American Society of Clinical Oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants.

PURPOSE: Because toxicities associated with chemotherapy and radiotherapy can adversely affect short- and long-term patient quality of life, can limit the dose and duration of treatment, and may be life-threatening, specific agents designed to ameliorate or eliminate certain chemotherapy and radiotherapy toxicities have been developed. Variability in interpretation of the available data pertaining to the efficacy of the three United States Food and Drug Administration-approved agents that have potential chemotherapy- and radiotherapy-protectant activity-dexrazoxane, mesna, and amifostine-and questions about the role of these protectant agents in cancer care led to concern about the appropriate use of these agents. The American Society of Clinical Oncology sought to establish evidence-based, clinical practice guidelines for the use of dexrazoxane, mesna, and amifostine in patients who are not enrolled on clinical treatment trials. METHODS: A multidisciplinary Expert Panel reviewed the clinical data regarding the activity of dexrazoxane, mesna, and amifostine. A computerized literature search was performed using MEDLINE. In addition to reports collected by individual Panel members, all articles published in the English-speaking literature from June 1997 through December 1998 were collected for review by the Panel chairpersons, and appropriate articles were distributed to the entire Panel for review. Guidelines for use, levels of evidence, and grades of recommendation were reviewed and approved by the Panel. Outcomes considered in evaluating the benefit of a chemotherapy- or radiotherapy-protectant agent included amelioration of short- and long-term chemotherapy- or radiotherapy-related toxicities, risk of tumor protection by the agent, toxicity of the protectant agent itself, quality of life, and economic impact. To the extent that these data were available, the Panel placed the greatest value on lesser toxicity that did not carry a concomitant risk of tumor protection. RESULTS AND CONCLUSION: Mesna: (1) Mesna, dosed as detailed in these guidelines, is recommended to decrease the incidence of standard-dose ifosfamide-associated urothelial toxicity. (2) There is insufficient evidence on which to base a guideline for the use of mesna to prevent urothelial toxicity with ifosfamide doses that exceed 2.5 g/m(2)/d. (3) Either mesna or forced saline diuresis is recommended to decrease the incidence of urothelial toxicity associated with high-dose cyclophosphamide use in the stem-cell transplantation setting. Dexrazoxane: (1) The use of dexrazoxane is not routinely recommended for patients with metastatic breast cancer who receive initial doxorubicin-based chemotherapy. (2) The use of dexrazoxane may be considered for patients with metastatic breast cancer who have received a cumulative dosage of 300 mg/m(2) or greater of doxorubicin in the metastatic setting and who may benefit from continued doxorubicin-containing therapy. (3) The use of dexrazoxane in the adjuvant setting is not recommended outside of a clinical trial. (4) The use of dexrazoxane can be considered in adult patients who have received more than 300 mg/m(2) of doxorubicin-based therapy for tumors other than breast cancer, although caution should be used in settings in which doxorubicin-based therapy has been shown to improve survival because of concerns of tumor protection by dexrazoxane. (5) There is insufficient evidence to make a guideline for the use of dexrazoxane in the treatment of pediatric malignancies, with epirubicin-based regimens, or with high-dose anthracycline-containing regimens. Similarly, there is insufficient evidence on which to base a guideline for the use of dexrazoxane in patients with cardiac risk factors or underlying cardiac disease. (6) Patients receiving dexrazoxane should continue to be monitored for cardiac toxicity. Amifostine: (1) Amifostine may be considered for the reduction of nephrotoxicity in patients receiving cisplatin-based chemoth

Color Doppler and two-dimensional echocardiographic determination of the mechanism of aortic regurgitation with surgical correlation.

