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Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), also known as post-COVID-19 condition or post-COVID syndrome, can affect anyone infected with SARS-CoV-2, regardless of age or the severity of the initial symptoms of COVID-19. Long COVID/PASC is the continuation or development of new symptoms after three months from the initial SARS-CoV-2 infection, which lasts for at least two months and has no other identifiable cause. Long COVID/PASC occurs in 10-20% of patients infected with SARS-CoV-2. The most common symptoms include fatigue, cognitive impairment (brain fog), and shortness of breath. However, more than 200 symptoms have been reported. No phenotypic or diagnostic biomarkers have been identified for developing long COVID/PASC, which is a multisystem disorder that can present with isolated or combined respiratory, hematological, immunological, cardiovascular, and neuropsychiatric symptoms. There is no cure. Therefore, individualized patient management requires a multidisciplinary clinical approach. Because millions of people have had and continue to have COVID-19, even in the era of vaccination and antiviral therapies, long COVID/PASC is now and will increasingly become a health and economic burden that the world must prepare for. Almost five years from the beginning of the COVID-19 pandemic, this article aims to review what is currently known about long COVID/PASC, the anticipated increasing global health burden, and why there is still an urgent need to identify diagnostic biomarkers and risk factors to improve prevention and treatment.

Aims: The performance of circulating soluble urokinase plasminogen activator receptor (suPAR) for predicting the composite endpoint of subsequent heart failure (HF) hospitalisation and/or death at 1 year was assessed in (i) patients with undifferentiated breathlessness, and generalisability was compared in (ii) disparate Western versus Asian sub-cohorts, and in (iii) the sub-cohort adjudicated with HF., Methods and Results: Patients with acute breathlessness were recruited from the emergency departments in New Zealand (NZ, n = 612) and Singapore (n = 483). suPAR measured in the presentation samples was higher in patients incurring the endpoint (n = 281) compared with survivors (5.2 ng/mL vs 3.1 ng/mL, P < 0.0001). The discriminative power of suPAR for endpoint prediction was c-statistic of 0.77 in the combined population, but was superior in Singapore than NZ (c-statistic: 0.83 vs 0.71, P < 0.0001). Although the highest suPAR tertile (>4.37 ng/mL) was associated with risks of >4-fold in NZ, >20-fold in Singapore, and ≥3-fold in HF for incurring the outcome, there was no interaction between country and suPAR levels after adjustment. Multivariable analysis indicated suPAR to be robust in predicting HF/death at 1-year [hazard ratio: 1.9 (95% CI:1.7 to 2.0) per SD increase] and improved risk discrimination for outcome prediction in HF (∆0.06) and for those with NT-proBNP >1000 pg/mL (∆0.02)., Conclusion: suPAR is a strong independent predictor of HF and/or death at 1 year in acutely breathless patients, in both Asian and Western cohorts, and in HF. suPAR may improve stratification of acutely breathless patients, and in acute HF, for risk of later onset of heart failure or mortality., Competing Interests: Declaration of competing interest AMR reports research grant support and speaker's honoraria from Roche Diagnostics, and in-kind support in the form of assay kit reagents from Abbott, Thermo Fisher, and Alere, during the conduct of the study. All other authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE., Design: All Swedish patients diagnosed with acute PE in 2005 ( n  = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 ( n  = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration., Results: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels., Conclusions: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea., Methods: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head., Results: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1-Q3: 18.4-74.2 ng/L vs. median: 19.4, Q1-Q3: 8.4-36.1 ng/L; p for comparison &lt;0.001) and NT-proBNP concentrations (median: 1,753.6, Q1-Q3: 464.2-6,862.0 ng/L vs. median 984, Q1-Q3 201-3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30-2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14-2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94-1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80-1.40)., Conclusion: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The diagnosis of heart failure (HF) remains essentially clinical-Based. However, the history, physical examination, and chest radiograph findings are often inadequate in the diagnosis because multiple other conditions that affect the cardiopulmonary system mimic the symptoms of HF. N-terminal pro-BNP (NT-proBNP) has long been used for diagnosing HF. N-terminal pro-BNP values vary with different patient parameters. There is a scarcity of Indian studies on this topic. Especially with the use of newer drugs like angiotensin receptor neprilysin inhibitor (ARNI), it is important to have data from our own population on the same., Aims and Objectives: (i) To assess the role of NT-proBNP in the diagnosis of HF. (ii) Achieve diagnostic clarity in cases having cardiorespiratory symptoms and signs like acute onset dyspnea, pedal edema, and basal crepitations. (iii) To study the effect of various factors like age, body mass index (BMI), and creatinine on NT-proBNP. (iv) Establish a relation between NT-proBNP levels and left ventricular ejection fraction (LVEF), disease severity, and etiology of HF., Materials and Methods: An observational prospective study of 50 patients presenting with acute onset breathlessness was carried out, fulfilling inclusion and exclusion criteria over a period of 10 months. Detailed history and examination of the patients were obtained. Venous sample for the measurement of NT-proBNP was collected within 24 hours of onset of symptoms. Other relevant blood and radiographic investigations were obtained. The NT-proBNP "cut-offs" set forth by the American Heart Association (AHA)/American College of Cardiology (ACC) were used to "rule in" or "rule out" HF. Two-dimensional echocardiography (2D Echo) was used to confirm the diagnosis. The correlation between NT-proBNP and various parameters like age, BMI, creatinine, and LVEF was obtained. Sensitivity and specificity tests were applied as well., Results: Out of the 50 patients presenting with acute onset dyspnea, the most common cause was ischemic heart disease (IHD) (44%) followed by dilated cardiomyopathy (DCM) (32%), chronic obstructive pulmonary disease (COPD) (10%), anemia (4%), followed by other causes. The median NT-proBNP value was the highest for IHD patients (9485 pg/mL), followed by DCM (8969 pg/mL), followed by COPD (2846 pg/mL), and followed by anemia (850 pg/mL). There is a significant positive correlation between NT-proBNP and age (coefficient of correlation r = 0.4007, significance level p = 0.0389, and class interval = 0.137-0.61). There is a significant negative correlation between creatinine clearance and NT-proBNP (coefficient of correlation r = -0.372, significance level p = 0.007, and class interval = -0.58 to -0.105). There was significant negative correlation between LVEF and NT-proBNP (coefficient of correlation r = -0.36, significance level p = 0.009, and class interval = -0.58 to -0.09). Higher LVEF is associated with lower NT-proBNP values. There is marked heterogeneity in the values though., Conclusion: It is seen that the values of NT-proBNP vary with factors like age, BMI, and creatinine clearance in addition to LVEF. This may lead to falsely positive or falsely negative diagnosis of HF. With the above observations in mind, it can be concluded that NT-proBNP can help diagnose HF but only in addition to clinical findings., (© Journal of the Association of Physicians of India 2011.)

