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doi:10.1111/jog.12437
J. Obstet. Gynaecol. Res. Vol. 40, No. 6: 1534–1539, June 2014
Takotsubo cardiomyopathy after cesarean: A case report and published work review of pregnancy-related cases Miki Minatoguchi1, Atsuo Itakura2, Eiji Takagi3, Manabu Nishibayashi4, Mariko Kikuchi1 and Osamu Ishihara1 1 Department of Obstetrics and Gynecology Saitama Medical University, Saitama, 2Department of Obstetrics and Gynecology, School of Medicine, Juntendo University, 4Department of Obstetrics and Gynecology, Nerima Hikarigaoka Hospital, Tokyo and 3 Division of Cardiology, Cardiovascular Center, Shioda Memorial Hospital, Chiba, Japan
Abstract Takotsubo cardiomyopathy (TCM) primarily affects postmenopausal women and is an important differential diagnosis of acute coronary syndrome. We describe a rare case of post-partum TCM, and present a published work review of the cases of pregnancy-associated TCM. A 24-year-old Japanese woman pregnant with twins suffered from premature membrane rupture at 31 gestational weeks. Following emergency cesarean delivery, she complained of sudden dyspnea. Transthoracic echocardiography revealed an inverted Takotsubo pattern (ejection fraction, 46%). On post-delivery day 8, wall motion abnormalities subsided, and she was discharged on post-delivery day 16. We reviewed 18 relevant cases of peripartum TCM from the published work. Among them, 16 cases were post-partum and two cases occurred during pregnancy. Most women (81%) underwent cesarean delivery, and the first symptoms of TCM appeared during surgery in 38% of the cases. The dominant symptoms were chest pain (44%) and dyspnea (28%). Most cases (94%) exhibited electrocardiogram abnormalities, including ST changes and T-wave inversion. Serum levels of cardiac enzymes were abnormally high in 92% of the cases. Repeated echocardiography documented normalized left ventricular systolic function within 6 months in all cases. This case and review emphasize that TCM may be concealed in post-partum women by symptoms undistinguishable from acute coronary syndrome, peripartum cardiomyopathy or pulmonary thromboembolism, and that echocardiography may be a useful tool to distinguish them. Key words: apical ballooning syndrome, cesarean delivery, preterm delivery, stress-induced cardiomyopathy, Takotsubo cardiomyopathy.
Introduction Takotsubo cardiomyopathy (TCM) is characterized by acute, profound, but reversible left ventricular dysfunction in the absence of significant coronary artery disease. The symptoms are triggered by acute emotional or physical stress identified by a distinctive pattern of ‘apical ballooning’.1 TCM is an important differential diagnosis of acute coronary syndrome (ACS).2 This phenomenon primarily affects postmenopausal women between 60 and 70 years old,
and is often preceded by emotional or physical stress associated with an elevation of plasma catecholamine levels.3 TCM was first described in the Japanese published work in 1990,4 and was initially thought to be restricted to the Japanese/Asian population. Recently, several cases of pregnancy or post-partum TCM have been reported in young women from Western countries. Here, we report a case of TCM that occurred after cesarean delivery and a global published work review of pregnancy-associated TCM (P-TCM).
Received: September 19 2013. Accepted: February 23 2014. Reprint request to: Professor Atsuo Itakura, Department of Obstetrics and Gynecology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: [email protected]
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Pregnancy-related Takotsubo cardiomyopathy
Case A 24-year-old pregnant Japanese woman (gravida 1, para 1) was transported to Saitama Medical University Hospital due to preterm labor. Her pregnancy was a spontaneous monochorionic diamniotic twin pregnancy. She had no known pre-existing cardiomyopathy or cardiovascular risk factors, such as obesity, smoking or a family history of cardiovascular diseases. After admission, ritodrine hydrochloride was administrated i.v. for tocolysis. To suppress the uterine contractions, the dose of ritodrine hydrochloride was gradually elevated to 200 μg/min and betamethasone (12 mg) was injected twice i.m. at 31 + 1/7 gestational weeks. At 31 + 4/7 gestational weeks, premature rupture of membranes was diagnosed. Accordingly, emergency cesarean delivery was performed under standard spinal anesthesia. Following the administration of spinal anesthesia, she became hypotensive and 8 mg ephedrine was administrated i.v. Just after the delivery of two girls (birthweights 1692 g and 1722 g; Apgar 8/9 and 8/9), her percutaneous oxygen saturation fell to 95%, and she was supplemented with 5 L/min oxygen. Otherwise, the cesarean delivery was uneventful. Thirty minutes after her transfer to the obstetric ward, the patient suddenly complained of dyspnea. Her percutaneous oxygen saturation fell abruptly from 97% to 85%, and she was supplemented with 5 L/min oxygen. Emergency computed tomography excluded pulmonary thromboembolism (PTE). Chest X ray, which was normal preoperatively (Fig. 1a), revealed cardiomegaly and pulmonary congestion after delivery (Fig. 1b). Electrocardiogram showed normal findings, except for sinus tachycardia. Bedside echocardiography revealed extensive hypokinesis. Therefore, she was transferred to the cardiology unit. Transthoracic echocardiography revealed extensive hypokinesis in the basal segments of the anterior, inferior and lateral walls, with preserved function in the apical segments, following an inverted Takotsubo pattern (Fig. 2).5 The ejection fraction was 46%. Laboratory data showed no elevation in serum myocardial enzymes, but an elevation of brain natriuretic peptide (65 pg/mL). After diagnosing this condition as TCM, carperitide, furosemide and dopamine hydrochloride were infused continuously. Magnetic resonance imaging revealed normal coronary arteries. Repeated transthoracic echocardiography on postdelivery day 8 showed a reduction of wall motion abnormalities, with an ejection fraction of 55%. The patient was discharged on post-delivery day 16. On
(a)
(b)
Figure 1 Chest X ray on the day of cesarean section. (a) Before operation, (b) 1 h after operation showing edema of the lungs.
