Journal of Electrocardiology 40 (2007) 3.e1 3.e10 www.elsevier.

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The early repolarization variantan electrocardiographic enigma with both QRS and J-STT anomaliesB
John P. Boineau, MD4
Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA Department of Biomedical Engineering, Washington University School of Medicine, St. Louis, MO, USA

Abstract

A detailed description of the electrocardiogram of the early repolarization variant, including its most common morphological variations is presented. Included is a recently identified anomaly of the QRS complex, which has not previously been reported. Ventricular activation data is presented to explain the unique QRS changes. A comparison with Wolff-Parkinson-White (preexcitation) reveals certain similarities related to a premature completion of depolarization in early repolarization variant. D 2007 Elsevier Inc. All rights reserved.
Electrocardiogram; Early repolarization variant; Left ventricular hypertrophy (bAthlete heart Q); Early depolarization

Keywords:

Introduction The electrocardiogram (ECG) of early repolarization variant (ERPV) is familiar to all cardiologists and considered to be a benign condition (Fig. 1). The most notable characteristic of the ECG is ST-segment elevation. If the subject is young, healthy, and in no distress, it is usually interpreted as benign early repolarization. However, if a patient presents with chest pain, he is often admitted to rule out acute myocardial infarction or pericarditis. Early repolarization is initiated by and, thus, immediately follows early depolarization. In addition, early repolarization and late depolarization are occurring simultaneously in the heart and their separate effects are superimposed near the end of QRS in the ECG. Because of this superimposition, ST elevation is only noticeable after the end of QRS with termination of the dominant activation wavefronts. Thus, there is usually some bnormalQ early repolarization in most ECGs, and perhaps, bexaggerated repolarizationQ would be a more appropriate designation for ERPV. Reports have described the features of ERPV in young adults and a predominance in blacks and other melanotic subjects.1-8 Early repolarization variant consists of different ECG
Supported in part by National Institutes of Health grant numbers 5 R01 HL33277 and 5 R01 HL33722 and Veterans Administration grant 1013. 4 Washington University School of Medicine, Box 8234, St. Louis, MO 63110, USA. Tel.: +1 314 362 8311; fax: +1 314 361 8706. E-mail address: schuesslerd@wustl.edu 0022-0736/$ see front matter D 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.jelectrocard.2006.05.001
B

anomalies involving both QRS and ST-T. Although the unusual repolarization features are well recognized, except for the frequently observed increases in voltage, the atypical QRS features have received no attention. In a subsequent report, the theory is advanced that several previously unrelated cardiac findings, including athletes heart, sudden death in active and apparently normal young individuals, cardiomyopathy, and some sudden death related to inappropriate adrenergic stimulation or drugs (cocaine, etc) may be related to a common mechanism which is expressed as ERPV in the ECG. Although there is no established link between ERPV and either sudden death or cardiomyopathy, one study reported an association between hypertrophic obstructive cardiomyopathy and ERPV.9 The purpose of the present report is to (1) describe the different morphological types of the early repolarization pattern which are quite variable, (2) point out previously unreported anomalies of the QRS complex in subjects with early repolarization ST elevation and J waves, and (3) demonstrate ventricular activation mechanisms of the unique QRS pattern, which have some similarities to those in the preexcitation syndrome. Electrocardiographic description of the ERPV Because of individual variability, poor resolution of standard gain and speed ECGs, and foremost, the lengthening effect of left ventricular hypertrophy (LVH) on the QRS and QT intervals, which is often associated with ERPV, quantitative

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Fig. 1. An example of ERPV with marked ST elevation in an apparently healthy 26-year-old black man. Only the chest leads (V1-V6) are shown. Note that the maximum ST elevation is in leads V3 and V4, has the typical bwestern saddleQ pattern, and is introduced by a prominent J wave.

comparisons between depolarization and repolarization durations in normal and ERPV subjects did not prove to be useful. Repolarization J-STT waveforms This interval begins with the end of the S wave of the QRS complex or at the J junction and is introduced by the positive J wave. It is assumed that the J wave represents a repolarization event, and mapping data will be presented later to confirm this. The pattern of the ST elevation varies in morphology, degree, and location. It can also be dynamic, the pattern changing in degree from one recording to the next. In addition, with sinus tachycardia, exercise, or dobutamine stress testing, much or all of the ST elevation disappears. In the most frequently observed pattern (Fig. 2, panels 1A-C), the elevated ST segment is introduced by a small positive knoblike deflection at the end of QRS, referred to as a J wave, resembling the Osborn wave of hypothermia.10 The J is followed by a cuplike ST-segment elevation and a terminal positive T wave. This pattern resembles a bwestern saddleQ with horn, seat, and back rest corresponding to the J wave, ST segment, and T wave, respectively. The T wave can be tall and peaked (panel 1C). In panel 1D, the ST is bdomedQ and associated with a terminally negative T wave; this type is most often confused with acute myocardial infarction. Less frequently observed is the type (panel 1E) where there is no obvious J wave, a domed ST elevation, and a small or indistinct T wave. The location of the maximal ST elevation is also variable. The most common pattern is for the maximal ST elevation

