Scrutinizing the Role of Venoarterial Extracorporeal Membrane Oxygenation: Has Clinical Practice Outpaced the Evidence?

The use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for temporary mechanical circulatory support in various clinical scenarios has been increasing consistently, despite the lack of sufficient evidence regarding its benefit and safety from adequately powered randomized controlled trials. Although the ARREST trial (Advanced Reperfusion Strategies for Patients with Out-of-Hospital Cardiac Arrest and Refractory Ventricular Fibrillation) and a secondary analysis of the PRAGUE OHCA trial (Prague Out-of-Hospital Cardiac Arrest) provided some evidence in favor of VA-ECMO in the setting of out-of-hospital cardiac arrest, the INCEPTION trial (Early Initiation of Extracorporeal Life Support in Refractory Out-of-Hospital Cardiac Arrest) has not found a relevant improvement of short-term mortality with extracorporeal cardiopulmonary resuscitation. In addition, the results of the recently published ECLS-SHOCK trial (Extracorporeal Life Support in Cardiogenic Shock) and ECMO-CS trial (Extracorporeal Membrane Oxygenation in the Therapy of Cardiogenic Shock) discourage the routine use of VA-ECMO in patients with infarct-related cardiogenic shock. Ongoing clinical trials (ANCHOR [Assessment of ECMO in Acute Myocardial Infarction Cardiogenic Shock, NCT04184635], REVERSE [Impella CP With VA ECMO for Cardiogenic Shock, NCT03431467], UNLOAD ECMO [Left Ventricular Unloading to Improve Outcome in Cardiogenic Shock Patients on VA-ECMO, NCT05577195], PIONEER [Hemodynamic Support With ECMO and IABP in Elective Complex High-risk PCI, NCT04045873]) may clarify the usefulness of VA-ECMO in specific patient subpopulations and the efficacy of combined mechanical circulatory support strategies. Pending further data to refine patient selection and management recommendations for VA-ECMO, it remains uncertain whether the present usage of this device improves outcomes.

Sex Differences in 10-Year Outcomes After Percutaneous Coronary Intervention With Drug-Eluting Stents: Insights From the DECADE Cooperation.

BACKGROUND: Although some studies have investigated sex-related outcomes up to 5 years after percutaneous coronary intervention (PCI), analyses at longer follow-up (ie, to 10 years) in large cohorts treated exclusively with drug-eluting stent (DES) platforms are lacking. Therefore, this study aimed to define whether sex-related differences in long-term outcomes after PCI persist both in the DES era and at longer-term follow-up. METHODS: Individual data of patients treated with DES in 5 randomized controlled trials with 10-year follow-up were pooled. Patients were divided into 2 groups by sex. The analysis of individual participant data was performed using a 1-stage approach by entering a clustering effect by parent study in all univariable and multivariable models focusing on sex. The main outcomes of interest for this analysis included cardiovascular death, myocardial infarction, repeat revascularization, and definite stent thrombosis to 10 years after PCI. Survival was analyzed by the Kaplan-Meier method to estimate the time to first event, and differences between the 2 groups were tested with the log-rank test. Hazard ratios (HRs) and 95% CIs were calculated with a Cox proportional hazards model. Conventional multivariable analyses with adjustment for relevant variables were performed. RESULTS: Among 9700 patients undergoing PCI with DES implantation included in the present analysis, 2296 were women and 7404 were men. Through to 10 years, cardiovascular death occurred in 407 of the 2296 female patients and 1012 of the 7404 male patients (adjusted HR [HRadj], 0.94 [95% CI, 0.80-1.11]). Female sex was associated with a lower risk of repeat revascularization of the target lesion (HRadj, 0.80 [95% CI, 0.74-0.87]), target vessel (HRadj, 0.81 [95% CI, 0.76-0.87]), and nontarget vessels (HRadj, 0.69 [95% CI, 0.62-0.77]). Compared with male patients, female patients displayed an increased risk of myocardial infarction in the first 30 days after PCI with DES (HRadj, 1.65 [95% CI, 1.24-2.19]) but a comparable risk of myocardial infarction thereafter. The risk of definite stent thrombosis was not significantly different between female and male patients (HRadj, 1.14 [95% CI, 0.89-1.47]). CONCLUSIONS: Through to 10-year follow-up after PCI with DES, female patients are at increased risk of early myocardial infarction, receive fewer repeat revascularizations, and have no difference in cardiovascular mortality compared with male patients.

