Author + information
- Arie Pieter Kappetein, MD, PhD∗ ( and )
- Stuart J. Head, MD, PhD
- ↵∗Reprint requests and correspondence:
Dr. Arie Pieter Kappetein, Department Thoracic Surgery, Room BD 569, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
Traditionally, the main choices available for aortic valve replacement were either mechanical prosthetic or biological heart valves. Mechanical valves were and still are characterized by excellent structural durability, but they require lifelong systemic anticoagulation. However, bioprostheses do not necessitate valve-related anticoagulation, but they are known for structural valve failure that may require reoperation 10 to 15 years after implantation. The introduction of transcatheter aortic valve replacement (TAVR) offered a third choice for treatment of symptomatic severe aortic stenosis. TAVR is now a well-established option for patients at higher surgical risk.
Thromboembolic complications of mechanical valves, surgical bioprostheses, and transcatheter heart valves (THVs) are well described, especially when they lead to clinically overt strokes. However, the incidence of hemodynamically obstructive surgical bioprosthetic or mechanical aortic valve thrombosis is rare, with an estimated lifetime incidence of approximately only 1% (1). Bioprosthetic valve thrombosis usually occurs in the early post-operative period when endothelialization of the suture ring is not yet complete. In patients with a mechanical valve, thrombosis is often related to poor international normalized ratio management. Until recently, data on the occurrence of TAVR thrombosis were limited to case reports (2); although in 2014, it received wider attention after St. Jude (St. Paul, Minnesota) needed to issue a suspension on the implantation of its Portico THV to investigate cases of reduced valve leaflet mobility that were reported from a small number of computed tomographic (CT) scans performed 30 days after implantation. It was detected on CT scans while it was missed on transthoracic echocardiography. In the following year, Makkar et al. (3) published a series on 39 patients with reduced leaflet motion identified on CT scans and indicated that restoration of leaflet motion could take place after beginning anticoagulation therapy. These 39 patients were pooled from the Portico investigational device exemption study and 2 clinical registries. This phenomenon did not seem to be limited to a particular type of valve because it also involved Portico (n = 21), Sapien (Edwards Lifesciences, Irvine, California) (n = 13), CoreValve (Medtronic, Minneapolis, Minnesota) (n = 2), and Lotus (Boston Scientific, Natick, Massachusetts) (n = 1), as well as surgical bioprostheses (n = 2). In their conclusion, they stated that “Better characterization of this observation is needed to determine its frequency and evaluate its clinical effect.”
In this issue of the Journal, Hansson et al. (4) appear to have taken this recommendation to heart by analyzing a large series of 460 consecutive patients who underwent TAVR with the Edwards Sapien XT or Sapien 3 valve with contrast-enhanced multidetector computed tomography (MDCT). The incidence of valve thrombosis was 7% at 3 months (n = 28), whereas 5 patients experienced clinically overt obstructive THV thrombosis. Patients who received anticoagulation therapy had a 5 times lower incidence of valve thrombosis, although a larger valve size seemed to be predictive of THV thrombosis. Warfarin effectively restored leaflet function in 85% of the patients. Currently, this is the largest and most detailed series on this particular topic. To place the current data in context, and to properly identify salient points moving forward in the investigation of valve thrombosis, we must understand the following key questions.
What Are the Incidences of Valve Thrombosis After Surgical Aortic Valve Replacement and TAVR?
Bioprosthetic valves are generally believed to be less thrombogenic than mechanical valves; in many patients, they obviate the need for long-term anticoagulation. Nevertheless, the risk of thromboembolic events is not insignificant, and a recent study showed that bioprosthetic valve thrombosis after surgical aortic valve replacement (SAVR) might be grossly underestimated (5). Several articles have reported decreased leaflet mobility both after TAVR and SAVR, indicating that bioprosthetic valve leaflet thrombosis may be a more important issue than previously realized. Because MDCT was not used earlier to determine valve thrombosis after SAVR, it is expected that the incidence is higher than the previously reported 1%. In cases of TAVR, the 7% incidence after 3-month follow-up from the current study (4) is so far the most trustworthy estimate of valve thrombosis after TAVR.
When Does It Occur?
