Management of bleeding in patients on direct oral anticoagulants in emergency department: where we are and where we are going.

Many patients who access in the emergency department for acute bleeding are on anticoagulants; before specific reversal agents were developed, bleeding on anticoagulants was burdened with a substantial increase in morbidity and mortality. Clinical trials demonstrated favourable risk-benefit profiles of direct-acting oral anticoagulants compared with vitamin K antagonists in patients with atrial fibrillation and compared with low molecular weight heparin in patients treated and prevented from venous thromboembolism. Even if they drastically reduced some types of bleeding, particularly intracranial haemorrhage, they have not completely eliminated this risk. The arrival of a patient with active bleeding in the emergency department is always a critical scenario that involves resources and costs. In critical setting, the diagnosis and treatment of bleeding should occurred simultaneously. Understanding the pathophysiological mechanisms that occur during bleeding is essential for establish the most appropriate therapies and improve the standard of care of the haemorrhagic patients.

Utility of Combining High-Sensitive Cardiac Troponin I and PESI Score for Risk Management in Patients with Pulmonary Embolism in the Emergency Department.

BACKGROUND AND OBJECTIVES: Pulmonary embolism (PE) has a major burden of morbidity and mortality, consequently the need for a prompt risk stratification for these subjects is crucial. In order to evaluate the risk management and final disposition of patients with PE in the Emergency Department (ED), we conducted a study that was divided in two phases: Phase I retrospective study (RS), Phase II prospective study (PS). MATERIALS AND METHODS: In Phase I, 291 patients were enrolled while in Phase II, 83 subjects were evaluated. In both study phases, the enrolled subjects were analyzed for final disposition in ED using PESI score, right ventricle (RV) imaging, and high-sensitive cardiac troponin I (hs-cTnI) data. The RS patients were divided into low risk and high risk according to the sPESI score, while PS patients were grouped in low, intermediate, and high risk classes according to PESI score. In both study phases, all the studied patients were further divided into negative (hs-cTnI-) or positive (hs-cTnI+) groups according to hs-cTnI levels within normal or above cutoff values, respectively. For all enrolled subjects, CT pulmonary angiography was analyzed to assess the RV/LV diameter and volume ratio as an indicator of RV involvement. RESULTS: In both RS and PS phases, hs-cTnI+ group showed a higher PESI score. Nevertheless, a significant percentage of hs-cTnI+ patients resulted to be in the low-risk PESI class. Patients with a positive RV/LV ratio were more likely to have a hs-cTnI+ (p < 0.01), while among those with a negative ratio, 24 to 32% showed as hs-cTnI+. In the hs-cTnI+ group from both study phases, patients were more likely to be admitted in an ICU (RR 3.7, IC: 2.1-6.5). CONCLUSIONS: In conclusion, in patients with PE in the ED compared PESI score alone, the combination of hs-cTnI and PESI seems to be of greater utility in improving risk stratification and final disposition decision-making.

30 Days Mortality Prognostic Value of POCT Bio-Adrenomedullin and Proenkephalin in Patients with Sepsis in the Emergency Department.

Background and Objective: Sepsis is a worldwide severe disease with a high incidence and mortality rate. Sepsis is a frequent cause of admission to the emergency department (ED). Although prognostic scores (Sequential Organ Failure Assessment, SOFA; New Early Warning Score, NEWS; Rapid Emergency Medicine Score, REMS) are commonly used for risk stratification in septic patients, many of these scores are of poor utility in the ED. In this setting, biomarkers are promising alternatives, easier to perform and potentially more specific. Bio-adrenomedullin (Bio-ADM) and Proenkephalin (PenKid) seem to have a key role in the development of organ dysfunctions induced by sepsis and, therefore, could help in the risk stratification of patients with sepsis at ED admission. The aim of this study was to evaluate the utility of Bio-ADM and PenKid, obtained through a point of care (POCT) device, in predicting 30 days mortality for patients presenting to the ED with sepsis. Methods and Results: In total, 177 consecutive adult patients with a diagnosis of sepsis presenting to the ED of San Giovanni Addolorata Hospital in Rome, Italy, between May 2021 and April 2022 were enrolled in this prospective observational study. For each patient, Bio-ADM and PenKid were obtained at ED admission together with SOFA, NEWS and REMS scores. Next, 30 days follow-up data were collected to evaluate patient mortality. Both biomarkers (Bio-ADM and PenKid) and clinical scores (SOFA, NEWS and REMS) were good predictors of mortality at 30 days, with Bio-ADM and REMS outperforming the others. Moreover, PenKid resulted in being linked with the worsening of kidney function. Conclusions: In patients presenting with sepsis in the ED, Bio-ADM and PenKid, evaluated with a POCT device, predicted 30-day mortality. These two biomarkers seem even more useful when integrated with clinical risk scores at ED admission.

