A Single High-Sensitivity Cardiac Troponin T Strategy for Ruling Out Myocardial Infarction.

Background: Ruling out acute myocardial infarction (AMI) in the emergency department (ED) is challenging. Studies have shown that a high-sensitivity cardiac troponin T (hs-cTnT) <5 ng/L or <6 ng/L at presentation (0 h) can be used to rule out AMI. The objective of this study was to identify whether an even higher hs-cTnT threshold can be used for a safe rule out of AMI in the ED. Methods: The derivation cohort consisted of 24,973 ED patients with a primary complaint of chest pain. In this cohort, we identified the highest concentration of 0 h hs-cTnT that corresponded to a negative predictive value (NPV) of ≥99.5% for the primary endpoint of AMI/all-cause death within 30 days and the secondary endpoint of all-cause death within one year. The results were validated in two cohorts consisting of 132,021 and 1167 ED chest pain patients. Results: The 0 h hs-cTnT threshold corresponding to a NPV of ≥99.5% for the primary endpoint was <9 ng/L (NPV: 99.6% and 95% CI: 99.5-99.7). This cutoff provided a sensitivity of 96.2% (95% CI: 95.2-97.1) and identified 59.7% of the patients as low risk compared to 35.8% and 43.9% with a 0 h hs-cTnT <5 ng/L and <6 ng/L, respectively. The results were similar in the validation cohorts and seemed to perform even better in patients where the 0 h hs-cTnT was measured >3 h after symptom onset and in those with a nonischemic ECG and nonhigh risk history. Conclusions: A 0 h hs-cTnT cutoff of <9 ng/L safely rules out AMI/death within 30 days in a majority of chest pain patients and is a more effective strategy than the currently recommended <5 ng/L and <6 ng/L cutoffs. This trial is registered with NCT03421873.

Bacteraemia with gram-positive bacteria-when and how do I need to look for endocarditis?

BACKGROUND: Patients with bacteraemia caused by gram-positive bacteria are at risk for infective endocarditis (IE). Because IE needs long antibiotic treatment and sometimes heart valve surgery, it is very important to identify patients with IE. OBJECTIVES: In this narrative review we present and discuss how to determine which investigations to detect IE that are needed in individual patients with gram-positive bacteraemia. SOURCES: Published original studies and previous reviews in English, within the relevant field are used. CONTENT: First, the different qualities of the bacteraemia in relation to IE risk are discussed. The risk for IE in bacteraemia is related to the species of the bacterium but also to monomicrobial bacteraemia and the number of positive cultures. Second, patient-related factors for IE risk in bacteraemia are presented. Next, the risk stratification systems to determine the risk for IE in gram-positive bacteraemia caused by Staphylococcus aureus, viridans streptococci, and Enterococcus faecalis are presented and their use is discussed. In the last part of the review, an account for the different modalities of IE-investigations is given. The main focus is on echocardiography, which is the cornerstone of IE-investigations. Furthermore, 18F-fluorodesoxyglucose positron emission tomography/computed tomography and cardiac computed tomography are presented and their use is also discussed. A brief account for investigations used to identify embolic phenomena in IE is also given. Finally, we present a flowchart suggesting which investigations to perform in relation to IE in patients with gram-positive bacteraemia. IMPLICATIONS: For the individual patient as well as the healthcare system, it is important both to diagnose IE and to decide when to stop looking for IE. This review might be helpful in finding that balance.

Risk factors for and consequences of positive valve cultures in patients who undergo cardiac surgery while receiving antimicrobial treatment for infective endocarditis.

