Invasive Treatment Strategy in Adults With Frailty and Non-ST-Segment Elevation Myocardial Infarction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The MOSCA-FRAIL randomized clinical trial compared invasive and conservative treatment strategies in patients with frailty with non-ST-segment elevation myocardial infarction (NSTEMI). It showed no differences in the number of days alive and out of the hospital at 1 year. Objective: To assess the outcomes of the MOSCA-FRAIL trial during extended follow-up. Design, Setting, and Participants: The MOSCA-FRAIL randomized clinical trial was conducted at 13 hospitals in Spain between July 7, 2017, and January 9, 2021, and included 167 adults (aged ≥70 years) with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. In this preplanned secondary analysis, follow-up was extended to January 31, 2023. Data analysis was performed from April 5 to 29, 2023, using the intention-to-treat principle. Interventions: Patients were randomized to a routine invasive (coronary angiography and revascularization if feasible [n = 84]) or a conservative (medical treatment with coronary angiography only if recurrent ischemia [n = 83]) strategy. Main outcomes and measures: The primary end point was the difference in restricted mean survival time (RMST). Secondary end points included readmissions for any cause, considering recurrent readmissions. Results: Among the 167 patients included in the analysis, the mean (SD) age was 86 (5) years; 79 (47.3%) were men and 88 (52.7%) were women. A total of 93 deaths and 367 readmissions accrued. The RMST for all-cause death over the entire follow-up was 3.13 (95% CI, 2.72-3.60) years in the invasive and 3.06 (95% CI, 2.84-3.32) years in the conservative treatment groups. The RMST analysis showed inconclusive differences in survival time (invasive minus conservative difference, 28 [95% CI, -188 to 230] days). Patients under invasive treatment tended to have shorter survival in the first year (-28 [95% CI, -63 to 7] days), which improved after the first year (192 [95% CI, 90-230] days). Kaplan-Meier mortality curves intersected, displaying higher mortality to 1 year in the invasive group that shifted to a late benefit (landmark analysis hazard ratio, 0.58 [95% CI, 0.33-0.99]; P = .045). Early harm was more evident in the subgroup with a Clinical Frailty Scale score greater than 4. No differences were found for the secondary end points. Conclusions and Relevance: In this extended follow-up of a randomized clinical trial of patients with frailty and NSTEMI, an invasive treatment strategy did not improve outcomes at a median follow-up of 1113 (IQR, 443-1441) days. However, a differential distribution of deaths was observed, with early harm followed by later benefit. The phenomenon of depletion of susceptible patients may be responsible for this behavior. Trial registration: ClinicalTrials.gov Identifier: NCT03208153.

Effect of Routine Invasive vs Conservative Strategy in Older Adults With Frailty and Non-ST-Segment Elevation Acute Myocardial Infarction: A Randomized Clinical Trial.

Importance: To our knowledge, no randomized clinical trial has compared the invasive and conservative strategies in frail, older patients with non-ST-segment elevation acute myocardial infarction (NSTEMI). Objective: To compare outcomes of invasive and conservative strategies in frail, older patients with NSTEMI at 1 year. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted at 13 Spanish hospitals between July 7, 2017, and January 9, 2021, and included 167 older adult (≥70 years) patients with frailty (Clinical Frailty Scale score ≥4) and NSTEMI. Data analysis was performed from April 2022 to June 2022. Interventions: Patients were randomized to routine invasive (coronary angiography and revascularization if feasible; n = 84) or conservative (medical treatment with coronary angiography for recurrent ischemia; n = 83) strategy. Main Outcomes and Measures: The primary end point was the number of days alive and out of the hospital (DAOH) from discharge to 1 year. The coprimary end point was the composite of cardiac death, reinfarction, or postdischarge revascularization. Results: The study was prematurely stopped due to the COVID-19 pandemic when 95% of the calculated sample size had been enrolled. Among the 167 patients included, the mean (SD) age was 86 (5) years, and mean (SD) Clinical Frailty Scale score was 5 (1). While not statistically different, DAOH were about 1 month (28 days; 95% CI, -7 to 62) greater for patients managed conservatively (312 days; 95% CI, 289 to 335) vs patients managed invasively (284 days; 95% CI, 255 to 311; P = .12). A sensitivity analysis stratified by sex did not show differences. In addition, we found no differences in all-cause mortality (hazard ratio, 1.45; 95% CI, 0.74-2.85; P = .28). There was a 28-day shorter survival in the invasive vs conservatively managed group (95% CI, -63 to 7 days; restricted mean survival time analysis). Noncardiac reasons accounted for 56% of the readmissions. There were no differences in the number of readmissions or days spent in the hospital after discharge between groups. Neither were there differences in the coprimary end point of ischemic cardiac events (subdistribution hazard ratio, 0.92; 95% CI, 0.54-1.57; P = .78). Conclusions and Relevance: In this randomized clinical trial of NSTEMI in frail older patients, there was no benefit to a routine invasive strategy in DAOH during the first year. Based on these findings, a policy of medical management and watchful observation is recommended for older patients with frailty and NSTEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03208153.

