- Email: [email protected]
Outcomes research review
OUTCOMES JOURNAL WATCH
Outcomes Research Review Pamela S. Douglas, MD, and Todd B. Seto, MD, MPH, Boston, Massachusetts
Outcomes Research: Why Now?
Variably defined and often misunderstood, outcomes research has undergone tremendous growth in this era of health care reform. In broad terms, the goal of outcomes research is to improve the health of a patient. It seeks to answer the questions, “Does this medication, test, or therapy help my patient feel better? Function more independently? Live a healthier and longer life?” Although the physiologic benefits of a medication (such as the lowering of blood pressure or cholesterol) or the diagnostic accuracy of a test are not ignored, the “bottom line” of outcomes research is whether or not the patient feels better and lives longer. The interest in outcomes research partly arises from our recognition that outcomes other than morbidity and mortality are important and meaningful to patients. The development of valid and reliable measures of quality of life, functional status, and patient satisfaction has shed light on the various ways medical interventions can affect patients. In practice, the influence of outcomes research can be detected each time we consider the most “cost-effective” way to treat a patient. The development and implementation of clinical practice guidelines are based on the assumption that limiting the variability and improving the process of care will improve clinical outcomes and efficiency.1 The collection and dissemination of physician-specific report cards, such as those reporting coronary artery bypass surgery mortality rates,2 are based on the assumption that improving consumer knowledge and physician feedback will change physician behavior and improve clinical outcomes. Why should readers of the Journal of the American Society of Echocardiography be interested in outcomes research? First, if we are to be experts in our field, we need to understand how echocardiography is being From the Charles A. Dana Research Institute and the Harvard– Thorndike Laboratory of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass. Reprint requests: Pamela S. Douglas, MD, Cardiovascular Division, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. E-mail: [email protected]. J Am Soc Echocardiogr 1998;11:916-20. Copyright © 1998 by the American Society of Echocardiography. 0894-7317/98 $5.00 1 0 27/1/92040
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used, which includes knowing its pattern of use and occasional misuse, understanding when it provides meaningful data that can significantly affect patient outcome, and recognizing when it does not. Second, with the push toward cost reduction and more streamlined medical care, outcomes research maintains our focus on improving the health of patients and is thus a means to ensure quality health care in the face of economic pressures.3 With this in mind we introduce “Outcomes Research Review.” Twice a year selected articles from the published literature that evaluate the effect of echocardiography on patient outcomes or costs of care will be reviewed briefly and discussed critically. Our goal is to increase awareness of the importance of the above questions and the available data by reviewing published studies, including both the well- and poorly designed studies and those supportive and critical of echocardiography. These reviews will provide a basis from which we can better understand the value of echocardiography as perceived by patients, payers, and other physicians. Cost-Effectiveness of Echocardiography After Stroke McNamara RL, Lima JAC, Whelton PK, Powe NR. Echocardiography Identification of Cardiovascular Sources of Emboli to Guide Clinical Management of Stroke: A Cost-Effectiveness Analysis. Ann Intern Med 1997;127:775-87. Stroke is the leading cause of long-term illness and the third leading cause of death in the United States, with an annual cost of 15 to 30 billion dollars. Because 15% to 45% of strokes may be caused by cardiac emboli, echocardiography is often part of the routine evaluation for stroke. However, the ability of transthoracic echocardiography (TTE) to detect atrial thrombi is poor, and transesophageal echocardiography (TEE) is invasive and expensive. Without clinical trial data, the appropriateness of any form of routine echocardiography after stroke is unknown. McNamara and colleagues developed a computerized cost-effectiveness model to evaluate the use of echocardiography in a patient who recently had a stroke. They studied 9 management strategies, including the routine use of TTE, the routine use of TEE, and 2
Journal of the American Society of Echocardiography Volume 11 Number 9
different approaches using sequential TTE and TEE. When an intracardiac thrombus was detected, patients were assumed to have received anticoagulation therapy, with the risk of major bleeding. Two additional strategies without echocardiography were also studied, 1 with anticoagulation therapy for all subjects and 1 without. All probabilities, including the risks of stroke and death, were derived from the published literature. Costs were derived from Medicare reimbursement rates and the published literature. With visualized atrial thrombi as the sole indication for anticoagulation, TEE performed only in patients with a history of cardiac problems was the most costeffective approach, followed by a strategy using TEE in all patients ($9,000 and $13,000 per quality-adjusted life-year [QALY], respectively). In contrast, strategies using TTE, either alone or in sequence with TEE, were not cost-effective. The results were dependent on baseline assumptions of the efficacy of anticoagulation therapy (reduction in risk of recurrent stroke) and of the risk of intracranial hemorrhage. Comment. This study recommends an expanded role for TEE (without TTE) in the management of patients with stroke that has no obvious cause (eg, atrial fibrillation, prosthetic valve, endocarditis), and suggests that using TEE alone can improve patient survival with little additional cost. Cost-effectiveness analysis is a common method by which to quantitatively approach a clinical problem when little (or conflicting) clinical trial data exist regarding the best therapy. However, in this study 1 