Background Frailty has been suggested as a valuable marker for predicting outcomes in older patients with cardiovascular disease. However, whether the association between frailty and adverse outcomes is similar in patients with chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) remains unclear. Methods Patients ≥70 years old referred for coronary angiography (CAG) due to CCS or ACS were included and followed for 12 months. Frailty was assessed using the Clinical Frailty Scale (CFS). Patients were grouped according to their CFS into frail/vulnerable (CFS≥4) and robust (CFS=1-3). Study endpoints included all-cause mortality and new hospital admissions for bleeding, myocardial infarction, unplanned revascularisation or stroke. Results 678 patients aged ≥70 years with available CFS underwent CAG due to CCS (n=223) or ACS (n=455) and completed 12-month follow-up. The prevalence of frailty/vulnerability was higher in patients referred with CCS compared to those with ACS (CCS:43.0% vs. ACS:32.2%, p=0.009). Frail/vulnerable patients referred with CCS were younger (CCS: 76.6(±4.7) years vs. ACS: 79.6(±5.7) years, p<0.001) and less frequently treated with percutaneous coronary intervention (CCS:40.6% vs. ACS:54.6%, p=0.043). Cumulative all-cause mortality was higher in frail/vulnerable patients referred with ACS but not in those referred with CCS, compared to robust patients (log-rank p<0.001). Conclusion Among patients ≥70 years old referred for CAG 30-40% are frail/vulnerable. Frailty/vulnerability was associated with higher all-cause mortality in patients referred for CAG due to ACS, but not in those referred due to CCS. This difference in outcome may reflect variations in clinical presentation as well as potential referral bias.

Background In patients with pulmonary embolism, a saddle-shaped embolus is perceived to be associated with disease severity. Although frequently observed in patients with acute intermediate-high risk pulmonary embolism, its prognostic significance remains unclear. In this study, we assessed the association between saddle embolism and short-term adverse outcomes in this risk subgroup. Methods We conducted a post hoc analysis of a multicentre randomized clinical trial of 210 patients with intermediate-high risk pulmonary embolism randomized to anticoagulation, systemic low-dose thrombolysis, or ultrasound-assisted catheter-directed low-dose thrombolysis. Saddle embolism was identified on baseline computed tomography pulmonary angiography. The primary outcome for this sub-study was a composite of in-hospital mortality and/or need for rescue thrombolysis. Secondary outcomes included saddle embolus resolution on follow-up imaging (after 48 – 96 hours) and other clinical outcomes. Results Saddle embolism was present in 58 patients (28%). There were no major differences in demographic or clinical characteristics between patients with and without saddle embolism. Saddle embolism was not associated with the primary composite outcome (adjusted OR 0.87, 95% CI 0.16 – 3.4, p = 0.85) or with other clinical outcomes compared to no saddle embolism. However, ultrasound-assisted catheter-directed thrombolysis was associated with higher odds of saddle embolus resolution compared to heparin alone (OR 5.5, 95% CI 1.06 – 35). Conclusion In patients with intermediate-high risk pulmonary embolism, we did not observe an association between saddle embolism and in-hospital mortality and/or need for rescue thrombolysis. Ultrasound-assisted catheter-directed thrombolysis plus heparin was associated with a higher rate of short-term saddle embolus resolution compared to heparin alone.

AIMS:Intermediate high-risk pulmonary embolism (PE) is associated with increased risk of haemodynamic deterioration and death, but balancing the risk of thrombolytics or catheter-based treatment and efficacy has been challenging. This trial compared the additional efficacy of catheter-based ultrasound low-dose thrombolysis (USAT) over intravenous low-dose thrombolysis or heparin alone. METHODS AND RESULTS:In an investigator-initiated randomized clinical multicentre trial, we randomized 210 adult patients with acute, intermediate high-risk PE admitted to emergency departments in two regions of Denmark. Patients were allocated 1:1:1 to one of three treatment strata: low-dose thrombolysis (20 mg alteplase administered over 6 h) by USAT, by intravenous administration, or heparin alone. The efficacy of the interventions was assessed by comparing the refined Modified Miller Score, rmMS, (0-40 points, higher score indicating higher thrombus burden) from CT angiographies performed at baseline and 48-96 h post-randomization. Two comparisons were investigated: the reduction of rmMS with low-dose thrombolysis (USAT or intravenously) compared to heparin alone and the reduction of rmMS with low-dose thrombolysis administered by USAT compared to the intravenous route. The safety endpoint included the risk of bleeding.We included 210 patients with acute PE, 49% were female, the mean age was 70 (IQR 62-76), and the mean body mass index was 30 (26-34). Compared to heparin alone, low-dose thrombolysis reduced the rmMS by 3.6 points (95% CI 2.2-5.0, P < 0.001), but the reduction in rmMS was not different in the ultrasound-assisted thrombolysis (USAT) vs. the intravenous route, mean difference -0.1 (95% CI: -1.9-1.7), P = 0.88. Bleeding complications were numerically more frequent with low-dose thrombolysis, albeit not statistically significant. No differences in other outcomes were observed. CONCLUSION:Low-dose thrombolysis reduced thrombus burden more than heparin alone in patients with acute intermediate high-risk PE. However, USAT did not show greater thrombus reduction than intravenous thrombolysis. The rate of death and risk of bleeding complications were increased with low-dose thrombolysis. TRIAL REGISTRATION:clinicaltrials.gov, NCT04088292.

