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Aims: Although dual antiplatelet therapy with aspirin and a potent P2Y12 receptor inhibitor is currently recommended in patients with acute coronary syndrome (ACS), its use in elderly patients remains challenging. The aim of this trial is to evaluate the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 vs. 90 mg twice daily among elderly patients (≥75 years) with ACS undergoing percutaneous coronary intervention (PCI)., Methods and Results: PLINY The ELDER (NCT04739384) was a randomized, crossover trial testing the non-inferiority of a lower vs. standard dose of ticagrelor with respect to the primary endpoint of P2Y12 inhibition as determined by pre-dose P2Y12 reaction units (PRU) using the VerifyNow-P2Y12 (Accumetrics, San Diego, CA, USA). Other pharmacodynamic tests included light transmittance aggregometry, multiple electrode aggregometry, and response to aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were also evaluated. A total of 50 patients (mean age 79.6 ± 4.0 years, females 44%) were included in the trial. Ticagrelor 60 mg was non-inferior to ticagrelor 90 mg according to VerifyNow-P2Y12 results (PRU 26.4 ± 32.1 vs. 30.4 ± 39.0; least squares mean difference: -4; 95% confidence interval: -16.27 to 8.06; P for non-inferiority = 0.002). Other pharmacodynamic parameters were similar between the two ticagrelor doses and there were no differences in response to aspirin. Plasma levels of ticagrelor (398.29 ± 312.36 ng/mL vs. 579.57 ± 351.73 ng/mL, P = 0.006) and its active metabolite were significantly lower during treatment with ticagrelor 60 mg., Conclusion: Although plasma concentrations were lower, ticagrelor 60 mg twice daily provided a similar magnitude of platelet inhibition compared with ticagrelor 90 mg twice daily among elderly patients undergoing PCI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Patients with peripheral artery disease (PAD) who undergo lower extremity revascularization (LER) are at high risk for cardiovascular and limb-related ischemic events. The role of antithrombotic therapy is to prevent thrombotic complications, but this requires balancing increased risk of bleeding events. The dual pathway inhibition (DPI) strategy including aspirin and low-dose rivaroxaban after LER has been shown to reduce major adverse cardiovascular and limb-related events without significant differences in major bleeding. There is now a need to implement the broad adoption of DPI therapy in PAD patients who have undergone LER in routine practice., Competing Interests: Disclosures Drs Canonico, Hess, Bonaca receive salary support from CPC, a non-profit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between July 2021 and July 2023 from the following organizations: Abbot Laboratories, Agios Pharmaceuticals., Alexion Pharma Godo Kaisha, Amgen Inc., Anthos Therapeutics, Inc., ARCA Biopharma., AstraZeneca Pharma India, AstraZeneca Pharmaceuticals LP, AstraZeneca UK, AstraZeneca, Produtos Farmaceuticos, LDA, Atentiv, LLC, Bayer, Bayer Limited, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, LLC, Bristol-Myers Squibb, CellResearch Corporation Pte Ltd, Cleerly, Inc., Colorado Department of Public Health and Environment, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc., EPG Communication Holdings Ltd., Esperion Therapeutics, Faraday Pharmaceuticals, Inc., HeartFlow, Insmed, Ionis Pharmaceuticals, IQVIA Inc., Janssen Pharmaceuticals, Inc, Janssen Research & Development, LLC, Janssen Scientific Affairs, LLC, Lexicon Pharmaceuticals, Inc., LSG Corporation, MedImmune Limited, Medpace, Inc., Medscape, Merck Sharp & Dohme Corp., Nectero Medical Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Osiris Therapeutics, Pfizer, PPD Development, L.P., Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado (aka UCD), Sanifit Therapeutics S.A., Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc., The Brigham & Women's Hospital, Inc., Thrombosis Research Institute, University of Colorado Denver, University of Pittsburgh, VarmX, WraSer, LLC. Dr Bonaca receives support from the AHA SFRN under award numbers 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN33960262 (BWH-DH Clinical Project). Dr Bonaca also reports stock in Medtronic and Pfizer.Dr Secemsky reports: Funding: NIH/NHLBIK23HL150290, Food & Drug Administration, SCAI Grants to Institution: Abbott/CSI,BD, Boston Scientific, Cook, Medtronic, Philips. Speaking/Consulting: Abbott/CSI, BD, BMS, Boston Scientific, Cagent, Conavi, Cook, Cordis, Endovascular Engineering, Gore, InfraRedx, Medtronic, Philips, RapidAI, Shockwave, Terumo, Thrombolex, VentureMed, Zoll., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Rivaroxaban 2.5 mg plus aspirin reduced limb and cardiovascular events and increased bleeding in patients with symptomatic peripheral artery disease (PAD) after lower extremity revascularization in the VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) study. Fragile patients are at heightened risk for ischemic and bleeding events., Objectives: The purpose of this study was to investigate the safety and efficacy of rivaroxaban 2.5 mg in fragile patients from VOYAGER PAD., Methods: Patients were categorized as fragile based on prespecified criteria (age >75 years, weight ≤50 kg, or baseline estimated glomerular filtration rate <50 mL/min/1.73 m 2 ). The primary efficacy outcome was the composite of acute limb ischemia, major amputation of a vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was TIMI major bleeding., Results: Of 6,564 randomized patients, a total of 1,674 subjects were categorized as fragile at baseline. In the placebo arm, fragile patients were at higher risk of the primary outcome (HR: 1.34; 95% CI: 1.12-1.61) and TIMI major bleeding (HR: 1.57; 95% CI: 0.83-2.96), compared with nonfragile patients. The effect of rivaroxaban on the primary endpoint was not modified by frailty status (fragile HR: 0.93; 95% CI: 0.75-1.15; nonfragile HR: 0.83; 95% CI: 0.72-0.97; P interaction = 0.37). Rivaroxaban increased TIMI major bleeding in fragile (HR: 1.54; 95% CI: 0.82-2.91) and nonfragile patients (HR: 1.37; 95% CI: 0.84-2.23; P interaction = 0.65)., Conclusions: Patients with PAD after lower extremity revascularization meeting fragile criteria are at higher risk of ischemic complications and bleeding. Rivaroxaban reduces ischemic risk and increases bleeding regardless of frailty status. These data may assist in personalization of antithrombotic therapy in fragile population., Competing Interests: Funding Support and Author Disclosures VOYAGER PAD was funded by Bayer and Janssen Pharmaceuticals. The Colorado Prevention Center Clinical Research held the database and performed all analyses, and the decision to submit this manuscript for publication was made by the VOYAGER PAD Publications Committee. Drs Canonico, Low Wang, Hsia, Nehler, Capell, Berkowitz, and Bonaca receive salary support from CPC, a nonprofit academic research organization affiliated with the University of Colorado, that receives or has received research grant/consulting funding between July 2021 and July 2023 from the following organizations: Abbott Laboratories, Agios Pharmaceuticals, Inc, Alexion Pharma Godo Kaisha, Amgen Inc, Anthos Therapeutics, Inc, ARCA biopharma, Inc, AstraZeneca Pharma India, AstraZeneca Pharmaceuticals LP, AstraZeneca UK Ltd, AstraZeneca Produtos Farmaceuticos, Lda, Atentiv, LLC, Bayer, Bayer (Proprietary) Limited, Bayer Aktiengesellschaft, Bayer Pharma AG, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, LLC, Bristol Myers Squibb, CellResearch Corporation Pte Ltd, Cleerly, Inc, Colorado Department of Public Health and Environment, Cook Regentec LLC, CSL Behring LLC, Eidos Therapeutics, Inc, EPG Communication Holdings Ltd, Esperion Therapeutics, Inc, Faraday Pharmaceuticals, Inc, HeartFlow Inc, Insmed, Ionis Pharmaceuticals, IQVIA Inc, Janssen Pharmaceuticals, Inc, Janssen Research and Development, LLC, Janssen Scientific Affairs LLC, Lexicon Pharmaceuticals, Inc, LSG Corporation, MedImmune Limited, Medpace, Inc, Medscape, Merck Sharp and Dohme Corp, Nectero Medical Inc, Novartis Pharmaceuticals Corporation, Novo Nordisk, Osiris Therapeutics, Inc, Pfizer, PPD Development, LP, Prothena Biosciences Limited, Regeneron, Regents of the University of Colorado (aka UCD), Sanifit Therapeutics SA, Sanofi, Silence Therapeutics PLC, Stanford University, Stealth BioTherapeutics Inc, The Brigham and Women's Hospital, Inc, Thrombosis Research Institute, University of Colorado Denver, University of Pittsburgh, VarmX, and WraSer, LLC. Dr Hsia owns stock in AstraZeneca. Dr Debus has received grant support from Cook and Terumo Aortic. Dr Patel has received grant support, advisory board fees, and consulting fees from AstraZeneca, Bayer, and Janssen; has received grant support from Medtronic and Philips Healthcare; and has received grant support and advisory board fees from Heartflow. Dr Anand has received lecture fees from Bayer and Janssen. Dr Muehlhofer was employed by Bayer. Dr Haskell was employed by Janssen Pharmaceuticals; and has owned stock in Johnson and Johnson. Dr Berkowitz was employed by Bayer during the operationalization of the VOYAGER PAD study. Dr Bauersachs has received consulting fees and lecture fees from Bayer, Bristol Myers Squibb, and Pfizer. Dr Bonaca has received support from the AHA SFRN under award numbers 18SFRN3390085 (BWH-DH SFRN Center) and 18SFRN33960262 (BWH-DH Clinical Project); and has stock in Medtronic and Pfizer. Dr Ycas has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is more common in patients with malignancies than in general population. The pathophysiological processes include the pro-inflammatory condition and the exaggerated inflammatory reaction to chemotherapy, radiotherapy, and surgery interventions. Thus, it is pivotal to decrease morbidity and mortality in this group by providing appropriate care and prevention. In this subset, the risk of thromboembolic and bleeding events is high and the common risk score such as CHA2DS2-VASc and HAS-BLED employed in non-oncologic patients have limited evidence in cancer patients. A paucity of evidence in the setting in individuals having both malignancies and atrial fibrillation entangle the clinician when it comes to therapeutic management. Tailored management is recommended of anticoagulation treatment could be difficult, and there is. In this review, we try to explain the mechanism of AF in cancer patients as well as its management in this setting., (© 2024. The Author(s).)