post-delivery day 19, follow-up transthoracic echocardiography at the outpatient clinic revealed nearly normalized cardiac function.
Discussion Takotsubo cardiomyopathy, also known as ‘stressinduced cardiomyopathy’ or ‘apical ballooning syndrome’, was originally described in Japan in the 1990s.4 In Western countries, this condition is particularly associated with pregnancy, and seems to be underreported. A large case series showed that patients with TCM had a mean age of 69 years (range, 30–90)
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Figure 2 Transthoracic echocardiograph still-frame of the apical four-chamber view revealing hypokinesis of the basal segments (arrows) with preserved function in the apical segments.
and were most commonly (81%) postmenopausal (aged >50 years).1 Therefore, P-TCM is considered a special type of TCM. In 2011, a published work review of cesarean delivery-related TCM only identified five cases in the English published work, using MEDLINE and Cochrane databases, including one Japanese case.6 The focus has been on women undergoing elective cesarean delivery, with the onset of TCM symptoms during surgery or in the immediate postoperative period. Therefore, the characteristics for this special form of TCM have not been fully elucidated. Here, we describe a published work review of symptomatic P-TCM, including reports in Japanese. We identified a total of 29 cases of symptomatic P-TCM that manifested within 5 months after delivery, and were reported in English or Japanese. We used PubMed (1966 to December 2012), Japana Centra Revuo Medicina (1983 to December 2012). The search terms were ‘apical ballooning’, ‘broken heart’, ‘cardiomyopathy’, ‘delivery’, ‘peripartum’, ‘pregnancy’, ‘stress induced’ and ‘Takotsubo’. Our inclusion criteria in this review were similar to those of Zdanowicz et al.,6 with the exception of language, pregnancy stage and delivery mode. Our criteria were as follows: no pre-existing cardiomyopathy or any other known cardiac defect, no pre-existing fetal malformations, the presence of characteristic symptoms and signs of TCM (Guidelines for Diagnosis of Takotsubo Cardiomyopathy),7 and the onset of TCM symptoms during pregnancy or within the first 5 months
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after delivery. Publications in English and Japanese were included. Eleven cases were excluded from the present analysis due to inadequate data for the diagnosis of P-TCM (eight cases), or complications such as pheochromocytoma and bromocriptineinduced coronary spasm (three cases). Thus, a total of 18 cases (Table 1) were analyzed in this study.6,8–23 According to our published work review, repeated echocardiography of all cases documented normalized left ventricular systolic function within 6 months after the onset of P-TCM. Short-term prognosis is likely to be favorable, although long-term outcome remains unknown. Incidentally, no case of subsequent pregnancy has been reported. The symptoms of TCM are triggered by physical or emotional stress. For pregnant women, the most common physical stressors are perioperative and postoperative procedures.1 A previous review discussed catecholamines/vasoconstrictive substances administrated during cesarean section with regard to P-TCM.6 Unfortunately, some of the studies did not describe the management during cesarean section in detail. We found the description about the administration of catecholamines/vasoconstrictive substances during cesarean section in 38% of the 13 cases (Table 1). Although estrogen deficiency after delivery may be a stressor, the majority of these cases had initial symptoms within a day after delivery (Fig. 3). Among the post-partum cases, physical or emotional stress related to spontaneous or cesarean delivery may be a dominant trigger. Most cases of post-delivery P-TCM underwent cesarean