QJM. 2003 Aug;96(8):563-73.
The clinical features of takotsubo cardiomyopathy.
Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Koike H, Sasaka K.
Division of Cardiology, Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan. johnny@marianna-u.ac.jp
BACKGROUND: Cardiologists have recently recognized a reversible form of heart failure of unknown origin characterized by a takotsubo-shaped hypokinesis of the left ventricle on left ventriculography. AIM: To clarify the clinical features of this cardiomyopathy. DESIGN: Observational study.
METHODS: Seven patients with reversible ventricular dysfunction were followed for 4.5 years. Clinical course, routine examinations, and cardiac catheterizations in each patient were documented. RESULTS: The cardiomyopathy developed in six elderly female and one male patients (mean age 75.3 years), all of whom had been exposed to stress. Cardiac enzymes did not significantly increase, but serum norepinephrine increased remarkably (1.19 ng/ml). Coronary angiography revealed normal coronary arteries. However, left ventriculography showed akinesis in the apical segments,
together with hyperkinesis in the basal segments (a takotsubo shape). The abnormal kinesis normalized within 17.4 hospital days without any treatment in five patients, and with haemodynamic support for 3 days in the other two. Endocardial biopsies did not suggest any specific pathology.
The cardiac events did not recur over a 1-4 year follow-up. DISCUSSION: Coronary vasospasm, myocarditis and other substantial diseases previously described were ruled out as the cause of takotsubo cardiomyopathy in our subjects. Prognosis was good without any form of treatment, provided that the patients survived the severe heart failure state. Catecholaminergic or adrenoceptor-hyperactive cardiomyopathy may be the cause of this cardiomyopathy.
J Nucl Med. 2004 Jul;45(7):1121-7.
123I-MIBG myocardial scintigraphy in patients with "takotsubo" cardiomyopathy.
Akashi YJ, Nakazawa K, Sakakibara M, Miyake F, Musha H, Sasaka K.
Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. johnny@marianna-u.ac.jp
The clinical characteristics of reversible left ventricular dysfunction due to "takotsubo" cardiomyopathy have been described, but the origin of this condition remains unclear. This study investigated (123)I-metaiodobenzlguanidine ((123)I-MIBG) myocardial scintigraphy in patients with takotsubo cardiomyopathy. METHODS: Eight consecutive patients with takotsubo cardiomyopathy were studied. Left ventricular wall motion was monitored by echocardiography until wall motion normalized. (123)I-MIBG myocardial scintigrams were performed within 3 d of admission (0 mo) and after the
improvement of left ventricular dysfunction (3 mo). Early images were obtained at 30 min after radioisotope injection and delayed images were obtained after 4 h. The heart-to-mediastinum ratio (H/M ratio) and the washout rate were calculated. RESULTS: The mean left ventricular ejection fraction improved significantly (from 42.8% +/- 8.7% to 66.5% +/- 7.9%; P < 0.0001) and normalized after 19.4 +/- 5.4 hospital days. The early H/M ratio was significantly higher than the late ratio at 0 mo (2.16 +/- 0.25 vs. 1.89 +/- 0.24, respectively; P < 0.05), but not at 3 mo. The washout rate was
significantly greater at 0 mo than at 3 mo (39.1% +/- 10.2% vs. 25.4% +/- 6.3%, respectively; P < 0.05). CONCLUSION: In patients with takotsubo cardiomyopathy, initial (123)I-MIBG myocardial scintigraphy depicted a unique pattern of ventricular asynergy and indicated the existence of cardiac sympathetic hyperactivity, although coronary blood flow was maintained. These findings strongly suggest that takotsubo cardiomyopathy could be
caused by neurogenic myocardial stunning.
Circ J. 2003 Aug;67(8):687-90.
Specific findings of the standard 12-lead ECG in patients with 'Takotsubo' cardiomyopathy: comparison with the findings of acute anterior myocardial
infarction.
Ogura R, Hiasa Y, Takahashi T, Yamaguchi K, Fujiwara K, Ohara Y, Nada T, Ogata T, Kusunoki K, Yuba K, Hosokawa S, Kishi K, Ohtani R.
