Clinical Investigator Clin Investig (1994) 72:466-469 Case Rep0rl © Springer-Verlag 1994 Severe complications following thrombolytic therapy of an acute thrombosis of a prosthetic mitral valve M.M. Hirschl 1, M. Gwechenberger 2, M. Zehetgruber 2, H. Weber 2 1 Abteilung f/Jr Noffallmedizin, Universit/it Wien, Wfihringer Giirtel 18-20, A-1090 Wien, Austria 2 Klinik fiir Inhere Medizin II, Abteilung fiir Kardiologie, Universitfit Wien, W/ihringer Giirtel 18-20, A-1090 Wien, Austria Received: 10 November 1993 / Returned: 16 December 1993 / Accepted: 7 February 1994 Abstract. Thrombosis of prosthetic cardiac valves is a rare but potentially lethal complication. As emergency surgical intervention of thrombotic prosthetic cardiac valves is correlated with high mortality, fibrinolytic therapy has been recently recommended as a therapy with high efficacy and no severe side effects. We report on a patient with thrombosis of a prosthetic mitral valve who developed severe embolic complications following the administration of the thrombolytic agent. On admission the patient showed signs of incipient cardiogenic shock. The diagnosis of thrombotic obstruction of the prosthetic mitral valve was confirmed by transesophageal echocardiography. The effective valve area was 0.41 cm 2. Pulmonary arterial blood pressure and wedge pressure were significantly elevated. A fibrinolytic therapy with recombinant tissue-type plasminogen activator according to the Neuhaus scheme was attempted. Within 60 min after start of treatment the effective valve area increased (1.41 cm2), and the pulmonary capillary wedge pressure decreased. However, peripheral and cerebral embolism occurred. Occlusion of the right brachial and right femoral artery was ascertained by Doppler ultrasound. Embolism into the right leg made an embolectomy with a Fogarty catheter necessary. Computed tomography revealed two lesions located in the occipital and left temporal area of the brain. Correlated with the lesions evaluated in computed tomography, right hemiplegia and complete aphasia was observed. The neurological status of the patient has only slightly improved to the present. To our knowledge no severe persistent neurological deficits following thrombolytic therapy have been reported. We therefore assume that the risk of severe neurologiAbbreviations: PAP=pulmonary arterial pressure; PCWP= pulmonary capillary wedge pressure; rt-Pa=recombinant tissue-type plasminogen activator Correspondence to: M.M. Hirschl cal complications is underestimated. It is suggested that fibrinolytic therapy is a reasonable alternative in severely compromized patients with thrombotic prosthetic cardiac valves, but the final value of this treatment cannot be ascertained due to the small number of patients and the underestimation of severe embolic complications. Key words: Prosthetic heart valve - Thrombosis Fibrinolysis - Embolism - Neurological deficits Thrombosis of prosthetic cardiac valves is a rare but potentially lethal complication. Treatment of such emergencies is a matter of controversy in the published data [4, 13, 14]. Its classic treatment is surgery, associated with a high perioperative mortality rate, especially in critically ill patients [11]. Emergency operations of thrombotic prosthetic heart valves are associated with a mortality rate of 17.5-55% [2, 10, 11]. Due to the high perioperative mortality rate other authors have attempted fibrinolytic therapy in patients with thrombosis of prosthetic heart valves [1, 3-9, 12, 14, 15]. In addition to hemorrhagical complications, a major concern regarding fibrinolytic therapy for prosthetic valve thrombosis is embolization of thrombotic material. However, reported embolic events, either peripheral or cerebral, have always classified as minor and transient complications. In the case of cerebral embolism no persistent neurological deficits have been described. In contrast, we present a case report in which fibrinolytic therapy of a thrombotic prosthetic mitral valve resulted in a persistent severe neurological deficit due to cerebral embolism. This report presents our experience of this case and a review of the literature. Case report A 63-year-old woman underwent aortic and mitral valve replacement with Carbomedics prothesis in 467 Fig. 1. Velocity flow profile of a thrombotic prosthetic mitral valve using a continuous wave Doppler analysis before (A) and after thrombolytic therapy (B) 1989. Four years later a permanent intracardial pacemaker was inserted due to a sick sinus syndrome. Postoperatively a hematothorax