delivery (13/16 including ours), and the first symptoms were manifested during surgery in five cases. These cases demonstrate the clinical implications of cesarean delivery. In 33% of the 18 cases (and our case), acute cardiopulmonary collapse occurred on the day of delivery, with symptoms mimicking those of PTE24 and peripartum cardiomyopathy (PCM).25 In addition, most cases initially complained of chest symptoms, including chest pain or dyspnea, which are identical to those of ACS. Electrocardiogram abnormalities, ranging from ST changes to T-wave inversion, were reported in 94% (17/18) of the cases. Furthermore, the serum level of at least one cardiac enzyme was elevated in 92% (12/13) of the cases, which is also similar to ACS.26 Therefore, P-TCM does not have pathognomonic symptoms because the primary symptoms are similar to those of other complications. Consequently, P-TCM is an important disorder in the
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Italy
White
Brazil
32
23
37
5
NA 36 40 NA
38
NA 37
NA
NA
Multiparous 23
NA
2P 2P Multiparous Primipara
Primipara
NA Primipara
Multiparous 37
VD
VD
VD
VD C/S C/S C/S
C/S
C/S
C/S C/S
C/S
C/S C/S
C/S C/S C/S VD
○ ○ ○ NA ○ NA × × NA × × × × × ×
× × ×
○ × ○ × ○ × × × × × × × × × ×
× × ×
40 days after delivery
23rd GW
6th GW
16 days 1h Intraoperatively A few hours after
Intraoperatively
Intraoperatively
Intraoperatively 2h
1h
1 day 5 days
Intraoperatively Just after operation 3h 3 days
Dizziness, syncope
Chest pain, shortness of breath Chest pain Substernal chest pain Chest heaviness Paresis, painful paresthesia, vegetative symptoms Very tired, stomachache Chest pain
Dyspnea Chest discomfort, dyspnea Chest discomfort, developed breathlessness Dyspnea Breathlessness, chest heaviness Chest pain
Dyspnea Dyspnea Dyspnea, chest pain Shortness of breath
Symptom
NA
○
○
○ ○ ○ ○
○
○
○ ○
○
○ ○
○ NA NA NA
×/○
○/×
×/○
○/× ○/× ×/○ ×/○
×/○
×/○
○/○ ×/○
×/○
○/○ ×/○
×/× ×/○ ×/○ ○/×
○ × × NA
CA/ VC
30 days
16 weeks
9 days
6 weeks 4 weeks 4 days 15 days
8 days
3 months
2 weeks 22 days
1 day
NA
NA
NA
NA × ○ ×
○
○
× ○
×
Within 3 weeks × 2 weeks ×
2 weeks 92 days Normal 3 months
Elevation ST changes/T Recovery of enzyme inversion in ECG
C/S, cesarean section; CA/VC, catecholamines/vasoconstrictive substances during cesarean section; ECG, electrocardiogram; GW, gestational weeks; NA, not applicable; P, parity; VD, vaginal delivery. Enzyme includes creatinine kinase-MB isozyme and cardiac troponins.
12 13 14 15
16 D’Amato et al.21 17 Brezina and Isler22 18 Freitas et al.23
White
42
USA Caucasian USA White
Caucasian Multiparous 38
32
10 Zdanowicz et al.6 11 Citro et al.16
32 30 31 32
Korean Korean
28 37
8 Kim et al.14 9 Jo et al.15
Yaqub et al.17 Muller et al.18 Crimi et al.19 Parodi et al.20
Indian
31
37 NA
7 Sengupta et al.13
NA NA
Japanese Korean
31 38 30 NA
GW Mode of Multiple Use of Onset delivery pregnancy tocolysis
41 30
Primipara Primipara Multiparous Primipara
Primipara/ multiparous
Japanese Japanese Japanese Japanese
Age Country, Race, Descent
24 28 30 25
Current case Niki et al.8 Shoji et al.9 Shimamoto et al.10 5 Sato et al.11 6 Lee et al.12
1 2 3 4
Author
Table 1 Characteristics of the cases
Pregnancy-related Takotsubo cardiomyopathy
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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occurring during surgery may be diagnosed as PCM. Therefore, the etiology of PCM may be considered partially identical to that of P-TCM. No case of P-TCM occurring during prepartum management of preterm labor has been reported. If they overlap, these risk factors may contribute to the occurrence of P-TCM. In conclusion, we must be aware that P-TCM may be hidden in post-partum women with symptoms undistinguishable from ACS, PCM or PTE. Echocardiography may be a useful tool to identify P-TCM based on akinesis and basal hyperkinesis.
