Cangrelor - Expanding therapeutic options in patients with acute coronary syndrome.

Cangrelor is the only intravenous P2Y12 receptor antagonist. It is an adenosine triphosphate analog that selectively, directly, and reversibly binds to the platelet P2Y12 receptors exerting its antiaggregatory effect. Cangrelor is characterized by linear, dose-dependent pharmacokinetics and rapid onset of action providing potent platelet inhibition exceeding 90%. Cangrelor is rapidly metabolized by endothelial endonucleotidase; thus, its half-life is 2.9 to 5.5 min, and its antiplatelet effect subsides within 60 to 90 min. Data originating from three pivotal cangrelor trials (CHAMPION PLATFORM, CHAMPION PCI, and CHAMPION PHOENIX) indicate that cangrelor reduces the risk of periprocedural thrombotic complications during percutaneous coronary intervention at the expense of mild bleedings. Its unique pharmacological properties allow it to overcome the limitations of oral P2Y12 receptor inhibitors, mainly related to the delayed and decreased bioavailability and antiplatelet effect of these agents, which are often observed in the setting of acute coronary syndrome. Subgroups of patients who could theoretically benefit the most from cangrelor include those in whom pharmacokinetics and pharmacodynamics of oral P2Y12 receptor antagonists are most disturbed, namely patients with ST-segment elevation myocardial infarction, those treated with opioids, with mild therapeutic hypothermia, or in cardiogenic shock. Cangrelor could also be useful if bridging is required in patients undergoing surgery. According to the current guidelines cangrelor may be considered in P2Y12 receptor inhibitor-naïve patients undergoing percutaneous coronary intervention in both acute and stable settings.

Statins and the risk of pancreatic cancer: A systematic review and meta-analysis of 2,797,186 patients.

BACKGROUND: Statin use in many studies is related to the improvement of a patients' condition including reducing the risk of various malignancies. Herein, is a systematic review and meta-analysis to examine the evidence on the association between statin therapy and the risk of the occurrence of pancreatic cancer, mainly in terms of decreased risk of developing pancreatic cancer among patients using statin therapy in the long-term perspective. METHODS: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception to December 1st, 2021. Random effect models were used to estimate summary odds ratios (OR) and the corresponding 95% confidence intervals (CI). RESULTS: A total of 26 studies comprising 2,797,186 patients were included. Polled analysis showed that pancreatic cancer occurrence in statin vs. no-statin group varied and amounted to 0.4% vs. 0.6% (RR = 0.83; 95% CI: 0.72-0.96; I² = 84%; p = 0.01). CONCLUSIONS: In summary, the present analysis shows that overall statins use is significantly associated with a reduction in risk of pancreatic cancer. However, these results were not confirmed for the randomized controlled trial subgroup. Further prospective studies are needed to confirm the current results.

The plague of unexpected drug recalls and the pandemic of falsified medications in cardiovascular medicine as a threat to patient safety and global public health: A brief review.

Valsartan, losartan, and irbesartan, are widely used in the treatment strategies of cardiovascular medicine diseases, including hypertension and heart failure. Recently, many formulations for the aforementioned diseases contained active pharmaceutical ingredients and had been abruptly recalled from the market due to safety concerns mainly associated with unwanted impurities - nitrosamines, which are highly carcinogenic substances accidentally produced during manufacturing. Along with cardiovascular medications, formulations containing ranitidine were also recalled from the market. This poses a particular threat to public health due to the non-prescription status of these drugs. Regulatory authorities, including the Food and Drug Administration and European Medicines Agency among others, have taken action to minimize patient risk and improve the manufacturing quality as well as re-checking current guidelines and recommendations. While these steps are necessary to avoid further recalls, authorities should remember the growing concerns of patients regarding the safety and efficacy of pharmacotherapy. Apart from the genuine manufacturing mistakes mentioned above, falsified and counterfeit medications should be at the heart of global attention. The lack of a well-accepted definition of falsified/counterfeit medications has impeded political and scientific efforts to mitigate risk of this phenomenon. Falsified Medicines Directive should be considered the most pivotal legislation recently enacted to harmonize international cooperation. In summary, one should remember that only international and direct collaboration between patients, stakeholders, and authorities be considered a remedy for a pandemic of falsified medicines and plague of unexpected recalls due to safety concerns.

Diagnostic and Prognostic Value of miRNAs after Coronary Artery Bypass Grafting: A Review.

