Ross procedure after prosthetic valve thrombosis in a patient with antiphospholipid syndrome and recurrent bleeding

The Ross procedure allows replacement of a diseased aortic valve with pulmonary root autograft, possibly avoiding the highly thrombotic mechanical valves and immunologic deterioration of tissue valves in antiphospholipid syndrome (APS). Here, we present the use of the Ross procedure in a 42‐year‐old woman with mild intellectual disability, APS, and a complex anticoagulation history after she presented with thrombosis of her mechanical On‐X aortic valve previously implanted for non‐bacterial thrombotic endocarditis.


| INTRODUC TI ON
Antiphospholipid syndrome (APS) can affect the heart valves through the deposition of immune complexes. Surgery is indicated in severe valvular dysfunction, but valve selection can be difficult.
Here, we demonstrate the utility of the Ross procedure in a young patient with primary APS and an On-X valve implanted for prior nonbacterial thrombotic endocarditis (NBTE) suffering prosthetic valve thrombosis (PVT) due to poor anticoagulant adherence. MN, USA) trans-septal mitral valve repair due to significant clot burden involving the anterior mitral leaflet. One month before the current presentation, she was admitted with hemoptysis to an outside hospital where her warfarin was withheld for 1 week, diffuse alveolar hemorrhage was ruled out, and she was diagnosed with pneumonia. She had resumed her warfarin without the prescribed enoxaparin bridge and was currently unsure of her international normalized ratio (INR) levels.

| C A S E REP ORT
The patient had a mild intellectual disability but was independent with instrumental activities of daily living and had strong family support. Her anticoagulation history was complicated primarily by menorrhagia leading to poor compliance and recurrent deep vein thromboses and pulmonary emboli. She had failed rivaroxaban and resumed warfarin with inferior vena cava filter placement 7 months before the NBTE. She was bridged from heparin to warfarin following AVR (INR goal 2.0-3.0) and continued low-dose aspirin. INR monitoring was planned with her family physician close to home.
Transthoracic echocardiography (TTE) 3 months post-operation had shown a peak/mean aortic valve gradient of 49/30 mm Hg from 28/17 mm Hg immediately post-operation ( Figure 1A,B), which was being monitored given the lack of symptoms. Her history was otherwise significant for hypertension, hyperlipidemia, diabetes, heart failure with preserved ejection fraction, chronic kidney disease stage 3b, and class 3 obesity (body mass index: 45.7 kg/m 2 ).
On evaluation, the patient had a systolic murmur, jugular vein distention, and 2+ bilateral lower extremity edema. She was admitted to our inpatient cardiology service for further evaluation. Admission The patient was seen in our cardiology clinic 2 weeks postoperation and was asymptomatic. She was therapeutic on warfarin (INR goal 2.5-3.5) and low-dose aspirin without recurrence of bleeding. Her menorrhagia was controlled with a progestin intrauterine device and with plans to transition to medroxyprogesterone acetate injections. Repeat TTE 4 (peak/mean of 13/7 mm Hg) and 12 (peak/ mean of 9/4 mm Hg) months post-operation were stable without change in the degree of AR or valve gradients. Plans were made to utilize chromogenic factor X testing should fluctuations in INR recur.

Valve selection can be controversial in hypercoagula-
ble states, such as antiphospholipid syndrome, given the concern for the immunologic deterioration of tissue valves in younger patients and the higher thrombotic risk of mechanical valves despite their superior durability.
2. The Ross procedure is an option worth considering in young patients with such disorders to minimize the risk of prosthetic valve deterioration or thrombosis through pulmonary autograft.

| DISCUSS ION
APS is characterized by recurrent vascular thrombosis and/or pregnancy morbidity with laboratory evidence of positivity for antiphospholipid antibodies. 1 Valvular dysfunction, such as NBTE, can occur due to immune complex deposition on valve leaflets, mainly affecting the mitral over aortic valve (61.9% vs 23.8%). 1,2 Most cases of NBTE cause mild dysfunction and are medically treated with prompt anticoagulation. 2 The role of surgery for NBTE is unclear, with common indications being large vegetations, severe valvular dysfunction, and recurrent thromboembolism. 2 Valve selection is controversial in APS given the concern for the immunologic deterioration of tissue valves in younger patients and the higher thrombotic risk of mechanical valves (MVs) despite their superior durability. 3 PVT is a rare but potentially fatal complication of MVs. 1 The On-X valve is a bileaflet MV with a novel design to create laminar flow with limited turbulence and reduced thrombogenicity; however, reports of its use in hypercoagulable states are limited. 4  Patients with APS can be heterogenous in their antiphospholipid antibody profile with different thrombotic risks based on the pattern of positivity. 6 Because of this, risk scores have been proposed, which expand the role of antibody testing from qualitative diagnostic markers to quantitative risk assessment. The antiphospholipid score (aPL-S) was the first to use the antiphospholipid profile to predict future thrombotic events. 7 However, this score requires extensive information, including antibody titers and immunoglobin subtypes, hence the development of the modified aPL-S to simplify its use. 8 Following aPL-S, the Global Anti-Phospholipid Syndrome Score (GAPSS) was proposed, which included simplified antibody information but also had classical thrombotic risk factors (hypertension and hyperlipidemia). 9 Both risk scores are promising with validation across different cohorts, but their clinical use has been limited given the inclusion of the rarely performed anti-phosphatidylserine/prothrombin antibody testing in both scores, lack of standardized enzyme-linked immunoassay techniques for antibody testing in different institutions, and score development in autoimmune patients from single-center cohorts. 6 The latter concern particularly alters their utility in nonautoimmune patients. normalize INR; however, its use is limited by cost and availability. 1 Our patient's serology was positive for anticardiolipin and beta-2 glycoprotein antibodies but indeterminate for lupus anticoagulant on 2 separate occasions with plans to repeat. Although she had previously failed rivaroxaban, she had never failed warfarin since her thrombosis occurred when she was subtherapeutic with her INR on both point-of-care and whole blood testing with self-reported poor adherence. Therefore, the decision was made for continued anticoagulation with warfarin and closer whole blood INR monitoring by our institution through a remote laboratory near her home.

| CON CLUS IONS
We present the complex case of a patient with APS and prior NBTE who had PVT of an On-X valve due to recurrent bleeding and limiting anticoagulation adherence. In addition to ensuring close followup and medication adherence, novel methods must be considered to lower the risk of PVT recurrence as feasible. The promising data around the Ross procedure from experienced centers may indicate it as a treatment option in hypercoagulable states.

AUTH O R CO NTR I B UTI O N S
Acquisition and interpretation of data: SM, OZB, HW; drafting the

FU N D I N G I N FO R M ATI O N
None.

CO N S E NT
The patient gave written informed consent to use anonymized clinical data and pictures for publication.