ABSTRACT Background Sex-related disparities in acute coronary syndrome (ACS) recognition and management remain an important global health concern. Women frequently present with less common symptoms and may experience delays in diagnostic evaluation. This study examined sex-based differences in clinical presentation, management, and outcomes among patients with acute chest pain attended by emergency medical services (EMS) across Brazil. Methods We conducted a retrospective multicenter study using a national registry database from 14 Brazilian states between January 2020 and June 2024, within a large private hospital network. All patients presenting with acute chest pain were classified by trained cardiologists as unstable angina (UA), ST-elevation myocardial infarction (STEMI), or non–ST-elevation myocardial infarction (NSTEMI). Multivariable regression models, with men as the reference group, evaluated sex differences in diagnosis, treatment, and outcomes; categorical outcomes were modeled with logistic or multinomial logistic regression and continuous outcomes with linear regression. Sensitivity analyses included state-clustered standard errors and E-value quantification of potential unmeasured confounding. Results Among 7,171 patients with confirmed ACS (68.2% male), the median age was 63.0 years [IQR 20.0]; women were older than men (67.0 [20.0] vs 61.0 [19.0] years). Final diagnoses were UA in 46.7%, STEMI in 18.8%, and NSTEMI in 34.6% of patients. Men accounted for 75.5% of STEMI and 69.7% of NSTEMI cases. Overall, 91.7% received aspirin and 89.6% received at least one additional antiplatelet agent. After multivariable adjustment, women had higher odds of chest pain classified as probably ischemic and possibly ischemic compared with definitely ischemic chest pain (adjusted OR 1.51 [95% CI 1.33–1.72] and 1.60 [1.37–1.86], respectively) and lower odds of STEMI and NSTEMI relative to unstable angina (adjusted OR 0.59 [0.51–0.68] and 0.74 [0.66–0.83], respectively). Door-to-ECG time was longer in women in the unadjusted analysis (β=1.53 minutes [0.24–2.82]) but the difference was no longer significant after adjustment (β=1.04 minutes [−0.27 to 2.36]). In-hospital mortality did not differ between sexes in unadjusted analysis, and there was no evidence of excess short-term mortality in women. Conclusions Within a large private hospital network in Brazil, women with confirmed ACS were more often classified with less definitely ischemic type of chest pain and were less frequently classified as STEMI or NSTEMI than men. Differences in door-to-ECG time did not persist after adjustment, and in-hospital mortality did not differ by sex. These findings highlight the relevance of sex-sensitive triage and diagnostic protocols within EMS systems to reduce inequities in ACS recognition and treatment.

Resumo Fundamento A fibrilação atrial (FA) é a arritmia cardíaca mais prevalente e sua apresentação difere de acordo com a idade e o sexo. Estudos recentes revelaram diferenças na FA entre vários grupos demográficos, incluindo a população latino-americana. Objetivos Melhor compreender as possíveis disparidades na prevalência da FA e nas estratégias de tratamento na população brasileira por meio de dados de um registro prospectivo multicêntrico de grande escala. Métodos O registro de FA da Rede D’Or é um estudo observacional prospectivo multicêntrico que incluiu pacientes com idade ≥ 18 anos com FA atendidos no pronto-socorro de 32 hospitais terciários no Brasil. Os pacientes foram caracterizados de acordo com o sexo e outras características basais e classificados de acordo com o uso prévio de anticoagulantes. Foi analisada a falta de uso de anticoagulantes em pacientes com indicações prévias. A significância estatística foi estabelecida em 5%. Resultados Os dados do estudo foram provenientes de um total de 1.955 pacientes inscritos. O sexo masculino foi mais prevalente e os homens eram mais jovens que as mulheres. Devido ao aumento da prevalência de episódios anteriores de FA e a um escore CHA2DS2-VASc mais elevado, mais mulheres tiveram indicação de terapia anticoagulante; no entanto, uma proporção significativa não estava recebendo esse tratamento. Dos 29 óbitos intra-hospitalares, 15 pacientes tinham indicação prévia para anticoagulação, mas apenas 3 estavam em uso de anticoagulantes. Conclusão O presente estudo revelou diferenças relacionadas ao sexo na população brasileira de pacientes com FA que são consistentes com tendências em países de alta renda. A promoção de uma melhor implementação de terapias anticoagulantes e antitrombóticas para reduzir o risco de óbito e eventos tromboembólicos entre mulheres com FA no Brasil é crucial.

