Gender equality in medical research: A cardiology-informed examination.

Despite a perceived increase in attention to gender differences in medicine, a comprehensive assessment of gender equality research, particularly in cardiology, remains underexplored. This observational retrospective study, focusing on documents related to "Gender Equality" according to the Sustainable Development Goals, reveals cardiology as a significant area for gender equality research, albeit with a decline in publications post-2018. The analysis highlighted a concentrated effort in the United States and a considerable impact gap between gender-focused and general cardiology research. The global academic community must intensify research into gender disparities, which is essential for achieving professional gender equality and addressing the burden of cardiovascular diseases.

Percutaneous interventions for pulmonary embolism.

Pulmonary embolism (PE) ranks as a leading cause of in-hospital mortality and the third most common cause of cardiovascular death. The spectrum of PE manifestations varies widely, making it difficult to determine the best treatment approach for specific patients. Conventional treatment options include anticoagulation, thrombolysis, or surgery, but emerging percutaneous interventional procedures are being investigated for their potential benefits in heterogeneous PE populations. These novel interventional techniques encompass catheter-directed thrombolysis, mechanical thrombectomy, and hybrid approaches combining different mechanisms. Furthermore, inferior vena cava filters are also available as an option for PE prevention. Such interventions may offer faster improvements in right ventricular function, as well as in pulmonary and systemic haemodynamics, in individual patients. Moreover, percutaneous treatment may be a valid alternative to traditional therapies in high bleeding risk patients and could potentially reduce the burden of mortality related to major bleeds, such as that of haemorrhagic strokes. Nevertheless, the safety and efficacy of these techniques compared to conservative therapies have not been conclusively established. This review offers a comprehensive evaluation of the current evidence for percutaneous interventions in PE and provides guidance for selecting appropriate patients and treatments. It serves as a valuable resource for future researchers and clinicians seeking to advance this field. Additionally, we explore future perspectives, proposing "percutaneous primary pulmonary intervention" as a potential paradigm shift in the field.

Periprocedural myocardial infarction and injury.

Periprocedural myocardial infarction (PMI) and injury, pertinent to both cardiac and non-cardiac procedures, have gained increasing recognition in clinical practice. Over time, diverse definitions for diagnosing PMI have been developed and validated among patient populations undergoing coronary revascularization. However, this variety in definitions presents considerable challenges in clinical settings and complicates both the design and interpretation of clinical trials. The necessity to accurately diagnose PMI has spurred significant interest in establishing universally accepted and prognostically meaningful thresholds for cardiac biomarkers elevation and supportive ancillary criteria. In fact, elevations in cardiac biomarkers in line with the 4th Universal Definition of Myocardial Infarction, have been extensively confirmed to be associated with increased mortality and cardiovascular events. In the context of non-coronary cardiac procedures, such as Transcatheter Aortic Valve Implantation, there is a growing acknowledgment of both the high incidence rates and the adverse impact of PMI on patient outcomes. Similarly, emerging research underscores the significance of PMI and injury in non-cardiac surgery, highlighting the urgent need for effective prevention and risk management strategies in this domain.

