Conference Update

Treatment approach for thrombus formation after TAVR may require reconsideration

Cardiology
10 months ago, OP Editor

Possibility of higher subclinical leaflet thrombosis risk occurred in transcatheter aortic valve replacement (TAVR) as compared to surgical aortic valve replacement (SAVR) has been reported. For the effective treatment of subclinical leaflet thrombosis via novel oral anticoagulants (NOACs) and warfarin, but not dual antiplateles, was supported in an observational study. In order to provide more practical insights in this area, conclusive data of relevant studies were presented at the American College of Cardiology (ACC) 2017 Scientific Sessions.1

Transcatheter aortic valve replacement (TAVR) is a minimally invasive surgical procedure for treating intermediate-to-high-risk-patients with severe symptomatic aortic stenosis, particularly for the elderly or patients who are not qualified for invasive surgical aortic valve replacement (SAVR).2 While this fairly recent innovation is widely accepted by the cardiologists and eligible patients in the Western countries, comparative outcomes among patients treated with TAVR and SAVR have been evaluated. In a previous study, therapeutic anticoagulation was found to lower the prevalence of reduced leaflet motion in patients who underwent TAVR or SAVR, suggesting an association with subclinical leaflet thrombosis after bioprosthetic aortic valves replacement which leads to reduced leaflet motion.3 Further investigation has recently generated new data on the prevalence of subclinical leaflet thrombosis in TAVR and SAVR and the effect of novel oral anticoagulants (NOACs) on the thrombus formation, valve haemodynamics and other clinical outcomes.1

Combination cohort from the US and the EU generated new data by TAVR VS. SAVR

The 931 enrolled patients of this study were from two physician-initiated ongoing registries: the Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Thrombosis and Its Treatment with Anti-coagulation (RESOLVE) registry in Los Angeles and the Subclinical Aortic Valve Bioprosthesis Thrombosis Assessed with Four-Dimensional Computed Tomography (SAVORY) registry in Copenhagen. CT images were obtained from all enrolled patients with a dedicated four-dimensional volume-rendered imaging protocol after TAVR or SAVR in various points of time. Patients with impaired renal function (estimated glomerular filtration rate of <30 mL/min) were excluded from the study.1

Thicker leaflets and reduced leaflet motion were found in those underwent TAVR

Hypoattenuated leaflet thickening of the valve leaflets was recorded. Leaflet motion were also categorized and assessed. 890 interpretable CT scans results from 752 (84%) patients underwent TAVR and 138 (16%) patients underwent SAVR were analysed. Reduced leaflet motion was identified in 106 (12%) patients, including 5 underwent SAVR and 101 underwent TAVR, all by the thickness of the affected valves as well as the extent of leaflet motion restriction. Significantly thicker leaflets (5.01 mm [SD: 1.81] vs. 1.85 mm [SD: 0.77]; p=0.0004) and reduced leaflet motion (71.0% [SD: 13.8] vs. 56.9% [SD: 6.5]; p=0.004) were found in transcatheter valves in comparison to surgical valves. Besides the choice of aortic valve replacement, other factors contributed to this result could also be the increased age (more likely to experience comorbidities), low ejection fraction, and absence of anticoagulation at the time of the index CT scan.1

Prevalence of reduced leaflet motion was the lowest in patients treated with anticoagulation or NOACs, but not DAPT

Among the study sample, 224 patients were receiving anticoagulants at the time of first CT scan, including 117 patients treated with warfarin and 107 treated with NOACs. Patients received anticoagulation (warfarin and NOACs) were found to have the same and the lowest prevalence of reduced leaflet motion compared to those treated with dual antiplatelet therapy (DAPT) and monoantiplatelet therapy or without anticoagulation. Among 58 (55%) patients with reduced leaflet motion, 36 patients who were treated with anticoagulation for 3 months showed the restoration of normal leaflet motion, whereas 20 (91%) of 22 patients with no anticoagulation showed persisted or progressed reduced leaflet motion.1

Associations found between leaflet motion and aortic valve gradient as well as strokes and TIAs