and most obvious J wave to be located in chest leads V3 and V4, referred to here as apical early repolarization (Fig. 2, panel 1). Maximal ERPV can also occur more laterally (leads I, aVL, V5, and V6), inferiorly (leads II, III, and aVF; Fig. 2, panel 3), and anteriorly (leads V1 and V2; Fig. 2, panel 2). The ST segment can be reciprocally depressed in lead aVR which bviewsQ the basal left ventricular (LV) opening and the negative side of the repolarization field projecting toward the apex. These patterns suggest variation in the regional distribution of the early repolarization. Certain ECGs with anterior ERPV resemble Brugada syndrome. QRS waveforms QRS is also anomalous in many ECGs of subjects with ERPV, exhibiting increased amplitude and a unique morphologic asymmetry. An increased amplitude of QRS is often present and has been described. The QRS voltage is greatest in young subjects with ERPV and can persist into late adult life. Initial QRS is also atypical in many subjects with ERPV. In many subjects with ERPV, there is an initial slurring (slowing), which is subtly similar to the delta wave in Wolff-Parkinson-White (WPW). This deflection can be followed by an ascending R wave with a reduced slope angle. The slower ascending R contrasts with the more rapid descent of the intrinsicoid deflection (Fig. 2, panel 1B [arrow]). This results in a QRS complex which resembles a bleaning tower.Q The ID is so fast that the QRS appears to end prematurely. In some subjects, this is associated with apparent QRS brevity ( b70 milliseconds). In other subjects, the upward sloping part of QRS can take

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Fig. 2. Different ECG patterns of early repolarization. Panels numbered 1, 2, 3 designate three different spatial locations of maximal ST elevation and J-waves. A, B, C, etc, refer to morphologic variations in the pattern of early repolarization within each group.

longer to reach its maximum peak, and even the fast ID cannot abbreviate the total interval. In certain subjects, the short QRS duration and fast descent of the intrinsicoid deflection are more prominent than the ST elevation, which may be minimal. These individuals might not be identified with the ERPV group except for a prominent J wave and atypical QRS features. Variations in ERPV Variations in the ECG patterns of ERPV are shown for 8 subjects in Fig. 3. Only the chest leads are displayed. Fig. 3A represents the most frequently observed pattern with the western saddle J wave, STE, and positive T wave, all maximal in leads V3, V4, and V5. Electrocardiograms A through E exhibit a short QRS duration and rapid

intrinsicoid deflection. Initial QRS slurring with sloping ascending R wave (leaning tower) is shown in 3B. The ST segment in 3C is domelike, and the T wave is inverted. Fig. 3D illustrates another example in which the J wave is not as obvious. Panels E through H represent patterns of anterior ERPV where the principal features, including the J wave and STE, are maximal in leads V1 and V2. Fig. 3E illustrates anterior ERPV, where ST elevation and J wave are maximal and associated with early R-wave progression in chest leads V1 and V2. Panels F and G are examples of anterior ERPV in association with an rsr V complex in V1 and V2. Note the fusion of separate late QRS forces and the J wave. Panel H represents anterior ERPV with a broad rV complex merging gradually with a down sloping STE in the anterior chest leads (Brugada-like).

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Fig. 3. Different ECG examples of early repolarization. Panels A through D demonstrate morphologic variations in QRS and ST-T in four subjects. Panels E through H are four other subjects in which the ST elevation and J-wave are expressed maximally in the anterior chest leads, VI and V2.