Utility of Measuring Circulating Bio-Adrenomedullin and Proenkephalin for 30-Day Mortality Risk Prediction in Patients with COVID-19 and Non-COVID-19 Interstitial Pneumonia in the Emergency Department.

Background and Objectives: In order to accelerate the risk stratification of patients referred to the Emergency Department (ED) with interstitial pneumonia, it could be useful to provide new and effective laboratory tests for use. The aim of our study was to evaluate the prognostic role of two biomarkers, bio-adrenomedullin (Bio-ADM) and proenkephalin (penKid), in patients with interstitial pneumonia (IP) at ED admission. Materials and Methods: In 153 consecutive patients with IP, both from COVID-19 or non-COVID-19 etiology, we measured, in a prospective observational manner, penKid and Bio-ADM at ED admission and after 24 h. In order to evaluate patient outcomes, 30-day follow-ups were also performed. The endpoints were 24 h, 10-day, and 30-day mortality. Results: Both biomarkers were shown to be good predictors of adverse events at 30 days, with Bio-ADM outperforming penKid. Bio-ADM was linked with 24 h and 10-day patient mortality. Moreover, PenKid was related to parameters defining worsening kidney function. Conclusions: Both in patients with COVID-19 or non-COVID-19 interstitial pneumonia at ED admission, Bio-ADM and penKid were good predictors of patient mortality. To evaluate these two biomarkers could be considered to be useful during the first evaluation in the ED when integrated with clinical scores.

Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension.

BACKGROUND: Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined. METHODS: Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed. RESULTS: A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO2 peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO2 peak ≥14 ml/kg/min and SVI >30 ml/m2; Group 2, score between 2 and 5 (112 patients) with VO2 peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m2; Group 3, score >5 (46 patients) with VO2 peak <10 ml/kg/min and SVI <30 ml/m2. The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3. CONCLUSIONS: Combinations of VO2 peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH.

Usefulness of High-Sensitivity Troponin I in Risk Stratification and Final Disposition of Patients with Acute Heart Failure in the Emergency Department: Comparison between HFpEF vs. HFrEF.

Background and Objectives: In patients with acute heart failure (AHF), there is no definite evidence on the relationship between high-sensitivity cardiac troponin (hs-cTnI) and the left ventricular ejection fraction (LVEF) comparing the reduced and preserved EF conditions. Materials and Methods: Between January and April 2022, we retrospectively analyzed the data from 386 patients admitted to the emergency departments (ED) of five hospitals in Rome, Italy, for AHF. The criteria for inclusion were a final diagnosis of AHF; a cardiac ultrasound and hs-cTnI evaluations in the ED; and age > 18 yrs. We excluded patients with acute coronary syndrome (ACS). Based on echocardiography and hs-cTnI evaluations, the patients were grouped for (1) preserved (HFpEF) or (2) reduced LVEF (HFrEF) and a a) negative (within the normal range value) or b) positive (above the normal range value) of hs-cTnI, respectively. Results: There was a significant negative relationship between a positive test for hs-cTnI and LVEF. When compared to the group with a negative hs-cTnI test, the patients with a positive test, both from the HFpEF and HFrEF subgroups, were significantly more likely to have an adverse outcome, such as being admitted to the intensive care unit (ICU) or dying in the ED. Moreover, a reduced ejection fraction was linked with a final disposition to a higher level of care. Conclusions: In patients admitted to the ED for AHF without ACS, there is a negative relationship between hs-cTnI and a reduced LVEF, although a significant percentage of patients with a preserved LVEF also resulted to have high levels of hs-cTnI. In the absence of ACS, hs-cTnI seems to be a reliable biomarker of myocardial injury in AHF in the ED and should be considered as a risk stratification parameter for these subjects regardless of the left ventricular function. Further larger prospective studies are needed to confirm these preliminary data.