Venoarterial extracorporeal membrane oxygenation in patients with infarct-related cardiogenic shock: an individual patient data meta-analysis of randomised trials.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used in patients with cardiogenic shock despite the lack of evidence from adequately powered randomised clinical trials. Three trials reported so far were underpowered to detect a survival benefit; we therefore conducted an individual patient-based meta-analysis to assess the effect of VA-ECMO on 30-day death rate. METHODS: Randomised clinical trials comparing early routine use of VA-ECMO versus optimal medical therapy alone in patients presenting with infarct-related cardiogenic shock were identified by searching MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and trial registries until June 12, 2023. Trials were included if at least all-cause death rate 30 days after in-hospital randomisation was reported and trial investigators agreed to collaborate (ie, providing individual patient data). Odds ratios (ORs) as primary outcome measure were pooled using logistic regression models. This study is registered with PROSPERO (CRD42023431258). FINDINGS: Four trials (n=567 patients; 284 VA-ECMO, 283 control) were identified and included. Overall, there was no significant reduction of 30-day death rate with the early use of VA-ECMO (OR 0·93; 95% CI 0·66-1·29). Complication rates were higher with VA-ECMO for major bleeding (OR 2·44; 95% CI 1·55-3·84) and peripheral ischaemic vascular complications (OR 3·53; 95% CI 1·70-7·34). Prespecified subgroup analyses were consistent and did not show any benefit for VA-ECMO (pinteraction ≥0·079). INTERPRETATION: VA-ECMO did not reduce 30-day death rate compared with medical therapy alone in patients with infarct-related cardiogenic shock, and an increase in major bleeding and vascular complications was observed. A careful review of the indication for VA-ECMO in this setting is warranted. FUNDING: Foundation Institut für Herzinfarktforschung.

Immediate versus staged complete revascularisation in patients presenting with acute coronary syndrome and multivessel coronary disease (BIOVASC): a prospective, open-label, non-inferiority, randomised trial.