The character of the color flow Doppler jet provides information on the mechanism and pathologic elements of valve dysfunction. This has been useful in the evaluation of mitral regurgitation, a repairable problem, but has not been described comprehensively for the aortic valve. The purpose of our study was to correlate the color flow Doppler characteristics of the aortic regurgitant jet and two-dimensional echocardiographic findings of valve mobility with surgical pathology. Prepump intraoperative echocardiography and color flow Doppler echocardiography were performed on 124 patients with aortic regurgitation and used to categorize leaflet motion as excessive, restricted, or normal, jet direction as eccentric or central, and jet origin between the cusps as eccentric, central, or diffuse. Bicuspid disease and tricuspid aortic valve prolapse were associated with excessive valve mobility and eccentric jet direction and origin. Conversely, annular dilation, rheumatic disease, sclerosis, and perforation were associated with normal or reduced cusp mobility and a central jet direction and origin (p = 0.001). Overall, an eccentric jet direction occurred in 69% of patients with excessive cusp mobility, whereas 71% of patients with normal or reduced cusp mobility had a central jet (p = 0.001). Therefore color flow Doppler determination of the eccentricity of regurgitant jet direction and origin is useful in predicting the mechanism and disease of aortic valve dysfunction. These observations may suggest the presence of prolapse and thus the potential for aortic valve repair.

A practical guide to assessment of ventricular diastolic function using Doppler echocardiography.

Doppler assessment of diastolic function has become a standard part of routine echocardiographic examination and imparts information relevant to a patient's functional class, management and prognosis. This review describes the Doppler patterns of diastolic function relative to physical signs and physiology. A continuum of doppler patterns of diastolic function exists, including normal diastolic function, impaired relaxation, pseudonormal filling, restriction, constriction and tamponade. These patterns evolve from one to another in a single individual, with changes in disease evolution, treatment and loading conditions. New applications of continuous wave Doppler, color Doppler M-mode and Doppler tissue imaging are refining our understanding of diastolic function.

Reference values for normal adult transesophageal echocardiographic measurements.

Normal transesophageal echocardiographic measurements have not been presented previously relative to the effects of age, sex, and body surface area. This comparison was obtained by measuring cardiac and aortic dimensions in 60 patients (20 to 75 years old; 33 women) with normal transesophageal echocardiograms. We found a variable and usually important relationship between body surface area and 11 of 20 structures measured. A gender effect was not significant after indexing for body surface area for all but one structure. Age correlated with the diameter of the aortic root, descending aorta, superior vena cava, and right pulmonary artery. Similar dimensions were noted for certain paired structures as the two atria, the mitral and tricuspid annuli, and the aortic root and right ventricular outflow tract. Although multiple factors underlie what is normal in a given individual, our reference values serve to facilitate recognition of cardiac and aortic disease.

Differentiation of constrictive pericarditis from restrictive cardiomyopathy by Doppler transesophageal echocardiographic measurements of respiratory variations in pulmonary venous flow.

OBJECTIVES: The purpose of this study was to test the utility of measuring respiratory variation in pulmonary venous flow by transesophageal echocardiography. BACKGROUND: Respiratory variation of atrioventricular and central venous flow velocities by Doppler echocardiography has been used to differentiate constrictive pericarditis from restrictive cardiomyopathy. METHODS: We performed pulsed wave Doppler transesophageal echocardiography of the left or right pulmonary veins in 31 patients with diastolic dysfunction. Fourteen patients had constrictive pericarditis, and 17 had restrictive cardiomyopathy. We measured the pulmonary venous peak systolic and diastolic flow velocities and the systolic/diastolic flow ratio with transesophageal echocardiography during expiration and inspiration. The percent change in Doppler flow velocity from expiration to inspiration (%E) was calculated. RESULTS: Pulmonary venous peak systolic flow in both inspiration and expiration was greater in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak systolic flow tended to be higher in constrictive pericarditis (19% vs. 10%, p = 0.09). In contrast, pulmonary venous peak diastolic flow during inspiration was lower in constrictive pericarditis than in restrictive cardiomyopathy. The %E for peak diastolic flow was larger in constrictive pericarditis (29% vs. 16%, p = 0.008). The pulmonary venous systolic/diastolic flow ratio was greater in constrictive pericarditis in both inspiration and expiration. The combination of pulmonary venous systolic/diastolic flow ratio > or = 0.65 in inspiration and a %E for peak diastolic flow > or = 40% correctly classified 86% of patients with constrictive pericarditis. CONCLUSIONS: The relatively larger pulmonary venous systolic/diastolic flow ratio and greater respiratory variation in pulmonary venous systolic, and especially diastolic, flow velocities by transesophageal echocardiography can be useful signs in distinguishing constrictive pericarditis from restrictive cardiomyopathy.

