2010 by the Texas Heart Institute, Houston

Volume 37, Number 1, 201088 Atypical Cardiomyopathies with Inverted Takotsubo Pattern

Atypical Transient Stress-Induced Cardiomyopathies with an Inverted Takotsubo Patternin Sepsis and in the Postpartal State

Several cases of inverted Takotsubo cardiomyopathya variant form with hyperdynamic left ventricular apex and akinesia of the left ventricular base and mid-portionhave been reported recently, especially in association with cerebrovascular accidents and catechol-amine cardiomyopathies. Herein, we describe 2 cases of inverted Takotsubo cardiomyop-athy: one that occurred in a middle-aged woman who had a septic condition, and another in a young woman who was in the postpartal state. Such cases have not been reported previously. (Tex Heart Inst J 2010;37(1):88-91)

S tress-induced cardiomyopathy is characterized by a transient abnormality of left ventricular (LV) apical wall motion, electrocardiographic changes, and minimal cardiac enzyme release. The condition mimics acute coronary syn-drome in patients who have no angiographic stenosis upon coronary angiography. Recently, atypical stress-induced cardiomyopathies without involvement of the LV apex have been reported.1 Most of the cases were transient midventricular ballooning syndrome with midventricular akinesia and normal wall motion of the LV base and apex,1-3 and some were the inverted Takotsubo pattern cardiomyopathy that is char-acterized by a hyperdynamic LV apex and akinesia of the LV base and mid-portion.4-6 Here, we describe 2 cases of inverted Takotsubo cardiomyopathy, one of which oc-curred in a middle-aged woman with a septic condition and one in a young woman who was in the postpartal state.

Case Reports

Patient 1In June 2007, a 41-year-old woman was referred to us by the general surgery depart-ment at our institution because she suddenly developed hemodynamic instability with blood pressure of 70/40 mmHg and heart rate of 120 beats/min. Her medical his-tory included hospitalization for 6 months after a jejunostomy with bowel resection, and reoperation because of a metastatic myometrial sarcoma. The patients condition was stable during that time; she was receiving total parenteral nutrition via the sub-clavian root, along with anticancer treatment. Now, upon physical examination, she was semicomatose and febrile, with a body temperature of 38.5 C. She was intubat-ed, and an arterial blood-gas analysis gave the following values: pH, 7.3; partial pres-sure of oxygen, 176 mmHg; carbon dioxide pressure, 49 mmHg; bicarbonate, 25.7 mEq/L; and fraction of inspired oxygen, 0.8. Clinical and laboratory findings sug-gested a septic condition with multiorgan damage: white blood cell count, 24,330/mm3; hemoglobin, 11.6 g/dL; platelet count, 22,000/mm3; C-reactive protein, 16.56 mg/dL; alanine aminotransferase, 365 U/L; aspartate aminotransferase, 137 U/L; total bilirubin, 11.6 mg/dL; and serum creatinine, 1.5 mg/dL. N-terminal pro-brain natriuretic peptide was elevated to 3,500 pg/mL, and cardiac enzymes peaked at creatine kinaseMB fraction, 19.47 ng/mL (reference range, 07 ng/mL) and tropo-nin T, 0.393 ng/mL (reference range,

Texas Heart Institute Journal Atypical Cardiomyopathies with Inverted Takotsubo Pattern 89

tion. Echocardiography revealed severe LV systolic dys-function with akinesia of the LV base and mid- portion, together with hypercontractility of the apex (Figs. 1A and 1B). Coronary angiography on the same day re-vealed that both coronary arteries were intact (Figs. 1C and 1D). Left ventriculography showed akinesia of the LV base and mid-portion except for the apex (Figs. 1E and 1F). Because of the patients hemodynamic insta-bility, intra-aortic balloon pumping was begun, and medical treatment that included inotropic agents and antibiotics was started. She responded quickly to the treatment, and intra-aortic balloon pumping was dis-continued 2 days later. Follow-up echocardiography 1 week later indicated complete recovery of LV systol-ic function.

Patient 2In July 2007, a 30-year-old woman with no history of cardiac disease was referred to us from the obstetrics de-partment at our institution because of chest discomfort and dyspnea (New York Heart Association functional class III), 5 days after a cesarean delivery. Her symptoms had developed 1 day after delivery and had progressed even after treatment with diuretics. On physical exam-ination, she was afebrile, with blood pressure of 130/80 mmHg, heart rate of 90 beats/min, and respiration rate

of 24 breaths/min. The heart sounds were regular, with an S3 and a holosystolic murmur (grade 4/6) in the mi-tral area. Laboratory f indings included a white blood cell count of 7,800/mm3, a hemoglobin level of 11 g/dL, and a platelet count of 236,000/mm3. Cardiac en-zymes peaked at creatine kinaseMB fraction, 7.12 ng/mL (reference range, 07 ng/mL) and troponin T, 0.12 ng/mL (reference range,

Volume 37, Number 1, 201090 Atypical Cardiomyopathies with Inverted Takotsubo Pattern

