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Critical care cardiology (CCC) in the modern era is shaped by a multitude of innovative treatment options and an increasingly complex, ageing patient population. Generating high-quality evidence for novel interventions and devices in an intensive care setting is exceptionally challenging. As a result, formulating the best possible therapeutic approach continues to rely predominantly on expert opinion and local standard operating procedures. Fostering the full potential of CCC and the maturation of the next generation of decision-makers in this field calls for an updated training concept, that encompasses the extensive knowledge and skills required to care for critically ill cardiac patients while remaining adaptable to the trainee’s individual career planning and existing educational programs. In the present manuscript, we suggest a standardized training phase in preparation of the first ICU rotation, propose a modular CCC core curriculum, and outline how training components could be conceptualized within three sub-specialization tracks for aspiring cardiac intensivists.

Recombinant adeno-associated viruses (rAAVs) are promising gene delivery vectors in the emerging field of in vivo gene therapies. To ensure their consistent quality during manufacturing and process development, multiple analytical techniques have been proposed for the characterization and quantification of rAAV capsids. Despite their indisputable capabilities for performing this task, current analytical methods are rather time-consuming, material intensive, complicated, and costly, restricting their suitability for process development in which time and sample throughput are severe constraints. To eliminate this bottleneck, we introduce here an affinity-based high-performance liquid chromatography method that allows the determination of the capsid titer and the full/empty ratio of rAAVs within less than 5 min. By packing the commercially available AAVX affinity resin into small analytical columns, the rAAV fraction of diverse serotypes can be isolated from process-related impurities and analyzed by UV and fluorescence detection. As demonstrated by both method qualification data and side-by-side comparison with AAV enzyme-linked immunosorbent assay results for rAAV8 samples as well as by experiments using additional rAAV2, rAAV8, and rAAV9 constructs, our approach showed good performance, indicating its potential as a fast, simple and efficient tool for supporting the development of rAAV gene therapies.

The climate impact of aviation can be reduced using powertrains based on hydrogen fuel cells and batteries. Combining both technologies in a direct-hybrid without a DC/DC converter is a promising approach for light-weight systems. Depending on the power demand, both the fuel cell and battery are used to provide power or only the fuel cell is connected to the powertrain. The system voltage in a direct-hybrid is determined by the fuel cell and battery, but the performance of fuel cells is affected by low-ambient pressure at high altitudes and the battery voltage is affected by state of charge and discharge rate. Taking this into account, the presented work demonstrates how a direct-hybrid system must be designed based on a scaled mission profile of a 40-seater aircraft. The fuel cell and battery are configured and sized according to the power demand in different flight phases while considering voltage limits given by the powertrain. The energy requirement from the fuel cell and the battery is calculated for a flight based on a realistic mission profile and different battery and fuel cell configurations are evaluated. By optimizing the battery and fuel cell size, the energy required from the battery was reduced by 57% and the total weight of the fuel cell and battery was reduced by 11%.

Hybrid electric aircraft with a powertrain based on fuel cells and batteries can reduce climate-active emissions in aviation. In a direct hybrid powertrain, the fuel cell and the battery are connected in parallel, without a DC/DC converter balancing their voltage levels. Switches make it possible to select different operational modes (fuel cell only, hybrid or battery charging) depending on the power demand during different flight phases. To exploit the high specific energy of hydrogen, the system should change from Hybrid Mode during take-off to Fuel Cell Mode in cruise. During descent, the battery can be charged if Charging Mode is selected. To avoid voltage and current peaks and consequent damage to components when switching between modes, certain conditions must be fulfilled. Those switching conditions were defined, and switching procedures for changing from one mode to the other during flight were developed and tested in a lab system. In a direct hybrid, the system voltage depends on the required power. When switching from Hybrid Mode to Fuel Cell Mode, a short reduction in power of 65% is necessary for the examined system to meet the switching requirements. It is also shown how this power loss can be reduced to 25% by distributed propulsion with a second powertrain or even eliminated by a change in the hybrid ratio.

