Clinical Proﬁle of Patients With High-Risk Tako-Tsubo Cardiomyopathy Scott W. Sharkey, MDa,*, Victoria R. Pink, RNb, John R. Lesser, MDa, Ross F. Garberich, MSa, Martin S. Maron, MDc, and Barry J. Maron, MDa,b Although tako-tsubo cardiomyopathy (TTC) is regarded as a reversible condition with favorable outcome, a malignant clinical course evolves in some subjects. In this singleinstitution experience, we describe the clinical proﬁle of patients with adverse TTC outcome. A cohort of 249 consecutive patients with TTC was interrogated for those with acute unstable presentation during the ﬁrst 24 hours. Forty-seven patients (19%) experienced early complicated clinical course with cardiac arrest in 9 (ventricular ﬁbrillation, n [ 4, pulseless electrical activity, n [ 3, and asystole, n [ 2) or marked hypotension in 38 (systolic blood pressure £90 mm Hg requiring vasopressors and/or balloon pump). Of the 47 patients, Killip class III to IV heart failure was present in 30 (64%). Despite treatment, 8 patients (3%; all women) died inhospital due to respiratory failure, cardiogenic shock, or anoxic brain injury. All 8 inhospital deaths occurred among the 47 patients with unstable presentation, including 2 after cardiac arrest and 6 with marked hypotension. Post-TTC event mortality for a period of 4.7 – 3.4 years signiﬁcantly exceeded that in a matched general US population (standardized mortality ratio 1.4; 95% conﬁdence interval 1.1 to 1.9; p [ 0.005) largely due to noncardiac co-morbidities. In conclusion, contrary to widespread perception, TTC is not an entirely benign and reversible condition. Among this large cohort, a high-risk subgroup was identiﬁed with cardiac arrest or hemodynamic instability, accounting for all hospital deaths. Hospital nonsurvivors had a variety of irreversible comorbid conditions with the potential to compromise clinical status and adversely affect short-term survival. Long-term survival after hospital discharge was also reduced compared with the general population because of noncardiac co-morbidities. Ó 2015 Elsevier Inc. All rights reserved. (Am J Cardiol 2015;-:-e-)
Tako-tsubo (stress) cardiomyopathy (TTC) is a distinctive cardiac condition with unique left ventricular (LV) contraction proﬁle, often triggered by stressful events, which has been considered reversible and associated with favorable outcome.1e8 However, our experience in a large, single-institution cohort has suggested that this benign characterization of TTC may not be as consistent as previously regarded.5 Therefore, we report here a high-risk subset of TTC patients with malignant clinical presentation. Such observations provide a more robust proﬁle of the TTC clinical spectrum, useful in guiding effective management strategies for patients with this complex but incompletely understood condition. Methods From August 2001 to March 2012, 249 consecutive patients presented with a ﬁrst TTC event to the Minneapolis Heart a Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota; bThe Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota; and c Division of Cardiology, Tufts Medical Center, Boston, Massachusetts. Manuscript received March 28, 2015; revised manuscript received and accepted May 20, 2015. See page 7 for disclosure information. This study was funded by the Minneapolis Heart Institute Foundation, Minneapolis, MN. *Corresponding author: Tel: (612) 863-7372; fax: (612) 863-6441. E-mail address: [email protected] (S.W. Sharkey).
