THE CASE OF TAKOTSUBO CARDIOMYOPATHY IN PATIENT WITH CORONARY HEART DISEASE Konyushenko D.A., Kulikov A.N., Nagorny M.B., Sukhov V.Y., Zheleznyak I. S., Shulenin S. N. Military Medical Academy, Department of Propedeutics, St. Petersburg, Russia e-mail: daryan@bk.ru Takotsubo cardiomyopathy is a clinical syndrome characterized by acute reversible apical ventricular dysfunction. Main features are chest pain, dramatic (pseudoischemic) ECG changes, transient apical akinesis with basal hyperkinesis (takotsubo-shaped heart), minimal elevation of cardiac biomarkers and good prognosis. One of the criteria to exclude this diagnosis is presence of significant stenosis of one or more coronary arteries on angiography. Herein, we report a case of takotsubo cardiomyopathy associated with obstructive coronary heart disease (CHD). So we suppose that coronary heart disease is not contrary to diagnosis of takotsubo cardiomyopathy
1. INTRODUCTION Cardiologists have recently recognized a reversible form of heart failure of unknown origin characterized by a takotsubo-shaped hypokinesis of the left ventricle (tako-tsubo is a pot for trapping octopuses in Japan). Takotsubo cardiomyopathy was firstly observed by Japanese cardiologist Satoh et al. [1] in 1991, and the number of revealed cases is constantly increasing. It occurs most frequently in women over 50 years old and is often preceded by emotional or physical stress. The main clinical feature of this syndrome is transient dysfunction of left ventricle, its apical and mid-segments akinesis with basal hyperkinesis, that causes decreasing of ejection fraction from 20 to 49% [2] and sometimes (in 15,8% [2]) – dynamic intraventricular pressure gradient. The left ventricular function dramatically improves over a period of days to weeks. Patients usually suffer from a chest pain and symptoms of acute heart failure and sometimes we observe a slight elevation of cardiac biomarkers level [2] and ST-segment elevation with T-wave inversion. So takotsubo cardiomyopathy mimics an acute coronary syndrome (ACS) in 2,2% of cases of ACS [3]. We can often see a typical dynamics of ECG-changes with Q-waves, T-wave inversion and prolongation of QT-interval. The prognosis is favourable, in most cases patients recover without any specific treatment. In reported cases all patients didn’t have an obstructive coronary lesions (more than 50% luminal stenosis) in coronary angiography made in acute phase (except one patient [4], who had 70% stenosis of LAD), and so the diagnosis of ACS was excluded. With the exception of coronary angiography performed in acute phase, there are no clinical, laboratory and instrumental characteristics that allow clinician to diagnose takotsubo cardiomyopathy with certainty and to withhold urgent reperfusion therapy [2]. We present a case of supposed takotsubo cardiomyopathy in patient with documented obstructive CHD.
2. METHODS
Cardiac biomarker (CK-MB) was measured at admission, 6 and 24 hours later. 12-leads ECG was recorded several times in the day of admission, then every day during the hospitalization and on the 3 rd and 6th month at follow-up. Echocardiography was recorded at admission, on the 3 rd day and 6th week. Our patient also underwent stress-echocardiography and SPECT with dobutamine, heart MRI with gadolinium and ATP and chest computed tomography with heart angiography in 2 weeks after admission.
3. RESULTS A 74-year-old woman who had a myocardial infarction in 2001 and stable angina from that time was admitted to our department with chest discomfort after a long period of emotional stress. Electrocardiography revealed abnormal Q-wave, ST-segment elevation in leads I, AVL, V2 through V6 (fig. 1, b). The creatinekinase-MB level was slightly elevated (24,7 U/l) and cholesterol level was 7,63 mmol/l. Echocardiography showed apical akinesis and basal hyperkinesis with left ventricular outflow tract obstruction, hyperthrophy of left ventricular myocardium (fig. 2, a-c), EF(Simpson) = 0,52; outflow tract grad. = 65 mm Hg. An acute myocardial infarction was supposed, so she underwent thrombolysis (after 7 hours from beginning of chest discomfort) with streptokinase. Subcutaneous heparine, oral metoprolol, enalapril, aspirin and simvastatin were given. We haven’t seen any reperfusion signs and CKMB level elevations (25,8 U/l at admission). ST-segment elevation persisted to 12 hours after admission, and then abnormal Q-wave reduced (then disappeared), T-wave inverted and QT-interval became prolonged (fig.1 c-d). These changes of repolarization have become highly apparent up to 2 nd week after admission and gradually recovered to initial (before the heart attack) in 6 months (fig. 1, e-g). Transthoracic echocardiography performed on the 3 rd day after initial presentation revealed improved left ventricular apical wall motion and absence of LV outflow tract obstruction, EF = 0,60. Follow-up echocardiography revealed normal left ventricular function (fig.2, d-f). Chest computed tomography with heart angiography showed coronary calcification and not less than 50% stenosis of RCA, LAD. Heart MRI with gadolinium and stress agent ATP revealed an area of cardiosclerosis of LV anterior wall and multiple subendocardial perfusion defects. Patient also underwent SPECT with stress-agent dobutamine that revealed perfusion defects on the LV anterior wall at high drug dose (40 mcg/kg/min) without any chest pain. Stressechocardiography didn’t find any LV-wall motion abnormalities at high drug dose.
