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Mechanical Aortic Valve Thrombus in Pregnancy: A Case Report

Meng, Marie-Louise MD*; Landau, Ruth MD*; Haythe, Jennifer MD; Takayama, Hiroo MD, PhD; Spellman, Jessica MD*

doi: 10.1213/XAA.0000000000000984
Case Reports
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Cardiac disease is one of the leading causes of maternal mortality in developed countries. The presence of a mechanical valve is a predictor of cardiac complications in obstetric patients, likely due to the challenges associated with pregnancy hypercoagulability and the imperative of meticulous management of anticoagulation throughout pregnancy, delivery, and the postpartum and to prevent the devastating event of a mechanical valve thrombosis. We report on the management of a pregnant woman with a mechanical aortic valve found to have a thrombus at 37 weeks gestation. It was decided to perform cesarean delivery to allow for a reoperative mechanical aortic valve replacement 24 hours thereafter.

From the Departments of *Anesthesiology

Medicine

Surgery, Columbia University Medical Center, New York, New York.

Accepted for publication January 14, 2019.

Funding: None.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal’s website.

Address correspondence to Marie-Louise Meng, MD, Department of Anesthesiology, 622 W. 168th St., New York, NY 10032. Address e-mail to mm3847@cumc.columbia.edu.

Cardiac disease is a leading cause of maternal mortality in developed countries. Pregnant women with mechanical heart valves have a 42% chance of morbidity due to the challenges of anticoagulation combined with underlying heart disease.1 Close anticoagulation monitoring and education regarding adherence to anticoagulation are essential. Options for anticoagulation during pregnancy are limited due to fetal complications associated with warfarin and challenges with achieving adequate anticoagulation with low-molecular-weight heparin.2 Valve durability and the need for chronic anticoagulation are considered when choosing a valve prosthesis in women of childbearing age. We report a pregnant woman with a mechanical aortic valve presenting at 37 weeks with a valve thrombus. The patient provided written consent for this publication.

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CASE

A 27-year-old pregnant woman G4P1 with a history of rheumatic heart disease requiring mechanical aortic valve replacement (St. Jude #23) at age 12 years presented at 37 weeks with acute-onset chest pain radiating to the back and arms. Her prior pregnancy was uneventful, managed with low-molecular-weight heparin throughout pregnancy, and trial of labor with epidural analgesia resulted in an uncomplicated term vaginal delivery. Anticoagulation was managed with warfarin between pregnancies.

During this pregnancy, therapeutic anticoagulation with 90 mg enoxaparin twice daily to a desired antifactor Xa level of 0.8–1.2 U/mL was intended, although the patient admitted to poor adherence. First trimester transthoracic echocardiogram revealed elevated peak velocity of 4.2 m/s across the mechanical aortic valve, elevated mean gradient of 37 mm Hg, and normal biventricular function.

On admission, maternal vital signs were as follows: blood pressure, 118/61 mm Hg; heart rate, 81 beats per minute; room air saturation, 100%; and temperature, 36.3°C. A 12-lead electrocardiogram revealed T-wave inversions in leads V1 through V3. Troponin levels peaked at 0.27 ng/mL (normal, <0.01 ng/mL). Coagulation tests were nontherapeutic. Trimester transthoracic echocardiogram demonstrated a mobile, tissue density mass (>1 cm) arising from the ventricular aspect of the aortic prosthesis consistent with the thrombus, pannus, degenerative changes, or vegetation (Supplemental Digital Content, Video, http://links.lww.com/AACR/A253; Figure 1). Peak velocity across the mechanical valve was 4.8 m/s with mean gradient of 56 mm Hg (Figure 2). Intravenous heparin was initiated at 1300–1800 U/h to achieve an activated partial thromboplastin time of twice the upper limit of normal. To mitigate the risk of a stroke or myocardial infarction, the decision was made to perform a semiurgent cesarean delivery and an aortic valve replacement 24 hours thereafter.

Figure 1.