After detection of reduced leaflet motion, the use of pharmacotherapy for all patients in the SAVORY registry remained the same while in the RESOLVE registry, the decision to initiate, continue or discontinue anticoagulation depended on the bleeding risk and preference of the physicians and patients. Reduced leaflet motion reoccurred 164 days after discontinuing anticoagulation in four of eight patients while none reoccurred in 15 patients who were continuously treated with anticoagulation (p=0.008). The study also suggested there was an association between patients with reduced leaflet motion and higher measure of aortic valve gradient. Furthermore, significantly decrease of aortic valve mean gradient in patients treated with anticoagulation for 3 months was reported. On the other hand, reduced leaflet motion was found to be associated with increased rates of all transient ischemic attacks (TIAs) and strokes or TIAs when comparing the rates of non-procedural neurological events (occurring after 27 h of the procedure) and post-CT events (after a diagnosis of reduced leaflet motion is made).1

Conclusion to be drawn from further studies

Full understanding of the possible causes of reduced leaflet motion and subclinical leaflet thrombosis are yet to be determined. Although dual antiplatelet therapy (DAPT) is the standard of care for patients after TAVR, reduction of subclinical leaflet thrombosis in this study has not been found in patients on monoantiplatelet therapy or DAPT. Therefore, results from the ongoing trials, such as GALILEO (Global study comparing a Rivaroxaban-Based Antithrombotic Strategy to an Antiplatelet-Based Strategy After Transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes)4 and ATLANTIS (Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis)5, would be important investigations to follow on the efficacy and safety of anticoagulation therapy in preventing and treating reduced leaflet motion and subclinical leaflet thrombosis after bioprosthetic aortic valves replacement.

Although the results of this study are intriguing, Dr Raj Makkar, senior author of the publication of this study, agreed it is premature to draw any definite conclusion based on the findings by the team at this moment. “I think what our findings do is to stimulate the discussion, but ultimately the changes have to come from clinical trials.”6

Different challenges faced by Asia

While these findings are crucial for establishing potential new treatment guidelines in countries which have increased number of patients undergoing TAVR, one fundamental concern regarding the use of transcatheter aortic valve needs to be addressed for the Asian population, i.e. Asian patients generally have anatomical features (such as body mass indexes, annulus dimensions and iliofemoral arteries) smaller than those of Western patients, therefore increased risk of major complications and worse long-term outcomes may occur.7 It is hoped this concern will be addressed by further studies and a standardized post-market registry can be established in Asians so that advancing the use of TAVR can be well analysed and justified in Asia.

 

1. Chakravarty T, Sondergaard L, Friedman J, et al. Subclinical leaflet thrombosis in surgical and transcatheter bioprosthetic aortic valves: an observational study. The Lancet.

2. Hu PP. TAVR and SAVR: Current Treatment of Aortic Stenosis. Clinical Medicine Insights Cardiology. 2012;6:125-139.

3. Markkar RR, Fontana G, Jilaihawi G, et al. Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves. New England Journal of Medicine. 2015;373:2015-2024.

4. Global Study Comparing a Rivaroxaban-Based Antithrombotic Strategy to an Antiplatelet-Based Strategy After transcatheter Aortic Valve Replacement to Optimize Clinical Outcomes (GALILEO). (Accessed 7 May 2017, at http://clinicaltrials.gov/ct2/show/NCT02556203)

5. Anti-Thrombotic Strategy After Trans-Aortic Valve Implantation for Aortic Stenosis (ATLANTIS). (Accessed 7 May 2017, at http://clinicaltrials.gov/ct2/show/NCT02664649)

6. Higher Subclinical Leaflet Thrombosis Risk With TAVR Than SAVR, Dual Antiplatelets Not Protective. Medscape, 2017. (Accessed 7 May 2017, at http://www.medscape.com/viewarticle/877469#vp_1)

7. Yoon SH, Ahn JM, Hayashida K, et al. Clinical Outcomes Following Transcatheter Aortic Valve Replacement in Asian Population. JACC Cardiovasc Interv. 2016;9(9):926-933.

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