Incidence of contrast-associated acute kidney injury: a prospective cohort / Incidência de lesão renal aguda associada ao contraste: uma coorte prospectiva

ABSTRACT Introduction: Contrast-associated acute kidney injury (CA-AKI) is a deterioration of kidney function that occurs after the administration of a iodinated contrast medium (ICM). Most studies that defined this phenomenon used older ICMs that were more prone of causing CA-AKI. In the past decade, several articles questioned the true incidence of CA-AKI. However, there is still a paucity of a data about the safety of newer ICM. Objective: To assess the incidence of CA-AKI in hospitalized patients that were exposed to computed tomography (CT) with and without ICM. Methods: Prospective cohort study with 1003 patients who underwent CT in a tertiary hospital from December 2020 through March 2021. All inpatients aged > 18 years who had a CT scan during this period were screened for the study. CA-AKI was defined as a relative increase of serum creatinine of ≥ 50% from baseline or an absolute increase of ≥ 0.3 mg/dL within 18 to 48 hours after the CT. Chi-squared test, Kruskal-Wallis test, and linear regression model with restricted cubic splines were used for statistical analyses. Results: The incidence of CA-AKI was 10.1% in the ICM-exposed group and 12.4% in the control group when using the absolute increase criterion. The creatinine variation from baseline was not significantly different between groups. After adjusting for baseline factors, contrast use did not correlate with worse renal function. Conclusion: The rate of CA-AKI is very low, if present at all, with newer ICMs, and excessive caution regarding contrast use is probably unwarranted.

RESUMO Introdução: Lesão renal aguda associada ao contraste (LRA-AC) é uma deterioração da função renal que ocorre após a administração de meio de contraste iodado (MCI). A maioria dos estudos que definiram esse fenômeno utilizaram MCI mais antigos, mais propensos a causar LRA-AC. Na última década, diversos artigos questionaram a verdadeira incidência de LRA-AC. Entretanto, ainda há escassez de dados sobre a segurança dos MCI mais novos. Objetivo: Avaliar a incidência de LRA-AC em pacientes hospitalizados expostos à tomografia computadorizada (TC) com e sem MCI. Métodos: Estudo de coorte prospectivo com 1.003 pacientes submetidos a TC em hospital terciário, de dezembro/2020 a março/2021. Todos os pacientes internados com idade ≥ 18 anos que realizaram TC nesse período foram selecionados. A LRA-AC foi definida como aumento relativo de creatinina sérica de ≥ 50% em relação ao valor basal ou aumento absoluto de ≥ 0,3 mg/dL dentro de 18 a 48 horas após a TC. Utilizamos o teste qui-quadrado, teste de Kruskal-Wallis e modelo de regressão linear com splines cúbicos restritos para análises estatísticas. Resultados: A incidência de LRA-AC foi 10,1% no grupo exposto ao MCI e 12,4% no grupo controle ao usar o critério de aumento absoluto. A variação da creatinina em relação ao valor basal não foi significativamente diferente entre os grupos. Após ajuste para fatores basais, o uso de contraste não se correlacionou com pior função renal. Conclusão: A taxa de LRA-AC é muito baixa, caso exista, com MCIs mais novos, e a cautela excessiva quanto ao uso de contraste provavelmente não se justifica.

Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.

BACKGROUND: Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering. METHODS: In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were changes in levels of APOC3, apolipoprotein B, non-high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. RESULTS: A total of 154 patients underwent randomization at 24 sites in North America. The median age of the patients was 62 years, and the median triglyceride level was 241.5 mg per deciliter. The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons). As compared with placebo, each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, with no significant change in the LDL cholesterol level. The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups. CONCLUSIONS: In patients with predominantly moderate hypertriglyceridemia at elevated cardiovascular risk, olezarsen significantly reduced levels of triglycerides, apolipoprotein B, and non-HDL cholesterol, with no major safety concerns identified. (Funded by Ionis Pharmaceuticals; Bridge-TIMI 73a ClinicalTrials.gov number, NCT05355402.).

Reductions in remnant cholesterol and VLDL cholesterol through inhibition of ANGPTL3 protein synthesis: an analysis from the TRANSLATE-TIMI 70 trial.

