Ischaemic stroke in women with atrial fibrillation: temporal trends and clinical implications.

BACKGROUND AND AIMS: Female sex has been linked with higher risk of ischaemic stroke (IS) in atrial fibrillation (AF), but no prior study has examined temporal trends in the IS risk associated with female sex. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study included all patients with AF in Finland from 2007 to 2018. Ischaemic stroke rates and rate ratios were computed. RESULTS: Overall, 229 565 patients with new-onset AF were identified (50.0% women; mean age 72.7 years). The crude IS incidence was higher in women than in men across the entire study period (21.1 vs. 14.9 events per 1000 patient-years, P < .001), and the incidence decreased both in men and women. In 2007-08, female sex was independently associated with a 20%-30% higher IS rate in the adjusted analyses, but this association attenuated and became statistically non-significant by the end of the observation period. Similar trends were observed when time with and without oral anticoagulant (OAC) treatment was analysed, as well as when only time without OAC use was considered. The decrease in IS rate was driven by patients with high IS risk, whereas in patients with low or moderate IS risk, female sex was not associated with a higher IS rate. CONCLUSIONS: The association between female sex and IS rate has decreased and become non-significant over the course of the study period from 2007 to 2018, suggesting that female sex could be omitted as a factor when estimating expected IS rates and the need for OAC therapy in patients with AF.

Highly Sensitive Immunoassay for Long Forms of Cardiac Troponin T Using Upconversion Luminescence.

BACKGROUND: Long cardiac troponin T (cTnT) has been proposed to be a promising and more specific biomarker of acute myocardial infarction (AMI). As it represents a subfraction of circulating cTnT, detection of very low concentrations is a requirement. The aim of this study was to develop a novel, highly sensitive immunoassay for long cTnT. METHODS: A two-step sandwich-type immunoassay for long cTnT was developed, utilizing upconverting nanoparticles (UCNPs) as reporters. The limits of detection and quantitation were determined for the assay. Linearity and matrix effects were evaluated. Performance with clinical samples was assessed with samples from patients with non-ST elevation myocardial infarction (NSTEMI, n = 30) and end-stage renal disease (ESRD, n = 37) and compared to a previously developed time-resolved fluorescence (TRF)-based long cTnT assay and a commercial high-sensitivity cTnT assay. RESULTS: The novel assay reached a 28-fold lower limit of detection (0.40 ng/L) and 14-fold lower limit of quantitation (1.79 ng/L) than the previously developed TRF long cTnT assay. Li-heparin and EDTA plasma, but not serum, were found to be suitable sample matrixes for the assay. In a receiver operating characteristics curve analysis, the troponin ratio (long/total cTnT) determined with the novel assay showed excellent discrimination between NSTEMI and ESRD with an area under the curve of 0.986 (95% CI, 0.967-1.000). CONCLUSIONS: By utilizing upconversion luminescence technology, we developed a highly sensitive long cTnT assay. This novel assay can be a valuable tool for investigating the full potential of long cTnT as a biomarker for AMI. ClinicalTrials.gov Registration Number: NCT04465591.

Temporal trends of gender disparities in oral anticoagulant use in patients with atrial fibrillation.

AIMS: To investigate sex-specific temporal trends in the initiation of oral anticoagulant (OAC) therapy among patients diagnosed with atrial fibrillation (AF) in Finland between 2007 and 2018. METHODS: The registry-linkage Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) Study included all patients with incident AF in Finland from 2007 to 2018. The primary outcome was the initiation of any OAC therapy. RESULTS: We identified 229,565 patients with new-onset AF (50.0% women; mean age 72.7 years). The initiation of OAC therapy increased continuously during the observation period. While women were more likely to receive OAC therapy overall, after adjusting for age, stroke risk factors and other confounding factors, female sex was associated with a marginally lower initiation of OACs (unadjusted and adjusted hazard ratios comparing women to men: 1.08 (1.07-1.10) and 0.97 (0.96-0.98), respectively). Importantly, the gender disparities in OAC use attenuated and reached parity by the end of the observation period. Furthermore, when only patients eligible for OAC therapy according to the contemporary guidelines were included in the analyses, the gender inequalities in OAC initiation appeared minimal. Implementation of direct OACs for stroke prevention was slightly slower among women. CONCLUSION: This nationwide retrospective cohort study covering all patients with incident AF in Finland from 2007 to 2018 observed that although female sex was initially associated with a lower initiation of OAC therapy, the sex-related disparities resolved over the course of the study period.

Cardiac troponin elevation and mortality in takotsubo syndrome: New insights from the international takotsubo registry.

BACKGROUND: The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS). METHODS: Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis. RESULTS: Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001). CONCLUSION: This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up.