BACKGROUND: In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged. METHODS: This prospective, open-label, non-inferiority, randomised trial was done at 29 hospitals across Belgium, Italy, the Netherlands, and Spain. We included patients aged 18-85 years presenting with ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndrome and multivessel (ie, two or more coronary arteries with a diameter of 2·5 mm or more and ≥70% stenosis based on visual estimation or positive coronary physiology testing) coronary artery disease with a clearly identifiable culprit lesion. A web-based randomisation module was used to randomly assign patients (1:1), with a random block size of four to eight, stratified by study centre, to undergo immediate complete revascularisation (PCI of the culprit lesion first, followed by other non-culprit lesions deemed to be clinically significant by the operator during the index procedure) or staged complete revascularisation (PCI of only the culprit lesion during the index procedure and PCI of all non-culprit lesions deemed to be clinically significant by the operator within 6 weeks after the index procedure). The primary outcome was the composite of all-cause mortality, myocardial infarction, any unplanned ischaemia-driven revascularisation, or cerebrovascular events at 1 year after the index procedure. Secondary outcomes included all-cause mortality, myocardial infarction, and unplanned ischaemia-driven revascularisation at 1 year after the index procedure. Primary and secondary outcomes were assessed in all randomly assigned patients by intention to treat. Non-inferiority of immediate to staged complete revascularisation was considered to be met if the upper boundary of the 95% CI of the hazard ratio (HR) for the primary outcome did not exceed 1·39. This trial is registered with ClinicalTrials.gov, NCT03621501. FINDINGS: Between June 26, 2018, and Oct 21, 2021, 764 patients (median age 65·7 years [IQR 57·2-72·9] and 598 [78·3%] males) were randomly assigned to the immediate complete revascularisation group and 761 patients (median age 65·3 years [58·6-72·9] and 589 [77·4%] males) were randomly assigned to the staged complete revascularisation group, and were included in the intention-to-treat population. The primary outcome at 1 year occurred in 57 (7·6%) of 764 patients in the immediate complete revascularisation group and in 71 (9·4%) of 761 patients in the staged complete revascularisation group (HR 0·78, 95% CI 0·55-1·11, pnon-inferiority=0·0011). There was no difference in all-cause death between the immediate and staged complete revascularisation groups (14 [1·9%] vs nine [1·2%]; HR 1·56, 95% CI 0·68-3·61, p=0·30). Myocardial infarction occurred in 14 (1·9%) patients in the immediate complete revascularisation group and in 34 (4·5%) patients in the staged complete revascularisation group (HR 0·41, 95% CI 0·22-0·76, p=0·0045). More unplanned ischaemia-driven revascularisations were performed in the staged complete revascularisation group than in the immediate complete revascularisation group (50 [6·7%] patients vs 31 [4·2%] patients; HR 0·61, 95% CI 0·39-0·95, p=0·030). INTERPRETATION: In patients presenting with acute coronary syndrome and multivessel disease, immediate complete revascularisation was non-inferior to staged complete revascularisation for the primary composite outcome and was associated with a reduction in myocardial infarction and unplanned ischaemia-driven revascularisation. FUNDING: Erasmus University Medical Center and Biotronik.

Sex-associated differences in cardiac ageing: Clinical aspects and molecular mechanisms.

Despite the extensive clinical and scientific advances in prevention, diagnostics and treatment, cardiovascular diseases (CVD) remain the leading cause of morbidity and mortality worldwide for people aged 65 and over. Of all ageing-related diseases, CVD are responsible for almost one-third of deaths in the elderly, being above all cancers combined. Age is an independent and unavoidable risk factor contributing to the impairment of heart and blood vessels. As the average age of the population in industrialized countries has doubled in the last century, and almost a fifth of the world's population is predicted to be over 65 in the next decade, we can assume that the burden of CVD will fall primarily on the elderly. Evidence from basic and clinical science has shown that sex significantly influences the onset and severity of CVD. In women, CVD usually develop later than in men and with atypical symptomatology. After menopause, however, the incidence and severity of CVD increase in women, reaching equality in both sexes. Although intrinsic sexual dimorphism in cardiovascular ageing may contribute to the sex differences in CVD progression, the molecular mechanisms associated with cardiovascular ageing and their clinical value are not known in detail. In this review, we discuss the scientific knowledge available, focusing on structural, hormonal, genetic/epigenetic and inflammatory pathways, seeking to transfer these findings to the cardiovascular clinic in terms of prevention, diagnosis, prognosis and management of these pathologies and proposing possible validation of target specifics.

Ten-year clinical outcomes after drug-eluting stents implantation according to clinical presentation-Insights from the DECADE cooperation.

BACKGROUND: Investigations of very long-term outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) according to clinical presentation are scarce. Here, we investigated the 10-year clinical outcomes of patients undergoing DES-PCI according to clinical presentation. METHODS: Patient-level data from five randomized trials with 10-year follow-up after DES-PCI were pooled. Patients were dichotomized into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) groups as per clinical presentation. The primary outcome was all-cause death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST) and repeat revascularization involving the target lesion (TLR), target vessel (TVR) or non-target vessel (nTVR). RESULTS: Of the 9700 patients included in this analysis, 4557 presented with ACS and 5143 with CCS. Compared with CCS patients, ACS patients had a higher risk of all-cause death and nTVR in the first year, but comparable risk thereafter. In addition, ACS patients had a higher risk of MI [adjusted hazard ratio 1.21, 95% confidence interval (1.04-1.41)] and definite ST [adjusted hazard ratio 1.48, 95% confidence interval (1.14-1.92)], while the risk of TLR and TVR was not significantly different up to 10-year follow-up. CONCLUSIONS: Compared to CCS patients, ACS patients treated with PCI and DES implantation have an increased risk of all-cause death and repeat revascularization of remote vessels up to 1 year, with no significant differences thereafter and up to 10-year follow-up. ACS patients have a consistently higher risk of MI and definite ST. Whether these differences persist with current antithrombotic and secondary prevention therapies requires further investigation.