Background . Lower extremity peripheral artery disease (LEPAD) frequently coexists with coronary artery disease (CAD) in patients with multisite vascular disease (MVD). While percutaneous revascularization is well-established for both LEPAD and CAD, limited evidence exists for patients eligible for both procedures. Specifically, the feasibility of concomitant LEPAD and CAD percutaneous revascularization remains unknown. Objectives . To compare the efficacy and safety of concomitant coronary and lower extremity elective percutaneous revascularization. Methods . Between 2012 and 2021, we included 135 patients in an observational, retrospective single-center registry. The population was stratified into two groups: 45 patients (concomitant group) underwent simultaneous coronary and peripheral percutaneous interventions, and 90 patients (deferred group) underwent two separate procedures within one year. The primary efficacy endpoint was major adverse cardiovascular events (MACE) at one year, while the primary safety endpoint was in-hospital contrast-induced nephropathy (CIN). Results . Study groups were well-balanced in baseline characteristics. In terms of coronary features, the concomitant revascularization group more often underwent single-vessel percutaneous coronary intervention (PCI), while the deferred group had multivessel PCI with diffuse coronary disease. No differences were detected in the number of LEPAD lesions between groups. For the primary efficacy endpoint, the incidence of MACE at one year was 37.8% in the concomitant group vs. 34.4% in the deferred group (HR 1.20, 95% CI 0.64-2.10; p = 0.61). No significant differences were found in CIN occurrence between the concomitant and deferred groups (11.1% vs. 8.9%; OR 1.30; 95% CI 0.36-4.21; p = 0.68). Conclusions . Multisite vascular disease patients eligible for CAD and LEPAD percutaneous revascularization exhibited a high cardiovascular risk profile with diffuse multivessel coronary and lower extremity disease. Our study suggests the efficacy and safety of concomitant coronary and lower extremity percutaneous revascularization based on one-year MACE incidence and in-hospital CIN. However, dedicated studies are warranted to confirm the short- and long-term outcomes of the concomitant revascularization strategy.

