The Differential Diagnosis of Acute Pericarditis from the Normal Variant:

Transcription

1 The Differential Diagnosis of Acute Pericarditis from the Normal Variant: Ne Electrocardiographic Criteria LEONARD E. GINZTON, M.D., AND MICHAEL M. LAKS, M.D. SUMMARY We eamined the quantitative electrocardiographic differentiation of acute pericarditis from normal variant ST/T changes. The ECGs of 19 patients ith acute pericarditis ere compared ith those of 2 subjects ith typical normal variant changes. Patients ere ecluded if their ECGs demonstrated conditions that markedly altered repolariation. The positive predictive values (PPV) and negative predictive values (NPV) of previously reported criteria ere not high (PPV =.5-.83, NPV = ). In contrast, in the present study, a T-ave amplitude in lead VB of <.3 mv diagnosed acute pericarditis (p <.5, PPV =.85, NPV =.85), but there as overlap of patients beteen the groups. The ratio of the amplitude of the onset of the ST segment to the amplitude of the T ave in that lead (ST/T ratio in V.) proved to be the most reliable discriminator. An ST/T ratio.25 diagnosed all patients ith acute pericarditis (p <.5, PPV = 1., NPV = 1.). The ST/T ratio.25 in V,, V5 (both p <.5, PPV =.87, NPV = 1.) and I (p <.5, PPV =.8, NPV =.81) ere also significant discriminators. Thus, if V, is unavailable, an ST/T ratio.25 in V,, V, or I is highly suggestive of acute pericarditis. An ST/T ratio >.25 in V. discriminated the ECGs of all patients ith acute pericarditis from normal variants in this study. Donloaded from by on November 15, 218 THE PROBLEM of differentiating the ECG of acute pericarditis from the normal variant ith early repolariation has long concerned the clinician and electrocardiographer.1'5 Acute pericarditis is a common cause of chest pain and abnormal ECGs (fig. 1), especially in young adults.' The ST-T changes present in the normal variant ECG (fig. 2) have been reported in 2% of healthy young adults5 and may present a diagnostic dilemma if the person presents ith chest pain or an acute febrile illness. Distinguishing the to conditions on the basis of a single ECG is difficult.2 7 The ECG changes of acute pericarditis consist of STsegment elevation ith an ST vector that is directed toard the area of pericarditis, and are thought to represent an injury current in response to an inflammatory epimyocarditis," 8, 9 and usually undergo a typical evolution over days to eeks.9 On the other hand, although similar in appearance,1 the repolariation changes seen in the normal variant ECG are thought to be due to autonomic nervous system imbalance in the myocardium resulting in varying rates of repolariation and tend to be stable over a period of years.2 5, 11 Investigations attempting to distinguish these to conditions have yielded conflicting results,"1 3'and the differential criteria have been comple. Other investigators have concluded that it is not possible to differentiate beteen acute pericarditis and normal ST-T variations on the basis of a single ECG, and that serial ECGs in conjunction ith the clinical setting are required.2' Furthermore, ith the increased use of computeried ECG interpretive From the Department of Medicine, Division of Cardiology, Harbor-UCLA Medical Center, Torrance, California. Supported in part by training grant 27-lG9, American Heart Association, Greater Los Angeles Affiliate. Address for correspondence: Leonard E. Ginton, M.D., Division of Cardiology, Harbor-UCLA Medical Center, 1 West Carson Street, Torrance, California 959. Received December 18, 198; revision accepted July 23, Circulation 65, No. 5, systems, the need for validated criteria as a data base has been emphasied.'2 The purpose of this study as to determine the diagnostic accuracy of present criteria for differentiating normal variant repolariation changes from acute pericarditis and to test the accuracy of ne criteria established in our laboratory. Materials and Methods Patient Selection Because the purpose of the study as to differentiate normal variant ECGs from acute pericarditis, patients ere ecluded if their ECGs revealed conditions that markedly altered repolariation, such as left bundle branch block, severe right or left ventricular hypertrophy or acute myocardial infarction. Over 3 years, 77 patients had a discharge diagnosis of acute pericarditis, and 58 of their records ere available for revie. Nineteen patients ere considered to have acute pericarditis. Tenty-four patients did not fulfill the criteria and ere considered misdiagnoses. Eight patients did not have serial ECGs available for analysis; because serial electrocardiographic changes consistent ith the evolution of acute pericarditis ere required for the diagnosis to be confirmed, these patients ere ecluded. Nine patients had significant electrocardiographic abnormalities: to acute anterolateral myocardial infarction, si severe left ventricular hypertrophy and one patient severe right ventricular hypertrophy. Group 1 consisted of 19 consecutive patients ith unequivocal acute pericarditis. All had serial ECG changes consistent ith the evolution of acute pericarditis9 and a pericardial friction rub documented by at least to observers. Of the 19 patients, 15 had chest pain, 16 ere febrile and 12 had leukocytosis (WBC > 11,). M-mode echocardiograms ere recorded in 17 patients and in 13 revealed a pericardial effusion. The ECG chosen for analysis as the one that corresponded to Spodick's stage I.1" 1

