Oxidative stress, which results in the damage of diverse biological molecules, is a ubiquitous cellular process implicated in the etiology of many illnesses. The sulfhydryl-containing tripeptide ...glutathione (GSH), which is synthesized and maintained at high concentrations in all cells, is one of the mechanisms by which cells protect themselves from oxidative stress. N-acetylcysteine (NAC), a synthetic derivative of the endogenous amino acid L-cysteine and a precursor of GSH, has been used for several decades as a mucolytic and as an antidote to acetaminophen (paracetamol) poisoning. As a mucolytic, NAC breaks the disulfide bonds of heavily cross-linked mucins, thereby reducing mucus viscosity. In vitro, NAC has antifibrotic effects on lung fibroblasts. As an antidote to acetaminophen poisoning, NAC restores the hepatic GSH pool depleted in the drug detoxification process. More recently, improved knowledge of the mechanisms by which NAC acts has expanded its clinical applications. In particular, the discovery that NAC can modulate the homeostasis of glutamate has prompted studies of NAC in neuropsychiatric diseases characterized by impaired glutamate homeostasis. This narrative review provides an overview of the most relevant and recent evidence on the clinical application of NAC, with a focus on respiratory diseases, acetaminophen poisoning, disorders of the central nervous system (chronic neuropathic pain, depression, schizophrenia, bipolar disorder, and addiction), cardiovascular disease, contrast-induced nephropathy, and ophthalmology (retinitis pigmentosa).
Vitamin D deficiency is a prevalent condition, occurring in about 30–50% of the population, observed across all ethnicities and among all age groups. Besides the established role of vitamin D in ...calcium homeostasis, its deficiency is emerging as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and major CVDs, such as coronary artery disease, heart failure, and atrial fibrillation. Moreover, in all these clinical settings, vitamin deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this review, we aimed to summarize the currently available evidence supporting the link between vitamin D deficiency and major CVDs in terms of its prevalence, clinical relevance, prognostic impact, and potential therapeutic implications.
Aims Circulating microRNAs (miRNAs) may represent a novel class of biomarkers; therefore, we examined whether acute myocardial infarction (MI) modulates miRNAs plasma levels in humans and mice. ...Methods and results Healthy donors (n = 17) and patients (n = 33) with acute ST-segment elevation MI (STEMI) were evaluated. In one cohort (n = 25), the first plasma sample was obtained 517 ± 309 min after the onset of MI symptoms and after coronary reperfusion with percutaneous coronary intervention (PCI); miR-1, -133a, -133b, and -499-5p were ∼15- to 140-fold control, whereas miR-122 and -375 were ∼87–90% lower than control; 5 days later, miR-1, -133a, -133b, -499-5p, and -375 were back to baseline, whereas miR-122 remained lower than control through Day 30. In additional patients (n = 8; four treated with thrombolysis and four with PCI), miRNAs and troponin I (TnI) were quantified simultaneously starting 156 ± 72 min after the onset of symptoms and at different times thereafter. Peak miR-1, -133a, and -133b expression and TnI level occurred at a similar time, whereas miR-499-5p exhibited a slower time course. In mice, miRNAs plasma levels and TnI were measured 15 min after coronary ligation and at different times thereafter. The behaviour of miR-1, -133a, -133b, and -499-5p was similar to STEMI patients; further, reciprocal changes in the expression levels of these miRNAs were found in cardiac tissue 3–6 h after coronary ligation. In contrast, miR-122 and -375 exhibited minor changes and no significant modulation. In mice with acute hind-limb ischaemia, there was no increase in the plasma level of the above miRNAs. Conclusion Acute MI up-regulated miR-1, -133a, -133b, and -499-5p plasma levels, both in humans and mice, whereas miR-122 and -375 were lower than control only in STEMI patients. These miRNAs represent novel biomarkers of cardiac damage.
Contrast-induced nephropathy (CIN) frequently occurs in patients with acute ST-segment elevation myocardial infarction (STEMI) who are undergoing primary percutaneous coronary intervention, and CIN ...is associated with a more complicated clinical course and increased mortality.
To investigate the association between absolute and weight- and creatinine-adjusted contrast volume, CIN incidence, and clinical outcome in the era of mechanical reperfusion of STEMI.
Prospective, observational study.
A university cardiology center in Milan, Italy.
561 consecutive patients with STEMI who were undergoing primary percutaneous coronary intervention.
For each patient, the maximum contrast dose was calculated, according to the formula (5 x body weight kg)/serum creatinine, and the contrast ratio, defined as the ratio between the contrast volume administered and the maximum dose calculated, was assessed. An increase in serum creatinine of more than 25% from baseline was defined as CIN.
