- Email: [email protected]
Safety of ibuprofen for acute myocardial infarction pericarditis
896
LETTERS
were done during the first month: clinical (pain, pericardial rub], echocardiographic (M-mode and Z-dimensional echocardioeraphy] and biologic (sedimentation, fib&emia and C reactive-protein). The initial evaluation was done before the 36th hour after the onset of the pain, and the others on days 5,10 and 30. Pericarditis wasdefined by the presence of echocardiographic PE associatedwithorwithoutclinicalsymptoms:group A [n = 151, P- (without pericarditisl and group B (n = 211P% (with pericarditis]. Then, group B was randomly allocated to nonsteroidtreatment(indomethacin,15Omg,3times daily for 10 days) or no nonsteroid treatment: Bl (n = lo], nonsteroid treatment +, B2 (n = 111,nonsteriod treatment -. Our results showed: Pericarditiswasfrequentlynotedin58% of cases(2lof36)andPEwasobservedin19of24 (P+]. PE was detected at the first echocardiographic examination [l2 of 191,was usually small or moderate (16 of 191. but never showed bad hemodynamic tolerance. Pericarditis was associated with higher peak creatinine kinase level, yet not significant (P+: 1,709 f 1,051; P-: 1,126 f 878 LB; difference not significant] and, conversely, with a significantly higher biologic syndrome (sedimentation:42f17~~76&35mm/hour,p <0.05;fibrinemia:6.3 f 22~~7.2 f 1.6g/liter, p <0.02; C reactive protein: 0.043 f 0.030 vs 0.105 f 0.068 UI, p
l.KaplanK, DavisonR,ParkerM,PrzybylekJ,Light A, Bresnahan D, kibner H, Talano J. Frequency of pericardial effusion as determined by m-mode echocardiography in acute myocardial infarction. Am J Cardiol 1985;55:335-337. 2. Roeske WR, Savage RM, O’Rourke RA, Bloor CM. Chnicopathologic correlations in patients after myocardial infarction. Circulation 1981;63:3645.
LATETHROMBOLYSIS: CONTROLLED CLINICAL TRIALOVERDUE Shapiro et al1demonstrate the apparent safety and possible efficacy of coronary thrombolysis relatively late after the onset of acute myocardialinfarctioninpatientswithpostinfarction angina. They noted that this was not an appropriately designed, randomized controlled studv.2 However. as Chalmers3 and Spodick4 point out, “pilot studies” are often misleading, waste time and preempt organization of controlled trials by prematurely popularizing a new treatment. Moreover, when one first tries new treatments or new applications of old treatments, one has high hopes, but cannot know whether it will bring net help or harm to the patient. Therefore, controlled clinical trials should beein with thefirstpatient, bothtoaccomplishtheobjective these investigators propose for future work and to give the patients a 50:50chance nottogettherisksorbenefitsofthenewtherapy. On scientific grounds, one can randomize from the first patient as described in the AJC.4 Moreover, this also should be done on ethica13,5and behaviora15v6grounds. An example of the diminishing likelihood that a controlled trial will be accomplished despite the undisputed good intentions of Shapiro et al is the case of emergency bypass surgery for acute myocardial infarction. The first report in 1979was qualified by its workers as inconclusive in the absence of appropriately designed controlled clinical trials.7 Four years later, a report of the same, now burgeoning, series was again accompanied by a call for a controlled clinical trial.8 That the absence of a trial was ascribed to administrative resistance rather than the investigators’ good intentions.9 is just another argument for starting out right-randomizing the first patient-before scientific, ethical and behavioral standards can be circumvented. DavidIf. Spodick,MD, DSe Worcester, MA 2 July 1985
1. Shapiro EP, Brinker JA, Gottlieb SO, Guzman PA, Bulkley BH. Introcoronary thrombolysis 3 to 13 days after acute myocardial infarction for postinfarction angina pectoris. Am J Cardiol 1985; 55:1453-1458. 2. Spodick DH. Revascularization ofthe heart-numerators in search of denominators [editorial]. Am Heart J 1971;81:149-157, 3.ChalmersTC.EthicalaspectsofcJinicaItrials.Am J OphthalmoI1975;79:753-758. 4. Spodick DH. Randomize the first patient: scientific, ethical and behavioral bases. Am J Cardiol 1983;51:916-917. 5. SpodickDH. The randomized controlled clinical trial: scientific and ethical bases.Am J Med 1982; 73~420-425. 6.SpodickDH. Barrierstoacceptanceofcontrolled phase III clinical trials: behavioral factors. Biomed Pharmacother 1983;37:60-61. 7. DeWood MA, Spores J, Notske RN, Lang HT, Shields JP, Simpson CS, Rudy LW. Grunwald R. Medical and surgical management of myocardial infarction. Am J Cardiol 1979;44:1356-1364. 8. DeWood MA, Heit J, Spores J. Berg R Jr, Selinger SL, Rudy LW. Hensley GR, Shields JP.Anterior transmural myocardial infarction: effects of surgical coronary reperfusion on global and regional left ventricular function. JACC 1983;1:12231234.