Following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a significant proportion of individuals develop prolonged symptoms, a serious condition termed post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) or long COVID. Predictors of PACS are needed. In a prospective multicentric cohort study of 215 individuals, we study COVID-19 patients during primary infection and up to one year later, compared to healthy subjects. We discover an immunoglobulin (Ig) signature, based on total IgM and IgG3 levels, which - combined with age, history of asthma bronchiale, and five symptoms during primary infection - is able to predict the risk of PACS independently of timepoint of blood sampling. We validate the score in an independent cohort of 395 individuals with COVID-19. Our results highlight the benefit of measuring Igs for the early identification of patients at high risk for PACS, which facilitates the study of targeted treatment and pathomechanisms of PACS., (© 2022. The Author(s).)

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.

The purpose of this study was to examine the physiological mechanisms of persistent dyspnoea in COVID-19 survivors. Non-critical patients (n = 186) with varying degrees of COVID-19 severity reported persistent symptoms using a standardized questionnaire and underwent pulmonary function and 6-minute walk testing between 30 and 90 days following the onset of acute COVID-19 symptoms. Patients were divided into those with (n = 70) and without (n = 116) persistent dyspnoea. Patients with persistent dyspnoea had significantly lower FVC (p = 0.03), FEV 1 (p = 0.04), D LCO (p = 0.01), 6-minute walk distance (% predicted, p = 0.03), and end-exercise oxygen saturation (p < 0.001), and higher Borg 0-10 ratings of dyspnoea and fatigue (both p < 0.001) compared to patients without persistent dyspnoea. We have shown that dyspnoea is a common persistent symptom across varying degrees of initial COVID-19 severity. Patients with persistent dyspnoea had greater restriction on spirometry, lower D LCO , reduced functional capacity, and increased exertional desaturation and symptoms. This suggests that there is a true physiological mechanism that may explain persistent dyspnoea after COVID-19., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Our objective was to perform an economic evaluation of an N-terminal pro B-type natriuretic peptide (NT-proBNP)-supported diagnostic strategy in dyspneic patients suspected of acute heart failure in the emergency department (ED). A decision-tree model was developed to evaluate clinical outcomes and costs for NT-proBNP-supported assessment compared with clinical assessment alone over 6 months from the United States (US) Medicare perspective. The model considered rule-in/rule-out cutoffs identified in the ICON and ICON-RELOADED studies. Acute heart failure prevalence, diagnostic accuracies, and medical resource use conditional on disease status and test results were derived from ICON-RELOADED. Several assumptions based on previous studies of NT-proBNP acute dyspnea and verified with clinicians were applied to medical resource use and assessed in sensitivity analyses. Compared with clinical assessment alone, NT-proBNP-supported assessment improved overall probability of correct diagnosis by a relative 7% (18% for true-positive and 5% for true-negative). This led to relative reductions in medical resource use in ED and hospital, including fewer initial hospitalizations (-14%), required echocardiograms (-31%), cardiology admissions (-16%), intensive care unit admissions (-12%), ED readmissions (-3%), and hospital readmissions (-22%). NT-proBNP use decreased average inpatient management costs by a relative 10%, yielding cost savings of US$2,337 per patient ED visit. These findings were robust in sensitivity analyses. In conclusion, based on a contemporary trial of patients with acute dyspnea, this analysis reaffirmed that using NT-proBNP as a diagnostic tool may improve the management of patients with dyspnea presenting to EDs and is likely to be cost-saving from the US Medicare perspective., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To assess if cardiac troponins can improve diagnostics of acute heart failure (AHF) and provide prognostic information in patients with acute dyspnea., Methods: We measured cardiac troponin T with a high-sensitivity assay (hs-cTnT) in 314 patients hospitalized with acute dyspnea. The index diagnosis was adjudicated and AHF patients were stratified into AHF with reduced or preserved ejection fraction (HFrEF/HFpEF). The prognostic and diagnostic merit of hs-cTnT was compared to the merit of N-terminal pro-B-type natriuretic peptide (NT-proBNP)., Results: In the total population, median age was 73 (quartile [Q] 1-3 63-81) years and 48% were women. One-hundred-forty-three patients were categorized as AHF (46%) and these patients had higher hs-cTnT concentrations than patients with non-AHF-related dyspnea: median 38 (Q1-3 22-75) vs. 13 (4-25) ng/L; p < 0.001. hs-cTnT concentrations were similar between patients with HFrEF and HFpEF (p = 0.80), in contrast to NT-proBNP, which was higher in HFrEF (p < 0.001). C-statistics for discriminating HFpEF from non-AHF-related dyspnea was 0.80 (95% CI 0.73-0.86) for hs-cTnT, 0.79 (0.73-0.86) for NT-proBNP, and 0.83 (0.76-0.89) for hs-cTnT and NT-proBNP in combination. Elevated hs-cTnT remained associated with HFpEF in logistic regression analysis after adjusting for demographics, comorbidities and renal function. During median 27 months of follow-up, 114 (36%) patients died in the total population. Higher hs-cTnT concentrations were associated with increased risk of all-cause mortality after adjustment for clinical variables and NT-proBNP: hazard ratio 1.30 (95% CI 1.07-1.58), p = 0.009., Conclusion: hs-cTnT measurements improve diagnostic accuracy for HFpEF and provide independent prognostic information in unselected patients with acute dyspnea., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Critically ill patients with coronavirus disease 2019 (COVID-19) present with hypoxaemia and are mechanically ventilated to support gas exchange. We performed a retrospective, observational study of blood gas analyses (n = 3518) obtained from patients with COVID-19 to investigate changes in haemoglobin oxygen (Hb-O 2 ) affinity. Calculated oxygen tension at half-saturation (p 50 ) was on average (±SD) 3·3 (3·13) mmHg lower than the normal p 50 value (23·4 vs. 26·7 mmHg; P < 0·0001). Compared to an unmatched historic control of patients with other causes of severe respiratory failure, patients with COVID-19 had a significantly higher Hb-O 2 affinity (mean [SD] p 50 23·4 [3·13] vs. 24·6 [5.4] mmHg; P < 0·0001). We hypothesise that, due to the long disease process, acclimatisation to hypoxaemia could play a role., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function., Aim: To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea., Population and Methods: Patients aged ≥ 18 years seeking at emergency department (ED) during daytime on weekdays between December 2013 and July 2018, with diabetes and acute dyspnea, identified at the triage process, were included. Participants (n = 291) were triaged according to Medical Emergency Triage and Treatment System-Adult score, and blood samples were collected. Association between TNFR1 and TNFR2, respectively, and 90-day mortality were estimated by Cox regression models adjusted for age, sex, BMI, creatinine and CRP., Results: Univariate models showed significant associations between TNFR1 and TNFR2, respectively, and CRP, age and creatinine. TNFR1 and TNFR2 tended to be elevated in patients with the highest triage level, compared to patients with lower triage levels (ns). In longitudinal analyses, TNFR1 but not TNFR2 was associated with increased short-term mortality, HR adjusted for age, BMI and creatinine 1.43 (95% CI 1.07-1.91), but not in the model also adjusted for CRP, HR 1.29 (95% CI 0.94-1.77). In secondary analysis for quartile 4 versus quartiles 1-3 of TNFR1, corresponding HRs were 2.46 (95% CI 1.27-5.15) and 2.21 (95% CI 1.07-2.56)., Conclusions: We found a trend for the association between circulating TNFR1 levels and short-term mortality in patients with diabetes and acute dyspnea at the ED, possibly suggesting an inflammatory pathway for the association.

