Thomas Engstrøm

Aims: The ORBI Risk Score predicts in-hospital cardiogenic shock after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Whether high-risk patients also have more systemic inflammation, larger infarcts, and higher long-term mortality is not known. Methods and results: In a DANAMI-3 sub-study, 1574 STEMI patients without cardiogenic shock were classified as high (ORBI ≥8, n = 273) or low risk (n = 1301). Inflammation was assessed by routine C-reactive protein (CRP), leucocyte count, and neutrophil-to-lymphocyte ratio (NLR) within 72 h of PCI, and admission mid-regional pro-adrenomedullin (MR-proADM). Infarct size was measured by cardiac magnetic resonance. Ten-year all-cause mortality was obtained from the Danish Civil Registration System. Cox models were adjusted for age, sex, comorbidity, kidney function, and randomized allocation. High-risk patients had higher peak CRP (72 vs. 11 mg/L), leucocyte count (12.8 vs. 10.4 × 109/L), NLR (6.2 vs. 3.5), and MR-proADM (0.73 vs. 0.62 nmol/L; all P < 0.001), as well as larger infarcts (final infarct size 15.7% vs. 10.1% of left ventricular mass). Ten-year mortality was 41% vs. 20% [hazard ratio (HR) 2.56, 95% CI 2.05–3.20; adjusted 1.47, 1.16–1.85]. The adjusted HR was 4.79 within 30 days and 1.27 after the first year. The score discriminated 10-year mortality less well than age alone (area under the curve 0.67 vs. 0.79). Conclusion: The ORBI Risk Score identifies STEMI patients with more inflammation, larger infarcts, and higher mortality, especially in the first year. Beyond the first year, the association was largely explained by age. Whether anti-inflammatory treatment benefits these patients is a question for randomized trials.

Aims: Apolipoprotein B (apoB)-containing lipoproteins contribute heterogeneously to atherosclerosis. While apoB particles are major determinants of plaque burden, Lp(a) has been linked to plaque inflammation and instability. We investigated the associations of non-Lp(a) apoB, Lp(a), and their relative balance with coronary plaque burden and vulnerability. Methods and results: Among 854 patients with recent myocardial infarction enrolled in the PROSPECT II near-infrared spectroscopy–intravascular ultrasound (NIRS-IVUS) study, total apoB was converted to nmol/L and non-Lp(a) apoB calculated by subtracting Lp(a) in nmol/L. The non-Lp(a) apoB/Lp(a) ratio was used to characterize the relative predominance of these lipoprotein classes. Higher non-Lp(a) apoB was independently associated with greater plaque burden [plaque percentage volume; β = 0.19, 95% confidence interval (CI) 0.05–0.33; P = 0.009], but not with lipid core burden index. In contrast, lower non-Lp(a) apoB/Lp(a) ratio tertile were associated with higher odds of plaque burden ≥70% [odds ratio (OR) 1.47, 95% CI 1.04–2.07; P = 0.029] and the composite vulnerability endpoint of plaque burden ≥70% and maxLCBI4mm ≥324.7 (OR 1.62, 95% CI 1.12–2.33; P = 0.011). In an exploratory external cohort from the CASABLANCA study, lower ratios identified an Lp(a)- and oxidized phospholipid-enriched phenotype and were associated with higher unadjusted cardiovascular risk. Conclusion: Non-Lp(a) apoB and Lp(a) demonstrate distinct associations with coronary plaque burden and vulnerability. Differentiating Lp(a)-associated from non-Lp(a)-associated apoB particle pools provides complementary information on coronary plaque phenotype, and the non-Lp(a) apoB/Lp(a) ratio summarizes their relative predominance. Clinical Trial Information: PROSPECT II- https://ClinicalTrial.gov Identifier: NCT02171065 CASABLANCA- https://ClinicalTrial.gov Identifier: NCT00842868. One-sentence summary: In patients with recent heart attack, the balance between conventional cholesterol-carrying particles and lipoprotein(a) identifies different types of coronary artery disease phenotypes and may help explain why some plaques are more likely to become dangerous. Key findings: Conventional apoB-containing lipoproteins (primarily LDL-related particles) were associated with greater overall coronary plaque burden, whereas a relative predominance of lipoprotein(a) was associated with plaques that had features linked to a higher risk of future cardiovascular events. A simple ratio comparing non-lipoprotein(a) apoB particles with lipoprotein(a) particles summarized these distinct biological processes and may provide complementary information for future studies evaluating cardiovascular risk and therapies targeting lipoprotein(a).

