BACKGROUND: Differentiating Takotsubo cardiomyopathy (TTC) from acute coronary syndrome involving the left anterior descending coronary artery (LAD-ACS) is difficult due to left ventricular apical wall motion abnormality pattern in both and typically requires an invasive coronary angiography (ICA) study for diagnostic confirmation.
OBJECTIVE: To identify differences in the regional wall motion abnormality (RWMA) pattern using a comprehensive comparative analysis of the transthoracic echocardiographic (TTE) findings in patients with TTC versus LAD-ACS.
METHODS: This was a retrospective, randomized, blinded comparison study including a derivation cohort of 105 patients with TTC (N=52) or LAD-ACS (N=53) with concomitant TTE and ICA identified from our institutional database. A comprehensive echocardiographic wall motion analysis was performed (unblinded) to search for subtle differences in RWMA patterns by marking the exact locations of the end-systolic hinge points (HP) - defined as the intersection between the normal and abnormal regional myocardial thickening - in all apical views. The HP location relative to mitral annulus in each apical view was compared for symmetry and the apical 2-chamber (A2C) view was identified as having the most consistent, quantitative difference between TTC and LAD-ACS. This A2C quantitative model was then prospectively studied in a randomized, blinded, validation cohort of 30 subjects with either TTC or LAD-ACS by eight echocardiographic readers with all levels of clinical experience.
RESULTS: In the unblinded derivation cohort, the A2C view showed that the ratio (1.02) and the absolute distance between the anterior HP (3.57 cm) and the inferior HP (3.53 cm) in TTC was significantly different than the ratio (0.761) and the absolute differences between the AHP (4.5 cm) and the IHP (5.93 cm) in LAD-ACS. An AHP: IHP of 0.96 for men and 0.84 for women was able to correctly categorize 84.8% of male and 91.7% of female patients. When applied to the validation cohort, the model showed fairly accurate results with a 74% prediction rate in diagnosing TTC in female patients.
CONCLUSIONS: We propose a relatively simple 2-D TTE diagnostic tool emphasizing subtle differences in the RWMA pattern in the A2C view alone as a semi-quantitative imaging parameter to help differentiate TTC from LAD-ACS.

UNASSIGNED: Takotsubo syndrome (TTS) is an acute form of transient systolic heart failure that occurs predominantly among women and in association with emotional or physical stressors. The Smidt Heart Institute Takotsubo Registry aims to establish a database through an online patient-advocate registry for deep phenotyping of this syndrome.
UNASSIGNED: The Takotsubo Registry is a retrospective and prospective observational registry of individuals with a prior history of TTS. Participants are sourced through physician referrals, medical records review, peer- and self-referrals using social media. Research Electronic Data Capture (REDCap) and Mitra® microsamplers are used to collect questionnaire data and blood samples to facilitate completely remote study enrollment and participation for most participants.
UNASSIGNED: From January 2019 to May 2021, 125 participants (99% female, mean age: 61.5 ± 9.9 years) enrolled in the registry across 25 US states and 3 international countries, with reported first TTS event a median of 2 years prior to enrollment. Psychosocial characteristics determined by standardized questionnaires at baseline include relatively high anxiety trait (44%), moderate to severe depression severity (19%), moderate to high severity of posttraumatic stress disorder symptoms (58%) and a history of childhood trauma/abuse (50%).
UNASSIGNED: The Smidt Heart Institute Takotsubo Registry will contribute to advancing the management of TTS by deep phenotyping to understand its pathophysiology, and identify treatment targets in a participant base for future clinical trials.

Takotsubo cardiomyopathy (TC) is a commonly observed complication among patients with intracerebral hemorrhage (ICH); however, the incidence of TC in patients with ICH have not been investigated yet. The goal of this study was to examine the incidence of TC in ICH and identify its risk factors, incidence rate, and outcomes of TC in patients with ICH in a US nationwide scale.
Data for patients with ICH between the years of 2015 and 2018 were extracted from the Nationwide Inpatient Sample and stratified based on the diagnosis of TC.
Our results showed that the incidence rate of TC in ICH discharges was 0.27% (95% confidence interval [CI] 0.24-0.31). The mean age of patients with ICH developing TC was 66.28 years ± 17.11. There were significantly more women in the TC group, with an odds ratio (OR) of 3.65 (95% CI 2.63-5.05). Acute myocardial infarction (OR 7.91, 95% CI 5.80-10.80) was significantly higher in the TC group. The mortality rate of patients with ICH who had TC was significantly higher (33.48%, p < 0.0001). Length of stay (mean days; 15.72 ± 13.56 vs. 9.56 ± 14.10, p < 0.0001) significantly increased in patients with ICH who had TC. Patients with intraventricular ICH (OR 2.46, 95% CI 1.88-3.22) had the highest odds of TC.
Takotsubo cardiomyopathy is associated with a higher mortality, longer hospitalization period, and more acute myocardial infarctions in patients with ICH. It is illustrated that intraventricular ICH is associated with higher odds of TC.

