The effect of computed tomography (CT) vs invasive coronary angiography (ICA) on health status outcomes is unknown. To evaluate CT and ICA first-test strategies on quality of life (QOL) and angina. The Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial, conducted between October 2015 and April 2019 in 26 European centers, followed up patients with stable chest pain and intermediate probability of coronary artery disease for a median 3.5 years. Data analysis was from December 2023 to July 2024. Random assignment to CT or ICA. Patient-reported Euro QOL 5-dimensions descriptive system (EQ-5D-3L) visual analog scale (EQ-5D-3L-VAS) and 12-item Short Form Health Survey (SF-12) physical component score (SF-12-PCS) were primary prespecified QOL outcomes. Angina was the primary prespecified chest pain outcome. The EQ-5D-3L-VAS, summary index (EQ-5D-3L-SI), mental component summary (SF-12-MCS), and Hospital Anxiety and Depression Scale–anxiety subscale (HADS-A) and Hospital Anxiety and Depression Scale–anxiety subscale (HADS-D) were also evaluated. Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 1735 (96.0%) in the CT group and 1671 (95.3%) in the ICA group completed at least 1 health status assessment during 3.5 years of follow-up. Health status outcomes were similar between groups, with significant improvements in all QOL outcomes (eg, mean EQ-5D-3L-VAS 3.5 year minus baseline score: CT = 4.0; 95% CI, 3.1-4.9; P < .001; ICA = 4.6; 95% CI, 3.6-5.6; P =.002), except HADS-D, which improved only in the CT group (mean EQ-5D-3L-VAS 3.5 year minus baseline score: CT = −0.2; 95% CI, −0.4 to 0; P = .04; ICA = −0.2; 95% CI, −0.4 to 0; P = .12). Female patients had worse baseline and follow-up QOL than male patients (eg, baseline EQ-5D-3L-VAS difference between men and women = 5.2; 95% CI, 4.0-6.3; P <.001 and at 3.5 years = 3.1; 95% CI, 1.9-4.4; P < .001) but showed greater improvements in EQ-5D-3L-VAS (−1.9; 95% CI, −3.4 to −0.5; P = .009), SF-12-PCS (−1.4; −2.1 to −0.7; P < .001), and HADS-A (0.3; 0-0.7; P = .04). Angina outcomes were comparable between groups at 3.5 years, with similar 1-year rates in the CT group but higher rates in female than male patients in the ICA group (10.2% vs 6.2%; P = .007). Results of this secondary analysis of the DISCHARGE randomized clinical trial reveal that there was no significant difference in QOL or chest pain outcomes with CT vs ICA at 3.5 years. Female patients had worse health status than male patients at baseline and follow-up, and CT or ICA did not affect these differences. ClinicalTrials.gov Identifier: NCT02400229

Importance The effect of computed tomography (CT) vs invasive coronary angiography (ICA) on health status outcomes is unknown. Objective To evaluate CT and ICA first-test strategies on quality of life (QOL) and angina. Design, Setting, and Participants The Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial, conducted between October 2015 and April 2019 in 26 European centers, followed up patients with stable chest pain and intermediate probability of coronary artery disease for a median 3.5 years. Data analysis was from December 2023 to July 2024. Interventions Random assignment to CT or ICA. Main Outcomes and Measures Patient-reported Euro QOL 5-dimensions descriptive system (EQ-5D-3L) visual analog scale (EQ-5D-3L-VAS) and 12-item Short Form Health Survey (SF-12) physical component score (SF-12-PCS) were primary prespecified QOL outcomes. Angina was the primary prespecified chest pain outcome. The EQ-5D-3L-VAS, summary index (EQ-5D-3L-SI), mental component summary (SF-12-MCS), and Hospital Anxiety and Depression Scale-anxiety subscale (HADS-A) and Hospital Anxiety and Depression Scale-anxiety subscale (HADS-D) were also evaluated. Results Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 1735 (96.0%) in the CT group and 1671 (95.3%) in the ICA group completed at least 1 health status assessment during 3.5 years of follow-up. Health status outcomes were similar between groups, with significant improvements in all QOL outcomes (eg, mean EQ-5D-3L-VAS 3.5 year minus baseline score: CT = 4.0; 95% CI, 3.1-4.9; P < .001; ICA = 4.6; 95% CI, 3.6-5.6; P =.002), except HADS-D, which improved only in the CT group (mean EQ-5D-3L-VAS 3.5 year minus baseline score: CT = -0.2; 95% CI, -0.4 to 0; P = .04; ICA = -0.2; 95% CI, -0.4 to 0; P = .12). Female patients had worse baseline and follow-up QOL than male patients (eg, baseline EQ-5D-3L-VAS difference between men and women = 5.2; 95% CI, 4.0-6.3; P <.001 and at 3.5 years = 3.1; 95% CI, 1.9-4.4; P < .001) but showed greater improvements in EQ-5D-3L-VAS (-1.9; 95% CI, -3.4 to -0.5; P = .009), SF-12-PCS (-1.4; -2.1 to -0.7; P < .001), and HADS-A (0.3; 0-0.7; P = .04). Angina outcomes were comparable between groups at 3.5 years, with similar 1-year rates in the CT group but higher rates in female than male patients in the ICA group (10.2% vs 6.2%; P = .007). Conclusions and Relevance Results of this secondary analysis of the DISCHARGE randomized clinical trial reveal that there was no significant difference in QOL or chest pain outcomes with CT vs ICA at 3.5 years. Female patients had worse health status than male patients at baseline and follow-up, and CT or ICA did not affect these differences. Trial Registration ClinicalTrials.gov Identifier: NCT02400229

