Keywords
Bioprosthetic valve thrombosis - human menopausal gonadotropin - in vitro fertilization
Introduction
Bioprosthetic valves are the most common artificial valves used in women of childbearing
age. It has good hemodynamic properties and obviating the need for long-term anticoagulation.[1] The incidence of bioprosthetic valve thrombosis (BPVT) is low, but it may result
in fatal consequences.[1] BPVT has high mortality, and the treatment varies from medical treatment in mild
cases to surgical intervention in severely symptomatic patients.[1] Human menopausal gonadotropin (hMG) is commonly used to induce ovulation during
in vitro fertilization (IVF). In fact, various adverse effects have been reported
including venous and arterial thrombosis.[2]
Case Report
A 39-year-old female had a history of mitral bioprosthetic valve replacement (Medtronic
Mosaic®) due to rheumatic heart disease 2 years prior to hospitalization. Regular
follow-ups with her cardiologists were maintained, and the patient was asymptomatic
with a normal prosthetic function on serial echocardiograms. One month prior, the
patient sought treatment with in vitro fertilization and received 14 injections of
(450 IU) hMG. Few days later, she started complaining of progressively worsening shortness
of breath until she presented to the emergency department with a blood pressure level
of 70/40 mmHg, heart rate of 125 beat/min, and oxygen saturation around 84%. She was
hemodynamically unstable needing inotropic and ventilatory support. Ultimately, she
was transferred to the Intensive Care Unit for further management.
An emergent echocardiogram was performed. This was followed by a transesophageal echocardiography
(TEE) that showed ejection fraction of 55%, two oval-shaped masses on the mitral valve
leaflets (arrow) with restricted leaflet motion and a mean gradient of 34 mmHg, a
peak gradient of 51 mmHg, and velocity time integral (VTI) of 93 cm. The findings
with highly suggestive of BPVT are shown in [Figure 1].{Figure 1}
Figure 1: (a) Transesophageal echocardiography: two‑dimensional showed thickened mitral
valve leaflets (arrow) and color Doppler showed diastolic mitral inflow flow aliasing
jet due to blood flow acceleration, and (b) Continuous wave Doppler of mitral valve
inflow showed a significant increase in velocity
The initial complete blood count showed white blood cells of 8.1 × 103/μL, hematocrit
of 27.9%, and platelet count of 114 × 103/μL. Blood urea nitrogen was 36.7 mmol/l,
creatinine of 264 μmol/l, alanine transaminase (ALT) of 64 U/l, and international
normalized ratio was 1.9.
Cardiac surgery was immediately consulted, and the patient underwent emergent redo
mitral valve replacement surgery with a St. Jude mechanical valve. Intraoperative
findings of the thrombosed mitral valve are seen in [Figure 2]. While on cardiopulmonary bypass and after replacing the valve, a freely mobile
thrombus was seen in the left atrium [Figure 3]a and [Video 1] impinging on the leaflets of the mechanical valve [Figure 3]b. After exploring the pulmonary veins and removal of any existing thrombi, the final
TEE confirms normally functioning metallic mitral valve [Video 2]. Patient had uneventful
postoperative course and discharged 16 days after surgery; the follow-up echocardiography
showed normal mechanical valve function [Figure 4].
Figure 2: Intraoperative image showed a large thrombus in the bioprosthetic mitral
valve (arrows)
Figure 3: (a) First intraoperative transesophageal echocardiography showed freely
mobile large thrombus in the left atrium (arrows) and (b) second intraoperative transesophageal
echocardiography revealed immobile mitral valve leaflet (arrowhead)
Figure 4: Follow‑up echocardiography. (a) The mitral mean gradient 8.7 mmHg peak gradient
25 mmHg, pressure half‑time of 68 ms, and (b) the VTImv/ VTIlvot = 1.8, indicating
a normal prosthetic valve function
Discussion
Although the exact mechanisms of BPVT are not well understood, there are various underlying
factors related to valve thrombosis such as hemostatic activation which results in
hypercoagulable state, leaflets wall shear stress produced by blood flow perturbations,
and patient-related factors such as atrial fibrillation, renal insufficiency, obesity,
diabetes mellitus, and low cardiac output states.[3] The incidence of valve thrombosis is around (6%) post bioprosthetic mitral valve
implantation;[4],[5] moreover, BPVT represents 11.6% of totally explanted valves due to bioprosthetic
valve dysfunction.[6]
The diagnosis and differentiation of BPV dysfunction as a result of pannus versus
thrombus formation is challenging. However, thrombosed prosthetic valves have more
acute onset of symptoms which our patient had.[1] BPVT can be asymptomatic and detected by a routine echocardiography.[7] On the other hand, BPVT can be life-threatening and may result in severe symptoms,
hemodynamic instability, and rapid deterioration.[1] Commonly used echocardiographic features to help diagnose BPVT are an increase in
the mean transvalvular gradient >50% above baseline values within 5 years, thickened
leaflets, and restriction in leaflets mobility.[1],[8],[9]
The initial treatment of subclinical or mild BPVT in hemodynamically stable individuals
is a Vitamin K antagonist if no contraindications to anticoagulation.[1] However, in severely symptomatic and hemodynamically unstable patients, surgical
valve replacement might be indicated.[1]
Thromboembolic disease associated with ovarian stimulation syndrome is an uncommon
yet potentially fatal complication of IVF. A literature review by Jing and Yanping
[2] reported that a total of 112 cases of thromboembolism associated with ovulation
induction, 35.7% were arterial in origin, and 64.3% were venous, but no BPVT was reported.
Interestingly, Udell et al.[10] conducted a population-based cohort of 1,186,753 women, of whom 6979 gave birth
after fertility therapy and reported that women who had received fertility treatment
had significantly lower death, hospitalization for a major adverse cardiovascular,
thromboembolism, and heart failure after 10 years of follow-up. However, a very recent
analysis by Sennström et al.[11] reported that IVF results in twofold increase in the risk of thromboembolic events
when compared to non-IVF pregnancies. Moreover, hospitalized IVF patients due to ovarian
hyperstimulation syndrome had 100-fold increased risk of thromboembolic events when
compared to non-IVF pregnant population.
Conclusion
To the best of our knowledge, this is the first case of BPVT induced by hMG treatment
for IVF, successfully treated with surgery.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patient(s) has/have given his/her/their consent for his/her/their
images and other clinical information to be reported in the journal. The patients
understand that their names and initials will not be published and due efforts will
be made to conceal their identity, but anonymity cannot be guaranteed.