9. DeWood M. Reply to Spodick DH [letter]. JACC 1983;2:1249-1242.
SAFETY OFIBUPROFEN FORACUTE MYOCARDIAL INFARCTION PERICARDITIS Boden and Sadaniantzl present observations on 3 patients with ventricular septal rupture during ibuprofen therapy for acute myocardial infarction (AMI]-associated pericarditis. They hedge their message by pointing to its anecdotal nature, admitting “no conclusive proof that a causal relationship exists”1 They also appropriately cite Brown et al, 2who observed scar thinning associated with ibuprofen during experimental AMI. In the same issueofthe AJC, Cannonetalsreportthebeneficial effect of ibuprofen duringexperimental AMI, including promotion of collagen deuosition with no deleterious effect on subsequent scar formation. They point out that Brown et al2 used experimental conditions which may have promoted scar thinning. The Editor had offered me the paper by Boden and Sadaniantz for review. I declined to review it because of involvement in a clinical trial of ibuprofen, which included mainly patients with AMI-associated acute pericarditis. Since 1978,we have used ibuprofen regularly on a service with approximately 350 “rule ins” for AM1 each year, 6 to 7% with clinically recognizable pericarditis.4 Between 1983 and 1985 we entered a formal study of ibuprofen in acute pericarditis against placebo. Thus, there were obviously many AM1 patients treated informally with ibuprofen, while 15 probably received the drug on protocol. In no patient did we diagnose ventricular septal rupture. Moreover, we used larger doses than did Boden andSandaniantz:600mgevery6hoursusually; 800mg every 6 hours for protocol patients. Because AM1 pericarditis is almost always unassociated with diagnostic electrocardiographic changes, the pericardial rub is the sole objective diagnostic sign of AM1 pericarditis4 (Pain alone is not reliable.) Thus, one ‘must assume that Boden and Sadaniantz identified their patients by detecting rubs. Auscultation and phonocardiography show thatpericardialrubsarenotrarelymonophasic and are best heard and recorded at the left mid- to low sternal border.5 It is in precisely the same area that precordial murmurs typical of ventricular seotal defect with left-toright shunt are best heard. An early “leak” of aseptaldefectmayhavebeeninterpretedasa pericardial rub. Yet, Boden is experienced in coronary artery diseases so we can assume thatthepatientsdidhaverubs.Therefore,the occurrence in a relatively short period of several patients with ventricular septal rupture wascertainlynoteworthy(i.e., publishable] if anecdotal. Although this obliged me to report here our entirely benign experience with large numbers of patients taking ibuprofen,
we will remain alert to the possibility. However, the report by Cannon et al3 makes ibuprofen an unlikely culprit. DavidH. Spodick,MD Worcester,
Massachusetts 3 July 1985
April I,1986
l.Boden WE,SadaniantzA. VentricuIarseptairupture during ibuprofen therapy for pericarditis after acute myocardial infarction. Am 1 Cardioi 1985; 56:X31-1632. ~.BrownEJ.KlonerRA,SchoenFJ,HammermanH, Hale S, Braunwald E. Scar thinning due to ibuprofen administration after exnerimental mvocardial infarction. Am J CaidioI 1$83;51:877-883: 3. Cannon RO, RodriguezR, Speir E, Yamaguchi M. Butany J,McManus BM, BolliR, Ferrans VJ. Effect of ibuprofen on the healing phase of experimental myocardial infarction in the rat. Am J Cardiof
THE AMERICAN
ELECTROCARDIOGRAPHIC, ENZY SCINTICRAPHIC CRITERIA FOR OFACUTE ~YO~ARDIA~ INFAR~TID
With their estimates of the sensitivity (91%] andspecificity[64%) of pyrophosphate scanning in the MILIS studies, Turi et all contributed important information on the diagnosis of acute myocardial infarction (AMI). However, their estimates for the sensitivity (96%) 19t?5:55:mJ9-1613. and specificity (59%) of serial electrocardio4. Krainin FM, Flessas AP, SpodickDH. Infarctiongrams do not enjoy the same validity. associated pericarditis: rarity of diagnostic electroIndependence of patient selection from cardiogram. N EngI J Med 1984;311:1211-1214. 5. Spodick DH. The pericardial rub: a prospective, test results is a key element of study design in the estimation of sensitivity and specificity. multiple observer investigation of pericardial fricThe MILIS eligibility criteria performed extion in 100 patients. Am J CardioI1975;35:357-362. 6. Boden WE, Capone RJ.Coronary Care. Philadelcellently in selecting patients with AMI, as phia: WB Saunders, 1984. the Table IA of Turi et al demonstrates for 635 AM1 patients. These eligibility
