Thrombosis of a Starr-Edwards tricuspid prosthesis: Diagnosis by Doppler echocardiography and treatment with thrombolysis

Volume

127, Number

American

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every 7 days; on the last day of the weekly incubation, the supernatants were collected and assayedfor IL-Iol, IL-l& IL-2, IL-6, and tumor necrosisfactor (TNF)-a by ELISAs. The level of IL-6 in the supernatant from the cells of case 1was216,000pg/ml at week 2 and decreasedwith time. The values were 96,400, 46,600, and 1,500 pg/ml at weeks 4, 6, and 12, respectively. The cells of case 2 also produced IL-6 at the concentrations of 6,350 pg/ml at week 2, and 2,000 pg/ml at week 4. Levels of other cytokines were undetectable. Time course of IL-6 production by the cells from case 1 was determined in a control period (vehicle in medium), a dexamethasone treatment period (10 nM in medium), and a recovery period after the removal of dexamethasone (vehicle in medium), consecutively. For each period the cells were washed three times with fresh medium, replenished with experimental medium containing dexamethasone or its vehicle, and incubated for 3 hours. Dexamethasone effectively inhibited the production of IL-6, and the

removal of it partially reversedthis inhibition (Fig. 1). RPMI-1640

medium

from Otsuka Assay Labs (Tokushima,

Japan).

The biologic activity of cytokine IL-6 includesthe stimulation of immunoglobulin secretion, T-cell activation, inof the acute-phase

response, and pyrogenicity.

It is

synthesized by many types of cells, including human monocytes,3fibroblasts,4 and endothelial cells5if an appropriate

stimulation

exists. These

cells also secrete cy-

tokines suchasIL-l, TNF, and interferon. The expression of IL-6 messengerribonucleic acid (mRNA) in human fibroblasts

is induced

by some of these cytokines

and is in-

hibited by dexamethasone.4,6*7 This inhibition of IL-6 mRNA expressionis mainly the result of decreasesin stability of the IL-6 mRNA by dexamethasone.7We concluded

that

Kohase M, Henriksen-Destefano D, Sehgal PB, Vilcek J. Dexamethasone inhibits feedback regulation of the mitogenic activity of tumor necrosis factor, interleukin-1, and epidermal growth factor in human fibroblasts. J Cell Physiol 1987; 132:271-8. Tobler A, Meier R, Seitz M, Dewald B, Baggiolini M, Fey MF. Glucocorticoids down-regulate gene expression of GM-CSF, NAP-l/IL-8, and IL-6, but not of M-CSF in human fibroblasts. Blood 1992;79:45-51.

Thrombosis of a Starr-Edwards tricuspid prosthesis: Diagnosis by Doppler echocardiography and treatment with thrombolysis Taya V. Glotzer, MD, Paul A. Tunick, MD, Howard Kloth, MD, Aubrey C. Galloway, MD, and Itzhak Kronzon, MD New York, N.Y.

and fetal bovine serum were obtained

from Flow Laboratory (Irvine, Scotland). An ELISA kit for IL-6 was obtained from Toray-Fuji Bionics Inc. (Tokyo, Japan). ELISA kits for IL-la, IL-lfi, IL-2, and TNF-a were

duction

705

cardiac

myxoma

cells produce

substantial

amounts of IL-6. Dexamethasoneinhibits this IL-6 production, presumably at the posttranscriptional level. REFERENCES

1. Hirano T, Taga T, Yasukawa K, Nakajima K, Nakano N, Takatsuki F, Shimizu M, Murashima A, Tsunasawa S, Sakivama F. Kishimoto T. Human B-cell differentiation factor defined by an anti-peptide antibody and its possible role in autoantibody production. Proc Nat1 Acad Sci U S A 1987; 84:228-31. 2. Jourdan M, Bataille R, Seguin J, Zhang XG, Chaptal PA, Klein B. Constitutive production of interleukin-6 and immunologic features in cardiac myxomas. Arthritis Rheum 1990; 33:398-402. 3. Aardan LA, De Groot ER, Schaap OL, Lansdorp PM. Production of hybridoma growth factor by human monocytes. Eur J Immunol 1987;17:1411-6. 4. Helfgott DC, May LT, Sthoeger Z, Tamm I, Sehgal PB. Bacterial lipopolysaccharide (endotoxin) enhances expression and secretion of 02 interferon by human fibroblasts. J Exp Med 1987;166:1300-9. 5. Jirik FR, Podor TJ, Hirano T, Kishimoto T, Loskutoff DJ, Carson DA, Lotz M. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol 1989;142:144-7.

