Abstract Background Previously considered a rare and relatively benign cardiac condition, Takotsubo syndrome (TTS) has undergone a significant shift in perception over the last two decades. This shift was mainly driven by results indicating that TTS is associated with signicant mortality and morbidity. Consequently, also the criteria for diagnosing TTS have been updated to reflect its recognition as a complex, multifactorial disease. Purpose The aim of the present study was to investigate trends in clinical presentation, demographics, and outcomes of patients with TTS. Methods The study analyzed 3,675 patients diagnosed with TTS from 2004 to 2021. Participants were divided into groups based on diagnosis, using three-year intervals, to perform trend analyses on demographics, risk factors, clinical presentations, and outcomes. The Cochran-Mantel-Haenszel test was used for categorical data trends, while the Mann-Kendall test assessed numerical variables. Mortality rates were compared using the log-rank test. Findings: The study period saw a steady increase in male patients (from 10% to 15%, p = 0.003). While apical TTS continued to be the most common type, the occurrence of midventricular TTS increased (from 18% to 37%, p = 0.002). Emotional triggers remained constant, whereas the prevalence of physical triggers significantly rose (from 35% to 50%, p = 0.034). The incidence of cardiogenic shock increased (from 11% to 20%, p=0.030), leading to a rise in in-hospital mortality rates (from 2% to 9%, p<0.001). A landmark analysis showed a significant increase in 60-day mortality rates (p < 0.001), but no difference in one-year mortality over the years (p = 0.140, Figure 1). Summary: This study of temporal trends in TTS highlights a shift in patients demographic with agrowing prevalence among males, increasing recognition of midventricular TTS type, and increased rates of cardiogenic shock and mortality in recent years. This shift aligns with the rising prevalence of physical triggers, as an expression of increased recognition of TTS in association with acute comorbidities.

Abstract Background Severe functional mitral regurgitation (FMR) may benefit from transcatheter mitral valve repair (TMVR), but selection of patients remains to be optimised. Objectives The aim of this study was to use Machine-Learning (ML) approaches to uncover concealed connections between clinical, echocardiographic, and hemodynamic data associated with patients' outcomes. Methods Consecutive patients undergoing TMVR from 2009 to 2020 were included in the MITRA-AI registry. Eleven relevant clinical and echocardiographic variables were selected in a clustering-based model. The primary endpoint was a composite of cardiovascular death or heart failure hospitalisation at one year, while its single components were secondary endpoints. External validation was performed on the Mitrascore dataset and comparison between clustering and Mitrascore was performed with Net Reclassification Index (NRI). Moreover cluster assignment was performed also on a cohort of patients with moderate-to-severe MR treated with medical therapy alone. Results 822 patients were included in the derivation cohort. The composite primary endpoint occurred in 250 (30%) patients. Four clusters with decreasing risk of the primary endpoint were identified (42%, 37%, 25% and 20% from cluster 1 to cluster 4, respectively). Clusters were combined into a high-risk (clusters 1 and 2) and a low-risk phenotype (clusters 3 and 4). High-risk phenotype patients had larger LVs (> 107 ml/m2), lower LVEF (< 35%) and more prevalent ischemic aetiology (51% to 60% vs. 30% to 40%) compared to low-risk phenotype patients. Moreover, within the high-risk group, patients with diabetes mellitus and with advanced age were at increased risk. Within the low-risk group, ischemic aetiology increased the risk of cardiovascular death, while permanent atrial fibrillation amplified that of HF hospitalizations. In the Mitrascore validation cohort of 1119 patients, incidence of the primary end point varied consistently (48%, 52%, 35% and 42%). Clustering achieved a NRI in 27% of the patients in the derivation cohort and 7% in the validation group compared to Mitrascore. In the validation group of 207 patients treated medically, the incidence of the primary endpoint decreased from the first to the fourth cluster (53%, 42%, 30% and 30%). Conclusions A ML analysis identified meaningful clinical phenotypic presentations in FMR undergoing TMVR, with significant differences in terms of cardiovascular death and heart failure hospitalizations, confirmed in an external validation cohort. ML phenotyping also discriminated prognosis of medically treated patients with severe MR.Central Figure