ANOMALOUS ORIGIN OFLEFT MAINCORONARY ARTERY FROM RIGHT SINUSOFVALSALVA I was interested in the large number of angiographicallydiagnosedcasesofanomalousorigin of the left main coronary artery from the right sinus of Valsalva
reported by Kimbiris
recently.1 If your readers study the article carefully, however, and apply the radiologic criteria described in the immediately following study by Ishikawa and myself,z they will find that the 5 casesillustratedin Figures 1 to 4 all showed features of a septal course, not the interarterial course claimed for them by Kimbiris. Peter W.T.Brad Auckland,
New Zealand 5 July 1985
1. Kimbiris D. Anomalous origin of the left main coronary artery from the right sinus of Valsalva. Am J Cardiol 1985;55:765-769. 2.IshikawaT,Brandt PWT.AnomaJousoriginofthe Ieft main coronary artery from the right anterior aortic sinus: angiographic definition of anomalous course. Am 1 CordioIl985;55:770-776.
STILLMORE ONTHEVENTICULAR PREMATURE COMPLEX Iwasmostinterestedtoreadyourchallenging editorial “I Still Prefer Ventricular Premature Complex.“i You do not, however, addressyourselftoarelevantissue. Whatdoyou call concealed ventricular extrasystoles and concealed atrioventricular junctional extrasystoles? Do you refer to them as concealed ventricular premature complexes and concealedatrioventricularjunctionalpremature complexes? And, if so, can a complex be concealed? Leo Schamroth,MD Johannesburg,
South Africa 6 July 1985
l.RobertsWC. IStiiIPrefer VentricularPremature Complex. Am J CardioI1985;55:1117.
criteria rested
in oart on electrocardioaraohic JECGIabnorm&ties: “new or presumably new 4 waves of at least 30-ms duration and Z-mm depth(l0 mm = 1.0mV); ...new or presumably new STsegment elevation or depression of at least 1 mm...” These abnormalities are correlated with the classification criteria Turi et all used to estimate sensitivity and specificity: “Patients were considered to have infarction associated with Q-wave development if new Q waves appeared...” The MILIS clinical unit staff recruited patients for the randomized ”
-
study by selecting their patients so that as far as clinical unit staff were concerned, all had
baseline ECG abnormalities that supported a diagnosis of AMI. In the 2 by 2 tables from which sensitivity and specificity are usually calculated, test results are cross-tabulated by true diagnoses. TheeffectoftheMILISeligibilitycriteriawas not only to select from the large number of oatients screened the 726Datients eligible for ihe randomized study, bit also, in terms of ECG sensitivity and specificity for the diagnosis of AMI, to increase false positives relative to true negatives and true positives relative to false negatives. Consequently, the observed true negatives/(false positives + irue negatives) underestimates the specific-
ity, and the observed true positives/(true positives + false negatives] overestimates the
sensitivity. In an earlier MILIS report, there are data on 3,697patients screened for MILIS.Z Cross tabulation of those data generated an estimate of 81% sensitivity and 69% specificity for test diagnosis based on the presence of 1 or more of the baseline ECG eligibility criteria againstlocal creatine kinase measurement as the diagnostic standard. These patients were not analyzed for serial ECG results; however, that an ECG series is at least as specific as a
single electrocardiogram is a conservative assumption. Other studies estimating the sensitivity and specificity of electrocardiograms in diagnosinn AM1 found them less sensitive and more sp&ific than did Turi et al,1 as would be expected.3r4 Because MILIS eligibility did not deuend on the results of DvrouhosDhate scans, the estimates of sensitivity and specificity for the radionuclide study are extraor_”
REPLY: I do not know the answer to Dr. Schamroth’s questions. WilliamC Roberts,MD Bethesda, Maryland 9 July 1985
.
