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Misdiagnosis of atrial fibrillation and its clinical consequences
Arrhythmias
Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)? Methods: In AFFIRM, 4060 patients (mean age 70 years) were randomly assigned either to rhythm or rate control. Survival data were analyzed, along with the resources used after randomization. Resources consisted of hospitalization days, cardiac procedures, cardioversion, emergency room visits, and medications. Costs were estimated by multiplying the number of each resource used by its unit cost from the perspective of a third-party payer and expressed in 2002 dollars. Results: The mean survival time was 4.6 years in the rhythm-control arm and 4.7 years in the rate-control arm. During a mean follow-up of 3.5 years, costs in the rhythmcontrol and rate-control arms were $25,623 and $20,546, respectively. The incremental cost of rhythm control of $5077 was attributable to more hospitalizations, cardioversions, and emergency room visits. Conclusions: Compared to a rate-control strategy, a rhythmcontrol strategy does not improve survival and is more costly. Therefore, rate control is the more cost-effective strategy for management of AF. Perspective: It should be kept in mind that these results apply only to patients similar to the AFFIRM population (i.e., elderly patients, generally with mild or no symptoms). Furthermore, this study did not include quality of life (QOL) in the cost-effectiveness analysis. In younger patients whose QOL is severely impaired by AF, the benefits of rhythm control are obvious, and adjustment of cost-effectiveness for QOL might well demonstrate an advantage of rhythm control over rate control. FM
Abstracts Comparative Effects of Antiplatelet, Anticoagulant, or Combined Therapy in Patients With Valvular and Nonvalvular Atrial Fibrillation Perez-Gomez F, Alegria E, Berjon J, et al. J Am Coll Cardiol 2004;44:1557– 66. Study Question: How effective are an antiplatelet agent (triflusal) and an anticoagulant (acenocumerol), alone or in combination, for preventing thromboembolic events in patients with atrial fibrillation (AF)? Methods: This was an unblinded, randomized comparison of triflusal and acenocumerol in 1209 patients with AF and risk factors for stroke. High-risk patients (n⫽495) with mitral stenosis or prior stroke were randomized either to acenocumerol with a target international normalized ratio (INR) of 2–3, or to a combination of triflusal, 600 mg daily plus acenocumerol with a target INR of 1.4 –2.4. A third arm in intermediate-risk patients (n⫽714) was triflusal, 600 mg daily. The mean duration of follow-up was 2.7 years. Primary end points were vascular death, transient ischemic attack or nonfatal stroke/embolism. Results: Primary end point events were less common with combined therapy than with acenocumerol in the intermediate-risk group (hazard ratio [HR] 0.33) and in the highrisk group (HR 0.5). Compared with individual therapy, combined therapy was associated with a 61% lower risk of primary end point events plus severe bleeding. There was no difference in bleeding events between combined therapy and acenocumerol. Conclusions: Combined therapy with acenocumerol plus triflusal is associated with fewer thromboembolic events than acenocumerol by itself in patients with AF, and does not increase the risk of hemorrhagic complications. Perspective: This is the first study to show that an antiplatelet agent lowers the risk of thromboembolism from AF when added to an anticoagulant. Neither acenocumerol nor triflusal is available in the U.S. Acenocumerol is very similar to warfarin, but triflusal causes less bleeding than aspirin. Therefore, it is unclear whether the results apply to a warfarin/aspirin combination. FM
Misdiagnosis of Atrial Fibrillation and Its Clinical Consequences Bogun F, Anh D, Kalahasty G, et al. Am J Med 2004;117:636 – 42. Study Question: How often do computer algorithms incorrectly diagnose atrial fibrillation (AF), and what is the clinical impact of the computer errors? Methods: Two electrophysiologists reviewed 2298 electrocardiograms (ECGs) (from 1085 patients) with a preliminary computer-generated diagnosis of AF. The ECGs were over-read by a cardiologist, with a 2–5-day lag between the day the ECG was performed and the time the final interpretation was available in the hospital computer system. When the computer-generated diagnosis of AF was incorrect, a chart review was performed to determine whether the incorrect diagnosis had resulted in any unnecessary testing or therapy. Results: The computer-generated diagnosis of AF was incorrect in 382 patients (mean age 74 years) and in 19% of all ECGs. The actual diagnosis most commonly was sinus rhythm with premature beats or artifact. In 39 of the 382
Cost-Effectiveness of Rhythm Versus Rate Control in Atrial Fibrillation Marshall DA, Levy AR, Vidaillet H, et al. Ann Intern Med 2004; 141:653– 61. Study Question: How does the cost of a rhythm-control strategy compare with that of a rate-control strategy in patients with atrial fibrillation (AF) enrolled in the Atrial
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Epidemiology and Prognostic Implications of Syncope in Young Competing Athletes
