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.

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.

Long-term prognostic impact of beta-blockers in patients with Takotsubo syndrome: Results from the RETAKO Registry.

BACKGROUND: No evidence-based therapy has yet been established for Takotsubo syndrome (TTS). Given the putative harmful effects of catecholamines in patients with TTS, beta-blockers may potentially decrease the intensity of the detrimental cardiac effects in those patients. OBJECTIVE: The purpose of this study was to assess the impact of beta-blocker therapy on long-term mortality and TTS recurrence. METHODS: The cohort study used the national Spanish Registry on TakoTsubo Syndrome (RETAKO). A total of 970 TTS post-discharge survivors, without pheochromocytoma, left ventricular outflow tract obstruction, sustained ventricular arrhythmias, and significant bradyarrhythmias, between January 1, 2003, and July 31, 2018, were assessed. Cox regression analysis and inverse probability weighting (IPW) propensity score analysis were used to evaluate the association between beta-blocker therapy and survival free of TTS recurrence. RESULTS: From 970 TTS patients, 582 (60.0%) received beta-blockers. During a mean follow-up of 2.5±3.3 years, there were 87 deaths (3.6 per 100 patients/year) and 29 TTS recurrences (1.2 per 100 patient/year). There was no significant difference in follow-up mortality or TTS recurrence in unadjusted and adjusted Cox analysis (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.59-1.27, and 0.95, 95% CI 0.57-1.13, respectively). After weighting and adjusting by IPW, differences in one-year survival free of TTS recurrence between patients treated and untreated with beta-blockers were not found (average treatment effect -0.01, 95% CI -0.07 to 0.04; p=0.621). CONCLUSIONS: In this observational nationwide study from Spain, there was no significant association between beta-blocker therapy and follow-up survival free of TTS recurrence.

Antiplatelet therapy at discharge and long-term prognosis in Takotsubo syndrome: Insights from the Spanish National Registry (RETAKO).

INTRODUCTION: Endothelial dysfunction and platelet activation have been highlighted as possible mediators in Takotsubo syndrome (TTS). Nevertheless, to date, evidence on the usefulness of antiplatelet therapy in TTS remains controversial. The aim of our study is to evaluate long-term prognosis in TTS patients treated with antiplatelet therapy (APT) at hospitalization discharge. MATERIAL AND METHODS: An ambispective cohort study from the Spanish National Takotsubo Registry database was performed (June 2002 to March 2017). Patients were divided into two groups: those who received APT at hospital discharge (APT cohort) and those who did not (non-APT cohort). Primary endpoint was all-cause death. Secondary endpoints included the composite of recurrence or readmission and a composite of death, recurrence or readmission. RESULTS: From a total of 741 patients, 728 patients were alive at discharge. Follow-up was performed in 544 patients, who were included in the final analysis: 321 patients (59.0%) in the APT cohort and 223 patients (41.0%) in the non-APT cohort. The APT cohort had a better clinical presentation and received more heart failure and acute coronary syndrome-like therapies (angiotensin converting enzyme inhibitors/angiotensin receptor blockers: 75.1% vs. 51.1%; p<0.001, betablockers: 71.3% vs. 50.7%; p<0.001, statins: 67.9% vs. 33.2%; p<0.001). After adjusting for confounder factors, APT at discharge was a protective factor for all-cause death (adjusted hazard ratio (HR) 0.315, 95% confidence interval (CI): 0.106-0.943; p=0.039) and the composite endpoint of all-cause death, recurrence or readmission (adjusted HR 0.318, 95% CI: 0.164-0.619; p=0.001) at month 25 of follow-up. CONCLUSION: Patients with TTS receiving APT at discharge presented better prognosis up to two-years of follow-up compared with their counterparts not receiving APT.

Happy Heart Syndrome: Frequency, Characteristics, and Outcome of Takotsubo Syndrome Triggered by Positive Life Events.