BACKGROUND:Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, and its presentation differs according to age and sex. Recent studies have revealed differences in AF among various demographic groups, including the Latin American population. OBJECTIVES:To better understand potential disparities in AF prevalence and treatment strategies in the Brazilian population through data from a large multicentric prospective registry. METHODS:The Rede D'Or AF registry is a multicenter prospective observational study including patients aged ≥ 18 years with AF who were seen in the emergency department of 32 tertiary hospitals in Brazil. Patients were characterized according to sex and other baseline characteristics and were classified according to previous anticoagulant use. The lack of anticoagulant use in patients with previous indications was analyzed. Statistical significance was set at 5%. RESULTS:The study data were from a total of 1955 patients enrolled. Male sex was more prevalent, and men were younger than the women. Due to an increased prevalence of previous AF episode and a higher CHA2DS2-VASc score, more women had indications for anticoagulant therapy; however, a significant proportion was not receiving this treatment. From 29 in-hospital deaths, 15 patients had previous indication for anticoagulation, but only 3 were using anticoagulants. CONCLUSION:This study revealed sex-related differences in the Brazilian population of patients with AF that are consistent with trends in high-income countries. The promotion of better implementation of anticoagulant and antithrombotic therapies to reduce the risk of death and thromboembolic events among women with AF in Brazil is crucial.

During pregnancy, it is not expected for pregnant women to experience a heart attack, considering their age group and the incidence of comorbidities in this population. However, we should always be mindful of relevant precautions because, although rare, a heart attack can indeed occur in pregnant women. The classic symptom of a heart attack is chest pain, and it is not uncommon to face diagnostic challenges since numerous more common conditions during pregnancy can mimic this symptom, such as reflux, anxiety, and musculoskeletal pain. If a pregnant woman experiences any episode of chest pain during pregnancy, clinical evaluation is necessary, bearing in mind that although rare, it is among the possible types of heart attacks. The treatment of a heart attack during pregnancy is extremely complex due to the scarcity of clinical data, challenges in drug management, and the physiological changes of pregnancy, as well as the stress of child birth leading to an increase in cardiac effort. Adequate prenatal care and support from referral hospital scan make a difference. In this report, we present a case of a pregnant patient with ST-segment Elevation Myocardial Infarction (STEMI).

Background We explored the effect of discontinuing versus continuing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) on clinical outcomes in patients with COVID-19 according to baseline disease severity.Methods We randomized 659 patients with a confirmed diagnosis of COVID-19 and classified them as having mild or moderate COVID-19 disease severity at hospital presentation using blood oxygen saturation and lung imaging. The primary outcome was the mean ratio of number of days alive and out of the hospital at 30 days according to disease severity.Results At presentation, 376 patients (57.1%) had mild and 283 (42.9%) had moderate COVID-19. In patients with mild disease, there was no significant difference in the number of days alive and out of the hospital between ACEI/ARB discontinuation (mean 23.5 [SD 6.3] days) and continuation (mean 23.8 [SD 6.5] days), with a mean ratio of 0.98 (95% CI 0.92-1.04). However, in patients with moderate disease, there were fewer days alive and out of the hospital with ACEI/ARB discontinuation (mean 19.6 [SD 9.5] days) than continuation (mean 21.6 [SD 7.6] days), with a mean ratio of 0.90 (95% CI 0.81-1.00; P-interaction = .01). The impact of discontinuing versus continuing ACEIs/ARBs on days alive and out of hospital through 30 days differed according to baseline COVID-19 disease severity.Conclusions Unlike patients with mild disease, patients with moderate disease who continued ACEIs/ARBs had more days alive and out of hospital through 30 days than those who discontinued ACEIs/ARBs. This suggests that ACEIs/ARBs should be continued for patients with moderate COVID-19 disease severity.Clinical Trial Registration ClinicalTrials.gov (NCT04364893). (Am Heart J 2022;249:86-97.)

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.

Background: Cardiovascular comorbidities such as hypertension and inflammatory response dysregulation are associated with worse COVID-19 prognoses. Different cytokines have been proposed to play vital pathophysiological roles in COVID-19 progression, but appropriate prognostic biomarkers remain lacking. We hypothesized that the combination of immunological and clinical variables at admission could predict the clinical progression of COVID-19 in hypertensive patients. Methods: The levels of biomarkers, including C-reactive protein, lymphocytes, monocytes, and a panel of 29 cytokines, were measured in blood samples from 167 hypertensive patients included in the BRACE-CORONA trial. The primary outcome was the highest score during hospitalization on the modified WHO Ordinal Scale for Clinical Improvement. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and biomarkers associated significantly with the primary outcome. Results: During hospitalization, 13 (7.8%) patients showed progression to more severe forms of COVID-19, including three deaths. Obesity, diabetes, oxygen saturation, lung involvement on computed tomography examination, the C-reactive protein level, levels of 15 cytokines, and lymphopenia on admission were associated with progression to severe COVID-19. Elevated levels of interleukin-10 and interleukin-12 (p70) combined with two or three of the abovementioned clinical comorbidities were associated strongly with progression to severe COVID-19. The risk of progression to severe disease reached 97.5% in the presence of the five variables included in our model. Conclusions: This study demonstrated that interleukin-10 and interleukin-12 (p70) levels, in combination with clinical variables, at hospital admission are key biomarkers associated with an increased risk of disease progression in hypertensive patients with COVID-19.