0002-9149/15/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2015.05.054
Institute at the Abbott Northwestern Hospital (Minneapolis, Minnesota). As previously described,4 patients with TTC shared the following features: (1) acute presentation typically with chest pain/discomfort or dyspnea, (2) systolic dysfunction with marked LV contraction abnormality, extending beyond the geographic territory of a single coronary artery, assessed with contrast LV angiography, cardiovascular magnetic resonance imaging (CMR), or 2-dimensional echocardiography, (3) absence of obstructive coronary stenosis (i.e., 50% luminal narrowing of the major coronary arteries by angiography) or evidence of acute plaque rupture. The left anterior descending coronary artery was carefully examined since myocardial ischemia in this distribution can cause an LV contraction abnormality mimicking TTC9, (4) absence of myocarditis or ischemic transmural late gadolinium enhancement on CMR. The magnitude of acute heart failure was quantitated using the Killip classiﬁcation.10 Selected data from 136 study patients have been published previously.1,4 On admission, the ejection fraction (EF) and LV contraction pattern were assessed by LV angiography (n ¼ 149), 2-dimensional echocardiography (n ¼ 95), CMR (n ¼ 2), computed tomography angiography (n ¼ 2), or nuclear imaging (n ¼ 1). LV contraction patterns were categorized: “apical ballooning” (abnormal contraction of mid and apical LV segments), “midventricular ballooning” (abnormal contraction limited to the mid-LV segments), and “basal ballooning” (abnormal contraction limited to the basal LV segments). CMR imaging was performed after admission www.ajconline.org
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Figure 1. Flow diagram showing acute clinical status and outcome at hospital discharge in 249 patients with TTC events. * Requiring administration of vasopressor agents and/or IABP. CHF ¼ congestive heart failure; No. ¼ number.
(n ¼ 154) at the discretion of the attending cardiologist. Details of CMR imaging methods have been recently published.4 Two-dimensional echocardiography included analysis of LV and right ventricular (RV) wall motion, degree of mitral regurgitation, and mitral valve systolic anterior motion (SAM). Left ventricular outﬂow tract gradients were estimated with continuous wave Doppler. Post-hospital EF was measured with echocardiography or CMR. The clinical status of the 249 study patients after the TTC event was assessed as of September 1, 2014, by telephone interview, clinic visit, review of electronic medical records, or interrogation of the US Social Security Death Index. Follow-up was achieved for 233 patients (94%) for a period of 4.7 3.4 years (median 4.2; range 0.1 to 12.8 years). For patients with TTC discharged from the hospital after the initial event, the fraction surviving at each follow-up time was estimated using the Kaplan-Meier method. The expected fraction surviving at each time was computed by assigning to each patient the probability of surviving after presentation, appropriate to patient age at diagnosis and gender, and based on the US Census data. Actual and expected surviving fractions were compared using the 1sample log-rank test, which also provides an estimate and conﬁdence interval (CI) for the standardized mortality ratio and 95% CI. All computations used the “survival” package (version 2.34-1) of the R Software System, version 2.7.2 R (Development Core Team 2008, R Foundation for Statistical Computing, Vienna, Austria). Data are displayed as mean and SD for continuous variables with number and percentage for categorical variables. Categorical variables were analyzed using the
Table 1 Clinical features of 249 tako-tsubo patients with or without acute unstable clinical presentation Variable
Pearson’s chi-square or Fisher’s exact tests. Continuous variables were assessed using the Student’s t test. A value of p <0.05 was considered signiﬁcant, p values are 2 sided where appropriate. Variables with p <0.05 for univariable associations (e.g., gender, heart rate, EF, peak troponin, smoker, and physical TTC trigger) were entered into stepwise multivariable logistic regression models. In this model, variables with p
Figure 2. Ventricular ﬁbrillation on presentation in a 59-year-old man with acute TTC. The patient had a panic attack during outpatient withdrawal from chronic narcotic use and presented to the emergency department with chest pain. Ten minutes after arrival, he became unresponsive with ventricular ﬁbrillation on telemetry monitor, which responded to a single shock without CPR or epinephrine. After stabilization, an electrocardiogram showed ST-segment elevation in anterior leads, and angiography demonstrated normal coronary arteries and midventricular ballooning with an EF of 30%. The patient completely recovered with an EF of 60% and received a secondary prevention implantable deﬁbrillator before discharge.