Discussion

Stress-induced cardiomyopathy, also called transient LV apical ballooning or Takotsubo cardiomyopathy, is a clinical entity that was first described in Japan.7 It is characterized by a transient abnormality of LV apical wall motion (which gives the heart the appearance of a Japanese octopus trap or takotsubo), electrocardiograph-ic changes, and minimal cardiac enzyme release, and the condition mimics acute coronary syndrome in patients who have no angiographic stenosis upon coronary angi-ography. The underlying pathogenesis remains incom-pletely understood, although some possible mechanisms have been suggested.8 One such mechanism is myocardi-al ischemia due to microvascular spasm. Increased sym-pathetic activity is another possibility, because exposure to internal or external stresses is confirmed in most cases. Sympathetic activity is also implicated in the neurogenic stunned myocardium during acute cerebrovascular acci-dent and in catecholamine cardiomyopathy during the endocrine crisis of pheochromocytoma. Atypical stress-induced cardiomyopathies without in-volvement of the LV apex have been reported recently.1 Most of the cases were instances of transient midven-tricular ballooning syndrome with midventricular aki-nesia and normal wall motion of the LV base and apex,

although some cases displayed the inverted Takotsubo pattern of cardiomyopathy, which is characterized by a hyperdynamic LV apex and akinesia of the LV base and mid-portion. Inverted Takotsubo cardiomyopa-thies have been reported in patients who experienced an acute cerebrovascular accident,4 pheochromocyto-ma,5,6 paraglioma,9 acute pancreatitis,10 amphetamine use,11 or shoulder surgery.12 Most patients experienced a cerebrovascular accident or pheochromocytoma, which explains the state of catecholamine excess. Inverted Ta-kotsubo cardiomyopathy triggered by a septic condition or parturition has not been reported. Our reports are unique in that the cardiomyopathies presented during sepsis in a middle-aged woman and after parturition in a young woman. It remains unclear why the LV apex is selectively vul - nerable and subsequently forms a balloon in typical Ta-kotsubo cardiomyopathy. Several anatomic and physio-logic factors might contribute to LV apical wall-motion abnormalities, including the lack of a 3- layered myocar-dial structure at the LV apex and the easy loss of elastic-ity of the LV apex after excessive expansion.8 Although myocardial responsiveness to adrenergic stimulation in-creases in the apical myocardium, the norepinephrine content is lower in the apex than in the base; the human heart has a heterogeneous nerve-distribution pattern.13

Fig. 2 Patient 2. Echocardiography shows severe hypokinesia of the left ventricular base and mid-portion, and hypercontractility of the left ventricular apex (A and B). Coronary angiography shows that the C) left and D) right coronary arteries are intact. Left ventriculogra-phy reveals severe global hypokinesia except in the left ventricular apex (E and F).

A

B

C

D

E

F

Texas Heart Institute Journal Atypical Cardiomyopathies with Inverted Takotsubo Pattern 91

However, the apex may notin all patientsbe a struc-ture more vulnerable to catecholamine excess than is the mid-ventricle or the base, and the observation of invert-ed Takotsubo cardiomyopathy in some individuals sug-gests this possibility.

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et al. The clinical features of transient left ventricular nonapi-cal ballooning syndrome: comparison with apical ballooning syndrome. Am Heart J 2007;154(6):1166-73.

2. Hurst RT, Askew JW, Reuss CS, Lee RW, Sweeney JP, Fortuin FD, et al. Transient midventricular ballooning syndrome: a new variant. J Am Coll Cardiol 2006;48(3):579-83.

3. Tamura A, Kawano Y, Watanabe T, Aso T, Abe Y, Yano S, Kadota J. A report of 2 cases of transient mid-ventricular bal-looning. Int J Cardiol 2007;122(2):e10-2.

4. Ennezat PV, Pesenti-Rossi D, Aubert JM, Rachenne V, Bau-chart JJ, Auffray JL, et al. Transient left ventricular basal dys-function without coronary stenosis in acute cerebral disorders: a novel heart syndrome (inverted Takotsubo). Echocardiogra-phy 2005;22(7):599-602.

5. Sanchez-Recalde A, Costero O, Oliver JM, Iborra C, Ruiz E, Sobrino JA. Images in cardiovascular medicine. Pheochromo-cytoma-related cardiomyopathy: inverted Takotsubo contrac-tile pattern. Circulation 2006;113(17):e738-9.

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a case of patient resuscitation with extracorporeal life support. J Thorac Cardiovasc Surg 2008;135(2):434-5.

7. Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardi-al stunning due to simultaneous multivessel coronary spasms: a review of 5 cases [in Japanese]. J Cardiol 1991;21(2):203-14.

8. Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, et al. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina Pectoris-Myo-cardial Infarction Investigations in Japan. J Am Coll Cardiol 2001;38(1):11-8.

9. Kim HS, Chang WI, Kim YC, Yi SY, Kil JS, Hahn JY, et al. Catecholamine cardiomyopathy associated with paraganglio-ma rescued by percutaneous cardiopulmonary support: invert-ed Takotsubo contractile pattern. Circ J 2007;71(12):1993-5.

10. Van de Walle SO, Gevaert SA, Gheeraert PJ, De Pauw M, Gillebert TC. Transient stress-induced cardiomyopathy with an inverted takotsubo contractile pattern. Mayo Clin Proc 2006;81(11):1499-502.

11. Movahed MR, Mostafizi K. Reverse or inverted left ventricu-lar apical ballooning syndrome (reverse Takotsubo cardiomy-opathy) in a young woman in the setting of amphetamine use. Echocardiography 2008;25(4):429-32.

12. Nanda S, Pamula J, Bhatt SP, Chan I, Turki MA, Dale TH. Takotsubo cardiomyopathy--a new variant and widening dis-ease spectrum. Int J Cardiol 2007;120(2):e34-6.

13. Park AM, Armin S, Azarbal A, Lai A, Chen PS, Fishbein MC. Distribution of cardiac nerves in patients with diabe-tes mellitus: an immunohistochemical postmortem study of human hearts. Cardiovasc Pathol 2002;11(6):326-31.