Introduction
Takotsubo syndrome (TTS) is a transient left and/or right ventricular dysfunction, which is often preceded by emotional or physical stress. It occurs mainly in postmenopausal women.1 Multiple diagnostic criteria have been proposed for TTS, with the most current International Takotsubo Diagnostic Criteria.2
One of the criteria for diagnosing TTS suggests that it occurs predominantly in postmenopausal women. Although most patients with TTS are postmenopausal women and the possible pathomechanism is related to female hormones, including estrogens, men can also suffer from TTS.3 Therefore, we chose the potential difference in clinical characteristics and the course of the disease between men and women as the topic of this study. The goal of the study was to compare the prevalence, course of the disease, and prognosis in men and women with TTS in 2 large Polish university hospitals, which are experienced in the diagnosis and treatment of TTS and participate in the International Takotsubo Registry. However, this study was designed in Warsaw and Gdańsk, independently of the above-mentioned registry.
Patients and methods
Our analysis included 232 patients with TTS hospitalized at the 1st Chair and Department of Cardiology at the Medical University of Warsaw and the 1st Department of Cardiology at the Medical University of Gdańsk from 2009 to 2018. In all patients, the diagnosis was based on echocardiography showing a typical transient left ventricular dysfunction and characteristic levels of cardiac biomarkers. Angiography was performed in all but 2 patients in whom it was contraindicated. In case of doubt, magnetic resonance imaging was performed. In all patients, follow-up echocardiography showed the typical full resolution of the ventricular systolic dysfunction.
Data on the diagnosis, comorbidity, course of TTS, and the results of electrocardiography, echocardiography, and angiography were collected and analyzed.
Statistical analysis
The normality of the distribution of continuous variables was assessed using the Shapiro–Wilk test. All continuous variables were nonnormally distributed and presented as median and interquartile range. For categorical variables, absolute and relative frequencies were presented. The difference in the categorical variables between men and women was tested using the Fisher exact test, while the difference in the continuous variables between both groups was assessed by the Mann–Whitney test. Risk factors of the composite endpoint (atrial fibrillation, ventricular tachycardia, ventricular fibrillation, cardiogenic shock, death) were evaluated with a logistic regression analysis. Because of the low number of events per variable, multivariate logistic regression analysis was not performed. A P value of less than 0.05 was considered significant for all tests. Statistical analysis was performed using the SAS software, version 9.4 (SAS Institute Inc., Cary, North Carolina, United States).
The study was approved by an ethics committee (decision no., 25/2011) and all patients provided written informed consent to participate in the study.
Results
The analysis included 232 patients, 211 (91.4%) of whom were women. The patient characteristics are shown in Table 1. Laboratory parameters and the results of electrocardiography and echocardiography are presented in Table 2. All data come from 2 centers, except for the levels of the N-terminal prohormone of brain natriuretic peptide (NT-proBNP), which were reported only for the patients from the Warsaw registry.
