Impact of symptom duration and mechanical circulatory support on prognosis in cardiogenic shock complicating acute myocardial infarction.

BACKGROUND: Mortality rates in patients with cardiogenic shock complicating acute myocardial infarction (AMICS) remain high despite advancements in AMI care. Our study aimed to investigate the impact of prehospital symptom duration on the prognosis of AMICS patients and those receiving mechanical circulatory support (MCS). METHODS AND RESULTS: We conducted a retrospective cohort study with data registered in the Netherlands Heart Registration. A total of 1,363 patients with AMICS who underwent percutaneous coronary intervention between 2017 and 2021 were included. Patients presenting after out-of-hospital cardiac arrest were excluded. Most patients were male (68%), with a median age of 69 years (IQR 61-77), predominantly presenting with ST-elevation myocardial infarction (86%). The overall 30-day mortality was 32%. Longer prehospital symptom duration was associated with a higher 30-day mortality with the following rates: < 3 h, 26%; 3-6 h, 29%; 6-24 h, 36%; ≥ 24 h, 46%; p < 0.001. In a subpopulation of AMICS patients with MCS (n = 332, 24%), symptom duration of > 24 h was associated with significantly higher mortality compared to symptom duration of < 24 h (59% vs 45%, p = 0.029). Multivariate analysis identified > 24 h symptom duration, age and in-hospital cardiac arrest as predictors of 30-day mortality in MCS patients. CONCLUSION: Prolonged prehospital symptom duration was associated with significantly increased 30-day mortality in patients presenting with AMICS. In AMICS patients treated with MCS, a symptom duration of > 24 h was an independent predictor of poor survival. These results emphasise the critical role of early recognition and intervention in the prognosis of AMICS patients.

Coronary Angiography after Cardiac Arrest without ST-Segment Elevation.

BACKGROUND: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. METHODS: In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit. RESULTS: At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P = 0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points. CONCLUSIONS: Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, NTR4973.).

Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm. DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial. SETTING: Nineteen hospitals in The Netherlands. PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups. CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Development and Internal Validation of a Practical Model to Identify Observe Patients of the European Society of Cardiology 0/1-h Algorithm at Low Risk of a Coronary Diagnosis.

BACKGROUND: Patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) assigned to the "observe" zone of the European Society of Cardiology (ESC) 0/1-h algorithm form a heterogeneous group known to have an unfavourable prognosis. We aim to elucidate the clinical characteristics and management of these patients and generate a model that is predictive of a coronary diagnosis at index visit to the emergency department (ED). METHODS: A retrospective observational cohort study, including adult patients presenting to the ED with suspected NSTE-ACS assigned to the "observe" zone of the ESC 0/1-h algorithm. Multivariable logistic regression analysis was performed for the prediction of a coronary diagnosis. Internal validation was performed using bootstrap resampling. RESULTS: A total of 750 patients were included; mean age 66 ± 13 years, 35% women, 50% with prior history of coronary artery disease (CAD). In 372 (50%) patients a diagnosis was established within 30 days of index presentation, of whom 169 (45%) patients had a coronary-related event. Multivariable logistic regression analysis generated a 12-point risk score incorporating 5 variables for the prediction of such event, including type of angina, chest pain occurring during inspiration, prior history of CAD, ST-segment deviation on electrocardiogram, and estimated glomerular filtration rate <60. The final model had an optimism-corrected c-statistic of 0.78 (95% confidence interval [CI]: 0.74-0.82). A score <6 ruled out a coronary event in 276 (37%) patients, with a sensitivity and negative predictive value of 90% (95% CI: 84-94) and 94% (91-96), respectively. CONCLUSION: A score <6 identifies patients at low risk of a coronary diagnosis and can guide clinical decision-making in choosing the appropriate diagnostic test.

Undetectable High-Sensitivity Troponin T as a Gatekeeper for Coronary Computed Tomography Angiography in Patients Suspected of Acute Coronary Syndrome.

