BACKGROUNDIschemic 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. METHODSIn 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. RESULTSAt 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. CONCLUSIONSAmong 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.

IMPORTANCE Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking.OBJECTIVE To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy. DESIGN, SETTING, AND PARTICIPANTSA prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019.INTERVENTIONS Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery.MAIN OUTCOMES AND MEASURES Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year.RESULTS At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64). CONCLUSIONS AND RELEVANCEIn this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes. TRIAL REGISTRATION trialregister.nl Identifier: NTR4973

Ticagrelor did not improve endothelial function or increased systemic adenosine plasma levels as compared with prasugrel and clopidogrel in stabilized patients who suffered from an ACS. (Hunting for the Off-Target Properties of Ticagrelor on Endothelial Function in Humans [HI-TECH]; NCT02587260).

IMPORTANCE Percutaneous coronary intervention (PCI) of nonculprit vessels among patients with ST-segment elevation myocardial infarction (STEMI) is associated with improved clinical outcome compared with culprit vessel-only PCI. Fractional flow reserve (FFR) and coronary flow reserve are hyperemic indices used to guide revascularization. Recently, instantaneous wave-free ratio was introduced as a nonhyperemic alternative to FFR. Whether these indices can be used in the acute setting of STEMI continues to be investigated. OBJECTIVE To assess the value of hemodynamic indices in nonculprit vessels of patients with STEMI from the index event to 1-month follow-up. DESIGN, SETTING, AND PARTICIPANTS This substudy of the Reducing Micro Vascular Dysfunction in Revascularized STEMI Patients by Off-target Properties of Ticagrelor (REDUCE-MVI) randomized clinical trial enrolled 98 patients with STEMI who had an angiographic intermediate stenosis in at least 1 nonculprit vessel. Patient enrollment was between May 1, 2015, and September 19, 2017.After successful primary PCI, nonculprit intracoronary hemodynamic measurements were performed and repeated at 1-month follow-up. Cardiac magnetic resonance imaging was performed from 2 to 7 days and 1 month after primary PCI. MAIN OUTCOMES AND MEASURESThe value of nonculprit instantaneous wave-free ratio, FFR, coronary flow reserve, hyperemic index of microcirculatory resistance, and resting microcirculatory resistance from the index event to 1-month follow-up. RESULTSOf 73 patients with STEMI included in the final analysis, 59 (80.8%) were male, with a mean (SD) age of 60.8 (9.9) years. Instantaneous wave-free ratio (SD) did not change significantly (0.93 [0.07] vs 0.94 [0.06]; P = .12) and there was no change in resting distal pressure/aortic pressure (mean [SD], 0.94 [0.06] vs 0.95 [0.06]; P = .25) from the acute moment to 1-month follow-up. The FFR decreased (mean [SD], 0.88 [0.07] vs 0.86 [0.09]; P = .001) whereas coronary flow reserve increased (mean [SD], 2.9 [1.4] vs 4.1 [2.2]; P < .001). Hyperemic index of microcirculatory resistance decreased and resting microcirculatory resistance increased from the acute moment to follow-up. The decrease in distal pressure from rest to hyperemia was smaller at the acute moment vs follow-up (mean [SD], 10.6 [11.2] mm Hg vs 14.1 [14.2] mm Hg; P = .05). This blunted acute hyperemic response correlated with final infarct size (ρ, -0.29; P = .02). The resistive reserve ratio was lower at the acute moment vs follow-up (mean [SD], 3.4 [1.7] vs 5.0 [2.7]; P < .001). CONCLUSIONS AND RELEVANCEIn the acute setting of STEMI, nonculprit coronary flow reserve was reduced and FFR was augmented, whereas instantaneous wave-free ratio was not altered. These results may be explained by an increased hyperemic microvascular resistance and a blunted adenosine responsiveness at the acute moment that was associated with infarct size.