| Variable | Women (n = 211) | Men (n = 21) | P value |
|---|---|---|---|
Age, y, median (IQR) | 71 (61–79) | 63 (54–72) | 0.06 |
BMI, kg/m2, median (IQR) | 24.5 (21.1–27.5) | 24 (22–25.8) | 0.73 |
Living alone | 13 (11.4); 114 | 5 (31.3); 16 | 0.047 |
Stress factors | |||
Emotional stress | 119 (56.4); 211 | 8 (40); 20 | 0.17 |
Physical stress | 30 (14.2); 211 | 7 (35); 20 | 0.02 |
Exacerbation of a chronic disease | 28 (13.3); 211 | 2 (9.5); 21 | >0.99 |
Signs and symptoms on admission | |||
Chest pain | 177 (84.3); 210 | 17 (81); 21 | 0.75 |
Dyspnea | 103 (49.3); 209 | 8 (38.1); 21 | 0.37 |
Symptom duration, h, median (IQR) | 2 (1–9) | 3.5 (1–12) | 0.58 |
HR, bpm, median (IQR) | 85 (73–98) | 80 (67–100) | 0.78 |
SBP, mm Hg, median (IQR) | 130 (120–145) | 140 (130–145) | 0.3 |
DBP, mm Hg, median (IQR) | 80 (70–83) | 80 (70–80) | 0.5 |
Risk factors | |||
Smoking | 51 (24.4); 209 | 12 (57.1); 21 | 0.01 |
Hypercholesterolemia | 94 (44.8); 210 | 8 (40); 20 | 0.82 |
Family history of CVD | 40 (19.6); 204 | 3 (14.3); 21 | 0.77 |
Hypertension | 144 (68.6); 210 | 12 (57.1); 21 | 0.33 |
Diabetes | 36 (17.2); 209 | 2 (9.5); 21 | 0.54 |
Comorbidities | |||
COPD | 27 (12.8); 211 | 4 (19.1); 21 | 0.50 |
Hyperthyroidism | 22 (10.6); 208 | 2 (10); 20 | >0.99 |
Malignancy | 25 (12); 209 | 3 (14.3); 21 | 0.73 |
Data are presented as number (percentage); total number of patients in whom a variable was analyzed unless otherwise indicated. Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease, DBP, diastolic blood pressure; HR, heart rate; IQR, interquartile range; SBP, systolic blood pressure | |||
| Variable | Women (n = 211) | Men (n = 21) | P value | |
|---|---|---|---|---|
Biomarkers | ||||
TnI on admission | N | 206 | 20 | 0.11 |
Median (IQR), ng/ml | 2.04 (0.53–5.59) | 0.61 (0.25–3.82) | ||
Peak TnI | N | 205 | 21 | 0.6 |
Median (IQR), ng/ml | 3.16 (1.3–6.55) | 1.76 (0.77–10.43) | ||
CK on admission | N | 94 | 9 | 0.49 |
Median (IQR), ng/ml | 129.5 (67–235) | 123 (101–208) | ||
CK-MB mass on admission | N | 153 | 15 | 0.83 |
Median (IQR), ng/ml | 5 (1.9–13.9) | 4.6 (1.8–14.4) | ||
Peak CK-MB mass | N | 152 | 16 | 0.41 |
Median (IQR), ng/ml | 7.1 (2.6–17.6) | 12.1 (2.6–15.9) | ||
NT-proBNP on admissiona | N | 94 | 11 | <0.001 |
Median (IQR) | 2.2 (0.04–20.5) | 1.3 (0.2–10.2) | ||
Peak NT-proBNPa | N | 127 | 11 | <0.001 |
Median (IQR) | 4.8 (0.1–38.4) | 4.7 (0.3–30) | ||
Electrocardiography | ||||
ST-segment elevation on admission | 129 (61.4); 210 | 12 (60); 20 | >0.99 | |
ST-segment depression on admission | 13 (6.2); 209 | 5 (25); 20 | 0.01 | |
LBBB on admission | 6 (2.9); 209 | 0 | >0.99 | |
QTc on admission, ms, median (IQR) | 456 (422–486) | 452 (417–480) | 0.69 | |
QTc on day 3, ms, median (IQR) | 477 (441–506) | 453 (432–488) | 0.12 | |
QTc on day 5, ms, median (IQR) | 455 (435–477) | 431 (399–478) | 0.33 | |
Echocardiography | ||||
Apical TTS | 178 (84.4); 211 | 18 (85.7); 21 | >0.99 | |
Reverse TTS | 8 (3.8); 211 | 1 (4.8); 21 | 0.58 | |
Midventricular TTS | 24 (11.4); 211 | 2 (9.5); 21 | >0.99 | |
LVEF, %, median (IQR) | Day 1 | 40 (35–45) | 40 (35–49) | 0.35 |
Day 3 | 48 (41–55) | 57.5 (46–61) | 0.18 | |
Day 5 | 53.5 (43–60) | 53.5 (44–59) | 0.96 | |
At discharge | 60 (54.5–65) | 50 (45–50) | 0.002 | |
RV dysfunction | 17 (16.8); 101 | 1 (6.3); 16 | 0.46 | |
Thrombus | 5 (2.4); 210 | 1 (4.8); 21 | 0.44 | |
Acute functional MR | 41 (38.7); 106 | 2 (12.5); 16 | 0.05 | |
Pericardial fluid | 10 (9.6); 104 | 1 (6.3); 16 | >0.99 | |
Data are presented as number (percentage); total number of patients in whom a variable was analyzed (N) unless otherwise indicated. a Upper limits of the normal range for N-terminal prohormone of brain natriuretic peptide Abbreviations: CK, creatine kinase; CK-MB mass, creatine kinase isoenzyme MB mass; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; MR, mitral regurgitation; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; RV, right ventricle; TnI, troponin I; QTc, QT interval corrected for heart rate; others, see Table 1 | ||||
Men tended to be younger than women (median [interquartile range] age, 63 [54–72] vs 71 [61–79] years; P = 0.055). Emotional stress was the most frequent cause of TTS in both men and women, but physical stress triggered TTS more often in men than in women (35% vs 14.2%; P = 0.02). Interestingly, men who developed TTS were more likely to live alone than women.