OBJECTIVES: The aim of this study was to characterize the safety and efficiency of a strategy employing the limit of detection (LoD) of high-sensitivity troponin T (hs-TnT) as a gatekeeper for coronary computed tomography angiography (CCTA) in suspected acute coronary syndrome (ACS) patients in the emergency department (ED). METHODS: We included suspected ACS patients who underwent CCTA and were evaluated with hs-TnT. Patients were categorized as below the LoD and at or above the LoD. The primary outcome was 30-day major adverse cardiac events (MACEs), defined as all-cause mortality, ACS, or coronary revascularization. RESULTS: The study population consisted of 177 patients (mean age 55 ± 10 years, 50.3% women), and 16 (9.0%) patients reached the primary outcome. None of the patients died, while 13 had an adjudicated diagnosis of ACS, and 3 underwent elective coronary revascularization. There were 77 patients (44%) with an hs-TnT value below the LoD (MACEs; n = 1 [1.3%]) and 100 (56%) with at or above the LoD levels (MACEs; n = 15 [15%]). None of 67 patients with an hs-TnT value below the LoD and <50% stenosis on CCTA experienced MACEs. Out of the 10 patients with an hs-TnT value below the LoD and ≥50% stenosis on CCTA, 1 patient underwent elective percutaneous coronary revascularization. In patients with an hs-TnT value at or above the LoD, 74 patients had <50% stenosis on CCTA, and 2 patients (3%) were diagnosed with myocardial infarction without obstructive coronary artery disease confirmed on invasive angiography. Thirteen (50%) patients with an hs-TnT value at or above the LoD and ≥50% stenosis on CCTA experienced MACEs (11 ACS and 2 elective percutaneous coronary revascularizations). CONCLUSION: Our findings support that implementing the LoD of hs-TnT as a gatekeeper may reduce the need for CCTA in suspected ACS patients in the ED.

Mechanical Support in Early Cardiogenic Shock: What Is the Role of Intra-aortic Balloon Counterpulsation?

PURPOSE OF REVIEW: We aim to summarize recent insights and provide an up-to-date overview on the role of intra-aortic balloon pump (IABP) counterpulsation in cardiogenic shock (CS). RECENT FINDINGS: In the largest randomized controlled trial (RCT) of patients with CS after acute myocardial infarction (AMICS), IABP did not lower mortality. However, recent data suggest a role for IABP in patients who have persistent ischemia after revascularization. Moreover, in the growing population of CS not caused by acute coronary syndrome (ACS), multiple retrospective studies and one small RCT report on significant hemodynamic improvement following (early) initiation of IABP support, which allowed bridging of most patients to recovery or definitive therapies like heart transplant or a left ventricular assist device (LVAD). Routine use of IABP in patients with AMICS is not recommended, but many patients with CS either from ischemic or non-ischemic cause may benefit from IABP at least for hemodynamic improvement in the short term. There is a need for a larger RCT regarding the role of IABP in selected patients with ACS, as well as in patients with non-ACS CS.

Microcirculatory assessment of patients under VA-ECMO.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an effective technique for providing emergency mechanical circulatory support for patients with cardiogenic shock. VA-ECMO enables a rapid restoration of global systemic organ perfusion, but it has not been found to always show a parallel improvement in the microcirculation. We hypothesized in this study that the response of the microcirculation to the initiation of VA-ECMO might identify patients with increased chances of intensive care unit (ICU) survival. METHODS: Twenty-four patients were included in this study. Sublingual microcirculation measurements were performed using the CytoCam-IDF (incident dark field) imaging device. Microcirculatory measurements were performed at baseline, after VA-ECMO insertion (T1), 48-72 h after initiation of VA-ECMO (T2), 5-6 days after (T3), 9-10 days after (T4), and within 24 h of VA-ECMO removal. RESULTS: Of the 24 patients included in the study population, 15 survived and 9 died while on VA-ECMO. There was no significant difference between the systemic global hemodynamic variables at initiation of VA-ECMO between the survivors and non-survivors. There was, however, a significant difference in the microcirculatory parameters of both small and large vessels at all time points between the survivors and non-survivors. Perfused vessel density (PVD) at baseline (survivor versus non-survivor, 19.21 versus 13.78 mm/mm2, p = 0.001) was able to predict ICU survival on initiation of VA-ECMO; the area under the receiver operating characteristic curve (ROC) was 0.908 (95 % confidence interval 0.772-1.0). CONCLUSION: PVD of the sublingual microcirculation at initiation of VA-ECMO can be used to predict ICU mortality in patients with cardiogenic shock.

The Value of Ischemic Cardiac Biomarkers to Predict Spontaneous Breathing Trial or Extubation Failure: A Systematic Review.

