Allopurinol versus Trimetazidine for the Treatment of Angina: A Randomized Clinical Trial. / Alopurinol Versus Trimetazidina para o Tratamento da Angina: Ensaio Clínico Randomizado.

BACKGROUND: Recently, it was demonstrated that allopurinol, a xanthine oxidase inhibitor, has cardiovascular and anti-ischaemic properties and may be a metabolic antianginal agent option.Objective: The objective of this study was to evaluate the antianginal effect of allopurinol as a third drug for patients with stable coronary artery disease (CAD). METHODS: This was a randomized clinical trial between 2018 and 2020 including patients with CAD who maintained angina despite initial optimization with beta-blockers and calcium channel blockers. The individuals were randomized 1:1 to 300 mg of allopurinol twice daily or 35 mg of trimetazidine twice daily. The main outcome was the difference in the angina frequency domain of the Seattle Angina Questionnaire (SAQ-AF). A probability (p) value < 0.05 was considered statistically significant. RESULTS: A hundred and eight patients were included in the randomization phase, with 54 (50%) in the allopurinol group and 54 (50%) in the trimetazidine group. Six (5.6%) individuals, 3 from each group, were lost to follow-up for the primary outcome. In the allopurinol and trimetazidine groups, the median SAQ-AF scores were 50 (30.0 to 70.0) and 50 (21.3 to 78.3), respectively. In both groups, the SAQ-AF score improved, but the median of the difference compared to baseline was lower in the allopurinol group (10 [0 to 30] versus 20 [10 to 40]; p < 0.001), as was the mean of the difference in the total SAQ score (12.8 ± 17.8 versus 21.2 ± 15.9; p = 0.014). CONCLUSION: Both allopurinol and trimetazidine improved the control of angina symptoms; however, trimetazidine presented a greater gain compared to baseline. Brazilian Registry of Clinical Trials - Registration Number RBR-5kh98y.

FUNDAMENTO: Recentemente, foi demonstrado que o alopurinol, um inibidor da xantina oxidase, possui propriedades cardiovasculares e anti-isquêmicas e pode ser uma opção de agente antianginoso metabólico. OBJETIVO: O objetivo do presente estudo foi avaliar o efeito antianginoso do alopurinol como terceiro medicamento para pacientes com doença arterial coronariana (DAC) estável. MÉTODOS: Trata-se de um ensaio clínico randomizado entre 2018 e 2020 incluindo pacientes com DAC que mantiveram angina apesar da otimização inicial com betabloqueadores e bloqueadores dos canais de cálcio. Os indivíduos foram randomizados 1:1 para 300 mg de alopurinol 2 vezes ao dia ou 35 mg de trimetazidina 2 vezes ao dia. O desfecho principal foi a diferença no domínio da frequência da angina do Questionário de Angina de Seattle (QAS-FA). Foram considerados estatisticamente significativos valores de probabilidade (p) < 0,05. RESULTADOS: Foram incluídos 108 pacientes na fase de randomização, com 54 (50%) no grupo alopurinol e 54 (50%) no grupo trimetazidina. Seis (5,6%) indivíduos, 3 de cada grupo, foram perdidos no seguimento para o desfecho primário. Nos grupos de alopurinol e trimetazidina, as pontuações medianas do QAS-FA foram 50 (30,0 a 70,0) e 50 (21,3 a 78,3), respectivamente. Em ambos os grupos, a pontuação do QAS-FA melhorou, mas a mediana da diferença em relação à linha de base foi menor no grupo alopurinol (10 [0 a 30] versus 20 [10 a 40]; p < 0,001), assim como a média da diferença na pontuação total do QAS (12,8 ± 17,8 versus 21,2 ± 15,9; p = 0,014). CONCLUSÃO: Tanto o alopurinol quanto a trimetazidina melhoraram o controle dos sintomas de angina; no entanto, a trimetazidina apresentou um ganho maior em relação à linha de base. Registro Brasileiro de Ensaios Clínicos ­ Número de Registro RBR-5kh98y.

