Comparison of Acute Versus Subacute Coronary Angiography in Patients With NON-ST-Elevation Myocardial Infarction (from the NONSTEMI Trial).

The optimal timing of coronary angiography (CAG) in high-risk patients with acute coronary syndrome without persisting ST-segment elevation (NST-ACS) remains undetermined. The NON-ST-Elevation Myocardial Infarction trial aimed to compare outcomes in NSTE-ACS patients randomized to acute CAG (STEMI-like approach) with patients randomized to medical therapy and subacute CAG. We randomized 496 patients with suspected NST-ACS based on symptoms and significant regional ST depressions and/or elevated point-of-care troponin T (POC-cTnT) (≥50 ng/l) to either acute CAG (<2 hours, n = 245) or subacute CAG (<72 hours, n = 251). The primary end point was a composite of all-cause death, reinfarction, and readmission with congestive heart failure within 1 year from randomization. A final acute coronary syndrome (ACS) diagnosis was assigned to 429 (86.5%) patients. The median time from randomization to revascularization was 1.3 hours in the acute CAG group versus 51.1 hours in the subacute CAG group (p <0.001). The composite end point occurred in 25 patients (10.2%) in the acute CAG group and 29 (11.6%) in the subacute CAG group, p = 0.62. The acute CAG group had a 1-year all-cause mortality of 5.7% compared with 5.6% in the subacute CAG group, p = 0.96. In conclusion, neither the composite end point of all-cause death, reinfarction, and readmission with congestive heart failure nor mortality differed between an acute and subacute CAG approach in NSTE-ACS patients. However, identification of NSTE-ACS patients in the prehospital phase and direct triage to an invasive center is feasible, safe and may facilitate early diagnosis and revascularization.

Predictive value of routine point-of-care cardiac troponin T measurement for prehospital diagnosis and risk-stratification in patients with suspected acute myocardial infarction.

OBJECTIVE: The purpose of this study was to determine the predictive value of routine prehospital point-of-care cardiac troponin T measurement for diagnosis and risk stratification of patients with suspected acute myocardial infarction. METHODS AND RESULTS: All prehospital emergency medical service vehicles in the Central Denmark Region were equipped with a point-of-care cardiac troponin T device (Roche Cobas h232) for routine use in all patients with a suspected acute myocardial infarction. During the study period, 1 June 2012-30 November 2015, prehospital point-of-care cardiac troponin T measurements were performed in a total of 19,615 cases seen by the emergency medical service and 18,712 point-of-care cardiac troponin T measurements in 15,781 individuals were matched with an admission. A final diagnosis of acute myocardial infarction was confirmed in 2187 cases and a total of 2150 point-of-care cardiac troponin T measurements (11.0%) had a value ≥50 ng/l, including 966 with acute myocardial infarction (sensitivity: 44.2%, specificity: 92.8%). Patients presenting with a prehospital point-of-care cardiac troponin T value ≥50 ng/l had a one-year mortality of 24% compared with 4.8% in those with values <50 ng/l, log-rank: p<0.001. The following variables showed the strongest association with mortality in multivariable analysis: point-of-care cardiac troponin T≥50 ng/l (hazard ratio 2.10, 95% confidence interval: 1.90-2.33), congestive heart failure (hazard ratio 1.93, 95% confidence interval: 1.74-2.14), diabetes mellitus (hazard ratio 1.42, 95% confidence interval: 1.27-1.59) and age, one-year increase (hazard ratio 1.08, 95% confidence interval: 1.08-1.09). CONCLUSIONS: Patients with suspected acute myocardial infarction and a prehospital point-of-care cardiac troponin T ≥50 ng/l have a poor prognosis irrespective of the final diagnosis. Routine troponin measurement in the prehospital setting has a high predictive value and can be used to identify high-risk patients even before hospital arrival so that they may be re-routed directly for advanced care at an invasive centre.

Increased (pro)renin receptor expression in the subfornical organ of hypertensive humans.

