Incidence, management, and prognostic impact of arrhythmias in patients with Takotsubo syndrome: a nationwide retrospective cohort study.

AIMS: Arrhythmia is a major complication of Takotsubo syndrome (TTS). However, its incidence, management, and prognostic impact remain to be elucidated in a large cohort. METHODS AND RESULTS: We retrospectively identified 16 713 patients hospitalized for TTS between July 2010 and March 2021 from the Japanese Diagnosis Procedure Combination database. Serious arrhythmias were defined as ventricular tachycardia/fibrillation (VT/VF), 2nd-/3rd-degree atrioventricular block (AVB), sick sinus syndrome (SSS), or unspecified arrhythmias requiring device treatment. Patient characteristics and outcomes were compared based on the occurrence of serious arrhythmias. The overall incidence proportion of serious arrhythmias was 6.2% (n = 1036; 449 VT/VF, 283 2nd-/3rd-degree AVB, 133 SSS, 55 multiple arrhythmias, 116 others), which remained stable over 11 years. The arrhythmia group was younger, more often male, and exhibited greater impairment in activities of daily living (ADLs) and consciousness than the non-arrhythmia group. Although crude in-hospital mortality was higher in the arrhythmia group (9.6% vs. 5.0%, P < 0.001), the significant association between arrhythmias and mortality disappeared after adjustment for confounders (odds ratio = 1.15, 95% confidence interval = 0.90-1.49). Meanwhile, age, sex, ADLs, consciousness level, and Charlson comorbidity index were significantly associated with mortality. In the arrhythmia group, 254 (24.5%) patients received pacemakers (18.4%) or defibrillators (6.1%), which were implanted at a median of 8 and 19 days after admission, respectively. CONCLUSION: Arrhythmias are not uncommon in TTS. Patients' background characteristics, rather than arrhythmia itself, may be associated with in-hospital mortality. Given the reversibility of cardiac dysfunction in TTS, there may be unnecessary device implantations for arrhythmias occurring as sequelae to TTS, warranting further investigations.

Left ventricular global longitudinal strain assessment in patients with takotsubo cardiomyopathy: a call for an echocardiography-based classification.

BACKGROUND: Takotsubo cardiomyopathy (TTC) is classified into 4 types depending on the anatomical area affected identified on gross visual assessment. We have sought to understand if it is feasible and advantageous to use left ventricular global longitudinal strain (LVGLS), LV segmental longitudinal strain and right ventricle free wall strain (RVFWS) to classify TTC. METHODS: We conducted a retrospective observational study on twenty-five patients who meet the Modified Mayo Clinic Criteria for TTC [1]. Two independent reviewers performed strain analysis, they were both blinded to patient's diagnosed classification and outcomes. RESULTS: Based on classification by traditional assessment the 92% (N.=23) were diagnosed with typical TTC, indicating apical involvement. The entire LV was affected, 67% (N.=16) had abnormal strain (STE>-18) in all three LV regions (base, mid-ventricle and apex). Seventy-one percent of patients (N.=17) had abnormal LVGLS (>-18). Abnormal strain across all three LV regions was associated with higher prevalence (70%, N.=8 Vs 30%, N.=4, respectively) of composite cardiovascular events and longer length of hospital stay. There was a statistically significant difference in average length of hospital stay in those patients who had abnormal strain in all three regions compared to those that did not have abnormal strain across all three regions (8 days compared to 3.44 days, P=0.02). CONCLUSIONS: A new classification of TCC based on strain analysis should be developed. The traditional model is arbitrary; it fails to recognize that in most patients the entire LV is affect, it does not have prognostic significance and the most prevalent typical variant indicates apical involvement. Our study suggests that the entire LV is affected, and strain analysis has prognostic significance.

Stress cardiomyopathy in hospitalized patients with cancer: machine learning analysis by primary malignancy type.