The useof thrombolytic agentsto treat thrombosis of mechanical valve prostheseshas recently received increased attention. At one major medical center, thrombolysis has now replaced surgery asthe first line of therapy for thombosedSt. Jude prostheses(St. Jude Medical, Inc., St. Paul, Minn.).’ Successfulthrombolysis hasbeen reported using streptokinase, urokinase, and tissue plasminogenactivator.lm4The only previous reported caseof thrombolysis for an obstructed Starr-Edwards tricuspid prosthesis(Baxter Healthcare Corp., Edwards Division, Irvine, Calif.) was published in 1971,and the diagnosiswasmade on clinical grounds alone, without echocardiography or catheterization.5 We report a caseof successfulthrombolysis of an obstructed Starr-Edwards tricuspid valve in a young woman with rheumatic heart disease,in whom the diagnosiswas suspectedclinically and was confirmed echocardiographitally. Therapy proceededbasedon the echocardiographic diagnosis,without subsequentcatheterization. A 3%year-old black woman with a history of rheumatic fever asa child presentedwith a heart murmur during her first pregnancy 14 years before admission.Approximately 1-X years before admission she began to experience episodesof marked dizziness. Work-up at that time revealed new atrial fibrillation. Echocardiography showed severe mitral stenosis,moderate mitral regurgitation, severe tricuspid regurgitation, and moderatetricuspid stenosis. Six months later she began to develop dyspnea, orthopnea, and paroxysmal nocturnal dyspnea. Catheterization confirmed the previous echocardiographicfindings, and the patient underwent mitral valve replacement with a No. 31 St. Jude prosthesisand tricuspid valve replaceFrom the Departments Medical

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Paul

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A. Tunick,

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1994$27:705-S.

CopyrIght 0c 1994 oooz-8703/94/$3.00

by Mosby-Year + 0 4/4/61954

Book,

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706

Glotzer

et al.

Fig. 1. A, Continuous wave Doppler echocardiogram of right ventricular inflow before urokinase. Note the high velocity and prolonged pressure half-time. In addition, the antegrade flow continues past the QRS seen on the electrocardiogram at the top. The interval between two vertical dots indicates 1 m/set. B, Continuous wave Doppler echocardiogram of right ventricular inflow after urokinase. Note the lower velocity and shorter pressure half-time compared with A. In addition, the valve closure sounds (large vertical lines extending from top to bottom of the figure) are more prominent than in A and the antegrade flow now ceases with the QRS and closure sound. The interval between two vertical dots indicates 1 m/set.

ment with a No. 4 Starr-Edwards valve. There were no surgical complications. The patient was asymptomatic over the ensuing year. Two weeks before admission, she noted a marked reduction in exercise tolerance. Physical examination revealed a new diastolic murmur and a decrease in the intensity of the first heart sound. There were no additional findings of left or right heart failure. The patient was

