Acute Myocardial Infarction during Puerperium. Report of Two Cases of Multivessel Involvement Treated with Primary Coronary Inte

Acute myocardial infarction (AMI) is a rare event in pre-menopausal women, with only 0.7% of the total number of AMIs appearing in young women.¹ The incidence of AMI in the Framingham study for women 35 to 44 years of age was 5.2 cases per 1,000 over a 10-year follow-up period.² AMI is also an exceptional occurrence during pregnancy, delivery or puerperium, with a prevalence of approximately 1 out of every 10,000–30,000 pregnancies.^1–3 Since the first description in 1922 by Katz,⁴ less than 200 cases have been reported. The condition is associated with a high mortality rate, both maternal and fetal, ranging from 20–50%.^1,3,5 The prognosis is worse when AMI occurs in the third trimester of pregnancy, during delivery or puerperium.¹ Most of the cases of AMI in the context of pregnancy have been reported in the third trimester, followed by the postpartum period,1 being less common during labor.⁵ The prevalence is higher among multipara or women older than 30 years, although it has been described in a wide range of ages (between 16 and 45 years). Often, single-vessel disease is found, and the most frequently involved (approximately 70% of cases) is the left anterior descending artery. Multivessel disease is rarely found in AMI related to pregnancy. Diagnosis is usually difficult due to the low degree of suspicion. During delivery and puerperium, electrocardiographic abnormalities which are not related to myocardial ischemia have been described.⁶ Moreover, creatine phosphokinase (CPK) and its MB fraction can increase during vaginal delivery.⁶ Cardiac troponin, a more specific marker of myocardial necrosis,7 and echocardiography have become the two most useful diagnostic tools. Case Reports Patient #1. The first patient is a 40-year-old woman who had no risk factors or history of cardiovascular disease and who 11 days prior, underwent an elective cesarean section after an uneventful pregnancy. She was brought to the emergency room after 20 hours of severe chest pain. The electrocardiogram (ECG) showed ST-elevation in I, aVL and V2–V4 (Figure 1A). She was taken to the intensive care unit, and after administration of aspirin, nitrates, beta blockers and heparin, she was taken to the cardiac catheterization laboratory where a diagnostic angiogram showed a complete occlusion of the mid left anterior descending artery (Figure 2A). After balloon angioplasty, two stents (MultiLink Zeta 2.75 x 13 and Pixel 2.5 x 18 mm, Guidant Corporation, California) were implanted, achieving TIMI 3 flow (Figure 2B) and normalization of the ST segment. The left circumflex and right coronary (RCA) arteries were normal (Figure 2C). A 300 mg dose of clopidogrel was administered. Six hours after the procedure she experienced sudden severe chest pain and ST-segment re-elevation in the anterolateral leads. With a suspected diagnosis of stent thrombosis, a new coronary angiogram was performed, showing patent stents and good flow in the LAD, but a thrombotic occlusion of the second diagonal branch was observed and successfully treated with balloon angioplasty and stent (Arthos Pico 2.5 x 12 mm, AMG, Germany). Postprocedure, an echocardiogram showed apical akinesis with preserved left ventricular function. Seventy-two hours later, the chest pain recurred and was associated with acute dyspnea and hypotension. The ECG (Figure 1B) showed second grade Mobitz I atrioventricular block and ST segment elevation in the inferior leads and V4R, and a chest X-ray revealed pulmonary edema. An urgent coronary angiography revealed acute thrombotic occlusion of the proximal RCA (Figure 2D) and severe stenosis, with thrombotic content proximal to the stent in the mid LAD. Direct stenting (MultiLink Zeta 4,00 x 15 mm, Guidant Corporation) of the proximal RCA was performed with full recovery of distal flow. Next, the mid LAD was treated with direct stent implantation (Multilink Zeta 3,00 x 18 mm). Due to proximal dissection, a second stent (Driver 3.50 x 25 mm, Medtronic Inc., Minnesota) was implanted and TIMI 3 flow was achieved, with no residual dissection image (Figure 2 E). The procedure was complicated by complete AV block, severe hypotension and respiratory arrest, which completely recovered after cardiopulmonary resuscitation maneuvers. The patient remained asymptomatic in the ICU and a new echocardiogram showed akinesis of the anterolateral, apical and distal inferior walls, with severe systolic left ventricular dysfunction (30% ejection fraction) and moderate