Rule-out of non-ST-segment elevation acute coronary syndrome by a single, pre-hospital troponin measurement: a randomized trial.

AIMS: Patients with suspected non-ST-segment elevation acute coronary syndrome (NSTE-ACS) are routinely transferred to the emergency department (ED). A clinical risk score with point-of-care (POC) troponin measurement might enable ambulance paramedics to identify low-risk patients in whom ED evaluation is unnecessary. The aim was to assess safety and healthcare costs of a pre-hospital rule-out strategy using a POC troponin measurement in low-risk suspected NSTE-ACS patients. METHODS AND RESULTS: This investigator-initiated, randomized clinical trial was conducted in five ambulance regions in the Netherlands. Suspected NSTE-ACS patients with HEAR (History, ECG, Age, Risk factors) score ≤3 were randomized to pre-hospital rule-out with POC troponin measurement or direct transfer to the ED. The sample size calculation was based on the primary outcome of 30-day healthcare costs. Secondary outcome was safety, defined as 30-day major adverse cardiac events (MACE), consisting of ACS, unplanned revascularization or all-cause death. : A total of 863 participants were randomized. Healthcare costs were significantly lower in the pre-hospital strategy (€1349 ± €2051 vs. €1960 ± €1808) with a mean difference of €611 [95% confidence interval (CI): 353-869; P < 0.001]. In the total population, MACE were comparable between groups [3.9% (17/434) in pre-hospital strategy vs. 3.7% (16/429) in ED strategy; P = 0.89]. In the ruled-out ACS population, MACE were very low [0.5% (2/419) vs. 1.0% (4/417)], with a risk difference of -0.5% (95% CI -1.6%-0.7%; P = 0.41) in favour of the pre-hospital strategy. CONCLUSION: Pre-hospital rule-out of ACS with a POC troponin measurement in low-risk patients significantly reduces healthcare costs while incidence of MACE was low in both strategies. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT05466591 and International Clinical Trials Registry Platform id NTR 7346.

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.

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Randomized evaluation of short-term dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: rationale and design of the REDUCE trial.

BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with drug eluting stents (DES) is still under debate. Recent meta-analyses on ≤6months versus 12months DAPT suggest that bleeding rates can be reduced, without a higher rate of thrombotic complications. In particular, the COMBO dual therapy stent, being associated with early re-endothelialization, may allow for a reduction of the duration of DAPT without increasing the thrombotic risk, while reducing the risk of bleeding complications. AIM: The aim of the REDUCE trial is to demonstrate the non-inferiority of a combined efficacy and safety endpoint of a short-term 3months DAPT strategy as compared to standard 12-month DAPT strategy in ACS patients treated with the COMBO stent. DESIGN: A prospective, multicenter, randomized study designed to enroll 1500 patients with ACS treated with the COMBO stent. Patients will be randomized before discharge in a 1:1 fashion to either 3 or 12months of DAPT. A clinical follow-up is scheduled at 3, 6, 12, and 24months. The primary endpoint is the time to event as defined by the occurrence of one of the following: all cause mortality, myocardial infarction, stent thrombosis, stroke, target vessel revascularization or bleeding (Bleeding Academic Research Council type II, III and V) within 12months. The study has recruited patients since July 2014, and the results are expected in 2017. SUMMARY: A reduction of the DAPT duration in ACS patients after PCI without affecting the thrombotic risk is an attractive option with regard to the associated bleeding risk. The REDUCE trial will be the first to investigate the efficacy and safety of a 3-month DAPT strategy compared to a 12-month DAPT strategy in an ACS only population treated with the COMBO stent.

Coronary angiography after cardiac arrest: Rationale and design of the COACT trial.

BACKGROUND: Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated. HYPOTHESIS: We hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post-cardiac arrest patients without signs of STEMI. DESIGN: In a prospective, multicenter, randomized controlled clinical trial, 552 post-cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90-day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment. SUMMARY: The COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post-cardiac arrest patients without STEMI on 90-day survival.