Rationale and design of the artificial intelligence scalable solution for acute myocardial infarction (ASSIST) study.

BACKGROUND: Acute coronary syndrome (ACS), specifically ST-segment elevation myocardial infarction is a major cause of morbidity and mortality throughout Europe. Diagnosis in the acute setting is mainly based on clinical symptoms and physician's interpretation of an electrocardiogram (ECG), which may be subject to errors. ST-segment elevation is the leading criteria to activate urgent reperfusion therapy, but a clear ST-elevation pattern might not be present in patients with coronary occlusion and ST-segment elevation might be seen in patients with normal coronary arteries. METHODS: The ASSIST project is a retrospective observational study aiming to improve the ECG-assisted assessment of ACS patients in the acute setting by incorporating an artificial intelligence platform, Willem™ to analyze 12­lead ECGs. Our aim is to improve diagnostic accuracy and reduce treatment delays. ECG and clinical data collected during this study will enable the optimization and validation of Willem™. A retrospective multicenter study will collect ECG, clinical, and coronary angiography data from 10,309 patients. The primary outcome is the performance of this tool in the correct identification of acute myocardial infarction with coronary artery occlusion. Model performance will be evaluated internally with patients recruited in this retrospective study while external validation will be performed in a second stage. CONCLUSION: ASSIST will provide key data to optimize Willem™ platform to detect myocardial infarction based on ECG-assessment alone. Our hypothesis is that such a diagnostic approach may reduce time delays, enhance diagnostic accuracy, and improve clinical outcomes.

Fractional flow reserve or 3D-quantitative-coronary-angiography based vessel-FFR guided revascularization. Rationale and study design of the prospective randomized fast III trial.

BACKGROUND: Physiological assessment of intermediate coronary lesions to guide coronary revascularization is currently recommended by international guidelines. Vessel fractional flow reserve (vFFR) has emerged as a new approach to derive fractional flow reserve (FFR) from 3D-quantitative coronary angiography (3D-QCA) without the need for hyperemic agents or pressure wires. STUDY DESIGN AND OBJECTIVES: The FAST III is an investigator-initiated, open label, multicenter randomized trial comparing vFFR guided versus FFR guided coronary revascularization in approximately 2228 patients with intermediate coronary lesions (defined as 30%-80% stenosis by visual assessment or QCA). Intermediate lesions are physiologically assessed using on-line vFFR or FFR and treated if vFFR or FFR ≤0.80. The primary end point is a composite of all-cause death, any myocardial infarction, or any revascularization at 1-year post-randomization. Secondary end points include the individual components of the primary end point and cost-effectiveness will be investigated. CONCLUSIONS: FAST III is the first randomized trial to explore whether a vFFR guided revascularization strategy is non-inferior to an FFR guided strategy in terms of clinical outcomes at 1-year follow-up in patients with intermediate coronary artery lesions.

Relationship between stent length and very long-term target lesion failure following percutaneous coronary intervention for ST-elevation myocardial infarction in the drug-eluting stents era: insights from the EXAMINATION-EXTEND study.