<0.05 were retained; only patients with complete data on all covariates were included in the multivariable analysis. Statistical calculations and plots were performed with Stata 11.2 (StataCorp. 2009. Stata Statistical Software: Release 11. College Station, TX: StataCorp LP). Institutional review board approval was obtained for data collection, follow-up, and data analysis. Results Forty-seven of the 249 study patients (19%) experienced an early complicated course with cardiac arrest in 9 patients (ventricular ﬁbrillation, n ¼ 4, pulseless electrical activity, n ¼ 3, and asystole, n ¼ 2) or marked hypotension in 38 patients (systolic blood pressure 90 mm Hg requiring intravenous vasopressors and/or intra-aortic balloon pump [IABP]; Figure 1, Table 1). Of these 47 patients, Killip class III to IV heart failure was present in 30 (64%), including 6 of those with cardiac arrest. When the 47 patients presenting with hemodynamic instability or cardiac arrest were compared with the other 202 patients with TTC, more markers of clinical severity were evident, including higher heart rates, lower EF, and higher peak troponin and also with a greater proportion of male gender and presence of physical stressor (Table 1). In this subset, a physical stressor was present in 7 of 8 men (88%) versus 24 of 39 women (62%; p ¼ 0.16). At multivariable analysis, variables associated with unstable presentation included male gender (p ¼ 0.003), physical trigger (p ¼ 0.007), and magnitude of troponin elevation (p ¼ 0.003). The remaining 202 patients all survived hospitalization and were stable at discharge. Thirty-eight of the 249 patients (15%) demonstrated an unstable clinical presentation within 24 hours of admission with acute hypotension, systolic blood pressure 90 mm Hg (range 59 to 90 mm Hg) requiring acute intervention with vasopressor drugs, and/or IABP. Clinical presentation for these 38 patients included dyspnea (n ¼ 16), chest pain (n ¼ 15), altered consciousness or focal neurologic
symptoms (n ¼ 4), syncope (n ¼ 2), or hypotension during general anesthesia (n ¼ 1). Of the 38 patients, 24 were in cardiogenic shock or with pulmonary edema (Killip class III or IV heart failure) and 14 were Killip class I or II heart failure (Figure 1). Lowest systolic blood pressure in these 38 patients was 59 to 79 mm Hg (n ¼ 26) or 80 to 90 mm Hg (n ¼ 12), and mechanical ventilation was necessary in 24 patients. Acute treatment with intravenous pharmacologic agents and/or IABP was judged obligatory in the 38 patients with unstable hemodynamic status, including administration of catecholamine drugs: dopamine (n ¼ 23), phenylephrine (n ¼ 19), norepinephrine (n ¼ 16), dobutamine (n ¼ 11), epinephrine (n ¼ 1), or other agents: vasopressin (n ¼ 7) and milrinone (n ¼ 1). A single drug was sufﬁcient to support blood pressure in 15, 2 drugs were required in 13, and 3 drugs in 10; an IABP was used in 8 patients. Ten of the 38 patients (26%) had SAM, and each was receiving a catecholamine drug (2 also with IABP), including 7 with mitral-septal contact and estimated gradients by Doppler echocardiography 30 mm Hg under conditions at rest, range 30 to 115 mm Hg (average 64 39 mm Hg). Of these 10 patients, 5 also had basal ventricular septal hypertrophy (18 to 21 mm thickness) without uncontrolled systemic hypertension, consistent with hypertrophic cardiomyopathy.11 The remaining 5 patients had normal LV wall thickness and SAM resolution after TTC treatment. Nine patients presented in cardiac arrest due to ventricular ﬁbrillation (n ¼ 4), pulseless electrical activity (n ¼ 3), and asystole (n ¼ 2; Figures 1 and 2, Table 2). In 8 patients, these events occurred immediately before admission and in the other patient in the cardiac catheterization laboratory before coronary angiography. After resuscitation and stabilization, 6 of these patients were judged to be in Killip class III or IV heart failure and the other 3 patients were Killip class I or II. Cardiac arrest patients were younger than the 38 patients with unstable hypotension (58 10 vs 69 14 years; p ¼ 0.03). Intravenous epinephrine was administered during resuscitation in 6 patients.
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Table 2 Nine patients with tako-tsubo cardiomyopathy and cardiac arrest Patient Age (yrs)/ Rhythm sex 1 2 3 4 5 6† 7†† 8 9
COPD ¼ chronic obstructive pulmonary disease; IABP ¼ intra-aortic balloon pump; ICD ¼ implantable cardioverter-deﬁbrillator; LOS ¼ length of hospital stay; ms ¼ milliseconds; PEA ¼ pulseless electrical activity; STE ¼ ST-elevation; VF ¼ ventricular ﬁbrillation. * Right bundle branch block. † Occurred in the emergency department. †† Occurred in catheterization laboratory before catheter insertion; all other cases are out-of-hospital.
