Subclinical Valve Research Articles

Sydenham's Chorea in Children with Acute Rheumatic Fever: An Echocardiographic Survey of Pediatric Patients in Northwestern Iran.

Although infrequent, Sydenham's chorea (SC) may occur as a result of injury to the basal ganglia in children with acute rheumatic fever (ARF) secondary to group A Streptococcal infection. Certain hallmarks of SC, such as movement disorders, could be utilized as a predictive marker for carditis. The present study aimed to investigate neurologic and cardiologic symptoms in children with suspected SC after ARF. All children aged 5-16 who were admitted at Shahid Madani Pediatric Hospital (Tabriz, Iran), with an initial diagnosis of ARF and SC between 2009 and 2022 were included for echocardiographic assessment and prospective follow-up within 6 and 12 months after the start point. The pattern and severity of valvulopathy, as well as the prevalence of Jones criteria for rheumatic fever, were used to assess the effect. The collected data were analyzed using SPSS Statistics software (version 22.0) using Chi square and Fisher's exact tests. P<0.05 was considered statistically significant. The study enrolled 85 children, 36 girls and 49 boys, with a mean age of 9.7±2.7. On the first echocardiography, 42.4% of patients had mitral valve regurgitation (MR), with a predominance of female patients (P=0.04). Of those diagnosed with SC (12 girls and 6 boys), 66.7% showed cardiac involvement, with a higher prevalence of MR in both sexes (P=0.04). The pattern of cardiac involvement after 6 months was significantly different between the groups (P=0.04). However, no such difference was observed during the one-year follow-up (P=0.07). Female sex was found to have a significant relationship with SC localization (P=0.01). In addition to its neurological manifestations, SC can be associated with clinical or subclinical cardiac valve dysfunction that might last for more than a year. In addition to attempting early detection and appropriate management, a precise cardiac and neurologic assessment during admission and follow-up is recommended.A preprint version of this manuscript is available at DOI: 10.21203/rs.3.rs-772662/v1 (https://www.researchsquare.com/article/rs-772662/v1).

Subclinical valve leaflet thrombosis following bioprosthetic aortic valve replacement.

Subclinical leaflet thrombosis (SLT) is often an incidental finding characterized by a thin layer of thrombus involving one, two or three leaflets, with typical appearance on multi-detector computed tomography (MDCT) of hypo-attenuating defect at the aortic side of the leaflet, also called hypo-attenuating leaflet thickening (HALT). SLT may occur following both transcatheter aortic replacement (TAVR) or biological surgical aortic valve replacement (SAVR). The aim of this review is to present an overview of the current state of knowledge on the incidence, diagnosis, clinical impact, and management of SLT following TAVR or SAVR. SLT occurs in 10-20% of patients following TAVR and is somewhat more frequent than following SAVR (5-15%). SLT may regress spontaneously without treatment in about 50% of the cases but may also progress to clinically significant valve thrombosis in some cases. Oral anticoagulation with vitamin K antagonist is reasonable if SLT is detected by echocardiography and/or MDCT during follow-up and is generally efficient to reverse SLT. SLT is associated with mild increase in the risk of stroke but has no impact on survival. SLT has been linked with accelerated structural valve deterioration and may thus impact valve durability and long-term outcomes. SLT is often an incidental finding on echocardiography or MDCT that occurs in 10-20% of patients following TAVR or 5-15% following biological SAVR and is associated with a mild increase in the risk of thrombo-embolic event with no significant impact on mortality but may be associated with reduced valve durability.

Impact of platelet reactivity on subclinical valve thrombosis in patients treated with TAVR