JOURNAL
OF CARDIOLOGY
Volume 57
897
1. Turi ZG, Rutherford JD, Roberts R, Muller JE,
JaffeAS, RudeRE,ParkerC, RaabeDS,StonePH, HartwellTD, Lewis SE, Parkey RW, Gold HK, Robertson TL, Sobel BE, Willerson IT. Braunwald E. and cooperating investigators ‘from the MILIS Study Group. Electrocardiographic, enzymatic and scintinraphic criteria of acute mvocardial infarctionasheierminedfromstudv of?26 natientsla ‘MILIS study]. Am J CaidioI 198$;5k14&-1468. ’ 2. Rude RE, Poole WK. Mu&r JE, Turi Z, Rutherford J, Parker C, Roberts R, Ra&be DS, Gold HK, Stone PH, Willerson JT, Braunwald E, and the MILIS Study Group. Electrocardiographic and clinicalcriteriafor recognitionofacutemyocardial infarction based on analysis of3,697 patients. Am [ CardioI1983;52:936-942. 3. Abreu-Lima C, Correia DM, Almeida J,AntunesLopes M, and Cerqueira-Gomes M. A new ECC classification system for myocardial infarction based on receiver operating characteristic curve analysis and information theory. Circulation 1983; 67:1252-1257. 4. Horan LG, Flowers NC, and Johnson JC. Signifi-
cance of the diagnostic Q wave of myocardial infarction. CircuIation 1971;43:428-436.
VERAPAMIL IN WIDECOMPLE TA~NYCARD~A Thesuggestion by Morgan and Brennanl that intravenousverapamilmaybeofvalueindifferentiating supiaventri&lar (SVT) from ventricular tachycardia [VT] should be further considered. The place of verapamil in the acute treatment of VT has been discussed,2and it is evident that some rare types of VT mav be safelv and effectivelv treated with fhe &ug.2e3However, in most”palients with VT, those with coronary artery disease, verapamilisineffectiveandoftencausesprofound hypotension necessitating immediate cardioversion.4~5 We described 24 patients with chronic recurrent VT who were repeatedly misdiagnosed as having SVT. Twenty of the patients received intravenous verapamil, some on many occasions. Sinus rhythm was achievedinonlylepisode, andspatientshad emergency cardioversions for profound hypotension.6 In the case described by Morgan and Brennan,* it shouldhave been possible to diagnose VT from the recording illustrated using currently accepted criteria. Thus, the QRS axis and configuration changed significantly between the electrocardiogram of sinus rhythm and right bundle branch block and that of wide complex tachycardia.7 Furthermore, analysisof theQRS complexconfiguration in the chest leads, according to the scheme of Wellens et al,* should have provided confirmatow evidence for a ventricular origin. We believe that established criteria fordistinguishing between SVT and VT should have been applied before choosing a potentially dangerous treatment. Mark Dancy,MD A. JohnCamm,MD avid E. Ward,MD London England 14 August 1985
-
dinarily useful. Michael I.. Terrin, MD, CM, MPH Baltimore, Maryland 1 August 1985
1. Morgan DE, Brennan JF. Diagnosticpotentioifor verapamil in vside QRS complex tachycardia. Am J CardioI1985;55:1428-1429. 2. Belhassen B, Horowitz LN. The use ofverapamil for ventricular tachycardia. Am 1 CardioJ 1984; 54:1131-3133.