Purpose of Review: To provide a comprehensive review of hypertension among patients with cancer. Several cancer therapies cause hypertension which has resulted in a growing and vulnerable population of patients with difficult to control hypertension which has significant downstream effects., Recent Findings: Hypertension affects up to 50% of cancer patients and higher comorbidity when compared to the general population. Many anticancer therapies can cause hypertension through their treatment effect. Antihypertensive treatment is crucial given cardiovascular mortality is a leading cause of death among cancer patients. It is already known that hypertension is poorly controlled in the general population, and there are additional challenges in management among patients with cancer. Patients with cancer suffer from multimorbidity, are on multiple medications creating concern for drug interactions, and often have blood pressure lability, which can worsen clinical inertia among patients and their providers. It is crucial to effectively treat hypertension in cancer patients to mitigate downstream adverse cardiovascular events., Summary: In recent years, there have been significant changes in management guidelines of hypertension and simultaneously as influx of new cancer therapeutics. We provide an update on hypertension treatment among patients with cancer on different chemotherapeutic agents., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Patients with lower extremity peripheral artery disease (PAD) are at high risk for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). This manuscript will review the current evidence for medical therapy in patients with PAD according to different clinical features and the overall cardiovascular (CV) risk., Recent Findings: The management of PAD encompasses non-pharmacologic strategies, including lifestyle modification such as smoking cessation, supervised exercise, Mediterranean diet and weight loss as well as pharmacologic interventions, particularly for high risk patients. Benefits for reduction of CV and limb outcomes have been demonstrated for new therapies, including antithrombotic therapy (i.e., low-dose rivaroxaban plus aspirin), lipid lowering therapy (i.e., proprotein convertase subtilisin/kexin type 9 inhibitors), and glucose lowering therapy (i.e., sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists). However, the adoption of these therapies in PAD remains suboptimal in practice. Implementation science studies have recently shown promising results in PAD patients. Comprehensive medical and non-medical management of PAD patients is crucial to improving patient outcomes, mitigating symptoms, and reducing the risk of MACE and MALE. A personalized approach, considering the patient's overall risk profile and preference, is essential for optimizing medical management of PAD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Elderly status is steadily increasing among patients with acute coronary syndrome (ACS). Dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 receptor inhibitor is the cornerstone of treatment to prevent recurrent thrombotic complications in patients with ACS. However, DAPT in older patients is challenged by a concurrent heightened risk of ischemia and bleeding. The aim of this study is to evaluate the pharmacodynamic and pharmacokinetic profile of a lower dose of ticagrelor (60 mg twice daily) among elderly patients during the early phase of ACS., Study Design: PLINY THE ELDER (PLatelet INhibition with two different doses of potent P2y12 inhibitors in THE ELDERly population) (NCT04739384) is a prospective, randomized, open-label, crossover trial to evaluate the non-inferiority of a lower dose of ticagrelor (60 mg twice daily) compared with a standard dose (90 mg twice daily) among elderly patients with ACS undergoing percutaneous coronary intervention (PCI). A total of 50 patients, aged 75 years or more, with indication to potent P2Y12 receptor inhibitors will be randomized within 3 days from PCI for the index ACS. Patients with indication to oral anticoagulant therapy, treatment with glycoprotein IIb/IIIa inhibitors, or active bleeding will be excluded. The primary endpoint is platelet reactivity determined by P2Y12 reaction units (PRU) (VerifyNow, Accumetrics, San Diego, CA, USA) after treatment with ticagrelor 60 or 90 mg twice daily for 14 days. Secondary endpoints will include other pharmacodynamic tests of ADP-induced aggregation (light transmittance aggregometry and multiple electrode aggregometry) and determination of pharmacokinetic profile (plasma levels of ticagrelor and its metabolite AR-C124910XX) by high performance liquid chromatography-tandem mass spectrometry., Conclusions: The PLINY THE ELDER trial will determine whether a lower dose of ticagrelor confers non-inferior platelet inhibition compared with the standard dose in the early phase of ACS among elderly patients undergoing PCI, informing future clinical investigation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Echocardiography represents the most important diagnostic tool in the evaluation of aortic stenosis. The echocardiographic assessment of its severity should always be performed through a standardized and stepwise approach in order to achieve a comprehensive evaluation. The latest technical innovations in the field of echocardiography have improved diagnostic accuracy, guaranteeing a better and more detailed evaluation of aortic valve anatomy. An early diagnosis is of utmost importance since it shortens treatment delays and improves patient outcomes. Echocardiography plays a key role also in the evaluation of all the structural changes related to aortic stenosis. Detailed evaluation of subtle and subclinical changes in left ventricle function has a prognostic significance: scientific efforts have been addressed to identify the most accurate global longitudinal strain cut-off value able to predict adverse outcomes. Moreover, in recent years the role of artificial intelligence is increasingly emerging as a promising tool able to assist cardiologists in aortic stenosis screening and diagnosis, especially by reducing the rate of aortic stenosis misdiagnosis.

