A New Frontier for Drug-Coated Balloons: Treatment of "De Novo" Stenosis in Large Vessel Coronary Artery Disease.

Background: Drug-coated balloons (DCB) are a well-established option for treating in-stent restenosis endorsed by European Guidelines on myocardial revascularization. However, in recent years, a strategy of "leaving nothing behind" with DCB in de novo coronary stenosis has emerged as an appealing approach. Methods: We performed a systematic review to evaluate the current literature on the use of drug-coated balloons in the treatment of de novo stenosis in large vessel disease. Results: Observational studies, as well as randomized studies, demonstrated the safety of DCB percutaneous coronary interventions (PCI) in large vessel disease. The rate of major adverse cardiac events is even lower compared to drug-eluting stents in stable coronary artery disease. Conclusions: DCB PCI is feasible in large vessel disease, and future large, randomized studies are ongoing to confirm these results.

Long term clinical outcome of sirolimus drug coated balloons in large coronary vessels.

BACKGROUND: Studies evaluating the safety and efficacy of drug coating balloons (DCB) for the treatment of lesions in large coronary vessel are limited. AIMS: Our study aimed to evaluate the performance of a sirolimus DCB in large coronary arteries. METHODS: We analyzed all the procedures included in the EASTBOURNE Registry (NCT03085823) enrolling patients with a clinical indication to percutaneous coronary intervention performed by a sirolimus DCB according to investigator judgment. In the present analysis, a cut-off of 2.75 mm was used to define large coronary arteries. Primary endpoint of the study was clinically driven target lesion revascularization (TLR) at 24 months whereas secondary endpoint included procedural success, myocardial infarction (MI), cardiac death and total mortality. RESULTS: Among the 2123 patients and 2440 lesions enrolled in the EASTBOURNE study between 2016 and 2020, 757 patients/810 lesions fulfilled the criteria for the present analysis. Mean reference vessel diameter was 3.2 ± 0.3 mm with mean lesion length of 22 ± 7 mm. Procedural success was high (96%) and at 2-year follow up the device showed a good efficacy with a TLR rate of 9%. There were 34 deaths (4.5%), 30 MIs (4%) and 8 BARC type 3-5 bleedings (1.1%). In-stent restenosis (629 lesions) and de novo lesions (181) were associated with 11% and 4% rates of TLR at 2 years, respectively (p = 0.003). CONCLUSIONS: Clinical performance of a sirolimus DCB in large coronary artery vessels shows promising signals at 2-year follow up, both in de novo and in-stent restenosis lesions.

Abbreviated or Standard Dual Antiplatelet Therapy by Sex in Patients at High Bleeding Risk: A Prespecified Secondary Analysis of a Randomized Clinical Trial.

Importance: Abbreviated dual antiplatelet therapy (DAPT) reduces bleeding with no increase in ischemic events in patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI). Objectives: To evaluate the association of sex with the comparative effectiveness of abbreviated vs standard DAPT in patients with HBR. Design, Setting, and Patients: This prespecified subgroup comparative effectiveness analysis followed the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated vs Standard DAPT Regimen (MASTER DAPT) trial, a multicenter, randomized, open-label clinical trial conducted at 140 sites in 30 countries and performed from February 28, 2017, to December 5, 2019. A total of 4579 patients with HBR were randomized at 1 month after PCI to abbreviated or standard DAPT. Data were analyzed from July 1 to October 31, 2022. Interventions: Abbreviated (immediate DAPT discontinuation, followed by single APT for ≥6 months) or standard (DAPT for ≥2 additional months, followed by single APT for 11 months) treatment groups. Main Outcomes and Measures: One-year net adverse clinical events (NACEs) (a composite of death due to any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (MACCEs) (a composite of death due to any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding (MCB). Results: Of the 4579 patients included in the analysis, 1408 (30.7%) were women and 3171 (69.3%) were men (mean [SD] age, 76.0 [8.7] years). Ischemic and bleeding events were similar between sexes. Abbreviated DAPT was associated with comparable NACE rates in men (hazard ratio [HR], 0.97 [95% CI, 0.75-1.24]) and women (HR, 0.87 [95% CI, 0.60-1.26]; P = .65 for interaction). There was evidence of heterogeneity of treatment effect by sex for MACCEs, with a trend toward benefit in women (HR, 0.68 [95% CI, 0.44-1.05]) but not in men (HR, 1.17 [95% CI, 0.88-1.55]; P = .04 for interaction). There was no significant interaction for MCB across sex, although the benefit with abbreviated DAPT was relatively greater in men (HR, 0.65 [95% CI, 0.50-0.84]) than in women (HR, 0.77 [95% CI, 0.53-1.12]; P = .46 for interaction). Results remained consistent in patients with acute coronary syndrome and/or complex PCI. Conclusions and Relevance: These findings suggest that women with HBR did not experience higher rates of ischemic or bleeding events compared with men and may derive particular benefit from abbreviated compared with standard DAPT owing to these numerically lower rates of events. Trial Registration: ClinicalTrials.gov Identifier: NCT03023020.

