thoracic aorta, and left atrial image, due to the location of these structures ..... septostomy and closure of baffle fenestrations following total caval pulmonary ...
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Cardiac Imaging
ECHOCARDIOGRAPHY
Transesophageal Echocardiography a report by
Bijoy K Khandheria, MD, FACC, FESC Professor of Medicine, Mayo Clinic College of Medicine, Chair, Cardiovascular Disease, Mayo Clinic Arizona, and President, American Society of Echocardiography (ASE)
Bijoy K Khandheria, MD, is the Chair of the Division of Cardiovascular Disease at Mayo Clinic. He holds a joint appointment as a consultant in the Division of Cardiovascular Diseases at the Mayo Clinic. He is also the Professor of Medicine at Mayo Clinic College of Medicine and sits as Chair of the Mayo Clinic Information Management and Technology Committee, which facilitates and implements an electronic environment and oversees all information technology projects for the Mayo Clinic. He assumed the presidency of ASE in June 2005, having previously served as Vice President, the Associate Editor for the Journal of the American Society of Echocardiography, and member of the Board of Directors. Dr Khandheria served as the Chair of the Echocardiography Committee for the American College of Cardiology (ACC). He co-chaired the 2003 ACC Annual Scientific Sessions and chaired the 2001 ASE Annual Scientific Sessions. Recently, he was honored as the Navin Nanda lecturer by the Indian Academy of Echocardiography. He has also been made an honorary member of the Thai Heart Association and the Italian Society of Echocardiography. Dr Khandheria has authored or coauthored over 100 articles in peerreviewed journals, edited two books on echocardiography, and has presented at several national and international meetings and symposiums. Dr Khandheria graduated from the Maharaja Sayajirao University Medical School in Baroda, India.
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Cardiovascular ultrasound is an established imaging modality in the practice of cardiovascular disease (CVD), whether this is provided by a CV specialist or health professionals with training in internal medicine. Transthoracic imaging wherein the transducer is placed on the chest wall has some limitations. These include inadequate quality of images resulting in poor information—approximately 5% of all patients undergoing transthoracic echocardiography may be the subject of poor quality images. Inability to view structures such as the arch of the aorta, descending thoracic aorta, and left atrial image, due to the location of these structures within the thorax, has led to innovations such as transesophageal ecocardiogram (ECG) (TEE) and intracardiac ECG. Over the last three decades, TEE has evolved as an essential ultrasonographic technique for a rapid tomographic evaluation of the CV system. Imaging from the confines of the gastroesophageal track reduces signal attenuation and permits use of higher ultrasound frequencies, thereby providing superb spatial resolution. Although interpretation of the structural and hemodynamic information from TEE needs additional training, the technique has been integrated in the standard practice of CV ultrasound (CV), particularly those that demand quick medical decision-making.The role of TEE has become established beyond the confines of the CV ultrasound imaging and hemodynamic laboratory, and is being used with increasing frequency in the operating room (OR), with percutaneous procedures such as closure of defects within the heart, percutaneous implantation of valves, and surgical procedures being performed in the catheterization or the electrophysiologic laboratory. An increasing number of anesthetists, surgeons. and intensivists now use it routinely for monitoring and guiding operative procedures, interventions, and managing critically ill patients. This article briefly reviews the indications and emerging trends in the application of TEE.
the introduction of flexible endoscope, miniaturization and improvements in transducer designs, serial improvement in scanning capabilities from monoplane, biplane to multiplane views, and the addition of spectral and color Doppler imaging.TEE is currently used either as complementary or stand-alone treatment to a routine transthoracic ECG in approximately 5% to 10% of patients being referred for CV ultrasound imaging test. Instrumentation, Procedure, and Complications
TEE can be performed as an out-patient or in-patient procedure. Fasting, as recommended for conscious sedation, appropriate intravenous (IV) access, careful history-taking to rule out the presence of laryngeal or gastroesophageal diseases, and removal of dentures are prerequisites. Absolute contraindications to TEE include esophageal stricture, diverticulum, tumor, and recent esophageal or gastric surgery. Topical spray, IV sedation, a drying agent to minimize oral secretion, and use of appropriate lubrication are helpful. Once in the esophagus, the transducer should be gently guided— the operator should never force this if they encounter resistance. Although the risk of bacterial endocarditis is extremely low and routine antibiotic prophylaxis before TEE is not advocated, it may be considered in high-risk patients such as those with a past history of infective endocarditis. Each operator should establish a standard approach to obtaining all of the views when performing this examination.The current best practice requires the use of a multiplane TEE transducer.The procedure should only be performed by adequately trained individuals. Procedural risks, though low in trained hands, include transient throat pain, laryngospasm, aspiration, hypotension, hypertension, tachycardia, mucosal bleeding, esophageal rupture, and a rare risk of death. Benzocaine topical spray can cause toxic methemoglobinemia. Clinical Applications
The initial acceptance of TEE was offset by the logistic difficulties of introducing rigid endoscopes.The ensuing technological developments that facilitated the transition of TEE to its present clinical status included
TEE has the unique advantage of portability and the ability to obtain high-resolution images of the normal and abnormal CV structures.Any condition where an BUSINESS BRIEFING: US CARDIOLOGY 2006
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Transesophageal Echocardiography echocardiographic evaluation is clinically indicated and in whom the transthoracic approach does not yield diagnostic quality images is therefore a potential indication for TEE. Some unique applications of TEE follow.
