1. Gilman JK, Jalal S, Naccarelli GV. Predicting and preventing sudden death from cardiac cause. Circulation 1994;90:1083–1092. 2. Kuller L, Lilienfeld A, Fisher R. An epidemiological study of sudden and unexpected deaths in adults. Medicine 1967;46:341–361. 3. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. N Engl J Med 1993;329:1677–1683. 4. Tanaka Y, Ohtomo N, Terachi S. Nonlinear time series analysis; the construction of a data analysis system “Memcalc.” Bull Fac Engin Hokkaido Univ 1992;160:11–23. 5. Spencer FA, Goldberg RJ, Becker RC, Gore JM. Seasonal distribution of acute myocardial infarction in the second National Registry of Myocardial Infarction. J Am Coll Cardiol 1998;31:1226 –1233. 6. Ornato JP, Peberdy MA, Chandra NC, Bush DE. Seasonal pattern of acute myocardial infarction in the National Registry of Myocardial Infarction. J Am Coll Cardiol 1996;28:1684 –1688. 7. Muller JE, Ludmer PL, Willich SN, Tofler GH, Aylmer G, Klangos I, Stone PH. Circadian variation in the frequency of sudden cardiac death. Circulation 1987;75:131–138. 8. Gnecchi-Ruscone T, Piccaluga E, Guzzetti S, Contini M, Montano N, Nicolis E. Morning and Monday: critical periods for the onset of acute myocardial infarction. The GISSI 2 Study experience. Eur Heart J 1994;15:7,882– 887. 9. Bayes de Luna A, Coumel P, Leclercq JF. Ambulatory sudden cardiac death: mechanisms of production of arrhythmia on the basis of data from 157 cases. Am Heart J 1989;117:1,151–159. 10. Olshausen KV, Witt T, Pop T, Treese N, Bethge KP, Meyer J. Sudden cardiac death while wearing a Holter monitor. Am J Cardiol 1991;67:381–386. 11. Pozzati A, Pancaldi LG, Di Pasquale G, Pinelli G, Bugiardini R. Transient sympathovagal imbalance triggers “ischemic” sudden death in patients undergoing electrocardiographic Holter monitoring. J Am Coll Cardiol 1996;27:847– 852. 12. Coumel P, Leclercq JF, Leenhardt A. Arrhythmias as predictors of sudden death. Am Heart J 1987;114:929 –937.
13. Schwartz PJ, Billman GE, Stone HL. Autonomic mechanisms in ventricular fibrillation induced by myocardial ischemia during exercise in dogs with healed myocardial infarction. An experimental preparation for sudden cardiac death. Circulation 1984;4:790 – 800. 14. Brodsky MA, Sato DA, Iseri LT, Wolff LJ, Allen BJ. Ventricular tachyarrhythmia associated with psychological stress. The role of the sympathetic nervous system. JAMA 1987;257:2064 –2067. 15. Caracciolo EA, Chaitman BR, Forman SA, Stone PH, Bourassa MG, Sopko G, Geller NL, Conti CR. Diabetics with coronary disease have a prevalence of asymptomatic ischemia during exercise treadmill testing and ambulatory ischemia monitoring similar to that of nondiabetic patients. An ACIP database study. ACIP Investigators. Asymptomatic Cardiac Ischemia Pilot Investigators. Circulation 1996;93:2097–2105. 16. Cabin HS, Roberts WC. Quantitative comparison of extent of coronary narrowing and size of healed myocardial infarct in 33 necropsy patients with clinically recognized and in 28 with clinically unrecognized (“silent”) previous acute myocardial infarction. Am J Cardiol 1982;50:677– 681. 17. Scheidt-Nave C, Barrett-Connor E, Wingard DL. Resting electrocardiographic abnormalities suggestive of asymptomatic ischemic heart disease associated with non-insulin-dependent diabetes mellitus in a defined population. Circulation 1990;81:899 –906. 18. Airaksinen KE, Huikuri HV. Antiarrhythmic effect of repeated coronary occlusion during balloon angioplasty. J Am Coll Cardiol 1997;29:1035–1038. 19. Cinca J, Warren M, Carreno A, Tresanchez M, Armadans L, Gomez P, Soler-Soler J. Changes in myocardial electrical impedance induced by coronary artery occlusion in pigs with and without preconditioning: correlation with local ST-segment potential and ventricular arrhythmias. Circulation 1997;96:3079 – 3086. 20. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124 –1136.