Figure 1.

Figure 2.

Figure 2.

Heparin infusion was held for 4 hours to allow normalization of coagulation before placement of neuraxial anesthesia for the cesarean delivery, although the goal-activated partial thromboplastin time was not yet achieved (28.7 seconds; normal range, 23.9–34.7 seconds) on intravenous heparin 1300 U/h. Arterial and central venous access were obtained. A combined spinal epidural was provided (intrathecal dose: 3 mg bupivacaine and 10 μg fentanyl; epidural dose: 2% lidocaine with 1:200,000 epinephrine to achieve a T4 surgical block). Intravenous infusions of norepinephrine (2–4 µg/min) and vasopressin (2 U/h) were started immediately after neuraxial anesthesia to maintain blood pressure at the patient’s baseline. Femoral venous and arterial sheaths were placed in case extracorporeal membrane oxygenator support was required urgently. Cesarean delivery was performed. A live infant (Apgar scores: 8 and 9) was delivered. An oxytocin infusion (15 U/250 mL over 6 hours) was initiated. During uterine externalization, the patient reported chest pain radiating to the back and arms without any changes in hemodynamics. Trimester transthoracic echocardiogram demonstrated normal wall motion with no change in the appearance of the valve mass. Hemostasis was achieved (estimated blood loss, 800 mL). Epidural morphine 3 mg was given, and the epidural catheter was removed. The patient was transferred to the critical care unit. Intravenous heparin was resumed 6 hours postdelivery with the same activated partial thromboplastin time target.

Figure 3.

Figure 3.

Aortic valve replacement was performed the following morning. Inspection of the prosthesis revealed pannus and a subacute thrombus on the ventricular side of the mechanical aortic valve (Figure 3). The patient expressed a strong desire for another mechanical valve, had a history of good adherence to oral warfarin when not pregnant, and did not desire more children and so the aortic valve was replaced with a 23 OnX mechanical valve. Postbypass, transesophageal echocardiography revealed normal left ventricular function, mildly increased right ventricular size, and mildly reduced right ventricular function. The patient was transferred to the intensive care unit on norepinephrine (2 µg/min) and vasopressin (2 U/h) and extubated 2 hours later. Heparin infusion was initiated 30 hours after valve surgery, with a transition to warfarin 1 day later. Hemodynamic parameters were stable throughout the presurgical and postsurgical hospitalization (blood pressure, 90–120 s/50–70 s; heart rate, 55–85). The patient was discharged home 6 days after the valve replacement.

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DISCUSSION

Pregnant patients with mechanical valves are at risk of severe complications due to thrombosis and associated anticoagulation.3 During pregnancy, valve thrombosis occurs in 4.4% of mechanical mitral and 2.6% of mechanical aortic valves.1 Issues in this case included management of anticoagulation and thrombosis during pregnancy in a patient with a mechanical valve.

There are few options for anticoagulation in the obstetric setting. Warfarin has the lowest rate of maternal mortality and thromboembolic complications, although its use in the first trimester is limited by teratogenicity as it crosses the placenta.4,5 Unfractionated and low-molecular-weight heparin can be used during the first trimester because heparin does not cross the placenta. However, efficacy of heparin is lower than warfarin because heparin requirements can fluctuate and are likely increased in pregnancy due to increase in volume of distribution, increased renal clearance, placental heparinases, and heparin neutralizing proteins. These factors also pose challenges for appropriate monitoring of heparin levels.4–7 The American College of Cardiology recommends warfarin use in the first trimester if therapeutic international normalized ratio can be maintained with <5 mg/d warfarin.2 If warfarin dosing is >5 mg/d to achieve therapeutic international normalized ratio, then low-molecular-weight heparin is recommended with a target of peak antifactor Xa level of 0.8–1.2 U/mL 4–6 hours after low-molecular-weight heparin dose; dosing at 1 mg/kg twice daily is likely not sufficient to achieve this target.8,9 Antifactor Xa troughs (1 hour before dose) may be monitored to ensure appropriate anticoagulation.10 The optimal frequency of antifactor Xa testing is unknown, and once every 2 weeks is a usual practice.8 Inadequate anticoagulation can occur during the transition from warfarin to low-molecular-weight heparin; therefore, in hospital, medication transition should be planned for adequate monitoring of anticoagulation during this time.9 Warfarin can be used during the second trimester in patients with high risk of thrombosis and transitioned to heparin when delivery and neuraxial anesthesia are imminent.4,5,7 Choosing between low-molecular-weight heparin and warfarin requires consideration of thrombotic risk versus fetal complications and maternal preference.

