MULTIPLE CASE ARTICLE
Acute coronary syndrome during pregnancy
J.G.P. Wassing, P.E. Polak, C.J.M. de Groot, J.W. Roos-Hesselink
Two cases of myocardial infarction during the second trimester of pregnancy are presented. Both patients were treated with thrombolytic therapy. In the first case the treatment was successful, in the other patient thrombolysis only temporarily relieved the symptoms. Therefore, angiography was performed and a significant stenosis in the left anterior descending coronary artry was successfally treated with balloon angioplasty. Both women delivered a healthy child, the first child was born at term, the second at a gestational age of 33 weeks. Percutaneous intervention versus thrombolytic therapy in pregnancy is discussed. (Neth Heartj 2005;13:360-5.)
diagnostic and therapeutic approaches is greatly influenced not only by maternal but also by foetal safety. We present two clinical cases of acute myocardial infarction in pregnant women and will discuss the modalities oftreatment, considering the potential risks for mother and child.
Case histories
J.G.P. Wassing J.W. Ro's--sellnk Department of Cardiology, Thoraxcentre, Erasmus Medical Centre, Rotterdam P.E. Polak Departrnent of Cardiology, Erasmus Medical Centre, Rotterdam and Sint Anna Hospital, Geldrop CJ.M. de Groot Obstetric Department, Erasmus Medical Centre, Rotterdam
Case one A 36-year-old woman with hypercholesterolaemia, a positive family history of heart disease, and smoking behaviour presented to our hospital with a two-day history of chest pain. She was four months pregnant. Physical examination showed a blood pressure of 180/95 mmHg, heart rate of 108 beats/min, normal venous pressure, and normal heart sounds, with no additional murmurs. Xanthelasmata were clearly present around her eyes. The electrocardiogram showed marked ST elevation in VI to V4 and reciprocal depression in the inferior leads in accordance with an acute anterior myocardial infarction (figure 1). She was treated with thrombolysis (reteplase), and the pain and ST elevation on the electrocardiogram resolved (figure 2). Cardiac markers were slightly raised, with a troponin I of 48.7 ug/l and a CKvalue of maximal 246 U/1. In conclusion, an acute anterior myocardial infarction was successfuilly treated with thrombolysis. Echocardiography afterwards showed mild hypokinesia in the anterior wall and apex. The patient was treated with acetylsalicylate acid, metoprolol and isosorbide mononitrate. After delivering a healthy child vaginally, she suffered from atypical chest pains. A diagnostic coronary angiogram was performed which showed a 50% stenosis of the left anterior descending artery after the first diagonal branch; the diagonal branch showed a 70% stenosis. She was treated conservatively.
Correspondence to: J.W. Roos-Hesselink Department of Cardiology, Thoraxcentre, Erasmus Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam E-mail: [email protected]
Case two A 39-year-old woman with hypertension, a positive family history of cardiac disease, smoking and hyper-
Key words: pregnancy, myocardial infarction, thrombolysis, percutaneously intervention, PTCA
The prevalence ofcoronary artery disease in female patients is increasing due to changed patterns of lifestyle including smoking and stress. Up to 10% of the female patients with myocardial infarction are under the age of35.1 During pregnancy there is a higher risk ofthrombotic events due to hypercoaguability. Because women are delaying childbearing until an older age, we will more frequently encounter acute myocardial infarction during pregnancy. When this happens, it constitutes a major problem for the patient and the treating physician, because the selection of
360
Ne3herlands Heart Journal, Volume 13, Number 10, October 2005
CW
Acute coronary syndrome during pregnancy
Figure 1. Case 1. ECG during acute anterior myocardial infarction.
cholesterolaemia, presented with collapse. She was gravida 3 para 0, 17 weeks pregnant. She was admitted to the cardiology department. Physical examination showed a blood pressure of 140/90 mmHg, heart rate of 90 beats/min and xanthelasmata above her left eye. She had normal heart sounds with a grade one ejection murmur. The ECG
on admission showed normal sinus rhythm. Cardiac markers at admission were normal, cholesterol was 7.3 mmol/l, glucose 6.7 mmol/A and a haemoglobin of 7.6 mmol/l. That night she developed ventricular fibrillation which was successfully defibrillated. The ECG at that time showed acute anterior myocardial ischaemia with
Figure 2. Case 1. ECG after treatment with thrombolysis.
qc
Netherands Heart Journal, Volume 13, Number 10, October 2005
361
Acute coronary syndrome during pregnancy
AAR
1I
I-
-Y2
Uir
1. I]I
Vs
IR3
,..