AIMS: Remnant cholesterol and very low-density lipoprotein cholesterol (VLDL-C) are increasingly recognized risk factors for atherosclerotic disease with few therapeutic options. Angiopoietin-like 3 (ANGPTL3), a key protein in the metabolism of triglyceride-rich lipoproteins, is a promising target. METHODS AND RESULTS: TRANSLATE-TIMI 70 was a double-blind, placebo-controlled randomized trial testing seven dose regimens of vupanorsen, an antisense oligonucleotide against ANGPTL3, in adults with non-HDL-C ≥ 100 mg/dL and triglycerides 150-500 mg/dL. The primary endpoint of this analysis was percentage change in remnant cholesterol (total cholesterol minus directly measured LDL-C minus HDL-C) and VLDL-C (directly measured) over 24 weeks. Two hundred eighty-six patients were enrolled, with a median age of 64 years and 44% female. Median baseline remnant cholesterol and VLDL-C were 42 and 31 mg/dL, respectively (reference: <30 mg/dL). Vupanorsen lowered remnant cholesterol by 42-59% at 24 weeks over placebo (P < 0.001), achieving a median level of 18 mg/dL at the highest dose. Over the same period, VLDL-C was reduced by 52-67% over placebo (P < 0.001), with a median achieved level of 2.5 mg/dL at the highest dose. The effect of vupanorsen on remnant cholesterol and VLDL-C reduction was dose-dependent and directly associated with the degree of ANGPTL3 inhibition: at 90% ANGPTL3 reduction, there was a 61% and 81% decrease in remnant cholesterol and VLDL-C, respectively. CONCLUSION: Inhibition of ANGPTL3 protein synthesis significantly lowered remnant cholesterol and VLDL-C in patients with hypertriglyceridaemia. The magnitude of reduction was associated with the degree of ANGPTL3 inhibition. These findings support ANGPTL3 inhibition as a promising target for lowering cholesterol on triglyceride-rich lipoproteins.

In this randomized controlled trial of 286 participants with elevated triglycerides, treatment with vupanorsen, an ANGPTL3 inhibitor, lowered remnant cholesterol by up to 59% and VLDL cholesterol by up to 67% over placebo. The effect of the treatment was sustained throughout 24 weeks and consistent across key patient subgroups. ANGPTL3 inhibition may be a promising approach to treat patients with elevated triglycerides.

Trends in Scientific Collaboration Between Men and Women Following the #MeToo Movement.

BACKGROUND: The #MeToo movement raised global awareness about harassment in the workplace. Concerns were raised, however, that the movement may have unintendedly harmed women in academia by decreasing collaboration invitations from men in senior positions, who might be more reluctant to collaborate. OBJECTIVE: To analyze whether collaborations between first author women and last author men decreased after the #MeToo movement. DESIGN: Retrospective observational study. PARTICIPANTS: Names of first and last authors of 122,450 US review articles from the PubMed database published between 2014 and 2020. MAIN MEASURES: Change in the proportion of review articles with a first author woman and a last author man following the peak of the #MeToo movement in October 2017. Additionally, among review articles with a last author man, trends of women first authorship in the USA and Europe (control group) were compared. KEY RESULTS: We analyzed 122,450 review articles with first and last authors from US institutions. Of 85,015 articles by a man last author, 37.5% (31,902) had a woman first author. In contrast, when the last author was a woman, the first author was also a woman in 53.6% of articles (20,078) (p<0.001 for difference). Among review articles with a last author man, there was no change in the proportion of articles with a woman first author before versus after the peak of the #MeToo movement (e.g., p=0.13 for difference between the 12 months following October 2017 compared to the pre-#Me-too period). Among European institutions, of 72,036 articles by a man last author, 43.4% (31,294) had a woman first author, higher than the proportion observed in the USA. Trends in collaboration between first author women and last author men were similar in the USA and Europe after the peak of the #MeToo movement (p=0.65). CONCLUSIONS: The #MeToo movement was not associated with a reduction in the rate of scientific review article authorship collaborations between first author women and last author men in the life sciences. These findings, if generalizable, suggest it is possible to promote accountability for harassment in the workplace without limiting decreases in collaboration.

Incidence of contrast-associated acute kidney injury: a prospective cohort.

INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is a deterioration of kidney function that occurs after the administration of a iodinated contrast medium (ICM). Most studies that defined this phenomenon used older ICMs that were more prone of causing CA-AKI. In the past decade, several articles questioned the true incidence of CA-AKI. However, there is still a paucity of a data about the safety of newer ICM. OBJECTIVE: To assess the incidence of CA-AKI in hospitalized patients that were exposed to computed tomography (CT) with and without ICM. METHODS: Prospective cohort study with 1003 patients who underwent CT in a tertiary hospital from December 2020 through March 2021. All inpatients aged > 18 years who had a CT scan during this period were screened for the study. CA-AKI was defined as a relative increase of serum creatinine of ≥ 50% from baseline or an absolute increase of ≥ 0.3 mg/dL within 18 to 48 hours after the CT. Chi-squared test, Kruskal-Wallis test, and linear regression model with restricted cubic splines were used for statistical analyses. RESULTS: The incidence of CA-AKI was 10.1% in the ICM-exposed group and 12.4% in the control group when using the absolute increase criterion. The creatinine variation from baseline was not significantly different between groups. After adjusting for baseline factors, contrast use did not correlate with worse renal function. CONCLUSION: The rate of CA-AKI is very low, if present at all, with newer ICMs, and excessive caution regarding contrast use is probably unwarranted.

Hepatic fat changes with antisense oligonucleotide therapy targeting ANGPTL3.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is a novel therapeutic target for hyperlipidemia. Vupanorsen, an antisense oligonucleotide targeting ANGPTL3, reduced triglycerides up to 57% in a phase 2b trial, but caused dose-dependent increases in hepatic fat fraction (HFF). OBJECTIVE: To determine the degree of HFF progression with escalating doses of vupanorsen, differential HFF increases in key patient subgroups, and the correlation between changes in HFF and liver enzymes. METHODS: TRANSLATE-TIMI 70 was a randomized, placebo-controlled trial testing 7 dosing regimens of vupanorsen in 286 adults with hyperlipidemia. A total of 227 patients had HFF measured at baseline and 24 weeks and were included in this analysis. RESULTS: The median HFF at baseline was 8.5%. Vupanorsen led to dose-dependent relative increases in HFF of up to 76% at 24 weeks (p < 0.001), corresponding to an absolute increase of up to 7.0% at the highest dose (p < 0.001). Increases in HFF were numerically greater in patients who had elevated baseline HFF, body mass index, triglycerides, or diabetes. Vupanorsen also increased liver enzymes in a dose-dependent manner, and changes in HFF were moderately positively correlated with changes in aspartate transaminase (AST) (rho = 0.49, p < 0.001) and alanine transaminase (ALT) (rho = 0.50, p < 0.001). CONCLUSION: Vupanorsen, an inhibitor of ANGPTL3 protein synthesis, caused dose-dependent increases in HFF. Increases in HFF were only moderately correlated with elevations in AST and ALT, suggesting that liver enzymes are an imperfect indicator to detect increases in hepatic fat. These results highlight the need to monitor HFF in clinical trials of therapies targeting intracellular ANGPTL3 inhibition, especially those that are targeted to the liver.

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.

Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study. / Papel Incremental da Classificação da New York Heart Association e dos Índices do Teste de Exercício Cardiopulmonar para Prognóstico na Insuficiência Cardíaca: um Estudo de Coorte.

BACKGROUND: Central Illustration : Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study LVEF: left ventricular ejection fraction; HR: hazard ratio; CI: confidence interval; NYHA: New York Heart Association; VO 2: oxygen consumption. BACKGROUND: The accuracy of the New York Heart Association (NYHA) classification to assess prognosis may be limited compared with objective cardiopulmonary exercise test (CPET) parameters in heart failure (HF). OBJECTIVE: To investigate the prognostic value of the NYHA classification in addition to Weber class. METHODS: Adult outpatients with HF undergoing CPET in a Brazilian tertiary care center were included. The physician-assigned NYHA class and the CPET-derived Weber class were stratified into "favorable" (NYHA I or II; Weber A or B) or "adverse" (NYHA III or IV; Weber C or D). Patients with one favorable class and one adverse class were defined as "discordant." The primary endpoint was time to all-cause mortality. A 2-sided p value < 0.05 was considered statistically significant. RESULTS: A total of 834 patients were included. Median age was 57 years; 42% (351) were female, and median left ventricular ejection fraction was 32%. Among patients with concordant NYHA and Weber classes, those with adverse NYHA and Weber classes had significantly higher all-cause mortality compared to those with favorable classes (hazard ratio [HR]: 5.65; 95% confidence interval [CI]: 3.38 to 9.42). Among patients with discordant classes, there was no significant difference in all-cause mortality (HR: 1.38; 95% CI: 0.82 to 2.34). In the multivariable model, increments in NYHA class (HR: 1.55 per class increase; 95% CI: 1.26 to 1.92) and reductions in peak VO 2 (HR: 1.47 per 3 ml/kg/min decrease; 95% CI: 1.28 to 1.70) significantly predicted mortality. CONCLUSIONS: Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information for patients with HF.