Elevated gradients across a prosthetic valve are indicative of valve thrombosis, structural deterioration, prosthesis dysfunction, patient-prosthesis mismatch, or high-flow states (anemia, pregnancy). Here, the elevated gradients in the first trimester are suggestive of chronic pannus with subsequent acute thrombus. When valve thrombosis occurs in pregnancy, the decision to perform thrombolysis, thrombectomy, or valve surgery is made by considering clot burden, maternal instability, and fetal viability.9,11,12 Our symptomatic patient, with a term fetus, large pannus (>1 cm), and a history of elevated gradients suggestive of chronic pannus or structural valve deterioration, required urgent delivery and valve replacement.

In this case, thrombolysis and thrombectomy would likely not be effective based on size, chronicity, and underlying pannus. Thrombolysis with intravenous tissue plasminogen activator has been safely used in pregnancy. Tissue plasminogen activator does not cross

the placenta but carries the risks of systemic embolization and subchorionic bleeding, which can result in placental separation, uteroplacental insufficiency, fetal demise, and hemorrhage.13 A report of 28 episodes of valve thrombosis in preterm pregnant women demonstrated that a low-dose (25 mg), slow infusion of tissue plasminogen activator (6 hours) given up to 4 times resulted in successful resolution of thrombus with only 1 episode of placental hemorrhage.12 Fetal outcomes in this cohort included 5 miscarriages and 1 fetus with complete hearing loss.12 Therefore, if clot burden is low, thrombolysis is an option if the desire is to avoid surgery given that cardiac surgery performed during earlier gestations is associated with spontaneous abortion and preterm delivery.14 If the fetus is viable and surgery is necessary, it may be preferable to perform a cesarean delivery before valve surgery, because fetal mortality can be as high as 24% in women who undergo cardiopulmonary bypass.15

Sequential combined spinal epidural is the recommend anesthetic approach for cesarean delivery in patients with cardiac disease to avoid the risks of general anesthesia, which are greater in the context of cardiac disease and pregnancy.16 Our decision to provide a low-dose combined spinal epidural followed by supplemental epidural lidocaine created a titratable anesthetic without significant hemodynamic changes. The most likely explanation for the symptoms at the time of uterine externalization is venous air entry. Uterine externalization to a level above the right atrium causes micro-air bubbles to enter the venous circulation via exposed venous sinuses.17 Venous air increases pulmonary pressure compromising right heart function. Uterine externalization should be avoided in patients with compromised right heart function.

While mechanical valves are used for the benefit of durability in women of childbearing years, the optimal method for anticoagulation is unrefined. Valve thrombosis carries major risk, and thrombolysis may not be feasible, requiring valve replacement. Improved patient education is critical to prevent potential complications. E

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DISCLOSURES

Name: Marie-Louise Meng, MD.

Contribution: This author helped write and edit the manuscript.

Name: Ruth Landau, MD.

Contribution: This author helped edit the manuscript.

Name: Jennifer Haythe, MD.

Contribution: This author helped write and edit the manuscript.

Name: Hiroo Takayama, MD, PhD.

Contribution: This author helped edit the manuscript.

Name: Jessica Spellman, MD.

Contribution: This author helped write and edit the manuscript.

This manuscript was handled by: Kent H. Rehfeldt, MD.

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