Meta-analysis of Incidence, Predictors and Consequences of Clinical and Subclinical Bioprosthetic Leaflet Thrombosis After Transcatheter Aortic Valve Implantation

doi:10.1016/j.amjcard.2020.07.018

The American Journal of Cardiology

Volume 132, 1 October 2020, Pages 106-113

https://doi.org/10.1016/j.amjcard.2020.07.018 Get rights and content

Leaflet thrombosis (LT) has been claimed as a potential cause of hemodynamic dysfunction or bioprosthetic valve degeneration of transcatheter heart valves. Sparse and contrasting evidence exists, however, regarding LT occurrence, prevention and treatment. MEDLINE, ISI Web of Science and SCOPUS databases were searched for studies published up to January 2020. Only studies reporting data on incidence and outcomes associated to the presence/absence of clinical or subclinical LT, detected or confirmed with a multidetector computed tomography exam were included. The study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. Two reviewers independently screened articles for fulfillment of inclusion criteria. Data were pooled using a random-effect model. The primary end point was the incidence of LT. Secondary outcomes included: stroke and transient ischemic attacks and mean transvalvular gradients at different time-points in patients with and without LT. Of the initial 200 studies, 22 were finally included with a total of 11,567 patients. LT overall incidence was 8% (95% Confidence Interval [CI]: 5% to 13%, I² = 96.4%). LT incidence in patients receiving only antiplatelets was 13% (95% CI: 7% to 23%, p <0.0001); patients discharged on oral anticoagulants had a reported incidence of 4% (95% CI: 2% to 8%, p <0.0001). Patients with LT, either clinical or subclinical, were not at increased risk of stroke (OR 1.06, 95% CI: 0.75 to 1.50, p = 0.730, I² = 0.0%) or transient ischemic attacks (Odds Ratio 1.01, 95% CI: 0.40 to 2.57, p = 0.989, I² = 0.0%). LT was associated with higher mean transvalvular gradients compared with patients without LT at 30 days post-transcatheter implantation, but not at discharge or at 1 year. LT is a relatively common event that, even when clinically manifest, is not associated with an increased risk of cerebrovascular events. Although patients on anticoagulants appear to be at lower risk of LT, the available evidence does not allow formulation of recommendations for prophylactical anticoagulation nor routine computed tomography after transcatheter aortic valve replacement.

Section snippets

Methods

The study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements.¹⁸ MEDLINE, ISI Web of Science and SCOPUS databases were searched for studies published up to January 2020. Studies were identified using the major medical subject heading “TAVI or transcatheter heart valve and LT or clot and stroke or TIA or mortality or outcome”. English was set as a language restriction. Two authors (AS and PAG) independently examined the title and

Results

The initial search of published articles identified 200 articles, of which 27 were retrieved for more detailed evaluation, and 22 were finally included in the meta-analysis, enrolling 11,567 subjects (Supplementary Table 1, Supplementary Figure 1).5, 6, 7, 8, 9, 10, 11, 12^,¹⁴^,¹⁶^,¹⁷^,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34

The overall incidence of LT was 8% (95% CI: 5% to 13%, I² = 96.45%) (Figure 1). In the subgroup of studies assessing clinical LT. the incidence was estimated at 3% (9

Discussion

To the best of our knowledge, this is the first comprehensive meta-analysis including low-risk populations and assessing the incidence of LT after TAVI. The main results of this study are: (1) The overall incidence of THV thrombosis is 8% with a significant difference between clinical and subclinical LT. (2) The presence of LT, either clinical or subclinical, is not linked to the occurrence of cerebrovascular events. (3) The prevalence of LT post-TAVI is lower in patients on anticoagulant

Author contributions

Anna Sannino: Conceptualization; Methodology; Formal analysis; Investigation; Writing - Original Draft. Rebecca T. Hahn: Supervision; Writing - Review & Editing. Jonathon Leipsic: Supervision; Writing - Review & Editing. Michael J. Mack: Supervision; Writing - Review & Editing. Paul A. Grayburn: Conceptualization; Writing - Review & Editing; Supervision.