STEMI or non-STEMI: that is the question.

Acute coronary syndromes are usually classified on the basis of the presence or absence of ST elevation on the ECG: ST-elevation myocardial infarction or non-ST-elevation myocardial infarction (NSTEMI)patients with acute myocardial infarction (AMI) need immediate therapy, without unnecessary delay and primary percutaneous coronary intervention (PPCI) should preferably be performed within 90 min after first medical contact. However, in AMI patients without ST-segment elevation (pre) hospital triage for immediate transfer to the catheterisation laboratory may be difficult. Moreover, initial diagnosis and risk stratification take place at busy emergency departments and chest pain units with additional risk of 'PPCI delay'. Optimal timing of angiography and revascularisation remains a challenge. We describe a patient with NSTEMI who was scheduled for early coronary angiography within 24 h but retrospectively should have been sent to the cath lab immediately because he had a significant amount of myocardium at risk, undetected by non-invasive parameters.

Sex differences in plaque characteristics of fractional flow reserve-negative non-culprit lesions after myocardial infarction.

BACKGROUND AND AIMS: Recurrent events after myocardial infarction (MI) are common and often originate from native non-culprit (NC) lesions that are non-flow limiting. These lesions consequently pose as targets to improve long-term outcome. It is, however, largely unknown whether these lesions differ between sexes. The aim of this study was to assess such potential differences. METHODS: From the PECTUS-obs study, we assessed sex-related differences in plaque characteristics of fractional flow reserve (FFR)-negative intermediate NC lesions in 420 MI-patients. RESULTS: Among the included patients, 80 (19.1 %) were female and 340 (80.9 %) male. Women were older and more frequently had hypertension and diabetes. In total, 494 NC lesions were analyzed. After adjustment for clinical characteristics and accounting for within-patients clustering, lesion length was longer in female patients (20.8 ± 10.0 vs 18.3 ± 8.5 mm, p = 0.048) and minimum lumen area (2.30 ± 1.42 vs 2.78 ± 1.54 mm2, p < 0.001) and minimum lumen diameter (1.39 ± 0.45 vs 1.54 ± 0.44 mm, p < 0.001) were smaller. The minimum fibrous cap thickness was smaller among females (96 ± 53 vs 112 ± 72 µm, p = 0.025), with more lesions harboring a thin cap fibroatheroma (39.3 % vs 24.9 %, p < 0.001). Major adverse cardiovascular events at two years occurred in 6.3 % of female patients and 11.8 % of male patients (p = 0.15). CONCLUSIONS: FFR-negative NC lesions after MI harbored more high-risk plaque features in female patients. Although this did not translate into an excess of recurrent events in female patients in this modestly sized cohort, it remains to be investigated whether this difference affects clinical outcome.

Functional and morphological improvement of significant non-culprit coronary artery stenosis by LDL-C reduction with a PCSK9 antibody: Rationale and design of the randomized FITTER trial.

Non-culprit coronary artery lesions are commonly present in patients presenting with an acute coronary syndrome (ACS). Additional stenting of non-culprit lesions in addition to the culprit lesion intends to prevent secondary events caused by these lesions. At the same time, multiple trials have demonstrated the potential of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in reducing plaque size and changing plaque composition of non-culprit lesions. Whether intensive low-density lipoprotein cholesterol (LDL-C) reduction with PCSK9 inhibitor evolocumab improves non-culprit vessel hemodynamics, reduces the risk of plaque rupture of important non-culprit lesions, and might obviate the need for additional stenting has not been investigated. The "Functional Improvement of non-infarcT related coronary artery stenosis by Extensive LDL-C Reduction with a PCSK9 Antibody" (FITTER) trial is a multi-center, randomized, double-blind, placebo-controlled clinical trial for patients presenting with ACS and multivessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) is performed in non-culprit vessels amenable for percutaneous coronary intervention (PCI). Coronary intervention in patients with hemodynamically important non-critical lesions (FFR: 0.67-0.85) is staged after baseline imaging using near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS). Eligible patients are randomized and treated for 12 weeks with either evolocumab or placebo, in addition to high-intensity statin therapy. Follow-up angiography with repeat FFR and IVUS-NIRS is scheduled at 12 weeks. Staged PCI is performed at the operator's discretion.The FITTER trial is the first study to evaluate the effect of maximal LDL-C reduction by the PCSK9 inhibitor evolocumab on invasively measured FFR, plaque size, and plaque composition in hemodynamically important non-culprit lesions, during a treatment period of just 12 weeks after an ACS. Currently, all patients have been included (August 2023) and data analysis is ongoing. Trial registration number: clinicaltrials.gov NCT04141579.

