ST Segment Elevation

The ST-segment elevation (STE) is closely related to the diagnosis of the acute myocardial infarction (AMI). Both 1) the biochemical acute myocardial injury (stated as a fast change in a cardiac troponin plasma level—preferably the more specific troponin I), including at least one value beyond the 99th percentile of the upper reference limit) [1] and 2) the J point ST-segment elevation exceeding the thresholds dependent on gender, age, and electrocardiographic lead within at least two contiguous leads in a non-left bundle branch block (non-LBBB) and equally non-left ventricular hypertrophy (non-LVH) patient represent the keystone for the diagnosis of ST-elevation acute myocardial infarction (STEMI) [1,2,3]. As the stringency of the myocardial reperfusion therapy leaves almost no waiting room for the confirmatory troponin variation, the decision to treat in a timely fashion relies upon the ischaemia-looking ST-elevation in a patient with new-onset symptoms suggestive of myocardial ischaemia [4]. Should all ST-elevations and troponin rises have been ischaemic in nature, the STEMI diagnosis would be straightforward. As neither the chest pain nor the ST-elevation is exclusively ischaemic in origin, four possible categories of patients are thus derived: 1) ischaemic pain and ischaemic ST-elevation = STEMI, 2) non-ischaemic pain and ischaemic ST-elevation = spuriously painful STEMI, 3) ischaemic pain and non-ischaemic ST-elevation = acute myocardial infarction with false ST-elevation, and 4) nonischaemic pain and non-ischaemic ST-elevation = pseudo-STEMI. Whereas one patient falling into either the first or the second category is a true STEMI patient in need of immediate reperfusion therapy, those showing non-ischaemic ST-elevations belonging to any of the last two categories should logically avoid the non-zero innate haemorrhagic risk of a useless invasive angiography. The shorter active potential duration in the ventricular subepicardial layer relative to its subendocardial counterpart represents the basis of the so-called physiologic subepicardial early repolarization, seen as the normal T wave on the surface electrocardiogram [5]. The normal segment is isoelectric, except in leads V1 and V2 [6].

To avoid artifactual ST deviations, the upper limit (= cutoff) of low-frequency filtration (= high-pass frequency filtration) during manual (= real time monitoring) electrocardiographic recording should be set at (maximum) 0.05 Hz [7]. While doing so clears better the baseline drift, a higher cutoff creates spurious ST deviations (namely STE in leads with deep S waves and ST depressions in leads with high R waves, respectively), especially at low heart rates and for wide QRS complexes with tiny basal ST deviations [8]. The ST-segment deviation is measured against a horizontal reference level (defined by convention either as crossing the end of PR segment (= QRS onset) (advisable), or as itself being the TP segment (less advisable), and the measurement is currently carried out at the J point (= end of the QRS complex) for normal heart rates, whereas the measurement point is shifted 40-60-80 milliseconds rightwards (after the J point) during stress testing–induced tachycardia [9,10,11,12,13]. Except when it becomes depressed and thereby unusable against the background of the acute pericarditis, atrial infarction, or deep Ta wave of atrial repolarization, the end of the PR segment (and not the TP segment) is the recommended reference level for the measurement of ST-segment deviation, all the more so as during tachycardia the TP segment progressively shortens to zero [6,14]. Connecting by a straight line the endpoints of two consecutive PR segments is the right way to build up the isoelectric line [9]. By analogy with the „leading edge to leading edge” rule in echocardiography, both measurement levels (i.e., the endpoint of the PR segment and the J point) have to be chosen at the upper edges of an unusually wide electrocardiographic line tracing [1]. The measurement point must be specified, as the magnitude of ST deviation is highly dependent on it. The farther the measurement point is from the J point, the higher the sensitivity of the ST deviation for the acute coronary syndrome diagnosis, but the lower the specificity [13]. Whereas the 2009 AHA/ACCF/HRS Recommendations for the Standardization and Interpretation of the Electrocardiogram [3,10] and the 2018 Fourth Universal Definition of Myocardial Infarction [1] advocate the measurement of the ST deviation at the J point, some algorithms, especially derived to localize the acute coronary occlusion in STEMI, use the measurement of ST-segment deviation 60 milliseconds past the J point [15]. The validity of the results yielded by the culprit artery identification algorithms (such as making the difference between the right coronary artery and circumflex artery) relies upon the point chosen for measurement of the STE along the whole ST segment span (i.e., closer to, or well beyond, the J point) [16]. The wider the QRS complex, the more inaccurate the limit between its end and the beginning of the ST segment case whereupon a vertical line drawn through the J point already seen in one electrocardiographic lead allows the J point discovery in all other leads recorded simultaneously.

Most healthy (especially black) men display an upsloping and concave-upwards STE within the first precordial leads (V1–V3(V4)), soaring opposite to the main QRS deflection, followed by a positive T wave and designated as male-type physiologic ST-segment elevation [6,9,10,11,12,14,17]. Its utmost amplitude is usually seen in V2 (the lead displaying the deepest S wave among all precordials), where it reaches a maximum 2.5 mm before the age of 40 and 2 mm beyond this age, respectively [9,10,11,14]. Vagotonia pulls up the physiologic STE [18]. A similar shape of STE, but achieving no more than 1.5 mm in V2–V3, is allowed in healthy women irrespective of age, and this is called female-type physiologic ST-elevation [10,11]. Convex-upwards STE followed by a negative T wave in V1–V4 can be occasionally seen in young black athletes [19]. Juvenile pattern means negative T waves from V1 to V4 until the age of 16, and there is no related ST-elevation thitherwards [19].

The somewhat extensive array of causes of pathologic STE can be digested, as follows: 1) causes of thoracic/epigastric pain and/or acute dyspnoea: myocardial ischaemia [6,11,17,20] (vasospastic angina, ST-elevation acute myocardial infarction, left ventricular wall aneurysm), Takotsubo cardiomyopathy, [11] acute pericarditis, [6,11,17,20] acute myocarditis, [6,11,17,20,21,22] acute pulmonary embolism, [6,11,17,20] acute aortic dissection, [9,14]cardiac trauma, [11,20] left pneumothorax, [17] pneumonia, [23] acute pancreatitis, [14] acute cholecystitis, [14] and acute gastric distention; [23,24] 2) cardiac causes of potential arrhythmic syncope and/or potential sudden cardiac death, or non-cardiac causes of loss of consciousness: congenital J wave syndromes (Brugada syndrome, early repolarization syndrome), [6,11,17,20] Wolff-Parkinson-White (WPW) syndrome, [25] arrhythmogenic right ventricular cardiomyopathy, left ventricular tumor, [11] mediastinal tumor, [26,27] hyperkalaemia, [6,11,17] hypercalcaemia, [11,28] hypothermia, [11,28] class IC antiarrhythmic drugs and antidepressant drugs, [9,11] and intracranial haemorrhage; [1,11,20,29,30,31] 3) causes without life-threatening symptoms: secondary left ventricular hypertrophy (LVH), [2,6,11] left bundle branch block (LBBB), [6,11] non-specific intraventricular conduction disturbances, [12] ventricular pacing, [31] electrical cardioversion, [6,9,11] pectus excavatum, [32] heart compression either by hiatal hernia, [33] elevated left hemidiaphragm from an acute gastric distension, [23] or by ileus [34]. Beyond symptoms, all the single-cause ST elevations listed above can be ordered depending on their primary or secondary pattern, cardiac or non-cardiac cause, space extent, and time course (Table 1). As any STE connotes some degree of dispersion of repolarization, clustering of causes increases the risk of ventricular arrhythmias by the mechanism of reentry (such as STEMI afflicting an individual already having the early repolarization syndrome with horizontal/downsloping STE, or class IC antiarrhythmic drugs given fortuitously to a genuine Brugada syndrome patient) [26].

Ischaemic STE may arise from any of the following three conditions: ST-elevation acute myocardial infarction (STEMI), vasospastic angina, and left ventricular wall aneurysm.

