Abstract
Background
Patients with type 2 diabetes mellitus (T2DM) are considered as a homogeneous cohort of patients. However, the specific role of diabetic microvascular complications (DMC), in ...determining the features of coronary plaques is poorly known. We investigated whether the presence of DMC may identify a different phenotype of patients associated to specific clinical, angiographic, optical coherence tomography (OCT) features and different prognosis.
Methods
We prospectively enrolled consecutive T2DM patients with obstructive coronary artery disease (CAD) at their first coronary event. Patients were stratified according to the presence or absence of DMC, including diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. OCT assessment of the culprit vessel was performed in a subgroup of patients. The incidence of major adverse cardiac events (MACEs) was assessed at follow-up.
Results
We enrolled 320 T2DM patients (mean age 70.3 ± 8.8 years; 234 73.1% men, 40% acute coronary syndrome, 60% chronic coronary syndrome). Patients with DMC (172 53.75%) presented a different clinical and biochemical profile and, of importance, a higher prevalence of multivessel CAD (109 63.4% vs. 68 45.9%, p = 0.002). At OCT analysis, DMC was associated to a higher prevalence of large calcifications and healed plaques and to a lower prevalence of lipid plaques. Finally, MACEs rate was significantly higher (25 14.5% vs. 12 8.1%, p = 0.007) in DMC patients, mainly driven by a higher rate of planned revascularizations, and DMC predicted the occurrence of MACEs (mean follow-up 33.4 ± 15.6 months).
Conclusions
The presence of DMC identifies a distinct diabetic population with more severe CAD but with a more stable pattern of coronary atherosclerosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•The optimal antithrombotic regimen to be used in patients with AF and PCI or ACS is still debated.•Each of the six randomised controlled trials comparing double to triple therapy has ...limitations.•None was powered to assess differences between treatment arms in ischaemic event rates.•The contrasting results regarding ischaemic events within published meta-analyses can be explained by heterogeneity, incompleteness and varying definitions of stent thrombosis.•The overall reduced bleeding rates, but increased early definite and probable stent thrombosis rates with double versus triple antithrombotic therapy encourage consideration of triple therapy during the first weeks from PCI followed by double therapy.
Ticagrelor is a reversibly binding, direct-acting, oral, P
Y
antagonist used for the prevention of atherothrombotic events in patients with coronary artery disease (CAD). Ticagrelor blocks adenosine ...reuptake through the inhibition of equilibrative nucleoside transporter 1 (ENT-1) on erythrocytes and platelets, thereby facilitating adenosine-induced physiological responses such as an increase in coronary blood flow velocity. Meanwhile, adenosine plays an important role in triggering ischemic preconditioning through the activation of the A1 receptor. Therefore, an increase in ticagrelor-enhanced adenosine bioavailability may confer beneficial effects through mechanisms related to preconditioning activation and improvement of coronary microvascular dysfunction.
To determine whether ticagrelor can trigger ischemic preconditioning and influence microvascular function, we designed this prospective, open-label, pilot study that enrolled patients with stable multivessel CAD requiring staged, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI). Participants will be randomized in 1:1 ratios either to ticagrelor (loading dose (LD) 180 mg, maintenance dose (MD) 90 mg bid) or to clopidogrel (LD 600 mg, MD 75 mg) from 3 to 1 days before the scheduled PCI. The PCI operators will be blinded to the randomization arm. The primary endpoint is the delta (difference) between ST segment elevations (in millimeters, mm) as assessed by intracoronary electrocardiogram (ECG) during the two-step sequential coronary balloon inflation in the culprit vessel. Secondary endpoints are 1) changes in coronary flow reserve (CFR), index of microvascular resistance (IMR), and FFR measured in the culprit vessel and reference vessel at the end of PCI, and 2) angina score during inflations. This study started in 2018 with the aim of enrolling 100 patients. Based on the rate of negative FFR up to 30% and a drop-out rate up to 10%, we expect to detect an absolute difference of 4 mm among the study arms in the mean change of ST elevation following repeated balloon inflations. All study procedures were reviewed and approved by the Ethical Committee of the Catholic University of Sacred Heart.
Ticagrelor might improve ischemia tolerance and microvascular function compared to clopidogrel, and these effects might translate to better long-term clinical outcomes.
EudraCT No. 2016-004746-28. No. NCT02701140. TRIAL STATUS: Information provided in this manuscript refers to the definitive version (n. 3.0) of the study protocol, dated 31 October 2017, and includes all protocol amendments. Recruitment started on 18 September 2018 and is currently ongoing. The enrollment is expected to be completed by the end of 2019.
Fondazione Policlinico Universitario A. Gemelli - Roma, Polo di Scienze Cardiovascolari e Toraciche, Largo Agostino Gemelli 8, 00168 Rome, Italy.