Division of Cardiology, Tokushima Red Cross Hospital, Komatsushima, Japan.
The clinical course of 'Takotsubo' cardiomyopathy closely resembles that of acute myocardial infarction (AMI) and coronary angiography (CAG) is usually performed to distinguish the 2 conditions during the acute phase. The present study was designed to determine whether the standard 12-lead electrocardiogram (ECG) findings could help to distinguish 'Takotsubo' cardiomyopathy from anterior AMI. The study group comprised 13 patients with 'Takotsubo' cardiomyopathy and 13 consecutive patients with anterior AMI. Patients with 'Takotsubo' cardiomyopathy had abnormal Q waves less frequently than patients with anterior AMI (15% vs 69%, p=0.008). No reciprocal changes were seen in the inferior leads in patients with
'Takotsubo' cardiomyopathy (p=0.0003). The ratio of ST-segment elevation in leads V(4-6) to V(1-3) (SigmaSTeV(4-6)/V(1-3)) was significantly higher in patients with 'Takotsubo' cardiomyopathy (1.55+/-0.53 vs 0.57+/-0.58, p=0.0004). The QTc interval was significantly longer in patients with 'Takotsubo' cardiomyopathy. The absence of reciprocal changes, absence of abnormal Q waves, and a SigmaSTeV(4-6)/V(1-3) >/=1 all showed a high sensitivity and specificity for diagnosing 'Takotsubo' cardiomyopathy. Furthermore, the combination of the absence of reciprocal changes and a SigmaSTeV(4-6)/V (1-3) >/=1 had a greater specificity (100%) and overall accuracy (91%) than either criteria. Therefore, the standard 12-lead ECG
on admission can help to distinguish 'Takotsubo' cardiomyopathy from anterior AMI.
Intern Med. 2004 Apr;43(4):300-5.
Comment in:
Intern Med. 2004 Apr;43(4):275-6.
An atypical case of "Takotsubo cardiomyopathy" during alcohol withdrawal: abnormality in the transient left ventricular wall motion and a
remarkable elevation in the ST segment.
Suzuki K, Osada N, Akasi YJ, Suzuki N, Sakakibara M, Miyake F, Maki F, Takahashi Y.
Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki.
A 64-year-old man was admitted due to hypokalemia-related myopathy. He was heavy drinker. He felt the stress of alcohol withdrawal during his hospitalization. The patient suffered a cardiopulmonary arrest lasting approximately 5 minutes on the fifth hospital day. One day later, ST-segment elevation was observed in leads I, aV(L), and V(2-6). Emergent cardiac catheterization was performed for suspicion of acute myocardial infarction. Normal coronary arteries with anterior akinesis of the left ventricle were revealed during the procedure. The present case may be an atypical form of "Takotsubo cardiomyopathy" in which the left ventricular contraction is due to focal anterior wall motion abnormalities.
Ann Nucl Med. 2003 Apr;17(2):115-22.
Assessment of Takotsubo (ampulla) cardiomyopathy using 99mTc-tetrofosmin myocardial SPECT--comparison with acute coronary syndrome.
Ito K, Sugihara H, Katoh S, Azuma A, Nakagawa M.
