Initial clinical presentation of Takotsubo cardiomyopathy with-a focus on electrocardiographic changes: A literature review of cases

Abstract

AIM: To review the initial presentation and demonstrate the importance of Takotsubo cardiomyopathy.

METHODS: A PubMed search using the terms “Takotsubo cardiomyopathy (TC)” and “apical ballooning syndrome” yielded 211 publications. Only those that were relevant were fully reviewed. The gender, age, precipitating stressor, main complaint at presentation, electrocardiogram (ECG) at admission and serum cardiac markers of patients diagnosed with TC, were extracted as available. The data were organized in tables and graphics, and the incidence of the disorder was calculated and analyzed.

RESULTS: A total of 250 clinical cases were examined. The predominant gender that was affected was female, with a prevalence of 87.5%. The mean age of presentation was 64 ± 14 years. The cases were divided by age into 10-year intervals. The age interval of 60-69 years showed the highest frequency of TC, accounting for 79 cases. The most common precipitating stressor was physical (50% of cases). Chest pain was the primary complaint at presentation (58.8% of cases) followed by dyspnea (30% of cases). The ST segment changes category was the most common (60%), followed by T wave changes (39.6%). Of the 60% of cases with ST segment changes, 12% had concomitant T wave changes. This means that for 27.6% of the cases, the primary abnormality in the ECG was T wave changes; 87.6% of cases with TC had a change in the ST segment, in the T wave or in both. The percentage of ECGs presenting with changes in the anterior wall was 54.4% (35.6% of ST segment elevation + 1.6% of ST segment depression + 17.2% of T wave inversion). The percentage of patients presenting with changes in the lateral segment of the heart was 46.8%, while the percentage of patients with changes in the inferior heart was 21.6% and the percentage of patients with changes in the apical region was only 16%. The prevalence of elevated creatinine kinase and/or troponin on initial presentation was 89.3%.

CONCLUSION: It is essential that every physician consider Takotsubo cardiomyopathy as a possible differential diagnosis when a patient is classified with acute coronary syndrome. To do so, it is necessary to know the clinical presentation of this syndrome in its early stages.

Key Words: Apical ballooning syndrome, Broken heart syndrome, Stress cardiomyopathy, Takotsubo cardiomyopathy, Takotsubo syndrome

Core tip: Takotsubo cardiomyopathy is a syndrome that, while frequently not recognized, has a significant impact and represents a significant percentage of diagnosed acute coronary syndromes. The importance of its recognition by physicians should be stressed. There are no previously published articles that analyze a significant number of reported cases of Takotsubo cardiomyopathy, nor are prior literature reviews available that examine all the points discussed by this author relative to the initial stages of the disease.

INTRODUCTION

Takotsubo cardiomyopathy (TC), apical ballooning syndrome and stress cardiomyopathy have all been used to refer to a syndrome that was described for the first time in 1991 in Japan. Five such cases were shown to have left ventriculograms with transient akinesis in the apical diaphragmatic and/or anterolateral wall but hyperkinesis in the basal wall of the heart[1].

Many hypotheses have been proposed to explain the pathophysiology of TC, including multivessel coronary vasospasm, abnormalities of coronary microvascular function, and catecholamine-mediated cardiotoxicity[2]. Some authors consider estrogen an important factor because it changes the β1:β2 adrenoreceptor (AR) ratio in favor of the β2 AR-Gi protein, which protects the myocardium from catecholamines in stressful situations[3].

The typical initial presentation pattern as chest pain and/or dyspnea, the electrocardiographic changes and elevated serum cardiac markers observed in TC patients often result in the misdiagnosis of TC as acute coronary syndrome (ACS). For the diagnosis of TC, it is necessary to perform echocardiography to observe the wall motion abnormality and coronary angiography to confirm the absence of significant stenotic lesions[2-4]. For some authors, cardiac magnetic resonance imaging (CMRI) (Figure 1) is very important due to its unique ability to assist diagnosis with noninvasive techniques; certainly, CMRI is very helpful in the differential diagnosis of TC and myocarditis, and with patient follow-up[5].