Impact of Tricuspid Repair on Surgical Death in Patients Undergoing Mitral Valve Surgery Due to Rheumatic Disease.

Background: Tricuspid valve repair during mitral valve replacement surgery remains a controversial topic. The risk-benefit ratio in some populations remains uncertain, especially in rheumatic heart disease patients. Therefore, we aimed to evaluate the impact of concomitant tricuspid repair on surgical mortality in patients undergoing cardiac surgery due to rheumatic mitral valve disease who have moderate to severe functional tricuspid regurgitation. Methods: This is a prospective cohort study from January 1, 2017, to December 30, 2022. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with concomitant moderate to severe tricuspid regurgitation were included. The primary outcome was a surgical death. In an exploratory analysis, clinical and echocardiographic data were obtained 2 years after the procedure. Results: Of the 144 patients included, 83 (57.6%) underwent tricuspid valve repair. The mean age was 46.2 (±12.3) years with 107 (74.3%) female individuals, the median left ventricular ejection fraction was 61.0% (55-67), and systolic pulmonary artery pressure (sPAP) was 55.0 mmHg (46-74), with 45 (31.3%) individuals with right ventricular dysfunction. The total in-hospital mortality was 15 (10.4%) individuals, and there was no difference between the groups submitted or not to tricuspid repair: 10 (12.0%) vs. 5 (7.5%); p = 0.46, respectively. There was an association with one variable independently: the sPAP value, relative risk 1.04 (1.01-1.07), p = 0.01. The estimated cut-off value of sPAP that indicates higher early mortality through the receiver operating characteristic curve (area 0.70, p = 0.012) was 73.5 mmHg. Conclusions: Performing tricuspid repair in individuals who were undergoing cardiac surgery to correct rheumatic mitral valve disease was not associated with increased surgical mortality. Our results suggest the safety of tricuspid repair even in this high-risk population, reinforcing the recommendations in current guidelines.

Alopurinol Versus Trimetazidina para o Tratamento da Angina: Ensaio Clínico Randomizado / Allopurinol versus Trimetazidine for the Treatment of Angina: A Randomized Clinical Trial

Resumo Fundamento Recentemente, foi demonstrado que o alopurinol, um inibidor da xantina oxidase, possui propriedades cardiovasculares e anti-isquêmicas e pode ser uma opção de agente antianginoso metabólico. Objetivo O objetivo do presente estudo foi avaliar o efeito antianginoso do alopurinol como terceiro medicamento para pacientes com doença arterial coronariana (DAC) estável. Métodos Trata-se de um ensaio clínico randomizado entre 2018 e 2020 incluindo pacientes com DAC que mantiveram angina apesar da otimização inicial com betabloqueadores e bloqueadores dos canais de cálcio. Os indivíduos foram randomizados 1:1 para 300 mg de alopurinol 2 vezes ao dia ou 35 mg de trimetazidina 2 vezes ao dia. O desfecho principal foi a diferença no domínio da frequência da angina do Questionário de Angina de Seattle (QAS-FA). Foram considerados estatisticamente significativos valores de probabilidade (p) < 0,05. Resultados Foram incluídos 108 pacientes na fase de randomização, com 54 (50%) no grupo alopurinol e 54 (50%) no grupo trimetazidina. Seis (5,6%) indivíduos, 3 de cada grupo, foram perdidos no seguimento para o desfecho primário. Nos grupos de alopurinol e trimetazidina, as pontuações medianas do QAS-FA foram 50 (30,0 a 70,0) e 50 (21,3 a 78,3), respectivamente. Em ambos os grupos, a pontuação do QAS-FA melhorou, mas a mediana da diferença em relação à linha de base foi menor no grupo alopurinol (10 [0 a 30] versus 20 [10 a 40]; p < 0,001), assim como a média da diferença na pontuação total do QAS (12,8 ± 17,8 versus 21,2 ± 15,9; p = 0,014). Conclusão Tanto o alopurinol quanto a trimetazidina melhoraram o controle dos sintomas de angina; no entanto, a trimetazidina apresentou um ganho maior em relação à linha de base. Registro Brasileiro de Ensaios Clínicos - Número de Registro RBR-5kh98y