developed, and anticoagulation therapy was stopped for 24 h. Then the anticoagulation therapy with heparin was resumed. However, the patient developed the clinical signs of pulmonary edema and cardiogenic shock and was admitted to the intensive care unit. On admission her thrombin time was 75 s. Thrombotic occlusion of the mitral or aortic valve was suspected. Clinical diagnosis of a thrombotic mitral valve was confirmed by transthoracal and later by transesophageal echocardiography. The aortic valve showed no abnormalities. The Doppler examination revealed an abnormally high blood flow velocity and a pressure half time of 0.53 s. The effective valve area was 0.41 cm 2 (Fig. 1A). Because of the progressive respiratory failure the patient was sedated and intubated, and controlled respiration was established. In addition, cardiogenic shock was observed, with a systemic arterial blood pressure of 70/45 mmHg, and acute renal failure developed. Therefore, dobutamine (10 gg kg -1 rain -1) and suprarenine (1 t~g kg ~ min t) were infused continuously. A Swan-Ganz catheter was inserted via the left subclavian vein. Pulmonary arterial pressure (PAP) was 56/47 mmHg, wedge pressure (PCWP) 45 mmHg, and cardiac output was 1.92 1/min. Because of the low output and the high risk of emergency surgery fibrinolytic therapy with recombi- nant tissue-type plasminogen activator (rt-PA) was attempted. According to the scheme published by Neuhaus et al. [17] a 15-mg rt-PA intravenous bolus was given, followed by intravenous infusion of 50-mg rt-PA over 30 min and a further 35 mg over the following 60 min. Within 60 min after the start of therapy the patient's general condition had improved markedly. PAP decreased to 26/21 m m H g and PCWP from 45 to 13 mmHg, and cardiac output increased from 1.92 1/min to 3.39 1/min. The level of catecholamines was reduced continuously. Echocardiographic examination revealed a decreased pressure half time of 0.15 s and a marked reduction in blood velocity across the mital valve (Fig. 1B). The calculated mitral valve area increased to 1.41 cm 2. However, no complete lysis of the thrombosis of the valve could be established. Therefore surgical intervention was planned for the next day. During fibrinolytic therapy peripheral and cerebral embolism was observed. Occlusion of the right brachial and right femoral artery was ascertained by Doppler ultrasound. In addition, cerebral embolism was suspected because a side difference in the pupils was observed. Computed tomography revealed two lesions located in the occipital and left temporal area of the brain. Embolism into the right leg made embolectomy with a Fogarty catheter necessary. However, postoperatively a compartment syndrome developed, and a fasciotomy of the right lower limb was performed. After the end of sedation severe neurological deficits became obvious. A right hemiplegia and complete aphasia were observed. The neurological deficits correlated well with the results of the computed tomography. The postoperative course of the patient was complicated by sepsis with pseudomonas aeruginosa; the focus of the sepsis was the fasciotomy wound of the right leg. The patient is still in the hospital 10 weeks after the operation. A slight improvement in her neurolgical status has been observed. The patient is now able to speak a few words, but the hemiplegia of the right side persists. Discussion Our case report demonstrates a severe and persistent neurological deficit due to cerebral embolism folllowing fibrinolytic therapy of thrombotic obstruction of a prosthetic mitral valve. Reviewing the literature, we have found 82 additional cases in which fibrinolysis of left-sided thrombotic prosthetic heart valves has been attempted. The findings of recently published reports are summarized 468 Table 1. Data in 75 patients of left-sided prosthetic valve thrombosis after episodes of thrombolytic therapy Authors Patients/ Episodes Position Success Surgery Complications Drug (dosage) Witchitz et al. [19] 12/13 8 M/4A complete 8 partial 2 failure 3 3 (3rd, 8th, 75th day) hemopericardium 1, uterine bleeding 1, cerebral embolism 1 Ledain et al. [8] 26/28 15 M/11A complete 23, partial 3, failure 2 6 peripheral embolism 3, cerebral embolism 2 7 SK (bolus: 500.000 I.U. and 100.000 I.U./h over 12-96 h) 6 U K (bolus: 150.000 and 75.000-150.000 I.U over 24-48 h) 19 SK (bolus: 500.000 I.U and 1.500.000 I.U. over 10 h) 9 U K (4.500 I.U./kg/h over 12 tl) Kurzrok et al. [71 Gagnon et al. [5] Wright [20] 1/1 1M Complete No Splenic infarction SK (bolus: 