Division of Cardiology, Murakami Memorial Hospital, Asahi University, Gifu, Japan. kazuki@poppy.ocn.ne.jp
We assessed Takotsubo (ampulla) cardiomyopathy compared with acute coronary syndrome (ACS) using two-dimensional echocardiography and 99mTc-tetrofosmin myocardial SPECT. METHODS: We examined 10 patients with Takotsubo cardiomyopathy and 16 with ACS at the time of emergency admission (acute phase), at three to nine days after the attack (subacute phase) and at one month after the attack (chronic phase). The left ventricle was divided into nine regions on echocardiograms and SPECT images, and the degree of abnormalities in each region was scored in five grades from normal (0) to severely abnormal (4). RESULTS: Coronary angiography revealed total or subtotal occlusion in patients with ACS but no stenotic legions in those with Takotsubo cardiomyopathy. The amount of ST segment elevation (mm) was 7.9 +/- 3.4 in patients with Takotsubo cardiomyopathy and 7.3 +/- 3.7 in those with ACS (N.S.). Abnormal wall motion scores on echocardiograms were 13.8 +/- 4.4, 4.4 +/- 3.8 and 1.8 +/- 2.3 during the acute, subacute and chronic phases in patients with Takotsubo cardiomyopathy, and 13.9 +/- 4.0, 11.7 +/- 3.7, 7.6 +/- 4.2, respectively in patients with ACS. The value of MB fraction of creatine phosphokinase (IU/l) was 34 +/- 23 in patients with Takotsubo cardiomyopathy and 326 +/- 98 in those with ACS (p < 0.001). Abnormal myocardial perfusion scores on 99mTc-tetrofosmin myocardial SPECT were 11.4 +/- 3.2, 3.2 +/- 3.3 and 0.7 +/- 1.1 during the acute, subacute and chronic phases respectively, in patients with Takotsubo cardiomyopathy, and 15.8 +/- 4.1, 13.5 +/- 4.4, 8.2 +/-
4.4, respectively, in those with ACS. The numbers of myocardial segments that did not uptake 99mTc-tetrofosmin during the acute phase were 0.5 +/- 0.8 and 3.6 +/- 2.8 in patients with Takotsubo cardiomyopathy and ACS, respectively. CONCLUSION: Impaired coronary microcirculation might be a causative mechanism of Takotsubo cardiomyopathy.
J Cardiol. 2004 Feb;43(2):75-80.
Tako-tsubo-like transient left ventricular dysfunction with apical thrombus formation: a case report
Yasuga Y, Inoue M, Takeda Y, Kitazume R, Hayashi N, Nakagawa Y, Mitsusada N, Nojima Y, Sumitsuji S, Nagai Y.
Cardiology of Heart Center, Rinku General Medical Center, Rinku Orai-kita 2-23, Izumisano, Osaka 598-8577.
A 76-year-old woman with oppressive chest pain was admitted to our hospital. Initial electrocardiography revealed normal sinus rhythm with ST-segment elevation in leads V2-V5. The patient underwent emergent coronary angiography, which demonstrated no significant coronary stenosis. Left ventriculography revealed marked hypokinesis and akinesis of the mid and distal segments of all ventricular walls, with hyperkinesis of the base. Six days after admission, transthoracic echocardiography revealed immobile apical thrombus. The thrombus disappeared without any embolic episode
after 2 weeks of anticoagulant therapy with heparin and warfarin. Left ventricular walls returned to normal 3 months after the attack. Tako-tsubo-like cardiomyopathy with apical thrombus has only been reported in three cases. Left ventricular function normalizes within several days or weeks in most cases of tako-tsubo-like transient left ventricular dysfunction. Therefore, if the thrombus remains within the left ventricle, the risk of embolism might be relatively high. Careful management must be required in patients with tako-tsubo-like transient left ventricular dysfunction.
Circ J. 2003 Jun;67(6):556-8.
Left ventricular apical thrombus formation in a patient with suspected tako-tsubo-like left ventricular dysfunction.
Kurisu S, Inoue I, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, Umemura T, Nakamura S, Yoshida M, Sato H.
Division of Cardiology, Hiroshima City Hospital, Japan. skurisu@nifty.com
A 74-year-old woman with hypertension and bronchial asthma had chest discomfort at rest and 4 days later was admitted to her nearby hospital because of the sudden onset of right hemiparesis. The hemiparesis had almost disappeared within 24 h of onset, but because an electrocardiogram showed sinus tachycardia and diffuse symmetrical T-wave inversion, she was referred for cardiac examination. Coronary angiography did not reveal any significant coronary artery stenosis, but left ventriculography revealed severe hypokinesis of the left ventricular apical region, which contained a
4 x 4-mm solid thrombus moving freely with a wavy motion. Moreover, the activity of both protein C and protein S had decreased. The thrombus disappeared after 2 weeks of anticoagulant treatment with warfarin. Her clinical course suggested that the transient cerebral ischemic attack was caused by embolism of the left ventricular thrombus associated with 'tako-tsubo-like left ventricular dysfunction'.
