Prognostic Value of Right Ventricular Dysfunction Markers for Serious Adverse Events in Acute Normotensive Pulmonary Embolism.

BACKGROUND: Right ventricular dysfunction (RVD) in pulmonary embolism (PE) has been associated with increased morbidity. Tools for RVD identification are not well defined. The prognostic value of RVD markers to predict serious adverse events (SAE) during hospitalization is unclear. OBJECTIVE: Prospectively compare the incidence of SAE in normotensive emergency department patients with PE based upon RVD by goal-directed echocardiography (GDE), cardiac biomarkers, and right-to-left ventricle ratio by computed tomography (CT). Simplified Pulmonary Embolism Severity Index (sPESI) was calculated. Deaths and readmissions within 30 days were recorded. METHODS: Consecutive normotensive PE patients underwent GDE focused on RVD (RV enlargement, hypokinesis, or septal bowing), serum troponin, and brain natriuretic peptide (BNP), and evaluation of the CT ventricle ratio. In-hospital SAE and complications within 30 days were recorded. RESULTS: We enrolled 123 normotensive PE patients (median age 59 years, 49% female). Twenty-six of 123 (26%) patients had one or more SAE. RVD was detected in 26% by GDE, in 39% by biomarkers, and in 38% with CT. In-hospital SAE included one death, six respiratory interventions, six dysrhythmias, three major bleeding episodes, and 21 hypotension episodes. Forty-one percent of patients RVD positive by GDE had SAE, compared to the 18% RVD negative by GDE. Odds ratios for GDE, CT, BNP, troponin, and sPESI for SAE were 3.2 (95% confidence interval [CI] 1.2-8.5), 2.0 (95% CI 0.8-5.1), 3.3 (95% CI 1.3-8.6), 4.2 (95% CI 1.4-13.5), and 2.9 (95% CI 1.1-8.3), respectively. Five patients had non-PE-related deaths within 30 days. CONCLUSION: The incidence of SAE within days of PE was significant in our cohort. Those with RVD had an increased risk of nonmortality SAE.

Diagnostic Accuracy of Right Ventricular Dysfunction Markers in Normotensive Emergency Department Patients With Acute Pulmonary Embolism.

STUDY OBJECTIVE: We determine the diagnostic accuracy of goal-directed echocardiography, cardiac biomarkers, and computed tomography (CT) in early identification of severe right ventricular dysfunction in normotensive emergency department patients with pulmonary embolism compared with comprehensive echocardiography. METHODS: This was a prospective observational study of consecutive normotensive patients with confirmed pulmonary embolism. Investigators, blinded to clot burden and biomarkers, performed qualitative goal-directed echocardiography for right ventricular dysfunction: right ventricular enlargement (diameter greater than or equal to that of the left ventricle), severe right ventricular systolic dysfunction, and septal bowing. Brain natriuretic peptide and troponin cutoffs of greater than or equal to 90 pg/mL and greater than or equal to 0.07 ng/mL and CT right ventricular:left ventricular diameter ratio greater than or equal to 1.0 were also compared with comprehensive echocardiography. RESULTS: One hundred sixteen normotensive pulmonary embolism patients (111 confirmed by CT, 5 by ventilation-perfusion scan) were enrolled. Twenty-six of 116 patients (22%) had right ventricular dysfunction on comprehensive echocardiography. Goal-directed echocardiography had a sensitivity of 100% (95% confidence interval [CI] 87% to 100%), specificity of 99% (95% CI 94% to 100%), positive likelihood ratio (+LR) of 90.0 (95% CI 16.3 to 499.8), and negative likelihood ratio (-LR) of 0 (95% CI 0 to 0.13). Brain natriuretic peptide had a sensitivity of 88% (95% CI 70% to 98%), specificity of 68% (95% CI 57% to 78%), +LR of 2.8 (95% CI 2.0 to 3.9), and -LR of 0.17 (95% CI 0.06 to 0.43). Troponin had a sensitivity of 62% (95% CI 41% to 80%), specificity of 93% (95% CI 86% to 98%), +LR of 9.2 (95% CI 4.1 to 20.9), and -LR of 0.41 (95% CI 0.24 to 0.62). CT had a sensitivity of 91% (95% CI 72% to 99%), specificity of 79% (95% CI 69% to 87%), +LR of 4.3 (95% CI 2.8 to 6.7), and -LR of 0.11 (95% CI 0.03 to 0.34). CONCLUSION: Goal-directed echocardiography was highly accurate for early severe right ventricular dysfunction identification and pulmonary embolism risk-stratification. Brain natriuretic peptide was sensitive but less specific, whereas troponin had lower sensitivity but higher specificity. CT had good sensitivity and moderate specificity.

