Ischemic heart disease (IHD) is commonly recognized as the consequence of coronary atherosclerosis and obstructive coronary artery disease (CAD). However, a significant number of patients may present ...angina or myocardial infarction even in the absence of any significant coronary artery stenosis and impairment of the coronary microcirculation has been increasingly implicated as a relevant cause of IHD. The term “coronary microvascular dysfunction” (CMD) encompasses several pathogenic mechanisms resulting in functional and/or structural changes in the coronary microcirculation and determining angina and myocardial ischemia in patients with angina without obstructive CAD (“primary” microvascular angina), as well as in several other conditions, including obstructive CAD, cardiomyopathies, Takotsubo syndrome and heart failure, especially the phenotype with preserved ejection fraction. The pathogenesis of CMD is complex and involves the combination of functional and structural alterations leading to impaired coronary blood flow and resulting in myocardial ischemia. In the absence of therapies specifically targeting CMD, attention has been focused on the role of modifiable risk factors. Here, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD, with a particular focus on the role of cardiovascular risk factors and comorbidities. Moreover, we discuss the specific pathogenic mechanisms of 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.
Inflammation is an important player both for the initiation and progression of coronary artery disease and for coronary plaque instability. Moreover, inflammation contributes to stent thrombosis and ...in-stent restenosis after percutaneous coronary intervention. In the past several decades, most studies evaluated the involvement of cellular effectors of classic inflammatory responses, such as monocytes/macrophages, neutrophils, and T cells. Yet, besides classic inflammation, mounting evidence derived from both experimental and clinical studies suggests an important, often unrecognized, role for effector cells of allergic inflammation in both the pathogenesis of coronary artery disease and adverse events following stent implantation. In this review, we discuss the role of effector cells of allergic inflammation in the setting of coronary artery disease progression and instability, and in the occurrence of adverse events following stent implantation, as well. Moreover, we discuss possible therapeutic approaches targeting different specific pathways of allergic inflammatory activation.
Patients presenting with acute coronary syndrome (ACS) may have different plaque morphologies at the culprit lesion. In particular, plaque rupture (PR) has been shown as the more frequent culprit ...plaque morphology in ACS. However, its prognostic value is still unknown. In this study, we evaluated the prognostic value of PR, compared with intact fibrous cap (IFC), in patients with ACS.
We enrolled consecutive patients admitted to our Coronary Care Unit for ACS and undergoing coronary angiography followed by interpretable optical coherence tomography (OCT) imaging. Culprit lesion was classified as PR and IFC by OCT criteria. Prognosis was assessed according to such culprit lesion classification. Major adverse cardiac events (MACEs) were defined as the composite of cardiac death, non-fatal myocardial infarction, unstable angina, and target lesion revascularization (follow-up mean time 31.58 ± 4.69 months). The study comprised 139 consecutive ACS patients (mean age 64.3 ± 12.0 years, male 73.4%, 92 patients with non-ST elevation ACS and 47 with ST-elevation ACS). Plaque rupture was detected in 82/139 (59%) patients. There were no differences in clinical, angiographic, or procedural data between patients with PR when compared with those having IFC. Major adverse cardiac events occurred more frequently in patients with PR when compared with those having IFC (39.0 vs. 14.0%, P = 0.001). Plaque rupture was an independent predictor of outcome at multivariable analysis (odds ratio 3.735, confidence interval 1.358-9.735).
Patients with ACS presenting with PR as culprit lesion by OCT have a worse prognosis compared with that of patients with IFC. This finding should be taken into account in risk stratification and management of patients with ACS.
The paradigm for the management of patients presenting with angina and/or myocardial ischemia has been historically centered on the detection and treatment of obstructive coronary artery disease ...(CAD). However, in a considerable proportion (30–50%) of patients undergoing coronary angiography, obstructive CAD is excluded. Thus, functional mechanisms may be involved in determining myocardial ischemia and should be investigated. In particular, coronary vasomotor disorders both at epicardial and at microvascular level may play a crucial role, but a definitive diagnosis of these disorders can at times be difficult, given the transience of symptoms, and often requires the use of coronary provocative tests. Of importance, these tests may provide relevant information on the pathogenic mechanism of myocardial ischemia, allowing physicians to tailor the therapies of their patients. Furthermore, several studies underscored the important prognostic information deriving from the use of coronary provocative tests. Nevertheless, their use in clinical practice is currently limited and mainly restricted to specialized centers, with only a minority of patients receiving a benefit from this diagnostic approach.
