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.

Prevention of cardiotoxicity in childhood cancer survivors: In physical exercise, we trust.

In recent years, the mean survival rate of children after a cancer diagnosis has significantly improved. At the same time, a growing interest in short and long-term cardiovascular (CV) complications of cancer therapy, as well as long-term CV risk in childhood cancer survivors (CCS) developed, along with proposals of protocols for the diagnosis, management, and prevention of cancer therapy-related CV toxicity (CTR-CVT) in this population. Many clinical and individual risk factors for CTR-CVT have been identified, and a non-negligible prevalence of traditional CV risk factors has been described in this population, potentially associated with a further worsening in both CTR-CVT and long-term CV risk. Physical exercise (PE) represents a promising, free-of-cost and free-of-complications, helpful therapy for primary and secondary prevention of CTR-CVT in CCS. The present narrative review aims to summarize the most critical evidence available about CTR-CVT in CCS, focusing on the role of PE in this clinical scenario.

Left Atrial Strain to Predict Postoperative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery being associated with poorer outcomes. Revealing before the operation of left atrial subtle structural/functional abnormalities may help to identify patients at increased risk of POAF. We investigated the role of left atrial strain parameters by preoperative speckle tracking echocardiography as independent predictors of POAF in patients undergoing coronary artery bypass graft. METHODS: Consecutive patients undergoing isolated coronary artery bypass graft were prospectively enrolled at three Italian centers. All patients underwent transthoracic echocardiography before the operation. The occurrence of POAF up to discharge was monitored. RESULTS: Overall, a total of 310 patients were included. POAF was demonstrated in 103 patients (33%). At receiver operating characteristic curve analysis, lower global peak atrial longitudinal strain (PALS) values significantly predicted the risk of POAF (area under the curve, 0.74; P<0.001). The optimal cutoff value for the arrhythmia prediction was a global PALS value <28%, with a specificity of 86% and a sensitivity of 36%. The incidence of POAF was 51% in patients with global PALS <28% versus 14% in those with PALS ≥28% (P<0.001), with a POAF-free survival at Kaplan-Meier analysis of 45.4% and 85.7%, respectively (P<0.001). At multivariate analysis, a global PALS <28% carried a 3.6-fold higher risk of POAF (hazard ratio, 3.6 [95% CI, 2.2-5.9]; P<0.001). The risk increase was even higher when PALS <28% was associated with age ≥70 years (adjusted hazard ratio, 11.2 [4.7-26.6], P<0.001). CONCLUSIONS: A presurgery global PALS <28% is a specific parameter to stratify patients at increased risk of POAF after coronary artery bypass graft. This assessment can be useful to identify patients at higher arrhythmic risk in whom perioperative preventive strategies and stricter monitoring aimed at early diagnosing and treating POAF may be applied.

A real-world multicenter study on left atrial appendage occlusion: The Italian multi-device experience.

Background: Transcatheter left atrial appendage occlusion (LAAO) has emerged as an alternative treatment for stroke prevention in patients with atrial fibrillation (AF) at high risk of thromboembolism, who cannot tolerate long-term oral anticoagulation (OAC). Questions persist regarding effectiveness and safety of this treatment and the optimal post-interventional antithrombotic regimen after LAAO. Methods: We retrospectively gathered data from 428 patients who underwent percutaneous LAAO in 6 Italian high-volume centres, aimed at describing the real-world utilization, safety, and effectiveness of LAAO procedures, also assessing the clinical outcomes associated with different antithrombotic strategies. Results: Among the entire population, 20 (4.7 %) patients experienced a combination of pericardial effusion and periprocedural major bleeding: 8 (1.9 %) pericardial effusion, 1 (0.3 %) fatal bleeding, and 3 (0.7 %) non-fatal procedural major bleeding. Patients were discharged with different antithrombotic regimens: dual (DAPT) (27 %) or single (SAPT) (26 %) antiplatelet therapy, OAC (27 %), other antithrombotic regimens (14 %). Very few patients were not prescribed with antithrombotic drugs (6 %). At a medium 523 ± 58 days follow-up, 14 patients (3.3 %) experienced all-cause death, 6 patients (1.4 %) cardiovascular death, 3 patients (0.7 %) major bleeding, 10 patients (2.6 %) clinically relevant non-major bleeding, and 3 patients (0.7 %) ischemic stroke. At survival analysis, with DAPT as the reference group, OAC therapy was associated with better outcomes. Conclusions: Our findings confirm that LAAO is a safe procedure. Different individualized post-discharge antithrombotic regimens are now adopted, likely driven by the perceived thrombotic and hemorrhagic risk. The incidence of both ischemic and bleeding events tends to be low.