BACKGROUND: Little data exist on the relationship between total stent length (TSL) and cardiovascular outcomes at very-long follow-up in patients with ST-elevation myocardial infarction (STEMI) in the 2nd generation drug-eluting stents (DES) era. AIM: To analyze the relationship between TSL and 10-year target-lesion failure (TLF) in STEMI patients treated with percutaneous coronary intervention enrolled in the EXAMINATION-EXTEND. METHODS: The EXAMINATION-EXTEND was an extended-follow-up study of the EXAMINATION trial, which randomized 1:1 STEMI patients to receive DES or bare metal stent (BMS). The primary endpoint was TLF, defined as a composite of target lesion revascularization (TLR), target vessel myocardial infarction (TVMI), or definite/probable stent thrombosis (ST). Relationship between stent length and TLF was evaluated in the whole study group in a multiple-adjusted Cox regression model with TSL as a quantitative variable. Subgroup analysis was also performed according to stent type, diameter, and overlap. RESULTS: A total of 1,489 patients with a median TSL of 23 mm (Q1-Q318-35 mm) were included. TSL was associated with TLF at 10 years (adjusted HR per 5 mm increase of 1.07; 95% CI, 1.01-1.14; P = .02). This effect was mainly driven by TLR and was consistent regardless of stent type, diameter, or overlap. There was no significant relationship between TSL and TV-MI or ST. CONCLUSIONS: In STEMI patients, there is a direct relationship between TSL implanted in the culprit vessel and the risk of TLF at 10 years, mainly driven by TLR. The use of DES did not modify this association.

Amphilimus- vs. zotarolimus-eluting stents in patients with diabetes mellitus and coronary artery disease: the SUGAR trial.

AIM: Patients with diabetes mellitus are at high risk of adverse events after percutaneous revascularization, with no differences in outcomes between most contemporary drug-eluting stents. The Cre8 EVO stent releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, and has shown clinical benefits in diabetes. We aimed to compare Cre8 EVO stents to Resolute Onyx stents (a contemporary polymer-based zotarolimus-eluting stent) in patients with diabetes. METHODS AND RESULTS: We did an investigator-initiated, randomized, controlled, assessor-blinded trial at 23 sites in Spain. Eligible patients had diabetes and required percutaneous coronary intervention. A total of 1175 patients were randomly assigned (1:1) to receive Cre8 EVO or Resolute Onyx stents. The primary endpoint was target-lesion failure, defined as a composite of cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularization at 1-year follow-up. The trial had a non-inferiority design with a 4% margin for the primary endpoint. A superiority analysis was planned if non-inferiority was confirmed. There were 106 primary events, 42 (7.2%) in the Cre8 EVO group and 64 (10.9%) in the Resolute Onyx group [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.44-0.96; Pnon-inferiority < 0.001; Psuperiority = 0.030]. Among the secondary endpoints, Cre8 EVO stents had significantly lower rate than Resolute Onyx stents of target-vessel failure (7.5% vs. 11.1%, HR: 0.67, 95% CI: 0.46-0.99; P = 0.042). Probable or definite stent thrombosis and all-cause death were not significantly different between groups. CONCLUSION: In patients with diabetes, Cre8 EVO stents were non-inferior to Resolute Onyx stents with regard to target-lesion failure composite outcome. An exploratory analysis for superiority at 1 year suggests that the Cre8 EVO stents might be superior to Resolute Onyx stents with regard to the same outcome. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT03321032.

Five-year outcomes after state-of-the-art percutaneous coronary revascularization in patients with de novo three-vessel disease: final results of the SYNTAX II study.

AIMS: The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial. METHODS AND RESULTS: SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P < 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P < 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P < 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P < 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P < 0.001). Major adverse cardiac and cerebrovascular events' outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35). CONCLUSIONS: Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.

Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease.

BACKGROUND: Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established. METHODS: We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction. RESULTS: At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], -0.9 to 6.5; P = 0.13). Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1). In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, -1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, -1.3 to 4.2) were not significantly different. All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, -1.9 percentage points; 95% CI, -3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, -0.8 percentage points; 95% CI, -2.4 to 0.9). Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0). CONCLUSIONS: In patients with left main coronary artery disease of low or intermediate anatomical complexity, there was no significant difference between PCI and CABG with respect to the rate of the composite outcome of death, stroke, or myocardial infarction at 5 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776.).