Speech-induced atrial tachycardia: A narrative review of putative mechanisms implicating the autonomic nervous system.

Despite being uncommon, speech-induced atrial tachycardias carry significant morbidity and affect predominantly healthy individuals. Little is known about their mechanism, treatment, and prognosis. In this review, we seek to identify the underlying connections and pathophysiology between speech and arrhythmias while providing an informed approach to evaluation and management.

Reply to the letter "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients".

This is a reply to the letter titled "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients" by Eva Rully Kurniawati et al. In response to the concerns raised about our paper published in BMC Cardiovascular Disorders, titled "Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study," we have addressed the confounding bias on the population included and the use of VA-ECMO and Impella CP. Furthermore, we have provided new data on the correlation of oxygen supply and lactate levels at admission of cardiogenic shock.

Functional assessment based on cardiopulmonary exercise testing in mild heart failure: A multicentre study.

AIMS: In this multicentre study, we compared cardio-pulmonary exercise test (CPET) parameters between heart failure (HF) patients classified as New York Heart Association (NYHA) class I and II to assess NYHA performance and prognostic role in mild HF. METHODS AND RESULTS: We included consecutive HF patients in NYHA class I or II who underwent CPET in three Brazilian centres. We analysed the overlap between kernel density estimations for the per cent-predicted peak oxygen consumption (VO2 ), minute ventilation/carbon dioxide production (VE/VCO2 ) slope, and oxygen uptake efficiency slope (OUES) by NYHA class. Area under the receiver-operating characteristic curve (AUC) was used to assess the capacity of per cent-predicted peak VO2 to discriminate between NYHA class I and II. For prognostication, time to all-cause death was used to produce Kaplan-Meier estimates. Of 688 patients included in this study, 42% were classified as NYHA I and 58% as NYHA II, 55% were men, and mean age was 56 years. Median global per cent-predicted peak VO2 was 66.8% (IQR 56-80), VE/VCO2 slope was 36.9 (31.6-43.3), and mean OUES was 1.51 (±0.59). Kernel density overlap between NYHA class I and II was 86% for per cent-predicted peak VO2 , 89% for VE/VCO2 slope, and 84% for OUES. Receiving-operating curve analysis showed a significant, albeit limited performance of per cent-predicted peak VO2 alone to discriminate between NYHA class I vs. II (AUC 0.55, 95% CI 0.51-0.59, P = 0.005). Model accuracy for probability of being classified as NYHA class I (vs. NYHA class II) across the spectrum of the per cent-predicted peak VO2 was limited, with an absolute probability increment of 13% when per cent-predicted peak VO2 increased from 50% to 100%. Overall mortality in NYHA class I and II was not significantly different (P = 0.41), whereas NYHA class III patients displayed a distinctively higher death rate (P < 0.001). CONCLUSIONS: Patients with chronic HF classified as NYHA I overlapped substantially with those classified as NYHA II in objective physiological measures and prognosis. NYHA classification may represent a poor discriminator of cardiopulmonary capacity in patients with mild HF.

Associations Between New York Heart Association Classification, Objective Measures, and Long-term Prognosis in Mild Heart Failure: A Secondary Analysis of the PARADIGM-HF Trial.