MiRNAs are noncoding, 21-24 nucleotide-long RNA particles that control over 60% of genes. MiRNAs affect gene expression through binding to the 3'-untranslated region of messenger RNA (mRNA), thus inhibiting mRNA translation or inducing mRNA degradation. MiRNAs have been associated with various cardiovascular diseases, including heart failure, hypertension, left ventricular hypertrophy, or ischemic heart disease. In addition, miRNA expression alters during coronary artery bypass grafting (CABG) surgery, which could be used to predict perioperative outcomes. CABG is an operation in which complex coronary arteries stenosis is treated by bypassing atherosclerotic lesions with venous or arterial grafts. Despite a very low perioperative mortality rate and excellent long-term survival, CABG is associated with postoperative complications, including reperfusion injury, graft failure, atrial fibrillation and perioperative myocardial infarction. So far, no reliable diagnostic and prognostic tools to predict prognosis after CABG have been developed. Changes in the perioperative miRNA expression levels could improve the diagnosis of post-CABG myocardial infarction and atrial fibrillation and could be used to stratify risk after CABG. Herein, we describe the expression changes of different subtypes of miRNAs during CABG and review the diagnostic and prognostic utility of miRNAs in patients undergoing CABG.

Procedural and 1-year outcomes following large vessel coronary artery perforation treated by covered stents implantation: Multicentre CRACK registry.

BACKGROUND: Data regarding the clinical outcomes of covered stents (CSs) used to seal coronary artery perforations (CAPs) in the all-comer population are scarce. The aim of the CRACK Registry was to evaluate the procedural, 30-days and 1-year outcomes after CAP treated by CS implantation. METHODS: This multicenter all-comer registry included data of consecutive patients with CAP treated by CS implantation. The primary endpoint was the composite of major adverse cardiac events (MACEs), defined as cardiac death, target lesion revascularization (TLR), and myocardial infarction (MI). RESULTS: The registry included 119 patients (mean age: 68.9 ± 9.7 years, 55.5% men). Acute coronary syndrome, including: unstable angina 21 (17.6%), NSTEMI 26 (21.8%), and STEMI 26 (21.8%), was the presenting diagnosis in 61.3%, and chronic coronary syndromes in 38.7% of patients. The most common lesion type, according to ACC/AHA classification, was type C lesion in 47 (39.5%) of cases. A total of 52 patients (43.7%) had type 3 Ellis classification, 28 patients (23.5%) had type 2 followed by 39 patients (32.8%) with type 1 perforation. Complex PCI was performed in 73 (61.3%) of patients. Periprocedural death occurred in eight patients (6.7%), of which two patients had emergency cardiac surgery. Those patients were excluded from the one-year analysis. Successful sealing of the perforation was achieved in 99 (83.2%) patients. During the follow-up, 26 (26.2%) patients experienced MACE [7 (7.1%) cardiac deaths, 13 (13.1%) TLR, 11 (11.0%) MIs]. Stent thrombosis (ST) occurred in 6 (6.1%) patients [4(4.0%) acute ST, 1(1.0%) subacute ST and 1(1.0%) late ST]. CONCLUSIONS: The use of covered stents is an effective treatment of CAP. The procedural and 1-year outcomes of CAP treated by CS implantation showed that such patients should remain under follow-up due to relatively high risk of MACE.

Kawasaki disease shock syndrome or toxic shock syndrome in children and the relationship with COVID-19.

Most pediatric patients with COVID-19 are asymptomatic or show only mild symptoms. However, in the last two months, first in Europe and recently in the United States, a small number of children have developed a more severe inflammatory syndrome associated with COVID-19, which often leads to hospitalization and sometimes requires intensive care. A potential relationship was observed, especially between the occurrence of the Kawasaki disease and viral upper respiratory tract infections.

Sex-dependent differences in clinical characteristics and in-hospital outcomes in patients with takotsubo syndrome.

INTRODUCTION: Takotsubo syndrome (TTS) is an acute reversible left ventricular dysfunction, which occurs mainly in postmenopausal women. OBJECTIVES: The goal of this study was to compare the course of the disease and prognoses in men and women with TTS in 2 large Polish university hospitals. PATIENTS AND METHODS: The analysis included 232 patients (211 women and 21 men) hospitalized at the 1st Chair and Department of Cardiology at the Medical University of Warsaw and at the 1st Department of Cardiology at the Medical University of Gdansk. RESULTS: Men who developed TTS were more likely to live alone than women. Physical stress triggered TTS more often in men than in women. There were no differences in the prevalence of risk factors and comorbidities, except for a higher prevalence of smoking in men. With regard to the cardiac biomarkers, both admission and peak levels of N­terminal prohormone of brain natriuretic peptide were higher in women. ST­segment depression was found more frequently in men than in women (25% vs 6.2%). Despite the same length of hospitalization, ejection fraction at discharge was lower in men than in women (50% vs 60%). In­hospital outcomes (arrhythmias, mechanical complications, cardiogenic shock, mortality rate) were similar in both groups. ß-Adrenolytics and statins were more often prescribed to women than to men (74.5% vs 52.4% and 68.3% vs 38.1%). Moreover, there was a tendency toward more frequent use of P2Y12 inhibitors in men than in women (23.8% vs 10.4%). CONCLUSIONS: Differences occurred in the clinical course of TTS between men and women. However, in­hospital outcomes were similar in both groups.

Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry.

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre.

