David S. Rubenson

Is Pocket Mobile Echocardiography the Next-Generation Stethoscope? A Cross-sectional Comparison of Rapidly Acquired Images With Standard Transthoracic Echocardiography

BACKGROUND A pocket mobile echocardiography (PME) device is commercially available for clinical use, but public data documenting its accuracy compared with standard transthoracic echocardiography (TTE) are not available. OBJECTIVE To compare the accuracy of rapidly acquired PME images with those acquired by standard TTE. DESIGN Cross-sectional study. At the time of referral for TTE, ultrasonographers acquired PME images first in 5 minutes or less. Ultrasonographers were not blinded to the clinical indication for imaging or to the PME image results when obtaining standard TTE images. Two experienced echocardiographers and 2 cardiology fellows who were blinded to the indication for the study and TTE results but not to the device source interpreted the PME images. SETTING Scripps Clinic Torrey Pines and Scripps Green Hospital, La Jolla, California. PATIENTS Convenience sample of 97 patients consecutively referred for echocardiography. MEASUREMENTS Visualizability and accuracy (the sum of proportions of true-positive and true-negative readings and observer variability) for ejection fraction, wall-motion abnormalities, left ventricular end-diastolic dimension, inferior vena cava size, aortic and mitral valve pathology, and pericardial effusion. RESULTS Physician-readers could visualize some but not all echocardiographic measurements obtained with the PME device in every patient (highest proportions were for ejection fraction and left ventricular end-diastolic dimension [95% each]; the lowest proportion was for inferior vena cava size [75%]). Accuracy also varied by measurement (aortic valve was 96% [highest] and inferior vena cava size was 78% [lowest]) and decreased when nonvisualizability was accounted for (aortic valve was 91% and inferior vena cava size was 58%). Observer agreement was fair to moderate for some measurements among less-experienced readers. LIMITATION The study was conducted at a single setting, there was no formal estimate of accuracy given the small convenience sample of patients, and few abnormal echocardiographic measurements occurred. CONCLUSION The rapid acquisition of images by skilled ultrasonographers who use PME yields accurate assessments of ejection fraction and some but not all cardiac structures in many patients. Further testing of the device in larger patient cohorts with diverse cardiac abnormalities and with untrained clinicians obtaining and interpreting images is required before wide dissemination of its use can be recommended. PRIMARY FUNDING SOURCE National Institutes of Health.

The use of echocardiography in diagnosing culture-negative endocarditis.

We reviewed M-mode and two-dimensional echocardiographic findings in 11 patients with abacteremic endocarditis to study the application of echocardiography in this setting. All patients had negative blood cultures but underwent surgery that confirmed the presence of active infective endocarditis. The infection involved native valves in five patients and prosthetic valves in six patients. Valvular masses were identified in eight patients. The other three patients, who had prosthetic aortic valves, had diastolic mitral valve vibration characteristic of aortic regurgitation. One of these three also showed dehiscence of the prosthesis.Three patients had poorly defined clinical illnesses and echocardiography was a prime element in the diagnosis because valvular masses were identified. The operation was facilitated by knowledge of the mass indicated by echocardiography in these eight cases. Also, the surgical approach was affected by knowledge of dehiscence and perivalvular abscess formation in two cases each.

The Biomedical Resource Ontology (BRO) to enable resource discovery in clinical and translational research

The biomedical research community relies on a diverse set of resources, both within their own institutions and at other research centers. In addition, an increasing number of shared electronic resources have been developed. Without effective means to locate and query these resources, it is challenging, if not impossible, for investigators to be aware of the myriad resources available, or to effectively perform resource discovery when the need arises. In this paper, we describe the development and use of the Biomedical Resource Ontology (BRO) to enable semantic annotation and discovery of biomedical resources. We also describe the Resource Discovery System (RDS) which is a federated, inter-institutional pilot project that uses the BRO to facilitate resource discovery on the Internet. Through the RDS framework and its associated Biositemaps infrastructure, the BRO facilitates semantic search and discovery of biomedical resources, breaking down barriers and streamlining scientific research that will improve human health.