Background: It is unclear whether other cardiac biomarkers than NT-proBNP can be useful in the risk stratification of patients weaning from mechanical ventilation. The aim of this study is to summarize the role of ischemic cardiac biomarkers in predicting spontaneous breathing trial (SBT) or extubation failure. Methods: We systematically searched Embase, MEDLINE, Web of Science, and Cochrane Central for studies published before January 2024 that reported the association between ischemic cardiac biomarkers and SBT or extubation failure. Data were extracted using a standardized form and methodological assessment was performed using the QUIPS tool. Results: Seven observational studies investigating four ischemic cardiac biomarkers (Troponin-T, Troponin-I, CK-MB, Myoglobin) were included. One study reported a higher peak Troponin-I in patients with extubation failure compared to extubation success (50 ng/L [IQR, 20-215] versus 30 ng/L [IQR, 10-86], p = 0.01). A second study found that Troponin-I measured before the SBT was higher in patients with SBT failure in comparison to patients with SBT success (100 ± 80 ng/L versus 70 ± 130 ng/L, p = 0.03). A third study reported a higher CK-MB measured at the end of the SBT in patients with weaning failure (SBT or extubation failure) in comparison to weaning success (8.77 ± 20.5 ng/mL versus 1.52 ± 1.42 ng/mL, p = 0.047). Troponin-T and Myoglobin as well as Troponin-I and CK-MB measured at other time points were not found to be related to SBT or extubation failure. However, most studies were underpowered and with high risk of bias. Conclusions: The association with SBT or extubation failure is limited for Troponin-I and CK-MB and appears absent for Troponin-T and Myoglobin, but available studies are hampered by significant methodological drawbacks. To more definitively determine the role of ischemic cardiac biomarkers, future studies should prioritize larger sample sizes, including patients at risk of cardiac disease, using stringent SBTs and structured timing of laboratory measurements before and after SBT.

Characteristics, Treatment Strategies and Outcome in Cardiogenic Shock Complicating Acute Myocardial Infarction: A Contemporary Dutch Cohort.

Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high morbidity and mortality. Our study aimed to gain insights into patient characteristics, outcomes and treatment strategies in CS patients. Patients with CS who underwent percutaneous coronary intervention (PCI) between 2017 and 2021 were identified in a nationwide registry. Data on medical history, laboratory values, angiographic features and outcomes were retrospectively assessed. A total of 2328 patients with a mean age of 66 years and of whom 73% were male, were included. Mortality at 30 days was 39% for the entire cohort. Non-survivors presented with a lower mean blood pressure and increased heart rate, blood lactate and blood glucose levels (p-value for all <0.001). Also, an increased prevalence of diabetes, multivessel coronary artery disease and a prior coronary event were found. Of all patients, 24% received mechanical circulatory support, of which the majority was via intra-aortic balloon pumps (IABPs). Furthermore, 79% of patients were treated with at least one vasoactive agent, and multivessel PCI was performed in 28%. In conclusion, a large set of hemodynamic, biochemical and patient-related characteristics was identified to be associated with mortality. Interestingly, multivessel PCI and IABPs were frequently applied despite a lack of evidence.

Adult patients with congenital heart disease in the intensive care unit.

OBJECTIVE: Current data on intensive care unit (ICU) admissions in patients with adult congenital heart disease (ACHD) are limited and focus on admissions after elective cardiac surgery. This study describes non-elective ICU admissions in patients with ACHD. METHODS: A retrospective matched cohort study was performed from January 2000 until December 2015 in a tertiary care centre ICU (there was no cardiac care unit). Primary outcomes were short-term (during hospital stay or <30 days after discharge) and long-term (>30 days after discharge until end of follow-up) mortality. Outcomes were compared with non-ACHD non-elective ICU admissions, matched 1:1 on age, sex and admission diagnosis. RESULTS: A total of 138 admissions in 104 patients with ACHD (65.9% male, median age 30 years) were included, during 8.6 years of follow-up. The majority had a moderate-to-severe heart defect. Arrhythmia was the most common admission diagnosis (44.2%), followed by haemorrhage (10.9%), heart failure (8.7%) and pulmonary disease (8.7%). Short-term mortality and total mortality were lower in the ACHD admissions than in the non-ACHD admissions (4.8% vs 16.3%, p=0.005 and 17.3% vs 28.9%, p=0.030), whereas long-term (12.5% vs 12.6%, p=0.700) did not differ. Severe CHD (HR 3.1, 95% CI 1.1 to 8.6) at baseline, and mechanical circulatory support device use (8.3, 1.4 to 47.4) and emergency intervention (0.2, 0.1 to 0.7) during the ICU stay were independently associated with mortality in the ACHD group. CONCLUSIONS: Non-elective ICU admissions in patients with ACHD are most often for arrhythmia and in patients with moderate-to-severe CHD. Reassuringly, short-term and total mortality are lower compared with patients without ACHD, however, long-term mortality is higher than expected for patients with ACHD.

