An Unusual Case of Takotsubo Cardiomyopathy with Cardiac Arrest: The Importance of Clinical Context in Implanted Cardioverter Defibrillator Candidacy.

Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, is characterized by acute heart failure, reversible left ventricular dysfunction, and other complications such as life-threatening arrhythmias. The management of TTS is challenging due to its unpredictable clinical course and the lack of evidence-based treatment recommendations. In this case report, we present a 71-year-old female who developed TTS with ventricular tachycardia (VT) cardiac arrest following septic shock and an exploratory laparotomy for appendicitis. Despite the presence of VT cardiac arrest and a left ventricular ejection fraction of 30-35%, an implanted cardioverter-defibrillator (ICD) was not indicated due to the rapid and satisfactory recovery of the patient's ventricular function. This case highlights the importance of considering the clinical context and the transient nature of TTS in the decision-making process for ICD candidacy.

Takotsubo cardiomyopathy following pacemaker insertion complicated with polymorphic ventricular tachycardia: a case report.

BACKGROUND: Takotsubo cardiomyopathy is a novel form of rapidly reversible heart failure occurring secondary to a stressor that mimics an acute coronary event. The underlying etiology of the stressor is highly variable and can include medical procedures. Pacemaker insertion is an infrequent cause of Takotsubo cardiomyopathy. CASE PRESENTATION: An 86-year-old Caucasian woman underwent an uncomplicated pacemaker insertion for symptomatic complete heart block in the background of slow atrial fibrillation. A transient episode of polymorphic ventricular tachycardia was noted on day 1 following the procedure; however, her pacemaker was checked and, as she remained stable, she was discharged home. She presented again 5 days later with symptomatic heart failure. Chest X-ray confirmed pulmonary edema. Echocardiography confirmed new onset severe left ventricle dysfunction. Pacemaker checks were normal and lead placement was confirmed. Though her troponin I was elevated, her coronary angiogram was normal. Contrast enhanced echocardiography suggested apical ballooning favoring Takotsubo cardiomyopathy. She was treated for heart failure and made a good recovery. Her follow-up echocardiography a month later showed significant improvement in left ventricle function. CONCLUSIONS: Takotsubo cardiomyopathy is mediated by a neuro-cardiogenic mechanism due to hypothalamic-pituitary-adrenal axis activation. It generally has a good prognosis. Complications though uncommon, can occur and include arrhythmias. Pacemaker insertion as a precipitant stressor is an infrequent cause of Takotsubo cardiomyopathy. As pacemaker insertions are more frequent in the elderly age group, this phenomenon should be recognized as a potential complication.

Predictors of Polymorphic Ventricular Tachycardia and Ventricular Fibrillation in Patients With Takotsubo Syndrome.

Polymorphic ventricular tachycardia (PVT) and ventricular fibrillation (VF) are life-threatening complications of takotsubo syndrome (TTS). Data regarding risk factors for PVT/VF based on the TTS variant are lacking. This study aimed to identify demographic and clinical factors associated with PVT and VF in patients with TTS. Patients meeting the InterTak criteria for TTS between 2010 and 2022 were retrospectively identified. The occurrence of PVT/VF with each risk factor was analyzed using logistic regression. Sensitivity analysis was performed to assess the interaction between risk factors. PVT/VF occurred in 27 of 296 patients with TTS (9.1%). Patients with PVT/VF were younger (52 vs 62 years, p = 0.019) and more frequently used stimulants in the 4 weeks before admission (22.2% vs 8.2%, odds ratio [OR] 3.20, p = 0.023). All PVT/VF occurred within 24 hours of hospitalization. An initial QTc threshold of 490 ms had the highest sensitivity and specificity for the occurrence of PVT/VF (area under the curve = 0.687). Patients with PVT/VF were more likely to have a QTc >490 ms on admission (55.6% vs 18.7%, OR 5.45, p <0.01), apical variant TTS (78% vs 56%, OR 2.69, p = 0.038), and an admission ejection fraction <30% (63% vs 41.5%, OR 2.39, p = 0.032); each factor was independently associated with PVT/VF irrespective of QTc duration on sensitivity analysis. In conclusion, nearly 1 in 10 patients with TTS had PVT/VF. A QTc >490 ms, recent stimulant use, apical variant TTS, and severe left ventricular systolic dysfunction on admission are associated with higher PVT/VF risk, with the first 24 hours being a high-risk period.