AIMS:Data on glycoprotein IIb/IIIa inhibitor (GPI) use in real-world acute coronary syndrome (ACS) patients following the introduction of potent P2Y12 inhibitors and newer-generation stents are scant. Here, we aimed to assess the utilization, effectiveness, and safety of GPI in a large prospective multicentre cohort of contemporary ACS patients. METHODS AND RESULTS:SPUM-ACS prospectively recruited patients presenting with ACS between 2009 and 2017. The primary endpoint of the present study was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 year. Secondary endpoints were defined as any bleeding events, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, and net adverse cardiovascular events (NACE). A total of 4395 ACS patients were included in the analysis. GPI-treated patients had more total coronary artery occlusion (56% vs. 35%, P < 0.001) and thrombus (60% vs. 35%, P < 0.001) at angiography. Among the propensity score-matched (PSM) population (1992 patients equally split into two groups), GPI-treated patients showed lower risk of MACE [PSM adjusted hazard ratio (HR) 0.70, 95% CI 0.49-0.99], but a higher risk of any (PSM adjusted HR 1.46, 95% CI 1.06-1.99) and major bleedings (PSM adjusted HR 1.73, 95% CI 1.09-2.76), resulting in a neutral effect on NACE (PSM adjusted HR 0.87, 95% CI 0.65-1.17). These results remained consistent across all subgroups. CONCLUSIONS:In patients with ACS undergoing percutaneous coronary intervention and receiving potent P2Y12 inhibitors, we observed a reduced risk of MACE and an increased risk of major bleedings at 1 year in patients treated with GPI. Although the routine use of GPI is currently not recommended, they might be considered in selected patients following a personalized balancing between ischaemic and bleeding risks.

Background and Aims Cardiogenic shock (CS) remains the primary cause of in-hospital death after acute coronary syndromes (ACS), with its plateauing mortality rates approaching 50%. To test novel interventions, personalized risk prediction is essential. The ORBI (Observatoire R & eacute;gional Breton sur l'Infarctus) score represents the first-of-its-kind risk score to predict in-hospital CS in ACS patients undergoing percutaneous coronary intervention (PCI). However, its sex-specific performance remains unknown, and refined risk prediction strategies are warranted. Methods This multinational study included a total of 53 537 ACS patients without CS on admission undergoing PCI. Following sex-specific evaluation of ORBI, regression and machine-learning models were used for variable selection and risk prediction. By combining best-performing models with highest-ranked predictors, SEX-SHOCK was developed, and internally and externally validated. Results The ORBI score showed lower discriminative performance for the prediction of CS in females than males in Swiss (area under the receiver operating characteristic curve [95% confidence interval]: 0.78 [0.76-0.81] vs. 0.81 [0.79-0.83]; P =.048) and French ACS patients (0.77 [0.74-0.81] vs. 0.84 [0.81-0.86]; P = .002). The newly developed SEX-SHOCK score, now incorporating ST-segment elevation, creatinine, C-reactive protein, and left ventricular ejection fraction, outperformed ORBI in both sexes (females: 0.81 [0.78-0.83]; males: 0.83 [0.82-0.85]; P < .001), which prevailed following internal and external validation in RICO (females: 0.82 [0.79-0.85]; males: 0.88 [0.86-0.89]; P < .001) and SPUM-ACS (females: 0.83 [0.77-0.90], P = .004; males: 0.83 [0.80-0.87], P = .001). Conclusions The ORBI score showed modest sex-specific performance. The novel SEX-SHOCK score provides superior performance in females and males across the entire spectrum of ACS, thus providing a basis for future interventional trials and contemporary ACS management.

