New Electrocardiographic CritePericarditis and Myocardial InfXavier Rossello, MD,a Rob F. Wiegerinck, PhD,a Joan AlguersuMario Sutil, MD,a Andreu Ferrero, BSc,a Juan Cinca, MD, PhDaaServicio de Cardiologa, Hospital de la Santa Creu I Sant Pau, IIb-SaCardiologa, Hospital Son Espases, Palma de Mallorca, Spain; cServiciode Cardiologa, Hospital Arnau de Vilanova, IRBLLEIDA, Lleida, Spai

ABSTRACT

CLINICAL RESEARCH STUDYThe characteristic electrocardiogram (ECG) ndings inpatients with acute pericarditis are a diffuse elevation of theST segment and an upright deviation of the PR segmentwith ST-segment depression in lead aVR.1-3 By contrast, inpatients with acute transmural myocardial ischemia, theST-segment elevation is limited to the ECG leads overlyingthe ischemic region, and this is often associated withreciprocal ST-segment depression in leads related to distantnonischemic regions.4 In a proportion of patients with acutepericarditis, the ECG ndings are not fully characteristic,5,6

Funding: This work was supported by a grant from the Spanish Min-istry of Science and Innovation, Redes de Investigacin del Instituto deSalud Carlos III [REDINSCOR RD06/0003], and Fondo Europeo deDesarrollo Regional (FEDER).

Conict of Interest: None.Authorship: All authors had access to the data and played a role in

writing this manuscript.Requests for reprints should be addressed to Juan Cinca, MD, PhD,Cardiology ServicClaret 167, Barcel

E-mail address

0002-9343 201http://dx.doi.org/1OBJECTIVE: Transmural myocardial ischemia induces changes in QRS complex and QT interval durationbut, theoretically, these changes might not occur in acute pericarditis provided that the injury is nottransmural. This study aims to assess whether QRS and QT duration permit distinguishing acute pericarditisand acute transmural myocardial ischemia.METHODS: Clinical records and 12-lead electrocardiogram (ECG) at 2 magnication were analyzed in 79patients with acute pericarditis and in 71 with acute ST-segment elevation myocardial infarction (STEMI).RESULTS: ECG leads with maximal ST-segment elevation showed longer QRS complex and shorter QTinterval than leads with isoelectric ST segment in patients with STEMI (QRS: 85.9 13.6 ms vs 81.3 10.4 ms, P .01; QT: 364.4 38.6 vs 370.9 37.0 ms, P .04), but not in patients with pericarditis(QRS: 81.5 12.5 ms vs 81.0 7.9 ms, P .69; QT: 347.9 32.4 vs 347.3 35.1 ms, P .83). QTinterval dispersion among the 12-ECG leads was greater in STEMI than in patients with pericarditis (69.8 20.8 ms vs 50.6 20.2 ms, P

leads with ST-segmentg epicardial and trans-

transmural myocardialning in leads with ST-olongation in the sameinfarction.11 In patients

ot transmural and it isdition, no changes in QTleads with ST-segment

hesis that changes in thenterval will improve theh acute pericarditis andnfarction (STEMI).

patients recovered from prolongation of the Qsecondary to drugs or

nonidiopathic (seconda

Study Variables andIn all patients we recordcharacteristics and alsoECG, and echocardiogra

The admission 12-lead2 magnication of theparameters were measurethe PR segment from the2) ST-segment deviationdownward (ST depressiothe isoelectric line exprduration as the time elawave to the end of the S

ICA

eninadsn paevat), bu.

trocadiffSTEriaent

TheStudy PopulationThis is a multicentric case-control study on 150 patientswith acute chest pain associated with ST-segment elevationon the admission ECG, recruited in 4 tertiary hospitals fromApril 2007 to June 2010. Seventy-nine patients had acutepericarditis and 71 presented with STEMI secondary toacute occlusion of the right (n 43), left anteriorsegment elevation. These ndinthat changes in QRS duration inelevation could help differentiatinmural injury.

Moreover, patients with acuteinfarction show initial QT shortesegment elevation and late QT prleads 24-48 hours after the onset ofwith pericarditis, the injury is nconceivable that in this clinical coninterval length will be detected inelevation.