major caveat should be noted. The risk of recurrent stroke is unknown for patients receiving anticoagulation therapy in this population, and the authors’ estimates were based on clinical trials that studied a very different group of patients: those treated with warfarin for chronic atrial fibrillation. By assuming that the number of recurrent strokes will be reduced by 33% as a result of anticoagulation therapy when the percentage may be much smaller, this study likely overestimates the true value of TEE. In addition, it does not address the current clinical use of anticoagulation therapy in patients without evidence of thrombus on TEE, nor does it consider published evidence that TEE results rarely change the physician’s decision to prescribe anticoagulation therapy in real life. Decision Analytic Model of Recurrent Stroke Prevention in Patients with Patent Foramen Ovale Nendaz MR, Sarasin FP, Junod AF, Bogousslavsky J. Preventing Stroke Recurrence in Patients with Patent Foramen Ovale: Antithrombotic Therapy, Foramen
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Closure, or Therapeutic Abstention? A Decision Analytic Perspective. Am Heart J 1998;135:532-41. Transthoracic echocardiography is often performed in ischemic stroke patients to locate possible sources of cerebral emboli, such as left atrial or ventricular thrombi. Several studies report that patients with patent foramen ovale (PFO) and/or interatrial septal aneurysms are at risk for recurrent stroke, but the magnitude of this risk and the benefits of treatment are unknown. Nendaz and colleagues used decision analysis methods to compare approaches to prevent recurrent stroke in subjects with a PFO. In their computerbased model, patients who had a recent stroke without an obvious cause received 3 months of oral anticoagulant therapy and followed 1 of 4 management strategies: (1) no further treatment, (2) daily aspirin, (3) long-term oral anticoagulant therapy, or (4) surgical closure of the PFO by open heart surgery. Baseline probabilities were based on published data, and outcomes were measured as quality-adjusted lifeyears. As expected, the benefits of therapy were dependent on the probability of recurrent stroke. For subjects with a low risk of recurrence (0.7% per year), strategy 1 (no further treatment) was as effective as daily aspirin therapy, long-term oral anticoagulation, or surgical closure of the PFO. For subjects with an intermediate risk of recurrent stroke (1.5% per year), surgical closure was the most effective approach (23.4 QALYs), followed by long-term oral anticoagulation (23.2 QALYs), daily aspirin (22.8 QALYs), and no treatment (22.7 QALYs). For patients with a high risk of recurrent stroke (7% per year), the magnitude of the differences between the 4 strategies increased. To further test the sensitivity of the results to the baseline assumptions, the authors evaluated key variables over a wide range of clinically relevant baseline probabilities. In addition to the risk of stroke recurrence, estimates of the risks of surgery and of complications from anticoagulant therapy were identified as important. Similarly, the benefits of treatment varied with subject age, with subjects older than 50 years experiencing minimal benefit for surgical repair. Comment. This study addresses a familiar clinical dilemma. Patients who have had a recent ischemic stroke frequently are referred for echocardiography to rule out a cardiac cause, and a PFO or interatrial septal aneurysm is noted. What should be done? Because no consensus exists on the risk of recurrent stroke for patients with PFO or on the benefits of anticoagulation or surgical therapy, Nendaz and col-
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leagues used published data to build a decision analysis model to compare the effectiveness of 4 treatment strategies. In addition to quantitatively evaluating treatment strategies in the face of little or conflicting data, decision analysis allows the identification of key variables that influence the decision-making process. The authors nicely illustrate the dependence of the preferred strategy on the risk of recurrent stroke, the age of the patient, and the risk of surgical or anticoagulation therapy. This study also demonstrates the pitfalls of decision analysis. Because no information exists on the effectiveness of aspirin or long-term oral anticoagulation therapy on the risk of recurrent stroke in this population, data from trials of very different patient populations were used: studies of warfarin therapy for patients with chronic atrial fibrillation and aspirin therapy for the prevention of venous thrombosis and pulmonary embolism. It is unclear whether the reductions in thromboembolic risk in these studies are of similar magnitude to the reduction in recurrent stroke risk in patients with PFO. In addition, as the authors point out, the method used to calculate the yearly risk of recurrent stroke requires that this risk remain constant, rather than decrease, over time. Thus it is possible that the benefits of treating patients with PFO may have been overestimated. Finally, an analysis including the costs of therapy would have been useful in providing an estimate of the value of resources necessary to achieve the benefits of treating patients with PFO. Cardioversion Guided by Transesophageal Echocardiography in Patients with Atrial Fibrillation Klein AL, Grimm RA, Black IW, Leung DY, Chung MK, Vaughn SE, Murray D, Miller DP, Arheart KL. Cardioversion Guided by Transesophageal Echocardiography: The ACUTE Pilot Study. Ann Intern Med 1997:126:200-9. Conventional therapy for patients with atrial fibrillation of more than 2 days’ duration includes 3 to 4 weeks of anticoagulation therapy before elective cardioversion to decrease the risk of cardioversion-related stroke. Because TEE has a high sensitivity and specificity for left atrial thrombi, some physicians advocate its use to screen for early cardioversion in patients with atrial fibrillation without evidence of atrial thrombi. The benefits of this approach include a shortened duration (minimum of 3 to 4 weeks) of anticoagulation therapy before cardioversion for those without TEE evidence of thrombi. All patients should receive 3 to 4 weeks of anticoagulation therapy after cardioversion.