The Predictive Power of the 14-51 Ng/L High Sensitive Troponin T (hsTnT) Values for Predicting Cardiac Revascularization in a Clinical Setting.

Background: high sensitive Troponin T (hsTnT) values between 14−50 ng/L represent a challenge in diagnosing acute coronary syndrome (ACS) at the Emergency Department (ED). The European Society for Cardiology (ESC) recommends a second hsTnT measurement 3 h later to distinguish between ACS and other causes depending on the Δ hsTnT. Our study aims to evaluate the predictive power this approach in a clinical setting by following patients presenting at the ED with hsTnT values 14−51 ng/L. Materials and methods: patients presenting with chest pain or dyspnea and a hsTnT value between 14 and 50 ng/L at the Erasmus MC ED in 2012−2013 were included and retrospectively monitored for 90 days after initial presentation for the occurrence of a cardiac revascularization. Patient records were reviewed according to the standing protocol, which depended on the Δ hsTnT. The "event-group" consists of patients receiving cardiac revascularization within 90 days after the ED visit, whereas the "no event-group" consisted of patients without revascularization. Results: a total of 889 patients patient records were reviewed. After excluding out-of-hospital-cardia-arrests (60), non-cardiological chest pain (373) and incomplete follow-up (100), 356 patients remained for final analysis. In 207 patients, a second hsTnT was actually performed (58%). From these 207 patients, 68 (33%) had a Δ hsTnT ≥7 ng/L. In these patients, 37 (54%) experienced an event within 90 days. In the 139 patients with a Δ hsTnT < 7 ng/L, 23 (17%) presented with an event within 90 days. Conclusion: our study demonstrated a sensitivity of 62%, a specificity of 79%, a positive predicted value (PPV) of 54% and a negative predictive value (NPV) of 83% for using a 3-h Δ hsTnT ≥7 ng/L cut-off, related to risk of an event in 90 days following ED presentation.

Ischaemic electrocardiogram patterns and its association with survival in out-of-hospital cardiac arrest patients without ST-segment elevation myocardial infarction: a COACT trials' post-hoc subgroup analysis.

AIMS: ST-depression and T-wave inversion are frequently present on the post-resuscitation electrocardiogram (ECG). However, the prognostic value of ischaemic ECG patterns is unknown. METHODS AND RESULTS: In this post-hoc subgroup analysis of the Coronary Angiography after Cardiac arrest (COACT) trial, the first in-hospital post-resuscitation ECG in out-of-hospital cardiac arrest patients with a shockable rhythm was analysed for ischaemic ECG patterns. Ischaemia was defined as ST-depression of ≥0.1 mV, T-wave inversion in ≥2 contiguous leads, or both. The primary endpoint was 90-day survival. Secondary endpoints were rate of acute unstable lesions, levels of serum troponin-T, and left ventricular function. Of the 510 out-of-hospital cardiac arrest patients, 340 (66.7%) patients had ischaemic ECG patterns. Patients with ischaemic ECG patterns had a worse 90-day survival compared with those without [hazard ratio 1.51; 95% confidence interval (CI) 1.08-2.12; P = 0.02]. A higher sum of ST-depression was associated with lower survival (log-rank = 0.01). The rate of acute unstable lesions (14.5 vs. 15.8%; odds ratio 0.90; 95% CI 0.51-1.59) did not differ between the groups. In patients with ischaemic ECG patterns, maximum levels of serum troponin-T (µg/L) were higher [0.595 (interquartile range 0.243-1.430) vs. 0.359 (0.159-0.845); ratio of geometric means 1.58; 1.13-2.20] and left ventricular function (%) was worse (44.7 ± 12.5 vs. 49.9 ± 13.3; mean difference -5.13; 95% CI -8.84 to -1.42). Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival. CONCLUSION: Post-arrest ischaemic ECG patterns were associated with worse 90-day survival. A higher sum of ST-depression was associated with lower survival. Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival.

Cost Analysis From a Randomized Comparison of Immediate Versus Delayed Angiography After Cardiac Arrest.