No abstract

BackgroundObesity is key feature of the metabolic syndrome and is associated with high cardiovascular morbidity and mortality. Obesity is associated with macrovascular endothelial dysfunction, a determinant of outcome in patients with coronary artery disease. Here, we compared the influence of obesity on microvascular endothelial function to that of established cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolemia, and smoking in patients with suspected coronary artery disease.Methods and ResultsEndothelial function was assessed during postocclusive reactive hyperemia of the brachial artery and downstream microvascular beds in 108 patients who were scheduled for coronary angiography. In all patients, microvascular vasodilation was assessed using peripheral arterial tonometry; laser Doppler flowmetry and digital thermal monitoring were performed. Body mass index was significantly associated with decreased endothelium‐dependent vasodilatation measured with peripheral arterial tonometry (r=0.23, P=0.02), laser Doppler flowmetry (r=0.30, P<0.01), and digital thermal monitoring (r=0.30, P<0.01). In contrast, hypertension, hypercholesterolemia, and smoking had no influence on microvascular vasodilatation. Especially in diabetic patients, endothelial function was not significantly reduced (control versus diabetes mellitus, mean±SEM or median [interquartile range], peripheral arterial tonometry: 1.90±0.20 versus 1.67±0.20, P=0.19, laser Doppler flowmetry: 728% [interquartile range, 427–1110] versus 589% [interquartile range, 320–1067] P=0.28, and digital thermal monitoring: 6.6±1.0% versus 2.5±1.7%, P=0.08). In multivariate linear regression analysis, body mass index was the only risk factor that significantly attenuated endothelium‐dependent vasodilatation using all 3 microvascular function tests.ConclusionsHigher body mass index is associated with reduced endothelial function in patients with suspected coronary artery disease, even after adjustment for treated diabetes mellitus, hypertension, hypercholesterolemia, and smoking.

Background: Despite successful restoration of epicardial vessel patency with primary percutaneous coronary intervention (pPCI), coronary microvascular injury (MVI) occurs in a large proportion of STEMI patients, adversely affecting clinical and functional outcome. Ticagrelor has been reported to increase plasma adenosine levels, which might have a protective effect on the microcirculation. We investigated if ticagrelor maintenance therapy after revascularized STEMI is associated with less MVI compared to prasugrel maintenance therapy. Methods: A total of 110 STEMI patients received a loading dose of ticagrelor and were randomized to maintenance therapy of ticagrelor (n=56) or prasugrel (n=54) after pPCI. The primary outcome was MVI at 1 month, as determined with the index of microcirculatory resistance (IMR) in the infarct-related artery. Cardiovascular magnetic resonance imaging was performed during the acute phase and at one month. Results: The primary outcome of IMR was not superior in ticagrelor or prasugrel treated patients (ticagrelor 21 [15-39] U, prasugrel 18 [11-29] U, p=0.08). Recovery of microcirculatory resistance over time was not better in patients with ticagrelor versus prasugrel (ticagrelor-13.9 U vs. prasugrel-13.5 U, p=0.54). Intramyocardial hemorrhage was observed less frequently in patients with ticagrelor (23% vs. 43%, p=0.04). At one month no difference in infarct size was observed (ticagrelor 7.6 [IQR 3.7-14.4] g, prasugrel 9.9 [IQR 5.7-16.6] g, p=0.17). The occurrence of microvascular obstruction was not different in patients on ticagrelor (28%) or prasugrel (41%, p=0.35). Plasma adenosine concentrations were not different during the index procedure and during maintenance therapy with ticagrelor or prasugrel. Conclusions: In patients with STEMI, ticagrelor maintenance therapy was not superior to prasugrel in preventing MVI in the infarct-related territory as assessed by IMR and this resulted in a comparable infarct size at one month.

BackgroundTherapeutic hypothermia (TH) is recommended to reduce ischemic brain injury after cardiac arrest. The variables that predict heat generation by patients receiving TH are uncertain, as is how this heat generation relates to neurologic outcome. We hypothesized that patient characteristics, medication use, inflammation, and organ injury would be associated with heat generation. We further hypothesized that neurologic outcome would be most strongly associated with heat generation.Methods and ResultsSurface and intravascular cooling devices were used to provide TH in 57 consecutive cardiac arrest patients. Device water temperatures during the maintenance (33°C) phase were collected. Patient heat generation was quantified as the “heat index” (HI), which was the inverse average water temperature over a minimum of 2 hours of maintenance hypothermia. Variables measuring reduced ischemic injury and improved baseline health were significantly associated with HI. After controlling for presenting rhythm, a higher HI was independently associated with favorable disposition (OR=2.2; 95% CI 1.2 to 4.1; P=0.014) and favorable Cerebral Performance Category (OR=1.8; 95% CI 1.0 to 3.1; P=0.035). Higher HI predicted favorable disposition (receiver‐operator area under the curve 0.71, P=0.029). HI was linearly correlated with arteriovenous CO2 (r=0.69; P=0.041) but not O2 (r=0.13; P=0.741) gradients.ConclusionsIn cardiac arrest patients receiving TH, greater heat generation is associated with better baseline health, reduced ischemic injury, and improved neurologic function, which results in higher metabolism. HI can control for confounding effects of patient heat generation in future clinical trials of rapid TH and offers early prognostic information.