Differential impact of fentanyl and morphine doses on ticagrelor-induced platelet inhibition in ST-segment elevation myocardial infarction: a subgroup analysis from the PERSEUS randomized trial.

Introduction: Among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), intravenous fentanyl does not enhance ticagrelor-induced platelet inhibition within 2 h compared to morphine. The impact of the total dose of fentanyl and morphine received on ticagrelor pharmacodynamic and pharmacokinetic responses in patients with STEMI remains however undetermined. Materials and methods: We performed a post-hoc subanalysis of the prospective, open-label, single-center, randomized PERSEUS trial (NCT02531165) that compared treatment with intravenous fentanyl vs. morphine among symptomatic patients with STEMI treated with primary PCI after ticagrelor pretreatment. Patients from the same population as PERSEUS were further stratified according to the total dose of intravenous opioids received. The primary outcome was platelet reactivity using P2Y12 reaction units (PRU) at 2 h following administration of a loading dose (LD) of ticagrelor. Secondary outcomes were platelet reactivity and peak plasma levels of ticagrelor and AR-C124910XX, its active metabolite, at up to 12 h after ticagrelor LD administration. Generalized linear models for repeated measures were built to determine the relationship between raw and weight-weighted doses of fentanyl and morphine. Results: 38 patients with STEMI were included between December 18, 2015, and June 22, 2017. Baseline clinical and procedural characteristics were similar between low- and high-dose opioid subgroups. At 2 h, there was a significant correlation between PRU and both raw [regression coefficient (B), 0.51; 95% confidence interval (CI), 0.02-0.99; p = 0.043] and weight-weighted (B, 0.54; 95% CI, 0.49-0.59; p < 0.001) doses of fentanyl, but not morphine. Median PRU at 2 h was significantly lower in patients receiving low, as compared to high, doses of fentanyl [147; interquartile range (IQR), 63-202; vs. 255; IQR, 183-274; p = 0.028], whereas no significant difference was found in those receiving morphine (217; IQR, 165-266; vs. 237; IQR, 165-269; p = 0.09). At 2 h, weight-weighted doses of fentanyl and morphine were significantly correlated to plasma levels of ticagrelor and AR-C124910XX. Conclusion: In symptomatic patients with STEMI who underwent primary PCI after ticagrelor pretreatment and who received intravenous opioids, we found a dose-dependent relationship between the administration of intravenous fentanyl, but not morphine, and ticagrelor-induced platelet inhibition.

Acute Response of the Noninfarcted Myocardium and Surrounding Tissue Assessed by T2 Mapping After STEMI.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) is associated with a systemic and local inflammatory response with edema. However, their role at the tissue level is poorly characterized. OBJECTIVES: This study aims to characterize T2 values of the noninfarcted myocardium (NIM) and surrounding tissue and to investigate prognostic relevance of higher NIM T2 values after STEMI. METHODS: A total of 171 consecutive patients with STEMI without prior cardiovascular events who underwent cardiac magnetic resonance after primary percutaneous coronary intervention were analyzed in terms of standard infarct characteristics. Edema of the NIM, liver, spleen, and pectoralis muscle was assessed based on T2 mapping. Follow-up was available for 130 patients. The primary endpoint was major adverse cardiac events (MACE), defined as cardiovascular death, myocardial infarction, unplanned coronary revascularization or rehospitalization for heart failure. The median time from primary percutaneous coronary intervention to cardiac magnetic resonance was 3 days (IQR: 2-5 days). RESULTS: Higher (above the median value of 45 ms) T2 values in the NIM area were associated with larger infarct size, microvascular obstruction, and left ventricular dysfunction and did not correlate with C-reactive protein, white blood cells, or T2 values of the pectoralis muscle, liver, and spleen. At a median follow-up of 17 months, patients with higher (>45 ms) NIM T2 values had increased risk of MACE (P < 0.001) compared with subjects with NIM T2 values ≤45 ms, mainly caused by a higher rate of myocardial reinfarction (26.3% vs 1.4%; P < 0.001). At multivariable analysis, higher NIM T2 values independently predicted MACE (HR: 2.824 [95% CI: 1.254-6.361]; P = 0.012). CONCLUSIONS: Higher NIM T2 values after STEMI are independently associated with worse cardiovascular outcomes, mainly because of higher risk of myocardial infarction.