Summarizing, the ECG in ERPV is characterized by (1) increased QRS voltage, (2) an asymmetric QRS complex with slurring and a reduced slope angle of the ascending positive R wave, (3) an extremely rapid intrinsicoid deflection, (4) a prominent J wave, and (5) different morphologic forms and spatial distributions of ST elevation. Short and nonuniform QT interval in ERPV The J-STT interval appears atypically short in some subjects with ERPV and can become exceedingly short with sinus tachycardia (Fig. 4). In Fig. 4, note that in addition to the uniformly shortened QT in panel A, there are bifed T waves in the ECGs of subjects shown in panels C and D. This bifed morphology can be interpreted as a form of repolarization heterogeneity in which the first T peak (T1) represents a greater degree of Q-T shortening in one area and less shortening in other areas (T2). In addition, it is not rare to observe a third peak in certain subjects. Whether this represents a third region of latest repolarization or a nonrepolarizaton U wave event is unclear. As mentioned, the repolarization duration is difficult to assess using standard QT interval rate correcting algorithms. There is a

tendency for LVH to prolong the QT electromechanical interval which further complicates comparative QT assessment in ERPV. Although the J-STT can be short, the QT may be normal due to the effect of LVH, which tends to prolong QRS. Thus, if both QRS and J-STT intervals are short, the QT is short. However, if J-STT is short and QRS is long, then QT will be normal or prolonged. In spite of this ambiguity, nonuniform repolarization shortening may be detected as T-wave asymmetry. Left ventricular hypertrophy with ERPV Unlike other subjects with typical LVH with secondary ST depression and T-wave inversion (typical LV strain pattern; Fig. 5A), the ECG in patients with combined LVH and ERPV can exhibit ST elevation in association with T-wave inversion. Instead of the usual degree of ST elevation of ERPV, the J junction can be depressed, but ST demonstrates a domelike upward convexity (Fig. 5B) in contrast to the typical LV strain pattern (Fig. 5A). This represents the combined and opposed interaction of repolarization changes due to LVH and the ERPV. In ERPV with LVH, the ECG can exhibit marked anterior

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Fig. 4. Short and nonuniform QT in ERPV. Note the ST elevation with short QT in A and B and with nonuniform short QT in C and D, which demonstrate two T-peaks.

Fig. 5. Left ventricular hypertrophy and early repolarization. Classical LVH QRS and ST-T patterns are shown in A to compare with LVH plus early repolarization in B and C.

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T-wave inversion (V1-V3) due to exaggeration of the type of ERPV shown in Fig. 3C and is incorrectly referred to as banterior ischemia.Q QRS duration is often increased in subjects with typical LVH (90-130 milliseconds). However, in some subjects with LVH and ERPV, QRS duration may be normal or appear paradoxically abbreviated. In patients who have both ERPV and LVH, the slurring/sloping of the initial QRS limb is even further exaggerated and often associated with prominent notching (Fig. 5C). Note the slurring and sloping of the ascending R wave, which contrasts with the rapid intrinsicoid deflection. Also note the earlier T peak (T1) and later T (T2 or U wave) in lead V4. Occasionally, as many as 3 repolarization peaks (T1, T2,and a U) are observed in subjects with LVH and ERPV. In Fig. 5C, although the total durations of QRS and Q-U are prolonged, the rapid QRS intrinsicoid deflection and earlier T peak are consistent with local regions of shortened activation and repolarization.

fibers intramurally to a mid-LV level (arrows). This effect of increased trabeculation decreases the transmural distance that the wavefronts travel at the normal velocity and shortens the transmural activation time to 25 milliseconds. This unique type of LV activation results in an approximately 37% reduction in the transmural activation time. Note that the axial component is faster than the endocardial-to-epicardial spread, which is related to the predominant fiber orientation, because activation is faster in the long axis of parallel fiber bundles than crossfiber spread.11 Activation data in a human subject with ERPV Fig. 8A illustrates lead V4 in a patient with ERPV before epicardial activation mapping at the time of coronary artery bypass grafting. Note the short QRS duration, fast intrinsicoid deflection, and J wave introducing the elevated ST segment. QRS duration from onset to peak is 40 milliseconds, and the intrinsicoid deflection from R peak to J wave is 15 milliseconds. Excluding the J wave, total QRS duration is only 55 to 60 milliseconds in this lead. Fig. 8B demonstrates the anterolateral and posteroinferior aspects of the heart, and epicardial activation times are indicated for 36 locations recorded simultaneously. Activation time numbers also represent