Efficacious and safe application of recombinant proteins in humans as drugs depends on their high purity accomplished by downstream processing. The present study evaluates the effects of kosmotropic salts used in the flow-through mode of mixed-mode anion exchange (MMAEX) chromatography to remove high molecular weight (HMW) impurities efficiently from monoclonal antibody (mAb) products. For this purpose, the impact of different kosmotropic salts at varying concentrations along with changes of the pH were systematically assessed by high throughput screens on a set of mAbs differing in their relative hydrophobicity. In contrast to the more hydrophobic mAbs, for the more hydrophilic mAbs, a clear and consistent removal of HMW species to values > 80% (achieving up to 2.5-fold improvement) occurred with the addition of increasing amounts of a kosmotropic salt (sodium chloride, sodium sulfate, ammonium sulfate, potassium chloride and potassium sulfate) to the loads applied to MMAEX chromatography. Overall, the herein described effect on the removal of HMW species by MMAEX resins was specific for kosmotropic salts, independent of conductivity, and facilitated by slightly basic pH conditions. These findings were confirmed at lab-scale operation achieving > 99% purity, indicating the potential to implement MMAEX in combination with kosmotropic salts as a polishing step for hydrophilic mAbs.

BackgroundThe new types of mRNA-containing lipid nanoparticle vaccines BNT162b2 and mRNA-1273 and the adenovirus-based vaccine AZD1222 were developed against SARS-CoV-2 and code for its spike (S) protein. Several studies have investigated short-term antibody (Ab) responses after vaccination.ObjectiveHowever, the impact of these new vaccine formats with unclear effects on the long-term Ab response – including isotype, subclass, and their type of Fc glycosylation – is less explored.MethodsHere, we analyzed anti-S Ab responses in blood serum and the saliva of SARS-CoV-2 naïve and non-hospitalized pre-infected subjects upon two vaccinations with different mRNA- and adenovirus-based vaccine combinations up to day 270.ResultsWe show that the initially high mRNA vaccine-induced blood and salivary anti-S IgG levels, particularly IgG1, markedly decrease over time and approach the lower levels induced with the adenovirus-based vaccine. All three vaccines induced, contrary to the short-term anti-S IgG1 response with high sialylation and galactosylation levels, a long-term anti-S IgG1 response that was characterized by low sialylation and galactosylation with the latter being even below the corresponding total IgG1 galactosylation level. Instead, the mRNA, but not the adenovirus-based vaccines induced long-term IgG4 responses – the IgG subclass with inhibitory effector functions. Furthermore, salivary anti-S IgA levels were lower and decreased faster in naïve as compared to pre-infected vaccinees. Predictively, age correlated with lower long-term anti-S IgG titers for the mRNA vaccines. Furthermore, higher total IgG1 galactosylation, sialylation, and bisection levels correlated with higher long-term anti-S IgG1 sialylation, galactosylation, and bisection levels, respectively, for all vaccine combinations.ConclusionIn summary, the study suggests a comparable “adjuvant” potential of the newly developed vaccines on the anti-S IgG Fc glycosylation, as reflected in relatively low long-term anti-S IgG1 galactosylation levels generated by the long-lived plasma cell pool, whose induction might be driven by a recently described TH1-driven B cell response for all three vaccines. Instead, repeated immunization of naïve individuals with the mRNA vaccines increased the proportion of the IgG4 subclass over time which might influence the long-term Ab effector functions. Taken together, these data shed light on these novel vaccine formats and might have potential implications for their long-term efficacy.