Disclosure

Declaration of interests: The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this paper.

AS Disclosures: Research grant support from Cardiovalve, Edwards Lifesciences and W. L. Gore.

PAG Disclosures: grants from Abbott Vascular, Medtronic, Boston-Scientific, Edwards, Tendyne, ValTech Cardio, NeoChord. Consultant for Abbott Vascular, NeoChord, ValTech Cardio.

RTH Disclosures: Dr. Hahn is the

References (44)

RA Nishimura et al.
2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines
J Am Coll Cardiol
(2017)
SS Basra et al.
Clinical leaflet thrombosis in transcatheter and surgical bioprosthetic aortic valves by four-dimensional computed tomography
Ann Thorac Surg
(2018)
T Chakravarty et al.
Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study
Lancet
(2017)
NC Hansson et al.
Transcatheter aortic valve thrombosis: incidence, predisposing factors, and clinical implications
J Am Coll Cardiol
(2016)
J Jose et al.
Clinical bioprosthetic heart valve thrombosis after transcatheter aortic valve replacement: incidence, characteristics, and treatment outcomes
JACC Cardiovasc Interv
(2017)
M Marwan et al.
Leaflet thrombosis following transcatheter aortic valve implantation
J Cardiovasc Comput Tomogr
(2018)
R Waksman et al.
Transcatheter aortic valve replacement in low-risk patients with symptomatic severe aortic stenosis
J Am Coll Cardiol
(2018)
R Yanagisawa et al.
Incidence, predictors, and mid-term outcomes of possible leaflet thrombosis after TAVR
JACC Cardiovasc Imaging
(2017)
D Moher et al.
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement
Int J Surg
(2010)
A Sannino et al.
Meta-analysis of effect of body mass index on outcomes after transcatheter aortic valve implantation
Am J Cardiol
(2017)

A Mangieri et al.

Single-antiplatelet therapy in patients with contraindication to dual-antiplatelet therapy after transcatheter aortic valve implantation

Am J Cardiol

(2017)

F Huchet et al.

Could anticoagulation avoid bioprosthesis subclinical thrombosis in patients undergoing transcatheter aortic valve replacement

Arch Cardiovasc Dis

(2018)

P Ruile et al.

Medium-term follow-up of early leaflet thrombosis after transcatheter aortic valve teplacement

JACC Cardiovasc Interv

(2018)

L Tang et al.

Prospective evaluation for hypoattenuated leaflet thickening following transcatheter aortic valve implantation

Am J Cardiol

(2019)

E De Marchena et al.

Thrombus formation following transcatheter aortic valve replacement

JACC Cardiovasc Interv

(2015)

SL Sellers et al.

Transcatheter aortic heart valves: histological analysis providing insight to leaflet thickening and structural valve degeneration

JACC Cardiovas Imaging

(2019)

H Jilaihawi et al.

Systematic CT methodology for the evaluation of subclinical leaflet thrombosis

JACC Cardiovasc Imaging

(2017)

P Blanke et al.

Computed tomography imaging in the context of transcatheter aortic valve implantation (TAVI)/transcatheter aortic valve eplacement (TAVR): an expert consensus document of the society of cardiovascular computed tomography

JACC Cardiovasc Imaging

(2019)

MB Leon et al.

Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery

New Eng J Med

(2010)

MJ Reardon et al.

Surgical or transcatheter aortic-valve replacement in intermediate-risk patients

N Engl J Med

(2017)

CR Smith et al.

Transcatheter versus surgical aortic-valve replacement in high-risk patients

N Engl J Med

(2011)

A Franzone et al.

