Most patients with out-of-hospital cardiac arrest do not achieve sustained return of spontaneous circulation (ROSC). Resuscitative endovascular balloon occlusion of the aorta (REBOA) may increase blood pressure proximal to the ballon. If this technique is used during advanced life support (ALS), and occlusion is performed in the thoracic aorta, it may augment aortic pressure and coronary perfusion pressure. We investigated whether prehospital REBOA as an adjunct to ALS increased the rate of ROSC. REBOARREST was a pragmatic, parallel-group, multicentre, randomised controlled trial conducted at 12 sites in Norway, Denmark, and Italy. Adult patients (18–80 years) with non-traumatic out-of-hospital cardiac arrest were randomly assigned (1:1) to either a control group that received ALS or to an intervention group that received ALS combined with REBOA as an adjunct. Fulfilment of eligibility criteria was determined by the physician on scene and sealed envelopes were used to allocate patients. The statistician that performed the analyses was blinded for group allocation. The primary outcome was sustained ROSC, defined as lasting ≥ 20 min, assessed in the intention-to-treat population. From June 7, 2021, to June 28, 2025, 200 patients were randomly assigned to the study groups. Due to lack of consent 21 patients dropped out of the trial, hence data from 179 patients are presented, 88 in the intervention group and 91 in the control group. Most patients were male (76

AIMS:To investigate the effect of long-term beta-blocker therapy on physical activity (PA) level after myocardial infarction (MI) in patients without heart failure. METHOD:The BETAMI trial, randomised patients hospitalised with a MI without heart failure (LVEF ≥40%) to beta-blocker or no beta-blocker. In this pre-planned sub-study PA level was assessed by guideline-recommended PA level (≥30 minutes moderate activity ≥5 days/week) or not and self-reported hours/week with light to moderate and vigorous PA. Between-group differences in PA from baseline before randomisation to 18-months were estimated by linear mixed models. Exploratory analysis assessed treatment effects on a composite of all-cause mortality and major adverse cardiovascular events using Cox proportional hazards model. RESULTS:Of the 2867 randomised patients, 2185 (76%) responded to the PA questions and were included in this analysis. Mean age was 62.5 (SD 10.1) years, 20.6% were women. No differences in guideline-recommended PA level or mean hours of light to moderate and vigorous PA were reported between the beta-blocker and non-beta-blocker group at baseline or during 18-months follow-up. At 12-month follow-up, 37.0% in the beta-blocker group and 36.7% in the no beta-blocker group reported guideline-recommended PA level (OR 0.97, 95% CI 0.69-1.37). Exploratory, hypothesis-generating analyses did not demonstrate a statistically significant interaction (p for interaction = 0.06) between treatment assignment and baseline PA level for recurrent clinical events. CONCLUSIONS:Beta-blocker therapy did not result in a change in PA level in post-MI patients without heart failure during the 18 months follow-up.

Abstract Background Invasive coronary angiography (CAG) remains widely used in Norway, with 37% of procedures in 2022 yielding normal findings, indicating potential overuse. Methods A national multidisciplinary task force performed a retrospective registry-based analysis and reviewed the European Society of Cardiology (ESC) guidelines to identify strategies aimed at reducing the utilization of CAG in patients with suspected coronary disease. Results Significant regional variation in CAG and Coronary Computed Tomography Angiography (CCTA) utilization was observed. Complication rates for CAG in stable patients were low, 0.6%. In patients with low and moderate pre-test probability and suspected Chronic Coronary Syndrome (CCS), CCTA is recommended as a first-line imaging test. Conclusion Standardization of CCTA protocols and reports, using CAD-RADS 2.0, mandatory CCTA registration in Norwegian Registry of Invasive Cardiology (NORIC), and formal collaboration between radiologists and cardiologists are essential initiatives. The aim is to reduce invasive procedures not resulting in revascularization by 5–10 percentage points nationally.

