Impact of Polyvascular Disease in Patients undergoing unprotected Left Main Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) has demonstrated its safety and efficacy in treating left main coronary artery disease (LM-CAD) in select patients. Polyvascular disease (PolyVD) is associated with adverse events in all-comers with CAD. However, there is little data examining the interplay between PolyVD and LM-PCI, which we sought to investigate in a retrospective single-center study. We included patients undergoing unprotected LM-PCI at a tertiary center from 2012-2019. The patient population was stratified based on the presence or absence of PolyVD (i.e. medical history of cerebrovascular and/or peripheral artery disease in addition to LM-CAD). The primary outcome was major adverse cardiovascular events (MACE) combining all-cause mortality and spontaneous myocardial infarction within one year after index PCI. Overall, 869 patients were included, and 23.8% of the population had PolyVD. Individuals with PolyVD were older and had a greater burden of comorbidities. After 1 year follow-up individuals with PolyVD exhibited significantly higher rates of both MACE (22.8% vs. 9.4%; p<0.001) and bleeding events compared to those without PolyVD. MACE was primarily driven by an increase in all-cause mortality (18.3% vs. 7.1%; p<0.001). Results persisted after adjusting for confounders. In conclusion, among patients undergoing LM-PCI, the presence of PolyVD is linked to an increased risk of MACE and bleeding after 1 year of follow-up, which highlights the vulnerability of this patient population.

Sirolimus-coated balloon in all-comer population of coronary artery disease patients: the EASTBOURNE DIABETES prospective registry.

BACKGROUND: The outcomes of percutaneous coronary intervention (PCI) in diabetic patients are still suboptimal, and it is unclear if diabetic patients might derive a benefit from the use of drug-coated balloons. AIMS: To evaluate the impact of diabetes mellitus on the outcomes of patients undergoing PCI with sirolimus-coated balloon (SCB) MagicTouch (Concept Medical, India). METHODS: We conducted a subgroup analysis of the prospective, multicenter, investigator-initiated EASTBOURNE registry, evaluating the performance of MagicTouch SCB in patients with and without diabetes. The study primary endpoint was target lesion revascularization (TLR) at 12-month follow-up. Secondary clinical endpoints were major adverse clinical events (MACE), death, myocardial infarction (MI), and BARC 2-5 bleedings. RESULTS: Among 2,083 enrolled patients, a total of 864 suffered from diabetes (41.5%). Patients with diabetes had a numerically higher occurrence of TLR (6.5% vs. 4.7% HR 1.38, 95%CI 0.91-2.08), all-cause death (3.8% vs. 2.6%, HR 1.81, 95%CI 0.95-3.46), and MACE (12.2% vs. 8.9%; HR 1.26 95%CI 0.92-1.74). The incidence of spontaneous MI was significantly higher among diabetic patients (3.4% vs. 1.5%, HR 2.15 95%CI 1.09-4.25); bleeding events did not significantly differ. The overall incidence of TLR was higher among in-stent restenosis (ISR) as compared to de-novo coronary lesions, irrespectively from diabetes status. CONCLUSIONS: In the EASTBOURNE DIABETES registry, diabetic patients treated with the MagicTouch SCB did not have a significant increase in TLR when compared to non-diabetic patients; moreover, diabetic status did not affect the study device performance in terms of TLR, in both de-novo lesions and ISR.

Antithrombotic therapy in patients with acute coronary syndrome: similarities and differences between a European expert consensus document and the 2023 European Society of Cardiology guidelines.

Antithrombotic therapy represents the cornerstone of the pharmacological treatment in patients with acute coronary syndrome (ACS). The optimal combination and duration of antithrombotic therapy is still matter of debate requiring a critical assessment of patient comorbidities, clinical presentation, revascularization modality, and/or optimization of medical treatment. The 2023 European Society of Cardiology (ESC) guidelines for the management of patients with ACS encompassing both patients with and without ST segment elevation ACS have been recently published. Shortly before, a European expert consensus task force produced guidance for clinicians on the management of antithrombotic therapy in patients with ACS as well as chronic coronary syndrome. The scope of this manuscript is to provide a critical appraisal of differences and similarities between the European consensus paper and the latest ESC recommendations on oral antithrombotic regimens in ACS patients.

