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Early Thrombosis of a Tricuspid Annuloplasty Ring and Mild Hyperhomocysteinemia
Early Thrombosis of a Tricuspid Annuloplasty Ring and Mild Hyperhomocysteinemia Mario Castaño, MD, PhD, Javier Gualis, MD, PhD, Carlos E. Martín, MD, Jesús Gómez-Plana, MD, Pilar Mencía, MD, David Alonso, MD, and José A. Rodríguez, MD, PhD Departments of Cardiac Surgery, Cardiology, and Hematology, Hospital de León, León, Spain
Tricuspid annuloplasty ring thrombosis is an extremely infrequent pathology, and no evidence-based antithrombotic management has been described. We present the case of a 40-year-old female with isolated mild hyperhomocysteinemia and early ring thrombus formation after surgical primary closure of an atrial septal defect and ring tricuspid annuloplasty. Clinical management, antithrombotic treatment, and hyperhomocysteinemia implications are discussed. (Ann Thorac Surg 2011;92:e125– 6) © 2011 by The Society of Thoracic Surgeons
T
hromboembolic complications after mitral valve repair procedures are infrequent but well recognized. However, early thrombosis of a tricuspid annuloplasty ring is exceedingly rare, and no consensus exists about its prevention or management. We report the case of a 40-year-old female with no preoperative comorbidities and a history of primary atrial septal defect (ASD) closure and a tricuspid annuloplasty with a 30-mm Edwards MC-3 ring (Edwards Lifesciences, Irvine, CA) for a secundum type ASD, moderate tricuspid regurgitation (TR), significant tricuspid annular dilatation, and mild pulmonary hypertension. The postoperative course was uneventful and no postoperative antithrombotic therapy was administered. During routine transthoracic echocardiography 1 month after surgery, no interatrial shunt or tricuspid regurgitation were observed, mean transtricuspid gradient was 6 mm Hg, and two mobile masses (up to 19 mm in diameter; Fig 1) were detected over the prosthetic ring. The patient was asymptomatic. White blood cell count, c-reactive protein, procalcitonin, fibrin degradation products, and d-dimers were within normal ranges. No signs of pulmonary embolism were apparent on a computed tomographic scan. Bacterial and fungal blood cultures and serologies were persistently negative. Because of suspected tricuspid annuloplasty ring thrombosis (TART), double anticoagulation therapy with acenocoumarol (initial international normalized ratio (INR) target of 2 to 3) plus full anticoagulation doses of lowmolecular-weight heparin (LMWH) and low-dose aspirin (100 mg daily) were administered. The mass size was significantly reduced after 1 week. LMWH was administered for during 3 additional weeks and then stopped. Preliminary hypercoagulability tests showed isolated
Accepted for publication June 22, 2011. Address correspondence to Dr Castaño, Department of Cardiac Surgery, Hospital de León, Altos de Nava s/n 24080 León, Spain; e-mail: [email protected].
© 2011 by The Society of Thoracic Surgeons Published by Elsevier Inc
Fig 1. Tricuspid annuloplasty ring thrombus (arrow).
mild hyperhomocysteinemia without MTHFR mutation and dietary modification was prescribed. Three months later the patient remained asymptomatic, but a control transthoracic echocardiography revealed persistent thrombus. LMWH treatment was restarted until an INR target of 3 to 4 was achieved, and the daily aspirin dose was increased to 300 mg. Complete thrombus disappearance was confirmed echocardiographically 6 months after the initial diagnosis. Complete hypercoagulability screening panel during oral anticoagulant therapy bridging with LWMH revealed no additional disorders and homocysteine levels normalization. Oral anticoagulant and antiplatelet therapy was kept unchanged during 6 additional months. After echocardiographic confirmation of no recurrent thrombosis, oral anticoagulation treatment was stopped. Nine months after isolated high-dose antiplatelet therapy and diet vitamin supplementation, the patient remains asymptomatic with no evidence of intracardiac thrombus and normal transtricuspid gradients.
