Immuno-related cardio-vascular adverse events associated with immuno-oncological treatments: an under-estimated threat for cancer patients.

Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10 years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management.

Optimizing Management of Stable Angina: A Patient-Centered Approach Integrating Revascularization, Medical Therapy, and Lifestyle Interventions.

Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology.

Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials.

INTRODUCTION: Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS. METHODS: Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity. RESULTS: Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005). CONCLUSIONS: PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

Management of patients treated with oral anticoagulant therapy undergoing percutaneous coronary intervention with stent implantation: the PERSEO Registry.

In patients on oral anticoagulant (OAC) therapy undergoing percutaneous coronary intervention with stent (PCI), international guidelines endorse the use of direct oral anticoagulants (DOAC) rather than vitamin K antagonists (VKA) and dual antithrombotic therapy (DAT) rather than triple antithrombotic therapy (TAT). Aim of this study was to evaluate contemporary real-world data on antithrombotic regimens and outcome in patients on OAC undergoing PCI with stent. Consecutive patients on OAC undergoing PCI were enrolled in the multicentre, prospective, observational PERSEO registry (NCT03392948). Primary end-point was net adverse clinical events (NACE) with VKA vs DOAC, whereas a secondary pre-specified end-point was NACE with DAT vs TAT both at 1-year follow-up. From February 2018 to February 2022, 1234 consecutive patients were included. The main indication for OAC was atrial fibrillation (86%) and the mean CHA2DS2VASc and HAS-BLED scores were 4±2 and 3.6±1, respectively. Of the 1228 patients discharged alive, 222 (18%) were on VKA and 1006 (82%) on DOAC (p<0.01). DAT was employed in 197 patients whereas TAT in 1028. At follow-up, NACE rate was significantly higher with VKA compared to DOAC (23% vs 16%, p=0.013) and confirmed after propensity score adjustment. TAT and DAT did not differ as regards NACE rate (17% vs 19%, p=0.864) even though, compared to TAT, DAT was associated with less major bleedings (2% vs 5%, p= 0.014), confirmed after propensity score adjustment. In conclusion, in patients on OAC undergoing PCI, DOAC, compared to VKA, was associated with a significantly lower occurrence of NACE and DAT reduced bleedings compared to TAT.

Full-Moon Coronary Calcification as Detected With Computed Tomography Angiography in Chronic Total Occlusion Percutaneous Coronary Intervention.

"Full moon" is a central calcification that occludes the entire vessel on coronary computed tomography angiography (CCTA). We examined the association of full moon calcification as identified by CCTA, on clinical and procedural outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We studied patients who underwent elective CTO-PCI in 2 European centers and had preprocedural CCTA. The primary end point was the inability to cross the lesion and/or the need for extensive debulking techniques. Secondary end points were procedural success, in-hospital cardiac mortality, the need for extensive debulking techniques, myocardial infarction, major adverse cardiac events (defined as in-hospital death, myocardial infarction, and clinically driven target vessel revascularization), and stent thrombosis. Secondary procedural end points included procedural time, fluoroscopy time, number of guidewires and balloons, stent length, number and diameter, and contrast volume. Multivariable logistic regression analysis was performed, identifying potential covariates related to the primary outcome according to knowledge and previous studies. Subsequently, a stepwise selection approach was performed to select factors with the greatest predictive value. Of 140 patients included, 28 (20%) had a full moon calcified CTO plaque. Patients in the full moon group were older and had more cardiovascular risk factors. There was not significant difference in the need for retrograde approach and anterograde dissection and reentry techniques between the full moon group and the other groups (32.1% vs 37.5%, p = 0.59 and 0% vs 1.7%, p = 0.47, respectively). Patients in the full moon group had greater incidence of the primary outcome than did those who did not have full moon morphology (53.5% vs 12.5%, p <0.001). On multivariable analysis that included chronic kidney failure and previous coronary artery bypass surgery, full moon calcification was associated with greater incidence of the primary end point (odds ratio 6.5, 95% confidence interval 2.1 to 20.5, p = 0.001). Moreover, less procedural success (71.4% vs 87.5%, p = 0.03), greater incidence of coronary perforations (14.2% vs 3.5%, p <0.02), and greater procedural (172.5 [118.0 to 237.5] vs 144.0 [108.50 to 174.75], p = 0.02) and fluoroscopic time (62.6 [38.1 to 83.0] vs 42.8 [29.5 to 65.7], p = 0.03) were observed in the full moon group. Overall major adverse cardiac events did not differ between the 2 groups (1 patient in the full moon group vs 1 patient in the non-full moon group; 3.5% vs 0.8%, p = 0.29). In conclusion, full moon calcification on CCTA was independently associated with procedural complexity and adverse outcomes in CTO-PCI.