INTRODUCTION:Takotsubo syndrome (TS) is a cardiac condition that mimics myocardial infarction (MI). Long-term readmission data remain limited. Previous studies in other conditions suggest that socioeconomic factors, such as low income and unemployment, may influence readmission rates, but this has not been explored in TS. This study aims to investigate the risk factors of 1-year readmissions in TS patients and the impact of socioeconomic factors, comparing results with matched individuals from the general population and those with MI. METHODS:A nationwide cohort study was conducted using national registers. Patients discharged alive from Danish hospitals with an incident TS diagnosis between 2008 and 2018 were identified through the Danish National Patient Registry. Each TS patient was matched with four individuals from the general population and patients with MI by sex and age. In the analyses of 1-year readmission of TS, we included socioeconomic factors such as cohabitation, labor market attachment, education, family income psychological distress, and comorbidities. RESULTS:A total of 1,022 individuals with TS were identified, with a median age of 70 years (IQR 61-77), and 89% were women. Compared to the general population, TS patients had higher rates of cardiovascular comorbidities, respiratory diseases, and psychotropic medication use but fewer cardiac conditions except for heart failure in the MI population. TS patients were more likely to receive incapacity pensions, have basic education, and belong to the lowest income percentile compared to the general population. In the first year, 36% of TS patients were readmitted, compared to 4% in the general population and 44% in the MI group. The most common causes of readmission in the TS cohort were cardiac (27%), "other" conditions (22%), respiratory (20%). Readmission rates were higher among TS patients in vulnerable socioeconomic groups compared to the general population: 37% vs. 6% for those in the lowest income percentile, 42% vs. 6% for those with basic education, and 37% vs. 4% for those on incapacity pension but overall lower compared to the MI population. Most readmissions occurred within the first 2 months. The two lowest income quintiles, vocational/high school and below, and living alone all predicted readmission. The lowest income had a hazard ratio of 1.64 and 95% confidence intervals of 1.01-2.69. CONCLUSION:Although TS patients exhibit a disadvantaged socioeconomic profile and a substantial comorbidity burden, our analyses suggest that socioeconomic factors are associated with readmission risk, with part of this association potentially mediated through comorbidity burden. These findings indicate that, even in healthcare systems with free access such as Denmark's, socioeconomic inequalities may remain relevant for readmission risk in TS patients.

Introduction: This study evaluated the performance of automated dual-energy computed tomography (DECT)-based quantification of perfusion defects (PDs) in acute pulmonary embolism and examined its correlation with clinical parameters. Methods: We retrospectively analyzed data from 171 patients treated for moderate-to-severe acute pulmonary embolism, who underwent DECT imaging at two separate time points. PDs were quantified using a fully automated AI-based segmentation method that relied exclusively on iodine perfusion maps. This was compared with a semi-automatic clinician-guided segmentation, where radiologists manually adjusted thresholds to eliminate artifacts. Clinical variables including the Miller obstruction score, right-to-left ventricular diameter ratio, oxygen saturation, and patient-reported symptoms were also collected. Results: The semiautomatic method demonstrated stronger correlations with embolic burden (Miller score; r = 0.4, p < 0.001 at follow-up) and a negative correlation with oxygen saturation (r = −0.2, p = 0.04). In contrast, the fully automated AI-based quantification consistently produced lower PD values and demonstrated weaker associations with clinical parameters. Conclusions: Semiautomatic quantification of PDs currently provides superior accuracy and clinical relevance for evaluating lung PDs in acute pulmonary embolism. Future multimodal AI models that incorporate both anatomical and clinical data may further enhance diagnostic precision.

