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Massive thromboembolic stroke and death after fibrinolytic therapy of St. Jude prosthetic mitral valve thrombosis: Documentation by transthoracic Doppler echocardiography
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Massive thromboembolic stroke and death after fibrinolytic therapy of St. Jude prosthetic mitral valve thrombosis: Documentation by transthoracic Doppler echocardiography Linda A. Pape, MD, Donald G. Love, MD, and Joel M. Gore, MD Worcester, Mass.
From the Division of Cardiovascular Medicine, University of Massachusetts Medical Center. Reprint requests: Linda A. Pape, MD, Division of Cardiovascular Medicine, University of Massachusetts Medical Center, Worcester, MA 01655.
AM HEARTJ 1994;128:406-9 Copyright @ 1994 by Mosby-Year Book, Inc. OOOZ-8703/94/$3.00 + 0 4/4/65712
Valve thrombosis is a potentially life-threatening complication of prosthetic cardiac valves for which surgery has been the past treatment of choice. Recently, however, medical therapy hasbeenreported asan alternative treatment. Silber et a1.l reported a high successrate and no deaths or major complications in 12 patients with thrombosed St. Jude aortic and mitral valves treated with thrombolytic therapy (n = 10) or intravenous heparin (n = 2).l The excellent results amongthis small group of patients formed the basisfor their recommendation that thrombolytic therapy shouldbe usedasfirst-line treatment for prosthetic valve thrombosis.We report the catastrophic result of stroke and death in a patient with a thrombosed St. Jude mitral valve to highlight the potential risks of thrombolytic therapy in left heart valve thrombosis. A 66-year-old womanwith chronic atrial fibrillation was seen 3 years after St. Jude mitral valve replacement for mitral regurgitation. After 3 weeks of extreme fatigue, malaise,and anorexia, she was hospitalized and found to
1. Before thrombolysis. A, Echogenic massin parasternal long-axis view asit movesinto left ventricular inflow tract in diastole (arrow). B, Color Doppler demonstratesflow passingaround massand into left ventricle. C, Mass is demonstrated in (arrow) apical four-chamber view in diastole. D, Narrow color flow Doppler jet (arrow) demonstratesrestricted left ventricular inflow around mass.LA, Left atrium; LV, left ventricle; RV, right ventricle. Fig.
406
Volume 128, Number 2 American Heart Journal
Pape. Low, and Gore
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2. After thrombolysis. A, Apical four-chamber view in diastole showssmall residual thrombus on ventricular aspectof prosthesis(arrow). B, Doppler color flow showsunrestricted, broad mitral inflow pattern.
Fig.
have a fever. A urinary tract infection wasdiagnosed,and the patient received gentamicin. No other sourceof infection wasidentified; six blood cultures were negative. Prothrombin time was19.3 seconds(international normalized ratio 2.5). There had been no known interruption of coumadin therapy. Echocardiogram revealed decreasedleft ventricular ejection fraction and a mean mitral valve gradient of 13 mm Hg. No thrombus wasseen.On transfer to our hospital the patient was noted to be a thin, frailappearingwomanin moderate respiratory distress.Central venous pressurewas estimated at 14 mm Hg with prominent V waves. Rales were heard over both lung fields. A right ventricular heavewaspresent.Prosthetic valve sounds were normal to auscultation. A tricuspid regurgitation murmur and diastolic mitral rumble were heard. Repeat transthoracic echocardiogram showed right ventricular
and right atria1 dilation and estimated pulmonary artery systolic pressureof 65 to 70 mm Hg. The left ventricle was dilated, with an estimated ejection fraction of 35%. A 1 to 2 cm echogenicmasswasseenon the left ventricular side of the mitral prosthesisin diastole (Fig. I). The massmoved upward toward the valve plane with ventricular systole. Doppler color flow mapping showed that the massobstructed diastolic flow into the LV. Only mild mitral regurgitation waspresent.The mitral valve peak and mean gradients were 30 and 20 mm Hg, respectively. Prosthetic valve thrombosis was diagnosed.Becauseof the patient’s poor clinical condition, reduced left ventricular function, and technical complications during the previous valve replacement,the consulting surgeonbelieved the patient was at high risk for surgery. She wastherefore given recombinant tissue-type plasminogenactivator administered as a
408
Pape, Love, and Gore
American
August 1994 Heart Journal
Fig. 3. Spectral Doppler tracing of mitral valve flow. A, Prethrombolysis peak velocity is elevated at 2.77 m/set with meangradient of 20 mm Hg. B, Postthrombolysis peak velocity of 1.8 m/set and meangradient of 7 mm Hg.
