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QRS complex and ST segment manifestations of ventricular ischemia: The effect of regional slowing of ventricular activation
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ScienceDirect Journal of Electrocardiology 46 (2013) 497 – 504 www.jecgonline.com
QRS complex and ST segment manifestations of ventricular ischemia: The effect of regional slowing of ventricular activation Ljuba Bacharova, MD, DSc, MBA, a, b,⁎ Vavrinec Szathmary, RNDr, PhD, c Anton Mateasik, RNDr, PhD a a International Laser Center, Bratislava, Slovak Republic Institute of Pathophysiology, Medical Faculty, Comenius University, Bratislava, Slovak Republic c Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic b
Abstract
Objective: Reduction or interruption of the blood supply to myocardium due to occlusion of coronary artery and consequent ischemia leads to changes of electrogenesis: changes in morphology and duration of action potentials and slowing of conduction velocity in the affected area. In this study we simulated the effects of localized changes in depolarization sequence on the QRS and ST segment patterns, using computer modeling. Methods: The model defines the geometry of cardiac ventricles analytically as parts of ellipsoids and allows changing the velocity of impulse propagation in the myocardium. An intramural electrically inactive area encircled by a transmural area with slowed impulse propagation velocity was introduced in anteroseptal and inferior locations. The effects on the QRS complex and the ST segment of the 12-lead electrocardiogram are presented. Results: The intramural electrically inactive area caused QRS changes typical for corresponding locations of a myocardial infarction observed in patients, which were further considerably modified by slowed impulse propagation velocity in the surrounding area. Additionally, areas of slowed impulse propagation velocity led to ST segment deviations in the “reciprocal” leads, shifting the ST segment towards the affected areas. Conclusion: Using computer modeling we showed that the localized alteration of impulse propagation not only modified the QRS complex, but produced also changes in the ST segment consistent with changes which are usually interpreted as the effect of “injury current”. © 2013 Elsevier Inc. All rights reserved.
Keywords:
Myocardial infarction; Regional ischemia; Slowed ventricular activation; QRS complex; ST segment deviation
Introduction Reduction or interruption of myocardial blood supply due to the occlusion of a coronary artery and the consequent ischemia results in changes in the active and passive electrical properties of the myocardium. At the cellular level, a decreased transmembrane resting potential, as well as changes in action potential morphology, was documented in the affected area, 1–3 with slowing of ventricular activation. 4,5 The decrease in transmembrane resting potential in the affected area leads to voltage difference between the unaffected and the ischemic area resulting in current flow – the injury current – manifested by ST segment deviation. Alterations of the action potential observed in the ischemic areas result in changes in the ST segment and T wave. However, the slowing ⁎ Corresponding author. International Laser Center, Ilkovicova 3, 841 04 Bratislava, Slovak Republic. E-mail address: [email protected] 0022-0736/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jelectrocard.2013.08.016
in ventricular activation is seldom considered in the classical interpretation of ECG changes in ischemia. The impact of slowed conduction on the QRS complex and ST segment has been repeatedly described in animal and clinical studies. 6–10 Slowed conduction is also mentioned in the recent AHA consensus report on intraventricular conduction disturbances, 11 which recommends the use of two ischemia-related terms: possible peri-infarction block characterized by the changes in QRS, and peri-ischemic block, defined as a transient increase in QRS duration accompanying the ST segment deviation observed in acute injury. However, the AHA consensus reports on ECG interpretation, considering acute ischemia/infarction, 12 as well as the report on ST segment, T and U wave 13 morphologies, do not mention this mechanism. Since there is solid evidence of increased occurrence and sustainability of ventricular tachyarrhythmias and sudden death with ventricular activation abnormalities, 14–17
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the recognition of their presence and progress is of critical clinical significance. The aim of this study was to demonstrate the effect of areas of slowed ventricular activation and of areas of electrically inactive myocardium on the resultant QRS and ST patterns using a computer simulation.