Sex- and age-specific differences in the use of antiarrhythmic therapies among atrial fibrillation patients: a nationwide cohort study.

AIMS: Atrial fibrillation (AF) patients frequently require active rhythm control therapy to maintain sinus rhythm and reduce symptom burden. Our study assessed whether antiarrhythmic therapies (AATs) are used disproportionately between men and women after new-onset AF. METHODS AND RESULTS: The nationwide Finnish anticoagulation in AF registry-based linkage study covers all patients with new-onset AF in Finland during 2007-2018. Study outcomes included initiation of AATs in the form of antiarrhythmic drugs (AADs), cardioversion, or catheter ablation. The study population constituted of 229 565 patients (50% females). Women were older than men (76.6 ± 11.8 vs. 68.9 ± 13.4 years) and had higher prevalence of hypertension or hyperthyroidism, but lower prevalence of vascular disease, diabetes, renal disease, and cardiomyopathies than men. Overall, 17.6% of women and 25.1% of men were treated with any AAT. Women were treated with AADs more often than men in all age groups [adjusted subdistribution hazard ratio (aSHR) 1.223, 95% confidence interval (CI) 1.187-1.261]. Cardioversions were also performed less often on women than on men aged <65 years (aSHR 0.722, 95% CI 0.695-0.749), more often in patients ≥ 75 years (aSHR 1.166, 95% CI 1.108-1.227), while no difference between the sexes existed in patients aged 65-74 years. Ablations were performed less often in women aged <65 years (aSHR 0.908, 95% CI 0.826-0.998) and ≥75 years (aSHR 0.521, 95% CI 0.354-0.766), whereas there was no difference in patients aged 65-74 years. CONCLUSION: Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.

Association of income and educational levels on initiation of oral anticoagulant therapy in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

AIMS: Socioeconomic disparities have been reported in the outcomes of patients with atrial fibrillation (AF). We assessed the hypothesis that AF patients with higher income or educational level are more frequently initiated with oral anticoagulant (OAC) therapy for stroke prevention. METHODS: The nationwide registry-based Finnish AntiCoagulation in Atrial Fibrillation cohort covers all patients with AF from all levels of care in Finland. Patients were divided into income quartiles according to their highest annual income during 2004-2018 and into three categories based on educational attainment. The outcome was the first redeemed OAC prescription. RESULTS: We identified 239 222 patients (mean age 72.7 ± 13.2 years, 49.8% female) with incident AF during 2007-2018. Higher income was associated with higher OAC initiation rate: compared to the lowest income quartile the adjusted SHRs (95% CI) for OAC initiation were 1.09 (1.07-1.10), 1.13 (1.11-1.14) and 1.13 (1.12-1.15) in the second, third and fourth income quartiles, respectively. Patients in the highest educational category had a slightly lower OAC initiation rate than patients in the lowest educational category (adjusted SHR 0.92 [95% CI 0.90-0.93]). Income-related disparities were larger and education-related disparities only marginal among patients at high risk of ischemic stroke. The socioeconomic disparities in OAC initiation within 1-year follow-up decreased from 2007 to 2018. The adoption of direct OACs as the initial anticoagulant was faster among patients with higher income or educational levels. CONCLUSION: These findings highlight potential missed opportunities in stroke prevention, especially among AF patients with low income, whereas the education-related disparities in OAC initiation appear controversial.

Rural-urban and geographical differences in prognosis of atrial fibrillation in Finland: a nationwide cohort study.

AIMS: Rural-urban disparities have been reported in the outcomes of cardiovascular diseases. We assessed whether rural-urban or other geographical disparities exist in the risk of ischemic stroke (IS) and death in patients with atrial fibrillation (AF) in Finland. METHODS: The registry-based FinACAF cohort study covers all patients with AF from all levels of care in Finland from 2007 to 2018. Patients were divided into rural-urban categories and into hospital districts (HDs) based on their municipality of residence. RESULTS: We identified 222,051 patients (50.1% female; mean age 72.8 years; mean follow-up 3.9 years) with new-onset AF, of whom 15,567 (7.0%) patients suffered IS and 72,565 (32.7%) died during follow-up. The crude IS rate was similar between rural and urban areas, whereas the mortality rate was lower in urban areas (incidence rate ratios (IRRs) with 95% confidence intervals (CIs) 0.97 (0.93-1.00) and 0.92 (0.91-0.93), respectively). However, after adjustments, urban residence was associated with slightly higher IS and mortality rates (IRRs with 95% CIs 1.05 (1.01-1.08) and 1.06 (1.04-1.07), respectively). The highest crude IS rate was in the East Savo HD and the lowest in Åland, whereas the highest crude mortality rate was in the Länsi-Pohja HD and the lowest in the North Ostrobothnia HD (IRRs with 95% CIs compared to Helsinki and Uusimaa HD for IS 1.46 (1.28-1.67) and 0.79 (0.62-1.01), and mortality 1.24 (1.16-1.32) and 0.97 (0.93-1.00), respectively. CONCLUSIONS: Rural-urban differences in prognosis of AF in Finland appear minimal, whereas considerable disparities exist between HDs.