3. Ward DE, Nathan AW, Camm AJ. Fascicular
LETTERS
were done during the first month: clinical (pain, pericardial rub], echocardiographic (M-mode and Z-dimensional echocardioeraphy] and biologic (sedimentation, fib&emia and C reactive-protein). The initial evaluation was done before the 36th hour after the onset of the pain, and the others on days 5,10 and 30. Pericarditis wasdefined by the presence of echocardiographic PE associatedwithorwithoutclinicalsymptoms:group A [n = 151, P- (without pericarditisl and group B (n = 211P% (with pericarditis]. Then, group B was randomly allocated to nonsteroidtreatment(indomethacin,15Omg,3times daily for 10 days) or no nonsteroid treatment: Bl (n = lo], nonsteroid treatment +, B2 (n = 111,nonsteriod treatment -. Our results showed: Pericarditiswasfrequentlynotedin58% of cases(2lof36)andPEwasobservedin19of24 (P+]. PE was detected at the first echocardiographic examination [l2 of 191,was usually small or moderate (16 of 191. but never showed bad hemodynamic tolerance. Pericarditis was associated with higher peak creatinine kinase level, yet not significant (P+: 1,709 f 1,051; P-: 1,126 f 878 LB; difference not significant] and, conversely, with a significantly higher biologic syndrome (sedimentation:42f17~~76&35mm/hour,p <0.05;fibrinemia:6.3 f 22~~7.2 f 1.6g/liter, p <0.02; C reactive protein: 0.043 f 0.030 vs 0.105 f 0.068 UI, p
l.KaplanK, DavisonR,ParkerM,PrzybylekJ,Light A, Bresnahan D, kibner H, Talano J. Frequency of pericardial effusion as determined by m-mode echocardiography in acute myocardial infarction. Am J Cardiol 1985;55:335-337. 2. Roeske WR, Savage RM, O’Rourke RA, Bloor CM. Chnicopathologic correlations in patients after myocardial infarction. Circulation 1981;63:3645.
LATETHROMBOLYSIS: CONTROLLED CLINICAL TRIALOVERDUE Shapiro et al1demonstrate the apparent safety and possible efficacy of coronary thrombolysis relatively late after the onset of acute myocardialinfarctioninpatientswithpostinfarction angina. They noted that this was not an appropriately designed, randomized controlled studv.2 However. as Chalmers3 and Spodick4 point out, “pilot studies” are often misleading, waste time and preempt organization of controlled trials by prematurely popularizing a new treatment. Moreover, when one first tries new treatments or new applications of old treatments, one has high hopes, but cannot know whether it will bring net help or harm to the patient. Therefore, controlled clinical trials should beein with thefirstpatient, bothtoaccomplishtheobjective these investigators propose for future work and to give the patients a 50:50chance nottogettherisksorbenefitsofthenewtherapy. On scientific grounds, one can randomize from the first patient as described in the AJC.4 Moreover, this also should be done on ethica13,5and behaviora15v6grounds. An example of the diminishing likelihood that a controlled trial will be accomplished despite the undisputed good intentions of Shapiro et al is the case of emergency bypass surgery for acute myocardial infarction. The first report in 1979was qualified by its workers as inconclusive in the absence of appropriately designed controlled clinical trials.7 Four years later, a report of the same, now burgeoning, series was again accompanied by a call for a controlled clinical trial.8 That the absence of a trial was ascribed to administrative resistance rather than the investigators’ good intentions.9 is just another argument for starting out right-randomizing the first patient-before scientific, ethical and behavioral standards can be circumvented. DavidIf. Spodick,MD, DSe Worcester, MA 2 July 1985
1. Shapiro EP, Brinker JA, Gottlieb SO, Guzman PA, Bulkley BH. Introcoronary thrombolysis 3 to 13 days after acute myocardial infarction for postinfarction angina pectoris. Am J Cardiol 1985; 55:1453-1458. 2. Spodick DH. Revascularization ofthe heart-numerators in search of denominators [editorial]. Am Heart J 1971;81:149-157, 3.ChalmersTC.EthicalaspectsofcJinicaItrials.Am J OphthalmoI1975;79:753-758. 4. Spodick DH. Randomize the first patient: scientific, ethical and behavioral bases. Am J Cardiol 1983;51:916-917. 5. SpodickDH. The randomized controlled clinical trial: scientific and ethical bases.Am J Med 1982; 73~420-425. 6.SpodickDH. Barrierstoacceptanceofcontrolled phase III clinical trials: behavioral factors. Biomed Pharmacother 1983;37:60-61. 7. DeWood MA, Spores J, Notske RN, Lang HT, Shields JP, Simpson CS, Rudy LW. Grunwald R. Medical and surgical management of myocardial infarction. Am J Cardiol 1979;44:1356-1364. 8. DeWood MA, Heit J, Spores J. Berg R Jr, Selinger SL, Rudy LW. Hensley GR, Shields JP.Anterior transmural myocardial infarction: effects of surgical coronary reperfusion on global and regional left ventricular function. JACC 1983;1:12231234.