Material and methods Model description Details of the model were described previously. 18 In brief, the model is defined in a three-dimensional grid of elements. The geometry of the ventricles in this model is defined analytically as segments of ellipsoids representing their inner (endocardial) and outer (epicardial) surfaces (Fig. 1). The myocardial cellular elements of the model are represented as cubiform parts of the excitable cardiac tissue, with defined model ventricular transmembrane action potentials (MAPs). The depolarization sequence in the ventricular walls from predetermined starting elements is performed by a procedure simulating the Huygens principle of wavefront propagation. After depolarization of a model cell, its consecutive repolarization is governed by its MAPs. Simulated changes The following changes, intended to represent the conditions in acute ischemic events, were simulated in the
anteroseptal and inferior locations of the left ventricle, respectively (Fig. 2): • An intramural area of electrically inactive myocardium; • A transmural area of slowed ventricular activation. The ventricular activation was slowed by one model step, i.e. about 33% in the left ventricular layers LL1and LS1 representing the model Purkinje fiber mesh of the left ventricle, and by one model step i.e. 50% in the left ventricular layers LL2–LL5 and LS2 representing the working myocardium of the left ventricle. • Superimposition of the two above described alterations simulating a combined effect of electrically inactive area surrounded by the area of slowed ventricular activation. The affected area in the anteroseptal location involved the anterior wall of the left ventricle and adjacent parts of interventricular septum and apex. The affected area in the inferior location involved a part of the inferior wall of the left ventricle. The shape and the extent of the affected areas are presented in Fig. 2. The resultant heart vectors were adjusted for the anatomical position of the model ventricles in the thorax, and vectorcardiographic vectors were calculated. The vectorcardiographic vectors were converted to 12-lead electrocardiograms, using the Dower transformation matrix. 19
Fig. 1. Long axis cross-section of the model ventricles. (A) Partition of the ventricular walls into 5 layers described in frontal cross-section of the model. LLi indicates i-th layer in the left ventricular wall; LRi, i-th layer in the right ventricular wall; LSi, i-th layer in the septum, mdu: model distance unit. (B) Simplified shape of the model action potential (MOP). APD(LXi) indicates action potential duration; AM(LXi), amplitude of action potential; DP(LXi), duration of plateau; DTR(LXi), duration of terminal repolarization of elements localized in the layer LXi.
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Fig. 2. Location and extent of simulated lesions. Long and short axes cross-sections of the model heart, dashed lines indicating the level of the sections. White: The intramural area of electrically inactive tissue (layers L2–L4 of the model), pink: the transmural area of slowed ventricular activation (layers L1–L5 of the model). The numbers indicate the volume of affected myocardium.
Results Anteroseptal location of altered ventricular activation Changes in ECG patterns due to altered ventricular activation in the anteroseptal location are presented in Fig. 3. The effect of slowed ventricular activation The duration of depolarization was prolonged by 32%. The time interval from the beginning of the depolarization to the end of repolarization was prolonged by 1%. There was no overlap between depolarization and repolarization (Table 1). Slowed ventricular activation in anteroseptal location resulted in changes of the QRS complex, namely in the amplitude of R and S waves, and in a shift of the electrical axis in the frontal plane to the left. A small Q wave was observed in aVL. The transition zone was shifted to V2. The amplitude of R wave increased in leads V3–V5, and S waves in leads V3–V6 were not present. Terminal notches of the QRS complex appeared in II and V2. The effect of electrically inactive area surrounded by an area of slowed ventricular activation The duration of depolarization was prolonged by 132%. The time interval from the beginning of the depolarization to
the end of repolarization was prolonged by 23%. As is shown in the Fig. 4, the depolarization and repolarization were overlapping for 23 model time units (mtu), i.e. about 69 ms (1 mtu is approximately equal to 3 ms). Combination of an electrically inactive area surrounded by slowed ventricular activation in the anteroseptal area resulted in changes in both QRS complex and ST segment. Low amplitude R waves were noted in the precordial leads and the transition zone was shifted to V5. Deep Q wave appeared in aVL. Slight ST segment elevations occurred in I, aVL, V5, V6 and “reciprocal” depression in III, V1. The effect of electrically inactive area The duration of depolarization was prolonged by 48%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 3%. There was a minimal overlap of depolarization and repolarization (2 mtu/6 ms). The electrically inactive area in anteroseptal location affected only the QRS complex. The electrical axis was shifted to the right and a QS configuration appeared in aVL. In the precordial leads, low amplitude R waves were observed with increased S amplitude in V4–V5, and low QRS amplitude in V5, V6. The transition zone was shifted to V6.