Figure 1 Graphic showing total cases grouped by age intervals.

Many authors mention that the electrocardiographic changes that are seen in the presentation of TC are similar to those of ACS, particularly ST segment elevation myocardial infarction (STEMI); the similarities may include ST segment changes, T wave changes and QT interval changes[6].

This article analyzes the initial clinical presentation of a large number of cases of TC that have been described in the literature and assesses various parameters with a focus on electrocardiographic changes.

MATERIALS AND METHODS

The reviewed articles were found on PubMed using the search terms “Takotsubo cardiomyopathy” and “apical ballooning syndrome”. Three filters, namely “case reports”, “free text available” and “humans”, were used. After setting those filters, 211 articles were found. Of these, only those relevant to TC, which accounted for 197 articles, were fully reviewed. Of these, eight were eliminated because they did not include electrocardiograms or because the final diagnosis was not TC. Therefore, the study was conducted using 189 articles in total.

The criteria used to define TC, were those used by each author in each clinical case. One case of right ventricular Takotsubo[7] and several cases of reverse Takotsubo, broken-heart syndrome and stress cardiomyopathy were also included.

The following data were extracted upon availability: gender, age, precipitating stressor, main complaint at presentation, electrocardiogram (ECG) at admission and serum cardiac markers.

There was no age restriction for inclusion of cases in the study. Cases were classified by age using intervals of 10 years for better management of information. Two patients, a 16-year-old and a 90-year-old, fell outside the first interval of 20-29 years and the last interval of 80-89 years. The median and mean age of the patients and the standard deviations of these values were calculated.

The precipitating stressors were grouped into four categories: physical (physical effort, organic disease or medical condition); emotional (psychological, anxiety or family situation); undetermined (unclear whether the precipitating stressor was emotional, physical or both); no stressor (no identifiable stressor in the history); and not available (not available in the review article). The prevalence of each precipitating stressor was then calculated.

Due to the variable nomenclature assigned by the authors to the main complaint at presentation, it was decided that this nomenclature should be merged into single terms that described all patients who showed similar symptoms. The term “chest pain” was used to include chest discomfort, chest tightness and retrosternal discomfort. “Dyspnea” was used to include respiratory distress, shortness of breath, orthopnea and pulmonary congestion. “Hypotension” included hemodynamic instability, right heart failure and cardiogenic shock. “Loss of consciousness” included ventricular fibrillation and cardiopulmonary arrest, and “palpitations” included tachycardia. After all signs and symptoms were classified, they were listed and their prevalence was calculated based on the total number of cases.

The presence of a minimum of one ECG description was set when choosing the articles. The first ECG was extracted and was preferred for every case. If the time at which the test was taken was not specified, the test made available in the article was assumed to be the first and only test performed and was used in this study. If multiple tests were performed during the initial case presentation, the test that was performed first was extracted. All electrocardiographic descriptions of each case were obtained. The ECG data were grouped into the following categories: ST segment changes, T wave changes, Q wave changes, QT prolonged, normal category and others. If the ECG showed documented long-standing changes such as LBBB (left bundle branch block) or AV block, the cases were not considered in this study. The incidence of each of these categories in the ECG data was calculated (Table 1).

Table 1 Electrocardiographic findings organized by frequency in presentation.

Electrocardiogram description	Cases (n)	Incidence (%)
ST segment changes	150	60.00
T wave changes	99	39.60
Prolonged QT	26	10.40
Normal	16	6.40
Q wave	11	4.40
AV block	7	2.80
LBBB	6	2.40
RBBB	6	2.40
AF	5	2.00
VT	3	1.20
VF	3	1.20
Ventricular bigeminy	2	0.80
Other1	1	0.40

¹Other: U wave, Osborn wave, Torsade de Pointes, ventricular atrial retrograde conduction, ventricular pace rhythm, premature ventricular contractions, ventricular ectopic beats, multifocal ventricular contractions, ventricular asystole and escape junctional rhythm. AV block: First, second and third degree atria-ventricular block; LBBB: Left bundle branch block; RBBB: Right bundle branch block; AF: Atrial fibrillation; VT: Ventricular tachycardia; VF: Ventricular fibrillation.