Journal of the American Society of Echocardiography September 1998
The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) Pilot Study was a multicenter clinical trial designed to compare the feasibility and safety of TEE-guided cardioversion with conventional therapy for patients with atrial fibrillation. Of the 62 patients who underwent the TEE-guided approach, 56 (90%) successfully completed the TEE, and the cardioversion of 7 (13%) was postponed after an atrial thrombus was detected. Cardioversion was successfully performed in 38 (84%) of 45 patients, and no thromboembolic events occurred. Of the 64 patients assigned to conventional therapy, 28 (76%) of 37 had successful cardioversion. One patient had a peripheral embolic event. The mean time from enrollment to cardioversion was significantly shorter in the TEE-guided cardioversion group (0.6 vs 4.8 weeks, P , .01), and a trend existed toward more hemodynamic instability and bleeding in the conventional therapy group. Comment. This pilot study provides useful information on the impact of echocardiography on the management of atrial fibrillation and on the rate of postcardioversion stroke. When performed by experienced operators and if patients receive therapeutic anticoagulation before cardioversion, TEE-guided cardioversion appears to be associated with a very low risk of postcardioversion thromboembolism and possibly a lower rate of hemorrhagic complications than conventional therapy. Although the time to cardioversion was significantly shorter in the TEE-guided cardioversion group, its clinical significance and effect on patient outcome has yet to be determined. Data from this pilot study and from other investigators suggest that TEE-guided cardioversion is a safe and practical alternative to conventional therapy. The ASE recently funded the ACUTE investigators for a cost analysis of actual data for subjects randomly assigned to this pilot study. The Impact of Echocardiography on the Management of Patients with Suspected Mitral Valve Prolapse Heidenreich PA, Bear J, Browner W, Foster E. The Clinical Impact of Echocardiography on Antibiotic Prophylaxis Use in Patients with Suspected Mitral Valve Prolapse. Am J Med 1997;102:337-43. Mitral valve prolapse (MVP) occurs in 4% of the population and is associated with a small but significant risk of endocarditis and other cardiac problems. Echocardiography is considered the diagnostic test of choice and is used to identify patients at high risk for endocarditis who would benefit from antibiotic prophylaxis. However, whether echocardiography actu-
Journal of the American Society of Echocardiography Volume 11 Number 9
ally provides new information and affects the management of patients with MVP is uncertain. Heidenreich and colleagues evaluated 147 consecutive echocardiographic studies performed to rule out MVP to determine the frequency of the following: (1) provision of new information by echocardiograph that could influence management decisions and (2) actual changes in management in response to that information. Prophylaxis was considered to be indicated if MVP with at least mild mitral regurgitation or thickening of the mitral valve leaflets was detected. Thirty-six (25%) of 147 subjects had a clinical diagnosis of MVP; 23 were using antibiotic prophylaxis. Nineteen (52%) of these 36 subjects did not have MVP by echocardiographic criteria. Based on echocardiography a change in antibiotic prophylaxis was indicated in 20 (14%) subjects (14 should discontinue prophylaxis and 6 should start prophylaxis). However, only 4 (20%) of 20 subjects actually had a change in their prophylaxis regimen (3 started prophylaxis and 1 stopped prophylaxis). The authors conclude that whereas echocardiography frequently altered the patients’ diagnosis, its results rarely led to changes in the antibiotic prophylaxis management of patients with MVP. Comment. This study highlights the difference between the ability of a diagnostic test to provide new information and the impact of that test on the care of a patient. In this study echocardiography definitely provided new information: MVP was ruled out in more than one half of subjects whose diagnosis of MVP was based on clinical criteria, and a change in management was indicated for 14% of subjects. However, the findings that the management of MVP changed very little despite this information suggest that the impact of echocardiography on clinical care is small. This study also notes the distinction between the process of care and the outcome of care. The process of care includes what is actually done in the care of a patient (the procedures and tests performed, the diagnoses made, the therapies given), whereas the outcome of care includes measures of patient health (health status, satisfaction, morbidity, mortality). This study evaluated the impact of echocardiography on the diagnosis of MVP. The assumption that the improvement in this process measure will lead to improved patient outcome is reasonable given the benefit of antibiotic prophylaxis in the prevention of endocarditis, but it was not shown in this study of current clinical practice. This study demonstrates that the value of echocardiography lies not only in its diagnostic capabilities but also in how the data obtained are applied to patient care.