Usefulness of Pharmacologic Stress Echocardiography in a Chest Pain Center Andre´s Orlandini, MD, Enrique Tuero, MD, Ernesto Paolasso, Oscar Go´mez Vilamajo´, MD, and Rafael Dı´az, MD ccurate evaluation of patients with chest pain without electrocardiographic changes is difficult A because of the low specificity of clinical variables. 1– 4
Increasing interest has been focused on a diagnostic algorithm to rule out ischemic syndromes in these patients.5 The purpose of this study was to investigate the role of pharmacologic stress echocardiography in a diagnostic algorithm for patients with acute chest pain without electrocardiographic changes. •••
Consecutive patients presenting to the emergency room with acute chest pain were evaluated. Only patients without acute ischemic electrocardiographic changes (ST-T-segment elevation ⬎1 mm, ST-T depression ⬎1 mm, or acute T-wave inversion) were included in the study. All patients included were sent to the chest pain center where a diagnostic algorithm (Figure 1) that consisted of blood enzyme measures, serial electrocardiographic monitoring, and stress testing was followed. When 1 of these tests was positive, the algorithm was interrupted and the patient was admitted to the coronary care unit. If all of them were From the Instituto Cardiovascular de Rosario, Rosario, Argentina. Dr. Orlandini’s address is: Estudios Cardiologicos LatinoAmerica, Oron˜o 500 Rosario 2000, Argentina. E-mail:
[email protected]. Manuscript received February 9, 2000; revised manuscript received and accepted June 8, 2000. ©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 December 1, 2000
MD,
negative, the patient was discharged. Thirty-five day follow-up was performed to evaluate cardiac events. All patients were defined as having angina or atypical chest pain according to the emergency room doctor’s criterion. After admission, the patient was connected to permanent electrocardiographic monitoring to detect arrhythmia. When the patient had a new chest pain episode, an electrocardiogram was recorded to observe acute ischemic electrocardiographic changes. If life-threatening arrhythmia or acute ischemic electrocardiographic changes during a chest pain episode was observed, the patient was admitted to the coronary care unit. Creatine phosphokinase and creatine phosphokinase-MB isoenzyme or troponin T were measured on admission. If there was an increase of twice the normal range of creatine phosphokinase and of ⬎10% of creatine phosphokinase-MB, or troponin T was positive, the patient was admitted to the coronary care unit. Otherwise, a new measurement was obtained approximately 4 hours later, and, again, if there was an increase in any enzyme, the patient was admitted to the coronary care unit. If the patient had no ischemic electrocardiographic changes and no enzymatic increase, he or she was sent to the echocardiography laboratory to undergo pharmacologic stress echocardiography. Dipyridamole/atropine stress echocardiography was chosen as a firstline test because according to published data and our 0002-9149/00/$–see front matter PII S0002-9149(00)01211-X
1247
every 3 minutes)13 followed by atropine infusion (up to 1 mg in 4 minutes). Maximal symptom-limited exercise testing according to the modified Bruce protocol was performed in patients who were unable to undergo echocardiography. An exercise electrocardiographic test was considered abnormal or positive when it showed ST-segment downsloping depression or an elevation of ⱖ1 mm 0.08 second after the J point. Thirty-five-day follow-up data were obtained by personal interviews or by telephone. The clinical events recorded were the occurrence of cardiac death, nonfatal myocardial infarction, a revascularization procedure (percutaneous transluminal coronary angioplasty or coronary artery bypass surgery), and cineangiographic study. The patient was FIGURE 1. Diagnostic algorithm. CCU ⴝ coronary care unit; DIP ⴝ dipyridamole/ considered as having an event when he atropine stress echocardiography; ECG ⴝ electrocardiographic; ECHO LAB ⴝ or she had 1 of the events recorded. With echocardiography laboratory; EXE ⴝ exercise electrocardiographic test; DOB ⴝ dobutamine/atropine stress echocardiography. angiography, the patient was considered as having an event if coronary artery disease was proven during this study. experience, it is as accurate6 as dobutamine/atropine Results are reported as