Timing of previous heart failure hospitalization as a prognostic factor for emergency department heart failure patients.

To investigate whether the timing of a previous hospital admission for acute heart failure (AHF) is a prognostic factor for AHF patients revisiting the emergency department (ED) in the subsequent 12-month follow-up. All ED AHF patients enrolled in the previously described EAHFE registry were stratified by the presence or absence of an AHF hospitalization admission in the prior 12 months. The primary outcome was 12-month all-cause mortality post ED visit. Secondary end points were hospital admission, prolonged hospitalization (> 7 days), mortality during hospitalization and a 90-day post-discharge adverse composite event (ACE) rate, defined as ED revisits due to AHF, hospitalizations due to AHF, or all-cause mortality. Outcomes were adjusted for baseline and AHF episode characteristics.Of 5,757 patients included, the median age was 84 years (IQR 77-88); 57% were women, and 3,759 (65.3%) had an AHF hospitalization in the previous 12 months. The 12-month mortality was 37% (41.7% vs. 28.3% p < 0.001), hospital admission was 76.1% (78.8% vs. 71.1% p < 0.001) ACE was 60.2% (65.1% vs. 50.5% p < 0.001). In the adjusted analysis, patients with AHF hospitalization in the prior 12 months had a higher mortality (HR = 1.41; 95% CI 1.27-1.56), 90-day ACE rate (HR = 1.45: 95% CI 1.32-1.59), and more hospital admissions (OR = 1.32; 95% CI 1.16-1.51), with shorter times since the previous hospitalization being related to the outcomes analyzed. One-year mortality, adverse events at 90 days, and readmission rates are increased in ED AHF patients previously admitted within the last 12 months.

Treatment of hypertension with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and resting metabolic rate: A cross-sectional study.

Hypertension in obese and overweight patients is associated with an elevated resting metabolic rate (RMR). The aim of this study was to determine whether RMR is reduced in hypertensive patients treated with angiotensin-converting enzyme inhibitors (ACEI) and blockers (ARB). The RMR was determined by indirect calorimetry in 174 volunteers; 93 (46.5 %) were hypertensive, of which 16 men and 13 women were treated with ACEI/ARB, while 30 men and 19 women with untreated hypertension served as a control group. Treated and untreated hypertensives had similar age, BMI, physical activity, and cardiorespiratory fitness. The RMR normalized to the lean body mass (LBM) was 15% higher in the untreated than ACEI/ARB-treated hypertensive women (p = .003). After accounting for LBM, whole-body fat mass, age, the double product (heart rate x systolic blood pressure), and the distance walked per day, the RMR was 2.9% lower in the patients taking ACEI/ARB (p = .26, treatment x sex interaction p = .005). LBM, age, and the double product explained 78% of the variability in RMR (R2  = 0.78, p < .001). In contrast, fat mass, the distance walked per day, and total T4 or TSH did not add predictive power to the model. Compared to men, a greater RMR per kg of LBM was observed in untreated hypertensive overweight and obese women, while this sex difference was not observed in patients treated with ACEI or ARBs. In conclusion, our results indicate that elevated RMR per kg of LBM may be normalized by antagonizing the renin-angiotensin system.

Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.

Mortality in patients treated for COVID-19 in the emergency department of a tertiary care hospital during the first phase of the pandemic: Derivation of a risk model for emergency departments. / Análisis de mortalidad de los pacientes atendidos por COVID-19 en el servicio de urgencias de un hospital de tercer nivel en la fase incial de la pandemia. Derivación de un modelo de riesgo para urgencias.

OBJECTIVES: To develop a risk model to predict 30-day mortality after emergency department treatment for COVID-19. MATERIAL AND METHODS: Observational retrospective cohort study including 2511 patients with COVID-19 who came to our emergency department between March 1 and April 30, 2020. We analyzed variables with Kaplan Meier survival and Cox regression analyses. RESULTS: All-cause mortality was 8% at 30 days. Independent variables associated with higher risk of mortality were age over 50 years, a Barthel index score less than 90, altered mental status, the ratio of arterial oxygen saturation to the fraction of inspired oxygen (SaO2/FIO2), abnormal lung sounds, platelet concentration less than 100 000/mm3, a C-reactive protein concentration of 5 mg/dL or higher, and a glomerular filtration rate less than 45 mL/min. Each independent predictor was assigned 1 point in the score except age, which was assigned 2 points. Risk was distributed in 3 levels: low risk (score of 4 points or less), intermediate risk (5 to 6 points), and high risk (7 points or above). Thirty-day risk of mortality was 1.7% for patients who scored in the low-risk category, 28.2% for patients with an intermediate risk score, and 67.3% for those with a high risk score. CONCLUSION: This mortality risk stratification tool for patients with COVID-19 could be useful for managing the course of disease and assigning health care resources in the emergency department.

