Prognostic Utility of Society for Cardiovascular Angiography and Interventions Shock Stage Approach for Classifying Cardiogenic Shock Severity in Takotsubo Syndrome.

BACKGROUND: Cardiogenic shock (CS) is a significant complication of Takotsubo syndrome (TTS), contributing to heightened mortality and morbidity. Despite this, the Society for Cardiovascular Angiography and Interventions (SCAI) staging system for CS severity lacks validation in patients with TTS and CS. This study aimed to characterize a patient cohort with TTS using the SCAI staging system and assess its utility in cases of TTS complicated by CS. METHODS AND RESULTS: From a TTS national registry, 1591 consecutive patients were initially enrolled and stratified into 5 SCAI stages (A through E). Primary outcome was all-cause in-hospital mortality; secondary end points were TTS-related in-hospital complications and 1-year all-cause mortality. After exclusions, the final cohort comprised 1163 patients, mean age 71.0±11.8 years, and 87% were female. Patients were categorized across SCAI shock stages as follows: A 72.1%, B 12.2%, C 11.2%, D 2.7%, and E 1.8%. Significant variations in baseline demographics, comorbidities, clinical presentations, and in-hospital courses were observed across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage showed a significant association with increased in-hospital mortality (adjusted odds ratio: 1.77-29.31) compared with SCAI shock stage A. Higher SCAI shock stages were also associated with increased 1-year mortality. CONCLUSIONS: In a large multicenter patient cohort with TTS, the functional SCAI shock stage classification effectively stratified mortality risk, revealing a continuum of escalating shock severity with higher stages correlating with increased in-hospital mortality. This study highlights the applicability and prognostic value of the SCAI staging system in TTS-related CS.

Comparative electrocardiographic analysis of midventricular and typical takotsubo syndrome.

Introduction: Takotsubo syndrome (TTS) encompasses distinct variants, with midventricular (MV) as the most common atypical subtype. While electrocardiogram (ECG) abnormalities are well documented in typical TTS, they are less explored in MV-TTS. Methods: A retrospective case-control study was conducted where ECGs were reviewed at three time points from symptom onset (within the first 12 h, at 48 h, and at 5-7 days) and compared between patients with typical TTS (n = 33) and those with MV-TTS (n = 27), as classified by ventriculography. Results: 12-h ECG findings revealed that typical TTS featured ST-segment elevation through anterior leads V3-V6, with maximal deviation in V3 (0.98 ± 0.99 mm) and V4 (0.91 ± 0.91 mm), whereas MV-TTS featured ST-segment depression in inferior leads (-0.24 ± 0.57 mm in II, -0.30 ± 0.52 mm in III, and -0.32 ± 0.47 mm in aVF) and in precordial leads V4-V6. In 48-h ECG findings, the most significant change was T wave inversion, which was more widespread and deeper in typical TTS, with the most pronounced negative T wave depths, exceeding 3 mm, observed in leads V3-V5; in contrast, in MV-TTS, T wave inversion was evident in fewer leads and showed less depth, with the most pronounced negative T waves reaching 1 mm at most in leads I, aVL, and V2. While the QTc interval was prolonged in both groups at 48 h, this prolongation was more pronounced in typical TTS than in MV-TTS (523 ± 52 ms vs. 487 ± 66 ms; p = 0.029). In ECGs at 5-7 days, results essentially returned to baseline. Conclusion: Patients with MV-TTS exhibited a distinctive pattern of ECG abnormalities, marked by ST-segment depression in inferolateral leads, less profound and less extensive T wave inversion that mostly affected leads I, aVL and V2, and attenuated QT interval prolongation compared to typical TTS.