Abstract Background/Introduction Spontaneous coronary artery dissection (SCAD) characterized by its non-atherosclerotic nature, poses challenges in diagnosis and management. While recent efforts shed light on SCAD's clinical aspects, the specific utility of CMR demands deeper investigation for enhanced diagnosis and patient care. Purpose This study aims to analyze the characteristics of patients with an angiographically diagnosed SCAD, evaluate qualitative and quantitative parameters of baseline CMR and investigate predictors of myocardial injury and the association between CMR parameters and clinical outcome (major adverse cardiac events, MACE). Methods The study is a prospective single-center analysis of 59 patients, presented acutely in our hospital, from March 2018 to November 2023, with an angiographically detected SCAD. CMR was performed after a median of 4 days (IQR 1.5-7) from the acute onset of symptoms. SCAD Types were angiographically categorized according to the Yip-Saw classification. Most patients (71%) were screened for fibromuscular dysplasia (FMD) with a brain MR and at least one contrast-enhanced abdominal vessels investigation (CT or MR). CMR imaging was performed on a clinical 1.5 T Scanner. T1-weighted, T2-weighted turbo-spin-echo (TSE) Black-Blood (BB) and Short-Tau-Inversion-Recovery (STIR) sequences in short-axis orientation were acquired. The scan protocol included standard cine and T1/T2-weighted TSE BB and Mapping sequences. Late gadolinium enhanced (LGE) images were acquired ≏10 min after the contrast injection and were visually assessed for the presence and extension of LGE areas. LGE quantification was assessed semiautomatically. Results 40 (68%) were females. 54(92%) complained of chest pain, in 55 (93%) high-sensitive Troponin T was eleveted (>14 ng/l) and 24 (41%) presented with the clinical picture of STEMI on admission. From an angiographic point of view, the majority (69.5%) were classified as SCAD Type 2 (a+b). Among patients who underwent a proper screening, 7 patients (16%) were diagnosed with FMD. Baseline CMR showed signs of active injury in 81% and LGE in 93% of the population; however, it was often moderate in size (median of LGE segments 3, IQR 2-5). Most patients had a preserved LVEF (55±10%). STEMI presentation is an independent predictor of LGE extension (p=0.02, OddsRatio(95% CI)=7(2-24)). ScadType1 (p=0.01, OR=10( 2-39)) and N°LGE transmural segments >3 (p=0.03, OR=5.4(1.2-25)) were found to be significant predictor of MACE. 6 of the 11 MACEs were SCAD recurrence/progression, and 4 out of these 11 had already shown signs of previous myocardial injury in the baseline CMR. Conclusion(s) This study emphasized the significance of CMR, which may provide further insights into extend of myocardial damage and may aid in patients’ risk stratification.

Abstract Background Patients with a recent acute coronary syndrome (ACS) remain at high residual cardiovascular risk to which cholesterol, inflammation, and yet-to-be-identified pathways jointly contribute (1). The novel Junctional Protein Associated with Coronary Artery Disease (JCAD) protein drives incident cardiovascular events via pathways, among them fibrinolysis, that act independently from lipid metabolism and inflammation (2). Purpose Whether circulating JCAD provides predictive utility over and above established risk factors among ACS patients at residual lipid risk (RLR), residual inflammatory risk (RIR), or both (RILR), remains unknown. Methods Among patients participating in the multicentre SPUM-ACS study, patients at RLR (on-statin LDL-C ≥70.0 mg/dl), RIR (on-statin hs-CRP ≥2.0 mg/l) or both (RILR; on-statin LDL-C ≥70.0 mg/dl and CRP ≥2.0 mg/l),(1,3) and propensity-score matched (PSM) controls were identified, and the contributions of plasma hs-CRP, LDL-C and JCAD toward recurrent major adverse cardiovascular events (MACE; defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) were studied by fitting uni- and multivariable-adjusted Cox proportional hazard regression models. Results Patients at RLR, RIR, or both (RILR) were at higher MACE risk compared to controls (hazard ratio [HR] per log2 increase, 1.51; 95% confidence interval (CI), 1.05-2.17; HR, 1.78; 95% CI, 1.23-2.58; and HR 1.75; 95% CI, 1.12-2.74; Figure 1). Among those at RLR, MACE risk increased with increasing levels of hs-CRP and JCAD, respectively, in uni- (HR, 1.17; 95% CI, 1.06–1.30; HR, 1.29; 95% CI, 1.03-1.62) and multivariable-adjusted models (adjusted [a]HR, 1.16; 95% CI, 1.03–1.30; aHR, 1.27; 95% CI, 1.01-1.60), whereas no association of LDL-C and future MACE risk was noted. Similarly, among patients at RIR, MACE risk increased by 1.28-fold per log2 increase in plasma JCAD (HR, 1.28; 95% CI, 1.03–1.59), which prevailed in multivariable-adjusted models accounting for potential confounders (aHR, 1.31; 95% CI, 1.04–1.65). In ACS patients at both residual inflammatory and lipid risk, MACE risk associated almost linearly with increasing JCAD levels (HR, 1.45; 95% CI, 1.09–1.92), independently of potential confounders (aHR, 1.47; 95% CI, 1.11–1.97). Meanwhile, no association of LDL-C or hs-CRP with MACE risk was identified among these high-risk patients (Figure 2). Conclusions ACS patients at RIR, RLR, or both are at high ischaemic risk, with JCAD ranking among the top predictors of MACE across the broad spectrum of residual risk. Our data highlight the importance of novel pathways to address residual cardiovascular risk, with JCAD ranking among most promising candidates.

Abstract Background Dipeptidyl peptidase 3 (DPP3) is mechanistically involved in the degradation of angiotensin II and in the depression of systolic left ventricular function thereby disturbing peripheral blood pressure regulation. Small pilot studies suggested that circulating DPP3 (cDPP3) portends poor outcomes in acute heart failure and may refine risk assessment in patients with acute coronary syndromes (ACS). Purpose We aimed to assess the predictive value of cDPP3 in contemporary patients with ACS. Methods Circulating DPP3 was studied in 4311 patients with ACS in the prospective multicentre SPUM-ACS study. DPP3 levels were centrally measured in EDTA plasma by blinded study personnel using an established sandwich-type luminometric immunoassay. Kaplan-Meier survival curves and multivariable-adjusted regression models adjusted for sex, age, heart rate, systolic blood pressure, history of diabetes, levels of creatinine, centrally measured high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein, and the Global Registry of Acute Coronary Events (GRACE) risk score. Results At baseline, median cDPP3 levels were 19.0 ng/ml (interquartile range [IQR] 15.0-26.0) with higher levels observed in patients with ST-segment elevation myocardial infarction than in those with non-ST-segment elevation ACS (20.1 [15.9-28.2] vs. 18.0 [14.1-23.9], respectively, P<0.001). High cDPP3 was linked to longer hospitalization and higher risk to require vasopressor use or mechanical circulatory support (per log2 increase: odds ratio [OR] 1.91, 95% confidence interval [CI] 1.62-2.24, P<0.001; adjusted OR 1.35 95% CI 1.08-1.69, P=0.008). In line, high cDPP was strongly associated with increased mortality at 30 days (per log2 increase: hazard ratio [HR] 1.96, 95% CI 1.48-2.59, P<0.001) and at 1 year (HR 1.51, 95% CI 1.24-1.83, P<0.001). When accounting for established risk factors, cDPP3 remained an independent predictor of premature death with doubling in cDPP3 levels translating into an 58% and 40% increase in 30-day and 1-year mortality risk, respectively (adjusted HR 1.58, 95% CI 1.06-2.34, P<0.023, adjusted HR 1.40, 95% CI 1.10-1.77, P=0.006, respectively). Conclusion We identified cDPP3 as a novel marker of cardiogenic shock and increased mortality in patients with ACS. Circulating DPP3 provides prognostic information beyond established risk factors and improves early risk assessment.DPP3 is linked to hemodynamic impairmentDPP3 independently predicts mortality

Abstract Background Patients with a total coronary occlusion (TCO) of the infarct-related artery (IRA) frequently present as ST-segment elevation myocardial infarction (STEMI). However, patients presenting as non-ST-segment elevation acute coronary syndromes (NSTE-ACS) on a routine ECG may actually have TCO at angiography, typically involving left circumflex (LCx) or right coronary artery (RCA) as the IRA. These patients might be at higher risk of MACE due to a delayed diagnosis and, consequently, an inappropriately prolonged time window to revascularization. Herein, we aimed to describe clinical characteristics and outcomes of IRA location in patients presenting with ACS enrolled in a real-world prospective cohort. Methods Between 2009 and 2017, 4,787 ACS patients were prospectively recruited in the SPUM-ACS prospective study. The primary outcome measure was major adverse cardiovascular events (MACE), a composite of all-cause death, non-fatal myocardial infarction and non-fatal stroke at one year. Multivariable-adjusted Cox regression models were fit using backward selection. Coronary angiographies were reviewed by operators of each site to assess the IRA location and TCO was defined in the presence of TIMI 0 flow. Results 4,542 ACS patients (95% of the total cohort) had angiographic studies available. Patients with left main (n=75) and bypass graft (n=55) as culprit artery were excluded and a final sample size of 4,412 patients were included in the present analysis; 56% (n=2469) presented with ST-elevation myocardial infarction (STEMI) and 44% (n=1943) with NSTE-ACS. Overall, the IRA was the right coronary artery (RCA) in 33.9% (n=1494), the left-anterior descending coronary artery (LAD) in 45.6% (n=2013) and the left circumflex (LCx) in 20.5% (n=905). In those presenting with STEMI, patients with LAD as IRA had an increased risk of MACE (1.43, 95% CI 1.02-2.00, p = 0.04) as compared to those with RCA and LCx. In those presenting with NSTE-ACS, LCx and RCA as IRA had more frequently a TCO compared to the LAD (27% and 24%, respectively, vs. 9%, p<0.001). Features of patients with NSTE-ACS associated with TCO of the IRA included elevated lymphocyte and neutrophil counts, higher hs-CRP and hs-TnT, lower eGFR, and absent history of MI. Among patients with NSTE-ACS, LCx as IRA but not LAD and RCA was associated with an increased risk of MACE at one 1 year (fully adjusted HR 1.68, 95% CI 1.10-2.59, p=0.02; reference: RCA and LAD). Conclusion Among all ACS patients included in the SPUM-ACS, those with NSTE-ACS at initial ECG and RCA and LCx involvement had more often a TCO of the IRA, but only LCx as IRA was an independent predictor of MACE during follow-up. Hs-CRP levels, lymphocytes and neutrophils counts, hs-TnT, eGFR and history of MI at admission were found to be independent predictors of IRA occlusion at angiography. Thus, NSTE-ACS patients showing such features should further be evaluated for timely PCI.