Comorbidity
Risk factors like obesity, hypertension, hypercholesterolemia, diabetes, and family history of cardiovascular disease were equally frequent in men and women. The only difference was observed in smoking habits: 24.4% of women and 57.1% of men were smokers. The prevalence of TTS as a comorbidity of chronic obstructive pulmonary disease, cancer, or hyperthyroidism did not differ between men and women.
Biomarkers
The elevated levels of biomarkers with high levels of NT-proBNP and relatively low elevation of troponin levels in both men and women were suggestive of TTS.4 In both groups, similarly elevated levels of markers of myocardial necrosis were found: troponin, creatine kinase, and creatine kinase isoenzyme MB mass. Both the peak NT-proBNP levels and the NT-proBNP levels measured on admission to hospital were higher in women.
Electrocardiography
The most frequent abnormality detected by electrocardiography on admission was ST-segment elevation. Isolated ST-segment depression was found more frequently in men than in women (25% vs 6.2%). The QT interval corrected for heart rate (QTc) was the same for men and women, both on admission and on days 3 and 5 after admission. The QTc prolongation of more than 450 ms was found in 53% of men on day 1, in 60% on day 3, and in 30% on day 5 after admission. The QTc prolongation of more than 460 ms was found in 44% of women on day 1, in 60% on day 3, and in 49% on day 5 after admission.
Echocardiography
Most frequently, TTS occurred in both men and women in its apical form, which was found in 85.7% of men and 84.4% of women. The reverse and midventricular types were less frequent. There were no differences in the prevalence of particular types of TTS (apical, midventricular, reverse) between women and men. Regional wall motion abnormalities in the right ventricular function were found in 16.8% of women and 6.3% of men, but this difference between the groups was not significant. There were also no differences between the 2 groups in the prevalence of pericardial effusion or thrombus formation. Acute functional mitral valve regurgitation tended to be more frequent in women than in men (38.7% vs 12.5%; P = 0.05). Left ventricular ejection fraction (LVEF) was similar for men and women on admission and on days 3 and 5 after admission, but appeared to be lower in men at discharge despite the same length of hospitalization in both groups.
Course of the disease
Clinical symptoms were similar in men and women. The most frequent symptom on admission was chest pain, which was present in 84.3% of women and in 81% of men. The median time from symptom onset to hospitalization did not differ between the groups. Heart rate and systolic and diastolic pressure were similar in both groups. Furthermore, a similar percentage of men and women needed catecholamines, an intra-aortic balloon pump, and mechanical ventilation.
The prevalence and types of complications during hospitalization are presented in Table 3. There were no differences between men and women in the prevalence of arrhythmias: atrial fibrillation, ventricular fibrillation, and ventricular tachycardia. The prevalence of ventricular septal rupture and cardiogenic shock was similar in both patient groups, and so was the length of hospitalization. Six women and no men died, but this did not show a significant difference.