Transcatheter aortic valve thrombosis: incidence, clinical presentation and long-term outcomes

Eur Heart J Cardiovasc Imaging

(2018)

Cited by (16)

Antithrombotic Treatment After Transcatheter Valve Interventions: Current Status and Future Directions
2024, Clinical Therapeutics
The optimal antithrombotic strategy after transcatheter valve interventions is a subject of ongoing debate. Although there is evidence from randomized trials in patients undergoing transcatheter aortic valve replacement (TAVR), current evidence on optimal antithrombotic management after transcatheter mitral or tricuspid valve interventions is sparse. This article appraises the current evidence on this topic.
This narrative review presents key research findings and guideline recommendations, as well as highlights areas for future research.
After TAVR, randomized trial evidence suggests that single antiplatelet therapy is reasonable for patients without pre-existing indications for oral anticoagulation (OAC). If there is a concurrent indication for OAC, the addition of antiplatelet therapy increases bleeding risk. Whether direct oral anticoagulants achieve better outcomes than vitamin K antagonists is uncertain in this setting. Although OAC has been shown to reduce subclinical leaflet thrombosis (which may progress to structural valve degeneration), bleeding events are unacceptably high. There is a lack of randomized trial data comparing antithrombotic strategies after transcatheter mitral or tricuspid valve replacement or after mitral or tricuspid transcatheter edge-to-edge repair. Single antiplatelet therapy after mitral or tricuspid transcatheter edge-to-edge repair may be appropriate, whereas at least 3 months of OAC is suggested after transcatheter mitral valve replacement or transcatheter tricuspid valve replacement.
Randomized studies are warranted to address the knowledge gaps in antithrombotic therapy after transcatheter valve interventions and to optimize outcomes.
Right Heart Remodeling and Outcomes in Patients With Tricuspid Regurgitation: A Literature Review and Meta-Analysis
2024, JACC: Cardiovascular Imaging
Functional tricuspid regurgitation (TR) can develop either because of right ventricular (RV) remodeling (ventricular functional TR) and/or right atrial dilation (atrial functional TR).
This meta-analysis aimed to investigate the association between right heart remodeling and long-term (>1 year) all-cause mortality in patients with significant TR (at least moderate, ≥2+).
MEDLINE, ISI Web of Science, and SCOPUS databases were searched. Studies reporting data on at least 1 RV functional parameter and long-term all-cause mortality in patients with significant TR were included. This study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements.
Out of 8,902 studies, a total of 14 were included, enrolling 4,394 subjects. The duration of follow-up across the studies varied, ranging from a minimum of 15.5 months to a maximum of 73.2 months. Overall, long-term all-cause mortality was 31% (95% CI: 20%-41%; P ≤ 0.001). By means of meta-regression analyses, an inverse relation was found between tricuspid annular plane systolic excursion (11 studies enrolling 3,551 subjects, −6.3% [95% CI: −11.1% to −1.4%]; P = 0.011), RV fractional area change (9 studies, 2,975 subjects, −4.4% [95% CI: −5.9% to −2.9%]; P < 0.001), tricuspid annular dimension (7 studies, 2,986 subjects, −4.1% [95% CI: −7.6% to −0.5%]; P = 0.026), right atrial area (6 studies, 1,920 subjects, −1.9% [95% CI: −2.5% to −1.3%]; P < 0.001) and mortality.
RV dysfunction parameters are associated to worse clinical outcomes in patients with TR, whereas right atrial dilatation is linked to a better prognostic outcome. Further studies are needed to unravel the pathophysiological differences within the functional TR spectrum. (Right heart remodeling and outcomes in patients with tricuspid regurgitation; CRD42023418667)
Valve Thrombosis After TAVR: Beyond HALT and RELM
2023, JACC: Cardiovascular Interventions
Oral anticoagulation after transcatheter aortic valve implantation
2023, NPG Neurologie - Psychiatrie - Geriatrie
Transcatheter aortic valve implantation (TAVI) has hitherto been considered the main treatment for elderly, high-surgical-risk, or short-life-expectation patients. After TAVI, patients receive antithrombotics to prevent thrombotic risk, but this increases their bleeding risk. Thus, the risk of thrombotic and bleeding events is a major concern for TAVI patients. Choosing an appropriate antithrombotic is challenging, especially in presence of other concomitant indications for antithrombotic therapy. The aim of this article is to discuss different antithrombotic regimens and to explore the use of oral anticoagulation with and without other indications for oral anticoagulation, and evidence supporting its use.
