Abstract
Background
Hypoattenuated leaflet thickening (HALT) represents subclinical leaflet thrombosis in bioprosthetic valves with risk of occurrence peaking at 12 to 24 months after implantation. However, late presentations can occur.
Case Summary
A 77-year-old woman developed severe mitral stenosis 17 years after receiving a bioprosthetic mitral valve. Cardiac CT revealed extensive hypoattenuated leaflet thrombosis affecting all leaflets. After 3 months of therapeutic warfarin, repeat imaging demonstrated significant HALT resolution, avoiding valve-in-valve intervention.
Discussion
This represents an unusual late HALT presentation, causing bioprosthetic mitral valve dysfunction, which exceeds usual follow-up periods. The significant response to warfarin supports anticoagulation effectiveness and thrombotic etiology.
Take-Home Messages
Since HALT can occur very late after valve replacement, long-term monitoring needs to be considered. Warfarin anticoagulation can effectively resolve HALT even in late presentations, helping to avoid surgical intervention.
Key words: anticoagulation, mitral valve, stenosis, thrombosis, valve replacement
Graphical Abstract
With the increasing frequency of surgical and transcatheter bioprosthetic mitral valve (MV) replacements, understanding postprocedural complications has become crucial. Hypoattenuated leaflet thrombosis (HALT) is an imaging characteristic of subclinical leaflet thrombosis in bioprosthetic heart valves.1 HALT usually has an early onset after valve replacement, with an incidence of 10% at 30 days postprocedure, and 24% of patients having HALT at 1 year.2 These rates are mainly based on studies of aortic bioprostheses, as data on MV HALT remain limited, with a reported prevalence of only 5.7% in surgical MV replacements.1 Our case represents an unusual presentation with HALT occurring 17 years after valve implantation, exceeding the follow-up periods in most studies.
Take-Home Messages
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This case highlights that hypoattenuated leaflet thrombosis can develop decades after bioprosthetic mitral valve replacement, beyond the typical early postoperative period, underscoring the importance of long-term surveillance.
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Cardiac computed tomography is useful for diagnosing and monitoring treatment progress, showing clear improvements in leaflet thickening and motion following proper anticoagulation therapy.
Multiple anticoagulants have been studied to prevent MV HALT, and the choice of anticoagulation is tailored to the patient, weighing the risk of HALT against the risk of bleeding.3 However, the optimal duration of anticoagulants and long-term therapeutic outcomes remain areas for further investigation given the possibility of late presentations as shown in our case.
We report a rare case of MV HALT 17 years after replacement, with objective imaging-based improvement after warfarin. This case adds to the limited literature on delayed MV HALT and underscores the importance of considering this diagnosis in the context of long-term bioprosthetic heart valve dysfunction.
Case Presentation
A 77-year-old woman presented with a history of MV disease and congestive heart failure (NYHA functional class II), paroxysmal atrial fibrillation, chronic kidney disease, transient ischemic attack, implantable cardioverter defibrillator, peripheral arterial disease, and previous bioprosthetic MV endocarditis. Twenty-one years ago, she had mechanical MV replacement at another hospital due to Staphylococcus aureus endocarditis. Four years later, she developed fungal endocarditis of the mechanical MV, which required reoperation, during which she received a 27-mm Hancock porcine bioprosthetic MV. She then developed paroxysmal atrial fibrillation 10 years later and was started on apixaban. Her medical history includes several courses of prednisone over the last 7 years to manage chronic lung disease and lumbar spine pain. Seventeen years following the procedure, she presented to us with an abnormal echocardiogram study. The patient reported no shortness of breath or fatigue, remained active, and her heart failure symptoms were well-managed.