Impact of electrical cardioversion for atrial fibrillation on left atrial appendage function and spontaneous echo contrast: characterization by simultaneous transesophageal echocardiography.

OBJECTIVES: This study assessed the function of the left atrial appendage in the pericardioversion period to gain insights into mechanisms involved in thromboembolism after cardioversion of atrial fibrillation. BACKGROUND: Systemic embolization associated with electrical cardioversion of atrial fibrillation is thought to originate from the left atrium or left atrial appendage, or both. However, the mechanism involved is poorly understood. METHODS: We studied left atrial appendage function with transesophageal echocardiography in 20 patients with atrial fibrillation before and after successful electrical cardioversion. We measured left atrial appendage emptying and filling velocities by pulsed wave Doppler echocardiography, characterized Doppler emptying patterns, measured atrial appendage areas and assessed the presence or absence of spontaneous echo contrast or thrombus. RESULTS: Organized left atrial appendage function returned in 16 (80%) of 20 patients immediately after cardioversion. Atrial appendage emptying velocities before cardioversion were greater in patients without (0.39 +/- 0.02 m/s) than in those with (0.25 +/- 0.12 m/s) spontaneous echo contrast (p = 0.045). Furthermore, emptying velocities before cardioversion were significantly greater than late diastolic emptying velocities after cardioversion (0.31 +/- 0.15 vs. 0.14 +/- 0.12 m/s, p = 0.0001), as well as in both the group with (0.25 +/- 0.12 vs. 0.13 +/- 0.13 m/s, p = 0.001) and the group without (0.39 +/- 0.02 vs. 0.15 +/- 0.12 m/s, p = 0.01) spontaneous echo contrast. In addition, left atrial and atrial appendage spontaneous echo contrast developed in 4 of 20 patients and increased in intensity in 3 of 20 patients in the immediate postcardioversion period. CONCLUSIONS: Organized left atrial appendage function returns in most patients immediately after cardioversion of atrial fibrillation. However, its function is impaired compared with that before cardioversion. Furthermore, spontaneous echo contrast increased in 7 (35%) of 20 patients after cardioversion. These observations suggest that stunned left atrial appendage function after cardioversion may predispose the chamber to thrombus formation, which may play a role in the mechanism involved in the occurrence of embolization after cardioversion.

The frequency of acquisition and quality of images obtained by transesophageal echocardiography: a prospective study of 100 consecutive cases.

Although transesophageal echocardiography is capable of generating detailed images of the heart and aorta, the quality of these images and the frequency of their acquisition has not been previously defined. We performed monoplane transesophageal echocardiograms in 100 consecutive patients to determine the quality and frequency of acquisition of 10 standard, transverse views of the heart and aorta. Each image was graded for quality by ascribing a value from 0 (poor quality or not obtained) to 3 (excellent quality). The effect of age on image acquisition and quality was determined for patients less than or equal to 60 years (n = 54) versus greater than 60 years old (n = 46). For the 10 image planes, the average image quality score and the frequency of image acquisition (%) was (1) 2.23 and 100% for the four-chamber view, (2) 1.96 and 98% for the right ventricular inflow view and coronary sinus, (3) 2.17 and 99% for the five-chamber view, (4) 1.80 and 84% for the aortic valve short axis, (5) 1.54 and 82% for the mitral valve short axis, (6) 1.84 and 91% for the mid-left ventricular short axis, (7) 1.02 and 59% for the left ventricular apical short axis, (8) 1.79 and 93% for the ascending aorta, (9) 1.23 and 77% for the aortic arch, and (10) 1.88 and 92% for the descending thoracic aorta view. Ascending aorta and aortic valve short-axis views were obtained with a significantly higher frequency in patients less than or equal to 60 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of mitral stenosis on pulmonary venous flow as measured by Doppler transesophageal echocardiography.