Introduction The global pandemic caused by the new coronavirus (COVID-19) has been promoting major challenges and unprecedented clinical decisions in the medical scenario. Currently, according to the World Health Organization, the disease affects over 185 countries, with over 12 million people infected and nearly 500 thousand deaths. Among the most serious manifestations of the syndrome, the high prevalence of thromboembolic events, up to 31% of the patients hospitalized in intensive care units, according to an international series, calls attention.– Different [...]

Importance:It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with coronavirus disease 2019 (COVID-19).Objective:To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days.Design, Setting, and Participants:A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020).Interventions:Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs.Main Outcomes and Measures:The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression.Results:Among 659 patients, the median age was 55.1 years (interquartile range [IQR], 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days [SD, 8 days]) vs patients in the continuation group (mean, 22.9 days [SD, 7.1 days]) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio [OR], 0.97 [95% CI, 0.38-2.52]), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 [95% CI, 0.19-42.12]), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 [95% CI, 0.95-1.80]). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%).Conclusions and Relevance:Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment.Trial Registration:ClinicalTrials.gov Identifier: NCT04364893.

Introduction The current global pandemic caused by the new coronavirus (COVID-19) already reaches 185 countries with approximately 3 million infected people and more than 200 thousand deaths. , With continental dimensions and an elevated socioeconomic disparity, Brazil, by the beginning of May, presents with increasing infection rates and mortality close to 8%. The numbers may be higher considering the lack of adequate testing of the population and healthcare professionals. According to the World Health Organization (WHO), cardiovascular diseases represent the [...]

Background Angiotensin-converting enzyme-2 (ACE2) expression may increase due to upregulation in patients using angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). Because renin-angiotensin system blockers increase levels of ACE2, a protein that facilitates coronavirus entry into cells, there is concern that these drugs could increase the risk of developing a severe and fatal form of COVID-19. The impact of discontinuing ACEI and ARBs in patients with COVID-19 remains uncertain. Design BRACE CORONA is a pragmatic, multicenter, randomized, phase IV, clinical trial that aims to enroll around 500 participants at 34 sites in Brazil. Participants will be identified from an ongoing national registry of suspected and confirmed cases of COVID-19. Eligible patients using renin-angiotensin system blockers (ACEI/ARBs) with a confirmed diagnosis of COVID-19 will be randomized to a strategy of continued ACEI/ARB treatment versus temporary discontinuation for 30 days. The primary outcome is the median days alive and out of the hospital at 30 days. Secondary outcomes include progression of COVID-19 disease, all-cause mortality, death from cardiovascular causes, myocardial infarction, stroke, transient ischemic attack, new or worsening heart failure, myocarditis, pericarditis, arrhythmias, thromboembolic events, hypertensive crisis, respiratory failure, hemodynamic decompensation, sepsis, renal failure, and troponin, B-type natriuretic peptide (BNP), N-terminal-proBNP, and D-dimer levels. Summary BRACE CORONA will evaluate whether the strategy of continued ACEI/ARB therapy compared with temporary discontinuation of these drugs impacts clinical outcomes among patients with COVID-19.

COVID-19 is a new disease caused by the Sars-CoV-2 virus and the vast majority of patients have symptoms similar to a flu-like syndrome. A small portion of those infected ends up being hospitalized and may develop with the most severe presentation of the disease. Data from Chinese series report that hypertension appears to be a condition that imposes a greater risk of unfavorable evolution of patients. Some studies have reported that Sars-CoV-2 uses the angiotensin-converting enzyme to access its target cells. There are theories that differ about the protective or harmful role that drugs that act in the renin angiotensin aldosterone system in these patients. A British study suggests that patients using angiotensin-converting enzyme inhibitors had a lower incidence of severe forms of the disease. Another study carried out a retrospective and multicenter analysis showing that mortality was lower in the group that had used the drugs when compared to the other group (3,7 vs. 9,8%; p=0,01). The various hypotheses raised through pathophysiology are not yet able to really predict the best course of action for patients using drugs that act on the renin angiotensin system. Thus, a randomized study becomes important to try to answer definitively and with a high degree of reliability to this question.