Summary: Background: Afucosylated IgG1 responses have only been found against membrane-embedded epitopes, including anti-S in SARS-CoV-2 infections. These responses, intrinsically protective through enhanced FcγRIIIa binding, can also trigger exacerbated pro-inflammatory responses in severe COVID-19. We investigated if the BNT162b2 SARS-CoV-2 mRNA also induced afucosylated IgG responses. Methods: Blood from vaccinees during the first vaccination wave was collected. Liquid chromatography-Mass spectrometry (LC-MS) was used to study anti-S IgG1 Fc glycoprofiles. Responsiveness of alveolar-like macrophages to produce proinflammatory cytokines in presence of sera and antigen was tested. Antigen-specific B cells were characterized and glycosyltransferase levels were investigated by Fluorescence-Activated Cell Sorting (FACS). Findings: Initial transient afucosylated anti-S IgG1 responses were found in naive vaccinees, but not in antigen-experienced ones. All vaccinees had increased galactosylated and sialylated anti-S IgG1. Both naive and antigen-experienced vaccinees showed relatively low macrophage activation potential, as expected, due to the low antibody levels for naive individuals with afucosylated IgG1, and low afucosylation levels for antigen-experienced individuals with high levels of anti-S. Afucosylation levels correlated with FUT8 expression in antigen-specific plasma cells in naive individuals. Interestingly, low fucosylation of anti-S IgG1 upon seroconversion correlated with high anti-S IgG levels after the second dose. Interpretation: Here, we show that BNT162b2 mRNA vaccination induces transient afucosylated anti-S IgG1 responses in naive individuals. This observation warrants further studies to elucidate the clinical context in which potent afucosylated responses would be preferred. Funding: LSBR 1721, 1908; ZonMW 10430012010021, 09150161910033, 10430012010008; DFG 398859914, 400912066, 390884018; PMI; DOI4-Nr. 3; H2020-MSCA-ITN 721815.

Inaccurate cell segmentation has been the major problem for cell-type identification and tissue characterization of the in situ spatially resolved transcriptomics data. Here we show a robust cell segmentation-free computational framework (SSAM), for identifying cell types and tissue domains in 2D and 3D.

Abstract The specific hemocompatibility properties of mechanical-circulatory-support (MCS)-pump technologies have not previously been described in a comparable manner. We thus investigated the hemocompatibility-indicating marker of a new magnetically-levitated (MagLev) centrifugal pump (MT-Mag) in a human, whole-blood mock-loop for 360 min using the MCS devices as a driving component. We compared those results with the CentriMag adult (C-Mag) device under the same conditions according to ISO10993-4. Blood samples were analyzed via enzyme-linked-immunosorbent-assay (ELISA) for markers of coagulation, complement system, and the inflammatory response. The time-dependent activation of the coagulation system was measured by detecting thrombin-anti-thrombin complexes (TAT). The activation of the complement system was determined by increased SC5b-9 levels in both groups. A significant activation of neutrophils (PMN-elastase) was detected within the C-Mag group, but not in the MT-Mag group. However, the amount of PMN-elastase at 360 min did not differ significantly between groups. The activation of the complement and coagulation system was found to be significantly time-dependent in both devices. However, coagulation activation as determined by the TAT level was lower in the MT-Mag group than in the C-Mag group. This slight disparity could have been achieved by the optimized secondary flow paths and surface coating, which reduces the interaction of the surface with blood.

Coronavirus disease 2019 (COVID-19) is a viral infection affecting multiple organ systems of great significance for metabolic processes. Thus, there is increasing interest in metabolic and lipoprotein signatures of the disease, and early analyses have demonstrated a metabolic pattern typical for atherosclerotic and hepatic damage in COVID-19 patients. However, it remains unclear whether this is specific for COVID-19 and whether the observed signature is caused by the disease or rather represents an underlying risk factor. To answer this question, we have analyzed 482 serum samples using nuclear magnetic resonance metabolomics, including longitudinally collected samples from 12 COVID-19 and 20 cardiogenic shock intensive care patients, samples from 18 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody-positive individuals, and single time point samples from 58 healthy controls. COVID-19 patients showed a distinct metabolic serum profile, including changes typical for severe dyslipidemia and a deeply altered metabolic status compared with healthy controls. Specifically, very-low-density lipoprotein and intermediate-density lipoprotein particles and associated apolipoprotein B and intermediate-density lipoprotein cholesterol were significantly increased, whereas cholesterol and apolipoprotein A2 were decreased. Moreover, a similarly perturbed profile was apparent when compared with other patients with cardiogenic shock who are in the intensive care unit when looking at a 1-week time course, highlighting close links between COVID-19 and lipid metabolism. The metabolic profile of COVID-19 patients distinguishes those from healthy controls and also from patients with cardiogenic shock. In contrast, anti-SARS-CoV-2 antibody-positive individuals without acute COVID-19 did not show a significantly perturbed metabolic profile compared with age- and sex-matched healthy controls, but SARS-CoV-2 antibody-titers correlated significantly with metabolic parameters, including levels of glycine, ApoA2, and small-sized low- and high-density lipoprotein subfractions. Our data suggest that COVID-19 is associated with dyslipidemia, which is not observed in anti-SARS-CoV-2 antibody-positive individuals who have not developed severe courses of the disease. This suggests that lipoprotein profiles may represent a confounding risk factor for COVID-19 with potential for patient stratification.