| Variable | Women (n = 211) | Men (n = 21) | P value |
|---|---|---|---|
Unstable on admission | 26 (12.3); 211 | 3 (14.3); 21 | 0.73 |
Mechanical ventilation | 13 (6.2); 211 | 1 (4.8); 21 | >0.99 |
IABP | 0 (0); 210 | 1 (4.8); 21 | 0.09 |
AF | 11 (5.2); 210 | 2 (9.5); 21 | 0.33 |
VT | 9 (4.3); 210 | 0 (0); 21 | >0.99 |
VF | 14 (6.7); 210 | 1 (4.8); 21 | >0.99 |
Ventricular septal rupture | 1 (0.48); 210 | 0 (0); 21 | >0.99 |
Left ventricular free wall rupture | 0 (0); 210 | 0 (0); 210 | >0.99 |
Cardiogenic shock | 20 (9.5); 211 | 1 (4.8); 21 | 0.70 |
Death | 6 (2.9); 210 | 0 (0); 21 | >0.99 |
Length of hospitalization, d, median (IQR) | 7 (5–12) | 6 (5–6) | 0.17 |
Beta adrenolytics | 152 (74.5); 204 | 11 (52.4); 21 | 0.04 |
ACEI | 150 (73.5); 204 | 17 (81); 21 | 0.60 |
CCB | 9 (4.5); 202 | 2 (9.5); 21 | 0.28 |
ASA | 146 (72.6); 201 | 14 (66.7); 21 | 0.61 |
VKA/NOAC | 11 (5.5); 201 | 1 (4.8); 21 | >0.99 |
P2Y12 inhibitors | 21 (10.4); 202 | 5 (23.8); 21 | 0.08 |
Statins | 138 (68.3); 202 | 8 (38.1); 21 | 0.008 |
Data are presented as number (percentage); total number of patients in whom a variable was analyzed unless otherwise indicated. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ASA, acetylsalicylic acid; CCB, calcium channel blocker; IABP, intra-aortic balloon pump; NOAC, novel oral anticoagulants; VF, ventricular fibrillation; VKA, vitamin K antagonists; VT, ventricular tachycardia | |||
We performed the logistic regression analysis of predictors of in-hospital complications including atrial fibrillation, ventricular tachycardia, ventricular fibrillation, cardiogenic shock, and death. The predictors of composite endpoint were: chest pain on admission (odds ratio [OR], 0.44; 95% CI, 0.20–0.97), dyspnea on admission (OR, 2.50; 95% CI, 1.70–6.98), heart rate on admission (OR, 1.03; 95% CI, 1.01–1.04), and LVEF on admission (OR, 0.90; 95% CI, 0.86–0.95). Sex was not considered a predictor of in-hospital complications (Table 4).
| Variable | Univariate analysis | ||
|---|---|---|---|
| OR | 95% CI | P value | |
Female sex | 2.5 | 0.56–11.15 | 0.23 |
Age | 1.02 | 0.99–1.05 | 0.17 |
Unstablea | 54.17 | 17.18–170.74 | <0.001 |
Chest paina | 0.44 | 0.20–0.97 | 0.04 |
Dyspneaa | 3.45 | 1.70–6.98 | <0.001 |
Symptom duration | 0.97 | 0.94–1.01 | 0.14 |
HRa | 1.03 | 1.01–1.04 | <0.001 |
SBPa | 0.99 | 0.98–1.01 | 0.20 |
DBPa | 0.99 | 0.96–1.01 | 0.23 |
Peak TnI | 1.02 | 0.99–1.05 | 0.27 |
Peak NT-proBNP | 1.00 | 1.00–1.00 | 0.14 |
LVEF | 0.90 | 0.86–0.95 | <0.001 |
a Assessed or measured on admission. Abbreviations: OR, odds ratio; others, see Tables 1 and 2 | |||
Treatment
Angiotensin-converting enzyme inhibitors were the most frequently prescribed drugs at discharge. β-Adrenolytics and statins were more often prescribed to women than to men, and acetylsalicylic acid was recommended in about 70% of patients, regardless of sex. There was a tendency toward more frequent use of P2Y12 inhibitors in men than in women (23.8% vs 10.4%; P = 0.08). No difference was observed in medications and mechanical circulatory assist devices utilized in both centers.