Purpose of Review: The purpose of this review is to analyze and discuss the most recent data on in hospital prescription of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors in patients with acute coronary syndrome (ACS)., Recent Findings: Recent randomized clinical trials (RTCs) have demonstrated a beneficial effect of monoclonal antibodies (mAb) PCSK9i prescription in patients with ACS on rapid reduction of low-density lipoprotein cholesterol (LDL-C) and on coronary atherosclerosis assessed by intracoronary imaging. Additionally, the safety profile of mAb PCSK9i was confirmed in all RTCs. Available RCTs show the effectiveness and rapid achievement of LDL-C levels according to American College of Cardiology/American Heart Association and European Society of Cardiology guidelines for ACS patients. However, RCTs addressing cardiovascular outcomes of PCSK9i in-hospital initiation in ACS patients are currently ongoing., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Transcatheter aortic valve implantation (TAVI) is a widely adopted treatment option for patients with severe aortic stenosis. Its popularity has grown significantly in recent years due to advancements in technology and imaging. As TAVI use is increasingly expanded to younger patients, the need for long-term assessment and durability becomes paramount. This review aims to provide an overview of the diagnostic tools to evaluate the hemodynamic performance of aortic prosthesis, with a special focus on the comparison between transcatheter and surgical aortic valves and between self-expandable and balloon-expandable valves. Moreover, the discussion will encompass how cardiovascular imaging can effectively detect long-term structural valve deterioration.

Sudden cardiac arrest is a leading cause of death in Europe. High-quality cardiopulmonary resuscitation (CPR) and guidelines compliance of rescuers have been associated with better outcomes after cardiac arrest. However, wide variability in attempting bystander CPR manoeuvres has been reported. Educational programmes for teaching CPR to medical students and fellows are highly advisable in this context. However, there is no homogeneity regarding the CPR education offered by academic institutions. We surveyed 208 Italian medical students and 162 fellows in cardiology regarding the educational offer and needs in CPR. Among the 11 medical schools surveyed, 8 (73%) offer basic (BLS) courses but only 3 (38%) with formal certification of 'BLS provider', while none offers advanced (ACLS/ALS) courses. Among the 30 specialization schools in cardiology surveyed, 10 (33%) offer a BLS course (6 with formal certification of 'BLS provider'), and 8 (27%) offer an ACLS/ALS course (5 with formal certification). Only a minority of students and fellows perceive themselves as highly proficient either in BLS or ACLS/ALS, although most of the fellows were involved at least once in rescuing a cardiac arrest. The present position paper analyses and suggests the strategies that should be adopted by Italian medical and specialization schools to spread the CPR culture and increase the long-standing retention of CPR-related technical and nontechnical skills., (Copyright © 2022 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Transcatheter aortic valve implantation (TAVI) is an increasingly popular treatment option for patients with severe aortic stenosis. Recent advancements in technology and imaging tools have significantly contributed to the success of TAVI procedures. Echocardiography plays a pivotal role in the evaluation of TAVI patients, both before and after the procedure. This review aims to provide an overview of the most recent technical advancements in echocardiography and their use in the follow-up of TAVI patients. In particular, the focus will be on the examination of the influence of TAVI on left and right ventricular function, which is frequently accompanied by other structural and functional alterations. Echocardiography has proven to be key also in detecting valve deterioration during extended follow-up. This review will provide valuable insights into the technical advancements in echocardiography and their role in the follow-up of TAVI patients.

