Incidence and Predictors of Cerebrovascular Accidents in Patients Undergoing Transcatheter Mitral Valve Repair with Mitraclip.

BACKGROUND: Transcatheter mitral edge-to-edge repair (TEER) with transcatheter devices has become a mainstay in the minimally invasive treatment of patients with severe mitral regurgitation at increased surgical risk. Despite its apparently favorable risk profile, there is uncertainty on the risk and features of cerebrovascular accidents (CVA) early and long after TMVR. We aimed at appraising incidence and predictors of CVA in patients undergoing TEER. METHODS: We explicitly queried the dataset of an ongoing multicenter prospective observational study dedicated to TEER with MitraClip (Abbott Vascular, Santa Clara, CA, USA). Incidence of CVA after TEER was formally appraised, and we explored also potential predictors of such event. Descriptive, bivariate and diagnostic accuracy analyses were performed. RESULTS: Out of 2238 patients undergoing TEER, CVA occurred in 33 (1.47% [95% confidence interval 1.02% to 2.06%]), including 6 (0.27% [0.10% to 0.58%]) inhospital strokes and 27 events after discharge (0.99% [0.66% to 1.44%]) over a median follow-up of of 14 months. Most CVA were major ischemic strokes, during the inhospital phase as well as subsequently. Overall, CVA were more common in patients with atrial fibrillation (p=0.018), renal dysfunction (p=0.032), higher EuroSCORE II (p=0.033), and, as expected, higher CHA2DS2-VASc score (p=0.033), despite the limited prognostic accuracy of such score. Notably, the occurrence of CVA did not confer a significantly increased risk of long-term death (p=0.136) or cardiac death (p=0.397). CONCLUSIONS: The incidence of CVA in patients undergoing TEER is low, with most events occurring after discharge, and being associated with pre-existing risk features. These findings, while reassuring on the safety of TEER, call for proactive antithrombotic therapy whenever CVA risk is increased before, as well as after such intervention.

Investigative agents for atrial fibrillation: agonists and stimulants, progress and expectations.

INTRODUCTION: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Its prevalence has increased due to worldwide populations that are aging in combination with the growing incidence of risk factors associated. Recent advances in our understanding of AF pathophysiology and the identification of nodal players involved in AF-promoting atrial remodeling highlights potential opportunities for new therapeutic approaches. AREAS COVERED: This detailed review summarizes recent developments in the field antiarrhythmic drugs in the field AF. EXPERT OPINION: The current situation is far than optimal. Despite clear unmet needs in drug development in the field of AF treatment, the current development of new drugs is absent. The need for a molecule with absence of cardiac and non-cardiac toxicity in the short and long term is a limitation in the field. Improvement in the understanding of AF genetics, pathophysiology, molecular alterations, big data and artificial intelligence with the objective to provide a personalized AF treatment will be the cornerstone of AF treatment in the coming years.

DOXORUBICIN-RELATED CARDIOTOXICITY: REVIEW OF FUNDAMENTAL PATHWAYS OF CARDIOVASCULAR SYSTEM INJURY.

Over the years, advancements in the field of oncology have made remarkable strides in enhancing the efficacy of medical care for patients with cancer. These modernizations have resulted in prolonged survival and improved the quality of life for these patients. However, this progress has also been accompanied by escalation in mortality rates associated with anthracycline chemotherapy. Anthracyclines, which are known for their potent antitumor properties, are notorious for their substantial cardiotoxic potential. Remarkably, even after six decades of research, a conclusive solution to protect the cardiovascular system against doxorubicin-induced damage has not yet been established. A comprehensive understanding of the pathophysiological processes driving cardiotoxicity combined with targeted research is crucial for developing innovative cardioprotective strategies. This review seeks to explain the mechanisms responsible for structural and functional alterations in doxorubicin-induced cardiomyopathy.

Acute Hyperglycemia-Induced Injury in Myocardial Infarction.

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate.

Exploring the landscape of academic retractions in medicine: a comprehensive umbrella review.

INTRODUCTION: The escalating trend of academic article retractions over the last decades raises concerns about scientific integrity, but heterogeneity in retractions and reasons for them pose a major challenge. We aimed to comprehensively overview systematic reviews focusing on retractions in the biomedical literature. EVIDENCE ACQUISITION: We abstracted salient features and bibliometric details from shortlisted articles. The Joanna Briggs Institute (JBI) Checklist for Systematic Reviews and Research Syntheses was used for validity appraisal. EVIDENCE SYNTHESIS: A total of 11 reviews were included, published between 2016 and 2023, and reporting on a total of 1851 retracted studies. Several major reasons for retractions were identified, spanning both misconduct (e.g., falsification, duplication, plagiarism) and non-misconduct issues (e.g., unreliable data, publishing problems). Correlates include author-related factors (number of authors, nationality) and journal-related factors (impact factor), with repeat offenders contributing significantly. Impacts of retractions is profound, affecting scholarly credibility, public trust, and resource utilization. CONCLUSIONS: In order to prevent retractions and amend their adverse effects, rigorous and transparent reporting standards, enhanced training in research ethics, strengthened peer review processes, and the establishment of collaborative and integrated research integrity offices are proposed.