Abstract Background and introduction High residual platelet reactivity (HPR) in patients undergoing percutaneous coronary intervention with dual antiplatelet therapy (DAPT) is associated with an increased risk of thrombotic events. The relationship between HPR and the presence of subclinical valve thrombosis (SVT) following transcatheter aortic valve replacement (TAVR) is unknown. Purpose The aim of this study was to determine whether HPR is associated with the occurrence of SVT in patients undergoing TAVR treated with DAPT and to determine independent predictors of SVT. Methods This is a prospective, multicentre study. Patients with symptomatic aortic stenosis successfully treated with TAVR followed by DAPT (aspirin + clopidogrel) for 3 months were included. Patients with monotherapy, oral anticoagulation, or severe renal impairment were excluded. For the purpose of the study, platelet reactivity was measured either with Multiplate analyzer or VerifyNow point-of-care assay at baseline, at 1-2 days post, and 1-3 months post-TAVR. HPR was defined as ≥ 468AU, or ≥208PRU, respectively. The primary endpoint was the incidence of SVT measured by multi-slice CT at 3-months post TAVR in relation to HPR. Secondary objectives included the relationship between HPR following TAVR and the incidence of major adverse cardiac and cerebral clinical events (MACCE), to determine whether a pro-thrombotic inflammatory response is associated with the appearance of SVT and to evaluate factors associated with the occurrence of SVT. Results A total of 169 patients were included, the mean age was 81.5±5 and 51% were female. The overall rate of SVT was 22%. Patients with HPR demonstrated a similar incidence of SVT to those without (23,7% vs 33,6%: p=0,29). The overall bleeding rate was 4,9%. No differences in the rate of stroke at 1-year follow-up were observed (no SVT group 1.5% vs SVT group 2.6%: p=0.6). Independent predictors of SVT, were: dyslipemia OR 0,38 (0,15-0,96) p=0,039, creatinine clearance 0.98 (0.96.1.0, p=0.04), self-expandable valve OR 3,57 (1,40-9,06); p=0,006 and prosthesis size 0,78 (0,64-0,96): p=0,009. Patients with SVT expressed increased inflammatory parameters at 6 months compared to those without SVT CD14+ CD16-: 76,6±9,9 vs 70,7±13,9: p=0.02. Conclusion In contrast to coronary interventions, for the first time we have demonstrated that HPR does not appear to be associated with the development of SVT in TAVR patients treated with DAPT.

High rates of high on-aspirin platelet reactivity in patients after transcatheter aortic valve implantation

Abstract Background Guidelines recommend aspirin monotherapy in patients after transcatheter aortic valve replacement (TAVR) without an indication for oral anticoagulation. The prevalence of high on-aspirin platelet reactivity (HAPR) varies from 1% to 34% and may be associated with long-term ischemic risk or subclinical valve thrombosis which occurs in 17-40% of the patients after TAVR. Purpose To determine the prevalence of HAPR and its association with subclinical valve thrombosis in patients undergoing TAVR using methods that directly indicate the degree of platelet cyclooxygenase inhibition. Methods Data were collected in a prospective, single-center, observational cohort study between October 2020 and June 2022. Patients were enrolled after TAVR, and platelet function was assessed during the hospital stay with light-transmittance platelet aggregation (LTA) and thrombelastography (TEG) platelet mapping. Platelet aggregation was induced with arachidonic acid (AA)-induced LTA (final concentration [fc] 1.64 mM) and TEG (fc 1.0mM). The maximum percent aggregation (%aggr) was recorded. According to the literature, HAPR was defined as &amp;gt;20% aggregation by LTA or &amp;gt;50% aggregation by TEG, respectively. All patients were under maintenance of 100 mg aspirin or received a loading dose of 300-600mg aspirin before measurement. 47 of 75 patients underwent computed tomography (CT) to detect valve thrombosis (VT) 6 months after TAVR. Results Data from 75 patients under maintenance of aspirin were analyzed. The median age was 82 years (interquartile range, IQR 79-85), and 52% were male. 12 patients (16%) had a history of stroke or TIA, and 7 (9%) had suffered a previous myocardial infarction. TEG and LTA were performed during the hospital stay between days 0 and 17 post-TAVR. Median AA-induced maximum aggregation by LTA was 17 % (interquartile range, IQR 13-38) and by TEG was 29 % (IQR 5-64). When determining platelet function using LTA, 33 patients (44%) had residual platelet function (i.e., %aggrLTA &amp;gt;20%) despite aspirin treatment. According to the TEG results, 27 patients (36 %) were identified as HAPR (i.e., %aggrTEG &amp;gt;50%). The agreement (Kappa=0.06) and correlation (r=0.32, Figure 1) between the two tests were low to moderate. 13 patients had HAPR in both methods. 19 of 47 patients (40%) had VT on CT 6 months after TAVI. 12 of these 19 patients (63%) with VT responded well to aspirin in the TEG and LTA, while 7 (37%) had HAPR in both tests. HAPR was not significantly associated with HALT when measured with TEG or LTA (OR 0.90 [95% CI 0.27.2.76], p=0.86 and 0.58 [95% CI 0.17-2.04], p=0.37, respectively; Table 1). Conclusion HAPR assessed by LTA and TEG is frequent in patients undergoing TAVR. In this exploratory study, HAPR was not significantly associated with the occurrence of HALT. Further studies are required to evaluate the long-term risk of leaflet thrombosis or thromboembolic events in patients with HAPR.