Background Evidence suggests that acute coronary syndrome (ACS) is underdiagnosed in sub-Saharan Africa. Triage-based interventions have improved ACS diagnosis and management in high-income settings but have not been evaluated in sub-Saharan African emergency departments (EDs). Our objective was to estimate the effect of a triage-based screening protocol on ACS diagnosis and care in a Tanzanian ED. Methods and Results All adults presenting to a Tanzanian ED with chest pain or shortness of breath were prospectively enrolled. Treatments and clinician-documented diagnoses were observed and recorded. In the preintervention phase (August 2018 through January 2019), ACS testing and treatment were dictated by physician discretion, as per usual care. A triage-based protocol was then introduced, and in the postintervention phase (January 2019 through October 2019), research assistants performed ECG and point-of-care troponin I testing on all patients with chest pain or shortness of breath upon ED arrival. Pre-post analyses compared ACS care between phases. Of 1020 total participants (339 preintervention phase, 681 postintervention phase), mean (SD) age was 58.9 (19.4) years. Six (1.8%) preintervention participants were diagnosed with ACS, versus 83 (12.2%) postintervention participants (odds ratio [OR], 7.51; 95% CI, 3.52-19.7; P <0.001). Among all participants, 3 (0.9%) preintervention participants received aspirin, compared with 50 (7.3%) postintervention participants (OR, 8.45; 95% CI, 3.07-36.13; P <0.001). Conclusions Introduction of a triage-based ACS screening protocol in a Tanzanian ED was associated with significant increases in ACS diagnoses and aspirin administration. Additional research is needed to determine the effect of ED-based interventions on ACS care and clinical end points in sub-Saharan Africa.

Objective: The study aimed to evaluate whether high-flow oxygen therapy (HFOT) during training was more effective than oxygen in improving exercise capacity in hypoxemic chronic obstructive pulmonary disease (COPD)., Methods: A total of 171 patients with COPD and chronic hypoxemia were consecutively recruited in 8 rehabilitation hospitals in a randomized controlled trial. Cycle-ergometer exercise training was used in 20 supervised sessions at iso inspiratory oxygen fraction in both groups. Pre- and post-training endurance time (Tlim), 6-minute walking distance (6MWD), respiratory and limb muscle strength, arterial blood gases, Barthel Index, Barthel Dyspnea Index, COPD Assessment Test, Maugeri Respiratory Failure questionnaire, and patient satisfaction were evaluated., Results: Due to 15.4% and 24.1% dropout rates, 71 and 66 patients were analyzed in HFOT and Venturi mask (V-mask) groups, respectively. Exercise capacity significantly improved after training in both groups with similar patient satisfaction. Between-group difference in post-training improvement in 6MWD (mean: 17.14 m; 95% CI = 0.87 to 33.43 m) but not in Tlim (mean: 141.85 seconds; 95% CI = -18.72 to 302.42 seconds) was significantly higher in HFOT. The minimal clinically important difference of Tlim was reached by 47% of patients in the V-mask group and 56% of patients in the HFOT group, whereas the minimal clinically important difference of 6MWD was reached by 51% of patients in the V-mask group and 69% of patients in the HFOT group, respectively., Conclusion: In patients with hypoxemic COPD, exercise training is effective in improving exercise capacity., Impact Statement: The addition of HFOT during exercise training is not more effective than oxygen through V-mask in improving endurance time, the primary outcome, whereas it is more effective in improving walking distance., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Patients with coronavirus disease (COVID-19) are described as exhibiting oxygen levels incompatible with life without dyspnea. The pairing-dubbed happy hypoxia but more precisely termed silent hypoxemia-is especially bewildering to physicians and is considered as defying basic biology. This combination has attracted extensive coverage in media but has not been discussed in medical journals. It is possible that coronavirus has an idiosyncratic action on receptors involved in chemosensitivity to oxygen, but well-established pathophysiological mechanisms can account for most, if not all, cases of silent hypoxemia. These mechanisms include the way dyspnea and the respiratory centers respond to low levels of oxygen, the way the prevailing carbon dioxide tension (Pa CO 2 ) blunts the brain's response to hypoxia, effects of disease and age on control of breathing, inaccuracy of pulse oximetry at low oxygen saturations, and temperature-induced shifts in the oxygen dissociation curve. Without knowledge of these mechanisms, physicians caring for patients with hypoxemia free of dyspnea are operating in the dark, placing vulnerable patients with COVID-19 at considerable risk. In conclusion, features of COVID-19 that physicians find baffling become less strange when viewed in light of long-established principles of respiratory physiology; an understanding of these mechanisms will enhance patient care if the much-anticipated second wave emerges.

Objective: To assess the accuracy of focused cardiac ultrasound (FOCUS) and point-of-care N-terminal proBNP assay in the emergency setting for differentiation of cardiac from noncardiac causes of respiratory distress in cats., Design: Prospective diagnostic accuracy study between 2014 and 2016., Setting: Emergency room at an urban university teaching hospital., Animals: Forty-one client-owned cats presenting for evaluation of respiratory distress., Interventions: Emergency clinicians made an initial diagnosis of noncardiac or cardiac cause of respiratory distress based on physical examination (PE) findings and history. The diagnoses were updated after performing FOCUS and point-of-care N-terminal B-type natriuretic peptide (POC-BNP). Reference standard diagnosis was determined by agreement of a board-certified cardiologist and critical care specialist with access to subsequent radiographs and echocardiograms., Measurements and Main Results: Forty-one cats were enrolled. Three cats with incomplete data and 1 cat with an uncertain reference standard diagnosis were excluded. The remaining 37 cats were used for analysis: 21 cardiac and 16 noncardiac cases. The ratio of left atrial to aortic root diameter (LA:Ao) measured by FOCUS was significantly correlated with LA:Ao measured by echocardiography (R = 0.646, P < 0.0001). Emergency clinicians correctly diagnosed 27 of 37 (73.0%), yielding a PE positive percent agreement = 76.2% (95% CI, 52.8-91.8%) and negative percent agreement = 68.8% (95% CI, 41.3-89.0%). Five noncardiac and 5 cardiac cats were misdiagnosed. Post FOCUS, overall percent agreement improved to 34 of 37 (91.9%), with positive percent agreement = 95.2% (95% CI, 76.2-99.9%) and negative percent agreement = 87.5% (95% CI, 61.7-98.5%). The POC-BNP yielded an overall percent agreement = 32/34 (94.1%), positive percent agreement = 100% (95% CI, 82.4-100.0%), and negative percent agreement = 86.7% (95% CI, 59.5-98.3%) in differentiating cardiac versus noncardiac cases., Conclusions: FOCUS evaluation of basic cardiac structure and LA:Ao by trained emergency clinicians improved accuracy of diagnosis compared to PE in cats with respiratory distress. FOCUS and POC-BNP are useful diagnostics in the emergent setting., (© Veterinary Emergency and Critical Care Society 2020.)