BACKGROUND:Lipidomics, the comprehensive profiling of circulating lipid species, has emerged as a powerful tool to investigate metabolic alterations underlying coronary atherosclerosis. Understanding the mechanisms driving high-risk vulnerable plaque formation and progression to myocardial infarction remains a key therapeutic priority. This study investigates associations between circulating lipid metabolites and imaging-defined features of vulnerable coronary plaque. METHODS:Following revascularization, patients with myocardial infarction underwent 3-vessel coronary artery imaging with near-infrared spectroscopy and intravascular ultrasound to assess nonflow-limiting plaques for lipid core burden index and plaque burden. Multivariable models evaluated associations between 424 lipid metabolites in plasma, quantified by mass spectrometry, pan-coronary lipid, pan-coronary plaque burden, and high-risk vulnerable plaque measures (maximum lipid core burden index within any 4-mm segment across the entire lesion ≥324.7 and/or plaque burden ≥70%) in 877 patients. Findings were validated in the SCAPIS study (Swedish Cardiopulmonary Bioimage Study) using coronary computed tomography angiography-based measures of coronary artery calcium score and segment involvement score. RESULTS:We identified 156 significant associations (P<0.05) between lipid metabolites and coronary plaque characteristics across 39 metabolic pathways. Sphingomyelins were inversely associated with all plaque metrics, and 1-palmitoyl-2-oleoyl-GPE (glycero-3-phosphoethanolamine; 16:0/18:1), a phosphatidylethanolamine, was positively associated with all plaque metrics. After correcting for multiple testing, 27 lipid species across 7 pathways remained significant (q<0.05). The majority were linked to pan-coronary lipid burden, with the strongest inverse association observed for sphingomyelin d18:1/22:1, d18:2/22:0, and d16:1/24:1. Similar inverse patterns were seen for select dihydrosphingomyelins and fatty acid dicarboxylates. In contrast, 1-palmitoyl-2-oleoyl-GPE (16:0/18:1) remained positively associated with pan-coronary lipid. In the SCAPIS validation cohort, 19 of the 27 significant lipid associations were successfully replicated (q<0.05). CONCLUSIONS:This study is the first to demonstrate that sphingomyelins are negatively and 1-palmitoyl-2-oleoyl-GPE (16:0/18:1) positively associated with vulnerable coronary plaque features based on multimodality intracoronary imaging in patients with myocardial infarction. Moreover, these associations were validated in a large cohort using coronary computed tomography angiography-derived measures of plaque burden. These novel results may enable the development of new diagnostic and therapeutic strategies.

CT-FFR provides noninvasive estimates of Fractional Flow Reserve (FFR) from Coronary Computed Tomography Angiography (CCTA) by combining computational fluid dynamics (CFD) with vessel geometry. While deep learning has advanced medical image segmentation, even state-of-the-art methods often result in discontinuous coronary topologies in critical stenosis regions, which may lead to false diagnosis. We present a two-stage segmentation approach for extraction of CFD-viable coronary geometry based on Swin UNEt TRansformers (Swin UNETR). In the first stage, the main coronary topology was found through ensemble voting from a set of trained models. Next, a series of dilation operations was performed to generate a region of interest (ROI) around the coronary arteries. The final segmentation was predicted by a Swin UNETR model where the ROI was provided as an input. The two-stage ROI-approach was compared with a baseline/single Swin UNETR model for a set of 15 CCTAs with ground truth segmentations performed by two independent operators. The average DICE score for the single Swin UNETR approach was 0.891, which was improved to 0.912 by the two-stage approach. In comparison, the interobserver DICE score was 0.906. The automatic segmentations were integrated in a CT-FFR pipeline to facilitate automatic prediction of FFR. CT-FFR predictions corresponding to the two-stage approach achieved better agreement with invasive FFR (r: 0.77, std. error: 0.089) compared to predictions based on manual segmentations (r: 0.63, std. error: 0.123 for operator 1 and, r: 0.47, std. error: 0.119 for operator 2). In contrast, the segmentations based on the baseline Swin UNETR resulted in disconnected segments in critical stenosis regions and poor CT-FFR agreement (r: 0.14, std.error: 0.180).