Mental health conditions and risk of first-ever ischaemic stroke and death in patients with incident atrial fibrillation: A nationwide cohort study.

BACKGROUND: Atrial fibrillation (AF) patients with mental health conditions (MHCs) have higher incidence of ischaemic stroke (IS) than patients without MHC, but whether this results from direct impact of MHCs or relates to higher prevalence of comorbidities and differences in the use of oral anticoagulant (OAC) therapy is unclear. We assessed the hypothesis that MHCs independently increase the risk of IS in patients with incident AF. METHODS: The nationwide FinACAF cohort covered all 203,154 patients diagnosed with incident AF without previous IS or transient ischaemic attack in Finland during 2007-2018. MHCs of interest were depression, bipolar disorder, anxiety disorder, schizophrenia and any MHC. The outcomes were first-ever IS and all-cause death. RESULTS: The patients' (mean age 73.0 ± 13.5 years, 49.0% female) mean follow-up time was 4.3 (SD 3.3) years and 16,272 (8.0%) experienced first-ever IS and 63,420 (31.2%) died during follow-up. After propensity score matching and adjusting for OAC use, no MHC group was associated with increased IS risk (adjusted SHRs (95% CI): depression 0.961 (0.857-1.077), bipolar disorder 1.398 (0.947-2.006), anxiety disorder 0.878 (0.718-1.034), schizophrenia 0.803 (0.594-1.085) and any MHC 1.033 (0.985-1.085)). Lower rate of OAC use partly explained the observed higher crude IS incidence in patients with any MHC. Depression, schizophrenia and any MHC were associated with higher all-cause mortality (adjusted HRs [95% CI]: 1.208 [1.136-1.283], 1.543 [1.352-1.761] and 1.149 [1.116-1.175], respectively). CONCLUSIONS: In this nationwide retrospective cohort study, MHCs were not associated with the incidence of first-ever IS in patients with AF.

Mechanocardiography in the Detection of Acute ST Elevation Myocardial Infarction: The MECHANO-STEMI Study.

Novel means to minimize treatment delays in patients with ST elevation myocardial infarction (STEMI) are needed. Using an accelerometer and gyroscope on the chest yield mechanocardiographic (MCG) data. We investigated whether STEMI causes changes in MCG signals which could help to detect STEMI. The study group consisted of 41 STEMI patients and 49 control patients referred for elective coronary angiography and having normal left ventricular function and no valvular heart disease or arrhythmia. MCG signals were recorded on the upper sternum in supine position upon arrival to the catheterization laboratory. In this study, we used a dedicated wearable sensor equipped with 3-axis accelerometer, 3-axis gyroscope and 1-lead ECG in order to facilitate the detection of STEMI in a clinically meaningful way. A supervised machine learning approach was used. Stability of beat morphology, signal strength, maximum amplitude and its timing were calculated in six axes from each window with varying band-pass filters in 2-90 Hz range. In total, 613 features were investigated. Using logistic regression classifier and leave-one-person-out cross validation we obtained a sensitivity of 73.9%, specificity of 85.7% and AUC of 0.857 (SD = 0.005) using 150 best features. As a result, mechanical signals recorded on the upper chest wall with the accelerometers and gyroscopes differ significantly between STEMI patients and stable patients with normal left ventricular function. Future research will show whether MCG can be used for the early screening of STEMI.

Mechanocardiography-Based Measurement System Indicating Changes in Heart Failure Patients during Hospital Admission and Discharge.

Heart failure (HF) is a disease related to impaired performance of the heart and is a significant cause of mortality and treatment costs in the world. During its progression, HF causes worsening (decompensation) periods which generally require hospital care. In order to reduce the suffering of the patients and the treatment cost, avoiding unnecessary hospital visits is essential, as hospitalization can be prevented by medication. We have developed a data-collection device that includes a high-quality 3-axis accelerometer and 3-axis gyroscope and a single-lead ECG. This allows gathering ECG synchronized data utilizing seismo- and gyrocardiography (SCG, GCG, jointly mechanocardiography, MCG) and comparing the signals of HF patients in acute decompensation state (hospital admission) and compensated condition (hospital discharge). In the MECHANO-HF study, we gathered data from 20 patients, who each had admission and discharge measurements. In order to avoid overfitting, we used only features developed beforehand and selected features that were not outliers. As a result, we found three important signs indicating the worsening of the disease: an increase in signal RMS (root-mean-square) strength (across SCG and GCG), an increase in the strength of the third heart sound (S3), and a decrease in signal stability around the first heart sound (S1). The best individual feature (S3) alone was able to separate the recordings, giving 85.0% accuracy and 90.9% accuracy regarding all signals and signals with sinus rhythm only, respectively. These observations pave the way to implement solutions for patient self-screening of the HF using serial measurements.