Serum microRNAs are key predictors of long-term heart failure and cardiovascular death after myocardial infarction.

BACKGROUND: Patients with acute myocardial infarction (MI) are at high risk of upcoming events, in particular heart failure (HF), but reliable stratification methods are lacking. Our goal was to evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients presenting with MI. METHODS AND RESULTS: We conducted a prospective study among 311 consecutive patients hospitalized with MI (65% ST-segment elevation MI & median age of 55 years) with long-term follow-up. An initial screening was conducted to select candidate miRNAs, with subsequent study of 14 candidate miRNAs. The primary outcome was the composite of hospital admission for HF or cardiovascular death. During a mean follow-up of 2.1 years miR-21-5p, miR-23a-3p, miR27b-3p, miR-122-5p, miR210-3p, and miR-221-3p reliably predicted the primary outcome. Multivariate Cox regression analyses highlighted that miR-210-3p [hazard ratio (HR) 2.65 per 1 SD increase, P < 0.001], miR-23a-3p (HR 2.11 per 1 SD increase, P < 0.001), and miR-221-3p (HR 2.03 per 1 SD increase, P < 0.001) were able to accurately predict the primary outcome, as well as cardiovascular death, HF hospitalizations, and long-term New York Heart Association (NYHA) functional class. These three miRNAs clearly improved the performance of multivariate clinical models: ΔC-statistic = 0.10 [95% confidence interval (CI), 0.03-0.17], continuous net reclassification index = 34.8% (95%CI, 5.8-57.4%), and integrated discrimination improvement (P < 0.001). CONCLUSIONS: This is the largest study evaluating the prognostic value of circulating miRNAs for HF-related events among patients with MI. We show that several miRNAs predict HF hospitalizations, cardiovascular mortality, and poor long-term NYHA status and improve current risk prediction methods.

Theranostic Contribution of Extracellular Matrix Metalloprotease Inducer-Paramagnetic Nanoparticles Against Acute Myocardial Infarction in a Pig Model of Coronary Ischemia-Reperfusion.

BACKGROUND: Rapid screening and accurate diagnosis of acute myocardial infarction are critical to reduce the progression of myocardial necrosis, in which proteolytic degradation of myocardial extracellular matrix plays a major role. In previous studies, we found that targeting the extracellular matrix metalloprotease inducer (EMMPRIN) by injecting nanoparticles conjugated with the specific EMMPRIN-binding peptide AP9 significantly improved cardiac function in mice subjected to ischemia/reperfusion. METHODS: In a porcine model of coronary ischemia/reperfusion, we tested the theragnostic effects of administering 0.1 mg/kg gadolinium-containing nanoparticles conjugated with AP9 (NAP9), a synthetic peptide that targets EMMPRIN or a control nanoparticle (NAPSC). Cardiac magnetic resonance assessment of the infarct progression, ventricular function, and nanoparticle distribution was performed the next 7 days. We also measured the infarcted area of the heart and cardiac remodeling at 7 or 21 days after ischemia/reperfusion. RESULTS: After 21 days of ischemia/reperfusion, NAP9 reduced the extension of cardiac necrosis (14.1±9.7 versus 35.5±1.8) and the levels of collagenolytic activity of MMPs (matrix metalloproteases), along with a significant reduction in collagen deposition (7.5±4.5 versus 41.3±20); including the ratio of type I versus III collagen fibers in the necrotic myocardium. In terms of cardiac function, the response to NAP9 administration resulted in a significant improvement of cardiac performance overtime, as evidenced by the left ventricle ejection fraction (64.0±7.8), when compared with those present in the NAPSC group (47.3±4.7). As shown by magnetic resonance imaging, noninvasive molecular imaging of NAP9 enabled us to find a significant reduction in cardiac necrosis, myocardial edema, hemorrhage, and microvascular obstruction, suggesting that NAP9 may reduce myocardial injury and preserve left ventricular function, at least, by preventing the effect of EMMPRIN on extracellular matrix degradation. CONCLUSIONS: Our data point towards NAP9 as a promising theragnostic tool in managing acute myocardial infarction, by inhibiting EMMPRIN-induced extracellular matrix degradation and allowing noninvasive visualization of cardiac necrosis progression over time.