BACKGROUND: The association with a preceding stressor is a characteristic feature of takotsubo syndrome (TTS). Negative emotions before TTS are common and led to the popular term "broken heart syndrome." In contrast, pleasant triggers ("happy heart syndrome") are rare and are scarcely investigated. OBJECTIVES: The authors analyzed the frequency, clinical characteristics, and prognostic implications of positive emotional stressors in the multicenter GEIST (GErman-Italian-Spanish Takotsubo) Registry. METHODS: Patients enrolled in the registry were categorized according to their stressors. This analysis compared patients with pleasant emotional events with patients with negative emotional events. RESULTS: Of 2,482 patients in the registry, 910 patients (36.7%) exhibited an emotional trigger consisting of 873 "broken hearts" (95.9%) and 37 "happy hearts" (4.1%). Consequently, the prevalence of pleasant emotional triggers was 1.5% of all TTS cases. Compared with patients with TTS with negative preceding events, patients with happy heart syndrome were more frequently male (18.9% vs 5.0%; P < 0.01) and had a higher prevalence of atypical ballooning patterns (27.0% vs 12.5%; P = 0.01), particularly midventricular ballooning. In-hospital complications, including death, pulmonary edema, cardiogenic shock, or stroke (8.1% vs 12.3%; P = 0.45), and long-term mortality rates (2.7% vs 8.8%; P = 0.20) were similar in "happy hearts" and "broken hearts." CONCLUSIONS: Happy heart syndrome is a rare type of TTS characterized by a higher prevalence of male patients and atypical, nonapical ballooning compared with patients with negative emotional stressors. Despite similar short- and long-term outcomes in our study, additional data are needed to explore whether numerically lower event rates in "happy hearts" would be statistically significant in a larger sample size. (GErman-Italian-Spanish Takotsubo Registry [GEIST Registry]; NCT04361994).

Association of renin-angiotensin system blockers with COVID-19 diagnosis and prognosis in patients with hypertension: a population-based study.

BACKGROUND: The effect of renin-angiotensin system (RAS) blockade either by angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs) on coronavirus disease 2019 (COVID-19) susceptibility, mortality and severity is inadequately described. We examined the association between RAS blockade and COVID-19 diagnosis and prognosis in a large population-based cohort of patients with hypertension (HTN). METHODS: This is a cohort study using regional health records. We identified all individuals aged 18-95 years from 87 healthcare reference areas of the main health provider in Catalonia (Spain), with a history of HTN from primary care records. Data were linked to COVID-19 test results, hospital, pharmacy and mortality records from 1 March 2020 to 14 August 2020. We defined exposure to RAS blockers as the dispensation of ACEi/ARBs during the 3 months before COVID-19 diagnosis or 1 March 2020. Primary outcomes were: COVID-19 infection and severe progression in hospitalized patients with COVID-19 (the composite of need for invasive respiratory support or death). For both outcomes and for each exposure of interest (RAS blockade, ACEi or ARB) we estimated associations in age-, sex-, healthcare area- and propensity score-matched samples. RESULTS: From a cohort of 1 365 215 inhabitants we identified 305 972 patients with HTN history. Recent use of ACEi/ARBs in patients with HTN was associated with a lower 6-month cumulative incidence of COVID-19 diagnosis {3.78% [95% confidence interval (CI) 3.69-3.86%] versus 4.53% (95% CI 4.40-4.65%); P < 0.001}. In the 12 344 patients with COVID-19 infection, the use of ACEi/ARBs was not associated with a higher risk of hospitalization with need for invasive respiratory support or death [OR = 0.91 (0.71-1.15); P = 0.426]. CONCLUSIONS: RAS blockade in patients with HTN is not associated with higher risk of COVID-19 infection or with a worse progression of the disease.

Serum Metabolomic Analysis Suggests Impairment of Myocardial Energy Production in Takotsubo Syndrome.

INTRODUCTION: Takotsubo syndrome is a complex entity that, although it usually has a good prognosis, can be life threatening. While recent advances have improved the knowledge of takotsubo syndrome, many aspects of its etiology still remain uncertain. Metabolomics, a hypothesis generating approach, could provide novel pathophysiology information about this disease. METHODS AND RESULTS: Serum samples were obtained from takotsubo (n = 19) and acute myocardial infarction patients (n = 8) at the cath lab and, in the case of takotsubo, again once the patient had recovered, 3 months after the main event. 1H NMR spectra of the serum were acquired at 9.4T using a CPMG pulse sequence (32 ms effective delay). Supervised and unsupervised pattern recognition approaches where applied to the data. Pattern recognition was able to differentiate between takotsubo and acute myocardial infarction during the acute phase with 95% accuracy. Myocardial infarction patients showed an increase in lipid signals, a known risk factor for the disease while takotsubo patients showed a relative increase in acetate that could suggest a reduced turnover of the Krebs cycle. When comparing acute and recovered phases, we could detect an increase in alanine and creatine once patients recovered. CONCLUSIONS: Our results demonstrate that takotsubo syndrome is metabolically different than AMI, showing limited myocardial energy production capacity during the acute phase. We achieved high classification success against AMI; however, this study should be considered as a proof of concept regarding clinical application of metabolic profiling in takotsubo cardiomyopathy.

