Recovery of Left Ventricular Function and Long-Term Outcomes in Patients With Takotsubo Syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is a form of transient left ventricular (LV) dysfunction that usually resolves within days to weeks. OBJECTIVES: We aimed to assess the predictors and prognostic impact of time-to-LV recovery after TTS. METHODS: Prospective serial imaging data from the nationwide, multicenter RETAKO (REgistry on TAKOtsubo Syndrome) were comprehensively reviewed to assess the timing of LV recovery. Multivariable logistic regression was used to assess factors associated with late (≥10 days) vs early (<10 days) recovery. The long-term risk of all-cause mortality was compared between the late and early recovery groups using fully adjusted Cox models, and using flexible parametric survival models with recovery time included as a continuous variable. RESULTS: Of 1,463 patients included (median age 73 years, 13% men), 373 (25%) had late and 1,090 (75%) had early LV recovery. Older age, history of neurological disorders, bystander coronary artery disease, active cancer, physical triggers, elevated inflammatory biomarkers, cardiogenic shock, and lower LV ejection fraction at admission were independent predictors of late recovery. At 4-year follow-up, the adjusted risk of death was significantly higher in patients with late recovery compared with those with early recovery (16.0% vs 8.6%, adjusted HR: 1.31; 95% CI: 1.12-1.60), with the risk of death increasing by 8% for every additional 10-day delay in time-to-LV recovery (adjusted HR: 1.08; 95% CI: 1.04-1.13). CONCLUSIONS: Late recovery of LV function after TTS is associated with reduced short- and long-term survival. In TTS patients without early LV recovery, closer clinical follow-up might be considered.

The Role of Cardiac Magnetic Resonance in mRNA COVID-19 Vaccine-Related Myopericarditis: An Evolutive Case Series.

Numerous cases of myocarditis related to mRNA vaccines for COVID-19 have recently been described, usually in young men. Long-term evolutive cardiac magnetic resonance imaging (CMR) data are lacking. We describe four consecutive cases of COVID-19 vaccine-induced myocarditis. The pathological findings of cardiac magnetic resonance confirmed the diagnosis in the acute phase, showing edema, as well as pericardial enhancement, with light pericardial effusion and late gadolinium enhancement (LGE), predominantly in the inferolateral wall. These cases highlight the unique value of cardiac magnetic resonance in patients with suspected myocarditis induced by COVID-19 RNAm vaccines as a tool to confirm the diagnosis, avoiding other invasive techniques, as well as for the long-term follow-up of patients. Our iterative CMR imaging demonstrated frequent long-term LGE persistence.

New risk classification adapting SCAI shock stages to patients with pulmonary embolism (RISA-PE).

BACKGROUND: Pulmonary embolism (PE) treatment is based on risk stratification according to European Society of Cardiology (ESC) guidelines. However, emerging therapies in acute PE may require a more granular risk classification. Therefore, the objective of the present study was to propose a new RIsk claSsification Adapting the SCAI shock stages to right ventricular failure due to acute PE (RISA-PE). METHODS: This registry included consecutive intermediate-high risk (IHR) or high-risk (HR)-PE patients selected for catheter-directed interventions (CDI) from 2018 to 2023 in 15 Spanish centers (NCT06348459). Patients were grouped according to RISA-PE classification as A (right ventricular dysfunction and troponin elevation); B (A + serum lactate >2 mmol/L OR shock index ≥1); C (persistent hypotension); D (obstructive shock); and E (cardiac arrest). In-hospital adverse events were assessed to evaluate RISA-PE performance. RESULTS: A total of 334 patients were included (age 62.1±15.2 years, 55.7% males). The incidence of in-hospital all-cause death was progressively higher with increasing RISA-PE stage (1.2%, 6.4%, 19.0%, 25.6%, and 57.7% for stages A, B, C, D, and E, respectively, P value for linear trend<0.001). However, using the ESC classification, there was an abrupt difference between IHR- and HR-PE patients regarding mortality (4.3% vs. 29.3%, P<0.001). The incidence of in-hospital major bleeding and acute kidney injury followed a similar pattern. CONCLUSIONS: The user-friendly RISA-PE classification may improve the granularity in stratifying PE patients' risk and warrants evaluation in larger studies with different therapeutic approaches in order to detect its utility as a decision-making scale.

Thrombocytopenia after transcatheter aortic valve implantation.