The ST segment category was also divided into four groups based on the following specific changes: ST segment elevation, ST segment depression, flattened ST segment and non-specific ST segment changes (Table 2). The incidence of each based on the ST segment changes category and on the total population was calculated.

Table 2 ST segment, T wave change categories organized by incidence.

	Cases (n)	Categoryincidence1 (%)	Global inci-dence2 (%)
ST segment changes
ST segment elevation	135	90.00	54.00
ST segment depression	113 (214)	7.30	4.40
ST segment non-specific changes	3	2.00	1.20
ST segment flattened	1	0.70	0.40
T wave changes
T wave inversion	91	91.90	36.40
Hyperacute T wave	4	4.00	1.60
Flattened T wave	2	2.00	0.80
Non-specific T wave changes	2	2.00	0.80

¹Percentage calculated based on total ST segment changes cases (150); percentage calculated based on total cases with T wave changes (99);

²Percentage calculated based on total cases in the study (250); percentage calculated based on total cases in the study (250);

³Total number of cases presenting with ST segment depression alone (without concomitant ST segment elevation);

⁴Total number of cases presenting with ST segment depression.

The analysis of the T wave changes was also divided into four groups: T wave inversion, hyperacute T wave, flattened T wave and non-specific T wave changes (Table 2), and the incidence of each based on both the T wave category and the total cases was calculated.

The ECG findings were classified by anatomical region of the heart into inferior, lateral, septal, anterior and non-specific, based on the altered leads[8]. The incidence of abnormalities in each region was calculated and further analyzed (Table 3).

Table 3 Incidence of electrocardiographic change categories shown by anatomical region.

Category and Localization	Cases (n)	Category inci-dence1 (%)	Global inci-dence2 (%)
ST segment elevation
Anterior	89	65.90	35.60
Lateral	66	48.90	26.40
Inferior	26	19.30	10.40
Septal (apical)	24	17.80	9.60
Not specified	22	16.30	8.80
ST segment depression3
Anterior	4	36.40	1.60
Lateral	6	54.50	2.40
Inferior	5	45.50	2.00
Septal (apical)	0	0.00	0.00
Not specified	2	18.20	0.80
T wave changes4
Anterior	43 (25)	43.40	17.20
Lateral	45 (15)	45.50	18.00
Inferior	23	23.20	9.20
Septal (apical)	16	16.20	6.40
Not specified	15	15.20	6.00

¹Percentage calculated based on the total number of cases in each category;

²Percentage calculated based on the total number of cases in the study (250);

³Only cases with ST segment depression as the main finding;

⁴Only cases with T wave changes as the main finding, does not include T wave changes accompanying ST segment elevation or ST segment depression;

⁵Only 3 cases that were not T wave inversions.

The serum cardiac markers creatinine kinase (CK-MB) and/or troponin were classified as normal or elevated; the latter category included mild, moderate and severe elevation. The results extracted were the first test during the admission or the first test result after suspecting a case. The prevalence of each marker elevation was calculated.

RESULTS

One hundred and eighty-nine case report articles, each of which included one or more individual clinical cases, were analyzed; in total, 250 clinical cases were examined (Table 4).

Table 4 Total number of cases analyzed tables.