A Rare Case of Recurrent Takotsubo Cardiomyopathy Complicated by Thromboemboli.

Takotsubo syndrome (TTS) is a transient ventricular dysfunction with apical ballooning triggered by emotional and/or physical stress. A few risk factors have been observed in patients with recurrent TTS, for example, excessive sympathetic stimuli, medications, stress, and tumors. Clinical features can vary from chest pain to overt hemodynamic instability. Diagnosis requires both electrocardiographic features and invasive imaging such as angiography to rule out other causes of cardiomyopathy prior to diagnosis. In addition, renal infarcts presenting as a complication of TTS are relatively uncommon. In this case report, we discuss the case of a 61-year-old African American woman with a prior history of TTS being managed for abdominal pain who developed a recurrence of the TTS during the hospital course. Prompt diagnosis and management of the condition is crucial to improve outcomes especially in patients with thromboembolic phenomenon or hemodynamic instability. Further large-scale studies are warranted to determine outcomes of patients with recurrent Takotsubo cardiomyopathy with thromboembolic phenomenon.

Takotsubo cardiomyopathy in Guillain-Barré syndrome.

BACKGROUND AND PURPOSE: Takotsubo cardiomyopathy (TCM) is a serious autonomic complication of Guillain-Barré syndrome (GBS). However, the association between TCM and GBS has not been investigated in detail. We investigated the characteristics of GBS patients with TCM (GBS-TCM). METHODS: Clinical features and anti-ganglioside antibody between the GBS-TCM patients and 62 classical GBS patients without TCM as control patients were compared. RESULTS: Eight GBS-TCM patients were identified, in whom TCM was diagnosed at a mean of 6.5 [range 3-42] days after the onset of GBS. The age at onset of GBS was elder in the GBS-TCM patients than in the control GBS patients (76.5 [56-87] vs. 52 [20-88] years, p < 0.01). Notably, cranial nerve deficits, particularly in the lower cranial nerves, were observed in all GBS-TCM patients (100% vs. 41.9%, p < 0.01). Additionally, the GBS-TCM patients showed a higher GBS disability score at nadir (5 [4-5] vs. 4 [1-5], p < 0.01), and lower Medical Research Council sum scores at admission and nadir (37 [30-44] vs. 48 [12-60] at admission, p < 0.05, and 20 [12-44] vs. 40 [0-60] at nadir, p < 0.05, respectively). Mechanical ventilation was more frequently required in the GBS-TCM patients (62.5% vs. 11.3%, p < 0.01). Three GBS-TCM patients were positive for anti-ganglioside antibodies. CONCLUSIONS: TCM occurred at a relatively early phase of GBS. The characteristics of GBS-TCM were the elder, lower cranial nerve involvements, severe limb weakness, and respiratory failure.

Electromechanical Window and Spontaneous Ventricular Tachyarrhythmias in Takotsubo Syndrome.

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat. Of the 84 patients with TTS, 74 (88%) were female and the mean age was 70 ± 11 years. The mean left ventricular ejection fraction was 42 ± 8%. The EMW was negative in 81 patients (96%), and the mean EMW was -69 ± 50 ms. Ventricular tachyarrhythmias occurred in 7 patients (8%). The EMW of patients who experienced ventricular tachyarrhythmias was more negative than patients who did not (-133 ± 23 ms vs -63 ± 48 ms, p = 0.001). In the univariate analysis, EMW and QT were associated with ventricular tachyarrhythmias (univariate odds ratio [OR]EMW 1.03, 95% confidence interval [CI] 1.01 to 1.05, p = 0.003 and univariate ORQTc 1.02, 95% CI 1.01 to 1.03, p = 0.02); however, only EMW remained significant in the multivariate analysis (OREMW 1.03 95% CI 1.03 to 1.05, p = 0.023). EMW was more effective than corrected QT interval in identifying patients who had ventricular tachyarrhythmias (AUCEMW: 0.89, 95% CI 0.82 to 0.97 vs AUCQTc 0.77, 95% CI 0.61 to 0.93, p = 0.02), and a cut-off value of -108 ms was predictive of ventricular tachyarrhythmias with a sensitivity of 86% and a specificity of 79%. In conclusion, EMW is negative in patients with TTS and is associated with increased risk for ventricular tachyarrhythmias. The role of EMW in the risk stratification of patients with TTS warrants further investigation.