Sirolimus-Coated Balloon in an All-Comer Population of Coronary Artery Disease Patients: The EASTBOURNE Prospective Registry.

BACKGROUND: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications. OBJECTIVES: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease. METHODS: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee. RESULTS: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881). CONCLUSIONS: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

Sport in ischemic heart disease: Focus on primary and secondary prevention.

Ischemic heart disease (IHD) is one of the leading causes of death and morbidity in the world. The role of primary prevention is particularly relevant since IHD can be for a long time asymptomatic until the occurrence of a condition that could lead to plaque instabilization or increased oxygen demand. Secondary prevention is also essential to improve patients' prognosis and quality of life. The aim of this review is to provide a detailed and updated description of the role of sport and physical activity both in primary prevention and secondary prevention. In primary prevention, sport and physical activity are effective through the control of the main cardiovascular risk factors, such as hypertension and dyslipidemia. In secondary prevention, sport and physical activity can lead to a reduction in subsequent coronary events. Every effort must be made to encourage the performance of physical and sports activity both in asymptomatic subjects at risk and those with a history of IHD.

Design of the PERSEO Registry on the management of patients treated with oral anticoagulants and coronary stent.

AIM: Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting. METHODS: The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up. CONCLUSION: The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

Sirolimus-coated balloon versus everolimus-eluting stent in de novo coronary artery disease: Rationale and design of the TRANSFORM II randomized clinical trial.

BACKGROUND: Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation is a widely adopted strategy for the treatment of de novo coronary artery disease. DES implantation conveys an inherent risk for short- and long-term complications, including in-stent restenosis and stent thrombosis. Drug-coated balloons are emerging as an alternative approach to fulfill the "leaving nothing behind" principle and avoid long-term DES-related complications. DESIGN: TRANSFORM II is an investigator-initiated, multicenter, noninferiority, randomized clinical trial, testing a sirolimus-coated balloon (SCB) versus the standard of care for native coronary vessels with a 2-3 mm diameter, in terms of 12-month target lesion failure (TLF; primary endpoint) and net adverse cardiovascular events (coprimary endpoint). Patients undergoing PCI will be randomized to be treated with either SCB or new-generation everolimus-eluting stent and will be followed up clinically for up to 60 months. Assuming a TLF rate of 8% at 12 months with DES, a sample size of 1325 patients was chosen to ensure an 80% power to detect a 1.5% lower incidence in the SCB group with a type I error rate of 0.05. The TRANSFORM II trial is registered on clinicaltrials.gov (identification number NCT04893291). Several substudies, including an optical coherence tomography assessment at 9 months (intracoronary imaging substudy), will investigate the study device in different clinical and lesion settings. CONCLUSIONS: The randomized TRANSFORM II trial will determine whether a novel SCB is noninferior to a current everolimus-eluting stent when adopted for the treatment of de novo lesions in coronary vessels with a diameter between 2 and 3 mm.

ANMCO position paper on antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

In-hospital antithrombotic therapy and outcomes of elderly patients on warfarin undergoing percutaneous coronary intervention: Insights from the WAR-STENT registry.

In the patients on warfarin undergoing percutaneous coronary intervention included in the prospective, multicentre, observational WAR-STENT registry, age ≥75 years was associated with a significant increase in in-hospital major bleeding, length of hospitalization, and use of bare-metal stents, with no differences in the peri-procedural management and antithrombotic therapy.

[ANMCO Position paper: Antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes]. / Position paper ANMCO: Trattamento antitrombotico nei pazienti con fibrillazione atriale e sindromi coronariche acute o croniche sottoposti ad angioplastica coronarica con impianto di stent.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand antithrombotic therapy should reduce the risk related to recurrent ischemic events and/or stent thrombosis, on the other hand care should be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

Reduction in emergency access for acute myocardial infarction during the COVID-19 pandemic: a survey from the greater area of Rome.