American

March 1994 Heart Journal

hospitalized for evaluation, and on admission her prothrombin time was 15.5 seconds. Review of her records revealed that her prothrombin times over the previous 6 months had ranged from 12 to 35 seconds. Transthoracic echocardiography revealed a markedly diminished excursion of the ball of the tricuspid prosthesis, which moved only 2 to 3 mm during the cardiac cycle. Doppler examination revealed a peak velocity across the tricuspid prosthesis of 2.2 m/set, with a mean tricuspid gradient of 15 mm Hg and a tricuspid pressure half time of 445 msec. In addition, the antegrade flow continued past the QRS complex and valve closure sound (Fig. 1, A). There was no tricuspid insufficiency. Transesophageal echocardiography confirmed the presence of abnormal tricuspid prosthesis ball movement and flow velocities, and showed that the St. Jude mitral prosthesis had a normal echocardiographic appearance with normal flow characteristics on Doppler and the normal small amount of mitral regurgitation usually seen with these valves. Both atria were moderately dilated, the interatrial septum bowed markedly toward the left atrium, and there was a right atria1 thrombus (Fig. 2) that was not appreciated on the transthoracic study. The patient was treated with heparin and was transferred to the intensive care unit for treatment with urokinase. She received a 4400 units/kg intravenous bolus of urokinase over 15 minutes, followed by 4400 units/kg/hr for 72 hours. She experienced low-grade fever, nausea, and rare vomiting during the infusion. Repeat transthoracic echocardiography on the third day of urokinase infusion showed improved excursion of the prosthetic ball and a decrease in the peak velocity across the prosthesis, from 2.2 to 1.5 m/set. The mean tricuspid gradient had decreased from 15 to 5 mm Hg, and the pressure half time had also decreased, from 445 to 74 msec. In addition, the valve closure sounds were more prominent than on the echocardiogram before thrombolysis, and the antegrade flow ceased with the QRS complex and closure sound (Fig. 1, B). Physical examination revealed that the diastolic murmur had disappeared and the first heart sound had returned to its normal intensity. Twenty-four hours after the completion of the urokinase infusion, transthoracic echocardiography was unchanged from the study on the final day of urokinase infusion. Transesophageal echocardiography showed that the right atria1 thrombus was still present, but it was smaller in size. The patient was discharged on a regimen of warfarin, with a prothrombin time of 20 seconds. Her exercise tolerance has returned to normal and she has remained well. The reported overall incidence of mechanical disc valve thrombosis is 0.5% to 5%) with a high mortality rate (40%)).~ In the tricuspid position, the incidence of disc valve thrombosis is approximately 20 % .‘a ’ The first and only previous case report of thrombolysis of a StarrEdwards valve in the tricuspid position that we are aware of was published in 1971,3 and in that case the diagnosis was made without the use of echocardiography or catheterization, on clinical grounds alone. Since that time, over 100 cases of mechanical valve thrombolysis have been reported

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Fig. 2. Transesophagealechocardiogramof the right atrium before urokinase. Note the 3.5 x 1.7 cm thrombus (small arrows) and the interatrial septum, which bulgestoward the left atrium becauseof the high right atria1 pressure(large arrows). LA, Left atrium; RA, right atrium.

in the literature,‘, ‘, 4,g but none of these involved a StarrEdwards tricuspid prosthesis.These reports describedthe use of both streptokinase and urokinase, with similar successrates.The streptokinasedosesreported were similar in all cases,usually 250,000units administeredas an intravenousbolus over 30 minutes, followed by a maintenanceinfusion of 100,000unit&r for 72 hours.The urokinasedoses werealsosimilar, usually 4400units/kg administeredasan intravenous bolus over 10 to 15 minutes, followed by a maintenance infusion of 4400 units/kg/hi- for 72 hours. These are the sameregimens used for the treatment of acute pulmonary embolus.Recently there have been several casereports using tissue plasminogenactivator at a doseof approximately 100mg over 12 hours.3,4The numbers are as yet too small to allow analysis of the success rates. Overall success rateshave varied from 755~to 83%.l, 2,4,5 There has been an incidence of rethrombosisof approximately 15% to 20%; these casescan be retreated successfully with repeat thrombolysis. Complications have been carefully documented. Complications such as fever, epistaxis, uterine bleeding,bleeding from venepuncture or arterial puncture sites, hemoperitoneum,and hemarthrosis have been reported in approximately 50% of treated patients. The incidence of systemic embolization hasbeen approximately 15% .l, 6 However, most manifestations of embolization (hemianopia,splenic infarction, transient ischemic attack, and upper and lower limb ischemia) resolved spontaneouslywithin 2 days. Lower extremity embolectomy was required in one patient.6 Despite the fact that no deaths were reported in three recent large studies involving 86patients, l, 2,6there have beenfive deathsfrom