Ivabradine induces cardiac protection by preventing cardiogenic shock-induced extracellular matrix degradation.

INTRODUCTION AND OBJECTIVES: Ivabradine reduces heart rate by blocking the I(f) current and preserves blood pressure and stroke volume through unknown mechanisms. Caveolin-3 protects the heart by forming protein complexes with several proteins, including extracellular matrix (ECM)-metalloproteinase-inducer (EMMPRIN) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HN4), a target of ivabradine. We hypothesized that ivabradine might also exert cardioprotective effects through inhibition of ECM degradation. METHODS: In a porcine model of cardiogenic shock, we studied the effects of ivabradine on heart integrity, the levels of MMP-9 and EMMPRIN, and the stability of caveolin-3/HCN4 protein complexes with EMMPRIN. RESULTS: Administration of 0.3 mg/kg ivabradine significantly reduced cardiogenic shock-induced ventricular necrosis and expression of MMP-9 without affecting EMMPRIN mRNA, protein, or protein glycosylation (required for MMP activation). However, ivabradine increased the levels of the caveolin-3/LG-EMMPRIN (low-glycosylated EMMPRIN) and caveolin-3/HCN4 protein complexes and decreased that of a new complex between HCN4 and high-glycosylated EMMPRIN formed in response to cardiogenic shock. We next tested whether caveolin-3 can bind to HCN4 and EMMPRIN and found that the HCN4/EMMPRIN complex was preserved when we silenced caveolin-3 expression, indicating a direct interaction between these 2 proteins. Similarly, EMMPRIN-silenced cells showed a significant reduction in the binding of caveolin-3/HCN4, which regulates the I(f) current, suggesting that, rather than a direct interaction, both proteins bind to EMMPRIN. CONCLUSIONS: In addition to inhibition of the I(f) current, ivabradine may induce cardiac protection by inhibiting ECM degradation through preservation of the caveolin-3/LG-EMMPRIN complex and control heart rate by stabilizing the caveolin-3/HCN4 complex.

Factores de riesgo de muerte hospitalaria en pacientes con infarto agudo de miocardio durante la pandemia de la COVID-19 / Risk factors for in-hospital mortality in patients with acute myocardial infarction during the COVID-19 outbreak

INTRODUCCIÓN Y OBJETIVOS: A pesar de los avances en el tratamiento del infarto agudo de miocardio (IAM), este sigue presentando un pronóstico desfavorable. Hay poca evidencia acerca de la evolución de los pacientes con IAM y la enfermedad coronavírica de 2019 (COVID-19). El objetivo del estudio es describir la presentación clínica, las complicaciones y los factores predictores de mortalidad hospitalaria en pacientes con IAM durante el brote de COVID-19 en España. MÉTODOS: Se realizó un estudio de cohortes, prospectivo y multicéntrico de todos los pacientes consecutivos con IAM en tratamiento invasivo durante el brote de COVID19 (15 de marzo a 15 de abril de 2020). Se compararon las características clínicas de los pacientes positivos para COVID-19 con las de los negativos, y se evaluó el efecto de la COVID-19 en la mortalidad mediante emparejamiento por puntuación de propensión y regresión logística. RESULTADOS: Se incluyó a 187 pacientes con IAM: 111 con elevación del segmento ST y 76 sin elevación. De ellos, 32 (17%) resultaron positivos para COVID-19. Las puntuaciones GRACE y Killip-Kimball y varios marcadores inflamatorios resultaron significativamente mayores en los pacientes con COVID-19. La mortalidad total y cardiovascular fueron significativamente mayores en los pacientes con COVID-19 (el 25 frente al 3,8%; p < 0,001; y el 15,2 frente al 1,8%; p = 0,001). La puntuación GRACE > 140 (OR = 23,45; IC95%, 2,52-62,51; p = 0,005) y la COVID-19 (OR = 6,61; IC95%, 1,82-24,43; p = 0,02) resultaron factores independientes de mortalidad hospitalaria. CONCLUSIONES: Durante el brote epidémico, la puntuación GRACE elevada y la COVID19 fueron los factores independientes de mortalidad hospitalaria en los pacientes con IAM