Multivessel revascularization in non-ST segment elevation acute coronary syndromes: A systematic review and meta-analysis of 182,798 patients.

BACKGROUND: Patients experiencing non-ST segment elevation acute-coronary-syndromes (NSTE-ACS) often present with multivessel-coronary-artery-disease (MVD). An immediate complete multivessel revascularization (MVR) - within the index hospitalization - may be considered the default therapeutic strategy, although its risk-to-benefit profile has not been definitively established through dedicated clinical trials. METHODS: A systematic review and meta-analysis, adhering to MOOSE and PRISMA guidelines, was conducted to assess studies comparing immediate MVR versus a conservative culprit-only revascularization (COR) in NSTE-ACS with MVD. The main endpoints were all-cause death, major adverse cardiovascular events (MACE) and non-fatal myocardial infarction (MI). The incidence of any revascularization or further percutaneous-coronary-interventions (PCIs) were also collected. The primary analyses for the main endpoints were conducted on propensity-matched groups only. RESULTS: A total of 22 studies (182,798 patients) were identified. 7 studies, encompassing 11,372 patients, were included in the primary analysis of propensity score-matched groups. Immediate MVR significantly increased (28%) survival (OR 0.72, 95% CI 0.58-0.90, P < 0.01) along with a 35% reduction in MACE (OR 0.65, 95% CI 0.47-0.88, P = 0.01) and a 60% decrease in MI (OR 0.40, 95% CI 0.25-0.63, P < 0.01) during a mean 3-years follow-up compared to the propensity score-matched COR group. Results were consistent in the unmatched analyses. CONCLUSIONS: This meta-analysis supports an immediate MVR for improving clinical outcomes in patients with NSTE-ACS and MVD as compared to a conservative immediate COR. These data prompt further evaluations regarding optimal strategies in the pursuit of MVR, including patient selection, revascularization modality, and assessment methods of revascularization completeness.

Using ChatGPT to perform a systematic review: a tutorial.

This tutorial provides a comprehensive guide on leveraging ChatGPT for systematic literature reviews, leveraging actual applications in cardiovascular research. Systematic reviews, while essential, are resource-intensive, and ChatGPT offers a potential solution to streamline the process. The tutorial covers the entire review process, from preparation to finalization. In the preparation phase, ChatGPT assists in defining research questions and generating search strings. During the screening phase, ChatGPT can efficiently screen titles and abstracts, processing multiple abstracts simultaneously. The tutorial also introduces an intermediate step of generating study summaries that leads to the generation of reliable data extraction tables. For assessing the risk of bias, ChatGPT can be prompted to perform these tasks. Using each tool's explanation document to generate an appropriate prompt is an efficient method of reliable risk of bias assessments using ChatGPT. However, users are cautioned about potential hallucinations in ChatGPT's outputs and the importance of manual validation. The tutorial emphasizes the need for vigilance, continuous refinement, and gaining experience with ChatGPT to ensure accurate and reliable results. The methods presented have been successfully tried in several projects, but they remain in nascent stages, with ample room for improvement and refinement.

Interplay between gender and pollution on the prognosis of resuscitated out-of-hospital cardiac arrest.

BACKGROUND: Differences between men and women in prognosis after sudden pre-hospital out-of-hospital cardiac arrest (OHCA) have been described in many studies, but the interplay between gender and pollution have not been characterized in detail. We aimed at appraising the interplay between gender and pollution on the prognosis of OHCA. METHODS: Details on patients with OHCA in whom return of spontaneous circulation was obtained and transferred to a large teaching hospital were obtained from the medical charts of the ambulance service and the Polish National Health Fund. Matching pollutant concentrations (PM 2.5, PM10, As, Ni, Cd, Pb) were obtained from the Polish National Environmental Protection Inspectorate. RESULTS: Details on 948 resuscitated OHCA, 325 (34.3%) of them in women, and occurring between 2018 and 2021, were retrieved. Notably, OHCA in women was associated with significantly higher daily concentrations of PM10 (23.37 [17.09, 37.04] vs. 21.92 [16.32, 29.98] µg/m3, P=0.023) and PM2.5 (16.83 [11.87, 28.24] vs. 15.27 [11.64, 22.72] µg/m3, P=0.026), as well as heightened concentrations of Cd, daily (0.32 [0.19, 0.44] vs. 0.27 [0.17, 0.40] ng/m3, P=0.027) and over 30 days (0.34 [0.20, 0.44] vs. 0.29 [0.18, 0.43] ng/m3, P=0.027). Concurrently, OHCA in females was associated with lower daily temperatures on the day of the incident (8.40 [0.20, 15.40] vs. 9.90 [1.40, 15.90] °C, P=0.042). Despite these differences, survival at 30 days and 12 months was similar in women and men (both P>0.05). CONCLUSIONS: OHCA events with successful resuscitation in women occurred in concomitance with higher daily contaminant levels, yet short-term and long-term prognosis was similar in men and women. The interplay between gender and air pollution on OHCA outcomes requires further population-based studies.