How Patients Feel with Telemedicine Devices as an Enabling Factor for Personalised Medicine: A Preliminary Study.

Telemonitoring tools have become essential in today's healthcare, representing fundamental resources for chronic disease home management supporting early detection of clinical worsening with great reduction of hospitalization costs. Therefore the investigation of the patient compliance is a key enabling point. We aim to assess how patients with chronic coronary syndromes evaluate a telemonitoring device meant for ongoing health monitoring. Twenty-six patients used the device for a week and subsequently filled out a well-designed questionnaire. The survey questions were about the device's ease of use, satisfaction levels, perceived effectiveness, and its influence on the patients' healthcare experiences. This study emphasizes the significance of focusing on patient needs in telemedicine and the importance of addressing these concerns to improve telehealth interventions.

Mechanisms of Cardiovascular Calcification and Experimental Models: Impact of Vitamin K Antagonists.

Cardiovascular calcification is a multifactorial and complex process involving an array of molecular mechanisms eventually leading to calcium deposition within the arterial walls. This process increases arterial stiffness, decreases elasticity, influences shear stress events and is related to an increased risk of morbidity and mortality associated with cardiovascular disease. In numerous in vivo and in vitro models, warfarin therapy has been shown to cause vascular calcification in the arterial wall. However, the exact mechanisms of calcification formation with warfarin remain largely unknown, although several molecular pathways have been identified. Circulating miRNA have been evaluated as biomarkers for a wide range of cardiovascular diseases, but their exact role in cardiovascular calcification is limited. This review aims to describe the current state-of-the-art research on the impact of warfarin treatment on the development of vascular calcification and to highlight potential molecular targets, including microRNA, within the implicated pathways.

Underlying mechanisms and cardioprotective effects of SGLT2i and GLP-1Ra: insights from cardiovascular magnetic resonance.

Originally designed as anti-hyperglycemic drugs, Glucagon-Like Peptide-1 receptor agonists (GLP-1Ra) and Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated protective cardiovascular effects, with significant impact on cardiovascular morbidity and mortality. Despite several mechanisms have been proposed, the exact pathophysiology behind these effects is not yet fully understood. Cardiovascular imaging is key for the evaluation of diabetic patients, with an established role from the identification of early subclinical changes to long-term follow up and prognostic assessment. Among the different imaging modalities, CMR may have a key-role being the gold standard for volumes and function assessment and having the unique ability to provide tissue characterization. Novel techniques are also implementing the possibility to evaluate cardiac metabolism through CMR and thereby further increasing the potential role of the modality in this context. Aim of this paper is to provide a comprehensive review of changes in CMR parameters and novel CMR techniques applied in both pre-clinical and clinical studies evaluating the effects of SGLT2i and GLP-1Ra, and their potential role in better understanding the underlying CV mechanisms of these drugs.

Clinical impact of cerebral protection during transcatheter aortic valve implantation.

BACKGROUND: Embolization of debris can complicate transcatheter aortic valve implantation (TAVI) causing stroke. Cerebral embolism protection (CEP) devices can divert or trap debris. PURPOSE: To evaluate the efficacy of CEP during TAVI vs the standard procedure. DATA SOURCES: PubMed, SCOPUS and DOAJ 1/01/2014-04/12/2023. STUDY SELECTION: Randomized and observational studies comparing CEP versus standard TAVI, according to PRISMA. PRIMARY OUTCOME: stroke. SECONDARY OUTCOMES: death, bleeding, vascular access complications, acute kidney injury and infarct area. DATA EXTRACTION: Two investigators independently assessed study quality and extracted data. DATA SYNTHESIS: Twenty-six articles were included (540.247 patients). The primary endpoint was significantly lower (RR = 0.800 95%CI:0.682-0.940; p = 0.007) with CEP. Similarly, death rates were significantly lower with CEP (RR = 0.610 95%CI:0.482-0.771; p < 0.001). No difference was found for bleeding (RR = 1.053 95%CI:0.793-1.398; p = 0.721), vascular complications (RR = 0.937 95%CI:0.820-1.070; p = 0.334) or AKI (RR = 0.982 95%CI:0.754-1.279; p = 0.891). CONCLUSIONS: Use of CEP during TAVI is associated with improved outcomes. Future studies will identify patients who benefit most from CEP.