No.	Age (yr)	Ref.	No.	Age (yr)	Ref.	No.	Age (yr)	Ref.
1	30	Muller et al[8]	85	69	Haghi et al[70]	169	68	Lisi et al[140]
2	67	Yaoita et al[9]	86	69	Haghi et al[70]	170	71	Rotondi et al[141]
3	73	Izumi et al[10]	87	43	Haghi et al[70]	171	82	Kawano et al[142]
4	62	Kobayashi et al[11]	88	69	Haghi et al[70]	172	79	Hutchings et al[143]
5	65	Ker et al[12]	89	52	Di Valentino et al[71]	173	55	Hutchings et al[143]
6	78	Lau et al[13]	90	68	Stähli et al[72]	174	82	Zuhdi et al[144]
7	62	Hayashi et al[14]	91	65	Vivo et al[73]	175	45	Stout et al[145]
8	65	Peraira Moral et al[15]	92	81	Sacha et al[74]	176	76	Daly et al[146]
9	81	Wedekind et al[16]	93	53	Fiol et al[75]	177	78	Daly et al[146]
10	81	Davin et al[17]	94	61	Oberson et al[76]	178	65	Saito et al[147]
11	79	Teo[18]	95	29	Magno et al[77]	179	75	Silberbauer et al[148]
12	51	Arroyo et al[19]	96	82	Kim et al[78]	180	47	Biteker et al[149]
13	79	Consales et al[20]	97	71	Kume et al[79]	181	74	Merli et al[150]
14	64	Maruyama et al[21]	98	78	Kume et al[79]	182	72	Merli et al[150]
15	80	Nguyen et al[22]	99	77	Kume et al[79]	183	71	Merli et al[150]
16	84	Nishikawa et al[23]	100	74	Kume et al[79]	184	75	Merli et al[150]
17	53	Sakihara et al[24]	101	78	Kume et al[79]	185	57	Virani et al[151]
18	66	Ono et al[25]	102	78	Ahn et al[80]	186	64	Virani et al[151]
19	48	Daly et al[26]	103	55	Mahida et al[81]	187	44	Virani et al[151]
20	76	Iengo et al[27]	104	53	Bianchi et al[82]	188	64	Virani et al[151]
21	44	Pison et al[28]	105	61	Hwang et al[83]	189	69	Chia et al[152]
22	52	Pison et al[28]	106	55	Ikeda et al[84]	190	57	Yazdan-Ashoori et al[153]
23	81	Desmet et al[29]	107	75	Ikeda et al[84]	191	78	Shah et al[154]
24	78	Desmet et al[29]	108	64	Suzuki et al[85]	192	24	Volman et al[155]
25	65	Desmet et al[29]	109	88	Teraoka et al[86]	193	68	Salemi et al[156]
26	71	Desmet et al[29]	110	60	Hara et al[87]	194	50	Coutance et al[157]
27	48	Desmet et al[29]	111	89	Kurisu et al[88]	195	66	Parker et al[158]
28	66	Desmet et al[29]	112	77	Kurisu et al[88]	196	81	Oe et al[159]
29	52	Desmet et al[29]	113	73	Verberne et al[89]	197	68	Fazal et al[160]
30	48	Desmet et al[29]	114	60	Subramanyam et al[90]	198	46	Afonso et al[161]
31	45	Desmet et al[29]	115	41	Sanchez-Recalde et al[91]	199	38	Afonso et al[161]
32	66	Desmet et al[29]	116	41	Barriales-Villa et al[92]	200	52	Afonso et al[161]
33	57	Desmet et al[29]	117	60	Fuse et al[93]	201	54	Sacco et al[162]
34	60	Desmet et al[29]	118	80	Kawano et al[94]	202	73	Daly et al[163]
35	69	Desmet et al[29]	119	63	Wong et al[95]	203	55	Jabiri et al[164]
36	41	Manivannan et al[30]	120	54	Kimura et al[96]	204	58	Madaria Marijuan et al[165]
37	60	Prasad et al[31]	121	77	Varela et al[97]	205	50	Traullé et al[166]
38	65	Chandrasegaram et al[32]	122	55	Elkhateeb et al[98]	206	32	D’Amato et al[167]
39	84	Wang et al[33]	123	59	Kaushik et al[99]	207	44	Artukoglu et al[168]
40	73	Wani et al[34]	124	53	Uechi et al[100]	208	85	Shah et al[169]
41	54	Wani et al[34]	125	67	To et al[101]	209	61	Cruvinel et al[170]
42	63	Wani et al[34]	126	72	To et al[101]	210	55	Lateef[171]
