Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Cardiac troponin I degradation in serum of patients with hypertrophic obstructive cardiomyopathy undergoing percutaneous septal ablation.

INTRODUCTION: Troponin has become the most important marker for diagnosing acute myocardial infarction, yet knowledge is scarce regarding appearance of specific degradation fragments in the blood. We have recently described the appearance of intact cardiac troponin I (cTnI) and 7 degradation products in patients suffering from ST-elevation myocardial infarction (STEMI) using Western blot analysis. However, the time resolution in STEMI patients is hampered by the rather vague time point 'onset of pain'. We therefore sought to utilize a time-wise more reliable model of human myocardial necrosis: percutaneous transluminal septal myocardial ablation (PTSMA) of hypertrophic obstructive cardiomyopathy (HOCM). Here the iatrogenic induction of myocardial necrosis occurs in vivo, allowing us to investigate degradation of cTnI by the second. METHODS: Blood samples were obtained from 8 patients with HOCM just prior to initiation of PTSMA and up to 50 h following the procedure. Western blot analysis was performed with subsequent analysis of relative intensities of the bands as compared to the degradation of cTnI in STEMI patients from the ASSENT-2 troponin substudy. RESULTS: We demonstrate intact cTnI and 9 degradation products [molecular weight (MW) 12.0-23.5 kDa]. The bands were comparable in MW to degradation fragments in STEMI. Their early rise in intensity, occurring within few minutes after the alcohol injection, emphasizes how susceptible troponin bands are to chemical/ischemic insults. Moreover, two additional bands were visible in the PTSMA population. CONCLUSION: This work describes the degradation products of troponin I in HOCM patients undergoing PTSMA. The detected bands appear fast and are similar to degradations following STEMI. This model contributes to our knowledge of the degradation patterns of troponin in disease states, and may thus play a role in the interpretation of elevated troponin levels.

"Mirror-lake" serial relationship of electrocardiographic and biochemical indices for the detection of reperfusion and the prediction of salvage in patients with acute myocardial infarction.

BACKGROUND: Serial observations of biochemical markers in the blood and bioelectric markers on the electrocardiogram (ECG) have been used to evaluate the effectiveness of reperfusion therapy in acute myocardial infarction (AMI). This study presents a combined method for clinical use, based on the "mirror-lake" tendency of the serial changes in these markers. METHODS: Consecutive thrombolytic-treated patients with AMI (n = 43) had ST-segment monitoring (Mortara Eli 100) and frequent serum sampling of myoglobin (MG) concentration. Their acutely predicted and finally estimated AMI sizes and myocardial salvage extents were calculated from the 12-lead standard ECG. Patients having 2 positive reperfusion indices (ST resolution at least 50%, and an increase in MG at least 2.4 fold) at 2 hours after initiation of thrombolytic therapy were considered the "complete reperfusion" group, and patients with discordant or 2 negative reperfusion indices after 2 hours of thrombolytic therapy were considered the "limited reperfusion" group. RESULTS: Patients with complete reperfusion (n = 22) versus patients with limited reperfusion (n = 21) had +12% versus -1% myocardial salvage (P <.0001). The serial changes in the ST segment mirrored the serial changes in the MG concentration, and the rates of increase in MG correlated with the rates of resolution of the ST-segment elevation. CONCLUSION: Myocardial salvage (measured by ECG indices) is greatest when an early increase in serum MG is "mirrored" by early resolution of ST-segment elevation.

Use of biochemical markers of infarction for diagnosing perioperative myocardial infarction and early graft occlusion after coronary artery bypass surgery.

STUDY OBJECTIVES: Perioperative myocardial infarction (PMI) during coronary artery bypass grafting (CABG) is an important clinical problem because it is closely associated with increased morbidity and mortality. The diagnosis of PMI is, however, associated with several problems. Due to the surgical trauma, the usual indicators of myocardial infarction (pain, ECG changes, and elevated biochemical markers of infarction) have uncertain diagnostic value. The primary aim of this study was to illustrate the levels of the biochemical markers after uncomplicated bypass surgery defined as no clinical or ECG evidence of PMI, and no graft occlusion at 7 days by repeat angiography; and secondarily, to establish biochemical diagnostic discrimination limits for detection of in-hospital graft occlusion. METHODS AND RESULTS: One hundred three patients undergoing elective CABG were closely monitored by serial measurements of creatine kinase (CK)-MB mass, myoglobin, troponin T, and troponin I, and underwent a repeat angiography before discharge. Seven patients had ECG evidence of PMI. Peak troponin T and CK-MB values were significantly higher in these seven patients, although the diagnostic performances of the optimally chosen cutoff levels for diagnosing AMI were fair. Twelve patients had at least one occluded graft shown by repeat angiography. Peak values of CK-MB and troponin T were significantly higher in patients with graft occlusion (52.2 microg/L vs 24.7 microg/L, p = 0.01; and 3.7 microg/L vs 1.0 microg/L, p = 0.05, respectively). By multivariate analysis, a diagnostic discrimination level of 30 microg/L for CK-MB did not reach statistical significance; however, the independent diagnostic value of a cutoff level for troponin T at 3 microg/L reached a level of significance (p = 0.06). DISCUSSION: We have suggested normal values of four different biochemical markers of infarction after uncomplicated coronary bypass surgery. Patients with in-hospital graft occlusion had higher peak CK-MB and troponin T values. However, the overlap with patients without graft occlusion is substantial, and the patency status in the individual cannot be reliably predicted from these noninvasive tests.