Background In patients with out-of-hospital cardiac arrest without ST-segment elevation, immediate coronary angiography did not improve clinical outcomes when compared with delayed angiography in the COACT (Coronary Angiography After Cardiac Arrest) trial. Whether 1 of the 2 strategies has benefits in terms of health care resource use and costs is currently unknown. We assess the health care resource use and costs in patients with out-of-hospital cardiac arrest. Methods and Results A total of 538 patients were randomly assigned to a strategy of either immediate or delayed coronary angiography. Detailed health care resource use and cost-prices were collected from the initial hospital episode. A generalized linear model and a gamma distribution were performed. Generic quality of life was measured with the RAND-36 and collected at 12-month follow-up. Overall total mean costs were similar between both groups (EUR 33 575±19 612 versus EUR 33 880±21 044; P=0.86). Generalized linear model: (ß, 0.991; 95% CI, 0.894-1.099; P=0.86). Mean procedural costs (coronary angiography and percutaneous coronary intervention, coronary artery bypass graft) were higher in the immediate angiography group (EUR 4384±3447 versus EUR 3028±4220; P<0.001). Costs concerning intensive care unit and ward stay did not show any significant difference. The RAND-36 questionnaire did not differ between both groups. Conclusions The mean total costs between patients with out-of-hospital cardiac arrest randomly assigned to an immediate angiography or a delayed invasive strategy were similar during the initial hospital stay. With respect to the higher invasive procedure costs in the immediate group, a strategy awaiting neurological recovery followed by coronary angiography and planned revascularization may be considered. Registration URL: https://trialregister.nl; Unique identifier: NL4857.

Diagnostic approach for myocardial contusion: a retrospective evaluation of patient data and review of the literature.

PURPOSE: Myocardial contusion can be a life-threatening condition in patients who sustained blunt thoracic trauma. The diagnostic approach remains a subject of debate. The aim of this study was to determine the sensitivity and specificity of echocardiography, electrocardiography, troponins T and I (TnT and TnI), and creatine kinase muscle/brain (CK-MB) for identifying patients with a myocardial contusion following blunt thoracic trauma. METHODS: Sensitivity and specificity were first determined in a 10-year retrospective cohort study and second by a systematic literature review with meta-analysis. RESULTS: Of the 117 patients in the retrospective study, 44 (38%) were considered positive for myocardial contusion. Chest X-ray, chest CT scan, electrocardiograph, and echocardiography had poor sensitivity (< 15%) but good specificity (≥ 90%). Sensitivity to cardiac biomarkers measured at presentation ranged from 59% for TnT to 77% for hs-TnT, specificity ranged from 63% for CK-MB to 100% for TnT. The systematic literature review yielded 28 studies, with 14.5% out of 7242 patients reported as positive for myocardial contusion. The pooled sensitivity of electrocardiography, troponin I, and CK-MB was between 62 and 71%, versus only 45% for echocardiography and 38% for troponin T. The pooled specificity ranged from 63% for CK-MB to 85% for troponin T and 88% for echocardiography. CONCLUSION: The best diagnostic approach for myocardial contusion is a combination of electrocardiography and measurement of cardiac biomarkers. If abnormalities are found, telemonitoring is necessary for the early detection of life-threatening arrhythmias. Chest X-ray and CT scan may show other thoracic injuries but provide no information on myocardial contusion.

Coronary CT angiography for improved assessment of patients with acute chest pain and low-range positive high-sensitivity troponins: study protocol for a prospective, observational, multicentre study (COURSE trial).