43	70	Schmidt et al[35]	127	46	Mehta et al[102]	211	70	Potter et al[172]
44	46	Zaman et al[36]	128	63	Oomura et al[103]	212	73	Agarwal et al[173]
45	73	Meimoun et al[37]	129	27	Volz et al[104]	213	72	Opolski et al[174]
46	22	Sasaki et al[38]	130	79	Miyazaki et al[105]	214	67	Y-Hassan et al[175]
47	86	Surapaneni et al[39]	131	83	Akashi et al[106]	215	87	Kurisu et al[176]
48	24	Park et al[40]	132	81	Wissner et al[107]	216	78	Kurisu et al[176]
49	85	Cherian et al[41]	133	47	Papanikolaou et al[108]	217	70	Gotyo et al[177]
50	41	Lee et al[42]	134	62	Bonnemeier et al[109]	218	79	Singh et al[178]
51	30	Lee et al[42]	135	60	Haghi et al[110]	219	44	Núñez et al[179]
52	89	Korlakunta et al[43]	136	78	Rau et al[111]	220	62	Núñez et al[179]
53	69	Magri et al[44]	137	53	Dahdouh et al[112]	221	52	Núñez et al[179]
54	65	Rahman et al[45]	138	69	Moriya et al [113]	222	69	Núñez et al[179]
55	63	Khallafi et al[46]	139	44	Hasdemir et al[114]	223	69	Núñez et al[179]
56	75	Demirelli et al[47]	140	53	Mariano et al[115]	224	29	Jayaraman et al[180]
57	75	Latib et al[48]	141	36	Sun et al[116]	225	71	Carxvalho et al[181]
58	58	Altman et al[49]	142	75	Dandel et al[117]	226	78	Guttormsen et al[182]
59	65	Bagga et al[50]	143	65	Ionescu et al[118]	227	53	Mrdovic et al[183]
60	61	Buchholz et al[51]	144	16	Maruyama et al[119]	228	84	Auer et al[184]
61	61	Zhou et al[52]	145	70	Sato et al[120]	229	64	Auer et al[184]
62	74	Mittal et al[53]	146	63	Shah et al[121]	230	64	Auer et al[184]
63	47	Kim et al[54]	147	62	Lee et al[122]	231	82	Auer et al[184]
64	60	Doesch et al[55]	148	67	Merchant et al[123]	232	63	Arslan et al[185]
65	66	Lopes et al[56]	149	86	Merchant et al[123]	233	66	Arslan et al[185]
66	64	Lopes et al[56]	150	76	Merchant et al[123]	234	70	Arslan et al[185]
67	76	Lopes et al[56]	151	42	Merchant et al[123]	235	71	Arslan et al[185]
68	58	Lopes et al[56]	152	76	Nault et al[124]	236	76	Barriales Vila et al[186]
69	51	Lopes et al[56]	153	62	Nault et al[124]	237	78	Barriales et al[186]
70	63	Sealove et al[57]	154	71	Novo et al[125]	238	70	Barriales et al[186]
71	82	Inoue et al[58]	155	68	Blázquez et al[126]	239	74	Guardado et al[187]
72	25	Maréchaux et al[59]	156	74	Ramanath et al[127]	240	45	Cho et al[188]
73	77	Arias et al[60]	157	70	Biswas et al[128]	241	68	Gallego Page et al[189]
74	76	Vasconcelos Filho et al[61]	158	61	Preti et al[129]	242	64	Sousa et al[190]
75	61	Margey et al[62]	159	59	Selke et al[130]	243	68	Jakobson et al[191]
76	67	Purvis et al[63]	160	74	Alves et al[131]	244	49	Jakobson et al[191]
77	59	Biłan et al[64]	161	83	Yeh et al[132]	245	74	Otomo et al[192]
78	53	Lentschener et al[65]	162	68	Kurisu et al[133]	246	75	Otomo et al[192]
79	61	Kyuma et al[66]	163	57	Rotondi et al[134]	247	55	Gomes et al[193]
80	76	Kyuma et al[66]	164	84	Guevara et al[135]	248	61	Furushima et al[194]
81	76	Kyuma et al[66]	165	69	Ukita et al[136]	249	84	Sakai et al[195]
82	81	Figueredo et al[67]	166	73	van de Donk et al[137]	250	64	Hakeem et al[196]
83	60	Naganuma et al[68]	167	66	Mawad et al[138]
84	61	Laínez et al[69]	168	90	Xu et al[139]