Discussion
The available literature suggests that TTS in men is more frequent in Asian populations.5 In Western Europe, about 10% of patients with TTS are men.6,7 Our analysis shows a similar prevalence of TTS in men in the Polish population (9%). Some authors perceive the prevalence of TTS as still underestimated,8 especially in men, who are more frequently admitted to hospital after either successful or unsuccessful cardiopulmonary resuscitation, which precludes the diagnosis of TTS.6 In the Japanese population, autopsy in patients who had suffered sudden cardiac death, 85% of whom were men, revealed that a sudden, stress-induced cardiac dysfunction was the most likely cause of death in 19.8% of these patients.9
In most cases, the onset of TTS is preceded by an identifiable trigger.10 In our patient sample, emotional stress was the prevailing trigger of TTS. Physical stress triggered TTS more frequently in men than in women, and this confirms previous research findings.6,10-12 It is significant that men who developed TTS were more likely to be alone (defined as “living alone”) than women, and this might confirm the role of emotional triggers in TTS and suggest that lack of emotional support might increase predisposition to TTS.
We did not find any differences in the prevalence of most cardiovascular risk factors between men and women in our sample. The only difference we found concerned smoking habits: men with TTS were more likely to smoke than women, which is consistent with the literature.13
The majority of patients admitted to hospital with TTS show abnormalities on electrocardiogram.14 In our patient group, ST-segment elevation was the most common abnormality, and ST-segment depression, rarely found in the population with TTS, was detected more often in men than in women. No differences were found between men and women with regard to the QTc interval neither on admission nor on days 3 and 5 after admission. It should be noted, however, that men have a shorter QTc than women, which is why it is especially important to detect ventricular arrhythmias in that population. The meta-analysis of research data suggests that the risk of torsade de pointes is higher among men.15 In our study population, LVEF at discharge was lower in men, even though the length of hospital stay was similar in men and women. Despite no differences in LVEF on admission and similar prevalence of right ventricular dysfunction, pericardial effusion, and ventricular thrombus formation, the time required for the complete recovery of left ventricular systolic function was longer in men than in women. This might cause delays in the final diagnosis of TTS and suggest the need for longer hospitalization in men. However, lower LVEF at discharge is not correlated with the frequency of complications during hospitalization, including death. In the Polish population, we did not confirm observations made on a large patient sample from the United States in which a higher mortality rate was observed in men.13 Angiotensin-converting enzyme inhibitors were the medications most frequently prescribed at discharge, which probably reflected 2 phenomena: 1) that patients with TTS were often hypertensive and 2) that these medications have been proved to be beneficial in preventing recurrence of the disease.16 β-Adrenolytics were more frequently prescribed to women than to men. This was likely to be caused by doctors’ belief that these medications can be effective in patients with overactive sympathetic nervous system, persistent anxiety, or palpitations, which are more frequently experienced by women. While the prevalence of hypercholesterolemia was similar in both groups, statins were prescribed more frequently to women and it is something we cannot explain. Despite lack of evidence as to the benefits of antiplatelet therapies, acetylsalicylic acid was prescribed to approximately 70% of patients. We should emphasize that this analysis included patients hospitalized since 2009 and little was known about therapies for TTS at that time. Currently, the use of acetylsalicylic acid is not recommended in patients with TTS.17
It should also be noted that dual antiplatelet therapy was conducted in almost one-fourth of men and in about every tenth woman, which shows that over the years, TTS has been treated similarly to myocardial infarction. This is particularly apparent in men and associated with doctors’ limited experience that results from the low prevalence of TTS in the general population. Of note, the average hospitalization period for patients in our sample, drawn from 2 large Polish hospitals, was twice as long as that in the American study, which affects the cost-effectiveness of hospitalization. This might suggest that the extended length of hospitalization in Poland is unwarranted.13
Excessive catecholamine release in response to a stressor is the most widely accepted cause of TTS.18 The reason for the higher prevalence of TTS in women is not known. Some researchers suggest that lower estrogen production might be the culprit.19 Estrogens have a cardioprotective effect that works through a variety of mechanisms, such as inhibition of the renin-angiotensin system, modulation of the release of natriuretic peptide,20 weakening of the catecholamine and glucocorticoid response to stress, and improvement of noradrenaline-induced vascular contraction.21,23 Estrogen levels in postmenopausal women are lower than in premenopausal women and lower than in men of the same age,22 which could be the reason for the higher prevalence of TTS in postmenopausal women.24-26 Factors that predispose men to TTS are not known. Risk factors and the course of the disease in men and women differ in terms of several of the above-mentioned factors. Therefore, there is a need for further multicenter studies, which would include hormone analysis and psychological evaluation of patients.
