Statins for aortic valve stenosis

Thiago, Luciana; Tsuji, Selma Rumiko; Nyong, Jonathan; Puga, Maria Eduarda dos Santos; Góis, Aécio Flávio Teixeira de; Macedo, Cristiane R; Valente, Orsine; Atallah, Álvaro Nagib

doi:10.1002/14651858.cd009571.pub2

Cited by 15 publications

(10 citation statements)

References 36 publications

(2 reference statements)

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“…These amyloid depositions are believed to cause mineralization of calcified aortic valves by promoting apoptosis of valvular interstitial cells ( 15 ). However, there is no benefit of lipid-lowering therapy (statins) on severity or progression of aortic stenosis ( 17 ). TTR deposition may be explained by the shear stress caused by the accelerated flow of blood across the stenosed valve predisposing it to amyloidogenesis.…”

Section: Discussionmentioning

confidence: 99%

Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population

Singal¹,

Bansal²,

Singh³

et al. 2021

JACC: CardioOncology

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Background Prevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age. Dual disease (AS+myocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR). Objectives This study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis. Methods Symptomatic severe AS patients aged ≥65 years undergoing SAVR were enrolled. ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA. Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation. Results SAVR was performed in 46 AS patients (age 70 ± 5 years, 70% men). PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n = 3 of 32, 9.4%), suggestive of myocardial ATTR-CA. On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis. Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%]; P = 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms; P = 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%]; P = 0.030). At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%; P = 0.477). Conclusions Dual disease is not uncommon in India. Isolated valvular amyloidosis in severe AS is much more common.

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Section: Discussionmentioning

confidence: 99%

Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population

Singal¹,

Bansal²,

Singh³

et al. 2021

JACC: CardioOncology

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“…As suggested by a recent systematic review, large and high-quality trials should first of all identify patients at high risk for developing CAVS and then, investigate whether early statin treatment can prevent disease progression in these subjects [38]. Currently, the BICATOR trial (NCT02679261) is investigating whether atorvastatin is effective in reducing CAVS progression in patients with bicuspid AV and moderate valve dysfunction [39].…”

Section: Future Perspectivesmentioning

confidence: 99%

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis

Donato

Ferri

Lupo

et al. 2020

IJMS

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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.

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“…Calcific aortic valve disease (CAVD) is the most common heart valve disease and the principal cause of aortic stenosis (AS) in Western countries. Angiotensin converting enzyme (ACE) inhibitors have shown some promise but their efficacy in counteracting the progression of AS in the clinical setting is still uncertain [ 1 , 2 ], while statins, although able to counteract calcification in vitro, were found to be ineffective in large randomized clinical trials [ 3 , 4 ]. Currently, there is no pharmacological therapy specifically indicated for CAVD, which progresses rapidly, eventually requiring the replacement of the aortic valve.…”

Section: Introductionmentioning

confidence: 99%

COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

Sega

Fortini

Cimaglia

et al. 2020

IJMS

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Calcific aortic valve disease (CAVD) is the result of maladaptive fibrocalcific processes leading to a progressive thickening and stiffening of aortic valve (AV) leaflets. CAVD is the most common cause of aortic stenosis (AS). At present, there is no effective pharmacotherapy in reducing CAVD progression; when CAVD becomes symptomatic it can only be treated with valve replacement. Inflammation has a key role in AV pathological remodeling; hence, anti-inflammatory therapy has been proposed as a strategy to prevent CAVD. Cyclooxygenase 2 (COX-2) is a key mediator of the inflammation and it is the target of widely used anti-inflammatory drugs. COX-2-inhibitor celecoxib was initially shown to reduce AV calcification in a murine model. However, in contrast to these findings, a recent retrospective clinical analysis found an association between AS and celecoxib use. In the present study, we investigated whether variations in COX-2 expression levels in human AVs may be linked to CAVD. We extracted total RNA from surgically explanted AVs from patients without CAVD or with CAVD. We found that COX-2 mRNA was higher in non-calcific AVs compared to calcific AVs (0.013 ± 0.002 vs. 0.006 ± 0.0004; p < 0.0001). Moreover, we isolated human aortic valve interstitial cells (AVICs) from AVs and found that COX-2 expression is decreased in AVICs from calcific valves compared to AVICs from non-calcific AVs. Furthermore, we observed that COX-2 inhibition with celecoxib induces AVICs trans-differentiation towards a myofibroblast phenotype, and increases the levels of TGF-β-induced apoptosis, both processes able to promote the formation of calcific nodules. We conclude that reduced COX-2 expression is a characteristic of human AVICs prone to calcification and that COX-2 inhibition may promote aortic valve calcification. Our findings support the notion that celecoxib may facilitate CAVD progression.

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Statins for aortic valve stenosis

Cited by 15 publications

References 36 publications

Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population

Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population

Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis

COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

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