Coronary artery disease is becoming the leading cause of death in women in Western society. However, the available data shows that women are still underdiagnosed and undertreated with ...guideline-recommended secondary prevention therapy, leading to a significantly higher rate of in-hospital complications and in-hospital mortality.
The main objective of this work is to assess the approach to acute coronary syndrome (ACS) in Portugal, including form of presentation, in-hospital treatment and in-hospital complications, according to gender and in three different periods.
We performed an observational study with retrospective analysis of all patients included between 2002 and 2019 in the Portuguese Registry of Acute Coronary Syndromes (ProACS), a voluntary, observational, prospective, continuous registry of the Portuguese Society of Cardiology and the National Center for Data Collection in Cardiology.
A total of 49 113 patients (34 936 men and 14 177 women) were included. Obesity, hypertension, diabetes (p<0.001 for all) and dyslipidemia (p=0.022) were all more prevalent in women, who were more frequently admitted for non-ST segment elevation ACS (p<0.001), and more frequently presented with atypical symptoms. Women had more time until needle and until reperfusion, which is less accessible to this gender (p<0.001). During hospitalization, women had a significantly higher risk of in-hospital mortality (OR 1.94 1.78-2.12, p<0.001), major bleeding (OR 1.53 1.30-1.80, p<0.001), heart failure (OR 1.87 1.78-1.97, p<0.001), atrial fibrillation (OR 1.55 1.36-1.77, p<0.001), mechanical complications (OR 2.12 1.78-2.53, p<0.001), cardiogenic shock (OR 1.71 1.57-1.87, p<0.001) and stroke (OR 2.15 1.76-2.62, p<0.001). Women were more likely to have a normal coronary angiogram or coronary lesions with <50% luminal stenosis (p<0.001 for both), and thus a final diagnosis other than ACS. Both during hospitalization and at hospital discharge, women were less likely to receive guideline-recommended secondary prevention therapy.
In women admitted for ACS, revascularization strategies are still underused, as is guideline-recommended secondary prevention therapy, which may explain their higher incidence of in-hospital complications and higher unadjusted mortality.
A doença arterial coronária está-se a tornar a principal causa de morte no mundo ocidental no género feminino. Contudo, os dados de que dispomos mostram que as mulheres são ainda subdiagnosticadas e subtratadas com as terapias de prevenção secundária recomendadas, levando a taxas significativamente mais altas de complicações intra-hospitalares e mortalidade intra-hospitalar.
Avaliar a abordagem nacional às síndromas coronárias agudas, incluindo forma de apresentação, tratamento intra-hospitalar e complicações intra-hospitalares, de acordo com o género e em três períodos distintos.
Estudo observacional com análise retrospetiva de todos os doentes incluídos entre 2002 e 2019 no Registo Nacional de Síndromas Coronárias Agudas (RNSCA), um registo voluntário, observacional, prospetivo e contínuo da Sociedade Portuguesa de Cardiologia e do Centro Nacional de Coleção de Dados em Cardiologia.
Foram incluídos 49 113 doentes (34 936 homens e 14 177 mulheres). Obesidade, hipertensão arterial, diabetes mellitus (p < 0,001 para todos) e dislipidémia (p = 0,022) foram mais prevalentes nas mulheres, que são mais frequentemente admitidas por síndroma coronária aguda sem supradesnivelamento do segmento ST (p < 0,001) e mais frequentemente se apresentam com sintomas atípicos. As mulheres têm tempos mais longos até agulha e até reperfusão, esta última menos frequente neste género (p < 0,001). Durante hospitalização, as mulheres têm um risco significativamente maior de mortalidade intra-hospitalar (OR 1,94 1,78;2,12, p < 0,001), hemorragia major (OR 1,53 1,30;1,80, p < 0,001), insuficiência cardíaca (OR 1,87 1,78;1,97, p < 0,001), fibrilhação auricular (OR 1,55 1,36;1,77, p < 0,001), complicações mecânicas (OR 2,12 1,78;2,53, p < 0,001), choque cardiogénico (OR 1,71 1,57;1,87, p < 0,001) e acidente vascular cerebral (OR 2,15 1,76;2,62, p < 0,001). É mais provável que as mulheres tenham uma coronariografia normal ou lesão coronárias com estenose luminal < 50% (p < 0,001 para ambos) e, assim, um diagnóstico final alternativo a síndroma coronária aguda. Seja durante hospitalização ou à alta hospitalar, é menos provável que as mulheres recebam as terapias de prevenção secundária recomendadas.