AIMS: Previous studies have shown that patients with stress (Takotsubo) cardiomyopathy (SC) and cancer have higher in-hospital mortality than patients with SC alone. No studies have examined outcomes in patients with active cancer and SC compared to patients with active cancer without SC. We aimed to assess the potential association between primary malignancy type and SC and their shared interaction with inpatient mortality. METHODS AND RESULTS: We analysed SC by primary malignancy type with propensity score adjusted multivariable regression and machine learning analysis using the 2016 United States National Inpatient Sample. Of 30 195 722 adult hospitalized patients, 4 719 591 had active cancer, of whom 568 239 had SC. The mean age of patients with cancer and SC was 69.1, of which 74.7% were women. Among patients with cancer, those with SC were more likely to be female and have white race, Medicare insurance, hypertension, heart failure with reduced ejection fraction, obesity, cerebrovascular disease, anaemia, and chronic obstructive pulmonary disease (P < 0.003 for all). In machine learning-augmented, propensity score multivariable regression adjusted for age, race, and income, only lung cancer [OR 1.25; 95% CI: 1.08-1.46; P = 0.003] and breast cancer [OR 1.81; 95% CI: 1.62-2.02; P < 0.001] were associated with a significantly increased likelihood of SC. Neither SC alone nor having both SC and cancer was significantly associated with in-hospital mortality. The presence of concomitant SC and breast cancer was significantly associated with reduced mortality (OR 0.48; 95% CI: 0.25-0.94; P = 0.032). CONCLUSIONS: This analysis demonstrates that primary malignancy type influences the likelihood of developing SC. Further studies will be necessary to delineate characteristics in patients with lung cancer and breast cancer which contribute to development of SC. Additional investigation should confirm lower mortality in patients with SC and breast cancer and determine possible explanations and protective factors.

Concurring hypertrophic cardiomyopathy and takotsubo cardiomyopathy: Assessment and management.

The prevalence of takotsubo cardiomyopathy (TCM) has been on the rise, but co-occurrence with hypertrophic cardiomyopathy (HOCM) remains rare. Although presenting patient demographics were similar to those in TCM, the potential for hemodynamic compromise was significantly compounded by the presence of underlying HOCM. Management was similar to standalone TCM, although use of inotropic agents and mechanical support appears to be more prevalent. Despite the increased potential for complications and the paucity of data regarding management, outcomes appear to be mostly favorable in both the hospitalization period and at follow-up. Interestingly, despite a new diagnosis of HOCM in about half the cases described, which signifies no significant left ventricular outflow tract (LVOT) gradient prior to TCM, half of those patients had a persistently elevated LVOT gradient after resolution of TCM. This poses a question of whether or not TCM can predispose to LVOT obstruction in HOCM patients even after its resolution.

A review of diagnosis, etiology, assessment, and management of patients with myocardial infarction in the absence of obstructive coronary artery disease.

Myocardial infarction (MI) in the absence of obstructive coronary artery disease (MINOCA) is prevalent in around 5% of acute myocardial infarction (AMI) presentations. MINOCA is a heterogeneous entity with many different etiologies. It is important for health care providers to familiarize themselves with the disease process, presentation, and possible underlying causes in order to guide appropriate management strategies. In this article, the authors review the contemporary definition, etiologies and assessment, and management for AMI patients with MINOCA.

Prevalence, management, and outcome of adverse rhythm disorders in takotsubo syndrome: insights from the international multicenter GEIST registry.

One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients; p < 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients; p < 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%, p < 0.01) and in-hospital death (10.9% versus 3.6%; p < 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank p < 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1-6.9; p = 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.

[Clinical features and complications of Takotsubo syndrome in a peruvian social security referral center]. / Características clínicas y complicaciones del síndrome de Takotsubo en un centro de referencia de la seguridad social peruana.

In order to describe the clinical features and complications of Takotsubo syndrome, a case series study was conducted with patients admitted with this pathology to the National Cardiovascular Institute-INCOR in Lima-Peru between January 2013 and December 2018. Twenty-six patients (26) were included, with an average age of 69 years and female predominance (96.2%); additionally, a trigger was identified in 23 cases (88.5%). In the electrocardiogram, 61.5% had ST segment elevation; and, in the evolution, 92.3% showed negative T waves and 38.5% a QTc interval >500 ms. In-hospital complications were cardiogenic shock (11.5%), atrial fibrillation (7.7%) and ventricular tachycardia (7.7%). In this series, Takotsubo syndrome predominated in postmenopausal women, usually triggered by a stressor, with a low complication rate and no in-hospital mortality.