INTRODUCTION AND OBJECTIVES: Despite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic. METHODS: This prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model. RESULTS: In total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [P < .001] and 15.2% vs 1.8% [P = .001], respectively). GRACE score > 140 (OR, 23.45; 95%CI, 2.52-62.51; P = .005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P = .02) were independent predictors of in-hospital death. CONCLUSIONS: During this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality

La consulta telemática para el cardiólogo clínico en tiempos de la COVID-19: presente y futuro. Documento de consenso de la Sociedad Española de Cardiología / Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology

La pandemia producida por la infección por el coronavirus SARS-CoV-2 (COVID-19) ha cambiado la forma de entender nuestras consultas. Para reducir el riesgo de contagio de los pacientes más vulnerables (aquellos con cardiopatías) y del personal sanitario, se han suspendido la mayoría de las consultas presenciales y se han puesto en marcha las consultas telemáticas. Este cambio se ha implementado en muy poco tiempo, pero parece que ha venido para quedarse. No obstante, hay grandes dudas sobre aspectos organizativos, legales, posibilidades de mejora, etc. En este documento de consenso de la Sociedad Española de Cardiología, tratamos de dar las claves para mejorar la calidad asistencial en nuestras nuevas consultas telemáticas, revisando las afecciones que el cardiólogo clínico atiende con más frecuencia en su consulta ambulatoria y proponiendo unos mínimos en ese proceso asistencial. Estas enfermedades son la cardiopatía isquémica, la insuficiencia cardiaca y las arritmias. En los 3 escenarios tratamos de clarificar los aspectos fundamentales que hay que revisar en la entrevista telefónica, a qué pacientes habrá que atender en una consulta presencial y cuáles serán los criterios para su seguimiento en atención primaria. El documento también recoge distintas mejoras que pueden introducirse en la consulta telemática para mejorar la asistencia de nuestros pacientes

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care

[Risk factors for in-hospital mortality in patients with acute myocardial infarction during the COVID-19 outbreak]. / Factores de riesgo de muerte hospitalaria en pacientes con infarto agudo de miocardio durante la pandemia de la COVID-19.

INTRODUCTION AND OBJECTIVES: Despite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic. METHODS: This prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model. RESULTS: In total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [P < .001] and 15.2% vs 1.8% [P = .001], respectively). GRACE score > 140 (OR, 23.45; 95%CI, 2.52-62.51; P = .005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P = .02) were independent predictors of in-hospital death. CONCLUSIONS: During this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality.Full English text available from:www.revespcardiol.org/en.

Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology.

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care.

Ivabradine-Stimulated Microvesicle Release Induces Cardiac Protection against Acute Myocardial Infarction.

Ivabradine can reduce heart rate through inhibition of the current I(f) by still unexplored mechanisms. In a porcine model of ischemia reperfusion (IR), we found that treatment with 0.3 mg/kg Ivabradine increased plasma release of microvesicles (MVs) over Placebo, as detected by flow cytometry of plasma isolated from pigs 7 days after IR, in which a tenfold increase of Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) containing (both high and low-glycosylated) MVs, was detected in response to Ivabradine. The source of MVs was investigated, finding a 37% decrease of CD31+ endothelial cell derived MVs, while CD41+ platelet MVs remained unchanged. By contrast, Ivabradine induced the release of HCN4+ (mostly cardiac) MVs. While no differences respect to EMMPRIN as a cargo component were found in endothelial and platelet derived MVs, Ivabradine induced a significant release of EMMPRIN+/HCN4+ MVs by day 7 after IR. To test the role of EMMPRIN+ cardiac MVs (EMCMV), H9c2 cell monolayers were incubated for 24 h with 107 EMCMVs, reducing apoptosis, and increasing 2 times cell proliferation and 1.5 times cell migration. The in vivo contribution of Ivabradine-induced plasma MVs was also tested, in which 108 MVs isolated from the plasma of pigs treated with Ivabradine or Placebo 7 days after IR, were injected in pigs under IR, finding a significant cardiac protection by increasing left ventricle ejection fraction and a significant reduction of the necrotic area. In conclusion ivabradine induces cardiac protection by increasing at least the release of EMMPRIN containing cardiac microvesicles.

[Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology]. / La consulta telemática para el cardiólogo clínico en tiempos de la COVID-19: presente y futuro. Documento de consenso de la Sociedad Española de Cardiología.

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care.

Risk factors for in-hospital mortality in patients with acute myocardial infarction during the COVID-19 outbreak.

INTRODUCTION AND OBJECTIVES: Despite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic. METHODS: This prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model. RESULTS: In total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [P <.001] and 15.2% vs 1.8% [P=.001], respectively). GRACE score> 140 (OR, 23.45; 95%CI, 2.52-62.51; P=.005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P=.02) were independent predictors of in-hospital death. CONCLUSIONS: During this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality.

Una puntuación de riesgo genético predice recurrencias en pacientes jóvenes con infarto agudo de miocardio / A genetic risk score predicts recurrent events after myocardial infarction in young adults

INTRODUCCIÓN Y OBJETIVOS: Evaluar si una puntuación de riesgo genético (GRS) mejora la predicción de eventos recurrentes en pacientes jóvenes con infarto agudo de miocardio (IAM) e identifica una forma de aterosclerosis más agresiva. MÉTODOS: Se diseñó un estudio prospectivo con pacientes <55 años, no diabéticos, ingresados por IAM. Se realizó un test genético, una tomografía computarizada cardiaca y determinación de varios biomarcadores. Se analizó la asociación de un GRS compuesto por 11 variantes genéticas con la aparición de un objetivo primario combinado (muerte cardiovascular, evento recurrente u hospitalización cardiovascular). RESULTADOS: Se siguió a 81 pacientes durante una mediana de 4,1 años, y se documentaron 24 eventos. La prevalencia de variantes de riesgo fue superior en 9 de los 11 alelos frente a población general. El GRS se asoció con recurrencias, particularmente cuando los niveles basales de colesterol-LDL estaban elevados. En el modelo multivariado, teniendo como referencia el tercil de bajo riesgo genético, el HR para el grupo de riesgo intermedio fue de 10,2 (IC95% 1,1-100,3; p = 0,04) y de alto riesgo 20,7 (2,4-181,0; p = 0,006) si el colesterol-LDL era≥2,8 mmol/l (≥ 110mg/dl). La incorporación del GRS al modelo multivariado mejoró el estadístico C (ΔC-statistic=0,086), el cNRI (30%) y el IDI (0,05). El TC cardiaco detectó ateromatosis calcificada frecuentemente, pero tuvo un valor pronóstico limitado. No se detectó una asociación entre metaloproteinasas, GRS y recurrencias. CONCLUSIONES: En una población de pacientes jóvenes no diabéticos con IAM, una puntuación de riesgo genético puede predecir recurrencias y mejorar los modelos clínicos de estratificación pronóstica, especialmente en aquellos pacientes con colesterol-LDL basal elevado

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8 mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels

COVID-19 y shock cardiogénico: diferentes formas de presentación cardiovascular con alta mortalidad / COVID-19 and cardiogenic shock. Different cardiovascular presentations with high mortality

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Ivabradine in acute heart failure: Effects on heart rate and hemodynamic parameters in a randomized and controlled swine trial.