Temporal changes in coronary plaque as assessed by an artificial intelligence-based optical coherence tomography: from the first-in-human trial on DREAMS 3G scaffold.

AIMS: The aim of the study is to assess the impact of the baseline plaque composition on the DREAMS 3G luminal late loss and to compare the serial plaque changes between baseline and 6 and 12 months (M) follow-up. METHODS AND RESULTS: A total of 116 patients were enrolled in the BIOMAG-I trial. Patients were imaged with optical coherence tomography (OCT) pre- and post-DREAMS 3G implantation and at 6 and 12 M. OCTPlus software uses artificial intelligence to assess composition (i.e. lipid, calcium, and fibrous tissue) of the plaque. The differences between the OCT-derived minimum lumen area (MLA) post-percutaneous coronary intervention and 12 M were grouped into three terciles. Patients with larger MLA differences at 12 M (P = 0.0003) had significantly larger content of fibrous tissue at baseline. There was a reduction of 24.8% and 20.9% in lipid area, both P < 0.001, between the pre-DREAMS 3G OCT and the 6 and 12 M follow-up. Conversely, the fibrous tissue increased by 48.4% and 36.0% at 6 and 12 M follow-up, both P < 0.001. CONCLUSION: The larger the fibrous tissue in the lesion at baseline, the larger the luminal loss seen at 6 and 12 M. Following the implantation of DREAMS 3G, favourable healing of the vessel coronary wall occurs as shown by a decrease in the lipid area and an increase in fibrous tissue.

Real-world experience with ultrasound renal denervation utilizing home blood pressure monitoring: the Global Paradise System registry study design.

BACKGROUND: Hypertension is a major public health issue due to its association with cardiovascular disease risk. Despite the availability of effective antihypertensive drugs, rates of blood pressure (BP) control remain suboptimal. Renal denervation (RDN) has emerged as an effective non-pharmacological, device-based treatment option for patients with hypertension. The multicenter, single-arm, observational Global Paradise™ System (GPS) registry has been designed to examine the long-term safety and effectiveness of ultrasound RDN (uRDN) with the Paradise System in a large population of patients with hypertension. METHODS: The study aims to enroll up to 3000 patients undergoing uRDN in routine clinical practice. Patients will be recruited over a 4-year period and followed for 5 years (at 3, 6, and 12 months after the uRDN procedure and annually thereafter). Standardized home BP measurements will be taken every 3 months with automatic upload to the cloud. Office and ambulatory BP and adverse events will be collected as per routine clinical practice. Quality-of-Life questionnaires will be used to capture patient-reported outcomes. CONCLUSIONS: This observational registry will provide real-world information on the safety and effectiveness of uRDN in a large population of patients treated during routine clinical practice, and also allow for a better understanding of responses in prespecified subgroups. The focus on home BP in this registry is expected to improve completeness of long-term follow-up and provide unique insights into BP over time. Global Paradise System registry study design. ABP, ambulatory blood pressure; BP, blood pressure; FU, follow-up; M, month; OBP, office blood pressure.

Long-term outcomes with biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in ST-segment elevation myocardial infarction: 5-year follow-up of the BIOSTEMI randomised superiority trial.