20 mg intravenous bolusto be followed by an infusion of 10 mg/hr for 3 hours. Forty-five minutes after initiation of the infusion, the patient had a sudden large left hemispheric stroke. Repeat echocardiogram showed nearly complete disappearanceof the previously seen obstructing mass (Fig. 2), normal-appearing flow into the left ventricle, and mitral valve peak and mean gradients of 11 and 7 mm Hg (Fig. 3), respectively. Right ventricular size had decreased to near normal, tricuspid regurgitation wasonly mild, and estimated pulmonary artery systolic pressurewas 35 mm Hg. Computed tomography scanwas consistent with embolic stroke. The patient died 48 hours later from a massive stroke and related complications. Autopsy discloseda left middle cerebral artery embolus. Recent reports suggestthat thrombolytic therapy is a safeand effective first approach to thrombosed prosthetic
valves. Silber et a1.l reported an 83% initial successful outcome; two patients had late rethrombosis,one of whom received repeat lytic therapy. Although one patient had a transient ischemic episode, no patient had a significant embolic event. Vasan et ak2reported that only 2 of 16 consecutively treated patients with Bjiirk-Shiley valves had minor embolic episodes.Kurzrok et ah3reported on three patients plus 38 previously reported casesand noted four episodesof embolization in which all manifestations were gone by 4 days after treatment. On the other hand, in the largest series reported to date, Roudaut et al? found a higher incidence of embolic stroke. He reported the results of thrombolytic therapy in 64 consecutivepatients with 75 instances of prosthetic valve thrombosis: initial success rate was73%, and 9 deathsincluded 4 with major cerebral embolism.The overall embolicrate was 18.6%; stroke rate
Volume 128, Number 2 American Heart Journal
was 5 9%.Three of the four fatal strokes were in the 36 patients with mitral valve prostheses. Further experience with tissue-type plasminogen activator used for the treatment of prosthetic valve thrombosis should determine whether clinical efficacy and embolic complication rates vary with the specific thrombolytic agent used. We used a dosage regimen of rTPA similar to that used in the treatment of pulmonary embolism. Most of the patients reported on have been treated with streptokinase or urokinase.lm3Although only nine patients in the series of Roudaut et aL4 received rTPA (all with mitral prostheses), no apparent correlation between thrombolytic agent used and embolism was found. There is only anecdotal information correlating echocardiographically demonstrated thrombus and the likelihood of stroke after thrombolytic therapy. In the series of Roudaut et al., although transthoracic echocardiography was done in most patients, the results do not mention that thrombus was seen4 Transesophageal echocardiography, however, demonstrated thrombus in three of the nine patients in whom it was performed. Dzavik et aL5 reported the use of transesophageal echocardiography in three patients with four episodes of prosthetic valve thrombosis. In one patient with previous rheumatic mitral stenosis, a large mass involving the prosthesis was demonstrated. Twelve hours after initiation of thrombolytic therapy, she had a massive stroke and died. Another patient with visible thrombus had a peripheral embolic event. In none of these patients did transthoracic echo demonstrate thrombus. Our patient was unique in that prosthetic valve thrombus was seen by transthoracic echocardiography alone. The diagnosis and initial success of thrombolysis was documented by transthoracic echocardiography and Doppler alone. Further study of patients with transthoracic and transesophageal echocardiography is needed to determine whether size, location, or mobility of thrombus are predictive of increased embolic risk from thrombolytic therapy. Patients with large mobile echogenic masses associated with left-sided prosthetic valves are probably at increased risk of major embolism and stroke when treated with thrombolytic therapy.