Importance: Heart failure (HF) treatment recommendations are centered on New York Heart Association (NYHA) classification, such that most apparently asymptomatic patients are not eligible for disease-modifying therapies. Objectives: To assess within-patient variation in NYHA classification over time, the association between NYHA class and an objective measure of HF severity (N-terminal pro-B-type natriuretic peptide [NT-proBNP] level), and their association with long-term prognosis in the PARADIGM-HF trial. Design, Setting, and Participants: All patients in PARADIGM-HF were in NYHA class II or higher at baseline and were treated with sacubitril-valsartan during a 6- to 10-week run-in period before randomization. Patients classified as NYHA class I, II, and III in PARADIGM-HF were compared at randomization. Exposures: NYHA class at randomization after 6 to 10 weeks of the run-in period. Main Outcomes and Measures: Primary outcome was cardiovascular death or first HF hospitalization. Logistic regression models, areas under the receiver operating characteristic curve (AUC), kernel density estimation overlaps, and Cox proportional hazards models were used. Results: The analysis included 8326 patients with known NYHA classification at randomization. Of 389 patients in NYHA class I, 228 (58%) changed functional class during the first year after randomization. Level of NT-proBNP was a poor discriminator of NYHA classification: for NYHA class I vs II, the AUC was 0.51 (95% CI, 0.48-0.54). For NT-proBNP level, estimated kernel density overlap was 93% between NYHA class I vs II, 79% between NYHA I vs III, and 83% between NYHA II vs III. Patients classified as NYHA III displayed a distinctively higher rate of cardiovascular events (NYHA III vs I, hazard ratio [HR], 1.84; 95% CI, 1.44-2.37; NYHA III vs II, HR, 1.49; 95% CI, 1.35-1.64). Patients in NYHA class I and II revealed lower event rates (NYHA II vs I, HR, 1.24; 95% CI, 0.97-1.58). Stratification by NT-proBNP level (<1600 pg/mL or ≥1600 pg/mL) identified subgroups with distinctive risk, such that NYHA class I patients with high NT-proBNP levels (n = 175) had a numerically higher event rate than patients with low NT-proBNP levels from any NYHA class (vs I, HR, 3.43; 95% CI, 2.03-5.87; vs II, HR, 2.12; 95% CI, 1.58-2.86; vs III, HR, 1.37; 95% CI, 1.00-1.88). Conclusions and Relevance: In this study, patients in NYHA class I and II overlapped substantially in objective measures and long-term prognosis. Physician-defined "asymptomatic" functional class concealed patients who were at substantial risk for adverse outcomes. NYHA classification might be limited to differentiate mild forms of HF. Trial Registration: ClinicalTrials.gov Identifier: NCT01035255.

Papel Incremental da Classificação da New York Heart Association e dos Índices do Teste de Exercício Cardiopulmonar para Prognóstico na Insuficiência Cardíaca: um Estudo de Coorte / Incremental Role of New York Heart Association Class and Cardiopulmonary Exercise Test Indices for Prognostication in Heart Failure: A Cohort Study

Resumo Fundamento A precisão da classificação da New York Heart Association (NYHA) para avaliar o prognóstico pode ser limitada em comparação com os parâmetros objetivos do teste de exercício cardiopulmonar (TECP) na insuficiência cardíaca (IC). Objetivo Investigar o valor prognóstico da classificação da NYHA e da classe Weber. Métodos Foram incluídos pacientes ambulatoriais adultos com IC submetidos a TECP em um centro terciário brasileiro. A classe NYHA atribuída pelo médico e a classe Weber derivada do TECP foram estratificadas como "favorável" (NYHA I ou II com Weber A ou B) ou "adversa" (NYHA III ou IV com Weber C ou D). Pacientes com uma classe favorável e uma classe adversa foram definidos como "discordantes". O desfecho primário foi o tempo para mortalidade por todas as causas. Um valor de p bilateral < 0,05 foi considerado estatisticamente significativo. Resultados Foram incluídos 834 pacientes. A mediana de idade foi de 57 anos; 42% (351) eram do sexo feminino e a mediana da fração de ejeção do ventrículo esquerdo foi de 32%. Entre os pacientes com classes NYHA e Weber concordantes, aqueles com classes NYHA e Weber adversas tiveram mortalidade por todas as causas significativamente maior em comparação com aqueles com classes favoráveis ( hazard ratio [HR]: 5,65; intervalo de confiança de 95%: 3,38 a 9,42). Entre os pacientes com classes discordantes, não houve diferença significativa na mortalidade por todas as causas (HR: 1,38; intervalo de confiança de 95%: 0,82 a 2,34). No modelo multivariado, incrementos na classe NYHA (HR: 1,55 por aumento na classe; intervalo de confiança de 95%: 1,26 a 1,92) e reduções no VO 2 pico (HR: 1,47 por diminuição de 3 ml/kg/min; intervalo de confiança de 95%: 1,28 a 1,70) previu significativamente a mortalidade. Conclusões A classe NYHA atribuída pelo médico e as medidas objetivas do TECP fornecem informações prognósticas complementares para pacientes com IC.