The aim of this in vitro study is to investigate the bonding properties of a 3D-printable permanent composite material in comparison to milled composite materials. The tested materials are 3D-printed BEGO VarseoSmile Crown plus (VA1_ab, VA1_nt, VA2_ab, VA2_nt), Vita Enamic (EN1, EN2), and 3M Lava Ultimate (UL1, UL2) (N = 64; n = 8). For this purpose, all crowns are luted to polymer tooth stumps #46 (FDI) using dual-curing luting composite, strictly according to the manufacturer’s instructions. VA1_ab and VA2_ab are additionally airborne-particle abraded. 4 groups (VA2_ab, VA2_nt, EN2, UL2) are artificially aged (1,200,000 cycles, 50 N, 10,000 thermocycles), whereby no specimen has failed. All 64 specimens undergo pull-off testing until retention loss. The mean forces of retention-loss is 786.6 ± 137.6 N (VA1_nt, *), 988.6 ± 212.1 N (VA2_nt, *, Ɨ), 1223.8 ± 119.2 N (VA1_ab, Ɨ, ǂ), 1051.9 ± 107.2 N (VA2_ab, *, Ɨ), 1185.9 ± 211.8 N (EN1, Ɨ, ǂ), 1485.0 ± 198.2 N EN2, ǂ), 1533.8 ± 42.4 N (UL1, ǂ), and 1521.8 ± 343.4 N (UL2, ǂ) (one-way ANOVA (Scheffé method); p < 0.05; *, Ɨ, ǂ: group distribution). No characteristic failure modes can be detected. In conclusion, all of the pull-off forces reflect retention values that seem to be sufficiently high for clinical use. Additional airborne-particle abrasion of VA does not result in significantly better retention but can be recommended.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of several human malignancies, particularly metastatic skin cancer. However, immune-related myocarditis (irM), an immune-mediated adverse event (irAE), is often fatal. In the absence of a reliable biomarker, measurement of pre-ICI therapy serum troponin concentration has been proposed to identify patients at risk of developing irM, although real-world studies examining this strategy are lacking. Thus, we retrospectively analyzed the case records of all patients who commenced ICI therapy between January 2018 and December 2019 in a single university skin cancer center (n = 121) to (i) determine the incidence of irM, (ii) establish the frequency of pretreatment serum hsTnT elevations, and (iii) to establish whether this identified patients who subsequently developed irM. Only one patient developed irM, resulting in an overall incidence of 0.8%. Pretreatment hsTnT was measured in 47 patients and was elevated in 13 (28%). Elevated serum hsTnT concentrations were associated with chronic renal failure (p = 0.02) and diabetes (p < 0.0002). Pretreatment hsTnT was not elevated in the patient who developed fulminant irM. Pre-immunotherapy serum hsTnT concentrations were often asymptomatically elevated in patients with advanced skin cancer, none of whom subsequently developed irM during ICI therapy. However, large studies are required to assess the positive and negative predictive values of hsTnT for the development of irM. In the meantime, elevated hsTnT concentrations should be investigated before initiation of immunotherapy and closely monitored during early treatment cycles, where the risk of irM is greatest.

Objectives In Europe, there is a distinction between two different healthcare organisation systems, the tax-based healthcare system (THS) and the social health insurance system (SHI). Our aim was to investigate whether the characteristics, treatment and mortality of older, critically ill patients in the intensive care unit (ICU) differed between THS and SHI.Setting ICUs in 16 European countries.Participants In total, 7817 critically ill older (≥80 years) patients were included in this study, 4941 in THS and 2876 in the SHI systems.Primary and secondary outcomes measures We chose generalised estimation equations with robust standard errors to produce population average adjusted OR (aOR). We adjusted for patient-specific variables, health economic data, including gross domestic product (GDP) and human development index (HDI), and treatment strategies.Results In SHI systems, there were higher rates of frail patients (Clinical Frailty Scale>4; 46% vs 41%; p

Background Intravenous morphine administration can adversely affect platelet inhibition induced by P2Y12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury. Methods and Results Patients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P=0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P=0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P=0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14–0.93 [P=0.035]). There was no significant difference in infarct size (P=0.491) and extent (P=0.753) or presence (P=0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group. Conclusions In this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02627950.