Of the 9 patients with cardiac arrest, 5 had signiﬁcant anoxic brain injury (reversible in 3), each of whom was treated with therapeutic hypothermia. Initial electrocardiogram demonstrated ST-segment elevation in 5 patients and QTc prolongation 500 ms in 2 patients; torsades de pointes ventricular tachycardia was absent in all. Important co-morbid medical conditions were present in 6 of the 9 cardiac arrest patients including acute respiratory failure from advanced chronic obstructive lung disease (n ¼ 3), subarachnoid hemorrhage (n ¼ 1), submassive pulmonary embolism (n ¼ 1), and drug overdose (opiates, alcohol, and citalopram) (n ¼ 1). Circulatory support for hypotension or acute heart failure was required in 7 of these 9 patients including intravenous vasopressors (n ¼ 6) and IABP (n ¼ 2). After cardiac arrest, 7 of the 9 patients survived to discharge without permanent neurologic or cardiac disability. Initial EF improved from 24 7% to 60 5% at follow-up (p <0.001). In 3 patients (each with ventricular ﬁbrillation), a secondary prevention implantable cardioverter-deﬁbrillator was placed before discharge, and none have experienced an implantable cardioverter-deﬁbrillator intervention. After hospital discharge, 3 additional cardiac arrest patients died: at 1 month (chronic obstructive pulmonary disease [COPD]), at 3 months (suicide), and at 4 years (COPD). The 4 surviving cardiac arrest patients have had no recurrent cardiac events at follow-up for a period of 2 to 10 years. Of the 249 study patients, 241 survived their acute event and were discharged from the hospital, with EF improved from 32 10% on admission to 57 10% at follow-up (p <0.001). The 8 inhospital deaths occurred in the 47 patients with hemodynamically unstable TTC presentation, including 2 with cardiac arrest (pulseless electrical activity) and 6 with marked hypotension. Mechanism of death included cardiogenic shock (n ¼ 4), respiratory failure from pneumonia (n ¼ 2), and anoxic encephalopathy (n ¼ 2). Of the 39 survivors with unstable TTC presentation, EF improved from 24 8% on admission to 59 6% at followup (41 81 days; p <0.001).
Nonsurvivors and survivors differed signiﬁcantly with respect to the presence of major co-morbid conditions (8 [100%] vs 12 [31%]; p <0.001) and body weight (57 17 vs 72 18 kg; p ¼ 0.04). However, no signiﬁcant differences were present with respect to: age (75 13 vs 66 14 years; p ¼ 0.09), female gender (8 [100%] vs 31 [79%]; p ¼ 0.16), initial heart rate (114 21 vs 101 29 beats/ min; p ¼ 0.27), EF (30 11 vs 24 8%; p ¼ 0.09), presence of physical stressor (7 [88%] vs 24 [62%]; p ¼ 0.16), apical ballooning pattern (6 [75%] vs 21 [54%]; p ¼ 0.27), RV segmental wall motion abnormality (4 [50%] vs 8 [21%]; p ¼ 0.08), Killip class III to IV heart failure (6 [75%] vs 24 [62%]; p ¼ 0.47), LV end-diastolic pressure (21 5 vs 23 7 mm Hg; p ¼ 0.5), moderately severe or severe mitral regurgitation (2 [25%] vs 6 [15%]; p ¼ 0.51), vasopressor drug use (8 [100%] vs 36 [92%]; p ¼ 0.51), or IABP use (1 [13%] vs 9 [23%]; p ¼ 0.45). Average age at inhospital death was 75 13 years (range 58 to 92), all were women (7 of 8 with a physical stressor), and admission EF 30 11%. Notably, each of the 8 patients who died had an irreversible co-morbid condition judged to be an important contributor to demise, including cardiac arrest with anoxic encephalopathy (n ¼ 2), subarachnoid hemorrhage without cardiac arrest (n ¼ 1), particularly advanced age >90 years (n ¼ 1), dementia (n ¼ 1), lung cancer (n ¼ 1), Crohn’s disease with short bowel syndrome (n ¼ 1), and meningioma with cerebral edema (n ¼ 1; Table 3). Four of these patients also had pneumonia. We achieved recent follow-up for 233 of 249 patients (94%), of whom 165 (71%) are known to have survived (mean age 71 13 years; 41% to 75 years; Figures 3 and 4). Sixty-eight patients (29%) died after their TTC event, including the 8 inhospital deaths and 60 postdischarge deaths (time to death after TTC event, 2.6 2.6 years; range 0 to 9.7). Over the long-term follow-up, all-cause mortality after the TTC event for the entire cohort exceeded that in the ageand gender-matched US general population (standardized mortality ratio 1.4; 95% CI: 1.1 to 1.9; p ¼ 0.005;
BMI ¼ body mass index; COPD ¼ chronic obstructive pulmonary disease.
