ReviewTakotsubo cardiomyopathy, a new concept of cardiomyopathy: Clinical features and pathophysiology
Section snippets
Diagnostic criteria
The diagnostic criteria are advocated by both Mayo Clinic [1] and the Japanese Circulation Society [2] (Table 1). Characteristics associated with pheochromocytoma are excluded in both criteria but cerebrovascular disease is differently considered. It is excluded from the diagnostic criteria of the Japanese Circulation Society but is not listed as an exclusion criterion of Mayo Clinic. Both diagnostic criteria require the absence of significant lesion on coronary angiograms. As mentioned above,
Epidemiology
Most of takotsubo cardiomyopathy cases have been conventionally reported from Japan. Therefore, this disease was once estimated to be peculiar to Japan. Reports from outside of Japan have been rapidly increased since 2000 and clinical studies of many cases have appeared on wide variety of medical journals (Table 2). This disease presents pathology mimicking acute coronary syndrome and therefore the differential diagnosis of such pathology is confusable. It was reported that the occurrence of
Laboratory tests
The concentration level of plasma brain natriuretic peptide (BNP) increases in acute phase. This change is considered to reflect the ventricular wall stretch. Whereas, changes in cardiac biomarkers, such as creatinine phosphokinase and troponin T, are relatively slight than the expectation compared to the level of wall motion abnormalities. Elevation in the concentration level of the plasma catecholamine has been also reported. The elevation is more remarkable as demonstrated in patients with
Electrocardiogram
ST-segment elevation and subsequent T-wave inversion are almost always observed in precordial lead in acute phase. In some cases, these are associated with QT interval prolongation. A transient appearance of Q waves can be sometimes noted. Afterwards, inverted T wave flattens once and becomes prominent again. These phenomena are closely similar to those of acute anteroseptal myocardial infarction. As the differential diagnosis points, the absence of ST-segment elevation in V1 and the presence
Ultrasonic echocardiography
In an early stage of the onset, echocardiography is needed to assess systolic dynamics and check for the presence of mitral valve insufficiency. Complication of left ventricular outflow tract stenosis is presented in 18 to 25% of patients with this disease. Anterior motion of mitral valve resulting from tethering by apical akinesis, as well as hyperdynamic basal contraction, is involved in this phenomenon. In some cases, sigmoid septum is considered to be involved in such pathology. Especially,
Magnetic resonance and radionuclide imaging
Magnetic resonance imaging technique is helpful to assess not only a cardiac function with takotsubo cardiomyopathy but also myocardial tissue characteristics. Myocardial edema in the regions corresponding to the regions presenting systolic dysfunction is frequently detected on a T2-weighted image of this disease in acute phase. Positive delayed enhancement is detected in a few cases. However, it is still not revealed how these findings are associated with the subsequent clinical outcomes [10].
Cardiac catheterization
One of the criteria of the diagnosis of this disease is the absence of identifiable lesion explaining wall motion abnormalities on the coronary angiographic image. The findings of plaque rupture or others suggesting acute coronary syndrome should be excluded. In some cases, coronary arterial spasm is observed in provocation tests. In such cases, the regions of the induced coronary vasospasms do not match the regions of wall motion abnormalities. Because of delayed filling of the contrast media
Myocardial histopathological findings
Histopathological findings similar to catecholamine-induced cardiomyopathy are predicted, in terms of excessive catecholamine secretion supposed as one of the key factors in the onset of takotsubo cardiomyopathy. Myocardial biopsy findings have not been studied in detail so far. Nef et al. have reported detailed studies using pathological specimens obtained from myocardial biopsy of patients with takotsubo cardiomyopathy. In the immunohistochemical staining, decrease in α-actinin in the central
Complications
Pump failure is a relatively common complication. In other cases, this disease is complicated by diverse arrhythmias such as atrial fibrillation and flutter, atrioventricular block, and the ventricular tachycardia and fibrillation. This disease is complicated by mural thrombus through hyperactivation of platelet function and coagulability probably caused by sympathetic activation, as well as through blood stagnation caused by apical contractile abnormality. This often results in complication of
Medical management
It may be possible to diagnose this disease in acute phase to some extent by subjective symptoms, electrocardiogram, and echocardiography. This disease can be successfully diagnosed with the presence of normal coronary arteries detected by urgent cardiac catheterization as well as the presence of characteristic left ventricular angiographic findings. Most of cases having a good prognosis without complications can be managed with follow-up alone. However, for patients complicated with shock or
Prognosis
Most of the reports on takotsubo cardiomyopathy have been focused on case examples; results of follow-up of many cases were conventionally hardly reported. Among them, analyses on the epidemiological data of many cases from the inpatient database of the United States were presented. In the analytical results on 6837 cases extracted from the database of 2008, in which age, gender, and patient's underlying factors were analyzed, the incidence of this disease was 8.8 times higher in women than in
Molecular mechanisms of takotsubo cardiomyopathy
Factors of pathogenic mechanism underlying this disease are still uncertain but sympathetic hyperexcitation, coronary vasospasm, microcirculatory disorder, and lack of estrogen have been regarded as the most likely factors since earlier studies (Fig. 2).
Conclusion
Pathological concept of takotsubo cardiomyopathy has been almost established, but a number of questions still remain, such as establishment of acute phase treatment, risk assessment, prophylactic measures against recurrence, and long-term prognosis. Many questions still also remain regarding the pathogenic mechanisms underlying takotsubo cardiomyopathy. Further research in all aspects and approaches are expected by accumulating large amount of database.
Conflict of interest
None.
Author contribution
Tsutomu Yoshikawa collects all the information and final disposition of the manuscript.
Funding source
None.
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