BACKGROUND: Stress cardiomyopathy, or Takotsubo syndrome (TTS), is an acute and reversible syndrome developing in strong association with psychological or physiological stressors. While a surge in the circulating catecholamine level is suspected as one of its pathophysiologies, the contribution of treatment with sympathomimetic drugs to the development of TTS remains uncertain.
METHODS: We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database containing more than 500,000 patient cases recorded between April 2004 and March 2019, to detect TTS (\'stress cardiomyopathy\') as adverse event signals associated with adrenergic agonist drugs usage by calculating reporting odds ratio (ROR).
RESULTS: Among 306 TTS cases reported to JADER, we identified 58 TTS cases with exposure to adrenergic agonist drugs, predominantly of women (52/58, 89.7%) and those in the median age-decades of the 70s. After adjusting for age in decades and sex, most of the intravenous catecholamines showed significantly higher reporting (lower 95% ROR > 1) for TTS, including adrenaline, noradrenaline, dobutamine, dopamine, phenylephrine, and ephedrine. In addition, peroral midodrine, transdermal tulobuterol, inhaled salbutamol, and inhaled procaterol also showed significantly higher ROR for TTS. We also identified a small number of TTS cases with Parkinson\'s disease taking midodrine or droxidopa, but not receiving other adrenergic agonists.
CONCLUSIONS: The current pharmacovigilance study showed significantly higher RORs for TTS following the use of some of the adrenergic drugs, being mostly consistent with the TTS-related adrenergic drugs reported in earlier literature. A potential association of taking midodrine or droxidopa with the development of TTS was also suggested.

The pathophysiology of Takotsubo syndrome (TTS) is incompletely understood. A sympathetic overdrive with coronary microvascular dysfunction might play a central role. The aim of our study was to assess the status of the systemic microcirculation (MC) of patients with TTS, compared to patients with myocardial infarction (MI) and healthy subjects. The systemic microvascular function of 22 TTS patients, 20 patients with MI and 20 healthy subjects was assessed via sublingual sidestream dark-field imaging. In TTS and MI patients, measurements were performed during the acute phase (day 1, 3 and 5) and after 3 months. The measurement in healthy subjects was performed once. The assessed parameters were number of vessel crossings, number of perfused vessel crossings, proportion of perfused vessels, total vessel density and perfused vessel density. The results did not show relevant differences between the investigated groups. Some minor, albeit statistically significant, differences occurred rather randomly. The MC parameters of the TTS group did not show any relevant changes in the temporal course. A systemic microvascular dysfunction could not be identified as a contributing factor in the pathogenesis of TTS. A possible microvascular dysfunction might instead be caused by a local effect restricted to the coronary microvascular bed.

Several reports have described Takotsubo syndrome (TTS) secondary to thyrotoxicosis. A complex interaction of central and peripheral catecholamines with thyroid homeostasis has been suggested. In this study, we analysed sequential thyroid hormone profiles during the acute phase of TTS.
Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at predefined time points in 32 patients presenting with TTS or acute coronary syndrome (ACS, n = 16 in each group) in a 2-year period in two German university hospitals. Data were compared to age- and sex-matched controls (10 samples, each of 16 subjects), and an unsupervised machine learning (ML) algorithm identified patterns in the hormone signature. Subjects with thyroid disease and patients receiving amiodarone were excluded from follow-up.
Among patients with TTS, FT4 concentrations were significantly higher when compared to controls or ACS. Four subjects (25%) suffered from subclinical or overt thyrotoxicosis. Two additional patients developed subclinical or overt thyrotoxicosis during stay in hospital. In four subjects (25%), FT4 concentrations were increased, despite nonsuppressed TSH concentration, representing an elevated set point of thyroid homeostasis. The thyroid hormone profile was normal in only six patients (38%) presenting with TTS.
Abnormal thyroid function is frequent in patients with TTS. Primary hyperthyroidism and an elevated set point of thyroid homeostasis are common in TTS, suggesting a stress-dependent endocrine response or type 2 thyroid allostasis. Thyroid function may be a worthwhile target in treating or preventing TTS.