Safety and Efficacy of Ticagrelor Monotherapy in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: An Individual Patient Data Meta-Analysis of TWILIGHT and TICO Randomized Trials.

BACKGROUND: Dual antiplatelet therapy with a potent P2Y12 inhibitor coupled with aspirin for 1 year is the recommended treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). As an alternative, monotherapy with a P2Y12 inhibitor after a short period of dual antiplatelet therapy has emerged as a bleeding reduction strategy. METHODS: We pooled individual patient data from randomized trials that included patients with ACS undergoing PCI treated with an initial 3-month course of dual antiplatelet therapy followed by ticagrelor monotherapy versus continued ticagrelor plus aspirin. Patients sustaining a major ischemic or bleeding event in the first 3 months after PCI were excluded from analysis. The primary outcome was Bleeding Academic Research Consortium type 3 or 5 bleeding occurring between 3 and 12 months after index PCI. The key secondary end point was the composite of death, myocardial infarction, or stroke. Hazard ratios and 95% CIs were generated using Cox regression with a one-stage approach in the intention-to-treat population. RESULTS: The pooled cohort (n=7529) had a mean age of 62.8 years, 23.2% were female, and 55% presented with biomarker-positive ACS. Between 3 and 12 months, ticagrelor monotherapy significantly reduced Bleeding Academic Research Consortium 3 or 5 bleeding compared with ticagrelor plus aspirin (0.8% versus 2.1%; hazard ratio, 0.37 [95% CI, 0.24-0.56]; P<0.001). Rates of all-cause death, myocardial infarction, or stroke were not significantly different between groups (2.4% versus 2.7%; hazard ratio, 0.91 [95% CI, 0.68-1.21]; P=0.515). Findings were unchanged among patients presenting with biomarker-positive ACS. CONCLUSIONS: Among patients with ACS undergoing PCI who have completed a 3-month course of dual antiplatelet therapy, discontinuation of aspirin followed by ticagrelor monotherapy significantly reduced major bleeding without incremental ischemic risk compared with ticagrelor plus aspirin. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42023449646.

Personalized Approaches to Antiplatelet Treatment for Cardiovascular Diseases: An Umbrella Review.

Antiplatelet therapy is the cornerstone of antithrombotic prevention in patients with established atherosclerosis, since it has been proven to reduce coronary, cerebrovascular, and peripheral thrombotic events. However, the protective effect of antiplatelet agents is counterbalanced by an increase of bleeding events that impacts on patients' mortality and morbidity. Over the last years, great efforts have been made toward personalized antithrombotic strategies according to the individual bleeding and ischemic risk profile, aiming to maximizing the net clinical benefit. The development of risk scores, consensus definitions, and the new promising artificial intelligence tools, as well as the assessment of platelet responsiveness using platelet function and genetic testing, are now part of an integrated approach to tailored antithrombotic management. Moreover, novel strategies are available including dual antiplatelet therapy intensity and length modulation in patients undergoing myocardial revascularization, the use of P2Y12 inhibitor monotherapy for long-term secondary prevention, the implementation of parenteral antiplatelet agents in high-ischemic risk clinical settings, and combination of antiplatelet agents with low-dose factor Xa inhibitors (dual pathway inhibition) in patients suffering from polyvascular disease. This review summarizes the currently available evidence and provides an overview of the principal risk-stratification tools and antiplatelet strategies to inform treatment decisions in patients with cardiovascular disease.

Drug-Coated Balloon Angioplasty for De Novo Lesions on the Left Anterior Descending Artery.