Pre-hospital rule-out of non-ST-segment elevation acute coronary syndrome by a single troponin: final one-year outcomes of the ARTICA randomised trial.

BACKGROUND AND AIMS: The healthcare burden of acute chest pain is enormous. In the randomized ARTICA trial, we showed that pre-hospital identification of low-risk patients and rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with point-of-care (POC) troponin measurement reduces 30-day healthcare costs with low major adverse cardiac events (MACE) incidence. Here we present the final 1-year results of the ARTICA trial. METHODS: Low-risk patients with suspected NSTE-ACS were randomized to pre-hospital rule-out with POC troponin measurement or emergency department (ED) transfer. Primary 1-year outcome was healthcare costs. Secondary outcomes were safety, quality of life (QoL), and cost-effectiveness. Safety was defined as a 1-year MACE consisting of ACS, unplanned revascularization, or all-cause death. QoL was measured with EuroQol-5D-5L questionnaires. Cost-effectiveness was defined as 1-year healthcare costs difference per QoL difference. RESULTS: Follow-up was completed for all 863 patients. Healthcare costs were significantly lower in the pre-hospital strategy (€1932 ± €2784 vs. €2649 ± €2750), mean difference €717 [95% confidence interval (CI) €347 to €1087; P < 0.001]. In the total population, the 1-year MACE rate was comparable between groups [5.1% (22/434) in the pre-hospital strategy vs. 4.2% (18/429) in the ED strategy; P = 0.54]. In the ruled-out ACS population, 1-year MACE remained low [1.7% (7/419) vs. 1.4% (6/417)], risk difference 0.2% (95% CI -1.4% to 1.9%; P = 0.79). QoL showed no significant difference between strategies. CONCLUSIONS: Pre-hospital rule-out of NSTE-ACS with POC troponin testing in low-risk patients is cost-effective, as expressed by a sustainable healthcare cost reduction and no significant effect on QoL. One-year MACE remained low for both strategies.

The Prognostic Value of Troponin-T in Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation: A COACT Substudy.

Background: In out-of-hospital cardiac arrest (OHCA) without ST-elevation, predictive markers that can identify those with a high risk of acute coronary syndrome are lacking. Methods: In this post hoc analysis of the Coronary Angiography after Cardiac Arrest (COACT) trial, the baseline, median, peak, and time-concentration curves of troponin-T (cTnT) (T-AUC) in OHCA patients without ST-elevation were studied. cTnT values were obtained at predefined time points at 0, 3, 6, 12, 24, 36, 28, and 72 hours after admission. All patients who died within the measurement period were not included. The primary outcome was the association between cTnT and 90-day survival. Secondary outcomes included the association of cTnT and acute thrombotic occlusions, acute unstable lesions, and left ventricular function. Results: In total, 352 patients were included in the analysis. The mean age was 64 ± 13 years (80.4% men). All cTnT measures were independent prognostic factors for mortality after adjustment for potential confounders age, sex, history of coronary artery disease, witnessed arrest, time to BLS, and time to return of spontaneous circulation (eg, for T-AUC: hazard ratio, 1.44; 95% CI, 1.06-1.94; P = .02; P value for all variables ≤.02). Median cTnT (odds ratio [OR], 1.58; 95% CI, 1.18-2.12; P = .002) and T-AUC (OR, 2.03; 95% CI, 1.25-3.29; P = .004) were independent predictors for acute unstable lesions. Median cTnT (OR, 1.62; 95% CI, 1.17-2.23; P = .003) and T-AUC (OR, 2.16; 95% CI, 1.27-3.68; P = .004) were independent predictors for acute thrombotic occlusions. CTnT values were not associated with the left ventricular function (eg, for T-AUC: OR, 2.01; 95% CI, 0.65-6.19; P = .22; P value for all variables ≥.14). Conclusion: In OHCA patients without ST-segment elevation, cTnT release during the first 72 hours after return of spontaneous circulation was associated with clinical outcomes.