Antithrombotic therapy with Transcatheter aortic valve replacement.

Aortic valve replacement is a necessary management strategy for patients with severe aortic stenosis. The use of transaortic valve replacement (TAVR) has increased significantly over the last decade and now exceeds traditional surgical aortic valve replacement. Since the valve systems used in TAVR consist of bioprosthetic valve tissue encased in a metal stent frame, antithrombotic therapy recommendations cannot be extrapolated from prior data with differently constructed surgical bioprosthetic or mechanical valves. Data on the use of antithrombotic therapy with TAVR are a rapidly developing area of medicine. Choice of agents depends on several patient factors. Patients undergoing TAVR also have a relatively high incidence of subclinical valve thrombosis. The clinical impact of this phenomenon and the implications for antithrombotic therapy continue to evolve. It is critical for clinicians who treat patients undergoing TAVR to have a firm understanding of practice guidelines, the evolving evidence, and its implications for the use of antithrombotic therapy in these patients.

Direct oral anticoagulants versus vitamin K antagonists in the first 3 months after bioprosthetic valve replacement: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis of randomized controlled trials comparing direct oral anticoagulants (DOACs) to vitamin K antagonists (VKAs) in the first 90 days after bioprosthetic valve implantation. We systematically searched Embase, Medline and CENTRAL. We screened titles, abstracts and full texts, extracted data and assessed the risk of bias in duplicate. We pooled data using the Mantel-Haenzel method and random effects modelling. We conducted subgroup analyses based on the type of valve (transcatheter versus surgical) and timing of initiation of anticoagulation (<7 vs >7 days after valve implantation). We assessed the certainty of evidence using the Grading of Recommendations, Assessments, Development and Evaluation approach. We included 4 studies of 2284 patients with a median follow-up of 12 months. Two studies examined transcatheter valves (1877/2284 = 83%) and 2 examined surgical valves (407/2284 = 17%). We found no statistically significant differences between DOACs and VKAs with regard to thrombosis, bleeding, death or subclinical valve thrombosis. However, there was a subgroup trend towards more bleeding with DOACs when initiated within 7 days of valve implantation. In the existing randomized literature on DOACs versus VKAs in the first 90 days after bioprosthetic valve implantation, there appears to be no difference with regard to thrombosis, bleeding or death. Interpretation of the data is limited by small numbers of events and wide confidence intervals. Future studies should focus on surgical valves and should include long-term follow-up to assess any potential impact of randomized therapy on valve durability.

Antithrombotic therapy after TAVI: Better alone than with a bad company.

Key Points In transcatheter aortic valve implantation (TAVI) subset, previous randomized controlled trials reported increased mortality when anticoagulant therapy was used in subjects without a previous oral anticoagulation (OAC) indication. The current meta‐analysis confirms the worse clinical outcomes in anticoagulated patients as compared to subjects treated with antiplatelet, tough less subclinical valve thrombosis was found in the OAC group. At present, antiplatelet therapy (especially SAPT) seems the most reasonable approach in TAVI patients without indications for chronic OAC.

Patient-specific fluid simulation of transcatheter mitral valve replacement in mitral annulus calcification.

Transcatheter mitral valve replacement is a promising alternative to open-heart surgery in elderly patients. Patients with severe mitral annulus calcification (MAC) are a particularly high-risk population, where postprocedural complications can have catastrophic effects. Amongst these, obstruction of the left ventricular outflow tract can lead to ventricular hypertrophic remodeling and subsequent heart failure, while subclinical valve thrombosis can result in early bioprosthetic valve failure. To elucidate the mechanisms of left ventricular outflow tract obstruction and valve thrombosis following valve-in-MAC procedures, we used image processing and Computational Fluid Dynamics (CFD) software to generate patient- and device-specific models based on preprocedural CT data. Personalized computer simulations were performed to predict the left ventricular haemodynamics after implantation in three patients with severe MAC. The simulations have successfully captured the increased pressure gradient in the left ventricular outflow tract as a result of the partial obstruction due to the implanted valve. Regions of wall shear stress above the threshold value for platelet activation were also observed on the bioprosthetic frame as a result of the reduced outflow tract area, which led to increases in flow resistance and blood residence time inside the ventricle. Consistent with these findings, areas of slow recirculating flow and blood stasis formed near the valve frame, creating potential pro-thrombotic conditions. This study provides insight into the relationship between size and shape of the outflow tract post-implantation, pressure gradients and pro-thrombotic flow metrics such as wall shear stress and blood residence time. Results show the potential of CFD modeling to bring key functional metrics into preprocedural assessment for a comprehensive evaluation of post-procedural risks beyond anatomical factors. Following further validation and extension to the atrial chamber, this approach can provide an in-depth analysis of the likelihood of valvular thrombosis.

