Utility of the Physical Examination in Detecting Pulmonary Hypertension. A Mixed Methods Study

<div><p>Introduction</p><p>Patients with pulmonary hypertension (PH) often present with a variety of physical findings reflecting a volume or pressure overloaded right ventricle (RV). However, there is no consensus regarding the diagnostic utility of the physical examination in PH.</p><p>Methods</p><p>We conducted a systematic review of publications that evaluated the clinical examination and diagnosis of PH using MEDLINE (1946–2013) and EMBASE (1947–2013). We also prospectively evaluated the diagnostic utility of the physical examination findings. Patients who underwent right cardiac catheterization for any reason were recruited. After informed consent, participants were examined by 6 physicians (3 “specialists” and 3 “generalists”) who were unaware of the results of the patient's hemodynamics. Each examiner independently assessed patients for the presence of a RV lift, loud P2, jugular venous distension (JVD), tricuspid insufficiency murmur and right-sided 4th heart sound at rest and during a slow inspiration. A global rating (scale of 1–5) of the likelihood that the patient had pulmonary hypertension was provided by each examiner.</p><p>Results</p><p>31 articles that assessed the physical examination in PH were included in the final analysis. There was heterogeneity amongst the studies and many did not include control data. The sign most associated with PH in the literature was a loud pulmonic component of the second heart sound (P2). In our prospective study physical examination was performed on 52 subjects (25 met criteria for PH; mPAP ≥25 mmHg). The physical sign with the highest likelihood ratio (LR) was a loud P2 on inspiration with a LR +ve 1.9, 95% CrI [1.2, 3.1] when data from all examiners was analyzed together. Results from the specialist examiners had higher diagnostic utility; a loud P2 on inspiration was associated with a positive LR of 3.2, 95% CrI [1.5, 6.2] and a right sided S4 on inspiration had a LR +ve 4.7, 95% CI [1.0, 15.6]. No aspect of the physical exam, could consistently rule out PH (negative LRs 0.7–1.3).</p><p>Conclusions</p><p>The presence of a loud P2 or audible right-sided 4th heart sound are associated with PH. However the physical examination is unreliable for determining the presence of PH.</p></div

2×2 contingency tables and derived test characteristics from relevant studies.

<p>2×2 contingency tables and derived test characteristics from relevant studies.</p

Summary of literature search and identification of publications.

<p>Summary of literature search and identification of publications.</p

ROC curves for each physician's estimate of the probability that the patient either did have or did not have PH.

<p>ROC curves for each physician's estimate of the probability that the patient either did have or did not have PH.</p

Summary of test characteristics for each component of the physical examination that was performed, with comparisons between specialists and generalists.

<p>Summary of test characteristics for each component of the physical examination that was performed, with comparisons between specialists and generalists.</p

Baseline characteristics of study population.

<p>Baseline characteristics of study population.</p

Whole Genome Sequence Typing to Investigate the <em>Apophysomyces</em> Outbreak following a Tornado in Joplin, Missouri, 2011

<div><p>Case reports of <em>Apophysomyces</em> spp. in immunocompetent hosts have been a result of traumatic deep implantation of <em>Apophysomyces</em> spp. spore-contaminated soil or debris. On May 22, 2011 a tornado occurred in Joplin, MO, leaving 13 tornado victims with <em>Apophysomyces trapeziformis</em> infections as a result of lacerations from airborne material. We used whole genome sequence typing (WGST) for high-resolution phylogenetic SNP analysis of 17 outbreak <em>Apophysomyces</em> isolates and five additional temporally and spatially diverse <em>Apophysomyces</em> control isolates (three <em>A. trapeziformis</em> and two <em>A. variabilis</em> isolates). Whole genome SNP phylogenetic analysis revealed three clusters of genotypically related or identical <em>A. trapeziformis</em> isolates and multiple distinct isolates among the Joplin group; this indicated multiple genotypes from a single or multiple sources. Though no linkage between genotype and location of exposure was observed, WGST analysis determined that the Joplin isolates were more closely related to each other than to the control isolates, suggesting local population structure. Additionally, species delineation based on WGST demonstrated the need to reassess currently accepted taxonomic classifications of phylogenetic species within the genus <em>Apophysomyces</em>.</p> </div

WGST phylogeny of outbreak and background Apophysomyces isolates.

<p>A single maximum parsimony tree was reconstructed using ∼28K SNPs from 22 whole genome sequences, resulting in a CI of 0.62. The tree was rooted with Apo-7449 (A. variabilis). The root was derived from an expanded phylogenetic analyses that included a distant outgroup, which enabled the identification of the most basal member of the samples in the dataset described in this figure (data not shown). Genomes are labeled with a Strain ID # (APO-XXXX) and a Cluster ID #-Letter (CX-A). Clusters of identical and nearly identical genome SNP profiles are also labeled. Branch lengths represent genetic distance based on the number of SNP differences; bar represents 1000 SNPs. Tree constructed using MEGA5.</p

List of strains used in study, by isolation site, species and geographic location, along with sequencing coverage results.

<p>NA = Not Applicable; N/A = Not Available; C = Cluster;</p>*<p>indicates multiple isolates from the same patient.</p

<i>De novo</i> assembled reference statistics for Strain Apo-097.

<p><i>De novo</i> assembled reference statistics for Strain Apo-097.</p