standard exists for diagnosing a potentially cardioembolic lesion; hence, risk stratification schemes have been suggested based on strength of the association of a given lesion with ischemic strokes. Atrial Fibrillation
Infective Endocarditis
Despite technological advancements and the use of harmonic imaging, TEE continues to be superior to transthoracic ECG for more effective delineation of the shape and size of vegetations. Left-sided vegetations pose an increased risk of systemic embolism. The risk of embolism has been shown to increase with increasing size of vegetation. TEE is also important for assessing the structural complications such as myocardial abscess, fistulas, mycotic aneurysms, valvular aneurysms or perforations, flail leaflets, or prosthetic valve dehiscence. TEE has a higher sensitivity (76% to 100%) and specificity (94%) than transthoracic ECG for diagnosing perivalvular extension of infection. The cost-effectiveness and incremental utility of TEE when used in conjunction with the clinical information is particularly high in patients who have an intermediate clinical likelihood of infective endocarditis. A negative TEE in a patient with suspected infective endocarditis virtually rules out an infection of the native valve, except in a very early phase of the disease when vegetations may not be detected. When clinical suspicion of infective endocarditis is high and results from TEE are negative, a repeat TEE is warranted within seven to 10 days, which may demonstrate previously undetected vegetations or abscess. Evaluation of the Patient with P r o s t h e t i c Va l v e s
TEE is the procedure of choice for detecting abnormalities of mitral valve prostheses and prosthetic valve dysfunction related to perivalvular regurgitations, cusp abnormalities in tissue prosthesis, embolic events, patient-prosthesis mismatch, and malfunction of repaired valves and implanted rings. Embolic Events
TEE has been shown to have a higher accuracy in identifying abnormal lesions such as thrombus in atria, atrial appendage, plaques in the aorta, and patent foramen ovale in patients with cardio-embolic strokes. The diagnostic yield of TEE for a cardiac source of emboli in a group of patients presenting with unexplained stroke or transient ischemic attacks is high with potential lesions identified in over 50% of the studies. However, one-third of patients who have a cardio-embolic stroke also have concomitant cerebral or vascular atherosclerosis, and this can confound the diagnosis in a given case. Moreover, no absolute clinical or laboratory gold BUSINESS BRIEFING: US CARDIOLOGY 2006
Atrial arrhythmias predispose to emboli formation. A sustained impairment or transient stunning results in poor emptying and enlargement of left atrium and left atrial appendage, leading consequently to stasis and thrombus formation. An annual thromboembolic event rate of 12% has been observed in patients with spontaneous echocardiography contrast compared with 3% in patients without it. Echocardiographic risk factors include left ventricular (LV) systolic dysfunction, LV hypertrophy, left atrial enlargement and spontaneous echocardiographic contrast. The absolute risk of stroke in atrial fibrillation shows marked variation with age and co-existing CVDs, ranging from 2% to 18% per year depending on the investigated patient population. Short-term anticoagulation, combined with TEE before cardioversion, has been suggested to be an effective alternative to three to four weeks of empiric anticoagulation before cardioversion. Economic analysis of TEE-facilitated acute cardioversion has been shown to result in a higher initial treatment costs but a lower subsequent outcomeassociated costs, resulting in no significant cost difference between the two strategies. Aortic Diseases
Transesophageal examination is a valuable clinical modality for managing patients with aortic diseases. It is particularly advantageous in patients with aortic dissections, intramural injury, and aortic trauma. In a comparative imaging of multiplane TEE with spiral computed tomography (CT) and magnetic resonance imaging (MRI), the sensitivity and specificity of TEE for diagnosing aortic dissections has been reported as 98% and 95%, respectively; however, care needs to be taken to differentiate reverberation artifacts. TEE has also been found useful in screening patients with suspected aortic trauma and for diagnosing aortic intramural hematomas. Studies have shown an association between large atheromas in the ascending aorta and the aortic arch, and an increased risk of cerebral embolic events in patients older than 60. In a recent study, the association between previous ischemic strokes, transient ischemic episodes, and aortic atherosclerosis was found to be insignificant once age- and gender-related adjustments were made. The overall importance of aortic atherosclerosis in the pathogenesis of cerebrovascular