In this study we tested the hypotduration of QRS complex and QT iaccuracy of the ECG to distinguisST-segment elevation myocardial i

MATERIALS AND METHODScontribute to better differentiating acute pericarditis andacute transmural myocardial ischemia.

Changes in QRS complex and QT interval duration occurin the presence of acute myocardial ischemia, but these ECGndings have not yet been applied to the current clinicaldiagnostic algorithm of acute pericarditis and acutemyocardial infarction. Transmuralmyocardial ischemia slows thepropagation of local activationfront. This results in prolongationof the QRS complex duration andenlargement of the R-wave am-plitude in local electrograms aswell as in ECG leads overlyingthe ischemic region (monophasicpotentials).9 Because myocardialinjury in patients with acute peri-carditis is restricted mainly to theepicardium, no local transmuralconduction delay and hence, theo-retically, no widening of the QRScomplex should occur. Indeed, ina porcine model of potassium-induced local epicardial depolari-zation mimicking acute pericardialinjury, we have veried that leads showing potassium-induced ST-segment elevation do not present widening ofthe QRS complex. By contrast, coronary occlusion in thesame animal model induced local conduction slowing andQRS widening in leads depicting ischemia-induced ST-

10 gs support the concept

CLINICAL SIGNIF

QRS complex widshortening in leelevation occur iST-segment elinfarction (STEMIacute pericarditis

These new elecmay improve theof pericarditis andthe classical criteterns of ST-segmdeviations.

234descending (n 28), or circumex (n 10) coronaryduration as the time from the beginning of the q wave to theend of the T wave at the point of interjection with theisoelectric line (Figure 1).

The ECG tracings were coded for anonymity andmeasurements were done blinded to the clinical data.Thereafter, allocation of patients to either the pericarditis orSTEMI group was done according to the nal diagnosis at

hospital discharge.sudden death;T interval, either congenital orelectrolyte imbalance; andry) pericarditis.

Protocoled the demographic and clinicaldata on laboratory tests, 12-leadm.ECG was analyzed manually on aoriginal recording. The followingd in each recording: 1) deviation ofisoelectric line expressed in mV;as the upright (ST elevation) or

n) displacement of the J point fromessed in mV; 3) QRS complexpsed from the beginning of the qwave (J point); and 4) QT intervalarteries. In all cases of the STEMI group, the infarct-relatedcoronary artery was the only vessel presenting signicantlumen stenosis.

All patients included in the pericarditis group presentedwith acute chest pain, mainly central with pleuritic charac-teristics (sharp, respirophasic, worsens on recumbency)

associated with acute ST-segmentchanges. A portion of thesepatients presented with elevatedcardiac biomarkers with no regionalleft ventricular wall motion abnor-malities on the echocardiogram. Inthese cases, the presence of myo-pericarditis was suspected and insome of them, a coronary angiog-raphy was performed to rule outSTEMI. The diagnosis of STEMIwas based on typical chest painassociated with ST-segment eleva-tion and increased plasma levelsof myocardial biomarkers. In allSTEMI cases, the presence andlocation of acute coronary occlu-sion was documented by emergentcoronary angiography.

Exclusion criteria to enter in the study were:

prior Q-wave myocardial infarction; secondary alterations of QRS/ST segment caused bybundle branch block, ventricular pre-excitationsyndromes, or cardiac pacing;

NCE

g and QT intervalwith ST-segmenttients with acuteion myocardialt not in those with

rdiogram criteriaerential diagnosisMI when added tobased on the pat-and PR-interval

American Journal of Medicine, Vol 127, No 3, March 2014

ecording cFigure 1 (A) 12-lead electrocardiogram rMagnied recording of leads II and III show

Rossello et al ECG Changes in Pericarditis and InfarctionData AnalysisCategorical variables were presented as frequencies, andthe differences between groups were assessed with thechi-squared or Fishers exact test whenever necessary.Continuous variables were expressed as mean SD, anddifferences were compared using the t-test. Two-sidedP

Table 1 Demographic and Clinical Characteristics of the 150 Patients Included in the Study

Acute Pericarditis (n 79) STEMI (n 71) P-ValueCardiovascular risk factors

Age (years) 44.8 19.45 57.3 11.97

Rossello et al ECG Changes in Pericarditis and Infarction 237duration: 83.2 10.06 vs 80.00 12.81, P .237; and QTdispersion: 52.2 19.28 vs 49.8 21.59, P .616).

