Rethinking Tako-tsubo Cardiomyopathy: The Contribution of Myocardial Pathology and Molecular Imaging.

BACKGROUND: Despite substantial research, the mechanisms behind stress Tako-tsubo cardiomyopathy (TTC) remain rather elusive. OBJECTIVE: The purpose of this paper was to provide a detailed review of the mainstream factors underlying the pathophysiology of TTC, highlighting the novel contributions of molecular pathology and in-vivo molecular imaging. METHODS: A careful literature review selected all papers discussing TTC, specifically those providing novel insights from myocardial pathology and cardiac molecular imaging. RESULTS: Results concerning myocardial pathology, defect extension, sites and relationships between functional parameters underline the existence of a causal relationship between a determinant (e.g., the release of catecholamines induced by stress) and an outcome for TTC, which is not limited to a reversible contractile cardiomyopathy, but it includes reversible changes in myocardial perfusion and a long-lasting residual deficit in sympathetic function. Besides, they reinforce the hypothesis that sympathetic nerves may exert a complex control on cardiac contractile function, which is likely to be direct or indirect through metabolism and microvascular perfusion changes during anaerobic and aerobic conditions. CONCLUSION: TTC is characterized by acute transient left ventricular systolic dysfunction, which can be challenging to distinguish from myocardial infarction at presentation. Catecholamineinduced myocardial injury is the most established theory, but other factors, including myocardial metabolism and perfusion, should be considered of utmost importance. Each effort to clarify the numerous pathways and emerging abnormalities may provide novel approaches to treat the acute episode, avoid recurrences, and prevent major adverse cardiovascular events.

The natural history of takotsubo syndrome: a two-year follow-up study with myocardial sympathetic and perfusion G-SPECT imaging.

PURPOSE: To investigate changes in sympathetic activity, perfusion, and left ventricular (LV) functionality in takotsubo cardiomyopathy (TTC) patients from onset (T0) to post-onset conditions at 1 month (T1), 1-2 years (T2, T3). METHODS: Twenty-two patients (70 ± 11 years) underwent serial gated single photon emission tomography (G-SPECT) studies with 123I-mIBG and 99mTc-Sestamibi. Statistics were performed using ANOVA/Sheffé post-hoc, correlation test, and receiver operating characteristic (ROC) curve analysis (p < 0.05). RESULTS: Patients presented at T0 with LV ballooning and reduced early-late mIBG uptake (95%, 100%), left ventricular ejection fraction (LVEF)G-SPECT (86%) and perfusion (77 %). Adrenergic dysfunction was greater in apex, it overlaps with contractile impairment, and both were more severe than perfusion defect. During follow-up, LVEFG-SPECT, contractility, and perfusion were normal, while 82% and 90% of patients at T1 and 50% at T2 and T3 continued to show a reduced apical early-late mIBG distribution. These patients presented at T0-T1 with greater impairment of adrenergic function, contractility, and perfusion. A relationship was present within innervation and both perfusion and contractile parameters at T0 and T1, and between the extent of adrenergic defect at T3 and both the defect extent and age at T0 (cut-off point 42.5%, 72 years). CONCLUSION: Outcome for TTC is not limited to a reversible contractile and perfusion abnormalities, but it includes residual adrenergic dysfunction, depending on the level of adrenergic impairment and age of patients at onset. The number of patients, as well as degree of perfusion abnormalities were found to be higher than those previously reported possibly depending on the time-interval between hospital admission and perfusion scan.

[Epidemiology of Tako-tsubo cardiomyopathy: the Tuscany Registry for Tako-tsubo Cardiomyopathy ]. / Epidemiologia della sindrome di tako-tsubo nel mondo reale: dati del Registro Toscano della Miocardiopatia da stress tipo Tako-tsubo.

BACKGROUND: Tako-tsubo (stress) cardiomyopathy (TTC) is a recently described acute cardiac syndrome that mimics ST-segment elevation myocardial infarction. The TTC Tuscany Registry is an observational prospective multicenter registry established to define the prevalence, epidemiology and prognosis of TTC in the Tuscany area. METHODS: From January 1 to December 31, 2009, 105 consecutive patients hospitalized in the 14 Cardiology Units of the Tuscany Region with a diagnosis of TTC, were enrolled in the registry. TTC diagnosis was made using the Mayo Clinic modified criteria. Clinical, instrumental, laboratory and 6-month follow-up data were collected. Results. TTC represented 1.2% of all myocardial infarctions in the Tuscany Region during 2009, and it was diagnosed in 0.6% of the angiographic exams performed during the same year. The data collected showed that TTC affects mainly the female gender (91%) in the post-menopausal period (70 ± 11 years), though 5% of patients were ≤50 years old. An antecedent stressful event was frequently detected (74%). The main clinical presentation was chest pain (86%), associated with ST-segment elevation (59%). Mean left ventricular ejection fraction on admission was 40 ± 9%, and was associated with apical (37%), midapical (49%) or midventricular (5%) wall motion abnormalities. Left ventricular ejection fraction recovered to 51 ± 9% in 7 ± 9 days. Heart failure was the most common complication in the acute phase (14%), and 4 patients presented with cardiogenic shock. No patient died during the index hospitalization. At 6-month follow-up, no patient had TTC recurrence, 9 patients were rehospitalized (7 for noncardiac disease) and 2 patients died of noncardiac causes. CONCLUSIONS: Our data, which represent the largest prospective series of patients with a diagnosis of TTC, show that the prevalence of TTC in Tuscany is similar that described in other national and international studies. Moreover, the data highlight that TTC may occur also in male patients and in patients aged <50 years. The mid-term prognosis is good, but the risk of acute complications related to heart failure cannot be neglected.