Comment Thromboembolic complications after mitral valve repair have been described. Although some recommend vitamin-K antagonists after these procedures for 3 months [1], there is no definite consensus because of a lack of evidence-based data. Although suture line thrombosis of primary closure ASD has been previously reported and systematic postoperative oral anticoagulant therapy after these procedures has been advised [2], to our knowledge there are no previous reports of early postoperative TART in this or, more surprisingly, other more common settings. For this reason, although right-sided prosthetic materials have demonstrated a higher thrombotic potential than their left-sided counterparts, there are no postoperative antithrombotic management recommendations after tricuspid valve repair in current practice guidelines. The silent course of most right-sided thromboembolisms and the extremely frequent association between 0003-4975/$36.00 doi:10.1016/j.athoracsur.2011.06.072
e126
CASE REPORT CASTAÑO ET AL TRICUSPID ANNULOPLASTY RING THROMBOSIS AND HOMOCYSTEINE
tricuspid procedures and other indications for postoperative anticoagulation (e.g., concomitant atrial fibrillation, left-sided valvular surgery) may contribute to the exceedingly low incidence of this diagnosis. Emerging evidence suggests that preoperative tricuspid annular dilatation is a long-term predictor for persistent, increasing, or recurrent TR and poor outcomes after mitral valve procedures [3]. For this reason, more liberal indications for tricuspid ring annuloplasty are being postulated. Our patient had increased homocysteine levels. Hyperhomocysteinemia is a common finding in the general population, specifically in cardiac surgical patients because of significant epidemiologic evidence linking homocysteine with cardiovascular disease. Approximately two in five patients undergoing cardiac surgery have elevated homocysteine values [4]. Homocysteine is an amino acid produced by conversion of methionine and low plasmatic levels are normally found; however, genetic enzymatic defects can increase them. Vitamin B12 and folic acid intake may enhance the reduced methylation potential induced by homocysteine. Even mild, hyperhomocysteinemia reduces natural endothelial thromboresistance and decreases plasma fibrinolytic capacity [5]. In addition, homocysteine increases thromboxane production and platelet aggregation [6]. As a consequence, hyperhomocysteinemia is an established risk factor for coronary disease, stroke, and deep venous thrombosis. In a recent report, hyperhomocysteinemia has been independently related with worse outcomes after cardiac surgical procedures [4], but interestingly no relationship between this entity and valve-related thromboembolic events has been previously highlighted. Our patient had no other procoagulant disorder but mildly increased homocysteine levels. When valvular prosthetic thrombosis is diagnosed, there is no consensus about the treatment of choice. The American Heart Association (AHA) guidelines [7] consider that fibrinolytic therapy is reasonable for thrombosed right-sided prosthetic heart valves with a large clot burden. This strategy has been successful in postoperative ASD patients as well [2]; however, in our case, the early presentation after a recent major surgical procedure precluded its use. Excellent results have been published recently with a prolonged combination of heparin and vitamin-K antagonist for early nonobstructive thrombosis of mechanical mitral prostheses [8]. Similar treatment is recommended by AHA guidelines after partially successful thrombolysis of left-sided prosthesis thrombosis [7]. Given the absence of clinical, thromboembolic or hemodynamic compromise in our patient, a nonsurgical management was indicated and anticoagulation with a relatively high INR target (finally, INRs between 3 and 4 were needed) and two periods of reinforcing LMWH were administered. Aspirin irreversibly blocks the formation of thromboxane A2 in platelets. High-dose aspirin was added for homocysteine-induced thromboxane A2 reduction and additional inhibition of
Ann Thorac Surg 2011;92:e125– 6
platelet activation and aggregation. As previously stated, complete thrombus disappearance was not evident until 6 months of combined therapy. A close clinical, analytical, and echocardiographic follow-up was performed for prevention and early detection of thromboembolic or bleeding complications. In conclusion, we think that mildly preoperative elevated homocysteine levels with no additional thromboembolic risk factors may warrant a not yet established period of postoperative anticoagulation and, probably, long-life antiplatelet treatment and vitamin supplementation in patients with isolated tricuspid valve repair and other similar clinical scenarios. This recommendation remains speculative and needs to be tested in future investigations, but more attention to preoperative homocysteine levels is surely advisable. In addition, in the setting described herein, TART may be treated with a variable period of double anticoagulation therapy plus anti-aggregation followed by high doses of oral anticoagulation and aspirin. Isolated long-life antiplatelet treatment is probably advisable after thrombus resolution in patients without MTHFR mutation. We should reserve surgical intervention for persistent or recurrent thrombosis complicated with thromboembolic or valveobstruction related events.