9. DeWood M. Reply to Spodick DH [letter]. JACC 1983;2:1249-1242.
SAFETY OFIBUPROFEN FORACUTE MYOCARDIAL INFARCTION PERICARDITIS Boden and Sadaniantzl present observations on 3 patients with ventricular septal rupture during ibuprofen therapy for acute myocardial infarction (AMI]-associated pericarditis. They hedge their message by pointing to its anecdotal nature, admitting “no conclusive proof that a causal relationship exists”1 They also appropriately cite Brown et al, 2who observed scar thinning associated with ibuprofen during experimental AMI. In the same issueofthe AJC, Cannonetalsreportthebeneficial effect of ibuprofen duringexperimental AMI, including promotion of collagen deuosition with no deleterious effect on subsequent scar formation. They point out that Brown et al2 used experimental conditions which may have promoted scar thinning. The Editor had offered me the paper by Boden and Sadaniantz for review. I declined to review it because of involvement in a clinical trial of ibuprofen, which included mainly patients with AMI-associated acute pericarditis. Since 1978,we have used ibuprofen regularly on a service with approximately 350 “rule ins” for AM1 each year, 6 to 7% with clinically recognizable pericarditis.4 Between 1983 and 1985 we entered a formal study of ibuprofen in acute pericarditis against placebo. Thus, there were obviously many AM1 patients treated informally with ibuprofen, while 15 probably received the drug on protocol. In no patient did we diagnose ventricular septal rupture. Moreover, we used larger doses than did Boden andSandaniantz:600mgevery6hoursusually; 800mg every 6 hours for protocol patients. Because AM1 pericarditis is almost always unassociated with diagnostic electrocardiographic changes, the pericardial rub is the sole objective diagnostic sign of AM1 pericarditis4 (Pain alone is not reliable.) Thus, one ‘must assume that Boden and Sadaniantz identified their patients by detecting rubs. Auscultation and phonocardiography show thatpericardialrubsarenotrarelymonophasic and are best heard and recorded at the left mid- to low sternal border.5 It is in precisely the same area that precordial murmurs typical of ventricular seotal defect with left-toright shunt are best heard. An early “leak” of aseptaldefectmayhavebeeninterpretedasa pericardial rub. Yet, Boden is experienced in coronary artery diseases so we can assume thatthepatientsdidhaverubs.Therefore,the occurrence in a relatively short period of several patients with ventricular septal rupture wascertainlynoteworthy(i.e., publishable] if anecdotal. Although this obliged me to report here our entirely benign experience with large numbers of patients taking ibuprofen,
we will remain alert to the possibility. However, the report by Cannon et al3 makes ibuprofen an unlikely culprit. DavidH. Spodick,MD Worcester,
Massachusetts 3 July 1985
April I,1986
l.Boden WE,SadaniantzA. VentricuIarseptairupture during ibuprofen therapy for pericarditis after acute myocardial infarction. Am 1 Cardioi 1985; 56:X31-1632. ~.BrownEJ.KlonerRA,SchoenFJ,HammermanH, Hale S, Braunwald E. Scar thinning due to ibuprofen administration after exnerimental mvocardial infarction. Am J CaidioI 1$83;51:877-883: 3. Cannon RO, RodriguezR, Speir E, Yamaguchi M. Butany J,McManus BM, BolliR, Ferrans VJ. Effect of ibuprofen on the healing phase of experimental myocardial infarction in the rat. Am J Cardiof
THE AMERICAN
ELECTROCARDIOGRAPHIC, ENZY SCINTICRAPHIC CRITERIA FOR OFACUTE ~YO~ARDIA~ INFAR~TID
With their estimates of the sensitivity (91%] andspecificity[64%) of pyrophosphate scanning in the MILIS studies, Turi et all contributed important information on the diagnosis of acute myocardial infarction (AMI). However, their estimates for the sensitivity (96%) 19t?5:55:mJ9-1613. and specificity (59%) of serial electrocardio4. Krainin FM, Flessas AP, SpodickDH. Infarctiongrams do not enjoy the same validity. associated pericarditis: rarity of diagnostic electroIndependence of patient selection from cardiogram. N EngI J Med 1984;311:1211-1214. 5. Spodick DH. The pericardial rub: a prospective, test results is a key element of study design in the estimation of sensitivity and specificity. multiple observer investigation of pericardial fricThe MILIS eligibility criteria performed extion in 100 patients. Am J CardioI1975;35:357-362. 6. Boden WE, Capone RJ.Coronary Care. Philadelcellently in selecting patients with AMI, as phia: WB Saunders, 1984. the Table IA of Turi et al demonstrates for 635 AM1 patients. These eligibility