Investigations
Previous transthoracic echocardiography (TTE) follow-up studies from 2018 to 2021 noted mild mitral stenosis (MS) with a mean diastolic gradient of 4 to 6 mm Hg, and moderate MS with a gradient of 7 to 10 mm Hg in 2023. She underwent TTE in 2024, which revealed severe MS with a mean diastolic gradient of 10 mm Hg. Transesophageal echocardiography (TEE) revealed a large immobile thrombus in the left atrium and confirmed severe MS with diffuse leaflet thickening, more pronounced on the posterior leaflet, with restricted motion. The mean diastolic gradient was 11 mm Hg at a heart rate of 43 beats/min (Figure 1). Severe tricuspid regurgitation was also noted in the study, and her systolic function remained preserved. A cardiac computed tomography (CT) scan was performed for further evaluation, revealing severe hypoattenuated thickening of all leaflets (Figures 2A, 3A, 4A, and 5A), along with reduced leaflet motion during both systolic and diastolic phases (Video 1), consistent with bioprosthetic valve thrombosis. The mural left atrial thrombus was also seen, measuring 31 × 24 × 15 mm (Figure 4A). Regarding her coagulation parameters, 8 years ago, while she was on apixaban, her international normalized ratio (INR) was 1.2 with a prothrombin time of 12.9, possibly indicating subtherapeutic anticoagulation in a patient with atrial fibrillation and a bioprosthetic MV. No other coagulation parameters, including D-dimer or fibrinogen, were available, which limited more detailed analysis of the patient's coagulation profile.
Figure 1.
Continuous-Wave Doppler Echocardiography Shows Severe Mitral Stenosis Before Treatment, With a Mean Diastolic Gradient of 11 mm Hg at a Heart Rate of 43 beats/min
Figure 2.
Cardiac Computed Tomography Images of the Bioprosthetic Mitral Valve
Three-dimensional multiplanar reconstruction images acquired in diastole displaying a three-chamber view. (A) The pretreatment image shows hypoattenuated leaflet thickening with restricted opening (arrows). (B) The post-treatment image shows improvement in leaflet thickening and decreased restriction (arrows).
Figure 3.
Cardiac Computed Tomography Images of the Bioprosthetic Mitral Valve
Three-dimensional multiplanar reconstruction images acquired in diastole show a short-axis view. (A) Pretreatment image reveals hypoattenuated leaflet thickening involving all bioprosthetic mitral valve leaflets (arrows). (B) Post-treatment image demonstrates near-complete resolution of leaflets thickening (arrows).
Figure 4.
Cardiac Computed Tomography Images of the Bioprosthetic Mitral Valve
Three-dimensional multiplanar reconstruction images acquired during diastole showing a 4-chamber view. (A) The pretreatment image shows hypoattenuated leaflet thickening with restricted opening (yellow arrows) and reveals a thrombus along the posterior wall of the left atrium (red arrow). (B) The post-treatment image displays improved leaflet thickening (yellow arrows) and less restriction of the opening, along with a reduction in thrombus size (red arrow).
Figure 5.
Three-Dimensional Volume-Rendered Cardiac Computed Tomography Images Showing an Atrial View of the Bioprosthetic Mitral Valve During Diastole
(A) The pretreatment image displays leaflet thickening and limited diastolic opening. (B) The post-treatment image shows resolution of leaflet thickening and improved diastolic opening, although the anteroseptal leaflet remains thickened.
Management
Based on these findings, the patient was started on warfarin with a target INR of 2.0 to 3.0, along with 81 mg of aspirin daily, which she was already taking for her peripheral arterial disease.
Outcome and Follow-Up
A follow-up CT performed after 3 months of warfarin therapy showed significant regression of HALT, with only mild-to-moderate diffuse thickening of the anteroseptal leaflet, involving approximately two-thirds of its length and limiting leaflet motion. The anterolateral and posterior leaflets had preserved leaflet motion (Video 2) with no significant thickening. The left atrial thrombus was also smaller (20 × 24 × 10 mm) (Figures 2B, 3B, 4B, 5B). Consistent with these CT findings, her TTE revealed a significant drop in the mitral diastolic mean gradient to 3 mm Hg at 58 beats/min (Figure 6). Given her stable condition and HALT improvement, the valve team decided to delay intervention (valve-in-valve transcatheter MV replacement) and instead recommend close clinical follow-up with serial echocardiograms and cardiac CT. The patient continues on medical therapy, maintaining therapeutic warfarin anticoagulation with an INR of 2 to 3 and remains asymptomatic.