Abstract Background Takotsubo syndrome has long been thought to be a benign condition once the acute event has been overcome. However, an increasing number of studies suggest that there might be long-term consequences. The aim of the present study was to evaluate long term functional cardiac changes in patients after Takotsubo Syndrome. Methods In the present study, a total of 131 TTS patients were prospectively included and age and gender matched with 131 ACS patients. Out of this cohort, a total of 66 patients (TTS: N=33, ACS: N=33) without any known respiratory diseases (e.g. Asthma or COPD) had a follow-up examination one to six months after the index event, including cardiopulmonary exercise testing (CPET) and echocardiography. CPET indices were compared between TTS and ACS patients in those who achieved an RER of at least 1.05. Results Mean age of patients was 65.4 in the TTS group and 65.0 in the ACS group (p=0.541). In each group, 118 (90%) patients were female. At follow-up, TTS patients had a significantly higher LVEF (%, TTS: 59 [56 to 63] vs ACS: 56.5 [51 to 60], p<0.001) and significantly lower levels of BNP (ULN, TTS: 0.5 [0.2 to 0.9] vs ACS: 1.0 [0.5 to 2.6], p<0001), compared to TTS patients. TTS patients were significantly more frequently suffering from persistent symptoms compared to ACS patients (TTS: 78 [60%] vs. ACS: 60 [45.8%], p=0.035, figure 1). Twenty-four TTS Patients (72%) had an RER over 1.05 and were age and gender matched with 24 ACS patients. VO2max was comparable between the two groups (TTS: 20.2 [±5.4] vs ACS: 18.9 [±7.6], p=0.47) as well as Peak Mets (TTS: 5.7 (±1.6) vs ACS: 5.5 (±1.9), p=0.68). However, there was a trend towards a lower oxygen pulse in TTS compared to ACS patients (TTS: 9.4 [±2.2] vs ACS: 10.9 [±3.1], p=0.055) and a significant higher oxygen cost of work (ΔV’O2/ΔW, TTS: 12.9 [11.3 to 15.5] vs ACS: 10.9 [9.7 to 12.2], p=0.019). Conclusion TTS patients were more frequently suffering from persistent symptoms compared to ACS patients. Moreover, TTS patients demonstrated long-term functional cardiac changes reflected in impaired CPET parameters comparable to or worse than those of ACS patients. These findings highlight the long-term consequences of TTS and further challenge the concept that TTS is a benign disease.

BACKGROUND In patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease, the time at which complete revascularization of nonculprit lesions should be performed remains unknown. METHODS We performed an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients in a hemodynamically stable condition who had STEMI and multivessel coronary artery disease were randomly assigned to undergo immediate multivessel percutaneous coronary intervention (PCI; immediate group) or PCI of the culprit lesion followed by staged multivessel PCI of nonculprit lesions within 19 to 45 days after the index procedure (staged group). The primary end point was a composite of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year after randomization. The percentages of patients with a primary or secondary end-point event are provided as Kaplan-Meier estimates at 6 months and at 1 year. RESULTS We assigned 418 patients to undergo immediate multivessel PCI and 422 to undergo staged multivessel PCI. A primary end-point event occurred in 35 patients (8.5%) in the immediate group as compared with 68 patients (16.3%) in the staged group (risk ratio, 0.52; 95% confidence interval, 0.38 to 0.72; P<0.001 for noninferiority and P<0.001 for superiority). Nonfatal myocardial infarction and unplanned ischemia-driven revascularization occurred in 8 patients (2.0%) and 17 patients (4.1%), respectively, in the immediate group and in 22 patients (5.3%) and 39 patients (9.3%), respectively, in the staged group. The risk of death from any cause, the risk of stroke, and the risk of hospitalization for heart failure appeared to be similar in the two groups. A total of 104 patients in the immediate group and 145 patients in the staged group had a serious adverse event. CONCLUSIONS Among patients in hemodynamically stable condition with STEMI and multivessel coronary artery disease, immediate multivessel PCI was noninferior to staged multivessel PCI with respect to the risk of death from any cause, nonfatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275.)