Exposure to serum from exclusive heated tobacco product smokers induces mTOR activation and fibrotic features in human cardiac stromal cells.

Chronic smokers have increased risk of fibrosis-related atrial fibrillation. The use of heated-tobacco products (HTPs) is increasing exponentially, and their health impact is still uncertain. We aim to investigate the effects of circulating molecules in exclusive HTP chronic smokers on the fibrotic behavior of human atrial cardiac stromal cells (CSCs). CSCs were isolated from atrial tissue of elective cardiac surgery patients, and exposed to serum lots from young healthy subjects, stratified in exclusive HTP smokers, tobacco combustion cigarette (TCC) smokers, or nonsmokers (NS). CSCs treated with TCC serum displayed impaired migration and increased expression of pro-inflammatory cytokines. Cells cultured with HTP serum showed increased levels of pro-fibrotic markers, and reduced expression of connexin-43. Both TCC and HTP sera increased collagen release and reduced secretion of angiogenic protective factors from CSCs, compared to NS serum. Paracrine support to tube-formation by endothelial cells and to viability of cardiomyocytes was significantly impaired. Treatment with sera of both smokers groups impaired H2O2/NO release balance by CSCs and reduced early phosphorylation of several pathways compared to NS serum, leading to mTOR activation. Cotreatment with rapamycin was able to reduce mTOR phosphorylation and differentiation into aSMA-positive myofibroblasts in CSCs exposed to TCC and HTP sera. In conclusion, the circulating molecules in the serum of chronic exclusive HTP smokers induce fibrotic behavior in CSCs through activation of the mTOR pathway, and reduce their beneficial paracrine effects on endothelial cells and cardiomyocytes. These results point to a potential risk for cardiac fibrosis in chronic HTP users.

Empagliflozin: primum inter pares among sodium-glucose cotransporter-2 inhibitors?

Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a novel class of anti-diabetic medications which have proved capable of providing breakthrough cardiovascular benefits in a variety of clinical scenarios, including patients with heart failure or obesity, irrespective of diabetic status. Several SGLT2 inhibitors are available, but the most prominent ones are canagliflozin, dapagliflozin, and empagliflozin. Several studies have focused on empagliflozin, and its effects on the risk of heart failure incidence and recurrences. Most recently, empagliflozin has been recently tested in patients with recent myocardial infarction in the EMPAgliflozin on Hospitalization for Heart Failure and Mortality in Patients With aCuTe Myocardial Infarction (EMPACT-MI) randomized trial, with apparently ambiguous findings. The present viewpoint succinctly illustrates the main features of SGLT2 inhibitors as a pharmacologic class, their ever expanding role as a cardiovascular medication, and the comparative effectiveness of different individual SGLT2 inhibitors, explicitly commenting on the recent data on empagliflozin in patients with acute myocardial infarction. The reader will find in this article a poignant perspective on this novel avenue for cardiovascular prevention and treatment, which greatly expands the management armamentarium of cardiovascular practitioners. Indeed, we make the case that SGLT2 inhibitors have a clearly favorable class effect, with differences between individual agents mainly suitable for personalization of care and minimization of side effects.

Management of Cardiovascular Complications in Antiphospholipid Syndrome: A Narrative Review with a Focus on Older Adults.

Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-ß2-glycoprotein I (ß2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS.

Prediction of 30-day mortality after surgery for infective endocarditis using risk scores: Insights from a European multicenter comparative validation study.