Patients with peripheral artery disease (PAD) are at an increased risk of major adverse cardiovascular events, and those with disease in the lower extremities are at risk of major adverse limb events primarily driven by atherothrombosis. Traditionally, PAD refers to diseases of the arteries outside of the coronary circulation, including carotid, visceral and lower extremity peripheral artery disease, and the heterogeneity of PAD patients is represented by different atherothrombotic pathophysiology, clinical features and related antithrombotic strategies. The risk in this diverse population includes systemic risk of cardiovascular events as well as risk related to the diseased territory (e.g., artery to artery embolic stroke for patients with carotid disease, lower extremity artery to artery embolism and atherothrombosis in patients with lower extremity disease). Moreover, until the last decade, clinical data on antithrombotic management of PAD patients have been drawn from subanalyses of randomized clinical trials addressing patients affected by coronary artery disease. The high prevalence and related poor prognosis in PAD patients highlight the pivotal role of tailored antithrombotic therapy in patients affected by cerebrovascular, aortic and lower extremity peripheral artery disease. Thus, the proper assessment of thrombotic and hemorrhagic risk in patients with PAD represents a key clinical challenge that must be met to permit the optimal antithrombotic prescription for the various clinical settings in daily practice. The aim of this updated review is to analyze different features of atherothrombotic disease as well as current evidence of antithrombotic management in asymptomatic and secondary prevention in PAD patients according to each arterial bed.

Peripheral artery disease (PAD) commonly refers to atherosclerotic narrowing of noncoronary arteries, primarily those supplying the lower extremities. The risk factors for PAD include smoking, hyperlipidemia, hypertension, and diabetes mellitus. Patients with PAD are at a heightened risk of major adverse cardiovascular events (including myocardial infarction, stroke, and cardiovascular death) and major adverse limb events (including progressive symptoms or limb ischemia requiring peripheral revascularization, amputation, and acute limb ischemia), highlighting the need for guideline-directed therapies. Lifestyle modifications and medical therapies are utilized to improve function and outcomes in this patient population. Adherence to a healthy diet and smoking cessation are both associated with better outcomes in patients with PAD. Medical therapies targeting axes of risk, including lipid-modifying therapies, antithrombotic therapies, and targeted diabetes therapies, are available to reduce this risk in patients with PAD; however, significant residual risk remains. Unfortunately, despite guideline recommendations and efforts at education, even available medical therapies remain underutilized in patients with PAD. Continued development of novel therapies and efforts to improve the provision of care in patients with PAD are needed., (© 2022 The Author(s).)

Background: The coupling of the right ventricle (RV) to the pulmonary circulation is an indicator of RV performance that can be non-invasively estimated by echocardiography. There are no data about its use in patients affected by fibrotic interstitial lung diseases (f-ILD). Methods: Fifty f-ILD patients, including 27 cases with idiopathic pulmonary fibrosis (IPF) (M = 37; mean age 67 ± 7 years), were studied with standard and speckle-tracking echocardiography and compared with 30 age-matched healthy volunteers. The mean patient follow-up was 70 ± 4 months. Results: Fibrotic ILD patients had a larger right ventricle (RV) and worse diastolic function because the RV global longitudinal strain (GLS) was significantly lower and the systolic pulmonary artery pressure (sPAP) estimates were higher in comparison with those of controls. Conversely, tricuspid annular systolic excursion (TAPSE) did not differ between controls and patients. Median values of TAPSE/sPAP and RV GLS/sPAP were significantly reduced in f-ILD patients (p < 0.0001). Patients with an RV GLS/sPAP below the median value had a shorter survival time (61 vs. 74 months, p = 0.01); this parameter was an independent predictor of a worse outcome. Conclusion: Low estimates of RV GLS/sPAP are predictive of worse outcomes in f-ILD patients. RV coupling seems to be a promising surrogate biomarker of RV performance to discriminate the patient phenotype with significant management and prognosis implications.

Hepatitis C virus (HCV) is one of the leading causes of chronic liver disease affecting over 71 million people worldwide. An increased incidence of atherothrombotic events [e.g. coronary artery disease (CAD), atrial fibrillation (AF)] has been observed in HCV seropositive patients. On the other hand, an increased bleeding risk is another clinical issue, particularly in subjects with liver cirrhosis, gastroesophageal varices, portal hypertension, thrombocytopenia and alcohol consumption. The introduction and progressively greater use of direct-acting antivirals (DAAs) (instead of protease and polymerase inhibitors) during the last decade has enabled a sustained virological response to be achieved in a significant percentage of patients. However, due to the high cardiovascular risk profile in HCV-infected patients, the concomitant use of antithrombotic therapies is often required, bearing in mind the possible contraindications. For example, despite better pharmacokinetic and pharmacodynamic properties compared with vitamin K-antagonists, plasma level fluctuations of direct oral anticoagulants (DOACs) due to pathological conditions (e.g. chronic kidney diseases or hepatic cirrhosis) or drug-drug interactions (DDIs) may be of great importance as regards their safety profile and overall clinical benefit. We aimed to examine and briefly summarize the significant DDIs observed between antithrombotic and HCV antiviral drugs., Competing Interests: The study was supported by an unrestriced grant from Chiesi S.p.A. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Canonico, Sanna, Siciliano, Scudiero, Esposito and Parodi.)

