Transcatheter Aortic Valve Replacement in Rheumatic Aortic Stenosis: A Comprehensive Review

Okor, Ivana; Bob‐Manuel, Tamunoinemi; Garikapati, Kiran; Baldawi, Harith; Gillies, Connor; Ibebuogu, Uzoma N.

doi:10.1016/j.cpcardiol.2021.100843

Cited by 13 publications

(11 citation statements)

References 38 publications

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“…The survival rates of asymptomatic patients with aortic stenosis are comparable to those of age- and sex-matched control cases [ 3 ]. However, the long-term survival in symptomatic cases without aortic valve replacement is merely 2 to 3 years [ 4 ]. Aortic valve calcification remains a mystery despite advancements in drastic therapies, such as valve replacement, and established interventional therapies for treating aortic stenosis.…”

Section: Introductionmentioning

confidence: 99%

Identification of MMP9 as a Novel Biomarker to Mitochondrial Metabolism Disorder and Oxidative Stress in Calcific Aortic Valve Stenosis

Liu

Cao

et al. 2022

Oxidative Medicine and Cellular Longevity

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Calcific aortic valve stenosis (CAVS) is the most common heart valve disorder among humans. To date, no effective method has been identified to prevent this disease. Herein, we aimed to identify novel diagnostic and mitochondria-related biomarkers of CAVS, based on two machine learning algorithms. We further explored their association with infiltrating immune cells and studied their potential function in CAVS. The GSE12644, GSE51472, and GSE83453 expression profiles were downloaded from the Gene Expression Omnibus (GEO) repository. The GSE12644 and GSE51472 datasets were integrated to identify differentially expressed genes (DEGs). GSE12644 contains 10 normal and 10 CAVS samples, whereas GSE51472 contains 5 normal and 10 CAVS samples. GO and KEGG assays of DEGs were conducted, and the correlation between matrix metalloproteinase 9 (MMP9) expression and immune cell infiltration was explored, using CIBERSORT. The LASSO regression model and SVM-RFE analysis were used to identify diagnostic genes. The expression of MMP9 in CAVS and non-CAVS samples was measured using RT-PCR, western blotting and immunohistochemistry. A series of functional experiments were performed to explore the potential role of MMP9 in mitochondrial metabolism and oxidative stress during CAVS progression. Twenty-two DEGs were identified, of which six genes (SCG2, PPBP, TREM1, CCL19, WIF1, and MMP9) were ultimately distinguished as diagnostic genes in CAVS. Of these, MMP9 was indicated as a mitochondria-related gene, the expression and diagnostic value of which were further confirmed in the GSE83453 dataset. Correlation analysis revealed a positive correlation between MMP9 and infiltrating immune cells. In our cohort, MMP9 expression was distinctly increased in CAVS samples, and its inhibition attenuated the calcification of valve interstitial cells (VICs) by suppressing mitochondrial damage and oxidative stress. Taken together, our findings suggest MMP9 as a novel mitochondrial dysfunction biomarker and therapeutic target for CAVS.

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Section: Introductionmentioning

confidence: 99%

Identification of MMP9 as a Novel Biomarker to Mitochondrial Metabolism Disorder and Oxidative Stress in Calcific Aortic Valve Stenosis

Liu

Cao

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…In the present study, procedural outcomes, including technical success and valve performance, were similar in patients with rheumatic and degenerative AS. Postinflammatory commissural fusion and fibrinous thickening of the aortic valve with limited calcification12 25 raised concern about adequate anchoring of THVs, and was one of the reasons why this population has been excluded from major randomised trials 9 10 12. However, in the present study, patients with rheumatic AS had a similar amount of aortic valvular complex calcification compared with patients with degenerative AS.…”

Section: Discussionmentioning

confidence: 66%

“…Patients with rheumatic AS were, however, excluded from landmark trials, and the available evidence is limited to small case series and data from insurance claims without granularity on imaging features and concomitant valvular disease 6–10. Primary concerns to expand TAVI to patients with rheumatic AS relate to the typical morphological features of RHD with fibrinous thickening of the leaflets, commissural fusion, limited calcification and the frequent combination of AS with other valvular lesions less amenable to transcatheter interventions 3–5 7 8 11 12…”

Section: Introductionmentioning

confidence: 99%

Transcatheter aortic valve implantation in patients with rheumatic aortic stenosis

