D. M. Courtney

Prospective multicenter evaluation of the pulmonary embolism rule-out criteria

Summary.  Backgound: Over‐investigation of low‐risk patients with suspected pulmonary embolism (PE) represents a growing problem. The combination of gestalt estimate of low suspicion for PE, together with the PE rule‐out criteria [PERC(−): age < 50 years, pulse < 100 beats min−1, SaO2 ≥ 95%, no hemoptysis, no estrogen use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative testing for PE. We hypothesized that low suspicion and PERC(−) would predict a post‐test probability of VTE(+) or death below 2.0%. Methods: We enrolled outpatients with suspected PE in 13 emergency departments. Clinicians completed a 72‐field, web‐based data form at the time of test order. Low suspicion required a gestalt pretest probability estimate of <15%. The main outcome was the composite of image‐proven VTE(+) or death from any cause within 45 days. Results: We enrolled 8138 patients, 85% of whom had a chief complaint of either dyspnea or chest pain. Clinicians reported a low suspicion for PE, together with PERC(−), in 1666 patients (20%). At initial testing and within 45 days, 561 patients (6.9%, 95% confidence interval 6.5–7.6) were VTE(+), and 56 others died. Among the low suspicion and PERC(−) patients, 15 were VTE(+) and one other patient died, yielding a false‐negative rate of 16/1666 (1.0%, 0.6–1.6%). As a diagnostic test, low suspicion and PERC(−) had a sensitivity of 97.4% (95.8–98.5%) and a specificity of 21.9% (21.0–22.9%). Conclusions: The combination of gestalt estimate of low suspicion for PE and PERC(−) reduces the probability of VTE to below 2% in about 20% of outpatients with suspected PE.

The impact of early standard therapy on dyspnoea in patients with acute heart failure: the URGENT-dyspnoea study

AIMS The vast majority of acute heart failure (AHF) trials to date have targeted dyspnoea. However, they enrolled patients relatively late and did not standardize their methods of dyspnoea measurement. URGENT Dyspnoea was designed to determine changes in dyspnoea in response to initial, standard therapy in patients presenting with AHF using a standardized approach. METHODS AND RESULTS URGENT Dyspnoea was an international, multi-centre, observational cohort study of AHF patients managed conventionally and enrolled within 1 h of first hospital medical evaluation. Patient-assessed dyspnoea was recorded in the sitting position at baseline and at 6 hours by Likert and visual analog scales. Less symptomatic patients were placed supine to determine whether this provoked worsening dyspnoea (orthopnoea). Of the 524 patients with AHF, the mean age was 68 years, 43% were women, and 83% received intravenous diuretics. On a 5-point Likert scale, dyspnoea improvement was reported by 76% of patients after 6 h of standard therapy. Supine positioning (orthopnoea test) led to worse dyspnoea in 47% of patients compared to sitting upright. CONCLUSION When sitting upright, dyspnoea in the sitting position improves rapidly and substantially in patients with AHF after administration of conventional therapy, mainly intra-venous diuretics. However, many patients remain orthopnoeic. Improving the methodology of clinical trials in AHF by standardizing the conditions under which dyspnoea is assessed could enhance their ability to identify effective treatments. Relief of orthopnoea is clinically valuable and may represent a useful goal for clinical trials.

Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter double‐blind, placebo‐controlled randomized trial

Acute pulmonary embolism (PE) can worsen quality of life due to persistent dyspnea or exercise intolerance.

D‐dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography

Summary.  Background:  Increasing the threshold to define a positive D‐dimer could reduce unnecessary computed tomographic pulmonary angiography (CTPA) for a suspected pulmonary embolism (PE) but might increase rates of a missed PE and missed pneumonia, the most common non‐thromboembolic diagnosis seen on CTPA.

Prospective multicenter assessment of interobserver agreement for radiologist interpretation of multidetector computerized tomographic angiography for pulmonary embolism

Summary.  Background: Emergency physicians rely on the interpretation of radiologists to diagnose and exclude pulmonary embolism (PE) on the basis of computerized tomographic pulmonary angiography (CTPA). Few data exist regarding the interobserver reliability of this endpoint. Objective: To quantify the degree of agreement in CTPA interpretation between four academic hospitals and an independent reference reading (IRR) laboratory. Methods: Hospitalized and emergency department patients who had one predefined symptom and sign of PE and underwent 64‐slice CTPA were enrolled from four academic hospitals. CTPA results as interpreted by board‐certified radiologists from the hospitals were compared against those from the IRR laboratory. CTPAs were read as indeterminate, PE− or PE+, and percentage obstruction was computed by the IRR laboratory, using a published method. Agreement was calculated with weighted Cohen’s kappa. Results: We enrolled 492 subjects (63% female, age 54 ± 1 years, and 16.7% PE+ at the site hospitals). Overall agreement was 429/492 (87.2%; 95% confidence interval 83.9–90.0). We observed 13 cases (2.6%) of complete discordance, where one reading was PE+ and the other reading was PE−. Weighted agreement was 92.3%, with kappa = 0.75. The median percentage obstruction for all patients was 9% (25th–75th percentile interquartile range: 5% to − 30%). For CTPAs interpreted at the site hospitals as PE− or indeterminate but read as PE+ by the IRR laboratory, the median of percentage obstruction was 6% (4–7%). Conclusion: We found in this sample a good level of agreement, with a weighted kappa of 0.75, but with 2.6% of patients having total discordance. Overall, a large proportion of clots were distal or minimally occlusive clots.