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Role of Echocardiography in Patients with Staphylococcus aureus Bacteremia Fowler VG, Li J, Corey GR, Boley J, Marr KA, Gopal AK, Kong LK, Gottlieb G, Donovan CL, Sexton DJ, Ryan T. Role of Echocardiography in Evaluation of Patients with Staphylococcus aureus Bacteremia: Experience in 103 Patients. J Am Coll Cardiol 1997;30:1072-8. Patients with Staphylococcus aureus bacteremia are at risk of infective endocarditis, with a reported incidence ranging from 5% to 64%. Because the ability of TTE to detect vegetations (the most common echocardiographic evidence of endocarditis) is low, many physicians advocate the use of TEE in patients with suspected endocarditis. Fowler and colleagues performed TTE and TEE in 103 subjects with staphylococcal bacteremia to determine their role in the diagnosis and prognosis of infective endocarditis. The Duke criteria were used as the gold standard for the diagnosis of endocarditis. The criteria provide a validated scheme incorporating major (persistently positive blood cultures, valvular abnormalities on echocardiography) and minor (fever, predisposing valvular disease, intravenous drug use) criteria. In this study definite endocarditis was present in 26 subjects (25%). The sensitivity and specificity of TTE was 32% and 100%, respectively. For TEE, the sensitivity and specificity were 100% and 99% (1 false-positive result), respectively. Predictably, the higher sensitivity of TEE was largely the result of its ability to detect small vegetations. Staphylococcal infection was cured with similar frequency in subjects with and without endocarditis, although subjects with endocarditis (15% vs 1.3%) were more likely to die of staphylococcal sepsis. The authors conclude that TEE plays an essential role in the diagnosis of endocarditis in patients with staphylococcal bacteremia and in the detection of associated complications. Comment. This study examines the sensitivity (ability to detect the presence of vegetations) and specificity (ability to exclude the presence of vegetations) of echocardiography in patients with suspected endocarditis. When evaluating a diagnostic test such as echocardiography, the choice of an appropriate “gold standard” for comparison is important. The Duke criteria used in this study are a well-recognized method to diagnose endocarditis, although they also have their own sensitivity and specificity when compared with a “true” gold standard (eg, microorganism demonstrated by culture or histologic study in a vegetation). Although the high sensitivity and specificity of TEE are not surprising, the impact of TEE on the diagnosis and management of all patients with suspected endo-
Journal of the American Society of Echocardiography September 1998
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carditis is unclear. In many cases the diagnosis of endocarditis can be made without the use of echocardiography, or the necessary data can be obtained from TTE rather than TEE. In addition, patients are often treated for endocarditis even in the absence of a significantly abnormal echocardiogram. In this study TEE was superior to TTE in detecting complications of endocarditis, such as aortic root abscess or valve perforation. Although the detection of these complications by TEE is not linked specifically to changes in clinical events or general health, it is reasonable to assume that such a discovery would help improve patient outcomes. However, further work is needed to determine whether echocardiography should be performed in all patients with S. aureus bacteremia or only in selected patients at high risk for complications, such as those with persistent fever or bacteremia. ACC/AHA Guidelines for the Clinical Application of Echocardiography Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davidson TW, Davis JL, Douglas PS, Gillam LD, Lewis RP, Pearlman AS, Philbrick JT, Shah PM, Williams RG, Ritchie JL, Eagle KA, Gardner TJ, Garson A, Gibbons RJ, O’Rourke RA, Ryan TJ. ACC/AHA Guidelines for the Clinical Application of Echocardiography. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography) [executive summary]. J Am Coll Cardiol 1997;29:862-879. and Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davidson TW, Davis JL, Douglas PS, Gillam LD, Lewis RP, Pearlman AS, Philbrick JT, Shah PM, Williams RG. ACC/AHA Guidelines for the Clinical Application of Echocardiography. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography) [complete text]. Circulation 1997;95:1686-1744. These guidelines, written by an ad hoc group composed of experts in the field of echocardiography, senior clinical cardiologists, and generalists, were developed after an extensive review of the literature. Following the classification used in other ACC/AHA guidelines, the recommendations on the use of echocardiography were divided into Class I (evidence or agreement on usefulness/efficacy), Class II (conflicting or inadequate evidence or opinion on usefulness/ efficacy), and Class III (evidence or agreement that echocardiography is not useful/effective).
The guidelines addressed the use of echocardiography in both specific cardiovascular diseases (eg, valvular stenosis/regurgitation or cardiomyopathy) and in the evaluation of common cardiovascular symptoms or signs (eg, chest pain or syncope). For example, the indications for echocardiography in patients with MVP include the assessment of hemodynamic severity and leaflet morphology in patients with clinical signs of MVP (Class I), the exclusion of MVP in patients with a diagnosis of MVP but who do not have clinical evidence of it (Class II), and the exclusion of MVP in patients with ill-defined symptoms but without clinical or physical findings consistent for MVP (Class III). Comment. One of the goals of clinical practice guidelines is to succinctly and practically summarize current knowledge on the effectiveness of a diagnostic test or therapy. With a test as widely used as echocardiography, practice guidelines offer an opportunity to explicitly state when an echocardiographic study would likely provide clinically meaningful information. Guidelines are often a consensus statement agreed on by an expert panel after careful review of the available literature. They are designed to be evidence-based rather than empirical—to rely on studies that demonstrate a benefit of the diagnostic test or therapy on patient outcome. The assumption is that guidelines will improve the overall quality of care, while promoting a more efficient use of resources. However, the actual effect of guidelines on changing physician practice patterns is often difficult to detect and has not been well studied. Because it is difficult to directly measure the effect of a diagnostic test on patient outcomes, evaluating the clinical utility of a diagnostic test is much more difficult than evaluating the clinical utility of a therapeutic intervention. Thus the guidelines for echocardiography focus on data regarding test sensitivity, specificity, and diagnostic accuracy, with the assumption that maximizing test efficiency will improve patient outcomes. Whereas outcomes data are incorporated whenever possible, little is available for most diagnostic tests, including echocardiography. As more studies become available that evaluate the impact of echocardiography on patient outcomes, they will be incorporated into practice guidelines and offer a link between the performance of an echocardiogram and improvement in patient health.
REFERENCES 1. Donabedian A. The quality of care. How can it be assessed? JAMA 1988;260:1743-8. 2. Green J, Wintfeld N. Report cards on cardiac surgeons. Assessing New York State’s approach. N Engl J Med 1995;332: 1229-32. 3. Epstein AM. The outcomes movement—will it get us where we want to go? N Engl J Med 1990;323:266-70.