Left atrial sphericity index (LASI) is an echocardiographic index easily obtained; its use in patients with heart failure (HF) has never been investigated so far. This single-centre study aimed to investigate the usefulness of LASI in an unselected cohort of patients hospitalized for acute HF, and its potential correlation with the amino-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) levels and with New York Heart Association (NYHA) functional class. Ninety-four consecutive HF patients underwent a transthoracic echocardiogram with a detailed study of the left atrium (LA) including LASI (calculated from the apical four-chamber view as the ratio between the transverse and longitudinal diameters), and blood tests (including NT-proBNP) on the same day. Median age was 75.5 (interquartile range-IQR 62-82) years and 55% were males, 58.5% had a NYHA class III-IV, and median NT-proBNP was 3284 (IQR 1215-7055) pg/ml. The LA was dilated in 94%, and median biplane LA volume index was 62 ml/m 2 . Patients with advanced NYHA class showed more advanced LA remodeling. Mean LASI was 0.78 ± 0.09 and did not correlate with NT-proBNP levels (r 0.03; p 0.75) or with patient NYHA class (R 2 0.011; p 0.287). None of the echocardiographic indices of LA structural and functional remodeling proved to be independently associated with a high NYHA class on multivariate regression analysis. In conclusion, LA remodeling is almost invariably present in patients with HF. LASI does not correlate with NT-proBNP levels or with NYHA functional class. Further studies are needed to describe the complex patterns of atrial remodeling in HF., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The prevalence of type 2 diabetes (T2D) continues to rise in the United States and worldwide. Cognitive behavioral therapy (CBT) has been shown to improve glycemic control in patients with T2D, but broad implementation has been limited by inherent access and resource constraints. Digital therapeutics have the potential to overcome these obstacles., Hypothesis: To describe the rationale and design of a trial evaluating the efficacy and safety of a digital therapeutic providing CBT to improve glycemic control in adults with T2D., Methods: This randomized, controlled, multicenter, Phase 3 trial evaluates the hypothesis that BT-001, an investigational digital therapeutic intended to help patients with T2D improve their glycemic control, on top of standard of care therapy, will lower hemoglobin A1c (HbA1c) compared to a control app across a broad range of patients in a real-world setting. The study is designed to provide evidence to support FDA review of this device as a digital therapeutic. The intervention is provided within the digital application (app) and includes no person-to-person coaching. The primary endpoint is the difference in HbA1c change from baseline to 90 days for BT-001-allocated subjects compared with those assigned to the control app. Safety assessment includes adverse events and adverse device effects. The study incorporates pragmatic features including entirely remote conduct with at-home visits for physical measures and blood sample collection., Conclusions: This randomized, controlled trial evaluates a cognitive behavioral intervention delivered via smartphone app which has the potential to provide a scalable treatment option for patients with T2D., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Purpose: The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19., Methods: This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants., Results: Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients CONCLUSION: Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19., (© 2021. The Author(s).)

Background: The influence of age and gender on strain-imaging-derived myocardial work (MW) was recently investigated in healthy subjects. No information is available on the impact of heart rate (HR) on MW. Methods: 177 healthy subjects (47% men, mean age 42 years) underwent an echo-Doppler exam, including quantification of global longitudinal strain (GLS). Cuff blood pressure was used as a surrogate of left ventricular peak pressure to estimate global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE). Statistical analyses were performed according to age and HR tertiles. Results: GWW was higher in the third HR tertile, i.e., ≥74 bpm (74.7 ± 33.6 mmHg %) than in the first HR tertile (<66 bpm) (61.0 ± 32.5 mmHg %) (p < 0.02). In the pooled population, by adjusting for systolic blood pressure, GLS, E/e’ ratio and left atrial volume index, age was independently associated with GCW (β = 0.748) and GWI (β = 0.685) (both p < 0.0001) and HR with GWW (β = 0.212, p = 0.006) and GWE (β = −0.204, p = 0.007). Conclusions: In healthy subjects age shows a mild influence on GCW. HR exerts an independent negative impact on GWW and GWE: the higher HR the greater wasted work and lower myocardial efficiency.

Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk-benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug-drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.

The characteristics and clinical course of hospitalized patients with coronavirus disease 2019 (COVID-19) have been widely described, while long-term data are still poor. The aim of this study was to evaluate the long-term clinical outcome and its association with right ventricular (RV) dysfunction in hospitalized patients with COVID-19. This was a prospective multicenter study of consecutive COVID-19 patients hospitalized at seven Italian Hospitals from 28 February to 20 April 2020. The study population was divided into two groups according to echocardiographic evidence of RV dysfunction. The primary study outcome was 1-year mortality. The propensity score matching was performed to balance for potential baseline confounders. The study population consisted of 224 patients (mean age 69 ± 14, male sex 62%); RV dysfunction was diagnosed in 63 cases (28%). Patients with RV dysfunction were older (75 vs. 67 years, p < 0.001), had higher prevenance of coronary artery disease (27% vs. 11%, p = 0.003), and lower left ventricular ejection fraction (50% vs. 55%, p < 0.001). The rate of 1-year mortality (67% vs. 28%; p ≤ 0.001) was significantly higher in patients with RV dysfunction compared with patients without. After propensity score matching, patients with RV dysfunction showed a worse long-term survival (62% vs. 29%, p < 0.001). The multivariable Cox regression model showed an independent association of RV dysfunction with 1-year mortality. RV dysfunction is a relatively common finding in hospitalized COVID-19 patients, and it is independently associated with an increased risk of 1-year mortality.