Is There a Risk of Misinterpretation of Potassium Concentration from Undetectable Hemolysis Using a POCT Blood Gas Analyzer in the Emergency Department?

Background and Objectives: Hemolysis is reported to be present in up to 10% of blood gas specimens in the central lab; however, few data on the incidence of hemolysis using a point-of-care testing (POCT) blood gas analysis are available in the setting of the emergency department. The aims of this study were: (1) to analyze the prevalence of hemolysis in blood gas samples collected in the ED using a POCT device; and (2) to evaluate the impact of hemolysis on blood sample results and its clinical consequences. Materials and Methods: We collected 525 consecutive POCT arterial blood gas samples using syringes with electrolyte-balanced heparin within 3 different EDs in the metropolitan area of Rome. Immediately after the collection, the blood samples were checked for the presence of hemolysis with a POCT instrument (i.e., HEMCHECK, H-10 ®). The samples were then subsequently processed for blood gasses, and an electrolytes analysis by a second operator blinded for the hemolysis results. A venous blood sample was simultaneously collected, analyzed for it's potassium value, and used as a reference. Results: Of the samples, 472 were considered for the statistics, while 53 were excluded due to the high percentage of hemolysis due to operator fault in carrying out the measurement. The final mean hemolysis per operator was 12% (±13% SD), and the total final hemolysis was 14.4%.Potassium (K+) was significantly higher in the hemolyzed group compared with the non-hemolyzed sample (4.60 ± 0.11 vs. 3.99 ± 0.03 mEq/L; p < 0.001), and there were differences between arterial potassium versus venous potassium (D(a-v) K+, 0.29 ± 0.06 vs.−0.19 ± 0.02 mEq/L, p < 0.01). A Bland−Altman analysis confirmed that hemolysis significantly overestimated blood potassium level. Conclusion: Almost 12% of POCT blood gas analysis samples performed in the ED could be hemolyzed, and the presence of this hemolysis is not routinely detected. This could cause an error in the interpretation of the results, leading to the consideration of potassium concentrations being below the lower limit within the normal limits and also leading to the diagnosis of false hyperkalemia, which would have potential clinical consequences in therapeutic decision-making in the ED. The routine use of a POCT hemolysis detector could help prevent any misdiagnoses.

In-hospital mortality in the emergency department: clinical and etiological differences between early and late deaths among patients awaiting admission.

OBJECTIVE: Given that there are no studies on diseases that occur by waiting for hospitalization, we aimed to evaluate the main causes of death in the emergency room (ER) and their relationship with overcrowding. METHODS: Patients who died in the ER in the past 2 years (pediatrics and trauma victims excluded) were divided into two groups: patients who died within 6 hours of arrival (emergency department [ED] group) and patients who died later (LD group). We compared the causes of death, total vital signs, diagnostic tests performed, and therapy between the groups. We assessed for possible correlation between the number of monthly deaths per group and four variables of overcrowding: number of patients treated per month, waiting time before medical visit (W-Time), mean intervention time (I-Time), and number of patients admitted to the ward per month (NPA). RESULTS: During the two years, 175 patients had died in our ER (52% in ED group and 48% in LD group). The total time spent in the ER was, respectively, 2.9±0.2 hours for ED group and 17.9± 1.5 hours for LD group. The more frequent cause of death was cardiovascular syndrome (30%) in ED group and sepsis (27%) and acute respiratory failure (27%) in LD group. Positive correlations between number of monthly deaths and W-Time (R2 0.51, P<0.001), I-Time (R2 0.73, P< 0.0001), and NPA (R2 0.37, P<0.01) were found only in LD group. CONCLUSION: Patients with sepsis and acute respiratory failure die after a long stay in the ER, and the risk increases with overcrowding. A fast-track pathway should be considered for hospital admission of critical patients.