BACKGROUND: Biodegradable polymer sirolimus-eluting stents improve early stent-related clinical outcomes compared to durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. The long-term advantages of biodegradable polymer sirolimus-eluting stents after complete degradation of its polymer coating in patients with STEMI remains however uncertain. METHODS: BIOSTEMI Extended Survival (BIOSTEMI ES) was an investigator-initiated, follow-up extension study of the BIOSTEMI prospective, multicentre, single-blind, randomised superiority trial that compared biodegradable polymer sirolimus-eluting stents with durable polymer everolimus-eluting stents in patients with STEMI undergoing primary percutaneous coronary intervention at ten hospitals in Switzerland. All individuals who had provided written informed consent for participation in the BIOSTEMI trial were eligible for this follow-up study. The primary endpoint was target lesion failure, defined as a composite of cardiac death, target vessel myocardial re-infarction, or clinically indicated target lesion revascularisation, at 5 years. Superiority of biodegradable polymer sirolimus-eluting stents over durable polymer everolimus-eluting stents was declared if the Bayesian posterior probability for a rate ratio (RR) of less than 1 was greater than 0·975. Analyses were performed according to the intention-to-treat principle. The study was registered with ClinicalTrials.gov, NCT05484310. FINDINGS: Between April 26, 2016, and March 9, 2018, 1300 patients with STEMI (1622 lesions) were randomly allocated in a 1:1 ratio to treatment with biodegradable polymer sirolimus-eluting stents (649 patients, 816 lesions) or durable polymer everolimus-eluting stents (651 patients, 806 lesions). At 5 years, the primary composite endpoint of target lesion failure occurred in 50 (8%) patients treated with biodegradable polymer sirolimus-eluting stents and in 72 (11%) patients treated with durable polymer everolimus-eluting stents (difference of -3%; RR 0·70, 95% Bayesian credible interval 0·51-0·95; Bayesian posterior probability for superiority 0·988). INTERPRETATION: In patients undergoing primary percutaneous coronary intervention for STEMI, biodegradable polymer sirolimus-eluting stents were superior to durable polymer everolimus-eluting stents with respect to target lesion failure at 5 years of follow-up. The difference was driven by a numerically lower risk for ischaemia-driven target lesion revascularisation. FUNDING: Biotronik.

Modification of the GRACE Risk Score for Risk Prediction in Patients With Acute Coronary Syndromes.

Importance: The Global Registry of Acute Coronary Events (GRACE) risk score, a guideline-recommended risk stratification tool for patients presenting with acute coronary syndromes (ACS), does not consider the extent of myocardial injury. Objective: To assess the incremental predictive value of a modified GRACE score incorporating high-sensitivity cardiac troponin (hs-cTn) T at presentation, a surrogate of the extent of myocardial injury. Design, Setting, and Participants: This retrospectively designed longitudinal cohort study examined 3 independent cohorts of 9803 patients with ACS enrolled from September 2009 to December 2017; 2 ACS derivation cohorts (Heidelberg ACS cohort and Newcastle STEMI cohort) and an ACS validation cohort (SPUM-ACS study). The Heidelberg ACS cohort included 2535 and the SPUM-ACS study 4288 consecutive patients presenting with a working diagnosis of ACS. The Newcastle STEMI cohort included 2980 consecutive patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Data were analyzed from March to June 2023. Exposures: In-hospital, 30-day, and 1-year mortality risk estimates derived from an updated risk score that incorporates continuous hs-cTn T at presentation (modified GRACE). Main Outcomes and Measures: The predictive value of continuous hs-cTn T and modified GRACE risk score compared with the original GRACE risk score. Study end points were all-cause mortality during hospitalization and at 30 days and 1 year after the index event. Results: Of 9450 included patients, 7313 (77.4%) were male, and the mean (SD) age at presentation was 64.2 (12.6) years. Using continuous rather than binary hs-cTn T conferred improved discrimination and reclassification compared with the original GRACE score (in-hospital mortality: area under the receiver operating characteristic curve [AUC], 0.835 vs 0.741; continuous net reclassification improvement [NRI], 0.208; 30-day mortality: AUC, 0.828 vs 0.740; NRI, 0.312; 1-year mortality: AUC, 0.785 vs 0.778; NRI, 0.078) in the derivation cohort. These findings were confirmed in the validation cohort. In the pooled population of 9450 patients, modified GRACE risk score showed superior performance compared with the original GRACE risk score in terms of reclassification and discrimination for in-hospital mortality end point (AUC, 0.878 vs 0.780; NRI, 0.097), 30-day mortality end point (AUC, 0.858 vs 0.771; NRI, 0.08), and 1-year mortality end point (AUC, 0.813 vs 0.797; NRI, 0.056). Conclusions and Relevance: In this study, using continuous rather than binary hs-cTn T at presentation, a proxy of the extent of myocardial injury, in the GRACE risk score improved the mortality risk prediction in patients with ACS.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy.

BACKGROUND: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. OBJECTIVES: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. METHODS: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. RESULTS: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). CONCLUSIONS: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844).