Abstract Background Recently, it was demonstrated that allopurinol, a xanthine oxidase inhibitor, has cardiovascular and anti-ischaemic properties and may be a metabolic antianginal agent option.Objective: The objective of this study was to evaluate the antianginal effect of allopurinol as a third drug for patients with stable coronary artery disease (CAD). Methods This was a randomized clinical trial between 2018 and 2020 including patients with CAD who maintained angina despite initial optimization with beta-blockers and calcium channel blockers. The individuals were randomized 1:1 to 300 mg of allopurinol twice daily or 35 mg of trimetazidine twice daily. The main outcome was the difference in the angina frequency domain of the Seattle Angina Questionnaire (SAQ-AF). A probability (p) value < 0.05 was considered statistically significant. Results A hundred and eight patients were included in the randomization phase, with 54 (50%) in the allopurinol group and 54 (50%) in the trimetazidine group. Six (5.6%) individuals, 3 from each group, were lost to follow-up for the primary outcome. In the allopurinol and trimetazidine groups, the median SAQ-AF scores were 50 (30.0 to 70.0) and 50 (21.3 to 78.3), respectively. In both groups, the SAQ-AF score improved, but the median of the difference compared to baseline was lower in the allopurinol group (10 [0 to 30] versus 20 [10 to 40]; p < 0.001), as was the mean of the difference in the total SAQ score (12.8 ± 17.8 versus 21.2 ± 15.9; p = 0.014). Conclusion Both allopurinol and trimetazidine improved the control of angina symptoms; however, trimetazidine presented a greater gain compared to baseline. Brazilian Registry of Clinical Trials - Registration Number RBR-5kh98y

Pre-Existing Atrial Fibrillation in Hospitalized Patients with COVID-19: Insights from the CARDIO COVID 19-20 Registry.

Pre-existing (chronic) atrial fibrillation (AF) has been identified as a risk factor for cardiovascular complications and mortality in patients with COVID-19; however, evidence in Latin America (LATAM) is scarce. This prospective and multicenter study from the CARDIO COVID 19-20 database includes hospitalized adults with COVID-19 from 14 countries in LATAM. A parsimonious logistic regression model was used to identify the main factors associated with mortality in a simulated case-control setting comparing patients with a history of AF to those without. In total, 3260 patients were included, of which 115 had AF. The AF group was older, had a higher prevalence of comorbidities, and had greater use of cardiovascular medications. In the model, AF, chronic kidney disease, and a respiratory rate > 25 at admission were associated with higher in-hospital mortality. The use of corticosteroids did not reach statistical significance; however, an effect was seen through the confidence interval. Thus, pre-existing AF increases mortality risk irrespective of other concomitant factors. Chronic kidney disease and a high respiratory rate at admission are also key factors for in-hospital mortality. These findings highlight the importance of comorbidities and regional characteristics in COVID-19 outcomes, in this instance, enhancing the evidence for patients from LATAM.

Hemodiafiltration versus Hemodialysis in End-Stage Kidney Disease: A Systematic Review and Meta-Analysis.