115 (20.5%) patients developed CIN. In-hospital mortality was higher among patients with CIN than those without CIN (21.4% vs. 0.9%; P < 0.001). The maximum contrast dose was exceeded in 130 (23%) patients. Patients who received more than the maximum contrast dose (contrast ratio >1) had a more complicated in-hospital clinical course and higher mortality rate (13% vs. 2.8%; P < 0.001) than did patients with a contrast ratio less than 1. Development of CIN was associated with both contrast volume and contrast ratio.
The association between contrast volume and outcomes was observed in a single center and could be due to comorbid conditions, disease severity, or an unknown factor.
During primary percutaneous coronary intervention for STEMI, higher contrast volume is associated with higher rates of CIN and mortality; however, further study is needed to determine whether limiting contrast volume would improve patient outcome.
Centro Cardiologico Monzino, Institute of Cardiology, University of Milan.
The outbreak of coronavirus disease 2019 (COVID-19) has rapidly become a worldwide pandemic. On top of respiratory complications, COVID-19 is associated with major direct and indirect cardiovascular ...consequences, with the latter probably being even more relevant, especially in the setting of time-dependent cardiovascular emergencies. A growing amount of data suggests a dramatic decline in hospital admissions for acute myocardial infarction (AMI) worldwide during the COVID-19 pandemic, mostly since patients did not activate emergency medical systems because hospitals were perceived as dangerous places regarding the infection risk. Moreover, during the COVID-19 pandemic, patients with AMI had a significantly higher in-hospital mortality compared to those admitted before COVID-19, potentially due to late arrival to the hospital. Finally, no consensus has been reached regarding the most adequate healthcare management pathway for AMI and shared guidance on how to handle patients with AMI during the pandemic is still needed. In this review, we will provide an update on epidemiology, clinical characteristics, and outcomes of patients with AMI during the COVID-19 pandemic, with a special focus on its collateral cardiac impact.
Owing to the COVID-19 outbreak in Lombardy, Italy) there is an urgent need to manage cardiovascular emergencies, including acute coronary syndrome (ACS), with appropriate standards of care and ...dedicated preventive measures and pathways against the risk of SARS-CoV-2 infection. For this reason, the Government of Lombardy decided to centralize the treatment of ACS patients in a limited number of centers, including our university cardiology institute, which in the past 4 weeks became a cardiovascular emergency referral center in a regional hub-and-spoke system. Therefore, we rapidly developed a customized pathway to allocate patients to the appropriate hospital ward, and treat them according to ACS severity and risk of suspected SARS-CoV-2 infection. We present here the protocol dedicated to ACS patients adopted in our center since March 13, 2020, and our initial experience in the management of ACS patients during the first 4 weeks of its use. Certainly, the protocol has room for further improvement as everyone’s experience grows, but we hope that it could be a starting point, adaptable to different realities and local resources.
En raison de l'épidémie de COVID-19 en Lombardie (Italie), il est impératif de gérer les urgences cardiovasculaires, y compris les syndromes coronariens aigus (SCA), en suivant des normes de soins appropriées ainsi que des modes d’action et mesures préventives spécifiques contre le risque d'infection par le SARS-CoV-2. C'est pourquoi le Gouvernement de Lombardie a décidé de centraliser le traitement des patients atteints de SCA dans un nombre limité de centres, dont notre institut universitaire de cardiologie, qui est devenu au cours des quatre dernières semaines un centre de référence pour les urgences cardiovasculaires au sein d’un système régional en étoile. Par conséquent, nous avons rapidement mis au point une méthode personnalisée pour affecter les patients au service hospitalier approprié afin de les traiter en fonction de la gravité du SCA et du risque d'infection au SARS-CoV-2 suspectée. Nous présentons ici le protocole dédié aux patients atteints de SCA qui a été adopté dans notre centre depuis le 13 mars 2020, et notre premier bilan de la prise en charge des patients atteints de SCA durant les quatre premières semaines de son application. Certes, le protocole peut encore être amélioré au fur et à mesure que l'expérience de chacun se développe, mais nous espérons qu'il pourra constituer un point de départ, adaptable aux différentes réalités et ressources locales.
Abstract Background There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ...ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload. Methods and Results Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; n = 27). The primary end point of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 5.5 and 7.9 ± 9.0 kg, respectively; P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04–0.48; P = .002). Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group ( P = .33). Conclusions In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.
Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic ...variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect.
We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable ...(SA) and Unstable (UA) angina.
An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated.
Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA.
This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.
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