Em mulheres admitidas com síndroma coronária aguda as estratégias de revascularização são subutilizadas, assim como as terapias de prevenção secundária recomendadas, podendo justificar a maior incidência de complicações intra-hospitalares e maior mortalidade não ajustada.
Inhibitory junction potentials (IJP) are responsible for smooth muscle relaxation in the gastrointestinal tract. The aim of this study was to pharmacologically characterize the neurotransmitters ...nitric oxide (NO) and adenosine triphosphate (ATP) and receptors involved at the inhibitory neuromuscular junctions in the rat colon using newly available P2Y(1) antagonists.
Organ bath and microelectrode recordings were used to evaluate the effect of drugs on spontaneous mechanical activity and resting membrane potential. IJP and mechanical relaxation were studied using electrical field stimulation (EFS).
N(omega)-nitro-L-arginine (L-NNA) inhibited the slow component of the IJP and partially inhibited the mechanical relaxation induced by EFS. MRS2179, MRS2500 and MRS2279, all selective P2Y(1) receptor antagonists, inhibited the fast component of the IJP without having a major effect on the relaxation induced by EFS. The combination of both L-NNA and P2Y(1) antagonists inhibited the fast and the slow components of the IJP and completely blocked the mechanical relaxation induced by EFS. Sodium nitroprusside caused smooth muscle hyperpolarization and cessation of spontaneous motility that was prevented by oxadiazolo4,3-alphaquinoxalin-1-one. Adenosine 5'-O-2-thiodiphosphate, a preferential P2Y agonist, hyperpolarized smooth muscle cells and decreased spontaneous motility. This effect was inhibited by P2Y(1) antagonists.
The co-transmission process in the rat colon involves ATP and NO. P2Y(1) receptors mediate the fast IJP and NO the slow IJP. The rank order of potency of the P2Y(1) receptor antagonists is MRS2500 greater than MRS2279 greater than MRS2179. P2Y(1) receptors might be potential pharmacological targets for the regulation of gastrointestinal motility.
•The prognosis of patients with acute coronary syndrome (ACS) depends on early diagnosis and treatment.•Chest pain onset presents more than 6 h prior to ED arrival in up to 38.5% of patients with ...chest pain and a final diagnosis of ACS.•Chest pain aggravated by exercise and recurrent chest pain were associated with both late presentation and a final diagnosis of ACS.•Educational initiatives should highlight these features as potential warnings for ACS and thereby encourage patients to seek prompt medical advice.
We investigated which factors predict late presentation (LP) to the emergency department (ED) in patients with non-traumatic chest pain (CP).
All CP cases attended at a single ED (2008–2017) were included. LP was considered if time from CP onset to ED arrival was>6 h. We analyzed associations between 42 patient/CP-related characteristics and LP in the whole cohort and in patients with CP due to acute coronary syndrome (ACS).
The cohort included 25,693 cases (LP=50.6%; ACS=19.0%). Twenty factors were associated with LP, and 8 were also found in patients with ACS: CP of short-duration, aggravated by exertion or breathing/movement, undulating or recurrent CP increased the risk of LP, whereas CP accompanied by diaphoresis, irradiated to the throat, and chronic treatment with nitrates decreased the risk of LP. Exertional and recurrent CP were associated with both, LP and ACS.
Some characteristics, mainly CP-related, may lead to LP to the ED. CP aggravated by exercise and recurrent CP were associated with both LP and a final diagnosis of ACS.
Patient educational initiatives should consider these two features as potential warnings for ACS and thereby encourage patients to seek early medical consultation.