Aims: The benefit of complete revascularization after primary percutaneous coronary intervention (PCI) is well established in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the long-term effect in older patients remains uncertain. We aimed to evaluate the 10-year outcome of complete revascularization in older patients (aged ≥75 years) compared with younger patients. Methods and results: Patients with STEMI and multivessel disease were randomized to either culprit-only or fractional flow reserve-guided complete revascularization in the DANAMI-3–PRIMULTI trial. This long-term sub-study stratified the included 627 patients by <75 years (517) and ≥75 years (110). The primary outcome was a composite of all-cause mortality, recurrent myocardial infarction, or any revascularization occurring during a median follow-up of 10.5 years. Of the older patients, 50 underwent complete and 60 culprit-only revascularization, and of the younger patients, 264 were completely revascularized compared to 253 who had culprit-only PCI performed. In the older group, complete revascularization showed no association with the primary outcome (adjusted hazard ratio [HR] 1.29, 95% confidence interval [CI]: 0.82–2.03, P = 0.27). In contrast, complete revascularization was associated with a lower risk of the primary outcome (adjusted HR 0.68, 95% CI: 0.53–0.88, P = 0.003) in younger patients, primarily driven by a reduction in any revascularization (adjusted HR 0.60, 95% CI: 0.44–0.83, P = 0.002. Conclusion: In patients aged ≥75 years, clear evidence of a long-term (10 years) benefit of complete revascularization was not demonstrated. However, the elderly subgroup was small with limited events, and the finding should be interpreted as inconclusive. In contrast, complete revascularization was associated with a 32% lower risk of adverse outcomes among younger patients, primarily driven by a reduction in repeat revascularization, without evidence of reduced all-cause death or recurrent myocardial infarction.

BACKGROUND: Optimal treatment of coronary artery disease in patients undergoing transcatheter aortic valve implantation remains debated. Here, our aim was to analyze the impact of the diameter and location of coronary stenosis on outcomes in patients undergoing percutaneous coronary intervention (PCI) with transcatheter aortic valve implantation. METHODS: This study was a prespecified subanalysis of the NOTION-3 trial (Nordic Aortic Valve Intervention), which randomized patients with severe symptomatic aortic stenosis and physiologically significant stable coronary artery disease to receive either PCI or conservative treatment of coronary artery disease with transcatheter aortic valve implantation. In this substudy, patients were stratified according to diameter stenosis (P for interaction=0.051). PCI reduced major adverse cardiovascular events in case of proximal stenosis (26% versus 38%; hazard ratio, 0.61 [95% CI, 0.40–0.93]), although the difference in effect remained nonsignificant when compared with patients with nonproximal stenosis (28% versus 32%; hazard ratio, 0.91 [95% CI, 0.52–1.61]; P for interaction=0.27). CONCLUSIONS: The beneficial effect of PCI in patients undergoing transcatheter aortic valve implantation with physiologically significant stable coronary artery disease was seemingly pronounced in patients with high-grade stenosis, while stenosis location was not found to modify the outcome despite an almost similar beneficial effect with PCI in patients with proximal stenosis.

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 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 (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.

Background: Angina is common in patients with coronary artery disease and severe aortic stenosis. Whether angina should guide coronary revascularization in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) remains uncertain. Aims: To assess whether angina modifies the effect of percutaneous coronary intervention (PCI) on clinical outcomes and whether percutaneous coronary intervention influences angina burden after TAVI. Methods and results: This prespecified secondary analysis of the NOTION-3 trial included patients with severe aortic stenosis and significant coronary artery disease randomized to TAVI with percutaneous coronary intervention or optimal medical therapy (OMT). Baseline angina was assessed by Seattle Angina Questionnaire-7 Angina Frequency score, supplemented by Canadian Cardiovascular Society class when questionnaire data were missing. Of 454 patients, 229 (50%) had angina and 225 (50%) had no angina. In the baseline angina subgroup, the primary outcome MACE, a composite of death from any cause, myocardial infarction, or urgent revascularization, occurred in 27% randomized to PCI versus 37% randomized to OMT. Without angina, rates were 26% versus 35%. Hazard ratios for PCI versus OMT were 0.71 (95%-CI 0.45–1.13) in patients with angina and 0.69 (95%-CI 0.43–1.12) in those without, with no interaction by baseline angina (P=0.97). SAQ-7 summary scores improved at 1 year in angina groups, with no between-group difference in change (16 vs. 17; P=0.78). Conclusion: We found no evidence that baseline angina modified the relative effect of PCI on clinical outcomes, although the study was not powered to exclude clinically meaningful heterogeneity.