The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity and Na+ and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension. Here, we examined the expression level and cellular distribution of PRR in the SFO of postmortem human brains to assess its association with the pathogenesis of human hypertension. Postmortem SFO tissues were collected from hypertensive and normotensive human subjects. Immunolabeling for the PRR and a retrospective analysis of clinical data were performed. We found that human PRR was prominently expressed in most neurons and microglia, but not in astrocytes, in the SFO. Importantly, PRR levels in the SFO were elevated in hypertensive subjects. Moreover, PRR immunoreactivity was significantly correlated with systolic blood pressure but not body weight, age, or diastolic blood pressure. Interestingly, this correlation was independent of antihypertensive drug therapy. Our data indicate that PRR in the SFO may be a key molecular player in the pathogenesis of human hypertension and, as such, could be an important focus of efforts to understand the neurogenic origin of hypertension. NEW & NOTEWORTHY This study provides evidence that, in the subfornical organ of the human brain, the (pro)renin receptor is expressed in neurons and microglia cells but not in astrocytes. More importantly, (pro)renin receptor immunoreactivity in the subfornical organ is increased in hypertensive humans and is significantly correlated with systolic blood pressure.

Editor's Choice-Acute versus subacute angiography in patients with non-ST-elevation myocardial infarction - the NONSTEMI trial phase I.

BACKGROUND: The 2015 European Society of Cardiology non-ST-elevation myocardial infarction (NSTEMI) guidelines recommend angiography within 24 h in high-risk patients with NSTEMI. An organized STEMI-like approach with pre-hospital or immediate in-hospital triage for acute coronary angiography (CAG) may be of therapeutic benefit but it remains unknown whether the patients can be properly diagnosed in the pre-hospital setting. We aim to evaluate whether it is feasible to diagnose patients with NSTEMI in the pre-hospital phase or immediately upon admission. METHODS AND RESULTS: We randomized 250 patients to either acute or subacute CAG (i.e. <72 h of admission). Pre-hospital electrocardiogram acquisition and point-of-care troponin-T measurement ensured that 148 (59%) patients were identified already in the ambulance, whereas the remaining 102 (41%) patients were identified immediately after hospital admission. An acute coronary syndrome was verified in 215 (86%) and NSTEMI in 159 (64%) patients. The CAG rate was significantly higher in the acute CAG group (98% vs. 87%, p<0.001). A culprit lesion was identified in 74% and 64% of the patients underwent coronary revascularization: acute CAG group: 53% percutaneous coronary intervention, 5% hybrid, 7% coronary artery bypass grafting; conventional treatment: 48% percutaneous coronary intervention, 2% hybrid, 14% coronary artery bypass grafting, p=0.32. In patients randomized to acute CAG, time from randomization to CAG was 1.1 h; in patients randomized to subacute CAG it was two days. Time from randomization to initial revascularization was 1.3 h versus 2.4 days, and the median hospital stay was 4.0 days versus 4.5 days. Among patients randomized to subacute CAG, 17% crossed over to acute CAG and 5% developed STEMI before catheterization. CONCLUSION: Diagnosing NSTEMI patients in the pre-hospital phase or immediately upon hospital admission is feasible. Acute CAG may impact the mode of revascularization and is associated with earlier revascularization and shorter hospital stay. The clinical benefit of acute CAG in NSTEMI patients remains to be clarified.

The potential of optimizing prehospital triage of patients with suspected acute myocardial infarction using high-sensitivity cardiac troponin T and copeptin.

PURPOSE: In patients with a suspected acute myocardial infarction (AMI), to evaluate the potential for early triage based on measurement of high-sensitivity cardiac troponin T (hs-cTnT) and copeptin in blood samples collected in the prehospital phase. MATERIALS AND METHODS: In this retrospective study, we measured hs-cTnT and copeptin in blood samples collected in the ambulance form 962 patients with suspected AMI. The diagnostic accuracy was estimated by receiver-operating characteristic (ROC) curve area under the curve (AUC) for both biomarkers and a combined model. Multivariable Cox regression modelling was used to estimate the predictive value of both biomarkers. RESULTS: In total, 178 (19%) cases had AMI. The AUC for hs-cTnT was 0.81. Adding copeptin increased the AUC to 0.85 (p = 0.004) and the combined model allowed a prehospital rule-out of 45% of cases without AMI (negative predictive value, NPV 98%). Both biomarkers are highly predictive of outcome. CONCLUSIONS: A future application of hs-cTnT and copeptin measurement, performed already in the prehospital phase, could potentially improve the prehospital diagnostic and prognostic classification of patients with a suspected AMI.

The ST injury vector: electrocardiogram-based estimation of location and extent of myocardial ischemia.

