La proteína meteorin-like se asocia a un perfil de mayor riesgo y predice un peor pronóstico en pacientes con IAMCEST / Meteorin-like protein is associated with a higher risk profile and predicts a worse outcome in patients with STEMI

Introducción y objetivos: La proteína meteorin-like (Metrnl) es una citocina implicada en la atenuación de la inflamación asociada a mal pronóstico en la insuficiencia cardiaca. En este estudio se evalúan los niveles circulantes de Metrnl y su valor pronóstico en el infarto agudo de miocardio con elevación del segmento ST (IAMCEST).Métodos: Se incluyó a pacientes con IAMCEST tratados con angioplastia primaria. Se determinaron los niveles de Metrnl en sangre periférica a las 12 horas del inicio de los síntomas. El criterio de evaluación primario fue muerte por cualquier causa o infarto de miocardio no mortal a 3 años.Resultados: Se estudiaron 381 pacientes (edad media 61 años, 21% mujeres, 8% clase Killip III/IV). Los niveles de Metrnl se asociaron con la edad, los factores de riesgo cardiovascular y la extensión de la enfermedad coronaria, pero también con complicaciones del infarto, especialmente insuficiencia cardíaca y shock cardiogénico. En la regresión multivariante de Cox Metrnl fue un predictor independiente del criterio de evaluación combinado (HR = 1,86; IC95%, 1,23-2,81; p=0,003). Además, los pacientes en el tercil más alto (> 491,6 pg/ml) presentaron mayor riesgo que en los terciles inferiores (HR = 3,24; IC95%, 1,92-5,44; p <0,001), incluso después de ajustar por edad, diabetes, paro cardíaco, clase Killip-Kimball III/IV, fracción de eyección y aclaramiento de creatinina (HR = 1,90; IC95%, 1,10-3,29; p=0,021).Conclusiones: En los pacientes con IAMCEST, los niveles circulantes de Metrnl se asocian con las complicaciones durante la fase aguda y predicen de forma independiente un peor pronóstico.(AU)

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.(AU)

Análisis de una red de atención al IAMCEST: impacto pronóstico del tipo de primer contacto médico / Performance analysis of a STEMI network: prognostic impact of the type of first medical contact facility

Introducción y objetivos: El tipo de primer contacto médico (PCM) en una red de angioplastia (ICPP) para el infarto con elevación del ST (IAMCEST) se asocia con diferentes grados de demora hasta ICPP y podría condicionar el pronóstico. Métodos: Registro de IAMCEST tratados con ICPP (2010-2020) en la red Codi Infart. Analizamos la mortalidad al año por cualquier causa según el tipo de PCM: servicio de emergencias médicas (SEM), hospital comarcal (HC), hospital de angioplastia (H-ICP) y centro de atención primaria (CAP). Resultados: Incluimos 18.332 pacientes (SEM 34,3%; HC 33,5%; H-ICP 12,3%; CAP 20,0%). La proporción de clases Killip III-IV fue: SEM 8,43%, HC 5,54%, H-ICP 7,51%, CAP 3,76% (p <0.001). Comorbilidades y complicaciones en el PCM fueron más frecuentes en los grupos SEM y H-ICP (p <0.05), y menores en el grupo CAP. El grupo H-ICP obtuvo el mejor tiempo PCM-ICPP (mediana 82 min); el grupo SEM consiguió el menor tiempo total de isquemia (mediana 151 min); el grupo HC obtuvo los mayores retrasos (p <0.001). En un modelo de regresión logística ajustado, los grupos H-ICP y HC se asociaron con mayor mortalidad, OR=1,22 (IC95% 1,00-1,48; p=0.048) y OR=1,17 (IC95% 1,02-1,36; p=0,030) respectivamente, y el grupo CAP con menor mortalidad que el grupo SEM, OR=0,71 (IC95% 0,58-0,86; p <0.001). Conclusiones: El PCM con H-ICP y HC se asoció con mayor mortalidad ajustada a 1 año en comparación con el SEM. El grupo CAP se asoció con mejor pronóstico a pesar de reperfusiones más tardías.(AU)

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.(AU)

Meteorin-like protein is associated with a higher risk profile and predicts a worse outcome in patients with STEMI.

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.

Performance analysis of a STEMI network: prognostic impact of the type of first medical contact facility.

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.

Mechanical complications in STEMI: prevalence and mortality trends in the primary PCI era. The Ruti-STEMI registry.

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.