Trastornos del ritmo cardiaco en pacientes con síndrome de Tako-tsubo / Heart rate disorders in patients with Tako-tsubo syndrome

Objetivos El presente estudio pretende evaluar la incidencia, el pronóstico y el tratamiento de los trastornos del ritmo (TdR) en el síndrome de Tako-tsubo (STT). Antecedentes El STT se asocia frecuentemente a TdR. El valor pronóstico de estos TdR aún no está bien caracterizado en el STT. Material y métodos Se analizaron los TdR de los pacientes incluidos en el REgistro nacional multicéntrico sobre síndrome de Tako-tsubo, ingresados entre 2002 y 2018, aportados por 38 hospitales de todo el país. Analizamos en los pacientes TdR previos, en el ingreso y en el seguimiento a largo plazo. Resultados Se describió cualquier tipo de TdR en 259 (23,5%) casos, de una cohorte de 1.097 pacientes consecutivos con STT. Los TdR se presentan más en pacientes con diabetes mellitus, tabaquismo, hiperuricemia, apnea del sueño y anemia, además de con una fracción de eyección del ventrículo izquierdo (FEVI) menor al ingreso. El TdR más frecuente fue el inicio de fibrilación auricular. Durante el ingreso hospitalario, los pacientes con TdR mostraron más complicaciones, como shock al ingreso, hemorragia mayor, insuficiencia renal aguda y el combinado de infecciones. En el seguimiento, presentaron mayor mortalidad y numéricamente más episodios adversos combinados. Conclusiones Los TdR no son infrecuentes en fase aguda del STT. El STT asociado a TdR se presenta con más complicaciones y peor pronóstico tanto hospitalario como a largo plazo (AU)

Objectives This study sought to evaluate the incidence, prognosis and treatment of heart rhythm disorders (HRD) in Tako-tsubo syndrome (TTS). Background TTS is associated with HRD. The HRD prognostic value is not well characterized in TTS yet. Methods The HRD of patients included in the National Registry of Tako-tsubo syndrome, admitted between 2002 and 2018 and coming from 38 hospitals throughout the country, was analyzed. We analyzed any heart rhythm disorder in patients presented before admission, at admission and in long-term follow-up. Results All types of HRD were described in 259 (23.5%) cases, from a cohort of 1,097 consecutive patients with TTS. HRD was more associated with diabetes mellitus, smoking, hyperuricemia, sleep apnea, anemia with a worse LVEF on admission. The most frequent HRD was a new onset of atrial fibrillation. During hospitalization, patients with HRD showed more complications such as shock on admission, major bleeding, acute renal failure, and combined infections. At follow-up, they presented higher mortality and more major adverse cardiac events, but with a non-significant correlation. Conclusions The incidence of HRD in patients with TTS is not infrequent. TTS, when associated with HRD, presents more complications and a worse prognosis both in hospital and in the long term (AU)

Takotsubo Syndrome, Stressful Triggers, and Risk of Recurrence.

The risk of recurrence in takotsubo syndrome (TTS) appears to be low, although previous studies have shown conflicting results and factors associated with recurrences are unclear. The aim of this study is to evaluate the incidence and predictors of TTS recurrences. Adult patients included in the Spanish Multicenter REgistry of TAKOtsubo syndrome (RETAKO) between January 2003 and September 2019 were identified. Patients were categorized based on recurrences during follow-up and a multivariate logistic regression model was used to identify factors associated with recurrences. A total of 1097 patients (mean age 71.0±11.9 years, 87% females) were included, repeated TTS events were documented in 44 patients (4.0%), including 13 patients with prior TTS and 31 patients with recurrent TTS during a median follow-up of 279 days. Two patients (0.02%) had two episodes of recurrence. Compared to patients who had no recurrence of TTS, those with recurrent TTS more frequently had no identifiable stressful trigger in the index admission (20 [64.5%] vs 352 [33.0%], p <0.001). Primary TTS, defined as TTS without physical trigger, was also more common in the recurrence group (93.5% vs 68.3%, p <0.001). The only factor independently associated with recurrences was the absence of an identifiable trigger (odds ratio 3.7 [95% confidence interval 1.8-7.8], p=0.001). In conclusion, our data indicate that for patients presenting with TTS, the rate of early recurrent TTS is approximately 4% per year. Among TTS patients, those who have no identifiable trigger events appear to have a higher rate of recurrence.