ANOMALOUS ORIGIN OFLEFT MAINCORONARY ARTERY FROM RIGHT SINUSOFVALSALVA I was interested in the large number of angiographicallydiagnosedcasesofanomalousorigin of the left main coronary artery from the right sinus of Valsalva
reported by Kimbiris
recently.1 If your readers study the article carefully, however, and apply the radiologic criteria described in the immediately following study by Ishikawa and myself,z they will find that the 5 casesillustratedin Figures 1 to 4 all showed features of a septal course, not the interarterial course claimed for them by Kimbiris. Peter W.T.Brad Auckland,
New Zealand 5 July 1985
1. Kimbiris D. Anomalous origin of the left main coronary artery from the right sinus of Valsalva. Am J Cardiol 1985;55:765-769. 2.IshikawaT,Brandt PWT.AnomaJousoriginofthe Ieft main coronary artery from the right anterior aortic sinus: angiographic definition of anomalous course. Am 1 CordioIl985;55:770-776.
STILLMORE ONTHEVENTICULAR PREMATURE COMPLEX Iwasmostinterestedtoreadyourchallenging editorial “I Still Prefer Ventricular Premature Complex.“i You do not, however, addressyourselftoarelevantissue. Whatdoyou call concealed ventricular extrasystoles and concealed atrioventricular junctional extrasystoles? Do you refer to them as concealed ventricular premature complexes and concealedatrioventricularjunctionalpremature complexes? And, if so, can a complex be concealed? Leo Schamroth,MD Johannesburg,
South Africa 6 July 1985
l.RobertsWC. IStiiIPrefer VentricularPremature Complex. Am J CardioI1985;55:1117.
criteria rested
in oart on electrocardioaraohic JECGIabnorm&ties: “new or presumably new 4 waves of at least 30-ms duration and Z-mm depth(l0 mm = 1.0mV); ...new or presumably new STsegment elevation or depression of at least 1 mm...” These abnormalities are correlated with the classification criteria Turi et all used to estimate sensitivity and specificity: “Patients were considered to have infarction associated with Q-wave development if new Q waves appeared...” The MILIS clinical unit staff recruited patients for the randomized ”
-
study by selecting their patients so that as far as clinical unit staff were concerned, all had
baseline ECG abnormalities that supported a diagnosis of AMI. In the 2 by 2 tables from which sensitivity and specificity are usually calculated, test results are cross-tabulated by true diagnoses. TheeffectoftheMILISeligibilitycriteriawas not only to select from the large number of oatients screened the 726Datients eligible for ihe randomized study, bit also, in terms of ECG sensitivity and specificity for the diagnosis of AMI, to increase false positives relative to true negatives and true positives relative to false negatives. Consequently, the observed true negatives/(false positives + irue negatives) underestimates the specific-
ity, and the observed true positives/(true positives + false negatives] overestimates the
sensitivity. In an earlier MILIS report, there are data on 3,697patients screened for MILIS.Z Cross tabulation of those data generated an estimate of 81% sensitivity and 69% specificity for test diagnosis based on the presence of 1 or more of the baseline ECG eligibility criteria againstlocal creatine kinase measurement as the diagnostic standard. These patients were not analyzed for serial ECG results; however, that an ECG series is at least as specific as a
single electrocardiogram is a conservative assumption. Other studies estimating the sensitivity and specificity of electrocardiograms in diagnosinn AM1 found them less sensitive and more sp&ific than did Turi et al,1 as would be expected.3r4 Because MILIS eligibility did not deuend on the results of DvrouhosDhate scans, the estimates of sensitivity and specificity for the radionuclide study are extraor_”
REPLY: I do not know the answer to Dr. Schamroth’s questions. WilliamC Roberts,MD Bethesda, Maryland 9 July 1985
.