INTRODUCTION: Cardiac surgery is required in up to half of the patients with infective endocarditis (IE). Positive valve cultures have been associated with higher in-hospital mortality. The aims were to identify risk factors for positive valve cultures and its relation to outcome. METHODS: Patients subjected to heart valve cultures due to surgery for IE in Skåne University Hospital, Lund, between 2012 and 2021 were identified through microbiology records. Risk factors for positive valve cultures and information on mortality and relapse were retrieved through medical records. Univariable and multivariable logistic regressions were performed. RESULTS: A total of 345 episodes with IE in 337 patients subjected to cardiac surgery were included and valve cultures were positive in 78 (23%) episodes. In multivariable logistic regression, preoperative fever (adjusted odds ratio (AOR) 2.6, 95% confidence interval (CI) 1.2-5.6, p = 0.02), prosthetic heart valve (AOR 3.3, CI 1.4-7.9, p = 0.01), a single affected valve (AOR 4.8, CI 1.2-20, p = 0.03), blood culture findings of S. aureus, enterococci, or coagulase negative staphylococci compared to viridans streptococci (AOR 20-48, p < 0.001), and a shorter duration of antibiotic treatment (p < 0.001), were associated to positive valve culture. One-year mortality was 13% and a relapse was identified in 2.5% of episodes. No association between positive valve cultures and one-year mortality or relapse was identified. CONCLUSIONS: Positive valve cultures were associated to short preoperative antibiotic treatment, IE caused by staphylococci, preoperative fever and prosthetic valve but not to relapse or mortality.

Treatment refractory arthritis and stroke - A case of infective endocarditis caused by Tropheryma whipplei.

Whipple´s disease is a rare multisystem condition affecting < 1/1.000.000 per year. The condition often presents with polyarthritis, diarrhea, and intestinal malabsorption. Endocarditis is seen in a minority of these patients, and is typically culture negative, as the causative agent Tropheryma whipplei does not grow in ordinary culture media. We present the case of a 78-year-old man with a history of seronegative polyarthritis that was refractory to treatment with several biological agents for a duration of 5 years prior to presentation to the emergency department with stroke. Echocardiography revealed aortic valve endocarditis with a 3.6 cm vegetation and multiple smaller vegetations. The patient underwent surgery with aortic valve replacement followed by prolonged antibiotic treatment. 16 S rDNA PCR analysis of the resected valve revealed T. whipplei as the causative agent. Two years after surgery and treatment with antibiotics, the patient's previously longstanding arthritis had totally disappeared and all rheumatological treatment had been discontinued.

Bacteraemia and infective endocarditis with Streptococcus bovis-Streptococcus equinus-complex: a retrospective cohort study.

BACKGROUND: Streptococcus bovis/equinus complex (SBSEC) comprise several species and subspecies and is a common cause of infective endocarditis (IE). S. gallolyticus subsp. gallolyticus (Sg gallolyticus) accounts for a majority of SBSEC IE, but the risk of IE for other subspecies is largely unknown. We aimed to investigate the clinical presentation of bacteraemia, and proportion of patients with IE in bacteraemia with the most common subspecies. METHODS: A retrospective cohort study of SBSEC-bacteraemia identified in clinical laboratory databases, in Skåne Region, Sweden, 2003-2018. Bacteraemia with Sg gallolyticus, S. gallolyticus subsp. pasteurianus (Sg pasteurianus), S. lutetiensis and S. infantarius subsp. infantarius (Si infantarius) were included. Subspecies was identified by whole genome sequencing. Medical charts were reviewed according to a predetermined protocol, IE was defined by the criteria from European Society of Cardiology. RESULTS: In total, 210 episodes of SBSEC-bacteraemia were included. Definite IE was identified in 28/210 (13%) episodes. Of these, 7/28 (25%) were prosthetic valve-IE, 1/28 (4%) related to a cardiovascular implantable electronic device and 10/28 (36%) required heart valve surgery. The proportions of IE among different subspecies were: Sg gallolyticus 17/52 (33%), Si infantarius 5/31 (16%), Sg pasteurianus 4/83 (5%) and S. lutetiensis 2/44 (5%) (p < 0.001). Sg pasteurianus and S. lutetiensis were more often associated with intra-abdominal- and polymicrobial infection. CONCLUSION: The proportion of IE in SBSEC-bacteraemia varies substantially depending on subspecies. Echocardiography should always be considered in bacteraemia with Sg gallolyticus and Si infantarius, and can sometimes be omitted in bacteraemia with Sg pasteurianus and S. lutetiensis.

Safety of early hospital discharge following admission with ST-elevation myocardial infarction treated with percutaneous coronary intervention: a nationwide cohort study.