Background: The coronavirus disease (COVID-19) pandemic imposed diverse challenges on the health care system. Morbidity and mortality of non-COVID-19 emergencies might also have changed because hospitals may not be able to provide optimal care due to restructured resources and uncertainties how to deal with potentially infected patients. It has been recommended to stratify treatment of cardiovascular emergencies according to cardiovascular risk. However, data on the prevalence of asymptomatic SARS-CoV-2 infection in patients presenting with cardiac emergencies remain scarce.Methods: We retrospectively analyzed patients' data from a tertiary cardiology department between April 15 and May 31, 2020. All patients were screened on admission for COVID-19 symptoms using a questionnaire and body temperature measurements. All hospitalized patients were routinely screened using nasopharyngeal swab testing.Results: In total, we counted 710 urgent and emergency admissions. Nasopharyngeal swab tests were available in 689 (97%) patients, 409 and 280 of which presented as urgent and emergency admissions, respectively. Among 280 emergency admissions, none tested positive for SARS-CoV-2.Conclusion: In cardiac emergency patients which were screened negative for COVID-19 symptoms, the prevalence of SARS-CoV-2 infection in regions with a modest overall prevalence is low. This finding might be helpful to better determine timing of emergency procedures and reasonable usage of protective equipment during the COVID-19 crisis and the future.

Abstract Background In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs. Methods This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality. Results Patients had a median age of 84 [IQR 82–87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival. Conclusions The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany. Trial registration The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807) on May 1, 2017.

Besides mediating hemostatic functions, platelets are increasingly recognized as important players of inflammation. Data from experiments in mice and men revealed various intersection points between thrombosis, hemostasis, and inflammation, which are addressed and discussed in this review in detail. One such example is the intrinsic coagulation cascade that is initiated after platelet activation thereby further propagating and re-enforcing wound healing or thrombus formation but also contributing to the pathophysiology of severe diseases. FXII of the intrinsic pathway connects platelet activation with the coagulation cascade during immune reactions. It can activate the contact system thereby either creating an inflammatory state or accelerating inflammation. Recent insights into platelet biology could show that platelets are equipped with complement receptors. Platelets are important for tissue remodeling after injury has been inflicted to the endothelial barrier and to the subendothelial tissue. Thus, platelets are increasingly recognized as more than just cells relevant for bleeding arrest. Future insights into platelet biology are to be expected. This research will potentially offer novel opportunities for therapeutic intervention in diseases featuring platelet abundance.

Background: Ambulatory Blood Pressure (BP) as well as central BP are better predictors for overall cardiovascular risk and mortality than brachial BP. Renal Denervation (RDN) has been shown to reduce office brachial and central BP as well as ambulatory brachial BP, but data on central ambulatory BP are limited. We therefore aimed to study the effect of RDN also on central hemodynamics assessed under ambulatory conditions. Methods: In total 94 patients with treatment resistant hypertension (TRH) (office BP ≥140/90 mmHg, and diagnosis confirmed by mean daytime brachial ambulatory BP ≥135/85 mmHg) who underwent RDN (using Medtronic Symplicity™ RDN radiofrequency ablation catheter system) were included. Ambulatory BP, including central pressures, hemodynamics and arterial stiffness, were measured at baseline and 3, 6, 12 months after RDN by an oscillometric device (MobiloGraph™, I.E.M., Germany). Results: Office BP was significantly reduced at all time points (p for all