OBJETIVO: Derivar un modelo de riesgo para estimar la probabilidad de mortalidad a los 30 días de la visita a urgencias de pacientes con COVID-19. METODO: Estudio observacional de cohortes retrospectivo de 2.511 pacientes con COVID-19 atendidos en el servicio de urgencias hospitalario (SUH) del 1 de marzo al 30 de abril de 2020. Se realizó análisis de supervivencia mediante Kaplan Meier y regresión de Cox. RESULTADOS: La mortalidad por cualquier causa a los 30 días fue de un 8%. Los factores asociados de forma independiente a mayor mortalidad fueron: edad 50 años, índice de Barthel 90 puntos, alteración del nivel de consciencia, índice de SaO2/FIO2 400, auscultación respiratoria anómala, cifra de plaquetas 100.000/mm3, PCR 5 mg/dL y filtrado glomerular 45 mL/min. A estos factores se les asignó una puntuación de 1, excepto a la edad, que se le asignó un valor de 2 puntos. Se dividió el modelo de riesgo en 3 categorías: riesgo bajo (menor o igual a 4 puntos), riesgo intermedio (5-6 puntos) y riesgo alto (igual o superior a 7 puntos). Para los pacientes clasificados como de bajo riesgo la probabilidad de mortalidad a los 30 días fue del 1,7%, en los casos de riesgo intermedio fue del 28,2% y para los de alto riesgo fue del 67,3%. CONCLUSIONES: Disponer de una herramienta para estratificar el riesgo de mortalidad de los pacientes con COVID-19 que consultan a un SUH podría ser de utilidad para la gestión de los recursos sanitarios disponibles.

Resting metabolic rate is increased in hypertensive patients with overweight or obesity: Potential mechanisms.

The purpose of this investigation was to determine whether differences in body composition, pharmacological treatment, and physical activity explain the increased resting metabolic rate (RMR) and impaired insulin sensitivity in hypertension. Resting blood pressure, RMR (indirect calorimetry), body composition (dual-energy X-ray absorptiometry), physical activity (accelerometry), maximal oxygen uptake (VO2 max) (ergospirometry), and insulin sensitivity (Matsuda index) were measured in 174 patients (88 men and 86 women; 20-68 years) with overweight or obesity. Hypertension (HTA) was present in 51 men (58%) and 42 women (49%) (p = .29). RMR was 6.9% higher in hypertensives than normotensives (1777 ± 386 and 1663 ± 383 kcal d-1 , p = .044). The double product (systolic blood pressure × heart rate) was 18% higher in hypertensive than normotensive patients (p < .001). The observed differences in absolute RMR were non-significant after adjusting for total lean mass and total fat mass (estimated means: 1702 kcal d-1 , CI: 1656-1750; and 1660 kcal d-1 , CI: 1611-1710 kcal d-1 , for the hypertensive and normotensive groups, respectively, p = .19, HTA × sex interaction p = .37). Lean mass, the double product, and age were the variables with the higher predictive value of RMR in hypertensive patients. Insulin sensitivity was lower in hypertensive than in normotensive patients, but these differences disappeared after accounting for physical activity and VO2max . In summary, hypertension is associated with increased RMR and reduced insulin sensitivity. The increased RMR is explained by an elevated myocardial oxygen consumption due to an increased resting double product, combined with differences in body composition between hypertensive and normotensive subjects.

Factors associated with revisits by patients with SARS-CoV-2 infection discharged from a hospital emergency department. / Factores asociados a revisita en pacientes con diagnóstico de infección por SARS-CoV-2 dados de alta de un servicio de urgencias hospitalario.