BACKGROUND: The Second Primary Angioplasty in Myocardial Infarction (PAMI-II) risk score is recommended by guidelines to identify low-risk patients with ST-elevation myocardial infarction (STEMI) for an early discharge strategy. AIMS: We aimed to assess the safety of early discharge (≤2 days) for low-risk STEMI patients treated with primary percutaneous coronary intervention (PCI). METHODS: Using nationwide data from the SWEDEHEART registry, we identified patients with STEMI treated with primary PCI during the period 2009-2017, of whom 8,092 (26.4%) were identified as low risk with the PAMI-II score. Low-risk patients were stratified according to their length of hospital stay (≤2 days vs >2 days). The primary endpoint was major adverse cardiovascular events (MACE, including death, reinfarction treated with PCI, stroke or heart failure hospitalisation) at one year, assessed using a Cox proportional hazards model with propensity score as well as an inverse probability weighting propensity score of average treatment effect to adjust for confounders. RESULTS: A total of 1,449 (17.9%) patients were discharged ≤2 days from admission. After adjustment, the one-year MACE rate was not higher for patients discharged at >2 days from admission than for patients discharged ≤2 days (4.3% vs 3.2%; adjusted HR 1.31, 95% confidence interval [CI]: 0.92-1.87, p=0.14), and no difference was observed regarding any of the individual components of the main outcome. Results were consistent across all subgroups with no difference in MACE between early and late discharge patients. CONCLUSIONS: Nationwide observational data suggest that early discharge of low-risk patients with STEMI treated with PCI is not associated with an increase in one-year MACE.

Capnocytophaga canimorsus tricuspid valve endocarditis.

Capnocytophaga canimorsus is an uncommon cause of infective endocarditis (IE) and mainly affects persons with compromised immune-systems who have been in contact with dogs. We describe a case of C. canimorsus tricuspid valve IE in a 70 year-old dog-owner where diagnosis and treatment were delayed. The reason for the delayed diagnosis in this case was likely due to that initial blood cultures were negative due to preceding antibiotic treatment, discrepancies between echocardiographic investigations, and a thymoma and colonic polyps which were thought to explain the symptoms. A multi-diciplinary approach in cases with suspected IE might help to avoid diagnostic delays.

Short time to blood culture positivity in Enterococcus faecalis infective endocarditis.

Time to blood culture positivity (TTP) is an indirect measure of bacterial concentration in blood. A short TTP has been linked to the presence of infective endocarditis (IE) and to poor prognosis in Staphylococcus aureus bacteremia. We analyze factors influencing TTP in bacteremia with Enterococcus faecalis. This retrospective observational study of medical records included adults diagnosed with monomicrobial E. faecalis bacteremia between 2015 and 2018 in the Skåne region (Sweden). For each episode, the shortest TTP was recorded. Median TTP was compared between patients grouped based on age, sex, comorbidity, site of acquisition, and focus of infection. Using a dichotomized TTP (shorter or longer than 12 h), a multivariable logistic regression for factors associated to TTP was performed. The association between TTP and IE or mortality was evaluated. Three hundred sixty-seven episodes with monomicrobial E. faecalis bacteremia with the corresponding TTP were identified. Median TTP for the entire cohort was 11.6 (IQR 9.9-14.1) h and a significantly shorter TTP was noted for episodes which represented IE (n = 55, 9.4 (IQR 6.4-10.6) h). Only IE remained associated with a short TTP (≤ 12 h) in binary logistic regression analysis. Factors associated with IE were investigated and TTP was associated with IE also when adjusted for age, gender, comorbidity, and nosocomial acquisition. There was no association between TTP and mortality. A low TTP is associated with IE in E. faecalis bacteremia and could be used as a help in determining the need for echocardiography in patients with this condition.

Time to blood culture positivity in Staphylococcus aureus bacteraemia to determine risk of infective endocarditis.