Outcomes Research Review Pamela S. Douglas, MD, and Todd B. Seto, MD, MPH, Boston, Massachusetts
Outcomes Research: Why Now?
Variably defined and often misunderstood, outcomes research has undergone tremendous growth in this era of health care reform. In broad terms, the goal of outcomes research is to improve the health of a patient. It seeks to answer the questions, “Does this medication, test, or therapy help my patient feel better? Function more independently? Live a healthier and longer life?” Although the physiologic benefits of a medication (such as the lowering of blood pressure or cholesterol) or the diagnostic accuracy of a test are not ignored, the “bottom line” of outcomes research is whether or not the patient feels better and lives longer. The interest in outcomes research partly arises from our recognition that outcomes other than morbidity and mortality are important and meaningful to patients. The development of valid and reliable measures of quality of life, functional status, and patient satisfaction has shed light on the various ways medical interventions can affect patients. In practice, the influence of outcomes research can be detected each time we consider the most “cost-effective” way to treat a patient. The development and implementation of clinical practice guidelines are based on the assumption that limiting the variability and improving the process of care will improve clinical outcomes and efficiency.1 The collection and dissemination of physician-specific report cards, such as those reporting coronary artery bypass surgery mortality rates,2 are based on the assumption that improving consumer knowledge and physician feedback will change physician behavior and improve clinical outcomes. Why should readers of the Journal of the American Society of Echocardiography be interested in outcomes research? First, if we are to be experts in our field, we need to understand how echocardiography is being From the Charles A. Dana Research Institute and the Harvard– Thorndike Laboratory of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass. Reprint requests: Pamela S. Douglas, MD, Cardiovascular Division, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. E-mail: [email protected]. J Am Soc Echocardiogr 1998;11:916-20. Copyright © 1998 by the American Society of Echocardiography. 0894-7317/98 $5.00 1 0 27/1/92040
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used, which includes knowing its pattern of use and occasional misuse, understanding when it provides meaningful data that can significantly affect patient outcome, and recognizing when it does not. Second, with the push toward cost reduction and more streamlined medical care, outcomes research maintains our focus on improving the health of patients and is thus a means to ensure quality health care in the face of economic pressures.3 With this in mind we introduce “Outcomes Research Review.” Twice a year selected articles from the published literature that evaluate the effect of echocardiography on patient outcomes or costs of care will be reviewed briefly and discussed critically. Our goal is to increase awareness of the importance of the above questions and the available data by reviewing published studies, including both the well- and poorly designed studies and those supportive and critical of echocardiography. These reviews will provide a basis from which we can better understand the value of echocardiography as perceived by patients, payers, and other physicians. Cost-Effectiveness of Echocardiography After Stroke McNamara RL, Lima JAC, Whelton PK, Powe NR. Echocardiography Identification of Cardiovascular Sources of Emboli to Guide Clinical Management of Stroke: A Cost-Effectiveness Analysis. Ann Intern Med 1997;127:775-87. Stroke is the leading cause of long-term illness and the third leading cause of death in the United States, with an annual cost of 15 to 30 billion dollars. Because 15% to 45% of strokes may be caused by cardiac emboli, echocardiography is often part of the routine evaluation for stroke. However, the ability of transthoracic echocardiography (TTE) to detect atrial thrombi is poor, and transesophageal echocardiography (TEE) is invasive and expensive. Without clinical trial data, the appropriateness of any form of routine echocardiography after stroke is unknown. McNamara and colleagues developed a computerized cost-effectiveness model to evaluate the use of echocardiography in a patient who recently had a stroke. They studied 9 management strategies, including the routine use of TTE, the routine use of TEE, and 2
Journal of the American Society of Echocardiography Volume 11 Number 9
different approaches using sequential TTE and TEE. When an intracardiac thrombus was detected, patients were assumed to have received anticoagulation therapy, with the risk of major bleeding. Two additional strategies without echocardiography were also studied, 1 with anticoagulation therapy for all subjects and 1 without. All probabilities, including the risks of stroke and death, were derived from the published literature. Costs were derived from Medicare reimbursement rates and the published literature. With visualized atrial thrombi as the sole indication for anticoagulation, TEE performed only in patients with a history of cardiac problems was the most costeffective approach, followed by a strategy using TEE in all patients ($9,000 and $13,000 per quality-adjusted life-year [QALY], respectively). In contrast, strategies using TTE, either alone or in sequence with TEE, were not cost-effective. The results were dependent on baseline assumptions of the efficacy of anticoagulation therapy (reduction in risk of recurrent stroke) and of the risk of intracranial hemorrhage. Comment. This study recommends an expanded role for TEE (without TTE) in the management of patients with stroke that has no obvious cause (eg, atrial fibrillation, prosthetic valve, endocarditis), and suggests that using TEE alone can improve patient survival with little additional cost. Cost-effectiveness analysis is a common method by which to quantitatively approach a clinical problem when little (or conflicting) clinical trial data exist regarding the best therapy. However, in this study 1 major caveat should be noted. The risk