BACKGROUND: Drug-coated balloons (DCB) are an emerging tool for modern percutaneous coronary intervention (PCI), but evidence on their use for de novo lesions on large vessels is limited. METHODS: Consecutive patients undergoing DCB-based PCI on the left anterior descending artery in 2 Italian centers from 2018 to 2022 were retrospectively enrolled and compared with patients who received left anterior descending PCI with contemporary drug-eluting stents (DES). In-stent restenosis was excluded. The DCB group included both patients undergoing DCB-only PCI and those receiving hybrid PCI with DCB and DES combined. The primary end point was target lesion failure at 2 years, defined as the composite of target lesion revascularization, cardiac death, and target vessel myocardial infarction. RESULTS: We included 147 consecutive patients undergoing DCB-based treatment on the left anterior descending artery and compared them to 701 patients who received conventional PCI with DES. In the DCB group, 43 patients (29.2%) were treated with DCB only and 104 (70.8%) with a hybrid approach; DCB length was greater than stent length in 55.1% of cases. Total treated length was higher in the DCB group (65 [40-82] versus 56 [46-66] mm; P=0.002), while longer DESs were implanted (38 [24-62] versus 56 [46-66] mm; P<0.001) and a higher rate of large vessels were treated (76.2% versus 83.5%; P=0.036) in the DES cohort. The cumulative 2-year target lesion failure incidence was not significantly different between the 2 groups (DCB, 4.1% versus DES, 9.8%; hazard ratio, 0.51 [95% CI, 0.20-1.27]; P=0.15). After a 1:1 propensity score matching resulting in 139 matched pairs, the DCB-based treatment was associated with a lower risk for target lesion failure at 2 years compared with DES-only PCI (hazard ratio, 0.2 [95% CI, 0.07-0.58]; P=0.003), mainly driven by less target lesion revascularization. CONCLUSIONS: A DCB-based treatment approach for left anterior descending revascularization allows a significantly reduced stent burden, thereby potentially limiting target lesion failure risk at midterm follow-up.

[SICI-GISE/SICOA Consensus document: Clinical follow-up of patients after acute coronary syndrome or percutaneous coronary intervention]. / Documento di consenso SICI-GISE/SICOA: La gestione del follow-up del paziente dopo sindrome coronarica acuta e/o angioplastica coronarica.

In the last decades, advances in percutaneous coronary intervention (PCI) strategies have significantly reduced the risk of procedural complications and in-hospital mortality of patients with acute coronary syndromes (ACS), thus increasing the population of stable post-ACS patients. This novel epidemiological scenario emphasizes the importance of implementing secondary preventive and follow-up strategies. The follow-up of patients after ACS or elective PCI should be based on common pathways and on the close collaboration between hospital cardiologists and primary care physicians. However, the follow-up strategies of these patients are still poorly standardized. This SICI-GISE/SICOA consensus document was conceived as a proposal for the long-term management of post-ACS or post-PCI patients based on their individual residual risk of cardiovascular adverse events. We defined five patient risk classes and five follow-up strategies including medical visits and examinations according to a specific time schedule. We also provided a short guidance for the selection of the appropriate imaging technique for the assessment of left ventricular ejection fraction and of non-invasive anatomical or functional tests for the detection of obstructive coronary artery disease. Physical and pharmacological stress echocardiography was identified as the first-line imaging technique in most of cases, while cardiovascular magnetic resonance should be preferred when an accurate evaluation of left ventricular ejection fraction is needed. The standardization of the follow-up pathways of patients with a history of ACS or elective PCI, shared between hospital doctors and primary care physicians, could result in a more cost-effective use of resources and potentially improve patient's long-term outcome.

A Keynesian perspective on the health economics of kidney transplantation would strengthen the value of the whole organ donation and transplantation service.

Background: In this study, the Keynesian principle "savings may be used as investments in resources" is applied to Kidney Transplantation (KT), contextualizing the whole Organs Donation and Transplantation (ODT) service as a unique healthcare entity. Our aim was to define the financial resources that may be acquired in the form of savings from the KT activity. Methods: We analyzed registry and funding data for ODT in our region, between 2015 and 2019. Our hypotheses aimed to evaluate whether the savings would offset the Organ Donation (OD) costs, define the scope for growth, and estimate what savings could be generated by higher KT activity. To facilitate the evaluation of the resources produced by KT, we defined a coefficient generated from the combination of clinical outcomes, activity, and costs. Results: The ODT activity reached a peak in 2017, declining through 2018-2019. The savings matured in 2019 from the KT activity exceeded €15 million while the OD costs were less than €9 million. The regional KT activity was superior to the national average but inferior to international benchmarks. The estimated higher KT activity would produce savings between €16 and 20 million. Conclusion: The financial resources produced by KT contribute to defining a comprehensive perspective of ODT finance. The optimization of the funding process may lead to the financial self-sufficiency of the ODT service. The reproducible coefficient allows a reliable estimate of savings, subsequently enabling adequate investments and budgeting. Applying such a perspective jointly with reliable estimates would establish the basis for an in-hospital fee-for-value funding methodology for ODT.