Abstract Background/Introduction The obesity paradox has been described in different cardiovascular conditions. Data on the association between obesity and outcomes in patients with Takotsubo syndrome (TTS) are lacking. Purpose The aim of this study was to determine the relation of body weight to mortality in TTS patients. Methods Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to July 2021 and with available data on BMI were included in the analysis. Patients were stratified according to BMI (underweight, <18.5 kg/m2; normal weight, 18.5–24.9 kg/m2; overweight, 25.0–29.9 kg/m2; obese, 30.0–34.9 kg/m2; and very obese, ≥35.0 kg/m2). The primary endpoint was mortality at 1 year. Results Of the 2'707 patients, 222 (8.2%) were underweight, 1340 (49.5%) of normal weight, 759 (28.0%) overweight, 268 (9.9%) obese, and 118 (4.4%) very obese. Mortality at 1 year as a function of BMI with 95% confidence interval is given in Figure 1. Mortality at 1 year was 11.3%, 6.9%, 5.5%, 4.9%, and 9.3% in underweight, normal weight, overweight, obese, and very obese patients (p=0.02, Figure 2). Being overweight or obese was significantly associated with a lower mortality at 1 year (HR 0.70, 95% CI 0.51–0.96, p=0.03), and associations remained significant after multivariable adjustments (adjusted HR 0.67, 95% CI 0.46–0.97, p=0.03). Associations were observed when including patients without emotional stressors (adjusted HR 0.64, 95% CI 0.43–0.94, p=0.02), but not when including those with emotional stressors (adjusted HR 1.14, 95% CI 0.30–4.27, p=0.85). Conclusion A U-shaped mortality curve across BMI categories was observed in TTS patients, with lowest mortality rates in obese patients. These observations provide first evidence for the existence of the obesity paradox in TTS. Funding Acknowledgement Type of funding sources: Foundation.

Abstract Introduction Conflicting data exist upon whether patients presenting with acute coronary syndromes (ACS) during on- or off-hours differ regarding outcomes. Moreover, definitions of on- and off-hours vary in literature. The notion of a weekend effect with increased mortality has been raised, mostly seen in relation to lesser use of invasive treatment. Purpose This multi-center study investigated the baseline characteristics and associated outcomes of patients presenting with ACS undergoing coronary angiography on weekdays compared to those presenting on weekends or holidays. Methods Data from the prospective SPUM-ACS (Special Program University Medicine Acute Coronary Syndromes and Inflammation) Cohort were examined, with patients recruited between 2009 and 2012. Patients were divided into two groups according to whether they presented for coronary angiography for ACS on workdays (Monday-Friday, 00:00–23:59) or on rest days (Saturday or Sunday, 00:00–23:59, and public holidays shared by all centers). Time of presentation was defined as time point of catheter sheath insertion. Results From a total of 2168 patients (21.4% females), 1828 (84.3%) presented on workdays, 340 (15.7%) on rest days without difference in female/male ratio. On rest days, patients more often showed signs of advanced heart failure (Killip Class III–IV 3.9% vs. 7.1%, p=0.009). Patients presented more frequently with ST-segment elevation ACS (STE-ACS) than non-ST-segment elevation ACS (STE-ACS on workdays vs. rest days: 50.4% vs. 65.0%, p<0.001). In- and out-of-hospital time delay metrics did not differ between groups, apart from symptom onset-to-balloon time, which was shorter on rest days (598 vs. 520 min, p=0.040). There was a trend towards more frequent use of percutaneous (89.2% vs. 92.6%, p=0.053) or surgical (3.3% vs 5.0%, p=0.131) revascularization on rest days. 30-day all-cause mortality was higher on rest days for any ACS (1.75% vs 3.82%, p=0.007) and for STE-ACS only (2.39% vs 4.98%, p=0.019, Fig. 1). Notably, the same trend was seen when comparing only patients presenting with Killip Class III/IV, both for any ACS (11.27% vs. 20.83%, p=0.119) and for STE-ACS (14.00% vs. 26.32%, p=0.114). On rest days, female patients showed higher 30-day all-cause mortality than males for any ACS (7.46% vs 2.93%, p=0.042); the same trend was observed for STE-ACS (8.89% vs. 3.98%, p=0.088). Conclusions On rest days, patients more often presented with STE-ACS and more frequently showed signs of advanced heart failure, with similar use of invasive revascularization as for patients presenting on workdays. This might contribute to higher early mortality observed in ACS patients on rest days. These differences persisted within the subgroups STE-ACS and Killip Class III/IV. Interestingly, female patients showed increased early mortality on rest days compared to males. Thus, patients presenting with ACS on rest days warrant particular attention. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation (SNSF)

Objectives: Von Willebrand’s Factor (vWF) as a marker of endothelial dysfunction is associated with adverse outcome in cardiovascular disease, such as coronary artery disease, atrial fibrillation, pulmonary, or arterial hypertension and heart failure due to noncongenital heart disease. We aimed to evaluate the prognostic value of vWF on heart failure and death (HF/Death) in adult congenital heart disease (ACHD).