Background: Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose: To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods: This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results: Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m 2 , respectively. No interaction was found between CT or ICA and BMI for MACE ( P = .29), the expanded MACE composite ( P = .38), or major procedure-related complications ( P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m 2 exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion: There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups.

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. (C) 2020 by the American College of Cardiology Foundation.

Background: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is not well defined. We tested the hypothesis, that a strategy of very early invasive coronary angiography (ICA) and possible revascularization within 12 hours of diagnosis, is superior to an invasive strategy performed within 48-72 hours in terms of clinical outcomes. Methods: Patients admitted with clinical suspicion of NSTE-ACS in the Capital Region of Copenhagen, Denmark were screened for inclusion in the VERDICT trial (ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia and/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 48-72 hours. The primary endpoint was a combination of all-cause death, non-fatal recurrent myocardial infarction, hospital admission for refractory my...

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.

This paper describes a substantial part of the international mentoring network of students and young investigators in electrocardiology that developed around Dr. Galen Wagner (1939–2016), including many experiences of his mentees and co-mentors.The paper is meant to stimulate thinking about international mentoring as a means to achieve important learning experiences and personal development of young investigators, to intensify international scientific cooperation, and to stimulate scientific production.

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.

Recombinant activated coagulation factor VII (rFVIIa) (NovoSeven) was developed for treatment of bleeding in hemophilia patients with inhibitors (antibodies) against factors VIII or IX. rFVIIa initiates the coagulation cascade by binding to tissue factor at the site of injury and causes the formation of sufficient amounts of thrombin to trigger coagulation. Patients with a variety of other coagulation deficiencies than hemophilia characterized by an impaired thrombin generation and life-threatening bleeding have been reported as successfully treated with rFVIIa. Data are now entered into clinical registries established to further monitor this experimental treatment with NovoSeven. rFVIIa is produced free of any added human protein. The amino acid sequence of rFVIIa is identical to plasma-derived FVIIa (pdFVIIa). Posttranslational modifications (i.e., gamma-carboxylations, N- and O-glycosylations) are qualitatively identical in pdFVIIa and rFVIIa although some quantitative differences exist. The activities of rFVIIa and pdFVIIa are indistinguishable. Manufacturing of rFVIIa involves expression in baby hamster kidney (BHK) cells followed by purification, including three ion-exchange and one immunoaffinity chromatography steps. The last anion-exchange chromatography step ensures completion of the autoactivation of recombinant factor VII (rFVII) to rFVIIa. This review describes the mechanism of action, characterization, manufacturing, and preclinical and current clinical evidence for the efficacy and safety of rFVIIa.

Admission serum myoglobin 1Mb) and troponin-T(TNT) levels were evaluated vs admission CK-MB (mass assay) levels and the admission ECG ST elevation (ST↑)&gt;2 m V. for their diagnostic values in patients with suspected acute myocardial infarction (AMI) before thrombolytic treatment.