Con el objetivo de describir las características clínicas y complicaciones del síndrome de Takotsubo, se realizó un estudio de serie de casos de pacientes que ingresaron con esta patología al Instituto Nacional Cardiovascular-INCOR en Lima-Perú, entre enero de 2013 a diciembre de 2018. Se incluyeron 26 pacientes, con una edad promedio de 69 años y predominio del sexo femenino (96,2%), además un desencadenante se identificó en 23 casos (88,5%). En el electrocardiograma, el 61,5% tuvo supradesnivel del segmento ST; y en la evolución el 92,3% mostró ondas T negativas y el 38,5% un intervalo QTc >500 ms. Las complicaciones intrahospitalarias fueron choque cardiogénico (11,5%), fibrilación auricular (7,7%) y taquicardia ventricular (7,7%). En esta serie, el síndrome de Takotsubo predominó en mujeres posmenopáusicas, generalmente desencadenado por un factor estresante, con una baja tasa de complicaciones y ausencia de mortalidad intrahospitalaria.

Assessment of the German and Italian Stress Cardiomyopathy Score for Risk Stratification for In-hospital Complications in Patients With Takotsubo Syndrome.

Importance: Takotsubo syndrome (TTS) is an acute, reversible heart failure syndrome featured by significant rates of in-hospital complications. There is a lack of data for risk stratification during hospitalization. Objective: To derive a simple clinical score for risk prediction of in-hospital complications among patients with TTS. Design, Setting, and Participants: In this prognostic study, 1007 consecutive patients were enrolled in the German and Italian Stress Cardiomyopathy (GEIST) registry from July 1, 2007, through December 31, 2017, and identified as the derivation cohort; 946 patients were enrolled in the Spanish Registry for Takotsubo Cardiomyopathy (RETAKO) as the external score validation. An admission risk score was developed using a stepwise multivariable regression analysis from 2 registries. Data analysis was performed from March 1, 2018, through July 31, 2018. Main Outcomes and Measures: In-hospital complications were defined as death, pulmonary edema, need for invasive ventilation, and cardiogenic shock. Four variables were identified as independent predictors of in-hospital complications and were used for the score: male sex, history of neurologic disorder, right ventricular involvement, and left ventricular ejection fraction (LVEF). Results: Of the 1007 patients enrolled in the GEIST registry, 107 (10.6%) were male, with mean (SD) age of 69.8 (11.4) years. Overall rate of in-hospital complications was 23.3% (235 of 1007) (death, 4.0%; pulmonary edema, 5.8%; invasive ventilation, 6.4%; and cardiogenic shock, 9.1%). The GEIST prognosis score was derived by providing 20 points each for male sex and history of neurologic disorders and 30 points for right ventricular involvement and then subtracting the value in percent of LVEF (decimal values between 0.15 and 0.70). Score accuracy on area under the receiver operating characteristic curve analysis was 0.71, with a negative predictive power of 87% with scores less than 20. External validation in the RETAKO population (124 [13.1%] male; mean [SD] age, 69.5 [14.9] years) revealed an area under the curve of 0.73 (P = .46 vs GEIST derivation cohort). Stratification into 3 risk groups (<20, 20-40, and >40 points) classified 316 patients (40.9%) as having low risk; 342 (44.3%) as having intermediate risk, and 114 (14.8%) as having high risk of complications. The observed in-hospital complication rates were 12.7% for low-risk patients, 23.4% for intermediate-risk patients, and 58.8% for high-risk patients (P < .001 for trend). After 2.6 years of follow-up, patients with in-hospital complications had significantly higher rates of mortality than those without complications (40% vs 10%, P = .01). Conclusions and Relevance: The GEIST prognostic score may be useful in early risk stratification for TTS. High-risk patients with TTS may require an intensive care unit stay, and low-risk patients with TTS could be discharged within a few days. In-hospital complications in patients with TTS may be associated with increased risk of long-term mortality.

