Serological short-chain fatty acid and trimethylamine N-oxide microbial metabolite imbalances in young adults with acute myocardial infarction.

Acute myocardial infarction (AMI) is associated with systemic inflammatory processes and metabolic alterations. Microbial-derived metabolites, such as short-chain fatty acids and trimethylamine N-oxide (TMAO), have emerged in recent years as key players in the modulation of inflammation, with potential implications for cardiovascular diseases. We performed a prospective observational study that monitored the serological concentration of bacterial metabolites in 45 young patients (<55 years) without cardiovascular risk factors but with AMI, at hospital admission and at 3 months of follow-up, and compared them with a control group. TMAO and acetate levels were significantly higher in AMI, whereas butyrate and propionate were significantly lower. The acetate/propionate ratio showed the most discrimination between AMI and controls by receiver operating characteristic analysis (area under the curve 0.769, P < 0.0001). A multivariate logistic regression model revealed that this ratio was independently associated with AMI. Short-chain fatty acid concentrations, but not TMAO, exhibited significant correlations with inflammatory and coagulation parameters. Three months after the acute AMI event, all metabolite levels returned to those observed in healthy controls except butyrate. In conclusion, our study reveals disturbances of the serological concentration of microbiota-derived metabolites in AMI that are also related to inflammatory and coagulation parameters. These findings highlight an interesting field of study in the potential role of microbial metabolites from gut in cardiovascular disease.

Coronariografía urgente en los pacientes con parada cardiaca extrahospitalaria sin elevación del segmento ST. Ensayo clínico COUPE / Coronary angiography in patients without ST-segment elevation following out-of-hospital cardiac arrest. COUPE clinical trial

Introducción y objetivos El papel de la coronariografía urgente y angioplastia, si procede, en los pacientes con parada cardiaca extrahospitalaria (PCEH) recuperada que no presentan elevación del segmento ST es controvertido. Nuestro objetivo fue evaluar si la coronariografía urgente y la angioplastia mejoran la supervivencia con buen pronóstico neurológico en esta población. Métodos En este ensayo clínico multicéntrico, aleatorizado, abierto, incluimos 69 pacientes supervivientes a una PCEH sin elevación del ST y se aleatorizaron a recibir una coronariografía urgente (CU) o diferida (CD). El objetivo primario de eficacia fue el combinado de supervivencia hospitalaria libre de dependencia. El objetivo de seguridad fue un compuesto de eventos cardiacos mayores, incluyendo muerte, reinfarto, sangrado y arritmias ventriculares. Resultados Se incluyó a 66 pacientes en el análisis primario (95,7%). La supervivencia hospitalaria fue 62,5% en el grupo CU y 58,8% en el grupo CD (HR = 0,96; IC95%, 0,45-2,09; p=0,93). La supervivencia hospitalaria con buen pronóstico neurológico fue 59,4% en el grupo CU y 52,9% en el grupo CD (HR = 1,29; IC95%, 0,60-2,73; p=0,4986). No se encontraron diferencias en los objetivos secundarios, salvo por la incidencia de fracaso renal agudo, que fue más frecuente en el grupo CU (15,6 frente a 0%, p=0,002) y de infecciones, más prevalentes en el grupo CD (46,9 frente a 73,5%, p=0,003). Conclusiones En este estudio aleatorizado de pacientes con una PCEH sin elevación del ST, una CU no fue beneficiosa en términos de supervivencia con buen pronóstico neurológico comparada con una CD (AU)

Introduction and objectives The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest (OHCA) in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. We aimed to assess whether emergency CAG and PCI would improve survival with good neurological outcome in this population. Methods In this multicenter, randomized, open-label, investigator-initiated clinical trial, we randomly assigned 69 survivors of OHCA without STEMI to undergo immediate CAG or deferred CAG. The primary efficacy endpoint was a composite of in-hospital survival free of severe dependence. The safety endpoint was a composite of major adverse cardiac events including death, reinfarction, bleeding, and ventricular arrhythmias. Results A total of 66 patients were included in the primary analysis (95.7%). In-hospital survival was 62.5% in the immediate CAG group and 58.8% in the delayed CAG group (HR, 0.96; 95%CI, 0.45-2.09; P=.93). In-hospital survival free of severe dependence was 59.4% in the immediate CAG group and 52.9% in the delayed CAG group (HR, 1.29; 95%CI, 0.60-2.73; P=.4986). No differences were found in the secondary endpoints except for the incidence of acute kidney failure, which was more frequent in the immediate CAG group (15.6% vs 0%, P=.002) and infections, which were higher in the delayed CAG group (46.9% vs 73.5%, P=.003). Conclusions In this underpowered randomized trial involving patients resuscitated after OHCA without STEMI, immediate CAG provided no benefit in terms of survival without neurological impairment compared with delayed CAG (AU)

Coronary angiography in patients without ST-segment elevation following out-of-hospital cardiac arrest. COUPE clinical trial.