Antithrombotic treatment strategies in patients with established coronary atherosclerotic disease.

Multiple guidelines and consensus papers have addressed the role of antithrombotic strategies in patients with established coronary artery disease (CAD). Since evidence and terminology continue to evolve, the authors undertook a consensus initiative to guide clinicians to select the optimal antithrombotic regimen for each patient. The aim of this document is to provide an update for clinicians on best antithrombotic strategies in patients with established CAD, classifying each treatment option in relation to the number of antithrombotic drugs irrespective of whether the traditional mechanism of action is expected to mainly inhibit platelets or coagulation cascade. With the aim to reach comprehensiveness of available evidence, we systematically reviewed and performed meta-analyses by means of both direct and indirect comparisons to inform the present consensus document.

Within and beyond 12-month efficacy and safety of antithrombotic strategies in patients with established coronary artery disease: two companion network meta-analyses of the 2022 joint clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association for Acute CardioVascular Care (ACVC), and European Association of Preventive Cardiology (EAPC).

AIMS: To appraise all available antithrombotic treatments within or after 12 months following coronary revascularization and/or acute coronary syndrome in two network meta-analyses. METHODS AND RESULTS: Forty-three (N = 189 261 patients) trials within 12 months and 19 (N = 139 086 patients) trials beyond 12 months were included for efficacy/safety endpoints appraisal. Within 12 months, ticagrelor 90 mg bis in die (b.i.d.) [hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.49-0.88], aspirin and ticagrelor 90 mg (HR, 0.85; 95% CI, 0.76-0.95), or aspirin, clopidogrel and rivaroxaban 2.5 mg b.i.d. (HR, 0.66; 95% CI, 0.51-0.86) were the only treatments associated with lower cardiovascular mortality, compared with aspirin and clopidogrel, without or with greater bleeding risk for the first and the other treatment options, respectively. Beyond 12 months, no strategy lowered mortality; compared with aspirin; the greatest reductions of myocardial infarction (MI) were found with aspirin and clopidogrel (HR, 0.68; 95% CI, 0.55-0.85) or P2Y12 inhibitor monotherapy (HR, 0.76; 95% CI: 0.61-0.95), especially ticagrelor 90 mg (HR, 0.54; 95% CI, 0.32-0.92), and of stroke with VKA (HR, 0.56; 95% CI, 0.44-0.76) or aspirin and rivaroxaban 2.5 mg (HR, 0.58; 95% CI, 0.44-0.76). All treatments increased bleeding except P2Y12 monotherapy, compared with aspirin. CONCLUSION: Within 12 months, ticagrelor 90 mg monotherapy was the only treatment associated with lower mortality, without bleeding risk trade-off compared with aspirin and clopidogrel. Beyond 12 months, P2Y12 monotherapy, especially ticagrelor 90 mg, was associated with lower MI without bleeding trade-off; aspirin and rivaroxaban 2.5 mg most effectively reduced stroke, with a more acceptable bleeding risk than VKA, compared with aspirin.Registration URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifiers: CRD42021243985 and CRD42021252398.

P2Y12 Inhibitors Monotherapy in Patients Undergoing Complex vs Non-Complex Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Trials.