Limitations
The main limitation of the study is lack of hormone analysis as well as investigation of psychological factors and patient’s personality. We are aware that the number of male patients is small but it results from the rare occurrence of TTS in men in the general population. This may be the reason for underestimating the incidence of complications. In addition, the difference between primary and secondary TTS in men and women cannot be reliably assessed. Moreover, a long-term follow-up is needed, which is the subject of our further analyses.
Conclusions
The prevalence of TTS in men is lower than in women. Clinical characteristics and the course of the disease were similar in both groups. However, some differences were noted. Physical stress was a more common cause of TTS in men. Men who developed TTS lived alone more often than women. The only difference with regard to risk factors and comorbidities was observed in smoking habits: men smoked more frequently than women. The NT-proBNP levels, both peak and measured on admission, were higher in women. The isolated ST-segment depression was detected more often in men. Moreover, men had lower LVEF at discharge.
Despite these differences, in-hospital outcomes (atrial fibrillation, ventricular tachycardia, ventricular fibrillation, cardiogenic shock) and mortality rate were similar in both groups.
Monika Budnik, PhD, 1st Chair and Department of Cardiology, Medical University of Warsaw, ul. Banacha 1a, 02-097 Warszawa, Poland, phone: +48225992958, email: moni.budnik@gmail.com
September 1, 2019.
September 6, 2019.
September 13, 2019.
MB, MF, MJ, MG, and GO conceived the concept and design of the study. MB, RN, JKo, and RP were responsible for the acquisition of data. MB, EN, MP, and JKu performed the analysis and interpretation of data. MB, RN, MF, JKu, and GO drafted the article. MB, EN, JKo, RP, MP, MJ, and MG revised it critically for important intellectual content. All authors approved the final version of the article.
None declared.
Budnik M, Nowak R, Fijałkowski M, et al. Sex-dependent differences in clinical characteristics and in-hospital outcomes in patients with takotsubo syndrome. Pol Arch Intern Med. 2020; 130: 25-30. doi:10.20452/pamw.14970
- 1.
- Watanabe M, Izumo M, Akashi YJ. Novel understanding of Takotsubo syndrome. Int Heart J. 2018; 59: 250-255.Crossref
- 2.
- Ghadri JR, Wittstein IS, Prasad A, et al. International expert consensus document on Takotsubo syndrome (part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J. 2018; 39: 2032-2046.Crossref
- 3.
- Deshmukh A, Kumar G, Pant S, et al. Prevalence of Takotsubo cardiomyopathy in the United States. Am Heart J. 2012; 164: 66-71.Crossref
- 4.
- Budnik M, Kochanowski J, Piatkowski R, et al. Simple markers can distinguish Takotsubo cardiomyopathy from ST segment elevation myocardial infarction. Int J Cardiol. 2016; 219: 417-420.Crossref
- 5.
- Aizawa K, Suzuki T. Takotsubo cardiomyopathy: Japanese perspective. Heart Fail Clin. 2013; 9: 243-247.Crossref
- 6.
- Schneider B, Athanasiadis A, Stollberger C, et al. Gender differences in the manifestation of takotsubo cardiomyopathy. Int J Cardiol. 2013; 166: 584-588.Crossref
- 7.
- Zalewska-Adamiec M, Małyszko J, Bachórzewska-Gajewska H, et al. Takotsubo syndrome and chronic kidney disease: a deadly duet in long-term follow-up. Pol Arch Intern Med. 2018; 128: 518-523.Crossref
- 8.
- Templin C, Napp LC, Ghadri JR. Takotsubo syndrome: underdiagnosed, underestimated, but understood? J Am Coll Cardiol. 2016; 67: 1937-1940.Crossref
- 9.