mean ⫾ SD. Univariate stress echocardiography and technically easier7 (with analysis was performed using Student’s t test for inat least a comparable prognostic capability8) and prob- terval data and the chi-square test for categorical data. ably safer.9 Among 655 patients referred to our institute for Two-dimensional echocardiography and 9-lead evaluation of acute chest pain, 453 had ischemic elecelectrocardiographic monitoring were performed in trocardiographic changes and were admitted to the combination with dipyridamole and atropine infusion coronary care unit (168 with acute myocardial infarc(0.56 mg/kg body weight over 4 minutes, followed by tion and 285 with unstable angina). The remaining 4 minutes of no dose, and then 0.28 mg/kg over 2 205 patients without acute ischemic electrocardiominutes [the cumulative dose was therefore 0.84 graphic changes were prospectively enrolled in the mg/kg during 10 minutes10], and finally atropine 1 mg study (52 [25%] with nonspecific electrocardiographic over 4 minutes11). Aminophyline (240 mg), which changes). promptly reverses the effect of dipyridamole, and an Chest pain was considered as angina in 85 patients intravenous  blocker were always available. Two- (41%) and as atypical chest pain in 120 patients dimensional echocardiograms were continuously re- (58%). The average age was 51 ⫾ 11 years, and most corded intermittently during and up to 10 minutes patients were men (143 of 205, 70%). Most patients after the dipyridamole/atropine infusion. A commer- had ⬍2 risk factors for coronary artery disease (156 of cially available, wide-angle, phased-array imaging 205, 76%) and 24 patients (12%) had previous corosystem (Hewlett-Packard Sonos 2500, Andover, Mas- nary artery disease. The mean time to the first availsachusetts) was used. able blood enzymatic measurement was 1 ⫾ 0.18 In the baseline studies, all standard echocardio- hour, and to the second one was 5 ⫾ 1.9 hour. Eleven graphic views were used when possible. The 16-seg- of 205 enrolled patients had an enzymatic increase or ment model of the left ventricle was used.12 During recurrent chest pain with electrocardiographic changes the test, new areas of abnormal motion were identified and were admitted to the coronary care unit. The in a qualitative manner on multiple views by moving remaining 196 patients were sent to the echocardiogthe ultrasound transducer through various positions. raphy laboratory to perform a stress echocardiography Wall motion was graded as normal, hypokinetic, aki- test (mean time 5.9 ⫾ 3.4 hours). All but 1 patient had netic, and dyskinetic. The echocardiograms were an- normal wall motion at rest. One patient with a history alyzed by 1 experienced observer and a positive test of inferior myocardial infarction and a Q wave in was defined as one showing transient asynergy of inferior leads on electrocardiography had inferior akicontraction that was absent on the baseline examina- nesia on the echocardiogram at rest. This abnormality tion. was considered not to be acute and the stress test was When the patient had contraindications for dipy- performed with normal results. ridamole infusion, a dobutamine infusion was adminThe tests performed were dipyridamole/atropine istered intravenously (with an infusion pump at in- stress echocardiography in 166 patients, dobutamine/ creasing doses of 5, 10, 20, and 40 mg/kg body weight atropine in 11 because of contraindications to dipyrid1248 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 86
DECEMBER 1, 2000
FIGURE 2. Algorithm results. Abbreviations as in Figure 1.
TABLE 1 Univariate Analysis Cardiovascular Events
Algorithm (⫺) Age Atypical chest pain ⬎2 risk factors Men
Yes
No
p Value
0/13 60 ⫾ 8 2/13 (15%) 6/13 (46%) 12/13 (92%)
184/191 (96%) 50 ⫾ 11 117/191 (61%) 43/191 (22%) 130/191 (68%)
0.0000 0.0016 0.0021 0.0861 0.1146