mitral regurgitation. Total cholesterol levels, HDL and LDL, were within normal range. A hypercoagulability study, which included lupic anticoagulant, anticardiolipin IgG and IgM, Factor V Leiden, prothrombin 20210, antithrombin III, protein C and protein S, was normal. An autoimmunity study was also normal, with negative ANA, ANCA, anti Scl70, anti Sm, antiRo and anti La, and normal values of C3 and C4. High-sensitivity CRP during follow-up was between 3 and 5 mg/dl. Homocysteinemia was 6.1 mcmol/l (normal Patient #2. A 26-year-old primigravida who smoked 10 cigarettes per day, underwent an elective cesarean section due to twin pregnancy. During pregnancy, she suffered from anemia and the threat of premature labor that required oral ritodrine. Delivery through cesarean section was uneventful, and methylergometrine (0.4 mg every 8 hours intramuscular) was administered after surgery due to vaginal bleeding. Forty-eight hours later, she developed acute chest pain and dyspnea. On physical examination she had normal blood pressure, a third heart sound and bilateral pulmonary rales. The ECG showed ST-segment depression in the inferior leads and in V3–V6 (Figure 3), and an X-ray showed typical signs of pulmonary edema. An emergency coronary angiogram was performed, showing acute occlusion at four levels: the proximal LAD, the second and third marginal branches of the circumflex artery, and the proximal right posterior descending (RPD) artery (Figures 4 A–C). Balloon angioplasty followed by a Cypher™ Stent (Cordis Corp., Miami, Florida) implantation was performed in the proximal LAD (Figure 4D), and the RPD was treated with 2 mm balloon angioplasty. The patient had an uncomplicated recovery. Maximal values of troponin and CPK were 5.05 ng/ml and 490 U/ml, respectively. An echocardiogram performed before hospital discharge revealed apical akinesis, lateral hypokinesis and an ejection fraction of 55%, with mild mitral regurgitation. No abnormalities were found in a wide hypercoagulability study and the patient’s CRP levels were normal. Discussion Different pathogenic mechanisms, such as atherosclerosis, vasospasm, thrombosis and coronary dissection, have been related to the development of AMI during pregnancy. If AMI occurs in the antepartum period in women over 30 years of age with coronary risk factors, coronary artery disease (CAD) is the most common finding. On the other hand, if AMI occurs in younger women during labor or puerperium, it is frequently related to coronary dissection or thrombosis.^2,3 Coronary atherosclerotic lesions have been reported in only 20–43% of the overall necropsic and angiographic published studies, whereas 30–47% of the coronary arteries are described as normal. Coronary thrombosis and spontaneous coronary dissection were observed in approximately 20% and 15% of cases, respectively. Vasculitis, hemostatic disorders, Kawasaki’s disease or coronary dissection secondary to acute aortic syndrome are much less frequently reported etiologies.^1,3,6,8 Coronary atherosclerosis, the main pathogenic mechanism in the general population, is present in less than 50% of these patients, usually in women over 35 years of age and with cardiovascular risk factors, most commonly hypertension and cigarette smoking.^1,3 As more women are getting pregnant at a later age, and since women have a high prevalence of cigarette smoking, an increase in the incidence of acute coronary events related to pregnancy is predictable. Vasospasm can be associated with this entity, and could be the cause of AMI in the presence of normal coronary arteries. During pregnancy, several factors, such as changes in endothelial function, as well as an increased vascular reactivity to angiotensin II and norepinephrine,^1,3 may contribute to coronary vasoconstriction. Moreover, several drugs administered during labor and puerperium, such as ergotamine and its derivatives or bromocriptine, can also induce coronary artery spasm.^6,9 Coronary thrombosis is also a frequent finding in AMI associated with pregnancy. During pregnancy, there is a predominance of procoagulant factors against fibrinolytic mechanisms due to several changes in the coagulation system that leads to a “prothrombotic state”. A decrease in plasmatic concentration of proteins S and C and of tissue plasminogen activator factor (t-PA), in contrast with an increase of plasminogen activator inhibitor (PAI) levels, has been described.⁶ Coronary artery dissection is a rare event, more frequent in women and often associated with delivery or postpartum periods.