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Introduction and Objectives: Meteorin-like protein (Metrnl) is a cytokine involved in the attenuation of inflammation. In patients with heart failure, high levels of this biomarker are associated with a worse outcome. In this study, we evaluated the circulating levels and prognostic value of Metrnl in patients with ST-segment elevation myocardial infarction (STEMI)., Methods: We enrolled STEMI patients undergoing primary percutaneous coronary intervention. Circulating Metrnl levels were measured in peripheral blood 12hours after symptom onset. The primary endpoint was a composite of all-cause mortality or nonfatal myocardial infarction (MI) at 3 years., Results: We studied 381 patients (mean age 61 years, 21% female, 8% Killip class III/IV). Metrnl levels were associated with age, cardiovascular risk factors and the extent of coronary artery disease, as well as with STEMI complications, particularly heart failure and cardiogenic shock. Multivariable Cox regression analysis revealed that Metrnl independently predicted all-cause death or nonfatal MI at 3 years (HR, 1.86; 95%CI, 1.23-2.81; P=.003). Moreover, patients in the highest tertile (> 491.6 pg/mL) were at higher risk for the composite endpoint than those in the lowest tertiles (HR, 3.24; 95%CI, 1.92-5.44; P <.001), even after adjustment by age, diabetes mellitus, cardiac arrest, Killip-Kimball III/IV class, left ventricular ejection fraction, and creatinine clearance (HR, 1.90; 95%CI, 1.10-3.29; P=.021)., Conclusions: Circulating Metrnl levels are associated with complications during the acute phase of STEMI and independently predict a worse outcome in these patients., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Prognosis in ST-elevation myocardial infarction (STEMI) is determined by delay in primary percutaneous coronary intervention (PPCI). The impact of first medical contact (FMC) facility type on reperfusion delays and mortality remains controversial., Methods: We performed a prospective registry of primary coronary intervention (PCI)-treated STEMI patients (2010-2020) in the Codi Infart STEMI network. We analyzed 1-year all-cause mortality depending on the FMC facility type: emergency medical service (EMS), community hospital (CH), PCI hospital (PCI-H), or primary care center (PCC)., Results: We included 18 332 patients (EMS 34.3%; CH 33.5%; PCI-H 12.3%; PCC 20.0%). Patients with Killip-Kimball classes III-IV were: EMS 8.43%, CH 5.54%, PCI-H 7.51%, PCC 3.76% (P <.001). All comorbidities and first medical assistance complications were more frequent in the EMS and PCI-H groups (P <.05) and were less frequent in the PCC group (P <.05 for most variables). The PCI-H group had the shortest FMC-to-PCI delay (median 82 minutes); the EMS group achieved the shortest total ischemic time (median 151 minutes); CH had the longest reperfusion delays (P <.001). In an adjusted logistic regression model, the PCI-H and CH groups were associated with higher 1-year mortality, OR, 1.22 (95%CI, 1.00-1.48; P=.048), and OR, 1.17 (95%CI 1.02-1.36; P=.030), respectively, while the PCC group was associated with lower 1-year mortality than the EMS group, OR, 0.71 (95%CI 0.58-0.86; P <.001)., Conclusions: FMC with PCI-H and CH was associated with higher adjusted 1-year mortality than FMC with EMS. The PCC group had a much lower intrinsic risk and was associated with better outcomes despite longer revascularization delays., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Mechanical complications confer a dreadful prognosis in ST-elevation myocardial infarction (STEMI). Their prevalence and prognosis are not well-defined in the current era of primary percutaneous coronary intervention (pPCI) reperfusion networks. We aimed to analyze prevalence and mortality trends of post-STEMI mechanical complications over 2 decades, before and after the establishment of pPCI networks., Methods: Prospective, consecutive registry of STEMI patients within a region of 850 000 inhabitants over 2 decades: a pre-pPCI period (1990-2000) and a pPCI period (2007-2017). We analyzed the prevalence of mechanical complications, including ventricular septal rupture, papillary muscle rupture, and free wall rupture (FWR). Twenty eight-day and 1-year mortality trends were compared between the 2 studied decades., Results: A total of 6033 STEMI patients were included (pre-pPCI period, n=2250; pPCI period, n=3783). Reperfusion was supported by thrombolysis in the pre-pPCI period (99.1%) and by pPCI in in the pPCI period (95.7%). Mechanical complications developed in 135 patients (2.2%): ventricular septal rupture in 38 patients, papillary muscle rupture in 24, and FWR in 73 patients. FWR showed a relative reduction of 60% in the pPCI period (0.8% vs 2.0%, P<.001), without significant interperiod changes in the other mechanical complications. After multivariate adjustment, FWR remained higher in the pre-pPCI period (OR, 1.93; 95%CI, 1.10-3.41; P=.023). At 28 days and 1 year, mortality showed no significant changes in all the mechanical complications studied., Conclusions: The establishment of regional pPCI networks has modified the landscape of mechanical complications in STEMI. FWR is less frequent in the pPCI era, likely due to reduced transmural infarcts., (Copyright © 2022. Published by Elsevier España, S.L.U.)