Non-STEMI vs. STEMI Cardiogenic Shock: Clinical Profile and Long-Term Outcomes.

Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI). In AMI-CS, the ST segment deviation on ECG may be elevated (STEMI-CS) or non-elevated (NSTEMI-CS), which may influence prognosis. Our aim was to analyze the clinical profile, acute-phase prognosis, and long-term outcomes of CS relative to the ST pattern on admission. In a prospective registry of 4647 AMI patients admitted to the intensive cardiac care unit of a university hospital between 2010 and 2019, we compared the clinical characteristics, 30-days case fatality, and long-term outcomes of AMI-CS, based on the presence of ST-segment deviation. AMI-CS developed in 239 (5.1%) patients (26.4% women): 190 (79.5%) STEMI-CS and 49 (20.5%) NSTEMI-CS. The mean age was 69.7 years. The STEMI-CS patients had larger infarcts and more mechanical complications than the NSTEMI-CS patients. The NSTEMI-CS patients had a greater prevalence of hypertension, diabetes, peripheral vascular disease, previous cardiovascular comorbidities, three-vessel disease, and left main disease than the STEMI-CS patients. The STEMI-CS patients had higher 30-day mortality than the NSTEMI-CS (59.5% vs. 36.7%; p = 0.004), even after multivariable adjustment (HR 1.91; 95% CI 1.16-3.14), but no differences in mortality were observed at 3 years. In conclusion, the 30-day case-fatality is higher in STEMI-CS, but the long-term outcome is similar in both groups.

Circulating virome and inflammatory proteome in patients with ST-elevation myocardial infarction and primary ventricular fibrillation.

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.

Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation.

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.

Trends in Short- and Long-Term ST-Segment-Elevation Myocardial Infarction Prognosis Over 3 Decades: A Mediterranean Population-Based ST-Segment-Elevation Myocardial Infarction Registry.

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.

Circulating Omega-3 Fatty Acids and Incident Adverse Events in Patients With Acute Myocardial Infarction.

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.

Short- and Long-Term Mortality Trends in STEMI-Cardiogenic Shock over Three Decades (1989-2018): The Ruti-STEMI-Shock Registry.

AIMS: Cardiogenic shock (CS) is an ominous complication of ST-elevation myocardial infarction (STEMI), despite the recent widespread use of reperfusion and invasive management. The Ruti-STEMI-Shock registry analysed the prevalence of and 30-day and 1-year mortality rates in ST-elevation myocardial infarction (STEMI) complicated by CS (STEMI-CS) over the last three decades. METHODS AND RESULTS: From February 1989 to December 2018, 493 STEMI-CS patients were consecutively admitted in a well-defined geographical area of ~850,000 inhabitants. Patients were classified into six five-year periods based on their year of admission. STEMI-CS mortality trends were analysed at 30 days and 1 year across the six strata. Cox regression analyses were performed for comparisons. Mean age was 67.5 ± 11.7 years; 69.4% were men. STEMI-CS prevalence did not decline from period 1 to 6 (7.1 vs. 6.2%, p = 0.218). Reperfusion therapy increased from 22.5% in 1989-1993 to 85.4% in 2014-2018. Thirty-day all-cause mortality declined from period 1 to 6 (65% vs. 50.5%, p < 0.001), with a 9% reduction after multivariable adjustment (HR: 0.91; 95% CI: 0.84-0.99; p = 0.024). One-year all-cause mortality declined from period 1 to 6 (67.5% vs. 57.3%, p = 0.001), with an 8% reduction after multivariable adjustment (HR: 0.92; 95% CI: 0.85-0.99; p = 0.030). Short- and long-term mortality trends in patients aged ≥ 75 years remained ~75%. CONCLUSIONS: Short- and long-term STEMI-CS-related mortality declined over the last 30 years, to ~50% of all patients. We have failed to achieve any mortality benefit in STEMI-CS patients over 75 years of age.

Transitioning from a coronary to a critical cardiovascular care unit: trends over the past three decades.