Continuous Positive Airway Pressure (CPAP) in Non-Apneic Asthma: A Clinical Review of Current Evidence.

The use of continuous positive airway pressure (CPAP) in asthma has been a point of debate over the past several years. Various studies, including those on animals and humans have attempted to understand the role and pathophysiology of CPAP in patients with either well controlled or poorly controlled asthma. The aim of this manuscript is to review the currently available literature on the physiologic and clinical effects of CPAP in animal models of asthma and on humans with stable asthma.

Exercise energy expenditure in patients with idiopathic pulmonary arterial hypertension: Impact on clinical severity and survival.

Patient with idiopathic pulmonary hypertension (IPAH) develop peripheral inefficiency which could lead to an increase total energy expenditure and that could have a significant prognostic impact. To test the hypothesis, fifty-five consecutive stable IPAH patients (mean age 51±17 years) and 24 matched controls underwent an incremental exercise test and followed for a 5 years' period. Total energy expenditure was assessed as the ratio between total [Formula: see text] uptake (during both effort and recovery) and total external work ( [Formula: see text] ). Patients with IPAH had a lower exercise capacity and a significantly higher [Formula: see text] than controls ( [Formula: see text] 0.33 ± 0.09 ml/j vs 0.22 ± 0.04 ml/j, p < 0.0001). Among patients, [Formula: see text] was higher in whom died during follow up compared to survivors (0.41 ± 0.11 ml/j vs 0.30 ± 0.06 ml/j, p < 0.0001). In multivariate Cox regression analysis [Formula: see text] , gender, PETCO2 peak, [Formula: see text] were independent risk factors for death. Patients with IPAH have shown a less efficient muscular oxygen utilization than controls. Notably the high energy expenditure has a relevant independent prognostic impact.

Noninvasive ventilation: education and training. A narrative analysis and an international consensus document.

Noninvasive ventilation (NIV) is an increasingly used method of respiratory support. The use of NIV is expanding over the time and if properly applied, it can save patients' lives and improve long-term prognosis. However, both knowledge and skills of its proper use as life support are paramount. This systematic review aimed to assess the importance of NIV education and training. Literature search was conducted (MEDLINE: 1990 to June, 2018) to identify randomized controlled studies and systematic reviews with the results analyzed by a team of experts across the world through e-mail based communications. Clinical trials examining the impact of education and training in NIV as the primary objective was not found. A few studies with indirect evidence, a simulation-based training study, and narrative reviews were identified. Currently organized training in NIV is implemented only in a few developed countries. Due to a lack of high-grade experimental evidence, an international consensus on NIV education and training based on opinions from 64 experts across the twenty-one different countries of the world was formulated. Education and training have the potential to increase knowledge and skills of the clinical staff who deliver medical care using NIV. There is a genuine need to develop structured, organized NIV education and training programs, especially for the developing countries.

The added value of cardiopulmonary exercise testing in the follow-up of pulmonary arterial hypertension.

BACKGROUND: The added value of cardiopulmonary exercise testing (CPET) in the follow-up of patients with stable pulmonary arterial hypertension (PAH) remains undefined. METHODS: Idiopathic, heritable, and drug-induced PAH patients free from clinical worsening (CW) after 1 year of treatment were enrolled in derivation (n = 80) and validation (n = 80) cohorts at an interval of 6 years and followed for 3 years. Prognostic models were constructed and validated in low-risk patients in World Health Organization (WHO) Functional Class I or II with cardiac index (CI) ≥2.5 liters/min/m2 and right atrial pressure (RAP) <8 mm Hg. Discrimination and calibration were assessed. RESULTS: Forty-one derivation cohort patients had CW (51.2%) during 722 ± 349 days. Changes (∆) in WHO classification and CI and absolute value of RAP were independent predictors of CW. With addition of CPET variables, peak oxygen uptake (VO2 peak) and ∆CI independently improved the power of the prognostic model. Receiver operating characteristic (ROC)-derived cut-off values for ∆CI and VO2 peak were 0.40 liter/min/m2 and 15.7 ml/kg/min (≥60% predicted value), respectively. Twenty-nine validation cohort patients had CW (36.2%) during 710 ± 282 days. Different combinations of cut-off values of VO2 peak and ∆CI defined 4 groups. The event-free survival rates at 1, 2, and 3 years were 100%, 100%, and 100%, respectively, for the high ∆CI with high VO2 peak combination; 100%, 88%, and 71% for low ∆CI/high VO2 peak; 80%, 54%, and 40% for high ∆CI/low VO2 peak; and 72%, 54%, and 33% for low ∆CI/low VO2 peak. CONCLUSIONS: The combinations of baseline VO2 peak and change in CI during follow-up is important in prognostication of low-risk patients with idiopathic, heritable, and drug-induced PAH.