Figure 3. Flow diagram showing long-term follow-up of 249 patients with TTC. * Less common causes of death: respiratory failure (n ¼ 4), renal failure (n ¼ 2), trauma (n ¼ 1), suicide (n ¼ 1), intracranial hemorrhage (n ¼ 1), advanced dementia (n ¼ 1), interstitial lung disease with pulmonary hypertension (n ¼ 1); 20 are unknown. No. ¼ number.
Figure 4). All-cause mortality at 1 year after TTC event was also signiﬁcantly greater than the general US population (standardized mortality ratio 2.9; 95% CI: 1.9 to 4.6; p <0.001). Of the 68 deaths, 26 (38%) were during the ﬁrst year after TTC event, more commonly from the subset with an initial acute unstable presentation (12 of 47; 26%) than in those with relatively stable presentation (14 of 202; 7%; p <0.001). Causes of death were noncardiac in each patient, most commonly cancer (n ¼ 15), COPD (n ¼ 8), and sepsis (n ¼ 6; Figure 3). Of 11 patients (5%) with recurrent TTC, 7 were alive at follow-up, and none of the 4 deaths were related to TTC. Of the 5 patients with probable hypertrophic cardiomyopathy, 3 were alive at follow-up (ages 77 to 101 years).
Discussion TTC is generally considered to have a benign clinical course and favorable short-term outcome.5 However, in our large, single-center cohort, about 1/5 of patients had acute, hemodynamically unstable, and particularly severe clinical presentation characterized by either cardiac arrest (4%) or marked hypotension necessitating emergent mechanical and/or pharmacologic support (15%). These patients had lower EF and higher heart rates and troponin peaks than the other patients with TTC, suggesting a greater degree of acute myocardial injury. Also, these patients experienced particularly severe heart failure, with cardiogenic shock (Killip class IV) present in almost 40% and acute pulmonary edema (Killip class III) in 25%. The degree of hypotension
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Figure 4. Kaplan-Meier survival curves for patients with TTC versus expected in the general population. Kaplan-Meier survival curves for 249 patients with TTC (solid line) compared with expected in an age- and gender-matched US general population (broken line). SMR ¼ standardized mortality ratio.