OBJECTIVES: Patients with Staphylococcus aureus bacteraemia (SAB) at risk for infective endocarditis (IE) need to be identified because they should undergo echocardiography. We validated previous scoring systems for IE risk determination and evaluated whether time to blood culture positivity (TTP) could improve scoring systems. METHODS: This retrospective population-based study included adults with SAB in 2016 in a derivation cohort and those from 2017 in a validation cohort. TTP was compared between patients with and without IE. A new score including TTP was constructed using a least absolute shrinkage selection operator. The new POSITIVE score was compared to the previously described PREDICT and VIRSTA scores. RESULTS: A total of 465 episodes with SAB were included in the derivation cohort, of which 38 (8.2%) represented IE. Median (interquartile range) TTP was significantly shorter in episodes with IE, at 8.7 (7.7-10.6) hours compared to those without, at 13.3 (10.5-16.5) hours. When using a cutoff at 13 hours, TTP had a sensitivity of 100% (95% confidence interval (CI), 91-100) and specificity of 52% (95% CI, 47-57) for IE. The POSITIVE score included TTP, intravenous drug use, embolizations and presence of preexisting heart conditions. It had a sensitivity of 93% (95% CI, 76-99) and a specificity of 70% (95% CI, 66-74) in the validation cohort. The performance of POSITIVE was superior to PREDICT, and the specificity was higher than that of VIRSTA. CONCLUSIONS: TTP, either by itself or as part of the POSITIVE score, can be used to identify patients with SAB at low risk for IE. Further validation is needed because TTP is sensitive to several external factors.

Circulating Levels of Brain-Enriched MicroRNAs Correlate with Neuron Specific Enolase after Cardiac Arrest-A Substudy of the Target Temperature Management Trial.

Outcome prognostication after cardiac arrest (CA) is challenging. Current multimodal prediction approaches would benefit from new biomarkers. MicroRNAs constitute a novel class of disease markers and circulating levels of brain-enriched ones have been associated with outcome after CA. To determine whether these levels reflect the extent of brain damage in CA patients, we assessed their correlation with neuron-specific enolase (NSE), a marker of brain damage. Blood samples taken 48 h after return of spontaneous circulation from two groups of patients from the Targeted Temperature Management trial were used. Patients were grouped depending on their neurological outcome at six months. Circulating levels of microRNAs were assessed by sequencing. NSE was measured at the same time-point. Among the 673 microRNAs detected, brain-enriched miR9-3p, miR124-3p and miR129-5p positively correlated with NSE levels (all p < 0.001). Interestingly, these correlations were absent when only the good outcome group was analyzed (p > 0.5). Moreover, these correlations were unaffected by demographic and clinical characteristics. All three microRNAs predicted neurological outcome at 6 months. Circulating levels of brain-enriched microRNAs are correlated with NSE levels and hence can reflect the extent of brain injury in patients after CA. This observation strengthens the potential of brain-enriched microRNAs to aid in outcome prognostication after CA.

Circulating Levels of miR-574-5p Are Associated with Neurological Outcome after Cardiac Arrest in Women: A Target Temperature Management (TTM) Trial Substudy.

PURPOSE: Postresuscitation neuroprognostication is guided by neurophysiological tests, biomarker measurement, and clinical examination. Recent investigations suggest that circulating microRNAs (miRNA) may help in outcome prediction after cardiac arrest. We assessed the ability of miR-574-5p to predict neurological outcome after cardiac arrest, in a sex-specific manner. METHODS: In this substudy of the Target Temperature Management (TTM) Trial, we enrolled 590 cardiac arrest patients for which blood samples were available. Expression levels of miR-574-5p were measured by quantitative PCR in plasma samples collected 48 h after cardiac arrest. The endpoint of the study was poor neurological outcome at 6 months (cerebral performance category scores 3 to 5). RESULTS: Eighty-one percent of patients were men, and 49% had a poor neurological outcome. Circulating levels of miR-574-5p at 48 h were higher in patients with a poor neurological outcome at 6 months (p < 0.001), both in women and in men. Circulating levels of miR-574-5p were univariate predictors of neurological outcome (odds ratio (OR) [95% confidence interval (CI)]: 1.5 [1.26-1.78]). After adjustment with clinical variables and NSE, circulating levels of miR-574-5p predicted neurological outcome in women (OR [95% CI]: 1.9 [1.09-3.45]), but not in men (OR [95% CI]: 1.0 [0.74-1.28]). CONCLUSION: miR-574-5p is associated with neurological outcome after cardiac arrest in women.