2 ACUTE VS ECG/Ginton and Laks 15 L U-1-1- t so. ON,.;. W: :.m :: 1: J= 1::1 1:::: F t, 't A... it FIGURE 1. ECG of acute pericarditis. There is PR deviation in both frontal and horiontal planes and the frontal plane ST vector is horiontal and to the left of the QRS vector. The ST/ T ratio in V5., V and I are all greater than.25. Donloaded from by on November 15, 218 d Group 2, hich included patients ith the normal variant, as composed of 2 healthy adults ithout clinical or historical evidence of cardiovascular disease hose 12-lead ECGs demonstrated typical normal variant repolariation changes.2'5'7 Measurements To determine PR-segment abnormalities, the TP segment as used as the baseline (fig. 3). For all other measurements, the end of the PR segment as used as the baseline. The mean frontal and horiontal plane vectors ere calculated for the P ave, PR segment, QRS, ST segment and T ave. The amplitude of the onset of the ST segment and T ave ere measured in leads I, II, V2, V,, V5 and V,. Differences beteen ST and T vectors (in degrees) ere calculated by subtracting the mean T vector from the mean ST vector. Thus, a positive angle meant that the mean ST vector as to the right of the T vector, and a negative angle meant that the mean ST vector as to the left of the mean T vector. Likeise, the QRS-ST angle as obtained by subtracting the QRS vector from the ST vector. The ST/T ratio as obtained by dividing the amplitude of the onset of the ST segment by the aplitude of the T ave in that lead. The ST/T ratio in lead V. as calculated in to ays: using both the TP segment and H~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~IA I :l,l'i-ftihtr!tftls jli 1J1@s ilils[t]!1 l TII't,, 1t t' [1,tHf ll.ii; WI r-' -, "M ai- N! l the end of the PR segment as the baseline for measuring ST-segment and T-ave amplitudes. A flat or negative T ave resulted in an ST/T ratio that could not be calculated for that lead. Statistical Methods The mean and standard errors of the mean ere calculated for all groups of data. The statistical significance as calculated using the t test for nonpaired variables.13 The sensitivity, specificity and positive and negative predictive values ere calculated by standard methods.' The positive predictive value is an epression of ho often a test is correct hen its result is positive; the negative predictive value epresses ho often a test is correct hen its result is negative. The predictive value is if the test is never correct and is 1. if the test is alays correct. Results Patient Population Group 1 consisted of 13 males and si females, 1 hites and nine blacks. The mean age as years (range years). The etiology of the pericarditis as idiopathic (presumed to be of viral origin) in seven, chest trauma in five, postpericardiotomy in thmiil llii 'i a 'III FIGURE 2. Normal variant repolariation ECG. The ST vector is directed to the left, anterior and inferior, and the lateral T ave amplitude is high (greater than.5 m V). The ST/T ratio in V6 is less than.25.

3 16 CIRCULATION VOL 65, No 5, MAY 1982 Donloaded from by on November 15, PR ST T WAVE SEGMENT SEGMENT AMPLITUDE END ONSET FIGURE 3. The locations of the electrocardiographic measurements for the PR segment, STsegment and T ave. The PR segment end as used as the baseline for the ST-segment onset and T-ave maimal amplitude. to, associated ith metastatic neoplasms in to (one lung carcinoma and one osteogenic sarcoma), autoimmune disease in to, and chronic renal failure in one. Echocardiograms ere obtained in 17 patients and ere interpretable in 16. A pericardial effusion as not demonstrable in three patients, as small in five, moderate in si, and large in to. One patient had hemodynamic evidence of cardiac tamponade. Group 2, the normali variant popu'lati'on, as composed of 2 males, mean age of 26. years (range 2-3 years). There ere 17 hites and three orientals. Previous criteria for differentiating acute pericarditis and normal variant ECGs ere revieed', 8, 9, 15 >LI C,) YESAO N o -25- ) - o '< 5-- -J a. -J I 75- I-- Ih. and applied to the present study population (fig. ). PR Segments In the pericarditis group, PR segments ere displaced from the baseline in five of 19 patients in both the frontal plane and horiontal plane, in the frontal plane only in si and in the horiontal plane in none. In the normal variant group, one of 2 patients had displaced PR segments in both the frontal and horiontal planes and none had PR-segment displacement isolated to the frontal or horiontal plane. The positive predictive value for PR-segment deviations in both the frontal and horiontal planes indicating 8 + l is _IV X --- J-I C, U) Or U. o 8 1o NPV.58 PPV a.83 NPV *a.57 PPV a O.7 8 p<.25 NOR MAL 6 NPV*a.58 PPV a.5 p<.25 FIGURE. Previously reported criteria for differentiation of pericarditis from the normal variant.' The positive and negative predictive values ofall criteria are lo and there is marked overlap ofdata beteen the pericarditis patients and normal variant subjects. The dashed line represents the previously used breakpoint beteen pericarditis and normal variants.