patients (10%), the incorrect preliminary diagnosis of AF triggered additional testing, consultations, or treatment with anticoagulants or antiarrhythmic agents. The inappropriate management was not affected by a correct rhythm diagnosis in the final ECG interpretation. Conclusions: A computer-generated diagnosis of AF often is incorrect. Failure of treating physicians to identify the incorrect diagnosis of AF may lead to unnecessary testing and treatment with potentially harmful medications. Perspective: This study exposes a problem with ECG interpretation that exists at many medical centers—there often is lag of ⱖ2 days between the time an ECG is first performed and the time that a final interpretation becomes available. Given the frequency with which computer-generated rhythm diagnoses are incorrect, one is left wondering whether the preliminary computer interpretation does more harm than good. FM
Colivicchi F, Ammirati F, Santini M. Eur Heart J 2004;25: 1749 –53. Study Question: What is the prevalence and prognostic significance of syncope in young athletes? Methods: Cardiovascular evaluation was performed in 7568 athletes with a mean age of 16 years. Information was obtained on the incidence of syncope before evaluation. Patients with structural heart disease were disqualified from competition. No pharmacologic therapy was used to prevent vasodepressor syncope. The mean duration of follow-up was 6.4 years. Results: A mean of 1.3 episodes of syncope had occurred during the 5 years before evaluation in 6% of individuals. Eighty-seven percent of syncopal episodes were unrelated to exercise, 12% occurred postexercise, and 1% occurred during exercise. The history was consistent with neurocardiogenic syncope in all patients, with syncope unrelated to exercise, and with postural hypotension in all patients with postexercise syncope. Among the 6 individuals with syncope during exercise, 1 had hypertrophic cardiomyopathy, 1 had idiopathic ventricular tachycardia, and 4 were believed to have neurocardiogenic syncope. The recurrence rate of syncope was approximately 20% at 10 years of follow-up in individuals with nonexertional and postexertional syncope, and there were no major cardiac events. Conclusions: Syncope in young athletes is most commonly neurocardiogenic in etiology, and participation in athletic events is safe as long as structural heart disease has been ruled out. Perspective: This large study provides reassuring data indicating that syncope in young athletes is usually neurocardiogenic. Even when syncope occurs during or shortly after exercise, the most common mechanism is neurocardiogenic, in which case the prognosis is benign and competition can be continued safely. However, more serious causes of syncope must be ruled out, particularly if syncope has occurred during exercise. FM
A Randomized, Double-Blind, Placebo-Controlled Study of Permanent Cardiac Pacing for the Treatment of Recurrent Tilt-Induced Vasovagal Syncope. The Vasovagal Syncope and Pacing Trial (SYNPACE) Raviele A, Giada F, Menozzi, et al. Eur Heart J 2004;25:1741– 8. Study Question: Does treatment with a dual-chamber pacemaker (DCP) prevent vasovagal syncope (VVS)? Methods: A DCP was implanted in 29 patients (mean age 53 years) with a history of frequent episodes of VVS and with a positive head-up tilt test demonstrating a cardioinhibitory component. The patients were randomly assigned in double-blind fashion to having the DCP programmed on (ON group) or off (OFF group). The primary end point of the study was the time to first recurrence of VVS. Results: During a median follow-up of 715 days, VVS recurred in 45% of patients, with no difference between the ON and OFF groups. The time to first recurrence of VSS was longer in the ON group (97 days) than in the OFF group (20 days), but the difference was not statistically significant. Conclusions: Treatment with a DCP does not prevent VVS. Perspective: It is tempting to recommend a DCP for patients with a severe, cardioinhibitory type of VVS who have not responded to behavioral or pharmacologic therapies, particularly because several studies have demonstrated a benefit from pacing. However, the present study and the only other study that also assessed the efficacy of pacing in a double-blind fashion demonstrate that if there is any benefit from a DCP, it is attributable to a placebo effect. The lack of efficacy of pacing is explained by the fact that VVS almost always has a prominent vasodepressor component, even in patients who have several seconds of asystole during syncope. FM
Microvolt T-Wave Alternans Distinguishes Between Patients Likely and Patients Not Likely to Benefit From Implanted Cardiac Defibrillator Therapy. A Solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II Conundrum Bloomfield DM, Steinman RC, Namerow PB, et al. Circulation 2004;110:1885–9. Study Question: How useful is microvolt T-wave alternans (MTWA) as a risk-stratifier in MADIT-II–like patients? Methods: An MTWA exercise test was performed in 177 patients (mean age 61 years) with prior myocardial infarction and an ejection fraction ⱕ0.30 who were in sinus rhythm. The MTWA tests that were either positive or inde-