A local ST vector proportional to the ischaemic myocardial mass elevated at right angles to the surface and pointing outwards represents the electrical testimony of the acute “subepicardial” ischaemia (practically acute transmural ischaemia) hitting but one ventricular segment. The single subepicardial coronary artery occlusion driven ischaemia enlaces some adjoining ventricular segments (notably an entire ventricular wall), and a regional ST vector conveying the sum of individual ST vectors of those ailing ventricular segments is wherefore expressed. Two substantial aftermaths ensue from the vectorial nature of the sum, as follows: 1) as the ST vector of a heavier (basal) ventricular segment is larger than the corresponding ST vector of a lighter (apical) segment, any summation vector is tilted towards the heaviest myocardial segment (is pointing towards the site of the coronary occlusion), instead of being oriented symmetrically (namely perpendicular to the surface of the middle segment), and 2) two local ST vectors stemming from parietal segments with antipodal locations and similar sizes can cancel each other out, accounting for incidental cases of electrically silent acute transmural ischaemia. The image of the ST summation vector pointing to the site of the acute subepicardial coronary occlusion is represented by a) ST-segment elevation (= the native image of transmural ischaemia) in any lead perpendicular to the ischaemic wall surface and having its positive pole closer to the subepicardium than to the subendocardium (called direct lead) and possibly with b) ST-segment depression (denominated mirror image/reciprocal depression) in any other lead directly opposite to the direct lead (called indirect lead) (Figure 1). Accordingly, the classic picture of transmural ischaemia produced by the acute occlusion of a single subepicardial coronary artery is represented by STE within one set of contiguous direct electrocardiographic leads, and/or reciprocal ST depression (STD) within another set of continguous indirect leads (be they conventional or not) [3]. The spatial distribution of those ST-segment changes depends on 1) which artery is occluded (left anterior descending (LAD) versus left circumflex (LCX) versus right coronary artery (RCA)), 2) how long the artery is (long = dominant versus short = non-dominant), and 3) where the occlusion is located (proximal versus distal). Depending on whether it surrounds the tip of the heart (providing the blood supply to the apical fourth of the left ventricular inferior wall—as seen in right anterior oblique angiographic view) or not, the LAD coronary artery qualifies as long (= dominant) or short (= non-dominant) [35]. Depending on whether the posterior descending artery (responsible for blood delivery to the inferior third of the interventricular septum, left ventricular inferior wall and the posteromedial papillary muscle) comes off the RCA or not, RCA is labelled dominant or non-dominant (where the RCA dominance is synonymous with the well-known meaning of right coronary dominance). Ultimately, LCX is either dominant, or non-dominant, as it generates the posterior descending artery, or not (where the LCX dominance is synonymous with the conventional meaning of left coronary dominance). Although any coronary artery is nominally divided into proximal, middle, and distal anatomic segments, the present-day identification algorithms dualize a coronary artery into proximal and distal (= non-proximal) segments. The proximal LAD extends from left main trunk bifurcation to the opening of either the first diagonal or the first septal branch, whichever of them is the farthest. The proximal RCA spreads till the aperture of the first right ventricular branch, whereas the proximal LCX goes up to the porthole of the first obtuse marginal. There is a basic (fundamental) set of electrocardiographic leads for every coronary artery, always revealing ST-segment changes (commonly STE, sometimes ST depression only—in case of LCX occlusion) highly suggestive of its acute occlusion, regardless of both its dominance/non-dominance and proximal/distal occlusion site. Usually, the ST changes recorded by the fundamental set of derivations match the case of distal occlusion of the non-dominant artery, whilst each one of the other three cases (namely the proximal occlusion of the non-dominant artery, distal occlusion of the dominant artery and the proximal occlusion of the dominant artery) can add ST-segment changes in other (additional) leads. As the ST changes recorded within the fundamental set of leads are derived from adjacent segments of the same ventricular wall, they cannot cancel each other out and therefore account for the everlasting part of the electric image of the coronary artery occlusion. Contrariwise, the ST changes seen in all other groups of leads but the fundamental one express the simultaneous transmural ischaemia of those myocardial segments supplied by other branches from the remaining variants of artery length and occlusion site, accounting for the variable part of the electric image. On the one hand, if wall segments are not diametrically opposite, their STE inform correctly about the size of myocardium at risk. On the other hand, when wall segments are diametrically opposite, their STE are subtracted from each other (and this turns out during the proximal occlusion of a dominant coronary artery). Further on, 1) as the diametrically opposite wall segments supplied by a dominant coronary artery running parallel to the longitudinal cardiac axis have clearly different sizes, the STE of the proximal (basal) wall segment overrides the STE of the distal (apical) segment of its diametrically opposite wall. The classic example is featured by the acute proximal occlusion of a long (dominant) left anterior descending artery (which wraps around the heart tip), where the ST vectors of transmural ischaemia of basal anterior septum and basal anterior wall override the ST vector of transmural ischaemia of the apical inferior wall, presenting as STE in (V1)V2–V4 with reciprocal ST depression in DII, DIII, and aVF (as if it were an acute proximal occlusion of a short (non-dominant) left anterior descending artery). 2) As the directly opposite wall segments supplied by a coronary artery running parallel to the short heart axis have often similar sizes, their STE can readily cancel each other out. Here, a common example is given by the acute proximal occlusion of a dominant right coronary artery, where the STE in right precordial leads (showing the transmural ischaemia of the right ventricle) and the STE within V7–V9 (the upshot of the transmural ischaemia of the inferolateral left ventricular wall) can sometimes (but fortunately not always) nullify each other, yielding a false reassuring STE confined to the fundamental set of the inferior leads and thereby mimicking an acute distal occlusion of a non-dominant right coronary artery. Anatomical variability of the patients precludes any absolute rule when dealing with reciprocal subtraction of STE arising from opposite walls, like in examples 1) and 2) above. The fundamental set of leads defining the LAD territory is represented by direct leads V2–V4, whereas the additional groups assisting the electrocardiographic variants are 1) aVR,V1, 2) DI,aVL, 3) V5,V6, and 4) DIII, aVF, DII. The fundamental set of leads defining the RCA territory is represented by direct leads DIII,aVF,DII, whereas the additional groups assisting the electrocardiographic variants are 1) V4R,V3R,aVR,V1 and 2) V5–V9. The fundamental set of leads defining the LCX territory is (eventually) represented by indirect leads V1–V3 and/or direct leads V7–V9 (keeping in mind that many cases of acute distal occlusion of a non-dominant LCX are electrically silent), whereas the additional groups assisting the electrocardiographic variants are 1) aVL,DI,V5,V6 and 2) DII,aVF,DIII (Figures 2a and 2b).

Figure 1

Figure 2a

Figure 2b

The lead groups are currently used by several algorithms providing the likely single coronary occlusion site in the acute setting [3,15,17,36,37,38,39,40,41,42]. Dedicated algorithms focus on each one of the two main left ventricular territories (anteroapical and inferolateral, respectively), where their choice depends on the group of leads featuring the highest STE. The highest ST-elevations noticed in the precordial leads (usually V2–V4) signify an ST vector pointing anteriorly as a result of acute LAD occlusion and prompt the selection of the LAD algorithm (Figure 3). Part 1: a reciprocal ST depression in the inferior leads (deepest in DIII), eventually twinned with a direct STE in aVL and DI, smartens up superiorly and to the left the orientation of the already anteriorly pointing ST vector and represents the LAD occlusion upstream the origin of the first diagonal branch (being conventionally labelled proximal LAD occlusion), usually irrespective of the LAD length. Further away, a rightward extension of the precordial STE towards V1 +/− aVR, eventually coupled with reciprocal ST depression in V6, sophisticates the already anterior and upward orientation of the ST vector slightly to the right and sets out the proximal LAD occlusion before the origin of the first septal branch. Unlike the immediately above, the proximal LAD occlusion is located between the origins of the first septal and the first diagonal branch, when neither extension of precordial STE to the right of V2 nor reciprocal ST depression in V6 exist. As the right branch of the bundle of His receives the blood supply from the first septal branch of LAD, a right bundle branch block newly appeared against the background of the acute coronary syndrome strongly supports the hypothesis of acute occlusion of the first septal branch, or above it [42]. Part 2: The absence of significant reciprocal ST depression in the inferior leads results from the absence of superior orientation of the ST vector and represents the LAD occlusion downstream the origin of the first diagonal branch (conventionally labelled as distal LAD occlusion). Further away, an isoelectric ST segment in the inferior leads means a horizontal ST vector, resulting from the distal occlusion of a short (non-dominant) LAD. Finally, STE in the inferior leads means an ST vector pointing inferiorly and either a) to the left (when ST-elevation in DII is higher than ST-elevation in DIII), resulting from the distal occlusion of a long (dominant) LAD, or b) to the right, when STE in DIII is higher than STE in DII, going along with the signs of isolated first septal occlusion (ST elevation in V1 +/− aVR and reciprocal ST depression in V6), DI, and aVL, and resulting from the occlusion between the origins of the first diagonal and the first septal branches of the uncommon anatomic variant of LAD (where the first septal comes off after the first diagonal). Two examples of acute LAD occlusion are shown in Figure 4.