Rationale & Objective: The use of hemodiafiltration (HDF) as a kidney replacement therapy (KRT) in patients with end-stage kidney disease (ESKD) has sparked a debate regarding its advantages over conventional hemodialysis (HD). The present study aims to shed light on this controversy by comparing mortality rates and cause-specific deaths between ESKD patients receiving HDF and those undergoing HD. Study Design: Systematic review and meta-analysis of randomized controlled trials (RCTs). The search was conducted using PubMed, EMBASE, and Cochrane Central on July 1, 2023. Setting & Participants: Adult patients with ESKD on regular KRT. Exposure: Studies with participants undergoing HDF. Outcomes: Primary outcomes were all-cause mortality, cardiovascular (CV) mortality, deaths related to infections, and kidney transplant. We also evaluated the endpoints for deaths related to malignancy, myocardial infarction, stroke, arrhythmias, and sudden death. Analytical Approach: We included RCTs evaluating HDF versus HD. Crossover trials and studies with overlapping populations were excluded. Two authors independently extracted the data following predefined search criteria and quality assessment. The risk of bias was assessed with Cochrane's RoB2 tool. Results: We included 5 RCTs with 4,143 patients, of which 2,078 (50.1%) underwent HDF, whereas 2,065 (49.8%) were receiving HD. Overall, HDF was associated with a lower risk of all-cause mortality (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.73-0.91; P < 0.001; I2 = 7%) and a lower risk of CV-related deaths (RR, 0.75; 95% CI, 0.61-0.92; P = 0.007; I2 = 0%). The incidence of infection-related deaths was also significantly different between therapies (RR, 0.69; 95% CI, 0.50-0.95; P = 0.02; I2 = 26%). Limitations: In individual studies, the HDF groups achieved varying levels of convection volume. Conclusions: Compared with those undergoing HD, patients receiving HDF experienced a reduction in all-cause mortality, CV mortality, and infection-related mortality. These results provide compelling evidence supporting the use of HDF as a beneficial intervention in ESKD patients undergoing KRT. Registration: Registered at PROSPERO: CRD42023438362.

The efficacy of fluconazole for anti-fungal prophylaxis in peritoneal dialysis patients: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The efficacy of fluconazole as a prophylactic strategy in patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) with prior antibiotic exposure is controversial in the current literature. This study aimed to compare a strategy of fluconazole prophylaxis versus no-prophylaxis for patients in PD on antibiotics for previous episodes of peritonitis. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing fluconazole prophylaxis with no prophylaxis for PD-related peritonitis. The search was conducted on PubMed, EMBASE, and Cochrane Central in January 23, 2023. The outcome of interest was the occurrence of fungal peritonitis (FP). RESULTS: We included six studies (1 RCT, 5 observational) with 4515 occurrences of peritonitis, of which 1098 (24.8%) received fluconazole prophylaxis in variable doses, whereas 3417 (75.6%) did not receive prophylaxis during peritonitis episodes. Overall, fluconazole prophylaxis was associated with a lower incidence of FP (OR 0.22; 95% CI 0.12-0.41; p<0.001; I2=0%). Subgroup analysis of studies that administered daily doses of fluconazole also demonstrated a reduced incidence of FP in patients who received antifungal prophylaxis (OR 0.31; CI 0.14-0.69; p=0.004; I2=0%). CONCLUSIONS: In this meta-analysis of 4515 episodes of PD-related peritonitis, prophylaxis with fluconazole significantly reduced episodes of FP as compared with no antifungal prophylaxis.

The efficacy of fluconazole for anti-fungal prophylaxis in peritoneal dialysis patients: A systematic review and meta-analysis / Eficacia de fluconazol para profilaxis antifúngica en los pacientes de diálisis peritoneal: revisión sistemática y metaanálisis

Introduction and objectives: The efficacy of fluconazole as a prophylactic strategy in patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) with prior antibiotic exposure is controversial in the current literature. This study aimed to compare a strategy of fluconazole prophylaxis versus no-prophylaxis for patients in PD on antibiotics for previous episodes of peritonitis. Materials and methods: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing fluconazole prophylaxis with no prophylaxis for PD-related peritonitis. The search was conducted on PubMed, EMBASE, and Cochrane Central in January 23, 2023. The outcome of interest was the occurrence of fungal peritonitis (FP). Results: We included six studies (1 RCT, 5 observational) with 4515 occurrences of peritonitis, of which 1098 (24.8%) received fluconazole prophylaxis in variable doses, whereas 3417 (75.6%) did not receive prophylaxis during peritonitis episodes. Overall, fluconazole prophylaxis was associated with a lower incidence of FP (OR 0.22; 95% CI 0.12–0.41; p<0.001; I2=0%). Subgroup analysis of studies that administered daily doses of fluconazole also demonstrated a reduced incidence of FP in patients who received antifungal prophylaxis (OR 0.31; CI 0.14–0.69; p=0.004; I2=0%). Conclusions: In this meta-analysis of 4515 episodes of PD-related peritonitis, prophylaxis with fluconazole significantly reduced episodes of FP as compared with no antifungal prophylaxis.(AU)