Vascular Access in Percutaneous Coronary Intervention of Chronic Total Occlusions: A State-of-the-Art Review.

The outcomes of chronic total occlusion percutaneous coronary intervention have considerably improved during the last decade with continued emphasis on improving procedural safety. Vascular access site bleeding remains one of the most frequent complications. Several procedural strategies have been implemented to reduce the rate of vascular access site complications. This state-of-the-art review summarizes and describes the current evidence on optimal vascular access strategies for chronic total occlusion percutaneous coronary intervention.

A new resorbable magnesium scaffold for de novo coronary lesions (DREAMS 3): one-year results of the BIOMAG-I first-in-human study.

BACKGROUND: The third-generation coronary sirolimus-eluting magnesium scaffold, DREAMS 3G, is a further development of the DREAMS 2G (commercial name Magmaris), aiming to provide performance outcomes similar to drug-eluting stents (DES). AIMS: The BIOMAG-I study aims to assess the safety and performance of this new-generation scaffold. METHODS: This is a prospective, multicentre, first-in-human study with clinical and imaging follow-up scheduled at 6 and 12 months. The clinical follow-up will continue for 5 years. RESULTS: A total of 116 patients with 117 lesions were enrolled. At 12 months, after completion of resorption, in-scaffold late lumen loss was 0.24±0.36 mm (median 0.19, interquartile range 0.06-0.36). The minimum lumen area was 4.95±2.24 mm² by intravascular ultrasound and 4.68±2.32 mm² by optical coherence tomography. Three target lesion failures were reported (2.6%, 95% confidence interval: 0.9-7.9), all clinically driven target lesion revascularisations. Cardiac death, target vessel myocardial infarction and definite or probable scaffold thrombosis were absent. CONCLUSIONS: Data at the end of the resorption period of DREAMS 3G showed that the third-generation bioresorbable magnesium scaffold is clinically safe and effective, making it a possible alternative to DES. CLINICALTRIALS: gov: NCT04157153.

Impact of alirocumab on plaque regression and haemodynamics of non-culprit arteries in patients with acute myocardial infarction: a prespecified substudy of the PACMAN-AMI trial.

BACKGROUND: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilisation. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown. AIMS: This study aimed to investigate the effects of the PCSK9 inhibitor alirocumab on coronary haemodynamics as assessed by quantitative flow ratio (QFR) and DS% by three-dimensional quantitative coronary angiography (3D-QCA) in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients. METHODS: This was a prespecified substudy of the randomised controlled PACMAN-AMI trial, comparing alirocumab versus placebo on top of rosuvastatin. QFR and 3D-QCA were assessed at baseline and 1 year in any non-IRA ≥2.0 mm and 3D-QCA DS% >25%. The prespecified primary endpoint was the number of patients with a mean QFR increase at 1 year, and the secondary endpoint was the change in 3D-QCA DS%. RESULTS: Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. At 1 year, QFR increased in 50/94 (53.2%) patients with alirocumab versus 40/99 (40.4%) with placebo (Δ12.8%; odds ratio 1.7, 95% confidence interval [CI]: 0.9 to 3.0; p=0.076). DS% decreased by 1.03±7.28% with alirocumab and increased by 1.70±8.27% with placebo (Δ-2.50%, 95% CI: -4.43 to -0.57; p=0.011). CONCLUSIONS: Treatment of AMI patients with alirocumab versus placebo for 1 year resulted in a significant regression in angiographic DS%, whereas no overall improvement of coronary haemodynamics was observed. CLINICALTRIALS: gov: NCT03067844.

Ultrathin-strut vs thin-strut drug-eluting stents for multi and single-stent lesions: A lesion-level subgroup analysis of 2 randomized trials.