[Endocarditis team in the Scania region - experiences from the first year]. / Multidisciplinärt endokarditteam på plats i Skåne - Första årets erfarenhet visar riktningen framåt.

International guidelines recommend that the treatment of patients with infective endocarditis (IE) should be directed by a multidisciplinary endocarditis team. The aim of this study was to describe the first-year experience of multidisciplinary rounds by the endocarditis team in Scania, Sweden. This was a retrospective study on all possible and definitive IE episodes that were assessed by the endocarditis team from January 1st to December 31st, 2017. Descriptive statistics were used. A total of 145 multidisciplinary rounds were held and addressed 100 episodes in 97 patients. The median age was 71 years and 66% were males. The most common causative pathogens were alpha-hemolytic streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and enterococci. The endocarditis team recommended surgery in 40 % of episodes. The transfer of patients between different hospitals was facilitated by the team.  The IE team evaluated a large proportion of patients with IE in the region and provided a rapid expert opinion on the optimal management of complicated cases of IE.

The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest.

BACKGROUND: Data suggests that the plasma levels of the liver-specific miR-122-5p might both be a marker of cardiogenic shock and a prognostic marker of out-of-hospital cardiac arrest (OHCA). Our aim was to characterize plasma miR-122-5p at admission after OHCA and to assess the association between miR-122-5p and relevant clinical factors such all-cause mortality and shock at admission after OHCA. METHODS: In the pilot trial, 10 survivors after OHCA were compared to 10 age- and sex-matched controls. In the main trial, 167 unconscious survivors of OHCA from the Targeted Temperature Management (TTM) trial were included. RESULTS: In the pilot trial, plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. In the main trial, plasma miR-122-5p at admission was independently associated with lactate and bystander cardiopulmonary resuscitation. miR-122-5p at admission was not associated with shock at admission (p = 0.14) or all-cause mortality (p = 0.35). Target temperature (33 °C vs 36 °C) was not associated with miR-122-5p levels at any time point. CONCLUSIONS: After OHCA, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission.

Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest.

Rationale. The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts. Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest. The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest. Methods. We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial). Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation. The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score. The secondary end-point was survival at the end of the trial. Results. Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial. Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p<0.001), independently of targeted temperature management regimen. Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]). In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]). In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial. Conclusion. Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.

A 0-Hour/1-Hour Protocol for Safe, Early Discharge of Chest Pain Patients.

OBJECTIVES: Guidelines recommend a 0-hour/1-hour high-sensitivity cardiac troponin T (hs-cTnT) diagnostic strategy in acute chest pain patients. There are, however, little data on the performance of this strategy when combined with clinical risk stratification. We aimed to evaluate the diagnostic accuracy of an accelerated diagnostic protocol (ADP) using the 0-hour/1-hour hs-cTnT strategy together with an adapted Thrombolysis In Myocardial Infarction (TIMI) score and electrocardiogram (ECG) for ruling out major adverse cardiac events (MACE) within 30 days. METHODS: This prospective observational study enrolled consecutive emergency department (ED) chest pain patients. TIMI score variables, ED physicians' assessments of the ECG, and 0- and 1-hour hs-cTnT were collected. Thirty-day MACE was defined as acute myocardial infarction (AMI), unstable angina (UA), cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of cardiac or unknown cause. RESULTS: A total of 1,020 patients were included in the final analysis. The combination of an adapted TIMI score ≤1, a nonischemic ECG, and either a 0-hour hs-cTnT < 5 ng/L or a 0-hour hs-cTnT < 12 ng/L combined with a 1-hour increase < 3 ng/L identified 432 (42.4%) patients as very low risk with a negative predictive value of 99.5% (95% confidence interval [CI] = 98.3%-99.9%) and a negative likelihood ratio of 0.04 (95% CI = 0.01-0.14) for 30-day MACE. The ADP missed only two patients with UA and no patients with AMI or other forms of MACE. CONCLUSION: An ADP using the guideline recommended 0-hour/1-hour hs-cTnT strategy rapidly identified patients with a very low risk of 30-day MACE including UA where no further cardiac testing would be needed. This could potentially allow safe early discharge of about 40% of ED chest pain patients.