Introducción y objetivos: La eficacia de fluconazol como estrategia profiláctica en los pacientes con enfermedad renal crónica (ERC) sometidos a diálisis peritoneal (DP) con exposición antibiótica previa es controvertida en la literatura actual. El objetivo de este estudio fue comparar la estrategia de profilaxis con fluconazol frente a no profilaxis para los pacientes de DP con régimen antibiótico por episodios previos de peritonitis. Materiales y métodos: Realizamos una revisión sistemática y metaanálisis de estudios observacionales y ensayos controlados aleatorizados (ECA), comparando la profilaxis con fluconazol y la no profilaxis para la peritonitis relacionada con DP. Dicha búsqueda se realizó en PubMed, EMBASE y Cochrane Central el 23 de enero de 2023. El resultado de interés fue la aparición de peritonitis fúngica (PF). Resultados: Incluimos seis estudios (1 ECA, 5 observacionales) con 4.515 episodios de peritonitis, de los cuales 1.098 (24,8%) recibieron profilaxis de fluconazol en dosis variables, mientras que 3.417 (75,6%) no recibieron profilaxis durante los episodios de peritonitis. En general, la profilaxis de fluconazol estuvo asociada a una menor incidencia de PF (OR: 0,22; IC 95%: 0,12-0,41; p<0,001; I2=0%). El análisis de subgrupo de los estudios que administraron dosis diarias de fluconazol también demostró una incidencia reducida de PF en los pacientes que recibieron profilaxis antifúngica (OR: 0,31; IC 95%: 0,14-0,69; p=0,004, I2=0%). Conclusiones: En este metaanálisis de 4.515 episodios de peritonitis relacionada con DP, la profilaxis con fluconazol redujo significativamente los episodios de PF, en comparación con la no profilaxis antifúngica.(AU)

Cardiovascular Complications in Patients with Heart Failure and COVID-19: CARDIO COVID 19-20 Registry.

Since early 2020, different studies have shown an increased prevalence of COVID-19 and poorer prognosis in older adults with cardiovascular comorbidities. This study aimed to assess the impact of heart failure (HF) on cardiovascular complications, intensive care unit (ICU) admissions, and in-hospital mortality in patients hospitalized with COVID-19. The CARDIO COVID 19-20 registry includes 3260 hospitalized patients with a COVID-19 serological diagnosis between May 2020 and June 2021 from Latin American countries. A history of HF was identified in 182 patients (5.6%). In patients with and without previous HF, the incidence of supraventricular arrhythmia was 16.5% vs. 6.3%, respectively (p = 0.001), and that of acute coronary syndrome was 7.1% vs. 2.7%, respectively (p = 0.001). Patients with a history of HF had higher rates of ICU admission (61.5% vs. 53.1%, respectively; p = 0.031) and in-hospital mortality (41.8% vs. 24.5%, respectively; p = 0.001) than patients without HF. Cardiovascular mortality at discharge (42.1% vs. 18.5%, respectively; p < 0.001) and at 30 days post-discharge (66.7% vs. 18.0%, respectively) was higher for patients with a history of HF than for patients without HF. In patients hospitalized with COVID-19, previous history of HF was associated with a more severe cardiovascular profile, with increased risk of cardiovascular complications, and poor in-hospital and 30-day outcomes.

Using a mobile application to reduce potentially inappropriate prescribing for older Brazilian adults in primary care: a triple-blind randomised clinical trial.