BACKGROUND: Coronary care units were established in the 1960s to reduce acute-phase mortality in acute coronary syndrome. In the 21st century, the original coronary care unit concept has evolved into an intensive cardiovascular care unit. The aim of this study was to analyse trend changes in characteristics and mortality of patients admitted to a coronary care unit over the past three decades. METHOD: Between February 1989 and December 2017, a total of 18,334 patients was consecutively admitted to the coronary care unit of a university hospital in Barcelona. Data were analysed in five time frames: 1989-1994, 1995-1999, 2000-2004, 2005-2009 and 2010-2017. We analysed demographic profile, diagnoses at admission and trend changes in mortality across periods. RESULTS: During the periods, the patients' ages and comorbidities increased. Diagnoses at admission have evolved. Acute coronary syndrome cases declined from the first to the last period (72.6% vs. 62.8%) while heart failure (6.0% vs. 8.6%) and malignant arrhythmias (0.8% vs. 4.0%) increased significantly. Overall, coronary care unit mortality decreased 34% from the first to the last period (6.8% vs. 4.5%, P<0.001). Furthermore, the cause of death has changed, those due to acute coronary syndrome declining (66.7% vs. 45.5%), and death from malignant arrhythmias increasing (1.9% vs. 16.2%) from the first to the last period. CONCLUSIONS: Although acute coronary syndrome remained the main diagnosis, heart failure and arrhythmias have increased. Despite the aging and comorbidities, overall mortality in the coronary care unit decreased by 34% in the past three decades. Deaths due to acute coronary syndrome have declined, whereas those due to malignant arrhythmias have increased.

Molecular signature of cardiogenic shock.

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.

Transitioning from a coronary to a critical cardiovascular care unit: trends over the past three decades.

BACKGROUND: Coronary care units were established in the 1960s to reduce acute-phase mortality in acute coronary syndrome. In the 21st century, the original coronary care unit concept has evolved into an intensive cardiovascular care unit. The aim of this study was to analyse trend changes in characteristics and mortality of patients admitted to a coronary care unit over the past three decades. METHOD: Between February 1989 and December 2017, a total of 18,334 patients was consecutively admitted to the coronary care unit of a university hospital in Barcelona. Data were analysed in five time frames: 1989-1994, 1995-1999, 2000-2004, 2005-2009 and 2010-2017. We analysed demographic profile, diagnoses at admission and trend changes in mortality across periods. RESULTS: During the periods, the patients' ages and comorbidities increased. Diagnoses at admission have evolved. Acute coronary syndrome cases declined from the first to the last period (72.6% vs. 62.8%) while heart failure (6.0% vs. 8.6%) and malignant arrhythmias (0.8% vs. 4.0%) increased significantly. Overall, coronary care unit mortality decreased 34% from the first to the last period (6.8% vs. 4.5%, P<0.001). Furthermore, the cause of death has changed, those due to acute coronary syndrome declining (66.7% vs. 45.5%), and death from malignant arrhythmias increasing (1.9% vs. 16.2%) from the first to the last period. CONCLUSIONS: Although acute coronary syndrome remained the main diagnosis, heart failure and arrhythmias have increased. Despite the aging and comorbidities, overall mortality in the coronary care unit decreased by 34% in the past three decades. Deaths due to acute coronary syndrome have declined, whereas those due to malignant arrhythmias have increased.

Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA). METHODS: Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed. RESULTS: Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3-5). Patients with CPC 3-5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1-20.4] ng/mL) compared to those with CPC 1-2 (7.6 [IQR, 4.1-13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01-1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61-40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84-34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32-10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48-1.44), which allowed reclassification of 37.1% of patients. CONCLUSIONS: After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification.

Dinámica de microARN circulantes en pacientes con infarto agudo de miocardio con elevación del segmento ST con shock cardiogénico / Circulating MiRNA dynamics in ST-segment elevation myocardial infarction-driven cardiogenic shock

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Protein-based cardiogenic shock patient classifier.

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.

Ventricular fibrillation in a patient with Wolff-Parkinson-White syndrome unrelated to pre-excited atrial fibrillation.

A 52-year-old man was admitted due to out-hospital cardiac arrest. Recurrent ventricular fibrillation (VF) occurred under therapeutic hypothermia thereafter. Previously inadverted full pre-excitation was documented exclusively and immediately prior to 4 out of the 5 VF relapses. Coronary vasospasm and early repolarization were also documented. An electrophysiological study demonstrated poor anterograde conduction over a left-sided accessory pathway. We theorize that maximum pre-excitation favored in-hospital VF by augmenting the repolarization vulnerability induced by therapeutic hypothermia, with coronary vasospasm accounting as the probable cause of out-hospital VF. A plausible VF mechanism in WPW syndrome unrelated to pre-excited atrial fibrillation is discussed.

Acute-phase dynamics and prognostic value of growth differentiation factor-15 in ST-elevation myocardial infarction.

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.