BACKGROUND: Although rapid recovery of cardiac contraction is a hallmark of Takotsubo cardiomyopathy (TTC), the time course of recovery is still ill-defined. We aimed to investigate the time course of left ventricular (LV) functional recovery using 2D speckle tracking echocardiography and electrocardiography (ECG).
METHODS: Thirty-two consecutive patients (65 ± 16 years, 26 women) with TTC were prospectively recruited. ECG and echocardiography were performed at baseline (No. 1), before discharge (No. 2), and at 1 week (No. 3) and 5 weeks (No. 4) after discharge. Echocardiographic images and ECGs were analyzed to measure ejection fraction (LVEF), global and regional longitudinal strain (GLS, RLS), and T wave inversion (TWI) scores.
RESULTS: At baseline, LVEF, GLS, and TWI score were 39 ± 8.8%, -11 ± 4.3%, and 1.8 ± 3.0, respectively. Both LVEF and GLS continued to improve from baseline at the No. 2, No. 3, and No. 4 timepoints (49 ± 9.3%, 56 ± 7.5%, 58 ± 6.8%, respectively, for LVEF and -15 ± 4.2%, -17 ± 3.9%, -19 ± 3.4%, respectively, for GLS). TWI score was decreased at the No. 3 ECG relative to baseline and then increased (No. 2: -2.5 ± 3.0, No. 3: -2.9 ± 5.2, No. 4: -0.3 ± 4.4). In the apical subgroup, the reverse base-to-apex gradient of RLS had disappeared by the No. 3 echocardiography.
CONCLUSIONS: Contractile function as assessed by LVEF and GLS recovered continuously in patients with TTC throughout the acute and subacute phases, with rapid recovery in the acute phase. Negative T wave progressed during the acute phase and recovered more slowly during the subacute phase.

Free-living cetaceans are exposed to a wide variety of stressful situations, including live stranding and interaction with human beings (capture myopathy), vessel strikes, and fishing activities (bycatch), which affect their wellbeing and potentially lead to stress cardiomyopathy (SCMP).
Here, the authors aimed to characterise SCMP of stranded cetaceans as an injury resulting from extreme stress responses, based on pathological analyses (histological, histochemical and immunohistochemical). Specifically, the authors examined heart samples from 67 cetaceans found ashore (48 live strandings, seven dead from ship collision and 12 dead from bycatch) on the coast of Spain, more specifically in the Canary Islands from 2000 to 2016 and Andalusia from 2011 to 2014.
The microscopic findings were characterised by vascular changes, acute or subacute cardiac degenerative necrotic lesions, interstitial myoglobin globules, and infiltration of inflammatory cells. Immunohistochemically, cardiac troponin I, cardiac troponin C and myoglobin were depleted, along with fibrinogen being expressed in the degenerated/necrotic cardiomyocytes. A perivascular pattern was also identified and described in the damaged cardiomyocytes.
This study advances current knowledge about the pathologies of cetaceans and their implications on conserving this group of animals by reducing mortality and enhancing their treatment and subsequent rehabilitation to the marine environment.

Sympathetic nervous system hyperactivity and elevated catecholamine levels are known features of chronic kidney disease (CKD). On the other hand, CKD itself is a high risk for Cardiovascular disease (CVD) and in fact most patients with CKD die before reaching dialysis. Furthermore, Many CKD risk factors such as obesity, hypertension, diabetes are also associated with sympathetic hyperactivity. Sympathetic hyperactivity and elevated catecholamine levels also play a key role in the pathogenesis of takotsubo cardiomyopathy (TKCM). Owing to the high sympathetic tone and elevated catecholamine levels in CKD/ESRD patients, an acute stress such as infection/sepsis or surgery makes these patients highly susceptible to TKCM. Multiple isolated case reports of TKCM in CKD/ESRD patients have been reported. We here present the first scoping study of such cases. The purpose of this review is to identify the characteristic features of ESRD/CKD who developed TKCM. Analysis of 30 cases of TKCM in CKD/ESRD primarily happens in women (87% of the cases) with a mean age of 64 ± 13 yrs (Median 63 yrs). Dyspnea (60%) was most presenting complaint, followed by chest pain (37%), fatigue (10%), lower limb edema (3%), seizures (3%) and confusion (3%). The majority of TKCM was noted after exposure to an acute physiological or psychological stressor. Physicians should have a high clinical suspicion for TKCM amongst other differential diagnosis in CKD/ESRD patients who present with chest pain or dyspnea in the setting of acute physiological or psychological stressor.

Takotsubo syndrome (TTS) can be induced by a large variety of physical/emotional triggers; several cases, however, are related to either an overt or occult malignancy, as shown in retrospective studies and case reports. The aim of this study was therefore to evaluate the clinical outcome of patients with TTS and cancer in a meta-analysis study. In June 2018, a Pubmed systematic research was conducted for studies assessing outcome in patients with TTS and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for adverse events at follow-up. After paper retrieval, four studies were included in the meta-analysis, with a total of 123,563 patients. The prevalence of current or previous malignancy among patients admitted with TTS was 6.7% (8258 patients). When compared to control patients, patients with cancer showed an increased risk of clinical events (RR 3.24, 95% CI 3.04-3.45, p < 0.01). The risk of in-hospital events was significantly higher in the cancer group (RR 2.08 95% CI, 1.50-2.87, p < 0.01) and was mainly due to higher need for respiratory support (RR 1.67, 95% CI, 1.58-1.77, p < 0.01). The risk of adverse events at follow-up was also higher in the cancer group (RR 3.30, 95% CI 3.09-3.51, p < 0.01). Cancer, either history or active, is associated with an increased risk of adverse events in TTS.