INTRODUCTION AND OBJECTIVES: Thrombocytopenia frequently occurs after transcatheter aortic valve implantation (TAVI) but its impact is poorly understood. We aimed to analyze the incidence, clinical impact, and predictors of acquired thrombocytopenia after TAVI. METHODS: This retrospective multicenter registry included 3913 patients undergoing TAVI with a baseline platelet count of ≥ 100 *109/L. Acquired thrombocytopenia was defined as a decrease in baseline platelet count of ≥ 50% (early nadir ≤ 3 days and late nadir ≥ 4 days) post-TAVI. The primary endpoint was 30-day all-cause mortality and secondary endpoints were procedural safety and 2-year all-cause mortality. RESULTS: The incidence of acquired thrombocytopenia was 14.8% (early nadir: 61.5%, late nadir: 38.5%). Thirty-day mortality occurred in 112 (3.0%) patients and was significantly higher in those with thrombocytopenia (8.5% vs 2.0%, adjusted OR, 2.3; 95%CI, 1.3-4.2). Procedural safety was lower and 2-year mortality was higher in patients with thrombocytopenia vs those without (52.1 vs 77.0%; P <.001, and 30.2% vs 16.8%; HR, 2.2, 95%IC, 1.3-2.7) and especially in those with late nadir thrombocytopenia (45.8% vs 54.5%; P=.056, and 38.6% vs 23.8%, HR, 2.1; 95%CI, 1.5-2.9). Independent predictors of thrombocytopenia comprised baseline and procedural factors such as body surface area, absence of diabetes, poorer renal function, peripheral vascular disease, nontransfemoral access, vascular complications, type of transcatheter heart valve, and earlier TAVI procedures. CONCLUSIONS: Acquired thrombocytopenia was common (15%) after TAVI and was associated with increased short- and mid-term mortality and decreased procedural safety. Moreover, late thrombocytopenia compared with early thrombocytopenia was associated with significantly worse clinical outcomes. Further investigations are needed to elucidate the etiologic mechanisms behind these findings.

Renin angiotensin system inhibitors and outcome in patients with takotsubo syndrome: A propensity score analysis of the GEIST registry.

BACKGROUND: Few data are available on long-term drug therapy and its potential prognostic impact after Takotsubo syndrome (TTS). Aim of the study is to evaluate clinical characteristics and long-term outcome of TTS patients on Renin Angiotensin system inhibitors (RASi). METHODS: TTS patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Median follow-up was 31 (Interquartile range 12-56) months. Comparison of RASi treated vs. untreated patients was performed within the overall population and after 1:1 propensity score matching for age, sex, comorbidities, type of trigger and in-hospital complications. REGISTRATION: clinicaltrials.gov, NCT04361994, https://clinicaltrials.gov/study/NCT04361994 RESULTS: Of the 2453 TTS patients discharged alive, 1683 (68%) received RASi therapy. Patients with RASi were older (age 71 ± 11 vs 69 ± 13 years, P = .01), with higher prevalence of hypertension (74% vs 53%, P < .01) and diabetes (19% v s15%, P = .01), higher admission left ventricular ejection fraction (LVEF) (41 ± 11% vs 39 ± 12%, P < .01) and lower rates of in-hospital complications (18.9% vs 29.6%, P < .01). At multivariable analysis, RASi therapy at discharge was independently associated with lower mortality (HR 0.63, 95% CI 0.45-0.87, P < .01). Survival analysis showed that at long term, patients treated with RASi had lower mortality rates in the overall cohort (log-rank P = .001). However, this benefit was not found among patients treated with RASi in the matched cohort (log-rank P = .168). Potential survival benefit of RASi were present, both in the overall and matched cohort, in 2 subgroups: patients with admission LVEF ≤ 40% (HR 0.54 95% CI 0.38-0.78, P = .001; HR 0.59, 95% CI 0.37-0.95, P = .030) and diabetes (HR 0.41, 95% CI 0.23-0.73, P = .002; HR 0.41, 95% CI 0.21-0.82, P = .011). CONCLUSIONS: Long-term therapy with RASi after a TTS episode was not associated with lower mortality rates at propensity score analysis. However, potential survival benefit can be found among patients with admission LVEF ≤ 40% or diabetes.

Left Ventricular Outflow Tract Morphology as a Predictor of Conductance Disturbances Following Transcatheter Aortic Valve Replacement.