BACKGROUND: Acute heart failure patients could benefit from heart rate reduction, as myocardial consumption and oxidative stress are related to tachycardia. Ivabradine could have a clinical role attenuating catecholamine-induced tachycardia. The aim of this study was to evaluate hemodynamic effects of ivabradine in a swine model of acute heart failure. METHODS: Myocardial infarction was induced by 45 min left anterior descending artery balloon occlusion in 18 anesthetized pigs. An infusion of dobutamine and noradrenaline was maintained aiming to preserve adequate hemodynamic support, accompanied by fluid administration to obtain a pulmonary wedged pressure ≥ 18 mmHg. After reperfusion, rhythm and hemodynamic stabilization, the animals were randomized to 0.3 mg/kg ivabradine intravenously (n = 9) or placebo (n = 9). Hemodynamic parameters were observed over a 60 min period. RESULTS: Ivabradine was associated with a significant reduction in heart rate (88.4 ± 12.0 bpm vs. 122.7 ± 17.3 bpm after 15 min of ivabradine/placebo infusion, p < 0.01) and an increase in stroke volume (68.8 ± 13.7 mL vs. 52.4 ± 11.5 mL after 15 min, p = 0.01). There were no significant differences in systemic or pulmonary arterial pressure, or significant changes in pulmonary capillary pressure. However, after 15 min, cardiac output was significantly reduced with ivabradine (-5.2% vs. +15.0% variation in ivabradine/placebo group, p = 0.03), and central venous pressure increased (+4.2% vs. -19.7% variation, p < 0.01). CONCLUSIONS: Ivabradine reduces heart rate and increases stroke volume without modifying systemic or left filling pressures in a swine model of acute heart failure. However, an excessive heart rate reduction could lead to a decrease in cardiac output and an increase in right filling pressures. Future studies with specific heart rate targets are needed.

A genetic risk score predicts recurrent events after myocardial infarction in young adults.

INTRODUCTION AND OBJECTIVES: To evaluate whether a genetic risk score (GRS) improves prediction of recurrent events in young nondiabetic patients presenting with an acute myocardial infarction (AMI) and identifies a more aggressive form of atherosclerosis. METHODS: We conducted a prospective study with consecutive nondiabetic patients aged <55 years presenting with AMI. We performed a genetic test, cardiac computed tomography, and analyzed several biomarkers. We studied the association of a GRS composed of 11 genetic variants and a primary composite endpoint (cardiovascular mortality, a recurrent event, and cardiac hospitalization). RESULTS: A total of 81 patients were studied and followed up for a median of 4.1 years. There were 24 recurrent cardiovascular events. Compared with the general population, study participants had a higher prevalence of 9 out of 11 risk alleles. The GRS was significantly associated with recurrent cardiovascular events, especially when baseline low-density lipoprotein cholesterol (LDL-C) levels were elevated. Compared with the low-risk GRS tertile, the multivariate-adjusted HR for recurrences was 10.2 (95%CI, 1.1-100.3; P=.04) for the intermediate-risk group and was 20.7 (2.4-181.0; P=.006) for the high-risk group when LDL-C was≥2.8mmol/L (≥ 110mg/dL). Inclusion of the GRS improved the C-statistic (ΔC-statistic=0.086), cNRI (continuous net reclassification improvement) (30%), and the IDI (integrated discrimination improvement) index (0.05). Cardiac computed tomography frequently detected coronary calcified atherosclerosis but had limited value for prediction of recurrences. No association was observed between metalloproteinases, GRS and recurrences. CONCLUSIONS: A multilocus GRS may identify individuals at increased risk of long-term recurrences among young nondiabetic patients with AMI and improve clinical risk stratification models, particularly among patients with high baseline LDL-C levels.

Role of rivaroxaban in the prevention of atherosclerotic events.

Introduction: The current approach of using only antiplatelet therapy for secondary prevention leaves a substantial risk of recurrent cardiovascular complications and mortality. Areas covered: In this manuscript, the role of coagulation in atherothrombosis is reviewed, as well as the impact of vascular doses of rivaroxaban on major cardiovascular outcomes and major adverse limb events. Expert opinion: In COMPASS, among patients with coronary heart disease and/or peripheral artery disease, compared to aspirin, the addition of rivaroxaban 2.5 mg twice daily to aspirin, significantly reduced the risk of major atherosclerotic outcomes, cardiovascular death and death for any cause, with a significant increase in the risk of major bleeding, but not fatal or intracranial bleedings. Preclinical data strongly suggest that rivaroxaban exerts vascular protection through different mechanisms, including improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties, and platelet-dependent thrombin generation. All these data indicate that among patients with atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg may provide further vascular protection.