Drug-Eluting Stent Implantation for Acute Myocardial Infarction during Pregnancy with Use of Glycoprotein IIb/IIIa Inhibitor,

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J INVASIVE CARDIOL 2008;20:E146-E149

Acute myocardial infarction (AMI) is reported to occur in 3–10 cases per 100,000 deliveries.^1,2 It is a rare but devastating event with a fatality rate as high as 37–50%³ that can claim the life of the mother and her unborn baby and make a substantial contribution to maternal mortality.
Management of AMI in pregnancy has included all currently used therapies, but published reports are so few, making risk assessment of each therapy very difficult. Fibrinolysis has been used with success in more than one case.^4–7 There are only a few reports of percutaneous coronary intervention (PCI) with or without stenting in AMI during pregnancy,^6,8–17 and only one case reported the use of drug-eluting stent (DES) implantation.¹⁸ Abciximab has been used in only one published case,¹¹ and there are limited reports and experience of use of clopidogrel in pregnancy.^19–22 Bypass surgery has been performed successfully with or without heart-lung bypass.^4,8,23,24
We report the successful management of AMI in a 44-yearold, 8-week pregnant woman with intracoronary stent placement and antiplatelet medication, glycoprotein IIb/IIIa inhibitor, eptifibatide, aspirin and clopidogrel.

Case Report. A 44-year-old primigravida woman at 8 weeks of gestation presented to the emergency department with a 3 1/2- hour history of retrosternal chest pain when at rest, consistent with AMI. Her cardiovascular risk factors were relevant for gestational diabetes. She denied drug abuse, and her only medication was prenatal minerals and vitamins. She was distressed with chest pain, hemodynamically stable and her cardiovascular examination was within normal limits. Initial electrocardiography (ECG) (Figure 1) showed a QS pattern with ST-segment elevation in leads V1–V2. Echocardiography demonstrated an akinetic midseptum with hypokinesia of the rest of the septal and anterior wall. Her left ventricular ejection fraction was 46%. After 5 hours of chest pain, the patient’s cardiac troponin T was 0.37 ng/ml, her creatine kinase, was 350 u/L, and her creatine kinase-MB was 46.5 ng/ml.
The patient’s chest pain persisted despite treatment with oral aspirin, propranolol, intravenous nitrate and heparin infusion. Electrocardiographic monitoring displayed frequent short runs of nonsustained ventricular tachycardia with no hemodynamic compromise. She was taken for coronary angiography and possible intervention. An obstetric team was present for continuous fetal monitoring and was prepared for urgent cesarean section if needed. Abdominal shielding was placed to protect the fetus from radiation, and fluoroscopic time was minimized. Using the right femoral approach, the angiography showed normal left main, circumflex and right coronary arteries; the left anterior descending coronary artery (LAD) had a 90% occlusion of the mid-part with thrombolysis in myocardial infarction (TIMI) 2 flow distally (Figure 2A).

Bearing in mind the reported risks of fibrinolytic therapy in such a patient, increased maternal mortality (1.2%), pregnancy loss (5.8%) and bleeding (8.1%),7 and because the risk to the mother and fetus was thought to be less with PCI, we elected to treat her with angioplasty. She was loaded with 600 mg of clopidogrel and a heparin bolus to achieve an activated clotting time > 250 seconds. After balloon dilatation of the LAD stenosis, the flow remained TIMI 2. TIMI 3 flow is critical for an optimal outcome, so we proceeded with stenting. TIMI 3 flow was obtained by deploying 2 Taxus^® Liberté monorail stents (Boston Scientific Corp., Natick, Massachusetts) across the lesion, a 3.0 x 24 mm for the proximal and a 2.5 x 16 mm stent for the mid- LAD lesion (Figure 2B). An eptifibatide bolus (180 μg/kg) was given, followed by a 2 μg/kg/minute intravenous infusion for the following 24 hours.
In the coronary care unit, she was maintained on oral clopidogrel, aspirin and propranolol. Electrocardiographic monitoring showed no significant dysrhythmias. Troponin T peaked at 2.18 ng/ml, creatine kinase at 1170 u/L and creatine kinase-MB at 189.2 ng/ml. She was discharged on 75 mg of clopidogrel, 100 mg of aspirin daily (our standard cardiological practice) and 20 mg of propranolol 3 times daily.
At 36 weeks of gestation, she was admitted for planned delivery, but while in the hospital, she underwent a semi-urgent cesarean section because of fetal distress. It was considered that in a primigravida patient with AMI and left ventricular dysfunction (ejection fraction 46%), a cesarean section would be safer than prolonged spontaneous vaginal delivery. Aspirin and clopidogrel were withheld on the morning of surgery.
The cesarean section was uneventful. She remained hemodynamically stable intraoperatively, and there were no ischemic changes on ECG or intra- or postoperative bleeding. There was a total blood loss of around 500 cc, and the birth of a healthy baby. The next day, clopidogrel and aspirin were resumed and she remained well until discharge 3 days later.