of recurrent stroke is unknown for patients receiving anticoagulation therapy in this population, and the authors’ estimates were based on clinical trials that studied a very different group of patients: those treated with warfarin for chronic atrial fibrillation. By assuming that the number of recurrent strokes will be reduced by 33% as a result of anticoagulation therapy when the percentage may be much smaller, this study likely overestimates the true value of TEE. In addition, it does not address the current clinical use of anticoagulation therapy in patients without evidence of thrombus on TEE, nor does it consider published evidence that TEE results rarely change the physician’s decision to prescribe anticoagulation therapy in real life. Decision Analytic Model of Recurrent Stroke Prevention in Patients with Patent Foramen Ovale Nendaz MR, Sarasin FP, Junod AF, Bogousslavsky J. Preventing Stroke Recurrence in Patients with Patent Foramen Ovale: Antithrombotic Therapy, Foramen
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Closure, or Therapeutic Abstention? A Decision Analytic Perspective. Am Heart J 1998;135:532-41. Transthoracic echocardiography is often performed in ischemic stroke patients to locate possible sources of cerebral emboli, such as left atrial or ventricular thrombi. Several studies report that patients with patent foramen ovale (PFO) and/or interatrial septal aneurysms are at risk for recurrent stroke, but the magnitude of this risk and the benefits of treatment are unknown. Nendaz and colleagues used decision analysis methods to compare approaches to prevent recurrent stroke in subjects with a PFO. In their computerbased model, patients who had a recent stroke without an obvious cause received 3 months of oral anticoagulant therapy and followed 1 of 4 management strategies: (1) no further treatment, (2) daily aspirin, (3) long-term oral anticoagulant therapy, or (4) surgical closure of the PFO by open heart surgery. Baseline probabilities were based on published data, and outcomes were measured as quality-adjusted lifeyears. As expected, the benefits of therapy were dependent on the probability of recurrent stroke. For subjects with a low risk of recurrence (0.7% per year), strategy 1 (no further treatment) was as effective as daily aspirin therapy, long-term oral anticoagulation, or surgical closure of the PFO. For subjects with an intermediate risk of recurrent stroke (1.5% per year), surgical closure was the most effective approach (23.4 QALYs), followed by long-term oral anticoagulation (23.2 QALYs), daily aspirin (22.8 QALYs), and no treatment (22.7 QALYs). For patients with a high risk of recurrent stroke (7% per year), the magnitude of the differences between the 4 strategies increased. To further test the sensitivity of the results to the baseline assumptions, the authors evaluated key variables over a wide range of clinically relevant baseline probabilities. In addition to the risk of stroke recurrence, estimates of the risks of surgery and of complications from anticoagulant therapy were identified as important. Similarly, the benefits of treatment varied with subject age, with subjects older than 50 years experiencing minimal benefit for surgical repair. Comment. This study addresses a familiar clinical dilemma. Patients who have had a recent ischemic stroke frequently are referred for echocardiography to rule out a cardiac cause, and a PFO or interatrial septal aneurysm is noted. What should be done? Because no consensus exists on the risk of recurrent stroke for patients with PFO or on the benefits of anticoagulation or surgical therapy, Nendaz and col-
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leagues used published data to build a decision analysis model to compare the effectiveness of 4 treatment strategies. In addition to quantitatively evaluating treatment strategies in the face of little or conflicting data, decision analysis allows the identification of key variables that influence the decision-making process. The authors nicely illustrate the dependence of the preferred strategy on the risk of recurrent stroke, the age of the patient, and the risk of surgical or anticoagulation therapy. This study also demonstrates the pitfalls of decision analysis. Because no information exists on the effectiveness of aspirin or long-term oral anticoagulation therapy on the risk of recurrent stroke in this population, data from trials of very different patient populations were used: studies of warfarin therapy for patients with chronic atrial fibrillation and aspirin therapy for the prevention of venous thrombosis and pulmonary embolism. It is unclear whether the reductions in thromboembolic risk in these studies are of similar magnitude to the reduction in recurrent stroke risk in patients with PFO. In addition, as the authors point out, the method used to calculate the yearly risk of recurrent stroke requires that this risk remain constant, rather than decrease, over time. Thus it is possible that the benefits of treating patients with PFO may have been overestimated. Finally, an analysis including the costs of therapy would have been useful in providing an estimate of the value of resources necessary to achieve the benefits of treating patients with PFO. Cardioversion Guided by Transesophageal Echocardiography in Patients with Atrial Fibrillation Klein AL, Grimm RA, Black IW, Leung DY, Chung MK, Vaughn SE, Murray D, Miller DP, Arheart KL. Cardioversion Guided by Transesophageal Echocardiography: The ACUTE Pilot Study. Ann Intern Med 1997:126:200-9. Conventional therapy for patients with atrial fibrillation of more than 2 days’ duration includes 3 to 4 weeks of anticoagulation therapy before elective cardioversion to decrease the risk of cardioversion-related stroke. Because TEE has a high sensitivity and specificity for left atrial thrombi, some physicians advocate its use to screen for early cardioversion in patients with atrial fibrillation without evidence of atrial thrombi. The benefits of this approach include a shortened duration (minimum of 3 to 4 weeks) of anticoagulation therapy before cardioversion for those without TEE evidence of thrombi. All patients should receive 3 to 4 weeks of anticoagulation therapy after cardioversion.