Background High-sensitivity cardiac troponin (hs-cTn) assays are prone to negative and positive interferences caused by endogenous cardiac troponin-specific autoantibodies (cTnAAbs). Large macrotroponin complexes formed of cardiac troponin (cTn) and cTnAAbs may result in falsely elevated hs-cTn results. This is potentially due to reduced clearance of macrotroponin, but direct evidence is still lacking. In this study, we investigated the possible effects of cTnAAbs on the elimination of cTn. Methods Twenty patients with ST-elevation myocardial infarction (MI) underwent plasmapheresis within 24 h after revascularization to harvest plasma with a high cTn concentration. After clinical recovery, patients returned to the hospital for autologous plasma re-transfusion. Following re-transfusion, blood samples were collected at fixed time points and analyzed with 5 commercial hs-cTn assays. The presence of cTnAAbs in the samples and the epitope specificity of cTnAAbs were investigated with in-house immunoassays. Results Altogether, 2 out of 20 patients (10%) were cTnAAb-positive. With 4 commercial hs-cTn assays, cTnAAb-positive patients mainly showed longer elimination half-lives and slower cTn clearances than most cTnAAb-negative patients. One hs-cTn assay was prone to negative cTnAAb interference but correspondingly less prone to positive macrotroponin interference. The central part of cardiac troponin I (cTnI) was predominantly affected by cTnAAbs. Conclusions Endogenous cTnAAbs were for the first time shown to prolong the elimination half-life and reduce the clearance of cTn in the circulation. Additionally, the extent of analytical interference from cTnAAbs and their reactivity to macrotroponin varies among commercial hs-cTn assays, an important consideration for laboratories to ensure accurate diagnosis of MI.

Catheter-based therapies such as catheter-direceted thrombolysis, ultrasound-assisted thrombolysis, and mechanical embolectomy are emerging as alternatives for intermediate-high risk pulmonary embolism, offering targeted treatment with reduced bleeding risk. Early studies show promising outcomes but evidence remains limited. Ongoing randomized trials, including HI-PEITHO and PEERLESS II, aim to clarify efficacy and safety. Until results are available, treatment should be guided by individual risk assessment, local expertise, and centre capabilities, as argued in this review.

Studies have shown that frailty is associated with worse outcome in older patients with acute coronary syndrome (ACS). However, findings related to the coronary angiography (CAG) and outcome related to the level of revascularization status at discharge in these patients, is not well investigated. We wanted to investigate CAG findings in ACS patients ≥70 years old, related to the level of frailty at admission, and to examine whether 12-month outcome was associated to the level of revascularization status and frailty at the time of discharge. This is a substudy from a prospective study including all patients ≥70 years referred for invasive treatment for ACS from September 2020 to September 2021. Patients were undergoing frailty assessment with the clinical frailty scale (CFS) at the time of arrival to the department. A CFS score of 1-3 were defined as robust, 4 as vulnerable and 5-9 as frail. Primary endpoint was all-cause mortality at 12-month follow-up. 455 patients had their level of frailty assessed and were followed for 12 months, 69 (15%) patients were frail, 79 (17%) were vulnerable and 307 (68%) were robust. Frail patients were significantly older (frail: 80.9 (±5.6) years, vulnerable: 78.5 (±5.7) years and robust: 76.7 (±4.8) years, p<0.001), more often women (frail: 46.4%, vulnerable: 37.2%, and robust: 30.1%, p=0.028), and had higher Charlson index score (frail: 4.5 [4.0-5.0], vulnerable: 4.0 [4.0-6.0] and robust: 4.0 [3.0-4.0], p<0.001). Frail patients had more often multivessel disease (frail: 27.5%, vulnerable: 21.8% and robust: 23.5%, p=0.018), but were less often undergoing PCI (frail: 56.5%, vulnerable: 53.2% and robust: 68.6%, p=0.014). In patients undergoing PCI, there were no differences in lesions treated and the number of stents used, although frail and vulnerable patients were more often incomplete revascularized (frail: 48.5%, vulnerable: 44.3% and robust: 30.7%, p=0.016), table 1. In Kaplan Meier analyses, frail patients undergoing revascularization had a lower cumulated incidence of all-cause mortality in 12-month follow up (log-rank p=0.053) compared with frail who were not revascularized, figure 1. There were no differences in mortality according to revascularization status in vulnerable (log-rank p=0.29) or robust patients (log-rank p=0.54). In this study of patients ≥70 years old referred for invasive treatment of ACS, frail patients had more severe coronary artery disease, but were less often treated with PCI. However, in frail patients undergoing revascularization, the cumulated all-cause mortality in 12-month follow-up were lower as compared to frail who were not revascularized. These findings may represent a selection bias and need to be further investigated in randomized trials.