BACKGROUND: On March 9, 2020, the Italian government imposed a national lockdown to tackle the COronaVIrus Disease 19 (COVID-19) pandemic, including stay at home recommendations. The precise impact of COVID-19 scare and lockdown on emergency access for acute myocardial infarction (MI) is still subject to debate. METHODS: Data on all patients undergoing invasive coronary angiography at 9 hospitals in the greater area of Rome, Italy, between February 19, 2020 and March 29, 2020 were retrospectively collected. Incidence of ST-elevation MI (STEMI), and non-ST-elevation MI (NSTEMI), as well as corresponding percutaneous coronary intervention (PCI), was compared distinguishing two different 20-day time periods (before vs. on or after March 10, 2020). RESULTS: During the study period, 1068 patients underwent coronary angiography, 142 (13%) with STEMI and 169 (16%) with NSTEMI. The average daily number of STEMI decreased from 4.3 before the lockdown to 2.9 after the lockdown (P=0.021). Similarly, the average daily number of NSTEMI changed from 5.0 to 3.5 (P=0.028). The average daily number of primary PCI changed from 4.2 to 2.9 (P=0.030), while the average daily number of PCI for NSTEMI changed from 3.5 to 2.5 (P=0.087). For STEMI patients, the time from symptom onset to hospital arrival (onset-to-door time less than three hours) showed a significant increase after the lockdown (P=0.018), whereas door-to-balloon time did not change significantly from before to after the lockdown (P=0.609). CONCLUSIONS: The present study, originally reporting on the trends in STEMI and NSTEMI in the Rome area, highlights that significant decreases in the incidence of both acute coronary syndromes occurred between February 19, 2020 and March 29, 2020, together with increases in time from symptom onset to hospital arrival, luckily without changes in door-to-balloon time.

The last resort during complex retrograde percutaneous coronary chronic total occlusion intervention: Extraplaque intracoronary lithotripsy to externally crush a heavy calcified occluded stent.

Chronic total occlusions (CTO) due to in-stent restenosis represent a challenging lesion subset for percutaneous coronary intervention in particular when associated with coronary calcification. Sometimes CTO lesions require antegrade or retrograde dissection-re-entry techniques with extraplaque dilation. Recently intravascular lithotripsy (IVL) emerged as a therapeutic option for the treatment of severely calcified coronary lesions but its role in extraplaque dilation is not described. In this report, we present a case of retrograde complex percutaneous coronary chronic total occlusion revascularization accomplished by the use of extraplaque IVL necessary to externally crush a heavy calcified previous implanted stent.

[Periprocedural management of anticoagulation therapy and in-hospital outcomes in patients with warfarin indication undergoing percutaneous coronary intervention. Data from the WAR-STENT registry]. / Gestione periprocedurale della terapia anticoagulante ed esiti intraospedalieri nei pazienti con indicazione a warfarin sottoposti ad angioplastica coronarica. Informazioni dal registro WAR-STENT.

BACKGROUND: In patients with an indication for oral anticoagulation (OAC) with warfarin, the management of OAC peri-procedure of percutaneous coronary intervention (PCI) is still not fully defined. To investigate clinical practice and outcomes associated with continuation vs interruption of OAC, with or without bridging with low-molecular-weight heparin (LMWH), we examined the database of the observational, prospective, multicenter Italian WAR-STENT registry. METHODS: The WAR-STENT registry was conducted in 2008-2010 in 37 Italian centers and included 411 consecutive patients in 157 of whom the peri-procedural international normalized ratio (INR) value was available. In relation to the continuation vs interruption of OAC, patients were divided into group 1 (n = 106) and group 2 (n = 51) respectively, and compared. RESULTS: The basal characteristics of the two groups were similar. The most frequent indication for OAC was atrial fibrillation and for PCI acute coronary syndromes, respectively. The pre-procedural mean value of INR was significantly different in group 1 vs group 2 (2.3 ± 0.4 vs 1.5 ± 0.2; p <0.001), while the use of antithrombotic drugs did not differ, except for LMWH which, albeit limited to only 14% of cases, was used significantly more frequently in group 2 (14% vs 2%; p=0.006). The radial approach was used significantly more often in group 1 vs group 2 (72% vs 45%; p=0.002). The in-hospital incidence of major bleeding complications was similar in groups 1 and 2 (4% vs 8%; p=0.27), as well as the occurrence of major adverse cardio-cerebrovascular events, including cardiovascular death, non-fatal myocardial infarction, re-revascularization of the treated vessel, stent thrombosis, stroke and venous thromboembolism (6% vs 6%; p=0.95). There was a tendency towards a higher incidence of minor access-site bleeding complications in group 1 patients treated by the femoral route. CONCLUSIONS: In unselected patients with an indication for OAC with warfarin and undergoing PCI, the continuation vs interruption of OAC (essentially without LMWH bridging) strategies appears similar in terms of efficacy and safety. In consideration of the superior convenience, peri-procedural continuation of OAC should therefore generally be preferred, with the possible exception of patients in whom the femoral approach is required for the procedure.

Acute kidney injury and multivessel percutaneous coronary interventions in chronic renal disease: the AMICI study.

