Natural History of Dilated Cardiomyopathy Due to c.77T>C (p.Val26Ala) in Emerin Protein.

(1) Introduction: Dilated cardiomyopathy (DCM) mainly affects young individuals and is the main indication of heart transplantation. The variant c.77T>C (p.Val26Ala) of the gene coding for emerin (EMD) in chromosome Xq28 has been catalogued as a pathogenic variant for the development of DCM, exhibiting an X-linked inheritance pattern. (2) Methods: A retrospective study was conducted covering the period 2015-2023 in patients with DCM of genetic origin. The primary endpoint was patient age at onset of the first composite major cardiac event, in the form of a first episode of heart failure, malignant ventricular arrhythmia, or end-stage heart failure, according to the presence of truncating variant in titin gene (TTNtv) versus the p.Val26Ala mutation in the EMD protein. (3) Results: A total of 31 and 22 patients were included in the EMD group and TTNtv group, respectively. The primary endpoint was significantly higher in the EMD group, with a hazard ratio of 4.16 (95% confidence interval: 1.83-9.46; p = 0.001). At 55 years of age, all the patients in the EMD group had already presented heart failure, nine presented malignant ventricular arrhythmia (29%), and 13 required heart transplantation (42%). (4) Conclusions: DCM secondary to the c.77T>C (p.Val26Ala) mutation in the EMD gene is associated to an increased risk of major cardiac events compared to patients with DCM due to TTNtv, with a large proportion of transplanted patients in the fifth decade of life.

Mitochondrial Melatonin: Beneficial Effects in Protecting against Heart Failure.

Cardiovascular disease is the cause of physical infirmity and thousands of deaths annually. Typically, during heart failure, cardiomyocyte mitochondria falter in terms of energy production and metabolic processing. Additionally, inflammation and the accumulation of non-contractile fibrous tissue contribute to cardiac malfunction. Melatonin, an endogenously produced molecule, experimentally reduces the initiation and progression of atherosclerotic lesions, which are often the basis of coronary artery disease. The current review critically analyzes published data related to the experimental use of melatonin to forestall coronary artery pathologies. Collectively, these studies document melatonin's anti-atherosclerotic actions in reducing LDL oxidation and triglyceride levels, lowering endothelial malfunction, limiting adhesion molecule formation, preventing macrophage polarization to the M1 pro-inflammatory phenotype, changing cellular metabolism, scavenging destructive reactive oxygen species, preventing the proliferation and invasion of arterial smooth muscle cells into the lesioned area, restricting the ingrowth of blood vessels from the vasa vasorum, and solidifying the plaque cap to reduce the chance of its rupture. Diabetic hyperglycemia, which aggravates atherosclerotic plaque formation, is also inhibited by melatonin supplementation in experimental animals. The potential value of non-toxic melatonin as a possible inhibitor of cardiac pathology in humans should be seriously considered by performing clinical trials using this multifunctional molecule.

Urinary catheterization of patients with acute heart failure in a hospital emergency department: a factor associated with prognosis. / El sondaje vesical de los pacientes con insuficiencia cardiaca aguda en un servicio de urgencias hospitalario se asocia al pronóstico.

OBJECTIVES: To analyze whether urinary catheterization in a hospital emergency department (ED) affects short-term prognosis in patients with acute heart failure (AHF). MATERIAL AND METHODS: We prospectively recorded baseline and other clinical data in a consecutive cohort of ED patients treated for AHF. Crude and adjusted associations were calculated between catheterization and a primary composite outcome (30-day readmission for AHF and/or death) and secondary outcomes (in-hospital mortality, urinary tract infection [UTI], and duration of hospital stay.). RESULTS: Nine hundred ninety-one patients were admitted for AHF. The mean (SD) age was 66 (10.5) years; 71% were women. Catheterization was required for 29.2% in the ED. The primary composite outcome was observed in 7.7% of the patients who were not catheterized and 12.8% of the catheterized patients (P = .02). In-hospital mortality occurred in 5.9% and 9.7% of non-catheterized and catheterized patients, respectively (P = .04), and UTIs occurred in 19.1% and 26.6% (P = .01). Twelve of the non-catheterized patients (1.7%) were readmitted for AHF (vs 11 (3.8%) of the catheterized patients (P = .06), and there were no differences between the groups in hospital stay (11 vs 10.9 days, P = .78). In the adjusted analysis of associations between catheterization and the primary outcome the odds and hazard ratios (OR and HR, respectively) were OR, 1.7 (95% CI, 1.1-2.7) (P = .02) and HR, 1.6 (95% CI, 1.1-2.5) (P = .03). For secondary outcomes, significant associations emerged between catheterization and UTIs (OR, 1.8 [95% CI, 1.1-2.2]; P = .008) and readmission for AHF (OR, 2.9 [95% CI, 1.2-7.3]; P = .02). CONCLUSION: Routine insertion of a urinary catheter in patients with AHF in the ED is associated with worse 30-day clinical outcomes.