References 1. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007;28:230 – 68. 2. Dinckal MH, Davutoglu V, Soydinc S, Akdemir I, Aksoy M. Large thrombus at the site of primary sutured atrial septal defect associated with pulmonary embolism and treatment by thrombolysis. Echocardiography 2003;20:535– 8. 3. Raja SG, Dreyfus GD. Basis for intervention on functional tricuspid regurgitation. Semin Thorac Cardiovasc Surg 2010; 22:79 – 83. 4. Ranucci M, Ballotta A, Frigiola A, et al. Preoperative homocysteine levels and morbidity and mortality following cardiac surgery. Eur Heart J 2009;30:995–1004. 5. Colucci M, Cattaneo M, Martinelli I, Semeraro F, Binetti BM, Semeraro N. Mild hyperhomocysteinemia is associated with increased TAFI levels and reduced plasma fibrinolytic potential. J Thromb Haemost 2008;6:1571–7. 6. Coppola A, Davi G, De Stefano V, Mancini FP, Cerbone AM, Di Minno G. Homocysteine, coagulation, platelet function, and thrombosis. Semin Thromb Hemost 2000;26:243–54. 7. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease). Circulation 2008;118: e523– 61. 8. Laurent M, Lelong B, Verhoye JP, et al. Prolonged heparin and vitamin-K-antagonist regimen for early non-obstructive thrombosis of mechanical mitral valve prostheses. J Heart Valve Dis 2008;17:533– 41.
Tricuspid annuloplasty ring thrombosis is an extremely infrequent pathology, and no evidence-based antithrombotic management has been described. We present the case of a 40-year-old female with isolated mild hyperhomocysteinemia and early ring thrombus formation after surgical primary closure of an atrial septal defect and ring tricuspid annuloplasty. Clinical management, antithrombotic treatment, and hyperhomocysteinemia implications are discussed. (Ann Thorac Surg 2011;92:e125– 6) © 2011 by The Society of Thoracic Surgeons
T
hromboembolic complications after mitral valve repair procedures are infrequent but well recognized. However, early thrombosis of a tricuspid annuloplasty ring is exceedingly rare, and no consensus exists about its prevention or management. We report the case of a 40-year-old female with no preoperative comorbidities and a history of primary atrial septal defect (ASD) closure and a tricuspid annuloplasty with a 30-mm Edwards MC-3 ring (Edwards Lifesciences, Irvine, CA) for a secundum type ASD, moderate tricuspid regurgitation (TR), significant tricuspid annular dilatation, and mild pulmonary hypertension. The postoperative course was uneventful and no postoperative antithrombotic therapy was administered. During routine transthoracic echocardiography 1 month after surgery, no interatrial shunt or tricuspid regurgitation were observed, mean transtricuspid gradient was 6 mm Hg, and two mobile masses (up to 19 mm in diameter; Fig 1) were detected over the prosthetic ring. The patient was asymptomatic. White blood cell count, c-reactive protein, procalcitonin, fibrin degradation products, and d-dimers were within normal ranges. No signs of pulmonary embolism were apparent on a computed tomographic scan. Bacterial and fungal blood cultures and serologies were persistently negative. Because of suspected tricuspid annuloplasty ring thrombosis (TART), double anticoagulation therapy with acenocoumarol (initial international normalized ratio (INR) target of 2 to 3) plus full anticoagulation doses of lowmolecular-weight heparin (LMWH) and low-dose aspirin (100 mg daily) were administered. The mass size was significantly reduced after 1 week. LMWH was administered for during 3 additional weeks and then stopped. Preliminary hypercoagulability tests showed isolated
Accepted for publication June 22, 2011. Address correspondence to Dr Castaño, Department of Cardiac Surgery, Hospital de León, Altos de Nava s/n 24080 León, Spain; e-mail: [email protected].