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery--LAA-CLOSURE trial protocol.

Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.

Minor troponin T elevation and mortality in patients with atrial fibrillation presenting to the emergency department.

BACKGROUND: There are limited data on the association of minor troponin elevation in unselected patients with atrial fibrillation (AF) presenting to the emergency department (ED) with adverse events. In this study, we sought to assess the early and mid-term mortality of these patients. METHODS: In this observational study, 2911 patients with AF were admitted to the ED. They were divided into 3 groups based on peak high-sensitivity troponin (TnT) levels: normal (<15 ng/L), 15-50 ng/L and 51-100 ng/L. The primary outcomes of this study were all-cause mortality at 30 days and 1 year. RESULTS: All-cause mortality was 6.7% (n = 196) at 30 days and 22.2% (n = 646) at 1 year. Mortality rate increased along with increasing levels of TnT irrespective of baseline covariates, primary discharge diagnosis and type of AF. A significant association between TnT levels and all-cause mortality was observed. The adjusted hazard ratio (HR) at 30 days was 6.02 (95% CI 2.62-13.83) for TnT 15-50 ng/L and 11.28 (95% CI 4.87-26.12) for TnT 51-100 ng/L (P<.001 for both) compared to TnT <15 ng/L. At 1 year, the adjusted HRs were 3.08 (95% CI 2.15-4.40) and 5.07 (95% CI 3.49-7.35), respectively (P < .001). When patients with TnT <15 ng/L were divided into two groups at the median value, TnT elevation of 10 to 14 ng/L was also associated with increased 1-year mortality (HR 2.51; 95% CI 1.09-5.74; P = .03). CONCLUSIONS: Among patients with AF admitted to the ED, increased TnT levels were associated with increased early and mid-term all-cause mortality irrespective of baseline covariates and type of AF.

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Coexistence and outcome of coronary artery disease in Takotsubo syndrome.

AIMS: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. METHODS AND RESULTS: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. CONCLUSIONS: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01947621.

Interatrial block, P terminal force or fragmented QRS do not predict new-onset atrial fibrillation in patients with severe chronic kidney disease.

BACKGROUND: The prevalence of left atrial enlargement (LAE) and fragmented QRS (fQRS) diagnosed using ECG criteria in patients with severe chronic kidney disease (CKD) is unknown. Furthermore, there is limited data on predicting new-onset atrial fibrillation (AF) with LAE or fQRS in this patient group. METHODS: We enrolled 165 consecutive non-dialysis patients with CKD stage 4-5 without prior AF diagnosis between 2013 and 2017 in a prospective follow-up cohort study. LAE was defined as total P-wave duration ≥120 ms in lead II ± > 1 biphasic P-waves in leads II, III or aVF; or duration of terminal negative portion of P-wave > 40 ms or depth of terminal negative portion of P-wave > 1 mm in lead V1 from a baseline ECG, respectively. fQRS was defined as the presence of a notched R or S wave or the presence of ≥1 additional R waves (R') or; in the presence of a wide QRS complex (> 120 ms), > 2 notches in R or S waves in two contiguous leads corresponding to a myocardial region, respectively. RESULTS: Mean age of the patients was 59 (SD 14) years, 56/165 (33.9%) were female and the mean estimated glomerular filtration rate was 12.8 ml/min/1.73m2. Altogether 29/165 (17.6%) patients were observed with new-onset AF within median follow-up of 3 [IQR 3, range 2-6] years. At baseline, 137/165 (83.0%) and 144/165 (87.3%) patients were observed with LAE and fQRS, respectively. Furthermore, LAE and fQRS co-existed in 121/165 (73.3%) patients. Neither findings were associated with the risk of new-onset AF within follow-up. CONCLUSION: The prevalence of LAE and fQRS at baseline in this study on CKD stage 4-5 patients not on dialysis was very high. However, LAE or fQRS failed to predict occurrence of new-onset AF in these patients.

Cardiac arrest in takotsubo syndrome: results from the InterTAK Registry.

AIMS: We aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS). METHODS AND RESULTS: We reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission. CONCLUSIONS: Cardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy.

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS: Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).