Natural 2'-modified nucleosides are the most widely used antiviral therapy. In their triphosphorylated form, also known as nucleotide analogues, they target the active site of viral polymerases. ...Viral polymerases have an overall right-handed structure that includes the palm, fingers and thumb domains. These domains are further subdivided into structurally conserved motifs A-G, common to all viral polymerases. The structural motifs encapsulate the allosteric/initiation (N1) and orthosteric/catalytic (N2) nucleotide-binding sites. The current study investigated how nucleotide analogues explore the N2 site of viral polymerases from three genera of the family Flaviviridae using a stochastic, biophysical, Metropolis Monte Carlo-based software. The biophysical simulations showed a statistical distinction in nucleotide-binding energy and exploration between phylogenetically related viral polymerases. This distinction is clearly demonstrated by the respective analogue contacts made with conserved viral polymerase residues, the heterogeneous dynamics of structural motifs, and the orientation of the nucleotide analogues within the N2 site. Being able to simulate what occurs within viral-polymerase-binding sites can prove useful in rational drug designs against viruses.
To determine short-term outcomes after an episode of acute heart failure in patients with mid-range ejection fraction (40%–49%; HFmrEF) compared with patients with reduced (<40%) and preserved (>49%) ...ejection fractions (HFrEF and HFpEF, respectively) and according to their final destination after emergency department (ED) care. This is an exploratory, secondary analysis of the Epidemiology of Acute Heart Failure in the Emergency departments Registry, which includes consecutive acute heart failure patients diagnosed in 41 Spanish EDs. Patients with echocardiography data were included and divided into HFrEF, HFmrEF, and HFpEF. The primary outcome was 30-day all-cause mortality, and secondary outcomes were in-hospital all-cause mortality, hospital length of stay >10 days, and 30-day postdischarge ED revisit due to AHF and combined end point (ED revisit and/or death). We included 6,856 patients (age 79 10; 52.1% women): 21.6% had HFrEF, 14.3% HFmrEF, and 64.1% HFpEF. The main destinations for the 982 HFmrEF patients after ED management were internal medicine (293, 29.8%), cardiology (194, 19.9%) and not hospitalized (241, 24.5%), whereas the remaining 254 patients were admitted to other departments, including geriatric wards, short-stay units and intensive care units. Outcomes for HFmrEF did not differ compared with either HFrEF or HFpEF. Compared with HFmrEF admitted to cardiology, internal medicine admission or direct ED discharge increased the 30-day postdischarge ED revisit (hazard ratio HR 1.713, 95% confidence interval CI 1.042 to 2.816; and HR 1.683, 95% CI 1.046 to 2.708, respectively) and the 30-day postdischarge combined end point (HR 1.732, 95% CI 1.070 to 2.803; and HR 1.727, 95% CI 1.083 to 2.756, respectively). In conclusion, patients in the newly created HFmrEF category suffering from an acute decompensation have similar short-term outcomes as those in the classical HFrEF and HFpEF categories; nonetheless, HFmrEF patients handled in cardiology wards during decompensation obtain better outcomes, and reasons for these differences have to be unmasked and corrected.
Both hyperkalemia (HK) and Acute Heart Failure (AHF) are associated with increased short-term mortality, and the management of either may exacerbate the other. As the relationship between HK and AHF ...is poorly described, our purpose was to determine the relationship between HK and short-term outcomes in Emergency Department (ED) AHF.
The EAHFE Registry enrolls all ED AHF patients from 45 Spanish ED and records in-hospital and post-discharge outcomes. Our primary outcome was all-cause in-hospital death, with secondary outcomes of prolonged hospitalization (>7 days) and 7-day post-discharge adverse events (ED revisit, hospitalization, or death). Associations between serum potassium (sK) and outcomes were explored using logistic regression by restricted cubic spline (RCS) curves, with sK =4.0 mEq/L as the reference, adjusting by age, sex, comorbidities, patient baseline status and chronic treatments. Interaction analyses were performed for the primary outcome.
Of 13,606 ED AHF patients, the median (IQR) age was 83 (76–88) years, 54% were women, and the median (IQR) sK was 4.5 mEq/L (4.3–4.9) with a range of 4.0–9.9 mEq/L. In-hospital mortality was 7.7%, with prolonged hospitalization in 35.9%, and a 7-day post-discharge adverse event rate of 8.7%. Adjusted in-hospital mortality increased steadily from sK ≥4.8 (OR = 1.35, 95% CI = 1.01–1.80) to sK = 9.9 (8.41, 3.60–19.6). Non-diabetics with elevated sK had higher odds of death, while chronic treatment with mineralocorticoid-receptor antagonists exhibited a mixed effect. Neither prolonged hospitalization nor post-discharge adverse events was associated with sK.