[Heart rate disorders in patients with Tako-tsubo syndrome]. / Trastornos del ritmo cardiaco en pacientes con síndrome de Tako-tsubo.

OBJECTIVES: This study sought to evaluate the incidence, prognosis and treatment of heart rhythm disorders (HRD) in Tako-tsubo syndrome (TTS). BACKGROUND: TTS is associated with HRD. The HRD prognostic value is not well characterized in TTS yet. METHODS: The HRD of patients included in the National Registry of Tako-tsubo syndrome, admitted between 2002 and 2018 and coming from 38 hospitals throughout the country, was analyzed. We analyzed any heart rhythm disorder in patients presented before admission, at admission and in long-term follow-up. RESULTS: All types of HRD were described in 259 (23.5%) cases, from a cohort of 1,097 consecutive patients with TTS. HRD was more associated with diabetes mellitus, smoking, hyperuricemia, sleep apnea, anemia with a worse LVEF on admission. The most frequent HRD was a new onset of atrial fibrillation. During hospitalization, patients with HRD showed more complications such as shock on admission, major bleeding, acute renal failure, and combined infections. At follow-up, they presented higher mortality and more major adverse cardiac events, but with a non-significant correlation. CONCLUSIONS: The incidence of HRD in patients with TTS is not infrequent. TTS, when associated with HRD, presents more complications and a worse prognosis both in hospital and in the long term.

Incremental prognostic value of global longitudinal strain to the coronary microvascular resistances in Takotsubo patients.

BACKGROUND: Global longitudinal strain (GLS) allows an accurate assessment of left ventricular function with prognostic value. We aimed to evaluate whether the assessment of GLS in the acute phase of Takotsubo syndrome (TTS) provides incremental prognostic value to the degree of impaired microvascular resistance (MR) in TTS patients at 1-year follow-up. METHODS: We recruited patients admitted for TTS who underwent cardiac angiography and echocardiography from January 2017 to June 2020. Left anterior descending coronary artery non-hyperaemic angiography-derived index of microcirculatory resistance (LAD NH-IMRangio) was calculated. NT-proBNP, high-sensitive cardiac troponin T (hs-cTnT), left ventricular ejection fraction (LVEF) and GLS were measured at admission. Major adverse cardiac events (MACE) were defined as the composite of cardiovascular death, repeat hospitalizations for heart failure (HF) and acute myocardial infarctions. RESULTS: 67 patients had both GLS and NH-IMRangio available and were included in the study. Median age was 75.2 years and 88% were women. Rate of MACE at 1-year was 13.4%. Kaplan-Meier curves showed higher rates of MACE at 1-year in patients with both higher LAD NH-IMRangio and GLS values compared with those with higher LAD NH-IMRangio and lower GLS values (33.3% vs. 11.1%; p = 0.049). NT-proBNP levels at admission and the recovery of LVEF were correlated with GLS values while MR and hs-cTnT were not. CONCLUSION: GLS provides incremental prognostic value to the degree of impaired MR in TTS patients. The combination of a poorer GLS with a higher degree of impaired MR was associated with a higher rate of MACE in these patients.

Prognostic Value of Microvascular Resistance at Rest in Patients With Takotsubo Syndrome.