4. DISCUSSION Clinical features of takotsubo cardiomyopathy is well known [5, 6, 7]: 1. primary occurrence of the syndrome in postmenopausal women; 2. presentation of acute chest pain or dyspnea after emotional or physical stress; 3. transient akinesis or hypokinesis of left ventricle apex and mid-segments with basal hyperkinesis; 4. recovery of left ventricle function within 2-4 weeks of presentation; 5. ST-segment elevation or depression, or T-wave changes; 6. prolonged QT-interval; 7. mild increase in cardiac enzymes;
8. presence of transient intracavitary pressure gradient. Criteria of exclusion are: 1. obstructive coronary lesions on angiography; 2. acute myocarditis; 3. pheochromocytoma; 4. sybarachnoidal haemorrhage; 5. hypertrophic cardiomyopathy. Several pathophysiological mechanisms have been proposed to explain the unusual features of this syndrome, such as multivessel coronary spasm, abnormalities in coronary microvascular function [8], catecholamine-mediated cardiotoxity. Very popular is Alexander R Lyon theory, considering the stresscardiomyopathy to be a form of myocardial stunning triggered by high levels of circulating epinephrine, signaling via b 2-adrenoceptors on the apex of LV and causing negative inotropic effect [9]. According to this theory we see no reason to exclude CHD from list of conditions that can associate with takotsubo cardiomyopathy. We see all the features of this syndrome in our patient except one: the history CHD – stable angina in present, myocardial infarction in the past, typical risk factors (increased cholesterol level, hypertrophy of LV myocardium), supposed multiple coronary stenoses. The probability of recurrent myocardial infarction was very high. But there are some conflicting clinical features: 1) late admission with completely “effective” reperfusion therapy and minimal CK-MB level; 2) the number of affected LV segments was not corresponding to the one of coronary arteries, like it could be in case of myocardial infarction; 3) atypical dynamic pattern of ECG; 4) absence of new fibrosis in the involved zone and complete apex contractility recovery; 5) inconsistency between slight clinical course and dramatic ECG and ECHO changes, favourable prognosis.
5. CONCLUSION To our knowledge, it is a first reported case of takotsubo cardiomyopathy in a woman with myocardial infarction history. So we suppose that CHD is not contrary to diagnosis of takotsubo cardiomyopathy. REFERENCES 1. Dote K., Satoh H., Tateishi H., Ishihara M. Myocardial stunning due to simultaneous multivessel coronary spasms: a review of 5 cases. J Cardiol 1991; 21: 203-214. 2. Gianni M., Dentali F., Grandi A.M., Sumner G., Hiralal R., Lonn E. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. In: European Heart Journal 2006; 27: 1523-1529. 3. Bybee K.A., Prasad A., Barsness G.W., Lerman A., Jaffe A.S., Murphy J.G., Wright R.S., Rihal C.S. Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am J Cardiol 2004; 94: 343-346. 4. Wittstein I.S., Thiemann D.R., Lima J.A., Baughman K.L., Schulman S.P., Gersteinblith G., Wu K.C., Rade J.J., Bivalacqua T.J., Champion H.C.
Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352: 539-548. 5. Metzi M.D., Altman E.J., Spevack D.M., Doddamani S., Travin M.I., Ostfeld R.J. A case of takotsubo carrdiomyoparhy mimicking an acute coronary syndrome. Nat Clin Pract Cardiovasc Med. 2006; 3(1): 53-56. 6. Virani S.S., Khan A.N., Mendoza C.E., Ferreira A.C., Marchena E. Takotsubo cardiomyopathy, or broken-heart syndrome. Tex Heart Inst J 2007; 34: 76-9. 7. Duplyakov D.V. Apical ballooning of left ventricle or takotsubo cardiomyopathy. Cardiology 2004; 11: 97-9. (in Russian). 8. Acashi Y.J., Nakazawa K., Sakakibara M., Miyake F., Musha H., Sasaka K. 123I-MIBG myocardial scintigraphy in patients with «takotsubo» cardiomyopathy. J Nucl Med 2004; 45: 1121-1127. 9. Lyon A.R., Rees P.S.C., Prasad S., Poole-Wilson P.A., Harding S.E. Stress (Takotsubo) cardiomyopathy – a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning. Nat Clin Pract Cardiovasc Med 2008; 5(1): 22-29.
Figure 1. The dynamics of ECG-changes in V-leads. a) initial ECG, b)ECG at admission, c) 1st day, d) 3rd day, e) 2 weeks, f) 3 months, g) 6 months.
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Figure 2. The dynamics of echocardiogram at admission and on the 3rd day. a) Echocardiography at admission, diastole. b) Echocardiography at admission, systole. Apical akinesis, basal hyperkinesis. c)Echocardiography at admission. Left ventricle outflow tract obstruction with high pressure gradient. d) Echocardiography on 3rd day, diastole. e) Echocardiography on 3rd day, systole. Normal left ventricle function. f)
Echocardiography at 3rd day. Absence of pressure gradient in left ventricle outflow tract