Pulmonary Hypertension Developing after Alglucerase Therapy in Two Patients with Type 1 Gaucher Disease Complicated by the Hepatopulmonary Syndrome

Gaucher disease is an autosomal-recessive disorder that is caused by a deficiency of the enzyme glucocerebrosidase and results in accumulation of an insoluble glucocerebroside in macrophages. Type 1 (chronic non-neuropathic or adult) Gaucher disease is usually characterized by hepatosplenomegaly, thrombocytopenia, and skeletal complications (including bone pain, osteonecrosis, and pathologic fractures) [1, 2]. With the exception of splenectomy, few options were available for treating this disorder until enzyme replacement therapy with alglucerase became available [3]. Pulmonary involvement has long been recognized as a rare complication of Gaucher disease. Pulmonary hypertension, severe hypoxemia, and infiltration of the lungs with Gaucher cells have been described in case reports and small case series. We report the results of therapy with alglucerase in two patients with severe hypoxemia and intrapulmonary vascular dilatations that appeared on agitated saline contrast echocardiography [4]. Case Reports Patient 1 A previous article [3] and two case series [2, 5] described patient 1. We first evaluated this patient in 1984 when she was 23 years of age. Progressive dyspnea began when the patient was about 20 years of age; by 1990, she would become breathless after walking a few steps. The patient was small (height, 159 cm; weight, 40 kg) and deeply cyanotic with clubbing of the fingers and a large liver. Bronchoalveolar lavage fluid and transbronchial lung biopsy specimens showed no Gaucher cells. Results of studies of lung function are shown in Table 1. Table 1. Pulmonary Function, Liver Volume, and Pulmonary Hemodynamics Therapy with alglucerase began in January 1990. The patient initially received alglucerase, 30 U/kg of body weight per month at 3.3 U/kg twice weekly. After 7 months, the dose was reduced to 2.3 U/kg twice weekly. After 33 months, the patient no longer needed administration of oxygen and was working full-time, but chest radiography showed enlarged pulmonary arteries (Figure 1, left and middle). Because the patient had no tricuspid regurgitation, we could not estimate pulmonary artery pressure from the echocardiogram [7]. After 6 years of therapy, no further progression of pulmonary hypertension has been seen on physical examination or chest radiography. Figure 1. Left. Middle. arrows Right. Patient 2 Patient 2 was 41 years of age at his first evaluation. He had had splenectomy at 13 years of age but remained otherwise asymptomatic for Gaucher disease until 38 years of age, at which time vertebral osteomyelitis, hypoxemia, and a cerebral abscess developed. Thoracotomy with ligation of a suspected arteriovenous malformation did not alleviate hypoxemia. Examination of open lung biopsy specimens showed no Gaucher cells in the lungs. However, medial hypertrophy of small muscular arteries and arterioles was seen (Figure 1, right), and some large pulmonary arteries showed intimal proliferation of the type occurring in the early stages of pulmonary hypertension. Patient 2 was thin and muscular (height, 178 cm; weight, 68.5 kg) and had moderate finger clubbing and a markedly enlarged liver. Results of studies of lung function are shown in Table 1. Therapy with alglucerase (120 U/kg per month for 7 months as part of a dose-ranging protocol, followed by 30 U/kg per month) was started in September 1991. After 20 months of treatment (total dose, 1230 U/kg), the patient had no symptoms and was following a vigorous exercise program. His chest radiograph showed an increase in the size of the main pulmonary artery, and progressive pulmonary hypertension was seen after catheterization of the right side of the heart. Discussion We describe two patients with type 1 Gaucher disease who presented with hepatomegaly, severe hypoxemia, and intrapulmonary vascular dilatations. Therapy with alglucerase decreased the size of the liver and almost completely eliminated the hypoxemia. However, the patients then developed pulmonary hypertension. Until recently, pulmonary involvement has been considered to be a rare complication of Gaucher disease. When lung tissue is available, examination of the tissue frequently shows that the lungs are infiltrated with Gaucher cells [8, 9]. Pulmonary hypertension has occasionally been reported with Gaucher disease; in some cases, the pulmonary capillaries were obstructed by Gaucher cells [9, 10]. In one patient, however, few Gaucher cells were found in the lungs, and the pathologic findings resembled those of primary pulmonary hypertension [11]. More recent studies have shown pulmonary involvement in Gaucher disease. In a large autopsy series [12] that included patients with type 2 and type 3 Gaucher disease, more than one third of