BACKGROUND:In patients with pulmonary embolism (PE), the impact of repeated troponin I or T (TnI/TnT) measurements remains unclear. METHODS:Using Danish national registries, we identified PE patients (≥18 years) hospitalized between 2013 and 2018 with initial TnI or TnT measurement within -1/+1 day from admission and >1 repeated measurement within three days. Trajectories of TnI and TnT were identified using latent class trajectory modeling. Hazard ratios for 30-day mortality were compared across trajectories via multivariable Cox regression. RESULTS:Among 1539 patients with TnI measurements and 1323 with TnT measurements, three distinct trajectories were identified. Trajectory I (nTnI = 286, nTnT = 472) exhibited consistently low TnI/TnT concentrations, trajectory II (nTnI = 1076, nTnT = 724) demonstrated initial elevated TnI/TnT decreasing within 24 h, and trajectory III (nTnI = 177, nTnT = 127) was characterized by elevated index TnI/TnT increasing within 10 h. 30-day mortality rates were higher in trajectory II and III compared to I in both the TnI (3 %, 7 % and 18 % across trajectory I to III) and the TnT (1 %, 9 % and 20 % across trajectory I to III) cohort. After adjustment hazard ratio of 30-day mortality for trajectory II vs. I was 7.42 (95 % CI 1.00-54.84, p = 0.04, TnI) and 2.93 (95 % CI 1.17-7.33, p = 0.02 TnT); and for trajectory III vs. I, 16.42 (95 % CI 2.42-127.29, p = 0.007, TnI) and 8.21 (95 % CI 2.78-24.19, p < 0.001, TnT). CONCLUSION:A steep increase in TnI or TnT concentration within 10 h of PE diagnosis significantly escalates 30-day mortality risk indicating that early serial sampling may enhance risk stratification of PE patients.

Abstract Background Cardiogenic shock (CS) occurs in 5–10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development. Methods This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 μg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h). The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24–48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed. Discussion Early inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up. Trial registration The Regional Ethics Committee : H-21045751. EudraCT: 2021–002028-19. ClinicalTrials.gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277–8523.

Aims Remnant cholesterol (RC) is the cholesterol content within triglyceride-rich lipoproteins. It promotes atherosclerotic cardiovascular disease beyond LDL cholesterol (LDL-C). The prognostic role of RC in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We aimed to estimate RC-related risk beyond LDL-C in patients with STEMI. Methods and results A total of 6602 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) from 1999 to 2016 were included. Remnant cholesterol was calculated as total cholesterol minus LDL-C minus HDL cholesterol. Adjusted Cox models were used to estimate the association between continuous RC levels and all-cause mortality, cardiovascular death, ischaemic stroke, and recurrent myocardial infarction (MI) at long-term (median follow-up of 6.0 years). Besides, discordance analyses were applied to examine the risk of the discordantly high RC (RC percentile rank minus LDL-C percentile rank > 10 units) compared with the discordantly low RC (LDL-C percentile rank minus RC percentile rank > 10 units). The concordance was defined as the percentile rank difference between RC and LDL-C <= 10 units. The median age of patients was 63 years [interquartile range (IQR) 54-72] and 74.8% were men. There were 2441, 1651, and 2510 patients in the discordantly low RC group, concordant group, and discordantly high RC group, respectively. All outcomes in the discordantly high RC group were higher than the other groups, and the event rate of all-cause mortality in this group was 31.87%. In the unadjusted analysis, the discordantly high RC was associated with increased all-cause mortality [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.63-2.04] and increased cardiovascular death (HR 1.79, 95% CI 1.55-2.06) compared with the discordantly low RC. In an adjusted model, RC was associated with higher all-cause mortality (HR 1.14, 95% CI 1.07-1.22). The discordantly high RC was associated with increased all-cause mortality (adjusted HR 1.55, 95% CI 1.37-1.75) and increased cardiovascular death (adjusted HR 1.47, 95% CI 1.25-1.72) compared with the discordantly low RC. There were no associations between RC and ischaemic stroke or recurrent MI. Conclusion In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C and discordantly high RC were independently associated with increased all-cause mortality.

BACKGROUND:Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans. METHODS:Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays. RESULTS:Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0). CONCLUSIONS:This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury.

