Takotsubo syndrome (TKS) usually mimics an acute coronary syndrome. However, several clinical forms have been reported. Our aim was to assess if different stressful triggers had prognostic influence on TKS, and to establish a working classification. We performed an analysis including patients with TKS between 2003–2013 from our prospective local database and the RETAKO National Registry, fulfilling Mayo criteria. Patients were divided in two groups regarding their potential triggers: (a) none/psychic stress as ‘primary forms’ and (b) physical factors (asthma, surgery, trauma, etc.) as ‘secondary forms’. Finally, 328 patients were included, 90.2% women, with a mean age of 69.7 years. Patients were divided into primary TKS (n=265) and 63 secondary TKS groups. Age, gender, previous functional class and cardiovascular risk profile displayed no differences between groups before admission. However, primary-TKS patients suffered a main complaint of chest pain (89.4% vs 50.7%, p<0.0001) with frequent vegetative symptoms. Regarding treatment before admission, there were no differences either. During admission, differences were related to more intensive antithrombotic and anxiolytic drug use in the primary TKS group. Inotropic and mechanical ventilation use was higher in the secondary cohort. After discharge, a more frequent prescription of beta-blockers and statins in primary-TKS patients was seen. Secondary forms displayed more in-hospital stay and evolutive complications: death (hazard ratio (HR): 3.41; 95% confidence interval (CI): 1.14–10.16, p=0.02), combined event variable (MACE) (HR: 1.61; 95% CI: 1.01–2.6, p=0.04) and recurrences (HR: 1.85; 95% CI: 1.06–3.22, p=0.02). Secondary TKS could present or mark worse short and long-term prognoses in terms of mortality, recurrences and readmissions. We propose a simple working nomenclature for TKS.

Aims: Cardiogenic shock (CS) is associated with high short-term mortality and a precise CS risk stratification could guide interventions to improve patient outcome. Here, we developed a circulating protein-based score to predict short-term mortality risk among patients with CS. Methods and results: Mass spectrometry analysis of 2654 proteins was used for screening in the Barcelona discovery cohort (n = 48). Targeted quantitative proteomics analyses (n = 51 proteins) were used in the independent CardShock cohort (n = 97) to derive and cross-validate the protein classifier. The combination of four circulating proteins (Cardiogenic Shock 4 proteins—CS4P), discriminated patients with low and high 90-day risk of mortality. CS4P comprises the abundances of liver-type fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1. Within the CardShock cohort used for internal validation, the C-statistic was 0.78 for the CardShock risk score, 0.83 for the CS4P model, and 0.84 (P = 0.033 vs. CardShock risk score) for the combination of CardShock risk score with the CS4P model. The CardShock risk score with the CS4P model showed a marked benefit in patient reclassification, with a net reclassification improvement (NRI) of 0.49 (P = 0.020) compared with CardShock risk score. Similar reclassification metrics were observed in the IABP-SHOCK II risk score combined with CS4P (NRI =0.57; P = 0.032). The CS4P patient classification power was confirmed by enzyme-linked immunosorbent assay (ELISA). Conclusion: A new protein-based CS patient classifier, the CS4P, was developed for short-term mortality risk stratification. CS4P improved predictive metrics in combination with contemporary risk scores, which may guide clinicians in selecting patients for advanced therapies.

The incidence of cardiogenic shock (CS) has increased remarkably over the past decade and remains a challenging condition with mortality rates of ∼50%. Cardiogenic shock encompasses cardiac contractile dysfunction; however, it is also a multiorgan dysfunction syndrome, often complicated by a systemic inflammatory response with severe cellular and metabolic dysregulations. Here, we review the evidence on the biochemical manifestations of CS, elaborating on current gold standard biomarkers and novel candidates from molecular signatures of CS. Glucose and lactate, both identified over a century ago, remain the only clinically used biomarkers in current predictive risk scores. Novel genomic, transcriptomic, and proteomic data are discussed, and a recently reported molecular score derived from unbiased proteomic discovery, the CS4P, which includes liver fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1 is comprehensively described. Recent advances in -omics technologies provide new insight into a more holistic molecular signature of CS. Thus, we need to open new diagnostic and therapeutic avenues if we aim to improve outcomes.