Angiography-derived physiology guidance vs usual care in an All-comers PCI population treated with the healing-targeted supreme stent and Ticagrelor monotherapy: PIONEER IV trial design.

BACKGROUND: Current ESC guidelines recommend the use of intra-coronary pressure guidewires for functional assessment of intermediate-grade coronary stenoses. Angiography-derived quantitative flow ratio (QFR) is a novel method of assessing these stenoses, and guiding percutaneous coronary intervention (PCI). METHODS/DESIGN: The PIONEER IV trial is a prospective, all-comers, multi-center trial, which will randomize 2,540 patients in a 1:1 ratio to PCI guided by angiography-derived physiology or usual care, with unrestricted use in both arms of the Healing-Targeted Supreme sirolimus-eluting stent (HT Supreme). The stent's fast, biologically healthy, and robust endothelial coverage allows for short dual-antiplatelet therapy (DAPT); hence the antiplatelet regimen of choice is 1-month DAPT, followed by ticagrelor monotherapy. In the angiography-derived physiology guided arm, lesions will be functionally assessed using on-line QFR, with stenting indicated in lesions with a QFR ≤0.80. Post-stenting, QFR will be repeated in the stented vessel(s), with post-dilatation or additional stenting recommended if the QFR<0.91 distal to the stent, or if the delta QFR (across the stent) is >0.05. Usual care PCI is performed according to standard clinical practice. The primary endpoint is a non-inferiority comparison of the patient-oriented composite endpoint (POCE) of all-cause death, any stroke, any myocardial infarction, or any clinically, and physiologically driven revascularization with a non-inferiority risk-difference margin of 3.2%, at 1-year post-procedure. Clinical follow-up will be up to 3 years. SUMMARY: The PIONEER IV trial aims to demonstrate non-inferiority of QFR-guided PCI to usual care PCI with respect to POCE at 1-year in patients treated with HT Supreme stents and ticagrelor monotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov UNIQUE IDENTIFIER: NCT04923191 CLASSIFICATIONS: Interventional Cardiology.

Vascular Injury After Stenting　- Insights of Systemic Mechanisms of Vascular Repair.

BACKGROUND: The role of circulating progenitor cells (CPC) in vascular repair following everolimus-eluting stent (EES) implantation is largely unknown. The aim of the study was to investigate the relationship between temporal variation in CPC levels following EES implantation and the degree of peri-procedural vascular damage, and stent healing, as measured by optical coherence tomography (OCT).Methods and Results: CPC populations (CD133+/KDR+/CD45low) included patients with stable coronary artery disease undergoing stent implantation, and were evaluated using a flow cytometry technique both at baseline and at 1 week. OCT evaluation was performed immediately post-implantation to quantify the stent-related injury and at a 9-month follow up to assess the mid-term vascular response. Twenty patients (mean age 66±9 years; 80% male) with EES-treated stenoses (n=24) were included in this study. Vascular injury score was associated with the 1-week increase of CD133+/KDR+/CD45low (ß 0.28 [95% CI 0.15; 0.41]; P<0.001) and with maximum neointimal thickness at a 9-month follow up (ß 0.008 [95% CI 0.0004; 0.002]; P=0.04). Inverse relationships between numbers of uncoated and apposed struts for the 9-month and the 1-week delta values of CD133+/KDR+/CD45low (ß -12.53 [95% CI -22.17; -2.90]; P=0.011), were also found. CONCLUSIONS: The extent of vessel wall injury influences early changes in the levels of CPC and had an effect on mid-term vascular healing after EES implantation. Early CPC mobilisation was associated with mid-term strut coverage.

Spontaneous Coronary Artery Dissection: Rediscovering an Old Cause of Myocardial Infarction.