Pulmonary venous flow as assessed by transesophageal echocardiography (TEE) is influenced by changes in left atrial pressure and function. In mitral stenosis (MS), normal left atrial hemodynamics are altered because there is a prolonged decay in diastolic pressure from the left atrium to the left ventricle and atrial function may be altered because of atrial fibrillation. To assess the effect of the prolonged atrial diastolic pressure decay caused by MS on pulmonary venous flow, we studied 27 patients with MS (mitral valve range 0.7 to 2.4 cm2) by pulsed-wave Doppler TEE of the left or right upper pulmonary vein, and compared results with those of 13 normal subjects. Of the 27 subjects with MS, 61% showed a blunted systolic flow pattern and 39% showed a normal flow pattern with greater systolic to diastolic flow ratio. Patients with atrial fibrillation had a predominantly blunted pattern, whereas patients with normal sinus rhythm exhibited both blunted and normal flow patterns. Patients with MS had a lower pulmonary venous peak systolic flow velocity and a longer diastolic pressure halftime than control subjects. Pulmonary venous peak systolic flow velocity was significantly decreased in the presence of atrial fibrillation (p = 0.004). The mitral valve pressure halftime significantly correlated with pulmonary venous diastolic pressure halftime (r = 0.54; p = 0.004) mitral valve area (r = -0.46; p = 0.02). In conclusion, it was found that MS alters pulmonary venous flow patterns, showing a decreased pulmonary venous systolic flow and a prolonged diastolic flow, which may be useful in assessing the hemodynamics of MS.

Transesophageal echocardiographic guidance of closed mitral commissurotomy.

We describe the utility of transesophageal echocardiography in a patient undergoing emergent closed mitral commissurotomy. Two-dimensional images provided an assessment of valve morphology and mobility while Doppler echocardiography was used to monitor the occurrence of mitral regurgitation and changes in valve gradient and area.

Importance of sampling both pulmonary veins in grading mitral regurgitation by transesophageal echocardiography.

Pulmonary venous flow patterns have been used to assess severity of mitral regurgitation; however, the issue of which pulmonary veins to sample has not been determined. We performed pulsed wave Doppler transesophageal echocardiography of both the left and right upper pulmonary veins in 80 patients who had mitral regurgitation determined by independent transesophageal echocardiography color flow mapping. Pulmonary venous flow patterns, peak systolic and diastolic flow, and the presence of reversed systolic flow were compared between the left and right pulmonary veins for each grade of mitral regurgitation. Flow patterns were discordant in 20 (25%) of the 80 patients. Of the 43 patients with 4+ mitral regurgitation, there was discordant flow in 16 (37%) of the patients with mainly reversed systolic flow in the right upper vein, while there was blunted or normal systolic flow in the left upper vein. Of the 16 patients with discordant flows, 14 had eccentric jets, mainly anteromedial jets. We conclude that if discordant flow can occur in 25% of patients with mitral regurgitation and in 37% of patients with 4+ mitral regurgitation, then both pulmonary veins must be evaluated when assessing the severity of mitral regurgitation with pulsed wave Doppler transesophageal echocardiography.

Effects of mitral regurgitation on pulmonary venous flow and left atrial pressure: an intraoperative transesophageal echocardiographic study.

OBJECTIVES AND BACKGROUND: Pulmonary venous flows recorded by pulsed wave Doppler transesophageal echocardiography examination can be used to assess the severity of mitral regurgitation. Pulmonary venous flows are also related to left atrial pressures; however, the determinants of these flows have yet to be characterized in the presence of mitral regurgitation. METHODS: We simultaneously recorded intraoperative pulmonary venous flows by transesophageal echocardiography and left atrial pressures by direct left atrial puncture in 16 patients with different grades of mitral regurgitation: 2+ (n = 5), 3+ (n = 4) and 4+ (n = 7). Pulmonary venous peak systolic and diastolic flow velocities and peak reversed systolic flow velocities were compared with left atrial pressure a and v waves, a-x and v-y descent values and left atrial volumes. RESULTS: Pulmonary venous systolic to diastolic flow ratios correlated with decreases in left atrial pressure a/v ratios and with increases in the v waves of patients with higher grades of mitral regurgitation. Univariate analysis revealed that the best determinants of the pulmonary venous systolic to diastolic flow ratio were the left atrial pressure v wave (r = -0.76), the v-y descent value (r = -0.73) and the a/v ratio (r = 0.71). Lower correlations were found for left atrial end-systolic (r = -0.48) and end-diastolic (r = -0.42) volumes. Reversed systolic flow was present in patients with 4+ mitral regurgitation, despite left atrial enlargement. CONCLUSIONS: Pulmonary venous flow can be used to assess the severity of mitral regurgitation and reflects the effects of mitral regurgitation severity on the left atrial pressure a and v waves.

