In eukaryotic cells, mitochondria are involved in a large array of metabolic and bioenergetic processes that are vital for cell survival. Phospholipids are the main building blocks of mitochondrial membranes. Cardiolipin (CL) is a unique phospholipid which is localized and synthesized in the inner mitochondrial membrane (IMM). It is now widely accepted that CL plays a central role in many reactions and processes involved in mitochondrial function and dynamics. Cardiolipin interacts with and is required for optimal activity of several IMM proteins, including the enzyme complexes of the electron transport chain (ETC) and ATP production and for their organization into supercomplexes. Moreover, CL plays an important role in mitochondrial membrane morphology, stability and dynamics, in mitochondrial biogenesis and protein import, in mitophagy, and in different mitochondrial steps of the apoptotic process. It is conceivable that abnormalities in CL content, composition and level of oxidation may negatively impact mitochondrial function and dynamics, with important implications in a variety of pathophysiological situations and diseases. In this review, we focus on the role played by CL in mitochondrial function and dynamics in health and diseases and on the potential of pharmacological modulation of CL through several agents in attenuating mitochondrial dysfunction.

Cardiovascular diseases are the leading cause of death among women, and the incidence among younger women has shown the greatest increase over the last decades, in particular for acute myocardial infarction (AMI). Moreover, the prognosis of women post-AMI is poor when compared with men of similar ages. Since the 1990s, an abundant literature has highlighted the existing differences between sexes with regard to presentation, burden, and impact of traditional risk factors and of risk factors pertaining predominantly to women, the perception of risk by women and men, and the pathophysiological causations, their treatment, and prognosis. These data that have been accumulated over recent years highlight several targets for improvement. The objective of this collaborative work is to define the actions required to reverse the growing incidence of AMI in women and improve the patient pathway and care, as well as the prognosis. We aim to provide practical toolkits for different health professionals involved in the care of women, so that each step, from cardiovascular risk assessment to symptom recognition, to the AMI pathway and rehabilitation, thus facilitating that from prevention to intervention of AMI, can be optimized.

BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment–elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium–defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile–third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P <0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3–22.6] %LVmass versus cangrelor, 16.3 [9.9–24.4] %LVmass; P =0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P =0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60–4.65] %LVmass versus cangrelor, 1.18 [0.53–3.37] %LVmass; P =0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium–defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment–elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03102723.

Background: In patients with de novo coronary artery disease (CAD), percutaneous coronary intervention (PCI) with drug eluting stent (DES) implantation is the gold standard therapy. New evidence is available with drug coated balloons (DCB) angioplasty. The objective of this meta‐analysis was to compare the efficacy and safety of DCB angioplasty versus DES‐based PCI for patients with de novo CAD. Methods: A systematic search of PubMed, Scopus, Web of Science, and EMBASE databases was performed from January 1, 2006 up until November 1, 2024. Inclusion criteria were random treatment assignment; PCI with DCB versus DES; patients with de novo CAD; clinical follow‐up available for ≥1 year; and studies published in a peer‐reviewed journal. Trial‐level incidence rate ratios (IRR) with 95% confidence intervals (CI) were pooled by random‐effects models with inverse variance weighting. The primary outcome was major adverse cardiac events (MACE). Secondary outcomes included cardiac death, all‐cause death, and target lesion revascularization. Results: A total of nine clinical trials comprising of 4284 patients were included. The risk of the primary compositive endpoint of MACE was comparable with DCB versus DES (IRR 0.95, 95% CI 0.61 to 1.48). Secondary endpoints including cardiac death (IRR 1.49, 95% CI 0.96 to 2.33), all‐cause death (IRR 1.18, 95% CI 0.80 to 1.74), and target lesion revascularization (IRR 1.17, 95% CI 0.68 to 2.01) were comparable though CIs around treatment effects were wide. Conclusions: DCB angioplasty for de novo CAD was associated with similar medium‐term clinical outcomes compared with DES. Additional evidence is warranted in view of numerical trends in important secondary endpoints. Trial Registration: The analysis was registered at PROSPERO (CRD42024581222).

Thrombotic and bleeding risks differ between sexes, partly in relation to distinct biology and hormonal status, but also due to differences in age, comorbidities, and body size at presentation. Women experience frequent fluctuations of prothrombotic and bleeding status related to menstrual cycle, use of oral contraceptives, hormone replacement therapy, or menopause. Although clinical studies tend to underrepresent women, available data consistently support sex-specific differences in the baseline thrombotic and haemorrhagic risks. Compared with men, women feature an increased risk of in-hospital bleeding related to invasive procedures, as well as long-term out-of-hospital bleeding events. In addition, the inappropriate dosing of antithrombotic drugs, which is not adapted to body weight or renal function, is more frequently associated with an increased risk of bleeding in women compared to men. While acute coronary syndrome (ACS) studies support similar antithrombotic drug efficacy, irrespective of sex, women may receive delayed treatment due to bias in their referral, diagnosis, and invasive treatment decisions. The current clinical consensus statement highlights the need for an increased awareness of sex-specific risks and biases in ACS management, with a focus on sex-specific bleeding mitigation strategies, antithrombotic management in special conditions (e.g., myocardial infarction with non-obstructive coronary arteries), and barriers to female representation in cardiovascular trials. This manuscript aims to provide expert opinion, based on the best available evidence, and consensus statements on optimising antithrombotic therapy according to sex, which is critical to improve sex-based disparities in outcome.