Spontaneous coronary artery dissection is an uncommon, but not insignificant cause of acute coronary syndrome that overwhelmingly affects middle-aged women. The pathophysiology of coronary dissection appears to be an outside-in mechanism, where the initiating event is not an intimal tear but rather the formation of an intramural hematoma, which compromises blood flow by reducing the arterial lumen. Considering this mechanism, it is clear to see how intracoronary imaging techniques, such as optical coherence tomography and intravascular ultrasound, are most accurate in the diagnosis. However, they carry a high rate of complications and are therefore generally avoided when the clinical scenario and angiographic appearance both support the diagnosis of spontaneous coronary artery dissection. The natural history of the disease is toward healing of the vessel wall and restoration of blood flow. Therefore, conservative medical management is the preferred approach unless there are high-risk factors such as hemodynamic instability, signs of ischemia and severe proximal or multivessel lesions, in which percutaneous or surgical revascularization should be considered. Perioperative evaluation of these patients must take into account several aspects of this disease. Most of these patients will be receiving single or dual antiplatelet therapy, so one must consider the timing of the event and the surgical hemorrhagic risk when deciding to stop these therapies. Extracoronary vascular disease also must be assessed because it can have an effect on patient monitoring and risk of postoperative complications.

A case-control, multicentre study of consecutive patients with COVID-19 and acute (myo)pericarditis: incidence, risk factors, clinical characteristics and outcomes.

OBJECTIVE: To estimate incidence, risk factors, clinical characteristics and outcomes of acute (myo)pericarditis (AMP) in patients with COVID-19. METHODS: Case-control, retrospective review, consecutive case inclusion performed in 62 Spanish EDs. All COVID-19 patients with AMP (cases) were compared in clinical characteristics and outcomes with COVID-19 without AMP (control group A) and non-COVID patients with AMP (control group B). We estimated unadjusted standardised incidence (SI, not adjusted by population's age/sex) of AMP in COVID-19 and non-COVID populations (per 100 000/year). RESULTS: We identified 67 AMP in COVID-19 patients (SI=56.5, OR with respect to non-COVID patients=4.43, 95% CI=3.98 to 4.94). Remarkably, COVID-19 cases presented with chest pain less frequently than non-COVID patients and had less typical ECG changes, higher NT-proBNP (N-terminal prohormone of brain natriuretic peptide), more left and right ventricular dysfunction in echocardiography and more need of inotropic/vasopressor drugs. Admission to intensive care was higher than control group A (OR=3.22, 95% CI=1.43 to 7.23), and in-hospital mortality was higher than control group B (OR=7.75, 95% CI=2.77 to 21.7). CONCLUSION: AMP is unusual as a form of COVID-19 presentation (about 1‰ cases), but SI is more than fourfold higher than non-COVID population, and it is less symptomatic, more severe and has higher in-hospital mortality; therefore, rapid recognition, echocardiographic assessment of myopericardial inflammation/dysfunction and treatment with vasoactive drugs when needed are recommended in AMP in patients with COVID-19.

Survival benefit of revascularization versus optimal medical therapy alone for chronic total occlusion management in patients with diabetes.

BACKGROUND: Chronic total occlusion (CTO) is common in patients with diabetes mellitus. Data on the long-term outcomes after treatment of CTOs in this high-risk population are scarce. AIM: To compare the long-term clinical outcomes of CTO revascularization either by coronary artery bypass graft (CABG) or successful percutaneous coronary intervention (PCI) versus optimal medical treatment (MT) alone in patients with diabetes. METHODS AND RESULTS: A total of 538 consecutive patients with diabetes and at least one CTO were identified from 2010 to 2014 in our center. In the present analysis, patients were stratified according to the CTO treatment strategy that was selected. MT was selected in 61% of patients whereas revascularization in the remaining 39%. Patients undergoing revascularization were younger, had higher left ventricular ejection fraction (LVEF), lower ACEF score, and more positive myocardial ischemia detection results compared to the MT group (p < .001).Patients referred for CABG had higher rates of left main disease compared to the PCI and MT groups (32% vs. 3% and 11%, respectively; p < .001). Complete revascularization was more often achieved in the CABG group, compared to the PCI group (62% vs. 32% p < .001). Multivariable analysis showed that revascularization with CABG was associated with lower rates of all-cause and cardiac mortality rates compared to MT, [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.70, p < .001 and HR 0.40, 95% CI 0.20-81, p = .011, respectively]. Successful CTO-PCI showed a trend towards benefit in all-cause mortality (HR 0.58, 95% CI 0.33-1.04, p = .06). CONCLUSION: In our registry, CTO revascularization in diabetic patients, especially with CABG, was associated with lower long-term mortality rates as compared to MT alone.