INTRODUCTION: Current evaluation of patients suspected of a non-ST-elevation acute coronary syndrome (NSTE-ACS) involves the use of algorithms that incorporate clinical information, electrocardiogram (ECG) and high-sensitivity cardiac troponins (hs-troponins). While primarily designed to rule out NSTE-ACS safely, these algorithms can also be used for rule in of NSTE-ACS in some patients. Still, in a substantial number of patients, these algorithms do not provide a conclusive work-up. These patients often present with an atypical clinical profile and low-range positive hs-troponin values without a characteristic rise or fall pattern. They represent a heterogeneous group of patients with various underlying conditions; only a fraction (30%-40%) will eventually be diagnosed with a myocardial infarction. Uncertainty exists about the optimal diagnostic strategy and their management depends on the clinical perspective of the treating physician ranging from direct discharge to admission for invasive coronary angiography. Coronary CT angiography (CCTA) is a non-invasive test that has been shown to be safe, fast and reliable in the evaluation of coronary artery disease. In this study, we will determine the usefulness of CCTA in patients with acute chest pain and low-range positive hs-troponin values. METHODS AND ANALYSIS: A prospective, double-blind, observational, multicentre study conducted in the Netherlands. Patients aged 30-80 years presenting to the emergency department with acute chest pain and a suspicion of NSTE-ACS, a normal or non-diagnostic ECG and low-range positive hs-troponins will be scheduled to undergo CCTA. The primary outcome is the diagnostic accuracy of CCTA for the diagnosis of NSTE-ACS at discharge, in terms of sensitivity and negative predictive value. ETHICS AND DISSEMINATION: This study was approved by the Medical Research Ethics Committee of Erasmus Medical Center in Rotterdam, the Netherlands (registration number MEC-2017-506). Written informed consent to participate will be obtained from all participants. This study's findings will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03129659).

Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial.

BACKGROUND: High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. METHODS: This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. DISCUSSION: Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. TRIAL REGISTRATION: ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL.

The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial.

BACKGROUND: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown. METHODS: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography. RESULTS: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32). CONCLUSION: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register number, NTR4973.

Sex differences in patients with out-of-hospital cardiac arrest without ST-segment elevation: A COACT trial substudy.

BACKGROUND: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear. OBJECTIVES: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI). METHODS: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes. RESULTS: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.76-1.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%;p < 0.001), but when present, they had a worse prognosis than women without CAD (HR 3.06; 95% CI 1.31-7.19;p = 0.01). This was not the case for men (HR 1.05; 95% CI 0.67-1.65;p = 0.83). In both sexes, immediate coronary angiography did not improve one-year survival compared to delayed angiography (women, odds ratio (OR) 0.87; 95% CI 0.58-1.30;p = 0.49; vs. men, OR 0.97; 95% CI 0.45-2.09;p = 0.93). CONCLUSION: In OHCA patients without STEMI, we found no sex differences in overall one-year survival. Women less often had significant CAD, but when CAD was present they had worse survival than women without CAD. This was not the case for men. Both sexes did not benefit from a strategy of immediate coronary angiography as compared to delayed strategy with respect to one-year survival. CLINICAL TRIAL REGISTRATION NUMBER: Netherlands trial register (NTR) 4973.

HEART score improves efficiency of coronary computed tomography angiography in patients suspected of acute coronary syndrome in the emergency department.

AIMS: Coronary computed tomography angiography is increasingly employed in the emergency department for suspected acute coronary syndrome patients. The HEART score has been proposed for initial risk stratification in these patients. The aim of this study was to investigate the diagnostic value and efficiency of the HEART score before coronary computed tomography angiography. METHODS AND RESULTS: We included patients suspected of acute coronary syndrome who underwent coronary computed tomography angiography in the emergency department. Based on the HEART score, patients were stratified as low-risk (HEART≤3), intermediate-risk (HEART4-6) and high-risk (HEART≥7). We assessed coronary computed tomography angiography for the presence of significant coronary artery disease (>50% stenosis). The primary outcome, the level of major adverse cardiac events, was a composite endpoint of all-cause mortality, acute coronary syndrome or coronary revascularisation within 30 days. The study population consisted of 340 patients (mean age: 55.6±10.1 years, 44.7% women), major adverse cardiac events occurred in 45 (13.2%) patients. The incidence of major adverse cardiac events in patients stratified as low-risk (35.0%), intermediate-risk (56.8%) and high-risk (8.2%) was 3.4%, 12.4% and 60.7%, respectively. All four low-risk patients with major adverse cardiac events had a HEART score of three. An algorithm where coronary computed tomography angiography is reserved for patients with HEART 3-6 resulted in a sensitivity of 97.8%, specificity of 84.1%, negative predictive value of 99.6% and positive predictive value of 48.4%, while reducing the need for coronary computed tomography angiography by 22% (n=75). CONCLUSION: The predictive value of coronary computed tomography angiography for 30-day major adverse cardiac events in suspected acute coronary syndrome patients is good, and reserving coronary computed tomography angiography for HEART score 3-6 patients reduces the number of needed coronary computed tomography angiograms without affecting diagnostic accuracy.

Data on sex differences in one-year outcomes of out-of-hospital cardiac arrest patients without ST-segment elevation.

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care.