Red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) have shown a prognostic value in various clinical settings. We aimed to investigate the association between RDW, NLR, and in-hospital mortality in patients with dyspnea. In this retrospective study with the Medical Information Mart for Intensive Care III database (version 1.4), adult patients who came to the emergency department with dyspnea were included. Patients' comorbidities, hematological parameters within the first 48 hours after admission to the emergency department, and in-hospital mortality were extracted. The relationships between RDW, NLR, and in-hospital mortality were analyzed with the receiver operating characteristic (ROC) curve analysis and multivariate logistic regression model. We found that hospital survivors had significantly lower NLR than those who died. However, RDW was not significantly increased in patients who died during the hospitalization. The area under the ROC curve of NLR for predicting in-hospital mortality was 0.62. On multivariate analysis, NLR was not independently associated with in-hospital mortality. On further analysis, lymphocyte percentage was independently associated with in-hospital mortality, with an odds ratio of 0.56. Therefore, we concluded that RDW and NLR are not reliable parameters to predict in-hospital mortality in critically ill patients admitted to the emergency department with dyspnea., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Li Yan and Zhi-De Hu.)

Background: In the field of palliative care, morphine is known to be effective for alleviating dyspnea in cancer patients. However, little is known regarding the safety and efficacy of morphine therapy for refractory dyspnea as palliative care in advanced heart failure (HF) patients., Methods: We retrospectively reviewed consecutive advanced HF patients who were referred to the Palliative Care Team at our institution and administered morphine for refractory dyspnea during hospitalization between September 2013 and December 2018. We investigated the details of morphine usage, vital signs, an 11-point quantitative symptom scale, and adverse events at baseline, 24 h, and 72 h after the start of treatment., Results: Morphine was administered for refractory dyspnea in 43 advanced HF patients [mean age: 73.5 years, male: 28 (65%), New York Heart Association functional class IV: 43 (100%), median left ventricular ejection fraction: 25%, median B-type natriuretic peptide level: 927 pg/ml, concurrent intravenous inotrope: 33 (77%)]. Median initial dose of morphine was 5 mg/day in both oral and intravenous administration and median duration of administration was 5 days. Significant decreases in an 11-point quantitative symptom scale [7 (5, 9) vs. 2 (1, 6); p <  0.01, (data available in 8 patients)] and respiratory rate (22.2 ± 6.1 vs. 19.7 ± 5.2 breaths per minute; p < 0.01) were observed 24 h after the start of morphine administration. Meanwhile, oxygen saturation, blood pressure, and heart rate were not significantly altered after treatment (NS). Common adverse events were delirium (18%) and constipation (8%); however, no lethal adverse event definitely related to morphine therapy occurred during treatment., Conclusions: This single-center retrospective study revealed the clinical practice of morphine therapy and suggested that morphine therapy might be feasible for refractory dyspnea as palliative care in advanced HF patients., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID-19 patients for clinical help. The clinical data of COVID-19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID-19 patients and explained the discharge rate and fatality rate with a single-arm meta-analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C-reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single-arm meta-analysis showed that the male took a larger percentage in the gender distribution of COVID-19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID-19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11])., (© 2020 Wiley Periodicals, Inc.)

Objectives: This study examined whether insulin-like growth factor binding protein-7 (IGFBP7) would aid in the diagnosis and prognosis of acute heart failure (HF) beyond N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration., Background: IGFBP7 is associated with impaired ventricular relaxation and worse prognosis., Methods: The ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) study was a prospective, multicenter clinical trial that enrolled subjects presenting with dyspnea. Six-month prognosis for death or repeat hospitalization was obtained., Results: Among 1,449 patients, 274 (18.9%) were diagnosed with acute HF. Those with IGFBP7 concentrations in the highest quartile were older, male, had hypertension and HF, had lower estimated glomerular filtration rate (eGFR) and lowest ejection fraction (41 ± 20%; all p < 0.001). Independent predictors of IGFBP7 were age, male sex, history of diabetes, history of HF, and eGFR. Median concentrations of NT-proBNP (2,844 ng/ml vs. 99 ng/ml) and IGFBP7 (146.1 ng/ml vs. 86.1 ng/ml) were higher in those with acute HF (both; p < 0.001). Addition of IGFBP7 to NT-proBNP concentrations improved discrimination, therefore increasing the area under the receiver operating curve for diagnosis of acute HF (from 0.91 to 0.94; p < 0.001 for differences). Addition of IGFBP7 to a complete model of independent predictors of acute HF improved model calibration. IGFBP7 significantly reclassified acute HF diagnosis beyond NT-proBNP (net reclassification index: +0.25). Higher log 2 -IGFBP7 concentrations in patients with acute HF predicted death or rehospitalization at 6 months (hazard ratio: 1.84 per log 2 -SD; 95% confidence interval: 1.30 to 2.61; p = 0.001). In Kaplan-Meier analyses, supramedian concentrations of IGFBP7 were associated with shorter event-free survival (log-rank: p < 0.001)., Conclusions: Among patients with acute dyspnea, concentrations of IGFBP7 add to NT-proBNP for diagnosis of acute HF and provide added prognostic utility for short-term risk., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to review the diagnostic value of mid-regional pro-atrial natriuretic peptide (MR-proANP) for heart failure (HF) in patients who presented to the emergency department (ED) with acute dyspnoea. Methods: Relevant studies were searched on the databases of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with publication date limited to 30 March 2018. Literature identification, quality assessment, data extraction, synthesis, and statistical analysis were performed by standard meta-analysis methods. Individual and pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. Results: A total of eight studies were retrieved, involving 1562 HF patients and 2249 non-HF patients. The sensitivity for each included study ranged from 80 to 97%, with a pooled sensitivity of 90% (95% CI: 88-91%), while the specificity ranged from 37 to 86%, with a pooled specificity of 68% (95% CI: 66-70%). The pooled PLR for included studies was 2.88(95% CI: 2.12-3.93), with a pooled NLR of 0.16 (95% CI: 0.11-0.24), and a pooled DOR of 18.97 (95% CI: 11.73-30.68). Conclusions: With a decent sensitivity, MR-proANP is a useful biomarker for correctly identifying HF in patients with acute dyspnoea.