Improvement in life expectancy of patients suffering from oncohematologic disorders has turned cancer from an acute into a chronic condition, making the management of comorbidities problematic, especially when it comes to both acute and chronic cardiovascular diseases. Treatment-related adverse events and drug-drug interactions often influence the therapeutic approach of patients with active malignancies and cardiovascular disease. Furthermore, tumor cells and platelets maintain a complex crosstalk that on one hand enhances tumor dissemination and on the other hand induces hemostasis abnormalities. Hence, clinicians should move carefully in the intricate land mines established by patients with active cancer under antithrombotic therapy. To date, there is no consensus on the antithrombotic treatment of patients with cardiovascular diseases and concomitant malignancies. The aim of this review is to collect the available scientific evidence, including the latest clinical trials and guidelines, in order to provide guidance on the management of antithrombotic treatment (both antiplatelet and anticoagulant therapy) in cancer patients with either pre-existent or new-onset coronary artery disease. Randomized-controlled trials on antithrombotic treatment in oncologic populations, which by far have thus far been excluded, have to be promoted to supply recommendations in the oncohematologic setting., Competing Interests: G.G. reports consultant fees from Daiichi Sankyo., (Thieme. All rights reserved.)

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. ICIs have shown great promise in the treatment of several advanced malignancies. However, therapy with these immunomodulatory antibodies may lead to a wide spectrum of immune-related adverse events in any organ and any tissue. Cardiologic immune-related events include pericarditis, pericardial effusion, various types of arrhythmias including the occurrence of complete atrioventricular block, myocardial infarction, heart failure, and myocarditis. Although relatively rare, myocarditis is associated with a very high reported mortality in comparison to other adverse events. Myocarditis often presents significant diagnostic complexity and may be under-recognized. When confronted with an unexpected change in the clinical picture, the physician must differentiate between immune-related adverse events, cancer worsening, or other causes unrelated to the cancer or its therapy. However, this is not always easy. Therefore, with the increasing use of checkpoint inhibitors in cancer, all providers who care for patients with cancer should be made aware of this rare, but potentially fatal, cardiologic immune-related adverse event, and able to recognize when prompt consultation with a cardiologist specialist is indicated. In this review, we evaluate currently available scientific evidence and discuss clinical manifestations and new potential approaches to the diagnosis and therapy of acute myocarditis induced by ICIs. Temporary or permanent discontinuation of the ICIs and high-dose steroids have been administered to treat myocarditis, but symptoms may worsen in some patients despite therapy.

The inability to advance the dedicated wire of the transradial sheath in a radial artery with a good pulsatile blood flow is a very rare event. In this case, the advancement of a high-performance 0.014 inch coronary wire is the only option to gain the vessel. Then, if the transradial sheath is stuck in the proximal radial artery wall, balloon angioplasty of the radial artery may allow successful reinsertion of the transradial sheath. This technique allows the preservation of radial artery access, avoiding a shift to an alternative arterial approach.

Aims: The inability to carry office visits was collateral damage caused by the Coronavirus (COVID-19) pandemic. Tele-health is a relatively new, and yet fundamental amid the current crisis, resource to bridge the gap between phisicians and patients., Methods and Results: We report our experience with telemedicine and describe the major events occured in our patients. 121 consecutive adult patients with arterial hypertension (F/M: 56/65; mean age: 66.8 years) were enrolled. 33 patients (27%) had also diabetes, 94 (78%) were also affected from dyslipidemia and 11 (9%) had CAD. They all referred to our ambulatory of hypertension, in most of case for several years. Given the impossibility to continue routine outpatient visits during lockdown, they were all phone called by three residents in order to detect their state of health or any events they could have experienced over this period. They were all asked about their own blood pressure values, the occurrence of new symptoms and of new-onset both cardiovascular and non cardiovascular events. We also followed a self-made preset form. 31 of them (26%) experienced cardiovascular symptoms/events during this period: 11 had hypertensive peaks, in one case associated with nausea and vomiting while 2 of them had hypotensive episodes; 10 had typical angina and/or dyspnoea while 4 had atypical angina; 6 had palpitations; 1 of them developed new onset atrial fibrillation resolved with pharmacologic cardioversion during hospitalization; 1 had syncope; 1 patient reported new onset peripheral oedema; 2 patients died during lockdown for non cardiovascular causes. 17 of them also developed non cardiovascular symptoms, 7 of whom were severe anxiety and/or panic attacks. Almost all patients had important lifestyle changes, in 15 cases (12.3%) associated with weight increase., Conclusion: The impossibility to access to routine outpatient visits during lockdown due to global pandemic of SARS-CoV2, has brought out the risk of underestimating consequences of chronic disease, in absence of appropriate Follow-up. Nevertheless, the two deaths we report were not related to cardiovascular disease. The risk is that both the missing of cardiovascular control visit and the extension of the waiting list, could provoke serious complications in patients suffering from chronic cardiovascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions please email: journals.permissions@oup.com.)