was often marked with systolic blood pressure <80 mm Hg in almost 70% of patients in the hemodynamically unstable subset. Hospital mortality in this large patient cohort was 3%, with each of the 8 hospital deaths in patients who presented with cardiac arrest or hemodynamic instability (requiring vasopressor drugs and/or IABP). Therefore, of the highest risk subgroup of 47 patients, hospital mortality rate was almost 20%. Previous reports of TTC-related inhospital deaths are limited. A recent series from the Italian TTC network included 6 patients (2.6%) with hospital death, of which 4 were caused by heart failure or cardiogenic shock and 2 by malignancy.12 A review of 14 international TTC study populations (286 patients) reported hospital death in <1%.13 A TTC registry from Germany and Austria (37 centers; 324 patients) reported hospital mortality rate of 2%, although the causes of death were not reported.14 Several case reports describe death due to cardiac rupture in patients with TTC.15 Of particular note, all 8 TTC nonsurvivors had important, irreversible co-morbid conditions with potential to adversely affect clinical status and survival.16,17 Co-morbid conditions have also been shown to determine outcome after recovery from a TTC event.4 Although adverse TTC prognosis has been associated with RV dysfunction (ballooning),18 this
ﬁnding in our patients did not explain the mechanism of death. Furthermore, although dynamic left ventricular outﬂow tract obstruction has been associated with severe heart failure in TTC,19 this ﬁnding was no more common in nonsurvivors than survivors in this cohort. The number of patients with TTC with cardiac arrest reported here is substantial and represents an important increase from our earlier report in 2008.4 This observation could represent increased TTC awareness, enhanced referral of cardiac arrest patients to our institution because of implementation of a regional therapeutic hypothermia program in 2006,20 or a random clustering of events. These ﬁndings are consistent with previous reports of cardiac arrest in TTC.4,21e24 With regard to the cardiac arrest patients, it remains unresolved whether the TTC event was the cause or alternatively the consequence of the arrhythmia. The physiologic stress of cardiac arrest and subsequent resuscitation (sometimes with epinephrine) is profound and could trigger TTC. In contrast, in 6 patients, an acute non-TTC medical condition (e.g., acute respiratory failure, subarachnoid hemorrhage, drug overdose) was present with the capacity to trigger both TTC and cardiac arrest. Nonetheless, in the 4 patients with ventricular ﬁbrillation, we believe TTC (psychological or physical stress induced) itself was the probable trigger for cardiac arrest.
Information regarding acute hemodynamic instability requiring vasopressor drugs or IABP in TTC is limited.13,25,26 A recent report documented severe LV systolic and diastolic dysfunction in TTC, and under these circumstances, clinically important acute heart failure may occur.27 In the TTC network, cardiogenic shock occurred in 8%, inotropic drugs were used in 6%, and IABP in 3%,12 whereas a single-center study of 52 patients cited inotropic drug use in 15% and IABP use in 7%.26 Whether catecholamine drugs are a safe and effective treatment for TTC-associated hypotension is unresolved.28,29 These agents in excessive or even therapeutic dosage have been reported to trigger TTC.30 Nevertheless, in the present cohort, we did not observe negative clinical consequences related to the intravenous administration of catecholamines, and our TTC survivors experienced complete cardiac recovery (including normalization of EF) associated with using these drugs. Our long-term follow-up analysis showed that survival after TTC event was reduced compared with that of an age- and gender-matched US population largely because of an increased mortality in the ﬁrst year after the initial event. Post-TTC deaths were most commonly from cancer or COPD, with none directly attributable to cardiac disease. Importantly, those patients with an unstable presentation had higher 1-year mortality than patients with a stable presentation. Because these deaths were unrelated to cardiac disease, a clinical linkage to TTC itself is tenuous. Finally, patients with recurrent TTC did not have a survival disadvantage. These ﬁndings underscore the importance of co-morbid noncardiac conditions in determining survival after a TTC event while raising the possibility that TTC could itself represent a marker for disease severity and overall adverse outcome. We report here a new paradigm in the increasingly expansive clinical spectrum of TTC. For the vast majority of patients, TTC is a survivable event with expectation for full cardiovascular recovery. In contrast, in an important minority of patients, TTC may lead to life-threatening arrhythmic events or even death, particularly when major co-morbid conditions are also present. Disclosures The authors have no conﬂicts of interest to disclose. 1. Sharkey SW, Lesser JR, Zenovich AG, Maron MS, Lindberg J, Longe TF, Maron BJ. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation 2005;111:472e479. 2. Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I; Angina Pectoris-Myocardial Infarction Investigations in Japan. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. Angina pectoris-myocardial infarction investigations in Japan. J Am Coll Cardiol 2001;38:11e18. 3. Kurisu S, Sato H, Kawagoe T, Ishihara M, Shimatani Y, Nishioka K, Kono Y, Umemura T, Nakamura S. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 2002;143: 448e455. 4. Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, Haas TS, Hodges JS, Maron BJ. Natural history and expansive clinical proﬁle of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol 2010;55:333e341. 5. Bybee KA, Prasad A. Stress-related cardiomyopathy syndromes. Circulation 2008;118:397e409.