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In Suboptimal Images, Your Instincts Tell You There’s
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DEFINITY®:The power to help turn suboptimal images into evaluable images. See it. www.definityimaging.com Indication: Activated DEFINITY® (Perflutren Lipid Microsphere) Injectable Suspension is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the
left ventricular endocardial border. Important Safety Information: Activated DEFINITY® should not be administered to patients with known cardiac shunts nor by direct intra-arterial injection. Extreme caution should be exercised in patients who may have cardiac shunts and in those with chronic pulmonary vascular disorders. The safety of activated DEFINITY® at mechanical indices of >0.8
and with end-systolic triggering has not been established. Administration of activated DEFINITY® occasionally may be associated with QTc prolongation. The overall incidence of treatmentrelated adverse events was 8.4%; those reported most frequently included headache, back or renal pain, flushing, nausea, chest pain, and dizziness. DEFINITY ®
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Something There. We Provide The Power To Help You See It.
will not be properly activated, and must not be used, unless it has completed the 45-second VIALMIX ® activation cycle. Please see Brief Summary on the next page.
DEFINITY® and VIALMIX® are registered trademarks of BristolMyers Squibb Medical Imaging, Inc. All rights reserved.
Printed in USA. © April 2005 T6-K0007
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Carcinogenesis, Mutagenesis, Impairment of Fertility Studies with activated DEFINITY® have not been performed to evaluate carcinogenic potential. Evidence of genotoxicity was not found in the following studies with activated DEFINITY®: 1) bacterial mutagenesis assay (Ames assay), 2) in vitro mammalian mutagenesis assay, 3) in vitro human lymphocyte chromosome aberration assay, and 4) in vivo rat micronucleus assay.
For Intravenous Use DESCRIPTION The DEFINITY® vial contains components that upon activation yield perflutren lipid microspheres, a diagnostic drug that is intended to be used for contrast enhancement during the indicated echocardiographic procedures. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic liquid, which upon activation with the aid of a Vialmix.™ provides a homogeneous, opaque, milky white injectable suspension of perflutren lipid microspheres. The suspension of activated DEFINITY® is administered by intravenous injection. INDICATIONS AND USAGE
Impairment of male or female fertility was not observed in rats and rabbits treated with activated DEFINITY® at up to 1 mL/kg (24x and 15x maximal human dose based on body surface area, respectively). Pregnancy Category B Reproduction toxicity studies have been performed in rats and rabbits at up to 3 mL/kg and, 1 mL/kg (24x and 15x maximal human dose based on body surface area for rats and rabbits, respectively). The studies revealed no evidence of an effect of activated DEFINITY® treatment on the developing fetus. Adequate and well-controlled studies in pregnant women have not been conducted. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Nursing Mothers
Activated DEFINITY® (Perflutren Lipid Microsphere) Injectable Suspension is indicated for use in patients with suboptimal echocardiograms to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border.
Studies to detect if activated DEFINITY® is excreted in human milk have not been conducted. Because many drugs are excreted in human milk, caution should be exercised when activated DEFINITY® is administered to a nursing woman.
CONTRAINDICATIONS
Pediatric Use
Activated DEFINITY® should not be administered to patients with known hypersensitivity to octafluoropropane or in patients with known cardiac shunts (see WARNINGS).
The safety and effectiveness of activated DEFINITY® have not been established in the pediatric population (see WARNINGS).