Características clínicas y complicaciones del síndrome de Takotsubo en un centro de referencia de la seguridad social peruana / Clinical features and complications of Takotsubo syndrome in a peruvian social security referral center

RESUMEN Con el objetivo de describir las características clínicas y complicaciones del síndrome de Takotsubo, se realizó un estudio de serie de casos de pacientes que ingresaron con esta patología al Instituto Nacional Cardiovascular-INCOR en Lima-Perú, entre enero de 2013 a diciembre de 2018. Se incluyeron 26 pacientes, con una edad promedio de 69 años y predominio del sexo femenino (96,2%), además un desencadenante se identificó en 23 casos (88,5%). En el electrocardiograma, el 61,5% tuvo supradesnivel del segmento ST; y en la evolución el 92,3% mostró ondas T negativas y el 38,5% un intervalo QTc >500 ms. Las complicaciones intrahospitalarias fueron choque cardiogénico (11,5%), fibrilación auricular (7,7%) y taquicardia ventricular (7,7%). En esta serie, el síndrome de Takotsubo predominó en mujeres posmenopáusicas, generalmente desencadenado por un factor estresante, con una baja tasa de complicaciones y ausencia de mortalidad intrahospitalaria.

ABSTRACT In order to describe the clinical features and complications of Takotsubo syndrome, a case series study was conducted with patients admitted with this pathology to the National Cardiovascular Institute-INCOR in Lima-Peru between January 2013 and December 2018. Twenty-six patients (26) were included, with an average age of 69 years and female predominance (96.2%); additionally, a trigger was identified in 23 cases (88.5%). In the electrocardiogram, 61.5% had ST segment elevation; and, in the evolution, 92.3% showed negative T waves and 38.5% a QTc interval >500 ms. In-hospital complications were cardiogenic shock (11.5%), atrial fibrillation (7.7%) and ventricular tachycardia (7.7%). In this series, Takotsubo syndrome predominated in postmenopausal women, usually triggered by a stressor, with a low complication rate and no in-hospital mortality.

Etiologies, predictors, and economic impact of readmission within 1 month among patients with takotsubo cardiomyopathy.

BACKGROUND: Limited data exist on readmission among patients with takotsubo cardiomyopathy (TC), a commonly reversible cause of heart failure. HYPOTHESIS: We sought to identify etiologies and predictors for readmission among TC patients. METHODS: We queried the National Readmissions Database for 2013-2014 to identify patients with primary admission for TC using ICD-9-CM code 429.83. Patients readmitted to hospital within 1 month after discharge were further evaluated to identify etiologies, predictors, and resultant economic burden of readmission. Additionally, we analyzed readmission for TC at 6 months. RESULTS: We studied 5997 patients admitted with TC, of whom 1.2% experienced in-hospital mortality. Median age was 67 years, with 91.5% being female. Among survivors, 10.3% were readmitted within 1 month; 25% of the initial 1-month readmissions occurred within 4 days, 50% within 10 days, and 75% within 20 days from discharge. The most common etiologies for readmission were cardiac (26%), respiratory (16%), and gastrointestinal (11%) causes. Heart failure was the most common cardiac etiology. Significant predictors of increased 1-month readmission included systemic thromboembolic events, length of stay ≥3 days, and underlying psychoses. Obesity and private insurance predicted lower 1-month readmission. The annual national cost impact for index admission and 1-month readmissions was ≈$112 million. Recurrent TC was seen among 1.9% of patients readmitted within 6 months. CONCLUSIONS: Though the overall rate of 1-month readmission following TC is low, associated economic burden from readmission is still significant. Patients are readmitted mostly for noncardiac causes. Readmission for another episode of TC within 6 months was uncommon.

Prevalence of malignant arrhythmia and sudden cardiac death in takotsubo syndrome and its management.