Coronary Angiography, Intravascular Ultrasound, and Optical Coherence Tomography for Guiding of Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Results from multiple randomized clinical trials comparing outcomes after intravascular ultrasound (IVUS)- and optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) with invasive coronary angiography (ICA)-guided PCI as well as a pivotal trial comparing the 2 intravascular imaging (IVI) techniques have provided mixed results. METHODS: Major electronic databases were searched to identify eligible trials evaluating at least 2 PCI guidance strategies among ICA, IVUS, and OCT. The 2 coprimary outcomes were target lesion revascularization and myocardial infarction. The secondary outcomes included ischemia-driven target lesion revascularization, target vessel myocardial infarction, death, cardiac death, target vessel revascularization, stent thrombosis, and major adverse cardiac events. Frequentist random-effects network meta-analyses were conducted. The results were replicated by Bayesian random-effects models. Pairwise meta-analyses of the direct components, multiple sensitivity analyses, and pairwise meta-analyses IVI versus ICA were supplemented. RESULTS: The results from 24 randomized trials (15 489 patients: IVUS versus ICA, 46.4%, 7189 patients; OCT versus ICA, 32.1%, 4976 patients; OCT versus IVUS, 21.4%, 3324 patients) were included in the network meta-analyses. IVUS was associated with reduced target lesion revascularization compared with ICA (odds ratio [OR], 0.69 [95% CI, 0.54-0.87]), whereas no significant differences were observed between OCT and ICA (OR, 0.83 [95% CI, 0.63-1.09]) and OCT and IVUS (OR, 1.21 [95% CI, 0.88-1.66]). Myocardial infarction did not significantly differ between guidance strategies (IVUS versus ICA: OR, 0.91 [95% CI, 0.70-1.19]; OCT versus ICA: OR, 0.87 [95% CI, 0.68-1.11]; OCT versus IVUS: OR, 0.96 [95% CI, 0.69-1.33]). These results were consistent with the secondary outcomes of ischemia-driven target lesion revascularization, target vessel myocardial infarction, and target vessel revascularization, and sensitivity analyses generally did not reveal inconsistency. OCT was associated with a significant reduction of stent thrombosis compared with ICA (OR, 0.49 [95% CI, 0.26-0.92]) but only in the frequentist analysis. Similarly, the results in terms of survival between IVUS or OCT and ICA were uncertain across analyses. A total of 25 randomized trials (17 128 patients) were included in the pairwise meta-analyses IVI versus ICA where IVI guidance was associated with reduced target lesion revascularization, cardiac death, and stent thrombosis. CONCLUSIONS: IVI-guided PCI was associated with a reduction in ischemia-driven target lesion revascularization compared with ICA-guided PCI, with the difference most evident for IVUS. In contrast, no significant differences in myocardial infarction were observed between guidance strategies.

Pharmacological and clinical appraisal of factor XI inhibitor drugs.

The evolution of anticoagulation therapy, from vitamin K antagonists to the advent of direct oral anticoagulants (DOACs) almost two decades ago, marks significant progress. Despite improved safety demonstrated in pivotal trials and post-marketing observations, persistent concerns exist, particularly regarding bleeding risk and the absence of therapeutic indications in specific subgroups or clinical contexts. Factor XI (FXI) has recently emerged as a pivotal contributor to intraluminal thrombus formation and growth, playing a limited role in sealing vessel wall injuries. Inhibiting FXI presents an opportunity to decouple thrombosis from haemostasis, addressing concerns related to bleeding events while safeguarding against thromboembolic events. Notably, FXI inhibition holds promise for patients with end-stage renal disease or cancer, where clear indications for DOACs are currently lacking. Various compounds have undergone design, testing, and progression to phase 2 clinical trials, demonstrating a generally favourable safety and tolerability profile. However, validation through large-scale phase 3 trials with sufficient power to assess both safety and efficacy outcomes is needed. This review comprehensively examines FXI inhibitors, delving into individual classes, exploring their pharmacological properties, evaluating the latest evidence from randomized trials, and offering insights into future perspectives.

Association of trial characteristics with simultaneous publication and its impact on citations and mentions: a cross-sectional study.

INTRODUCTION AND OBJECTIVES: Randomized trials are often presented at medical conferences and published simultaneously or later. Predictors of simultaneous publication and its consequences are undetermined. Our aim was to characterize the practice of simultaneous publication, identify its predictors, and evaluate its impact. METHODS: In this cross-sectional study, we included randomized trials presented at late-breaking science sessions of major cardiovascular conferences from 2015 to 2021. The association of trial characteristics with the timing of publication was analyzed. The impact of simultaneous vs nonsimultaneous publication was investigated on the number of 1-year citations and 1-month mentions, and the total citations and mentions at the longest observation follow-up. RESULTS: Of 478 trials included in the analysis, 48.7% were published simultaneously. Simultaneous publications were more likely to be presented in the main conference room (OR, 6.09; 95%CI, 1.34-36.92; P=.029) and were characterized by a shorter review time (OR, 0.95; 95%CI, 0.91-0.96; P<.001). Simultaneous publications were associated with higher 1-year citations (R2, 43.81; 95%CI, 23.89-63.73; P<.001), 1-month mentions (R2, 132.32; 95%CI, 85.42-179.22; P<.001) and total citations (R2, 222.89; 95%CI, 127.98-317.80; P<.001). CONCLUSIONS: Randomized trials presented in the main conference room and with shorter review time were more likely to be published simultaneously. Simultaneous publications were associated with more citations and mentions than nonsimultaneous publications.