High-sensitivity troponin-T as a prognostic marker after out-of-hospital cardiac arrest - A targeted temperature management (TTM) trial substudy.

AIM OF THE STUDY: Predicting outcome of unconscious patients after successful resuscitation is challenging and better prognostic markers are highly needed. Ischemic heart disease is a common cause of out-of-hospital cardiac arrest (OHCA). Whether or not high-sensitivity troponin T (hs-TnT) is a prognostic marker among survivors of OHCA with both ischemic and non-ischemic aetiologies remains to be determined. We sought to evaluate the ability of hs-TnT to prognosticate all-cause mortality, death due to cardiovascular causes or multi-organ failure and death due to cerebral causes after OHCA. The influence of the level of target temperature management on hs-TnT as a marker of infarct size was also assessed. METHODS: A total of 699 patients from the targeted temperature management (TTM) trial were included and hs-TnT was analyzed in blood samples from 24, 48 and 72h after return of spontaneous circulation (ROSC). The endpoints were 180 day all-cause mortality, death due to cardiovascular causes or multi-organ failure and death due to cerebral causes. Subgroups based on the initial ECG after ROSC (STEMI vs all other ECG presentations) were analyzed. RESULTS: Hs-TnT was independently associated with all-cause mortality which was driven by death due to cardiovascular causes or multi-organ failure and not cerebral causes (at 48h: OR 1.10, CI 1.01-1.20, p<0.05). Hs-TnT was also an independent predictor of death due to cardiovascular causes or multi-organ failure (at 48h: OR 1.13, CI 1.01-1.26, p<0.05). In patients with STEMI, hs-TnT was independently associated with death due to cardiovascular causes or multi-organ failure (at 48h: OR 1.47, CI 1.10-1.95, p<0.01). Targeted temperature management at 33°C was not associated with hs-TnT compared to 36°C. CONCLUSIONS: After OHCA due to both ischemic and non-ischemic causes, hs-TnT is an independent marker of both all-cause mortality and death due to cardiovascular causes or multi-organ failure. Targeted temperature management at 33°C did not reduce hs-TnT compared to 36°C. Hs-TnT may be a marker of poor prognosis after OHCA and this should be taken into consideration in patients that present with high troponin levels. TRIAL REGISTRATION: The TTM-trial is registered and accessible at Clinicaltrials.gov (identifier: NCT01020916).

Comparative Proteomic Analysis of Extracellular Vesicles Isolated by Acoustic Trapping or Differential Centrifugation.

Extracellular vesicles (ECVs), including microparticles and exosomes, are submicrometer membrane vesicles released by diverse cell types upon activation or stress. Circulating ECVs are potential reservoirs of disease biomarkers, and the complexity of these vesicles is significantly lower compared to their source, blood plasma, which makes ECV-based biomarker studies more promising. Proteomic profiling of ECVs is important not only to discover new diagnostic or prognostic markers but also to understand their roles in biological function. In the current study, we investigated the protein composition of plasma-derived ECVs isolated by acoustic seed trapping. Additionally, the protein composition of ECVs isolated with acoustic trapping was compared to that isolated with a conventional differential centrifugation protocol. Finally, the proteome of ECVs originating from ST-elevation myocardial infarction patients was compared with that of healthy controls using label-free LC-MS quantification. The acoustic trapping platform allows rapid and automated preparation of ECVs from small sample volumes, which are therefore well-suited for biobank repositories. We found that the protein composition of trapped ECVs is very similar to that isolated by the conventional differential centrifugation method.

Association of Circulating MicroRNA-124-3p Levels With Outcomes After Out-of-Hospital Cardiac Arrest: A Substudy of a Randomized Clinical Trial.