Myocardial bridging (MB) is the most frequent congenital coronary anomaly characterized by a segment of an epicardial coronary artery that passes through the myocardium. MB is an important cause of ...myocardial ischemia and is also emerging as a possible cause of myocardial infarction with non-obstructed coronary arteries (MINOCA). There are multiple mechanisms underlying MINOCA in patients with MB (i.e., MB-mediated increased risk of epicardial or microvascular coronary spasm, atherosclerotic plaque disruption and spontaneous coronary artery dissection). The identification of the exact pathogenetic mechanism is crucial in order to establish a patient-tailored therapy. This review provides the most up-to-date evidence regarding the pathophysiology of MINOCA in patients with MB. Moreover, it focuses on the available diagnostic tools that could be implemented at the time of coronary angiography to achieve a pathophysiologic diagnosis. Finally, it focuses on the therapeutic implications associated with the different pathogenetic mechanisms of MINOCA in patients with MB.
The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenetic mechanisms resulting in functional and/or structural changes in the coronary microcirculation. CMD often ...determines angina and myocardial ischemia in a broad spectrum of cardiovascular diseases, including patients with ischemia with non-obstructive coronary arteries or ischemia with obstructive coronary artery disease, infarction with non-obstructive coronary arteries, cardiomyopathies, the Takotsubo syndrome and heart failure, especially heart failure with preserved ejection fraction. In this article, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.
Graphite nano-sheets, having a thickness of the order of 10
nm, high shape asymmetry, and a well preserved crystalline order, have been prepared by a mechanical method based on the grinding of ...graphite powder under low energy pure shear milling using water as a lubricant. The small applied stress activates the plastic deformation process mainly on the easy gliding (0
0
1) hexagonal planes so that planar flakes bounded by the basal planes are obtained by a purely mechanical process.
•MgH2 was ball milled with TiO2 anatase phase and expanded graphite to prepare pellets.•Different pellets have been prepared at different compression load.•Pellets were repeatedly cycled under ...hydrogen pressure to simulate tank exercise and verify their stability.•The compression load highly affects the stability of the pellets to cycling.•Microstructural evolution of the particles due to cycling have been observed.
The interest in Mg-based hydrides for solid state hydrogen storage is associated to their capability to reversibly absorb and desorb large amounts of hydrogen.
In this work MgH2 powder with 5wt.% TiO2 was ball milled for 10h. The as-milled nanostructured powder was enriched with 5wt.% of Expanded Natural Graphite (ENG) and then compacted in cylindrical pellets by cold pressing using different loads. Both the powder and the pellets were subjected to kinetic and thermodynamic tests using a Sievert’s type gas reaction controller, in order to study the microstructural and kinetic changes which took place during repeated H2 absorption and desorption cycles.
The pellets exhibited good kinetic performance and durability, even if the pressure of compaction revealed to be an important parameter for their mechanical stability.
Scanning Electron Microscopy observations of as-prepared and cycled pellets were carried out to investigate the evolution of their microstructure. In turn the phase composition before and after cycling was analyzed by X-ray diffraction.
Primary percutaneous coronary intervention is nowadays the preferred reperfusion strategy for patients with acute ST-segment–elevation myocardial infarction, aiming at restoring epicardial ...infarct-related artery patency and achieving microvascular reperfusion as early as possible, thus limiting the extent of irreversibly injured myocardium. Yet, in a sizeable proportion of patients, primary percutaneous coronary intervention does not achieve effective myocardial reperfusion due to the occurrence of coronary microvascular obstruction (MVO). The amount of infarcted myocardium, the so-called infarct size, has long been known to be an independent predictor for major adverse cardiovascular events and adverse left ventricular remodeling after myocardial infarction. Previous cardioprotection studies were mainly aimed at protecting cardiomyocytes and reducing infarct size. However, several clinical and preclinical studies have reported that the presence and extent of MVO represent another important independent predictor of adverse left ventricular remodeling, and recent evidences support the notion that MVO may be more predictive of major adverse cardiovascular events than infarct size itself. Although timely and complete reperfusion is the most effective way of limiting myocardial injury and subsequent ventricular remodeling, the translation of effective therapeutic strategies into improved clinical outcomes has been largely disappointing. Of importance, despite the presence of a large number of studies focused on infarct size, only few cardioprotection studies addressed MVO as a therapeutic target. In this review, we provide a detailed summary of MVO including underlying causes, diagnostic techniques, and current therapeutic approaches. Furthermore, we discuss the hypothesis that simultaneously addressing infarct size and MVO may help to translate cardioprotective strategies into improved clinical outcome following ST-segment–elevation myocardial infarction.
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