Discussion
Pregnancy-related AMI is rare, but with a reported increasing incidence, possibly due to more births to older women with greater cardiac risk factors and also to improved diagnosis, notably tests for troponins. The other side of the coin is that advances in diagnosis and treatment are resulting in fewer fatalities.²⁵ Most deaths from AMI during pregnancy occur at the time of initial infarction — the prognosis being worse if the infarct occurs in late pregnancy or the mother is under 35 years of age. Cesarean section and delivery within 2 weeks of the infarct are also associated with a worse prognosis due to the increased myocardial demand of labor or surgery.³
Our patient presented with AMI within 3 hours of onset of her symptoms, and the diagnosis was clear from the history and the ECG. Her history of diabetes, the presence of diffusely diseased proximal and mid-segments of the LAD, and the absence of other causes for coronary occlusion suggested an etiology of atherosclerosis. Her persistent chest pain despite optimal medical therapy, the bursts of ventricular tachycardia, the presence of diabetes and pregnancy-related hypercoagulability collectively made early revascularization of considerable value.
Although there are reports of systemic^4–7 and intracoronary fibrinolysis^12,26 for AMI during pregnancy, we considered fibrinolytic therapy a relative contraindication due to the increased risk of maternal and fetal hemorrhage. On the other hand, there are reports of successful PCI, with or without stenting, as treatment of AMI during pregnancy^6,8–17 and coronary stenting have been shown not only to reduce the frequency of restenosis compared with conventional balloon angioplasty,^28,29 but also to decrease the need for target-vessel revascularization in diabetic patients.³⁰
Despite the fact that our patient displayed many of the factors associated with the possibility of restenosis: small vessel size,³¹ lesions in the LAD,²⁹ required stent length and diabetes mellitus,^32–38 the benefit of early revascularization of a large area of jeopardized myocardium outweighed these risks and those from the use of contrast medium and radiation (provided that there was adequate shielding of the fetus).
Preliminary reports suggest that DES are not associated with increased risk when used for primary PCI in patients with STelevation MI.³⁹ The Taxus Liberté stents that we used contained 1 μg/mm² of paclitaxel in a slow-release formulation in the polymer coating.⁴⁰ Paclitaxel is cytotoxic at high doses, but is cytostatic, anti-inflammatory and allows endothelialization at the much lower doses used in PCI.^41,42 Randomized trials, meta-analysis of trials and epidemiological studies have shown the superiority of DES over bare-metal stents in reducing late repeat revascularization,^43–45 but the safety and effectiveness of paclitaxel-eluting stents have not been established in pregnant or lactating women.
There are only limited reports and experience of adjuvant antiplatelet agents such as clopidogrel in pregnancy.19–22 Preclinical studies reported to the U.S. Food and Drug Administration showed no teratogenic effects of clopidogrel on pregnant rats and rabbits at doses 65 and 78 times the recommended human dose,⁴⁶ earning it a rating of pregnancy Class B. There is some evidence that clopidogrel may cause more hemorrhage at surgery,¹⁶ and perhaps at delivery, therefore, discontinuing clopidogrel 1 week before surgery has been recommended. Its use had no apparent adverse effects on our patient, even though she underwent a semi-urgent cesarean section with antiplatelets being withheld only on that morning, a finding compatible with a recent report by Balmain et al.¹⁹
Whether clopidogrel should be discontinued later in pregnancy is another matter. It works on a different pathway to aspirin, thus a similar effect on prostaglandins is unlikely, suggesting that clopidogrel is safe for use throughout pregnancy. However, experience with this medication in pregnancy is limited, and its use requires an assessment of the risks and benefits for the individual patient.
One PCI using a DES, although happily successful, is hardly a momentous event in the medical firmament, but it is hoped that it will now be considered as a possible alternative to other therapies for AMI in pregnancy and will be investigated further.

