Iron Deficiency is Highly Prevalent in Patients with Pulmonary Arterial Hypertension

Objective: The aim of this study was to assess the prevalence of iron deficiency in pulmonary hypertension, to compare it withother patient populations and to establish its prognostic value.Methods: This was a prospective, observational study. Serum iron parameters were measured in consecutive patients diagnosedwith pulmonary hypertension and compared with heart failure patients and healthy controls. A correlation was soughtbetween serum iron levels and functional class, distance walked in the 6-minute walk test and NT-proBNP.Results: A total of 107 patients were included in the study: 60 with pulmonary hypertension, 26 with heart failure and 21healthy controls. Iron deficiency was 78.3% in patients with pulmonary hypertension, 45.8% in those with heart failure and23.8% in healthy controls (p<0.001). The prevalence of anemia was 25% in pulmonary hypertension, 26.9% in heart failureand 19% in healthy controls (p<0.8). In patients with functional class I-II, iron deficiency was: 78% in pulmonary hypertensionvs. 43.5% in heart failure (p<0.005), and anemia was 17.1% vs. 28%, respectively (p<0.2). A significant correlation wasfound between serum iron and transferrin saturation with the distance walked in the 6-minute walk test (r: 0.35; p<0.01 andr: 0.34; p<0.01, respectively) and no correlation was found for transferrin and ferritin. Also, no significant correlation wasfound between iron deficiency and functional class or NT-proBNP.Conclusions: Iron deficiency is highly prevalent in pulmonary hypertension, and superior to that found in heart failure patientsand healthy controls. No relationship was established with anemia, which was similar in the three groups. Serum iron is clearlyrelated with the distance walked, but not with functional class, a result which may be attributed to the limited number of patients.Objetivos: Evaluar la prevalencia del déficit de hierro (DFe) en hipertensión pulmonar (HP) y compararlo con otras poblaciones de pacientes. Establecer su valor pronóstico. Materiales y Métodos: Estudio prospectivo, observacional. Se midieron parámetros de hierro sérico en pacientes consecutivos con diagnóstico de hipertensión pulmonar (HP). Se compararon con pacientes con insuficiencia cardiaca (IC) y con controles sanos (C). Se buscó correlación entre los valores séricos de hierro y la clase funcional, la distancia recorrida en TC6M y el NT-proBNP. Resultados: 107 pacientes: HP 60, IC 26, C 21. El DFe fue: HP 78,3%, IC 45,8%, C 23,8% (p 0,001), la prevalencia de anemia fue: HP 25%, IC 26,9%, C 19% (p 0,8). En el sub grupo de pacientes en CF 1-2 la prevalencia de DFe fue: HP 78% vs IC 43,5% (p 0,005) y la anemia: 17,1%% vs 28%% (p 0,2). Se halló correlación significativa entre Ferremia y Saturación de Transferrina con distancia caminada en TC6M (r 0,35; p 0,01 y r 0,34; p 0,01) y no hubo correlación para Ferritina y Transferrina. No se encontró significancia estadística entre DFe y CF o NT-proBNP. Conclusiones: El DFe en HP es altamente prevalente y superior al observado en IC y C, no estableciéndose relación con prevalencia de anemia, la cual fue similar en los tres grupos. El hierro sérico tiene una clara relación con la distancia caminada, no así con CF, lo que tal vez obedezca al bajo número de pacientes

Association between pre-operative statin use and major cardiovascular complications among patients undergoing non-cardiac surgery : the VISION study

AIMS: The aim of this study was to assess the effects of pre-operative statin therapy on cardiovascular events in the first 30-days after non-cardiac surgery. METHODS AND RESULTS: We conducted an international, prospective, cohort study of patients who were ≥45 years having in-patient non-cardiac surgery. We estimated the probability of receiving statins pre-operatively using a multivariable logistic model and conducted a propensity score analysis to correct for confounding. A total of 15 478 patients were recruited at 12 centres in eight countries from August 2007 to January 2011. The matched population consisted of 2845 patients (18.4%) treated with a statin and 4492 (29.0%) controls. The pre-operative use of statins was associated with lower risk of the primary outcome, a composite of all-cause mortality, myocardial injury after non-cardiac surgery (MINS), or stroke at 30 days [relative risk (RR), 0.83; 95% confidence interval (CI), 0.73–0.95; P = 0.007]. Statins were also associated with a significant lower risk of all-cause mortality (RR, 0.58; 95% CI, 0.40–0.83; P = 0.003), cardiovascular mortality (RR, 0.42; 95% CI, 0.23–0.76; P = 0.004), and MINS (RR, 0.86; 95% CI, 0.73–0.98; P = 0.02). There were no statistically significant differences in the risk of myocardial infarction or stroke. CONCLUSION: Among patients undergoing non-cardiac surgery, pre-operative statin therapy was independently associated with a lower risk of cardiovascular outcomes at 30 days. These results require confirmation in a large randomized trial. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov NCT0051210