Figure 3 Case 2. ECG showing acute anterior myocardial infarction.
ST elevation in leads V2 to V4 and reciprocal depression in leads II, III and aVF (figure 3). She was treated with thrombolysis (rt-PA), which relieved her symptoms and ECG changes (figure 4). Maximum CKwas 829
U/1. Two days later she experienced chest pain with ECG changes (pseudo-normalisation) in V5 and V6. She was transferred for diagnostic angiography. Angiography showed a diffuse atherosclerotic coronary artery system with a significant stenosis in the left anterior descending artery (figure 5). The angiography was complicated by thrombosis of the right femoral artery which was treated by embolectomy and a goretex patch was inserted. At first, conservative treatment with metoprolol, nifidipine and acenocoumarol (for the thrombotic process in the femoral artery) was started. Due to persistent angina an intervention was unavoidable and she was successfully treated with a balloon angioplasty (figure 6). Eventually she delivered a healthy boy vaginally at 33 weeks pregnancy. The woman remained symptomfree for five years follow-up; the boy showed signs of the attention deficit hyperactivity disorder. Discussion In the literature the risk of a myocardial infarction is estimated at one in 10,000 in women during preg-
362
nancy.2-4 Roth et al. reported that myocardial infarction can occur in all stages of the pregnancy but usually appears in the third trimester in women >33 years.5 In normal pregnancy, circulatory changes not only ensure an adequate supply of nutrients and oxygen to the developing foetus but also change the cardiac situation. Blood volume and cardiac output increase by 30 to 50%. The increase reaches a peak at around the 24th to 28th week, and stays high or slowly decreases until term. Furthermore, there is an increase in heart rate of 10 to 20 beats/min. Gestational hormones, circulating prostaglandins in combination with the low vascular resistance ofthe placenta and the uterus, decrease the peripheral vascular resistance and blood pressure. Additionally, labour and uterine contractions result in an increase in blood pressure and cardiac output. Finally, after delivery there is an important increase in cardiac preload as a result of decompression ofthe inferior vena cava and the return of uterine blood to the circulation. The reabsorption of extracellular fluids into the circulation in the postpartum period results in an increase in intravascular volume. Most haemodynamic adaptations will resolve within two to six weeks postpartum.6 The changed cardiac and haemodynamic situation and especially hypercoaguability during pregnancy and the postpartum period possibly contributes to the spectrum of
Netherlands Heart Journal, Volume 13, Number 10, October 2005
XC
Acute coronary syndrome during pregnancy
Figure 4. Case 2. ECG after treatment with thrombolysis. causes of myocardial infarction. Coronary atherosclerosis (with or without thrombus) was found in 43% and a thrombus without signs of atherosclerosis was present in 21% of the patients.5 Coronary dissection b
;,.;t
ri*
.,
.,..
:W.
.;.,
Figure 5. Case 2. Angiographic right anterior oblique view with a significantstenosis in the kft anterior descending artety.
t#
was found in 16% and was the primary cause of infarction in the postpartum period, while normal coronary arteries were reported in 20%. The suggested role of coronary spasm is a point of discussion.