L’implantation transcathéter de valve aortique (Tavi) est considérée comme le traitement principal pour les patients âgés, à haut risque chirurgical ou à courte espérance de vie ayant un rétrécissement aortique. Après Tavi, les patients utilisent des antithrombotiques pour prévenir le risque thrombotique, mais cela augmente leur risque hémorragique. Ainsi, le risque d’événements thrombotiques et hémorragiques est une préoccupation majeure chez les patients TAVI. Le choix d’un antithrombotique approprié est difficile, en particulier lorsqu’il existe d’autres indications concomitantes d’un tel traitement. Le but de cet article est de discuter des différents schémas thérapeutiques antithrombotiques et d’explorer l’utilisation de l’anticoagulation orale avec ou sans indications et les données à l’appui de cette utilisation.
Hypoattenuated leaflet thickening (HALT) and reduced leaflet motion (RELM) of aortic bioprostheses: An imaging finding or a complication?
2022, Progress in Cardiovascular Diseases
Citation Excerpt :
In the combined report of the RESOLVE and SAVORY registries,11 the overall incidence of subclinical leaflet thrombosis was 12% (106 patients from 890 who had interpretable CT scans), with greater frequency in transcatheter valves (13%, or 101 patients from 752) than surgical valves (4%, or 5 from 138 patients). A meta-analysis of 18 studies15 found subclinical leaflet thrombosis rates of 16.32% per year in patients after TAVI, and a further meta-analysis of 22 studies and 11,567 patients16 demonstrated rates of subclinical leaflet thrombosis of 15% after TAVI, and clinical valve thrombosis rates of 3%. The data on subclinical leaflet thrombosis after surgical valve replacement is more scant than that for transcatheter valves, although a small single-center study17 of sutureless bioprosthetic valves found high rates of HALT (38%) and RELM (28%).
Transcatheter aortic valve implantation is a safe and effective therapy for patients with symptomatic severe aortic stenosis, with randomized data demonstrating outcomes at least equivalent to surgical aortic valve replacement across the spectrum of surgical risk. There has been substantial recent interest in the occurrence of hypoattenuated leaflet thickening and reduced leaflet motion, which are imaging features detected on computed tomography of patients who have received aortic bioprostheses. These phenomena may represent subclinical leaflet thrombosis with theoretical potential downstream effects on valve durability or thrombotic complications in the form of stroke. This review will discuss definitions, predictors, mechanisms, diagnosis, and natural history. We will also examine the frequency with which hypoattenuated leaflet thickening and reduced leaflet motion occur after both transcatheter and surgical aortic bioprostheses, and the clinical implications and potential impact on valve function, as well as strategies for prophylaxis and treatment.
Valve thrombosis after transcatheter and surgical aortic valve replacement: Incidence and outcomes
2022, Journal of Thoracic and Cardiovascular Surgery

View all citing articles on Scopus

View full text

Meta-analysis of Incidence, Predictors and Consequences of Clinical and Subclinical Bioprosthetic Leaflet Thrombosis After Transcatheter Aortic Valve Implantation

Section snippets

Methods

Results

Discussion

Author contributions

Disclosure

J Am Coll Cardiol

Ann Thorac Surg

Lancet

J Am Coll Cardiol

JACC Cardiovasc Interv

J Cardiovasc Comput Tomogr

J Am Coll Cardiol

JACC Cardiovasc Imaging

Int J Surg

Am J Cardiol

Am J Cardiol

Arch Cardiovasc Dis

JACC Cardiovasc Interv

Am J Cardiol

JACC Cardiovasc Interv

JACC Cardiovas Imaging

JACC Cardiovasc Imaging

JACC Cardiovasc Imaging

Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery

New Eng J Med

Surgical or transcatheter aortic-valve replacement in intermediate-risk patients

N Engl J Med

Transcatheter versus surgical aortic-valve replacement in high-risk patients

N Engl J Med

Transcatheter aortic valve thrombosis: incidence, clinical presentation and long-term outcomes

Eur Heart J Cardiovasc Imaging