Effect of a Multifaceted Intervention on Use of Evidence-Based Therapies in Patients With Acute Coronary Syndromes in Brazil the BRIDGE-ACS Randomized Trial

Context Studies have found that patients with acute coronary syndromes (ACS) often do not receive evidence-based therapies in community practice. This is particularly true in low- and middle-income countries.Objective To evaluate whether a multifaceted quality improvement (QI) intervention can improve the use of evidence-based therapies and reduce the incidence of major cardiovascular events among patients with ACS in a middle-income country.Design, Setting, and Participants the BRIDGE-ACS (Brazilian Intervention to Increase Evidence Usage in Acute Coronary Syndromes) trial, a cluster-randomized (concealed allocation) trial conducted among 34 clusters (public hospitals) in Brazil and enrolling a total of 1150 patients with ACS from March 15, 2011, through November 2, 2011, with follow-up through January 27, 2012.Intervention Multifaceted QI intervention including educational materials for clinicians, reminders, algorithms, and case manager training, vs routine practice (control).Main Outcome Measures Primary end point was the percentage of eligible patients who received all evidence-based therapies (aspirin, clopidogrel, anticoagulants, and statins) during the first 24 hours in patients without contraindications.Results Mean age of the patients enrolled was 62 (SD, 13) years; 68.6% were men, and 40% presented with ST-segment elevation myocardial infarction, 35.6% with non-ST-segment elevation myocardial infarction, and 23.6% with unstable angina. the randomized clusters included 79.5% teaching hospitals, all from major urban areas and 41.2% with 24-hour percutaneous coronary intervention capabilities. Among eligible patients (923/1150 [80.3%]), 67.9% in the intervention vs 49.5% in the control group received all eligible acute therapies (population average odds ratio [ORPA], 2.64 [95% CI, 1.28-5.45]). Similarly, among eligible patients (801/1150 [69.7%]), those in the intervention group were more likely to receive all eligible acute and discharge medications (50.9% vs 31.9%; ORPA,, 2.49 [95% CI, 1.08-5.74]). Overall composite adherence scores were higher in the intervention clusters (89% vs 81.4%; mean difference, 8.6% [95% CI, 2.2%-15.0%]). In-hospital cardiovascular event rates were 5.5% in the intervention group vs 7.0% in the control group (ORPA, 0.72 [95% CI, 0.36-1.43]); 30-day all-cause mortality was 7.0% vs 8.4% (ORPA, 0.79 [95% CI, 0.46-1.34]).Conclusion Among patients with ACS treated in Brazil, a multifaceted educational intervention resulted in significant improvement in the use of evidence-based therapies.Brazilian Ministry of HealthHospital do CoracaoHCor Hosp Coracao, Res Inst, BR-04004030 São Paulo, BrazilUniversidade Federal de São Paulo, Paulista Sch Med, Brazilian Clin Res Inst, São Paulo, BrazilDuke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USAUniversidade Federal de São Paulo, Paulista Sch Med, Brazilian Clin Res Inst, São Paulo, BrazilWeb of Scienc

Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial.

BackgroundHalofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.MethodsWe conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.ResultsFrom September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.ConclusionsAmong non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days

Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients: The BaSICS Randomized Clinical Trial

Importance: Slower intravenous fluid infusion rates could reduce the formation of tissue edema and organ dysfunction in critically ill patients; however, there are no data to support different infusion rates during fluid challenges for important outcomes such as mortality. Objective: To determine the effect of a slower infusion rate vs control infusion rate on 90-day survival in patients in the intensive care unit (ICU). Design, Setting, and Participants: Unblinded randomized factorial clinical trial in 75 ICUs in Brazil, involving 11052 patients requiring at least 1 fluid challenge and with 1 risk factor for worse outcomes were randomized from May 29, 2017, to March 2, 2020. Follow-up was concluded on October 29, 2020. Patients were randomized to 2 different infusion rates (reported in this article) and 2 different fluid types (balanced fluids or saline, reported separately). Interventions: Patients were randomized to receive fluid challenges at 2 different infusion rates; 5538 to the slower rate (333 mL/h) and 5514 to the control group (999 mL/h). Patients were also randomized to receive balanced solution or 0.9% saline using a factorial design. Main Outcomes and Measures: The primary end point was 90-day survival. Results: Of all randomized patients, 10520 (95.2%) were analyzed (mean age, 61.1 years [SD, 17.0 years]; 44.2% were women) after excluding duplicates and consent withdrawals. Patients assigned to the slower rate received a mean of 1162 mL on the first day vs 1252 mL for the control group. By day 90, 1406 of 5276 patients (26.6%) in the slower rate group had died vs 1414 of 5244 (27.0%) in the control group (adjusted hazard ratio, 1.03; 95% CI, 0.96-1.11; P =.46). There was no significant interaction between fluid type and infusion rate (P =.98). Conclusions and Relevance: Among patients in the intensive care unit requiring fluid challenges, infusing at a slower rate compared with a faster rate did not reduce 90-day mortality. These findings do not support the use of a slower infusion rate. Trial Registration: ClinicalTrials.gov Identifier: NCT02875873