PCSK9 inhibitors: current status and emerging frontiers in lipid control.

INTRODUCTION: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, imposing substantial healthcare economic burdens. Among the modifiable risk factors, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in ASCVD development. Novel therapies such as PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors are emerging to address this concern. These inhibitors offer the potential to reduce ASCVD risk by directly targeting LDL-C levels. AREAS COVERED: The article reviews the structural and functional aspects of PCSK9, highlighting its role in LDL receptor regulation. The pharmacological strategies for PCSK9 inhibition, including monoclonal antibodies, binding peptides, gene silencing, and active immunization, are explored. Clinical evidence from various trials underscores the safety and efficacy of PCSK9 inhibitors in reducing LDL-C levels and potentially improving cardiovascular outcomes. Despite these promising results, challenges such as cost-effectiveness and long-term safety considerations are addressed. EXPERT OPINION: Among PCSK9 inhibitors, monoclonal antibodies represent a cornerstone. Many trials have showed their efficacy in reducing LDL-C and the risk for major adverse clinical events, revealing long-lasting effects, with special benefits particularly for statin-intolerant and familial hypercholesterolemia patients. However, long-term impacts, high costs, and patient selection necessitate further research.

Evaluating the pharmacokinetic and pharmacodynamic impact of different modes of ticagrelor administration.

INTRODUCTION: Alternative administration modes for oral P2Y12 inhibitors, particularly ticagrelor, have emerged as a potential alternative to overcome the limitations associated with the delayed onset of action of these drugs in patients who are unable to swallow or with impaired absorption. AREAS COVERED: This comprehensive literature review aims to provide an overview of the current state of knowledge on the pharmacokinetics and administration modes of ticagrelor, including factors that may affect its action. It also compares the pharmacokinetics of ticagrelor with that of other drugs with similar uses to provide a comprehensive understanding of the potential advantages and limitations of different modalities of P2Y12 administration. For this purpose, Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, Google Scholar, and ClinicalTrials.gov were searched from database inception to July 2023. EXPERT OPINION: Among the different alternatives, crushed formulations, especially for ticagrelor, have emerged as the most promising option, showing early and robust platelet inhibition. However, important questions remain unanswered, such as the comparative clinical benefits of crushed ticagrelor versus standard administration, the cost-effectiveness of alternative modes compared to intravenous P2Y12 inhibitors such as cangrelor, and the important limitations associated with the concomitant use of opioids, who have been proven to impair even the action of crushed ticagrelor.

Antithrombotic Therapy for Primary and Secondary Prevention of Ischemic Stroke: JACC State-of-the-Art Review.

Stroke is a devastating condition with significant morbidity and mortality worldwide. Antithrombotic therapy plays a crucial role in both primary and secondary prevention of stroke events. Single or dual antiplatelet therapy is generally preferred in cases of large-artery atherosclerosis and small-vessel disease, whereas anticoagulation is recommended in conditions of blood stasis or hypercoagulable states that mostly result in red thrombi. However, the benefit of antithrombotic therapies must be weighed against the increased risk of bleeding, which can pose significant challenges in the pharmacological management of this condition. This review provides a comprehensive summary of the currently available evidence on antithrombotic therapy for ischemic stroke and outlines an updated therapeutic algorithm to support physicians in tailoring the strategy to the individual patient and the underlying mechanism of stroke.

Complete Percutaneous Coronary Revascularization in Acute Coronary Syndromes With Multivessel Coronary Disease: A Systematic Review.