Methodsactivation mapping Normal transmural LV activation in canines Fig. 6 demonstrates activation across the LV wall, recorded in 2 dogs, and is intended as a normal reference for comparison with the atypical depolarization in Figs. 7 and 8. The maps of the isochronal depolarization sequence were constructed from 5 to 6 needle or bplungeQ electrodes inserted through the LV wall from epicardium to endocardium. Each needle contained from 15 to 20 electroderecording terminals with precisely 1-mm spacing. Bipolar potentials were recorded between adjacent electrode pairs. The isochrones were constructed by connecting points of equivalent activation time on each needle. Fig. 6A demonstrates a typical normal spread of the activation from the endocardium toward the epicardium. In Fig. 6B, in the region of the anterior papillary muscle, the depolarization is slightly more complex. Again, there is outward endocardialto-epicardial spread in the LV wall and, simultaneously, spread in the papillary muscle from its basal attachment inward toward the cavity. Mechanism of shortened depolarization in a canine Fig. 7A illustrates a cross section of the LV in another dog. A unique transmural activation pattern of this same cross section is shown in B. In contrast to the typical unidirectional endocardial-to-epicardial activation shown in Fig. 6, the earliest activation in this animal was initiated at a deep intramural level in the LV midwall. Thereafter, the wavefronts spread circumferentially (elliptically) in all directions, both toward the endocardium and epicardium simultaneously. The mechanism of this unique onset and spread of activation is indicated by the cross-sectional anatomy in panel C. This is an immediately adjacent section of the LV, only a few millimeters distant to the one mapped in panel A. Note that the endocardium is deeply invaginated into the wall, carrying the endocardial Purkinje

Fig. 6. Normal transmural depolarization in 2 dogs is illustrated. Panel A demonstrates typical activation isochrones representing the wave front spreading from the endocardial surface outward toward the epicardium. Panel B demonstrates normal activation in the region of the papillary muscle. Activation times are in milliseconds, and the positions of the wave front at each 10-millisecond interval are indicated at the boundary between the different time zones.

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Fig. 7. Bidirectional transmural activation from the mid-LV wall toward the endocardium and epicardium due to deep penetration (invagination) of the endocardium containing the Purkinje system in a dog in panel B, recorded from the LV cross section shown in panel A. Panel C illustrates the adjacent LV cross section demonstrating the marked endocardial invagination carrying the Purkinje fibers (arrows) deeply into the midmyocardium.

the locations of the electrodes, and the unipolar electrogram associated with each electrode is displayed to the right of the recording site. At the time of this early digital recording (1980), the purpose (then) was to focus only on activation. The total repolarization interval of the electrogram was not digitized and cannot be demonstrated. However, data relevant to ventricular depolarization, QRS brevity, and the J wave are present. Several points are emphasized: 1. A wide area of the LV surface anteriorly and posteriorly was depolarized between 50 and 60 milliseconds or within 10 milliseconds (gray zone), and this correlated with the rapid intrinsicoid deflection in the ECG. Only the lateral LV margin and basal regions of the posterior LV and right ventricle (RV) activated later than 60 milliseconds. This LV epicardial activation brevity with such a large surface completed within a 10-millisecond window is atypical.12 Note the prominent J waves (arrows) at several, but not all, epicardial sites. Particularly note the larger J complexes indicated by the larger arrows in the anterior LV at sites activating at 51 and 54 milliseconds and posteroinferiorly at LV and RV sites. Smaller arrows indicate less prominent J waves at additional epicardial sites in LV and RV.

3.

Observe that all of the J waves occur after completion of epicardial depolarization at each site, that is, after the rapid (negative) intrinsic deflections. These data indicate that the J wave is a postactivation complex and represents an anomaly of early repolarization.

2.

The circles on the anterior and posterior LV in panel B indicate the locations of two 20-point bplungeQ electrodes such as those used in the canines. The encircled values represent the activation times of the electrode points closest to the epicardium. Fig. 8C is a representative cross section approximately midway between apex and base, and superimposed is transmural activation recorded from these 2 locations. Although activation in the anterior wall began at the endocardium and spread unidirectionally and outward toward the epicardium, depolarization in the posteroinferior wall began deep intramurally at the midventricular level and spread bidirectionally toward epicardium and endocardium simultaneously. As a result, posterior wall activation terminated earlier (42 milliseconds), compared with 59 milliseconds in the anterior wall (D = 17 milliseconds). Although it cannot be demonstrated from this one electrode, it is assumed that the posterior depolarization spread circumferentially (elliptically) from this midwall site, forming a highly canceling electromotive field as in the dog in Fig. 7.