Gender

The predominant gender was female; it accounted for 219 cases with a prevalence of 87.5%.

Age

The age of the patients ranged from 16-90 years. The mean age at presentation was 64 ± 14 years, with a 95%CI of 64 ± 2 years and a median of 66 years. Figure 1 shows the number of cases grouped by 10-year intervals with respect to age. The age interval with the highest number of cases is 60-69 years; it includes 79 cases.

Precipitating stressor

Figure 2 shows the distribution of precipitating events among all cases. The 6 (2%) cases listed as “undetermined” were difficult to categorize. For example, a patient who had an operation was very stressed and anxious about the surgery results[9]. In the cases where the stressor was not available, the author did not mention whether there was a precipitating factor.

Figure 2 Graphic showing precipitating stressors grouped in categories for all cases studied.

Main complaint at presentation

Table 5 shows the frequency of presentation of all cases grouped with respect to symptoms and signs. Chest pain and dyspnea together were encountered in only 49 (20%) cases.

Table 5 Frequency of the main complaints reported in the cases studie.

Main complaint	Presentation frequency (%)
Chest pain	58.80
Dyspnea	30.00
Hypotension	8.40
Nausea and/or vomiting	8.00
Syncope	6.40
Palpitations	5.20
Asymptomatic	4.80
Loss consciousness	5.20
Headache	3.60
Epigastric pain	2.00
Dizziness	2.00
Weakness	2.00
Cough	1.60
Back pain	1.60
Pedal edema	1.20
Seizure	0.80
Othersa	0.40

Electrocardiogram at admission

Table 1 shows the incidences of various types of electrocardiographic abnormalities in the TC cases. Of the 60% of cases with ST segment changes, 12% had concomitant T wave changes, indicating that the main abnormality in the ECG for 27.6% of cases was T wave changes and that 87.6% of cases with TC had a change in the ST segment, in the T wave or both. Slow R progression was found in 3 cases, and tachycardia was found in 17 cases; one case of an anterior infarct of indeterminate age[10] was classified into the normal category.

Table 2 shows the incidence of specific ST segment changes. The incidence of ST segment depression in the total population (250 cases) and in the ST segment category (150 cases) was 4.4% and 7.3%, respectively. These calculations are based on 11 cases that presented with ST segment depression alone without concomitant ST segment elevation. The total number of cases regarding ST segment depression was 21; thus, 10 cases had concomitant ST segment elevation changes in the ECG. Table 2 shows the incidence of the T wave changes by group.

Table 3 shows the relative frequency at which various anatomical regions were affected in the electrocardiogram. The percentage of ECGs that showed changes in the anterior wall was 54.4% (35.6% of ST segment elevation + 1.6% of ST segment depression + 17.2% of T wave inversion), and the percentage that showed changes in the lateral segment of the heart was 46.8%. The percentage of ECGs showing changes in the inferior heart was 21.6%, while the percentage that showed changes in the apical region was only 16%.

Serum cardiac markers

The prevalence of elevated serum cardiac markers or normal cardiac markers was calculated from the extracted data. The “not available” data cases were not considered in the calculation. The prevalence of elevated CK-MB and/or troponin in patients initially presenting with TC was 89.3%, and the prevalence of negative or normal levels of these cardiac enzymes at presentation was 10.7%.