Primary ventricular fibrillation (PVF) is a life-threatening complication of ST-segment elevation myocardial infarction (STEMI). It is unclear what roles viral infection and/or systemic inflammation may play as underlying triggers of PVF, as a second hit in the context of acute ischaemia. Here we aimed to evaluate whether the circulating virome and inflammatory proteome were associated with PVF development in patients with STEMI. Blood samples were obtained from non-PVF and PVF STEMI patients at the time of primary PCI, and from non-STEMI healthy controls. The virome profile was analysed using VirCapSeq-VERT (Virome Capture Sequencing Platform for Vertebrate Viruses), a sequencing platform targeting viral taxa of 342,438 representative sequences, spanning all virus sequence records. The inflammatory proteome was explored with the Olink inflammation panel, using the Proximity Extension Assay technology. After analysing all viral taxa known to infect vertebrates, including humans, we found that non-PVF and PVF patients only significantly differed in the frequencies of viruses in the Gamma-herpesvirinae and Anelloviridae families. In particular, most showed a significantly higher relative frequency in non-PVF STEMI controls. Analysis of systemic inflammation revealed no significant differences between the inflammatory profiles of non-PVF and PVF STEMI patients. Inflammatory proteins associated with cell adhesion, chemotaxis, cellular response to cytokine stimulus, and cell activation proteins involved in immune response (IL6, IL8 CXCL-11, CCL-11, MCP3, MCP4, and ENRAGE) were significantly higher in STEMI patients than non-STEMI controls. CDCP1 and IL18-R1 were significantly higher in PVF patients compared to healthy subjects, but not compared to non-PVF patients. The circulating virome and systemic inflammation were not associated with increased risk of PVF development in acute STEMI. Accordingly, novel strategies are needed to elucidate putative triggers of PVF in the setting of acute ischaemia, in order to reduce STEMI-driven sudden death burden., (© 2022. The Author(s).)

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case-control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini-Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias., (© 2022. The Author(s).)

Background: Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function., Objectives: The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years' follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE., Methods: The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography., Results: During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox proportional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95% CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44 to 0.96, for a 1-SD increase)., Conclusions: Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Primary ventricular fibrillation is an ominous complication of ST-segment elevation myocardial infarction, and proper biomarkers for risk prediction are lacking. Growth differentiation factor-15 is a marker of inflammation, oxidative stress and hypoxia with well-established prognostic value in ST-segment elevation myocardial infarction patients. We explored the predictive value of growth differentiation factor-15 in a subgroup of ST-segment elevation myocardial infarction patients with primary ventricular fibrillation., Methods: Prospective registry of ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention from February 2011-August 2015. Growth differentiation factor-15 concentrations were measured on admission. Logistic regression and Cox proportional regression analyses were used., Results: A total of 1165 ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention (men 78.5%, age 62.3±13.1 years) and 72 patients with primary ventricular fibrillation (6.2%) were included. Compared to patients without primary ventricular fibrillation, median growth differentiation factor-15 concentration was two-fold higher in ST-segment elevation myocardial infarction patients with primary ventricular fibrillation (2655 vs 1367 pg/ml, p <0.001). At 30 days, mortality was 13.9% and 3.6% in patients with and without primary ventricular fibrillation, respectively ( p <0.001), and median growth differentiation factor-15 concentration in patients with primary ventricular fibrillation was five-fold higher among those who died vs survivors (13,098 vs 2415 pg/ml, p <0.001). In a comprehensive multivariable analysis including age, sex, clinical variables, reperfusion time, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, growth differentiation factor-15 remained an independent predictor of 30-day mortality, with odds ratios of 3.92 (95% confidence interval 1.35-11.39) in patients with primary ventricular fibrillation ( p =0.012) and 1.72 (95% confidence interval 1.23-2.40) in patients without primary ventricular fibrillation ( p =0.001)., Conclusions: Growth differentiation factor-15 is a robust independent predictor of 30-day mortality in ST-segment elevation myocardial infarction patients with primary ventricular fibrillation.