Abstract Background The accuracy of the New York Heart Association (NYHA) classification to assess prognosis may be limited compared with objective cardiopulmonary exercise test (CPET) parameters in heart failure (HF). Objective To investigate the prognostic value of the NYHA classification in addition to Weber class. Methods Adult outpatients with HF undergoing CPET in a Brazilian tertiary care center were included. The physician-assigned NYHA class and the CPET-derived Weber class were stratified into "favorable" (NYHA I or II; Weber A or B) or "adverse" (NYHA III or IV; Weber C or D). Patients with one favorable class and one adverse class were defined as "discordant." The primary endpoint was time to all-cause mortality. A 2-sided p value < 0.05 was considered statistically significant. Results A total of 834 patients were included. Median age was 57 years; 42% (351) were female, and median left ventricular ejection fraction was 32%. Among patients with concordant NYHA and Weber classes, those with adverse NYHA and Weber classes had significantly higher all-cause mortality compared to those with favorable classes (hazard ratio [HR]: 5.65; 95% confidence interval [CI]: 3.38 to 9.42). Among patients with discordant classes, there was no significant difference in all-cause mortality (HR: 1.38; 95% CI: 0.82 to 2.34). In the multivariable model, increments in NYHA class (HR: 1.55 per class increase; 95% CI: 1.26 to 1.92) and reductions in peak VO 2 (HR: 1.47 per 3 ml/kg/min decrease; 95% CI: 1.28 to 1.70) significantly predicted mortality. Conclusions Physician-assigned NYHA class and objective CPET measures provide complementary prognostic information for patients with HF.

Influenza vaccination strategy in acute coronary syndromes: the VIP-ACS trial.

AIMS: To evaluate whether a strategy of double-dose influenza vaccination during hospitalization for an acute coronary syndrome (ACS) compared with standard-dose outpatient vaccination (as recommended by current guidelines) would further reduce the risk of major cardiopulmonary events. METHODS AND RESULTS: Vaccination against Influenza to Prevent cardiovascular events after Acute Coronary Syndromes (VIP-ACS) was a pragmatic, randomized, multicentre, active-comparator, open-label trial with blinded outcome adjudication comparing two strategies of influenza vaccination following an ACS: double-dose quadrivalent inactivated vaccine before hospital discharge vs. standard-dose quadrivalent inactivated vaccine administered in the outpatient setting 30 days after randomization. The primary outcome was a hierarchical composite of all-cause death, myocardial infarction, stroke, unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory causes, analysed by the win ratio method. Patients were followed for 12 months. During two influenza seasons, 1801 participants were included at 25 centres in Brazil. The primary outcome was not different between groups, with 12.7% wins in-hospital double-dose vaccine group and 12.3% wins in the standard-dose vaccine group {win ratio: 1.02 [95% confidence interval (CI): 0.79-1.32], P = 0.84}. Results were consistent for the key secondary outcome, a hierarchical composite of cardiovascular death, myocardial infarction and stroke [win ratio: 0.94 (95% CI: 0.66-1.33), P = 0.72]. Time-to-first event analysis for the primary outcome showed results similar to those of the main analysis [hazard ratio 0.97 (95% CI: 0.75-1.24), P = 0.79]. Adverse events were infrequent and did not differ between groups. CONCLUSION: Among patients hospitalized with an ACS, double-dose influenza vaccination before discharge did not reduce cardiopulmonary outcomes compared with standard-dose vaccination in the outpatient setting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04001504.

An Empirical Assessment of Reviewer 2.

According to research lore, the second peer reviewer (Reviewer 2) is believed to rate research manuscripts more harshly than the other reviewers. The purpose of this study was to empirically investigate this common belief. We measured word count, positive phrases, negative phrases, question marks, and use of the word "please" in 2546 open peer reviews of 796 manuscripts published in the British Medical Journal. There was no difference in the content of peer reviews between Reviewer 2 and other reviewers for word count (630 vs 606, respectively, P = .16), negative phrases (8.7 vs 8.4, P = .29), positive phrases (4.2 vs 4.1, P = .10), question marks (4.8 vs 4.6, P = .26), and uses of "please" (1.0 vs 1.0, P = .86). In this study, Reviewer 2 provided reviews of equal sentiment to other reviewers, suggesting that popular beliefs surrounding Reviewer 2 may be unfounded.