Netherlands Heart Journal, Volume 13, Number 10, October 2005
Figure 6. Case 2. Angiographic right anterior oblique view of the left coronary artery after successful angioplasty. 363
Acute coronary syndrome during pregnancy
The estimated mortality for acute myocardial infarction in pregnancy is 20 to 37% for the mother and 17% for the child.78 The diagnosis is often missed because symptoms may occur during pregnancy and the physician does not expect myocardial infarction. In the acute phase, the treatment options for an acute myocardial infarction are percutaneous intervention, thrombolysis or CABG. At present the primary choice of treatment in the general population is PTCA with stenting. However, during pregnancy the selection of diagnostic and therapeutic approaches is greatly influenced not only by maternal but also by foetal safety. In PTCA and cardiac catheterisation radiation is necessary. Radiation exposure to the foetus is kept to the minimum if PTCA is performed through the radial artery. The amount of foetal exposure to radiation during chest radiography in PTCA results in a mean of 0.02 mSv and a maximum of 0.1 mSv in difficult PTCA procedures (National Council of Radiation Protection and Measurements 1998) (table 1). Therefore, PTCA can probably be considered safe but should only be used during pregnancy when absolutely necessary because of the possible detrimental effects on the foetus (table 2). The 8th to 15th week is the most sensitive period for the foetus concerning radiation.
As with PTCA, there is little experience with thrombolytic therapy during myocardial infarction. Streptokinase and rt-PA do not cross the placenta in animals. There is very little information available on the passage of streptokinase in the human placenta but it does not seem to cross the human placenta during late pregnancy.9"10 It is unknown whether rt-PA crosses the human placenta. In one case intracranial haemorrhage was reported in a newborn infant whose mother received rt-PA treatment during pregnancy."l The few available reports do not mention a teratogenic effect. Most experiences with thrombolytic therapy during pregnancy have been with streptokinase in patients with pulmonary embolism, deep venous thrombosis and cardiac valve thrombosis. Complications mentioned were maternal haemorrhage, uterine haemorrhages with emergency caesarean section, preterm delivery, foetal loss, fatal abruption placenta, postpartum
Table 1. Foetal dose and X-ray investigation (NCRP 1998).
Investigation
Foetal dose (mSv) Maxlmum Mean
Abdomen Colon Thorax CT thorax CT abdomen CT pelvis PTCA
1.4 6.8
Acute coronary syndrome during pregnancy
J.G.P. Wassing, P.E. Polak, C.J.M. de Groot, J.W. Roos-Hesselink
Two cases of myocardial infarction during the second trimester of pregnancy are presented. Both patients were treated with thrombolytic therapy. In the first case the treatment was successful, in the other patient thrombolysis only temporarily relieved the symptoms. Therefore, angiography was performed and a significant stenosis in the left anterior descending coronary artry was successfally treated with balloon angioplasty. Both women delivered a healthy child, the first child was born at term, the second at a gestational age of 33 weeks. Percutaneous intervention versus thrombolytic therapy in pregnancy is discussed. (Neth Heartj 2005;13:360-5.)
diagnostic and therapeutic approaches is greatly influenced not only by maternal but also by foetal safety. We present two clinical cases of acute myocardial infarction in pregnant women and will discuss the modalities oftreatment, considering the potential risks for mother and child.
Case histories
J.G.P. Wassing J.W. Ro's--sellnk Department of Cardiology, Thoraxcentre, Erasmus Medical Centre, Rotterdam P.E. Polak Departrnent of Cardiology, Erasmus Medical Centre, Rotterdam and Sint Anna Hospital, Geldrop CJ.M. de Groot Obstetric Department, Erasmus Medical Centre, Rotterdam
Case one A 36-year-old woman with hypercholesterolaemia, a positive family history of heart disease, and smoking behaviour presented to our hospital with a two-day history of chest pain. She was four months pregnant. Physical examination showed a blood pressure of 180/95 mmHg, heart rate of 108 beats/min, normal venous pressure, and normal heart sounds, with no additional murmurs. Xanthelasmata were clearly present around her eyes. The electrocardiogram showed marked ST elevation in VI to V4 and reciprocal depression in the inferior leads in accordance with an acute anterior myocardial infarction (figure 1). She was treated with thrombolysis (reteplase), and the pain and ST elevation on the electrocardiogram resolved (figure 2). Cardiac markers were slightly raised, with a troponin I of 48.7 ug/l and a CKvalue of maximal 246 U/1. In conclusion, an acute anterior myocardial infarction was successfuilly treated with thrombolysis. Echocardiography afterwards showed mild hypokinesia in the anterior wall and apex. The patient was treated with acetylsalicylate acid, metoprolol and isosorbide mononitrate. After delivering a healthy child vaginally, she suffered from atypical chest pains. A diagnostic coronary angiogram was performed which showed a 50% stenosis of the left anterior descending artery after the first diagonal branch; the diagonal branch showed a 70% stenosis. She was treated conservatively.