DISCUSSION

After an exhaustive search of articles describing clinical cases of TC, with emphasis on those that provided the minimum electrocardiographic data, a large number of articles and cases were found. These were analyzed to obtain the data required for this research.

The data obtained in this study indicate a pyramidal trend in age of occurrence of TC. The peak of TC incidence occurs in the 60 s; from this point, there is a gradual decrease in TC incidence as age increases or decreases, with a steeper slope in the direction of the younger population. The high female prevalence of the disease and the age distribution of its occurrence provide support for at least one hypothesis of its pathophysiology, i.e., that lack of estrogen is an important causal factor of this syndrome[11].

A newly diagnosed disease, an upcoming operation, the induction of anesthesia, a new medication, a stress test or a major physical effort are only some of the physical stressors that can cause TC. This research show that a physical stressor is by far the most common stressor reported in TC patients. Emotional stressors are reported in a quarter of all cases and can be as serious as the death of a relative[12]; they may also be less serious, such as watching a soccer team losing[13]. The asymptomatic presentations include patients undergoing anesthesia[14] and/or medical procedures, for example, tracheal intubations[15]. In these cases, the lack of symptoms can occur due to the sedation.

The chief complaint of the TC patients varied, depending on the causative factor, the trigger stressor and the presentation of each case. TC presents as an ACS; in the latter, the most common clinical presentation is chest pain and the second is dyspnea; this suggests that chest pain and dyspnea will be the most common presentation of stress cardiomyopathy[16]. In this study, chest pain was the most common initial symptom of the cases presented, and dyspnea was the second most common symptom. Hypotension and cardiopulmonary arrest were relatively common findings, most likely because of the severity of presentation in those patients. Furthermore, the initial symptoms of TC are often related to the factors causing stress cardiomyopathy. For example, a patient with a seizure[17,18] or a stroke[19] can only present neurological signs and symptoms.

A very important tool used by physicians in emergency departments and hospital settings to evaluate chest pain, ACS and preoperative patients is the electrocardiogram, which is very easy to perform and is associated with very low cost. Although percutaneous coronary intervention and CMRI are also sometimes useful tools, and the initial suspicion of the TC is usually confirm by echocardiography; it is very important for physicians to know how the TC present in terms of electrocardiography because these findings, together with the patient’s clinical characteristics, should orient the physician to consider this syndrome as a differential diagnosis.

Notably, the definitive diagnosis of TC is confirmed by echocardiographic follow-up performed days or weeks after the initial presentation and showing normalization of the wall motion and left ventricular abnormalities. The CMRI has demonstrated value in the evaluation and follow-up of patients with TC; however, the test of choice is the echocardiography due to its low cost and accessibility[20,21](Figure 3).

Figure 3 Cardiac magnetic resonance imaging for Takotsubo cardiomyopathy. A: Diastole: both ventricles are distended and full of blood; B and C: Systole: both ventricles contracting; D: End of systole: the right ventricle shows a normal pattern, while the left ventricle has a ballooning shape.

Changes in the ST segment of the ECG were the most common finding in all cases; these changes are typical of the presentation of ACS and are most likely the reason for the initial management of most TC cases as ACS[22,23]. Changes in the T wave are the second most common finding in the study population. Again, changes in the T wave are very common in acute myocardial ischemia and infarction[23], explaining the frequent initial diagnosis of ACS in patients with TC. Notably, for some authors, T wave changes are the most common findings among TC patients[24]. The QT interval is prolonged in approximately 10% of patients, a substantially high incidence. There is perhaps a relationship between the QT interval measurement and TC; there is a need for more research into this possibility. The ischemic heart can present with increased QT dispersion, but this observation has not yet been proven to have any practical usefulness[25]. For the physician, it is important to know that a small percentage (approximately 6%) of TC cases present with a normal ECG during admission. There were also a few cases of multiple presentations in the study; ventricular tachycardia or ventricular fibrillation, for example, can hide the expected electrocardiographic changes.