Background:In the PROSPECT-II study, near infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) was used to characterize atherosclerotic plaques in the coronary arteries. NIRS-derived lipid core burden index (LCBI) and IVUS-derived plaque burden (PB) were able to identify plaques strongly associated with adverse cardiovascular events. Aim:Our aim was to identify biomarkers associated with LCBI or PB in the coronary arteries. Methods:898 patients with recent myocardial infarction underwent percutaneous coronary intervention. Blood samples to analyze plasma levels of 179 proteins associated with cardiovascular disease were procured and a combined NIRS-IVUS catheter was used to analyze the coronary arteries. Adjusted linear regression models were calculated between the biomarkers and the outcomes of interest, adjusted for multiplicity testing. Kaplan-Meier survival curves of biomarkers divided by median were assessed with the log-rank test. Adjusted Cox proportional models were calculated for major adverse cardiovascular events. Results:A total of 24 proteins were associated with PB and 28 proteins with LCBI. Eight of these biomarkers were associated with both increased pan-coronary LCBI and PB; IL-18R1, CSF-1, VEGFA, EN-RAGE, cathepsin D, PCSK9, transferrin receptor protein 1 and OPN. After adjusting for multiplicity, angiopoietin like 3 (ANGPTL3) retained its association with LCBI, and IL-18R1 and CSF-1 retained their association with PB. Conclusion:We were able to identify distinct biomarker patterns associated with PB and LCBI. IL-18R1 and CSF-1 had a strong relationship with PB. ANGPTL3 was associated with lipid rich plaques but not with PB, supporting its role in lipid accumulation and development of vulnerable plaques.

BACKGROUND Hemodynamically obstructive coronary plaques may contain more vulnerable plaque characteristics than nonobstructive lesions. OBJECTIVES The authors aimed to assess whether pressure-wire-based physiologic indices in nonculprit lesions are associated with vulnerable plaque characteristics. METHODS In the PROSPECT II study, patients with recent myocardial infarction underwent coronary angiography and culprit lesion percutaneous coronary intervention plus combined near-infrared spectroscopy and intravascular ultrasound assessment of all 3 coronary arteries. Instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements were performed in intermediate lesions with angiographic stenosis >40%. RESULTS Among 898 patients, 319 angiographically intermediate lesions in 275 patients had matched intravascular ultrasound/near-infrared spectroscopy and FFR/iFR measurements; 96 (30.1%) lesions were physiologically significant (FFR <= 0.80 or iFR <= 0.89) and 223 (69.9%) were not. Physiologically significant lesions, compared with those that were not, more likely had a minimal lumen area <= 4.0 mm(2) (96.9% vs 83.9%), plaque burden >= 70% (92.7% vs 71.3%) and maximum lipid core burden index in any 4 mm segment of the lesion >= 324.7 (57.0% vs 45.4%). By multivariable analysis, lesion location in the left anterior descending artery, small minimal lumen area, and larger plaque burden were independently associated with physiologic significance, whereas maximum lipid core burden index in any 4 mm segment of the lesion was not. CONCLUSIONS In patients with recent myocardial infarction, angiographically intermediate but physiologically significant coronary lesions were more likely to have high-risk vulnerable plaque features compared with nonphysiologically significant stenoses. However, coronary lesions without physiological significance also had a moderate-to-high prevalence of high-risk plaque characteristics, which may explain the residual risk associated with conservative noninterventional management of these lesions.