Figure 3 Histogram of the number of pregnancyassociated Takotsubo cardiomyopathy cases occurring in each gestational or post-partum stage.
differential diagnosis of ACS, PTE and PCM for women with such symptoms occurring during pregnancy and the post-partum period. Clinical guidelines for pregnancy recommend appropriate imaging to diagnose PTE.27 Computed tomography pulmonary angiography is generally preferred because of the relatively high diagnostic accuracy for PTE.28 On the other hand, echocardiography also can be used for rapid and accurate risk stratification of patients with PTE.29 Echocardiography is the preferred screening method to assess cardiac function,28,30 and apical ballooning with akinesis and basal hyperkinesis are specific findings for TCM.7 Additionally, echocardiography is an ideal risk stratification approach because this portable device can be used at the bedside.29 Accordingly, echocardiography should take high priority for the differential diagnosis of ACS, PTE, PCM and TCM. Multiple pregnancies occurred in five cases, and four of them were administrated a tocolytic agent, which is ritodrine hydrochloride (β2-agonist).31 However, the administration of catecholamines is considered a stressor,1,32 and blocking β-adrenergic receptors was reported to reduce the risk of TCM.32,33 Therefore, the use of tocolytic agents during multiple pregnancies may be associated with the occurrence of TCM. Accordingly, a report on PCM recently published in Japan identified multiple gestation and tocolytic agent use as potential risk factors.34 A difference in the distribution and density of myocardial adrenoceptors may be responsible for the distinct clinical features of TCM.35,36 If myocardial adrenoceptors are distributed uniformly, the left ventricular systolic dysfunction
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Disclosure We hereby state that all authors have no conflict of interest. The study was funded entirely by the authors.
References 1. Eitel I, von Knobelsdorff-Brenkenhoff F, Bernhardt P et al. Clinical characteristics and cardiovascular magnetic resonance findings in stress (Takotsubo) cardiomyopathy. JAMA 2011; 306: 277–286. 2. Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E. Apical ballooning syndrome or takotsubo cardiomyopathy: A systematic review. Eur Heart J 2006; 27: 1523–1529. 3. Bybee KA, Kara T, Prasad A et al. Systematic review: Transient left ventricular apical ballooning: A syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med 2004; 141: 858–865. 4. Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: A review of five cases. J Cardiol 1991; 21: 203–214. 5. Kim S, Yu A, Filippone LA, Kolansky DM, Raina A. InvertedTakotsubo pattern cardiomyopathy secondary to pheochromocytoma: A clinical case and literature review. Circulation 2005; 111: 200–205. 6. Zdanowicz JA, Utz AC, Bernasconi I, Geier S, Corti R, Beinder E. ‘Broken heart’ after cesarean delivery. Case report and review of literature. Arch Gynecol Obstet 2011; 283: 687– 694. 7. Kawai S, Kitabatake A, Tomoike H. Guidelines for diagnosis of takotsubo (ampulla) cardiomyopathy. Takotsubo Cardiomyopathy Group. Circ J 2007; 71: 990–992. 8. Niki Y, Takasu A, Sakakibara K, Matsuzaki Y, Tsuboi H, Minakuchi K. A case report of postpartum pulmonary edema associated with long-term administration of ritodrine. J Jpn Soc Intensive Care Med 2003; 10: 201–205. (In Japanese.) 9. Shoji T, Takatori E, Oyama R et al. Tako-Tsubo cardiomyopathy caused immediately following cesarean section delivery of triplets: A case report. Gynecol Obstet Invest 2012; 74: 84–88. 10. Shimamoto H, Okamoto M, Sueda T et al. Transient regional wall motion abnormality and increased wall thickness of the left ventricle in acute myopericarditis occurring in the puerperium. Hiroshima J Med Sci 1986; 35: 285–287.