Introduction: Recent studies have suggested that patients with chronic obstructive pulmonary disease (COPD) may have a higher level of serum uric acid compared with individuals without COPD, although the data are still limited. The current systematic review and meta-analysis was conducted to summarize all available data., Material and Methods: A systematic review was performed using the MEDLINE and EMBASE databases from their inception to July 2019. Studies that were eligible for the meta-analysis must have consisted of two groups of participants, patients with COPD and individuals without COPD. The eligible studies must have reported either mean or median level of serum uric acid and its standard deviation (SD) or interquartile range of participants in both groups. Mean serum uric acid level and SD of participants in both groups were extracted from each study and the mean difference (MD) was calculated. Pooled MD was then computed by combining MDs of each study using random effects model., Results: A total of eight studies with 1,612 participants met the eligibility criteria and were included in the data analysis. The serum uric acid level among patients with COPD was significantly higher than individuals without COPD with the pooled MD of 0.91 mg/dL (95% CI: 0.45-1.38; I2 = 89%)., Conclusions: The current study found a significantly higher level of serum uric acid among patients with COPD than individuals without COPD.

Background: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported., Aim: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age., Results: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95% CI 1.31-3.44 p < 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p < 0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin., Conclusions: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3%., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The palliative care population is a complex and heterogeneous one. While transfusion therapy is a readily available intervention for many patients, inadequate knowledge for accurately identifying which patient subsets at end-of-life will benefit from a transfusion, along with an unclear understanding of the magnitude of attendant risks of transfusion in those receiving palliative care, complicates the risk-benefit assessment of this therapy. In this brief review, the current literature surrounding transfusion of red cells and platelets in the palliative care patient population will be reviewed and recommendations provided., Recent Findings: Benefits of transfusion therapy include subjective relief of fatigue and dyspnea, and improved sense of wellness, amongst other findings. However, these responses are not durable and there are currently no validated, objective metrics that correlate with symptomatic improvements. It is clear that transfusion-associated adverse reactions are underestimated in those receiving palliative care, with reaction rates similar to the general patient population. Additionally, based on the high mortality rates reported soon after transfusion, the impact of these blood components must be considered as an exacerbating or causative factor of mortality when evaluating declining condition or death. Hematinics are rarely assessed in anemic palliative care patients or, when measured, are often not corrected. The decision to transfuse palliative care patients is multifactorial, and benefits, risks, patient wishes, blood component inventories, and alternatives to transfusion should all be considered. There are many unknowns regarding transfusion in palliative care. Critical next steps for optimizing blood component therapy in this population include high-quality trials that help to identify validated measures of objective functional changes that parallel patient-reported outcomes and subsets of patients receiving end-of-life care that will most likely be positively impacted by transfusion therapy.

Aims: NT-proBNP is a useful biomarker for heart failure (HF) diagnosis. We aimed to determine NT-proBNP's ability to diagnose HF by age and renal function., Materials and Methods: We analyzed 3,699 consecutive and unique adults admitted for dyspnea at the Emergency Unit of St. Joseph St. Luc Hospital, Lyon, France, from December 1, 2012 to June 30, 2016, who had concomitant measurement of NT-proBNP and serum creatinine. We excluded patients with acute coronary syndrome and dialysis patients. Receiving operating characteristic (ROC) analysis assessed ability and cut-off points of NT-proBNP to diagnose HF., Results: Mean age was 79.1 ± 13.0 years. Mean estimated glomerular filtration rate (eGFR, CKD EPI formula) was 64 ± 26 mL/min/1.73m 2 . The ROC area under the curve (AUC) was 0.813 on average, optimal NT-proBNP cut-off point was 1,896 ng/L. AUC decreased (0.882, 0.813, 0.767) by age class (18 - 69, 70 - 84, 85+ years, respectively), and optimal cut-off points increased (1,041, 1,902, 2,321 ng/L). AUC decreased (0.881, 0.830, 0.783, 0.781, 0.705) by eGFR class (≥ 90, 60 - 89, 45 - 59, 30 - 44, < 30 mL/min/1.73m 2 ), and cut-off points increased (757, 1,362, 2,283, 4,108, 7,288 ng/L). The lowest value of cut-off points associated with highest sensitivity and specificity was detected in young patients with eGFR ≥ 90 (597 ng/L) while the worst value was found in age 85+ patients with eGFR < 30 (7,288 ng/L). AUC decreased below 0.8 in age 70+ patients with eGFR < 45 mL/min/1.73m 2 ;., Conclusion: The ability of NT-proBNP to diagnose HF decreased strongly with age and renal function. NT-proBNP's usefulness in diagnosing HF in age 70+ patients with eGFR < 45 mL/min/1.73m 2 remains uncertain.

A 67 years old woman with a Waldenström disease was admitted in the intensive care unit for dyspnea and fever. During hospitalization, episodes of undetectable glycemia were observed without any hypoglycemia symptoms. Plasma glucose was determined with the hexokinase method (recommended). From this observation, a literature review on PubMed was performed to investigate similar cases. In patients with protides in excess (e.g. immunoproliferative syndrome), absorption measurements could be disrupted by the precipitation of excess protein (IgM in most cases). Other parameters could be affected: bilirubin, phosphate, HDL cholesterol, GGT, CRP and calcemia. In our case, the main difficulty was to identify the cause of the interference and then correct it. Using a series of dilution, we prevented protide precipitation allowing correct glucose determination. Those interferences are rare, but present a real analytical difficulty. Biologists should be aware of those interferences because of dramatics consequences.

Background: Dyspnea is a cardinal but often underestimated symptom in amyotrophic lateral sclerosis (ALS). The newly developed Dyspnea-ALS-Scale (DALS-15) is highly relevant for therapeutic decisions because dyspnea is a separate criterion to consider noninvasive ventilation (NIV) in ALS. In comparison to the limited effects of neuroprotective compounds, NIV has the greatest impact on survival and improves quality of life., Objective: To investigate whether dyspnea corresponds to parameters of respiratory status mainly used in clinical neurological practice. We also investigated if the DALS-15 could help identify patients for consideration of NIV in whom neither spirometry nor blood gas parameters indicate the need for NIV (forced vital capacity (FVC) < 50% or probable <75%, pCO 2 ≥45  mmHg)., Methods: Seventy ALS patients with dyspnea according to the DALS-15 obtained blood gas analysis and spirometry (FVC in sitting and supine positions). The supine decline in FVC was calculated., Results: There was no linear relationship between dyspnea and spirometry as well as blood gases. 83% of our patients had an upright FVC still greater than 50% and no daytime hypercapnia., Conclusions: Our study clearly shows that dyspnea can occur independently of objective indicators of respiratory impairment like spirometry or blood gases. Hence, the DALS-15 covers another aspect of respiratory impairment than these tests and refers to the subjective component of respiratory impairment. It detects dyspnea in a considerable proportion of patients in whom NIV should thus be considered although their spirometric and blood gas results do not point towards NIV. The DALS-15 therefore may help to improve the stratification of patients with respiratory impairment for more efficient symptom management and timely coordination of care., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Biomarkers may help to rapidly differentiate heart failure from noncardiac causes of acute dyspnea. Natriuretic peptides are especially useful for this purpose and should be measured in all patients presenting with acute onset dyspnea. Due to their excellent negative predictive value, a normal serum concentration of natriuretic peptides makes acute heart failure unlikely. Assays exist for B‑type natriuretic peptide (BNP), N‑terminal pro-B-type natriuretic peptide (NT-proBNP) and midregional pro-atrial natriuretic peptide (MR-proANP) with established cut-offs in the acute setting. Importantly, in patients treated with an angiotensin receptor-neprilysin inhibitor (ARNI), NT-proBNP (or MR-proANP) should be used instead of BNP, since the latter is increased by ARNI treatment. Besides their established diagnostic value in heart failure patients, the measurement of natriuretic peptides provides prognostic information and may help in guiding therapy. Additionally, multiple other biomarkers reflect several pathophysiological processes involved in heart failure patients. Their diagnostic and prognostic impact in heart failure needs to be established.