How Did We Get Here? Antithrombotic Therapy after Bioprosthetic Aortic Valve Replacement: A Review.

Aortic stenosis is the most common valvular disease, and more than 90% of patients who undergo aortic valve replacement receive a bioprosthetic valve. Yet optimal antithrombotic therapy after bioprosthetic aortic valve replacement remains uncertain, and guidelines provide contradictory recommendations. Randomized studies of antithrombotic therapy after bioprosthetic aortic valve replacement are small and underpowered. Observational data present opposing, and likely confounded, results. Historically, changes to guidelines have not been informed by high-quality new data. Current guidelines from different professional bodies provide contradictory recommendations despite citing the same evidence. Insufficient antithrombotic therapy after bioprosthetic aortic valve replacement has serious implications: ischemic stroke, systemic arterial thromboembolism, and clinical and subclinical valve thromboses. Unnecessarily intense antithrombotic therapy, however, increases risk of bleeding and associated morbidity and mortality. Professional bodies have used the current low-quality evidence and generated incongruent recommendations. Researchers should prioritize generating high-quality, randomized evidence evaluating the risks and benefits of antiplatelet versus anticoagulant therapy after bioprosthetic aortic valve replacement.

Abstract 11101: Q Fever Endocarditis Combined With Thrombus and Antiphospholipid Syndrome

A 63-year-old-man presented to our institution with dyspnea. Transthoracic echocardiography (TTE) showed severe degenerative aortic stenosis with regurgitation and decreased left ventricular contractility. Subsequent transesophageal echocardiography (TEE) and cardiac computed tomography (CT) revealed an outpouching structure at aortomitral intervalvular fibrosa (AMIVF) (Fig A to D), which was compatible with pseudoaneurysm and suggested sequelae of previous infective endocarditis. On surgery, thickened AV leaflets were noted, especially on NCC and LCC (Fig E). When extracting the AV leaflets, subannular pouching was seen without evidence of active inflammation or infection (Fig F). AV replacement with 25-mm Sorin Mitroflow was performed.One-year TTE follow-up showed markedly increased transAV pressure gradient. TEE and cardiac CT revealed symmetric nodular thickening of bioprosthetic AV leaflets with opening limitation (Fig G to J). The patient was admitted on the diagnosis of subclinical bioprosthetic valve thrombosis, and anticoagulation with warfarin and aspirin was started. During the hospitalization, the patient had persistent fever with bicytopenia and hepatosplenomegaly, but repetitive blood cultures were negative. There was no definite fever focus even in 18F-FDG PET CT (Fig K). Since the patient worked on a farm in Dangjin, Chungcheongnam-Do, South Korea, where Q fever is prevalent, an indirect immunofluorescence assay for Coxiella burnetii was conducted and the result turned out to be positive. Additional coagulopathy laboratory findings showed positive for lupus anticoagulant, anti-cardiolipin IgM, and anti-beta2 GPI IgM. Finally, the patient was diagnosed with Q fever endocarditis combined with antiphospholipid syndrome and treated with doxycycline with hydroxychloroquine and maintained anticoagulation. Recent follow-up of TTE and cardiac CT showed complete resolution of prosthetic AV thrombus.

Innovative IntraValvular Impedance Sensing Applied to Biological Heart Valve Prostheses: Design and In Vitro Evaluation.