INTRODUCTION AND OBJECTIVES: The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest (OHCA) in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. We aimed to assess whether emergency CAG and PCI would improve survival with good neurological outcome in this population. METHODS: In this multicenter, randomized, open-label, investigator-initiated clinical trial, we randomly assigned 69 survivors of OHCA without STEMI to undergo immediate CAG or deferred CAG. The primary efficacy endpoint was a composite of in-hospital survival free of severe dependence. The safety endpoint was a composite of major adverse cardiac events including death, reinfarction, bleeding, and ventricular arrhythmias. RESULTS: A total of 66 patients were included in the primary analysis (95.7%). In-hospital survival was 62.5% in the immediate CAG group and 58.8% in the delayed CAG group (HR, 0.96; 95%CI, 0.45-2.09; P=.93). In-hospital survival free of severe dependence was 59.4% in the immediate CAG group and 52.9% in the delayed CAG group (HR, 1.29; 95%CI, 0.60-2.73; P=.4986). No differences were found in the secondary endpoints except for the incidence of acute kidney failure, which was more frequent in the immediate CAG group (15.6% vs 0%, P=.002) and infections, which were higher in the delayed CAG group (46.9% vs 73.5%, P=.003). CONCLUSIONS: In this underpowered randomized trial involving patients resuscitated after OHCA without STEMI, immediate CAG provided no benefit in terms of survival without neurological impairment compared with delayed CAG. CLINICALTRIALS: gov Identifier: NCT02641626.

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

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.

Seguridad de una estrategia de alta muy precoz en el síndrome coronario agudo con elevación del segmento ST / Safety of a very early discharge strategy for ST-segment elevation acute coronary syndrome

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The Role of Frailty in Acute Coronary Syndromes in the Elderly.

BACKGROUND: Myocardial infarction (MI) patients are increasingly older, and common risk scores include chronological age, but do not consider chronic comorbidity or biological age. Frailty status reflects these variables and may be independently correlated with prognosis in this setting. OBJECTIVE: This study investigated the impact of frailty on the prognosis of elderly patients admitted due to MI. METHODS: This prospective and observational study included patients ≥75 years admitted to three tertiary hospitals in Spain due to MI. Frailty assessment was performed at admission using the Survey of Health, Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the composite of death or non-fatal reinfarction during a follow-up of 1 year. Overall mortality, reinfarction, the composite of death, reinfarction and stroke, major bleeding, and readmission rates were also explored. RESULTS: A total of 285 patients were enrolled. Frail patients (109, 38.2%) were older, with a higher score in the Charlson Comorbidity Index and with a higher risk score addressed in the GRACE and CRUSADE indexes. On multivariate analysis including GRACE, CRUSADE, maximum creatinine level, culprit lesion revascularization, complete revascularization, and dual antiplatelet therapy at discharge, frailty was an independent predictor of the composite of death and reinfarction (2.81, 95% CI 1.16-6.78) and overall mortality (3.07, 95% CI 1.35-6.98). CONCLUSION: Frailty is an independent prognostic marker of the composite of mortality and reinfarction and of overall mortality in patients aged ≥75 years admitted due to MI.

Frailty is an independent prognostic marker in elderly patients with myocardial infarction.

BACKGROUND: Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age. HYPOTHESIS: This study aims to determine the prevalence of frailty and its influence on patients age ≥75 years with ACS. METHODS: Patients age ≥75 years admitted due to type 1 myocardial infarction were included in 2 tertiary hospitals, and clinical data were collected prospectively. Frailty was defined at admission using the previously validated Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the combination of death or nonfatal myocardial reinfarction during a follow-up of 6 months. Major bleeding (hemoglobin decrease ≥3 g/dL or transfusion needed) and readmission rates were also explored. RESULTS: A total of 234 consecutive patients were included. Frail patients (40.2%) had a higher-risk profile, based on higher age and comorbidities. On multivariate analysis, frailty was an independent predictor of the combination of death or nonfatal myocardial reinfarction (adjusted hazard ratio [aHR]: 2.54, 95% confidence interval [CI]: 1.12-5.79), an independent predictor of the combination of death, nonfatal myocardial reinfarction, or major bleeding (aHR: 2.14, 95% CI: 1.13-4.04), and an independent predictor of readmission (aHR: 1.80, 95% CI: 1.00-3.22). CONCLUSIONS: Frailty phenotype at admission is common among elderly patients with ACS and is an independent predictor for severe adverse events. It should be considered in future risk-stratification models.