BACKGROUND: Whether ultrathin-strut stents are particularly beneficial for lesions requiring implantation of more than 1 stent is unknown. METHODS: In a post-hoc lesion-level analysis of 2 randomized trials comparing ultrathin-strut biodegradable polymer Sirolimus-eluting stents (BP-SES) vs thin-strut durable polymer Everolimus-eluting stents (DP-EES), lesions were stratified into multistent lesions (MSL) vs single-stent lesions (SSL). The primary endpoint was target lesion failure (TLF), a composite of lesion-related unclear/cardiac death, myocardial infarction (MI), or revascularization, at 24 months. RESULTS: Among 5328 lesions in 3397 patients, 1492 (28%) were MSL (722 with BP-SES, 770 with DP-EES). At 2 years, TLF occurred in 63 lesions (8.9%) treated with BP-SES and 60 lesions (7.9%) treated with DP-EES in the MSL-group (subdistibution hazard ratio [SHR], 1.13; 95% CI, 0.77-1.64; P = .53), and in 121 (6.4%) and 136 (7.4%) lesions treated with BP-SES and DP-EES respectively (SHR, 0.86; 95% CI, 0.62-1.18; P = .35) in the SSL-group (P for interaction = .241). While the rates of lesion-related MI or revascularization were significantly lower in SSL treated with BP-SES as compared to DP-EES (3.5% vs 5.2%; SHR, 0.67; 95% CI 0.46-0.97; P = .036), no significant difference was observed in MSL (7.1% vs 5.4%; SHR, 1.31; 95% CI 0.85-2.03; P = .216) with significant interaction between groups (P for interaction = .014). CONCLUSIONS: Rates of TLF are similar between ultrathin-strut BP-SES and thin-strut DP-EES in MSL and SSL. The use of ultrathin-strut BP-SES vs thin-strut DP-EES did not prove to be particularly beneficial for the treatment of multistent lesions. TRIAL REGISTRATION: Post-hoc analysis from the BIOSCIENCE (NCT01443104) and BIOSTEMI (NCT02579031) trials.

[Challenges of coronary revascularization in diabetic patients in 2023]. / Défis de la revascularisation coronarienne du patient diabétique en 2023.

Diabetic patients remain at increased risk for major adverse cardiovascular events, compared to their non-diabetic counterparts. Coronary artery bypass grafting remains superior to percutaneous coronary intervention (PCI) among diabetic patients with chronic coronary syndrome and multivessel coronary artery disease. PCI represents an alternative in diabetic patient with low coronary anatomy complexity. The revascularization strategy should be discussed by a multidisciplinary Heart Team. Despite advances in DES technology, PCI in diabetic patients remains associated with a higher risk of adverse outcomes than in non-diabetic patients, but the long-term outcome results from recently published and ongoing large-scale randomized studies investigating novel DES designs may reshape the landscape of coronary revascularization for diabetic patient.

Les patients diabétiques présentent plus d'événements cardiovasculaires (CV) majeurs que les non diabétiques. Le pontage aortocoronarien reste supérieur à l'angioplastie chez les patients diabétiques avec une maladie coronarienne pluritronculaire stable. L'angioplastie coronarienne percutanée constitue une alternative en cas d'anatomie coronarienne peu complexe. La revascularisation chez ces patients doit être discutée en équipe multidisciplinaire. Malgré les progrès des stents à élution médicamenteuse (DES) de dernière génération, l'angioplastie percutanée reste associée à plus d'événements CV chez les patients diabétiques, mais les résultats du suivi à long terme d'essais randomisés, récemment publiés ou en cours, évaluant de nouvelles technologies de DES, pourraient modifier le panorama de la revascularisation du patient diabétique.

Safety and performance of the third-generation drug-eluting resorbable coronary magnesium scaffold system in the treatment of subjects with de novo coronary artery lesions: 6-month results of the prospective, multicenter BIOMAG-I first-in-human study.

