Abstract
Background
The Edwards SAPIEN M3 transcatheter mitral valve replacement (TMVR) has demonstrated safety and efficacy in the treatment of symptomatic patients with mitral valve disease for whom commercially available surgical or transcatheter treatment options are deemed unsuitable. We present a case of acute M3 thrombosis due to oral anticoagulation nonadherence, complicated by cardiogenic shock, successfully treated with valve-in-valve intervention.
Case Summary
A 58-year-old woman with recent M3 TMVR presented with cardiogenic shock, and was found to have prosthetic valve thrombosis with elevated gradients across the mitral valve and heavy clot burden causing severe mitral stenosis. After worsening hemodynamic parameters with thrombolytic therapy alone, emergent valve-in-valve TMVR was performed with successful implantation of a 29-mm Edwards SAPIEN S3 Ultra Resilia valve inside the Encircle M3 valve.
Discussion
We demonstrate the effective management of a rare but serious complication of TMVR with prosthetic valve thrombosis successfully treated with valve-in-valve reintervention.
Take-Home Messages
Valve thrombosis remains a clinically significant complication in next-generation transcatheter mitral valve systems, emphasizing the need for vigilant anticoagulation management and early diagnostic consideration. For patients with high surgical risk who present with acute thrombosis, ad hoc valve-in-valve reintervention is an effective treatment option.
Key words: cardiogenic shock, prosthetic valve thrombosis, transcatheter mitral valve replacement
Visual Summary
Visual Summary.
A Rare but Serious Complication: ViV Treatment of Acute M3 Thrombosis
TMVR = transcatheter mitral valve replacement; ViV = valve-in-valve.
History of Presentation
A 58-year-old woman presented with sudden onset shortness of breath, orthopnea, and oliguria 4 months after undergoing successful transcatheter mitral valve replacement (TMVR) with the Edwards SAPIEN M3 valve (Figure 1).1 She had previously been deemed a poor candidate for mitral transcatheter edge-to-edge repair due to thickened and restricted mitral valve leaflets and small mitral valve area. On presentation, the patient was hypotensive, requiring BiPAP for respiratory distress, and noted to have bibasilar crackles with significant lower extremity edema. She was started on dobutamine and norepinephrine and found to have severely elevated gradients across her mitral valve by transthoracic echocardiography (TTE). The patient noted that she had not been able to obtain her oral anticoagulant regimen of apixaban 5 mg twice a day for the preceding 10 days.
Take-Home Messages
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Valve thrombosis remains a clinically significant complication even in next-generation transcatheter mitral valve systems, emphasizing the need for vigilance in anticoagulation management and follow-up imaging.
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Early recognition through multimodality imaging and a multidisciplinary approach is crucial for timely diagnosis and intervention to prevent hemodynamic decline.
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For patients with high surgical risk that are presenting with this rare but conceivable complication, ViV reintervention remains a viable option.
Figure 1.
SAPIEN M3 System
SAPIEN M3 System used as part of ENCIRCLE trial.1
Past Medical History
The patient's past medical history included the following: hypertension, hyperlipidemia, nonischemic heart failure with reduced ejection fraction with biventricular implantable cardioverter-defibrillator, and chronic severe functional mitral regurgitation treated with TMVR with the Edwards M3 valve.
Differential Diagnosis
The differential diagnosis for elevated gradients across a recent mitral valve prosthesis included the following: obstructive and nonobstructive etiologies. Obstructive etiologies included prosthetic valve thrombosis, endocarditis, degeneration, and patient prosthesis mismatch, whereas nonobstructive etiologies included high flow states.
Investigations
Laboratory studies revealed significant renal dysfunction with serum creatinine 2.24 mg/dL (baseline: 1.2 mg/dL), N-terminal pro–B-type natriuretic peptide 13,500 pg/mL, and lactate of 7.19. The patient's initial white blood cell count was 15,000/μL. All other routine laboratory levels were within normal limits. A TTE revealed elevated gradients (16-20 mm Hg at heart rate of 130 beats/min) across the mitral valve.
Management
Given the high clinical suspicion for valve thrombosis, the patient was brought emergently to the cardiac catheterization laboratory. After intubation, subsequent transesophageal echocardiogram confirmed severely clotted mitral valve prosthesis with heavy clot burden, mainly on the ventricular aspect of the leaflets, leading to severe stenosis (Figure 2, Video 1, Video 2, Video 3). Right heart catheterization showed elevated right-sided pressures with a right atrial mean pressure of 25 mm Hg, mean pulmonary artery pressure of 72 mm Hg, and a pulmonary capillary wedge pressure of 44 mm Hg. Cardiac output by Fick was calculated to be 4.35 L/min, with a cardiac index of 2.12 L/min.
Figure 2.