Multivessel disease (MVD) affects approximately 50% of patients with acute coronary syndromes (ACS) and is significantly burdened by poor outcomes and high mortality. It represents a clinical challenge in patient management and decision making and subtends an evolving research area related to the pathophysiology of unstable plaques and local or systemic inflammation. The benefits of complete revascularization are established in hemodynamically stable ACS patients with MVD, and guidelines provide some reference points to inform clinical practice, based on an evidence level that is solid for ST-segment elevation myocardial infarction and less robust for non-ST-segment elevation myocardial infarction and cardiogenic shock. However, several areas of uncertainty remain, such as the optimal timing for complete revascularization or the best guiding strategy for intermediate stenoses. We performed a systematic review of current evidence in the field of percutaneous revascularization in ACS and MVD, also including future perspectives from ongoing trials that will directly compare different timing strategies and investigate the role of invasive and noninvasive guidance techniques. (Complete percutaneous coronary revascularization in patients with acute myocardial infarction and multivessel disease; CRD42022383123).

Eligibility to Intensified Antithrombotic Regimens for Secondary Prevention in Patients Who Underwent Percutaneous Coronary Intervention.

Single antiplatelet therapy (SAPT) and intensified antithrombotic regimens (prolonged dual antiplatelet therapy [DAPT] or dual pathway inhibition [DPI]) are recommended for secondary prevention in patients who underwent percutaneous coronary intervention (PCI) after initial DAPT. We aimed to characterize eligibility to such strategies and to explore to what extent guidelines are applied in clinical practice. Patients who underwent PCI for acute or chronic coronary syndrome who completed initial DAPT were analyzed from a prospective registry. Patients were categorized into SAPT, prolonged DAPT/DPI, or DPI groups as per guideline indication by using a risk stratification algorithm. Predictors of receiving intensified regimens and the divergency of practice from guidelines were investigated. Between October 2019 and September 2021, a total of 819 patients were included. Based on the guidelines, 83.7% of patients qualified for SAPT, 9.6% for any intensified regimen (i.e., prolonged DAPT or DPI), and 6.7% for DPI only. At multivariable analysis, patients were more likely to receive an intensified regimen if they had diabetes, dyslipidemia, peripheral artery disease, multivessel disease, or previous myocardial infarction. Conversely, they were less likely to receive an intensified regimen if they had atrial fibrillation, chronic kidney disease, or previous stroke. Guidelines were not followed in 18.3% of cases. In particular, only 14.3% of candidates to intensified regimens were treated accordingly. In conclusion, although the majority of patients who underwent PCI after the initial period of DAPT were eligible for SAPT, 1 out of 6 had an indication to intensified regimens. However, such intensified regimens were underused among eligible patients.

Pharmacology and Clinical Development of Factor XI Inhibitors.

Therapeutic anticoagulation is indicated for a variety of circumstances and conditions in several fields of medicine to prevent or treat venous and arterial thromboembolism. According to the different mechanisms of action, the available parenteral and oral anticoagulant drugs share the common principle of hampering or blocking key steps of the coagulation cascade, which unavoidably comes at the price of an increased propensity to bleed. Hemorrhagic complications affect patient prognosis both directly and indirectly (ie, by preventing the adoption of an effective antithrombotic strategy). Inhibition of factor XI (FXI) has emerged as a strategy with the potential to uncouple the pharmacological effect and the adverse events of anticoagulant therapy. This observation is based on the differential contribution of FXI to thrombus amplification, in which it plays a major role, and hemostasis, in which it plays an ancillary role in final clot consolidation. Several agents were developed to inhibit FXI at different stages (ie, suppressing biosynthesis, preventing zymogen activation, or impeding the biological action of the active form), including antisense oligonucleotides, monoclonal antibodies, small synthetic molecules, natural peptides, and aptamers. Phase 2 studies of different classes of FXI inhibitors in orthopedic surgery suggested that dose-dependent reductions in thrombotic complications are not paralleled by dose-dependent increases in bleeding compared with low-molecular-weight heparin. Likewise, the FXI inhibitor asundexian was associated with lower rates of bleeding compared with the activated factor X inhibitor apixaban in patients with atrial fibrillation, although no evidence of a therapeutic effect on stroke prevention is available so far. FXI inhibition could also be appealing for patients with other conditions, including end-stage renal disease, noncardioembolic stroke, or acute myocardial infarction, for which other phase 2 studies have been conducted. The balance between thromboprophylaxis and bleeding achieved by FXI inhibitors needs confirmation in large-scale phase 3 clinical trials powered for clinical end points. Several of such trials are ongoing or planned to define the role of FXI inhibitors in clinical practice and to clarify which FXI inhibitor may be most suited for each clinical indication. This article reviews the rationale, pharmacology, results of medium or small phase 2 studies, and future perspectives of drugs inhibiting FXI.