6. Sharkey SW, Shear W, Hodges M, Herzog CA. Reversible myocardial contraction abnormalities in patients with an acute noncardiac illness. Chest 1998;114:98e105. 7. Sharkey SW, Lesser JR, Madhav M, Parpart M, Maron MS, Maron BJ. Spectrum and signiﬁcance of electrocardiographic patterns, troponin levels, and thrombolysis in myocardial infarction frame count in patients with stress (tako-tsubo) cardiomyopathy and comparison to those in patients with ST-elevation anterior wall myocardial infarction. Am J Cardiol 2008;101:1723e1728. 8. Sharkey SW, Maron BJ. Epidemiology and clinical proﬁle of takotsubo cardiomyopathy. Circ J 2014;78:2119e2128. 9. Chao T, Lindsay J, Collins S, Woldeyes L, Joshi SB, Steinberg DH, Satler LF, Kent KM, Suddath WO, Pichard AD, Waksman R. Can acute occlusion of the left anterior descending coronary artery produce a typical “takotsubo” left ventricular contraction pattern? Am J Cardiol 2009;104:202e204. 10. Khot UN, Jia G, Moliterno DJ, Lincoff AM, Khot MB, Harrington RA, Topol EJ. Prognostic importance of physical examination for heart failure in non-ST-elevation acute coronary syndromes: the enduring value of Killip classiﬁcation. JAMA 2003;22:2174e2181. 11. Maron BJ, Ommen SR, Semsarian C, Spirito P, Olivotto I, Maron MS. Hypertrophic cardiomyopathy: present and future, with translation into contemporary cardiovascular medicine. J Am Coll Cardiol 2014;64: 83e99. 12. Citro R, Rigo F, D’Andrea A, Ciampi Q, Parodi G, Provenza G, Piccolo R, Mirra M, Zito C, Giudice R, Patella MM, AntoniniCanterin F, Bossone E, Piscione F, Salerno-Uriarte J; Tako-Tsubo Italian Network Investigators. Echocardiographic correlates of acute heart failure, cardiogenic shock, and in-hospital mortality in tako-tsubo cardiomyopathy. JACC Cardiovasc Imaging 2014;7: 119e129. 13. 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;27:1523e1529. 14. Schneider B, Athanasiadis A, Stollberger C, Pistner W, Schwab J, Gottwald U, Schoeller R, Gerecke B, Hoffmann E, Wegner C, Sechtem U. Gender differences in the manifestation of tako-tsubo cardiomyopathy. Int J Cardiol 2013;166:584e588. 15. Kumar S, Kaushik S, Nautiyal A, Choudhary SK, Kayastha BL, Mostow N, Lazar JM. Cardiac rupture in takotsubo cardiomyopathy: a systematic review. Clin Cardiol 2011;34:672e676. 16. Joe BH, Jo U, Kim HS, Park CB, Hwang HJ, Sohn IS, Jin ES, Cho JM, Park JH, Kim CJ. APACHE II score, rather than cardiac function, may predict poor prognosis in patients with stress-induced cardiomyopathy. J Korean Med Sci 2012;27:52e57. 17. Brinjikji W, El-Sayed AM, Salka S. In-hospital mortality among patients with takotsubo cardiomyopathy: a study of the National Inpatient Sample 2008 to 2009. Am Heart J 2012;164:215e221. 18. Elesber AA, Prasad A, Bybee KA, Valeti U, Motiei A, Lerman A, Chandrasekaran K, Rihal CS. Transient cardiac apical ballooning syndrome: prevalence and clinical implications of right ventricular involvement. J Am Coll Cardiol 2006;47:1082e1083. 19. El Mahmoud R, Mansencal N, Pilliere R, Leyer F, Abbou N, Michaud P, Nallet O, Digne F, Lacombe P, Cattan S, Dubourg O. Prevalence and characteristics of left ventricular outﬂow tract obstruction in takotsubo syndrome. Am Heart J 2008;156:543e548. 