Author + information
- Received July 26, 2019
- Revision received October 7, 2019
- Accepted October 9, 2019
- Published online December 18, 2019.
- Elona Rrapo Kaso, MD,
- Steve A. Noutong, MD,
- LeAnn N. Denlinger, MD,
- Mohammed Morsy, MD and
- Christopher M. Kramer, MD∗ ()
- Division of Cardiovascular Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia
- ↵∗Address for correspondence:
Dr. Christopher M. Kramer, Cardiovascular Division, University of Virginia Health System, 1215 Lee Street, Box 800158, Charlottesville, Virginia 22908.
Obstructive bioprosthetic valve thrombosis is associated with hemodynamic compromise, and evidence on management with fibrinolysis is limited. Echocardiography is required to assess thrombus size and its effects on valve gradients, area, and leaflet motion. This case demonstrates use of echocardiography guided slow-infusion low-dose fibrinolytic therapy in a patient with obstructive bioprosthetic valve thrombosis. (Level of Difficulty: Intermediate.)
A 66-year-old female with a bioprosthetic mitral valve presented to an outside hospital with symptoms and signs of congestive heart failure. Three years prior to the current presentation, her condition was diagnosed as multivessel coronary artery disease and severe ischemic mitral regurgitation during a hospitalization for non-ST-segment elevation myocardial infarction. At that time, she underwent mitral valve replacement (MVR) using a 27-mm tissue valve (Epic, St. Jude Medical, Memphis, Tennessee) and 3-vessel coronary artery bypass grafting. One year after the MVR procedure, endocarditis caused by Streptococcus mitis was diagnosed and treated medically. One and a half years after receiving treatment for endocarditis, the patient developed severe bioprosthetic mitral valve stenosis. She underwent a transcatheter MVR with a 26-mm valve-in-valve (Sapien S3, Edwards Lifescience, Irvine, California), using transfemoral access and a trans-septal puncture. She subsequently did well until the current admission when she presented with sudden onset of New York Heart Association functional class III to IV heart failure symptoms. A transthoracic echocardiogram (TTE) revealed severe mitral stenosis (heart rate [HR] = 84 beats/min) with a transmitral valve peak gradient (PG) of 50 mm Hg and mean gradient (MG) of 31 mm Hg (Figure 1) compared to 16 mm Hg and 8 mm Hg, respectively, 6 months prior. Left and right ventricular function was normal. She was transferred to our hospital for further management. On presentation, her blood pressure was 127/79 mm Hg; HR was 73 beats/min; respiratory rate was 40 breaths/min; peripheral capillary oxygen saturation [SpO2] was 98% on 5 l/min by nasal cannula; and temperature was 36.5°C. On physical examination, the patient appeared to be in moderate respiratory distress and had 2-pillow orthopnea. Jugular venous distention was 15 cm H2O at 45°. Cardiac examination revealed regular rate and muffled prosthetic valve sounds with 2/6 systolic murmur at the left lower sternal border. On lung examination, there were crackles occupying two-thirds of the lung fields bilaterally. There was 1+ pitting edema of lower extremities bilaterally.
• To understand the role of fibrinolytic therapy in the treatment of obstructive bioprosthetic valve thrombosis.
• To identify major risk factors of systemic embolic complications of thrombolytic therapy when treating prosthetic valve thrombosis.
• To summarize clinical outcomes of patients who receive thrombolytic therapy for treatment of obstructive prosthetic valve thrombosis.
The patient’s medical history included multiple sclerosis, insulin-dependent diabetes, breast cancer, status post-radiation 7 years previously, and liver cirrhosis (by prior computed tomography imaging). Home medications included aspirin, 81 mg; atorvastatin, 80 mg; metoprolol, 25 mg twice a day; furosemide, 80 mg daily; metformin, 1,000 mg twice daily; insulin; and baclofen.