Fractional Flow Reserve-Negative High-Risk Plaques and Clinical Outcomes After Myocardial Infarction.

Importance: Even after fractional flow reserve (FFR)-guided complete revascularization, patients with myocardial infarction (MI) have high rates of recurrent major adverse cardiovascular events (MACE). These recurrences may be caused by FFR-negative high-risk nonculprit lesions. Objective: To assess the association between optical coherence tomography (OCT)-identified high-risk plaques of FFR-negative nonculprit lesions and occurrence of MACE in patients with MI. Design, Setting, and Participants: PECTUS-obs (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI [ST-segment elevation MI] and NSTEMI [non-STEMI] in Patients With Residual Non-flow Limiting Lesions) is an international, multicenter, prospective, observational cohort study. In patients presenting with MI, OCT was performed on all FFR-negative (FFR > 0.80) nonculprit lesions. A high-risk plaque was defined containing at least 2 of the following prespecified criteria: (1) a lipid arc at least 90°, (2) a fibrous cap thickness less than 65 µm, and (3) either plaque rupture or thrombus presence. Patients were enrolled from December 14, 2018, to September 15, 2020. Data were analyzed from December 2, 2022, to June 28, 2023. Main Outcome and Measure: The primary end point of MACE, a composite of all-cause mortality, nonfatal MI, or unplanned revascularization, at 2-year follow-up was compared in patients with and without a high-risk plaque. Results: A total of 438 patients were enrolled, and OCT findings were analyzable in 420. Among included patients, mean (SD) age was 63 (10) years, 340 (81.0) were men, and STEMI and non-STEMI were equally represented (217 [51.7%] and 203 [48.3%]). A mean (SD) of 1.17 (0.42) nonculprit lesions per patient was imaged. Analysis of OCT images revealed at least 1 high-risk plaque in 143 patients (34.0%). The primary end point occurred in 22 patients (15.4%) with a high-risk plaque and 23 of 277 patients (8.3%) without a high-risk plaque (hazard ratio, 1.93 [95% CI, 1.08-3.47]; P = .02), primarily driven by more unplanned revascularizations in patients with a high-risk plaque (14 of 143 [9.8%] vs 12 of 277 [4.3%]; P = .02). Conclusions and Relevance: Among patients with MI and FFR-negative nonculprit lesions, the presence of a high-risk plaque is associated with a worse clinical outcome, which is mainly driven by a higher number of unplanned revascularizations. In a population with a high recurrent event rate despite physiology-guided complete revascularization, these results call for research on additional pharmacological or focal treatment strategies in patients harboring high-risk plaques.

Differences in risk and costs between prehospital identified low-risk men and women with chest pain.