the cases had interstitial infiltration, plugging of the capillaries, or filling of the air spaces with Gaucher cells. Kerem and colleagues [13] found that 68% of patients in a clinic for Gaucher disease had some abnormality of lung function. Our patients had no evidence of parenchymal lung infiltration with Gaucher cells. No Gaucher cells were seen in patient 1 on examinations of transbronchial biopsy specimens of the lung or bronchoalveolar lavage fluid. Patient 2 had an open lung biopsy, and no Gaucher cells were found on examination of the specimens. No lung infiltrates were seen on the chest radiograph of either patient. The hypoxemia thus seemed to be caused by intrapulmonary vascular dilatations. The hepatopulmonary syndrome is defined as the triad of liver disease, hypoxemia, and intrapulmonary vascular dilatations [14]. Our patients had little evidence of hepatocellular dysfunction, but both had a very enlarged liver. Improvement in the hypoxemia and disappearance of the intrapulmonary vascular dilatations were presumably related to the decreased liver size seen with treatment. Severe hypoxemia has been reversed after successful liver transplantation and with medical therapy; in some cases, intrapulmonary vascular dilatations are reversible if the underlying liver disease is treated [15]. Pelini and colleagues [16] described a patient with type 1 Gaucher disease and severe hypoxemia that showed remarkable improvement after therapy with alglucerase. Although this patient may have had the hepatopulmonary syndrome, Pelini and colleagues did not test for intrapulmonary vascular dilatations. The abnormalities in the patients lung function and the time taken to respond to treatment were similar to those of our patients. It is difficult to account for the progression of pulmonary hypertension in our patients, whose response to alglucerase was otherwise favorable. Pulmonary hypertension does not seem to be a feature of the hepatopulmonary syndrome. In fact, patients with severe hypoxemia and liver disease usually have low pulmonary artery pressure and pulmonary vascular resistance [17] that tend to increase after such patients receive liver transplants [18]. Patient 2 developed pulmonary hypertension when his intrapulmonary vascular dilatation decreased. Patient 1 had moderate pulmonary hypertension after treatment, but evidence that her pulmonary artery pressure increased after therapy is somewhat unconvincing. The size of the main pulmonary artery in patient 1 definitely increased, but only one catheterization of the right side of the heart was done for confirmation. The increase in pulmonary artery pressure may be partly explained by diminished dilatation of intrapulmonary vessels in a vascular bed that was already abnormally restricted. This explanation was suggested by the appearance of the small vessels in the lung biopsy specimens of patient 2 and by the low diffusing capacity that remained diminished after therapy in both patients. Decreased intrapulmonary vascular dilatation in patient 2 cannot be the only cause of pulmonary hypertension because his pulmonary artery pressure continued to increase after hypoxemia resolved. Progressive infiltration of the lung with Gaucher cells, leading to obstruction of small pulmonary arteries, also does not seem to explain the worsening pulmonary hypertension because the severe hepatomegaly improved remarkably after alglucerase therapy. Treatment of severe hypoxemia may have allowed patient 2 to survive long enough for progressive changes in the pulmonary vascular bed to become clinically evident. We also cannot exclude the possibility that alglucerase therapy aggravates pulmonary hypertension despite its beneficial effect on other manifestations of Gaucher disease. We cannot explain the reappearance of intrapulmonary vascular dilatation in patient 2, but the dilatation must have been relatively minor because the arterial oxygen tension remained normal. Alglucerase saved the lives of these two patients and allowed them to return to a normal lifestyle. The increase in pulmonary artery pressure seen in these patients was not expected. Our first suspicion of increasing pressure was based on changes in the physical examination findings and the chest radiograph; therefore, screening does not have to be expensive. For these reasons, we believe that patients treated for Gaucher disease should be carefully examined for signs of pulmonary hypertension. Dr. Garver: Department of Radiology, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, CA 92037. Dr. Kay: Sandoz Pharmaceutical Corporation, Building 419, Room 2111, 59 Route 10, East Hanover, NJ 07936. Dr. Bloor: Department of Pathology (8320), University of California at San Diego Medical Center, 225 Dickinson Street, San Diego, CA 92103. Dr. Beutler: Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037.