Diuresis-matched versus standard hydration in patients undergoing percutaneous cardiovascular procedures: meta-analysis of randomized clinical trials.

INTRODUCTION AND OBJECTIVES: Contrast-associated acute kidney injury (CA-AKI) is a potential complication of procedures requiring administration of iodinated contrast medium. RenalGuard, which provides real-time matching of intravenous hydration with furosemide-induced diuresis, is an alternative to standard periprocedural hydration strategies. The evidence on RenalGuard in patients undergoing percutaneous cardiovascular procedures is sparse. We used a Bayesian framework to perform a meta-analysis of RenalGuard as a CA-AKI preventive strategy. METHODS: We searched Medline, Cochrane Library and Web of Science for randomized trials of RenalGuard vs standard periprocedural hydration strategies. The primary outcome was CA-AKI. Secondary outcomes were all-cause death, cardiogenic shock, acute pulmonary edema, and renal failure requiring renal replacement therapy. A Bayesian random-effect risk ratio (RR) with corresponding 95% credibility interval (95%CrI) was calculated for each outcome. PROSPERO database number CRD42022378489. RESULTS: Six studies were included. RenalGuard was associated with a significant relative reduction in CA-AKI (median RR, 0.54; 95%CrI, 0.31-0.86) and acute pulmonary edema (median RR, 0.35; 95%CrI, 0.12-0.87). No significant differences were observed for the other secondary endpoints [all-cause death (RR, 0.49; 95%CrI, 0.13-1.08), cardiogenic shock (RR, 0.06; 95%CrI, 0.00-1.91), and renal replacement therapy (RR, 0.52; 95%CrI, 0.18-1.18)]. The Bayesian analysis also showed that RenalGuard had a high probability of ranking first for all the secondary outcomes. These results were consistent in multiple sensitivity analyses. CONCLUSIONS: In patients undergoing percutaneous cardiovascular procedures, RenalGuard was associated with a reduced risk of CA-AKI and acute pulmonary edema compared with standard periprocedural hydration strategies.

Delayed First Milking in Unassisted Overnight Calving Did Not Affect the Quality of Colostrum but Influenced Serum Brix Refractometry in Holstein Calves at Two Days of Life.

Timely administration of good-quality colostrum represents the first farm strategy to avoid the failure of passive transfer (FPT). However, calves born during the night are likely to be fed later than recommended. Our aim was to evaluate whether night-occurring calving and delayed first milking affected colostrum quality and immune passive transfer. The dataset included 463 calvings. Four liters of colostrum were administered by an esophageal tube feeder. The mean Brix% of colostrum was 27.43%, while serum Brix% at two days of life in calves was 10.19%. According to the Generalized Linear Model, parity ≥ 4, calving months of March, April, and from September to November positively influenced the quality of colostrum. Dams carrying a male calf produced lower quality colostrum compared with those carrying a female calf (−2.78 ± 1.04 Brix%, p = 0.008); heavier female calves were associated with greater colostrum quality (0.29 ± 0.05 for each kg increase, p < 0.001). Night- or day-calving had no effect on the quality of colostrum. The only factor influencing the serum Brix% of female Holstein calves at two days of life was the day- or night-occurring birth (−0.386 ± 0.188 Brix% in calves born during the night, p = 0.04). Our results showed that calves born overnight and fed the day after had decreased serum Total Protein concentrations as indicated by reduced Brix refractometer readings, compared with calves born during the day and fed quickly after birth. However, the administration of 4 L of high-quality colostrum likely improved their serum Brix% at two days of life. Alternatively, where the prevalence of good-quality colostrum is lower, improving calving supervision and ensuring timely feeding are important to reduce the risk of FPT.