BACKGROUND: Analysis of ST deviations from the 12-lead electrocardiogram allows for estimation of a spatial ST injury vector. The goal of the present study was to compare the location and extent of transmural myocardial ischemia evaluated by myocardial perfusion imaging with the direction and magnitude of the ST injury vector. METHODS: Twelve-lead electrocardiograms were recorded from 75 acute myocardial infarction patients with single-vessel disease and thrombolysis in myocardial infarction (TIMI) flow 0/1 (30 left anterior descending [LAD], 28 right coronary artery [RCA], 17 left circumflex artery [LCX]). ST deviations were measured in the J point in all leads and used to estimate ST injury vectors for each patient. Myocardial perfusion imaging was performed to evaluate the extent and location of myocardial ischemia at the time of coronary intervention. RESULTS: Ninety-two percent of the patients showed ST injury vectors within the expected directional range for the identified anatomic segment of ischemia by myocardial perfusion imaging. ST injury vector direction separated LAD, RCA, and LCX occlusion patients; 90% of the LAD patients showed anterior vectors, 82% of the RCA patients showed posteroinferoseptal vectors, and 59% of the LCX patients showed posteroinferolateral vectors. Eight patients did not fulfill the ST elevation criteria for ST elevation myocardial infarction but showed anterior ST depression and prominent ST injury vectors in the posterior torso direction. There was a moderate correlation between the extent of ischemia and ST injury vector magnitude for the ischemic patients, r = 0.29. CONCLUSION: We found strong agreement between the direction of the ST injury vector and the location of myocardial ischemia. The ST injury vector may be the key to higher diagnostic accuracy for inferobasal transmural ischemia and may help distinguishing between RCA and LCX occlusions in the acute phase.

Performance of an ST dipole model for description of ST deviations in myocardial ischemia.

BACKGROUND: Recent studies have proposed to include both ST depression and ST elevation in the diagnosis of myocardial ischemia, hence, considering all ST deviations relevant. In this study, we examined to which extent an ST dipole model accounts for the measured ST deviations in acute ischemia patients using 2 different sets of lead vectors. METHODS: 12-Lead electrocardiograms (ECGs) were recorded from 45 patients with occlusive single-vessel disease with thrombolysis in myocardial infarction (TIMI) flow 0/1 (15 anterior descending artery, 15 right coronary artery, 15 left circumflex artery), and ST deviations were measured in the J point in all leads. The dipole model was established by considering ST deviations as projections of a single dipole onto a set of lead vectors. A set of simplified unit length lead vectors and a set of lead vectors from the Dower transformation were compared. For each ECG and model, the best-fitting dipole was estimated by minimizing the sum of squared errors between measured and projected ST deviations across all leads. RESULTS: The goodness-of-fit metric (R(2)) for all recordings showed strong agreement between measured and projected ST deviations for both dipole models with R(2) of 0.77 to 0.83 (95% confidence interval [CI]) for the simplified model and R(2) of 0.91 to 0.93 (95% CI) for the Dower-based model. The Dower-based model showed superior performance for the whole population and for each of the occlusion artery subgroups (P < .05), but only small differences were seen between the estimated ST dipoles from the 2 models. CONCLUSION: A simple dipole model may be a useful descriptor of ST-segment deviations, reducing ST deviation measurements from 12 leads to a single 3-dimensional vector.

Is there any time left for primary percutaneous coronary intervention according to the 2007 updated American College of Cardiology/American Heart Association ST-segment elevation myocardial infarction guidelines and the D2B alliance?

Early reperfusion therapy is essential in the treatment of patients with ST-segment elevation myocardial infarction. Fibrinolytic therapy is a feasible reperfusion strategy to be initiated at any hospital and preferably in the pre-hospital phase. Primary percutaneous coronary intervention (PPCI) is acknowledged as a superior reperfusion strategy when initiated in a timely fashion. It is also the preferred reperfusion therapy in patients who exhibit cardiogenic shock and in patients with contraindications to fibrinolysis. However, in many regions, it is difficult to establish a successful PPCI strategy because it mandates optimal pre-hospital and in-hospital triage to ensure acceptable treatment delays. The 2007 updated American College of Cardiology/American Heart Association ST-Segment Elevation Myocardial Infarction Guidelines stress that "the focus for PPCI is from first medical contact because in regionalization strategies, extra time may be taken to transport patients to a center that performs the procedure" and that "time from Emergency Medical Services arrival to balloon inflation should be <90 minutes." When considering fibrinolysis, however, the guidelines accept a door-to-needle time of 30 min from arrival at the local hospital. Is there evidence to justify that, in the PPCI setting, the clock starts ticking upon the arrival of the Emergency Medical Services but, in the setting of in-hospital fibrinolysis, it does not start until a patient's arrival at the local hospital?