(Chest. 2001;120:681-683.)
© 2001
American College of Chest Physicians
Lysis of a Left Ventricular Thrombus With Recombinant Tissue Plasminogen Activator*
Benjamin T. Rester, MD;
James L. Warnock, MD;
Praful B. Patel, MD;
Michael R. McMullan, MD;
Thomas N. Skelton, MD and
Nancy A. Collop, MD, FCCP
*
From the Department of Internal Medicine, Divisions of Cardiology and Pulmonology/Critical Care, University of Mississippi Medical Center, Jackson, MS.
Correspondence to: Nancy A. Collop, MD, FCCP, Professor of Medicine, Pulmonary and Critical Care Medicine, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505; e-mail: ncollop{at}aol.com
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Abstract
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A 23-year-old woman with peripartum cardiomyopathy presented
with a 2.1 x 2.5-cm pedunculated, mobile, left ventricular thrombus
and evidence of systemic embolization. Due to the patient’s poor left
ventricular function, thrombectomy was not a viable option. Treatment
with high-dose IV heparin was initially utilized but was unsuccessful
as the thrombus appeared to enlarge on echocardiography. An accelerated
weight-adjusted dose of recombinant tissue plasminogen activator
(rt-PA) successfully lysed the thrombus without evidence of
embolization. Although rt-PA has been used for primary lysis of
high-risk ventricular thrombi, this is the first documentation of
successful lysis of a left ventricular thrombus in a patient with
peripartum cardiomyopathy.
Key Words: adult • cardiomyopathy • echocardiography • thrombolysis • thrombus
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Introduction
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This
case report describes a young woman with peripartum cardiomyopathy who
presented with a 2.1 x 2.5-cm pedunculated, mobile, left ventricular
thrombus and evidence of systemic embolization. Although recombinant
tissue plasminogen activator (rt-PA) has been used for primary lysis of
high-risk ventricular thrombi, this is the first documentation of
successful lysis of a left ventricular thrombus in a patient with
peripartum cardiomyopathy.
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Case Report
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A 23-year-old woman with pregnancy-induced hypertension
diagnosed at 20 weeks’ gestation and peripartum cardiomyopathy
diagnosed 1 month postpartum was admitted to the medical ICU with
worsening shortness of breath, fatigue, and bilateral flank pain. The
patient was 2 months postpartum and was receiving lisinopril,
furosemide, and digoxin for congestive heart failure. An echocardiogram
1 month prior to ICU admission showed a left ventricular ejection
fraction (LVEF) of 40%, moderate pulmonary hypertension, mild left
atrial enlargement, and mild mitral and tricuspid regurgitation with
anteroseptal and inferior wall hypokinesis.
On evaluation, vital signs were as follows: temperature (oral),
39.4°C; heart rate, 130 beats/min; and respiratory rate, 35
breaths/min. The patient was an obese woman in mild distress
because of pain, with elevated jugular venous pulsations, tachycardia
with an S3 gallop at the apex, and bilateral basilar rales on
auscultation. There was moderate, bilateral, lower-quadrant abdominal
tenderness without rebound or pain with percussion. Significant
laboratory data included the following: total leukocyte count,
21,000/µL with 70% segmented and 6% band cells; alkaline
phosphatase, 388 IU/L; aspartate aminotransferase, 407 IU/L; and
alanine aminotransferase, 368 IU/L. An ECG showed sinus tachycardia
with nonspecific ST-T segment abnormalities, and chest radiograph
revealed cardiomegaly with an infiltrate in the left lower lung field
consistent with pneumonia. Treatment with broad-spectrum antibiotics
was initiated secondary to concerns for a concomitant pulmonary and
intra-abdominal infection. A CT of the abdomen showed findings
suggestive of partial splenic and right renal ischemic infarction. A
two-dimensional Doppler echocardiogram on hospital day 2 exhibited
severely decreased LVEF (25%) and a 2.1 x 2.5-cm apical left
ventricular thrombus that was mobile and protruding into the left
ventricular cavity (Fig 1
,
2
). Although the patient had no complaints of chest pain, mild elevations
in cardiac troponin I isoenzyme were detected. This troponin elevation
was believed secondary to embolization into the coronary arteries with
resultant microinfarction and worsening left ventricular function.
Subsequently, the patient was administered a weight-based heparin
infusion. During the following 48 h, she developed a painful and
transiently pulseless right lower extremity. A repeat echocardiogram on
hospital day 4 revealed evidence of lucency in the center of the
thrombus, as well as an attached echo-dense area suggesting further
thrombus formation. Due to the high likelihood of continued
embolization, in light of a negative finding on CT of the head, the
patient was administered (following informed consent) an accelerated,
weight-adjusted infusion of rt-PA over the course of 90 min. A
follow-up echocardiogram approximately 8 to 10 h later showed near
complete resolution of the thrombus. There were no further clinical
signs of embolization during or after rt-PA infusion. An echocardiogram
on hospital day 8 showed persistently diminished LVEF with global
hypokinesis, but no evidence of residual or recurrent thrombus
formation. The patient was discharged receiving oral warfarin therapy.