OBJETIVO: Analizar si el sondaje vesical (SV) rutinario en un servicio de urgencias hospitalario (SUH) de pacientes diagnosticados de insuficiencia cardiaca aguda (ICA) está asociado con la evolución a corto plazo. METODO: Se recogieron prospectivamente datos basales y clínicos de una cohorte de pacientes consecutivos que ingresaron por ICA. Se analizó la asociación cruda y ajustada del SV con el evento combinado de muerte o reingreso por insuficiencia cardiaca a 30 días (objetivo primario), así como mortalidad intrahospitalaria, infección del tracto urinario (ITU) y estancia hospitalaria (objetivos secundarios). RESULTADOS: Se incluyeron 991 pacientes hospitalizados por ICA, la edad media fue de 66 años (DE 10,5) y el 71% fueron mujeres. Un 29,2% de los pacientes requirieron SV en el SUH. El evento combinado fue del 7,7% para el grupo no SV y 12,8% para grupo SV (p = 0,02); mortalidad intrahospitalaria fue del 5,9% en el grupo no SV y 9,7% en el grupo SV (p = 0,04); se diagnosticó ITU en el 19,1% de pacientes en el grupo no SV y en el 26,6% en el grupo SV (p = 0,01). A 30 días, 12 pacientes (1,7%) reingresaron por insuficiencia cardiaca en el grupo no SV versus 11 (3,8%) pacientes en el grupo SV (p = 0,06). No hubo diferencias en la estancia hospitalaria (11 versus 10,9 días); p = 0,78). En el análisis ajustado, el SV se asoció con el objetivo primario; [OR = 1,7 (IC 95%: 1,1-2,7; p = 0,02); HR = 1,6 (IC 95%: 1,1-2,5; p = 0,03)]; con la ITU (OR = 1,8; IC 95%: 1,1­2,2; p = 0,008) y con el reingreso por insuficiencia cardiaca (OR = 2,9; IC 95%: 1,2-7,3; p = 0,02). CONCLUSIONES: La inserción rutinaria del SV en el SUH en pacientes con ICA se asoció a peores resultados clínicos a los 30 días.

Effects of MIdazolam versus MOrphine in acute cardiogenic pulmonary edema and chronic obstructive pulmonary disease: An analysis of MIMO trial.

AIMS: Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure. The MIMO trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. In this post hoc analysis, we examined whether the presence/ absence of COPD modifies the reduced risk of midazolam over morphine. METHODS: Patients >18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine. In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without COPD. Calculating the CochranMantel-Haenszel interaction test, we evaluated if COPD modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. RESULTS: Overall, 25 (22.5%) of the 111 patients randomized had a history of COPD. Patients with COPD were more commonly men with a history of previous episodes of heart failure, than participants without COPD. In the COPD group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.36 (95%CI, 0.1-1.46). In the group without COPD, the RR was 0.44 (95%CI, 0.22-0.91). The presence of COPD did not modify the reduced risk of serious adverse events in the midazolam arm compared to morphine (p for interaction =0.79). CONCLUSIONS: The reduced risk of serious adverse events in the midazolam group compared with morphine is similar in patients with and without COPD.