Journal of the American Society of Echocardiography September 1998
The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) Pilot Study was a multicenter clinical trial designed to compare the feasibility and safety of TEE-guided cardioversion with conventional therapy for patients with atrial fibrillation. Of the 62 patients who underwent the TEE-guided approach, 56 (90%) successfully completed the TEE, and the cardioversion of 7 (13%) was postponed after an atrial thrombus was detected. Cardioversion was successfully performed in 38 (84%) of 45 patients, and no thromboembolic events occurred. Of the 64 patients assigned to conventional therapy, 28 (76%) of 37 had successful cardioversion. One patient had a peripheral embolic event. The mean time from enrollment to cardioversion was significantly shorter in the TEE-guided cardioversion group (0.6 vs 4.8 weeks, P , .01), and a trend existed toward more hemodynamic instability and bleeding in the conventional therapy group. Comment. This pilot study provides useful information on the impact of echocardiography on the management of atrial fibrillation and on the rate of postcardioversion stroke. When performed by experienced operators and if patients receive therapeutic anticoagulation before cardioversion, TEE-guided cardioversion appears to be associated with a very low risk of postcardioversion thromboembolism and possibly a lower rate of hemorrhagic complications than conventional therapy. Although the time to cardioversion was significantly shorter in the TEE-guided cardioversion group, its clinical significance and effect on patient outcome has yet to be determined. Data from this pilot study and from other investigators suggest that TEE-guided cardioversion is a safe and practical alternative to conventional therapy. The ASE recently funded the ACUTE investigators for a cost analysis of actual data for subjects randomly assigned to this pilot study. The Impact of Echocardiography on the Management of Patients with Suspected Mitral Valve Prolapse Heidenreich PA, Bear J, Browner W, Foster E. The Clinical Impact of Echocardiography on Antibiotic Prophylaxis Use in Patients with Suspected Mitral Valve Prolapse. Am J Med 1997;102:337-43. Mitral valve prolapse (MVP) occurs in 4% of the population and is associated with a small but significant risk of endocarditis and other cardiac problems. Echocardiography is considered the diagnostic test of choice and is used to identify patients at high risk for endocarditis who would benefit from antibiotic prophylaxis. However, whether echocardiography actu-
Journal of the American Society of Echocardiography Volume 11 Number 9
ally provides new information and affects the management of patients with MVP is uncertain. Heidenreich and colleagues evaluated 147 consecutive echocardiographic studies performed to rule out MVP to determine the frequency of the following: (1) provision of new information by echocardiograph that could influence management decisions and (2) actual changes in management in response to that information. Prophylaxis was considered to be indicated if MVP with at least mild mitral regurgitation or thickening of the mitral valve leaflets was detected. Thirty-six (25%) of 147 subjects had a clinical diagnosis of MVP; 23 were using antibiotic prophylaxis. Nineteen (52%) of these 36 subjects did not have MVP by echocardiographic criteria. Based on echocardiography a change in antibiotic prophylaxis was indicated in 20 (14%) subjects (14 should discontinue prophylaxis and 6 should start prophylaxis). However, only 4 (20%) of 20 subjects actually had a change in their prophylaxis regimen (3 started prophylaxis and 1 stopped prophylaxis). The authors conclude that whereas echocardiography frequently altered the patients’ diagnosis, its results rarely led to changes in the antibiotic prophylaxis management of patients with MVP. Comment. This study highlights the difference between the ability of a diagnostic test to provide new information and the impact of that test on the care of a patient. In this study echocardiography definitely provided new information: MVP was ruled out in more than one half of subjects whose diagnosis of MVP was based on clinical criteria, and a change in management was indicated for 14% of subjects. However, the findings that the management of MVP changed very little despite this information suggest that the impact of echocardiography on clinical care is small. This study also notes the distinction between the process of care and the outcome of care. The process of care includes what is actually done in the care of a patient (the procedures and tests performed, the diagnoses made, the therapies given), whereas the outcome of care includes measures of patient health (health status, satisfaction, morbidity, mortality). This study evaluated the impact of echocardiography on the diagnosis of MVP. The assumption that the improvement in this process measure will lead to improved patient outcome is reasonable given the benefit of antibiotic prophylaxis in the prevention of endocarditis, but it was not shown in this study of current clinical practice. This study demonstrates that the value of echocardiography lies not only in its diagnostic capabilities but also in how the data obtained are applied to patient care.