BACKGROUND: Intravascular imaging (IVI) during percutaneous coronary intervention (PCI) improves outcomes. Pullback pressure gradient characterizes coronary artery disease patterns as focal or diffuse; however, the benefit of IVI across this spectrum remains incompletely understood. We aimed to evaluate clinical outcomes after PCI with or without IVI guidance in patients with focal and diffuse disease defined by pullback pressure gradient. METHODS: Prospective, multicenter, single-arm study of 811 patients (840 vessels) undergoing PCI. Pullback pressure gradient was calculated from manual fractional flow reserve pullbacks to define focal (pullback pressure gradient ≥0.62) or diffuse coronary artery disease. IVI use was at the operator’s discretion. The primary outcome was target vessel failure at 1-year follow-up. RESULTS: IVI-guided PCI was performed in 41% of patients. In the overall cohort, target vessel failure was lower with IVI guidance (adjusted hazard ratio, 0.60 [95% CI, 0.36–0.99]; P =0.044), with a lower incidence of cardiac death ( P =0.042). The results were consistent irrespective of the baseline coronary artery disease pattern ( P _interaction =0.128). Among patients with focal disease, IVI-guided PCI was associated with a significantly lower incidence of target vessel failure compared with non-IVI-guided PCI (hazard ratio, 0.41 [95% CI, 0.18–0.91]; P =0.029). There was no statistical difference in target vessel failure with the use of IVI among patients with diffuse disease (hazard ratio, 0.91 [95% CI, 0.48–1.73]; P =0.771). CONCLUSIONS: In patients undergoing physiology-guided PCI, the use of IVI reduced clinical events at 1 year. These findings suggest that the benefit of IVI extends across the full spectrum of coronary artery disease.

Background: Findings from the recent NOTION-3 trial suggest that percutaneous coronary intervention (PCI) improves outcomes in patients with severe aortic stenosis and concomitant coronary artery disease undergoing transcatheter aortic valve implantation (TAVI). Whether the benefit of PCI is consistent across age groups is uncertain. Aims: To investigate the impact of age on outcomes from NOTION-3. Methods: A secondary analysis of 455 patients in the NOTION-3 trial, a randomized trial comparing PCI with conservative treatment in patients with aortic stenosis and coronary artery disease undergoing TAVI. Patients were stratified into four age groups based on the quartile distribution of age (<78, 78–81, 82–84, and ≥85 years) and followed for a median of 2 years (IQR: 1–4 years). The primary outcome was major adverse cardiac events defined as a composite of all-cause death, myocardial infarction, or urgent revascularization. Results: The risk difference for the primary endpoint comparing PCI and conservative treatment was most pronounced in patients aged 78–81 years [17% vs 42%; hazard ratio (HR): 0.36, 95% confidence interval (CI): 0.17–0.77, P = .008]. For the age groups <78, 82–84 and ≥85 years this risk difference between treatment groups was (HR: 1.08, 95% CI: 0.48–2.40), (HR: 0.69, 95% CI: 0.35–1.35), and (HR: 0.90, 95% CI: 0.50–1.62), respectively. Conclusion: In patients with coronary artery disease undergoing TAVI the benefit of PCI compared with conservative treatment on the composite of all-cause death, myocardial infarction, or urgent revascularization was most pronounced among patients aged 78–84 years.

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide, which can result in severe complications such as cardiac arrhythmia, heart failure, and sudden cardiac death. Genetic factors contribute to MI etiology and have been studied through genome-wide association studies (GWAS). This systematic review aims to summarize all GWAS of MI reporting single-nucleotide polymorphisms (SNPs) reaching genome-wide significance (p < 5 × 10⁻⁸) and elucidate on their biological relevance and potential clinical utility. A systematic review following PRISMA guidelines was conducted using PubMed and the GWAS Catalog to identify eligible studies. This review included nine GWAS published between 2007 and 2023, conducted in both European and non-European cohorts. GWAS have identified multiple loci associated with MI, pinpointing potential biological pathways underlying MI, and potential therapeutic targets and enhancing risk prediction. Nonetheless, significant challenges remain, particularly the underrepresentation of diverse ancestries and the need for functional follow-up studies to define causal variants and clarify the mechanisms linking genetic variation to MI pathogenesis.