Preoperative TEE
Preoperative transesophageal echocardiogram (TEE) showing a mean gradient of 15 mm Hg across the mitral valve concerning for mitral valve stenosis caused by prosthetic valve thrombosis.
An intra-aortic balloon was placed for initial hemodynamic management and an alteplase infusion was started at 25 mg over 6 hours. After 1 hour of infusion, there was no echocardiographic change in valve function and end-organ perfusion parameters continued to worsen in the catheterization laboratory.
An ad hoc heart team meeting was convened, and the patient was thought to be at prohibitive surgical risk. Pre-M3 implantation cardiac computed tomography was reviewed, and a note was made that a valve-in-valve (ViV) TMVR would land entirely within the M3 skirt frame, thus eliminating risk of obstruction of the left ventricular outflow tract. Cerebral embolic protection was implanted via the right radial artery using the Sentinel cerebral embolic protection device (Boston Scientific). ViV TMVR was performed successfully using a 29-mm SAPIEN S3 Ultra Resilia valve inside the M3 valve using standard TMVR technique with return of her mitral valve gradients back to baseline of 6 and 7 mm Hg at a heart rate of 100 beats/min (Figure 3, Video 4, Video 5, Video 6). During the procedure, she also underwent atrial septal defect closure due to significant right ventricular dysfunction and tricuspid regurgitation. On completion of the procedure, there was no debris in the filters of the cerebral embolic protection device.
Figure 3.
Post-Reintervention TEE
Transesophageal echocardiogram (TEE) done after valve-in-valve transcatheter mitral valve replacement procedure showing continuous wave spectral Doppler with improved mean gradient of 8 mm Hg across the mitral valve.
Outcome and Follow-up
The patient's postoperative course was managed with inotropic support and mechanical support with rapid improvement in end organ perfusion (Figure 4). The course was complicated by atrial fibrillation, atrial tachycardia, and ventricular tachycardia that was terminated by her implantable cardioverter-defibrillator. She was maintained on monotherapy with apixaban. Her 1-month postoperative TTE showed stable mitral valve gradients.
Figure 4.
Lactate Trend
The patient’s lactate trend over days 1 to 3 from presentation to peak with quick improvement to normal after reintervention.
At 12-month follow-up, she reported feeling well with baseline functional status and adherence to anticoagulant and guideline-directed medical therapy.
Discussion
Mitral regurgitation is a prevalent and undertreated valvular heart disease in adults, particularly in patients at prohibitive surgical risk. TMVR is an emerging treatment option for patients with symptomatic severe mitral valve disease for whom commercially available surgical or transcatheter treatment options are deemed unsuitable. In the absence of sufficient mitral annular calcification for TMVR anchoring, the M3 valve system requires a nitinol dock and full frame skirt to provide an anchor for the M3 valve, a balloon-expandable SAPIEN 3 valve adapted for the mitral position. The ENCIRCLE trial demonstrated that percutaneous transseptal TMVR with the SAPIEN M3 system effectively reduced mitral regurgitation with low rates of complications and mortality, thereby supporting it as a therapeutic option for patients who are unsuitable for surgery or transcatheter edge-to-edge repair.
Despite advances in device design and procedural technique, valve thrombosis remains a recognized complication after TMVR with an annual thrombotic risk of 6% to 8%.2 Bioprosthetic valve thrombosis (BPVT) is most common in the first 3 months after implantation; however, it has also been described in patients years after implantation.2 The M3 valve, with its full frame skirt, may increase risk of valve thrombosis, particularly in low flow states such as reduced left ventricular ejection fraction. BPVT appears to be more common with the transcatheter rather than surgical approach, and bioprostheses implanted in the mitral position carry a higher thromboembolic risk than those in the aortic position.3 For patients undergoing TMVR, current guidelines recommend postprocedural anticoagulation for at least 3 months; however, optimal antithrombotic regimen and duration remain uncertain, and recommendations are largely extrapolated from surgical and limited observational data.3 Protocol for the ENCIRCLE trial involved anticoagulating patients postoperatively for a minimum of 6 months. Continued antithrombotic therapy after 6 months was recommended, and the choice and duration of anticoagulant was left up to the investigator's discretion.2 In our patient, the presumed mechanism of acute thrombosis was her interruption in anticoagulation with potential contribution of the patient's reduced left ventricular ejection fraction coupled with the full valve frame nature of the M3's skirt.
For patients presenting with BPVT, data on medical management are limited and extrapolated from mechanical valve thrombosis data. Factors taken into consideration when considering fibrinolytic therapy vs surgery include surgical risk, first-time presentation, NYHA functional class, clot burden, and concomitant coronary artery disease or valve disease. Echocardiogram-guided, low-infusion, low-dose fibrinolytic protocol has shown hemodynamic success rates of >90%, with <2% embolic events and major bleeding rates each in recent studies.3,4 Therefore, systemic fibrinolysis remains an acceptable alternative to reoperation in patients at high or prohibitive surgical risk. In our patient, fibrinolytic therapy was attempted; however, the decision for reintervention was made due to worsening hemodynamics, mitral valve gradients, and NYHA functional class IV symptoms with cardiogenic shock.