BACKGROUND:A substantial number of patients with Takotsubo syndrome (TTS) exhibit right ventricular (RV) dysfunction which has been associated with adverse outcome. The aim of this study was to assess the clinical and prognostic value of RV myocardial strain in TTS using cardiovascular magnetic resonance myocardial feature tracking (CMR-FT). METHODS:CMR-FT was performed in a core laboratory to determine RV longitudinal strain in 134 TTS patients undergoing CMR in median 2 days after admission to 2 experienced centers. For comparison, RV involvement was evaluated by sole visual assessment concerning RV contraction abnormalities. Both approaches were analyzed regarding their long-term prognostic value. RESULTS:The peak global RV longitudinal strain was in median -19%. Segmental analyses located contraction abnormalities primarily in the apical parts of the right ventricle. Sole visual assessment identified 38 patients (28%) with RV involvement. These patients showed a numerically higher long-term mortality without reaching statistical significance (17.1% versus 10.5%; hazard ratio 1.38 [95% confidence interval 0.49-3.88]; p = 0.31). The optimal RV strain cutoff value for risk prediction was -17.24%. Stratification according to this threshold categorized 41% of TTS patients (n = 55) in the high-risk group which demonstrated a significantly increased long-term mortality compared to patients with preserved global RV strain (20.0% versus 7.0%; hazard ratio 2.98 [95% confidence interval 1.02-8.73]; p = 0.03). CONCLUSIONS:The assessment of RV myocardial strain using CMR-FT enables an accurate evaluation of RV involvement in TTS and represents a promising approach for optimized risk stratification.

BackgroundLeft ventricular (LV) thrombi during Takotsubo syndrome represent a potential complication and can be associated with cerebrovascular embolic events. The aim of this study was to evaluate the exact incidence, predictors, and management strategies of LV thrombi in patients with Takotsubo syndrome. Methods and ResultsWe enrolled 541 consecutive patients in a multicenter international registry. Clinical features and echocardiographic data at admission, during hospitalization, and after 3 months were evaluated. Survival rates for long‐term follow‐up (mean 984±908 days) were recorded. Twelve Takotsubo syndrome patients (2.2%) developed LV thrombi (all female presenting with apical ballooning pattern). All patients with LV thrombi were treated with oral anticoagulation therapy; however, 2 (17%) had a stroke before treatment initiation. These patients were characterized by a higher prevalence of ST‐elevation (56% versus 16%; P10 ng/mL was the only predictor for LV thrombosis (hazard ratio 6.6, confidence interval, 1.01–40.0; P=0.04). After 3 months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted in all patients except 1. At long‐term follow‐up, the survival rate was not different between patients with and without LV thrombi (84% versus 85%; P=0.99). ConclusionsLV thrombi have a relatively low incidence among patients with Takotsubo syndrome and were detected in female patients with apical ballooning pattern and increased troponin levels. Oral anticoagulation therapy for 3 months seems reasonable in these high‐risk patients.

BackgroundDisrupted atherosclerotic plaques in the left anterior descending coronary artery are discussed controversially as a potential pathophysiological mechanism in Takotsubo syndrome (TTS). Therefore, the aim of the present study was to assess plaque burden and morphology by using optical coherence tomography in patients with TTS. Methods and ResultsA total of 23 consecutive TTS patients were included in this single‐center study and underwent optical coherence tomography imaging of the left main coronary artery and the left anterior descending coronary artery at acute presentation. All patients fulfilled the established diagnostic criteria for TTS and the diagnosis was confirmed with a multimodality imaging approach including cardiac magnetic resonance in 16 patients (69.6%). Atherosclerotic plaques located in the left anterior descending coronary artery or both the left anterior descending coronary artery and the left main coronary artery were detected in 16 TTS patients (69.6%), with 6 patients exhibiting multiple plaque types. In addition to the predominant fibrocalcific (52.2%) and lipid‐rich plaques (30.4%), thin‐cap fibroatheromas were also found in 6 patients (26.1%). However, ruptured plaques or intracoronary thrombi were not observed. Vessel stenosis >50% was found in 3 patients (13.0%) by analyzing cross‐sectional areas. Clinical characteristics and cardiac magnetic resonance findings did not differ significantly between TTS patients with and without atherosclerotic plaques. ConclusionsUsing optical coherence tomography, the present study revealed a high prevalence of atherosclerotic plaques in patients with TTS, including a considerable number of highly vulnerable thin‐cap fibroatheromas. However, ruptured plaques or intracoronary thrombi were not observed and are therefore most likely not the underlying mechanism of TTS.