Fig. 3. Derived 12-lead electrocardiograms, resulted from electrical changes in anteroseptal location. (A) The effect of transmural area of slowed ventricular activation; (B) the effect of intramural electrically inactive area surrounded by area of slowed ventricular activation; (C) the effect of intramural electrically inactive area. Blue: the reference ECG, red: pathological ECG.
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Table 1 Time intervals of depolarization and repolarization.
Reference Slowing AS Slowing Inf Comb AS Comb Inf MI AS MI Inf
Depolarization mtu (ms) delta%
Depolarization onset–repolarization offset interval mtu (ms) delta %
Overlap mtu (ms)
25 33 38 58 57 37 34
104 (312) 0 106 (318) 1 111 (333) 6 128 (384) 23 128 (384) 23 108 (324) 3 108 (324) 3
0 0 2 (6) 23 (69) 22 (66) 2 (6) 0
(75) 0 (99) 32 (114) 52 (174) 132 (171) 128 (111) 48 (102) 36
Slowing: slowed ventricular activation; Comb: combination of electrically inactive area surrounded by the area of slowed ventricular activation; MI: electrically inactive area. AS: Anteroseptal location; Inf: Inferior location. mtu: model time units; ms: milliseconds. Overlap: the duration of overlapping depolarization and repolarization.
Inferior location of altered ventricular activation The changes in ECG patterns due to altered ventricular activation in the inferior location are presented in Figs. 5. The effect of slowed ventricular activation The duration of depolarization was prolonged by 52%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 3%. Depolarization and repolarization overlapped for 2 mtu (6 ms) (Table 1). In the inferior location, major changes were observed in QRS amplitudes: small Q waves in III and aVF, increased R wave amplitude in II, III, aVF and deep S waves in aVL, V2–V4. The effect of electrically inactive area surrounded by an area of slowed ventricular activation The duration of depolarization was prolonged by 128%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 23%. Depolarization and repolarization overlapped 22 mtu, i.e. about 66 ms. Fig. 6 shows the overlapping of depolarization and repolarization and its effects in the QRS-T pattern.
The combination of an electrically inactive area surrounded by slowed ventricular activation in the inferior area resulted in changes in both QRS complex and ST segment. Remarkable Q waves appeared in leads II, III, aVF, the electrical axis in the frontal plane was shifted to the left. ST segment elevations were seen in II, III and aVF, with “reciprocal” ST segment depression in aVL, and V1–V4. The effect of electrically inactive area The duration of depolarization was prolonged by 36%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 3%. There was no overlap between depolarization and repolarization. The electrically inactive area in the inferior location produced deep Q waves in leads III, aVF, and increased R wave amplitude in aVL, the electrical axis was shifted to the left. Terminal QRS notches were present in II, III, and aVF. Discussion Computer simulation has shown that the modification of depolarization sequence resulted in changes of both QRS
Fig. 4. Leads III and V1 with ST segment deviation observed in the case of the combination of intramural electrically inactive area surrounded by area of slowed ventricular activation in the anteroseptal location. Arrows indicate the duration of depolarization and repolarization. Blue: the reference ECG, red: pathological ECG. depol: depolarization. The units are model time units (mtu).
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Fig. 5. Derived 12-lead electrocardiograms, resulted from electrical changes in inferior location. (A) The effect of transmural area of slowed ventricular activation; (B) the effect of intramural electrically inactive area surrounded by area of slowed ventricular activation; (C) the effect of intramural electrically inactive area. Blue: the reference ECG, red: pathological ECG.