REFERENCES
1. Silber H, Kahn SS, Matloff JM, Chauz A, DeRobertis M, Gray R. The St. Jude Valve. Thromholysis as the first line of therapy for cardiac valve thrombosis. Circulation 1993;87:30-7. 2. Vasan RS, Kaul U, Sanghvi S, Kamlakar T, Negi PC, Shrivastava S, Rajani M, Venugopal P, Wasir HS. Thrombolytic therapy for prosthetic valve thrombosis: a study based on serial Doppler echocardiographic evaluation. AM HEART J 1992;
Samaha rlt al.
409
aneurysm Frederick F. Samaha, MD, Roberto Lang, MD, Katherine M. Abbo, MD, John D. Carroll, MD, Lynn Weinert, and Duane F. Follman, MD Chicago, 111.
High-frequency (20 to 30 mHz), catheter-mounted ultrasonographictransducershave beenused to generate highresolution coronary intravascular images.lThis technology allows imaging to a depth of field of 1.5 cm, providing cross-sectionalimagesfrom the lumen of epicardial coronary arteries. Several studieshave demonstratedthat these images yield qualitative and quantitative information regarding vesselcaliber and plaquecomposition.2Although the depth of field of the 20 to 30 mHz ultrasonic probesis acceptable for intracoronary imaging, a greater depth of field is required for intracardiac imaging. Recently percutaneous, catheter-mounted, high-resolution 10 to 15 mHz intracardiac ultrasonography has been developed. This new technique enablesimagingto a depth of field of about 4 cm, allowing visualization of the great vessels,cardiac chambers,and heart valves. This technologic improvement hasbeenachieved at the expenseof an increasein catheter size from 4.3F to 10 to llF.3 We report the use of intracardiac ultrasonography in the physiologic and anatomic delineation of a fistulous tract from the right posterior aortic sinus of ValsaIva into the right atrium. A 23-year-old white womanhad increasingfatigue, dyspenea,and chestpain of 3 to 4 months’ duration. Her medical history wasremarkable for a congential bicuspid aortic valve for which sheunderwent multiple percutaneous balloon aortic valvuloplasties at ages5,10, and 12years. At age 11 years, after complaining of pain and shortnessof breath, a ruptured sinus of Valsalva aneurysm with a fistulous tract to the right atrium wasdiagnosed.The latter wassurgically repaired, apparently without complications. Physical examination revealed blood pressure of 110/70 mm Hg with a pulse of 74 and respiratory rate of lG/min. The jugular venous pressure and carotid examinations were unremarkable. Her lungs were clear. Cardiac examinations revealed a regular rate and rhythm, a normal S1,a loud split Sz with a slightly increasedP2. A grade 2/6 holosystolic murmur washeard throughout the precordium.
123:1575-80.
3. Kurzrok S, Singh AK, Most AS, Williams DO. Thrombolvtic therapy for prosthetic valve thrombosis. J Am Co11 Car& 1987;9:592-8. 4. Roudaut R, Labbe T, Lorient-Roudaut M, Gosse P, Baudet E, Fontan F, Besse P Dallocchio. Mechanical cardiac valve thrombosis. Is fibrinolysis justified? Circulation 1992;86(supp II):II-8-15. 5. Dzavik V, Cohen G, Chan KL. Role of transesophageal echocardiography in the diagnosis and management of prosthetic valve thrombosis. J Am Co11 Cardiol 1991;18:1829-33.
From the Hans Hecht Hemodynamics Laboratory and The Non-invasive Cardiac Imaging Laboratory, Section of Cardiology, Department of Medicine, University of Chicago Medical Center. Reprint requests: D. F. Follman, MD, The University of Chicago Medical Center, Section of Cardiology, Department of Medicine, MC 5076.5641 S. Maryland Ave., Chicago, IL 60637-6063. AM HEART J 1994;128:409-12 Copyright II 1994 by Mosby-Year Book, Inc. 0002.8703/94/%X00
+ 0
4/4/55’708
Massive thromboembolic stroke and death after fibrinolytic therapy of St. Jude prosthetic mitral valve thrombosis: Documentation by transthoracic Doppler echocardiography Linda A. Pape, MD, Donald G. Love, MD, and Joel M. Gore, MD Worcester, Mass.
