Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.

Several studies have demonstrated that, beyond their antithrombotic effects, P2Y12 receptor inhibitors may provide additional off-target effects through different mechanisms. These effects range from the preservation of endothelial barrier function to the modulation of inflammation or stabilization of atherosclerotic plaques, with an impact on different cell types, including endothelial and immune cells. Many P2Y12 inhibitors have been developed, from ticlopidine, the first thienopyridine, to the more potent non-thienopyridine derivatives such as ticagrelor which may promote cardioprotective effects following myocardial infarction (MI) by inhibiting adenosine reuptake through sodium-independent equilibrative nucleoside transporter 1 (ENT1). Adenosine may affect different molecular pathways involved in cardiac fibrosis, such as the Wnt (wingless-type)/beta (ß)-catenin signaling. An early pro-fibrotic response of the epicardium and activation of cardiac fibroblasts with the involvement of Wnt1 (wingless-type family member 1)/ß-catenin, are critically required for preserving cardiac function after acute ischemic cardiac injury. This review discusses molecular signaling pathways involved in cardiac fibrosis post MI, focusing on the Wnt/ß-catenin pathway, and the off-target effect of P2Y12 receptor inhibition. A potential role of ticagrelor was speculated in the early modulation of cardiac fibrosis, thanks to its off-target effect.

The Longer the Catheter, the Lower the Risk of Complications: Results of the HERITAGE Study Comparing Long Peripheral and Midline Catheters.

BACKGROUND: Although widely used in clinical practice, long peripheral (LPCs) and midline catheters (MCs) are often misclassified because of their similar characteristics. Studies comparing complications associated to these devices are lacking. The study aim was to explore complications risks associated with polyurethane LPCs and MCs. METHODS: Prospective cohort study. All LPCs and MCs inserted during the study period were included. Catheter-failure within 30-days was the primary outcome, catheter-related bloodstream infection, thrombosis and fibroblastic sleeve were secondary outcomes. The average number of drugs infused per day was computed as a measure of the intensity of a catheter's use throughout its indwelling time. RESULTS: The incidence of catheter-failure was 5.7 and 3.4/1000 catheter-days for LPCs and MCs, respectively. MCs were associated with an adjusted lower risk of catheter-failure (HR 0.311; 95% CI 0.106-0.917; p=0.034). The average number of drugs infused per day was higher for MCs (p<0.001) and was associated to a greater risk of catheter-failure (p=0.021). The bivariate sensitivity analysis showed a decreased risk for catheter failure for MCs only starting from the 10th day from catheter positioning. The incidence of catheter-related bloodstream infection (0.9 vs 0.0/1000 catheter-days), thrombosis (8.7 vs 3.5/1000 catheter-days) and fibroblastic sleeve (14.0 vs 8.1/1000 catheters-days) was higher for LPCs catheters. CONCLUSIONS: Despite more intensive drug administration, MCs were associated with a longer uncomplicated indwelling time.

Transient Left Ventricular Dysfunction from Cardiomyopathies to Myocardial Viability: When and Why Cardiac Function Recovers.

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes.