Point-of-care lung ultrasound assessment for risk stratification and therapy guiding in COVID-19 patients: a prospective noninterventional study.

BACKGROUND: Lung ultrasound is feasible for assessing lung injury caused by coronavirus disease 2019 (COVID-19). However, the prognostic meaning and time-line changes of lung injury assessed by lung ultrasound in COVID-19 hospitalised patients are unknown. METHODS: Prospective cohort study designed to analyse prognostic value of lung ultrasound in COVID-19 patients by using a quantitative scale (lung ultrasound Zaragoza (LUZ)-score) during the first 72 h after admission. The primary end-point was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow and escalation of medical treatment during the first 72 h were secondary end-points. RESULTS: 130 patients were included in the final analysis; mean±sd age was 56.7±13.5 years. Median (interquartile range) time from the beginning of symptoms to admission was 6 (4-9) days. Lung injury assessed by LUZ-score did not differ during the first 72 h (21 (16-26) points at admission versus 20 (16-27) points at 72 h; p=0.183). In univariable logistic regression analysis, estimated arterial oxygen tension/inspiratory oxygen fraction ratio (PAFI) (hazard ratio 0.99, 95% CI 0.98-0.99; p=0.027) and LUZ-score >22 points (5.45, 1.42-20.90; p=0.013) were predictors for the primary end-point. CONCLUSIONS: LUZ-score is an easy, simple and fast point-of-care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated by PAFI) to further refine risk stratification.

Prognostic Impact of Induced Natriuresis in Acute Decompensated Heart Failure and Its Association with Intraabdominal Pressure and Other Congestion Markers: A Multimodal Approach to Congestion Assessment.

BACKGROUND: Congestion is an essential issue in patients with heart failure (HF). Standard treatments do not usually achieve decongestion, and various strategies have been proposed to guide treatment, such as determination of natriuresis. After starting treatment with loop diuretics, we postulate that initial natriuresis might help treatment titration, decongestion, and improve prognosis. METHODS: It was a prospective and observational study. Patients admitted with the diagnosis of HF decompensation were eligible. An assessment of congestion was performed during the first 48 h. RESULTS: A total of 113 patients were included. A poor diuretic response was observed in 39.8%. After the first 48 h, patients with a greater diuretic response on admission (NaU > 80 mmol/L) showed fewer pulmonary b lines (12 vs. 15; p = 0.084), a lower IVC diameter (18 mm vs. 22 mm; p = 0.009), and lower IAP figures (11 mmHg vs. 13 mmHg; p = 0.041). Survival analysis tests demonstrated significant differences showing a higher proportion of all-cause mortality (ACM) and HF rehospitalization in the poor-diuretic-response group (log-rank test = 0.020). CONCLUSIONS: Up to 40% of the patients presented a poorer diuretic response at baseline, translating into worse outcomes. Patients with an optimal diuretic response showed significantly higher abdominal decongestion at 48 h and a better prognosis regarding ACM and/or HF rehospitalizations.

Utility of plasma CA125 as a proxy of intra-abdominal pressure in patients with acute heart failure.

AIMS: Increased intra-abdominal pressure (IAP) is now considered a potential contributor to organ damage and disease progression in acute heart failure (AHF). In this work, we aimed to determine if antigen carbohydrate 125 (CA125) is associated with IAP and to identify a cutpoint of CA125 useful for ruling out intra-abdominal hypertension (defined as IAP ≥ 12 mmHg). METHODS AND RESULTS: We prospectively evaluated a cohort of 53 patients admitted with AHF in which IAP was measured within the first 24-h of admission. The mean age was 80 ± 8 years, 31 (58.5%) were female, and 31 (58.5%) had left ventricular ejection fraction ≥50%. The median plasma levels of NT-proBNP and CA125 were 3830 pg/mL (2417-8929) and 45.8 U/mL (29.8-114.0), respectively. The median of IAP was 15 mmHg (11-17), and 39 (73%) patients had an IAP ≥ 12 mmHg. The diagnostic performance of CA125 for identifying an IAP ≥ 12 mmHg was tested using the receiving operating characteristic (ROC) curve. The cut-off for CA125 of 17.1 U/mL showed a sensitivity of 92%, a specificity of 50%, and an area under the ROC curve of 0.71. After multivariate adjustment, CA125 remained non-linearly and positively associated with higher IAP (P-value = 0.003), explaining almost 28% of the model's variability (R2: 27.6%). CONCLUSIONS: Patients with AHF and intra-abdominal hypertension had higher CA125 plasma levels. A baseline concentration of CA125 below 17.1 U/mL will increase the odds of identifying a subset of patients with normal IAP.

Elevated urinary kidney injury molecule 1 at discharge strongly predicts early mortality following an episode of acute decompensated heart failure.

INTRODUCTION: Hospitalization for acute decompensation of heart failure (ADHF) is a frequent event associated with long­term adverse effects. Prognosis is even worse if acute kidney injury (AKI) occurs during hospitalization. OBJECTIVES: The study aimed to determine whether kidney damage biomarkers neutrophil gelatinase­associatedlipocalin (NGAL), kidney injury molecule 1 (KIM­1), and interleukin18 (IL­18) might predict AKI and have prognostic value in ADHF. PATIENTS AND METHODS: Serum NGAL on admission and urine NGAL, KIM­1, and IL­18 on discharge were determined in 187 ADHF patients enrolled in a prospective, observational, unblinded study. AKI was diagnosed using the Kidney Disease: Improving Global Outcomes criteria. Patients were followedfor 12 months to record all­cause mortality. RESULTS: A total of 22% patients died during the follow­up, with 52.5% dying within 4 months after discharge. Serum NGAL (P <0.001), urine NGAL (P = 0.047), and urinary KIM­1 (P = 0.014) levels were significantly higher in the deceased patients at discharge. After adjustment for estimated glomerular filtration rate (eGFR), only urinary KIM­1 independently predicted mortality at month 4 (hazard ratio [HR], 3.166; 95% CI, 1.203-8.334; P = 0.020) and month 12 (HR, 1.969; 95% CI, 1.123-3.454; P = 0.018) in Cox regression models. In receiver operating characteristic (ROC) analysis urinary KIM­1 (area under the ROC curve [AUC] = 0.830) outperformed other markers of renal function. The Kaplan-Meier survival analysis showed KIM­1 predictive value as additive to that of AKI incidence and admission eGFR. Admission serum NGAL was higher in AKI patients (P ≤0.001) with a modest diagnostic performance (AUC = 0.667), below that of urea (AUC = 0.732), creatinine (AUC = 0.696), or cystatin C (AUC = 0.676). CONCLUSIONS: Discharge urinary KIM­1 was a strong and independent predictor of mortality, particularly during the most vulnerable period shortly after hospitalization. Admission serum NGAL was inferior to conventional renal function parameters in predicting AKI during ADHF.

Chronic Obstructive Pulmonary Disease in Elderly Patients with Acute and Advanced Heart Failure: Palliative Care Needs-Analysis of the EPICTER Study.

Introduction: There are studies that evaluate the association between chronic obstructive pulmonary disease (COPD) and heart failure (HF) but there is little evidence regarding the prognosis of this comorbidity in older patients admitted for acute HF. In addition, little attention has been given to the extracardiac and extrapulmonary symptoms presented by patients with HF and COPD in more advanced stages. The aim of this study was to evaluate the prognostic impact of COPD on mortality in elderly patients with acute and advanced HF and the clinical manifestations and management from a palliative point of view. Methods: The EPICTER study ("Epidemiological survey of advanced heart failure") is a cross-sectional, multicenter project that consecutively collected patients admitted for HF in 74 Spanish hospitals. Demographic, clinical, treatment, organ-dependent terminal criteria (NYHA III-IV, LVEF <20%, intractable angina, HF despite optimal treatment), and general terminal criteria (estimated survival <6 months, patient/family acceptance of palliative approach, and one of the following: evidence of HF progression, multiple Emergency Room visits or admissions in the last six months, 10% weight loss in the last six months, and functional impairment) were collected. Terminal HF was considered if the patient met at least one organ-dependent criterion and all the general criteria. Both groups (HF with COPD and without COPD) were compared. A Kaplan−Meier survival analysis was performed to evaluate the presence of COPD on the vital prognosis of patients with HF. Results: A total of 3100 patients were included of which 812 had COPD. In the COPD group, dyspnea and anxiety were more frequently observed (86.2% vs. 75.3%, p = 0.001 and 35.4% vs. 31.2%, p = 0.043, respectively). In patients with a history of COPD, presentation of HF was in the form of acute pulmonary edema (21% vs. 14.4% in patients without COPD, p = 0.0001). Patients with COPD more frequently suffered from advanced HF (28.9% vs. 19.4%; p < 0.001). Consultation with the hospital palliative care service during admission was more frequent when patients with HF presented with associated COPD (94% vs. 6.8%; p = 0.036). In-hospital and six-month follow-up mortality was 36.5% in patients with COPD vs. 30.7% in patients without COPD, p = 0.005. The mean number of hospital admissions during follow-up was higher in patients with HF and COPD than in those with isolated HF (0.63 ± 0.98 vs. 0.51 ± 0.84; p < 0.002). Survival analysis showed that patients with a history of COPD had fewer survival days during follow-up than those without COPD (log Rank chi-squared 4.895 and p = 0.027). Conclusions: patients with HF and COPD had more severe symptoms (dyspnea and anxiety) and also a worse prognosis than patients without COPD. However, the prognosis of patients admitted to our setting is poor and many patients with HF and COPD may not receive the assessment and palliative care support they need. Palliative care is necessary in chronic non-oncologic diseases, especially in multipathologic and symptom-intensive patients. This is a clinical care aspect to be improved and evaluated in future research studies.

Ethnicity and Clinical Outcomes in Patients Hospitalized for COVID-19 in Spain: Results from the Multicenter SEMI-COVID-19 Registry.

(1) Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5−58.9) to 57.1 (44.1−67.1) vs. 71.5 (59.5−81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10−0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17−1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26−2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21−1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often.

Prognostic value of malnutrition in patients with acute heart failure and its influence on the interpretation of markers of systemic venous congestion. / Valor pronóstico de la desnutrición en pacientes con insuficiencia cardíaca aguda y su influencia en la interpretación de marcadores de congestión venosa sistémica.

BACKGROUND: Malnutrition is frequent in patients with heart failure (HF) and contributes to increased systemic congestion, but also hinders its correct assessment, especially during decompensations. Estimating the degree of malnutrition and its relationship with systemic congestion is important to optimize treatment during decompensations. MATERIAL AND METHODS: Retrospective cohort study in patients with acute HF. The population was stratified according to CONUT (Controlling Nutritional Status) and PNI (Prognostic Nutritional Index) nutrition indices in order to analyse their relationship with objective parameters of congestion and the prognostic value of malnutrition. RESULTS: 309 patients were included. More than half presented some degree of malnutrition upon admission. The degree of congestion was significantly higher in malnourished patients, with a higher proportion of «comet tail artifacts¼ and a higher relative plasma volume. NT-proBNP concentrations, both on admission and at discharge, were also significantly higher in malnourished patients, regardless of the scale used. The univariate analysis identified the CONUT and PNI index as factors associated with one-year mortality from any cause (HR 1.62 [1.22-2.14]; p = 0.001) and PNI (HR 65 [0.53-0.80]; p = < 0.001), respectively. CONCLUSIONS: A higher degree of malnutrition (determined by means of the CONUT and PNI indices) in patients with acute HF was associated with a higher presence of objective parameters of congestion and a higher one-year all-cause mortality.

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study.

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered.

Influence of blood pressure at the beginning of decompensations in the prognosis of patients with heart failure. / Influencia de la presión arterial al inicio de las descompensaciones en el pronóstico de pacientes con insuficiencia cardiaca.

BACKGROUND AND OBJECTIVE: An inverse relationship has been described between blood pressure and the prognosis in heart failure (HF). The characteristics of this relationship are not well unknown. The objective of this study was to determine if this relationship is maintained in a non-selected cohort of patients with HF and if it can be modified by treatment. MATERIAL AND METHODS: Prospective study of cohorts including patients hospitalized for decompensated HF in Internal Medicine departments and followed as outpatients in a monographic consultation. Patients were classified according to their levels of systolic (SBP) and diastolic blood pressure (DBP). Clinical characteristics, all-cause mortality and readmissions after the first, third and sixth month of follow-up were analysed. RESULTS: Two hundred and twenty-one patients were included after their admission to the hospital for acute HF. Mean patient age was 79.5 years(SD 8.09); 115 patients were male. No significant differences between SBP quartiles and basal characteristics were found. Patients with lower SBP (Q1) had higher mortality rates (20%, P<.05). No significant differences between mortality/readmissions and DBP were found. However, the Kaplan-Meier analysis showed higher all-cause mortality rates for the group of patients with lower SBP and DBP (log-rank=0.011 and 0.041, respectively). The pharmacological treatment did not differ significantly between both study groups. CONCLUSION: For non-selected patients suffering HF, higher SBP upon the admission is associated with significantly lower all-cause mortality rates during follow-up. Pharmacological treatment of HF does not seem to influence this inverse relationship between SBP at admission and patient mortality.

Usefulness of the Hepatocyte Growth Factor as a Predictor of Mortality in Patients Hospitalized With Acute Heart Failure Regardless of Ejection Fraction.

Hepatocyte growth factor (HGF) plays a role in the improvement of cardiac function and remodeling. Their serum levels are strongly related with mortality in chronic systolic heart failure (HF). The aim of this study was to study prognostic value of HGF in acute HF, interaction with ejection fraction, renal function, and natriuretic peptides. We included 373 patients (age 76 ± 10 years, left ventricular ejection fraction [LVEF] 46 ± 14%, 48% men) consecutively admitted for acute HF. Blood samples were obtained at admission. All patients were followed up until death or close of study (>1 year, median 371 days). HGF concentrations were determined using a commercial enzyme-linked immunosorbent assay (human HGF immunoassay). The predictive power of HGF was estimated by Cox regression with calculation of Harrell C-statistic. HGF had a median of 1,942 pg/ml (interquartile rank 1,354). According to HGF quartiles, mortality rates (per 1,000 patients/year) were 98, 183, 375, and 393, respectively (p <0.001). In Cox regression analysis, HGF (hazard ratio1SD = 1.5, 95% confidence interval 1.1 to 2.1, p = 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio1SD = 1.8, 95% confidence interval 1.2 to 2.6, p = 0.002) were independent predictors of mortality. Interaction between HGF and LVEF, origin, and renal function was nonsignificant. The addition of HGF improved the predictive ability of the models (C-statistic 0.768 vs 0.741, p = 0.016). HGF showed a complementary value over NT-proBNP (p = 0.001): mortality rate was 490 with both above the median versus 72 with both below. In conclusion, in patients with acute HF, serum HGF concentrations are elevated and identify patients at higher risk of mortality, regardless of LVEF, ischemic origin, or renal function. HGF had independent and additive information over NT-proBNP.