BACKGROUND: Microvascular resistance (MR) is increased in takotsubo syndrome (TTS) and can be assessed by a validated pressure-wire-free tool called nonhyperemic angiography-derived index of microcirculatory resistance (NH-IMRangio). OBJECTIVES: The authors aimed to study whether the degree and extent of an altered MR in TTS patients were associated with 1-year prognosis. METHODS: The authors recruited 181 consecutive patients with TTS who underwent cardiac angiography. Impaired MR was defined as an NH-IMRangio ≥25. The degree and extent of impaired MR were assessed by the value of maximum NH-IMRangio in each major coronary artery and by the number of coronary arteries with an NH-IMRangio ≥25, respectively. Major adverse cardiac events (MACE) were a composite of cardiovascular death, heart failure event, acute myocardial infarction, and hospitalization for symptomatic arrhythmias. RESULTS: A total of 166 patients had NH-IMRangio available. The mean age was 74.8 years, and 83% were women. The rate of MACE at 1 year was 21.1%, mainly due to heart failure events that were generally mild. Kaplan-Meier curves showed higher rates of MACE in patients with higher NH-IMRangio (28.9% vs 13.3%; P = 0.019) and in those with 3 coronary arteries with increased MR compared to those with 2 or 1 affected arteries (33.3% vs 15.9% vs 9.5%; P = 0.040 and P = 0.040, respectively). After a multivariable Cox regression analysis, higher values of NH-IMRangio (HR: 3.41 [95% CI: 1.54-7.52]; P = 0.002) and the presence of 3 coronary arteries with increased MR (HR: 6.39 [95% CI: 1.46-27.87]; P = 0.014) were independent predictors of MACE in TTS patients. CONCLUSIONS: The degree and extent of an impaired MR assessed by a validated pressure-wire-free tool were independent predictors of MACE at 1-year follow-up in TTS patients.

CD69 expression on regulatory T cells protects from immune damage after myocardial infarction.

Increasing evidence has pointed to the important function of T cells in controlling immune homeostasis and pathogenesis after myocardial infarction (MI), although the underlying molecular mechanisms remain elusive. In this study, a broad analysis of immune markers in 283 patients revealed significant CD69 overexpression on Tregs after MI. Our results in mice showed that CD69 expression on Tregs increased survival after left anterior descending (LAD) coronary artery ligation. Cd69-/- mice developed strong IL-17+ γδT cell responses after ischemia that increased myocardial inflammation and, consequently, worsened cardiac function. CD69+ Tregs, by induction of AhR-dependent CD39 ectonucleotidase activity, induced apoptosis and decreased IL-17A production in γδT cells. Adoptive transfer of CD69+ Tregs into Cd69-/- mice after LAD ligation reduced IL-17+ γδT cell recruitment, thus increasing survival. Consistently, clinical data from 2 independent cohorts of patients indicated that increased CD69 expression in peripheral blood cells after acute MI was associated with a lower risk of rehospitalization for heart failure (HF) after 2.5 years of follow-up. This result remained significant after adjustment for age, sex, and traditional cardiac damage biomarkers. Our data highlight CD69 expression on Tregs as a potential prognostic factor and a therapeutic option to prevent HF after MI.

Coronary Microvascular Dysfunction in Takotsubo Syndrome Assessed by Angiography-Derived Index of Microcirculatory Resistance: A Pressure-Wire-Free Tool.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been proposed as a key mechanism in Takotsubo syndrome (TTS). The non-hyperaemic angiography-derived index of microcirculatory resistance (NH-IMRangio) has been validated as a pressure-wire-free tool for the assessment of coronary microvasculature. We aimed to study the presence of CMD in TTS patients and its association with levels of cardiac biomarkers and systolic dysfunction patterns. METHODS: We recruited 181 consecutive patients admitted for TTS who underwent cardiac angiography at a tertiary center from January 2014 to January 2021. CMD was defined as an NH-IMRangio ≥ 25. Plasma levels of NT-proBNP, high-sensitive cardiac troponin T (hs-cTnT) and the left ventricular ejection fraction (LVEF) by echocardiography were measured at admission. RESULTS: Mean age was 75.3 years, 83% were women and median LVEF was 45%. All patients presented CMD (NH-IMRangio ≥ 25) in at least one epicardial coronary artery. The left anterior descending artery (LAD) showed higher median NH-IMRangio values than left circumflex (LCx) and right coronary arteries (RCA) (44.6 vs. 31.3 vs. 36.1, respectively; p < 0.001). NH-IMRangio values differed among ventricular contractility patterns in the LAD and RCA (p = 0.0152 and 0.0189, respectively) with the highest values in the mid-ventricular + apical and mid-ventricular + basal patterns. NT-proBNP levels, but not high-sensitive cardiac troponin T (hs-cTnT), were correlated with both the degree and the extent of CMD in patients with TTS. Lower LVEF was also associated with higher NH-IMRangio values. CONCLUSIONS: CMD is highly prevalent in patients admitted for TTS and is associated with both a higher degree of systolic dysfunction and higher BNP levels, but not troponin.