Implicaciones clínicas y pronósticas en síndrome de Takotsubo y cáncer: percepciones del registro RETAKO / Takotsubo syndrome and cancer, clinical and prognostic implications, insights of RETAKO

ANTECEDENTES Y OBJETIVO: Se ha postulado una relación entre neoplasias y síndrome de Takotsubo (STB). Nuestro objetivo fue determinar su prevalencia en enfermos con STB, comparar el perfil clínico de STB con cáncer o no y estudiar su evolución a largo plazo. MATERIALES Y MÉTODOS: Analizamos la situación oncológica de pacientes incluidos en el REgistro nacional sobre síndrome de TAKOtsubo (RETAKO), ingresados entre 2002 y 2019, aportados por 38 hospitales de todo el país. Se admitió cualquier antecedente de malignidad/tumor que, aun benigno, recibiera quimioterapia, radioterapia o cirugía específica, actual o pasado. RESULTADOS: Se describió cualquier tipo de neoplasia en 129 (11,8%) casos, dentro de una cohorte de 1.097 pacientes con STB. Los oncológicos, con menor porcentaje de mujeres (79,1 vs. 88,3%; p = 0,003), mostraron una tendencia no significativa a mayor edad, hiperuricemia, apnea del sueño, con un menor FEVI al ingreso, y un perfil de factores de riesgo cardiovascular similar, pero más anemia crónica e inmunosupresión. La neoplasia más frecuente fue el cáncer de mama. Durante su estancia hospitalaria, los oncológicos mostraron más complicaciones, destacando insuficiencia cardiaca/shock, insuficiencia renal aguda y una tendencia en el combinado de infecciones. En el seguimiento, presentaron mayor mortalidad y más sucesos combinados MACE, con una tendencia, no significativa, a la aparición de recurrencias o reingresos cardiovasculares. CONCLUSIONES: La prevalencia de neoplasias en pacientes con STB fue elevada. La presentación clínica fue diferente en relación con los pacientes que no las presentan y suponen probablemente un factor de riesgo de peor pronóstico, tanto hospitalario como a largo plazo

BACKGROUND AND OBJECTIVES: A relationship between neoplasms and Takotsubo syndrome (TS) has been postulated. Our goal was to determine its prevalence in patients with TS, compare the clinical profile of TS with or without cancer and study its long-term evolution. MATERIALS AND METHODS: The oncological situation of patients included in the National Registry on TAKOtsubo syndrome (RETAKO), admitted between 2002 and 2019, provided by 38 hospitals throughout the country is analysed. Any history of malignancy or tumour, even benign, that received chemotherapy, radiotherapy or specific surgery, current or past, was considered. RESULTS: Any type of neoplasm was described in 129 (11.8%), within a cohort of 1,097 patients with TS. The cohort of patients with neoplasm, with a lower percentage of women (79.1 vs. 88.3%; P=.003), showed a non-significant tendency at an older age, hyperuricaemia, sleep apnoea and lower LVEF on admission, with a similar cardiovascular risk factor profile, but more chronic anaemia and immunosuppression. The most common neoplasm was breast cancer. During their hospital stay, the cancer patients suffered more complications, highlighting heart failure/shock, acute renal failure and a trend towards combined infections. On follow-up, they presented higher mortality and more combined MACE events, with a non-significant trend in the occurrence of cardiovascular recurrences or readmissions. CONCLUSIONS: The prevalence of neoplasms in patients with TS is high. The clinical presentation is different in relation to patients who do not have neoplasms and they probably represent a risk factor for a worse hospital and long term prognosis

1H NMR serum metabolomic profiling of patients at risk of cardiovascular diseases performing stress test.