In this review, we explain the pathophysiological bases for the use of provocative tests, along with their clinical, prognostic and therapeutic implications.
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•Coronary vasomotor disorders may play a relevant role in the pathogenesis of ischemic syndromes.•The use of coronary provocative tests enables to unmask vasomotor disorders.•Provocative tests allow to tailor therapy targeted to the underlying mechanism of disease.•Provocative tests can provide relevant prognostic information.
Heart failure with preserved ejection fraction (HFpEF) is an increasingly studied entity accounting for 50% of all diagnosed heart failure and that has claimed its own dignity being markedly ...different from heart failure with reduced EF in terms of etiology and natural history (
Graziani et al., 2018
). Recently, a growing body of evidence points the finger toward microvascular dysfunction as the major determinant of the pathological cascade that justifies clinical manifestations (
Crea et al., 2017
). The high burden of comorbidities such as metabolic syndrome, hypertension, atrial fibrillation, chronic kidney disease, obstructive sleep apnea, and similar, could lead to a systemic inflammatory state that impacts the physiology of the endothelium and the perivascular environment, engaging complex molecular pathways that ultimately converge to myocardial fibrosis, stiffening, and dysfunction (
Paulus and Tschope, 2013
). These changes could even self-perpetrate with a positive feedback where hypoxia and locally released inflammatory cytokines trigger interstitial fibrosis and hypertrophy (
Ohanyan et al., 2018
). Identifying microvascular dysfunction both as the cause and the maintenance mechanism of this condition has opened the field to explore specific pharmacological targets like nitric oxide (NO) pathway, sarcomeric titin, transforming growth factor beta (TGF-β) pathway, immunomodulators or adenosine receptors, trying to tackle the endothelial impairment that lies in the background of this syndrome (
Graziani et al., 2018
;
Lam et al., 2018
). Yet, many questions remain, and the new data collected still lack a translation to improved treatment strategies. To further elaborate on this tangled and exponentially growing topic, we will review the evidence favoring a microvasculature-driven etiology of this condition, its clinical correlations, the proposed diagnostic workup, and the available/hypothesized therapeutic options to address microvascular dysfunction in the failing heart.
The main adverse reactions to coronary stents are in-stent restenosis (ISR) and stent thrombosis. Along with procedural factors, individual susceptibility to these events plays an important role. In ...particular, inflammatory status, as assessed by C-reactive protein levels, predicts the risk of ISR after bare-metal stent implantation, although it does not predict the risk of stent thrombosis. Conversely, C-reactive protein levels fail to predict the risk of ISR after drug-eluting stent (DES) implantation, although they appear to predict the risk of stent thrombosis. Of note, DES have abated ISR rates occurring in the classical 1-year window, but new concern is emerging regarding late restenosis and thrombosis. The pathogenesis of these late events seems to be related to delayed healing and allergic reactions to polymers, a process in which eosinophils seem to play an important role by enhancing restenosis and thrombosis. The identification of high-risk individuals based on biomarker assessment may be important for the management of patients receiving stent implantation. In this report, we review the evolving role of inflammatory biomarkers in predicting the risk of ISR and stent thrombosis.
Abstract Since the first transcatheter heart valve implantation in the pulmonary position in 2000 and in the aortic position in 2002, a large number of transcatheter heart valves have reached the ...clinical arena and thousands of high-risk patients have been treated successfully, in particular those with severe aortic stenosis. In contrast, the experience of transcatheter mitral valve repair or implantation started relatively more recently, and only a few devices are available at the moment. The aim of this review is to describe the different percutaneous systems for the treatment of mitral regurgitation.