Figure 3

Figure 4

The highest ST-elevations seen in the inferior leads signify a ST vector pointing inferiorly as a result of an acute RCA/LCX occlusion and prompt the selection of the RCA/LCX algorithm (Figure 5). RCA occlusion results in a further rightward and anterior shift of the ST vector manifested either as a) ST depression in DI, or b) maximal inferior leads STE seen in DIII, adjoined to a small (less than 1) ratio between the absolute value of the sum of reciprocal ST depressions in V1–V3 and the sum of ST-elevations in DII, DIII, and aVF. The RCA occlusion is thenceforth classified as proximal or distal, as the ST segment in aVR is elevated, or not, respectively. Vice versa, the LCX occlusion results in a further leftward and posterior shift of the ST vector, displayed as one of the following electrocardiographic novelties: a) STE in DI, b) maximal inferior leads STE noticed in DII, or c) big (more than 1) ratio between the absolute value of the sum of reciprocal ST depressions in V1–V3 and the sum of ST-elevations in DII, DIII, and aVF. Two examples of acute RCA occlusion are unfolded in Figure 6, whereas one example of acute proximal LCX occlusion is betoken in Figure 7.

Figure 5

Figure 6

Figure 7

On one hand, as the anteroapical left ventricular territory embodies several parietal segments receiving their blood supply always from LAD, regardless of its length and occlusion site (namely segments 7, 8, 13, 14, and 17, whose STE are exhibited in the precordial leads V2–V4), the fundamental set V2–V4 secures the identification of LAD across the first step of the localization algorithm. Later on, the ST deviations within the additional groups of leads help localize the LAD occlusion site. On the other hand, the inferolateral left ventricular territory counts in two parietal segments supplied exclusively by RCA (segments 4 and 10), several segments welcoming variable blood supply (RCA or LCX or LAD) and no segment with exclusive LCX dependency, hence accounting for the reasons why a) the identification of culprit coronary artery (RCA versus LCX) embosoms several steps of the discriminative algorithm and b) there is no claim to assign the LCX occlusion site [42]. The precision of the discriminative algorithms is reduced by the variability of blood supply of several ventricular parietal segments in the general population (provided by LAD or RCA for segments 9 and 15, LAD or LCX for segments 6, 12, and 16, and RCA or LCX for segments 5 and 11) [43] (Figure 8). As V2 is the closest precordial lead to the left ventricular anterolateral wall, the ST-elevation in V2 conflated with reciprocal ST depression in DIII and aVF points to the first diagonal occlusion [36,38,42,44], whereas the reciprocal ST depression in leads V1–V3 advocates for the first obtuse marginal occlusion, against the background of acute myocardial infarction with STE in aVL and DI [45] (Figure 9). Nowadays, other discriminative algorithms are less thoroughly validated [46,47]. The classical partition of anterior wall STEMI into anteroseptal/anteroapical/anterolateral/anteroextensive patterns bears little correlation with the actual infarction size and should therefore be replaced by dedicated algorithms, like those above [48]. Besides its classical advent in right ventricular myocardial infarction associated with the acute inferior wall myocardial infarction, the STE in V4R above 0.1 mV can also occur in acute anterior wall myocardial infarction, wherein its abiding existence beyond the percutaneous revascularization procedure portends a worse prognosis [49]. Although it strongly argues in favor of the ischaemic origin of a primary localized STE, the reciprocal ST depression is neither sensitive, nor specific. Whereas its sensitivity ranges between 30% in anterior wall myocardial infarctions and 70% in inferior wall myocardial infarctions, its specificity is far from perfect, too, as outside myocardial ischaemia the reciprocal ST depression is shared by LVH, LBBB, WPW syndrome, and even early repolarization syndrome (in aVR only). The distal occlusion of a short LAD has no reciprocal ST depression [50]. The thresholds for STE hold true for myocardial ischaemia provided no cause of secondary STE (LVH, LBBB) is present [1,2].

Figure 8

Figure 9

Although many STEMI cases observe the principle of clustering of STE within a set of contiguous leads, some exceptions still occur, either presenting with STE in both precordial and inferior leads, or STE merely outside the expected leads. On one hand, some scenarios about STE spreading over precordial and inferior leads are the following: 1) acute distal occlusion of a long (wrapping/dominant) LAD [51,52], as well as its very uncommon counterpart, namely the acute distal occlusion of a long posterior descending artery, which wraps up the tip of the heart to flush the apical segment of the anterior wall [53], 2) acute proximal occlusion of a short (non-dominant) RCA, featuring STE in leads DII,DIII,aVF,V1–V3 (whereabouts the decreasing order of STE amplitude from V1 towards V3 opposes against the increasing order of STE amplitude from V1 towards V3(V4) exhibited by LAD occlusion) [54,55,56], 3) acute proximal occlusion of a dominant LCX, introducing STE in DII,DIII,aVF,V5,V6 [35], and 4) acute occlusion of an RCA feeding aforetime by way of collaterals the viable territory of a chronic occluded LAD [35]. On the other hand, the acute proximal occlusion of a short (non-dominant) RCA causing lonesome acute right ventricular infarction is sometimes able to display ST-segment elevations decreasing from V1 towards V3, beyond those far-famed in V3R and V4R, yet none within the inferior leads, as usually one expects [54]. An additional algorithm has been derived to riddle out the cases where the amplitudes of the ST-elevations in precordial and inferior leads are alike, as follows: 1) when maximum STE in the precordial leads exceeds the maximum STE in the inferior leads, the T wave higher than the R wave in V3 suggests the LAD occlusion, whereas the opposite relationship points to the RCA/LCX occlusion; 2) contrariwise, when maximum STE in the inferior leads exceeds the maximum STE in the precordial leads, the STE in V2 greater than or equal to the absolute value of the ST-depression in aVL implies the LAD occlusion, whereas the opposite relationship hints the RCA/LCX occlusion [35].

Most late-emerging clustered/diffuse ST-elevations/ST-depressions after the coronary artery bypass grafting (past 48 hours) are non-specific, yielded by pericarditis (including post-pericardiotomy syndrome) or myocardial inflammation, whereas the acute occlusion of the graft is uncommon (3%) [57]. Although the definition of myocardial infarction coming out of the blue within 48 hours after completion of the coronary artery bypass graft (type 5 myocardial infarction) disregards any new/additional STE [1] (and least of all its amplitude) [50], a bulky and obstinate early STE against the background of a cardiac troponin elevated more than 10 times the upper limit of normal and increased by more than 20% from the baseline value must prompt the angiographic check-out [57]. Hereunder either the patient still under anaesthetic is unable to narrate his pain, or the pain is confounded by the fresh pericardial/skeletal postoperative inflammation, and last but not least, the quality of transthoracic ultrasound windows is often disappointing [57].

The pair between the backyard spontaneous/provoked STE and the reciprocal ST-depression occuring in vasospastic angina mimics an evanescent image of STEMI [58,59].

The iconic moving picture of ischaemic STE opens up with the ephemeral hyperacute T wave (Figure 10), which usually blossoms in the precordial, or lateral leads as a tall, broadly-based and mostly symmetric wave, lifting the J point, as well as elongating the QT interval thereupon. A minimal reciprocal ST-depression in remote leads is sometimes perceived [10,60,61,62]. Next comes the progressive evolving and upwards concave STE, which pulls up the end of the QRS complex (either hiking the R wave in qR-type complexes, or removing the S wave in Rs-type ones, by slowing the local depolarization) [42], then catches up with the T wave and finally all blend together. When fast enough, coronary reperfusion allows the ST segment to fall quickly to the baseline, while the T wave pursues its way back to normality, either by running anew through a hyperacute pattern [62], or by testing a negative shape, which lasts but a few days. Reocclusion makes the story going back to square one. To complicate life, similar wide and tall T waves can be seen in healthy people in V2–V4 (see the male type physiologic ST-segment elevation above), but building only a low T amplitude to R amplitude ratio and thus contrasting to the high T amplitude to R amplitude ratio in genuine hyperacute T waves [62]. The absence of coronary reperfusion in due time crops the R wave, carves the more or less hasty Q wave (meaning either stunning [42] or necrosis) and subsequently reverses the T wave. Changing polarity of the T wave from positive to negative contributes to the metamorphosis of the STE, from the early upwards concave, striking across a rectilinear shape, to end with the belated upwards convex appearance. A dismal prognosis seems to be heralded by two distinct geometries of the ischaemic STE, namely the tombstoning STE (notorious for mortality, reinfarction, and heart failure in the long run) [63], and the shark fin/lambda-like/triangular STE (this one blamed for mortality) [64] (Figure 11). Other shapes of the hyperacute T wave are still possible [60].