Rationale and Design of the Impact of Air Pollution Due to DESERT Dust in Patients with HEART Failure (DESERT HEART).

AIMS: The main objective of this study is to determine whether exposure to Saharan dust causes airway inflammation and oxidative stress in patients with stable chronic heart failure (HF) and a left ventricular ejection fraction of less than 40%. METHODS: A longitudinal study design is used, involving the inclusion of 40 patients with stable chronic HF and a left ventricular ejection fraction of less than 40%. Four sputum samplings will be taken from each patient, with one sampling taken each week over four consecutive weeks. The sputum samples will be used to analyze the degree of inflammation and oxidative stress. Air quality monitoring stations will be used to analyze the particulate matter (PM) exposure of each patient. The intrusion of desert dust will be identified using meteorological models. There will be 160 scheduled samplings in 40 patients with chronic HF. Mixed regression models will be used to assess the influence of the concentrations of PM (from the episodes of desert dust) upon the airway inflammation and oxidative stress markers. CONCLUSION: The results of this study will test the hypothesis that exposure to high concentrations of Saharan dust affects the normal function of the respiratory epithelium due to the imbalance between the production of free radicals and antioxidant enzymes, thus causing increased pulmonary inflammation and oxidative stress in patients with HF that in turn may facilitate decompensations of their background disease condition.

Análisis de la relación entre la contaminación del aire ambiente y la gravedad de las descompensaciones por insuficiencia cardiaca en dos metrópolis españolas (Barcelona y Madrid) / Analysis of the relationship between ambient air pollution and the severity of heart failure decompensations in two Spanish metropolises (Barcelona and Madrid)

Se estudiaron pacientes con IC descompensada en urgencias de 4 hospitales de Barcelona y 3 de Madrid. Se recogieron datos clínicos (edad, sexo, comorbilidades, situación funcional basal), atmosféricos (temperatura, presión atmosférica) y de contaminantes (SO2, NO2, CO, O3, PM10, PM2,5) el día de atención en urgencias. La gravedad de la descompensación se estimó mediante la mortalidad a 7 días (indicador primario) y la necesidad de hospitalización, mortalidad intrahospitalaria y hospitalización prolongada (indicadores secundarios). Se investigó la asociación ajustada por datos clínicos, atmosféricos y ciudad entre concentración de contaminantes y gravedad, mediante regresión logística (asunción de linealidad) y curvas spline cúbicas restringidas (no asunción de linealidad). Resultados Se incluyeron 5.292 descompensaciones, con edad mediana de 83 años (RIC=76-88) y 56% mujeres. Las medianas (RIC) de los promedios diarios de contaminantes fueron: SO2=2,5μg/m3 (1,4-7,0), NO2=43μg/m3 (34-57), CO=0,48mg/m3 (0,35-0,63), O3=35μg/m3 (25-48), PM10=22μg/m3 (15-31) y PM2,5=12μg/m3 (8-17). La mortalidad a 7 días fue del 3,9%, y la hospitalización, la mortalidad intrahospitalaria y la hospitalización prolongada, del 78,9, 6,9 y 47,5%, respectivamente. El SO2 fue el único contaminante que mostró asociación lineal con la gravedad de la descompensación, ya que cada unidad de incremento supuso una OR para necesidad de hospitalización de 1,04 (IC 95% 1,01-1,08). El estudio mediante curvas spline cúbicas restringidas tampoco mostró asociaciones nítidas entre contaminantes y gravedad, excepto para SO2 y hospitalización, con OR de 1,55 (IC 95% 1,01-2,36) y de 2,71 (IC 95% 1,13-6,49) para concentraciones de 15 y 24μg/m3, respectivamente, en relación con una concentración de referencia de 5μg/m3 (AU)