A comparison of flow convergence with other transthoracic echocardiographic indexes of prosthetic mitral regurgitation.

Prosthetic shadowing of the left atrium may prevent detection of mitral regurgitation during transthoracic echocardiography. In 60 patients with mitral valves, Carpentier-Edwards (n = 20), St. Jude (n = 22), and cage-ball (n = 18), we blindly evaluated the accuracy of three transthoracic Doppler signs of significant (> 2+) mitral regurgitation: (1) color Doppler flow convergence, (2) a color Doppler jet of significant regurgitation in the left atrium, and (3) an intense continuous wave Doppler signal. All 60 patients had transesophageal echocardiography, 26 had cardiac catheterization, and 28 had surgery. The sensitivity and specificity of flow convergence for significant regurgitation by transesophageal echocardiography was 73% and 70%, respectively, compared with 33% and 93% for left atrial color Doppler, and 15% and 97% for continuous wave Doppler. The sensitivity of flow convergence in Carpentier-Edwards, St. Jude, and cage-ball valves was 80%, 73%, and 67%, respectively; whereas the sensitivity of left atrial color Doppler was 70%, 27%, and 0%, and the sensitivity of continuous wave Doppler was 33%, 0%, and 13%. Flow convergence was the only sign of significant regurgitation in 12 of 30 patients (40%); 10 of these patients had mechanical valves. We conclude flow convergence is a more sensitive, though less specific, predictor of significant mitral regurgitation than color Doppler, spatial mapping of the left atrium, and continuous wave Doppler, especially when a mechanical valve is present.

Transesophageal echocardiographic diagnosis of right-sided cardiac masses in patients with central lines.

Transesophageal echocardiography provides excellent images of intracardiac masses; however, its use among a series of patients with central venous lines has not been fully described. Nineteen patients (aged 52 +/- 16 years; 10 women) had masses detected by transesophageal echocardiography in the presence of a permanent (0.2 to 16 years) pacing wire (n = 8), and a current (n = 9) or recent (n = 2) (1 to 281 days) indwelling catheter. Transthoracic echocardiography suggested the presence of a mass in 5 patients (26%), although in only 2 cases were its findings consistent with transesophageal findings. Transesophageal echocardiography indicated the presence of a mass in or near the superior vena cava in 13 patients, in the right atrium in 6, and adjacent to the tricuspid valve in 3. Discrete masses measured 1.6 +/- 2.1 cm2 in area during transesophageal echocardiography. Eleven patients had positive blood cultures, 7 with staphylococcal species. Mass size was not significantly altered by the type of line or sepsis, but showed a weak correlation with line age (r = 0.56). Transesophageal echocardiography altered the management of 9 patients, prompting surgery (n = 3) and line removal (n = 3), and antibiotic (n = 2) or anticoagulation (n = 3) therapy.

Intraoperative transesophageal echocardiographic localization of tumor embolus during pneumonectomy.

We describe a patient undergoing pneumonectomy for large-cell carcinoma, which at the time of surgery was found to invade the pulmonary veins. Transesophageal echocardiography was used to confirm and localize suspected tumor embolization during surgery. Although tumor embolization from the pulmonary veins has been previously reported in the literature, this is the first case, to our knowledge, of transesophageal echocardiographic documentation of such an occurrence. The use of echocardiography in patients at potential risk for tumor involvement of the pulmonary veins is discussed.

Doppler echocardiographic assessment of constrictive pericarditis, cardiac amyloidosis, and cardiac tamponade.

Doppler echocardiography is useful in assessing diastolic dysfunction. Pulsed-wave Doppler echocardiographic interrogation of the atrioventricular valves and the central veins has been used in conjunction with respiratory monitoring to characterize abnormal diastolic function of the heart in diseases such as constrictive pericarditis, restrictive cardiomyopathy, and cardiac tamponade. Constrictive pericarditis has distinct Doppler flows with marked respiratory variation because the pericardial shell separates the intracardiac pressures from intrathoracic pressure. This is not the case with restrictive cardiomyopathy, as in cardiac amyloidosis. Cardiac amyloidosis shows a spectrum of the Doppler flows which evolve as the disease progresses from abnormal relaxation in the early phase to pseudo-normal in the intermediate phase and to restrictive in the advanced phase. Doppler echocardiography can be used to assess the hemodynamic significance of pericardial effusion and to detect cardiac tamponade.