OBJECTIVE: Prehospital rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in low-risk patient with a point-of-care troponin measurement reduces healthcare costs with similar safety to standard transfer to the hospital. Risk stratification is performed identical for men and women, despite important differences in clinical presentation, risk factors and age between men and women with NSTE-ACS. Our aim was to compare safety and healthcare costs between men and women in prehospital identified low-risk patients with suspected NSTE-ACS. METHODS: In the Acute Rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART (History, ECG, Age, Risk factors and Troponin) score assessment and a single poInt of CAre troponin randomised trial, the HEAR (History, ECG, Age and Risk factors) score was assessed by ambulance paramedics in suspected NSTE-ACS patients. Low-risk patients (HEAR score ≤3) were included. In this substudy, men and women were compared. Primary endpoint was 30-day major adverse cardiac events (MACE), secondary endpoints were 30-day healthcare costs and the scores for the HEAR score components. RESULTS: A total of 863 patients were included, of which 495 (57.4%) were women. Follow-up was completed in all patients. In the total population, MACE occurred in 6.8% of the men and 1.6% of the women (risk ratio (RR) 4.2 (95% CI 1.9 to 9.2, p<0.001)). In patients with ruled-out ACS (97% of the total population), MACE occurred in 1.4% of the men and in 0.2% of the women (RR 7.0 (95% CI 2.0 to 14.2, p<0.001). Mean healthcare costs were €504.55 (95% CI €242.22 to €766.87, p<0.001) higher in men, mainly related to MACE. CONCLUSIONS: In a prehospital population of low-risk suspected NSTE-ACS patients, 30-day incidence of MACE and MACE-related healthcare costs were significantly higher in men than in women. TRIAL REGISTRATION NUMBER: NCT05466591.

Morphological characteristics of lesions with thin cap fibroatheroma-a substudy from the COMBINE (OCT-FFR) trial.

AIMS: To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). METHODS AND RESULTS: From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. CONCLUSION: Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

Long-term outcomes of patients with normal fractional flow reserve and thin-cap fibroatheroma.

BACKGROUND: The long-term prognostic implications of fractional flow reserve (FFR)-negative lesions hosting vulnerable plaques remain unsettled. AIMS: The aim of this study was to evaluate the association of non-ischaemic lesions hosting optical coherence tomography (OCT)-detected thin-cap fibroatheromas (TCFA) with first and recurrent cardiovascular events during follow-up up to 5 years in a diabetes mellitus (DM) patient population. METHODS: COMBINE OCT-FFR is a prospective, international, double-blind, natural history study. Patients with DM and with ≥1 FFR-negative lesion were classified into 2 groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint (PE) is a composite of cardiac mortality, target vessel-related myocardial infarction (TV-MI), clinically driven target lesion revascularisation (TLR), or unstable angina (UA) requiring hospitalisation during follow-up up to 5 years. RESULTS: Among 390 DM patients (age 67.5±9 years; 37% female) with ≥1 FFR-negative lesion, 292 (74.9%) were TCFA-negative while 98 (25.1%) were TCFA-positive. The PE occurred more frequently in TCFA-positive than in TCFA-negative patients (21.4% vs 8.2%, hazard ratio [HR] 2.89, 95% confidence interval [CI]: 1.61-5.20; p<0.001; 6.42 vs 2.46 events per 100 patient-years, rate ratio [RR] 2.61, 95% CI: 1.38-4.90; p=0.002). Furthermore, when TV-MI, TLR, and UA were treated as recurrent components of the PE, TCFA-positive patients experienced a higher risk of recurrent events (HR 2.89, 95% CI; 1.74-4.80; p<0.001; 13.45 vs 2.87 events per 100 patient-years, RR 4.69, 95% CI: 2.86-7.83; p<0.001). A multivariable analysis identified the presence of TCFA as an independent predictor of the PE (HR 2.76, 95% CI: 1.53-4.97; p<0.001). CONCLUSIONS: OCT-detected TCFA-positive lesions, although not ischaemia-generating, are associated with an increased risk of adverse events during long-term follow-up. CLINICALTRIALS: gov: NCT02989740.

Implementation of the ESC 0 h/1h algorithm and the HEART score in the emergency department: A prospective cohort study.