Masui. 2002 Oct;51(10):1114-6.
A case of intraoperative repeated coronary artery spasm with ST-segment depression
Mizutani K, Okada M.
Department of Anesthesia, Fuchu Hospital, Izumi 594-0076.
A 68-year-old man with good left ventricular function underwent subtotal gastrectomy for gastric cancer under general anesthesia. Twenty minutes after the start of surgery, ST-segment depression was noted on the electrocardiogram monitor without change in the hemodynamic state. Intravenous isosorbide dinitrate relieved the electrocardiographic signs of ischemia. Short episodes of the ST-segment depression recurred 5 times despite intravenous isosorbide dinitrate and nicorandil. Echocardiography immediately after the surgery revealed hypokinesia of the anterior, septal and
apical segments with an ejection fraction of 48%, suggesting acute myocardial infarction or the "Takotsubo"-shaped cardiomyopathy. However, a day after surgery, echocardiography showed improvement of regional wall motion with an ejection fraction of 57%. Coronary angiography showed normal coronary arteries on the 22nd day after the surgery. Patient manifested occlusive coronary artery spasm on ergonovine provocative test. We would like to stress that perioperative coronary artery spasm may demonstrate ST-segment depression and may result in severe consequences,
regressive but relatively prolonged, in left ventricular function.
Ann Nucl Med. 2001 Aug;15(4):351-5.
Assessment of ampulla (Takotsubo) cardiomyopathy with coronary angiography, two-dimensional echocardiography and 99mTc-tetrofosmin
myocardial single photon emission computed tomography.
Ito K, Sugihara H, Kawasaki T, Yuba T, Doue T, Tanabe T, Adachi Y, Katoh S, Azuma A, Nakagawa M.
Division of Cardiology, Murakami Memorial Hospital, Asahi University, Japan. kazuki@poppy.ocn.ne.jp
We studied the causative mechanism of ampulla (Takotsubo) cardiomyopathy. METHODS: We examined 7 patients with ampulla cardiomyopathy by means of coronary angiography, two-dimensional echocardiography and 99Tc-tetrofosmin myocardial SPECT at the time of emergency admission (acute phase), at 3 to 5 days after the attack (subacute phase) and at 1 month after the attack (chronic phase). The left ventricle was divided into 9 regions on two-dimensional echocardiograms and 99mTc-tetrofosmin myocardial SPECT images, then the degree of abnormalities in each region was
scored in four grades from normal (0) to severely abnormal (3). We injected nicorandil into the coronary arteries and determined the elevation in the ST segment before and after administration. RESULTS: Coronary angiography did not show stenotic lesions in any patient. The acute, subacute and chronic phase myocardial perfusion scores on 99mTc-tetrofosmin myocardial SPECT were 11.2 +/- 3.4, 2.7 +/- 2.3 and 0.4 +/- 0.5, respectively, and wall motion scores on echocardiograms were 13.0 +/- 3.6, 4.4 +/- 2.2 and 0.6 +/- 0.6, respectively, indicating improvement in all scores during the subacute phase (p < 0.01). The elevation in the ST segment (mm) on the electrocardiogram was improved from 8.3 +/- 2.7 to 4.9 +/- 1.9 after the
administration of nicorandil (p < 0.05). CONCLUSION: These findings indicated that coronary microvascular spasm is one causative mechanism of ampulla cardiomyopathy.
Masui. 2003 Oct;52(10):1104-6.
A case of undiagnosed "takotsubo" cardiomyopathy during anesthesia
Takigawa T, Tokioka H, Chikai T, Fukushima T, Ishizu T, Kosogabe Y.
Department of Anesthesiology, Okayama Rosai Hospital, Okayama 702-8055.