In ED AHF, initial sK >4.8 mEq/L was independently associated with in-hospital mortality, suggesting that this cohort may benefit from aggressive HK treatment.
Obtaining absolute binding free energies from unbiased ligand diffusion has attracted a significant amount of attention due to its implications in drug design. Several studies have used special ...purpose computers and software to achieve microsecond molecular dynamics which, combined with a Markov state model analysis, are capable of providing absolute binding free energies. We have recently developed a Monte Carlo based technique, PELE, capable of performing a dynamical exploration of the protein–ligand energy landscape including free ligand diffusion into the active site, at a fraction of the computational cost of molecular dynamics techniques. We demonstrate here the capabilities of our Monte Carlo technique in obtaining absolute binding free energies for a series of benzamidine like inhibitors into trypsin. Our results are in good agreement with experimental data and other molecular dynamics simulations, indicating that PELE can be a useful tool for quick estimates of binding free energies and mechanisms.
Increased collagen content of the myocardium modifies tissue reflectivity and integrated backscatter (IBS) indexes are suggested as markers of myocardial fibrosis (MF). We sought to assess the ...correlation between calibrated (c) IBS and bidimensional (2D) strain derived IBS with left ventricular (LV) MF in patients with severe aortic stenosis (AS).
We made a prospective observational cohort study including 157 patients with severe AS referred for surgical aortic valve replacement (AVR), with complete preoperative transthoracic echocardiography, cardiac magnetic resonance (CMR) and endomyocardial biopsy (EMB) obtained from the anterior basal septum at the time of surgery. Two groups of 30 patients were specifically evaluated, with and without late gadolinium enhancement (LGE) at CMR. IBS was obtained at QRS peak from both parasternal long axis (PLAX) and apical-three-chamber (AP3C) views and measured in decibels (dB). Whole-cardiac cycle IBS at basal anterior septum was obtained from 2D longitudinal strain. Correlation analysis of reflectivity indexes was performed with global and segmental (anterior basal septum) values of native T1 and extracellular volume (ECV), and EMB collagen volume fraction (CVF) (Masson´s Trichrome). IBS values were compared in both group of patients (LGE + vs. LGE -). 60 patients (74 36-74 years, 45% male) with high gradient (mean gradient: 63 ± 20mmHg), normal flow (45 ± 10mL/m
) AS and preserved left ventricular ejection fraction (60 ± 9%) were included. Basal septum cIBS was - 17.45 (-31.2-10.95) and - 9.17 ± 9.45dB from PLAX and A3C views, respectively. No significant correlations were found between IBS and both non-invasive CMR tissue characterization and CVF: median MF of 9.7(2.1-79.9)%. Acoustic indexes were not significantly different according to the presence of pre-operative LGE.
In this group of patients with classical severe AS, IBS reflectivity indexes are of no added value to discriminate the presence of MF.
Visible light communications (VLC) have received significant attention as a way of moving part of the saturated indoor wireless traffic to the wide and unregulated visible optical spectrum. Nowadays, ...VLC are considered as a suitable technology, for several applications such as high-rate data transmission, supporting internet of things communications or positioning. The signal processing originally derived from radio-frequency (RF) systems such as cooperative or precoding schemes can be applied to VLC. However, its implementation is not straightforward. Furthermore, unlike RF transmission, VLC present a predominant line-of-sight link, although a weak non-LoS component may appear due to the reflection of the light on walls, floor, ceiling and nearby objects. Blocking effects may compromise the performance of the aforementioned transmission schemes. There exist several surveys in the literature focused on VLC and its applications, but the management of the shadowing and interference in VLC requires a comprehensive study. To fill this gap, this work introduces the implementation of cooperative and precoding schemes to VLC, while remarking their benefits and drawbacks for overcoming the shadowing effects. After that, the combination of both cooperative and precoding schemes is analyzed as a way of providing resilient VLC networks. Finally, we propose several open issues that the cooperative and precoding schemes must face in order to provide satisfactory VLC performance in indoor scenarios.
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