Correspondence to: J.W. Roos-Hesselink Department of Cardiology, Thoraxcentre, Erasmus Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam E-mail: [email protected]
Case two A 39-year-old woman with hypertension, a positive family history of cardiac disease, smoking and hyper-
Key words: pregnancy, myocardial infarction, thrombolysis, percutaneously intervention, PTCA
The prevalence ofcoronary artery disease in female patients is increasing due to changed patterns of lifestyle including smoking and stress. Up to 10% of the female patients with myocardial infarction are under the age of35.1 During pregnancy there is a higher risk ofthrombotic events due to hypercoaguability. Because women are delaying childbearing until an older age, we will more frequently encounter acute myocardial infarction during pregnancy. When this happens, it constitutes a major problem for the patient and the treating physician, because the selection of
360
Ne3herlands Heart Journal, Volume 13, Number 10, October 2005
CW
Acute coronary syndrome during pregnancy
Figure 1. Case 1. ECG during acute anterior myocardial infarction.
cholesterolaemia, presented with collapse. She was gravida 3 para 0, 17 weeks pregnant. She was admitted to the cardiology department. Physical examination showed a blood pressure of 140/90 mmHg, heart rate of 90 beats/min and xanthelasmata above her left eye. She had normal heart sounds with a grade one ejection murmur. The ECG
on admission showed normal sinus rhythm. Cardiac markers at admission were normal, cholesterol was 7.3 mmol/l, glucose 6.7 mmol/A and a haemoglobin of 7.6 mmol/l. That night she developed ventricular fibrillation which was successfully defibrillated. The ECG at that time showed acute anterior myocardial ischaemia with
Figure 2. Case 1. ECG after treatment with thrombolysis.
qc
Netherands Heart Journal, Volume 13, Number 10, October 2005
361
Acute coronary syndrome during pregnancy
AAR
1I
I-
-Y2
Uir
1. I]I
Vs
IR3
,..
Figure 3 Case 2. ECG showing acute anterior myocardial infarction.
ST elevation in leads V2 to V4 and reciprocal depression in leads II, III and aVF (figure 3). She was treated with thrombolysis (rt-PA), which relieved her symptoms and ECG changes (figure 4). Maximum CKwas 829
U/1. Two days later she experienced chest pain with ECG changes (pseudo-normalisation) in V5 and V6. She was transferred for diagnostic angiography. Angiography showed a diffuse atherosclerotic coronary artery system with a significant stenosis in the left anterior descending artery (figure 5). The angiography was complicated by thrombosis of the right femoral artery which was treated by embolectomy and a goretex patch was inserted. At first, conservative treatment with metoprolol, nifidipine and acenocoumarol (for the thrombotic process in the femoral artery) was started. Due to persistent angina an intervention was unavoidable and she was successfully treated with a balloon angioplasty (figure 6). Eventually she delivered a healthy boy vaginally at 33 weeks pregnancy. The woman remained symptomfree for five years follow-up; the boy showed signs of the attention deficit hyperactivity disorder. Discussion In the literature the risk of a myocardial infarction is estimated at one in 10,000 in women during preg-
362
nancy.2-4 Roth et al. reported that myocardial infarction can occur in all stages of the pregnancy but usually appears in the third trimester in women >33 years.5 In normal pregnancy, circulatory changes not only ensure an adequate supply of nutrients and oxygen to the developing foetus but also change the cardiac situation. Blood volume and cardiac output increase by 30 to 50%. The increase reaches a peak at around the 24th to 28th week, and stays high or slowly decreases until term. Furthermore, there is an increase in heart rate of 10 to 20 beats/min. Gestational hormones, circulating prostaglandins in combination with the low vascular resistance ofthe placenta and the uterus, decrease the peripheral vascular resistance and blood