BACKGROUND: Monotherapy with P2Y12 inhibitors (P2Y12i) is emerging as alternative strategy to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). However, early withdrawal of aspirin as part of P2Y12i monotherapy regimens may pose concerns in high-risk patients, such as those undergoing complex PCI. Our aim was to evaluate the efficacy and safety of P2Y12i monotherapy after a short course of DAPT (1-3-month) compared with standard DAPT (≥12-month) according to PCI complexity. METHODS: We performed a meta-analysis of randomized trials using random effects models to combine hazard ratios (HRs) with 95% confidence intervals (CIs). Within-trial interactions were pooled to estimate heterogeneity between complex and noncomplex PCI strata. The study protocol was registered in the PROSPERO (CRD42021291027). RESULTS: We identified 5 trials including 31,627 patients, of whom 8,328 (26.3%) underwent complex PCI. P2Y12i monotherapy compared with standard DAPT was associated with a similar risk of all-cause death, stent thrombosis, and stroke, with no evidence for interaction between complex and noncomplex PCI. We found heterogeneity in the treatment effect of P2Y12i monotherapy vs standard DAPT with respect to myocardial infarction (P-interaction = 0.027). Compared with standard DAPT, P2Y12i monotherapy decreased the risk of myocardial infarction in complex PCI (HR 0.77, 95%CI 0.60-0.99, P = .042), but not in noncomplex PCI patients (HR 1.09, 95%CI 0.90-1.30, P = .382). The risk of major bleeding was significantly reduced by P2Y12i monotherapy with a consistent treatment effect (P-interaction = 0.699) in both complex and noncomplex PCI strata. CONCLUSIONS: Patients undergoing complex PCI may derive more benefit and less harm from P2Y12i monotherapy after early aspirin withdrawal compared with standard DAPT.

Tailored repetitive transcranial magnetic stimulation for depression and addictions.

Transcranial magnetic stimulation (TMS) has been widely applied for evaluation of the cortical eloquence through creation of the temporary "virtual lesion" allowing assessment of the evaluated function within the targeted region, which may be also employed for management of mental symptoms or modification of the abnormal behavior. It is believed that this non-invasive neuromodulation modality has a double impact on neurons-primary modulation of electrical activity and stimulation of neuroplasticity; the latter can be facilitated by repeated administration of TMS during multiple sessions over sufficiently long periods of time to induce consolidation of treatment effects through their recall at psychological, physiological, and cellular levels. These principles were employed in our data-driven, tailored strategy based on the modifications of TMS protocol and its adaptation to newly appearing changes of the clinical situation along with administration of prolonged and/or repeated courses of therapeutic stimulation, which showed high efficacy resulting in complete relief of depressive symptoms or substance use in 75% of treated patients at 1-year follow-up. Such results justify application of repetitive TMS for management of psychiatric disorders and warrant additional evaluation of its efficacy in further clinical studies.

Biochemical Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors by Cardiovascular Risk Profile and Volume Status in a Real-World Diabetic Population.

ABSTRACT: Despite large-scale randomized clinical trials (RCTs) highlighting a consistent prognostic benefit of sodium-glucose cotransporter 2 inhibitors (SGLT2is) both in diabetic patients at high cardiovascular risk and in those with heart failure, there is relative paucity of data on their biochemical effects in a real-world setting. We performed a retrospective analysis on consecutive diabetic patients who were prescribed a SGLT2i in a tertiary referral center and completed at least 1 year of treatment. Changes in glycated hemoglobin, weight, and hematocrit were compared across 2 cardiovascular risk categories, defined through the inclusion criteria of 3 large RCTs. Of the 459 patients screened, 312 completed 1 year of treatment (68.0%), 92 interrupted the treatment prematurely (20.0%), and 55 were lost to follow-up (12.0%). The most common cause of drug discontinuation was genital or urinary tract infections (9.4%). At 1 year, reduction in glycated hemoglobin concentration (-0.7 ± 1.5%, P < 0.001) and body weight (2.4 ± 4.6 kg, P < 0.001) was comparable between patients at high versus low cardiovascular risk, while hematocrit increase (2.3 ± 3.3%, P < 0.001) was more marked in patients with high cardiovascular risk and low baseline hematocrit. In a real-world population of diabetic patients, SGLT2is were well-tolerated at 1 year and led to improved glycemic control and weight loss. Hematocrit increase was more consistent in patients with high cardiovascular risk and signs of fluid overload, indicating euvolemic restoration as a potential cardioprotective mechanism mediated by these compounds.