Myocardial flow reserve recovery in patients with Takotsubo syndrome: Insights from positron emission tomography.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been implicated in the pathogenesis of Takotsubo syndrome (TTS). Positron emission tomography (PET) plays a key role in the assessment of CMD through myocardial flow reserve (MFR). However, there is limited information on the temporal progression of MFR and its relationship to coronary artery disease (CAD) in TTS patients. METHODS: This study evaluated patients with TTS who underwent cardiac catheterization and PET within one year of hospitalization. Patients were categorized into acute (≤10 days), subacute (11-30 days), and chronic (≥31 days) stages based on post-onset time of PET assessment. MFR values and prevalence of abnormal MFR (<2.0) were compared between stages. Temporal MFR changes in patients with obstructive CAD (≥70% stenosis by coronary angiography), non-obstructive CAD, and normal coronaries were compared. RESULTS: Of the 88 patients studied (mean age 70; 96% female), 52 (59%) were in the acute, 17 (19%) in the subacute, and 19 (22%) in the chronic stage. Median MFR in the acute stage was 2.0 (1.5-2.3), with 58% of patients showing abnormal MFR. A significant time-dependent improvement in MFR was observed (P = 0.002), accompanied by a decreased prevalence of abnormal MFR (P = 0.016). While patients with normal coronaries showed significant MFR improvement over time (P = 0.045), patients with obstructive or non-obstructive CAD demonstrated no improvement across three stages (P = 0.346 and 0.174, respectively). CONCLUSION: PET-derived MFR was impaired in TTS patients during the acute phase, with improvement suggesting potential recovery from CMD over time. The concurrent presence of obstructive CAD might impede this recovery process.

Possible association between lithium intoxication and Takotsubo syndrome.

More than 25 years after being diagnosed with bipolar disorder and receiving continuous treatment with lithium, a woman develops Takotsubo syndrome.

Renal impairment and outcome in Takotsubo syndrome: Insights from a national multicentric cohort.

INTRODUCTION: Data on the association between kidney function and Takotsubo syndrome (TTS) outcomes are scarce and conflictive. OBJECTIVE: To assess the impact of chronic kidney disease (CKD) and acute renal failure (ARF) in patients with TTS. MATERIAL AND METHODS: Patients from the prospective nation-wide (RETAKO) registry were included and divided into quartiles of maximum creatinine (Cr) level during hospitalization. RESULTS: The prevalence of CKD and ARF in the whole RETAKO cohort was 5.4% and 11.7%, respectively. Compared to Q1 (Cr <0.71), patients within Q4 (Cr > 1.1) had lower left ventricular ejection fraction on admission (38.5 ± 12 vs 43.3 ± 11.3, p = 0.002) and higher bleeding rates during hospitalization (6.7% vs 2%, p = 0.005). In addition, compared to Q1, Q4 patients have a greater incidence of cardiogenic shock (17.3% vs 5.6%, p < 0.001), and a higher rate of 5-year all-cause death and major adverse cardiovascular events (31.5% vs 15.8%, p < 0.001 and 22.5% vs 9.3%, p < 0.001, respectively). CONCLUSIONS: TTS patients with CKD have a higher incidence of ARF and exhibit greater Cr on admission, which were linked with higher rates of cardiogenic shock, bleeding during hospitalization as well as major adverse cardiovascular events and all-cause death during a 5-year follow-up.

Takotsubo syndrome outcomes predicted by thyroid hormone signature: insights from cluster analysis of a multicentre registry.