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11. Sato A, Yagihara N, Kodama M et al. Takotsubo cardiomyopathy after delivery in an estrogen-deficient patient. Int J Cardiol 2011; 149: e78–e79. 12. Lee S, Lee KJ, Yoon HS, Kang KW, Lee YS, Lee JW. Atypical transient stress-induced cardiomyopathies with an inverted Takotsubo pattern in sepsis and in the postpartal state. Tex Heart Inst J 2010; 37: 88–91. 13. Sengupta S, Alsi V, Mohan V, Kaur B, Mohan JC. Unique phenotypes of typical and inverted Takotsubo cardiomyopathy in young females. Indian Heart J 2010; 62: 348–350. 14. Kim SY, Yoon JH, Lee SH. Takotsubo-like severe left ventricular dysfunction after cesarean delivery in a 28-year old woman. Korean Circ J 2011; 41: 101–104. 15. Jo YY, Park S, Choi YS. Extracorporeal membrane oxygenation in a patient with stress-induced cardiomyopathy after cesarean section. Anaesth Intensive Care 2011; 39: 954– 957. 16. Citro R, Pascotto M, Provenza G, Gregorio G, Bossone E. Transient left ventricular ballooning (tako-tsubo cardiomyopathy) soon after intravenous ergonovine injection following cesarean delivery. Int J Cardiol 2010; 138: e31–e34. 17. Yaqub Y, Jenkins LA, Nugent KM, Chokesuwattanaskul W. Postpartum depression and apical ballooning syndrome (takotsubo syndrome). J Obstet Gynaecol Can 2009; 31: 736– 739. 18. Muller O, Roguelov C, Pascale P. A basal variant form of the transient ‘midventricular’ and ‘apical’ ballooning syndrome. QJM 2007; 100: 738–739. 19. Crimi E, Baggish A, Leffert L, Pian-Smith MC, Januzzi JL, Jiang Y. Images in cardiovascular medicine. Acute reversible stress-induced cardiomyopathy associated with cesarean delivery under spinal anesthesia. Circulation 2008; 117: 3052– 3053. 20. Parodi G, Antoniucci D. Transient left ventricular apical ballooning syndrome after inadvertent epidural administration of potassium chloride. Int J Cardiol 2008; 124: e14–e15. 21. D’Amato N, Colonna P, Brindicci P et al. Tako-Tsubo syndrome in a pregnant woman. Eur J Echocardiogr 2008; 9: 700–703. 22. Brezina P, Isler CM. Takotsubo cardiomyopathy in pregnancy. Obstet Gynecol 2008; 112: 450–452. 23. Freitas HF, Renault R, Ribeiro ES, Andrade FM, Brito FS Jr, Velloso LG. Sudden cardiac arrest due to puerperal transient left ventricular apical ballooning syndrome. Int J Cardiol 2011; 149: e12–e13. 24. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ III. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: A 30-year population based study. Ann Intern Med 2005; 143: 697– 706. 25. Kamiya CA, Kitakaze M, Ishibashi-Ueda H et al. Different characteristics of peripartum cardiomyopathy between patients complicated with and without hypertensive
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disorders. -Results from the Japanese Nationwide survey of peripartum cardiomyopathy. Circ J 2011; 75: 1975–1981. El-Deeb M, El-Menyar A, Gehani A, Sulaiman K. Acute coronary syndrome in pregnant women. Expert Rev Cardiovasc Ther 2011; 9: 505–515. McLintock C, Brighton T, Chunilal S et al. Councils of the Society of Obstetric Medicine of Australia and New Zealand; Australasian Society of Thrombosis and Haemostasis. Recommendations for the diagnosis and treatment of deep venous thrombosis and pulmonary embolism in pregnancy and the postpartum period. Aust N Z J Obstet Gynaecol 2012; 52: 14–22. Greer IA. Thrombosis in pregnancy: Updates in diagnosis and management. Hematology Am Soc Hematol Educ Program 2012; 2012: 203–207. Mookadam F, Jiamsripong P, Goel R, Warsame TA, Emani UR, Khandheria BK. Critical appraisal on the utility of echocardiography in the management of acute pulmonary embolism. Cardiol Rev 2010; 18: 29–37. European Society of Gynecology (ESG), Association for European Paediatric Cardiology (AEPC), German Society for Gender Medicine (DGesGM), Regitz-Zagrosek V, Blomstrom Lundqvist C, Borghi C et al. ESC Committee for Practice Guidelines. ESC Guidelines on the management of cardiovascular diseases during pregnancy: The Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC). Eur Heart J 2011; 32: 3147–3197. Minakami H, Hiramatsu Y, Koresawa M et al. Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2011 edition. J Obstet Gynaecol Res 2011; 37: 1174–1197. Kurisu S, Sato H, Kawagoe T et al. Takotsubo-like left ventricular dysfunction with ST segment elevation: A novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 2002; 143: 448–455. Wittstein IS, Thiemann DR, Lima JA et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352: 539–548. Elkayam U, Akhter MW, Singh H et al. Pregnancy-associated cardiomyopathy: Clinical characteristics and a comparison between early and late presentation. Circulation 2005; 111: 2050–2055. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE. Stress (takotsubo) cardiomyopathy – a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008; 5: 22–29. Litvinov IV, Kotowycz MA, Wassmann S. Iatrogenic epinephrine-induced reverse takotsubo cardiomyopathy: Direct evidence supporting the role of catecholamines in the pathophysiology of the ‘broken heart syndrome’. Clin Res Cardiol 2009; 98: 457–462.