Right ventricular dyssynchrony and exercise capacity in idiopathic pulmonary arterial hypertension.

Survival in patients with pulmonary arterial hypertension (PAH) is determined by right ventricular (RV) function adaptation to afterload. How altered RV function impacts on exercise capacity in PAH is not exactly known.104 idiopathic PAH (IPAH) patients aged 52±14 years underwent a diagnostic right heart catheterisation, a comprehensive echocardiography including two-dimensional speckle tracking for RV dyssynchrony evaluation and a cardiopulmonary exercise test. Multivariate analyses were performed to identify independent predictors of peak oxygen uptake (peak V'O2 ).A first multivariate analysis of only resting haemodynamic variables identified cardiac index, right atrial (RA) pressure and pulmonary arterial compliance as independent predictors, with low predictive capacity (r2=0.31; p<0.001). A second multivariate analysis model which considered only echocardiographic parameters but without RV dyssynchrony, identified RV fractional area change (FAC) and RA area as independent predictors with still low predictivity (r2=0.35; p<0.001). Adding RV dyssynchrony to the second model increased its predictivity (r2=0.48; p<0.001). Repetition of the three multivariate analyses in patients with preserved RVFAC confirmed that inclusion of RV dyssynchrony results in the highest predictive capability of peak V'O2 (r2=0.53; p=0.001).A comprehensive echocardiography with speckle tracking-derived assessment of the heterogeneity of RV contraction improves the prediction of aerobic exercise capacity in IPAH.

Echocardiography Combined With Cardiopulmonary Exercise Testing for the Prediction of Outcome in Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension. The aim of the study was to evaluate the incremental prognostic value of echocardiography of the right ventricle and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients. METHODS: One hundred and thirty treatment-naïve patients with idiopathic pulmonary arterial hypertension were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-min walk distance plus an increase in functional class, or nonelective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic, and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done. RESULTS: During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical, and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (model 1). With addition of echocardiographic and CPET variables (model 2), peak O2 pulse (peak V˙o2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (area under the curve, 0.81 vs 0.66, respectively; P = .005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC + low O2 pulse showed a 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk, 41.1 and 25.3, respectively), compared with high RVFAC + high O2 pulse (P = .0001). CONCLUSIONS: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration.

Right Intraventricular Dyssynchrony in Idiopathic, Heritable, and Anorexigen-Induced Pulmonary Arterial Hypertension: Clinical Impact and Reversibility.

OBJECTIVES: The aim of this study was to determine the prevalence of right intraventricular dyssynchrony, its determinants and prognostic impact in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension. BACKGROUND: Right ventricular dyssynchrony has been described in pulmonary arterial hypertension, but no evidence is available on its prognostic impact and evolution after therapy. METHODS: In 83 consecutive therapy-naïve patients, right ventricular dyssynchrony was evaluated by 2-dimensional speckle-tracking echocardiography calculating the standard deviation of the times to peak-systolic strain for the 4 mid-basal right ventricular segments (RV-SD4). After baseline (World Health Organization [WHO] class, pulmonary hemodynamics, 6-min walk test [6 MWT]), a second assessment was performed after 12 months or when clinical worsening occurred. RESULTS: Patients with right ventricular dyssynchrony (RV-SD4 >18 ms) had advanced WHO class, worse 6 MWT, right ventricular remodeling, and hemodynamic profile compared with patients ≤ 18 ms. Determinants of dyssynchrony included pulmonary vascular resistance, QRS duration, and right ventricular end-diastolic area (r(2) = 0.38; p < 0.000001). At 12 months, 32.5% of patients presented clinical worsening (actuarial rates: 19% at 6 months, 31% at 1 year). Multivariable models for clinical worsening prediction showed that the addition of RV-SD4 to clinical and hemodynamic variables (WHO IV, 6 MWT, and cardiac index) significantly increased the prognostic power of the model (0.74 vs. 0.81; p = 0.005, 95% confidence interval [CI]: 0.02 to 0.11). Receiver operating characteristic analysis identified RV-SD4 ≥ 23 ms as the best cutoff value for clinical worsening prediction (95% negative predictive value). At 12 months, normalization of dyssynchrony was achieved in patients with a large reduction of pulmonary vascular resistance (-42 ± 4%). CONCLUSIONS: Right ventricular dyssynchrony is frequent in pulmonary arterial hypertension, is an independent predictor of clinical worsening, and might regress during effective treatments.

