Peripartum cardiomyopathy

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. (CHEST 2001; 120:681-683)

Key words: adult; cardiomyopathy; echocardiography; thrombolysis; thrombus

Abbreviations: AMI = acute myocardial infarction; DCM = dilated cardiomyopathy; LVEF = left ventricular ejection fraction; rt-PA = recombinant tissue plasminogen activator

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.

CASE REPORT

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 [degrees] 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/[micro]L 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

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 al[4] 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 al[5] 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 al[6] 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.[8-11] Krogmann et al[8] successfully lysed a mobile and protruding left ventricular thrombus in a 2-year-old boy with congenital DCM. Kemennu and Riggs[9] 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 al[10] 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 al[11] 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.

CONCLUSION

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.

REFERENCES

[1] Alexander R, Schlant R, Fuster V, et al. Hurst's the heart, arteries, and veins. 9th ed. New York, NY: McGraw-Hill, 1998; 1553

[2] Gottdiener J, Gay J, VanVoorhees L, et al. Frequency and embolic potential of left ventricular thrombus in dilated cardiomyopathy: assessment by two-dimensional echocardiography. Am J Cardiol 1983; 52:1281-1285

[3] Falk R, Foster E, Coats M. Ventricular thrombi and thromboembolism in dilated cardiomyopathy: a prospective follow-up study. Am Heart J 1992; 123:136-142

[4] Haugland J, Asinger R, Mikell F. Embolic potential of left ventricular thrombi detected by two-dimensional echocardiography. Circulation 1984; 70:588-598

[5] Kremer P, Fiebig R, Tilsner V, et al. Lysis of left ventricular thrombi with urokinase. Circulation 1985; 72:112-118

[6] Mathey D, Siglow V, Kremer J, et al. Lysis therapy for left ventricular thrombi. Dtsch Med Wochenschr 1988; 1113: 1271-1214

[7] Fuster V, Verstraete M. Hemostasis, thrombosis, fibrinolysis, and cardiovascular disease. In: Brunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Philadelphia, PA: W.B. Saunders, 1997; 1833

[8] Krogmann ON, von Kries R, Rammos S, et al. Left ventricular thrombus in a 2-year-old boy with cardiomyopathy: lysis with recombinant tissue-type plasminogen activator. Eur J Pediatr 1991; 150:829-831

[9] Kemennu L, Riggs T. Tissue plasminogen activator lysis of a right ventricular thrombus. Am Heart J 1992; 123:1057-1058

[10] Janssens U, Klues H, Hanrath P. Successful thrombolysis of right atrial and ventricle thrombi in a patient with peripartum cardiomyopathy and extensive thromboembolism. Heart 1997; 78:515-516

[11] Yeh KH, Hung KC, Lin FC, et al. Successful lysis of right and left heart thrombus by tissue plasminogen activator. Cathet Cardiovasc Intervent 2000; 49:91-96

(*) From the Department of Internal Medicine, Divisions of Cardiology and Pulmonology/Critical Care, University of Mississippi Medical Center, Jackson, MS.

Manuscript received July 10, 2000; revision accepted February 5, 2001.

Correspondence to: Nancy A. Collop, MD, FCCP, Professor of Medicine, Pulmonary andCritical Care Medicine, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505; e-mail: ncollop@aol.com

COPYRIGHT 2001 American College of Chest Physicians
COPYRIGHT 2001 Gale Group