Background: A third-generation coronary drug-eluting resorbable magnesium scaffold (DREAMS 3G) was developed to enhance the performance of previous scaffold generations and achieve angiographic outcomes comparable to those of contemporary drug-eluting stents. Methods: This prospective, multicenter, non-randomized, first-in-human study was conducted at 14 centers in Europe. Eligible patients had stable or unstable angina, documented silent ischemia, or non-ST-elevation myocardial infarction, and a maximum of two single de novo lesions in two separate coronary arteries with a reference vessel diameter between 2.5 mm and 4.2 mm. Clinical follow-up was scheduled at one, six and 12 months and annually thereafter until five years. Invasive imaging assessments were scheduled six and 12 months postoperatively. The primary endpoint was angiographic in-scaffold late lumen loss at six months. This trial was registered at ClinicalTrials.gov (NCT04157153). Findings: Between April 2020 and February 2022, 116 patients with 117 coronary artery lesions were enrolled. At six months, in-scaffold late lumen loss was 0.21 mm (SD 0.31). Intravascular ultrasound assessment showed preservation of the scaffold area (mean 7.59 mm2 [SD 2.21] post-procedure vs 6.96 mm2 [SD 2.48]) at six months) with a low mean neointimal area (0.02 mm2 [SD 0.10]). Optical coherence tomography revealed that struts were embedded in the vessel wall and were already hardly discernible at six months. Target lesion failure occurred in one (0.9%) patient; a clinically driven target lesion revascularization was performed on post-procedure day 166. No definite or probable scaffold thrombosis or myocardial infarction was observed. Interpretation: These findings show that the implantation of DREAMS 3G in de novo coronary lesions is associated with favorable safety and performance outcomes, comparable to contemporary drug-eluting stents. Funding: This study was funded by BIOTRONIK AG.

Complex primary percutaneous coronary intervention with ultrathin-strut biodegradable versus thin-strut durable polymer drug-eluting stents in patients with ST-segment elevation myocardial infarction: A subgroup analysis from the BIOSTEMI randomized trial.

BACKGROUND: Ultrathin-strut biodegradable polymer sirolimus-eluting stents (BP-SES) are superior to thin-strut durable polymer everolimus-eluting stents (DP-EES) with respect to target lesion failure (TLF) at 2 years among patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the impact of primary percutaneous coronary intervention (pPCI) complexity on long-term clinical outcomes with BP-SES versus DP-EES in STEMI patients. METHODS: We performed a post hoc subgroup analysis from the BIOSTEMI (NCT02579031) randomized trial, which included individual data from 407 STEMI patients enrolled in the BIOSCIENCE trial (NCT01443104). STEMI patients were randomly assigned to treatment with ultrathin-strut BP-SES or thin-strut DP-EES, and further categorized into those undergoing complex versus noncomplex pPCI. Complex pPCI was defined by the presence of ≥1 of the following criteria: 3 vessel treatment, ≥3 stents implanted, ≥3 lesions treated, bifurcation lesion with ≥2 stents implanted, total stent length ≥60 mm, and/or chronic total occlusion treatment. The primary endpoint was TLF, a composite of cardiac death, target-vessel myocardial reinfarction, or clinically indicated target lesion revascularization, within 2 years. RESULTS: Among a total of 1707 STEMI patients, 421 (24.7%) underwent complex pPCI. Baseline characteristics were similar between groups. At 2 years, TLF occurred in 14 patients (7.1%) treated with BP-SES and 25 patients (11.6%) treated with DP-EES (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.32-1.19; p = 0.15) in the complex pPCI group, and in 28 patients (4.4%) treated with BP-SES and 49 patients (8.2%) treated with DP-EES (HR: 0.54; 95% CI: 0.34-0.86; p = 0.008; p for interaction = 0.74) in the noncomplex pPCI group. Individual TLF components and stent thrombosis rates did not significantly differ between groups. CONCLUSION: In a post hoc subgroup analysis from the BIOSTEMI randomized trial, ultrathin-strut BP-SES were superior to thin-strut DP-EES with respect to TLF at 2 years among STEMI patients undergoing both complex and noncomplex pPCI.

Instantaneous Wave-Free Ratio: Novel Adenosine-Free Method to Assess Intracoronary Physiology.

Fractional flow reserve assessment was accepted as a crucial strategy in stable patients undergoing coronary angiography without prior noninvasive evaluation in the presence of borderline lesions and in patients with multivessel coronary artery disease. Instantaneous wave-free ratio, measured during a specific diastolic interval, emerged as a nonhyperemic pressure ratio. Due to its advantages such as not requiring a vasodilating agent, rapidity of procedure, pullback phenomena for the assessment of individual stenosis in tandem lesions or diffusely infiltrated vessels, and virtual percutaneous coronary intervention which allows the assessment and justification 'of' optimal coronary revascularization, instantaneous wave-free ratio became a valuable option in the field of coronary physiology. This review aims to address coronary physiological concept with fractional flow reserve and emergence of instantaneous wave-free ratio through cornerstone studies as well as the use of instantaneous wave-free ratio in different clinical scenarios.