Objectives To analyze whether the high levels of air pollutants are related to a greater severity of decompensated heart failure (HF). Method Patients diagnosed with decompensated HF in the emergency department of 4 hospitals in Barcelona and 3 in Madrid were included. Clinical data (age, sex, comorbidities, baseline functional status), atmospheric (temperature, atmospheric pressure) and pollutant data (SO2, NO2, CO, O3, PM10, PM2.5) were collected in the city on the day of emergency care. The severity of decompensation was estimated using 7-day mortality (primary indicator) and the need for hospitalization, in-hospital mortality, and prolonged hospitalization (secondary indicators). The association adjusted for clinical, atmospheric and city data between pollutant concentration and severity was investigated using linear regression (linearity assumption) and restricted cubic spline curves (no linearity assumption). Results A total of 5292 decompensations were included, with a median age of 83 years (IQR=76-88) and 56% women. The medians (IQR) of the daily pollutant averages were: SO2=2.5μg/m3 (1.4-7.0), NO2=43μg/m3 (34-57), CO=0.48mg/m3 (0.35-0.63), O3=35μg/m3 (25-48), PM10=22μg/m3 (15-31) and PM2.5=12μg/m3 (8-17). Mortality at 7 days was 3.9%, and hospitalization, in-hospital mortality, and prolonged hospitalization were 78.9, 6.9, and 47.5%, respectively. SO2 was the only pollutant that showed a linear association with the severity of decompensation, since each unit of increase implied an OR for the need for hospitalization of 1.04 (95% CI 1.01-1.08). The restricted cubic spline curves study also did not show clear associations between pollutants and severity, except for SO2 and hospitalization, with OR of 1.55 (95% CI 1.01-2.36) and 2.71 (95% CI 1.13-6.49) for concentrations of 15 and 24μg/m3, respectively, in relation to a reference concentration of 5μg/m3 (AU)

Exercise and Prediabetes After Renal Transplantation (EXPRED-I): A Prospective Study.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) beyond 12 months (late PTDM) is a severe complication after renal transplantation. Late PTDM develops mostly in subjects with prediabetes. Although exercise may have a potential role in preventing late PTDM, there are no previous data on the effect of exercise in patients with prediabetes. MATERIAL AND METHODS: The design was a 12-month exploratory study to test the capacity of exercise in reverting prediabetes in order to prevent late-PTDM. The outcome was the reversibility of prediabetes, assessed every 3 months with oral glucose tolerance tests (OGTT). The protocol included an incremental plan of aerobic and/or strength training as well as an active plan for promoting adherence (telephone calls, digital technology, and visits). A priori, a sample size cannot be calculated which makes this an exploratory analysis. Based on previous studies, the spontaneous reversibility of prediabetes was 30% and the reversibility induced by exercise will account for another 30%, a total reversibility of 60% (p value < 0.05, assuming a potency of 85%). Ad interim analysis was performed during follow-up to test the certainty of this sample calculation. Patients beyond 12 months after renal transplantation with prediabetes were included. RESULTS: The study was interrupted early due to efficacy after the evaluation of the follow-up of 27 patients. At the end of follow-up, 16 (60%) patients reverted to normal glucose levels at fasting (from 102.13 mg/dL ± 11 to 86.75 ± 6.9, p = 0.006) and at 120 min after the OGTTs (154.44 mg/dL ± 30 to 113.0 ± 13.1, p = 0.002) and 11 patients had persistent prediabetes (40%). Also, insulin sensitivity improved with the reversibility of prediabetes, compared to those with persistent prediabetes: 0.09 [0.08-0.11] versus 0.04 [0.01-0.07], p = 0.001 (Stumvoll index). Most needed at least one increment in the prescription of exercise and compliance. Finally, measures aimed at the improvement of compliance were successful in 22 (80%) patients. CONCLUSION: Exercise training was effective to improve glucose metabolism in renal transplant patients with prediabetes. Exercise prescription must be conducted considering both the clinical characteristics of the patients and pre-defined strategy to promote adherence. The trial registration number of the study was NCT04489043.

[Analysis of the relationship between ambient air pollution and the severity of heart failure decompensations in two Spanish metropolises (Barcelona and Madrid)]. / Análisis de la relación entre la contaminación del aire ambiente y la gravedad de las descompensaciones por insuficiencia cardiaca en dos metrópolis españolas (Barcelona y Madrid).