As shown in Figure 3, logistic regression analysis formodel A (QRS complex duration and QT interval length)depicted an area under the ROC curve of 0.807 (95%condence interval [CI], 0.735-0.878; P

neighboring local extracellular electrograms in the ischemicmyocardial region.13 In this model, widening of the QRScomplex in local electrograms occurred when the ischemiccells lose the resting membrane potential and the localcellular activation is delayed. Likewise, the slowing oftransmural activation in the ischemic area is responsible forQRS complex prolongation in the conventional ECG.10,14

The lack of QRS prolongation in patients with acute peri-carditis is likely due to the fact that in this clinical condition,the area of myocardial injury is restricted to the outer cardiaclayers and therefore, no inner transmural conduction delay

238 The American Journal of Medicine, Vol 127, No 3, March 2014depression (Table 4). The internal validation of this modelwith bootstrap resampling showed a reduction of

Clinical Implications STEMI but not in pericarditis is likely the underlying

Electrocardiology. J Am Coll Cardiol. 2011;58(13):1309-1324.20. Maisch B, Ristic AD. Practical aspects of the management of peri-

Rossello et al ECG Changes in Pericarditis and Infarction 239The present study provides new clues that may improve thedifferential diagnostic yield of the ECG in patients withacute pericarditis and acute STEMI.

When the changes in QRS complex duration and QTinterval dispersion were applied to our patients, the areaunder the ROC curve attained a magnitude comparable tothat observed after application of classical ECG ndings(ie, deviation of the PR interval and J point level in leadaVR; and extension of leads with ST-segment elevation,ST-segment depression, and PR-segment depression).However, when the present new ECG ndings were addedto the classical criteria, the differential diagnostic yield ofthe ECG increased signicantly, giving rise to an area underthe ROC curve of 0.914.

The objective of this study was not to compare the diag-nostic yield of the clinical features with that of the ECG.Instead, we attempted to improve the differential diagnosis ofpericarditis and STEMI based on objective ECG parameters.

Because the magnitude of the changes in QRS complexand QT interval reported in this study may not be easilyappreciated in ECGs recorded at the conventional stan-dardization, we used a 2 magnication of the originalrecording. Automatic analysis of the QRS and QT intervalchanges could be done by developing specic software, ashas been done in the assessment of microvoltage T wavealternans.19 With further development of ECG criteria ofpericarditis, it might be possible to reduce the number ofpatients unnecessarily referred to an emergent coronaryangiography and, in addition, to afford a more appropriatemedical treatment.20

Study LimitationsThe nonrandomized design of this study does not permit adenitive clinical validation of the new ECG criteria.However, the bootstrapping internal validation showedstability of our model. Moreover, our ndings are inaccordance with previous observations in patients withSTEMI and in experimental models of pericarditis and acutecoronary artery occlusion.9,10,14

Although the ECGwas used to establish the nal diagnosisat hospital discharge, the validity of our new ECG criteriawould not be affected because changes in the duration of QRScomplex and QT interval length are not considered in thecurrent diagnostic algorithms of STEMI and acute pericarditis.

CONCLUSIONSProlongation of the QRS complex duration and shorteningof the QT interval in leads with ST-segment elevation isobserved in patients with STEMI but not in patients withacute pericarditis. These new ndings may improve thedifferential diagnostic yield of the ECG in acute pericarditisand STEMI. The transmural extension of the injury in cardial disease. Heart. 2003;89:1096-1103.mechanism of the observed different ECG features.

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14. Noriega FJ, Jorge E, Arzamendi D, Cinca J. Mechanism and diagnosticpotential of reciprocal ECG changes induced by acute coronary arteryocclusion in pigs. Heart Rhythm. 2013;10:883-890.

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19. Verrier RL, Klingenheben T, Malik M, et al. Microvolt T-wave alternansphysiological basis, methods of measurement, and clinical utilityconsensus guideline by International Society for Holter and Noninvasive

New Electrocardiographic Criteria to Differentiate Acute Pericarditis and Myocardial InfarctionMaterials And MethodsStudy PopulationStudy Variables and ProtocolData Analysis

ResultsClinical CharacteristicsECG Findings

DiscussionChanges in QRS Complex DurationChanges in QT Interval DurationClinical ImplicationsStudy Limitations

ConclusionsReferences