Activated DEFINITY® should not be administered by direct intra-arterial injection (see WARNINGS). WARNINGS CARDIAC SHUNTS: The safety of activated DEFINITY® in patients with right-to-left, bi-directional, or transient right-to-left cardiac shunts has not been studied. In these patients, phospholipid-encapsulated microspheres can bypass the pulmonary particle-filtering mechanisms and directly enter the arterial circulation. In an animal study utilizing intraarterial administration of activated DEFINITY,® microsphere trapping was seen in small arterioles < 15 µm, especially at branch points and in capillaries at all doses tested (1-6 times the maximal human dose (MHD) based on body surface area). An animal study utilizing an intravenous administration did not result in microvascular obstruction because of presumed filtering by the lungs. Extreme caution should be exercised when considering the administration of activated DEFINITY® in patients that may have cardiac shunts. PULMONARY VASCULAR COMPROMISE: The safety of activated DEFINITY® in humans with compromised pulmonary vascular beds or with small cross-sectional vascular areas has not been studied. Activated DEFINITY® given at a dose of 1 mL/kg (13.5x MHD based on body surface area) increased the respiratory rate and pulmonary arterial pressure (300% and 188%, respectively) in dogs. One dog died displaying clinical signs consistent with cardiopulmonary collapse. Clinical signs consistent with cardiopulmonary collapse were also noted in rats dosed with activated DEFINITY® (multiple-dose study) and included deaths at doses >0.3 mL/kg (2.5x MHD based on body surface area). Additionally, histopathological pulmonary lesions were detected in rats at doses above 0.1 mL/kg (0.8x MHD based on body surface area). In an animal model with artificially induced acute pulmonary hypertension, activated DEFINITY® did not alter pulmonary arterial pressures; however, this acute model does not test the effects on pulmonary occlusion of a histopathologically compromised vasculature that results from chronic disease. Therefore, activated DEFINITY® should be administered with caution to patients with chronic pulmonary vascular disorders (e.g., severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area). PRECAUTIONS
ADVERSE REACTIONS A total of 1716 subjects were evaluated in clinical trials of activated DEFINITY.® In this group, 1063 (61.9%) were male and 653 (38.1%) were female, 1328 (77.4%) were White, 258 (15.0%) were Black, 74 (4.3%) were Hispanic, and 56 (3.3%) were classified as other racial or ethnic groups. The mean age was 56.1 years (range 18 to 93). Of these, 144 (8.4%) had at least one treatment-related adverse reaction (Table 1). There were 8 deaths that were attributed to underlying disorders. There were 26 serious adverse events and 15 (0.9%) subjects discontinued because of an adverse event. Deaths and serious adverse events: Among the 1716 activated DEFINITY® patients, 19 (1.1%) suffered serious cardiopulmonary adverse events including eight deaths. The deaths occurred several days after activated DEFINITY® administration and appear to be related to the course of underlying disease. Of the 11 other serious adverse events, which appeared within days of the drug administration (2-15 days), all appeared to be a progression underlying cardiac and non-cardiac disease. Discontinuations: There were 10 discontinuations reported with a mean age of 41.5 years. Nine of these patients were discontinued after the first injection. One patient experienced a hypersensitivity reaction with urticaria and pruritus and all the other patients experienced dizziness, chest pain, dyspnea, or back pain. Adverse events appeared within minutes (1-15 min) of the drug administration and were of moderate intensity resolving usually without treatment within minutes or hours after onset. For all adverse events, the overall incidence of adverse experiences was similar for the 30 msec were noted in 64 (29%) subjects. Forty-six out of 64 subjects with QTc prolongations were further evaluated and 39% (18/46) showed associated cardiac rhythm changes. No malignant cardiac symptomatology or events of syncope were reported as a result of these ECG changes. The effects of concomitant drugs were not studied.
Vascular (extracardiac) disorders Flushing
19 19
(1.1) (1.1)
Information For Patients
Body as a Whole: Fatigue, fever, hot flushes, pain, rigors, and syncope Cardiovascular: Abnormal ECGs, bradycardia, tachycardia, palpitation, hypertension, and hypotension Digestive: Dyspepsia, dry mouth, tongue disorder, toothache, abdominal pain, diarrhea, and vomiting Hematology: Granulocytosis, leukocytosis, leukopenia, monocytosis, and eosinophilia Musculoskeletal: Arthralgia Nervous System: Leg cramps, hypertonia, vertigo, and paresthesia Platelet, Bleeding, and Clotting: Hematoma
Patients receiving activated DEFINITY® should be instructed to: 1. Inform your physician or health care provider if you may be pregnant, are trying to become pregnant, or are nursing. 2. Inform your physician or health care provider if you have a congenital heart defect (see CONTRAINDICATIONS and WARNINGS).
N=Sample size (1716 subjects who received activated DEFINITY®) A.E.=Adverse Experience n=Number of subjects reporting at least one A.E. Other treatment-related adverse experiences that occurred in