4 ACUTE VS ECG/Ginton and Laks 17 Donloaded from by on November 15, 218 pericarditis, as.83 and the negative predictive value as.58. Frontal Plane Mean ST-segment Vector The mean frontal plane ST vector for the pericarditis patients as closer to than the normal variants (p <.25). The positive predictive value of a frontal plane ST vector < 3 diagnosing acute pericarditis as.78 and the negative predictive value as.57. Horiontal Plane Mean ST-segment Vector The pericarditis patients had a mean horiontal plane ST vector to the left of the normal variant group, but fe ere less than 3. The positive predictive value of a horiontal plane ST vector < 3 as.6 and the negative predictive value as.56. Frontal Plane ST-T Vector Angle The angle beteen the mean frontal plane STsegment vector and the mean frontal plane T-ave vector as epressed as positive if the ST-segment vector as to the right of the T-ave vector and negative if to the left. The frontal plane ST-T-vector angle in pericarditis as not significantly different from that in the normal variant group (p >.1). Frontal Plane QRS-ST Vector Angle The QRS-ST angle as epressed as positive if the ST-segment vector as to the left of the QRS vector. The frontal plane QRS-ST angle in pericarditis as slightly to the left of the QRS-ST angle in the normal variants (p <.5). The positive predictive value of an ST-segment vector to the left of the QRS yector in the frontal plane indicating pericarditis as.5 and the negative predictive value as ] E 1.- H '.8- J.6- a-.- 3 >.2-.- XXXXXT ' NPV *.81 PPV *.8 p <.5 E I') I.- a.8- J a.6- I- cl T-ave Amplitude The T-ave amplitude in acute pericarditis as significantly less than normal variants (p <.5 to.5) in leads I, II, V2, V,, V, and V, (fig. 5). Ratio of ST-segment Amplitude to T-ave Amplitude (ST/T ratio) The ST/T ratios in acute pericarditis ere significantly greater than normal variants (p <.5) in leads I, II, V,, V, and V,. In lead I, the positive predictive value of an ST/T ratio..25 indicating pericarditis as.88 and the negative predictive value as.95 (fig. 6). In lead II, the positive predictive value of an ST/T ratio..25 as.75 and the negative predictive value as.81. The positive predictive value of an ST/T ratio in lead V..25 as 1. and the negative predictive value as.87. The positive predictive value for an ST/T ratio..25 in lead V5 as.88 and the negative predictive value as.95 (fig. 6). Although these values ere all highly significant, an overlap occurred in all leads beteen pericarditis and normal variant groups, as indicated by the positive and negative predictive values. ST/T Amplitude Ratio in Lead V. The ratio of ST-segment amplitude to T-ave amplitude in lead V, as.57 1±.6 in the pericarditis group and.13 ±.1 in the normal variant group ECGs (p <.5). No overlap occurred beteen the groups, in that the smallest ST/T ratio in pericarditis as.25 and the largest ST/T ratio in the normal variants as.2; therefore, the positive predictive value as 1. and the negative predictive value as also 1. (fig. 6). The ST/T ratio among the XXXX XXXX + XX XX XX PERIlCARDII NPV *.87 PPV- 1. X p<.5 E <.8-o LJ I- a. < T XX -l- XXXX +F Ei <.2- o.oo NPV *.85 PPV *.85 p<.5 FIGURE 5. T-ave amplitude. Although the T-ave amplitude is significantly higher in the normal variant group in I, V. and V., there is still overlap beteen the groups. The dashed lines represent breakpoints used in calculating tests of predictive accuracy.