Role of Integrated Intracoronary Imaging to Identify Surgical Clip as a Trigger for ACS-NSTE.

An 80-year-old post-coronary artery bypass graft (CABG) patient had an acute coronary syndrome with non-ST-segment elevation myocardial infarction (ACS-NSTE) with saphenous vein graft (SVG)-obtuse marginal stenosis. High-definition intravascular ultrasound revealed an underexpanded SVG stent with a hyperechoic structure. Optical coherence tomography confirmed surgical clip causing compression, resolved by post-dilation. This case underscores ACS-NSTE complexity post-CABG and the critical role of coronary imaging in optimizing interventions by addressing surgical clip-induced compression.

Commissural alignment during TAVR reduces the risk of overlap to coronary ostia.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) showed safety and efficacy in patients with severe aortic stenosis. Commissural alignment (CA) during TAVR has the potential to reduce the impact of the prostheses on accessibility of coronary arteries, as misalignment of the neocommissures could cause partial overlap with coronary ostia. Therefore, the aim of this study was to investigate the impact of CA on coronary overlap rates. METHODS: We examined the techniques of CA and their impact on coronary access. Eligible studies were searched for on Pubmed, SCOPUS and DOAJ and selected using PRISMA guidelines. The primary endpoint was the incidence of a severe coronary overlap or failed coronary re-access. Results of the analysis are expressed as Risk Ratio (RR) with 95% CI. RESULTS: Four studies were included in this analysis. In these, 681 patients underwent TAVR with CA and 210 underwent TAVR without CA. We examined Evolut valves and Acurate Neo valves. The primary endpoint occurred in 138 patients undergoing TAVR with CA and in 154 patients without CA (RR = 0.279; 95% CI 0.201-0.386; p < 0.001). Neither prosthesis-related, nor patient-related factors had a significant interaction with the measured effect. CONCLUSIONS: Commissural alignment was associated with significantly lower rates of commissure-to-coronary ostia overlap and failure of coronary access. Consequently, a modified insertion technique could reduce coronary overlap and coronary occlusion, particularly in supra-annular valves. Therefore, controlled orientation of prostheses by CA during TAVR could favour coronary access, especially in younger patients that could require coronary re-access after TAVR.

Management of high and intermediate-high risk pulmonary embolism: A position paper of the Interventional Cardiology Working Group of the Italian Society of Cardiology.

Pulmonary embolism (PE) is a potentially life-threatening condition that remains a major global health concern. Noteworthy, patients with high- and intermediate-high-risk PE pose unique challenges because they often display clinical and hemodynamic instability, thus requiring rapid intervention to mitigate the risk of clinical deterioration and death. Importantly, recovery from PE is associated with long-term complications such as recurrences, bleeding with oral anticoagulant treatment, pulmonary hypertension, and psychological distress. Several novel strategies to improve risk factor characterization and management of patients with PE have recently been introduced. Accordingly, this position paper of the Working Group of Interventional Cardiology of the Italian Society of Cardiology deals with the landscape of high- and intermediate-high risk PE, with a focus on bridging the gap between the evolving standards of care and the current clinical practice. Specifically, the growing importance of catheter-directed therapies as part of the therapeutic armamentarium is highlighted. These interventions have been shown to be effective strategies in unstable patients since they offer, as compared with thrombolysis, faster and more effective restoration of hemodynamic stability with a consistent reduction in the risk of bleeding. Evolving standards of care underscore the need for continuous re-assessment of patient risk stratification. To this end, a multidisciplinary approach is paramount in refining selection criteria to deliver the most effective treatment to patients with unstable hemodynamics. In conclusion, the current management of unstable patients with PE should prioritize tailored treatment in a patient-oriented approach in which transcatheter therapies play a central role.