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Role of Echocardiography in Patients with Staphylococcus aureus Bacteremia Fowler VG, Li J, Corey GR, Boley J, Marr KA, Gopal AK, Kong LK, Gottlieb G, Donovan CL, Sexton DJ, Ryan T. Role of Echocardiography in Evaluation of Patients with Staphylococcus aureus Bacteremia: Experience in 103 Patients. J Am Coll Cardiol 1997;30:1072-8. Patients with Staphylococcus aureus bacteremia are at risk of infective endocarditis, with a reported incidence ranging from 5% to 64%. Because the ability of TTE to detect vegetations (the most common echocardiographic evidence of endocarditis) is low, many physicians advocate the use of TEE in patients with suspected endocarditis. Fowler and colleagues performed TTE and TEE in 103 subjects with staphylococcal bacteremia to determine their role in the diagnosis and prognosis of infective endocarditis. The Duke criteria were used as the gold standard for the diagnosis of endocarditis. The criteria provide a validated scheme incorporating major (persistently positive blood cultures, valvular abnormalities on echocardiography) and minor (fever, predisposing valvular disease, intravenous drug use) criteria. In this study definite endocarditis was present in 26 subjects (25%). The sensitivity and specificity of TTE was 32% and 100%, respectively. For TEE, the sensitivity and specificity were 100% and 99% (1 false-positive result), respectively. Predictably, the higher sensitivity of TEE was largely the result of its ability to detect small vegetations. Staphylococcal infection was cured with similar frequency in subjects with and without endocarditis, although subjects with endocarditis (15% vs 1.3%) were more likely to die of staphylococcal sepsis. The authors conclude that TEE plays an essential role in the diagnosis of endocarditis in patients with staphylococcal bacteremia and in the detection of associated complications. Comment. This study examines the sensitivity (ability to detect the presence of vegetations) and specificity (ability to exclude the presence of vegetations) of echocardiography in patients with suspected endocarditis. When evaluating a diagnostic test such as echocardiography, the choice of an appropriate “gold standard” for comparison is important. The Duke criteria used in this study are a well-recognized method to diagnose endocarditis, although they also have their own sensitivity and specificity when compared with a “true” gold standard (eg, microorganism demonstrated by culture or histologic study in a vegetation). Although the high sensitivity and specificity of TEE are not surprising, the impact of TEE on the diagnosis and management of all patients with suspected endo-
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carditis is unclear. In many cases the diagnosis of endocarditis can be made without the use of echocardiography, or the necessary data can be obtained from TTE rather than TEE. In addition, patients are often treated for endocarditis even in the absence of a significantly abnormal echocardiogram. In this study TEE was superior to TTE in detecting complications of endocarditis, such as aortic root abscess or valve perforation. Although the detection of these complications by TEE is not linked specifically to changes in clinical events or general health, it is reasonable to assume that such a discovery would help improve patient outcomes. However, further work is needed to determine whether echocardiography should be performed in all patients with S. aureus bacteremia or only in selected patients at high risk for complications, such as those with persistent fever or bacteremia. ACC/AHA Guidelines for the Clinical Application of Echocardiography Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davidson TW, Davis JL, Douglas PS, Gillam LD, Lewis RP, Pearlman AS, Philbrick JT, Shah PM, Williams RG, Ritchie JL, Eagle KA, Gardner TJ, Garson A, Gibbons RJ, O’Rourke RA, Ryan TJ. ACC/AHA Guidelines for the Clinical Application of Echocardiography. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography) [executive summary]. J Am Coll Cardiol 1997;29:862-879. and Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davidson TW, Davis JL, Douglas PS, Gillam LD, Lewis RP, Pearlman AS, Philbrick JT, Shah PM, Williams RG. ACC/AHA Guidelines for the Clinical Application of Echocardiography. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography) [complete text]. Circulation 1997;95:1686-1744. These guidelines, written by an ad hoc group composed of experts in the field of echocardiography, senior clinical cardiologists, and generalists, were developed after an extensive review of the literature. Following the classification used in other ACC/AHA guidelines, the recommendations on the use of echocardiography were divided into Class I (evidence or agreement on usefulness/efficacy), Class II (conflicting or inadequate evidence or opinion on usefulness/ efficacy), and Class III (evidence or agreement that echocardiography is not useful/effective).
The guidelines addressed the use of echocardiography in both specific cardiovascular diseases (eg, valvular stenosis/regurgitation or cardiomyopathy) and in the evaluation of common cardiovascular symptoms or signs (eg, chest pain or syncope). For example, the indications for echocardiography in patients with MVP include the assessment of hemodynamic severity and leaflet morphology in patients with clinical signs of MVP (Class I), the exclusion of MVP in patients with a diagnosis of MVP but who do not have clinical evidence of it (Class II), and the exclusion of MVP in patients with ill-defined symptoms but without clinical or physical findings consistent for MVP (Class III). Comment. One of the goals of clinical practice guidelines is to succinctly and practically summarize current knowledge on the effectiveness of a diagnostic test or therapy. With a test as widely used as echocardiography, practice guidelines offer an opportunity to explicitly state when an echocardiographic study would likely provide clinically meaningful information. Guidelines are often a consensus statement agreed on by an expert panel after careful review of the available literature. They are designed to be evidence-based rather than empirical—to rely on studies that demonstrate a benefit of the diagnostic test or therapy on patient outcome. The assumption is that guidelines will improve the overall quality of care, while promoting a more efficient use of resources. However, the actual effect of guidelines on changing physician practice patterns is often difficult to detect and has not been well studied. Because it is difficult to directly measure the effect of a diagnostic test on patient outcomes, evaluating the clinical utility of a diagnostic test is much more difficult than evaluating the clinical utility of a therapeutic intervention. Thus the guidelines for echocardiography focus on data regarding test sensitivity, specificity, and diagnostic accuracy, with the assumption that maximizing test efficiency will improve patient outcomes. Whereas outcomes data are incorporated whenever possible, little is available for most diagnostic tests, including echocardiography. As more studies become available that evaluate the impact of echocardiography on patient outcomes, they will be incorporated into practice guidelines and offer a link between the performance of an echocardiogram and improvement in patient health.
REFERENCES 1. Donabedian A. The quality of care. How can it be assessed? JAMA 1988;260:1743-8. 2. Green J, Wintfeld N. Report cards on cardiac surgeons. Assessing New York State’s approach. N Engl J Med 1995;332: 1229-32. 3. Epstein AM. The outcomes movement—will it get us where we want to go? N Engl J Med 1990;323:266-70.