BACKGROUND Although lipoprotein(a) (Lp[a]) has been associated with acute myocardial infarction (MI), the relationship between Lp(a) and the presence of high-risk "vulnerable" coronary plaques has not been studied. OBJECTIVES The aim of this study was to investigate whether specific lipoproteins are associated with pancoronary plaque volume and lipid deposition vs the development of non-flow-limiting high-risk vulnerable plaques. METHODS In PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) II, 3-vessel coronary artery imaging was performed with a combined near-infrared spectroscopy and intravascular ultrasound catheter after treatment of all flow-limiting lesions in patients with recent MI. The relationships of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), HDL-C, Lp(a), and triglycerides to pancoronary plaque volume, pancoronary lipid core burden index (LCBI), and the presence of focal vulnerable plaques (plaque burden >= 70% and maximum LCBI over any 4-mm segment >= 324.7) were assessed in 865 patients. RESULTS By multivariable analysis, TC, LDL-C, and non-HDL-C (but not Lp[a]) were associated with pancoronary plaque volume and pancoronary LCBI (P < 0.01 for all), but not with the presence of vulnerable plaque. Conversely, Lp(a) (but not TC, LDL-C, or non-HDL-C) was associated with the presence of focal vulnerable plaques (P 1/4 0.01). CONCLUSIONS In PROSPECT II, elevated TC, LDL-C, and non-HDL-C were strongly associated with pancoronary atherosclerosis and lipid deposition, whereas elevated Lp(a) was strongly associated with the presence of focal vulnerable plaques. These findings may explain the association between high Lp(a) levels and future MI and suggest a unique role for Lp(a) role in atherosclerosis progression and plaque vulnerability. (PROSPECT II & PROSPECT ABSORB-An Integrated Natural History Study and Randomized Trial; NCT02171065) (JACC. 2025;85:2011-2024) (c) 2025 by the American College of Cardiology Foundation.

We present a novel autoregulation-aware model of microvascular resistance for CT-FFR computations. The model improves prediction accuracy compared with conventional approaches for modeling the hyperemic state. Integration of CCTA-derived anatomy and invasive pressures reveals sex- and territory-dependent microvascular responses to adenosine, highlighting the diagnostic role of combined assessment of epicardial and microvascular disease.

BACKGROUND:Inflammation is a driver of atherosclerosis and susceptibility to cardiovascular events. OBJECTIVES:The authors sought to evaluate whether high-sensitivity C-reactive protein (hsCRP) levels are associated with the prevalence of high-risk coronary plaques in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS:PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) II was a multicenter, prospective study enrolling patients with recent myocardial infarction. Following treatment of all flow-limiting lesions, 3-vessel imaging with near-infrared spectroscopy and intravascular ultrasound was used to characterize untreated nonculprit lesions. We investigated the association between baseline hsCRP and plaque morphology (lipid content, plaque burden, lumen area) in 501 NSTEMI patients. hsCRP levels were categorized as low (<1 mg/L), intermediate (1-3 mg/L), or high (>3 mg/L). RESULTS:The percentages of patients with at least 1 highly lipidic plaque (maximum lipid core burden index for any 4-mm pullback length ≥324.7) increased from 39.4% to 57.2% to 59.3% in the low, intermediate, and high hsCRP groups, respectively (P = 0.01). The proportion of patients with at least 1 highly lipidic plaque with ≥70% burden increased with hsCRP levels from 22.7% to 27.2% to 36.7%, respectively (P = 0.01). Multivariable analyses showed that increasing hsCRP was associated with higher total coronary artery lipid core burden index and plaque volume. Higher hsCRP increased the odds of having any highly lipidic plaque and those with ≥70% plaque burden. CONCLUSIONS:Among patients with recent NSTEMI, a high baseline hsCRP level was associated with the presence of pan-coronary atherosclerosis and focal high-risk plaques. (PROSPECT II & PROSPECT ABSORB - an Integrated Natural History Study and Randomized Trial; NCT02171065).