© 2011 by The Society of Thoracic Surgeons Published by Elsevier Inc
Fig 1. Tricuspid annuloplasty ring thrombus (arrow).
mild hyperhomocysteinemia without MTHFR mutation and dietary modification was prescribed. Three months later the patient remained asymptomatic, but a control transthoracic echocardiography revealed persistent thrombus. LMWH treatment was restarted until an INR target of 3 to 4 was achieved, and the daily aspirin dose was increased to 300 mg. Complete thrombus disappearance was confirmed echocardiographically 6 months after the initial diagnosis. Complete hypercoagulability screening panel during oral anticoagulant therapy bridging with LWMH revealed no additional disorders and homocysteine levels normalization. Oral anticoagulant and antiplatelet therapy was kept unchanged during 6 additional months. After echocardiographic confirmation of no recurrent thrombosis, oral anticoagulation treatment was stopped. Nine months after isolated high-dose antiplatelet therapy and diet vitamin supplementation, the patient remains asymptomatic with no evidence of intracardiac thrombus and normal transtricuspid gradients.
Comment Thromboembolic complications after mitral valve repair have been described. Although some recommend vitamin-K antagonists after these procedures for 3 months [1], there is no definite consensus because of a lack of evidence-based data. Although suture line thrombosis of primary closure ASD has been previously reported and systematic postoperative oral anticoagulant therapy after these procedures has been advised [2], to our knowledge there are no previous reports of early postoperative TART in this or, more surprisingly, other more common settings. For this reason, although right-sided prosthetic materials have demonstrated a higher thrombotic potential than their left-sided counterparts, there are no postoperative antithrombotic management recommendations after tricuspid valve repair in current practice guidelines. The silent course of most right-sided thromboembolisms and the extremely frequent association between 0003-4975/$36.00 doi:10.1016/j.athoracsur.2011.06.072
e126
CASE REPORT CASTAÑO ET AL TRICUSPID ANNULOPLASTY RING THROMBOSIS AND HOMOCYSTEINE
tricuspid procedures and other indications for postoperative anticoagulation (e.g., concomitant atrial fibrillation, left-sided valvular surgery) may contribute to the exceedingly low incidence of this diagnosis. Emerging evidence suggests that preoperative tricuspid annular dilatation is a long-term predictor for persistent, increasing, or recurrent TR and poor outcomes after mitral valve procedures [3]. For this reason, more liberal indications for tricuspid ring annuloplasty are being postulated. Our patient had increased homocysteine levels. Hyperhomocysteinemia is a common finding in the general population, specifically in cardiac surgical patients because of significant epidemiologic evidence linking homocysteine with cardiovascular disease. Approximately two in five patients undergoing cardiac surgery have elevated homocysteine values [4]. Homocysteine is an amino acid produced by conversion of methionine and low plasmatic levels are normally found; however, genetic enzymatic defects can increase them. Vitamin B12 and folic acid intake may enhance the reduced methylation potential induced by homocysteine. Even mild, hyperhomocysteinemia reduces natural endothelial thromboresistance and decreases plasma fibrinolytic capacity [5]. In addition, homocysteine increases thromboxane production and platelet aggregation [6]. As a consequence, hyperhomocysteinemia is an established risk factor for coronary disease, stroke, and deep venous thrombosis. In a recent report, hyperhomocysteinemia has been independently related with worse outcomes after cardiac surgical procedures [4], but interestingly no relationship between this entity and valve-related thromboembolic events has been previously highlighted. Our patient had no other procoagulant disorder but mildly increased homocysteine