References

1. Badui E, Enciso R. Acute myocardial infarction during pregnancy and puerperium: A review. Angiology 1996;47:739–756.
2. Roth A, Elkayam U. Acute myocardial infarction associated with pregnancy. Ann Intern Med 1996;125:751–762.
3. Hankins GD, Wendel GD Jr, Leveno KJ, Stoneham J. Myocardial infarction during pregnancy: A review. Obstet Gynecol 1985;65:139–146.
4. Koul AK, Hollander G. Moskovits N, et al. Coronary artery dissection during pregnancy and the postpartum period: Two case reports and review of the literature. Cathet Cardiovasc Diagn 2001;52:88–94.
5. Schumacher B, Belfort MA, Card RJ. The successful treatment of acute myocardial infarction during pregnancy with tissue plasminogen activator. Am J Obstet Gynecol 1997;176:716–719.
6. Schulte-Sasse U. Life-threatening myocardial ischemia associated with the use of prostaglandin E1 to induce abortion. BJOG 2000;107:700–702.
7. Turrentine M, Braems G, Ramirez M. Use of thrombolytics for the treatment of thromboembolic disease during pregnancy. Obstet Gynecol Surv 1995;50:534–541.
8. Klutstein MW, Tzivoni D, Bitran D, et al. Treatment of spontaneous coronary artery dissection: Report of three cases. Cathet Cardiovasc Diagn 1997;40:372–376.
9. Sutaria N, O’Toole L, Northridge D. Postpartum acute MI following routine ergometrine administration treated successfully by primary PTCA. Heart 2000;83:97–98.
10. Craig S, Ilton M. Treatment of acute myocardial infarction in pregnancy with coronary artery balloon angioplasty and stenting. Aust NZ J Obstet Gynaecol 1999;39:194–196.
11. Sebastian C, Scherlag M, Kugelmass A, Schechter E. Primary stent implementation for acute myocardial infarction during pregnancy. Cathet Cardiovasc Diagn 1998;45:275–279.
12. Glazier JJ, Eldin AM, Hirst JA, et al. Primary angioplasty using a urokinase coated hydrogel balloon in acute myocardial infarction during pregnancy. Cathet Cardiovasc Diagn 1995;36:216–219.
13. Sanchez-Ramos L, Chami YG, Bass TZ, et al. Myocardial infarction during pregnancy: Management with transluminal coronary angioplasty and metallic intracoronary stents. Am J Obstet Gynecol 1994;171:1392–1393.
14. Ascarelli MH, Grider AR, Hsu HW. Acute myocardial infarction during pregnancy managed with immediate percutaneous transluminal coronary angioplasty. Obstet Gynecol 1996;88:655–657.
15. Webber MD, Halligan RE, Schumacher JA. Acute infarction, intracoronary thrombolysis, and primary PTCA in pregnancy. Cathet Cardiovasc Diagn 1997;42:38–43.
16. Sullebarger JT, Fontanet HL, Matar FA, et al. Percutaneous coronary intervention for myocardial infarction during pregnancy: A new trend? J Invasive Cardiol 2003;15:725–728.
17. Agostoni P, Gasparini G, Destro G. Acute myocardial infarction probably caused by paradoxical embolus in a pregnant woman. Heart 2004;90: e12.
18. Cuthill JA, Young S, Greer A, Oldroyd K. Anesthetic considerations in a parturient with critical coronary artery disease and a drug-eluting stent presenting for caesarean section. Int J Obstet Anesth 2005;14:167–171.
19. Balmain S, Mccullough CT, Love C, et al. Acute myocardial infarction during pregnancy successfully treated with primary percutaneous coronary intervention. International J Cardiol 2007;116:e85–e87.
20. O'Shanahan N, Garcia M, Santana C, et al. Acute coronary syndrome without ST elevation during pregnancy. Med Intensiva 2006;30:180–182.
21. Martin M, Romero E, Moris C. Acute myocardial infarction during pregnancy. Treatment with clopidogrel. Med Clin (Bar) 2003;121:278–279.
22. Klinzing P, Markert UR, Liesaus K, Peiker G. Case report: Successful pregnancy and delivery after myocardial infarction and essential thrombocythemia treated with clopidogrel. Clin Exp Obstet Gynecol 2001;28:215–216.
23. Garry D, Leikin E, Fleisher AG, Tejani N. Acute myocardial infarction in pregnancy with subsequent medical and surgical management. Obstet Gynecol 1996;87:802–804.
24. Silberman S, Fink D, Berko RS, et al. Coronary artery bypass surgery during pregnancy. Eur J Cardiothorac Surg 1996;10:925–926.
25. Andra H, Margaret G, Mimi S, Leo R. Acute myocardial infarction in pregnancy United States population-based study. Circulation 2006;113:1564–1571.