Two-dimensional echocardiographic analysis of segmental left ventricular wall motion before and after coronary artery bypass surgery.

Twenty patients with coronary artery disease were studied with two-dimensional echocardiography the day before saphenous vein bypass graft surgery. Serial studies were obtained 7.4 +/- 2.5 (+/- SD) and 43.4 +/- 13.1 days postoperatively to qualitatively assess the effect of bypass surgery on regional wall motion. Changes in segmental wall motion were assessed semiquantitatively by assigning a segmental wall motion score to each of nine echocardiographically defined segments. Preoperatively, 18% of the segments moved abnormally. The mean overall segmental wall motion score did not change significantly, as shown by comparing the postoperative studies with the preoperative study. However, there was a significant worsening in the septal motion (apical and basal) and a significant improvement in posterior wall motion (apical and basal) after bypass surgery. Anterior and lateral wall motion were not significantly changed. Nonseptal segments that were normal preoperatively usually remained normal; abnormal nonseptal segments usually improved or were unchanged by surgery. The motion of septal segments, however, generally worsened postoperatively whether they were normal or abnormal preoperatively. We conclude that segmental wall motion assessed by two-dimensional echocardiography may improve after revascularization surgery, but the interventricular septum shows impaired motion. This effect of coronary artery bypass on wall motion is better demonstrated relatively late after operation than early in the postoperative course, as has been done in some previous studies.

Guidelines for the Performance of a Comprehensive Intraoperative Epiaortic Ultrasonographic Examination: Recommendations of the American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists; Endorsed by the Society of Thoracic Surgeons

The introduction of transesophageal echocardiography (TEE) in the mid-1980s extended the use of ultrasound to the intraoperative diagnosis and monitoring of cardiac and great vessel pathology. Intraoperative epicardial echocardiography has been used both as an adjunct to TEE, and as a primary diagnostic tool in patients with contraindications to TEE. The earliest applications of intraoperative epicardial imaging included the diagnosis of intracardiac pathology such as valvular heart disease. More recently, direct epivascular or epiaortic ultrasonographic (EAU) imaging of the ascending aorta and aortic arch has gained prominence as part of a multipronged intraoperative strategy to reduce atherosclerotic emboli. Although atheromatous disease of the descending aorta has been used to screen for disease in the ascending aorta, Konstadt et al. demonstrated that the interposition of the bronchus might prevent adequate visualization of the ascending aorta by TEE, making it unsatisfactory for a comprehensive atheroma evaluation. Furthermore, surgical palpation as a method of assessing atherosclerotic From the *Department of Anesthesiology, Emory University, Atlanta, GA; †Department of Anesthesiology, Duke University Medical Center, Durham, NC; ‡Department of Anesthesiology, Medical University of South Carolina, Charleston, South Carolina; §Department of Anesthesiology, College of Physicians and Surgeons, Columbia University, New York City, New York; Division of Cardiovascular Diseases, Scripps Clinic Medical Group, LA Jolla, California; ¶Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, North Carolina; and #Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. Accepted for publication January 15, 2008. Originally published in the Journal of The American Society of Echocardiography: J AM Soc Echocardiogr 2007;20:1227–35. Address correspondence and reprint requests to American Society of Echocardiography, 1500 Sunday Dr, Suite 102, Raleigh, NC 27607. Address e-mail to aprather@asecho.org. Copyright

Electrophysiologic effects of N-acetylprocainamide in human beings☆

The electrophysiologic properties of N-acetylprocainamide (NAPA) were studied in 10 patients undergoing cardiac catheterization. Each patient received two successive intravenous infusions: one loading infusion over 15 minutes and one maintenance infusion at a slower rate for 30 minutes. Eight patients received 10.5 mg/kg body weight and two received larger doses (16 and 21 mg/kg, respectively). NAPA plasma concentration was measured at 5 minute intervals from 0 to 25 minutes, and then at 15 and 30 minutes of the second infusion. Mean blood pressure and electrophysiologic data obtained by programmed stimulation were recorded before drug administration and at 15 and 30 minutes of the infusion when the concentration of NAPA was nearly constant in each patient (range 12 to 35 microgram/ml). NAPA decreased blood pressure (p less than 0.005), increased corrected Q-T interval (p less than 0.01) and increased the atrial and ventricular effective refractory periods from 267 +/- 40 to 307 +/- 41 ms (p less than 0.01) and from 278 +/- 37 to 301 +/- 32.8 ms (p less than 0.05), respectively. NAPA did not significantly change sinus cycle length or sinus nodal recovery time, conduction intervals (A-H, H-V, P-R, QRS), atrioventricular nodal functional refractory period or nodal Wenckebach cycle length. The patient receiving the largest dose experienced mild nausea when the plasma concentration was above 35 microgram/ml. These data show that the electrophysiology of NAPA in human beings is different from that reported for procainamide. At the plasma concentrations studied NAPA increases atrial and ventricular refractory periods without increasing cardiac conduction times

Echocardiography: M-Mode and Two-Dimensional Methods

We review the basic similarities and differences of currently used M-mode and two-dimensional (2D) echocardiography. Discrete categories of disease are used to show the relative strengths of M-mode and 2D methods. The format of 2D echocardiography is well suited to analyze congenital heart disease, consequences of coronary artery disease, and distortions of anatomy due to acquired heart disease. Rapid structure movement is preserved with M-mode recording, facilitating detailed analysis of motion. The vast clinical experience with M-mode echocardiography can now be augmented by 2D echocardiography, but combination of 2D and M-mode methods is optimal for understanding each type of ultrasound recording and for best serving the patient.