Cardiovascular diseases are the leading cause of death worldwide. Changes in lifestyle and/or pharmacological treatment are able to reduce the burden of coronary artery diseases (CAD) and early diagnosis is crucial for the timely and optimal management of the disease. Stress testing is a good method to measure the burden of CAD but it is time consuming and pharmacological testing may not fully mimic exercise test. The objectives of the present project were to characterize the metabolic profile of the population undergoing pharmacological and exercise stress testing to evaluate possible differences between them, and to assess the capacity of 1H NMR spectroscopy to predict positive stress testing. Pattern recognition was applied to 1H NMR spectra from serum of patients undergoing stress test and metabolites were quantified. The effects of the stress test, confounding variables and the ability to predict ischemia were evaluated using OPLS-DA. There was an increase in lactate and alanine concentrations in post-test samples in patients undergoing exercise test, but not in those submitted to pharmacological testing. However, when considering only pharmacological patients, those with a positive test result, showed increased serum lactate, that was masked by the much larger amount of lactate associated to exercise testing. In conclusion, we have established that pharmacological stress test does not reproduce the dynamic changes observed in exercise stress. Although there is promising evidence suggesting that 1H NMR based metabolomics could predict stress test results, further studies with much larger populations will be required in order to obtain a definitive answer.

Takotsubo syndrome and cancer, clinical and prognostic implications, insights of RETAKO. / Implicaciones clínicas y pronósticas en síndrome de Takotsubo y cáncer: percepciones del registro RETAKO.

BACKGROUND AND OBJECTIVES: A relationship between neoplasms and Takotsubo syndrome (TS) has been postulated. Our goal was to determine its prevalence in patients with TS, compare the clinical profile of TS with or without cancer and study its long-term evolution. MATERIALS AND METHODS: The oncological situation of patients included in the National Registry on TAKOtsubo syndrome (RETAKO), admitted between 2002 and 2019, provided by 38 hospitals throughout the country is analysed. Any history of malignancy or tumour, even benign, that received chemotherapy, radiotherapy or specific surgery, current or past, was considered. RESULTS: Any type of neoplasm was described in 129 (11.8%), within a cohort of 1,097 patients with TS. The cohort of patients with neoplasm, with a lower percentage of women (79.1 vs. 88.3%; P=.003), showed a non-significant tendency at an older age, hyperuricaemia, sleep apnoea and lower LVEF on admission, with a similar cardiovascular risk factor profile, but more chronic anaemia and immunosuppression. The most common neoplasm was breast cancer. During their hospital stay, the cancer patients suffered more complications, highlighting heart failure/shock, acute renal failure and a trend towards combined infections. On follow-up, they presented higher mortality and more combined MACE events, with a non-significant trend in the occurrence of cardiovascular recurrences or readmissions. CONCLUSIONS: The prevalence of neoplasms in patients with TS is high. The clinical presentation is different in relation to patients who do not have neoplasms and they probably represent a risk factor for a worse hospital and long term prognosis.

Advanced interatrial block and P-wave duration are associated with atrial fibrillation and stroke in older adults with heart disease: the BAYES registry.

AIMS: Advanced interatrial block (IAB), is an unrecognized surrogate of atrial dysfunction and a trigger of atrial dysrhythmias, mainly atrial fibrillation (AF). Our aim was to prospectively assess whether advanced IAB in sinus rhythm is associated with AF and stroke in elderly outpatients with structural heart disease, a group not previously studied. METHODS AND RESULTS: Prospective observational registry that included outpatients aged ≥70 years with structural heart disease and no previous diagnosis of AF. Patients were divided into three groups: normal P-wave duration (<120 ms), partial IAB (P-wave duration ≥120 ms, positive in the inferior leads), and advanced IAB [P-wave duration ≥120 ms, biphasic (plus/minus) morphology in the inferior leads]. Among 556 individuals, 223 had normal P-wave (40.1%), 196 partial IAB (35.3%), and 137 advanced IAB (24.6%). After a median follow-up of 694 days, 93 patients (16.7%) developed AF, 30 stroke (5.4%), and 34 died (6.1%). Advanced IAB was independently associated with AF -[hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.7-5.1; P < 0.001], stroke [HR 3.8, 95% CI 1.4-10.7; P = 0.010), and AF/stroke (HR 2.6, 95% CI 1.5-4.4; P = 0.001). P-wave duration (ms) was independently associated with AF (HR 1.05, 95% CI 1.03-1.07; P < 0.001), AF/stroke (HR 1.04, 95% CI 1.02-1.06; P < 0.001), and mortality (HR 1.04, 95% CI 1.00-1.08; P = 0.021). CONCLUSIONS: The presence of advanced IAB in sinus rhythm is independently associated with AF and stroke in an elderly population with structural heart disease and no previous diagnosis of AF. P-wave duration was also associated with all-cause mortality.