Subclinical valve thrombosis in heart valve prostheses is characterized by the progressive reduction in leaflet motion detectable with advanced imaging diagnostics. However, without routine imaging surveillance, this subclinical thrombosis may be underdiagnosed. We recently proposed the novel concept of a sensorized heart valve prosthesis based on electrical impedance measurement (IntraValvular Impedance, IVI) using miniaturized electrodes embedded in the valve structure to generate a local electric field that is altered by the cyclic movement of the leaflets. In this study, we investigated the feasibility of the novel IVI-sensing concept applied to biological heart valves (BHVs). Three proof-of-concept prototypes of sensorized BHVs were assembled with different size, geometry and positioning of the electrodes to identify the optimal IVI-measurement configuration. Each prototype was tested in vitro on a hydrodynamic heart valve assessment platform. IVI signal was closely related to the electrodes' positioning in the valve structure and showed greater sensitivity in the prototype with small electrodes embedded in the valve commissures. The novel concept of IVI sensing is feasible on BHVs and has great potential for monitoring the valve condition after implant, allowing for early detection of subclinical valve thrombosis and timely selection of an appropriate anticoagulation therapy.

Dual versus single antiplatelet therapy after transcatheter aortic valve replacement: a systematic review and meta-analysis

Abstract Background Transcatheter aortic valve replacement (TAVR) is the intervention of choice for patients with severe symptomatic aortic stenosis who have high or intermediate surgical risk. TAVR valves are at risk of thrombosis and serious sequelae including stroke, peripheral embolism, and valve dysfunction requiring intervention. The optimal method of antithrombotic therapy to reduce risk of thrombosis with an acceptable increase in risk of bleeding is uncertain. Objectives This systematic review and meta-analysis assesses the effects of dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT) on mortality, thrombosis and bleeding in patients undergoing TAVR. Methods We systematically searched EMBASE, MEDLINE and CENTRAL from January 1, 2002 until February 9, 2021 for randomized trials comparing DAPT to SAPT after TAVR. Two reviewers independently screened titles and abstracts, and then the full text of potentially relevant articles in duplicate. Data abstraction and risk of bias was also performed in duplicate. Risk ratios and 95% confidence intervals were pooled using the Mantel-Haenzel method and random effects modelling. We assessed the certainty of the evidence for each outcome using the Grading of Recommendations, Assessments, Development and Evaluation (GRADE) approach. Results We included 4 randomized controlled trials of 1086 patients. Risk of bias was low or somewhat concerning for all studies. We found no difference in mortality (risk ratio (RR) 1.02, 95% confidence interval (CI), 0.63 to 1.63) or stroke (RR 1.03, 95% CI 0.57–1.84), but a significant increase in major bleeding (RR 2.04, 95% CI, 1.31–3.19), with DAPT compared to SAPT. There were too few events to conduct meta-analysis for clinical valve thrombosis, subclinical valve thrombosis, transvalvular gradients on echocardiography, or aortic valve reintervention. The certainty of the evidence was low or very low due to risk of bias, inconsistency, and imprecision. Conclusions There is very low certainty evidence that DAPT has little to no effect compared to SAPT on mortality and stroke. There is low certainty evidence that DAPT likely causes more major bleeding than SAPT. Funding Acknowledgement Type of funding sources: None.

Apixaban and Valve Thrombosis After Transcatheter Aortic Valve Replacement: The ATLANTIS-4D-CT Randomized Clinical Trial Substudy.

Subclinical obstructive valve thrombosis after transcatheter aortic valve replacement (TAVR) is of uncertain frequency and clinical impact. The aim of this study was to determine the effects of apixaban vs standard of care on post-TAVR valve thrombosis detected by 4-dimensional (4D) computed tomography. The randomized ATLANTIS (Anti-Thrombotic Strategy to Lower All Cardiovascular and Neurologic Ischemic and Hemorrhagic Events After Trans-Aortic Valve Implantation for Aortic Stenosis) trial demonstrated that apixaban 5mg twice daily was not superior to standard of care (vitamin K antagonists or antiplatelet therapy) after successful TAVR and was associated with similar safety but with more noncardiovascular deaths. Three months after randomization, 4D computed tomography was proposed to all patients to determine the percentage of patients with≥1 prosthetic valve leaflet with grade 3 or 4 reduced leaflet motion or grade 3 or 4 hypoattenuated leaflet thickening (the primary endpoint) in the intention-to-treat population. Seven hundred sixty-two participants had complete multiphase datasets and were included in the 4D computed tomographic analysis. The primary endpoint occurred in 33 (8.9%) and 51 (13.0%) patients in the apixaban and standard-of-care groups, respectively. It was reduced with apixaban vs antiplatelet therapy (OR: 0.51; 95%CI: 0.30-0.86) but not vs vitamin K antagonists (OR: 1.80; 95%CI: 0.62-5.25) (Pinteraction=0.037). The composite of death, myocardial infarction, any stroke, or systemic embolism at 1 year occurred in 10.7% (n=9 of 84) and 7.1% (n=48 of 178) of patients with and without subclinical valve thrombosis at 90days, respectively (HR: 1.68; 95%CI: 0.82-3.44). Apixaban reduced subclinical obstructive valve thrombosis in the majority of patients who underwent TAVR without having an established indication for anticoagulation. This study was not powered for clinical outcomes. (Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis [ATLANTIS]; NCT02664649).