OBJECTIVES: To analyze emergency department (ED) revisits from patients discharged with possible coronavirus disease 2019 (COVID-19). MATERIAL AND METHODS: Retrospective observational study of consecutive patients who came to the ED over a period of 2 months and were diagnosed with possible COVID-19. We analyzed clinical and epidemiologic variables, treatments given in the ED, discharge destination, need to revisit, and reasons for revisits. Patients who did or did not revisit were compared, and factors associated with revisits were explored. RESULTS: The 2378 patients included had a mean age of 57 years; 49% were women. Of the 925 patients (39%) discharged, 170 (20.5%) revisited the ED, mainly for persistence or progression of symptoms. Sixty-six (38.8%) were hospitalized. Odds ratios (ORs) for the following factors showed an association with revisits: history of rheumatologic disease (OR, 2.97; 95% CI, 1.10-7.99; P = .03), digestive symptoms (OR, 1.73; 95% CI, 1.14-2.63; P = .01), respiratory rate over 20 breaths per minute (OR, 1.03; 95% CI, 1.0-1.06; P = .05), and corticosteroid therapy given in the ED (OR, 7.78; 95% CI, 1.77-14.21, P = .01). Factors associated with hospitalization after revisits were age over 48 years (OR, 2.57; 95% CI, 1 42-4.67; P = .002) and fever (OR, 4.73; 95% CI, 1.99-11.27; P = .001). CONCLUSION: Patients under the age of 48 years without comorbidity and with normal vitals can be discharged from the ED without fear of complications. A history of rheumatologic disease, fever, digestive symptoms, and a respiratory rate over 20 breaths per minute, or a need for corticosteroid therapy were independently associated with revisits. Fever and age over 48 years were associated with a need for hospitalization.

OBJETIVO: Analizar las revisitas y los factores asociados a la misma en pacientes con diagnóstico de posible COVID-19 dados de alta de un servicio de urgencias hospitalario (SUH). METODO: Estudio observacional, retrospectivo que incluyó pacientes consecutivos que consultaron al SUH en un periodo de 2 meses y fueron diagnosticados de posible de COVID-19. Se analizaron variables clínico-epidemiológicas, tratamiento administrado en urgencias, destino final, revisita al SUH y motivo de esta. Se hizo un análisis comparativo entre ambos grupos (revisita sí/no) y se identificaron factores asociados a la revisita. RESULTADOS: Se incluyeron 2.378 pacientes (edad media 57 años; 49% mujeres). De los pacientes dados de alta (39% del total; n = 925), 170 (20,5%) reconsultaron al SUH, principalmente por persistencia o progresión de síntomas, y 66 (38,8%) precisaron ingreso. Los factores relacionados con la revisita fueron: antecedentes de enfermedad reumatológica [OR: 2,97 (IC 95%: 1,10-7,99, p = 0,03)], síntomas digestivos [OR: 1,73 (IC 95%: 1,14-2,63, p = 0,01)], frecuencia respiratoria $ 20 [OR: 1,03 (IC 95%: 1,0-1,06, p = 0,05)] y haber recibido tratamiento con esteroides en urgencias [OR: 7,78 (IC 95%: 1,77-14,21, p = 0,01)]. Los factores asociados al ingreso en la revisita fueron la edad $ 48 años [OR: 2,57 (IC 95%: 1,42-4,67, p = 0,002)] y presentar fiebre [OR: 4,73 (IC 95%: 1,99-11,27, p = 0,001)]. CONCLUSIONES: Los pacientes con posible COVID-19 menores de 48 años, sin comorbilidad y con signos vitales normales podrían ser dados de alta desde urgencias sin temor a sufrir complicaciones. Los antecedentes de enfermedad reumatológica, fiebre, sintomas digestivos, frecuencia respiratoria $ 20/min o necesidad de tratamiento con esteroides fueron factores independientes de revisita, y la fiebre y edad $ 48 años de necesidad de ingreso.

Resting Energy Expenditure and Body Composition in Overweight Men and Women Living in a Temperate Climate.

This study aimed to determine whether the measured resting energy expenditure (REE) in overweight and obese patients living in a temperate climate is lower than the predicted REE; and to ascertain which equation should be used in patients living in a temperate climate. REE (indirect calorimetry) and body composition (DXA) were measured in 174 patients (88 men and 86 women; 20-68 years old) with overweight or obesity (BMI 27-45 kg m-2). All volunteers were residents in Gran Canaria (monthly temperatures: 18-24 °C). REE was lower than predicted by most equations in our population. Age and BMI were similar in both sexes. In the whole population, the equations of Mifflin, Henry and Rees, Livingston and Owen, had similar levels of accuracy (non-significant bias of 0.7%, 1.1%, 0.6%, and -2.2%, respectively). The best equation to predict resting energy expenditure in overweight and moderately obese men and women living in a temperate climate all year round is the Mifflin equation. In men, the equations by Henry and Rees, Livingston, and by Owen had predictive accuracies comparable to that of Mifflin. The body composition-based equation of Johnston was slightly more accurate than Mifflin's in men. In women, none of the body composition-based equations outperformed Mifflin's.

Impact of data averaging strategies on V̇O2max assessment: Mathematical modeling and reliability.