BACKGOUND: Potentially inappropriate prescribing (PIP) has been evaluated in several countries, and several strategies have been devised for deprescribing drugs in older adults. The aim of this study was to evaluate the efficacy of a mobile application in reducing PIP for older adults in primary care facilities in Brazil. METHODS: This randomised, triple-blind, parallel-group trial was conducted in 22 public primary care facilities in Brazil. During the intervention phase, the general practitioners (GPs) were randomly allocated to the intervention (MPI Brasil app provides information about PIP, therapeutic alternatives and deprescribing) or control (MedSUS app provides general information about medications) group. All GPs were trained on the Clinical Decision-Making Process and how to access an Evidence-Based Health website. The GPs received an Android tablet with an installed mobile application depending on their allocated group, which they used when caring for older patients over at least 3 months. At the end of this period, a sample of older patients aged ≥ 60 years who had been awaiting medical consultation by the participating GPs were interviewed and their prescriptions analysed. The primary outcome was the frequency of PIP in and between the groups. RESULTS: Among 53 GPs who were administered the baseline survey, 14 were included in the clinical trial. At baseline, 146 prescriptions were analysed: the PIP overall was 37.7% (55/146), in the intervention group was 40.6% (28/69), and in the control group was 35.1% (27/77). After the intervention, 284 prescriptions were analysed: the PIP overall was 31.7% (90/284), in the intervention group was 32.2% (46/143), and in the control group was 31.2% (44/141) (RR: 1.16; 95% CI, 0.76-1.76). In the within-group analysis, the PIP reduced from before to after the intervention in both groups-more significantly in the intervention than in the control group (p < 0.001). In the stratified analysis of PIP frequency by GPs, there was a relative risk reduction in 86% (6/7) of GPs in the intervention group compared to 71% (5/7) in the control group. CONCLUSION: We found that the MPI Brasil app effectively reduced PIP, suggesting that it may be useful to incorporate this tool into clinical practice. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02918643). First registration on 22/09/2016.

Multifaceted Strategy Based on Automated Text Messaging After a Recent Heart Failure Admission: The MESSAGE-HF Randomized Clinical Trial.

Importance: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. Objective: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. Design, Setting, and Participants: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. Intervention: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. Main Outcomes and Measures: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. Results: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). Conclusions and Relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT04062461.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial.

BACKGROUND: Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. METHODS: The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). RESULTS: The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70---1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71---1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48---1.39; P = 0.46). No serious adverse events were observed. CONCLUSION: In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Multifaceted strategy based on automated text messaging after a recent heart failure admission: the MESSAGE-HF Randomized Clinical Trial

IMPORTANCE: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. OBJECTIVE: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. INTERVENTION: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. MAIN OUTCOMES AND MEASURES: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. RESULTS: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). CONCLUSIONS and relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome.

Safety, Effectiveness, and Hemodynamic Performance of the Bovine Pericardium Organic Valvular Bioprosthesis.

OBJECTIVE: To assess actual data on the safety, effectiveness, and hemodynamic performance of Bovine Pericardium Organic Valvular Bioprosthesis (BVP). METHODS: The BIOPRO Trial is an observational, retrospective, non-comparative, non-randomized, and multicenter study. We collected data from 903 patients with symptomatic, moderate, or severe valve disease who underwent BVP implants in the timeframe from 2013 to 2020 at three Brazilian institutions. Death, valve-related adverse events (AEs), functional recovery, and hemodynamic performance were evaluated at the hospital, at discharge, and six months and one year later. Primary analysis compared late (> 30 days after implant) linearized rates of valve-related AEs, such as thromboembolism, valve thrombosis, major hemorrhage, major paravalvular leak, and endocarditis, following objective performance criteria (OPC). Analysis was performed to include at least 400 valve-years for each valve position (aortic and mitral) for complete comparisons to OPC. Kaplan-Meier survival and major adverse cardiovascular and cerebrovascular event analyses were also performed. RESULTS: This retrospective study analyzed follow-up data collected from 903 patients (834.2 late patient-years) who have undergone surgery for 455 isolated aortic valve replacement (50.4%), 382 isolated mitral valve replacement (42.3%), and 66 combined valve replacement or other intervention (7.3%). The linearized rates of valve-related AEs were < 2 × OPC. One-year survival rates were 95.1% and 92.7% for aortic and mitral valve replacement, respectively. This study demonstrated an improvement in the New York Heart Association classification from baseline and hemodynamic performance within an expected range. CONCLUSION: According to this analysis, BVP meets world standards for safety and clinical efficacy.