Figure 10

Figure 11

1) Sensibility—some STEMI cases are likely neglected because of either the amplitude of STE or the non-contiguity between the direct leads. Whereas the conventional thresholds used to define the ischaemic STE are somewhat proportional to the larger amplitude of the QRS complex in V2–V3 (as well as to the smaller amplitude of the QRS complex in V7–V9 compared with those of the bulk of other leads) [1,3], they do not pay attention to the tiny (i.e. less than 1 mm) STE in lead aVL, when featuring a small QRS complex. Such a patient risks denial of the urgent reperfusion therapy, simply due to not meeting the conventional minimum 1 mm ST-elevation amplitude in standard leads [36]. The absence of STE in conventional leads in many cases of distal occlusion of a non-dominant circumflex artery, as well as the mutual cancellation of ST-elevations from diametrically opposite segments represent other reasons to neglect some STEMI cases. Lastly, STEMI caused by the occlusion of the first diagonal artery displays sometimes STE in leads aVL and V2 and therefore risks underdiagnosis, by not meeting the condition of contiguity of direct leads. 2) Specificity—the ischaemic STE must be differentiated from conditions, as for example a) early repolarization and b) left bundle branch block [65,66].

The differential diagnosis in a timely fashion between the early repolarization in a person complaining of atypical pain and the subtle ischaemic STE well before the troponin rising onset can be difficult. Any one of the following items advocates for the LAD occlusion as the most likely reason for the STE in precordial leads: 1) STE of at least 5 mm in at least one precordial lead, 2) upwards convex STE in at least one lead from V2–V5, 3) concomitant ST depression in DII/DIII/aVF/V2–V6, 4) pathological Q wave in at least one of the leads V2–V4, 5) terminal QRS distortion, meaning the absence of both J and S waves in either of the leads V2 and V3, 6) LBBB/RBBB, 7) negative T wave in any of the leads V2–V6, and 8) LVH.

The absence of all the conditions above makes difficult the timely differential diagnosis within the precordial leads. Two algorithms derived by Smith et al. in order to assist the differential diagnosis rely upon the higher STE, the longer QTc interval, and the lower amplitudes of the total QRS voltage and of its R wave respectively in STEMI, compared with their counterparts seen in the early repolarization pattern: 1) the numeric result of (1.196 ST60V3 (mm) + 0.059 QTc (ms^1/2) – 0.326 RV4 (mm)) at least 23.4 has an 86% sensitivity, 91% specificity, and 88% diagnostic accuracy in predicting STEMI [62,67], whereas 2) the numeric result of (1.062 ST60V3 (mm) + 0.052 QTc (ms^1/2) – 0.151 QRSV2 (mm) – 0.268 RV4 (mm)) at least 18.2 has an 89% sensitivity, 95% specificity, and 92% accuracy in predicting STEMI [62,67].

Electrocardiographic STEMI diagnosis in the presence of already known LBBB (Figure 12) is difficult. Whereas the combination between the rapid shift of a cardiac troponin (preferably the more specific troponin I) and the ischaemic chest pain affirms the diagnosis of acute myocardial infarction, it is neither operative within 3 hours past the symptoms onset nor able to make the difference between STEMI and NSTEMI by itself. At least one of the following three modified Sgarbossa criteria, fulfilled in at least one electrocardiographic lead, has a sensitivity of 80% and specificity of 99% for the diagnosis of STEMI against the background of an old LBBB [62]: 1) concordant J point STE of at least 5 mm (5 points), 2) J point ST depression of at least 1 mm in at least one of the leads V1–V3 (3 points), and 3) heavily discordant J point STE having at least 1 mm and towering above 25% of the amplitude of its preceding S wave (at least 2 points) [66]. LBBB restrains the accurate electrocardiographic pinpointing of the occluded coronary artery [62,65,66,69].

Figure 12

Left main coronary (LMC) severe stenosis (Figure 13). The term „aVR sign” has been coined to phrase the combination between the simultaneous STE in aVR and ST depressions in many other leads [70]. The severe LMC stenosis—but not LMC occlusion—(or an equivalent bulk of severe stenoses of all coronary arteries) is the best known among the wilderness of causes of the aVR sign [70,71,72] along with other life-threatening (proximal acute aortic dissection whose intimal flap shrouds the orifice of the left main coronary every now and again [73], pulmonary embolism [70,73,74], myocarditis [70] early status after cardiac resuscitation (where only the long-standing aVR STE is predictive for coronary stenoses) [26], haemorrhagic shock [70] Brugada syndrome and its related phenocopies [73] or non-life-threatening pathologies (acute pericarditis) [73], paroxysmal supraventricular tachycardia (an orthodromic atrioventricular reentrant tachycardia using an accessory pathway is more likely than atrioventricular nodal reentrant tachycardia) [71], and LVH/LBBB [70]. The limited specificity of the aVR sign urges, therefore, a customized approach, based upon the clinical scenery. Increasing the myocardial stress during a hypertensive crisis, supraventricular tachycardia, or an acute heart failure episode can transiently emphasize the already-existing aVR sign due to electrocardiographic LVH/LBBB and even boost a small troponin wavering in a hypertensive/cardiomyopathy/aortic stenosis patient, without necessarily meaning left main coronary disease [50]. Contrariwise, the higher the amplitude of the aVR sign amid a normal baseline electrocardiogram, the more likely the LMC disease [70,73]. Three versions of the aVR sign are known heretofore: 1) severe LMC stenosis (or an equivalent load of all three coronary arteries severe stenoses) [1,44,70,71,72] expressing an ST vector pointing upwards, rightwards and anteriorly [77], and suggested by an STE higher than 1 mm in aVR, surrounded by progressively smaller ST-elevations from V1 to V3 +/− DIII [73], as well as by reciprocal ST depressions in many other leads (aVF, DII, DI, aVL, V4–V6 +/− DIII); the myriad of ST depressions reaches its profoundness in DII and V5, resulting in a ratio between the modulus of the ST depression in DII and the STE in V2 above 1 [76]; 2) severe proximal LCX stenosis, connoted by the aforesaid description, except the absence of ST depression in aVL [78,79]; 3) severe proximal LAD stenosis, hinted either by an STE in V1 higher than the STE in aVR [71] or by a less than 1 ratio between the modulus of the ST depression in DII and the STE in V2 [76]. Although ranked as a STEMI equivalent [1] instead of STEMI, the LMC near-occlusion delineated by the STE in aVR portends the same ominous prognosis as any STEMI [1] and calls for the same imperative percutaneous coronary intervention. An STE in aVR higher than 1 mm, adjoined to either an anterior or an inferior wall STEMI, worsens their prognosis [1].

Figure 13

The Wellens syndrome (Figure 14) is featured either by negative, deep and symmetrical (Wellens syndrome type B), or biphasic (+/−) T waves (Wellens syndrome type A) within at least V2 and V3, spreading commonly to their neighbouring precordials, adjoining minimum (less than 1 mm) ST-elevation and QT prolongation in a patient recalling a very recent history (from hours to days) of anginal pain and bringing forward a slightly increased troponin level at the very most [44,60]. The Wellens syndrome scenario consists of the following cycle of events: 1) transient thrombotic/spastic LAD occlusion, playing out as a “transient STEMI” whose ST-elevation vanishes before arrival to emergency room, 2) LAD reperfusion (either spontaneous, or fostered by the already-taken antiplatelet drugs) displaying as biphasic/symmetric negative T waves, becoming deeper as time goes by, 3) the eventual LAD reocclusion shifts the negative T wave to positive (the T wave pseudonormalizes), whilst the ST segment raises again. Several cycles of alternating coronary occlusions and reperfusions are possible in any patient, as well as in any coronary artery [44,60]. The Wellens syndrome is but one of a few causes of the negative T waves within the precordial leads, along with Takotsubo cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, pericarditis, pulmonary embolism, subarachnoid haemorrhage, and coronary-ventricular fistula [80].