Persisting burden and challenges of rheumatic heart disease.

Rheumatic heart disease (RHD) is the result of episodes of acute rheumatic fever with valvular (and other cardiac) damage caused by an abnormal immune response to group A streptococcal infections, usually during childhood and adolescence. As a result of improved living conditions and the introduction of penicillin, RHD was almost eradicated in the developed world by the 1980s. However, being a disease of poverty, its burden remains disproportionately high in the developing world, despite being a fundamentally preventable disease. Rheumatic heart disease generates relatively little attention from the medical and science communities, in contrast to other common infectious problems (such as malaria, HIV, tuberculosis), despite the major cardiovascular morbidity/mortality burden imposed by RHD. This relative neglect and paucity of funding have probably contributed to limited fundamental medical advances in this field for over 50 years. Given the importance of prevention before the onset of major valvular damage, the main challenges for RHD prevention are improving social circumstances, early diagnosis, and effective delivery of antibiotic prophylaxis. Early identification through ultrasound of silent, subclinical rheumatic valve lesions could provide an opportunity for early intervention. Simple echocardiographic diagnostic criteria and appropriately trained personnel can be valuable aids in large-scale public health efforts. In addition, a better understanding of the immunogenic determinants of the disease may provide potential routes to vaccine development and other novel therapies.

Chorea as the presenting feature of acute rheumatic fever in childhood; case reports from a low-prevalence European setting

BackgroundDespite a notable decrease in acute rheumatic fever (ARF) incidence in the past few decades, there are still cases in our setting. Sydenham chorea (SC) may be the initial manifestation for this condition in childhood in a significant proportion of children. We report two cases of choreoathetosis in children as the first manifestation of ARF.Case presentationA previously healthy 8-year-old boy presented with right hemichorea with a predominance in the brachial region, orofacial dyskinesias and speech difficulties for the past 2 weeks. The only medical history of interest was a common catarrhal illness 3 weeks before and nonspecific bilateral tenosynovitis in both feet since a year prior. A brain computerized tomography was normal and the echocardiogram showed mild mitral and aortic regurgitation, meeting ARF criteria. He demonstrated clinical improvement with treatment based on prednisone and carbamazepine.The second patient was a 10-year-old girl with choreic movements of the right half of the body and repetitive right eye closure of 1 week duration. She had symptoms of fever and rash the previous week and pharyngitis that resolved without antibiotic 2 months before. Blood tests revealed elevated C reactive protein (12 mg/dl) and erythrocyte sedimentation rate (96 mm/h). Brain magnetic resonance was normal and echocardiogram showed left ventricle dilation and mild mitral regurgitation, leading to the diagnosis of ARF. Due to neurological involvement, she received corticosteroids and intravenous immunoglobulin treatment, with worsening of neurological symptoms that required valproic acid with remission of the hemichorea. In addition skin lessions compatible with erythema marginatum appeared on the upper limbs.ConclusionsSC should be the main diagnostic consideration in cases of hemichorea with normal neuroimaging in children. The cases reported highlight the need to maintain a high index of suspicion even in settings where incidende of ARF is low and the need to perform cardiological investigations in all patients with suspected SC, due to the possibility of subclinical valve lesions. Good adherence to secondary prophylaxis is crucial to avoid chorea relapses and worsening valve disease.

Comparison of Warfarin to Dual Antiplatelet Therapy Following Transcatheter Aortic Valve Replacement.