Abstract Background Intermediate-high risk pulmonary embolism (PE) carries a significant risk of hemodynamic deterioration or death. Treatment should balance efficacy in reducing clot burden with the risk of complications, particularly bleeding. Previous studies on high-dose, short-term thrombolysis with alteplase (rtPA) showed a reduced risk of hemodynamic deterioration but no change in mortality and increased bleeding complications. Catheter-based techniques, including ultrasound-assisted thrombolysis (USAT), and low-dose thrombolysis may offer reasonable efficacy with lower risk. However, studies comparing these methods have been few. This trial aims to address this gap by randomizing patients to three treatment modalities. Methods Multicenter, randomized trial with 1:1:1 allocation of 210 patients with acute intermediate-high risk PE, excluding those with absolute contraindications to thrombolysis. Patients are eligible for inclusion if they are > 18 years of age, have had symptoms < 14 days, and are able to give informed consent. Patients are allocated 1:1:1 into three treatment strategies: (1) unfractionated heparin (UFH)/low molecular weight heparin (LMWH), (2) UFH/LMWH + 20 mg rtPA/6 h intravenously (IV), or (3) UFH + 20 mg rtPA/6 h via USAT. Co-primary outcomes include reduction in clot burden as assessed by refined Miller score from pre-treatment to follow-up (48–96 h) computed tomography pulmonary angiogram (CTPA) comparing low-dose rtPA (± USAT) groups to UFH/LMWH group (p < 0.01, N = 210) and reduction in refined Miller score on follow-up CT angiography comparing low-dose rtPA by USAT to intravenous rtPA, p < 0.04, N = 140). Secondary outcomes comprise bleeding complications, duration of index admission, FiO2, blood pressure, respiratory and heart rate at the time of follow-up CT angiography, mortality in the three groups, incidence of tricuspid regurgitation pressure gradient < 40 mmHg at 3 months follow-up echocardiography, 6-min walk test at 3 months comparing the three groups, and health-related quality of life at 3 months follow-up comparing the three groups. Discussion We hypothesize that in patients with intermediate-high risk PE (1) administration of 20 mg rtPA leads to a greater reduction in clot burden compared to heparins and (2) administration of 20 mg rtPA via USAT results in a greater reduction in clot burden compared to 20 mg rtPA intravenous. Trial registration ClinicalTrials.gov NCT04088292. Registered in September 2019 (retrospectively registered).

Spontaneous coronary artery dissection (SCAD) presents a life-threatening condition, prevalent among young women, comprising up to 35% of acute coronary syndrome cases. It involves sudden, trauma-free splitting of coronary artery walls, reducing blood flow and mimicking symptoms of acute myocardial infarction. Despite recent attention, treatment remains debated. Hormonal changes, stress, migraines, physical and psychological aspects impact the prognosis. Ongoing research aims to refine diagnostic and therapeutic approaches, addressing long-term outcomes. In this review, we have summarised current aspects of SCAD to increase awareness of the condition.

Abstract Background Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties. Methods This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB). Discussion Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints. Trial registration Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.

Context Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH). Objective We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH. Methods Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a). Results We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a). Conclusion Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.

Abstract Background Dyslipidemia is a known risk factor for cardiovascular disease. While statins are the primary treatment, some individuals require additional lipid-lowering therapies, such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Alirocumab and evolocumab have shown efficacy in reducing low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major cardiovascular events (MACE) but have not been directly compared in clinical trials. This study aims to assess the effects of PCSK9 inhibitors on LDL-C levels and evaluate the impact of a mandated switch from alirocumab to evolocumab. Methods Taking advantage of the mandated switch in PCSK9 treatment in Denmark, we conducted a register-based cohort study of 907 individuals with dyslipidemia treated with PCSK9 inhibitors in the Capital Region of Denmark from 2016 to 2022. We analyzed LDL-C levels, treatment retention, and MACE, adjusting for variables such as age, sex, dose, and concurrent lipid-lowering medications. Results We show that PCSK9 inhibitors treatment resulted in a 49% reduction in LDL-C levels. Following a mandated switch from alirocumab to evolocumab, no significant difference was observed in LDL-C levels or adverse clinical outcomes, including MACE. Treatment discontinuation was most likely within the first 100 days, and no significant difference in discontinuation rates was found between the two drugs. Conclusions Our study demonstrates that both alirocumab and evolocumab are effective in significantly reducing LDL-C levels in individuals with dyslipidemia. The mandated switch from alirocumab to evolocumab did not result in significant changes in LDL-C or clinical outcomes, suggesting that these treatments can be used interchangeably. These findings support the clinical equivalence of the two PCSK9 inhibitors and may guide therapeutic decisions in lipid management.