Figure 14

The Dressler–de Winter ST-T pattern (Figure 15) Although William Dressler has the priority of the discovery in 1947 and the merit of formulating an accurate physiopathologic hypothesis [81], this electrocardiographic pattern bears the name of its second discoverer in 2008, Robbert de Winter. It manifests during an anginal episode as an ascending ST depression, usually seen in a few precordial leads, beginning by a deeper than 1 mm J point and merging rapidly (when still under the isoelectric line) with the ascending limb of a positive, tall, and symmetrical T wave [44]. It means the coronary artery is near-occluded, though still open [85]. Its coupling with a tiny STE in aVR [82] makes it a STEMI equivalent. The Dressler–de Winter sign is seen in roughly 2% of proximal LAD near-occlusions [81] and seldom in first diagonal (where the STE in aVR is absent) [83,84], RCA, or LCX near-occlusions [50]. Once considered immovable, the Dressler–de Winter sign can be just one shackle of a chain composed of alternating occlusions and defective reperfusions, wherein it is preceded and followed by perishing ST-elevations [60]. As the sign bespeaks an impending coronary occlusion [86] and carries a life-threatening arrhythmic risk [87], one must activate the cathlab immediately. Apart from its well-known coronary near-occlusion significance, the same pattern can appear in acute myocarditis [22] or in hyperkalaemia [88]. Neither the Wellens syndrome nor the Dressler-de Winter sign has pathologic Q waves.

Figure 15

Unlike the shifting STE of STEMI, the unchanging STE revealed by the left ventricular aneurysm (Figure 16) has neither reciprocal ST depresions in opposite leads [7] nor deep T waves. Therefore, either a less than 0.22 ratio between the sum of amplitudes of the negative T waves and the sum of amplitudes of QS complexes in leads V1–V4, or the biggest ratio between the negative T wave amplitude and the QRS complex amplitude less than 0.36 argues in favor of the left ventricular aneurysm and not in favor of a true STEMI in a patient with QS-type complexes in most precordial leads [21,64].

Figure 16

Takotsubo cardiomyopathy (TCM) is composed of the following four items: 1) transient hypokinesia/akinesia/dyskinesia (lasting from days to weeks) of some parietal ventricular segments, usually left-sided (less commonly right-sided, or biventricular), usually concatenated in a circumferential distribution transgressing a classical coronary territory (less commonly isolated antero-lateral segments), and usually surrounding the apex (less commonly medioventricular, or at the base of the heart); 2) new electrocardiographic anomalies (STE and/or T wave inversion and/or bundle branch block); 3) cardiac distress markers uprise (troponin, NT-proBNP); and 4) normal subepicardial coronary arteries, in the absence of myocarditis (as proven by angiogram) [1,90,91,92]. The apical involvement creates the classical endsystolic apical ballooning pattern inspiring the Japanese „takotsubo” designation, whereas the basal involvement occurs during subarachnoid haemorrhage, or against the background of pheochromocytoma and is labeled „nutmeg”, or „artichoke” heart [91]. The electrocardiogram of TCM goes through four steps: 1) early and fleeting STE (for the first 24 hours), 2) first and low amplitude T wave inversion (days 1–3) coming into sight after ST segment normalization and showing often a beat-to-beat variation [93] 3) interim normalization of the T wave, and 4) late and deeper T wave inversion, dying out only after a couple of months [91,94] (Figure 17). The T wave inversion mimics the Wellens syndrome [80]. Unlike the STE in anterior STEMI, the STE of the classic type of TCM a) focuses around the tip of the heart (reaching its peak in lead “minus aVR” and mid-precordial leads V2-V4); b) tends to be scattered [1] (going beyond a single coronary allocation), lower than its ischaemic sibling and without being attended by reciprocal ST depressions; c) dissipates faster, being followed after a time span by the diffuse T wave inversion and by the QT interval prolongation; and 4) bears less often and more fugitive pathological Q waves, whereas the R waves recover sooner [91,94]. As classic TCM spares the basal segments, STE tends to be minimal/absent in leads exploring the base of the heart, such as V1 [94], whilst other anatomic TCM variants simulate miscellaneous acute coronary syndrome electrical images [91]. The cardiac injury markers rise earlier than in cases of STEMI but finally reach similar peak values [91].

Figure 17

On the one hand, acute pericarditis (AP) breeds an atrial injury current, oriented superiorly and rightwards, displayed as a PR segment elevation in aVR, as well as a diffuse PR segment depression in all other leads (best seen in DII, aVF, V4–V6). On the other hand, AP creates a subepicardial ventricular injury current, pointing inferiorly and leftwards, manifested as a concave upwards STE, usually widespread (trespassing against one single coronary territory, as does TCM, too) in most precordial leads, DI, DII, aVL and aVF (best seen in DII, V5 and V6), as well as an ST depression in aVR +/− V1 [11]. As the transient PR segment deviation can forego the transient ST segment deviation, it represents sometimes the earliest electrocardiographic picture of AP [29]. The TP segment descent of at least 1 mm in at least 2 leads argues in favor of AP and is called the Spodick sign [95]. Whatever its cause, an already inverted T wave remains inverted once AP begins and coexists with the AP-related ST-elevation [29]. The genuinely diffuse STE AP must be differentiated from the type 2 and mostly from type 3 early repolarization pattern, whereas the localized STE AP must be distinguished from type 1 early repolarization [29], as well as from STEMI [96]. Compared with AP of other aetiologies, the STEMI-associated AP yields an intrinsic STE uncommonly [97]. Usually, AP-related STE is higher than the STE of early repolarization, resulting in a ratio between the STE and T wave amplitudes in V4, V5, V6, and DI more than 0.25 in AP and less than 0.25 in early repolarization, respectively [12]. There is no J wave in AP [12]. As opposed to STEMI, AP alters neither QRS width nor the QT duration [98].

Figure 18

STE is but one of the myriad of insensitive, non-specific and cursory signs of acute myocarditis (AM), alongside of sinus tachycardia, PR segment deviation (reminding of acute pericarditis), low voltage QRS complexes, pathologic Q waves, bundle branch blocks, fragmented QRS complexes, ST depression (including the Dressler-de Winter sign), T wave inversion, QT interval prolongation, and supraventricular and ventricular brady- and tachyarrhythmias [22]. The STE is one of the early electric signs of AM, and it looks either as AP [22], or as an acute coronary syndrome (ACS) [9,11,21]. When resembling AP, the STE features the same diffuse PR segment depression, as well as the same diffuse, usually low-amplitude (less than 5 mm) and concave upwards STE (except a casual J wave displayed by myocarditis) [22]. When resembling ACS, the rectilineal/convex upwards STE is seen in at least two contiguous leads (without necessarily pertaining to the same coronary dependent area), without reciprocal ST depression, but pathologic Q wave is still possible [22]. The ACS-like STE is a sign of unfavourable prognosis, alongside the pathologic Q wave, wide QRS complex in sinus rhythm, prolonged QT interval, and sustained ventricular tachyarrhythmias [22,99,100]. The STE is a rough indicator of how much, but not of where, the injured myocardium is [22]. As chest pain is possible in acute myocarditis (by coronary spasm due to virus-related endothelial dysfunction and/or pleuritic pain) [100] and troponin rise is the rule in both myocarditis and STEMI, the electrocardiogram is a poor discriminating tool between acute myocarditis and STEMI. Besides the conjectural diagnosis, relying upon a combination of 1) at least one laboratory criterion from the following: a) electrocardiographic abnormality, b) biochemical myocardial injury, c) left/right ventricular cavity diameter and/or wall thickness increase and/or global/regional function anomaly detected by ultrasound, or by magnetic resonance imaging (MRI), d) MRI signs of myocardial oedema, hyperemia, and injury [101], and 2) at least a) one clinical sign/symptom, or b) at least one other laboratory criterion, the ultimate diagnosis of myocarditis requires angiographic exclusion of coronary artery disease, followed by validation of myocardial necrosis and inflammation, using endomyocardial biopsy [99].