5 18 CIRCULATION VOL 65, No 5, MAY 1982 i.2 -~ I.2- I <.8- -j I.6- Ir- N1..- U) > I.- -i XXX r- ct F -. X ~~r) U. a_ "+n, + X (.-' C: <. 8- -J a: cn XXXXXXX I+ MSEMI p Boo Donloaded from by on November 15, 218 NPV a.95 PPV *.88 p<.5 PRCRII NPV a.95 PPV.88 p<o. 5 NPV * 1. PPV * 1. p <. 5 FIGURE 6. ST/T ratio. An STIT ratio in V8 ofo.25 or greater diagnosed all patients ith pericarditis. The ST/T ratio in I and V, as also highly significant. The dashed lines represent the breakpoints used in calculating tests of predictive accuracy. patients ith pericarditis hen subdivided by se as: males.56 ±.6, females.8 ±.11, and the ratio hen subdivided by age as: younger than years.5 ±.6, greater than years.57 ±.9. In all the etiologic subsets of pericarditis, the ST/T ratio as.38 or greater. Thus, an ST/T ratio in lead VB of.25 or greater distinguished all pa.tients ith pericarditis from those ith normal ST-segment elevation in our study population. If the TP segment as used as the baseline in lead V,, 17 of 19 patients ith acute pericarditis had an ST/T ratio >.25 and all normal variant subjects had an ST/T ratio <.25. Thus, using the TP segment as the baseline, the positive predictive value of an ST/T ratio of >.25 diagnosing acute pericarditis as 1. and the negative predictive value as.91. Discussion Numerous authors have described qualitative ECG changes in acute pericarditis69, 16 and have commented on the difficulty of distinguishing these changes from acute myocardial infarction3s and early repolariation.2? Hoever, only Spodickl' 9, 15 provided criteria from hich quantitative conclusions may be made differentiating acute pericarditis from normal variants. Although Spodick's criteria alloed the differentiation beteen the means of these to groups (p <.25), the data significantly overlap (fig. ). Consequently, these criteria have limited value in interpreting individual ECGs. In evaluating the ability of a test to discriminate beteen the presence or absence of a condition, the use of a test of the statistical'difference beteen the means of the to study populations may be misleading. A highly significant difference beteen means can occur beteen to populations ith a marked overlap of data. Consequently, the evaluation of the usefulness of a test in making individual case decisions requires an estimate of its predictive accuracy. Although the specificity and sensitivity have been used for this purpose because they are epressions of ho frequently the test ill detect the presence or absence of a condition in the sample population, the positive predictive value and negative predictive value epress the reliability of a test if its result is positive or negative.1' 17 Because the value of 'a test in clinic'al practice is often more related to its ability to aid in individual case decisions than to distinguish to populations, or in detecting a condition in a population, e believe that the knoledge of the positive and negative predictive values is useful in clinical situations. After analying various potential electrocardiographic criteria for differentiating acute pericarditis from normal variants, in this study population e conclude that an ST/T ratio in lead V..25 as the best discriminator beteen the ECGs of acute pericarditis and normal patients. A revie of the 18 published ECGs of stage I acute pericarditis and normal variants1' 8 5 6, 8-1, 15, 18 also shos a high, although not complete, predictive accuracy of this criterion. There as one false-negative and one false-positive diagnosis of acute pericarditis using the ST/T ratio.25 in V8. Thus, hen applied to illustrations in the literature, the positive predictive value is.9 and the negative predictive value is.88. Although others have commented on the large amplitude of the T aves in normal variants,5' 18 no quantitative data have been presented. In the present study, the amplitude of the T ave in V, also proved to be a significant discriminator in that no patient ith acute pericarditis had a T ave greater tha'n.5 mv and no normal patient had a T ave less than.3 mv (fig. 5). Hoever, a T-ave amplitude of.3-.5 mv could be caused by either condition.