JOURNAL
OF CARDIOLOGY
Volume 57
897
1. Turi ZG, Rutherford JD, Roberts R, Muller JE,
JaffeAS, RudeRE,ParkerC, RaabeDS,StonePH, HartwellTD, Lewis SE, Parkey RW, Gold HK, Robertson TL, Sobel BE, Willerson IT. Braunwald E. and cooperating investigators ‘from the MILIS Study Group. Electrocardiographic, enzymatic and scintinraphic criteria of acute mvocardial infarctionasheierminedfromstudv of?26 natientsla ‘MILIS study]. Am J CaidioI 198$;5k14&-1468. ’ 2. Rude RE, Poole WK. Mu&r JE, Turi Z, Rutherford J, Parker C, Roberts R, Ra&be DS, Gold HK, Stone PH, Willerson JT, Braunwald E, and the MILIS Study Group. Electrocardiographic and clinicalcriteriafor recognitionofacutemyocardial infarction based on analysis of3,697 patients. Am [ CardioI1983;52:936-942. 3. Abreu-Lima C, Correia DM, Almeida J,AntunesLopes M, and Cerqueira-Gomes M. A new ECC classification system for myocardial infarction based on receiver operating characteristic curve analysis and information theory. Circulation 1983; 67:1252-1257. 4. Horan LG, Flowers NC, and Johnson JC. Signifi-
cance of the diagnostic Q wave of myocardial infarction. CircuIation 1971;43:428-436.
VERAPAMIL IN WIDECOMPLE TA~NYCARD~A Thesuggestion by Morgan and Brennanl that intravenousverapamilmaybeofvalueindifferentiating supiaventri&lar (SVT) from ventricular tachycardia [VT] should be further considered. The place of verapamil in the acute treatment of VT has been discussed,2and it is evident that some rare types of VT mav be safelv and effectivelv treated with fhe &ug.2e3However, in most”palients with VT, those with coronary artery disease, verapamilisineffectiveandoftencausesprofound hypotension necessitating immediate cardioversion.4~5 We described 24 patients with chronic recurrent VT who were repeatedly misdiagnosed as having SVT. Twenty of the patients received intravenous verapamil, some on many occasions. Sinus rhythm was achievedinonlylepisode, andspatientshad emergency cardioversions for profound hypotension.6 In the case described by Morgan and Brennan,* it shouldhave been possible to diagnose VT from the recording illustrated using currently accepted criteria. Thus, the QRS axis and configuration changed significantly between the electrocardiogram of sinus rhythm and right bundle branch block and that of wide complex tachycardia.7 Furthermore, analysisof theQRS complexconfiguration in the chest leads, according to the scheme of Wellens et al,* should have provided confirmatow evidence for a ventricular origin. We believe that established criteria fordistinguishing between SVT and VT should have been applied before choosing a potentially dangerous treatment. Mark Dancy,MD A. JohnCamm,MD avid E. Ward,MD London England 14 August 1985
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dinarily useful. Michael I.. Terrin, MD, CM, MPH Baltimore, Maryland 1 August 1985
1. Morgan DE, Brennan JF. Diagnosticpotentioifor verapamil in vside QRS complex tachycardia. Am J CardioI1985;55:1428-1429. 2. Belhassen B, Horowitz LN. The use ofverapamil for ventricular tachycardia. Am 1 CardioJ 1984; 54:1131-3133.
3. Ward DE, Nathan AW, Camm AJ. Fascicular