Figure 6.
Continuous-Wave Doppler Echocardiography Shows Significant Hemodynamic Improvement, With the Mitral Diastolic Mean Gradient Decreasing to 3 mm Hg at 58 beats/min After Treatment
Discussion
Bioprosthetic mitral valve thrombosis (bMVT) is an important complication after MV replacement, with an incidence of 5.05 per 100-patient-years3; notably higher than that observed with aortic bioprostheses, likely due to lower pressure gradients and larger surface areas.3 While early bioprosthetic MV thrombosis (within 90 days) is more commonly reported, literature indicates that its risk persists beyond this period, with a peak incidence at 12 to 24 months postprocedure.3 The current American College of Cardiology guidelines recommend 6 months of anticoagulation with warfarin after MV replacement.4 Our case, presenting 17 years postreplacement, represents a highly unusual incidence of delayed HALT.
Possible Contributors to Late Thrombosis
Several pathophysiological factors may explain this delayed presentation. A comprehensive review focused mainly on aortic valves noted that the mechanisms behind bioprosthetic valve thrombosis include low-flow states, stasis zones, residual valve disease, and impaired washout of the prosthetic surface.5 Studies suggest that HALT indicates thrombus deposition on bioprosthetic valve leaflets, and untreated leaflet thrombosis can progress into an organized fibrotic process, making it resistant to anticoagulation.6 Although we were unable to quantify attenuation values (Hounsfield units) in our case, the response to warfarin supports the diagnosis of HALT by leaflet thrombosis.
MV prostheses are naturally exposed to lower blood flow than aortic valves, increasing the risk of thrombosis.1 The patient's atrial fibrillation could have potentially contributed to irregular blood flow and stasis, which might have facilitated thrombogenesis. Furthermore, a history of recurrent endocarditis could have damaged the valve leaflets over time, creating uneven surfaces that serve as sites for thrombus development.5,7
Another potential factor is the subtherapeutic anticoagulation 8 years earlier for this patient, which is notable given that oral anticoagulation was associated with a 3.5-fold lower incidence of bMVT.3 Importantly, the hemodynamic improvement after warfarin therapy in our patient (mean gradient decreasing from 11 mm Hg to 3 mm Hg) demonstrates reversal of HALT, highlighting the thrombogenic etiology and the benefit of appropriate early anticoagulation.
Diagnostic Imaging
Imaging plays a vital role in the diagnosis and monitoring of bMVT. TTE is usually the first test, helpful for detecting valve dysfunction and measuring gradients.8 The next step is to proceed with advanced imaging, such as 3D-TEE or cardiac CT. Bioprosthetic valve thrombosis is diagnosed when there is diffuse or focal cusp thickness (more dense on TEE) or hypoattenuating leaflet thickening appearance on cardiac CT associated with reduced leaflet motion (best evaluated during diastole).8 These CT features were present in our case and improved with anticoagulation.
For structural valve deterioration caused by calcification or tears, this involves permanent acquired changes affecting components such as valve leaflets, stent, or sewing ring. On CT imaging, calcific changes appear as areas of high attenuation.9 In contrast, pannus is fibrous tissue ingrowth with intermediate attenuation characteristics on CT. HALT typically presents as hypoattenuating leaflet thickening with reduced motion, often reversible with anticoagulation.10 Overall, the final diagnosis should combine imaging results with clinical features and response to therapy over time.