levels. When valvular prosthetic thrombosis is diagnosed, there is no consensus about the treatment of choice. The American Heart Association (AHA) guidelines [7] consider that fibrinolytic therapy is reasonable for thrombosed right-sided prosthetic heart valves with a large clot burden. This strategy has been successful in postoperative ASD patients as well [2]; however, in our case, the early presentation after a recent major surgical procedure precluded its use. Excellent results have been published recently with a prolonged combination of heparin and vitamin-K antagonist for early nonobstructive thrombosis of mechanical mitral prostheses [8]. Similar treatment is recommended by AHA guidelines after partially successful thrombolysis of left-sided prosthesis thrombosis [7]. Given the absence of clinical, thromboembolic or hemodynamic compromise in our patient, a nonsurgical management was indicated and anticoagulation with a relatively high INR target (finally, INRs between 3 and 4 were needed) and two periods of reinforcing LMWH were administered. Aspirin irreversibly blocks the formation of thromboxane A2 in platelets. High-dose aspirin was added for homocysteine-induced thromboxane A2 reduction and additional inhibition of
Ann Thorac Surg 2011;92:e125– 6
platelet activation and aggregation. As previously stated, complete thrombus disappearance was not evident until 6 months of combined therapy. A close clinical, analytical, and echocardiographic follow-up was performed for prevention and early detection of thromboembolic or bleeding complications. In conclusion, we think that mildly preoperative elevated homocysteine levels with no additional thromboembolic risk factors may warrant a not yet established period of postoperative anticoagulation and, probably, long-life antiplatelet treatment and vitamin supplementation in patients with isolated tricuspid valve repair and other similar clinical scenarios. This recommendation remains speculative and needs to be tested in future investigations, but more attention to preoperative homocysteine levels is surely advisable. In addition, in the setting described herein, TART may be treated with a variable period of double anticoagulation therapy plus anti-aggregation followed by high doses of oral anticoagulation and aspirin. Isolated long-life antiplatelet treatment is probably advisable after thrombus resolution in patients without MTHFR mutation. We should reserve surgical intervention for persistent or recurrent thrombosis complicated with thromboembolic or valveobstruction related events.
References 1. Vahanian A, Baumgartner H, Bax J, et al. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J 2007;28:230 – 68. 2. Dinckal MH, Davutoglu V, Soydinc S, Akdemir I, Aksoy M. Large thrombus at the site of primary sutured atrial septal defect associated with pulmonary embolism and treatment by thrombolysis. Echocardiography 2003;20:535– 8. 3. Raja SG, Dreyfus GD. Basis for intervention on functional tricuspid regurgitation. Semin Thorac Cardiovasc Surg 2010; 22:79 – 83. 4. Ranucci M, Ballotta A, Frigiola A, et al. Preoperative homocysteine levels and morbidity and mortality following cardiac surgery. Eur Heart J 2009;30:995–1004. 5. Colucci M, Cattaneo M, Martinelli I, Semeraro F, Binetti BM, Semeraro N. Mild hyperhomocysteinemia is associated with increased TAFI levels and reduced plasma fibrinolytic potential. J Thromb Haemost 2008;6:1571–7. 6. Coppola A, Davi G, De Stefano V, Mancini FP, Cerbone AM, Di Minno G. Homocysteine, coagulation, platelet function, and thrombosis. Semin Thromb Hemost 2000;26:243–54. 7. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines 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 (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease). Circulation 2008;118: e523– 61. 8. Laurent M, Lelong B, Verhoye JP, et al. Prolonged heparin and vitamin-K-antagonist regimen for early non-obstructive thrombosis of mechanical mitral valve prostheses. J Heart Valve Dis 2008;17:533– 41.