Interobserver and Intraobserver Agreement on Qualitative Assessments of Right Ventricular Dysfunction With Echocardiography in Patients With Pulmonary Embolism.

OBJECTIVES: To evaluate observer agreement using qualitative goal-directed echocardiographic criteria for right ventricular (RV) dysfunction prognostication in submassive pulmonary embolism (PE). METHODS: Two emergency physicians and 2 cardiologists independently reviewed 31 packets of goal-directed echocardiographic video clips consisting of at least 3 windows obtained by emergency physicians from normotensive patients with PE. Nine packets were repeated to assess for intraobserver agreement. Right ventricular dysfunction criteria on goal-directed echocardiography were as follows: RV enlargement was present, with a right-to-left ventricular basal diameter ratio of 1.0 or higher and blunting of the apex of the RV in 2 or more different windows; RV systolic dysfunction was present if the tricuspid annulus moved toward the apex 10 mm or less and there was RV free wall hypokinesis; and septal deviation was present with any flattening or deviation of the ventricular septum toward the left ventricle. RESULTS: Among the 4 participants, there was 83.9% agreement on the presence or absence of RV enlargement (κ = 0.84), 74.2% agreement on the presence or absence of RV systolic dysfunction (κ = 0.69), and 71.0% agreement on the presence or absence of septal deviation (κ = 0.59). Intraobserver agreement was 100% for each RV dysfunction variable for each observer (κ = 1.0). CONCLUSIONS: Agreement was substantial for both severe RV enlargement and RV systolic dysfunction and moderate for septal deviation. Right ventricular dysfunction assessment with qualitative goal-directed echocardiographic criteria is reproducible for PE risk stratification.

Immune challenge and satiety-related activation of both distinct and overlapping neuronal populations in the brainstem indicate parallel pathways for viscerosensory signaling.

Caudal brainstem viscerosensory nuclei convey information about the body's internal state to forebrain regions implicated in feeding behavior and responses to immune challenge, and may modulate ingestive behavior following immune activation. Illness-induced appetite loss might be attributed to accentuated "satiety" pathways, activation of a distinct "danger channel" separate from satiety pathways, or both. To evaluate neural substrates that could mediate the effects of illness on ingestive behavior, we analyzed the pattern and phenotypes of medullary neurons responsive to consumption of a preferred food, sweetened milk, and to intraperitoneal lipopolysaccharide challenge that reduced sweetened milk intake. Brainstem sections were stained for c-Fos, dopamine beta-hydroxylase, phenylethanolamine-N-methyltransferase, and glucagon-like peptide-1 (GLP-1) immunoreactivity. Sweetened milk intake activated many neurons throughout the nucleus of the solitary tract (NTS), including A2 noradrenergic neurons in the caudal half of the NTS. LPS challenge activated a similar population of neurons in the NTS, in addition to rostral C2 adrenergic and mid-level A2 noradrenergic neurons in the NTS, many C1 and A1 neurons in the ventrolateral medulla, and in GLP-1 neurons in the dorsal medullary reticular nucleus. Increased numbers of activated GLP-1 neurons in the NTS were only associated with sweetened milk ingestion. Evidence for parallel processing was reflected in the parabrachial nucleus, where sweetened milk intake resulted in activation of the inner external lateral, ventrolateral and central medial portions, whereas LPS challenge induced c-Fos expression in the outer external lateral portions. Thus, signals generated in response to potentially dangerous physiological conditions seem to be propagated via specific populations of catecholaminergic neurons in the NTS and VLM, and likely include a pathway through the external lateral PBN. The data indicate that immune challenge engages multiple ascending neural pathways including both a distinct catecholaminergic "danger" pathway, and a possibly multimodal pathway derived from the NTS.