Electrocardiographic Characteristics and Associated Outcomes in Patients with Takotsubo Syndrome. Insights from the RETAKO Registry.

Electrocardiographic disturbances in Takotsubo syndrome have been previously partially described but their consequences remain mostly unknown. Our aim was to describe the prevalence and prognostic significance of different electrocardiographic features in patients with Takotsubo syndrome. Our data come from the Spanish multicenter REgistry of TAKOtsubo syndrome (RETAKO). All patients with an available 12-lead surface electrocardiogram at admission and 48 hours post-admission were included. A total of 246 patients were studied, mean age was 71.3 ± 11.5 and 215 (87.4%) were women. ST-segment elevation was seen in 143 patients (59.1%) and was present in ≥2 wall leads in 97 (39.8%). Exclusive elevation in inferior leads was infrequent (5% - 2.0%). After 48 hours, 198 patients (88.0%) developed negative T waves in a median of 8 leads with a mean amplitude of 0.7 ± 0.5 mV and 137 (60.9%) had pathological Q waves. The mean corrected QT interval was 520 ± 72 ms. Corrected QT interval was independently associated with the primary endpoint of all-cause death and nonfatal cardiovascular events (P = 0.002) and all-cause death (P = 0.008). A higher heart rate at admission was an independent predictor of the primary endpoint (P = 0.001) and of acute pulmonary edema (P = 0.04). ST-segment elevation with reciprocal depression was an independent predictor of all-cause death (P = 0.04). Absence of ST-segment deviation was a protective factor (P = 0.005) for the primary endpoint. Tachyarrhythmias were independently associated with cardiogenic shock (P< 0.001). Takotsubo syndrome patients present with distinct electrocardiographic features. Prolonged corrected QT interval, tachyarrhythmias, heart rate at admission, and more extensive repolarization alterations are associated with poor outcomes.

An Exceptional Cause of Acute Right Heart Failure: Isolated Right Ventricular Takotsubo Syndrome.

We describe a patient with of acute right ventricular dysfunction secondary to right ventricular isolated Takotsubo syndrome (TTS). The importance of appropriate differential diagnosis for acute right ventricular dysfunction differential diagnosis of acute right ventricular dysfunction and the differences in diagnosis and management of right ventricular TTS and typical left ventricular TTS are highlighted. (Level of Difficulty: Intermediate.).

Afección cardiaca por COVID-19, ¿importa la ecocardiografía? / Cardiac involvement in COVID-19: does echocardiography matter?

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Short- and Long-Term Prognosis of Patients With Takotsubo Syndrome Based on Different Triggers: Importance of the Physical Nature.

Background Takotsubo syndrome (TTS) is an acute reversible heart condition initially believed to represent a benign pathology attributable to its self-limiting clinical course; however, little is known about its prognosis based on different triggers. This study compared short- and long-term outcomes between TTS based on different triggers, focusing on various physical triggering events. Methods and Results We analyzed patients with a definitive TTS diagnosis recruited for the Spanish National Registry on TTS (RETAKO [Registry on Takotsubo Syndrome]). Short- and long-term outcomes were compared between different groups according to triggering factors. A total of 939 patients were included. An emotional trigger was detected in 340 patients (36.2%), a physical trigger in 293 patients (31.2%), and none could be identified in 306 patients (32.6%). The main physical triggers observed were infections (30.7%), followed by surgical procedures (22.5%), physical activities (18.4%), episodes of severe hypoxia (18.4%), and neurological events (9.9%). TTS triggered by physical factors showed higher mortality in the short and long term, and within this group, patients whose physical trigger was hypoxia were those who had a worse prognosis, in addition to being triggered by physical factors, including age >70 years, diabetes mellitus, left ventricular eyection fraction <30% and shock on admission, and increased long-term mortality risk. Conclusions TTS triggered by physical factors could present a worse prognosis in terms of mortality. Under the TTS label, there could be as yet undiscovered very different clinical profiles, whose differentiation could lead to individual better management, and therefore the perception of TTS as having a benign prognosis should be generally ruled out.