Given her clinical presentation of heart failure and severe stenosis of the bioprosthetic mitral valve by echocardiography, the differential diagnosis included obstructive thrombus, pannus, endocarditis, or patient-prosthesis mismatch.
Laboratory workup was significant for elevated B-type natriuretic peptide (2,400 pg/ml). Complete blood count, comprehensive metabolic panel, antinuclear antibodies, and coagulation laboratory values were unremarkable. Electrocardiography revealed normal sinus rhythm with a HR of 62 beats/min and was otherwise normal. Chest radiography showed bilateral pleural effusion and moderate interstitial edema. A transesophageal echocardiogram (TEE) confirmed severe bioprosthetic MV stenosis and also revealed a large echodensity encompassing the leaflets with restricted leaflet motion, which was concerning for valve thrombosis (Figure 2, Videos 1A and 1B).
Intravenous diuretics were administered with good response. The patient’s oxygenation requirements improved, and she was weaned to room air. A follow-up chest radiograph revealed improvement of pleural effusion and resolution of interstitial edema. Therapeutic enoxaparin, which had been started at the outside hospital, was continued during the patient’s current hospitalization.
Cardiothoracic surgery was consulted for consideration of surgical mitral valve replacement. Given multiple risk factors, including prior cardiac surgery including a left internal mammary artery graft to the left anterior descending artery, history of chest radiation for breast cancer, multiple sclerosis affecting the patient’s mobility, and concern for liver cirrhosis, she was deemed to be at prohibitive surgical risk. A multidisciplinary team, including cardiothoracic surgery and cardiology, discussed the risks and benefits of thrombolytic therapy with the patient as an alternative treatment option for prosthetic valve obstructive thrombus. Potential contraindications to thrombolytic therapy were evaluated. Because her liver appeared cirrhotic on imaging, an esophagogastroduodenoscopy was performed which revealed no esophageal or gastric varices.
The mechanism leading to obstructive bioprosthetic valve thrombosis (OBPVT) was thought to be due to the Sapien valve (Edwards Lifesciences) placed 6 months before in a previously placed surgical valve. As described by Puri et al. (1) “the underlying principles invariably relate to perturbations in blood flow and activation of various hemostatic factors involving mechanisms common to medical device-induced thrombosis.” A computed tomography scan of the valve was not performed. However, given the patient’s clinical presentation with sudden onset of symptoms, the timing of presentation relative to the Sapien valve implantation, as well as the appearance on TEE, the clinical suspicion was high for thrombus and low for pannus.
There are no randomized controlled trials to guide the use of thrombolytic therapy in patients with OBPVT. Most available data apply to patients with mechanical valve thrombosis. Studies using an echocardiography-guided, slow-infusion, low-dose fibrinolytic protocol in patients with mechanical PVT have demonstrated high success rates (>90%) and low complication rates (<2% embolic event rates and <2% major bleeding rates; 0.8% mortality rate) (2–4). In the PROMETEE (PROsthetic MEchanical valve Thrombosis and the prEdictors of outcomE) trial (2), 1 session of thrombolytic therapy achieved an initial success rate of 20%, and 8 sessions of slow-infusion, low-dose fibrinolytic therapy were required for a success rate of 90%. The present patient likely had the valve obstruction from a thrombus with recent onset given the successful result after 1 session of thrombolytic therapy. The 2017 American Heart Association/American College of Cardiology (AHA/ACC) focused update of the 2014 AHA/ACC Guidelines for the Management of Patients with Valvular Heart Disease recommends urgent initial treatment with either slow-infusion, low-dose fibrinolytic therapy or emergency surgery for patients with a thrombosed left-sided mechanical prosthetic heart valve presenting with symptoms of valve obstruction (5). Evidence from results of thrombolytic therapy in patients with OBPVT is largely limited to case reports, therefore only indirect observational data are available regarding efficacy and safety of thrombolytic therapy for OBPVT.