Ex Vivo Antiplatelet Effects of Oral Anticoagulants.

BACKGROUND: The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on platelet function is still unclear. We conducted a comprehensive ex vivo study aimed at assessing the effect of the four currently marketed NOACs on platelet function. METHODS: We incubated blood samples from healthy donors with concentrations of NOACs (50, 150 and 250 ng/mL), in the range of those achieved in the plasma of patients during therapy. We evaluated generation of thrombin; light transmittance platelet aggregation (LTA) in response to adenosine diphosphate (ADP), thrombin receptor-activating peptide (TRAP), human γ-thrombin (THR) and tissue factor (TF); generation of thromboxane (TX)B2; and expression of protease-activated receptor (PAR)-1 and P-selectin on the platelet surface. RESULTS: All NOACs concentration-dependently reduced thrombin generation compared with control. THR-induced LTA was suppressed by the addition of dabigatran at any concentration, while TF-induced LTA was reduced by factor-Xa inhibitors. ADP- and TRAP-induced LTA was not modified by NOACs. TXB2 generation was reduced by all NOACs, particularly at the highest concentrations. We found a concentration-dependent increase in PAR-1 expression after incubation with dabigatran, mainly at the highest concentrations, but not with FXa inhibitors; P-selectin expression was not changed by any drugs. CONCLUSIONS: Treatment with the NOACs is associated with measurable ex vivo changes in platelet function, arguing for antiplatelet effects beyond the well-known anticoagulant activities of these drugs. There are differences, however, among the NOACs, especially between dabigatran and the FXa inhibitors.

Role of CES1 and ABCB1 Genetic Polymorphisms on Functional Response to Dabigatran in Patients with Atrial Fibrillation.

Background: Dabigatran etexilate is a pro-drug hydrolyzed into dabigatran by carboxylesterases (CES) and is a substrate of the P-Glycoprotein encoded by the adenosine-triphosphate-binding cassette sub-family B member (ABCB)1 genes. We evaluated the functional response to dabigatran according to different CES1 and ABCB1 single-nucleotide polymorphisms (SNPs) in patients with atrial fibrillation (AF). Methods: A total of 100 consecutive patients with AF taking dabigatran were enrolled by two Italian centers. A venous blood sample was drawn for genetic determinations, as well as a measurement of the diluted thrombin time (dTT) and drug plasma concentrations, at the trough and peak. The main objective was the relationship between the dTT values and CES1 rs2244613, CES1 rs8192935 and ABCB1 rs4148738 SNP while on two different dabigatran doses (110 and 150 mg BID). Results: A total of 43 patients were on a 110 mg dabigatran dose and 57 on 150 mg. The DTT values at the trough and at peak were not different among patients with different CES1 rs2244613 and CES1 rs8192935 genotypes, regardless of the dabigatran dose. In patients on 150 mg dabigatran, the dTT values at the trough were 77 (44-111) ng/mL in patients with the ABCB1 rs4148738 heterozygous CT genotype vs. 127 (85-147) ng/mL in the wild-type CC genotype vs. 110 (47-159) ng/mL in the mutant trait TT genotype (p = 0.048). In patients with the ABCB1 rs4148738 CT genotype, OR for having dTT values at a trough below the median was 3.21, 95% CI 1.04-9.88 (p = 0.042). Conclusions: ABCB1 rs4148738 CT heterozygous is associated with the reduced anticoagulant activity of dabigatran at the trough in patients receiving the higher dose regimen.

Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.