Timely Management of Obstructive Prosthetic Valve Thrombosis

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ª 2019 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/).

CASE REPORT CLINICAL CASE

Timely Management of Obstructive Prosthetic Valve Thrombosis Elona Rrapo Kaso, MD, Steve A. Noutong, MD, LeAnn N. Denlinger, MD, Mohammed Morsy, MD, Christopher M. Kramer, MD

ABSTRACT 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.) (J Am Coll Cardiol Case Rep 2019;-:-–-) © 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

PRESENTATION

infarction. At that time, she underwent mitral valve replacement (MVR) using a 27-mm tissue valve (Epic,

A 66-year-old female with a bioprosthetic mitral valve

St. Jude Medical, Memphis, Tennessee) and 3-vessel

presented to an outside hospital with symptoms and

coronary artery bypass grafting. One year after the

signs of congestive heart failure. Three years prior

MVR procedure, endocarditis caused by Streptococcus

to the current presentation, her condition was

mitis was diagnosed and treated medically. One and a

diagnosed as multivessel coronary artery disease and

half years after receiving treatment for endocarditis,

severe ischemic mitral regurgitation during a hospi-

the patient developed severe bioprosthetic mitral

talization for non-ST-segment elevation myocardial

valve stenosis. She underwent a transcatheter MVR with a 26-mm valve-in-valve (Sapien S3, Edwards

LEARNING OBJECTIVES

Lifescience, Irvine, California), using transfemoral

 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.

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] ¼ 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, six months prior. Left and right ventricular function was normal. She was transferred to

From the Division of Cardiovascular Medicine, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia. 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. Manuscript received July 26, 2019; revised manuscript received October 7, 2019, accepted October 9, 2019.

ISSN 2666-0849

https://doi.org/10.1016/j.jaccas.2019.10.002

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ABBREVIATIONS

our hospital for further management. On

Cardiothoracic surgery was consulted for consid-

AND ACRONYMS

presentation, her blood pressure was 127/

eration of surgical mitral valve replacement. Given

79 mm Hg; HR was 73 beats/min; respiratory

multiple risk factors, including prior cardiac surgery

rate was 40 breaths/min; peripheral capillary

including a left internal mammary artery graft to the

oxygen saturation [SpO2 ] was 98% on 5 l/min

left anterior descending artery, history of chest radi-

by nasal cannula; and temperature was

ation for breast cancer, multiple sclerosis affecting

36.5  C. On physical examination, the patient

the patient’s mobility, and concern for liver cirrhosis,

appeared to be in moderate respiratory

she was deemed to be at prohibitive surgical risk.

distress and had 2-pillow orthopnea. Jugular

A multidisciplinary team, including cardiothoracic

valve thrombosis

venous distention was 15 cm H2O at 45  .

surgery and cardiology, discussed the risks and

PG = peak gradient

Cardiac examination revealed regular rate

benefits of thrombolytic therapy with the patient as

and muffled prosthetic valve sounds with 2/6

an alternative treatment option for prosthetic valve

echocardiogram

systolic murmur at the left lower sternal

obstructive thrombus. Potential contraindications

TTE = transthoracic

border. On lung examination, there were

to thrombolytic therapy were evaluated. Because

echocardiogram

crackles occupying two-thirds of the lung

her liver appeared cirrhotic on imaging, an esoph-

HR = heart rate MG = mean gradient MVR = mitral valve replacement

OBPVT = obstructive bioprosthetic valve thrombosis

OPVT = obstructive prosthetic

TEE = transesophageal

fields bilaterally. There was 1þ pitting edema of lower

agogastroduodenoscopy

extremities bilaterally.

revealed no esophageal or gastric varices.

MEDICAL HISTORY. The patient’s medical history

included multiple sclerosis, insulin-dependent dia-

was

performed

which

DISCUSSION

betes, breast cancer, status post-radiation 7 years previously, and liver cirrhosis (by prior computed

The mechanism leading to obstructive bioprosthetic

tomography imaging). Home medications included

valve thrombosis (OBPVT) was thought to be due to

aspirin, 81 mg; atorvastatin, 80 mg; metoprolol, 25 mg

the Sapien valve (Edwards Lifesciences) placed

twice a day; furosemide, 80 mg daily; metformin,

6 months before in a previously placed surgical valve.

1,000 mg twice daily; insulin; and baclofen. DIFFERENTIAL DIAGNOSIS. Given her clinical pre-

sentation of heart failure and severe stenosis of the bioprosthetic the

mitral

differential

valve

diagnosis

by

echocardiography,

included

obstructive

thrombus, pannus, endocarditis, or patient-prosthesis mismatch.

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

INVESTIGATIONS. Laboratory workup was signifi-

Sapien valve implantation, as well as the appearance

cant for elevated B-type natriuretic peptide (2,400 pg/

on TEE, the clinical suspicion was high for thrombus

ml). Complete blood count, comprehensive metabolic

and low for pannus.

panel, antinuclear antibodies, and coagulation labo-

There are no randomized controlled trials to guide

ratory values were unremarkable. Electrocardiog-

the use of thrombolytic therapy in patients with

raphy revealed normal sinus rhythm with a HR of 62

OBPVT. Most available data apply to patients with

beats/min and was otherwise normal. Chest radiog-

mechanical valve thrombosis. Studies using an

raphy showed bilateral pleural effusion and moderate

echocardiography-guided, slow-infusion, low-dose

interstitial edema. A transesophageal echocardiogram

fibrinolytic protocol in patients with mechanical PVT

(TEE) confirmed severe bioprosthetic MV stenosis and

have demonstrated high success rates (>90%) and low

also revealed a large echodensity encompassing the

complication rates (<2% embolic event rates and <2%

leaflets with restricted leaflet motion, which was

major bleeding rates; 0.8% mortality rate) (2–4). In

concerning for valve thrombosis (Figure 2, Videos 1A

the

and 1B).

Thrombosis and the prEdictors of outcomE) trial (2), 1

PROMETEE

(PROsthetic

MEchanical

valve

MANAGEMENT. Intravenous diuretics were adminis-

session of thrombolytic therapy achieved an initial

tered with good response. The patient’s oxygenation

success rate of 20%, and 8 sessions of slow-infusion,

requirements improved, and she was weaned to room

low-dose fibrinolytic therapy were required for a suc-

air. A follow-up chest radiograph revealed improve-

cess rate of 90%. The present patient likely had the

ment of pleural effusion and resolution of interstitial

valve obstruction from a thrombus with recent onset

edema. Therapeutic enoxaparin, which had been

given the successful result after 1 session of throm-

started at the outside hospital, was continued during

bolytic therapy. The 2017 American Heart Association/

the patient’s current hospitalization.

American College of Cardiology (AHA/ACC) focused

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Rrapo Kaso et al. Timely Management of Obstructive Prosthetic Valve Thrombosis

F I G U R E 1 TTE at Diagnosis

(A) Initial TTE shows thickening of the prosthetic valve leaflets, and (B) turbulent flow through the bioprosthetic valve on color Doppler, as well as elevated transmitral mean gradient, concerning for severe mitral stenosis of the bioprosthetic valve. TTE ¼ transthoracic echocardiography.

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F I G U R E 2 TEE Performed After Intravenous Diuresis

(A)TEE shows a large burden of thrombus. (B) Color Doppler shows turbulent flow through the bioprosthetic valve. (C) Continuous spectral Doppler confirms the elevated transmitral gradient with a mean gradient of 16.7 mm Hg after successful intravenous diuresis. See Videos 1A and 1B. TEE ¼ transesophageal echocardiography.

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F I G U R E 3 TTE after Treatment With Intravenous 25 mg of Alteplase Infused Over 25 Hours Without a Bolus

(A) Repeated TTE shows decreased thickening of the prosthesis leaflets, (B) laminar flow, and (C) improved transmitral mean gradient following fibrinolytic therapy. Abbreviations as in Figure 1.

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F I G U R E 4 TEE 24 Hours After Completion of Fibrinolytic Therapy

(A, B) TEE 24 h after completion of fibrinolytic therapy shows resolution of thrombus and (B) trace MR. (C) Continuous spectral Doppler shows a transmitral mean gradient of 4 mm Hg. See Videos 2A, 2B, 3A, and 3B. Abbreviation as in Figure 2.

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update of the 2014 AHA/ACC Guidelines for the Man-

regarding follow-up strategies, duration of anti-

agement of Patients with Valvular Heart Disease

coagulation, and adequacy of nonvitamin K antico-

recommends urgent initial treatment with either slow-

agulants. Novel oral anticoagulants for bioprosthetic

infusion, low-dose fibrinolytic therapy or emergency

valves have not been studied for efficacy and safety in

surgery for patients with a thrombosed left-sided

a large randomized trial (6). Most recent guidelines

mechanical prosthetic heart valve presenting with

(5) recommend that, for both aortic and mitral

symptoms of valve obstruction (5). Evidence from re-

bioprosthetic valves, in addition to aspirin, anti-

sults of thrombolytic therapy in patients with OBPVT

coagulation with warfarin, with an INR target of 2.5,

is largely limited to case reports, therefore only indi-

should be considered (Class IIa recommendation,

rect observational data are available regarding efficacy

weight of evidence/expert opinion is in favor of

and safety of thrombolytic therapy for OBPVT.