Antithrombotic therapy after transcatheter aortic valve implantation.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is a treatment option for patients with symptomatic severe aortic stenosis across the entire spectrum of surgical risk. TAVI conveys some risk for thrombotic complications, requiring antithrombotic drugs for their prevention. Bleeding events represent the major drawback of antithrombotic therapy, which should be carefully tailored over the individual patient's risk profile. AREAS COVERED: This review aimed at exploring the rationale for the adoption of a tailored antithrombotic therapy after successful TAVI, with a description and analysis of common complications and their impact on therapy selection. In addition, we aimed at reviewing and discussing current knowledge in this area, with a main focus on the high-quality evidence supporting latest guideline recommendations. Finally, ongoing studies and future directions on antithrombotic therapy after TAVI were outlined. EXPERT OPINION: Initial experience with antithrombotic therapy after TAVI was derived from percutaneous coronary intervention practice. Accruing evidence in the field led to the current monotherapy paradigm, which prioritizes oral anticoagulant and single antiplatelet therapy in patients with or without an established indication for long-term anticoagulation, respectively. Future studies will investigate the role of alternative antithrombotic strategies to improve clinical outcomes of TAVI patients by minimizing both thrombotic and bleeding complications.

Aortic stenosis is the most common primary valve disease requiring treatment. Transcatheter aortic valve implantation (TAVI) is a percutaneous treatment option for patients with symptomatic severe aortic stenosis across the entire spectrum of surgical risk. To prevent several complications of TAVI, antithrombotic drugs (i.e. antiplatelets or anticoagulants) are required after the intervention. The major drawback of such therapies is represented by bleeding, which makes important a careful consideration of the individual patient's risk profile. This review article explores the rationale for the adoption of a tailored antithrombotic therapy after TAVI, with a description and analysis of common complications and their impact on therapy selection. In addition, we reviewed and discussed current knowledge in this area, with a main focus on the evidence supporting latest guideline recommendations and their potential evolution. Finally, ongoing studies and future directions on antithrombotic therapy after TAVI were presented.

An Observational Study Assessing Immediate Complete Versus Delayed Complete Revascularisation in Patients with Multi-Vessel Disease Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: More than half of the patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have multi-vessel coronary artery disease. This is associated with worse outcomes compared with single vessel disease. Whilst evidence now exists to support complete revascularisation for bystander disease the optimal timing is still debated. This study aimed to compare clinical outcomes in patients with STEMI and multi-vessel disease who underwent complete revascularisation as inpatients in comparison to patients who had staged PCI as early outpatients. METHODS AND RESULTS: We conducted an observational cohort study consisting of 1522 patients who underwent primary PCI with multi-vessel disease from 2012 to 2019. Exclusions included patients with cardiogenic shock and previous CABG. Patients were split into 2 groups depending on whether they had complete revascularisation performed as inpatients or as staged PCI at later outpatient dates. The primary outcome of this study was major adverse cardiac events (consisting of myocardial infarction, target vessel revascularisation and all-cause mortality).834 (54.8%) patients underwent complete inpatient revascularisation and 688 patients (45.2%) had outpatient PCI (median 43 days post discharge). Of the inpatient group, 652 patients (78.2%) underwent complete revascularisation during the index procedure whilst 182 (21.8%) patients underwent inpatient bystander PCI in a second procedure. Overall, there were no significant differences between the groups with regards to their baseline or procedural characteristics. Over the follow-up period there was no significant difference in MACE between the cohorts (P = .62), which persisted after multivariate adjustment (HR 1.21 [95% CI 0.72-1.96]). Furthermore, in propensity-matched analysis there was no significant difference in outcome between the groups (HR: 0.86 95% CI: 0.75-1.25). CONCLUSIONS: Our study demonstrated that the timing of bystander PCI after STEMI did not appear to have an effect on cardiovascular outcomes. We suggest that patients with multi-vessel disease can potentially be discharged promptly and undergo early outpatient bystander PCI. This could significantly reduce length of stay in hospital.