Frailty predicts major bleeding within 30days in elderly patients with Acute Coronary Syndrome.

OBJECTIVE: Bleeding in ACS patients is an independent marker of adverse outcomes. Its prognostic impact is even worse in elderly population. Current bleeding risk scores include chronological age but do not consider biologic vulnerability. No studies have assessed the effect of frailty on major bleeding. The aim of this study is to determine whether frailty status increases bleeding risk in patients with ACS. METHODS: This prospective and observational study included patients aged ≥75years admitted due to type 1 myocardial infarction. Exclusion criteria were severe cognitive impairment, impossibility to measure handgrip strength, cardiogenic shock and limited life expectancy due to oncologic diseases. The primary endpoint was 30-day major bleeding defined as a decrease of ≥3g/dl of haemoglobin or need of transfusion. RESULTS: A total of 190 patients were included. Frail patients (72, 37.9%) were older, with higher comorbidity features and with a higher CRUSADE score at admission. On univariate analysis, frailty predicted major bleeding during 30-day follow-up despite less frequent use of a P2Y12 inhibitor (66.2% vs 83.6%, p=0.007) and decreased catheterisation rate (69.4% vs 94.1%, p<0.001). Major bleeding was associated with increased all-cause mortality at day 30 (18.2% vs 2.5%, p<0.001). On multivariate analysis, frailty was an independent predictor for major bleeding. CONCLUSION: Frailty phenotype, as a marker of biological vulnerability, is an independent predictor of major bleeding in elderly patients with ACS. Frailty can play an important role in bleeding risk stratification and objective indices should be integrated into routine initial evaluation of these patients.

Frailty is a short-term prognostic marker in acute coronary syndrome of elderly patients.

BACKGROUND: Frailty is a biological condition that reflects a state of decreased physiological reserve and vulnerability to stressors. The role of frailty in acute coronary syndrome patients has not been fully explored. Our study aims to assess the prevalence of frailty and its impact on in-hospital adverse outcomes of patients aged ⩾75 years admitted for acute coronary syndrome. METHODS: This prospective, observational study included patients aged ⩾75 years admitted due to type 1 myocardial infarction in four tertiary hospitals. Frailty was assessed by the SHARE-FI index. The primary endpoint was the combination of in-hospital death or non-fatal myocardial (re)infarction. Secondary endpoints included the assessment of individual rates of (re)infarction, mortality, stroke, major bleeding and the combination of in-hospital death, (re)infarction and mortality. RESULTS: A total of 202 patients were analysed. Frail patients (n=71, 35.1%) were older, more often women, had higher rates of comorbidities, and a higher risk profile according to GRACE, TIMI and CRUSADE scores at admission. The primary endpoint was significantly more frequent among frail patients (9.9% vs. 1.5%; P=0.006), as well as the combination of death, myocardial infarction and stroke (11.3% vs. 1.5%; P=0.002), driven mainly by a higher mortality rate (8.5% vs 0.8%; P=0.004). On multivariate analysis, frailty phenotype was an independent predictor of major adverse cardiac events (odds ratio 7.13; 95% confidence interval 1.43-35.42). CONCLUSIONS: Over one third of elderly patients with high-risk acute coronary syndrome are frail. Frailty phenotype is an important and independent prognostic marker in these patients.

Clinical Experience with Ivabradine in Acute Heart Failure.

OBJECTIVE: Ivabradine has been shown to improve symptoms and to reduce rehospitalization and mortality in patients with severe chronic heart failure (HF). Its indication in acute HF is not clear. Acute HF patients could also benefit from HR reduction, as myocardial consumption and oxidative stress are related to tachycardia. Moreover, beta-blockers are contraindicated in cardiogenic shock and should not be initiated with congestive signs. Accordingly, we evaluated the role of ivabradine in acute HF patients. METHODS: This was a retrospective analysis of 29 consecutive patients treated for acute HF in the Cardiac ICU, and for whom ivabradine was initiated during hospitalization between January 2011 and January 2014. All patients were in sinus rhythm and had a heart rate (HR) >70 bpm. Catecholamine use was necessary in 16 patients (57.1%) during the hospitalization, in 14 (87.5%) of these before ivabradine treatment. RESULTS: Systolic blood pressure showed no variation during the first 24 h of ivabradine administration or at discharge. HR showed an absolute reduction of 10 bpm at 6 h (p < 0.001), 11 bpm at 24 h (p = 0.004) and 19 bpm (p < 0.001) at discharge. No episodes of significant bradycardia or hypotension were recorded after starting the drug. CONCLUSIONS: HR reduction with ivabradine in acute HF is well tolerated. It represents an attractive option, especially when there is excessive catecholamine-related tachycardia; this should be appropriately evaluated in randomized trials.