Cardiac amyloidosis and aortic stenosis: a state-of-the-art review.

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aortic valve replacement. Diagnostic workup for cardiac amyloidosis in patients with aortic stenosis is based on a multi-parametric approach considering clinical assessment, electrocardiogram, haematologic tests, basic and advanced echocardiography, cardiac magnetic resonance, and technetium labelled cardiac scintigraphy like technetium-99 m (99mTc)-pyrophosphate, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, and 99mTc-hydroxymethylene diphosphonate. However, a biopsy is the traditional gold standard for diagnosis. The prognosis of patients with coexisting cardiac amyloidosis and aortic stenosis is still under evaluation. The combination of these two pathologies worsens the prognosis. Regarding treatment, mortality is reduced in patients with cardiac amyloidosis and severe aortic stenosis after undergoing transcatheter aortic valve replacement. Further studies are needed to confirm these findings and to understand whether the diagnosis of cardiac amyloidosis could affect therapeutic strategies. The aim of this review is to critically expose the current state-of-art regarding the association of cardiac amyloidosis with aortic stenosis, from pathophysiology to treatment.

Clinical impact of coronary revascularization over medical treatment in chronic coronary syndromes: A systematic review and meta-analysis.

OBJECTIVE: To provide a quantitative comparison between myocardial revascularization (REVASC) and optimal medical treatment (OMT) alone in patients with chronic coronary syndrome (CCS). METHODS: Pertinent studies were searched for in PubMed/Medline until 12/03/2023. Randomized controlled trials that compare REVASC to OMT reporting clinical outcomes were selected according to PRISMA guidelines. The primary outcome was cardiovascular death. Two investigators independently assessed the study quality and extracted data. RESULTS: Twenty-eight randomized controlled studies (RCTs) including 20692 patients were included in this meta-analysis. The rate of cardiovascular mortality was significantly lower among patients treated with myocardial revascularization [risk ratio (RR) 0.79, 95% CI 0.69-0.90]. Age (p = 0.03), multivessel disease (p < 0.001), and follow-up duration (p = 0.001) were significant moderators of CV mortality. Subgroup analyses showed a larger benefit in patients treated with drug-eluting stents and those without chronic total occlusion. Among secondary outcomes, myocardial infarction was less frequent in the REVASC group (RR = 0.74; p < 0.001), while no significant difference was found for all-cause mortality (p = 0.09) nor stroke (p = 0.26). CONCLUSIONS: The present analysis showed lower rates of CV mortality and myocardial infarction in CCS patients treated with myocardial revascularization compared to OMT. This benefit was larger with increasing follow-up duration. Personalized treatment based on patient characteristics and lesion complexity may optimize clinical outcomes in patients with CCS.

Distinctive phenogroup to differentiate diagnosis of cardiac myxoma vs cardiovascular disease examining blood-based circulating cell biomarkers.

Cardiac myxoma (CM) is a potentially life-threatening disease because frequently asymptomatic or debuts with aspecific manifestations. Definitive diagnosis is established by histopathological assessment including tumor and endothelial cell markers. To derive a specific panel of circulating cells antigenically detectable, pre-surgery peripheral blood samples of CM patients were analyzed. Pre-surgery peripheral blood samples from patients with CM were simultaneously analyzed for Circulating tumor cells (CTCs) and circulating endothelial cells (CECs) that were matched with tumor tissue profiles and with patient-derived xenografts (PDXs) distinguishing tumor regions. Moreover, CECs values in CM patients were further matched with CEC's levels in cardiovascular disease and control subjects. The blood-derived cytological specimens detected at least 1-3 CTCs/ml in 10 tested CM samples (p = 0.0001) showing specific CM features preserved in the central zones of the tumor. The central zone of the primary tumor, supported by a vessel density rate (55 ± 7%), with a proliferative profile of 32 ± 3% and a percentage of Calretininpos cells (p = 0.03), is the principal site of CTCs (r = 00) dissemination. The subsets of endothelial cells recognized in the blood were indifferent to their topological distribution within the tumor and corresponding PDXs. With further refinement and validation in large cohorts, multiparametric liquid biopsies can optimally integrate clinically informative datasets and maximize their utility in pre-surgery evaluation of CM patients. Blood-derived culture's protocol provides a versatile method capable of viable analysis of CTCs of non-hematological rare tumors which conventional antibody-mediated analytical platform is unable to perform. Distinctive blood- based cell phenotype contributes to differentiate CM from other differentials assuring its prompt surgical resection by combining blood-based cell biomarkers integrated with clinically informative datasets.