Coronary microvascular dysfunction (CMD) encompasses several pathogenetic mechanisms involving coronary microcirculation and plays a major role in determining myocardial ischemia in patients with ...angina without obstructive coronary artery disease, as well as in several other conditions, including obstructive coronary artery disease, nonischemic cardiomyopathies, takotsubo syndrome, and heart failure, especially the phenotype associated with preserved ejection fraction. Unfortunately, despite the identified pathophysiological and prognostic role of CMD in several conditions, to date, there is no specific treatment for CMD. Due to the emerging role of CMD as common denominator in different clinical phenotypes, additional research in this area is warranted to provide personalized treatments in this "garden variety" of patients. The purpose of this review is to describe the pathophysiological mechanisms of CMD and its mechanistic and prognostic role across different cardiovascular diseases. We will also discuss diagnostic modalities and the potential therapeutic strategies resulting from recent clinical studies.
Development of technologies which utilize hydrogen as energy vector requires the realization of efficient gas storage systems. Materials suitable for hydrogen storage at the solid state have to ...fulfill some specific requirements in order to be used inside the reactors. First of all it is necessary to have a material which could be cycled without observing reduction of performances in terms of kinetics and total hydrogen capacity. The reaction of the material with hydrogen must be reversible even after long time cycling, i.e. repeated absorption and desorption runs. For what concerns the efficiency of the reactors, one of the main parameters to be taken into account is the thermal conductivity of the bed of hydride. The use of powder is detrimental for thermal conductivity and also for gas permeability and particle entrainment by the gas flow in the reactor. Moreover powders after long term cycling tend to pack and sinter evidencing the problems reported before. For this reason powders of hydrides are compacted, generally in cylindrical shape, after mixing with agents for enhancing thermal conductivity and mechanical stability (for example Al, Cu, carbon-based materials). It has been reported that compacted systems during cycling tend to disaggregate returning to the form of powder in the loose form. This swelling mechanism causes rapid slowdown of the kinetics and all the problems correlated to the use of the powders. For this reason many efforts have been spent in order to extend the life of the compacted systems. In this work it is reported the study performed to improve the preparation of compacted powder systems by a procedure which includes the deposition of a thin layer of a metal on the surface of the pellet. The pellets prepared with this procedure demonstrated, after 50 cycles, variations of dimension eight time lower in comparison to those obtained on pellets prepared without coating. The quantity of metal deposited is less than 0.1% of the weight of the pellet and it doesn't affect hydrogen capacity and kinetics of reaction. Kinetics of reaction and microstructure have been studied with a volumetric Sievert's type apparatus and with Optical and Scanning Electron Microscopy respectively.
•Compacted powders were prepared by ball milling MgH2 with Nb2O5 and ENG.•A thin metal coating has been deposited on the pellet surface.•Pellet prepared following this procedure presented increased stability to cycling.•The coating remained continuous and intimately attached to the pellet surface.•Kinetics and total hydrogen capacity has not been affected by the coating.
Abstract
Aims
Functional alterations of epicardial coronary arteries or coronary microcirculation represent a frequent cause of myocardial infarction and non-obstructive coronary arteries (MINOCA). ...We aimed at assessing the prognostic value of intracoronary provocative tests in patients presenting with MINOCA and in which other causes of MINOCA have been excluded.
Methods and results
We prospectively evaluated patients with a diagnosis of MINOCA, excluding patients with aetiologies other than suspected coronary vasomotor abnormalities. Immediately after coronary angiography, an invasive provocative test using acetylcholine or ergonovine was performed. The incidence of death from any cause, cardiac death, and recurrence of acute coronary syndrome (ACS) was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires (SAQ). We enrolled 80 consecutive patients mean age 63.0 ± 10.7 years, 40 (50%) male. Provocative test was positive in 37 (46.2%) patients without any complication. Among patients with a positive test, epicardial spasm was detected in 24 (64.9%) patients and microvascular spasm in 13 (35.1%) patients. After a median follow-up of 36.0 (range 12.0–60.0) months, patients with a positive test had a significantly higher occurrence of death from any cause 12 (32.4%) vs. 2 (4.7%); P = 0.002, cardiac death 7 (18.9%) vs. 0 (0.0%); P = 0.005, and readmission for ACS 10 (27.0%) vs. 3 (7.0%); P = 0.015 as well as a worse angina status as assessed by SAQ Seattle score: 88.0 (33.0–100.0) vs. 100.0 (44.0–100.0); P = 0.001 when compared with patients with a negative test.
Conclusions
We demonstrate that in patients presenting with MINOCA and suspected coronary vasomotor abnormalities, a positive provocative test for spasm is safe and identifies a high-risk subset of patients.
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