A pilot study on the application of the current European guidelines for the management of acute coronary syndrome without elevation of ST segment (NSTEMI) in the Emergency Department setting in the Italian region Lazio.

BACKGROUND: In 2011 the European Society of Cardiology published the new guidelines for the treatment and management of acute coronary syndrome without elevation of the ST segment (NSTEMI). For the treatment of the syndrome, the use of P2Y12 inhibitors in addition to aspirin was strongly recommended (evidence IA). We studied the application of this recommendation in the setting of the emergency department in the vast and uneven area of the Italian region Lazio, three years after the release of these drugs in Italy. METHODS: 121 consecutive patients (65% older than 65 years) affected by NSTEMI were recruited between May and July 2013. During the transition in the emergency department data was collected on patient's symptoms, syndrome severity and type & timing of treatments chosen. Adherence to the guidelines was evaluated considering the number of "good treated" patients: these being the patients that received at least 80% of the main five recommendations on percutaneous coronary intervention (PCI) timing, antiplatelet and anti-coagulant therapy suggested by the European Cardiology Task Force (ESC guidelines, 2011) for the very acute phase of NSTEMI. RESULTS: Patients were treated with: 1) 35% of cases with double antiplatelet therapy and anticoagulation (DAPT+AC), 2) 22% of cases with single antiplatelet and anticoagulation (SAPT+AC), 3) 6% of cases with a single antiplatelet therapy (SAPT), 4) 6% of cases with a double antiplatelet therapy (DAPT) and 5) 24% of cases did not receive any therapy. Data on PCI was available for 95 patients and, of these, only 82% of the patients underwent the procedure. The percentage of "good treated" patients were among of 20-40%, depending on PCI timing--as guidelines suggested--was considered as mandatory (20,5%) or as the extreme time limit (40%). Significant differences were found between patients treated in a central hospital with a hemodynamic laboratory active 24/24hr (HUB) and patients treated in the other hospital (SPOKE). HUBs showed a higher percent of "good treated" patients, a higher percentage of early invasive treated and a better adherence to recommended pharmacological therapy. CONCLUSIONS: A significant number of patients did not receive adequate treatment during the emergency department stay. The absence of hemodynamic services increases the risk of inadequate treatment.

Minute ventilation and heart rate relationship for estimation of the ventilatory compensation point at high altitude: a pilot study.