Most cases of valve thrombosis seem to occur within 1 year after TAVR, with a median time of onset of 6 months (6). In SAVR, the risk appears highest within the first 3 months after implantation. However, recent data suggest that it can also occur up to the first 5 years after implantation of a surgical bioprosthesis (5), which can be a warning that valve thrombosis may also happen late after TAVR.
What Are the Predictors?
It seems logical that no warfarin therapy, an increase in the transvalvular gradient, increased cusp thickness, and abnormal cusp mobility are strong predictors and indicators of valve thrombosis (5). The relationship between flow dynamics and a higher incidence in patients with larger valve sizes (4) needs confirmation and further investigation.
What Are the Hemodynamic and Clinical Consequences?
Many patients show symptoms of a progressive rise in gradient with increasing dyspnea with valve thrombosis (6). When clinical outcomes, such as death, myocardial infarction, and stroke, were compared in the study from Hansson et al. (4), there were no differences between patients with or without reduced leaflet motion. However, in the study from Makkar et al. (3), those with reduced leaflet motion had a higher rate of stroke or transient ischemic attack than did patients with normal leaflet motion.
How Can We Detect It?
Currently, no formal clinical criteria exist for diagnosing ventricular tachycardia post-TAVR. However, the Valve Academic Research Consortium-3 document scheduled to be published later this year will try to provide guidelines.
Evaluation of leaflet visibility and mobility is limited due to artifacts from the prosthetic frame. Nevertheless, a careful evaluation of prosthetic valve leaflet thickening, mobility, and masses should be attempted.
Thrombus may be suspected when reduced systolic leaflet excursion is detected, particularly compared with the baseline study. Also, thrombus may be present when there is tissue density thickening of the leaflets and/or a tissue density mass within the neo-sinuses or attached to the leaflets. The consequences are increased valve gradients and reduced valve area.
Multidetector Computed Tomography
Hypoattenuating leaflet thickening or a focal hypoattenuating abnormality attached to the prosthetic leaflet or diffuse thickening of ≥1 prosthetic valve leaflets are identifiable on ≥2 reconstructed planes.
How Can We Treat It?
Although there is no consensus on how to treat THV thrombosis, anticoagulation results in resumption of normal leaflet motion, whereas patients who do not receive therapy continue to show abnormal motion. The optimal duration of warfarin therapy is also undetermined, but early discontinuation results in recurrence of valve thrombosis. Close echocardiographic follow-up is needed to evaluate the efficacy of the treatment. In cases of overt clinical symptoms and no resolution with anticoagulation therapy, SAVR should be considered.
What Are the Late Consequences?
It is not clear whether valve thrombosis and valve deterioration represent the same disease process at different points in time. The late consequence of valve thrombosis may be fibrotic organization of the thrombus, with an increase in valvular gradient; thus, it could be labeled as valve failure. Early detection of valve thrombosis is therefore key.
The study in this issue of the Journal manifests a high incidence of valve thrombosis and shows that anticoagulation is effective in restoring leaflet function (4). As always in medicine, it is better to prevent than to cure and points to the fact that antithrombotic therapy in the setting of TAVR has only been empirically determined. After TAVR, dual antiplatelet therapy with aspirin (80 to 325 mg/day) and clopidogrel (75 mg/day) has been used in most centers and studies. However, the use of a loading dose of clopidogrel (300 to 600 mg) before TAVR is typically not specified, and the duration of clopidogrel therapy has varied among studies. The same applies for SAVR, in which it is still unclear whether aspirin alone is enough, or if a vitamin K antagonist or a new oral anticoagulant should be added for 3 to 6 months. Without knowing the optimal peri- and post-procedural antithrombotic regimens, clinicians should have an increased awareness of valve thrombosis after SAVR and TAVR.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Kappetein has been a member of the Steering Committee for the SURATVI trial, sponsored by Medtronic, and the Steering Committee for the UNLOAD trial, sponsored by Edwards Lifesciences. Dr. Head has reported that he has no relationships relevant to the contents of this paper to disclose.
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- Corresponding Author
- What Are the Incidences of Valve Thrombosis After Surgical Aortic Valve Replacement and TAVR?
- When Does It Occur?
- What Are the Predictors?
- What Are the Hemodynamic and Clinical Consequences?
- How Can We Detect It?
- Transthoracic Echocardiography
- Transesophageal Echocardiography
- Multidetector Computed Tomography
- How Can We Treat It?
- What Are the Late Consequences?