¹⁰ During pregnancy there are several histologic changes in the arterial wall, such as reticular fiber fragmentation, loss of the normal disposition of the elastic fibers and a decrease in the mucopolysaccharide content. These histopathologic changes, along with hemodynamic stress during labor, may induce coronary artery dissection. When AMI occurs in the immediate postpartum period, spontaneous dissection is the most common pathogenic mechanism (33%). It is important to bear this risk in mind, because it can worsen if fibrinolytic therapy is administered.¹¹ We report two cases in which thrombosis without significant atherosclerosis is the main pathogenic mechanism. In both patients, multivessel involvement was present, which has been rarely reported.^11,12 Patient #1 had an acute occlusion of a previously normal coronary artery. The clinical course suggests a hypercoagulability state, probably related to hemostatic abnormalities associated with pregnancy. This patient also carried different heterozygotic mutations in several genes of the homocysteine metabolic chain that have been associated with prothrombotic disorders. It is well known that hyperhomocysteinemia can be secondary to different genetic polymorphisms that constitute a risk factor for early atherosclerosis, venous thromboembolic disease and stroke. Homozygosis for C677T mutation of methylenetetrahydrofolate reductase (MTHFR) is the best known polymorphism, and it is present in approximately 10% of the general population.¹⁴ It produces a thermolabile enzyme variant with reduced activity. In a meta-analysis described by Klerck et al.,¹⁴ individuals with this mutation showed a 16% increase in the relative risk for CAD, but only when low folate levels were present. Schwartz et al.,¹⁵ in a retrospective study in women younger than 45 years of age who suffered an acute MI, concluded that MTHFR-C677T homozygosis is related to hyperhomocysteinemia and folate deficit, but not to CAD. Heterozygosis for this MTHFR mutation is neither associated with increased plasma levels of homocysteine nor with major risk of CAD.¹⁶ There is a dearth of information about the clinical importance of other polymorphisms in the homocysteine metabolic chain enzymes or the association of various polymorphisms in the same patient, as it occurred in our first patient. In a study,¹⁷ mutation A1298C in MTHFR, even in heterozygosis, was described as a risk factor for early CAD, with no correlation to homocysteine plasma levels. Nevertheless, in another study, the same mutation was neither associated alone nor with the co-expression of C677T mutation to an increased risk of CAD.¹⁸ Our first patient had normal homocysteine and folate levels in association with diverse heterozygotic mutations. Therefore, there is no scientific evidence to support a pathogenic role of such mutations in the development of acute coronary syndrome. In our second patient, the ECG presentation, with diffuse changes, and the observed angiography findings, with triple-vessel disease and narrow, nonatherosclerotic coronary arteries, suggest a prolonged, diffuse vasospasm with secondary thrombosis. Along with the vascular hyperreactivity induced by the pregnancy, the previous administration of methylergometrine might have induced the coronary spasm, as reported before,^11,12,19 and for this reason, she did not receive calcium channels blockers after the acute phase. The recommended therapy for AMI during pregnancy is primary percutaneous coronary angioplasty,²⁰ being especially useful during puerperium. It decreases bleeding complications associated with fibrinolytic therapy, and allows the operator to identify and treat coronary artery dissection. Since the mid-1990s, primary PTCA during pregnancy has been reported,^21,22 with good results and low complication rates. Multivessel involvement in this context is rare and, as we report, can induce severe hemodynamic compromise secondary to significant myocardial damage and acute ventricular dysfunction, leading to a worse prognosis. In summary, pregnancy-related AMI is an uncommon occurrence that has a different pathogenesis and an uncertain prognosis. Multivessel involvement is also rare and leads to a worse prognosis. The two cases we report here involve multivessel involvement and advanced Killip Class. Our patients experienced favorable results with percutaneous coronary intervention. To our knowledge, this is the first description of multivessel primary PCI that is shown to be a safe, feasible and effective therapy, and that will likely improve the prognosis of pregnancy-related AMI.

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