Cardiovascular Revascularization Medicine, 2018-07-01, Volume 19, Issue 5, Pages 536-539, Copyright © 2017 Elsevier Inc. Abstract Trancatheter heart valve (THV) thrombosis is effectively treated with anticoagulation but alternative therapies are required when a faster gradient reduction is needed. Open heart surgery has been rarely performed due to the high perioperative mortality and only five cases have been described so far. Here we describe a case of emergent surgical explantation for THV thrombosis after a valve-in-valve. A 67 years old man underwent transcatheter aortic valve implantation for a failed surgical bioprosthesis Epic 21 mm (St. Jude Medical; St. Paul, Minnesota, US). A CoreValve 23 mm (Medtronic, Minneapolis, Minnesota, US) was implanted through femoral access under conscious sedation without complications. Mean transvalvular gradient was effectively reduced (33 mm Hg vs 16 mm Hg) with no more than mild residual aortic regurgitation. After 8 days the patient was discharged on dual antiplatelet therapy but was readmitted to the intensive care unit for pulmonary oedema 13 days later. Echocardiography showed a raised transvalvular mean gradient (mean gradient change from discharge = 15 mm Hg) without aortic regurgitation. Heart Team decided for emergent open heart surgery for the hemodynamic instability. On direct inspection THV was well positioned inside the surgical bioprosthesis but two cusps were covered by thrombus which markedly restricted their mobility. The THV and the former surgical valve were explanted and a new larger stented bioprosthesis was implanted. Thrombosis of the THV was confirmed on microscopic examination which showed no signs of inflammation or degeneration. The patient was discharged after 1 month and the 3 month follow up showed stable transvalvular gradients. Highlights Clinical Transcatheter Heart Valve thrombosis is uncommon. Anticoagulation is the treatment of choice. Surgical explantation is deserved for cases with haemodynamic deterioration or resistant to anticoagulation. The optimal antithrombotic management in specific subsets at increased valve thrombosis risk has not been clarified yet. 1 Introduction Transcatheter heart valve (THV) thrombosis is asymptomatic in the majority of patients. The most frequent diagnostic sign is a raised transvalvular gradient with or without direct thrombus visualization on imaging . THV thrombosis manifests earlier than structural valve degeneration and is reversible in the majority of cases if anticoagulation is promptly initiated. Open heart surgical explantation of the thrombosed THV is deserved for cases resistant to anticoagulantion or with hemodynamic instability and, to our knowledge, it has been performed only once after a valve in valve procedure (ViV). 2 Case presentation A 67 years old male underwent ViV for a failed biological stented aortic valve Epic 21 mm (St. Jude Medical; St. Paul, Minnesota, US) implanted 8 years before. The degenerated bioprosthesis was severely stenotic (mean transvalvular gradient = 33 mm Hg) and regurgitant. The patient was in New York Heart Association class III and left ventricular ejection fraction was reduced (ejection fraction = 35%). The Heart Team decided for a ViV procedure because reoperation was considered at high risk mainly for technical reasons (Society of Thoracic Surgeons predicted risk of mortality = 3.6%). A CoreValve 23 mm (Medtronic; Minneapolis, Minnesota, US) was delivered inside the failed surgical valve through trans-femoral access under conscious sedation ( Fig. 1 ). The procedure was successful with significant hemodynamic improvement (post-TAVI mean transvalvular gradient = 16 mm Hg) and only mild residual aortic regurgitation. The patient had no complications during the hospital stay and he was discharged after 8 days on aspirin plus clopidogrel for 3 months. 13 days after discharge he was admitted to the intensive care unit for heart failure needing inotropic support. Transvalvular gradients were increased from discharge (mean gradient = 31 mm Hg, peak gradient = 48 mm Hg, mean gradient change = 15 mm Hg) without significant aortic regurgitation ( Fig. 2 A ). The transthoracic echocardiography could not properly display the THV leaflets due to the presence of the previous surgical valve but the timing of presentation and the absence of regurgitation strongly suggested valve thrombosis ( Fig. 2 B). Due to the hemodynamic instability the Heart Team decided for bailout open heart surgery despite the high surgical risk. On direct inspection the THV was well positioned inside the surgical valve and the aortic surface of two cusps was covered by thrombus which restricted leaflets mobility ( Fig. 3 A ). The remaining leaflet was pliable and without thrombotic apposition. No evidence of calcifications, pannus or perforations was found on the THV on macroscopic examination. The histological analysis revealed the presence of calcifications on the surgical valve whereas the leaflets of the THV did not show any sign of degeneration. The presence of thrombus without inflammation was confirmed on the microscopic examination ( Fig. 3 B–D). Fig. 1 Transcatheter valve in valve procedure. A : Radiopaque sewing ring of the stented surgical bioprosthesis (Black Arrow). B : Severe Aortic Regurgitation before TAVI. C : Successful revalving with a CoreValve 23 mm. (Black Arrow: Sewing ring of the surgical valve). D : Supra-annular position (white arrow) of the CoreValve (Medtronic) (black line: sewing ring plane). Fig. 2 Transthoracic echocardiography. A : Increased transvalvular gradient. B : 4 chamber apical view showing the CoreValve. C : Hemodynamic parameters after the surgical explantation. D : Follow-up hemodynamic