OBJECTIVES: To analyze whether the high levels of air pollutants are related to a greater severity of decompensated heart failure (HF). METHOD: Patients diagnosed with decompensated HF in the emergency department of 4 hospitals in Barcelona and 3 in Madrid were included. Clinical data (age, sex, comorbidities, baseline functional status), atmospheric (temperature, atmospheric pressure) and pollutant data (SO2, NO2, CO, O3, PM10, PM2.5) were collected in the city on the day of emergency care. The severity of decompensation was estimated using 7-day mortality (primary indicator) and the need for hospitalization, in-hospital mortality, and prolonged hospitalization (secondary indicators). The association adjusted for clinical, atmospheric and city data between pollutant concentration and severity was investigated using linear regression (linearity assumption) and restricted cubic spline curves (no linearity assumption). RESULTS: A total of 5292 decompensations were included, with a median age of 83 years (IQR=76-88) and 56% women. The medians (IQR) of the daily pollutant averages were: SO2=2.5µg/m3 (1.4-7.0), NO2=43µg/m3 (34-57), CO=0.48mg/m3 (0.35-0.63), O3=35µg/m3 (25-48), PM10=22µg/m3 (15-31) and PM2.5=12µg/m3 (8-17). Mortality at 7 days was 3.9%, and hospitalization, in-hospital mortality, and prolonged hospitalization were 78.9, 6.9, and 47.5%, respectively. SO2 was the only pollutant that showed a linear association with the severity of decompensation, since each unit of increase implied an OR for the need for hospitalization of 1.04 (95% CI 1.01-1.08). The restricted cubic spline curves study also did not show clear associations between pollutants and severity, except for SO2 and hospitalization, with OR of 1.55 (95% CI 1.01-2.36) and 2.71 (95% CI 1.13-6.49) for concentrations of 15 and 24µg/m3, respectively, in relation to a reference concentration of 5µg/m3. CONCLUSION: Exposure to ambient air pollutants, in a medium to low concentration range, is generally not related to the severity of HF decompensations, and only SO2 may be associated with an increased need for hospitalization.

Midazolam versus morphine in acute cardiogenic pulmonary edema patients with and without atrial fibrillation: findings from the MIMO trial.

BACKGROUND AND IMPORTANCE: The MIMO clinical trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. Atrial fibrillation (AF) is a common comorbidity in heart failure and affects patient's outcome. OBJECTIVE: The primary endpoint of this substudy is to know if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. The first secondary endpoint is to know if AF modified the reduced risk of serious adverse events or death at 30 days in the midazolam arm. The second secondary objective of this substudy is to analyze whether AF modified the reduced risk of midazolam against morphine on the total number of serious adverse events per patient. DESIGN: We conducted a secondary analysis of the MIMO trial. Patients more than 18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine. OUTCOME MEASURES AND ANALYSIS: In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without AF. Calculating the Cochran-Mantel-Haenszel interaction test, we evaluated if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. MAIN RESULTS: One hundred eleven patients (median = 78.9 years; IQR, 72.3-83.7; women, 52.2%) were randomized in the MIMO trial, 55 to receive midazolam and 56 to morphine. All randomized patients received the assigned drug and there were no losses to follow-up. Forty-four patients (39.6%) had AF. In the AF group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.42 (95% CI, 0.14-1.3). In the group without AF, the RR was 0.46 (95% CI, 0.21-1). The presence of AF did not modify the reduced risk of serious adverse events in the midazolam arm compared with morphine ( P for interaction = 0.88). CONCLUSION: This post hoc analysis of the MIMO trial suggests that the reduced risk of serious adverse events in the midazolam group compared to morphine is similar in patients with and without AF.

Effects of midazolam vs morphine in patients with acute pulmonary edema with left ventricular systolic dysfunction: a secondary analysis of data from the MIMO trial. / Efectos del midazolam frente a la morfina en pacientes con edema agudo de pulmón con disfunción sistólica ventricular izquierda: un análisis secundario del ensayo MIMO.