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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doi:10.1111/jog.12437
J. Obstet. Gynaecol. Res. Vol. 40, No. 6: 1534–1539, June 2014
Takotsubo cardiomyopathy after cesarean: A case report and published work review of pregnancy-related cases Miki Minatoguchi1, Atsuo Itakura2, Eiji Takagi3, Manabu Nishibayashi4, Mariko Kikuchi1 and Osamu Ishihara1 1 Department of Obstetrics and Gynecology Saitama Medical University, Saitama, 2Department of Obstetrics and Gynecology, School of Medicine, Juntendo University, 4Department of Obstetrics and Gynecology, Nerima Hikarigaoka Hospital, Tokyo and 3 Division of Cardiology, Cardiovascular Center, Shioda Memorial Hospital, Chiba, Japan
Abstract Takotsubo cardiomyopathy (TCM) primarily affects postmenopausal women and is an important differential diagnosis of acute coronary syndrome. We describe a rare case of post-partum TCM, and present a published work review of the cases of pregnancy-associated TCM. A 24-year-old Japanese woman pregnant with twins suffered from premature membrane rupture at 31 gestational weeks. Following emergency cesarean delivery, she complained of sudden dyspnea. Transthoracic echocardiography revealed an inverted Takotsubo pattern (ejection fraction, 46%). On post-delivery day 8, wall motion abnormalities subsided, and she was discharged on post-delivery day 16. We reviewed 18 relevant cases of peripartum TCM from the published work. Among them, 16 cases were post-partum and two cases occurred during pregnancy. Most women (81%) underwent cesarean delivery, and the first symptoms of TCM appeared during surgery in 38% of the cases. The dominant symptoms were chest pain (44%) and dyspnea (28%). Most cases (94%) exhibited electrocardiogram abnormalities, including ST changes and T-wave inversion. Serum levels of cardiac enzymes were abnormally high in 92% of the cases. Repeated echocardiography documented normalized left ventricular systolic function within 6 months in all cases. This case and review emphasize that TCM may be concealed in post-partum women by symptoms undistinguishable from acute coronary syndrome, peripartum cardiomyopathy or pulmonary thromboembolism, and that echocardiography may be a useful tool to distinguish them. Key words: apical ballooning syndrome, cesarean delivery, preterm delivery, stress-induced cardiomyopathy, Takotsubo cardiomyopathy.
Introduction Takotsubo cardiomyopathy (TCM) is characterized by acute, profound, but reversible left ventricular dysfunction in the absence of significant coronary artery disease. The symptoms are triggered by acute emotional or physical stress identified by a distinctive pattern of ‘apical ballooning’.1 TCM is an important differential diagnosis of acute coronary syndrome (ACS).2 This phenomenon primarily affects postmenopausal women between 60 and 70 years old,
and is often preceded by emotional or physical stress associated with an elevation of plasma catecholamine levels.3 TCM was first described in the Japanese published work in 1990,4 and was initially thought to be restricted to the Japanese/Asian population. Recently, several cases of pregnancy or post-partum TCM have been reported in young women from Western countries. Here, we report a case of TCM that occurred after cesarean delivery and a global published work review of pregnancy-associated TCM (P-TCM).
Received: September 19 2013. Accepted: February 23 2014. Reprint request to: Professor Atsuo Itakura, Department of Obstetrics and Gynecology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Email: [email protected]
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Pregnancy-related Takotsubo cardiomyopathy
Case A 24-year-old pregnant Japanese woman (gravida 1, para 1) was transported to Saitama Medical University Hospital due to preterm labor. Her pregnancy was a spontaneous monochorionic diamniotic twin pregnancy. She had no known pre-existing cardiomyopathy or cardiovascular risk factors, such as obesity, smoking or a family history of cardiovascular diseases. After admission, ritodrine hydrochloride was administrated i.v. for tocolysis. To suppress the uterine contractions, the dose of ritodrine hydrochloride was gradually elevated to 200 μg/min and betamethasone (12 mg) was injected twice i.m. at 31 + 1/7 gestational weeks. At 31 + 4/7 gestational weeks, premature rupture of membranes was diagnosed. Accordingly, emergency cesarean delivery was performed under standard spinal anesthesia. Following the administration of spinal anesthesia, she became hypotensive and 8 mg ephedrine was administrated i.v. Just after the delivery of two girls (birthweights 1692 g and 1722 g; Apgar 8/9 and 8/9), her percutaneous oxygen saturation fell to 95%, and she was supplemented with 5 L/min oxygen. Otherwise, the cesarean delivery was uneventful. Thirty minutes after her transfer to the obstetric ward, the patient suddenly complained of dyspnea. Her percutaneous oxygen saturation fell abruptly from 97% to 85%, and she was supplemented with 5 L/min oxygen. Emergency computed tomography excluded pulmonary thromboembolism (PTE). Chest X ray, which was normal preoperatively (Fig. 1a), revealed cardiomegaly and pulmonary congestion after delivery (Fig. 1b). Electrocardiogram showed normal findings, except for sinus tachycardia. Bedside echocardiography revealed extensive hypokinesis. Therefore, she was transferred to the cardiology unit. Transthoracic echocardiography revealed extensive hypokinesis in the basal segments of the anterior, inferior and lateral walls, with preserved function in the apical segments, following an inverted Takotsubo pattern (Fig. 2).5 The ejection fraction was 46%. Laboratory data showed no elevation in serum myocardial enzymes, but an elevation of brain natriuretic peptide (65 pg/mL). After diagnosing this condition as TCM, carperitide, furosemide and dopamine hydrochloride were infused continuously. Magnetic resonance imaging revealed normal coronary arteries. Repeated transthoracic echocardiography on postdelivery day 8 showed a reduction of wall motion abnormalities, with an ejection fraction of 55%. The patient was discharged on post-delivery day 16. On
(a)
(b)
Figure 1 Chest X ray on the day of cesarean section. (a) Before operation, (b) 1 h after operation showing edema of the lungs.
post-delivery day 19, follow-up transthoracic echocardiography at the outpatient clinic revealed nearly normalized cardiac function.
