 19.1 (12.9-25.8) years. The total cumulative lifetime morbidity burden (from birth to age 90) was 86% (95% CI 82.5-89.7); cumulative lifetime progression to ≥ moderate aortic stenosis or regurgitation, aortic valve surgery, aortic aneurysm ≥45 mm or z-score ≥3, aorta surgery, infective endocarditis and aortic dissection was 80.3%, 68.5%, 75.4%, 27%, 6% and 1.6%, respectively. Survival of patients with typical valvulo-aortopathy [562 (86%), age 40 (28-55) years, 86% adults] was similar to age-sex-matched Minnesota population (P = .12). Conversely, survival of patients with complex valvulo-aortopathy [90 (14%), age 14 (3-26) years, 57% paediatric] was lower than expected, with a relative excess mortality risk of 2.25 (95% CI 1.21-4.19) (P = .01).
CONCLUSION
The BAV condition exhibits a high lifetime morbidity burden where valvulo-aortopathy is close to unavoidable by age 90. The lifetime incidence of infective endocarditis is higher than that of aortic dissection. The most common BAV clinical presentation is the typical valvulo-aortopathy with preserved expected long-term survival, while the complex valvulo-aortopathy presentation incurs higher mortality.
Topics: Adult; Humans; Child; Aged, 80 and over; Adolescent; Bicuspid Aortic Valve Disease; Aortic Valve; Heart Valve Diseases; Retrospective Studies; Aortic Dissection; Morbidity; Endocarditis
PubMed: 37611071
DOI: 10.1093/eurheartj/ehad477 -
Journal of the American College of... Aug 2023Bicuspid aortic valve is the most common congenital heart disease and exposes patients to an increased risk of aortic dilation and dissection. Aortic dilation is a slow,... (Review)
Review
Bicuspid aortic valve is the most common congenital heart disease and exposes patients to an increased risk of aortic dilation and dissection. Aortic dilation is a slow, silent process, leading to a greater risk of aortic dissection. The prevention of adverse events together with optimization of the frequency of the required lifelong imaging surveillance are important for both clinicians and patients and motivated extensive research to shed light on the physiopathologic processes involved in bicuspid aortic valve aortopathy. Two main research hypotheses have been consolidated in the last decade: one supports a genetic basis for the increased prevalence of dilation, in particular for the aortic root, and the second supports the damaging impact on the aortic wall of altered flow dynamics associated with these structurally abnormal valves, particularly significant in the ascending aorta. Current opinion tends to rule out mutually excluding causative mechanisms, recognizing both as important and potentially clinically relevant.
Topics: Humans; Bicuspid Aortic Valve Disease; Aortic Valve; Heart Valve Diseases; Dilatation; Aortic Diseases
PubMed: 37495282
DOI: 10.1016/j.jacc.2022.10.042 -
Heart (British Cardiac Society) Sep 2023
Topics: Humans; Aortic Valve; Aortic Valve Stenosis; Transcatheter Aortic Valve Replacement; Calcinosis; Multidetector Computed Tomography; Heart Valve Prosthesis; Treatment Outcome; Prosthesis Design; Heart Valve Prosthesis Implantation
PubMed: 37290901
DOI: 10.1136/heartjnl-2023-322771 -
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 -
JACC. Cardiovascular Interventions Dec 2023
Topics: Humans; Transcatheter Aortic Valve Replacement; Treatment Outcome; Hemorrhage; Aortic Valve; Aortic Valve Stenosis; Risk Factors
PubMed: 38151310
DOI: 10.1016/j.jcin.2023.10.060 -
JACC. Cardiovascular Imaging Apr 2024
Topics: Humans; Predictive Value of Tests; Aortic Valve; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Treatment Outcome
PubMed: 37943234
DOI: 10.1016/j.jcmg.2023.09.012 -
The New England Journal of Medicine Nov 2023
Topics: Humans; Aortic Valve; Aortic Valve Stenosis; Constriction, Pathologic; Heart Valve Prosthesis Implantation
PubMed: 37991860
DOI: 10.1056/NEJMe2311826 -
Cell Biology and Toxicology Dec 2023To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in...
OBJECTIVES
To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD).
BACKGROUND
The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited.
METHODS
In vivo, we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice and used high methionine diet (HMD) to assess of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). In vitro, the role of Herpud1 in the Hcy-related osteogenic differentiation of AVICs was investigated by manipulating of Herpud1 expression.
RESULTS
Herpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in HMD-fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis.
CONCLUSIONS
These findings identify a previously unknown mechanism of Herpud1 upregulation in Hcy-related CAVD, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression.
HIGHLIGHTS
• Herpud1 is upregulated in the leaflets of Hcy-treated mice and patients with CAVD. • In mice, global knockout of Herpud1 alleviates aortic valve calcification and Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of AVICs induced by Hcy. • 4-PBA suppressed Herpud1 expression to alleviate AVIC calcification in Hcy treated AVICs and to mitigate aortic valve calcification in mice.
Topics: Humans; Mice; Animals; Aortic Valve; Osteogenesis; Aortic Valve Stenosis; Transcription Factors; Lipoproteins, LDL; Cells, Cultured; Membrane Proteins
PubMed: 36746840
DOI: 10.1007/s10565-023-09794-w -
JACC. Cardiovascular Interventions Aug 2023Transcatheter aortic valve replacement (TAVR) in patients with pure severe native aortic valve regurgitation (NAVR) has been associated with suboptimal results. The...
BACKGROUND
Transcatheter aortic valve replacement (TAVR) in patients with pure severe native aortic valve regurgitation (NAVR) has been associated with suboptimal results. The available evidence concerns mostly outdated transcatheter heart valves (THVs).
OBJECTIVES
The aim of this study was to investigate the performance of new-generation THVs in patients treated for pure severe NAVR.
METHODS
The PANTHEON (Performance of Currently Available Transcatheter Aortic Valve Platforms in Inoperable Patients With Pure Aortic Regurgitation of a Native Valve) study retrospectively included patients who underwent TAVR with currently available devices (both self-expanding [SE] and balloon expandable [BE]) for severe NAVR. Technical and device success rates as well as a composite of all-cause mortality and heart failure rehospitalization at 1 year were evaluated. The rate and clinical consequences of acute transcatheter valve embolization or migration (TVEM) were also considered.
RESULTS
A total of 201 patients were included. Overall technical and device success rates were 83.6% and 76.1%, respectively, and did not differ between SE and BE devices. These figures were due mostly to TVEM occurrence (14.6% vs 16.1%; P = 0.47) and residual moderate or greater aortic regurgitation (9.2% vs 10.1%; P = 0.87). Patients who experienced TVEM compared with those without TVEM had a significantly higher incidence of the composite endpoint at 1 year (25.7% vs 15.8%; P = 0.05).
CONCLUSIONS
Despite improved THV platforms and techniques, TAVR for pure severe NAVR remains a challenging procedure, with significant risk for TVEM. SE and BE platforms demonstrated comparable performance in this setting. (Performance of Currently Available Transcatheter Aortic Valve Platforms in Inoperable Patients With Pure Aortic Regurgitation of a Native Valve [PANTHEON]; NCT05319171).
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve Insufficiency; Aortic Valve; Retrospective Studies; Treatment Outcome
PubMed: 37648345
DOI: 10.1016/j.jcin.2023.07.026 -
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