Okuno

Tomii

Buffle

et al. 2022

Heart

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BackgroundRheumatic heart disease (RHD) accounts for the highest number of deaths from valvular heart disease globally. Yet, rheumatic aortic stenosis (AS) was excluded from landmark studies investigating the safety and efficacy of transcatheter aortic valve implantation (TAVI). We aimed to describe the clinical and anatomical characteristics of patients with rheumatic AS undergoing TAVI, and to compare procedural and clinical outcomes with patients undergoing TAVI for degenerative AS.MethodsIn a prospective TAVI registry, patients with rheumatic AS were identified based on International Classification of Diseases version 10 codes and/or a documented history of acute rheumatic fever and/or the World Heart Federation criteria for echocardiographic diagnosis of RHD, and were propensity score-matched in a 1:4 ratio to patients with degenerative AS.ResultsAmong 2329 patients undergoing TAVI, 105 (4.5%) had rheumatic AS. Compared with patients with degenerative AS, patients with rheumatic AS were more commonly female, older, had higher surgical risk and more commonly suffered from multivalvular heart disease. In the unmatched cohort, both technical success (85.7% vs 85.9%, p=0.887) and 1-year cardiovascular mortality (10.0% vs 8.6%; HR 1.16, 95% CI 0.61 to 2.18, p=0.656) were comparable between patients with rheumatic and degenerative AS. In contrast, patients with rheumatic AS had lower rates of 30-day and 1-year cardiovascular mortality compared with matched patients with degenerative AS (1.9% vs 8.9%, adjusted HR (HRadj) 0.18, 95% CI 0.04 to 0.80, p=0.024; and 10.0% vs 20.3%, HRadj 0.44, 95% CI 0.24 to 0.84, p=0.012, respectively).ConclusionTAVI may be a safe and effective treatment strategy for selected elderly patients with rheumatic AS.Trial registration numberNCT01368250.

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“…31 However, in low income countries, where RHD is most prevalent, the access to cardiac surgery remains a challenge because of the lack of infrastructure and higher procedure costs. 31,32 Other potential limitations of SAVR are the need for lifelong anticoagulation in those young patients implanted with mechanical valves which can lead to poorer outcomes. 31,32 A recent publication with a Medicare cohort of 1159 patients with rheumatic AS who underwent SAVR or TAVR showed no difference in all-cause mortality and a lower rate of in-hospital complications in TAVR patients after a median follow up of 19 months, even though the TAVR population had more comorbidities and were more frail.…”

Section: Discussionmentioning

confidence: 99%

“…31,32 Other potential limitations of SAVR are the need for lifelong anticoagulation in those young patients implanted with mechanical valves which can lead to poorer outcomes. 31,32 A recent publication with a Medicare cohort of 1159 patients with rheumatic AS who underwent SAVR or TAVR showed no difference in all-cause mortality and a lower rate of in-hospital complications in TAVR patients after a median follow up of 19 months, even though the TAVR population had more comorbidities and were more frail. 33 Further analysis in the same study comparing TAVR for rheumatic versus nonrheumatic AS also demonstrated no difference in all-cause, in-hospital or 30-day mortality between groups.…”

Section: Discussionmentioning

confidence: 99%

Transcatheter Aortic Valve Replacement for Severe Symptomatic Aortic Stenosis in Rheumatic Heart Disease: A Systematic Review

Fernandes¹,

Fernandes²,

Grant³

et al. 2021

Cardiology in Review

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Transcatheter aortic valve replacement (TAVR) is well-established for severe symptomatic aortic stenosis (AS), but its use in rheumatic heart disease (RHD) has been limited. We systematically review the use of TAVR for severe symptomatic AS in RHD. Pubmed, Embase, and Scopus were searched for TAVR for symptomatic severe AS and proven or suspected RHD. Procedure characteristics, efficacy, and safety endpoints were collected and all definitions were based on the Valve Academic Research Consortium-2 (VARC-2) criteria. We included 3 case series and 12 case reports, with a total of 43 patients. Mean age was 76 years, 75% were female, and 85% had NYHA class III-IV symptoms. Follow up ranged from 1 to 29 months. Patients were moderate to high risk, with Society of Thoracic Surgery score ranging from 6.1% to 17.6%. The approach was transfemoral in 30 (83%) cases. Procedural success occurred in 37 (86%) patients. Of the 7 patients with periprocedural complications, 4 had valve dislodgement, 1 deployment failure, 1 unplanned cardiopulmonary bypass, and 1 moderate aortic regurgitation. Paravalvular leak was reported in 5 (11.6%) patients. Only 1 patient had heart block requiring pacemaker. Among 13 studies (23 patients), 30-day mortality was 0%. One case series with 19 patients had a 30-day, 1-year, 2-year, and 5-year mortality of 5%, 11%, 31%, and 48%, respectively. TAVR appears feasible for selected patients with rheumatic severe AS, albeit our results indicate a 14% incidence of device failure. Future randomized clinical trials may clarify the role of TAVR in this group.

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Transcatheter Aortic Valve Replacement in Rheumatic Aortic Stenosis: A Comprehensive Review

Cited by 13 publications

References 38 publications

Identification of MMP9 as a Novel Biomarker to Mitochondrial Metabolism Disorder and Oxidative Stress in Calcific Aortic Valve Stenosis

Identification of MMP9 as a Novel Biomarker to Mitochondrial Metabolism Disorder and Oxidative Stress in Calcific Aortic Valve Stenosis

Transcatheter aortic valve implantation in patients with rheumatic aortic stenosis

Transcatheter Aortic Valve Replacement for Severe Symptomatic Aortic Stenosis in Rheumatic Heart Disease: A Systematic Review

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