OBJECTIVES: The midazolam vs morphine (MIMO) trial showed that patients treated with midazolam had fewer serious adverse events than those treated with morphine. In many patients with acute pulmonary edema, the left ventricular ejection fraction (LVEF) is preserved, at 50% or higher. We aimed to determine whether left ventricular (LV) systolic dysfunction (D), defined by an LVEF of less than 50%, modifies the protective effect of midazolam vs morphine. MATERIAL AND METHODS: The MIMO trial randomized 111 patients with acute pulmonary edema to receive intravenous midazolam in 1-mg doses to a maximum of 3 mg (n = 55) or morphine in 2- to 4-mg doses to a maximum of 8 mg (n= 56). We calculated the relative risk (RR) for a serious adverse event in patients with and without systolic LVD. RESULTS: LVEF was preserved in 84 (75.7%) of the patients with acute pulmonary edema. In patients with systolic LVD, 4 patients (26.9%) in the midazolam arm vs 6 (50%) in the morphine arm developed serious adverse events (RR, 0.53; 95% CI, 0.2-1.4). In patients without systolic LVD, 6 patients (15%) in the midazolam arm vs 18 (40.9%) in the morphine arm experienced such events (RR, 0.37; 95% CI, 0.16-0.83). The presence of systolic LVD did not modify the protective effect of midazolam on serious adverse effects (P=.57). CONCLUSION: The effect of midazolam vs morphine in protecting against the development of serious adverse events or death is similar in patients with and without systolic LVD.

OBJETIVO: El ensayo clínico MIMO demostró que los pacientes con edema agudo de pulmón (EAP) tratados con midazolam tenían menos eventos adversos graves (EAG) que los tratados con morfina. Muchos pacientes con EAP tienen fracción de eyección del ventrículo izquierdo (FEVI) preservada ($ 50%). El objetivo fue conocer si la disfunción sistólica ventricular izquierda (DSVI) (fracción eyección ventrículo izquierdo 50%) modifica el efecto protector del midazolam frente a la morfina. METODO: El estudio MIMO asignó al azar 111 pacientes con EAP a tratamiento con midazolam (dosis de 1 mg intravenosa, hasta una dosis máxima de 3 mg, n = 55) o morfina (dosis de 2-4 mg, hasta una dosis máxima de 8 mg, n = 56). Se calculó el riesgo relativo (RR) de padecer un EAG en pacientes con y sin DSVI. RESULTADOS: La FEVI preservada estuvo presente en 84 (75,7%) pacientes con EAP. En el grupo con DSVI, 4 pacientes (26,9%) en el brazo midazolam frente a 6 (50%) en el brazo morfina presentaron EAG (RR = 0,53; IC 95: 0,2-1,4). En el grupo sin DSVI 6 pacientes (15%) del brazo midazolam frente a 18 (40,9%) del brazo morfina presentaron EAG (RR = 0,37; IC 95: 0,16-0,83). La DSVI no modificó el efecto protector del midazolam en la aparición de EAG con respecto a la morfina (p = 0,57). CONCLUSIONES: En pacientes con EAP el efecto protector del midazolam sobre la morfina en la aparición de EAG y EAG o muerte fue similar en pacientes con y sin DSVI.

Efectos del midazolam frente a la morfina en pacientes con edema agudo de pulmón con disfunción sistólica ventricular izquierda: un análisis secundario del ensayo MIMO / Effects of midazolam vs morphine in patients with acute pulmonary edema with left ventricular systolic dysfunction: a secondary analysis of data from the MIMO trial