BACKGROUND: It remains unclear today whether risk scores created specifically to predict early mortality after cardiac operations for infective endocarditis (IE) outperform or not the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II). METHODS: Perioperative data and outcomes from a European multicenter series of patients undergoing surgery for definite IE were retrospectively reviewed. Only the cases with known pathogen and without missing values for all considered variables were retained for analyses. A comparative validation of EuroSCORE II and 5 specific risk scores for early mortality after surgery for IE-(1) STS-IE (Society of Thoracic Surgeons for IE); (2) PALSUSE (Prosthetic valve, Age ≥70, Large intracardiac destruction, Staphylococcus spp, Urgent surgery, Sex (female), EuroSCORE ≥10); (3) ANCLA (Anemia, New York Heart Association class IV, Critical state, Large intracardiac destruction, surgery on thoracic Aorta); (4) AEPEI II (Association pour l'Étude et la Prévention de l'Endocardite Infectieuse II); (5) APORTEI (Análisis de los factores PROnósticos en el Tratamiento quirúrgico de la Endocarditis Infecciosa)-was carried out using calibration plot and receiver-operating characteristic curve analysis. Areas under the curve (AUCs) were compared 1:1 according to the Hanley-McNeil's method. The agreement between APORTEI score and EuroSCORE II of the 30-day mortality prediction after surgery was also appraised. RESULTS: A total of 1,012 patients from 5 European university-affiliated centers underwent 1,036 cardiac operations, with a 30-day mortality after surgery of 9.7%. All IE-specific risk scores considered achieved better results than EuroSCORE II in terms of calibration; AEPEI II and APORTEI score showed the best performances. Despite poor calibration, EuroSCORE II overcame in discrimination every specific risk score (AUC, 0.751 vs 0.693 or less, P = .01 or less). For a higher/lesser than 20% expected mortality, the agreement of prediction between APORTEI score and EuroSCORE II was 86%. CONCLUSION: EuroSCORE II discrimination for 30-day mortality after surgery for IE was higher than 5 established IE-specific risk scores. AEPEI II and APORTEI score showed the best results in terms of calibration.

A 25-year-long journey into interventional cardiology: looking back, and rushing forward.

Cardiovascular disease remains decade after decade a leading cause of mortality, morbidity and resource use globally as well as locally. We have had the opportunity of being involved in several iterative breakthroughs in invasive cardiovascular procedures, ranging from the advent of coronary stents to transcatheter mitral valve repair. Building up such extensive clinical and research experience, we hereby present 25 years of cardiovascular interventions at Pineta Grande Hospital and Casa di Salute S. Lucia, respectively in Castel Volturno, and S. Giuseppe Vesuviano, both in the Italian Campania region, where the same team of interventional cardiologists has managed to adopt and master several cardiovascular innovations for the benefit of thousands of patients. Our experience showcases the evolution of invasive cardiology, especially in diagnostic and therapeutic practices. Key highlights include advancements in coronary procedures, with the introduction of bare-metal stents, drug-eluting stents and drug-coated balloons, despite the setback of bioresorbable vascular scaffolds, as well as transcatheter aortic valve implantation and innovative approaches to mitral regurgitation. Furthermore, this overview scrutinizes procedural challenges, patient outcomes, and quality of life improvements, providing a rich tapestry of clinical experiences and research insights. It serves as a testament to the dynamic nature of interventional cardiology, offering a forward-looking perspective on future trends and technologies. We hope that this overview will prove an informative and insightful read for those seeking to understand the intricate journey of invasive cardiovascular care over the past decades and its trajectory into the future.

Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Acute normovolemic hemodilution in cardiac surgery: rationale and design of a multicenter randomized trial

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 mL as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY Registration: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Transcatheter Mitral Valve Repair With the MitraClip Device for Prior Mitral Valve Repair Failure: Insights From the GIOTTO-FAILS Study.

BACKGROUND: Minimally invasive mitral valve repair has a favorable risk-benefit profile in patients with significant de novo mitral regurgitation. Its role in patients with prior mitral valve repair is uncertain. We aimed to appraise the outcome of patients undergoing transcatheter edge-to-edge repair (TEER) with prior transcatheter or surgical mitral valve repair (SMVR). METHODS AND RESULTS: We queried the Italian multicenter registry on TEER with MitraClip, distinguishing naïve patients from those with prior TEER or (SMVR). Inhospital and long-term clinical/echocardiographic outcomes were appraised. The primary outcome was the occurrence of death or rehospitalization for heart failure. A total of 2238 patients were included, with 2169 (96.9%) who were naïve to any mitral intervention, 29 (1.3%) with prior TEER, and 40 (1.8%) with prior SMVR. Several significant differences were found in baseline clinical and imaging features. Respectively, device success was obtained in 2120 (97.7%), 28 (96.6%), and 38 (95.0%, P=0.261) patients; procedural success in 2080 (95.9%), 25 (86.2%), and 38 (95.0%; P=0.047); and inhospital death in 61 (2.8%), 1 (3.5%), and no (P=0.558) patients. Clinical follow-up after a mean of 14 months showed similar rates of death, cardiac death, rehospitalization, rehospitalization for heart failure, and their composite (all P>0.05). Propensity score-adjusted analysis confirmed unadjusted analysis, with lower procedural success for the prior TEER group (odds ratio, 0.28 [95% CI, 0.09-0.81]; P=0.019) but similar odds ratios and hazard ratios for all other outcomes in the naïve, TEER, and SMVR groups (all P>0.05). CONCLUSIONS: In carefully selected patients, TEER can be performed using the MitraClip device even after prior TEER or SMVR.