Discussion Takotsubo cardiomyopathy, also known as ‘stressinduced cardiomyopathy’ or ‘apical ballooning syndrome’, was originally described in Japan in the 1990s.4 In Western countries, this condition is particularly associated with pregnancy, and seems to be underreported. A large case series showed that patients with TCM had a mean age of 69 years (range, 30–90)
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M. Minatoguchi et al.
Figure 2 Transthoracic echocardiograph still-frame of the apical four-chamber view revealing hypokinesis of the basal segments (arrows) with preserved function in the apical segments.
and were most commonly (81%) postmenopausal (aged >50 years).1 Therefore, P-TCM is considered a special type of TCM. In 2011, a published work review of cesarean delivery-related TCM only identified five cases in the English published work, using MEDLINE and Cochrane databases, including one Japanese case.6 The focus has been on women undergoing elective cesarean delivery, with the onset of TCM symptoms during surgery or in the immediate postoperative period. Therefore, the characteristics for this special form of TCM have not been fully elucidated. Here, we describe a published work review of symptomatic P-TCM, including reports in Japanese. We identified a total of 29 cases of symptomatic P-TCM that manifested within 5 months after delivery, and were reported in English or Japanese. We used PubMed (1966 to December 2012), Japana Centra Revuo Medicina (1983 to December 2012). The search terms were ‘apical ballooning’, ‘broken heart’, ‘cardiomyopathy’, ‘delivery’, ‘peripartum’, ‘pregnancy’, ‘stress induced’ and ‘Takotsubo’. Our inclusion criteria in this review were similar to those of Zdanowicz et al.,6 with the exception of language, pregnancy stage and delivery mode. Our criteria were as follows: no pre-existing cardiomyopathy or any other known cardiac defect, no pre-existing fetal malformations, the presence of characteristic symptoms and signs of TCM (Guidelines for Diagnosis of Takotsubo Cardiomyopathy),7 and the onset of TCM symptoms during pregnancy or within the first 5 months
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after delivery. Publications in English and Japanese were included. Eleven cases were excluded from the present analysis due to inadequate data for the diagnosis of P-TCM (eight cases), or complications such as pheochromocytoma and bromocriptineinduced coronary spasm (three cases). Thus, a total of 18 cases (Table 1) were analyzed in this study.6,8–23 According to our published work review, repeated echocardiography of all cases documented normalized left ventricular systolic function within 6 months after the onset of P-TCM. Short-term prognosis is likely to be favorable, although long-term outcome remains unknown. Incidentally, no case of subsequent pregnancy has been reported. The symptoms of TCM are triggered by physical or emotional stress. For pregnant women, the most common physical stressors are perioperative and postoperative procedures.1 A previous review discussed catecholamines/vasoconstrictive substances administrated during cesarean section with regard to P-TCM.6 Unfortunately, some of the studies did not describe the management during cesarean section in detail. We found the description about the administration of catecholamines/vasoconstrictive substances during cesarean section in 38% of the 13 cases (Table 1). Although estrogen deficiency after delivery may be a stressor, the majority of these cases had initial symptoms within a day after delivery (Fig. 3). Among the post-partum cases, physical or emotional stress related to spontaneous or cesarean delivery may be a dominant trigger. Most cases of post-delivery P-TCM underwent cesarean delivery (13/16 including ours), and the first symptoms were manifested during surgery in five cases. These cases demonstrate the clinical implications of cesarean delivery. In 33% of the 18 cases (and our case), acute cardiopulmonary collapse occurred on the day of delivery, with symptoms mimicking those of PTE24 and peripartum cardiomyopathy (PCM).25 In addition, most cases initially complained of chest symptoms, including chest pain or dyspnea, which are identical to those of ACS. Electrocardiogram abnormalities, ranging from ST changes to T-wave inversion, were reported in 94% (17/18) of the cases. Furthermore, the serum level of at least one cardiac enzyme was elevated in 92% (12/13) of the cases, which is also similar to ACS.26 Therefore, P-TCM does not have pathognomonic symptoms because the primary symptoms are similar to those of other complications. Consequently, P-TCM is an important disorder in the
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
Italy
White
Brazil
32
23
37
5
NA 36 40 NA
38
NA 37
NA
NA
Multiparous 23
NA
2P 2P Multiparous Primipara
Primipara