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Discussion Comparison of early repolarization and preexcitation (WPW) To emphasize and explain certain features of the ERPV ECG, it is compared with the ECG in WPW for which mechanisms have been established.13,14 Fig. 9 compares the ECG of a subject with ERPV (panel A) with that of a patient with ventricular preexcitation (panel B). Only the lateral chest leads (V4-V6) are illustrated for this comparison. Note the subtle similarity of the initial QRS slurring and sloping in ERPV (panel A) to the delta wave and more exaggerated sloping in the patient with preexcitation (panel B). Thus, initial QRS in ERPV can resemble a mini delta wave. However, in contrast to WPW, the PR segment is not abolished, and the QRS is not wide. Slurring and reduced sloping of QRS is typically absent when there is normal rapid expansion and abrupt extinguishing of multiple opposing wavefronts. This action results in fast swings in the deflections. In contrast, slurring or exaggerated sloping of QRS occurs in conditions where focal, noncompeting activation is occurring, as in WPW. The mechanism of the early QRS changes in ERPV is

explained by the activation data obtained in that subject (Fig. 8). This initial slurring is related to the local depolarization of the anterior wall and septum in which the opposing effects of posterior wall activation have been minimized. Because of the deep midwall onset of activation in the posterolateral wall, with wavefronts spreading in all directions, that is, midwall to both epicardium and endocardium and axially, the spherical or closed electromotive surface of this wavefront results in maximal local cancellation effects. Thus, the outward, endocardial-toepicardial activation in the opposite anteroapical wall has minimal competition. Although not preexcited as in WPW, the local anterolateral activation in ERPV is, nevertheless, relatively unopposed early in QRS and dominates and produces the sloping and slurring. Thus, it is the unbalanced activation of the anterior LV succeeded by the rapid and premature termination of the remaining LV depolarization that coincides sequentially with the initial sloping of QRS, followed by the fast intrinsicoid deflection in ERPV. The initial QRS sloping is further enhanced by LVH because of the larger and longer-lasting wavefronts moving outward in the thickened septal and anterior walls. In some

Fig. 8. Ventricular activation in a patient with ERPV. Panel A illustrates the ECG recorded from lead V4. Panel B demonstrates the epicardial activation sequence and unipolar electrograms recorded from the anterior and inferoposterior aspects of the ventricles. Transmural activation in the same subject is shown in panel C. The data were recorded from two 20-point needle electrodes inserted into the anterior and posteroinferior LV. See text.

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Fig. 9. Comparison of ECGs V4-V6 in a subject with ERPV (A) and a patient with ventricular preexcitation (B). Note the similarities in both QRS and J, ST-T. See text for explanation.

is high-frequency notching of QRS complexes in some leads. These fine, fast notches are usually best visualized in low-voltage transitional leads where major activation events do not compete. This type of notching may result from changing discontinuities in wavefronts propagating through a highly trabeculated subendocardium. In addition to the similarities in QRS, note that there is also a pattern of ERPV ST elevation introduced by a J wave in the subject with WPW. This is due in part to the premature completion of depolarization which, by its advancement, exposes the J and early ST, which might otherwise be obscured by late QRS in both ERPV and WPW. In addition, because of the earlier termination and reordering of activation and, secondarily, repolarization in the posterior LV walls, there are diminished outward posterior repolarization forces to counterbalance those of the anterior LV, and this exaggerates the anteroapical J-STE deflections in both conditions. Thus, at least some part of the J-STT anomaly is contributed or exaggerated by alterations in the phase and distribution of activation and, secondarily, repolarization. An issue in ERPV is whether the QRS and ST-T anomalies are separate and unrelated but linked by some common genetic polymorphism or whether the ST-T changes are all secondary to the QRS changes. That the J-STE morphology can be seen in subjects with longer QRS duration and also that subjects with very narrow QRS can have minimal ST elevation implicate separate primary alterations in both depolarization and repolarization phases. As in most natural systems, different morphological features are usually associated with certain specific functions or effects, bnothing exists for no reason.Q In the following publication, a two-part theory involving both the electrophysiologic and electromechanical systems in ERPV, as well as possible consequences of these anomalies, is presented along with certain supporting clinical evidence for the concepts.

subjects with ERPV and LVH, a longer activation time of the anterior LV results in a wider QRS and later ID, which can overlap and mask the J-wave and the early ST elevation. In those subjects, the early J is obscured and its terminal component is merged with late QRS and appears as a terminal QRS notch or slope. Questions relating to what anatomic mechanisms underlie the atypical midwall activation process must also be addressed. It is postulated that this is due to exaggerated LV endocardial trabeculation. Both the canine and human activation data implicate an increased trabeculation with greater depths of endocardial invagination, carrying the Purkinje system deeper into the midmyocardium. Studies in various animal species demonstrate an increased trabeculation and endocardial invagination as a basis for a more rapid activation of a thicker LV wall.15 Diffusely distributed LV trabeculation should even further narrow the total QRS duration. Another feature sometimes observed in subjects with ERPV and short QRS duration

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