IMPORTANCE: The value of microRNAs (miRNAs) as biomarkers has been investigated in various clinical contexts. Initial small-scale studies suggested that miRNAs might be useful indicators of outcome after cardiac arrest. OBJECTIVE: To address the prognostic value of circulating miRNAs in a large cohort of comatose patients with out-of-hospital cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Target Temperature Management After Cardiac Arrest (TTM) trial, a multicenter randomized, parallel-group, assessor-blinded clinical trial, compared the 6-month neurologic outcomes and survival of patients with cardiac arrest after targeted temperature management at 33°C or 36°C. Five hundred seventy-nine patients who survived the first 24 hours after the return of spontaneous circulation and who had blood samples available for miRNA assessment were enrolled from 29 intensive care units in 9 countries from November 11, 2010, to January 10, 2013. Final follow-up was completed on July 3, 2013, and data were assessed from February 1, 2014, to February 1, 2016. INTERVENTIONS: Blood sampling at 48 hours after the return of spontaneous circulation. MAIN OUTCOMES AND MEASURES: The primary end point was poor neurologic outcome at 6 months (cerebral performance category score, 3 [severe neurologic sequelae], 4 [coma], or 5 [death]). The secondary end point was survival until the end of the trial. Circulating levels of miRNAs were measured by sequencing and polymerase chain reaction. RESULTS: Of the 579 patients (265 men [80.3%]; mean [SD] age, 63 [12] years), 304 patients (52.5%) had a poor neurologic outcome at 6 months. In the discovery phase with short RNA sequencing in 50 patients, the brain-enriched miR-124-3p level was identified as a candidate prognostic variable for neurologic outcomes. In the validation cohort of 529 patients, mean (SD) levels of miR-124-3p were higher in patients with a poor outcome (8408 [12 465] copies/µL) compared with patients with a good outcome (1842 [3025] copies/µL; P < .001). The miR-124-3p level was significantly associated with neurologic outcomes in the univariable analysis (odds ratio, 6.72; 95% CI, 4.53-9.97). In multivariable analyses using logistic regression, miR-124-3p levels were independently associated with neurologic outcomes (odds ratio, 1.62; 95% CI, 1.13-2.32). In Cox proportional hazards models, higher levels of miR-124-3p were significantly associated with lower survival (hazard ratio, 1.63; 95% CI, 1.37-1.93). CONCLUSIONS AND RELEVANCE: Levels of miR-124-3p can be used as prognostication tools for neurologic outcome and survival after out-of-hospital cardiac arrest. Thus, miRNA levels may aid in tailoring health care for patients with cardiac arrest. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01020916.

A 1-h Combination Algorithm Allows Fast Rule-Out and Rule-In of Major Adverse Cardiac Events.

BACKGROUND: A 1-h algorithm based on high-sensitivity cardiac troponin T (hs-cTnT) testing at presentation and again 1 h thereafter has been shown to accurately rule out acute myocardial infarction. OBJECTIVES: The goal of the study was to evaluate the diagnostic accuracy of the 1-h algorithm when supplemented with patient history and an electrocardiogram (ECG) (the extended algorithm) for predicting 30-day major adverse cardiac events (MACE) and to compare it with the algorithm using hs-cTnT alone (the troponin algorithm). METHODS: This prospective observational study enrolled consecutive patients presenting to the emergency department (ED) with chest pain, for whom hs-cTnT testing was ordered at presentation. Hs-cTnT results at 1 h and the ED physician's assessments of patient history and ECG were collected. The primary outcome was an adjudicated diagnosis of 30-day MACE defined as acute myocardial infarction, unstable angina, cardiogenic shock, ventricular arrhythmia, atrioventricular block, cardiac arrest, or death of a cardiac or unknown cause. RESULTS: In the final analysis, 1,038 patients were included. The extended algorithm identified 60% of all patients for rule-out and had a higher sensitivity than the troponin algorithm (97.5% vs. 87.6%; p < 0.001). The negative predictive value was 99.5% and the likelihood ratio was 0.04 with the extended algorithm versus 97.8% and 0.17, respectively, with the troponin algorithm. The extended algorithm ruled-in 14% of patients with a higher sensitivity (75.2% vs. 56.2%; p < 0.001) but a slightly lower specificity (94.0% vs. 96.4%; p < 0.001) than the troponin algorithm. The rule-in arms of both algorithms had a likelihood ratio >10. CONCLUSIONS: A 1-h combination algorithm allowed fast rule-out and rule-in of 30-day MACE in a majority of ED patients with chest pain and performed better than the troponin-alone algorithm.