Figure 19

The acute cor pulmonale secondary to acute pulmonary embolism (APE), shams once and again an inferior and anterior STEMI [6,9]. Whereas the negative, symmetric, wide, and rounded T waves populating the inferior and right precordial leads hold on for a long while, the STE from the inferior and anterior leads belongs to the early and ephemeral electrocardiographic signs of APE, alongside the tachyarrhythmias, right axis deviation in frontal plane, and incomplete right bundle branch block, all these conveying the acute rise of the right cardiac pressure [102]. Unlike the STE of a genuine “concomitant anteroseptal and inferior” STEMI, the inferior APE-related STE decreases from DIII to DII, the anterior APE-related STE can spread to aVR, is always too small as against the depth of the T waves, confederates with other electrocardiographic signs of right ventricular hypertension, and all these come and go [9]. The STE in any of leads DIII, V1, or aVR is a predictor of haemodynamic instability and death of APE [74,104]. The coexistence of STE with the S1Q3T3 pattern (the McGinn-White sign, where S1 acts for the reciprocal image of an incomplete right bundle branch block, and Q3T3 bespeaks the right ventricular pressure loading) [105] argues in favour of an APE-related STE [106], while the poor progression of the R waves in precordial leads is due to clockwise rotation in the horizontal plane and is coupled with the negative T waves [106].

Figure 20

Acute Proximal Aortic Dissection can activate STE either by enshrouding one coronary artery inlet by the the intimal flap, or by global myocardial ischaemia, when cardiac tamponade leads to cardiogenic shock [14]. The STE can uncommonly wander between various groups of leads [107], or even alternate with ST depression within the same group of leads [108].

The STE is but one of several electrocardiographic signs of intracranial haemorrhage (ICH), beside sinus bradycardia (an omen of impending brainstem hernia), negative and wide T waves (“cerebral T waves”), long QT interval, J wave, prominent U waves, and ST depression. The ICH-STE is low-sized, convex upwards, and usually abides within the precordial leads, but it sometimes can be diffuse. Neurogenic myocardial stunning can take place, too. The subarachnoid haemorrhage paves the way for supraventricular and ventricular brady- and tachyarrhythmias. Alongside ICH, the signs above occur in cerebral oedema (be it ischaemic or traumatic in origin), as well as in brain tumours [109].

The STE looks either confined (when iy ventures a STEMI elicited by myocardial bruise (the usual mechanism), coronary spasm, coronary dissection, or even a classical atherothrombotic event arised merely by chance), or widespread (by traumatic serous/haemorrhagic pericarditis). Haemopericardium is the reason for the low voltage and electrical alternans. The electrocardiogram is outperformed, however, by imaging methods needed to document without delay the pericardial effusion, myocardial laceration, and the potential right ventricular thrombosis. Aside from STE, the cardiac trauma is able to incite ST depression, ventricular arrhythmias, right intraventricular blocks, and non-specific T wave changes (the latter even in case of cardiac sparing trauma). STE urges coronary angiography to discriminate between myocardial contusion and subepicardial coronary injury [110].

The STE is one of the electrical signs in pneumothorax, alongside axis deviation, poor precordial R wave progression (even reaching QS complexes), electrical alternans, S1Q3T3 pattern, and T wave inversion [111,112]. Whereas right tension pneumothorax is able to bring out STE by right ventricular compression–driven ischaemia, right arterial pulmonary pressure surge, and systemic arterial pressure breakdown [113], the left pneumothorax can likewise mimic a STEMI, by STE in leads V2–V4, the more so as all these come bundled with chest pain and acute shortness of breath [9,113]. The STE (resembling type 2 Brugada phenocopy) is one of the electrical tokens in pectus excavatum, next to ST depression, incomplete RBBB, right-axis deviation, tall P wave, poor R wave progression, and negative T wave in right precordial leads, likely resulting from right ventricular outflow tract compression, as well as from the rotation of the heart [32].

The metastatic heart tumour can yield non-evolutive convex upwards STE piled up in leads close to the tumour, always attended by negative T wave, sometimes escorted by reciprocal ST depression, but never guarded by either pathologic Q wave or poor R wave progression [114]. Squeezing of the right heart by a mediastinal tumour can generate STE inside the right precordial leads, joined by reciprocal ST depression in reverse leads [26,27], or by J wave within inferior leads only [115].

The STE of congenital J wave syndromes originates in J wave/J point. The J point represents the junction between the QRS complex and the ST segment [11], standing for the boundary between the ventricular depolarization and repolarization. A normal J point deviates at most +/−0.1 mV from the baseline [116]. A J point either abnormally elevated by at least 0.1 mV above the baseline or split from the QRS complex becomes a J wave. Broadly speaking, a J wave is phrased by a J point that is lifted by at least 0.1 mV above the baseline or distinguished from the QRS complex (thus forming a recognizable J wave), either halfway (looking as a late QRS notch, usually upon the descending slope of the R wave), or simply severed from it (presenting as a rounded tip high frequency deflection of the proximal ST segment and boasting the same polarity as that of the main part of the QRS complex) [11]. Any clean-cut J wave has an onset Jo, a peak Jp, and an end Jt [116], where the peak Jp stems from the J point of yesteryear. The mere elevation of the J point equates with a partially discernible J wave (slurring), whose descending slope between Jp and Jt comes into sight, whereas the ascending slope is still hidden behind the end of the QRS complex [116]. Any upturned J point, or unequivocal J wave, elevates the first part of the ST segment, where the higher and wider the J wave, the higher the ST segment elevation [26]. Both the amplitude and duration of a J wave and thereby the elevation of the proximal ST segment are variable in time and space. Variability in space means the dependency of the J wave morphology upon the electrocardiographic lead (that is, slurring in one lead and distinct wave in another one) [117]. Variability in time includes a short-term and a long-term proportion. The short-term variability means J wave enhancement during parasympathetic stimulation, extreme temperatures [116], bradycardia, and vice versa, J wave decrease while hyperventilating [12], or during tachycardia [12,26,118,119]. This demeanour is typical of repolarization phenomena, empowering therefore the J wave to be discriminated from a late depolarization phenomena (as, for example, the R’ wave of RBBB, or the last part of a fragmented QRS), whose behaviour is antithetical (i.e., depolarization waves enlarge during tachycardia and diminish during bradycardia) [26,116]. The long-term variability refers to the age-related progressive decline of a J wave. The J wave syndrome is the term coined for the life-threatening ventricular arrhythmia's susceptibility against the background of a large and erratic J wave in sinus rhythm [28,116,120]. Until now, two congenital J wave syndromes have been discovered, namely Brugada syndrome and the early repolarization syndrome [11,28,120,121]. Except for some possible intracellular lipid storage and casual hypokinesia of the right ventricular outflow tract in Brugada syndrome, no other morphologic abnormalities have been found in congenital J wave syndromes so far [116]. Both Brugada and early repolarization syndromes display miscellaneous loss-of-function genetic defects of sodium and/or calcium depolarizing channels, whereupon a regional repolarizing gambit of I_t0 +/− I_KATP (bearing uncommonly gain-of-function defects) predominate [26,116]. As the J wave is incited by the increase within the ventricular subepicardium of the early transient repolarizing current I_t0 of potassium efflux during phase 2 of the action potential, the J wave is regarded as an early repolarization event, rather than a late depolarization one, albeit the J point stands midway between depolarization and repolarization [122]. The slow recovery kinetics of I_t0 channel enables its opening during bradycardia while preventing it during tachycardia and thereby explains the dependency of the J wave on the heart rate. Out of congenital J wave syndromes, J wave is sometimes seen in hypertrophic cardiomyopathy and in arrhythmogenic right ventricular cardiomyopathy [123], as well as in a few other conditions denominated together as acquired J wave syndromes: hypothermia, hypercalcaemia, myocardial ischaemia, subarachnoid haemorrhage [123] and myocarditis [22].