Advanced therapy medicinal products (ATMPs) are based on viable cells or tissues and show a complex mode of action. European approval relies on specific regulations and involves the European Medicines Agency’s Committee for Advanced Therapies. Here, the evaluation of German HTA authorities (Federal Joint Committee, G-BA) regarding the quality of evidence and possible options to improve the data basis for ATMPs (e.g. via evaluation of registry data) will be discussed. A list of all centrally or regionally approved ATMPs was retrieved from the Paul-Ehrlich-Institute and the EMA. Information regarding the assessment of the added medical benefit according to AMNOG, the evidence basis and the outcome of the assessment was collected from the website of G-BA. To date 21 ATMPs have been approved in Germany (eight gene therapeutics, two somatic cell therapeutics, one tumor vaccine, ten tissue engineered products). Five gene therapeutics and both somatic cell therapeutics were obliged to AMNOG assessments so far. None of the assessments revealed a quantifiable added benefit. ATMPs approved for Orphan Diseases reached a nonquantifiable added benefit due to specific regulations for Orphan Drugs in Germany. Three benefit assessments presented data of randomized controlled trials whereas four assessments are based on single arm studies. In three cases data from post authorization studies (e.g. registry data) were demanded for follow up assessment by G-BA. Approval studies in ATMPs often show limited evidence due to the small number of patients. RCTs have been conducted for some ATMPs but feasibility strongly depends on the size of patient population. For single arm studies, G-BA requested to submit additional evidence (RCT or registry data) to a later date. German authorities are currently preparing a draft law to make additional data acquisition (e.g. registries) legally binding if the approval data are insufficient for the benefit assessment according to AMNOG.

Abstract Background Scoring systems for risk stratification in takotsubo syndrome (TTS) are lacking. Purpose The present study aimed to develop a score to predict the overall mortality in TTS. Methods TTS patient were enrolled from a multicenter registry. Parameters known to be associated with adverse outcomes in TTS were identified based on current literature. A multivariable analysis including these parameters was conducted and those which were found to be significantly associated with mortality were considered in the scoring system. For each patient, the prognostic score was derived by summing the respective points of each prognostic factor. Based on cut-off values, patients were categorized into four groups including low, intermediate, high, and very high risk. Results A total of 1160 patients (90.8% females; mean age 66.5±13.0 years) were included in the present study. Regarding triggering factors, an emotional trigger was identified in 32.6% of TTS patients while 32.1% had preceding physical activities, medical conditions, or procedures and 5.7% had preceding neurologic disorders. The remaining patients (29.7%) had no identifiable triggering factors. According to the results from multivariable analysis, points were assigned to each parameter that was independently associated with long-term mortality: 15 points for neurologic trigger, 10 points for the other physical trigger, 8 points for Age >70 years, 7 points for male sex, 7 points for left ventricular ejection fraction ≤45%, 6 points for diabetes mellitus, 5 points for heart rate >94 bpm on admission, 5 points for systolic blood pressure >140 mmHg on admission, and 2 points for no identifiable trigger. Based on the total points, patients were categorized into four prognostic groups: low-risk ≤15 points (43.5%), intermediate-risk 16–22 points (28.0%), high-risk 23–29 points (18.0%), and very high-risk >29 points (10.5%). Conclusion This novel score for risk stratification in TTS only requires easy-obtainable variables to clinicians even in the acute phase and could identify low to very high risk of overall mortality. Thus, it could potentially serve as a useful clinical tool to predict prognosis in patients with TTS.