pressure. Additionally, labour and uterine contractions result in an increase in blood pressure and cardiac output. Finally, after delivery there is an important increase in cardiac preload as a result of decompression ofthe inferior vena cava and the return of uterine blood to the circulation. The reabsorption of extracellular fluids into the circulation in the postpartum period results in an increase in intravascular volume. Most haemodynamic adaptations will resolve within two to six weeks postpartum.6 The changed cardiac and haemodynamic situation and especially hypercoaguability during pregnancy and the postpartum period possibly contributes to the spectrum of
Netherlands Heart Journal, Volume 13, Number 10, October 2005
XC
Acute coronary syndrome during pregnancy
Figure 4. Case 2. ECG after treatment with thrombolysis. causes of myocardial infarction. Coronary atherosclerosis (with or without thrombus) was found in 43% and a thrombus without signs of atherosclerosis was present in 21% of the patients.5 Coronary dissection b
;,.;t
ri*
.,
.,..
:W.
.;.,
Figure 5. Case 2. Angiographic right anterior oblique view with a significantstenosis in the kft anterior descending artety.
t#
was found in 16% and was the primary cause of infarction in the postpartum period, while normal coronary arteries were reported in 20%. The suggested role of coronary spasm is a point of discussion.
Netherlands Heart Journal, Volume 13, Number 10, October 2005
Figure 6. Case 2. Angiographic right anterior oblique view of the left coronary artery after successful angioplasty. 363
Acute coronary syndrome during pregnancy
The estimated mortality for acute myocardial infarction in pregnancy is 20 to 37% for the mother and 17% for the child.78 The diagnosis is often missed because symptoms may occur during pregnancy and the physician does not expect myocardial infarction. In the acute phase, the treatment options for an acute myocardial infarction are percutaneous intervention, thrombolysis or CABG. At present the primary choice of treatment in the general population is PTCA with stenting. However, during pregnancy the selection of diagnostic and therapeutic approaches is greatly influenced not only by maternal but also by foetal safety. In PTCA and cardiac catheterisation radiation is necessary. Radiation exposure to the foetus is kept to the minimum if PTCA is performed through the radial artery. The amount of foetal exposure to radiation during chest radiography in PTCA results in a mean of 0.02 mSv and a maximum of 0.1 mSv in difficult PTCA procedures (National Council of Radiation Protection and Measurements 1998) (table 1). Therefore, PTCA can probably be considered safe but should only be used during pregnancy when absolutely necessary because of the possible detrimental effects on the foetus (table 2). The 8th to 15th week is the most sensitive period for the foetus concerning radiation.
As with PTCA, there is little experience with thrombolytic therapy during myocardial infarction. Streptokinase and rt-PA do not cross the placenta in animals. There is very little information available on the passage of streptokinase in the human placenta but it does not seem to cross the human placenta during late pregnancy.9"10 It is unknown whether rt-PA crosses the human placenta. In one case intracranial haemorrhage was reported in a newborn infant whose mother received rt-PA treatment during pregnancy."l The few available reports do not mention a teratogenic effect. Most experiences with thrombolytic therapy during pregnancy have been with streptokinase in patients with pulmonary embolism, deep venous thrombosis and cardiac valve thrombosis. Complications mentioned were maternal haemorrhage, uterine haemorrhages with emergency caesarean section, preterm delivery, foetal loss, fatal abruption placenta, postpartum
Table 1. Foetal dose and X-ray investigation (NCRP 1998).
Investigation
Foetal dose (mSv) Maxlmum Mean
Abdomen Colon Thorax CT thorax CT abdomen CT pelvis PTCA
1.4 6.8