6 ACUTE VS ECG/Ginton and Laks 19 Donloaded from by on November 15, 218 The ST/T ratio in leads I, V and V5 also discriminated beteen acute pericarditis and normal patients, although the positive and negative predictive values ere slightly loer than those in V. If lead V. is not available because baseline artifact or chest bandages are present, an ST/T ratio..25 in any of leads I, V, or V, is highly suggestive of acute pericarditis. The PR segment as chosen as the baseline for measuring repolariation changes for several reasons. First, atrial repolariation may alter the PR segment to a variable degree. This alteration occurs particularly in patients ith sinus tachycardia or ith high catecholamine states,'9 as occurs in patients ith respiratory distress. Thus, measurements from the TP interval ill not eclude atrial repolariation changes, hereas measurements made from the PR segment ill. Also, the TP segment may be very difficult to identify as a stable baseline. This problem is more pronounced in tachycardic patients in that the T ave may distort the P ave in the ECG. If the TP segment as taken as the baseline in the present series, 17 of 19 of the acute pericarditis patients (89%) still had an ST/T ratio in lead V, greater than.25. Although hat the baseline for measurement of ST segments should be is controversial, the use of the PR segment in this criterion appears to be a better discriminator. Spodick's criteria (PR-segment deviation in both the frontal and horiontal planes and a frontal plane ST segment vector that is horiontal and to the left of the QRS vector)" 9' 16 did not reliably distinguish beteen acute pericarditis and normal variants in our study population. A number of eplanations seem plausible. First, our sample population as small and may not have had the same range of underlying causes and associated diseases. Hoever, Bruce and Spodick'5 state that the presence of heart disease or underlying cause of the pericarditis are not associated ith particular ECG abnormalities. Our study confirms that concept: Our patient population had no significant difference in the ST/T ratio in V, hen subgrouped by age, se or cause of the pericarditis. Second, since the QRS, ST-segment and T-ave vectors are partly dependent on heart position and body habitus, our patients could have had a more heterogeneous body type, thereby producing more variation in Spodick's criteria. Since the ST/T ratio in V, is an epression of the relative magnitude of to vectors in a single lead, this ratio ill be less dependent on changes in heart position than ill criteria that rely on the absolute direction of vectors. Finally, the time of obtaining the ECG in the disease stage may have been different. Although e used the same criteria for stage I pericarditis as did Spodickl 9 and Bruce and Spodick,1 some criteria may be more or less sensitive in the very early, rapidly evolving stages of acute pericarditis. Acknoledgment The authors thank Pamela Carbajal for her secretarial assistance in the preparation of this manuscript. References 1. Spodick D: Differential characteristics of the electrocardiogram in early repolariation and acute pericarditis. N Engl J Med 295: 523, Wasserburger RH, Alt WJ, Lloyd CJ: The normal RS-T segment elevation variant. Am J Cardiol 8: 18, Rothfeld EL: The itinerant ST-T segment. Heart Lung 6: 857, Levine HJ: Mimics of coronary heart disease. Postgrad Med J 6: 58, Morace G, Padeletti L, Porciani MC, Fantini F: Effect of isoproterenol on the "early repolariation" syndrome. Am Heart J 97: 3, Harada K: Pericarditis in children. Jpn Circ J 2: 175, Paris A, Beckmann CH, Lancaster MC: The spectrum of ST segment elevation in the electocardiograms of healthy adult men. J Electrocardiol : 137, Suraic B, Lasseter KC: Electrocardiogram in pericarditis. Am J Cardiol 26: 71, Spodick DH: Pathogenesis and clinical correlations of electrocardiographic abnormalities of pericardial disease. Cardiovasc Clin 8: 21, Parker BM, Londera BR, Cupp GV, Dubiel JP: The noninvasive cardiac evaluation of long-distance runners. Chest 73: 376, Kambara P: Longterm evaluation of early repolariation syndrome. Am J Cardiol 38: 157, Laks MM: The gold standard for electrocardiographic computer criteria. Proceedings of Engineering Foundation Conference: Computeried Interpretation of the Electrocardiogram Rindge, NH, U.S. Dept. of Health, Education and Welfare, 1976, pp Bronlee KA: Statistical Theory and Methodology in Science and Engineering. Ne York, John Wiley & Sons, Feinstein AR: Clinical Biostatistics. St. Louis, CV Mosby, 1977, pp Bruce MA, Spodick DH: Atypical electrocardiogram in acute pericarditis: characteristics and prevalence. J Electrocardiol 13: 61, Yoneda S, Koyama M, Matsubara T, Toyama S: Electrocardiographic studies in acute pericarditis ith specific reference to ventricular involvement of non-specific pericarditis. Acta Cardiologica 32: 337, Vecchio TJ: Predictive values of a single diagnostic test in unselected populations. N Engl J Med 27: 1171, Chapman J: Intermittent left bundle branch block in the athletic heart syndrome: autonomic influence of intraventricular conduction. Chest 71: 776, Tranchesi J, Adelarvi V, De Oliveira JM: Atrial repolariation - its importance in clinical electrocardiography. Circulation 22: 635, 196