26. Brodie BR, Grines CL, Ivanhoe R, et al. Six month clinical and angiographic follow-up after direct angioplasty for myocardial infarction. Circulation 1994;90:156–162.
27. Van’t Hof AW, Henriques J, Ottervanger JP, et al. No mortality benefit of primary angioplasty over thrombolytic therapy in patients with nonanterior myocardial infarction at long-term follow-up: Results of the Zwolle trial. J Am Coll Cardiol 2003;41:369A.
28. Serruys PW, de Jaegere P, Kiemeneij F, et al. Acomparison of balloon-expandable- stent implantation with balloon angioplasty in patients with coronary artery disease: Benestent Study Group. N Engl J Med 1994;331:489–495.
29. Fischman DL, Leon MB, Baim DS, et al. A randomized comparison of coronary- stent placement and balloon angioplasty in the treatment of coronary artery disease: Stent restenosis study investigators. N Engl J Med 1994;331:496–501.
30. Gaxiola E, Vlietsra R, Browne KF, et al. Is the outcome of coronary stenting worse in elderly patients? J Intervent Cardiol 1998;11:37–40.
31. Dussaillant GR, Mintz GS, Pichard AD, et al. Small stent size and intimal hyperplasia contribute to restenosis: A volumetric intravascular ultrasound analysis. J Am Coll Cardiol 1995;26:720–724.
32. Kereiakes DJ, Midei M, Hermiller J, et al. Procedural and late outcomes following MULTI-LINK DUET coronary stent deployment. Am J Cardiol 1999;84:1385–1390.
33. Henderson RA, Pipilis A, Cooke R, et al. Angiographic morphology of recurrent stenoses after percutaneous transluminal coronary angioplasty: Are lesions longer at restenosis? Int J Card Imaging 1990;6:677–684.
34. Kitazume H, Ichiro K, Iwama T, Ageishi Y. Repeat coronary angioplasty as the treatment of choice for restenosis. Am Heart J 1996;132:711–715.
35. Erbel R, Haude M, Hopp HW, et al. Coronary-artery stenting compared with balloon angioplasty for restenosis after initial balloon angioplasty. Restenosis Stent Study Group. N Engl J Med 1998;339:1672–168.
36. Dussaillant GR, Mintz GS, Pichard AD, et al. Small stent size and intimal hyperplasia contribute to restenosis: A volumetric intravascular ultrasound analysis. J Am Coll Cardiol 1995;26:720–724.
37. Serruys PW, Kay IP, Disco C, et al. Periprocedural quantitative coronary angiography after Palmaz-Schatz stent implantation predicts the restenosis rate at six months: Results of a meta-analysis of the BElgian Netherlands Stent study (BENESTENT) I, BENESTENT II Pilot, BENESTENT II and MUSIC trials. Multicenter ultrasound stent in coronaries. J Am Coll Cardiol 1999;34:1067–1074.
38. Ellis SG, Savage M, Fischman D, et al. Restenosis after placement of Palmaz- Schatz stents in native coronary arteries: Initial results of a multicenter experi ence. Circulation 1992;86:1836–1844.
39. Lemos PA, Saia F, Hofma SH, et al. Short- and long-term clinical benefit of sirolimus-eluting stents compared to conventional bare stents for patients with acute myocardial infarction. J Am Coll Cardiol 2004;43:704–708.
40. Mark T, John O, Jeffrey P, et al. Polymer-based, paclitaxel-eluting TAXUS Liberté Stent in de novo lesions — The pivotal TAXUS ATLAS Trial. J Am Coll Cardiol 2007;49:1676–1683.
41. FDA. Summary of safety and effectiveness data (SSED). Available at http://origin.www.fda.gov/ohrms/dockets/dailys/ 04/sep04/090904/04m-0403- aav0001- 03-SSED-vol1.pdf. Accessed April 2006.
42. John ML, Gregg WS, Dawkins KD, et al. An overview of the TAXUS Express, paclitaxel-eluting stent clinical trial program. J Interven Cardiol 2006;19:422–431.
43. Babapulle MN, Joseph L, Belisle P, et al. A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents. Lancet 2004;364:583–591.
44. Schofer J, Schluter M. Are drug-eluting stents a panacea for patients with coronary heart disease? Lancet 2004;364:558–559.
45. Lemos PA, Serruys PW, van Domburg RT, et al. Unrestricted utilization of sirolimus-eluting stents compared with conventional bare stent implantation in the “real world”: The rapamycin-eluting stent evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry. Circulation 2004;109:190–195.
46. Reprotox Web site. Available at: http://www.reprotox.org.