NA Primipara
Multiparous 37
VD
VD
VD
VD C/S C/S C/S
C/S
C/S
C/S C/S
C/S
C/S C/S
C/S C/S C/S VD
○ ○ ○ NA ○ NA × × NA × × × × × ×
× × ×
○ × ○ × ○ × × × × × × × × × ×
× × ×
40 days after delivery
23rd GW
6th GW
16 days 1h Intraoperatively A few hours after
Intraoperatively
Intraoperatively
Intraoperatively 2h
1h
1 day 5 days
Intraoperatively Just after operation 3h 3 days
Dizziness, syncope
Chest pain, shortness of breath Chest pain Substernal chest pain Chest heaviness Paresis, painful paresthesia, vegetative symptoms Very tired, stomachache Chest pain
Dyspnea Chest discomfort, dyspnea Chest discomfort, developed breathlessness Dyspnea Breathlessness, chest heaviness Chest pain
Dyspnea Dyspnea Dyspnea, chest pain Shortness of breath
Symptom
NA
○
○
○ ○ ○ ○
○
○
○ ○
○
○ ○
○ NA NA NA
×/○
○/×
×/○
○/× ○/× ×/○ ×/○
×/○
×/○
○/○ ×/○
×/○
○/○ ×/○
×/× ×/○ ×/○ ○/×
○ × × NA
CA/ VC
30 days
16 weeks
9 days
6 weeks 4 weeks 4 days 15 days
8 days
3 months
2 weeks 22 days
1 day
NA
NA
NA
NA × ○ ×
○
○
× ○
×
Within 3 weeks × 2 weeks ×
2 weeks 92 days Normal 3 months
Elevation ST changes/T Recovery of enzyme inversion in ECG
C/S, cesarean section; CA/VC, catecholamines/vasoconstrictive substances during cesarean section; ECG, electrocardiogram; GW, gestational weeks; NA, not applicable; P, parity; VD, vaginal delivery. Enzyme includes creatinine kinase-MB isozyme and cardiac troponins.
12 13 14 15
16 D’Amato et al.21 17 Brezina and Isler22 18 Freitas et al.23
White
42
USA Caucasian USA White
Caucasian Multiparous 38
32
10 Zdanowicz et al.6 11 Citro et al.16
32 30 31 32
Korean Korean
28 37
8 Kim et al.14 9 Jo et al.15
Yaqub et al.17 Muller et al.18 Crimi et al.19 Parodi et al.20
Indian
31
37 NA
7 Sengupta et al.13
NA NA
Japanese Korean
31 38 30 NA
GW Mode of Multiple Use of Onset delivery pregnancy tocolysis
41 30
Primipara Primipara Multiparous Primipara
Primipara/ multiparous
Japanese Japanese Japanese Japanese
Age Country, Race, Descent
24 28 30 25
Current case Niki et al.8 Shoji et al.9 Shimamoto et al.10 5 Sato et al.11 6 Lee et al.12
1 2 3 4
Author
Table 1 Characteristics of the cases
Pregnancy-related Takotsubo cardiomyopathy
© 2014 The Authors Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology
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M. Minatoguchi et al.
occurring during surgery may be diagnosed as PCM. Therefore, the etiology of PCM may be considered partially identical to that of P-TCM. No case of P-TCM occurring during prepartum management of preterm labor has been reported. If they overlap, these risk factors may contribute to the occurrence of P-TCM. In conclusion, we must be aware that P-TCM may be hidden in post-partum women with symptoms undistinguishable from ACS, PCM or PTE. Echocardiography may be a useful tool to identify P-TCM based on akinesis and basal hyperkinesis.
Figure 3 Histogram of the number of pregnancyassociated Takotsubo cardiomyopathy cases occurring in each gestational or post-partum stage.
differential diagnosis of ACS, PTE and PCM for women with such symptoms occurring during pregnancy and the post-partum period. Clinical guidelines for pregnancy recommend appropriate imaging to diagnose PTE.27 Computed tomography pulmonary angiography is generally preferred because of the relatively high diagnostic accuracy for PTE.28 On the other hand, echocardiography also can be used for rapid and accurate risk stratification of patients with PTE.29 Echocardiography is the preferred screening method to assess cardiac function,28,30 and apical ballooning with akinesis and basal hyperkinesis are specific findings for TCM.7 Additionally, echocardiography is an ideal risk stratification approach because this portable device can be used at the bedside.29 Accordingly, echocardiography should take high priority for the differential diagnosis of ACS, PTE, PCM and TCM. Multiple pregnancies occurred in five cases, and four of them were administrated a tocolytic agent, which is ritodrine hydrochloride (β2-agonist).31 However, the administration of catecholamines is considered a stressor,1,32 and blocking β-adrenergic receptors was reported to reduce the risk of TCM.32,33 Therefore, the use of tocolytic agents during multiple pregnancies may be associated with the occurrence of TCM. Accordingly, a report on PCM recently published in Japan identified multiple gestation and tocolytic agent use as potential risk factors.34 A difference in the distribution and density of myocardial adrenoceptors may be responsible for the distinct clinical features of TCM.35,36 If myocardial adrenoceptors are distributed uniformly, the left ventricular systolic dysfunction
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Disclosure We hereby state that all authors have no conflict of interest. The study was funded entirely by the authors.
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