Cardiac tumors: diagnosis and management.

The first step towards the diagnosis of cardiac neoplasia is made when the clinician considers the diagnosis. While the classically described signs and symptoms of left-atrial myxomas are noteworthy, the vast majority of patients present with symptomatology that is less specific--either of a constitutional nature, or related to right- or left-sided congestion. Likewise, the physical examination may rarely disclose classic auscultatory signs, but is more likely to confirm the presence of the right- or left-sided congestion inferred from history. Peripheral, embolic, or vasculitis lesions should raise suspicion of the diagnosis. Nevertheless, the majority of patients will be diagnosed by the unexpected detection of a tumor at the time of echocardiography. Transthoracic echocardiography remains the procedure of choice in screening for cardiac neoplasia. It has excellent sensitivity for intracavitary and endocardial lesions. Myocardial lesions are also well imaged. Pericardial lesions, with or without extension into contiguous structures, are poorly visualized and, here, magnetic resonance imaging is unquestionably the superior investigative approach. Further, a limited degree of tissue characterization is possible with the latter technology. Transesophageal echocardiography is ideally suited for the examination of suspected tumors involving the atria, interatrial septum, superior vena cava, atrioventricular valves and, to a lesser extent, the ventricles. These three imaging modalities clearly complement one another and the choice of application will depend upon factors including the patient's transthoracic echogenicity, the availability of magnetic resonance imaging or transesophageal echocardiography, cost, and the physical status of the patient.

Complications of transesophageal echocardiography in ambulatory adult patients: analysis of 1500 consecutive examinations.

Transesophageal echocardiography is a new approach that can be used to image cardiac structures. It combines two existing technologies: cardiac ultrasound and endoscopy. To obtain a cardiac image, the transesophageal probe has to be positioned properly within the esophagus. The first 1500 consecutive transesophageal echocardiographic examinations in ambulatory adult patients from one center were analyzed to identify conditions associated with failed esophageal intubation and procedural complications. Esophageal intubation was not achieved in 11 patients (0.73%). The reasons for the failure of intubation were operator inexperience, hypersensitive pharynx despite topical anesthesia, and cervical spondylosis. Six of those patients also had a history of dysphagia. Procedural complications were identified in seven patients (0.47%). Tracheal intubation was present in four patients, with immediate development of stridor and incessant cough in two patients. Atrial fibrillation developed in two patients--one had atrial myxoma and one had mitral stenosis. Bronchospasm developed during the transesophageal examination in one patient who was receiving long-term treatment for bronchial asthma. We conclude that transesophageal echocardiography is feasible in most adult patients in the ambulatory setting and that the complication rate is very low. Proper patient selection and preparation are crucial to the successful performance of this procedure.

Doppler color flow image size: dependence on instrument settings.

Doppler color flow imaging provides important qualitative information about the location and spatial distribution of intracardiac blood flow. However, the effect of instrument-related variables on the size of color Doppler images requires further definition. Flow of a silicone particle solution was established in a tube or cylinder and scanned as color gain, pulse repetition frequency, depth, and transducer frequency were varied. The diameter of Doppler color flow images were measured during constant laminar or disturbed flow parallel to the ultrasound beam and during laminar flow perpendicular to the ultrasound beam. The diameter of color Doppler images of laminar flow perpendicular and parallel to the beam varied directly with color gain. Diameter varied inversely with transducer frequency for laminar flow parallel to the transducer and inversely with pulse repetition frequency for laminar flow perpendicular to the transducer. The diameter of laminar flow parallel to the transducer varied directly with the depth of the flow area below the transducer. The size of the color flow dropout of laminar flow exactly perpendicular to the ultrasound beam varied directly with transducer frequency and inversely with gain. During disturbed flow parallel to the transducer, the diameter of the image varied directly with gain and inversely with transducer frequency and pulse repetition frequency. Instrument settings have a significant impact on the size of color Doppler images. Understanding the effects of changes in these variables is important for reliable diagnostic use of Doppler color flow imaging.