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.

Sex differences in the 1H NMR metabolic profile of serum in cardiovascular risk patients.

Personalized diagnosis and risk stratification of cardiovascular diseases would allow optimizing therapeutic strategies and lifestyle changes. Metabolomics is a promising technique for personalized diagnosis and prognosis; however, various physiological parameters, including sex, influence the metabolic profile thus hampering its translation to the clinic. Knowledge of the variation in the metabolic profile associated with sex would facilitate metabolomic translation to the clinic. The objective of the present work was to investigate the possible differences in the metabolic 1H NMR profile associated to sex beyond lipoproteins. 1H NMR spectra from whole serum and methanol deproteinized samples from 39 patients (22 males, 17 females) between 55-70 years old with suspected coronary artery disease that underwent a stress test that was considered negative where included. Deproteinized serum could be used to differentiate sex based on higher levels of lactate and glucose in women. Lipoprotein region was the most variable area of the spectra between individuals, but spectra of whole serum were able to differentiate sex based on lipoproteins. There are sex-related differences in the 1H NMR metabolic profile of individuals with suspected cardiovascular disease beyond lipoproteins. These findings may help the translation of metabolomics to the clinic.

Metabolomics and Heart Diseases: From Basic to Clinical Approach.

BACKGROUND: The field of metabolomics has been steadily increasing in size for the last 15 years. Advances in analytical and statistical methods have allowed metabolomics to flourish in various areas of medicine. Cardiovascular diseases are some of the main research targets in metabolomics, due to their social and medical relevance, and also to the important role metabolic alterations play in their pathogenesis and evolution. Metabolomics has been applied to the full spectrum of cardiovascular diseases: from patient risk stratification to myocardial infarction and heart failure. However - despite the many proof-ofconcept studies describing the applicability of metabolomics in the diagnosis, prognosis and treatment evaluation in cardiovascular diseases - it is not yet used in routine clinical practice. Recently, large phenome centers have been established in clinical environments, and it is expected that they will provide definitive proof of the applicability of metabolomics in clinical practice. But there is also room for small and medium size centers to work on uncommon pathologies or to resolve specific but relevant clinical questions. OBJECTIVES: In this review, we will introduce metabolomics, cover the metabolomic work done so far in the area of cardiovascular diseases. CONCLUSION: The cardiovascular field has been at the forefront of metabolomics application and it should lead the transfer to the clinic in the not so distant future.

Short- and Long-Term Prognostic Relevance of Cardiogenic Shock in Takotsubo Syndrome: Results From the RETAKO Registry.