Aims: Although acute decompensated heart failure (ADHF) is a common cause of dyspnoea, its diagnosis still represents a challenge. Lung ultrasound (LUS) is an emerging point-of-care diagnostic tool, but its diagnostic performance for ADHF has not been evaluated in randomized studies. We evaluated, in patients with acute dyspnoea, accuracy and clinical usefulness of combining LUS with clinical assessment compared to the use of chest radiography (CXR) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in conjunction with clinical evaluation., Methods and Results: This was a randomized trial conducted in two emergency departments. After initial clinical evaluation, patients with acute dyspnoea were classified by the treating physician according to presumptive aetiology (ADHF or non-ADHF). Patients were subsequently randomized to continue with either LUS or CXR/NT-proBNP. A new diagnosis, integrating the results of both initial assessment and the newly obtained findings, was then recorded. Diagnostic accuracy and clinical usefulness of LUS and CXR/NT-proBNP approaches were calculated. A total of 518 patients were randomized. Addition of LUS had higher accuracy [area under the receiver operating characteristic curve (AUC) 0.95] than clinical evaluation alone (AUC 0.88) in identifying ADHF (P < 0.01). In contrast, use of CXR/NT-proBNP did not significantly increase the accuracy of clinical evaluation alone (AUC 0.87 and 0.85, respectively; P > 0.05). The diagnostic accuracy of the LUS-integrated approach was higher then that of the CXR/Nt-proBNP-integrated approach (AUC 0.95 vs. 0.87, p < 0.01). Combining LUS with the clinical evaluation reduced diagnostic errors by 7.98 cases/100 patients, as compared to 2.42 cases/100 patients in the CXR/Nt-proBNP group., Conclusion: Integration of LUS with clinical assessment for the diagnosis of ADHF in the emergency department seems to be more accurate than the current diagnostic approach based on CXR and NT-proBNP., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Background: Systemic congestion, evaluated by estimated plasma volume status (ePVS), is associated with in-hospital mortality in acute heart failure (AHF). However, the diagnostic and prognostic value of ePVS in patients with acute dyspnea has been insufficiently studied., Objectives: To assess the association between the first ePVS calculated from blood samples on admission in the emergency department (ED) and discharge diagnosis of AHF and in-hospital mortality in patients admitted for acute dyspnea., Methods: The study included 1369 patients admitted for dyspnea in the ED in 2015. ePVS was calculated from hematocrit and hemoglobin values at admission. Comparisons of baseline characteristics according to ePVS tertiles were carried out and then associations between ePVS and the two outcomes "AHF diagnosis" and "intra-hospital mortality" were assessed using a logistic regression model., Results: 36.6% had a BNP > 400 pg/mL and median ePVS was 4.58 dL/g [3.96-5.55]. Overall in-hospital mortality was 11.1% (n = 149). In multivariable analysis, the third ePVS tertile (> 5.12 dL/g) had a significantly increased risk of having AHF (OR = 1.64 [1.16-2.33], p = 0.005). In-hospital mortality rose across ePVS tertiles (8.4-13.8% p < 0.01). ePVS greater than the first or second tertile threshold (respectively, 4.17 dL/g and 5.12 dL/g) were both significantly associated with a higher risk of in-hospital mortality (OR for 2nd/3rd tertile = 2.06 [1.25-3.38], p = 0.004 and OR for 3rd tertile = 1.54 [1.01-2.36], p = 0.04)., Conclusion: Higher ePVS values determined from first blood sample at admission are associated with a higher probability of AHF and in-hospital mortality in patients admitted in the ED for acute dyspnea.

Objectives: The aim of this study was to evaluate the performance of a rapid cardiothoracic ultrasound protocol (CaTUS), combining echocardiographically derived E/e' and lung ultrasound (LUS), for diagnosing acute heart failure (AHF) in patients with undifferentiated dyspnea in an emergency department (ED)., Patients and Results: We enrolled 100 patients with undifferentiated dyspnea from a tertiary care ED, who all had CaTUS done immediately upon arrival in the ED. CaTUS was positive for AHF with an E/e' > 15 and congestion, that is bilateral B-lines or bilateral pleural fluid, on LUS. In addition, an inferior vena cava index was also recorded to analyze whether including a central venous pressure estimate would add diagnostic benefit to the CaTUS protocol. All 100 patients had a brain natriuretic peptide (BNP) sample withdrawn, and 96 patients underwent chest radiography in the ED, which was analyzed later by a blinded radiologist. The reference diagnosis of AHF consisted of either a BNP of more than 400 ng/l or a BNP of less than 100 ng/l in combination with congestion on chest radiography and structural heart disease on conventional echocardiography.CaTUS had a sensitivity of 100% (95% confidence interval: 91.4-100%), a specificity of 95.8% (95% confidence interval: 84.6-99.3%), and an area under the curve of 0.979 for diagnosing AHF (P<0.001). The diagnostic accuracy of CaTUS was higher than of either E/e' or LUS alone. Adding the inferior vena cava index to CaTUS did not improve diagnostic accuracy. CaTUS seemed helpful also for differential diagnostics of dyspnea, mainly regarding pneumonias and pulmonary embolisms., Conclusion: CaTUS, combining E/e' and LUS, provided excellent accuracy for diagnosing AHF.