Aims The preferred reperfusion strategy for early ST elevation myocardial infarction (STEMI, defined as time from symptoms onset ≤120 min) in non-capable percutaneous coronary intervention (PCI) centres remains controversial. We sought to compare mortality of in situ fibrinolysis vs. PCI transfer in a real-life consecutive cohort of early STEMI. Methods and results Prospective multicentre STEMI registry (Catalonia ‘Codi IAM’ network) of all-comers in a non-capable PCI centre with symptom onset to first medical contact (FMC) <120 min. Two groups were identified: in situ fibrinolysis and transfer to a PCI-capable centre. Primary endpoint was 30-day mortality. We included 2470 patients, of whom 2227 (90.2%) and 243 (9.8%) comprised the transfer and fibrinolysis groups, respectively. In the fibrinolysis group, diagnostic and system delays were shorter (24 vs. 31 min, P < 0.001; 45 vs. 119 min, P < 0.001, respectively). Thirty-day mortality was 7.7 and 5.1% in fibrinolysis and transfer groups, respectively (P = 0.09). However, patients in the transfer group whose time FMC-device was achieved within 140 min were associated with significantly lower mortality (2.0% for FMC-device <99 min, and 4.6% for FMC-device 99–140 min; P < 0.01 and P = 0.03, respectively vs. fibrinolysis). In multivariable logistic regression analysis, reperfusion with fibrinolysis was an independent 30-day mortality predictive factor (odds ratio: 1.91, 95% confidence interval: 1.01–3.50; P = 0.04), together with age and Killip–Kimball class (both P < 0.001). Conclusions In early STEMI patients assisted in non-capable PCI centres, in situ fibrinolysis had worse prognosis than patient transfer. Transfer to a PCI-capable centre seems recommended in patients with FMC-device delay <140 min.

Background: Coronary artery disease remains a major cause of death despite better outcomes of ST‐segment–elevation myocardial infarction (STEMI). We aimed to analyze data from the Ruti‐STEMI registry of in‐hospital, 28‐day, and 1‐year events in patients with STEMI over the past 3 decades in Catalonia, Spain, to assess trends in STEMI prognosis. Methods and Results: Between February 1989 and December 2017, a total of 7589 patients with STEMI were admitted consecutively. Patients were grouped into 5 periods: 1989 to 1994 (period 1), 1995 to 1999 (period 2), 2000 to 2004 (period 3), 2005 to 2009 (period 4), and 2010 to 2017 (period 5). We used Cox regression to compare 28‐day and 1‐year STEMI mortality and in‐hospital complication trends across these periods. Mean patient age was 61.6±12.6 years, and 79.3% were men. The 28‐day all‐cause mortality declined from period 1 to period 5 (10.4% versus 6.0%; P <0.001), with a 40% reduction after multivariable adjustment (hazard ratio [HR], 0.6; 95% CI, 0.46–0.80; P <0.001). One‐year all‐cause mortality declined from period 1 to period 5 (11.7% versus 9.0%; P =0.001), with a 24% reduction after multivariable adjustment (HR, 0.76; 95% CI, 0.60–0.98; P =0.036). A significant temporal reduction was observed for in‐hospital complications including postinfarct angina (−78%), ventricular tachycardia (−57%), right ventricular dysfunction (−48%), atrioventricular block (−45%), pericarditis (−63%), and free wall rupture (−53%). Primary ventricular fibrillation showed no significant downslope trend. Conclusions: In‐hospital STEMI complications and 28‐day and 1‐year mortality rates have dropped markedly in the past 30 years. Reducing ischemia‐driven primary ventricular fibrillation remains a major challenge.