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.

Background Growth differentiation factor 15 (GDF-15) in ST-elevation myocardial infarction (STEMI) is prognostic in first-generation radioimmunoassays. We examined GDF-15 temporal dynamics in STEMI and its predictive value using a first fully automated GDF-15 electrochemiluminescence assay. Methods In this prospective study, circulating GDF-15 concentration was measured at admission (0 h), 12 h and 24 h in 1026 consecutive STEMI patients treated between February 2011 and May 2016 with primary percutaneous coronary intervention. GDF-15 dynamics (0 h, 12 h, 24 h) and predictive value (30 days and 3 years) were examined. Results Median GDF-15 concentration was 1443 pg/mL at 0 h, 1731 pg/mL at 12 h and 1510 pg/mL at 24 h (p<0.001). During follow-up, 94 patients died (9.2%) and 154 (15.0%) were hospitalized. GDF-15 was a strong predictor of 30-day mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI], 1.33-2.34 at 0 h; HR 2.99 [95% CI, 2.18-4.09] at 12 h, and HR 1.97 [95% CI, 1.47-2.63] at 24 h) in multivariable Cox proportional hazards models. GDF-15 improved discrimination and reclassification of a clinical risk model. GDF-15 was also associated with 3-year mortality (HR 1.31 [95% CI, 1.04-1.65] at 0 h, HR 1.42 [95% CI, 1.10-1.84] at 12 h, and HR 1.51 [95% CI, 1.16-1.96] at 24 h) and 3-year composite of mortality and cardiovascular hospitalization (HR 1.17 [95% CI, 1.01-1.37] at 0 h, HR 1.20 [95% CI, 1.02-1.42] at 12 h, and HR 1.27 [95% CI, 1.08-1.50] at 24 h). Conclusions GDF-15 peaked at 12 h and remained elevated at 24 h in STEMI. GDF-15 measurement during the first 24 h in STEMI is valuable for predicting especially short- but also long-term outcomes, and may be a useful addition to risk stratification.