stroke during thrombolysis of prosthetic valves reported in the literature.iO, l1 Thrombolysis of 28 tricuspid valve mechanical prostheseshasbeenreported.2-4,lo*12-15 The therapy was initially successfulin 26 of 28 patients (93%), although six of these required retreatment that also proved successful.The two patients with treatment failure were sent for reoperation. Doppler echocardiography has not been previously reported for diagnosingthrombosisof a Starr-Edwards valve in the tricuspid position. Several studies quote normal pressurehalf-times and peak velocities for native, tissue, and disc tricuspid valves.16,l7 No data are available for the Starr-Edwards valve in the tricuspid position. The normal range of pressure half-times for tricuspid Bjork-Shiley (Shiley, Inc., Irvine, Calif.) and Carpentier-Edwards (Baxter Healthcare Corp., Edwards Division) valves is 38 to 197 msec.16The peak transvalvular flow velocity for normal tricuspid BjBrk-Shiley and Carpentier-Edwards valves is 0.6 to 1.6 m/sec.16,l7 Mean gradientscalculated by Doppler echocardiographyand confirmed at cardiac catheterization for these tricuspid prosthesesranged from 3 to 8 mm Hg.17-lgIn the current case,the initial pressurehalf-time was 445 msecand the initial peak velocity was 2.2 m/set (mean gradient 15 mm Hg), clearly representing obstruction. This diagnosis provided an explanation for the patient’s symptoms and led to corrective thrombolytic therapy. The successof valve thrombolysis is excellent for a diseasewith an otherwise high mortality. In the current case,the patient left the hospital free of symptoms and in normal sinusrhythm, with echocardiographicand Doppler evidence of improved tricuspid prosthesisfunction after thrombolysis with urokinase. The literature suggeststhat

708

Rollefson et al.

in a hemodynamically stable patient with evidence of mechanical valve thrombosis, there appears to be comparatively little risk in attempting thrombolytic therapy for this condition. This is especially true for valves in the tricuspid position, where there has been no reported mortality. As opposed to the situation with left-sided thrombosed prostheses, there is no safe way to measure the gradient across a thrombosed tricuspid prosthesis during catheterization. Therefore Doppler echocardiography is the technique of choice to diagnose the disorder and to monitor the progress of therapy. REFERENCES

1. Silber H, Khan SS, Matloff JM, Chaux A, DeRobertis M, Gray R. The St. Jude valve: thrombolysis as the first line of therapy for cardiac valve thrombosis. Circulation 1993;87:30-7. 2. Kurzrok S, Singh AK, Most AS, Williams DO. Thrombolytic therapy for prosthetic cardiac valve thrombosis. J Am Co11 Cardiol 1987;9:592-8. 3. Cohen ML, Barzilai B, Gutierrez F, Jaffe AS, Eisenberg P. Treatment of prosthetic tricuspid valve thrombosis with lowdose tissue plasminogen activator. AM HEART J 1990;120:978-

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17. Panidis IP, ROSS J, Mintz GS. Normal and abnormal proathetic valve function as assessed by Doppler echocardiography. J Am Co11 Cardiol 1986;8:317-26. 18. Burstow DJ, Nishimura RA, Bailey KR, Reeder GS, Holmes DR Jr, Seward JB, Tajik J. Continuous wave Doppler echocardiographic measurement of prosthetic valve gradients. Circulation 1989;80:504-14. 19. Wilkins GT, Gillam LD, Kritzer GL, Levine RA, Palacios IF, Weyman AE. Validation of continuous-wave Doppler echocardiographic measurements of mitral and tricuspid prosthetic valve gradients: a simultaneous Doppler-catheter study. Circulation 1986;74:786-95.

Traumatic dehiscence of a tricuspid annuloplasty ring: Diagnosis by transesophageal echocardiography William A. Rollefson, CAPT, MC, Timothy M. Winslow, MAJ, MC, Carl W. Adams, LTC, MC, and Michael Honolulu, Hawaii

H. Dang, MD

80. 4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14. 15. 16.