parameters. Fig. 3 Explanted transcatheter and surgical heart valve macroscopic and microscopic examination A : Thrombus covering the aortic surface of two CoreValve cusps B : Histology of the thrombus with fibrin, red blood cells and some trapped inflammatory cells (Hematoxylin-Eosin, 4 X) C : Site of thrombus implantation on the CoreValve cusp with fibrin, red blood cells and few macrophages. The underlying leaflet has no signs of inflammation or degeneration (Hematoxylin-Eosin, 10 X) D : Degenerated leaflet of the surgical valve with heavy calcifications (Hematoxylin-Eosin, 10 X). A stented valve Epic 25 mm (St. Jude Medical; St. Paul, Minnesota, US) was implanted. Post-operative mean gradient was 17 mm Hg (peak gradient = 30 mm Hg) and the patient was discharged after 30 days ( Fig. 2 C). A transthoracic echocardiogram 3 months after discharge showed stable hemodynamic parameters (mean gradient = 15 mm Hg, peak gradient = 25 mm Hg) ( Fig. 2 D). 3 Discussion Clinical THV thrombosis can cause flow obstruction, heart failure symptoms, stroke and may predispose to subsequent structural valve degeneration. Anticoagulation demonstrated to reduce transvalvular gradients in most patients and it is the first choice treatment. Anticoagulation needs days or weeks to be effective therefore alternative therapies have been used especially in symptomatic patients requiring a faster gradient reduction. Thrombolysis has been used to treat surgical valve thrombosis especially on mechanical prostheses but to the best of our knowledge it has never been used to treat THV thrombosis. Transcatheter revalving of the thrombosed valve can relieve the flow obstruction leading to hemodynamic improvement and can be an alternative option. This procedure was used to treat an early CoreValve (Medtronic; Minneapolis, Minnesota, US) dysfunction which was initially thought to be related to pannus formation. The patient died 16 days after the procedure and the autopsy revealed that thrombosis was the cause of the dysfunction of the first implanted THV and that also the second THV was involved. Open heart surgical explantation of the thrombosed valve is a last option because it carries a very high risk of perioperative mortality. At the present surgical explantation for THV thrombosis has been reported in five patients ( Table 1 ). Three underwent TAVI for native aortic valve stenosis, one for transcatheter CoreValve (Medtronic; Minneapolis, Minnesota, US) dysfunction with severe regurgitation and the last for a failed stented surgical bioprosthesis (Mosaic R 21 mm; Medtronic; Minneapolis, Minnesota, US). Only one of them was on anticoagulation and two events happened during the first month. Valve thrombosis involved three Sapien 23 mm (Edwards Lifesciences; Irvine, California, US), one Sapien 3 20 mm (Edwards Lifesciences; Irvine, California, US), and one CoreValve 26 mm (Medtronic; Minneapolis, Minnesota, US). All patients experienced worsening dyspnea or overt heart failure with a raised mean transvalvular gradient (from 11 ± 6 mm Hg to 44 ± 9 mm Hg). In addition Computed tomography or Transoesophageal echocardiography (TOE) showed findings compatible with thrombosis in three cases. Open heart surgery always confirmed THV thrombosis and one patient died after the operation. Table 1 Cases of surgical transcatheter heart valve explantation for valvular thrombosis. AS = Aortic Stenosis; NYHA = New York Heart Association; CT = Computed Tomography; TAVI = Transcatheter Aortic Valve Implantation; THV = Transcatheter Heart valve; TOE = Transoesophageal Echocardiography; NA : Not applicable. Recently valve in valve procedures along with the lack of anticoagulation have been associated with an increased risk of valve degeneration and thrombosis. ViV procedures can lead to a greater alteration of flow dynamic in the aortic root sinuses compared to TAVI for native valves. Moreover the THV is constrained inside the rigid sewing ring when stented prostheses are treated with an increased risk of under-expansion, especially if the internal diameter of the surgical prosthesis is small. All together these factors can increase thrombotic risk. In the present case the surgical bioprosthesis was small with a stent internal diameter of 19 mm (true internal diameter = 16.5 mm) and the risk of patient prosthesis mismatch was high. A self-expandable CoreVale 23 mm (Medtronic; Minneapolis, Minnesota, US) was implanted because the post-procedural effective area was expected to be higher owing to its supra-annular position but at the same time the high diameter oversizing (39%) might have caused valve under-expansion predisposing to the subsequent thrombosis. 4 Conclusion We reported the second case of surgical valve explantation for THV thrombosis after a valve in valve procedure; the first involving a self-expandable CoreValve (Medtronic; Minneapolis, Minnesota, US). Clinical THV thrombosis is a rare complication of TAVI and the cases which had required an urgent treatment are even less common. Specific subsets of patients, including those receiving a valve in valve, seem at increased risk and they should be carefully monitored to detect early signs of thrombosis. Recently the 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease gave a grade IIb (LOE B - NR) recommendation for Warfarin in the first three months after TAVI for patients at low bleeding risk. Ongoing trials will shed light on whether anticoagulation should be routinely prescribed after TAVI or it should be reserved for patients at increased thrombotic risk such as those treating small surgical bioprostheses. Authors have no conflicts of interest to disclose. No financial support for the realisation of this manuscript. 1 Co-first authors.