The presence of atrial fibrillation, New York Heart Association functional class IV status, and higher baseline thrombus area have been associated with lower likelihood of successful treatment of OPVT by thrombolytic therapy (2). Major risk factors for systemic embolic complications of thrombolytic therapy include thrombus size of more than 0.8 cm2 and a history of cerebrovascular event (3). In PVT, the thrombus size imaged using TEE is a significant independent predictor of outcome. Three-dimensional (3D) echocardiographic imaging has an important role in evaluation of mitral prosthesis, especially for visualizing nonobstructive thrombus, which may be missed with 2D echo.
Echocardiographically guided slow-infusion, low-dose fibrinolytic therapy was initiated 12 h after discontinuation of enoxaparin therapy, and coagulation laboratory values were confirmed to be within the normal range. Intravenous alteplase, 25 mg, was infused over 25 h with no bolus. Immediately after the alteplase infusion was completed, a heparin drip was initiated. TTE was performed which showed resolution of the MV obstruction, with improvement of transmitral PG to 15 mm Hg and MG to 6 mm Hg (Figure 3). A TEE performed 24 h later revealed resolution of the thrombus, unrestricted mitral valve leaflets motion, and PG of 9 mm Hg and MG of 4 mm Hg (Figure 4, Videos 2A, 2B, 3A, and 3B). There were no complications from the thrombolytic therapy. Warfarin therapy was initiated with an INR goal of 2 to 3, and she was subsequently discharged home. In addition, the patient was advised to continue taking aspirin, 81 mg, daily.
Even when medical therapy is successful in the treatment of OBPVT, additional questions remain regarding follow-up strategies, duration of anticoagulation, and adequacy of nonvitamin K anticoagulants. Novel oral anticoagulants for bioprosthetic valves have not been studied for efficacy and safety in a large randomized trial (6). Most recent guidelines (5) recommend that, for both aortic and mitral bioprosthetic valves, in addition to aspirin, anticoagulation with warfarin, with an INR target of 2.5, should be considered (Class IIa recommendation, weight of evidence/expert opinion is in favor of usefulness/efficacy as benefits outweighs risks.) in patients with a low risk of bleeding, for 3 to 6 months after surgery. However, there are no recommendations regarding anticoagulation therapy following treatment of valve-in-valve OBPVT with fibrinolytic therapy. The 2014 AHA/ACC valve guidelines state “in patients with a bioprosthetic valve with embolic events who are only on aspirin 75 mg to 100 mg daily, a possible approach includes consideration of anticoagulation with a VKA” (7). In addition, the duration of anticoagulation therapy is uncertain; however, recurrence of BPVT 6 months following cessation of anticoagulation therapy in a successfully treated aortic BPVT has been reported (8). Therefore, the authors recommend life-long anticoagulation therapy in this patient group (8). Recurrent OBPVT in the present patient, who is at high surgical risk, could potentially result in a fatal event, and after discussion with the patient, it was recommended that anticoagulation with warfarin would be life-long.
This case demonstrates the successful use of echocardiographically guided slow-infusion, low-dose fibrinolytic therapy in a patient with obstructive thrombus of a bioprosthetic valve without any complications. Further guidance is needed regarding the long-term management of patients with OBPVT after successful thrombolytic therapy.
Dr. Kramer is supported by National Heart, Lung, and Blood Institute grants U01HL117006-01A1 and 5R01 HL075792. Dr. Rrapo Kaso is supported by National Institute of Biomedical Imaging and Bioengineering grant 5T32EB003841. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Informed consent was obtained for this case.
- Abbreviations and Acronyms
- heart rate
- mean gradient
- mitral valve replacement
- obstructive bioprosthetic valve thrombosis
- obstructive prosthetic valve thrombosis
- peak gradient
- transesophageal echocardiogram
- transthoracic echocardiogram
- Received July 26, 2019.
- Revision received October 7, 2019.
- Accepted October 9, 2019.
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