From the Division of Cardiovascular Medicine, University of Massachusetts Medical Center. Reprint requests: Linda A. Pape, MD, Division of Cardiovascular Medicine, University of Massachusetts Medical Center, Worcester, MA 01655.
AM HEARTJ 1994;128:406-9 Copyright @ 1994 by Mosby-Year Book, Inc. OOOZ-8703/94/$3.00 + 0 4/4/65712
Valve thrombosis is a potentially life-threatening complication of prosthetic cardiac valves for which surgery has been the past treatment of choice. Recently, however, medical therapy hasbeenreported asan alternative treatment. Silber et a1.l reported a high successrate and no deaths or major complications in 12 patients with thrombosed St. Jude aortic and mitral valves treated with thrombolytic therapy (n = 10) or intravenous heparin (n = 2).l The excellent results amongthis small group of patients formed the basisfor their recommendation that thrombolytic therapy shouldbe usedasfirst-line treatment for prosthetic valve thrombosis.We report the catastrophic result of stroke and death in a patient with a thrombosed St. Jude mitral valve to highlight the potential risks of thrombolytic therapy in left heart valve thrombosis. A 66-year-old womanwith chronic atrial fibrillation was seen 3 years after St. Jude mitral valve replacement for mitral regurgitation. After 3 weeks of extreme fatigue, malaise,and anorexia, she was hospitalized and found to
1. Before thrombolysis. A, Echogenic massin parasternal long-axis view asit movesinto left ventricular inflow tract in diastole (arrow). B, Color Doppler demonstratesflow passingaround massand into left ventricle. C, Mass is demonstrated in (arrow) apical four-chamber view in diastole. D, Narrow color flow Doppler jet (arrow) demonstratesrestricted left ventricular inflow around mass.LA, Left atrium; LV, left ventricle; RV, right ventricle. Fig.
406
Volume 128, Number 2 American Heart Journal
Pape. Low, and Gore
407
2. After thrombolysis. A, Apical four-chamber view in diastole showssmall residual thrombus on ventricular aspectof prosthesis(arrow). B, Doppler color flow showsunrestricted, broad mitral inflow pattern.
Fig.
have a fever. A urinary tract infection wasdiagnosed,and the patient received gentamicin. No other sourceof infection wasidentified; six blood cultures were negative. Prothrombin time was19.3 seconds(international normalized ratio 2.5). There had been no known interruption of coumadin therapy. Echocardiogram revealed decreasedleft ventricular ejection fraction and a mean mitral valve gradient of 13 mm Hg. No thrombus wasseen.On transfer to our hospital the patient was noted to be a thin, frailappearingwomanin moderate respiratory distress.Central venous pressurewas estimated at 14 mm Hg with prominent V waves. Rales were heard over both lung fields. A right ventricular heavewaspresent.Prosthetic valve sounds were normal to auscultation. A tricuspid regurgitation murmur and diastolic mitral rumble were heard. Repeat transthoracic echocardiogram showed right ventricular
and right atria1 dilation and estimated pulmonary artery systolic pressureof 65 to 70 mm Hg. The left ventricle was dilated, with an estimated ejection fraction of 35%. A 1 to 2 cm echogenicmasswasseenon the left ventricular side of the mitral prosthesisin diastole (Fig. I). The massmoved upward toward the valve plane with ventricular systole. Doppler color flow mapping showed that the massobstructed diastolic flow into the LV. Only mild mitral regurgitation waspresent.The mitral valve peak and mean gradients were 30 and 20 mm Hg, respectively. Prosthetic valve thrombosis was diagnosed.Becauseof the patient’s poor clinical condition, reduced left ventricular function, and technical complications during the previous valve replacement,the consulting surgeonbelieved the patient was at high risk for surgery. She wastherefore given recombinant tissue-type plasminogenactivator administered as a
408
Pape, Love, and Gore
American
August 1994 Heart Journal
Fig. 3. Spectral Doppler tracing of mitral valve flow. A, Prethrombolysis peak velocity is elevated at 2.77 m/set with meangradient of 20 mm Hg. B, Postthrombolysis peak velocity of 1.8 m/set and meangradient of 7 mm Hg.