OBJECTIVES: This study sought to describe the incidence, determinants, and prognostic impact of cardiogenic shock (CS) in takotsubo syndrome (TTS). BACKGROUND: TTS can be associated with severe hemodynamic instability. The prognostic implication of CS has not been well characterized in large studies of TTS. METHODS: We analyzed patients with a definitive TTS diagnosis (modified Mayo criteria) who were recruited for the National RETAKO (Registry on Takotsubo Syndrome) trial from 2003 to 2016. Cox and competing risk regression models were used to identify factors associated with mortality and recurrences. RESULTS: A total of 711 patients were included, 81 (11.4%) of whom developed CS. Male sex, QTc interval prolongation, lower left ventricular ejection fraction at admission, physical triggers, and presence of "a significant" left intraventricular pressure gradient, were associated with CS (C index = 0.85). In-hospital complication rates, including mortality, were significantly higher in patients with CS. Over a median follow-up of 284 days (interquartile range: 94 to 929 days), CS was the strongest independent predictor of long-term, all-cause mortality (hazard ratio [HR]: 5.38; 95% confidence interval [CI]: 2.60 to 8.38); cardiovascular (CV) death (sub-HR: 4.29; 95% CI: 2.40 to 21.2), and non-CV death (sub-HR: 3.34; 95% CI: 1.70 to 6.53), whereas no significant difference in the recurrence rate was observed between groups (sub-HR: 0.76; 95% CI: 0.10 to 5.95). Among patients with CS, those who received beta-blockers at hospital discharge experienced lower 1-year mortality compared with those who did not receive a beta-blocker (HR: 0.52; 95% CI: 0.44 to 0.79; pinteraction = 0.043). CONCLUSIONS: CS is not uncommon and is associated with worse short- and long-term prognosis in TTS. CS complicating TTS may constitute a marker of underlying disease severity and could identify a masked heart failure phenotype with increased vulnerability to catecholamine-mediated myocardial stunning.

Síndrome de tako-tsubo en varones: infrecuente, pero con mal pronóstico / Tako-tsubo syndrome in men: rare, but with poor prognosis

Introducción y objetivos: El síndrome de tako-tsubo es un proceso patológico potencialmente grave durante la fase aguda. Simula un infarto de miocardio, sin que haya lesiones coronarias potencialmente responsables. El objetivo de este trabajo es analizar la evolución y el pronóstico de los pacientes con síndrome de tako-tsubo en función del sexo. Métodos: Se analizaron las características de los pacientes incluidos en el registro RETAKO durante los años 2003 a 2015, un registro multicéntrico en el que participaron 32 hospitales españoles. Resultados: De los 562 pacientes incluidos, 493 (87,7%) eran mujeres. El dolor torácico fue menos frecuente como síntoma inicial en los varones que en las mujeres (43 [66,2%] frente a 390 [82,8%]; p < 0,01). El pronóstico fue peor en los varones, con mayor mortalidad intrahospitalaria (3 [4,4%] frente a 1 [0,2%]; p < 0,01), duración más prolongada de ingreso en cuidados intensivos (4,2 ± 3,7 frente a 3,2 ± 3,2 días; p = 0,03) y mayor frecuencia de insuficiencia cardiaca grave (22 [33,3%] frente a 95 [20,3%]; p = 0,02). Sin embargo la aparición de obstrucción dinámica a nivel del tracto de salida del ventrículo izquierdo se observó exclusivamente en mujeres (39 [7,9%] frente a 0 [0,0%]; p = 0,02) y la incidencia de insuficiencia mitral funcional también fue mayor en ellas (52 [10,6%] frente a 2 [2,9%]; p = 0,04). Conclusiones: El síndrome de tako-tsubo es una enfermedad que muestra grandes diferencias en función del sexo en cuanto a su incidencia, presentación y evolución, con un peor pronóstico en los varones

Introduction and objectives: Tako-tsubo syndrome is a potentially serious disease during the acute phase. It mimics myocardial infarction, but with no potentially causative coronary lesions. The aim of this study was to analyze the clinical course and outcome of patients with tako-tsubo syndrome by sex. Methods: We analyzed the characteristics of patients included in the RETAKO registry from 2003 to 2015, a multicenter registry with participation of 32 Spanish hospitals. Results: Of 562 patients included, 493 (87.7%) were women. Chest pain was less frequent as an initial symptom in men than in women (43 [66.2%] vs 390 [82.8%]; P < .01). The prognosis was worse in men, with higher in-hospital mortality (3 [4.4%] vs 1 [0.2%]; P < .01), longer intensive care stay (4.2 ± 3.7 vs 3.2 ± 3.2 days; P = .03) and a higher frequency of severe heart failure (22 [33.3%] vs 95 [20.3%]; P = .02). However, dynamic obstruction at the left-ventricular outflow tract occurred exclusively in women (39 [7.9%] vs 0 [0.0%]; P = .02). The incidence of functional mitral regurgitation was also higher in women (52 [10.6%] vs 2 [2.9%]; P = .04). Conclusions: Tako-tsubo syndrome shows wide differences by sex in terms of its incidence, presentation, and outcomes. Prognosis is worse in men