amole, and an exercise electrocardiographic test in 18 patients because of a poor acoustic window or refusal to perform a pharmacologic stress test. No severe adverse events were found in any of these tests. Results in 9 patients were positive for ischemia, in 5 with the dipyridamole/atropine stress echocardiography test and in 4 with exercise electrocardiographic testing. No positive results were found after dobutamine/ atropine stress echocardiography. All patients with positive results were admitted to the coronary care unit (Figure 2). The mean hospitalization period was reduced compared with the period in a historical group with the same clinical characteristics in our institution (6.6 ⫾ 3.2 vs 43 ⫾ 47 hours). All patients but 1 underwent 35-day follow-up (99.5%). Of the 20 patients with a positive algorithm, 13 had cardiovascular events in the follow-up period—5 had myocardial infarctions, 3 underwent percutaneous transluminal coronary angiography, and 5 underwent coronary artery bypass graft surgery—implying a positive predictive value of 65%. Of the 185 patients with a negative algorithm, none had cardiovascular events in the follow-up period, implying a negative predictive value of 100%. Univariate analysis showed that the best variable to separate patients
with from patients without risk of having cardiovascular events was the result of an algorithm followed by age and by the clinical characteristic of pain (Table 1). There was no difference with regard to sex. •••
In this study we tested the value of an early-diagnosing algorithm, which included pharmacologic stress echocardiography performed in the chest pain center. Our data showed that the negative algorithm had superlative negative predictive value for cardiac events in a 35-day follow-up period (i.e., if we have a negative algorithm we are sure that the patient has a very low risk of having cardiovascular events, and because of this result we can send this patient home). When the algorithm was positive, we had a positive predictive value of 65%. Nevertheless, of the 7 patients with a positive algorithm and no events, none underwent cineangiography. These patients were admitted to the coronary care unit and treated for unstable angina. After 48 hours of receiving traditional therapies and because the patients did not have a new episode of angina and were in good functional class, the referral doctor decided not to perform cineangiography. We considered these patients to have a false-positive result; however, because this could not be considered a true diagnosis, the positive predictive value was more accurate. Pharmacologic stress echocardiography or an exercise electrocardiographic test helped to derive this algorithm diagnosis in about half of the patients with positive results. A clinical classification based on chest pain characteristics showed a poor positive predictive value of 12% and a relative good negative predictive value of 98%. This negative predictive value looks good; nevertheless, in our opinion it is not enough, because it means that approximately 2 high-risk patients out of 100 seen in the emergency room will be inappropriately discharged home. BRIEF REPORTS
1249
We conclude that a stress echocardiographybased algorithm allows a fast stratification of patients at high or low risk of having cardiovascular events. Because of this, an early discharge is possible in patients with a negative result. 1. Karlson BW, Herlitz J, Wiklund O, Richter A, Hjalmarson A. Early prediction of acute myocardial infarction from clinical history, examination and electrocardiogram in the emergency room. Am J Cardiol 1991;68:171–175. 2. Cohen MG, Kervokian R, Boissonnet C, Higa CC, Mule MF, Principato MB, Bang JH, Villegas M, Belziti C, Cagide A. Ana´lisis de los recurso utilizados en el manejo del dolor precordial. Rev Argent Cardiol 1997;65:41–54. 3. Stark ME, Vacek JL. The initial electrocardiogram during admission for myocardial infarction. Arch Intern Med 1987;147:843– 846. 4. Lee TH, Rouan GW, Weisberg MC, Brand DA, Acampora D, Stasiulewicz C, Walshon J, Terranova G, Gottlieb L, Goldstein-Wayne B, Copen D, Daley K, Brandt AA, Mellors J, Jakubowski R, Cook F, Goldman L. Clinical characteristics and natural history of patients with acute myocardial infarction sent home from the emergency room. Am J Cardiol 1987;60:219 –224. 5. Graff L, Joseph T, Andelman R, Bahr R, DeHart D, Espinosa J, Gibler B, Hoekstra J, Mathers-Dunbar L, Ornato JP, Page J, Severance H. American College of Emergency Physicians information paper: a report from the short-term observation services section. Am J Cardiol 1995;76:1036 –1039. 6. Picano E, Bedetti G, Varga A, Cseh E. The comparable diagnostic accuracies of dobutamine-stress and dipyridamole-stress echocardiographies: a meta-analysis. Coron Artery Dis 2000;11:151–159. 7. Beleslin BD, Ostojic M, Stepanovic J, Djordjevic-Dikic A, Stojkovic S, Nedeljkovic M, Stankovic G, Petrasinovic Z, Gojkovic L, Vasiljevic-Pokrajcic Z.