BACKGROUND: Recently, abnormal thyroid function was shown to be common in patients with Takotsubo syndrome (TTS), being classified into "endocrine-type" and "stress-type" responses. The aim of this study was to investigate the association between thyroid homeostasis and TTS in a larger international registry. METHODS: In total 288 patients with TTS were enrolled through the GEIST multicentre registry from Germany, Italy and Spain. Thyrotropin (TSH), free T4 (FT4) and free T3 (FT3) concentrations were analysed at admission. Data were collected both retrospectively and prospectively from 2017 onwards. Primary endpoints included in-hospital and all-cause fatality, determined by cluster analysis using an unsupervised machine learning algorithm (k-medoids). FINDINGS: Three clusters were identified, classifying TTS with low (TSLT), high (TSHT) and normal (TSNT) thyroid output, based on TSH and FT4 levels in relation to the median thyroid's secretory capacity (SPINA-GT). Although TSH and FT4 concentrations were similar among survivors and non-survivors, these clusters were significantly associated with patient outcomes. In the longitudinal Kaplan-Meier analysis including in- and out-of-hospital survival, the prognosis related to concentrations of TSH, FT4, and FT3 as well as SPINA-GT, deiodinase activity (SPINA-GD) and clusters. Patients in the TSHT cluster and with cardiogenic shock had a lower initial left ventricular ejection fraction (LVEF). INTERPRETATION: This study suggests that thyroid hormones may impact the evolution and prognosis of TTS. The findings indicate that thyroid-derived biomarkers may help identify high-risk patients and pave the way for novel personalized and preventive therapeutic options. FUNDING: This research was not funded by any public, commercial, or not-for-profit agencies.

Tricuspid annular disjunction with varying degrees of tricuspid regurgitation in the setting of Takotsubo syndrome.

Tricuspid annular disjunction (TAD) is concomitant in approximately half of mitral annular disjunction (MAD) cases. Here we report a case of echocardiographically isolated TAD detected during Takotsubo syndrome (TTS) complicated by a transient aggravation of tricuspid regurgitation. An 87-year-old female was admitted at the emergency department with ST segment elevation. Coronary angiography findings were consistent with TTS. Transthoracic echocardiography (TTE) showed a left ventricular apical aneurysm with incidental finding of TAD with 'torrential' tricuspid regurgitation. Importantly, no concomitant MAD was detected on TTE. No significant arrhythmias were detected on telemetry surveillance. Follow up TTE showed improvement in left ventricular function with reduced regional wall abnormalities. TAD was still present although the tricuspid regurgitation had reduced to 'moderate'. The patient was discharged home after 23 days of hospital stay. The present case illustrates the need of further investigations into TAD and its clinical implications for acute TR in TTS.

Body Mass Index and Outcomes in Patients with Takotsubo Syndrome: A Nationwide Retrospective Cohort Study.

BACKGROUND: Takotsubo syndrome (TTS) is a cardiac disorder that mimics acute coronary syndrome at presentation. While previous studies have demonstrated a relationship between body mass index (BMI) and outcomes in acute coronary syndrome, few have examined its relationship with TTS. METHODS: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 14,551 patients admitted for TTS between 2010 and 2021. By applying multivariable regressions with restricted cubic splines, we examined the association between BMI and in-hospital mortality after adjusting for potential confounders. RESULTS: Mean BMI was 21.1 kg/m2, classifying patients into severe underweight (<16.0 kg/m2, 7.1%), mild/moderate underweight (16.0-18.4 kg/m2, 18.3%), normal weight (18.5-22.9 kg/m2, 46.8%), overweight (23.0-27.4 kg/m2, 22.2%), and obese (≥27.5 kg/m2, 5.6%) groups. Patients with severe or mild/moderate underweight were older and had a higher prevalence of impaired physical activity, malignancy, chronic pulmonary disease, and pneumonia. In-hospital mortality was the highest (9.4%) in the severe underweight group, followed by the mild/moderate underweight group (5.4%), with the lowest being in the obese group (2.1%). Severe underweight (adjusted odds ratio = 2.05; 95% confidence interval [CI] = 1.54-2.73) and mild/moderate underweight (1.26; 95% CI = 1.01-1.57) were significantly associated with higher mortality compared with normal weight, while no significant association was noted with obesity. A nonlinear association between continuous BMI and mortality was observed, with mortality increasing when BMI decreased <20.0 kg/m2 but nearly plateauing in BMI >20.0 kg/m2. CONCLUSIONS: The present nationwide analysis demonstrated a nonlinear association between BMI and in-hospital mortality of TTS. BMI is an easily available and clinically relevant marker for the risk stratification of TTS.

Albumin Levels and Risk of Early Cardiovascular Complications After Ischemic Stroke: A Propensity-Matched Analysis of a Global Federated Health Network.