"Takotsubo" cardiomyopathy is characterized by transient left ventricular dysfunction. We have reported a case of "Takotsubo" cardiomyopathy unrecognized during anesthesia because of no ischemic changes in monitored electrocardiogram (ECG). The patient was an 80-year-old woman undergoing open reduction surgery for fractures of the left tibia and ulna. Anesthesia was maintained with O2, N2O, sevoflurane and fentanyl. Sinus tachycardia was noted throughout anesthesia which was unresponsive to fluid loading and blood transfusion. ECG of limb leads showed no ST-T changes or abnormal Q waves and the blood pressure was stable during anesthesia. Postoperative echocardiography showed extensively decreased left ventricular wall motion with akinesis of the anterior wall and anterior septum from the mid-papillary level to apex. ECG showed negative T waves
in V2-V6 without abnormal Q waves or ST changes. The increase in CPK-MB was very little. The abnormal left ventricular wall motion was completely recovered on the third postoperative day. Her perioperative cardiac event was diagnosed as "Takotsubo" cardiomyopathy by reversible ampulla-shaped ventricular dysfunction. She had no symptoms throughout the perioperative period and recovered without any sequela.
Masui. 2002 Oct;51(10):1114-6.
A case of intraoperative repeated coronary artery spasm with ST-segment depression
Mizutani K, Okada M.
Department of Anesthesia, Fuchu Hospital, Izumi 594-0076.
A 68-year-old man with good left ventricular function underwent subtotal gastrectomy for gastric cancer under general anesthesia. Twenty minutes after the start of surgery, ST-segment depression was noted on the electrocardiogram monitor without change in the hemodynamic state. Intravenous isosorbide dinitrate relieved the electrocardiographic signs of ischemia. Short episodes of the ST-segment depression recurred 5 times despite intravenous isosorbide dinitrate and nicorandil. Echocardiography immediately after the surgery revealed hypokinesia of the anterior, septal and
apical segments with an ejection fraction of 48%, suggesting acute myocardial infarction or the "Takotsubo"-shaped cardiomyopathy. However, a day after surgery, echocardiography showed improvement of regional wall motion with an ejection fraction of 57%. Coronary angiography showed normal coronary arteries on the 22nd day after the surgery. Patient manifested occlusive coronary artery spasm on ergonovine provocative test. We would like to stress that perioperative coronary artery spasm may demonstrate ST-segment depression and may result in severe consequences,
regressive but relatively prolonged, in left ventricular function.
QJM. 2004 Sep;97(9):599-607.
Plasma brain natriuretic peptide in takotsubo cardiomyopathy.
Akashi YJ, Musha H, Nakazawa K, Miyake F.
Department of Cardiology, St Marianna University, Yokohama-city Seibu Hospital, Yokohama, Japan. johnny@marianna-u.ac.jp
BACKGROUND: Takotsubo cardiomyopathy is a reversible left ventricular dysfunction with symptoms resembling acute myocardial infarction, but without coronary lesions. Patients have wall motion abnormalities (apical akinesis and basal hyperkinesis), and characteristic left ventricular morphology. AIM: To investigate plasma brain natriuretic peptide (BNP) concentrations in takotsubo cardiomyopathy. METHODS: Ten consecutive patients with takotsubo cardiomyopathy underwent cardiac catheterization on their first hospital day, and blood was collected to measure BNP. To evaluate acute basal hyperkinesis, the difference in diameter between systole and diastole was measured at 10 mm below the aortic valve (the deltaBase value). RESULTS: Coronary angiography revealed no significant stenosis in any patient. Initial ejection fraction was 42.2 +/- 7.3%, cardiac
index was 1.90 +/- 0.39 l/min/m(2), and plasma BNP was 522.5 +/- 632.9 pg/ml. Ventricular contraction and the ejection fraction were normalized on echocardiography after 17.9 +/- 6.3 days. BNP was significantly correlated with deltaBase, but not with other cardiac parameters. DISCUSSION: Initial deltaBase value seems to be a good indicator of the severity of basal hyperkinesis in patients with takotsubo cardiomyopathy. In contrast to
other diagnoses, a high BNP concentration is not associated with a poor prognosis in this condition.