20 mg intravenous bolusto be followed by an infusion of 10 mg/hr for 3 hours. Forty-five minutes after initiation of the infusion, the patient had a sudden large left hemispheric stroke. Repeat echocardiogram showed nearly complete disappearanceof the previously seen obstructing mass (Fig. 2), normal-appearing flow into the left ventricle, and mitral valve peak and mean gradients of 11 and 7 mm Hg (Fig. 3), respectively. Right ventricular size had decreased to near normal, tricuspid regurgitation wasonly mild, and estimated pulmonary artery systolic pressurewas 35 mm Hg. Computed tomography scanwas consistent with embolic stroke. The patient died 48 hours later from a massive stroke and related complications. Autopsy discloseda left middle cerebral artery embolus. Recent reports suggestthat thrombolytic therapy is a safeand effective first approach to thrombosed prosthetic
valves. Silber et a1.l reported an 83% initial successful outcome; two patients had late rethrombosis,one of whom received repeat lytic therapy. Although one patient had a transient ischemic episode, no patient had a significant embolic event. Vasan et ak2reported that only 2 of 16 consecutively treated patients with Bjiirk-Shiley valves had minor embolic episodes.Kurzrok et ah3reported on three patients plus 38 previously reported casesand noted four episodesof embolization in which all manifestations were gone by 4 days after treatment. On the other hand, in the largest series reported to date, Roudaut et al? found a higher incidence of embolic stroke. He reported the results of thrombolytic therapy in 64 consecutivepatients with 75 instances of prosthetic valve thrombosis: initial success rate was73%, and 9 deathsincluded 4 with major cerebral embolism.The overall embolicrate was 18.6%; stroke rate
Volume 128, Number 2 American Heart Journal
was 5 9%.Three of the four fatal strokes were in the 36 patients with mitral valve prostheses. Further experience with tissue-type plasminogen activator used for the treatment of prosthetic valve thrombosis should determine whether clinical efficacy and embolic complication rates vary with the specific thrombolytic agent used. We used a dosage regimen of rTPA similar to that used in the treatment of pulmonary embolism. Most of the patients reported on have been treated with streptokinase or urokinase.lm3Although only nine patients in the series of Roudaut et aL4 received rTPA (all with mitral prostheses), no apparent correlation between thrombolytic agent used and embolism was found. There is only anecdotal information correlating echocardiographically demonstrated thrombus and the likelihood of stroke after thrombolytic therapy. In the series of Roudaut et al., although transthoracic echocardiography was done in most patients, the results do not mention that thrombus was seen4 Transesophageal echocardiography, however, demonstrated thrombus in three of the nine patients in whom it was performed. Dzavik et aL5 reported the use of transesophageal echocardiography in three patients with four episodes of prosthetic valve thrombosis. In one patient with previous rheumatic mitral stenosis, a large mass involving the prosthesis was demonstrated. Twelve hours after initiation of thrombolytic therapy, she had a massive stroke and died. Another patient with visible thrombus had a peripheral embolic event. In none of these patients did transthoracic echo demonstrate thrombus. Our patient was unique in that prosthetic valve thrombus was seen by transthoracic echocardiography alone. The diagnosis and initial success of thrombolysis was documented by transthoracic echocardiography and Doppler alone. Further study of patients with transthoracic and transesophageal echocardiography is needed to determine whether size, location, or mobility of thrombus are predictive of increased embolic risk from thrombolytic therapy. Patients with large mobile echogenic masses associated with left-sided prosthetic valves are probably at increased risk of major embolism and stroke when treated with thrombolytic therapy.