Antithrombotic regimens for percutaneous coronary intervention of the left main coronary artery: The EXCEL trial.

OBJECTIVES: We compared the effect of bivalirudin or heparin and use or nonuse of glycoprotein IIb/IIIa inhibitors (GPI) on the outcome of left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the randomized EXCEL trial. BACKGROUND: The optimal antithrombotic regimen to support PCI of the LMCA remains controversial because of low representation of this subset in clinical trials. METHODS: The PCI cohort (n = 928) in EXCEL was divided according to bivalirudin versus heparin antithrombin treatment and compared for the primary composite endpoint of death, myocardial infarction (MI), or stroke at 30 days and 5 years. RESULTS: Bivalirudin was used in 319 patients (34.4%). The composite endpoint at 30 days occurred in 7.2% versus 3.8% bivalirudin and heparin patients, respectively, p = .02; at 5 years, the composite endpoint occurred in 26.3% versus 19.9% bivalirudin and heparin patients, respectively, p = .02. Major bleeding was more frequent in bivalirudin patients (4.1% versus 1.3%, p = .008). There were no differences in stent thrombosis between the groups. Bivalirudin use was an independent predictor of the 30-day composite endpoint (OR 2.88, 95% CI 1.28-6.48, p = .01) but not of the 5-year composite endpoint (OR 1.30, 95% CI 0.84-2.02, p = .23). GPI use was infrequent (n = 67, 7.2%) and was not associated with adverse outcomes. CONCLUSION: Among patients undergoing LMCA PCI in the EXCEL trial, procedural use of bivalirudin was associated with greater rates of periprocedural MI and the 30-day composite endpoint without reducing bleeding complications. Five-year outcomes were similar. GPIs were used infrequently and were not associated with clinical outcomes.

Two-year outcomes after percutaneous coronary intervention with drug-eluting stents or bare-metal stents in elderly patients with coronary artery disease.

OBJECTIVES: Report the results at 2 years of the patients included in the SENIOR trial. BACKGROUND: Patients above 75 years of age represent a fast-growing population in the cathlab. In the SENIOR trial, patients treated by percutaneous coronary intervention (PCI) with drug eluting stent (DES) and a short duration of P2Y12 inhibitor (1 and 6 months for stable and unstable coronary syndromes, respectively) compared with bare metal stents (BMS) was associated with a 29% reduction in the rate of all-cause mortality, myocardial infarction (MI), stroke, and ischaemia-driven target lesion revascularization (ID-TLR) at 1 year. The results at 2 years are reported here. METHODS AND RESULTS: We randomly assigned 1,200 patients (596[50%] to the DES group and 604[50%] to the BMS group). At 2 years, the composite endpoint of all-cause mortality, MI, stroke and ID-TLR had occurred in 116 (20%) patients in the DES group and 131 (22%) patients in the BMS group (RR 0.90 [95%CI 0.72-1.13], p = .37). IDTLR occurred in 14 (2%) patients in the DES group and 41 (7%) patients in the BMS group (RR 0.35 [95%CI 0.16-0.60], p = .0002). Major bleedings (BARC 3-5) occurred in 27(5%) patients in both groups (RR 1.00, [95%CI 0.58-1.75], p = .99). Stent thrombosis rates were low and similar between DES and BMS (0.8 vs 1.3%, (RR 0.52 [95%CI 0.01-1.95], p = .27). CONCLUSION: Among elderly PCI patients, a strategy combining a DES together with a short duration of DAPT is associated with a reduction in revascularization up to 2 years compared with BMS with very few late events and without any increased in bleeding complications or stent thrombosis.