Ventricular septal rupture in a case of myocardial infarction with normal coronary arteries: Case report.

Ventricular wall rupture has become an infrequent complication of myocardial infarction due to widespread use of prompt reperfusion strategies. Patients suffering myocardial infarction with normal coronary arteries seldom develop severe mechanical complications. We present the case of a patient who developed a ventricular septal rupture following an anteroseptal myocardial infarction and who presented normal coronary arteries at the time of coronary angiography.

Impact of thrombus burden on procedural and mid-term outcomes after primary percutaneous coronary intervention.

OBJECTIVE: Angiographic thrombus burden (TB) can be assessed early and enable a decision on intervention. The aim of this study was to analyze its effect on the incidence of cardiac events after a primary percutaneous coronary intervention. PATIENTS AND METHODS: We carried out a prospective study of 480 consecutive ST-segment elevation myocardial infarction patients treated by systematic primary percutaneous coronary intervention. Large TB was defined as thrombus length at least 2 vessel diameters or as solid thrombus obtained through catheter aspiration. The primary outcome measure was a composite of death, reinfarction, or target vessel revascularization. RESULTS: A total of 205 (47%) patients fulfilled the criteria for large TB. These patients were more frequently treated with abciximab (62.0 vs. 35.8%, P<0.001), showed more angiographic complications (26.6 vs. 13.7%, P=0.001), and had larger infarcts (peak troponin I, 74 vs. 50 ng/ml, P=0.015). During a follow-up of 19 ± 5 months, the rates of primary outcome were similar between groups of small and large TB (16.2 vs. 12.8%, hazard ratio: 0.88, 95% confidence interval: 0.46-1.67, P=0.691). There were no differences in the rates of definite stent thrombosis (0.5 vs. 2.2%, P=0.190). CONCLUSION: Large TB is associated with larger infarct size, but not with worse mid-term outcomes. Selective use of adjuvant therapies according to TB may be an effective approach to reduce thrombotic complications.

Ámbito de actuación de la cardiología en los nuevos escenarios clínicos. Documento de consenso de la Sociedad Española de Cardiología / The scope of cardiological competence in new clinical settings. Spanish Society of Cardiology Consensus Document

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Analysis of mortality and risk factors associated with native valve endocarditis in drug users: the importance of vegetation size.

BACKGROUND: Native valve endocarditis in drug-user patients had a microbiology, a frequency of involvement of different cardiac valves, and a prognosis that differ from those in non-drug users. A retrospective study of native valve endocarditis cases in intravenous drug users diagnosed from 1985 to 1999 in our institution was performed to analyze the inhospital mortality of drug users with native valve endocarditis and to identify factors predictive of mortality. METHODS: All patients fulfilled the Duke's criteria for definite or probable endocarditis. Analysis of predictors of inhospital mortality was restricted to right-sided infective endocarditis (IE) with definite diagnosis and echocardiographic data. The following variables were analyzed: sex, HIV serostatus, CD4 cell count < 200/mm3, time of IE diagnosis (before 1993 or after 1993), previous valvulopathy, polymicrobial IE, fungal etiology (mixed or alone), neurological complication, arterial emboli, pulmonary emboli, congestive heart failure, vegetation size (VS) > 2 cm, and inhospital cardiac surgery. Logistic regression was used in a multivariate model to identify factors independently associated with mortality. Adjusted odds ratios (OR) and 95% CIs were examined. RESULTS: Four hundred ninety-three cases of IE were diagnosed in this period. Two hundred twenty cases of native valve endocarditis in intravenous drug users were identified. Fourteen cases in this group died (6%). Mean time from diagnosis to death was 18.5 +/- 15 days (range, 3-52). Vegetation size was available in 111 cases. Univariate analysis identified the following variables associated with inhospital mortality in right-sided cases: VS > 2 cm and fungal etiology. In multivariate analysis, the variables associated with mortality that achieved statistical significance were size of vegetation > 2 cm (P = .014, OR 10.2, 95% CI 1.6-78.0) and fungal etiology (P = .009, OR 46.2, 95% CI 2.4-1100.9). CONCLUSIONS: The main prognostic factors of inhospital mortality in right-sided IE in drug users in our series were VS > 2 cm and fungal etiology. The role of early surgery in these patients should be reevaluated.