Objetivo. El ensayo clínico MIMO demostró que los pacientes con edema agudo de pulmón (EAP) tratados con midazolam tenían menos eventos adversos graves (EAG) que los tratados con morfina. Muchos pacientes con EAP tienen fracción de eyección del ventrículo izquierdo (FEVI) preservada ($ 50%). El objetivo fue conocer si la disfunción sistólica ventricular izquierda (DSVI) (fracción eyección ventrículo izquierdo < 50%) modifica el efecto protector del midazolam frente a la morfina.Método. El estudio MIMO asignó al azar 111 pacientes con EAP a tratamiento con midazolam (dosis de 1 mg intravenosa, hasta una dosis máxima de 3 mg, n = 55) o morfina (dosis de 2-4 mg, hasta una dosis máxima de 8 mg, n = 56). Se calculó el riesgo relativo (RR) de padecer un EAG en pacientes con y sin DSVI.Resultado. La FEVI preservada estuvo presente en 84 (75,7%) pacientes con EAP. En el grupo con DSVI, 4 pacientes (26,9%) en el brazo midazolam frente a 6 (50%) en el brazo morfina presentaron EAG (RR = 0,53; IC 95: 0,2-1,4). En el grupo sin DSVI 6 pacientes (15%) del brazo midazolam frente a 18 (40,9%) del brazo morfina presentaron EAG (RR = 0,37; IC 95: 0,16-0,83). La DSVI no modificó el efecto protector del midazolam en la aparición de EAG con respecto a la morfina (p = 0,57)Conclusiones. En pacientes con EAP el efecto protector del midazolam sobre la morfina en la aparición de EAG y EAG o muerte fue similar en pacientes con y sin DSVI. (AU)

Background and objective. The midazolam vs morphine (MIMO) trial showed that patients treated with midazolam had fewer serious adverse events than those treated with morphine. In many patients with acute pulmonary edema, the left ventricular ejection fraction (LVEF) is preserved, at 50% or higher. We aimed to determine whether left ventricular (LV) systolic dysfunction (D), defined by an LVEF of less than 50%, modifies the protective effect of midazolam vs morphine. Methods. The MIMO trial randomized 111 patients with acute pulmonary edema to receive intravenous midazolam in 1-mg doses to a maximum of 3 mg (n = 55) or morphine in 2- to 4-mg doses to a maximum of 8 mg (n= 56). We calculated the relative risk (RR) for a serious adverse event in patients with and without systolic LVD. Results. LVEF was preserved in 84 (75.7%) of the patients with acute pulmonary edema. In patients with systolic LVD, 4 patients (26.9%) in the midazolam arm vs 6 (50%) in the morphine arm developed serious adverse events (RR, 0.53; 95% CI, 0.2-1.4). In patients without systolic LVD, 6 patients (15%) in the midazolam arm vs 18 (40.9%) in the morphine arm experienced such events (RR, 0.37; 95% CI, 0.16-0.83). The presence of systolic LVD did not modify the protective effect of midazolam on serious adverse effects (P=.57). Conclusions. The effect of midazolam vs morphine in protecting against the development of serious adverse eventsor death is similar in patients with and without systolic LVD. (AU)

Antithrombotic Strategy in Secondary Prevention for High-Risk Patients with Previous Acute Coronary Syndrome: Overlap between the PEGASUS Eligibility and the COMPASS Eligibility in a Large Multicenter Registry.

BACKGROUND: Patients with previous acute coronary syndrome (ACS) are at high risk of recurrent adverse cardiovascular events. Recently, prolonged dual antiplatelet therapy (DAPT) and oral anticoagulation therapy (OAT) have been shown to reduce recurrent ischemic events to the expense of an increase in bleeding events. The number of patients potentially eligible for these therapies in real life remains to be determined. METHODS: Among ACS patients from five registries and one randomized controlled trial, we assessed the proportion of patients eligible for the PEGASUS strategy only and the proportion of patients eligible for the COMPASS strategy only, and set out the proportion of patients with an overlap between the strategies. FINDINGS: Among the 10,048 evaluable patients, we found that 5373 (53.4%) were eligible for the PEGASUS strategy and 3841 (38.2%) were eligible for the COMPASS strategy, with a group of 3444 (34.4%) overlapping between the two strategies. The number of patients eligible for the PEGASUS strategy only was 1929 (19.2%) and the number eligible for the COMPASS strategy only was 397 (4.0%); 4278 (42.6%) were eligible for neither a PEGASUS strategy nor a COMPASS strategy. INTERPRETATION: In a large cohort of ACS patients, one in three patients was eligible for either a prolonged DAPT with ticagrelor 60 mg and low-dose aspirin or a dual pathway inhibition approach with rivaroxaban 2.5 mg and low-dose aspirin.