Background: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related major morbidity and mortality. Diagnosing TACO is difficult because there are no pathognomonic signs and symptoms. TACO biomarkers may aid in diagnosis, decrease time to treatment, and differentiate from other causes of posttransfusion dyspnea such a transfusion-related acute lung injury., Study Design and Methods: A systematic review of literature was performed in EMBASE, PubMed, the TRIP Database, and the Cochrane Library, from inception to June 2018. All articles discussing diagnostic markers for TACO were included. Non-English articles or conference abstracts were excluded., Results: Twenty articles discussing biomarkers for TACO were included. The majority investigated B-type natriuretic peptide (BNP) and the N-terminal prohormone cleavage fragment of BNP (NT-proBNP), markers of hydrostatic pressure that can be determined within 1 hour. The data indicate that a post/pretransfusion NT-proBNP ratio > 1.5 can aid in the diagnosis of TACO. Posttransfusion levels of BNP less than 300 or NT-proBNP less than 2000 pg/mL, drawn within 24 hours of the reaction, make TACO unlikely. Cut-off levels that exclude TACO are currently unclear. In critically ill patients, the specificity of natriuretic peptides for circulatory overload is poor. Other biomarkers, such as cytokine profiles, cannot discriminate between TACO and transfusion-related acute lung injury., Conclusion: Currently, BNP and NT-proBNP are the primary diagnostic biomarkers researched for TACO. An NT-proBNP ratio greater than 1.5 is supportive of TACO, and low levels of BNP or NT-proBNP can exclude TACO. However, they are unreliable in critically ill patients. Other biomarkers, including cytokines and pulmonary edema fluid-to-serum protein ratio have not yet been sufficiently investigated for clinical use., (© 2018 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Patients with arterial hypertension (AH), especially women, often report exercise intolerance and dyspnea. However, these symptoms are not frequently reflected in standard assessments. The aim of the study was to evaluate the clinical value of impedance cardiography (ICG) in the hemodynamic assessment of patients with AH during exercise, particularly the differences between subgroups based on sex and the presence of dyspnea. Ninety-eight patients with AH (52 women; 54.5 ± 8.2 years of age) were evaluated for levels of N-terminal pro-B-type brain natriuretic peptide (NT-proBNP), exercise capacity (cardiopulmonary exercise testing (CPET) and the 6-min walk test (6MWT)), and exercise ICG. Patients with AH were stratified into the following four subgroups: males without dyspnea (MnD, n = 38); males with dyspnea (MD, n = 8); females without dyspnea (FnD, n = 27); and females with dyspnea (FD, n = 25). In comparison with the MnD subgroup, the FnD subgroup demonstrated significantly higher NT-proBNP levels; lower exercise capacity (shorter 6MWT distance, lower peak oxygen uptake (VO 2 ), lower O 2 pulse); higher peak stroke volume index (SVI); and higher SVI at the anaerobic threshold (AT). In comparison with the other subgroups, the FD subgroup walked a shorter distance during the 6MWT distance; had a steeper VE/VCO 2 slope; had lower values of peak stroke volume (SV) and peak cardiac output (CO); and had a smaller change in CO from rest to peak. However, no other differences were identified (NT-proBNP, left ventricular diastolic dysfunction, or CPET parameters). Exercise impedance cardiography revealed an impaired hemodynamic response to exercise in hypertensive females with dyspnea. In patients with unexplained exercise intolerance, impedance cardiography may complement traditional exercise tests.

Introduction: Obese patients with acute dyspnea may be prone to misorientation from the emergency department (ED), due to impaired gas exchange evaluation and altered basal respiratory profiles. This study aims to evaluate the prognostic value of arterial blood pH in obese ED patients with acute dyspnea in comparison to non-obese counterparts., Methods: Single-center observational study of a cohort of 400 consecutive ED patients with acute dyspnea. The primary endpoint was a composite of Intensive Care Unit admission (with critical care needs) or in ED mortality. Predictors of the primary endpoint were assessed using multivariable logistic regression and ROC curve analysis, in obese (BMI ≥ 30 kg·m -2 ) and non-obese patients., Results: 252 patients who had arterial blood gas testing were analyzed including 76 (30%) obese comparable to non-obese in terms of clinical history. 51 patients were admitted to ICU and 2 deceased before admission (20 obese (26%) vs 33 non-obese (19%); p = 0.17). Factors associated with ICU admission were arterial blood pH (pH < 7.36 vs pH ≥ 7.36) and gender. In multivariate models adjusted for risk factors, pH remained the sole independent predictor in obese patients, with no predictive value in non-obese patients (ROC AUC: 0.74, 95% CI [0.60; 0.87], optimal threshold for pH: 7.36, odds ratio: 10.5 [95% CI 3.18; 34.68])., Conclusion: Arterial blood pH may selectively predict critical care needs in ED obese patients with acute dyspnea, in comparison to non-obese. A falsely reassuring pH < 7.36 should be regarded as a marker of severity when assessing acute dyspnea in obese ED patients., (Copyright © 2018. Published by Elsevier Inc.)

Objective: This study was performed to determine whether a dual-biomarker approach using N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and galectin-3 optimizes the diagnosis and risk stratification of acute cardiac dyspnea. Atypical clinical manifestations and overlapping pathologies require objective and effective diagnostic methods to avoid treatment delays., Methods: This prospective observational study included 208 patients who presented to the emergency department for acute dyspnea. NT-proBNP and galectin-3 were measured upon admission. The patients were divided into two groups according to the etiology of their clinical manifestations: cardiac and non-cardiac dyspnea. The patients' New York Heart Association functional class, left ventricular ejection fraction, and discharge status were assessed., Results: Diagnostic criteria for acute heart failure were fulfilled in 61.1% of the patients. NT-proBNP and galectin-3 were strongly and significantly correlated. Receiver operating characteristic analysis revealed similar areas under the curve for both markers in the entire group of patients as well as in the high-risk subsets of patients., Conclusions: The diagnostic performance of NT-proBNP and galectin-3 is comparable for both the total population and high-risk subsets. Galectin-3 adds diagnostic value to the conventional NT-proBNP in patients with acute cardiac dyspnea, and its utility is of major interest in uncertain clinical situations.

COPD is characterized by a pulmonary and systemic inflammatory process. Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations. The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count. We performed a systematic literature review using the PRISMA statement. Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls. Compared with controls, COPD patients had significantly higher NLR values. We found a significant correlation between the NLR and clinical/functional parameters (FEV 1 , mMRC, and BODE index) in COPD patients. Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively). Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity. The NLR is an independent predictor of in-hospital and late mortality after exacerbation. In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: To compare the diagnostic and prognostic value of mid-regional pro-ANP (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea., Methods: MR-proANP and NT-proBNP were measured with commercial immunoassays at hospital admission (n = 313), on day 2 (n = 234), and before discharge (n = 91) and compared for diagnosing acute heart failure (HF; n = 143) and to predict mortality among patients with acute HF and acute exacerbation of chronic obstructive pulmonary disease (AECOPD; n = 84) separately., Results: The correlation coefficient between MR-proANP and NT-proBNP was 0.89 (p < 0.001) and the receiver-operating area under the curve (AUC) was 0.85 (95% CI 0.81-0.89) for MR-proANP and 0.86 (0.82-0.90) for NT-proBNP to diagnose acute HF. During a median follow-up of 816 days, mortality rates were 46% in acute HF patients and 42% in AECOPD patients. After adjustment for other risk variables by multivariate Cox regression analysis, MR-proANP and NT-proBNP concentrations were associated with mortality in patients with acute HF, but only MR-proANP were associated with mortality among patients with AECOPD: hazard ratio ( ln MR-proANP) 1.98 (95% CI 1.17-3.34)., Conclusion: MR-proANP and NT-proBNP concentrations provide similar diagnostic and prognostic information in patients with acute HF. In contrast to NT-proBNP, MR-proANP measurements also provided independent prognostic information in AECOPD patients.