Inflammation in Coronary Atherosclerosis: Insights into Pathogenesis and Therapeutic Potential of Anti-Inflammatory Drugs.

Atherosclerosis is a lipid-driven immune-inflammatory disease that affects the arteries, leading to multifocal plaque development. The inflammatory process involves the activation of immune cells and various inflammatory pathways. Anti-inflammatory drugs have been shown to be effective in reducing cardiovascular events in individuals with coronary disease. However, their use is still limited due to concerns about long-term follow-up, cost-effectiveness, adverse effects, and the identification of the ideal patient profile to obtain maximum benefits. This review aims to improve the understanding of inflammation in coronary atherosclerosis and explore potential therapeutic interventions, encompassing both traditional and non-traditional anti-inflammatory approaches. By addressing these concepts, we seek to contribute to the advancement of knowledge about this type of treatment for coronary artery disease.

Pleuroperitoneal communication in a patient on automated peritoneal dialysis: A rare but important complication.

Despite its rare frequency, a pleuroperitoneal communication is a well-documented complication for patients on peritoneal dialysis. It occurs in ~2% of continuous ambulatory peritoneal dialysis, with uncertain incidence for those on automated peritoneal dialysis. We report a case of a 30-year-old female patient with end-stage kidney disease with sudden dyspnea 2 days after starting automated peritoneal dialysis. Her chest x-ray revealed a significant pleural effusion on the right side. A thoracocentesis was performed, with a pleural glucose/plasma glucose of 1.08. Additionally, a computed tomography scan revealed a pleuroperitoneal communication upon dialysate infusion added with media contrast. A pleural-to-serum glucose gradient of greater than 50 mg/dL may indicate the diagnosis of a pleuroperitoneal communication in patients on peritoneal dialysis. Current literature also indicates that a pleural-to-serum glucose ratio above 1.0 may provide a more sensitive analysis. This case highlights the diagnosis process for this complication, with both laboratory and image findings corroborating the clinical hypotheses of a pleuroperitoneal communication in a patient on automated peritoneal dialysis.

Association of Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors with Cardiovascular Events and Death in Dialysis Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Anemia is a common finding among patients with advanced chronic kidney disease, especially those on dialysis. The recent introduction of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) has raised some concerns about the cardiovascular and thrombotic complications of this class of drugs. OBJECTIVES: This meta-analysis aimed to assess the safety of HIF-PHIs in patients with end-stage kidney disease (ESKD) versus standard therapy with erythropoiesis-stimulating agents (ESAs). METHODS: Databases were searched on April 2022. Studies that reported incidence of all-cause mortality; major cardiovascular adverse events (MACEs); myocardial infarction (MI); stroke and thrombotic events in the use of HIF-PHIs or ESA on ESKD patients in hemodialysis or peritoneal dialysis were evaluated. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. RESULTS: 12,821 patients from ten randomized controlled trials were included in this study. Most patients (83%) were on hemodialysis. 6,461 (50.3%) were using HIF-PHIs, and 6,360 (49.6%) were in the ESA group. The pooled estimated incidence of all-cause mortality was 769 in the HIF-PHIs group (relative-risk ratios (RR): 1.04; confidence interval (CI): 0.95-1.14; p = 0.52; I2 = 0%). There was no difference in the groups regarding the outcomes of MACE in the analysis of the three studies that reported this outcome (RR: 0.95; CI: 0.87-1.04; p = 0.69; I2 = 0%). In addition, there was no statistical difference among the outcomes of MI, stroke, or thrombotic events. CONCLUSIONS: Among patients with ESKD on dialysis, the use of HIF-PHIs was non-inferior regarding the safety outcomes when compared to standard of care therapy.