Safety and efficacy of extended urokinase infusion plus stent deployment for treatment of obstructed, older saphenous vein grafts.

This study was designed to determine the safety and efficacy of extended, continuous infusion of urokinase plus stent deployment to treat older saphenous vein bypass grafts obstructed by both thrombus and atheromatous material. Thirty patients with angiographic evidence of thrombus and atheromatous material obstructing older vein grafts (mean age 8.3 years) underwent the combined interventions of urokinase infusion and stent deployment. The continuous infusion of urokinase was administered directly into each obstructed vein graft over a mean of 20.5 +/- 8.1 hours (median dose 2.2 +/- 0.7 million units). Stents were deployed at the sites of atheromatous obstruction either before (5 patients) or after (25 patients) infusion of urokinase. Twenty-eight of the 30 patients were successfully treated with the combined interventions (success rate 93.3%). In these 28 patients, percent diameter stenosis at the site of obstruction decreased from 86.0% to -0.2% and Thrombolysis in Myocardial Infarction trial flow increased from 1.0 to 2.5. Two patients (6.7%) developed stent thrombosis followed by myocardial infarction (1 with Q-wave infarction, 3.3%) and congestive heart failure. Minor complications included non-Q-wave myocardial infarction (5 patients, 16.7%) and access-site hemorrhage (5 patients, 16.7%). At 2-week follow-up, anginal symptoms were decreased in all 28 successfully treated patients. At 7.2 +/- 3.7-month follow-up, 5 of the 28 successfully treated patients (17.9%) had reacceleration of angina and angiographically documented restenosis at the site of stent deployment.(ABSTRACT TRUNCATED AT 250 WORDS)

Can Hospital Rounds With Pocket Ultrasound By Cardiologists Reduce Standard Echocardiography

BACKGROUND Frequently, hospitalized patients are referred for transthoracic echocardiograms. The availability of a pocket mobile echocardiography device that can be incorporated on bedside rounds by cardiologists may be a useful and frugal alternative. METHODS This was a cross-sectional study designed to compare the accuracy of pocket mobile echocardiography images with those acquired by transthoracic echocardiography in a sample of hospitalized patients. Each patient referred for echocardiography underwent pocket mobile echocardiography acquisition and interpretation by a senior cardiology fellow with level II training in echocardiography. Subsequently, transthoracic echocardiography was performed by skilled ultrasonographers and interpreted by experienced echocardiographers. Both groups were blinded to the results of the alternative imaging modality. Visualizability and accuracy for all key echocardiographic parameters (ejection fraction, wall motion abnormalities, left ventricular end-diastolic dimension, inferior vena cava size, aortic and mitral valve pathology, and pericardial effusion) were determined and compared between imaging modalities. RESULTS A total of 240 hospitalized patients underwent echocardiography with pocket mobile echocardiography and transthoracic echocardiography. The mean age was 71 ± 17 years. Pocket mobile echocardiography imaging time was 6.3 ± 1.5 minutes. Sensitivity of pocket mobile echocardiography varied by parameter and was highest for aortic stenosis (97%) and lowest for aortic insufficiency (76%). Specificity also varied by parameter and was highest for mitral regurgitation (100%) and lowest for left ventricular ejection fraction (92%). Equivalence testing revealed the pocket mobile echocardiography outcomes to be significantly equivalent to the transthoracic echocardiography outcomes with no discernible differences in image quality between pocket mobile echocardiography and transthoracic echocardiography (P = 7.22 × 10(-7)). All outcomes remain significant after correcting for multiple testing using the false discovery rate. CONCLUSIONS The results from rapid bedside pocket mobile echocardiography examinations performed by experienced cardiology fellows compared favorably with those from formal transthoracic echocardiography studies. For hospitalized patients, this finding could shift the burden of performing and interpreting the echocardiogram to the examining physician and reduce the number and cost associated with formal echocardiography studies.