BACKGROUND: The ventilatory compensation point (VCP) is an exercise threshold which has been used in the design of training programs in sports medicine and rehabilitation. We recently demonstrated that changes in the slope of the minute ventilation to heart rate relationship (ΔV˙E/ΔHR) can be utilized for estimation of the VCP during incremental exercise at sea level (SL). We hypothesized that in hypoxic conditions, such as high altitude (HA), VCP can be also reliably estimated by ΔV˙E/ΔHR. METHODS: At SL and on immediate ascent to HA (5,050 m), six healthy subjects (42 ± 14 SD years) performed a maximal incremental exercise test on a cycle ergometer; O2 uptake (V˙O2), CO2 output (V˙CO2), V˙E, and HR were measured breath-by-breath. The ΔV˙E/ΔHR method for VCP estimation was compared to the standard method using the ventilatory equivalent for CO2 (V˙E/V˙CO2) and end-tidal PCO2 (PETCO2). The ΔV˙E/ΔHR slope values below (S1) and above (S2) VCP were computed by linear regression analysis. RESULTS: A significant difference between S1 and S2 was observed, at SL and HA, for both the ΔV˙E/ΔHR and V˙E/V˙CO2 methods for VCP estimation. A good agreement between the two methods (ΔV˙E/ΔHR vs. V˙E/V˙CO2) was found for both environmental conditions; the mean difference ± 2 SD of V˙O2 at VCP (VCP-V˙O2) was -22 ± 112 ml/min at SL and 39 ± 81 ml/min at HA. The VCP-V˙O2 was significantly lower at HA compared to SL; in addition, S1 and S2 mean values were significantly higher at HA compared to SL. CONCLUSION: At HA, VCP may be reliably estimated by the ΔV˙E/ΔHR method.

Pulmonary arterial dilatation in pulmonary hypertension: prevalence and prognostic relevance.

OBJECTIVES: Pulmonary arterial dilatation is considered a consequence of chronic pulmonary hypertension (PH), but despite its relatively common detection, its prevalence and prognostic impact have not yet been systematically investigated. The aim of the study was to investigate these factors in a relatively large cohort of severe PH patients. METHODS: One hundred and forty-one consecutive patients diagnosed with PH were monitored for a mean of 957 days. Data including functional class, exercise capacity, invasive hemodynamics and pulmonary artery (PA) echo/CT scan measurement were performed and outcomes prospectively collected. RESULTS: PA dilatation is a common feature, present in the 76.6% of cases in this cohort of severe PH patients. Survival at 1, 2 and 3 years was 83, 71 and 58%, respectively. On univariate analysis, the baseline variables associated with a poor outcome were related to pulmonary arterial hypertension associated with connective tissue disease (CDT-PAH), New York Heart Association (NYHA) functional class, 6-min walk test and right atrial pressure. On multivariate analysis only CDT-PAH and NYHA functional class remained independently associated with poor survival. CONCLUSIONS: PA dilatation is commonly detected in severe PH patients and is not associated with an increased risk of death.

Prognostic factors in severe pulmonary hypertension patients who need parenteral prostanoid therapy: the impact of late referral.

BACKGROUND: Oral drugs have made the treatment of pulmonary hypertension (PH) feasible in non-expert centers, which could delay patient access to prostanoid therapy. METHODS: Fifty-seven consecutive patients with precapillary PH received a prostanoid in our center. Data at prostanoid initiation included modality of center referral, medical history, New York Heart Association [NYHA] class, exercise capacity, echocardiographic parameters, and hemodynamics. RESULTS: Overall survival at 1, 2, and 3 years was 85%, 69%, 55%, respectively. Non-survivors had worse NYHA class III/IV (17/12) than survivors (27/1; p < 0.01) and exercise capacity on 6-minute-walk distance (254 ± 114 vs 354 ± 91 meters; p < 0.01). Non-survivors were more frequently referred on oral therapy (83% vs 36%; p < 0.01) and had a higher rate of urgent prostanoid treatment (69% vs 17%; p < 0.0001). Multivariate analysis (hazard ratio [95% confidence interval]) found the independent prognostic factors were urgent prostanoid therapy (2.0 [1.1-3.9]) and NYHA class (3.5 [1.5-8.2]). Survivors had a significant response to prostanoid, improving NYHA class from 2.8 ± 0.4 to 2.3 ± 0.5 (p = 0.002), 6-minute walk distance from 354 ± 91 to 426 ± 82 meters (p = 0.0001), and pulmonary hemodynamics (pulmonary artery pressure from 56 ± 13 to 44 ± 18 mm Hg [p < 0.05]; cardiac index from 2.0 ± 1.2 to 3.1 ± 1.2 liters/min/m(2) [p = 0.002], and pulmonary vascular resistance from 17 ± 10 to 8 ± 6 WU [p = 0.001]). CONCLUSIONS: Referral of patients on oral treatment to a tertiary PH center is delayed and significantly affects prognosis.