Aims: Recent studies have highlighted that takotsubo syndrome (TTS) is associated with a poor clinical outcome. Our study was conducted to determine the short- and long-term prevalence, recurrence rate and impact of life-threatening arrhythmias (LTA) on the clinical outcome of TTS. Methods and results: Our institutional database constituted a collective of 114 patients diagnosed with TTS between 2003 and 2015. The patient groups, divided according to the presence (n = 13, 11.4%) or absence (n = 101, 88.6%) of LTAs, were followed-up over a period of 3 years so as to determine the clinical outcome. Our analyses suggest that patients comprising the LTA group suffered significantly more often from an acute cardiovascular event including cases of a newly diagnosed atrial fibrillation (38.4% vs. 2.9%), cardiogenic shock with use of inotropic agents (53.8% vs. 14.8%) and cardiopulmonary resuscitation (61.5% vs. 1%). The short-term recurrence rate of a LTA episode was 15.3%, while the long-term recurrence rate of any LTA was around 5%. Whereas, in-hospital mortality was significantly higher in TTS associated with LTAs, the overall survival rate over 3 years was similar. A multivariate Cox regression analysis suggested atrial fibrillation, EF ≤ 35%, cardiogenic shock, and glomerular filtration rate <60 mL/min. as independent predictors of adverse outcome. Conclusion: The short- as well as the long-term prevalence and recurrence of LTAs in TTS patients is high. The long-term mortality rates were similar to the TTS patients presenting without any LTAs. LTAs in TTS could be triggered by a concomitant atrial fibrillation.

Takotsubo cardiomyopathy associated with rupture of the left ventricular apex: assessment of histopathological features of a fatal case and literature review.

Takotsubo cardiomyopathy, also known as "broken heart syndrome," is a cardiac entity characterized by transient left ventricular dysfunction without obstructive atherosclerotic coronary artery disease. An episode of emotional stress is believed to act as a trigger in the development of this syndrome, which typically occurs in female patients. We report a fatal case of a previously healthy 70-year-old woman who suffered an out-of-hospital cardiac arrest and cardiac rupture during emotional distress, due to Takotsubo cardiomyopathy. Ventricular rupture with Takotsubo cardiomyopathy is rare, but our case emphasizes the importance of dealing with this serious and potentially life-threatening disease. Takotsubo cardiomyopathy should be considered as a differential diagnosis in cases of early-developing heart failure, and clinicians should subsequently use adequate diagnostic and therapeutic options.

Multidisciplinary assessment of tako tsubo cardiomyopathy: a prospective case study.

BACKGROUND: The cause of tako tsubo cardiomyopathy remains unclear. We used a multidisciplinary approach to investigate if a common pathophysiological denominator could be outlined. METHODS: Within 3 days following symptom presentation and again after 3 months we investigated all patients coming to our institution and diagnosed with tako-tsubo cardiomyopathy. Patients underwent extensive biochemical screening. Left ventricular function was evaluated by echocardiography and contrast-enhanced cardiac magnetic resonance imaging. Cardiac autonomic function was studied by heart rate variability and signal-averaged electrocardiogram and posttraumatic stress and depression were investigated by questionnaires (the Posttraumatic Stress Syndrome 10-Questions Inventory, PTSS-10 and the Montgomery-Åsberg depression rating scale, self rated version, MADRS-S). RESULTS: During 2 years, 13 consecutive patients were included. Markers of myocardial damage and heart failure were slightly to moderately elevated and ejection fraction (echocardiography and MRi) was moderately reduced at hospitalization and improved to normal values in all patients. Signal averaged ECG demonstrated a statistically significant shorter duration of the filtered QRS complex in the acute phase as compared to follow-up. In heart rate variability analysis, SDNN and SDANN were shorter acutely compared to follow-up. Two patients fulfilled criteria for posttraumatic stress syndrome while 7 patients were in the borderline zone. There was a statistically significant inverse correlation between PTSS-10 score and QRS duration in the signal-averaged ECG (r = -0.66, P = 0.01). CONCLUSIONS: Patients with tako tsubo cardiomyopathy have altered cardiac autonomic function and a high incidence rate of borderline or definite posttraumatic stress syndrome acutely. This is in line with findings in patients with myocardial infarction and does not allow conclusions on cause and effect.