BACKGROUND: No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke. METHODS: Retrospective analysis with a federated research network (TriNetX) based on electronic medical records (International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching. RESULTS: Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels. CONCLUSIONS: Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation.

Age-Related Differences in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

BACKGROUND: The role of age in the short- and long-term prognosis of takotsubo syndrome (TTS) is controversial. The aim of the present study was to evaluate age-related differences and prognostic implications among patients with TTS. METHODS AND RESULTS: In total, 2492 consecutive patients with TTS enrolled in an international registry were stratified into 4 groups (<45, 45-64, 65-74, and ≥75 years). The median long-term follow-up was 480 days (interquartile range, 83-1510 days). The primary outcome was all-cause mortality (in-hospital and out-of-hospital mortality). The secondary end point was TTS-related in-hospital complications. Among the 2479 patients, 58 (2.3%) were aged <45 years, 625 (25.1%) were aged 45 to 64 years, 733 (29.4%) were aged 65 to 74 years, and 1063 (42.6%) were aged ≥75 years. Young patients (<45 years) had a higher prevalence of men (from youngest to oldest, 24.1% versus 12.6% versus 9.7% versus 11.4%; P<0.01), physical triggers (46.6% versus 27.5%, 33.9%, and 38.4%; P<0.01), and non-apical forms of TTS (25.9% versus 23.7%, 12.7%, and 9%; P<0.01) than those aged 45 to 64, 65 to 74, and ≥75 years. During hospitalization, young patients experienced a higher rate of in-hospital complications (32.8% versus 23.4%, 27.4%, and 31.9%; P=0.01), but in-hospital mortality was higher in the older group (0%, 1.6%, 2.9%, and 5%; P=0.001). Long-term all-cause mortality was significantly higher in the older cohort (5.6%, 6.4%, 11.3%, and 22.3%; log-rank P<0.001), as was long-term cardiovascular mortality (0%, 0.9%, 1.9%, and 3.2%; log-rank P=0.01). CONCLUSIONS: Young patients with TTS have a typical phenotype characterized by a higher prevalence of male sex, non-apical ballooning patterns, and in-hospital complications. However, in-hospital and long-term mortality are significantly lower in young patients with TTS. REGISTRATION: URL: https://classic.clinicaltrials.gov/ct2/show/NCT04361994. Unique identifier: NCT04361994.

Neurological Disorders in Takotsubo Syndrome: Clinical Phenotypes and Outcomes.

BACKGROUND: Neurological disorders as a risk factor for Takotsubo syndrome (TTS) are not well characterized. The aim of the study was to evaluate TTS-associated neurological phenotypes and outcome. METHODS AND RESULTS: Patients with TTS enrolled in the international multicenter GEIST (German Italian Spanish Takotsubo) registry were analyzed. Prevalence, clinical characteristics, and short- and long-term outcomes of patients with TTS were recorded. A subgroup analysis of the 5 most represented neurological disorders was performed. In total, 400 (17%) of 2301 patients had neurological disorders. The most represented neurological conditions were previous cerebrovascular events (39%), followed by neurodegenerative disorders (30.7%), migraine (10%), epilepsy (9.5%), and brain tumors (5%). During hospitalization, patients with neurological disorders had longer in-hospital stay (8 [interquartile range, 5-12] versus 6 [interquartile range, 5-9] days; P<0.01) and more often experienced in-hospital complications (27% versus 16%; P=0.01) mainly driven by cardiogenic shock and in-hospital death (12% versus 7.6% and 6.5% versus 2.8%, respectively; both P<0.01). Survival analysis showed a higher mortality rate in neurological patients both at 60 days and long-term (8.8% versus 3.4% and 23.5% versus 10.1%, respectively; both P<0.01). Neurological disorder was an independent predictor of both the 60-day and long-term mortality rate (odds ratio, 1.78 [95% CI, 1.07-2.97]; P=0.02; hazard ratio, 1.72 [95% CI, 1.33-2.22]; both P<0.001). Patients with neurodegenerative disorders had the worst prognosis among the neurological disease subgroups, whereas patients with TTS with migraine had a favorable prognosis (long-term mortality rates, 29.2% and 9.7%, respectively). CONCLUSIONS: Neurological disorders identify a high-risk TTS subgroup for enhanced short- and long-term mortality rate. Careful recognition of neurological disorders and phenotype is therefore needed.