Cardiac CT can be crucial for early detection of bMVT, as reduced leaflet motion is associated with early bioprosthetic failure.3 This allows for timely management before valve dysfunction develops. Hosoba et al1 highlighted the importance of ongoing evaluation over longer follow-up periods averaging 3.4 years. Both vitamin K antagonists and novel oral anticoagulants (NOACs) have been used to manage bioprosthetic valve thrombosis.8 A meta-analysis by Zorman et al3 reported a 3.2-fold lower incidence of bMVT in patients taking vitamin K antagonists than in those taking NOACs, with a significant decrease in bMVT incidence among patients on oral anticoagulants compared to those not on them. However, more controlled studies are needed to establish the role of NOACs in patients with bMVT and long-term prosthesis failure rates.
Conclusions
HALT can occur very late and lead to deterioration in valve hemodynamics. In this case, warfarin was associated with significant improvement, suggesting potential benefit over NOACs in similar cases. However, larger studies are needed to determine the best anticoagulation strategies.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
Visual Summary.
| Timeline | Events |
|---|---|
| Year 0 | Initial mechanical mitral valve replacement for Staphylococcus aureus endocarditis. |
| Year 4 | Developed fungal endocarditis of the mechanical valve; underwent reoperation with 27 mm Hancock porcine bioprosthetic mitral valve replacement. |
| Year 14 | Started apixaban for anticoagulation after developing paroxysmal atrial fibrillation. |
| Year 15-16 | Serial TTE showed mild mitral stenosis with a mean diastolic gradient of 4-6 mm Hg, progressing to moderate mitral stenosis with a mean diastolic gradient of 7-10 mm Hg. |
| Year 17 | Severe mitral stenosis detected (mean diastolic gradient 10-11) on TTE. TEE and cardiac CT confirmed HALT with reduced leaflet motion and a left atrial thrombus. Patient started on warfarin. |
| Year 17 + 3 mo and ongoing | Follow-up cardiac CT showed significant regression of HALT; TTE showed a mean diastolic gradient improvement to 3 mm Hg. Patient remained asymptomatic, continued medical therapy, and follow-up was planned. |
Appendix
Cardiac Computed Tomography Showing Diffuse Hypoattenuated Thickening of the Mitral Valve Leaflets With Markedly Decreased Leaflet Movement During Both Systole and Diastole
Left panels: long-axis views. Right panels: short-axis view through the base of the mitral prosthesis and the mid portion. Red arrows: Mitral valve. Black arrows: Left atrial thrombus. Asterisk: Pacemaker lead. AO = aorta; AV = aortic valve; LA = left atrium; LV = left ventricle; RA = right atrium.
Cardiac Computed Tomography Showing Near Resolution of the Hypoattenuated Leaflet Thickening of the Mitral Valve Leaflets, With a Residual Restriction in the Motion of one of the 3 Cusps
The right upper panel shows the short-axis view, while the other panels display long-axis views. Red arrows: mitral valve. Black arrows: left atrial thrombus. Asterisk: pacemaker lead. AO = aorta; AV = aortic valve; LA = left atrium; LV = left ventricle; RA = right atrium.
References
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Associated Data
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Supplementary Materials
Cardiac Computed Tomography Showing Diffuse Hypoattenuated Thickening of the Mitral Valve Leaflets With Markedly Decreased Leaflet Movement During Both Systole and Diastole
Left panels: long-axis views. Right panels: short-axis view through the base of the mitral prosthesis and the mid portion. Red arrows: Mitral valve. Black arrows: Left atrial thrombus. Asterisk: Pacemaker lead. AO = aorta; AV = aortic valve; LA = left atrium; LV = left ventricle; RA = right atrium.
Cardiac Computed Tomography Showing Near Resolution of the Hypoattenuated Leaflet Thickening of the Mitral Valve Leaflets, With a Residual Restriction in the Motion of one of the 3 Cusps
The right upper panel shows the short-axis view, while the other panels display long-axis views. Red arrows: mitral valve. Black arrows: left atrial thrombus. Asterisk: pacemaker lead. AO = aorta; AV = aortic valve; LA = left atrium; LV = left ventricle; RA = right atrium.