20. Mooney MR, Unger BT, Boland LL, Burke MN, Kebed KY, Graham KJ, Henry TD, Katsiyiannis WT, Satterlee PA, Sendelbach S, Hodges JS, Parham WM. Therapeutic hypothermia after out-of-hospital cardiac arrest: evaluation of a regional system to increase access to cooling. Circulation 2011;124:206e214. 21. Syed FF, Asirvatham SJ, Johnson F. Arrhythmia occurrence with takotsubo cardiomyopathy: a literature review. Europace 2011;13: 780e788. 22. Liang JJ, Cha YM, Oh JK, Prasad A. Sudden cardiac death: an increasingly recognized presentation of apical ballooning syndrome (Takotsubo cardiomyopathy). Heart Lung 2013;42:270e272. 23. Raddino R, Pedrinazzi C, Zanini G, Robba D, Portera C, Bonadei I, Vizzardi E, Dei Cas L. Out-of-hospital cardiac arrest caused by transient left ventricular apical ballooning syndrome. Int J Cardiol 2008;128:e31ee33. 24. Bortnik M, Verdoia M, Schaffer A, Occhetta E, Marino P. Ventricular ﬁbrillation as primary presentation of takotsubo cardiomyopathy after complicated cesarean section. World J Cardiol 2012;4:214e217.
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25. Song BG, Park SJ, Noh HJ, Jo HC, Choi JO, Lee SC, Park SW, Jeon ES, Kim DK, Oh JK. Clinical characteristics, and laboratory and echocardiographic ﬁndings in takotsubo cardiomyopathy presenting as cardiogenic shock. J Crit Care 2010;25:329e335. 26. Madhavan M, Rihal CS, Lerman A, Prasad A. Acute heart failure in apical ballooning syndrome (takotsubo/stress cardiomyopathy): clinical correlates and Mayo Clinic risk score. J Am Coll Cardiol 2011;57:1400e1401. 27. Medeiros K, O’Connor MJ, Baicu CF, Fitzgibbons TP, Shaw P, Tighe DA, Zile MR, Aurigemma GP. Systolic and diastolic mechanics in stress cardiomyopathy. Circulation 2014;129:1659e1667. 28. Bonacchi M, Valente S, Harmelin G, Gensini GF, Sani G. Extracorporeal life support as ultimate strategy for refractory
severe cardiogenic shock induced by tako-tsubo cardiomyopathy: a new effective therapeutic option. Artif Organs 2009;33: 866e870. 29. Fujiwara S, Takeishi Y, Isoyama S, Aono G, Takizawa K, Honda H, Otomo T, Mitsuoka M, Itoh Y, Terashima M, Kubota I, Meguro T. Responsiveness to dobutamine stimulation in patients with left ventricular apical ballooning syndrome. Am J Cardiol 2007;100: 1600e1603. 30. Abraham J, Mudd JO, Kapur N, Klein K, Champion HC, Wittstein IS. Stress cardiomyopathy after intravenous administration of catecholamines and beta-receptor agonists. J Am Coll Cardiol 2009;53: 1320e1325.
Cardiac arrest (CA) is relatively rare but lethal complication of takotsubo cardiomyopathy (TTC). In most instances, patients are diagnosed with TTC after CA, making it difficult to distinguish if TTC is the precipitant or the consequence of the inde
Although takotsubo cardiomyopathy (TTC) has been reported to have a favorable outcome, many complications may occur in the acute phase. Heart failure is the most common clinical complication in patients with TTC. We aimed to investigate determinants
Several acute complications related to takotsubo cardiomyopathy (TTC) have been documented recently. However, the incidence and clinical significance of acute thromboembolic events in TTC is not well established.
Both Takotsubo cardiomyopathy (TTC) and reverse TTC (r-TTC) are characterized by reversible regional wall motion abnormalities of the heart unrelated to coronary artery pathology. It remains unclear whether and/or how r-TTC differs from TTC. Subarach