BACKGROUND: Conduction disturbances represent one of the most common complications following transcatheter aortic valve replacement (TAVR). We sought to investigate the role of left ventricular outflow tract (LVOT) morphology in the development of conduction disturbances following TAVR. METHODS AND RESULTS: Consecutive patients who underwent TAVR in our center were included. The ratio between the LVOT area and the aortic annulus area was calculated. Patients were then divided into 2 groups on the basis of this ratio: group 1, which included patients with an LVOT area/aortic annulus area ratio <0.9; and group 2, which included patients with an LVOT area/aortic annulus area ratio ≥0.9. The primary end point was to assess the relationship between LVOT shape and the rate of permanent pacemaker implantation following TAVR. A multivariable analysis was performed to identify predictors of permanent pacemaker implantation following TAVR. From January 2018 to December 2020, 276 patients were included. Ninety-one patients with tapered LVOT morphology were assigned to group 1 and the rest (n=185 patients), tubular LVOT or flared LVOT shape, to group 2. The mean age was 81.5±5.7 years and 57% were women. After adjusting by confounding factors, tapered morphology of the LVOT and prior right bundle-branch block were found to be independent predictors of permanent pacemaker implantation (hazard ratio [HR], 2.6 [95% CI, 1.2-5.7]; P=0.014; and HR: 4.3 [95% CI 2.4-7.6], P<0.001); at a median follow-up time of 15.5 (interquartile range, 15) months. CONCLUSIONS: A tapered-LVOT morphology was associated with increased risk for permanent pacemaker implantation. LVOT morphology may be an additional factor to consider when choosing prosthesis size.

Percutaneous coronary interventions for aneurysmatic right coronary artery in acute coronary syndrome: RIGHTMARE registry outcomes.

BACKGROUND: The optimal strategy during percutaneous coronary intervention (PCI) of aneurysmatic right coronary artery (ARCA) remains uncertain and has never been tested in the acute setting. OBJECTIVES: To compare the in-hospital and long-term outcomes of immediate and staged PCI strategies for ARCA as culprit lesions during acute coronary syndrome (ACS). METHODS: Among 102.376 PCIs performed in 18 European centers, a total of 85 patients presenting with acute coronary syndrome undergoing ARCA PCI were finally included in the analysis. PCI strategy (stenting performed during the immediate vs staged procedure) and pharmacological approach adopted were collected. The primary outcome was procedural success (technical success without in-hospital MACE). RESULTS: The primary outcome occurred in 48.2 % of cases, with no significant differences observed between the immediate and staged PCI groups (50.9 % vs 43.3 %, p = 0.504). Patients in the staged-PCI group had a significantly higher rate of intravenous anticoagulant use (83.3 % vs 48.1 %, p = 0.002), BARC type 3 and 5 bleedings (12.9 % vs 1.9 %, p = 0.037), and longer in-hospital stay (7.40 ± 5.11 vs 9.5 ± 5.25 days, p = 0.049). After multivariate analysis, no independent predictors for procedural success were found in either group. Target lesion failure occurred in 24.1 % of cases without differences between groups at a median follow-up of three years. CONCLUSIONS: Among patients undergoing ARCA PCI in the setting of ACS, immediate or staged PCI were associated with similar in-hospital and long-term outcomes. However, staged PCI was associated with a higher risk of major bleeding events and longer length of stay compared to immediate PCI strategy.

Left ventricular outflow tract obstruction in Takotsubo syndrome with cardiogenic shock: prognosis and treatment.

BACKGROUND: Patients with Takotsubo syndrome (TTS) who develop cardiogenic shock may present with left ventricular outflow tract obstruction (LVOTO). The prognosis and treatment of this population have not been defined in previous studies. The aim of this study is to describe the clinical presentation, management, evolution and prognosis of a subgroup of patients with TTS and cardiogenic shock according to whether they present with LVOTO or not. METHODS: We analysed patients with TTS recruited from 2003 to 2022 in a multicentre registry. Patients were selected if they presented cardiogenic shock during their admission. This analysis was compared according to the presence or absence of LVOTO. RESULTS: 322 patients were included, 58 (18%) of whom had LVOTO. The majority were treated with vasoactive and inotropic therapy (VIT) and its use was strongly associated with having LVOTO (77.6% vs 57.6%, p<0.001). Only five (3.3%) patients without LVOTO and two (4.4%) in the LVOTO group treated with VIT developed or worsened the obstruction. Furthermore, patients with LVOTO presented higher in-hospital complications including ventricular arrhythmias (15.5% vs 8.7%, p=0.017), major bleeding (13.8% vs 6.1%, p=0.042) and acute kidney failure (48.3% vs 28.4%, p=0.003). However, at both 90 days and 5 years, the cumulative incidence of all-cause death was not significantly different between the patients with and without LVOTO (HR 1.20, 95% CI 0.60 to 2.40 for 90 days, and HR 1.69, 95% CI 0.89 to 3.21 for 5 years). CONCLUSIONS: LVOTO is not uncommon in patients with TTS and cardiogenic shock. It is associated with a more aggressive in-hospital course and our data is unable to rule out an association between the presence of LVOTO and long-term prognosis of patients with TTS. The development or worsening of LVOTO directly related to inotropic or vasoactive support was low.