Artificial Intelligence and Cardiovascular Risk Prediction: All That Glitters is not Gold.

Artificial intelligence (AI) is a broad term referring to any automated systems that need 'intelligence' to carry out specific tasks. During the last decade, AI-based techniques have been gaining popularity in a vast range of biomedical fields, including the cardiovascular setting. Indeed, the dissemination of cardiovascular risk factors and the better prognosis of patients experiencing cardiovascular events resulted in an increase in the prevalence of cardiovascular disease (CVD), eliciting the need for precise identification of patients at increased risk for development and progression of CVD. AI-based predictive models may overcome some of the limitations that hinder the performance of classic regression models. Nonetheless, the successful application of AI in this field requires knowledge of the potential pitfalls of the AI techniques, to guarantee their safe and effective use in daily clinical practice. The aim of the present review is to summarise the pros and cons of different AI methods and their potential application in the cardiovascular field, with a focus on the development of predictive models and risk assessment tools.

Mortality after bleeding versus myocardial infarction in coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: Bleeding is the principal safety concern of antithrombotic therapy and occurs frequently among patients with coronary artery disease (CAD). AIMS: We aimed to evaluate the prognostic impact of bleeding on mortality compared with that of myocardial infarction (MI) in patients with CAD. METHODS: We searched Medline and Embase for studies that included patients with CAD and that reported both the association between the occurrence of bleeding and mortality, and between the occurrence of MI and mortality within the same population. Adjusted hazard ratios (HRs) for mortality associated with bleeding and MI were extracted and ratios of hazard ratios (rHRs) were pooled by using inverse variance weighted random effects meta-analyses. Early events included periprocedural or within 30-day events after revascularisation or acute coronary syndrome (ACS). Late events included spontaneous or beyond 30-day events after revascularisation or ACS. RESULTS: A total of 141,059 patients were included across 16 studies; 128,660 (91%) underwent percutaneous coronary intervention. Major bleeding increased the risk of mortality to the same extent as MI (rHRsbleedingvsMI 1.10, 95% CI: 0.71-1.71, p=0.668). Early bleeding was associated with a higher risk of mortality than early MI (rHRsbleedingvsMI 1.46, 95% CI: 1.13-1.89, p=0.004), although this finding was not present when only randomised trials were included. Late bleeding was prognostically comparable to late MI (rHRsbleedingvsMI 1.14, 95% CI: 0.87-1.49, p=0.358). CONCLUSIONS: Compared with MI, major and late bleeding is associated with a similar increase in mortality, whereas early bleeding might have a stronger association with mortality.

[Integrated Procurement Model: A new approach to Tissue and Organ Procurement]. / Un modello integrato per l'identificazione dei potenziali donatori: un nuovo approccio nei trapianti di organi e tessuti.

INTRODUCTION: Literature has shown that the process of procurement of organs and tissues is fundamental in determining the number of donations. Starting from these assumptions, an integrated procurement model of organs and tissues has been designed and tested, where nurse specialists in organ donation coordinate the team and the entire process. AIM: To evaluate the effectiveness of the Integrated Procurement Models in terms of identifying potential donors and the number of donations. METHODS: A retrospective observational study was conducted before and after the introduction of the new procurement model in a large University Hospital in Rome. The data of potential donors identified, the number of donations made and the efficiency indicators of the donation process were compared. RESULTS: 692 potential donors were identified. The introduction of the integrated model increased the number of actual donors (from 31 to 51), brain death assessments (from 69 to 99), and the efficiency indicators of the donation process (from 0.25 to 0.29). From the comparison between the activities before and after the introduction of the integrated procurement model, statistically significant differences emerged regarding the number of donors and the amount of corneal tissue extracted. CONCLUSIONS: The adoption of the standardized Integrated Procurement Model would increase the number of potential donors and actual donations, thanks also to the key role assumed by the nurse specializing in organ donation as team and process coordinator.