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Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)? Methods: In AFFIRM, 4060 patients (mean age 70 years) were randomly assigned either to rhythm or rate control. Survival data were analyzed, along with the resources used after randomization. Resources consisted of hospitalization days, cardiac procedures, cardioversion, emergency room visits, and medications. Costs were estimated by multiplying the number of each resource used by its unit cost from the perspective of a third-party payer and expressed in 2002 dollars. Results: The mean survival time was 4.6 years in the rhythm-control arm and 4.7 years in the rate-control arm. During a mean follow-up of 3.5 years, costs in the rhythmcontrol and rate-control arms were $25,623 and $20,546, respectively. The incremental cost of rhythm control of $5077 was attributable to more hospitalizations, cardioversions, and emergency room visits. Conclusions: Compared to a rate-control strategy, a rhythmcontrol strategy does not improve survival and is more costly. Therefore, rate control is the more cost-effective strategy for management of AF. Perspective: It should be kept in mind that these results apply only to patients similar to the AFFIRM population (i.e., elderly patients, generally with mild or no symptoms). Furthermore, this study did not include quality of life (QOL) in the cost-effectiveness analysis. In younger patients whose QOL is severely impaired by AF, the benefits of rhythm control are obvious, and adjustment of cost-effectiveness for QOL might well demonstrate an advantage of rhythm control over rate control. FM
Abstracts Comparative Effects of Antiplatelet, Anticoagulant, or Combined Therapy in Patients With Valvular and Nonvalvular Atrial Fibrillation Perez-Gomez F, Alegria E, Berjon J, et al. J Am Coll Cardiol 2004;44:1557– 66. Study Question: How effective are an antiplatelet agent (triflusal) and an anticoagulant (acenocumerol), alone or in combination, for preventing thromboembolic events in patients with atrial fibrillation (AF)? Methods: This was an unblinded, randomized comparison of triflusal and acenocumerol in 1209 patients with AF and risk factors for stroke. High-risk patients (n⫽495) with mitral stenosis or prior stroke were randomized either to acenocumerol with a target international normalized ratio (INR) of 2–3, or to a combination of triflusal, 600 mg daily plus acenocumerol with a target INR of 1.4 –2.4. A third arm in intermediate-risk patients (n⫽714) was triflusal, 600 mg daily. The mean duration of follow-up was 2.7 years. Primary end points were vascular death, transient ischemic attack or nonfatal stroke/embolism. Results: Primary end point events were less common with combined therapy than with acenocumerol in the intermediate-risk group (hazard ratio [HR] 0.33) and in the highrisk group (HR 0.5). Compared with individual therapy, combined therapy was associated with a 61% lower risk of primary end point events plus severe bleeding. There was no difference in bleeding events between combined therapy and acenocumerol. Conclusions: Combined therapy with acenocumerol plus triflusal is associated with fewer thromboembolic events than acenocumerol by itself in patients with AF, and does not increase the risk of hemorrhagic complications. Perspective: This is the first study to show that an antiplatelet agent lowers the risk of thromboembolism from AF when added to an anticoagulant. Neither acenocumerol nor triflusal is available in the U.S. Acenocumerol is very similar to warfarin, but triflusal causes less bleeding than aspirin. Therefore, it is unclear whether the results apply to a warfarin/aspirin combination. FM
Misdiagnosis of Atrial Fibrillation and Its Clinical Consequences Bogun F, Anh D, Kalahasty G, et al. Am J Med 2004;117:636 – 42. Study Question: How often do computer algorithms incorrectly diagnose atrial fibrillation (AF), and what is the clinical impact of the computer errors? Methods: Two electrophysiologists reviewed 2298 electrocardiograms (ECGs) (from 1085 patients) with a preliminary computer-generated diagnosis of AF. The ECGs were over-read by a cardiologist, with a 2–5-day lag between the day the ECG was performed and the time the final interpretation was available in the hospital computer system. When the computer-generated diagnosis of AF was incorrect, a chart review was performed to determine whether the incorrect diagnosis had resulted in any unnecessary testing or therapy. Results: The computer-generated diagnosis of AF was incorrect in 382 patients (mean age 74 years) and in 19% of all ECGs. The actual diagnosis most commonly was sinus rhythm with premature beats or artifact. In 39 of the 382
Cost-Effectiveness of Rhythm Versus Rate Control in Atrial Fibrillation Marshall DA, Levy AR, Vidaillet H, et al. Ann Intern Med 2004; 141:653– 61. Study Question: How does the cost of a rhythm-control strategy compare with that of a rate-control strategy in patients with atrial fibrillation (AF) enrolled in the Atrial
ACC CURRENT JOURNAL REVIEW February 2005
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Epidemiology and Prognostic Implications of Syncope in Young Competing Athletes