Background: Non-invasive identification of high-risk coronary atherosclerosis remains a major clinical challenge. Lipidomics offers a promising tool to uncover metabolic signatures associated with plaque vulnerability and improve early risk assessment. Aim: To investigate the relationship between circulating lipid metabolites and imaging-derived characteristics of vulnerable coronary plaques. Method: In the multicentre PROSPECT II trial, 898 patients with recent myocardial infarction underwent three-vessel near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) imaging after revascularization. Non-flow limiting plaques were assessed for lipid core burden index (LCBI) and plaque burden (PB). Plasma samples were analyzed for 424 lipid metabolites using untargeted mass spectrometry. Associations between lipids and the three imaging outcomes; Pan-coronary PB, Pan-coronary lipid and High-risk vulnerable plaque (maxLCBI4mm ≥324.7 + PB ≥70%) were evaluated using multivariable models. The Benjamini-Hochberg procedure was applied to control the false discovery rate (FDR) and findings were validated in the SCAPIS cohort using the outcomes Segment Involvement Score (SIS) and Coronary Artery Calcium Score (CACS). Results: Sphingomyelins demonstrated robust and consistent inverse associations with all three imaging-defined plaque characteristics, with the strongest signal observed for Pan-coronary lipid, which remained statistically significant after FDR adjustment ( q < 0,05). In contrast, 1-palmitoyl-2-oleoyl-GPE (16:0/18:1), a phosphatidylethanolamine, showed strong positive associations across all plaque metrics, remaining significant after multiple testing for Pan-coronary lipid. These results were replicated in the SCAPIS cohort where similar trends were observed. Conclusion: Lower circulating levels of sphingomyelins are linked to greater lipid core and plaque burden, suggesting a protective or regulatory role in plaque stability. Conversely, elevated levels of 1-palmitoyl-2-oleoyl-GPE (16:0/18:1) may reflect or contribute to a pro-atherogenic lipid environment. These distinct lipid signatures may aid in early, non-invasive identification of vulnerable coronary plaques and offer insight into lipid-driven mechanisms of plaque destabilization.

BACKGROUND:The evidence supporting beta-blocker therapy after myocardial infarction was established before the introduction of modern coronary reperfusion therapy and secondary prevention strategies. METHODS:In an open-label, randomized trial with blinded end-point evaluation, conducted in Denmark and Norway, we assigned patients who had had a myocardial infarction and who had a left ventricular ejection fraction of at least 40%, in a 1:1 ratio, to receive long-term beta-blocker therapy within 14 days after the event or no beta-blocker therapy. The primary end point was a composite of death from any cause or major adverse cardiovascular events (new myocardial infarction, unplanned coronary revascularization, ischemic stroke, heart failure, or malignant ventricular arrhythmias). RESULTS:A total of 5574 patients underwent randomization and were included in the main analyses - 2783 in the beta-blocker group and 2791 in the no-beta-blocker group. After a median follow-up of 3.5 years (interquartile range, 2.2 to 4.6), a primary end-point event had occurred in 394 patients (14.2%) in the beta-blocker group and in 454 patients (16.3%) in the no-beta-blocker group (hazard ratio, 0.85; 95% confidence interval [CI], 0.75 to 0.98; P = 0.03). Death from any cause occurred in 4.2% of the patients in the beta-blocker group and in 4.4% of those in the no-beta-blocker group; myocardial infarction occurred in 5.0% and 6.7%, respectively (hazard ratio, 0.73; 95% CI, 0.59 to 0.92), unplanned coronary revascularization in 3.9% and 3.9%, ischemic stroke in 1.6% and 1.3%, heart failure in 1.5% and 1.9%, and malignant ventricular arrhythmias in 0.5% and 0.6%. No apparent differences in safety outcomes were observed between the groups. CONCLUSIONS:Among patients with a myocardial infarction and a left ventricular ejection fraction of at least 40%, beta-blocker therapy led to a lower risk of death or major adverse cardiovascular events than no beta-blocker therapy. (Funded by the Health South-East research program in Norway and others; BETAMI-DANBLOCK ClinicalTrials.gov numbers, NCT03646357 and NCT03778554.).