Among the ST segment changes, ST segment elevation was the most common finding, accounting for 90% of the ST changes. It is the most common presentation of a STEMI, and in this study it occurred in more than half of all cases. Although it was present in almost 10% of incidences, ST depression was not very prominent finding; in half of the cases in which it occurred, it was accompanied by other major findings such as ST segment elevation. Other ST segment presentations, such as flattened ST segments, were not commonly found in the initial ECG at admission.

T wave changes showed a distribution similar to that of ST segment changes. The incidence of the T wave inversion was very high, approximately 92% of all T wave changes. This pattern is very common in the ischemic heart. In fact, in this study, overall T wave presentation occurred in almost one third of the patients, a very significant number. When this type of electrocardiographic change is present, TC should be considered a probable diagnosis. Other T wave presentations, such as hyperacute T wave, flattened T wave and nonspecific changes, very uncommonly presented as the only finding in the ECG.

The anatomical site most commonly affected by stress cardiomyopathy is the left ventricle, but there have been cases with right ventricular akinesis[7] and even cases in which both ventricles are affected[10]. Electrocardiographic presentations of this syndrome are highly variable. In this study, it was documented that in TC the ECG changes in frequency starting from the anterior region as the most commonly affected, followed by the lateral, the inferior and finally the septal region. The clinician must remember these patterns when making a differential diagnosis and never rule out the possibility of a TC based on the ECG.

During the initial presentation of TC patients, there is a very high prevalence of serum cardiac marker elevation, making this diagnosis consistent with ACS (specifically STEMI and NSTEMI). Some authors have indicated that the distinction between TC and ACS is reflected in the level of cardiac enzyme elevation[26,27]. These finding contain important information that should raise the physician’s clinical suspicions regarding this syndrome.

COMMENTS

Background

Takotsubo syndrome has the same presentation as acute coronary syndrome (ACS) but is usually associated with history of a trigger stressor, which can be emotional or physical. Although a number of ideas have been proposed to explain its pathophysiology, there is evidence that catecholamines and estrogen play an important role. Many physicians do not readily think of Takotsubo cardiomyopathy (TC) when presented with a patient with cardiac chest pain or even with a ST segment elevation myocardial infarction (STEMI), and other physicians are not even aware of the existence of the syndrome. For this reason, it is likely that many patients are misdiagnosed. The presentation similarities of TC with ACS include symptoms, electrocardiogram (ECG) changes and serum cardiac marker levels.

Research frontiers

In some health facilities, the initial management of a STEMI is based on intravenous fibrinolysis, which is performed without confirmation of coronary artery obstruction using percutaneous coronary intervention (PCI). Takotsubo patients can have the same presentation as STEMI patients but normal or clean coronary arteries. This and other evidence makes the PCI management of choice in STEMI patients.

Innovations and breakthroughs

Although this article does not focus on patient prognosis, it is important that future research addresses the relationship between initial presentation/initial electrocardiographic changes and prognosis. Cardiac magnetic resonance imaging is a new tool that may prove useful in both initial diagnosis and noninvasive follow-up of this syndrome.

Applications

The results of the study are important in clinical practice. They can help inform physicians to include TC in the differential diagnosis of patients who present to the emergency department with cardiac chest pain.

Terminology

TC is a condition that has acquired many names over time; these include Takotsubo syndrome, stress cardiomyopathy, apical ballooning syndrome and TC. ACS is a term applied to situations in which the blood supplied to the heart muscle is suddenly blocked; it includes unstable angina, STEMI and non-ST segment elevation myocardial infarction. Troponin and creatinine kinase (CK-MB) are cardiac markers used to classify and assist with the diagnosis of myocardial infarction. CK-MB is an isoenzyme composed of a muscle portion and a brain portion; it is very specific for myocardial muscle.

Peer review

It is necessary for every physician to know the clinical presentation of TC in its early stages. As mentioned above, this entity should be included in the differential diagnosis of “ACS” patients. The present work represents an interesting examination of value for clinical practice and stresses an important issue in the field of cardiology.