patients (10%), the incorrect preliminary diagnosis of AF triggered additional testing, consultations, or treatment with anticoagulants or antiarrhythmic agents. The inappropriate management was not affected by a correct rhythm diagnosis in the final ECG interpretation. Conclusions: A computer-generated diagnosis of AF often is incorrect. Failure of treating physicians to identify the incorrect diagnosis of AF may lead to unnecessary testing and treatment with potentially harmful medications. Perspective: This study exposes a problem with ECG interpretation that exists at many medical centers—there often is lag of ⱖ2 days between the time an ECG is first performed and the time that a final interpretation becomes available. Given the frequency with which computer-generated rhythm diagnoses are incorrect, one is left wondering whether the preliminary computer interpretation does more harm than good. FM
Colivicchi F, Ammirati F, Santini M. Eur Heart J 2004;25: 1749 –53. Study Question: What is the prevalence and prognostic significance of syncope in young athletes? Methods: Cardiovascular evaluation was performed in 7568 athletes with a mean age of 16 years. Information was obtained on the incidence of syncope before evaluation. Patients with structural heart disease were disqualified from competition. No pharmacologic therapy was used to prevent vasodepressor syncope. The mean duration of follow-up was 6.4 years. Results: A mean of 1.3 episodes of syncope had occurred during the 5 years before evaluation in 6% of individuals. Eighty-seven percent of syncopal episodes were unrelated to exercise, 12% occurred postexercise, and 1% occurred during exercise. The history was consistent with neurocardiogenic syncope in all patients, with syncope unrelated to exercise, and with postural hypotension in all patients with postexercise syncope. Among the 6 individuals with syncope during exercise, 1 had hypertrophic cardiomyopathy, 1 had idiopathic ventricular tachycardia, and 4 were believed to have neurocardiogenic syncope. The recurrence rate of syncope was approximately 20% at 10 years of follow-up in individuals with nonexertional and postexertional syncope, and there were no major cardiac events. Conclusions: Syncope in young athletes is most commonly neurocardiogenic in etiology, and participation in athletic events is safe as long as structural heart disease has been ruled out. Perspective: This large study provides reassuring data indicating that syncope in young athletes is usually neurocardiogenic. Even when syncope occurs during or shortly after exercise, the most common mechanism is neurocardiogenic, in which case the prognosis is benign and competition can be continued safely. However, more serious causes of syncope must be ruled out, particularly if syncope has occurred during exercise. FM
A Randomized, Double-Blind, Placebo-Controlled Study of Permanent Cardiac Pacing for the Treatment of Recurrent Tilt-Induced Vasovagal Syncope. The Vasovagal Syncope and Pacing Trial (SYNPACE) Raviele A, Giada F, Menozzi, et al. Eur Heart J 2004;25:1741– 8. Study Question: Does treatment with a dual-chamber pacemaker (DCP) prevent vasovagal syncope (VVS)? Methods: A DCP was implanted in 29 patients (mean age 53 years) with a history of frequent episodes of VVS and with a positive head-up tilt test demonstrating a cardioinhibitory component. The patients were randomly assigned in double-blind fashion to having the DCP programmed on (ON group) or off (OFF group). The primary end point of the study was the time to first recurrence of VVS. Results: During a median follow-up of 715 days, VVS recurred in 45% of patients, with no difference between the ON and OFF groups. The time to first recurrence of VSS was longer in the ON group (97 days) than in the OFF group (20 days), but the difference was not statistically significant. Conclusions: Treatment with a DCP does not prevent VVS. Perspective: It is tempting to recommend a DCP for patients with a severe, cardioinhibitory type of VVS who have not responded to behavioral or pharmacologic therapies, particularly because several studies have demonstrated a benefit from pacing. However, the present study and the only other study that also assessed the efficacy of pacing in a double-blind fashion demonstrate that if there is any benefit from a DCP, it is attributable to a placebo effect. The lack of efficacy of pacing is explained by the fact that VVS almost always has a prominent vasodepressor component, even in patients who have several seconds of asystole during syncope. FM
Microvolt T-Wave Alternans Distinguishes Between Patients Likely and Patients Not Likely to Benefit From Implanted Cardiac Defibrillator Therapy. A Solution to the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II Conundrum Bloomfield DM, Steinman RC, Namerow PB, et al. Circulation 2004;110:1885–9. Study Question: How useful is microvolt T-wave alternans (MTWA) as a risk-stratifier in MADIT-II–like patients? Methods: An MTWA exercise test was performed in 177 patients (mean age 61 years) with prior myocardial infarction and an ejection fraction ⱕ0.30 who were in sinus rhythm. The MTWA tests that were either positive or inde-
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