BackgroundAbdominal aortic aneurysm (AAA) is a pathological enlargement of infrarenal aorta close to the aortic bifurcation, and it is an important cause of mortality in the elderly. Therefore, the biomarker identification for early diagnosis is of great interest for clinical benefit. It is known that microRNAs (miRNAs) have important roles via target genes regulation in many diseases. This study aimed to identify miRNAs and their target genes involved in the pathogenesis of AAA.MethodsTissue samples were obtained from patients who underwent AAA surgery and from organ donors (control group). Quantitative PCR Array was applied to assess 84 genes and 384 miRNAs aiming to identify differentially expressed targets (AAA n = 6, control n = 6), followed by validation in a new cohort (AAA n = 18, control n = 6) by regular qPCR. The functional interaction between validated miRNAs and target genes was performed by the Ingenuity Pathway Analysis (IPA) software.ResultsThe screening cohort assessed by PCR array identified 10 genes and 59 miRNAs differentially expressed (>= 2-fold change, p< 0.05). Among these, IPA identified 5 genes and 9 miRNAs with paired interaction. ALOX5, PTGIS, CX3CL1 genes, and miR-193a-3p, 125b-5p, 150-5p maintained a statistical significance in the validation cohort. IPA analysis based on the validated genes and miRNAs revealed that eicosanoid and metalloproteinase/TIMP synthesis are potentially involved in AAA.ConclusionPaired interactions of differentially expressed ALOX5, PTGIS, CX3CL1 genes, and miR193b-3p, 125b-5p, 150-5p revealed a potentially significant role of the eicosanoid synthesis and metalloproteinase/TIMP pathways in the AAA pathogenesis.

Atrial fibrillation (AF) is the most common arrhythmia after cardiac surgery. From a pathophysiological point of view, a myriad of factors such as trauma, atrial dilation, ischemia, mechanical myopericarditis, autonomic imbalance, loss of connexins, AF nest remodeling, inflammation, sutures, and dysfunction caused by postextracorporeal circulation can contribute to postoperative atrial fibrillation (POAF) resulting in a longer hospital stay and consequently higher cost. Recent studies showed that short fragments of RNA, called microRNA (miRNA), can contribute to the development of several cardiovascular diseases, including AF. The aim of this study was to evaluate the levels of circulating miRNAs (miR-1, -23a, and -26a) that can be involved in POAF. Patients submitted to coronary artery bypass graft surgery were grouped in POAF (24 patients) and without POAF (24 patients). Results showed older age, longer clamp-time, and more days in the intensive care unit as well as a longer total hospital stay in the POAF group. Preoperative levels of circulating miRNAs were similar. Analysis of miRNAs revealed significantly lower circulating levels of miRNA-23a (P  =  0.02) and -26a (P  =  0.01) in the POAF group during the postoperative period. Receiver operating characteristic (ROC) analysis showed the area under the ROC curve of miR-23a and miR-26a for predicting FA was 0.63 (95% confidence interval [CI]: 0.51-0.74; P  =  0.02) and 0.66 (95% CI: 0.55-0.77; P  =  0.01), respectively. Our data suggests that circulating miRNA-23a and -26a may be involved in the underlying biology of postoperative AF development.

BACKGROUND:Major advances have been made in heart transplantation, but there is a discrepancy between the number of patients potentially treatable by transplantation and the limited number of viable grafts. The aim of this study was to evaluate the reasons for refusal of donor hearts. METHODS:This was a retrospective analysis of donor data from an organ procurement organization in the state of São Paulo (Brazil) between 2010 and 2012. Fisher's exact test, Student's t-test, and the Mann-Whitney U-test were used in the statistical analysis. RESULTS:Only 26 (7.9%) of 328 potential heart donors actually became donors. Most donors were men (18/26, 69.2%), Caucasians (14/26, 53.8%), and had a mean age of 23.5 yr. There were significant associations of use of donor hearts with the variables: brain death after trauma (p = 0.002), history of hypertension (p = 0.001), electrocardiographic changes (p = 0.007), and age (p = 0.001). Older age (n = 101, 33.4%) was the main reason for refusal of donor hearts, followed by poor medical history (n = 44, 14.6%), cardiac arrest of the donor during donor care (n = 25, 8.3%), use of vasopressor drugs (n = 23, 7.6%), and hemodynamic instability (n = 20, 6.6%). CONCLUSIONS:Age, poor medical history, cardiac arrest, use of vasopressors, and hemodynamic instability were the most prevalent reasons for refusal of donor hearts. Echocardiogram evaluation is a potential intervention to improve heart transplantation conversion in Brazil.