Stress echocardiography in the detection of myocardial ischemia. Head-to-head comparison of exercise, dobutamine, and dipyridamole tests. Circulation 1994; 90:1168 –1176. 8. Pingitore A, Picano E, Varga A, Gigli G, Cortigiani L, Previtali M, Minardi G, Colosso MQ, Lowenstein J, Mathias W Jr, Landi P. Prognostic value of pharmacological stress echocardiography in patients with known or suspected coronary artery disease: a prospective, large-scale, multicenter, head-to-head comparison between dipyridamole and dobutamine test. Echo-Persantine International Cooperative (EPIC) and Echo-Dobutamine International Cooperative (EDIC) Study Groups. J Am Coll Cardiol 1999;34:1769 –1777 9. Orlandini AD, Tuero EI, Diaz R, Vilamajo OA, Paolasso EA. Acute cardiac rupture during dobutamine-atropine echocardiography stress test. J Am Soc Echo 2000;13:152–153. 10. Picano E, Lattanzi F, Masini M, Distante A, L’Abatte A. High dose dipyridamole echocardiography test in effort angina pectoris. J Am Coll Cardiol 1986;8:858 – 854. 11. Pingitore A, Picano E, Colosso MQ, Reisenhofer B, Gigli G, Lucarini AR, Petix N, Previtali M, Bigi R, Chiaranda G, Minardi G, de Alcantara M, Lowestein J, Sclavo MG, Palmieri C, Galati A, Seveso G, Heyman J, Mathias W Jr, Casazza F, Sicari R, Raciti M, Landi P, Marzilli M. The atropine factor in pharmacologic stress echocardiography. Echo Persantine (EPIC) and Echo Dobutamine International Cooperative (EDIC) Study groups. J Am Coll Cardiol 1996;27:1164 –1170. 12. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feingenbaum H, Gutgesell H, Reichek N, Shan D, Schinittger I, Silverman AH, Tajik AJ. American Society of Echocardiography Committee on standards, subcommittee on quantitation of two-dimensional echocardiograms: recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echo 1989;2:358 –367. 13. McNeill AJ, Fioretti PM, El-Said SM, Salustri A, Forster T, Roelandt JR. Enhanced sensitivity for detection of coronary artery disease by addition of atropine to dobutamine stress echocardiography. Am J Cardiol 1992;70:41– 46.
Lipid Treatment Goals Achieved in Patients Treated With Statin Drugs in Norwegian General Practice Arne Svilaas,
MD,
Knut Risberg,
MD,
Magne Thoresen,
he primary objective of this study was to determine to what extent the new European guidelines T for lipid values were achieved in general practice in 1
patients treated with a statin. Secondly, we wanted to evaluate the risk profile of these patients, and their lipid values before and during statin therapy. Our tertiary objective was to compare lipid profiles and patterns of statin prescription in primary and secondary prevention of atherosclerotic disease. •••
Eligible patients were men and women who had already received statin monotherapy as a lipid-lowering medication, independent of the indication for this prescription and without secondary causes of hypercholesterolemia. The survey was conducted in 412 general practices between January and August 1999. A total of 3,935 patients were examined (mean age 63 years; 43% were women) (Table 1). Data were recorded in all Norwegian counties except the most nordic, Finnmark. The areas were randomly chosen, and as many physicians as possible were recruited. Each participating physician had to examine 10 patients. Consecutive patients were interFrom the Lipid Clinic, Medical Department, Rikshospitalet, Oslo, Norway. This study was supported by grants from Merck Sharp & Dohme, Drammen, Norway. Dr. Svilaas’ address is: Nymoens Torg 9, N-3611 Kongsberg, Norway. E-mail:
[email protected]. Manuscript received February 15, 2000; revised manuscript received and accepted June 5, 2000.
1250
©2000 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 86 December 1, 2000
MSc,
and Leiv Ose,
MD, PhD
viewed and examined when they attended their regular check-ups, without any extraordinary recall. Before study entry, physicians were informed about the new European guidelines from 1998.1 For each patient, gender, age, family history of premature atherosclerotic disease in first-degree blood relatives (men ⬍55 and women ⬍65 years of age), smoking history, reason for statin therapy, personal history of hypertension and diabetes mellitus, and actual blood pressure value were recorded. Fasting serum lipid levels were registered before and during statin administration. Physicians used their ordinary external laboratories. Low-density lipoprotein (LDL) cholesterol was calculated by the Friedewald formula.2 Information regarding the type, dosage, and the year of initiation of the actual statin treatment were also obtained. The continuous variables are described by mean and SD (median and range). The proportion of patients who achieved the treatment goals in different groups is depicted in Figure 1 given with 95% confidence intervals. Patients who began statin treatment before 1995 (485 observations) had an average baseline total cholesterol level of 9.9 mmol/L (382 mg/dl) with primary prevention versus 8.3 mmol/L (320 mg/dl) with secondary prevention, compared with 8.6 mmol/L (332 mg/dl) versus 7.4 mmol/L (286 mg/dl) in patients who underwent treatment at or after 1995 (3,416 observations). Lipid values before and during statin administration are listed in Table 2. We found a 10% increase in 0002-9149/00/$–see front matter PII S0002-9149(00)01212-1