BACKGROUND: No consensus exists on how to average data to optimize V ˙ O2max assessment. Although the V ˙ O2max value is reduced with larger averaging blocks, no mathematical procedure is available to account for the effect of the length of the averaging block on V ˙ O2max. AIMS: To determine the effect that the number of breaths or seconds included in the averaging block has on the V ˙ O2max value and its reproducibility and to develop correction equations to standardize V ˙ O2max values obtained with different averaging strategies. METHODS: Eighty-four subjects performed duplicate incremental tests to exhaustion (IE) in the cycle ergometer and/or treadmill using two metabolic carts (Vyntus and Vmax N29). Rolling breath averages and fixed time averages were calculated from breath-by-breath data from 6 to 60 breaths or seconds. RESULTS: V ˙ O2max decayed from 6 to 60 breath averages by 10% in low fit ( V ˙ O2max  < 40 mL kg-1  min-1 ) and 6.7% in trained subjects. The V ˙ O2max averaged from a similar number of breaths or seconds was highly concordant (CCC > 0.97). There was a linear-log relationship between the number of breaths or seconds in the averaging block and V ˙ O2max (R2  > 0.99, P < 0.001), and specific equations were developed to standardize V ˙ O2max values to a fixed number of breaths or seconds. Reproducibility was higher in trained than low-fit subjects and not influenced by the averaging strategy, exercise mode, maximal respiratory rate, or IE protocol. CONCLUSIONS: The V ˙ O2max decreases following a linear-log function with the number of breaths or seconds included in the averaging block and can be corrected with specific equations as those developed here.

Enhancement of Exercise Performance by 48 Hours, and 15-Day Supplementation with Mangiferin and Luteolin in Men.

The natural polyphenols mangiferin and luteolin have free radical-scavenging properties, induce the antioxidant gene program and down-regulate the expression of superoxide-producing enzymes. However, the effects of these two polyphenols on exercise capacity remains mostly unknown. To determine whether a combination of luteolin (peanut husk extract containing 95% luteolin, PHE) and mangiferin (mango leave extract (MLE), Zynamite®) at low (PHE: 50 mg/day; and 140 mg/day of MLE containing 100 mg of mangiferin; L) and high doses (PHE: 100 mg/day; MLE: 420 mg/day; H) may enhance exercise performance, twelve physically active men performed incremental exercise to exhaustion, followed by sprint and endurance exercise after 48 h (acute effects) and 15 days of supplementation (prolonged effects) with polyphenols or placebo, following a double-blind crossover design. During sprint exercise, mangiferin + luteolin supplementation enhanced exercise performance, facilitated muscle oxygen extraction, and improved brain oxygenation, without increasing the VO2. Compared to placebo, mangiferin + luteolin increased muscle O2 extraction during post-exercise ischemia, and improved sprint performance after ischemia-reperfusion likely by increasing glycolytic energy production, as reflected by higher blood lactate concentrations after the sprints. Similar responses were elicited by the two doses tested. In conclusion, acute and prolonged supplementation with mangiferin combined with luteolin enhances performance, muscle O2 extraction, and brain oxygenation during sprint exercise, at high and low doses.

Mangifera indica L. Leaf Extract in Combination With Luteolin or Quercetin Enhances VO2peak and Peak Power Output, and Preserves Skeletal Muscle Function During Ischemia-Reperfusion in Humans.