Brugada Syndrome (BrS) (Figure 21) is the modern medical term for a condition probably known of yore in East Asian countries as “Lai-Tai” in Thailand, “Bangungut” in Philippines, and “Pokkuri” in Japan. The STE of BrS is forged by the abormal J wave. The BrS diagnosis is made up of a combination of criteria (each one being assigned a score inside of the Shanghai Brugada Scoring System) starting with an injunctive electrocardiographic criterion, to which another personal clinical criterion, a familial clinical one, and eventually the genetic test result are added optionally. Definite BrS requires a total score of at least 3.5 [116]. The type 1 Brugada electrocardiographic pattern features a coved STE of at least 2 mm and followed by a negative T wave in at least one precordial lead from V1 to V3, seated in at least one of the 2nd, 3rd or 4th left intercostal spaces. When spontaneous, or at most fever-induced, the type 1 Brugada electrocardiographic pattern is assigned 3.5 points and is wherefore diagnostic by itself of BrS (provided no other cause-mimicking type 1 Brugada STE exists), whereas the type 1 Brugada electrocardiographic pattern unmasked by an intravenous sodium channel blocker challenge test (using either of the following: ajmaline [preferably] [124], flecainide, procainamide, or pilsicainide) needs at least another personal, or familial clinical criterion to reach the minimum 3.5 score [116,125,126]. A mimicking cause is a pathology different from BrS, still able to induce an acquired STE resembling that of BrS (called Brugada phenocopy), in the absence of any criterion of the Shanghai Brugada Scoring System (including the absence of the genetic defect), and the list of the mimicking causes is the list of causes of right precordial leads STE [26,116,124,126,127,128]. Hardly ever, the BrS presents with coved-type STE in leads outside V1–V3 [129]. Unlike the R’ wave of a genuine RBBB, (featuring a sharp vertex and fast downsloping, followed by convex upwards ST depression and escorted by reciprocal wide S wave in left precordial leads), the J wave of BrS displays a rounded nose, slow downsloping, is followed by the salient convex upwards STE and has no reciprocal S wave [130].

Figure 21

At least the first part of ERS STE is due to the abnormal J wave. The early repolarization pattern (ERP) is phrased by Jp height of at least 0.1 mV (be it the onset of a slow QRS tail, the peak of an end QRS notch, or the top of a distinct J wave), keeping Jt above the isoelectric line and blended thenceforth with a concave upwards STE in at least two contiguous lateral and/or inferior electrocardiographic leads [116,122,131]. Three topographic types of ARP are defined hereunder: type 1 (set out as STE in lateral DI and V4–V6 leads) (Figure 22), type 2 (inferior and lateral leads), and type 3 (global type, with STE spread over the lateral, inferior, and anterior (i.e., the first three precordial) leads) [26,116,132]. Nearly half of the cases of early repolarization STE are attended by a reciprocal ST depression in aVR [1,133]. Whereas the type 1 early repolarization characterized by a small (1 mm) J wave followed by an upsloping STE bears a minimal arrhythmic risk, the early repolarization exhibiting a big (2 mm) J wave in both lateral and inferior leads followed by a horizontal/downsloping STE carries an arrhythmic risk significantly higher [116]. Analogous with BrS, the ERS diagnosis is based upon a combination of criteria (each one being assigned a score inside of the Shanghai ER Scoring System), where a personal clinical criterion, a familial clinical one, and eventually the genetic test result are optionally added to a pivotal electrocardiographic criterion. The definite ERS requires fulfilling a score of at least 5 [116]. The ERP can be dynamic, starting with an image barely visible in lateral leads, heaving and spreading ominously towards the inferior and anterior leads a short time before the ventricular fibrillation onset and flowing back after the resuscitation manoeuvers, likely because of endogenous and exogenous catecholamines overflow. Accordingly, a J wave-free sinus rhythm recorded shortly after a successful resuscitation is by no means a warranty against the resurgence of both the arrhythmogenic J wave and its subsequent ventricular fibrillation, whenever a transient parasympathetic activation occurs [134]. Albeit ERS-related STE looks somewhat alike the one of acute pericarditis and that one of STEMI, several distinctive elements do exist, however (Table 2).

Figure 22

STE is an uncommon electrocardiographic sign of at least moderate (K⁺ above 6.5 mEq/L) and fast-rising hyperkalaemia [88,135], usually seen in leads V1–V2 and mimicking there either the anterior wall STEMI or Brugada pattern [88,136]. Its emergence against the background of an array of persuasive signs of hyperkalaemia (as for example a) the narrow-based, tall, and sharply pointed T wave (the so-called “Eiffel Tower” sign [137]) in those leads featuring high-amplitude QRS complexes, b) the flattened P wave and c) the wide and abnormally oriented QRS complex) helps clarify its genuine dyselectrolytemic origin [135]. The sharp T wave of hyperkalaemia is a reason for an erroneous automatic double-counting of the heart rate (the “Littmann sign”) [88,138]. The same mechanisms of the classic electrocardiographic signs of hyperkalaemia, i.e., a) the sodium channel blocking by hyperkalaemia-induced resting potential depolarization and b) phase 3 repolarization speeding up) can also account for the hyperkalaemia-dependent STE, but some degree of fibrosis within the pulmonary infundibulum is thought to contribute, too [139]. Hyperkalaemia can imitate the de Winter T wave [88].

Figure 23

The STE is an uncommon electrocardiographic sign of severe hypercalcaemia, usually seen within the first precordial leads [11,26,137,140]. The most frequent sign of hypercalcaemia is the Q-peakT interval shortening (based upon ST segment shortening) [11], while proving at once a good correlation with the serum calcium level [140]. The Q-peakT interval shortens as the T wave approaches the QRS complex, increasing its upward slope while decreasing the downward slope, aiming to „stick the cheek to her QRS partner”. Severe hypercalcaemia widens the base and lowers the top of the T wave, until flattening occurs, followed by casual inversion [140]. J wave can arise in severe hypercalcaemia, too [140]. The STE derives either from the adherence of the T wave to the QRS complex, or from the J wave. Shortening of the phase 2 of the action potential and thus of the corresponding ST segment by hypercalcaemia is due to the shortening of the depolarization activity by a) elevating (and so moving away from the very negative membrane resting potential) the threshold potential of the sodium channels and b) hasty inactivation of Ca⁺²-L calcium channels via negative feedback induced by the massive calcium influx (therefore the action potential plateau can be no longer underset) [26]. J wave is the result of a) the activation by the massive initial calcium influx (during phase 1 of the action potential) of the calcium-dependent chloride influx transient repolarizing current I_Cl⁻ _(Ca⁺²₎ = I_t02 [140] and/or of b) blocking by hypercalcaemia the direct working mode (= depolarizing mode = 3Na⁺influx/1Ca⁺²efflux) of the 3Na^+/1Ca⁺² ionic exchanger, mainly within the ventricular subepicardium [141]. At the other end of the spectrum, severe hypocalcaemia can seldom send forth an STE across the precordial leads, purportedly by coronary spasm [140,142].

Hypothermia is defined as a lower than 35 °C core temperature. On the one hand, when central temperature decreases from 35 °C to 32 °C, the physiologic stress reaction to cold thrusts the human body to react by sinus tachycardia. On the other hand, central temperature below 32 °C slows the sinus rate, lengthens PR and QT intervals, widens the QRS complex, and promotes atrial premature ectopic activity (and sometimes atrial fibrillation, too). J wave (=Osborn wave, first detected by Tomaszewski in 1938 in a frozen man [28,131], while discovered by Osborn only in 1953 in dogs shivering with cold [11,121,123]) sees daylight amidst the inferior leads, then spreads towards the lateral ones, to finally fill up the precordial leads, too, and unfolds positive in most of the leads (except aVR and V1, where negative) [123]. The lower the temperature, the higher and more split the J wave from the QRS complex (resembling an iceberg falling magnificently apart from the ice sheet), likely following the enhancement of the subepicardial I_t0 current secondary to bradycardia, as well as its activation delay by cold [119]. The J wave enlargement elevates the initial part of the ST segment, whereas the remaining part of the ST segment features an ascending/horizontal/descending slope, being like the early repolarization pattern [123]. When central temperature falls below 30 °C, the elephantine widening of the QRS complex fosters ventricular fibrillation. Approaching 15 °C, cardiac arrest occurs [143,144].