Inherited pain hypersensitivity and increased anxiety-like behaviors are associated with genetic epilepsy in Wistar Audiogenic Rats: Short- and long-term effects of acute and chronic seizures on nociception and anxiety.

Anxiety and pain hypersensitivity are neurobehavioral comorbidities commonly reported by patients with epilepsies, and preclinical models are suitable to investigate the neurobiology of behavioral and neuropathological alterations associated with these epilepsy-related comorbidities. This work aimed to characterize endogenous alterations in nociceptive threshold and anxiety-like behaviors in the Wistar Audiogenic Rat (WAR) model of genetic epilepsy. We also assessed the effects of acute and chronic seizures on anxiety and nociception. WARs from acute and chronic seizure protocols were divided into two groups to assess short- and long-term changes in anxiety (1 day or 15 days after seizures, respectively). To assess anxiety-like behaviors, the laboratory animals were submitted to the open field, light-dark box, and elevated plus maze tests. The von Frey, acetone, and hot plate tests were used to measure the endogenous nociception in seizure-free WARs, and postictal antinociception was recorded at 10, 30, 60, 120, 180 min, and 24 h after seizures. Seizure-free WARs presented increased anxiety-like behaviors and pain hypersensitivity, displaying mechanical and thermal allodynia (to heat and cold stimuli) in comparison to nonepileptic Wistar rats. Potent postictal antinociception that persisted for 120 to 180 min was detected after acute and chronic seizures. Additionally, acute and chronic seizures have magnified the expression of anxiety-like behaviors when assessed at 1 day and 15 days after seizures. Behavioral analysis indicated more severe and persistent anxiogenic-like alterations in WARs submitted to acute seizures. Therefore, WARs presented pain hypersensitivity and increased anxiety-like behaviors endogenously associated with genetic epilepsy. Acute and chronic seizures induced postictal antinociception in response to mechanical and thermal stimuli and increased anxiety-like behaviors when assessed 1 day and 15 days later. These findings support the presence of neurobehavioral alterations in subjects with epilepsy and shed light on the use of genetic models to characterize neuropathological and behavioral alterations associated with epilepsy.

Safety, Effectiveness, and Hemodynamic Performance of the Bovine Pericardium Organic Valvular Bioprosthesis

ABSTRACT Objective: To assess actual data on the safety, effectiveness, and hemodynamic performance of Bovine Pericardium Organic Valvular Bioprosthesis (BVP). Methods: The BIOPRO Trial is an observational, retrospective, non-comparative, non-randomized, and multicenter study. We collected data from 903 patients with symptomatic, moderate, or severe valve disease who underwent BVP implants in the timeframe from 2013 to 2020 at three Brazilian institutions. Death, valve-related adverse events (AEs), functional recovery, and hemodynamic performance were evaluated at the hospital, at discharge, and six months and one year later. Primary analysis compared late (> 30 days after implant) linearized rates of valve-related AEs, such as thromboembolism, valve thrombosis, major hemorrhage, major paravalvular leak, and endocarditis, following objective performance criteria (OPC). Analysis was performed to include at least 400 valve-years for each valve position (aortic and mitral) for complete comparisons to OPC. Kaplan-Meier survival and major adverse cardiovascular and cerebrovascular event analyses were also performed. Results: This retrospective study analyzed follow-up data collected from 903 patients (834.2 late patient-years) who have undergone surgery for 455 isolated aortic valve replacement (50.4%), 382 isolated mitral valve replacement (42.3%), and 66 combined valve replacement or other intervention (7.3%). The linearized rates of valve-related AEs were < 2 × OPC. One-year survival rates were 95.1% and 92.7% for aortic and mitral valve replacement, respectively. This study demonstrated an improvement in the New York Heart Association classification from baseline and hemodynamic performance within an expected range. Conclusion: According to this analysis, BVP meets world standards for safety and clinical efficacy.