500000 IU and 100000 IU/h over 24 h) 1/1 1M Complete No No 1/1 1M Complete No subdural hematoma SK (bolus: 250000 IU and 200000 IU/h over 48 h) SK (600000 IU/h over 72 h) Page et al. [12] 3/3 2 M/1 A Complete 3 Not mentioned Peripheral embolism 2 Amann et al. [1] Lopez et al. [9] 1/1 1M Complete No Hematoma 7/10 7M Complete 10 4 (8th,15th, 19th day, 8 months) Allergic reaction 2, retroperitoneal hematoma 1, cerebral hemorrhage 1 3 SK (bolus: 250000-1500000 IU and 100000IU/h over 22-64 h) 3 U K (bolus: 250.000-300.000 I.U. and 100.000 I.U./h over 13-70 h 4 rt-PA (100 mg in 90-180 min) Ortuno et al. [11] Silber et al. [17] 1/1 1M Complete No No SK (3000000 IU over 45 h) 12/12 3 M/9 A Complete 9, partial 1, failure 2 No Rabago et al. [16] 10/11 Not known Complete 7, failure 4 4 Severe ecchymoses 1, hemarthrosis 1, cerebral embolism 1, hematoma 1 Embolism 4 2 SK (bolus 250000 IU and 100000 IU/h over 72 h) 8 U K (4.400 I.U/kg/h over 24 hour) 2 Heparin 11 SK (average 2500000 IU over 16 h) 2 U K (4500 IU/kg/h over 12 h) 1 U K + S K (4500 IU/kg/h over 12 h and 2000000 IU over the next 12 h) SK (bolus: 100000 IU and 60000 IU over 48 h) A, Aortic; M, mitral; SK, streptokinase; UK, urokinase in Table 1. Complete success was accomplished in 82% and clinical improvement with partial success in 7%. In 11 of the 82 cases fibrinolytic therapy failed to resolve the thrombotic obstruction. Surgical intervention after fibrinolysis was necessary in 17 patients. Reoperation was successful in 14 (82%), and 3 (18%) patients died postoperatively. Hemorrhagical complications were retroperitoneal hematoma, hemopericardium, subdural hematoma, and cerebral hemorraghe. Embolic events were observed in 13 patients (5 peripheral, 4 cerebral, 4 not defined). One of the peripheral embolic events required embolectomy. None of the cerebral events caused persistent neurological deficits. The overall rate of complications was 33%. 47 (57%) cases were treated with streptokinase, 28 (34%) with urokinase, 4 (5%) with rt-PA, 2 (3%) with heparin, and 1 with combined urokinase and streptokinase. The duration of treatment ranged from 90 min to 96 h. However, no correlation between the used drug, the duration of administration, and the risk of embolization could be established. In view of the fact that 85 fibrinolytic attempts have been performed in left-sided obstructions, the number of arterial embolizations seems rather low. We have also compared the incidence of arterial embolizations with the number of embolic events after fibrinolytic therapy of thrombotic tricuspid valves. No events of pulmonary embolism have been reported in these patients [18-20]. However, the number of patients with thrombotic tricuspid valves treated with fibrinolytic agents is very small. Due to this low rate of severe complications and the high perioperative mortality some authors have recommended fibrinolysis as the treatment of choice in thrombotic prosthetic heart valves [1, 7, 12]. We believe that an assessment of embolic complications is still not possible due to the small num- 469 ber of patients treated with fibrinolysis. F u r t h e r m o r e , the rate of severe c o m p l i c a t i o n s seems undere s t i m a t e d in the recent literature. As d e m o n s t r a t e d by o u r case r e p o r t , embolic c o m p l i c a t i o n s with persistent neurological deficit m a y occur following thrombolysis. We therefore feel t h a t patients in h e m o d y n a m i c a l l y stable conditions should u n d e r g o surgical intervention w i t h o u t any delay after the diagnosis of prosthetic valve t h r o m b o s i s . The m o r t a l i t y rate in these patients is a b o u t 8 - 1 2 % [2, 10] a n d does not necessarily c a r r y a high risk c o m p a r e d with elective valve surgery, p r o v i d e d the patient's condition is n o t unstable [4]. If a n t i c o a g u l a t i o n t h e r a p y is i n a d e q u a t e p r i o r to the t h r o m b o s i s of prosthetic h e a r t valve, a n d no life-threatening h e m o d y n a m i c d e c o m p e n s a t i o n exists, a trial of t h e r a p e u t i c a n t i c o a g u l a t i o n m a y be a t t e m p t e d to i m p r o v e prosthetic valve h e m o d y namics, as d e m o n s t r a t e d b y W a k s m o n s k i et al. [13]. If the patient is h e m o d y n a m i c a l l y c o m p r o m i s e d , an a t t e m p t should be m a d e to stabilize the h e m o d y n a m i c and r e s p i r a t o r y situation u n d e r the conditions of an intensive care unit. 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