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Discussion
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The development of intracavitary or mural cardiac thrombi in
patients with acute myocardial infarction (AMI), left ventricular
aneurysm, and dilated cardiomyopathy (DCM) is well
described.1
Although the exact mechanism remains unclear,
presumably an akinetic segment or globally hypokinetic ventricle leads
to stasis and subsequent thrombus formation. For the last 20 years,
two-dimensional echocardiography has been effectively and reliably
utilized to demonstrate the presence of ventricular thrombi, both mural
and intracavitary, with a 36 to 44% incidence of left ventricular
thrombosis.2
3
However, perhaps the more concerning aspect
regarding ventricular thrombosis is not its presence, but the potential
for systemic embolization. The morphologic characteristics of the clot
itself combined with the contractability of the ventricle are primary
determinants of embolic risk. Intuitively, a thrombus that protrudes
into the lumen of the ventricle and is subject to the flow of blood
vigorously pumped across its surface has a greater propensity to
detach and embolize than does a smooth, mural thrombus located in
a relatively akinetic wall segment. Haugland et al4
studied 60 patients with left ventricular thrombus visualized on
two-dimensional echocardiography. Of the 27% of patients with evidence
of systemic embolization, intracavitary motion combined with protrusion
and central echogenic lucency were the three most important
characteristics, in descending order, associated with embolization.
Although the incidence, frequency, and embolic potential of left
ventricular thrombi has been well studied and documented, there is no
generally accepted consensus published regarding its management. Over
the last 30 years, the primary therapeutic options have included
thrombectomy, anticoagulation, or, more recently, thrombolysis.
Before rt-PA was commercially available in the United States, the two
primary thrombolytic agents on the market were streptokinase and
urokinase. These agents have been used extensively to treat left
ventricular thrombus and, particularly, AMI. Kremer et al5
described 16 patients with recent AMI and mural thrombi who were
treated with urokinase. Successful lysis, which seemed to occur more
commonly in soft, newly formed clots, was noted in 10 of 16 patients
(62.5%). Two individuals developed hematuria, while another two
patients had no detectable change in the size or appearance of the
thrombus. Mathey et al6
likewise reported an approximate
66% rate of complete lysis with urokinase and similar complications of
hemorrhage and lack of any detectable thrombolysis. Although both
agents are effective plasminogen activators, streptokinase is
well-known for its potential for anaphylaxis (approximately 1%) and
antibody formation, potentially rendering the drug ineffective in
vivo. Urokinase has been removed from the United States market by
the Food and Drug Administration due to concerns of impurities in the
raw materials.
rt-PA is a highly fibrin-specific serine protease that catalyzes the
Arg560-Val561 peptide bond of plasminogen.7
Since 1991,
there have been four separate case reports where rt-PA was utilized for
primary lysis of intracardiac thrombi.8
9
10
11
Krogmann et
al8
successfully lysed a mobile and protruding left
ventricular thrombus in a 2-year-old boy with congenital DCM. Kemennu
and Riggs9
likewise used rt-PA for lysis of a large,
mobile, and protruding right ventricular thrombus in a 13-year-old girl
with congestive heart failure secondary to doxorubicin
toxicity. One hour after rt-PA infusion was completed, there was no
residual echocardiographic evidence of thrombus and no complications.
Janssens et al10
described successful lysis of right
atrial and ventricular thrombi in a patient with peripartum
cardiomyopathy and evidence of extensive pulmonary embolism. More
recently, Yeh et al11
reported three separate cases where
rt-PA was used successfully to lyse right-sided and left-sided
intracardiac thrombi with high-risk features. Two of the patients
developed thrombi as a complication of radiofrequency ablation, and one
patient had DCM related to chronic supraventricular tachycardia. In all
three patients, there were no bleeding or embolic complications during
or after administration of rt-PA.
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Conclusion
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To our knowledge, this is the first documented case in
which rt-PA was used for primary lysis of a left ventricular thrombus
in a patient with peripartum cardiomyopathy. Particularly when there is
evidence of extensive embolization and high-risk echocardiographic
features, we feel that early and aggressive thrombolysis with rt-PA is
a superior alternative to treatment with streptokinase, urokinase,
high-dose heparin, or thrombectomy.
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Footnotes
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Abbreviations: AMI = acute myocardial infarction;
DCM = dilated cardiomyopathy; LVEF = left ventricular ejection
fraction; rt-PA = recombinant tissue plasminogen activator
Received for publication July 10, 2000.
Accepted for publication February 5, 2001.
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References
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Alexander, R, Schlant, R, Fuster, V, et al (1998) Hurst’s the heart, arteries, and veins 9th ed. ,1553 McGraw-Hill New York, NY.
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Falk, R, Foster, E, Coats, M (1992) Ventricular thrombi and thromboembolism in dilated cardiomyopathy: a prospective follow-up study. Am Heart J 123,136-142[CrossRef][ISI][Medline]
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Haugland, J, Asinger, R, Mikell, F (1984) Embolic potential of left ventricular thrombi detected by two-dimensional echocardiography. Circulation 70,588-598[Abstract/Free Full Text]
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Kremer, P, Fiebig, R, Tilsner, V, et al (1985) Lysis of left ventricular thrombi with urokinase. Circulation 72,112-118[Abstract/Free Full Text]
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Mathey, D, Siglow, V, Kremer, J, et al (1988) Lysis therapy for left ventricular thrombi. Dtsch Med Wochenschr 1113,1271-1214
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Krogmann, ON, von Kries, R, Rammos, S, et al (1991) Left ventricular thrombus in a 2-year-old boy with cardiomyopathy: lysis with recombinant tissue-type plasminogen activator. Eur J Pediatr 150,829-831[CrossRef][ISI][Medline]
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Kemennu, L, Riggs, T (1992) Tissue plasminogen activator lysis of a right ventricular thrombus. Am Heart J 123,1057-1058[CrossRef][ISI][Medline]
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Abstract
Introduction