European and American suspected and confirmed pulmonary embolism populations: comparison and analysis

Summary.  Background: If the prevalence of pulmonary embolism (PE) differs significantly between the US and Europe, this observation could reduce the generalizability of diagnostic protocols for PE derived in either location.Objective: To determine possible causes and potential clinical consequences of these PE prevalence differences.Methods: Secondary analysis of three prospectively collected multicenter samples (two French and one from the US) including 3174 European and 7940 American PE‐suspected patients in Emergency departments (ED) (117 for Europe and 12 for US). Comparison of clinical features, resource use and outcomes of European‐ and US‐suspected PE populations in ED.Results: European patients evaluated for PE were significantly older and had a higher clinical pretest probability (CPP) for PE. The final PE prevalence was significantly higher in Europe, in the overall sample (26.5% vs. 7.6%) and in each level of CPP. Suspected European patients categorized as low CPP had a higher posttest probability than US low CPP patients. Suspected US patients categorized as high CPP had a much lower posttest probability of PE than in Europe. The mean number of tests performed for one PE diagnosis was lower in Europe (7.4 vs. 21.6). Among patients diagnosed with PE, European patients had a higher mean severity of illness score and a higher PE‐mortality rate (3.4% vs. 0.7%).Conclusions: Among patients suspected of a PE and those ultimately diagnosed with a PE, European patients had higher acuity, a higher pretest probability and worse outcome than US patients. The present study underscores the importance of disease prevalence for pretest probability scoring approaches and for significance interpretation of imaging tests.

More on: Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism [11] (multiple letters)

See also Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. J Thromb Haemost 2004; 2: 1247–56; Le Gal G, Bounameaux H. Diagnosing pulmonary embolism: running after the decreasing prevalence of cases among suspected patients. J Thromb Haemost 2004; 2: 1244–60; Kline JA, Mitchell AM, Kabrhel C, Richman PB, Courtney DM. More on: Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism. This issue, pp 190–1.

Randomized Trial of Tenecteplase or Placebo with Low Molecular Weight Heparin for Acute Submassive Pulmonary Embolism: Assessment of Patient-Oriented Cardiopulmonary Outcomes at Three Months

Acute submassive pulmonary embolism (PE) with right ventricular (RV) injury and/or concomitant deep venous thrombosis can cause persistent symptoms that degrade quality of life. We tested the hypothesis that intravenous tenecteplase would improve the probability of a favorable outcome at three

Severe pulmonary embolism decreases plasma l-arginine

To the Editor: Measurements from humans and animal models with pulmonary embolism (PE) have demonstrated increases in multiple vasoconstrictive molecules, including prostaglandins, platelet-activating factor and leukotrienes [1]. Nitric oxide (NO), produced tonically by vascular endothelial nitric oxide synthase (eNOS), plays a pivotal role in maintaining a normal pulmonary vascular resistance under these conditions [2]. These facts underlie the construct hypothesis that in different subjects, PE can obstruct the same degree of pulmonary vasculature but manifest widely different pulmonary arterial resistances. Preliminary evidence from animal models and humans suggests that acute PE is associated with intravascular haemolysis, related to the severity of PE [3–8]. Intravascular haemolysis liberates haemoglobin and diffusible haem, both of which directly bind NO. Ruptured erythrocytes also release large amounts of the enzyme arginase-1, which cleaves the eNOS substrate l-arginine, producing urea and l-ornithine. We hypothesised that patients with acute PE that causes significant tricuspid regurgitation (TR) will have acutely increased plasma concentrations of arginase-1, decreased l-arginine and increased asymmetric dimethylarginine (aDMA) compared with patients who have mild PE without TR as well as patients without PE. This was a secondary analysis of a four-centre prospective study of diagnostic accuracy conducted in patients with suspected PE (www.clinicaltrials.gov identifier NCT00368836) [9]. The enrolment and diagnostic criteria have been described previously [9]. Acute PE was considered present if two independent board-certified radiologists interpreted a filling defect consistent with acute PE on computed tomographic pulmonary angiography. Echocardiography was performed using techniques as previously described, …

Temperature modulation with an esophageal heat transfer device- a pediatric swine model study

BackgroundAn increasing number of conditions appear to benefit from control and modulation of temperature, but available techniques to control temperature often have limitations, particularly in smaller patients with high surface to mass ratios. We aimed to evaluate a new method of temperature modulation with an esophageal heat transfer device in a pediatric swine model, hypothesizing that clinically significant modulation in temperature (both increases and decreases of more than 1°C) would be possible.MethodsThree female Yorkshire swine averaging 23 kg were anesthetized with inhalational isoflurane prior to placement of the esophageal device, which was powered by a commercially available heat exchanger. Swine temperature was measured rectally and cooling and warming were performed by selecting the appropriate external heat exchanger mode. Temperature was recorded over time in order to calculate rates of temperature change. Histopathology of esophageal tissue was performed after study completion.ResultsAverage swine baseline temperature was 38.3°C. Swine #1 exhibited a cooling rate of 3.5°C/hr; however, passive cooling may have contributed to this rate. External warming blankets maintained thermal equilibrium in swine #2 and #3, demonstrating maximum temperature decrease of 1.7°C/hr. Warming rates averaged 0.29°C/hr. Histopathologic analysis of esophageal tissue showed no adverse effects.ConclusionsAn esophageal heat transfer device successfully modulated the temperature in a pediatric swine model. This approach to temperature modulation may offer a useful new modality to control temperature in conditions warranting temperature management (such as maintenance of normothermia, induction of hypothermia, fever control, or malignant hyperthermia).