Background: According to guidelines, single determination of B-type Natriuretic peptide (BNP) should be used for distinguishing between cardiac and non-cardiac acute dyspnea at the emergency room. BNP measurement is also recommended before hospital discharge in patients hospitalized for heart failure to assess prognosis and to evaluate treatment efficacy. In acute cardiogenic pulmonary edema, BNP is measured using a single BNP determination, but the temporal behavior of BNP during pulmonary edema recovery is unknown., Methods: Fifty chronic low ejection fraction (<40%) heart failure patients (age 77 ± 9 years, 17 M-33F) admitted for acute pulmonary edema were studied. Patients were grouped according to 50% dyspnea recovery time into 3 groups: ≤30 min (n = 14), 30 to 60 min (n = 19), and > 60 min (n = 17). BNP was measured at arrival and 4, 8, 12 and 24 h afterwards., Results: At arrival, BNP was elevated in all patients without significant difference among groups. In the entire population, BNP median and interquartile range value were 791 (528-1327) pg/ml, 785(559-1299) pg/ml, 1014(761-1573) pg/ml, 1049(784-1412) pg/ml, 805(497-1271) pg/ml at arrival and 4, 8, 12 and 24 h afterwards, respectively, showing higher values at 8 and 12 h. This peculiar temporal behavior of BNP was shared by all study groups. Patients with the longest edema resolution showed the highest BNP level 8 and 12 h after admission., Conclusions: In acute pulmonary edema, BNP increased up to 12 h after emergency admission regardless of dyspnea recovery time, making BNP quantitative meaning in the acute phase of pulmonary edema uncertain., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: The purpose of this study was to examine whether the addition of brain natriuretic peptide measurement to the routine diagnostic work-up by prehospital critical care team physicians improves triage in patients with severe dyspnoea., Methods: Prehospital critical care team physicians randomly assigned patients older than 18 years with severe dyspnoea to routine diagnostic work-up or diagnostic work-up with incorporated point-of-care N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement. The primary endpoint was the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology., Results: A total of 747 patients were randomly assigned and 711 patients consented to participate, 350 were randomly assigned to the NT-proBNP group and 361 to the routine work-up group. NT-proBNP was measured in 90% (315/350) of patients in the NT-proBNP group and in 19% (70/361) of patients in the routine work-up group. There was no difference in the proportion of patients with dyspnoea of primary cardiac origin triaged directly to a department of cardiology between the NT-proBNP group and the routine work-up group (75% vs. 69%, P=0.22) in the intention-to-treat analysis. Sensitivity analysis according to the de facto diagnostics performed showed results consistent with this. No differences in hospital length of stay, intensive care unit admission rates or mortality between the NT-proBNP group and the routine work-up group were observed., Conclusion: Routine supplementary point-of-care measurement of NT-proBNP in patients with severe dyspnoea did not improve triage of patients with dyspnoea primarily caused by heart disease. ClinicalTrials.gov identifier NCT02050282.

Platypnoea Orthodeoxia syndrome is defined by dyspnoea and hypoxaemia exacerbated by orthostatic positioning and alleviated in recumbency. This condition has been reported in association with pulmonary, hepatic and cardiac disease. We describe a case herein of a 79 year old female who developed severe hypoxaemia and dyspnoea post laparoscopic cholecystectomy. A difference in arterial blood gas oxygen tension was demonstrated in the supine and erect positions on arterial blood gas analysis. A Patent Foramen Ovale (PFO) with a right to left shunt was evident on echocardiogram employing colour doppler and agitated normal saline studies. Definitive management, with closure of the patent foramen ovale lead to a complete resolution of symptoms and normalisation of arterial blood gas parameters in both the supine and erect positions., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The rising incidence of and the cost associated with heart failure have made it increasingly imperative to accurately diagnose heart failure upon presentation. Correctly identifying heart failure in an Emergency Department is extremely challenging, and according to estimates, is only confirmatory in approximately 40-50% of patients. For an accurate diagnosis of heart failure and the consequent treatment, there needs to be more accurate test relying on biochemical factors as opposed to general symptoms that patients are experiencing. Natriuretic peptides are now utilized in routine tests for heart disease diagnosis in emergency departments as it is relatively low cost, easy to use and is a quick way to exclude heart failure as a reason for dyspnea. In this review, we detail the role and value of individual natriuretic peptides, particularly BNP, NT-proBNP, and MR-proANP, in diagnosing acute heart failure.

Background: Contemporary reconsideration of diagnostic N-terminal pro-B-type natriuretic peptide (NT-proBNP) cutoffs for diagnosis of heart failure (HF) is needed., Objectives: This study sought to evaluate the diagnostic performance of NT-proBNP for acute HF in patients with dyspnea in the emergency department (ED) setting., Methods: Dyspneic patients presenting to 19 EDs in North America were enrolled and had blood drawn for subsequent NT-proBNP measurement. Primary endpoints were positive predictive values of age-stratified cutoffs (450, 900, and 1,800 pg/ml) for diagnosis of acute HF and negative predictive value of the rule-out cutoff to exclude acute HF. Secondary endpoints included sensitivity, specificity, and positive (+) and negative (-) likelihood ratios (LRs) for acute HF., Results: Of 1,461 subjects, 277 (19%) were adjudicated as having acute HF. The area under the receiver-operating characteristic curve for diagnosis of acute HF was 0.91 (95% confidence interval [CI]: 0.90 to 0.93; p < 0.001). Sensitivity for age stratified cutoffs of 450, 900, and 1,800 pg/ml was 85.7%, 79.3%, and 75.9%, respectively; specificity was 93.9%, 84.0%, and 75.0%, respectively. Positive predictive values were 53.6%, 58.4%, and 62.0%, respectively. Overall LR+ across age-dependent cutoffs was 5.99 (95% CI: 5.05 to 6.93); individual LR+ for age-dependent cutoffs was 14.08, 4.95, and 3.03, respectively. The sensitivity and negative predictive value for the rule-out cutoff of 300 pg/ml were 93.9% and 98.0%, respectively; LR- was 0.09 (95% CI: 0.05 to 0.13)., Conclusions: In acutely dyspneic patients seen in the ED setting, age-stratified NT-proBNP cutpoints may aid in the diagnosis of acute HF. An NT-proBNP <300 pg/ml strongly excludes the presence of acute HF., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)