Disfunción ventricular derecha acompañada de insuficiencia respiratoria grave. Opciones terapéuticas con dispositivos de asistencia mecánica / Severe combined right ventricular and respiratory failure. Treatment options with mechanical assist devices

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Prevalence and Significance of Interatrial Block in Takotsubo Syndrome (from the RETAKO Registry).

Interatrial block (IAB) represents a conduction delay between right and left atria and is associated with an increased risk of atrial fibrillation and stroke. IAB has not been previously assessed in patients with Takotsubo syndrome (TS). Our aim was to describe the prevalence and prognostic significance of IAB in patients with TS. Data come from the Spanish National prospective registry of patients with definitive TS diagnosis. IAB was defined as a P-wave ≥120 ms and was considered partial when the P-wave was positive in inferior leads and advanced when it was biphasic (+/-). A total of 246 patients were included, normal P-wave was found in 151 (61%), partial IAB in 58 (24%), atrial fibrillation in 18 (7%), advanced IAB in 13 (5%), and 6 (2%) were pacemaker dependent. During a mean follow up of 12 months the composite of all-cause mortality and hospital readmission was significantly higher in patients with advanced IAB (31%) or atrial fibrillation (33%) than in the rest of the cohort (pacemaker stimulation 17%, normal P-wave 13%, partial IAB 12%), p < 0.01. The data regarding P wave characteristics were an independent predictor of the composite end point all-cause death and hospital readmission. IAB has a high prevalence in patients with TS. Advanced IAB and atrial fibrillation are associated with a poor prognosis.

Clinical and prognostic implications of delirium in elderly patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Elderly patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) may present delirium but its clinical relevance is unknown. This study aimed at determining the clinical associated factors, and prognostic implications of delirium in old-aged patients admitted for NSTE-ACS. METHODS: LONGEVO-SCA is a prospective multicenter registry including unselected patients with NSTE-ACS aged ≥ 80 years. Clinical variables and a complete geriatric evaluation were assessed during hospitalization. The association between delirium and 6-month mortality was assessed by a Cox regression model weighted for a propensity score including the potential confounding variables. We also analysed its association with 6-month bleeding and cognitive or functional decline. RESULTS: Among 527 patients included, thirty-seven (7%) patients presented delirium during the hospitalization. Delirium was more frequent in patients with dementia or depression and in those from nursing homes (27.0% vs. 3.1%, 24.3% vs. 11.6%, and 11.1% vs. 2.2%, respectively; all P < 0.05). Delirium was significantly associated with in-hospital infections (27.0% vs. 5.3%, P < 0.001) and usage of diuretics (70.3% vs. 49.8%, P = 0.02). Patients with delirium had longer hospitalizations [median 8.5 (5.5-14) vs. 6.0 (4.0-10) days, P = 0.02] and higher incidence of 6-month bleeding and mortality (32.3% vs. 10.0% and 24.3% vs. 10.8%, respectively; both P < 0.05) but similar cognitive or functional decline. Delirium was independently associated with 6-month mortality (HR = 1.47, 95% CI: 1.02-2.13, P = 0.04) and 6-month bleeding events (OR = 2.87; 95% CI: 1.98-4.16, P < 0.01). CONCLUSIONS: In-hospital delirium in elderly patients with NSTE-ACS is associated with some preventable risk factors and it is an independent predictor of 6-month mortality.