First-in-human robotic percutaneous coronary intervention by the ROSES robotic system: a case report.

Background: Robotic-assisted percutaneous coronary intervention (R-PCI) is increasingly gaining acceptance owing to several advantages. Case summary: Here, we report the first-in-human R-PCI performed with RObotic System for Endovascular Surgery (ROSES), an innovative robotic system designed to perform transcatheter angioplasty. We have reported a case of severe proximal posterolateral (PL) branch disease of the right coronary artery managed with R-PCI. Discussion: In this early clinical experience, the use of the ROSES robotic system seems to be safe and effective. However, this report still represents an early feasibility study, and the use of this technology in more challenging anatomies including the presence of severe tortuosity, severe calcification, or interventions requiring multiple wires and balloons needs to be further studied. A larger, prospective, multicentre pivotal clinical trial designed to test the ROSES robotic angioplasty system in a larger number of patients is currently ongoing.

Acquired cardiovascular disease in adults with congenital heart disease.

Rates of successful surgical repair and life expectancy for patients with congenital heart disease have increased dramatically in recent decades. Thanks to advances in diagnosis, treatment, and follow-up care, an ever-increasing number of individuals with congenital heart disease are reaching advanced age. The exposure to cardiovascular risk factors during their lifetime is modifying the outlook and late clinical trajectory of adult congenital heart disease (ACHD). Their disease burden is shifting from congenital to acquired, primarily atherosclerotic cardiovascular disease (ASCVD) with worrisome consequences. In addition, the complex background of ACHD often curbs appropriate preventive strategies by general practitioners or adult cardiologists. Comprehensive guidance for the prevention and management of acquired heart disease in ACHD patients is currently not available, as this topic has not been covered by the European Society of Cardiology (ESC) guidelines on cardiovascular disease prevention or the ESC guidelines for the management of ACHD. In this document, a state-of-the-art overview of acquired heart disease in ACHD patients and guidance on ASCVD prevention for both ACHD specialists and non-ACHD cardiologists are provided. The aim is to provide a clinical consensus statement to foster the development of a sustainable strategy for the prevention of ASCVD in a practical and simple-to-follow way in this ever-growing cardiovascular cohort, thus reducing their cardiovascular burden.

Clinical and Procedural Outcomes of IVUS-Guided vs. Angiography-Guided CTO-PCI: A Systematic Review and Meta-Analysis.

Chronic total occlusions (CTO) in coronary angiographies present a significant challenge nowadays. Intravascular ultrasound (IVUS) is a valuable tool during CTO-PCI, aiding in planning and achieving procedural success. However, the impact of IVUS on clinical and procedural outcomes in CTO-PCI remains uncertain. This meta-analysis aimed to compare IVUS-guided and angiography-guided approaches in CTO-PCI. The study included five studies and 2320 patients with stable coronary artery disease (CAD) and CTO. The primary outcome of major adverse cardiac events (MACE) did not significantly differ between the groups (p = 0.40). Stent thrombosis was the only secondary clinical outcome that showed a significant difference, favoring the IVUS-guided approach (p = 0.01). Procedural outcomes revealed that IVUS-guided procedures had longer stents, larger diameters, and longer procedure and fluoroscopy times (p = 0.007, p < 0.001, p = 0.03, p = 0.002, respectively). Stent number and contrast volume did not significantly differ between the approaches (p = 0.88 and p = 0.33, respectively). In summary, routine IVUS use did not significantly improve clinical outcomes, except for reducing stent thrombosis. Decisions in CTO-PCI should be individualized based on patient characteristics and supported by a multi-parametric approach.