BACKGROUND: Severe familial hypercholesterolemia (FH) individuals, refractory to conventional lipidlowering medications are at exceptionally high risk of cardiovascular events. The established therapeutic option of last choice is lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical usefulness of LA in a highly selected group of severe heterozygous FH (HeFH), as recently described by the International Atherosclerosis Society (IAS), for their efficacy in lipid reduction and safety. METHODS: Efficacy and safety of LA were investigated in 318 sessions of 7 severe HeFH females with cardiovascular disease, over a mean period of 26.9 ± 6.5 months. Relative reduction of low density lipoprotein cholesterol (LDL-C) ≥ 60%, clinical complications and vascular access problems were evaluated and compared between the direct adsorption of lipoproteins (DALI) and lipoprotein filtration (Membrane Filtration Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a) [Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fibrinogen concentrations were investigated. RESULTS: The relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 ± 12.9%, 59.7 ± 9.1, 51.5 ± ± 14.2% and 71.3 ± 14.4%, respectively. A similar efficacy was found in both systems in LDL-C removal. DALI system led to larger depletions of Lp(a) (80.0 [76-83]% vs. 73.0 [64.7-78.8]%; p < 0.001). The frequency of clinical side effects and vascular access problems were low (8.5%). CONCLUSIONS: Long-term LA in severe HeFH individuals is safe and efficiently reduces LDL-C and Lp(a). Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the need for individualized application of the LA system in severe HeFH individuals.

Implantation of bioresorbable scaffolds under guidance of optical coherence tomography: Feasibility and pilot clinical results of a systematic protocol.

BACKGROUND: Herein is hypothesised that a comprehensive optical coherence tomography (OCT)-guided implantation protocol for bioresorbable scaffolds (BRS) can improve expansion and apposition, thus resulting in better clinical outcomes, particularly in reducing thrombotic events. METHODS: Patients considered suitable for BRS therapy in de novo coronary lesions underwent OCT. The predominant type of plaque was classified as lipidic, fibrous or calcific. Accordingly they underwent tailored plaque preparation. After proper sizing, BRS was deployed and final OCT was acquired. Post-dilation was performed only in cases of suboptimal deployment. Procedural and 12 month clinical follow-up is reported. RESULTS: Twenty nine patients (41 lesions) who were considered clinically and angiographically suitable for BRS were enrolled, including challenging clinical scenarios such as ST-segment elevation myocardial infarction or CTOs. The OCT-guided protocol was feasible in 90.2% of the lesions: 14 (37.8%) lipidic, 11 (29.7%) fibrous, and 12 (32.4%) calcific. Three (8%) lesions classified as calcific were changed to treatment with metallic stent. BRS were implanted in 34 (91.9%) lesions, thereof 30 (88.2%) with optimal deployment in OCT. One (3.6%) periprocedural MI occurred, resulting in 3.6% target vessel failure and 0% scaffold thrombosis of any kind after a 12 month follow-up. CONCLUSIONS: OCT-guided BRS implantation is feasible in 90.2% of de novo lesions and results in optimal expansion and apposition, correlating with 3.6% incidence of target vessel failure and 0% scaffold thrombosis at 12 m follow-up, probably due to better selection of lesions amenable for BRS treatment and to a possibility of tailoring intervention to the type of plaque. These encouraging pilot results require confirmation in larger clinical studies.

Very late stent thrombosis in everolimus-eluting stent with predisposing mechanical factors: Differential features.

no abstract.

Macrophagic enhancement in optical coherence tomography imaging by means of superparamagnetic iron oxide nanoparticles.

BACKGROUND: The ability of optical coherence tomography (OCT) to visualise macrophages in vivo in coronary arteries is still controversial. We hypothesise that imaging of macrophages in OCT could be enhanced by means of superparamagnetic nanoparticles. METHODS: We compared the optical backscattering and attenuation of cell pellets containing RAW 264.7 macrophages with those of macrophagic cell pellets labelled with very small superparamagnetic oxydised nanoparticles (VSOP) by means of light intensity analysis in OCT. The labelled macrophages were incubated with VSOP at a concentration of 1 mM Fe, corresponding to intracellular iron concentrations of 8.8 pg/cell. To study the effect of intracellular accumulation on the backscattering, VSOP dilutions without cells were also compared. OCT pullbacks of the PCR tubes containing the cell pellets were obtained and light intensity analysis was performed on raw OCT images in polar view, after normalisation by the backscattering of the PCR tube. The backscattering was estimated by the peak normalised intensity, whilst the attenuation was estimated by the number of pixels between the peak and the normalised intensity 1 (peak-to-one). RESULTS: VSOP-loaded macrophages have higher backscattering than the corresponding unlabelled macrophages (peak normalised intensity 6.30 vs. 3.15) with also slightly higher attenuation (peak-toone 61 vs. 66 pixels). The backscattering of the nanoparticles in suspension was negligible in the light intensity analysis. CONCLUSIONS: VSOP increase significantly the optical backscattering of macrophages in the nearinfrared region, with minimal increase in signal attenuation. This finding enables the enhancement of macrophages in conventional OCT imaging with an easily implementable methodology.