Prieto Palomino MA, Ruiz de Elvira MJ, Sanchez Llorente F, Torrado E, Castillo JL, Gonzalez de Vega N, Garijo Galve A. Successful thrombolysis on a mechanical tricuspid prosthesis. Eur Heart J 1989;10:1115-7. Luluaga IT, Carrera N, D’Oliveira J, Cantaluppi CG, Santin H, Molteni L, Ferreira R, Zwolinski E, Luluaga II. Successful thrombolytic therapy after acute tricuspid valve obstruction. Lancet 1971;1:1067-8. Ledain LD, Ohayon JP, Colle JP, Lorient-Roudaut FM, Roudaut RP, Besse PM. Acute thrombotic obstruction with disc valve prostheses: diagnostic considerations and fibrinolvtic treatment. J Am Co11 Cardiol 1986:7:743-51. Thorburn CW, Morgan JJ, Shanahan M%, Chang VP. Longterm results of tricuspid valve replacement and the problem of prosthetic valve thrombosis. Am J Cardiol1983;51:1128-32. Ben-Ismail M, Abid F, Sirinelle A, Curran Y. Thromboses tardives sur protheses tricuspidiennes. Arch Ma1 Coeur 1981; 74:289-96. Czer LSC, Weiss M, Bateman TM, Pfaff JM, DeRobertis M, Eigler N, Vas R, Matloff JM, Gray RJ. Fibrinolytic therapy of St. Jude valve thrombosis under guidance of digital cinefluoroscopy. J Am Co11 Cardiol 1985;5:1244-9. Roudaut R, Labbe T, Lorient-Roudaut M-F, Gosse P, Baudet E, Fontan F, Besse P, Dallocchio M. Mechanical cardiac valve thrombosis: is fibrinolysis justified? Circulation 1992;86(suppl):II-8-15. 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. Braverman AC, Barzilai B, Waggoner AD. Prosthetic tricuspid valve thrombosis and thrombolytic therapy. Cardiology 1993;4:64K-P. Wright JO, Hiratzka LF, Brandt B III, Doty DB. Thrombosis of the Bjiirk-Shiley prosthesis. J Thorac Cardiovasc Surg 1982;84:138-44. Amann FW, Kiowski W, Pfisterer M, Gurckhardt D. Fibrinolytic treatment in thrombolytic obstruction of a tilting disc prosthesis. AM HEART J 1986;112:1084-8. Boskovic D, Elezovic I, Boskovic D, Simin N, Rolovic Z, Josipovic V. Late thrombosis of the Bjork-Shiley tilting disc valve in the tricuspid position. J Thorac Cardiovasc Surg 1986;91:1-8. Pye M, Weerasana N, Bain WH, Hutton I, Cobbe SM. Dopuler echocardiogranhic characteristics of normal and dysfunctioning prosthetic valves in the tricuspid and mitral position. Br Heart J 1990;63:41-4.

Tricuspid insufficiency is a well recognized but uncommon complication of blunt chest trauma. It usually occurs in the setting of major chest trauma associated with significant thoracic injury and other traumatic lesions of the heart.’ Dysfunction of the tricuspid valve may occur as the result of papillary muscle or chordal rupture or disruption of the leaflet or valve anulus. 1-Z Previous reports have involved traumatic disruption of native tricuspid valvular structures, but we could find no previous reports of traumatic tricuspid insufficiency caused by disruption of a tricuspid annuloplasty ring. Transesophageal echocardiography (TEE) has been recently reported to be useful in the diagnosis of tricuspid valve disease.” We report a case of traumatic tricuspid insufficiency resulting from dehiscence of a Carpentier-Edwards annuloplasty ring (Baxter Healthcare Corp., Edwards Div., Irvine, Calif.) caused by blunt chest trauma, which was diagnosed by TEE. A 67-year-old woman underwent a mitral valve replacement and a tricuspid annuloplasty with an Omni-Science prosthesis (Medical Incorporated, Inver Grove Heights, Minn.) and a Carpentier-Edwards ring for treatment of symptomatic rheumatic mitral valve disease with associated tricuspid insufficiency. Her postoperative course was unremarkable, and a transthoracic echocardiogram before discharge showed trivial tricuspid insufficiency and a norFrom the Cardiology Service, Surgery Service, Department Honolulu, Hawaii. Reprint Medicine,

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The opinions or assertions contained herein thors and are not to be construed as official Department of the Army or the Department

AM HEART J 1994;127:'708-10. 4/4/51962

Cardiothoracic Medical Center,

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are the private views of the auor as reflecting the views of the of the Defense.