A retrospective review of charts, TTCE, and imaging was conducted. One hundred fifty-five consecutive newly referred patients to the Toronto HHT Center (adult clinic) were screened with TTCE between June 2002 and September 2004. All patients with positive TTCE results were included in this study and underwent thoracic CT scanning. This was the routine screening protocol followed for all patients referred to the HHT Center from 2002 to 2004. For each patient, the TTCE was reviewed for the presence of a patent foramen ovale (PFO). The Toronto HHT Center at St. Michael’s Hospital and University of Toronto is a specialized clinic at a tertiary care, university-affiliated, teaching hospital that encompasses a national referral base from within Canada. The study protocol was approved by the hospital research ethics board.
Standard TTCE was performed on all patients as previously described. This procedure was implemented as our laboratory procedure several years prior, and all laboratory technicians and attending echocardiographers have been trained to follow this standard procedure. In each case, an IV line with saline solution lock was placed in the patient’s forearm (typically 19 gauge, 2.5 cm). A three-way stopcock was attached, and two 10-mL syringes were attached to the other two ports. One 10-mL syringe was empty, with air excluded, and the other was filled with saline solution. The agitated saline solution contrast was obtained by flushing the saline solution from one syringe to the other. The patient was positioned in the left lateral decubitus position, and 10 mL of agitated saline solution (bubbles) were injected by hand while echocardiographic images were obtained simultaneously in the apical four-chamber view. If the decubitus TTCE result was negative, the study was repeated in the sitting position in an attempt to increase the sensitivity for detection of shunting due to lower lobe PAVMs.
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TTCE results were defined as positive if saline solution contrast was observed in the left atrium after injection. All TTCEs were scored by an experienced echocardiographer (C.M.C.), who was blinded to the CT results, for delay (number of cardiac cycles before appearance of bubbles in the left atrium, after their first appearance in the right atrium) and graded for intensity of opacification. Relative opacification was graded as either 1 (minimal left ventricular opacification), 2 (moderate), 3 (extensive without outlining the endocardium), or 4 (extensive with endocardial definition), according the proposed grading system described by Barzilai et al. TTCE grade was also reported at the time of TTCE by an attending echocardiographer (one of five echocardiographers), and these results were for compared with the study TTCE grade by C.M.C., for calculation of interobserver agreement. Examples of the appearance of left ventricular opacification for each TTCE grade are illustrated in Figure 1.
CT of Thorax
All patients with positive TTCE results underwent thoracic CT. Twelve patients had previously undergone scanning at their referring institutions. The remaining 92 patients underwent imaging with a helical scanner (LightSpeed QXi; General Electric; Milwaukee, WI) at our center using the following protocol: noncontrast-enhanced helical acquisitions during a single breath-hold in the supine position, with a collimation of 7.5 mm, table speed of 11.25 cm/s with no overlap, 120 kilovolt peak, current of 200 mA, and exposure time of 0.8 s per rotation. Images were reconstructed at a slice thickness of 3.75 mm with 1.8 mm of overlap in both standard soft-tissue and lung algorithms. All CTs were reviewed by an experienced radiologist, blinded to the TTCE results, and scored as positive, negative, or indeterminate for PAVMs.
A Pearson x2 test for association was performed (SAS v8.2; SAS Institute; Cary, NC) in order to determine if there was a significant association between TTCE grade and presence of PAVMs on CT scan with a significance level of a = 0.05. The PPV of TTCE was calculated using CT as the reference standard. The PPV represents the percentage of the sample with a given TTCE grade that was determined to have PAVMs on CT. A multivariate logistic regression analysis with was also performed in SAS v8.2 to determine if there was a significant association between presence of PAVM and TTCE grade and/or number of cardiac cycles before bubble appearance (the level of significance utilized for this analysis was a = 0.05).
Figure 1. Appearance of left ventricular opacification following injection of agitated saline solution for each TTCE grade. Top left, A: grade 1, minimal left ventricular opacification; top right, B: grade 2, moderate left ventricular opacification; bottom left, C: grade 3, extensive left ventricular opacification without outlining the endocardium; and bottom right, D: grade 4, extensive left ventricular opacification with endocardial definition. RV = right ventricle; RA = right atrium; LV = left ventricle; LA = left atrium.