Current guidelines for management of left-sided BPVT recommend repeat surgical intervention in patients with symptomatic severe stenosis; however, transcatheter ViV procedure is reasonable for those with high or prohibitive surgical risk.3 Given the patient's acuity, preprocedural planning could not be performed. As the SAPIEN 3 valve would land entirely within the confines of the skirt frame, the risk of left ventricular outflow tract obstruction was thought not to be a consideration.
Among the 299 treated patients in the ENCIRCLE trial, 2.3% had a major structural complication and required mitral valve reintervention at 30-day follow-up. The overall rate of clinically significant valve thrombosis at 1 year was 6.7%, encompassing patients with both adequate and inadequate anticoagulation. Clinically significant valve thrombosis included leaflet thickening with impaired leaflet motion and mitral valve stenosis (increase in mean mitral valve gradient ≥5 mm Hg) and clinical signs and symptoms of mitral valve stenosis. Patients with inadequate anticoagulation, defined as a lapse of >1 day in anticoagulation or a subtherapeutic INR for those on a VKA, had higher rates of thrombosis regardless of anticoagulant type. Among the 223 patients receiving a direct oral anticoagulation regimen like our patient, 6.7% developed clinically significant device thrombosis at 1 year, and 8% of these cases occurred in the setting of inadequate anticoagulation.2
Our case illustrates that clinically significant valve thrombosis may occur even with guideline-directed therapy, highlighting the need for individualized management strategies and close imaging surveillance. Successful ViV performed in this patient was technically straightforward due to the antecedent knowledge of the left ventricular outflow tract and the implantation of a comparable valve inside the prior valve frame with alignment of the Sapien 3 valve frame with the ventricular aspect of the M3 valve frame. This underscores the feasibility of percutaneous reintervention and its potential role in managing device-related complications in the evolution of the novel TMVR device. In the context of a recent pivotal trial, this case adds to the limited literature on post-TMVR thrombosis and offers insight into the management and care of this growing patient population.
Funding Support and Author Disclosures
Dr Mihatov has received consulting and/or speaking fees from Edwards Lifesciences. Dr Reisman is an employee of Edwards Lifesciences. All other 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
Equipment List.
Imaging
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Appendix
Preoperative Bioprosthetic Valve Thrombosis TEE
Preoperative transesophageal echocardiogram (TEE) demonstrating severe thrombosis on the ventricular aspect of the implanted M3 valve.
Preoperative Bioprosthetic Valve Thrombosis TEE With Color Doppler
Preoperative transesophageal echocardiogram (TEE) with color Doppler demonstrating increased turbulence across the mitral valve, signifying increased gradients across the valve.
Preoperative Bioprosthetic Valve Thrombosis TEE
Preoperative transesophageal echocardiogram (TEE) 3-dimensional en face surgeon's view of the thrombosed mitral valve.
Intraoperative Fluoroscopy
Cine imaging of 29-mm Edwards Sapien 3 Ultra Resilia being deployed under rapid pacing within the M3 valve. The ventricular side of the Sapien 3 valve was aligned with the ventricular aspect of the M3 valve.
Post-Reintervention TEE
Transesophageal echocardiogram (TEE) after reintervention demonstrating well-placed valve-in-valve functioning well.
Post-Reintervention TEE
3-dimensional transesophageal echocardiogram (TEE) en face of the mitral valve after reintervention demonstrating well-placed valve-in-valve functioning well.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Preoperative Bioprosthetic Valve Thrombosis TEE
Preoperative transesophageal echocardiogram (TEE) demonstrating severe thrombosis on the ventricular aspect of the implanted M3 valve.
Preoperative Bioprosthetic Valve Thrombosis TEE With Color Doppler
Preoperative transesophageal echocardiogram (TEE) with color Doppler demonstrating increased turbulence across the mitral valve, signifying increased gradients across the valve.
Preoperative Bioprosthetic Valve Thrombosis TEE
Preoperative transesophageal echocardiogram (TEE) 3-dimensional en face surgeon's view of the thrombosed mitral valve.
Intraoperative Fluoroscopy
Cine imaging of 29-mm Edwards Sapien 3 Ultra Resilia being deployed under rapid pacing within the M3 valve. The ventricular side of the Sapien 3 valve was aligned with the ventricular aspect of the M3 valve.
Post-Reintervention TEE
Transesophageal echocardiogram (TEE) after reintervention demonstrating well-placed valve-in-valve functioning well.
Post-Reintervention TEE
3-dimensional transesophageal echocardiogram (TEE) en face of the mitral valve after reintervention demonstrating well-placed valve-in-valve functioning well.