- Owada M, Aizawa Y, Kurihara K, et al. Risk factors and triggers of sudden death in the working generation: an autopsy proven case-control study. Tohoku J Exp Med. 1999; 189: 245-258.Crossref
- 10.
- Templin C, Ghadri JR, Diekmann J, et al. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med. 2015; 373: 929-938.
- 11.
- Kurisu S, Inoue I, Kawagoe T, et al. Presentation of Tako-tsubo cardiomyopathy in men and women. Clin Cardiol. 2010; 33: 42-45.Crossref
- 12.
- Sharkey SW, Windenburg DC, Lesser JR, et al. Natural history and expansive clinical profile of stress (tako-tsubo) cardiomyopathy. J Am Coll Cardiol. 2010; 55: 333-341.Crossref
- 13.
- Krishnamoorthy P, Garg J, Sharma A, et al. Gender differences and predictors of mortality in takotsubo cardiomyopathy: analysis from the National Inpatient Sample 2009-2010 Database. Cardiology. 2015; 132: 131-136.Crossref
- 14.
- Frangieh AH, Obeid S, Ghadri JR, et al. ECG criteria to differentiate between Takotsubo (Stress) cardiomyopathy and myocardial infarction. J Am Heart Assoc. 2016; 5: e003418.Crossref
- 15.
- Samuelov-Kinori L, Kinori M, Kogan Y, et al. Takotsubo cardiomyopathy and QT interval prolongation: who are the patients at risk for torsades de pointes? J Electrocardiol. 2009; 42: 353-357.Crossref
- 16.
- Singh K, Carson K, Usmani Z, et al. Systematic review and meta-analysis of incidence and correlates of recurrence of Takotsubo cardiomyopathy. Int J Cardiol. 2014; 174: 696-701.Crossref
- 17.
- Ghadri JR, Wittstein IS, Prasad A, et al. International expert consensus document on takotsubo syndrome (part II): diagnostic workup, outcome, and management. Eur Heart J. 2018; 39: 2047-2062.Crossref
- 18.
- Nef HM, Möllmann H, Kostin S, et al. Tako-tsubo cardiomyopathy: intraindividual structural analysis in the acute phase and after functional recovery. Eur Heart J. 2007; 28: 2456-2464.Crossref
- 19.
- Kuo BT, Choubey R, Novaro GM. Reduced estrogen in menopause may predispose women to takotsubo cardiomyopathy. Gend Med. 2010; 7: 71-77.Crossref
- 20.
- Murakami T, Yoshikawa T, Maekawa Y, et al. Gender differences in patients with Takotsubo cardiomyopathy: multi-center registry from Tokyo CCU Network. PLoS One. 2015; 10: e0136655.Crossref
- 21.
- Komesaroff PA, Esler MD, Sudhir K. Estrogen supplementation attenuates glucocorticoid and catecholamine responses to mental stress in perimenopausal women. J Clin Endocrinol Metab. 1999; 84: 606-610.Crossref
- 22.
- Sung BH, Ching M, Izzo JL, et al. Estrogen improves abnormal norepinephrine-induced vasoconstriction in postmenopausal women. J Hypertens. 1999; 17: 523-528.Crossref
- 23.
- Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I. Estradiol in elderly men. Aging Male. 2002; 5: 98-102.Crossref
- 24.
- Ueyama T, Hano T, Kasamatsu K, et al. Estrogen attenuates the emotional stress-induced cardiac responses in the animal model of Takotsubo (ampulla) cardiomyopathy. J Cardiovasc Pharmacol. 2003; 42 (suppl 1): S117-S119.Crossref
- 25.
- Ueyama T, Kasamatsu K, Hano T, et al. Catecholamines and estrogen are involved in the pathogenesis of emotional stress-induced acute heart attack. Ann N Y Acad Sci. 2008; 1148: 479-485.Crossref
- 26.
- Kuo BT, Choubey R, Novaro GM. Reduced estrogen in menopause may predispose women to Takotsubo cardiomyopathy. Gend Med. 2010; 7: 71-77.Crossref