usefulness/efficacy as benefits outweighs risks.) in

The presence of atrial fibrillation, New York Heart

patients with a low risk of bleeding, for 3 to 6 months

Association functional class IV status, and higher

after surgery. However, there are no recommenda-

baseline thrombus area have been associated with

tions regarding anticoagulation therapy following

lower likelihood of successful treatment of OPVT by

treatment of valve-in-valve OBPVT with fibrinolytic

thrombolytic therapy (2). Major risk factors for sys-

therapy. The 2014 AHA/ACC valve guidelines state “in

temic embolic complications of thrombolytic therapy

patients with a bioprosthetic valve with embolic

include thrombus size of more than 0.8 cm 2 and a

events who are only on aspirin 75 mg to 100 mg daily,

history of cerebrovascular event (3). In PVT, the

a possible approach includes consideration of anti-

thrombus size imaged using TEE is a significant in-

coagulation with a VKA” (7). In addition, the duration

dependent predictor of outcome. Three-dimensional

of anticoagulation therapy is uncertain; however,

(3D) echocardiographic imaging has an important role

recurrence of BPVT 6 months following cessation of

in evaluation of mitral prosthesis, especially for

anticoagulation therapy in a successfully treated

visualizing nonobstructive thrombus, which may be

aortic BPVT has been reported (8). Therefore, the

missed with 2D echo.

authors recommend life-long anticoagulation therapy slow-

in this patient group (8). Recurrent OBPVT in the

infusion, low-dose fibrinolytic therapy was initiated

present patient, who is at high surgical risk, could

12 h after discontinuation of enoxaparin therapy, and

potentially result in a fatal event, and after discussion

coagulation laboratory values were confirmed to be

with the patient, it was recommended that anti-

within the normal range. Intravenous alteplase,

coagulation with warfarin would be life-long.

FOLLOW-UP. Echocardiographically

guided

25 mg, was infused over 25 h with no bolus. Immediately after the alteplase infusion was completed, a

CONCLUSIONS

heparin drip was initiated. TTE was performed which showed resolution of the MV obstruction, with

This case demonstrates the successful use of echo-

improvement of transmitral PG to 15 mm Hg and MG

cardiographically guided slow-infusion, low-dose

to 6 mm Hg (Figure 3). A TEE performed 24 h later

fibrinolytic therapy in a patient with obstructive

revealed resolution of the thrombus, unrestricted

thrombus of a bioprosthetic valve without any com-

mitral valve leaflets motion, and PG of 9 mm Hg and

plications. Further guidance is needed regarding the

MG of 4 mm Hg (Figure 4, Videos 2A, 2B, 3A, and 3B).

long-term management of patients with OBPVT after

There were no complications from the thrombolytic

successful thrombolytic therapy.

therapy. Warfarin therapy was initiated with an INR goal of 2 to 3, and she was subsequently discharged

ADDRESS FOR CORRESPONDENCE: Dr. Christopher

home. In addition, the patient was advised to

M. Kramer, Cardiovascular Division, University of

continue taking aspirin, 81 mg, daily.

Virginia Health System, 1215 Lee Street, Box 800158,

Even when medical therapy is successful in the treatment of OBPVT, additional questions remain

Charlottesville, Virginia 22908. E-mail: ckramer@ virginia.edu.

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Thrombosis and the prEdictors of outcomE: the ultra-slow PROMETEE trial. Am Heart J 2015;170: 409–18.

assessment of thrombolysis of prosthetic valve thrombosis: results of the international PRO-TEE registry. J Am Coll Cardiol 2004;43:77–84.

3. Tong AT, Roudaut R, özkan M, et al. Transesophageal echocardiography improves risk

4. Özkan M, Gündüz S, Biteker M, et al. Comparison of different TEE-guided thrombolytic

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regimens for prosthetic valve thrombosis: the TROIA trial. J Am Coll Cardiol Img 2013;6: 206–16. 5. Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2017;135: e1159–95.

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6. Sanaani A, Yandrapalli S, Harburger JM. Antithrombotic management of patients with prosthetic heart valves. Cardiol Rev 2018;26: 177–86. 7. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63:e57.

8. Yong MS, Grant R, Saxena P, Yadav S. Recurrent bioprosthetic valve thrombosis - should long-term anticoagulation be considered? Heart Lung Circ 2018;27:e70–2. KEY WORDS anticoagulants, bioprosthetic, mitral, thrombosis, thrombolysis, valves

AP PE NDIX For supplemental videos, please see the online version of this paper.