Background: The European Society of Cardiology (ESC) 0 h/1h algorithm is the preferred diagnostic strategy for chest pain patients in the emergency department (ED). It is suggested that adding clinical information to the algorithm improves its diagnostic performance. This study evaluates implementation of the ESC 0 h/1h algorithm in the ED and investigates the potential advantages of combining it with a clinical decision rule, which might be especially relevant in the heterogenous observation category. Methods: In this prospective cohort study, chest pain patients in whom the ESC 0 h/1h algorithm was applied were enrolled. HEART score components were collected. Diagnostic characteristics were determined for the algorithm with and without addition of the HEART score. Primary endpoint was a composite endpoint at 30-day follow-up, consisting of myocardial infarction and death. Results: A total of 668 patients were enrolled. The rule-in and rule-out categories consisted of 8.2% and 54.9% of the patients, respectively. Positive predictive value and specificity of the rule-in category were 67.3% and 97.1%, respectively. Negative predictive value (NPV) and sensitivity of the rule-out category were both 100%. In the observation category, a HEART score ≤ 3 yielded a NPV and sensitivity of 97.1% and 93.8%, respectively. Conclusion: The ESC 0 h/1h algorithm yielded a NPV and sensitivity of 100% for myocardial infarction and death at 30-day follow-up. Addition of the HEART score did not provide clinically relevant advantages. Although the HEART score can be used to guide diagnostic testing in the observation category, a low HEART score did not yield an NPV of > 99%.

Thin-Cap Fibroatheroma Rather Than Any Lipid Plaques Increases the Risk of Cardiovascular Events in Diabetic Patients: Insights From the COMBINE OCT-FFR Trial.

BACKGROUND: Autopsy studies have established that thin-cap fibroatheromas (TCFAs) are the most frequent cause of fatal coronary events. In living patients, optical coherence tomography (OCT) has sufficient resolution to accurately differentiate TCFA from thick-cap fibroatheroma (ThCFA) and not lipid rich plaque (non-LRP). However, the impact of OCT-detected plaque phenotype of nonischemic lesions on future adverse events remains unknown. Therefore, we studied the natural history of OCT-detected TCFA, ThCFA, and non-LRP in patients enrolled in the prospective multicenter COMBINE FFR-OCT trial (Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients). METHODS: In the COMBINE FFR-OCT trial, patients with diabetes and ≥1 lesion with a fractional flow reserve >0.80 underwent OCT evaluation and were clinically followed for 18 months. A composite primary end point of cardiac death, target vessel-related myocardial infarction, target-lesion revascularization, and hospitalization for unstable angina was evaluated in relation to OCT-based plaque morphology. RESULTS: A total of 390 patients (age 67.5±9 years; 63% male) with ≥1 nonischemic lesions underwent OCT evaluation: 284 (73%) had ≥1 LRP and 106 (27%) non-LRP lesions. Among LRP patients, 98 (34.5%) had ≥1 TCFA. The primary end point occurred in 7% of LRP patients compared with 1.9% of non-LRP patients (7.0% versus 1.9%; hazard ratio [HR], 3.9 [95% CI, 0.9-16.5]; P=0.068; log rank-P=0.049). However, within LRP patients, TCFA patients had a much higher risk for primary end point compared with ThCFA (13.3% versus 3.8%; HR, 3.8 [95% CI, 1.5-9.5]; P<0.01), and to non-LRP patients (13.3% versus 1.9%; HR, 7.7 [95% CI, 1.7-33.9]; P<0.01), whereas ThCFA patients had risk similar to non-LRP patients (3.8% versus 1.9%; HR, 2.0 [95% CI, 0.42-9.7]; P=0.38). Multivariable analyses identified TCFA as the strongest independent predictor of primary end point (HR, 6.79 [95% CI, 1.50-30.72]; P=0.013). CONCLUSIONS: Among diabetes patients with fractional flow reserve-negative lesions, patients carrying TCFA lesions represent only one-third of LRP patients and are associated with a high risk of future events while patients carrying LRP-ThCFA and non-LRP lesions portend benign outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02989740.

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.