Cardiovascular surgery and cardiology, current status of two sister specialties in Spain: the CARDIOXCARDIO study.

In recent years, there has been a notable shift in cardiovascular clinical practice within cardiology and surgery. The CARDIOXCARDIO study aimed to identify professionals' opinions on working practices and relations between specialties. A survey was simultaneously sent to the 4442 members of the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the Spanish Society of Cardiology (SEC), yielding 385 valid responses. More than half (59%) of respondents were men, mostly specialists (7.3% residents), and 74.8% worked in the field of cardiology, predominantly in public centers (88.3%). Using a Likert scale ranging from 1 to 5 (worst to best), respondents rated relations between surgery and cardiology with an average of 3.57±0.9 points. Cardiologists rated surgeons with a mean score of 3.83±0.8, while surgeons gave cardiologists a mean score of 3,92±0.72. In addition, respondents provided numerous suggestions for improvement, which are discussed in detail, highlighting certain discrepancies in criteria between specialties. Implementing strategies based on the suggestions of professionals, together with a proactive approach to continuous improvement, could substantially enhance the quality of cardiovascular care in Spain.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Risk prediction of major cardiac adverse events and all-cause death following covid-19 hospitalization at one year follow-up: The HOPE-2 score.

BACKGROUND: Long-term consequences of COVID-19 are still partly known. AIM OF THE STUDY: To derive a clinical score for risk prediction of long-term major cardiac adverse events (MACE) and all cause death in COVID-19 hospitalized patients. METHODS: 2573 consecutive patients were enrolled in a multicenter, international registry (HOPE-2) from January 2020 to April 2021 and identified as the derivation cohort. Five hundred and twenty-six patients from the Cardio-Covid-Italy registry were considered as external validation cohort. A long-term prognostic risk score for MACE and all cause death was derived from a multivariable regression model. RESULTS: Out of 2573 patients enrolled in the HOPE-2 registry, 1481 (58 %) were male, with mean age of 60±16 years. At long-term follow-up, the overall rate of patients affected by MACE and/or all cause death was 7.8 %. After multivariable regression analysis, independent predictors of MACE and all cause death were identified. The HOPE-2 prognostic score was therefore calculated by giving: 1-4 points for age class (<65 years, 65-74, 75-84, ≥85), 3 points for history of cardiovascular disease, 1 point for hypertension, 3 points for increased troponin serum levels at admission and 2 points for acute renal failure during hospitalization. Score accuracy at ROC curve analysis was 0.79 (0.74 at external validation). Stratification into 3 risk groups (<3, 3-6, >6 points) classified patients into low, intermediate and high risk. The observed MACE and all-cause death rates were 1.9 %, 9.4 % and 26.3 % for low- intermediate and high-risk patients, respectively (Log-rank test p < 0.01). CONCLUSIONS: The HOPE-2 prognostic score may be useful for long-term risk stratification in patients with previous COVID-19 hospitalization. High-risk patients may require a strict 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.

Pediatric takotsubo cardiomyopathy: A review and insights from a National Multicentric Registry.

Takotsubo syndrome (TTS) in the pediatric population is an infrequent but relevant cause of morbidity and mortality, with limited studies addressing its clinical course and prognosis. We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. We included a total of 54 patients from 4 different hospitals in Spain, as well as pediatric TTS patients from the published literature. Comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between pediatric and adult population features. Patients with pediatric TTS are more commonly male and exhibit a higher prevalence of physical triggers. The left ventricular ejection fraction (LVEF) was significantly lower in the pediatric population (30.5 + 10.4 vs 36.9 + 16.9, p < 0.05), resulting in more than fivefold rates of cardiogenic shock on admission compared to the general adult TTS population (Killip IV 74.1% vs 10.5%, p < 0.001) with similar rates of death and recurrence between groups. TTS in the pediatric population presents a distinctive clinical profile, with higher prevalence of atypical symptoms and physical triggers, as well as higher rates of cardiogenic shock on admission and similar mortality and recurrence rates than those of the adult population. This study provides valuable insights into understanding pediatric TTS and underscores the necessity for further research in this age group.

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.

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.

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.