REFERENCES
1. Silber H, Kahn SS, Matloff JM, Chauz A, DeRobertis M, Gray R. The St. Jude Valve. Thromholysis as the first line of therapy for cardiac valve thrombosis. Circulation 1993;87:30-7. 2. Vasan RS, Kaul U, Sanghvi S, Kamlakar T, Negi PC, Shrivastava S, Rajani M, Venugopal P, Wasir HS. Thrombolytic therapy for prosthetic valve thrombosis: a study based on serial Doppler echocardiographic evaluation. AM HEART J 1992;
Samaha rlt al.
409
aneurysm Frederick F. Samaha, MD, Roberto Lang, MD, Katherine M. Abbo, MD, John D. Carroll, MD, Lynn Weinert, and Duane F. Follman, MD Chicago, 111.
High-frequency (20 to 30 mHz), catheter-mounted ultrasonographictransducershave beenused to generate highresolution coronary intravascular images.lThis technology allows imaging to a depth of field of 1.5 cm, providing cross-sectionalimagesfrom the lumen of epicardial coronary arteries. Several studieshave demonstratedthat these images yield qualitative and quantitative information regarding vesselcaliber and plaquecomposition.2Although the depth of field of the 20 to 30 mHz ultrasonic probesis acceptable for intracoronary imaging, a greater depth of field is required for intracardiac imaging. Recently percutaneous, catheter-mounted, high-resolution 10 to 15 mHz intracardiac ultrasonography has been developed. This new technique enablesimagingto a depth of field of about 4 cm, allowing visualization of the great vessels,cardiac chambers,and heart valves. This technologic improvement hasbeenachieved at the expenseof an increasein catheter size from 4.3F to 10 to llF.3 We report the use of intracardiac ultrasonography in the physiologic and anatomic delineation of a fistulous tract from the right posterior aortic sinus of ValsaIva into the right atrium. A 23-year-old white womanhad increasingfatigue, dyspenea,and chestpain of 3 to 4 months’ duration. Her medical history wasremarkable for a congential bicuspid aortic valve for which sheunderwent multiple percutaneous balloon aortic valvuloplasties at ages5,10, and 12years. At age 11 years, after complaining of pain and shortnessof breath, a ruptured sinus of Valsalva aneurysm with a fistulous tract to the right atrium wasdiagnosed.The latter wassurgically repaired, apparently without complications. Physical examination revealed blood pressure of 110/70 mm Hg with a pulse of 74 and respiratory rate of lG/min. The jugular venous pressure and carotid examinations were unremarkable. Her lungs were clear. Cardiac examinations revealed a regular rate and rhythm, a normal S1,a loud split Sz with a slightly increasedP2. A grade 2/6 holosystolic murmur washeard throughout the precordium.
123:1575-80.
3. Kurzrok S, Singh AK, Most AS, Williams DO. Thrombolvtic therapy for prosthetic valve thrombosis. J Am Co11 Car& 1987;9:592-8. 4. Roudaut R, Labbe T, Lorient-Roudaut M, Gosse P, Baudet E, Fontan F, Besse P Dallocchio. Mechanical cardiac valve thrombosis. Is fibrinolysis justified? Circulation 1992;86(supp II):II-8-15. 5. Dzavik V, Cohen G, Chan KL. Role of transesophageal echocardiography in the diagnosis and management of prosthetic valve thrombosis. J Am Co11 Cardiol 1991;18:1829-33.
From the Hans Hecht Hemodynamics Laboratory and The Non-invasive Cardiac Imaging Laboratory, Section of Cardiology, Department of Medicine, University of Chicago Medical Center. Reprint requests: D. F. Follman, MD, The University of Chicago Medical Center, Section of Cardiology, Department of Medicine, MC 5076.5641 S. Maryland Ave., Chicago, IL 60637-6063. AM HEART J 1994;128:409-12 Copyright II 1994 by Mosby-Year Book, Inc. 0002.8703/94/%X00
+ 0
4/4/55’708