Growth/differentiation factor-15 (GDF-15) as a predictor of serious arrhythmic events in patients with nonischemic dilated cardiomyopathy.

INTRODUCTION: Cardiac biomarkers have been proposed as a new tool to improve risk stratification of serious arrhythmic events in patients with heart failure (HF) beyond estimates of left ventricular ejection fraction. Growth differentiation factor (GDF)-15, a stress-induced cytokine, has been found to correlate with markers of myocardial fibrosis and adverse clinical outcomes, but its role as a predictor of arrhythmic events in patients with nonischemic HF is uncertain. METHODS AND RESULTS: A prospective observational study was conducted in 148 nonischemic patients with HF who underwent comprehensive clinical and laboratory evaluation, including measurement of serum GDF-15. The study endpoints were serious arrhythmic events (which included appropriate implantable cardioverter-defibrillator therapy and sudden cardiac death) and all-cause mortality. Mean age of the cohort was 54.8 ± 12.7 years, and mean left ventricular ejection fraction (LVEF) was 27.4% ± 7.5%. During a mean follow-up time of 42 months, arrhythmic events occurred in 28 patients (19%), and 40 patients (27%) died. An increase in serum GDF-15 (log-transformed) correlated linearly with a higher risk of serious arrhythmic events (HR 1.14, 95% CI 1.01-1.28, p = 0.03) even after adjustment for other potential clinical predictors (HR 1.16, 95% CI 1.02-1.32, p = 0.02). GDF-15 was also strongly and independently associated with all-cause mortality (HR 1.17, 1.05-1.31, p = 0.004). CONCLUSION: In this cohort of nonischemic HF patients on optimized medical treatment, serum GDF-15 levels were independently associated with major arrhythmic events and overall mortality. This biomarker may add prognostic information to better stratify the risk of sudden death in this particular population.

Association of Maternal Cervical Disease With Human Papillomavirus Vaccination Among Offspring.

Importance: Barriers to childhood vaccination against vaccine-preventable diseases, such as those due to human papillomavirus (HPV), are well known. However, the role of salience bias-the change in perception of risk due to increased familiarity with the outcome-in decisions to vaccinate children has not been explicitly studied. Objective: To assess for salience bias in parental decisions to vaccinate children. Design, Setting, and Participants: This retrospective cohort study used a time-to-event (survival) analysis to compare vaccination rates of children whose mothers had a history of cervical cancer or a cervical biopsy, who have experienced adverse vaccine-preventable outcomes, and for whom vaccination may be more salient, with a control group of children whose mothers had no such history. Participants were accrued from the MarketScan Commercial Database, including US children who turned 11 years old, when HPV vaccination is recommended, from January 1, 2014, to December 31, 2018. Data were analyzed from December 29, 2020, to September 17, 2021. Exposures: Maternal history of cervical cancer or cervical biopsy. Main Outcomes and Measures: Vaccination against HPV. Results: A total of 757 428 children (370 878 girls [49.0%] and 386 550 boys [51.0%]) were identified, of whom 38 366 had mothers with a history of cervical biopsy alone and 1084 had mothers with a history of cervical cancer. Overall, 54.2% of children (55.7% of girls and 52.7% of boys) received at least 1 vaccination by 16 years of age. In a time-to-event analysis, HPV vaccination did not differ between children whose mothers had cervical cancer vs those whose mothers did not (hazard ratio [HR] for girls, 0.99 [95% CI, 0.86-1.13]; HR for boys, 1.08 [95% CI, 0.94-1.24]). Maternal history of cervical biopsy was associated with a minimally increased hazard of vaccination (HR for girls, 1.06 [95% CI, 1.04-1.09]; HR for boys, 1.04 [95% CI, 1.01-1.06]). There were no clinically meaningful differences between groups for the tetanus/diphtheria/acellular pertussis and meningococcal vaccinations, which are also recommended at 11 years of age. Conclusions and Relevance: In this analysis of salience bias in childhood vaccination decisions, mothers' personal history of cervical cancer or cervical biopsy was not associated with greater vaccination rates among children against HPV. These findings suggest that salience of vaccine-preventable outcomes may not have a major impact on childhood vaccine hesitancy in HPV; the role of salience should be investigated for other vaccines.