Dual antiplatelet therapy (DAPT) was the initial antithrombotic regimen of choice following transcatheter aortic valve replacement (TAVR). Subsequent identification of subclinical valve thrombosis in high-risk patients has questioned whether warfarin should be used as an alternative to DAPT for some patients. The aim of this study was to compare thromboembolic events, bleeding, and all-cause mortality between DAPT and warfarin following TAVR. This was a single-center, retrospective review of TAVR patients who received DAPT or warfarin following TAVR between 2008 and 2018. The primary endpoint was occurrence of thromboembolic events during the hospital stay and 1-year follow-up, while secondary endpoints included bleeding and all-cause mortality. Of the included 764 patients, 193 received DAPT and 571 received warfarin. The median Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) scores were 8.3% for the DAPT group and 6.5% for the warfarin group. The primary endpoint occurred 30 times (3.9%) during the study timeframe. No differences in thromboembolic events between the DAPT and warfarin groups were found (4.14% vs. 3.85%; p = 0.857), and there was no difference in bleeding (6.22% vs. 5.08%; p = 0.544) or risk of mortality (hazard ratio 0.59, 95% confidence interval 0.33-1.06; p = 0.076). In this study, warfarin had similar effectiveness and safety, compared with DAPT, for antithrombotic management post-TAVR. For patients whom the provider deemed anticoagulation is indicated, our data suggest warfarin is a well-tolerated option following TAVR in intermediate- and high-risk STS score patients.

Thrombus formation on bioprosthetic aortic valves

Abstract Background 18F-GP1 is a novel radiotracer with a high affinity for the platelet glycoprotein IIb/IIIa receptor. Subclinical bioprosthetic valve thrombus has been postulated as a trigger for accelerated valve degeneration. Purpose To determine the feasibility of 18F-GP1 positron-emission tomography-computed tomography (PET-CT) for the detection of subclinical bioprosthetic aortic valve thrombus. Methods (i) Explanted degenerated aortic valve prostheses underwent histology and imaging. (ii) In a prospective observational study, patients with bioprosthetic aortic valve replacement (AVR) underwent echocardiography and 18F-GP1 PET-CT. Valves were assessed for hypoattenuating leaflet thickening (HALT), hypo-attenuation affection leaflet motion (HAM) and GP1 uptake. Results (i) GP1 correlated with thrombus on explanted valves (Figure). (ii) The first 6 patients (Table) were asymptomatic and had normally functioning surgical bioprostheses on echocardiography. At a median of 166 (range 122–189) days post-AVR, no patients had HALT or HAM on CT. There was avid focal GP1 uptake on the leaflets of all 6 patients which appeared most prominent along the leaflet edges (Figure). Only one patient had focal uptake in the valve frame, remote from the leaflets. In a separate cohort undergoing 18F-GP1 PET-CT for other conditions, there was no uptake on normal, native aortic valves (n=8). Conclusion For the first time, we demonstrate that 18F-GP1 PET-CT is a highly sensitive method of assessing platelet activation on bioprosthetic aortic valves. Despite the absence of CT evidence, early thrombus appeared to be a universal finding on recently implanted valve prostheses. The biological and clinical implications of subclinical bioprosthetic aortic valve thrombus have yet to be established. GP1 uptake in AVR Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

A Finite Element Analysis Study from 3D CT to Predict Transcatheter Heart Valve Thrombosis.

Background: Transcatheter aortic valve replacement has proved its safety and effectiveness in intermediate- to high-risk and inoperable patients with severe aortic stenosis. However, despite current guideline recommendations, the use of transcatheter aortic valve replacement (TAVR) to treat severe aortic valve stenosis caused by degenerative leaflet thickening and calcification has not been widely adopted in low-risk patients. This reluctance among both cardiac surgeons and cardiologists could be due to concerns regarding clinical and subclinical valve thrombosis. Stent performance alongside increased aortic root and leaflet stresses in surgical bioprostheses has been correlated with complications such as thrombosis, migration and structural valve degeneration. Materials and Methods: Self-expandable catheter-based aortic valve replacement (Medtronic, Minneapolis, MN, USA), which was received by patients who developed transcatheter heart valve thrombosis, was investigated using high-resolution biomodelling from computed tomography scanning. Calcific blocks were extracted from a 250 CT multi-slice image for precise three-dimensional geometry image reconstruction of the root and leaflets. Results: Distortion of the stent was observed with incomplete cranial and caudal expansion of the device. The incomplete deployment of the stent was evident in the presence of uncrushed refractory bulky calcifications. This resulted in incomplete alignment of the device within the aortic root and potential dislodgment. Conclusion: A Finite Element Analysis (FEA) investigation can anticipate the presence of calcified refractory blocks, the deformation of the prosthetic stent and the development of paravalvular orifice, and it may prevent subclinical and clinical TAVR thrombosis. Here we clearly demonstrate that using exact geometry from high-resolution CT scans in association with FEA allows detection of persistent bulky calcifications that may contribute to thrombus formation after TAVR procedure.