Mayo Clin Proc. 2004 Jun;79(6):821-4.
Left ventricular rupture associated with Takotsubo cardiomyopathy.
Akashi YJ, Tejima T, Sakurada H, Matsuda H, Suzuki K, Kawasaki K, Tsuchiya K, Hashimoto N, Musha H, Sakakibara M, Nakazawa K, Miyake F.
Department of Cardiology, Tokyo Metropolitan Government Hiroo General Hospital, Tokyo, Japan. johnny@marianna-u.ac.jp
A 70-year-old woman was admitted to the hospital with chest discomfort after quarreling with her neighbors. Electrocardiography revealed ST-segment elevation in leads I, II, III, aVL, aVF, and V2 through V6. Coronary angiography demonstrated normal arteries, but left ventriculography showed apical akinesis and basal hyperkinesis. Takotsubo cardiomyopathy was diagnosed on the basis of these characteristic findings. The creatine kinase and creatine kinase-MB concentrations were elevated at admission and reached maximum levels 6 hours after admission. The plasma level of
brain natriuretic peptide was 10.7 pg/mL (reference range, <18.4 pg/mL) on the first hospital day. ST-segment elevation in leads I, II, III, aVL, aVF, and V2 through V6 persisted at 72 hours after admission. On the third hospital day, sudden rupture of the left ventricle occurred, and despite extensive resuscitation efforts, the patient died. Takotsubo cardiomyopathy presents in a manner similar to that of acute myocardial infarction, but ventricular systolic function usually returns to normal within a few weeks. To our knowledge, this is the first reported case of fatal left ventricular
rupture associated with takotsubo cardiomyopathy. We suggest that takotsubo cardiomyopathy may be a newly recognized cause of sudden cardiac death.
N Engl J Med. 2005 Feb 10;352(6):539-48.
Neurohumoral features of myocardial stunning due to sudden emotional stress.
Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC.
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA. iwittste@jhmi.edu
BACKGROUND: Reversible left ventricular dysfunction precipitated by emotional stress has been reported, but the mechanism remains unknown. METHODS: We evaluated 19 patients who presented with left ventricular dysfunction after sudden emotional stress. All patients underwent coronary angiography and serial echocardiography; five underwent endomyocardial biopsy. Plasma catecholamine levels in 13 patients with stress-related myocardial dysfunction were compared with those in 7 patients with Killip class III myocardial infarction. RESULTS: The median age of patients with stress-induced cardiomyopathy was 63 years, and 95 percent were women. Clinical presentations included chest pain, pulmonary edema, and cardiogenic shock. Diffuse T-wave inversion and a prolonged QT interval occurred in most patients. Seventeen patients had mildly elevated serum troponin I levels, but only 1 of 19 had angiographic evidence of clinically significant coronary disease. Severe left ventricular dysfunction was present on admission (median ejection fraction, 0.20; interquartile range, 0.15 to 0.30) and rapidly resolved in all patients (ejection fraction at two to four weeks, 0.60; interquartile range, 0.55 to 0.65; P<0.001). Endomyocardial biopsy showed mononuclear infiltrates and contraction-band necrosis. Plasma catecholamine levels at presentation were markedly higher among patients with stress-induced cardiomyopathy than among those with Killip class III myocardial infarction (median epinephrine level, 1264 pg per milliliter [interquartile range, 916 to 1374] vs. 376 pg per milliliter [interquartile range, 275 to 476]; norepinephrine level, 2284 pg per milliliter [interquartile range, 1709 to 2910] vs. 1100 pg per milliliter [interquartile range, 914 to 1320]; and dopamine level, 111 pg per milliliter [interquartile range, 106 to 146] vs. 61 pg per milliliter [interquartile range, 46 to 77]; P<0.005 for all comparisons). CONCLUSIONS: Emotional stress can precipitate severe, reversible left ventricular dysfunction in patients without coronary disease. Exaggerated sympathetic stimulation is probably central to the cause of this syndrome.
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