BACKGROUND: Patients with chronic kidney disease (CKD) often have multivessel coronary artery disease and the risk of acute kidney injury (AKI) after percutaneous coronary interventions (PCI) is high. The aim of this study was to evaluate the risk of AKI in patients with CKD who underwent single vessel PCI versus multivessel PCI. METHODS: We retrospectively screened all PCI performed from January 2011 to December 2017 and we included all the procedures performed in patients with a baseline glomerular filtration rate <60 mL/min/1.73 m2. PCI were divided in two groups according to the treatment of a single vessel (mono group) or multivessel PCI (multi group). The multi group was also divided in two subgroups according to the modality of PCI: multivessel PCI performed in one procedure (multi-single session group) or in multiple staged procedures (multi-staged group). RESULTS: From a total of 4517 PCI screened, 848 PCI were included, 530 in the mono group and 318 in the multi group. The global rate of AKI was around 15% without significant differences between the mono and the multi group (15.5% in the mono and 14.8% in the multi group, P=0.786). In the multi group, the risk of AKI was significantly higher in the Single session sub-group (21.4%) compared to the staged sub-group (11.2%, P=0.014). CONCLUSIONS: In patients with CKD, the risk of AKI did not differ in patients who underwent single vessel versus multivessel PCI, but multivessel PCI should be performed in multiple staged procedures rather than in a single session.

Vascular access and radiation exposure during percutaneous coronary procedures.

In the cardiology community, the use of transradial access for percutaneous coronary procedures is progressively increasing all around the world overtaking the use of transfemoral access. The advantages of the transradial access are based on a significant reduction in bleeding and vascular events compared to the femoral access and on a reduction in mortality in the setting of acute coronary syndromes. However, in recent years a slight but significant increase in radiation exposure for patients and operators associated with the radial approach has been detected, increasing concerns about possible long term increased stochastic risk. In particular interventional cardiologists are among physicians performing interventional procedures using X-rays, those exposed to the highest radiation dose during their activity and this exposure is not without possible long-term clinical consequences in term of deterministic and stochastic effects. All the operators should be aware of these risks and manage to reduce their radiation exposure. In this review we analysed the differences in term of radiation exposure comparing the radial and the femoral access for percutaneous coronary procedures. Then, we discussed the possible clinical consequences of these differences and finally we showed the available tools aimed to reduce the operator radiation exposure. In particular the use of adjunctive protective drapes placed on the patient might reduce operator radiation exposure in up to 81% of the dose.

[SICI-GISE Position paper: Enhancing radiation safety in the catheterization laboratory]. / Position paper SICI-GISE: Miglioramento della radioprotezione nel laboratorio di Emodinamica.

The radiation dose received by interventional cardiologists during their activity in the catheterization laboratory is a matter of concern in terms of possible deterministic and stochastic risk. At the same time, very often, the knowledge of the effect and consequences of radiation exposure in the interventional cardiology community is limited. This document endorsed by the Italian Society of Interventional Cardiology (SICI-GISE) provides recommendations for cardiologists' radiation protection. Radiation safety considerations dedicated to women and other staff personnel working in the catheterization laboratory are also discussed.

Impact of Insulin-Treated and Noninsulin-Treated Diabetes Mellitus in All-Comer Patients Undergoing Percutaneous Coronary Interventions With Polymer-Free Biolimus-Eluting Stent (from the RUDI-FREE Registry).

Patients with diabetes mellitus (DM) have worse outcomes after percutaneous coronary intervention (PCI). Recent evidences suggest a differential impact of insulin-treated and noninsulin-treated DM on prognosis. We evaluated the clinical outcome of diabetic patients after PCI with polymer-free biolimus-eluting stent from the RUDI-FREE Registry, investigating a possible different prognostic impact of insulin-treated and noninsulin-treated DM. A total of 1,104 consecutive patients who underwent PCI with polymer-free biolimus-eluting stent, enrolled in the RUDI-FREE observational, multicenter, single-arm registry, were stratified by diabetic status; diabetic population was further divided on the basis of insulin treatment. Primary end points of the study were target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, target lesion revascularization) and major adverse cardiac and cerebrovascular events (composite of cardiac death, stroke, and myocardial infarction). Multiple ischemic adverse events were also single-handedly considered as secondary end points. At 1 year, TLF was significantly higher in the diabetic cohort, as compared with nondiabetic patients (6.0% vs 3.1%, p 0.022). None of the end points resulted significantly different between nondiabetics and noninsulin-treated diabetic patients. Divergently, compared with nondiabetic, insulin-treated diabetic patients faced significant higher rates of TLF (10.8% vs 3.1%, p 0.003), major adverse cardiac and cerebrovascular events (10.8% vs 3.4%, p 0.004), and of most of the analyzed adverse events. In conclusion, patients with DM had a higher risk of TLF compared with nondiabetics; nonetheless, the worse outcome of the diabetic population seems to be driven by the insulin-treated diabetic subpopulation. This finding suggests a different risk profile of insulin-treated and noninsulin-treated diabetic patients in the modern era of PCI.