BACKGROUND:Clinical guidelines recommend different revascularization strategies for nonculprit lesions in patients with ST-segment-elevation myocardial infarction (STEMI) versus non-STEMI (NSTEMI). Whether the prevalence of untreated high-risk vulnerable plaques differs in STEMI and NSTEMI and affects their outcomes is unknown. METHODS:In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree II), a multicenter, prospective natural history study, patients with recent myocardial infarction underwent 3-vessel coronary angiography with coregistered near-infrared spectroscopy and intravascular ultrasound after successful percutaneous coronary intervention of obstructive lesions from 2014 through 2017. Two-feature high-risk plaques were defined as those with both plaque burden ≥70% and maximum lipid core burden index over any 4-mm segment ≥324.7. The primary end point was major adverse cardiovascular events arising from untreated nonculprit lesions during a median 3.7-year follow-up. RESULTS:Of 898 patients, 199 (22.2%) with 849 nonculprit lesions had STEMI and 699 (77.8%) with 2784 nonculprit lesions had NSTEMI. By intravascular ultrasound, the median nonculprit lesion length was 17.4 mm (interquartile range, 16.3-18.5) in STEMI and 17.7 mm (interquartile range, 17.1-18.4) in NSTEMI (P=0.63), and the median minimal lumen area was 5.5 mm2 (interquartile range, 5.3-5.7 mm2) in STEMI and 5.5 mm2 (interquartile range, 5.3-5.6 mm2) in NSTEMI (P=0.99). At the lesion level, the prevalence of 2-feature high-risk nonobstructive nonculprit plaques was slightly higher in patients with STEMI than in patients with NSTEMI (12.8% versus 10.1%; P=0.03). At the patient level, however, the prevalence of 2-feature high-risk plaques was similar in STEMI versus NSTEMI (38.8% versus 32.7%; P=0.11). The prevalence of patients with 1 or more lesions meeting at least 1 high-risk plaque criterion was also similar (plaque burden ≥70%, 63.3% versus 57.8% [P=0.16]; maximum lipid core burden index over any 4-mm segment ≥324.7, 63.3% versus 57.6% [P=0.15]). The 4-year rates of nonculprit lesion-related major adverse cardiovascular events were similar in STEMI versus NSTEMI (8.6% versus 7.8%; hazard ratio, 1.02 [95% CI, 0.57-1.81]; P=0.95), as were the rates of all major adverse cardiovascular events (14.2% versus 13.0%; hazard ratio, 1.06 [95% CI, 0.68-1.64]; P=0.80). CONCLUSIONS:In the PROSPECT II study, the per-patient prevalence of high-risk vulnerable plaques was comparable in STEMI versus NSTEMI, as was the overall long-term incidence of nonculprit lesion-related and all major adverse cardiovascular events. These results support a similar revascularization strategy for nonculprit lesions in patients with STEMI or NSTEMI after culprit lesion management. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02171065.

Aims To assess the diagnostic accuracy of dobutamine stress echocardiography (DSE) in symptomatic patients with a low to intermediate pretest probability of obstructive coronary artery disease (CAD) and a positive coronary CT angiography (CCTA).Methods We prospectively enrolled 104 consecutive patients undergoing coronary angiography for symptoms of stable CAD and a CCTA indicative of obstructive CAD. The diagnostic performance of DSE was evaluated against two intracoronary pressure indices: (a) fractional flow reserve (FFR) with a cut-off of ≤0.80 and (b) instantaneous wave-free ratio (iFR) with a cut-off of ≤0.89, indicating haemodynamically significant stenoses.Results Of 102 patients, 46 (45%) had at least one significant lesion as defined by FFR, as did 37 (36%) as defined by iFR. DSE showed positive results in 33% (34/102) of cases. The discriminative power of DSE for detecting significant CAD was moderate, with areas under the curve of 0.63 (p=0.024) compared with FFR and 0.64 (p=0.025) compared with iFR. The accuracy, sensitivity and specificity of DSE were, respectively, 61%, 43%, and 75% against FFR, and 64%, 46% and 74% against iFR. The diagnostic accuracy of DSE did not differ significantly between FFR and iFR as a reference (p=0.549).Conclusion In patients with positive CCTA, DSE has a moderate ability to identify haemodynamically significant CAD, with low sensitivity and moderate specificity. When assessed against FFR and iFR criteria, its additive diagnostic value is limited in patients with low to intermediate pretest probability of obstructive CAD.Trial registration number NCT03045601.