Comparative effects of fentanyl versus morphine on platelet inhibition induced by ticagrelor in patients with ST-segment elevation myocardial infarction: Full results of the PERSEUS randomized trial.

BACKGROUND: Morphine reduces absorption and delays action onset of potent oral P2Y12 receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI). We sought to determine the differential effects of fentanyl compared to morphine on the pharmacodynamics and pharmacokinetics of ticagrelor in STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS: PERSEUS (NCT02531165) was a prospective, single-center, open-label, randomized controlled study. Patients with STEMI who required analgesia were randomly assigned in a 1:1 ratio to treatment with intravenous fentanyl or morphine after ticagrelor loading dose (LD) administration. The primary endpoint was platelet reactivity at 2 hours after ticagrelor LD assessed by P2Y12 reaction units (PRU). RESULTS: The study was prematurely stopped in June 2017 after enrolment of 38 out of 56 planned patients. PRU at 2 hours following ticagrelor LD was 173.3 ± 89.7 in the fentanyl group and 210.3 ± 76.4 in the morphine group (p = 0.179). At 4 hours, PRU was significantly lower among patients treated with fentanyl as compared to those treated with morphine (90.1 ± 97.4 vs. 168.0 ± 72.2; p = 0.011). Maximal plasma concentrations of ticagrelor and its active metabolite AR-C124910XX tended to be delayed and numerically lower among patients treated with morphine compared to fentanyl. Total exposures to ticagrelor and AR-C124910XX within 6 hours after ticagrelor LD were numerically greater among patients treated with fentanyl compared to those treated with morphine. CONCLUSIONS: In patients with STEMI undergoing primary PCI, fentanyl did not improve platelet inhibition at 2 hours after ticagrelor pre-treatment compared with morphine. Fentanyl may, however, accelerate ticagrelor absorption and increase platelet inhibition at 4 hours compared to morphine.

Magmaris Resorbable Magnesium Scaffold Versus Conventional Drug-Eluting Stent in ST-Segment Elevation Myocardial Infarction: 1-Year Results of a Propensity-Score-Matching Comparison.

Magmaris® (Biotronik AG, Switzerland) is the first RMS and early experience has shown promising results in stable coronary artery disease. Acute coronary syndromes have been hypothesized as a potential target group for bioresorbable scaffolds, but the efficacy and safety of RMS has not been extensively studied in ST-segment elevation myocardial infarction (STEMI). BEST-MAG is a prospective multicenter trial designed to evaluate optical coherence tomography (OCT-)guided implantation of resorbable magnesium scaffold (RMS) in STEMI. Consecutive STEMI patients fulfilling inclusion/exclusion criteria were treated with RMS following a standardized OCT-based implantation technique including systematic pre- and post-dilatation, and baseline plus final OCT imaging. The primary endpoint was a device oriented composite endpoint (DOCE) including cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR) within 12 months. Clinical outcomes were compared after propensity score matching (PSM) to the results of the randomized controlled BIOSTEMI trial comparing biodegradable polymer sirolimus eluting (BP-SES) and durable polymer everolimus eluting stents (DP-EES) in STEMI. Between 15th February 2019 and 25th May 2020, 30 patients were included in 5 centers. Procedural success was achieved in all cases based on OCT control with final scaffold expansion of 82 ± 11%. At twelve-months, DOCE rate was 13.3% (n = 4), including 4 cases of TLR (13.3%) and one case of TV-MI (3.3%). No cardiac death occurred, and no scaffold thrombosis (ScT) was observed. Using PSM, DOCE rates in BP-SES and DP-EES groups were 10% and 6% respectively and TLR rates were 3.3% and 0.0%. In this study, OCT-guided RMS implantation in selected STEMI patients appeared feasible but was associated with numerically higher rates of TLR as compared with conventional drug-eluting stents, although the limited number of patients included in this analysis does not allow drawing statistically significant conclusions.

Distal Versus Conventional Radial Access for Coronary Angiography and Intervention: The DISCO RADIAL Trial.