There is a quite extensive array of drugs able to shape an STE within the right precordial leads (notably Brugada patterns type 1, or type 2), by at least one of the following mechanisms: I_Na⁺ blocking, I_Ca⁺²_−L blocking, I_to activation: antiarrhythmics, antianginal drugs (calcium channel blockers, potassium channel activators), psychoactive drugs, anaesthetics, H1-antihistamines, alcohol, cocaine, ergonovine [116,128,145]. Type 1 Brugada pattern induced by therapeutic doses of sodium channel blockers (especially ajmaline/flecainide/pilsicainide/procainamide) likely accounts for the latent form of Brugada syndrome, unmasked by drugs [128], while any other scenario (including the type 1 pattern created exclusively using supratherapeutic doses of sodium channel blockers) acts herein for a presumable Brugada phenocopy forged by drugs (but normalization of the ST segment after drug withdrawal does not warrant the phenocopy diagnosis, which must be secured wherefore by verifying the absence of all Shanghai criteria) [116,128].

Figure 24

The typical (strain-type) or atypical pattern of LVH-STE in right precordial leads can simulate an anterior STEMI, the more so as the LVH pictures often QS complexes within the same leads [12,146]. The combination of STE in aVR [12], V1–V2 and ST depression (STD) in leads beholding directly to the left ventricle (aVL, I, II, aVF, V4–V6), in the LVH patient complaining about ischaemic symptoms (either anginal pain, or anginal equivalents), is able to masquerade as a left main coronary trunk disease, so much the more as on one hand a) the amplitudes of the ST segment deviations increase during tachycardia and from afterload increase [50] and decrease during bradycardia, acute pulmonary oedema, and pleural effusion [2] and, on the other hand, b) hypertensive crisis, heart failure, and sustained tachyarrhythmias are all able to boost a cardiac troponin rise [1,50]. The LVH-ST deviations (STE in V1–V3 and STD in V4–V6) can hide the diagnosis of inferolateral STEMI (picked out by STE in V7–V9 as well as by reciprocal STD in V1–V3 [2], both types of ST deviations stated in relation to an isoelectric baseline before the acute coronary syndrome (ACS) onset and for normal amplitude QRS complexes) [1,146]. Failing clear-cut criteria, the suggestive (but not ultimate) electrocardiographic clincher favouring an ACS (particularly a STEMI) in a patient with baseline LVH-ST deviations is the short time variation (no specified lower limit, however) of the ST deviation amplitude (provided the precordial electrodes always observe fastening over the same accurate positions [2]), against the background of evolving ischaemic symptoms.

The ST segment and T wave are opposite to the last (i.e., blocked) deflection of the QRS complex of LBBB. The ST deviation is secondary to the depolarization abnormality within the same lead [11]. LBBB displays upsloping STE in right precordial leads (featuring a cluster pattern akin to that of the anterior STEMI) and downsloping STD in left leads (precordial and frontal leads alike). Once again, the combination of STE in aVR, V1–V3 and the STD in left leads (aVL, I, II, V5–V6), exhibiting every now and then variable amplitudes depending on the heart rate, is able to bolster up a false-positive diagnosis of LMC-related ACS in the patient bellyaching of angina and portraying a short-term troponin variation (= acute myocardial injury) of non-coronary cause [2,12]. The modified Sgarbossa criteria help assist the electrocardiographic diagnosis of STEMI in the setting of already known LBBB [66].

The modified Sgarbossa criteria are still useful to assist the electrocardiographic diagnosis of the acute coronary occlusion for the patient bearing a cardiac pacemaker with a classical right ventricular pacing electrode. The diagnostic sensitivity is lower (67%) than that in case of LBBB, however. The second Sgarbossa criterion considers at least a 1 mm deep concordant ST depression in any of the leads V1–V6, as opposed to LBBB case (where is counted in leads V1–V3 only) [62].

The ST segment deviation is a repolarization abnormality secondary to the two-ways, two-steps ventricular depolarization sequence in WPW syndrome. As the ST deviation is opposite to the delta wave, the STE appears in leads revealing a negative delta wave and moreover, the higher the preexcitation degree, the higher the STE [12]. Once the preexcitation vanishes, the phenomenon of electrical memory keeps the T wave (and its adjoining final part of the ST segment) pointing towards where the preexcited QRS complexes pointed heretofore. This is why the electrical memory can build up positive T waves and temporary end-ST segment elevation in right precordial leads, after left-sided preexcitation faded away [25].

Electric shock can sometimes yield a significant (5–10 mm), but short-lived (for a few minutes) non-ischaemic STE. Several high-energy shocks delivered within a short interval of time are able to evoke a transient rise of cardiac troponin [6,14]. The worse the ventricular function, the higher the likelihood of STE after the electric shock delivery [6].

The STE patient coming to the emergency room falls probably under at least one of the following scenarios: 1) STE and haemodynamic instability (cardiogenic shock +/− pulmonary oedema) while on sinus rhythm or during bradycardia, 2) STE and thoracic pain, 3) STE and syncope, and 4) STE and increased troponin.

Ste and haemodynamic instability represents the maximal emergency scenario while on sinus rhythm or during bradycardia. The following life-threatening causes must be quickly verified: left main coronary trunk stenosis (or a tantamount combination of proximal LAD and LCX stenoses thereof), acute inferior wall and right ventricular STEMI, high-risk acute pulmonary embolism, acute proximal aortic dissection with erratic veiling of a coronary artery origin, and acute myocarditis.

For neither the STE nor the chest pain is exclusively ischaemic, four categories of patients emerge therefore: 1) ischaemic pain and ischaemic ST-elevation = STEMI, 2) non-ischaemic pain and ischaemic ST-elevation = spuriously painful STEMI, 3) ischaemic pain and non-ischaemic ST-elevation = acute myocardial infarction with false ST-elevation, and 4) non-ischaemic pain and non-ischaemic ST-elevation = pseudo-STEMI. Category 1 covers STEMI with either iconic regional STE, or hardly localizing cases, STEMI conjoined with LBBB, as well as STEMI equivalents and forebodings (LMCT severe stenosis, Wellens syndrome and Dressler–de Winter ST-T pattern). Category 2 is actually a silent STEMI, whose emergency management cannot rely upon the ischaemic chest pain onset. Category 3 stands for a myocardial infarction merely by virtue of a cardiac troponin fast variation, otherwise bespeaking only for angina. LVH/LBBB/WPW/right ventricular–paced patients complaining of anginal pain fall within this category. There is always a danger of misinterpretation, for the ST deviation secondary to a too-high or a too-wide QRS complex lacks standardization thus far. Category 4 includes a manifold of common and uncommon blends of non-ischaemic STEs and non-ischaemic chest pains, outside the acute myocardial infarction. This obviously broad array of cases coming to the hospital can be handily divided into three classes (Table 3). The first class (A) embodies patients with both STE and chest pain claiming the same cardiac non-coronary cause (as, for example, the acute pericarditis, acute myocarditis, acute pulmonary embolism, Takotsubo cardiomyopathy, and cardiac trauma). The second class (B) encompasses patients with any combination of a first cardiac (non-coronary), or non-cardiac cause for the STE with a second different cardiac (non-coronary), or non-cardiac cause for the chest pain (as, for example, the patient with a cardiac non-ischaemic LVH-STE coming for thoracic aortic dissection with normal coronary flow, or the patient with pectus excavatum-dependent STE coming for oesophageal spasm, or the patient with early repolarization pattern coming for pneumonia, and so on). The third class (C) encloses patients with both STE and chest pain derived from the same non-cardiac cause (as, for example, the pneumothorax patient, or the acute pancreatitis one).

This scenario is illustrated by the patient bearing current STE and looking for help because of a recent transient/persisting loss of consciousness. Common cases are the acute inferior STEMI complicated by third-degree atrioventricular block with/without bradycardia-dependent torsades de pointes, hyperkalaemia-dependent bradyarrhythmia, or intracranial haemorrhage. The WPW patient arrives during atrial fibrillation with fast ventricular rhythm, whilst the WPW-related STE becomes evident only after the electrical conversion to sinus rhythm. Uncommon cases are the congenital J wave syndromes, arrhythmogenic right ventricular cardiomyopathy, IC class antiarrhythmic overdose, and the patient having left the pub just before midnight, fallen asleep on the side of the curb, and brought to the hospital in deep hypothermia.

Three types of combining STE with increased cardiac troponin do exist: 1) ischaemic STE and ischaemic troponin variation, 2) non-ischaemic STE and ischaemic but non-atherosclerotic troponin variation, and 3) non-ischaemic STE and non-ischaemic troponin variation (Table 4). The ischaemia-looking STE drives the indication for coronary angiography as for the first type of combination, whereas the angiography should be withheld regarding the second, and particularly the third type. Withholding angiography becomes challenging in case of evolving chest pain, however.