Subclinical valve thrombosis in transcatheter aortic valve implantation: A systematic review and meta-analysis

BackgroundRecent high-resolution computed tomography studies after transcatheter aortic valve insertion (TAVI) have reported a high prevalence of subclinical valve thrombosis (SCVT), potentially contributing to increased risk of late stroke. We aimed to investigate SCVT in patients after TAVI, with a focus on prevalence, predisposing factors, management, and potential sequelae. MethodsA comprehensive literature review of patients with SCVT after TAVI was carried out on all published studies in 3 major electronic databases from their inception until October 2019. Studies with sufficient data were included in a meta-analysis comparing the risk of stroke between patients with SCVT and those with normal valve function, as well as the protective effects of antiplatelet and anticoagulation on preventing SCVT. ResultsFrom 3456 patients examined in a comprehensive review, 398 patients (11.5%) demonstrated evidence of SCVT during follow-up. Dual antiplatelet therapy was given in 45.5% of cases, single antiplatelet therapy in 19.8%, and oral anticoagulation in 28.5%. A meta-analysis demonstrated that rates of stroke were more than 3 times greater in patients with SCVT compared with those without (logistic odds, 1.10; 95% confidence interval, 0.63-1.57, P < .0001). Oral anticoagulation was superior to dual antiplatelet therapy or single antiplatelet therapy, preventing the formation of SCVT (logistic odds, –1.05, 95% confidence interval, –1.71 to –0.39, P < .0001). ConclusionsSubclinical valve thrombosis is seen in 11.5% of patients after TAVI and is associated with increased risk of stroke. When oral anticoagulation is used postprocedurally, it is more effective than either dual or single-antiplatelet therapy in preventing subclinical valve thrombosis. These findings suggest that further studies are needed to define the optimal antithrombotic regimen to mitigate thrombotic and embolic sequelae after TAVI.

Aortic valve calcification as a risk factor for major complications and reduced survival after transcatheter replacement

BackgroundAortic valve calcification is supposed to be a possible cause of embolic stroke or subclinical valve thrombosis after transcatheter aortic valve replacement (TAVR). We aimed to assess the role of aortic valve calcification in the occurrence of in-hospital clinical complications and survival after TAVR. MethodsWe retrospectively analyzed preoperative contrast-enhanced multidetector computed tomography scans of patients who underwent TAVR on the native aortic valve in our center. Calcium volume was calculated for each aortic cusp, above and below the aortic annulus. Outcomes were recorded according to VARC-2 criteria. ResultsOverall, 581 patients were included in the study (SapienXT = 192; Sapien3 = 228; CoreValve/EvolutR = 45; Engager = 5; Acurate = 111). Median survival was 4.98 years (interquartile range 4.41–5.54). Logistic regression identified calcium load beneath the right coronary cusp in left ventricular outflow tract (LVOT) as significantly associated with stroke (odds ratio [OR] 1.2; 95% confidence interval [CI] 1.03–1.3; p = 0.0019) and in-hospital mortality (OR 1.1; 95% CI 1.004–1.2; p = 0.04), whereas total calcium volume of the LVOT was associated with both in-hospital and 30 day-mortality (OR 1.2; 95% CI 1.01–1.4; p = 0.03, and OR 1.2; 95% CI 1.02–1.43; p = 0.029, respectively). Cox regression identified total calcium of LVOT (hazard ratio [HR] 1.18; 95% CI 1.02–1.38; p = 0.026), male sex (HR 1.88; 95% CI 1.06–3.32; p = 0.031), baseline creatinine clearance (HR 0.96; 95% CI 0.93–0.98; p < 0.001), and baseline severe aortic regurgitation (HR 7.48; 95% CI 2.76–20.26; p < 0.001) as risk factors associated with lower survival. ConclusionLVOT calcification is associated with increased risk of peri-procedural stroke and mortality as well as shorter long-term survival.