A 53-year-old male was admitted to our department for unstable angina. Coronary angiography showed a subocclusive stenosis in the ostial-proximal tract of an intermediate branch in the context of a left dominance system. We proceeded with an ad hoc percutaneous coronary intervention considering this intermediate branch lesion in the setting of a bifurcation (Medina 0,0,1), where the proximal and distal main branches were represented by the left main and left anterior descending (LAD) arteries, respectively. After pre-dilation of the intermediate branch lesion, we advanced a "safety balloon" in order to protect the LAD branch and, simultaneously, we deployed a 3.0/22 mm drug-eluting stent in the intermediate branch. After in-stent post-dilation, we felt a strong resistance during the guidewire removal from the LAD indicating a wire entrapment. After a vigorous traction of the jailed guidewire, we observed the accidental removal of the just deployed stent from the guiding catheter. We re-advanced a guidewire on the LAD and a 3.25/23 mm drug-eluting stent was successfully implanted on the intermediate branch. We briefly discuss the occurred complication and some technical aspects regarding this case.

Introduction: At the end of 2019, a novel coronavirus was identified as the cause of a pneumonia cluster in Wuhan, China. Since then, the contagion has rapidly spread all over the world resulting in a global pandemic. Since frequent cardiovascular (CV) system involvement has soon been detected in patients occurring coronavirus disease 2019 (COVID-19), we would provide a simple review available to cardiologists who are going to be involved in the management of COVID-19 patients from several levels: from diagnosis to prevention and management of CV complications., Areas Covered: We investigate the role of CV diseases in COVID-19: from the incidence of CV comorbidities to their negative impact on prognosis. We also search Literature in order to identify the main CV manifestations in patients occurring virus infection and their management by cardiologists., Expert Opinion: Specific treatments for CV involvement associated with COVID-19 are still debated. Results from ongoing trials are needed to further clarify issues about the therapeutic approach, which is constantly changing according to the continuous flow of published evidence. Finally, it seems necessary to sensitize all population to raise awareness on CV diseases in the COVID era, to hinder the underestimation of both new-onset acute CV diseases and the consequences of chronic mistreated CV diseases.

Background: Left ventricular (LV) global longitudinal strain (GLS) can detect an early dysfunction in arterial hypertension. We investigated regional LV patterns of longitudinal strain (LS) and base-to-apex behaviour in newly diagnosed, never-treated hypertensive patients (HTN) without LV hypertrophy., Methods: 180 HTN and 115 healthy controls underwent standard echocardiography, including regional LS and GLS assessment (in absolute values). The average LS of six basal (BLS), six middle (MLS), and six apical (ALS) segments and relative regional strain ratio = [ALS/(BLS + MLS)] were also computed., Results: The two groups were comparable for sex, age and heart rate. Body mass index (BMI), systolic, diastolic and mean blood pressure (BP) (all p < 0.0001) were higher in HTN. Despite LV ejection fraction (EF) was comparable, GLS, BLS and MLS resulted lower in HTN (all p < 0.0001), without difference in ALS. Relative regional strain ratio resulted higher in HTN (p < 0.001). Dividing HTN group according to lower normal values derived from the controls, BLS was able to identify a higher rate of LV dysfunction than GLS. By a multiple linear regression analysis performed in the pooled population after adjusting for age, sex, BMI, end-systolic stress, relative wall thickness and LV mass index, the association between BLS and mean BP remained significant (β coefficient = -0.42, p < 0.0001), despite the significant impact of male sex. In a similar model, MLS and mean BP resulted also independently associated (β = -0.21, p < 0.002)., Conclusions: Despite normal LV EF, LS dysfunction is detectable in HTN, mainly involving basal and middle segments, resulting in higher relative regional strain ratio., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Left ventricular (LV) and right ventricular (RV) dysfunction is recognized in idiopathic pulmonary fibrosis (IPF). Little is known about cardiac involvement in non-idiopathic pulmonary fibrosis (no-IPF). This issue can be explored by advanced echocardiography. Methods: Thirty-three clinically stable and therapy-naive fibrotic IPF and 28 no-IPF patients, and 30 healthy controls were enrolled. Exclusion criteria were autoimmune systemic diseases, coronary disease, heart failure, primary cardiomyopathies, chronic obstructive lung diseases, pulmonary embolism, primary pulmonary hypertension. Lung damage was evaluated by diffusion capacity for carbon monoxide (DLCO sb ). All participants underwent an echo-Doppler exam including 2D global longitudinal strain (GLS) of both ventricles and 3D echocardiographic RV ejection fraction (RVEF). Results: We observed LV diastolic dysfunction in IPF and no-IPF, and LV GLS but not LV EF reduction only in IPF. RV diastolic and RV GLS abnormalities were observed in IPF versus both controls and no-IPF. RV EF did not differ significantly between IPF and no-IPF. DLCO sb and RV GLS were associated in the pooled pulmonary fibrosis population and in the IPF subgroup (β = 0.708, p < 0.001), independently of confounders including pulmonary arterial systolic pressure. Conclusion: Our data highlight the unique diagnostic capabilities of GLS in distinguishing early cardiac damage of IPF from no-IPF patients., Competing Interests: No conflict of interest.