Primary ventricular fibrillation (PVF) is a dreadful complication of ST segment elevation myocardial infarction (STEMI). Scarce data are available regarding PVF prognosis since primary percutaneous coronary intervention (PPCI) became routine practice in STEMI. Our aim was to compare 30-day and 1-year mortality for patients with and without PVF (including out-of-hospital and in-hospital PVF) within a regional registry of PPCI-treated STEMI patients. This prospective multicenter registry included all consecutive STEMI patients treated with PPCI from January 2010 to December 2014. Patients were classified as non-PVF or PVF, with further subdivision into out-of-hospital and in-hospital PVF. We analyzed 30-day and 1-year all-cause mortality in groups. The registry included 10,965 patients. PVF occurred in 949 patients (8.65%), including 74.2% out-of-hospital and 25.8% in-hospital PVF. Compared with the non-PVF group, PVF patients were younger; less commonly diabetic; more frequently had anterior wall STEMI, higher Killip-Kimball class, and left main disease; and showed significantly higher 24-hour (5.1% vs 1.1%), 30-day (18.5% vs 4.7%), and 1-year mortality (23.2% vs 7.9%) (all p <0.001). Mortality did not differ in out-of-hospital versus in-hospital PVF. After multivariable adjustment, PVF remained associated with all-cause 30-day (2.32, 95% CI: 1.91 to 2.82, p <0.001) and 1-year (HR: 1.59, 95% CI: 1.13 to 2.24, p = 0.008) mortality. In conclusion, we present the largest registry of PVF patients in the era of routine PPCI in STEMI. Although overall STEMI mortality has declined, PVF emerged as a predictor of both 30-day and 1-year mortality. These data warrant prospective validation and proper identification and protection of high-risk patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to evaluate the prognostic value of the Stanniocalcin-2/PAPP-A/IGFBP-4 axis in patients with ST-segment elevation myocardial infarction (STEMI)., Methods: Observational cohort study performed in 1085 consecutive STEMI patients treated with early reperfusion between February 2011 and August 2014. Stanniocalcin-2, PAPP-A, and IGFBP-4 were measured using state-of-the art immunoassays. The primary outcome was the composite endpoint of all-cause mortality and readmission due to heart failure (HF)., Results: Median follow-up was 3.3 years (IQR 1.0-3.7), during which 176 patients (16.2%) presented a composite endpoint. Multivariable cox regression analysis revealed that Stanniocalcin-2 (HR 2.06; 95% CI 1.13-3.75; p = 0.018), IGFBP-4 (HR 1.73; 95% CI 1.14-2.64; p = 0.010), Killip-Kimball class III-IV (HR 1.40; 95% CI 1.13-1.74; p = 0.002), NT-ProBNP (HR 1.21; 95% CI 1.07-1.37; p = 0.002), age (HR 1.06; 95% CI 1.04-1.08; p < 0.001) and left ventricular ejection fraction (HR 0.97; 95% CI 0.95-0.98; p < 0.001) were independent predictors of the composite endpoint. A model containing Stanniocalcin-2 and IGFBP-4 on top of clinical variables significantly improved C-index discrimination (p = 0.036). Stanniocalcin-2 was also identified as independent predictor of all-cause mortality (HR 2.23; 95% CI 1.16-4.29; p = 0.017) and readmission due to HF (HR 3.42; 95% CI 1.22-9.60; p = 0.020)., Conclusions: In STEMI patients, Stanniocalcin-2 and IGFBP-4 emerged as independent predictors of all-cause death and readmission due to HF. The Stanniocalcin-2/PAPP-A/IGFBP-4 axis exhibits a significant role in STEMI risk stratification.

Background: In ST-segment-elevation myocardial infarction (STEMI), troponins are not needed for diagnosis: symptoms and ECG data are sufficient to activate percutaneous coronary intervention. This study explored the prognostic value of new-generation troponins in a real-life cohort contemporarily treated for STEMI., Methods and Results: We studied 1260 consecutive patients with primary STEMI treated with percutaneous coronary intervention between February 22, 2011, and August 31, 2015. We collected data on clinical characteristics and major adverse cardiovascular and cerebrovascular events (MACCEs) at 30 days and 1 year. Peak high-sensitivity troponin T and sensitive-contemporary troponin I levels were recorded. MACCEs occurred in 75 patients (6.1%) by day 30 and in 124 patients (10.8%) between day 31 and 1 year. A short-term (0-30 days) multivariable Cox regression analysis revealed that age, Killip-Kimball class, and left ventricular ejection fraction were independent predictors of MACCEs. In adjusted analysis, peak high-sensitivity troponin T and sensitive-contemporary troponin I were not significant (hazard ratio, 1.23 [95% confidence interval, 0.98-1.54] [ P =0.071]; and hazard ratio, 1.15 [95% confidence interval, 0.93-1.43] [ P =0.200], respectively). A long-term (31 days-1 year) multivariable Cox regression analysis revealed that age, female sex, diabetes mellitus, prior coronary artery disease, Killip-Kimball class, and left ventricular ejection fraction were statistically significantly associated with MACCEs. However, peak high-sensitivity troponin T and peak sensitive-contemporary troponin I were not significantly associated with MACCEs (hazard ratio, 1.03 [95% confidence interval, 0.88-1.20] [ P =0.715]; and hazard ratio, 0.99 [95% confidence interval, 0.85-1.15] [ P =0.856], respectively)., Conclusions: In the modern era, new-generation troponins do not provide significant prognostic information for predicting clinical events in STEMI. We should reconsider the value of serial troponin measurements for risk stratification in STEMI., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)