It remains unknown whether polyphenols such as luteolin (Lut), mangiferin and quercetin (Q) have ergogenic effects during repeated all-out prolonged sprints. Here we tested the effect of Mangifera indica L. leaf extract (MLE) rich in mangiferin (Zynamite®) administered with either quercetin (Q) and tiger nut extract (TNE), or with luteolin (Lut) on sprint performance and recovery from ischemia-reperfusion. Thirty young volunteers were randomly assigned to three treatments 48 h before exercise. Treatment A: placebo (500 mg of maltodextrin/day); B: 140 mg of MLE (60% mangiferin) and 50 mg of Lut/day; and C: 140 mg of MLE, 600 mg of Q and 350 mg of TNE/day. After warm-up, subjects performed two 30 s Wingate tests and a 60 s all-out sprint interspaced by 4 min recovery periods. At the end of the 60 s sprint the circulation of both legs was instantaneously occluded for 20 s. Then, the circulation was re-opened and a 15 s sprint performed, followed by 10 s recovery with open circulation, and another 15 s final sprint. MLE supplements enhanced peak (Wpeak) and mean (Wmean) power output by 5.0-7.0% (P < 0.01). After ischemia, MLE+Q+TNE increased Wpeak by 19.4 and 10.2% compared with the placebo (P < 0.001) and MLE+Lut (P < 0.05), respectively. MLE+Q+TNE increased Wmean post-ischemia by 11.2 and 6.7% compared with the placebo (P < 0.001) and MLE+Lut (P = 0.012). Mean VO2 during the sprints was unchanged, suggesting increased efficiency or recruitment of the anaerobic capacity after MLE ingestion. In women, peak VO2 during the repeated sprints was 5.8% greater after the administration of MLE, coinciding with better brain oxygenation. MLE attenuated the metaboreflex hyperpneic response post-ischemia, may have improved O2 extraction by the Vastus Lateralis (MLE+Q+TNE vs. placebo, P = 0.056), and reduced pain during ischemia (P = 0.068). Blood lactate, acid-base balance, and plasma electrolytes responses were not altered by the supplements. In conclusion, a MLE extract rich in mangiferin combined with either quercetin and tiger nut extract or luteolin exerts a remarkable ergogenic effect, increasing muscle power in fatigued subjects and enhancing peak VO2 and brain oxygenation in women during prolonged sprinting. Importantly, the combination of MLE+Q+TNE improves skeletal muscle contractile function during ischemia/reperfusion.

Cerebral blood flow, frontal lobe oxygenation and intra-arterial blood pressure during sprint exercise in normoxia and severe acute hypoxia in humans.

Cerebral blood flow (CBF) is regulated to secure brain O2 delivery while simultaneously avoiding hyperperfusion; however, both requisites may conflict during sprint exercise. To determine whether brain O2 delivery or CBF is prioritized, young men performed sprint exercise in normoxia and hypoxia (PIO2 = 73 mmHg). During the sprints, cardiac output increased to ∼22 L min-1, mean arterial pressure to ∼131 mmHg and peak systolic blood pressure ranged between 200 and 304 mmHg. Middle-cerebral artery velocity (MCAv) increased to peak values (∼16%) after 7.5 s and decreased to pre-exercise values towards the end of the sprint. When the sprints in normoxia were preceded by a reduced PETCO2, CBF and frontal lobe oxygenation decreased in parallel ( r = 0.93, P < 0.01). In hypoxia, MCAv was increased by 25%, due to a 26% greater vascular conductance, despite 4-6 mmHg lower PaCO2 in hypoxia than normoxia. This vasodilation fully accounted for the 22 % lower CaO2 in hypoxia, leading to a similar brain O2 delivery during the sprints regardless of PIO2. In conclusion, when a conflict exists between preserving brain O2 delivery or restraining CBF to avoid potential damage by an elevated perfusion pressure, the priority is given to brain O2 delivery.

What limits performance during whole-body incremental exercise to exhaustion in humans?

To determine the mechanisms causing task failure during incremental exercise to exhaustion (IE), sprint performance (10 s all-out isokinetic) and muscle metabolites were measured before (control) and immediately after IE in normoxia (P(IO2) 143 mmHg) and hypoxia (P(IO2): 73 mmHg) in 22 men (22 ± 3 years). After IE, subjects recovered for either 10 or 60 s, with open circulation or bilateral leg occlusion (300 mmHg) in random order. This was followed by a 10 s sprint with open circulation. Post-IE peak power output (W(peak)) was higher than the power output reached at exhaustion during IE (P < 0.05). After 10 and 60 s recovery in normoxia, W(peak) was reduced by 38 ± 9 and 22 ± 10% without occlusion, and 61 ± 8 and 47 ± 10% with occlusion (P < 0.05). Following 10 s occlusion, W(peak) was 20% higher in hypoxia than normoxia (P < 0.05), despite similar muscle lactate accumulation ([La]) and phosphocreatine and ATP reduction. Sprint performance and anaerobic ATP resynthesis were greater after 60 s compared with 10 s occlusions, despite the higher [La] and [H(+)] after 60 s compared with 10 s occlusion recovery (P < 0.05). The mean rate of ATP turnover during the 60 s occlusion was 0.180 ± 0.133 mmol (kg wet wt)(-1) s(-1), i.e. equivalent to 32% of leg peak O2 uptake (the energy expended by the ion pumps). A greater degree of recovery is achieved, however, without occlusion. In conclusion, during incremental exercise task failure is not due to metabolite accumulation or lack of energy resources. Anaerobic metabolism, despite the accumulation of lactate and H(+), facilitates early recovery even in anoxia. This points to central mechanisms as the principal determinants of task failure both in normoxia and hypoxia, with lower peripheral contribution in hypoxia.