BACKGROUND: Currently, transradial access (TRA) is the recommended access for coronary procedures because of increased safety, with radial artery occlusion (RAO) being its most frequent complication, which will increasingly affect patients undergoing multiple procedures during their lifetimes. Recently, distal radial access (DRA) has emerged as a promising alternative access to minimize RAO risk. A large-scale, international, randomized trial comparing RAO with TRA and DRA is lacking. OBJECTIVES: The aim of this study was to assess the superiority of DRA compared with conventional TRA with respect to forearm RAO. METHODS: DISCO RADIAL (Distal vs Conventional Radial Access) was an international, multicenter, randomized controlled trial in which patients with indications for percutaneous coronary procedure using a 6-F Slender sheath were randomized to DRA or TRA with systematic implementation of best practices to reduce RAO. The primary endpoint was the incidence of forearm RAO assessed by vascular ultrasound at discharge. Secondary endpoints include crossover, hemostasis time, and access site-related complications. RESULTS: Overall, 657 patients underwent TRA, and 650 patients underwent DRA. Forearm RAO did not differ between groups (0.91% vs 0.31%; P = 0.29). Patent hemostasis was achieved in 94.4% of TRA patients. Crossover rates were higher with DRA (3.5% vs 7.4%; P = 0.002), and median hemostasis time was shorter (180 vs 153 minutes; P < 0.001). Radial artery spasm occurred more with DRA (2.7% vs 5.4%; P = 0.015). Overall bleeding events and vascular complications did not differ between groups. CONCLUSIONS: With the implementation of a rigorous hemostasis protocol, DRA and TRA have equally low RAO rates. DRA is associated with a higher crossover rate but a shorter hemostasis time.

Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial.

Importance: Coronary plaques that are prone to rupture and cause adverse cardiac events are characterized by large plaque burden, large lipid content, and thin fibrous caps. Statins can halt the progression of coronary atherosclerosis; however, the effect of the proprotein convertase subtilisin kexin type 9 inhibitor alirocumab added to statin therapy on plaque burden and composition remains largely unknown. Objective: To determine the effects of alirocumab on coronary atherosclerosis using serial multimodality intracoronary imaging in patients with acute myocardial infarction. Design, Setting, and Participants: The PACMAN-AMI double-blind, placebo-controlled, randomized clinical trial (enrollment: May 9, 2017, through October 7, 2020; final follow-up: October 13, 2021) enrolled 300 patients undergoing percutaneous coronary intervention for acute myocardial infarction at 9 academic European hospitals. Interventions: Patients were randomized to receive biweekly subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours after urgent percutaneous coronary intervention of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy (rosuvastatin, 20 mg). Main Outcomes and Measures: Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and optical coherence tomography were serially performed in the 2 non-infarct-related coronary arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-derived percent atheroma volume from baseline to week 52. Two powered secondary end points were changes in near-infrared spectroscopy-derived maximum lipid core burden index within 4 mm (higher values indicating greater lipid content) and optical coherence tomography-derived minimal fibrous cap thickness (smaller values indicating thin-capped, vulnerable plaques) from baseline to week 52. Results: Among 300 randomized patients (mean [SD] age, 58.5 [9.7] years; 56 [18.7%] women; mean [SD] low-density lipoprotein cholesterol level, 152.4 [33.8] mg/dL), 265 (88.3%) underwent serial IVUS imaging in 537 arteries. At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs -0.92% with placebo (difference, -1.21% [95% CI, -1.78% to -0.65%], P < .001). Mean change in maximum lipid core burden index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24 [95% CI, -70.71 to -11.77]; P = .006). Mean change in minimal fibrous cap thickness was 62.67 µm with alirocumab vs 33.19 µm with placebo (difference, 29.65 µm [95% CI, 11.75-47.55]; P = .001). Adverse events occurred in 70.7% of patients treated with alirocumab vs 72.8% of patients receiving placebo. Conclusions and Relevance: Among patients with acute myocardial infarction, the addition of subcutaneous biweekly alirocumab, compared with placebo, to high-intensity statin therapy resulted in significantly greater coronary plaque regression in non-infarct-related arteries after 52 weeks. Further research is needed to understand whether alirocumab improves clinical outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.