complex as well as ST segment patterns, namely in QRS duration and amplitude, in a shift of electrical axis, as well as in notching in the terminal portion of QRS and changes of repolarization. The areas of slowed ventricular activation represented myocardium with slowed conduction velocity during ischemia. Slowing of myocardial ventricular conduction was recorded in experimental studies, 4,10,14 and hypothetically considered to be present in areas of acute or chronic ischemia, and/or scattered fibrosis. 6–9,16,17,14,20,21 In our study simulation the MI was defined as an electrically inactive region. The location of affected areas represented occlusion of left anterior descending artery (LAD) for the anteroseptal location, and of left circumflex artery (LCx) and right coronary artery (RCA), respectively, for the inferior location. QRS complex prolongation As expected, the areas of slowed ventricular activation, as well as the areas of electrically inactive tissue increased the
duration of depolarization resulting in prolongation of QRS complex duration, but resulted in a slight prolongation of the interval from the onset of depolarization to the end of repolarization (the interval is analogical to the QT interval). A considerable prolongation of the depolarization was observed when the area of inactive myocardium was surrounded by an area of slowed ventricular activation, i.e. in the combination of “ischemic” and MI areas, and the interval from the onset of depolarization to the end of repolarization (“QT interval”) was significantly prolonged. Since our simulation allowed determining the duration of both depolarization and repolarization, it could be observed that their overlapping created patterns imitating ST segment deviations without changed QRS duration in the leads with expected ST segment deviations. In the studies considering slowed ventricular activation in ischemic heart disease, the prolongation is considered to be characteristic for a peri-ischemic block. 6,7 According to our results, the QRS duration depends on the interplay between the site, extent and severity of myocardial impairment that
Fig. 6. Leads III and V1 with ST segment deviation observed in the case of the combination of intramural electrically inactive area surrounded by area of slowed ventricular activation in the inferior location. Arrows indicate the duration of depolarization and repolarization. Blue: the reference ECG, red: pathological ECG. depol: depolarization. The units are model time units (mtu).
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could lead to overlapping of depolarization and repolarization processes.
complex can imitate patterns of early repolarization, however it was also caused by the prolonged depolarization.
QRS complex morphology
Interpretation of the QRS complex and ST segment changes in ischemic heart disease
The spectrum of changes in the QRS complex morphology due to slowed ventricular activation alone or in combination with MI was wide, including Q deflections, decrease or/increase of QRS amplitude, shift of the electrical axis, fascicular block patterns, as well as terminal notching of QRS. Anteroseptal slowing of ventricular activation led to Q waves in aVL, and slowing in inferior location to Q waves in III and aVF. While Q waves are expected in myocardial necrosis, transient Q waves have been observed also in patients with Prinzmetal’s angina, 22,23 or during a treadmill test. 24,25 It is possible that slowed ventricular activation due to transient regional ischemia could be considered in these cases. Changes in R and S wave amplitudes occurred in the case of simulated slowed ventricular activation in both anteroseptal and inferior locations. Reference to changes in R and S wave amplitudes can be found in both animal 26 and human studies. 6–8,27,28 The QRS complex changes in addition to conventional ST segment deviations indicate severe ischemia, a faster progression of irreversible myocardial necrosis and more serious prognosis. These changes include the increase in the R wave amplitude in inferior leads, and disappearance of S waves in leads V1–V3. 29–31 The combination of changes in R and S wave amplitudes in limb leads resulted in changes in electrical axis comparable with a fascicular block pattern. This finding is consistent with clinical studies, fascicular-block-like patterns were previously reported by Selvester et al. 21 in patients undergoing percutaneous transluminal angioplasty of the left anterior descending coronary artery. Transient “septal fascicular blocks” were reported also by others. 23,32 The tissue of the conduction system is relatively more resistant to ischemia as compared to myocardium, 33 therefore the delayed ventricular activation due to regional ischemia can produce ECG patterns consistent with fascicular block also in cases with unaffected conduction system. 21 ST segment deviations and notching in terminal part of QRS In this simulation study we observed ST segment changes imitating visually ST segment deviation if the area of slowed ventricular activation surrounded the electrically inactive area, i.e. in a combination of “ischemia” and “myocardial infarction”. Moreover, the ST segment deviations were present in leads known to occur in patients with known location of ischemia: in the anteroseptal location in leads I, aVL and in lateral precordial leads, with “reciprocal” depression in lead III, and in the inferior location the ST segment elevations in III and aVF with “reciprocal” ST segment depressions in anterior precordial leads. These changes were observed during overlapping of the prolonged depolarization and the regular onset of repolarization. Our simulations did not include changes in the action potential, therefore the concept of the “injury current” cannot be applied. The observed notching in the terminal part of QRS
The traditional interpretation of QRS complex changes in ischemic heart disease/myocardial infarction is focused on identifying the presence of Q wave, assuming necrosis or fibrotic scar in the affected area. The ST segment deviations are usually interpreted as a manifestation of the flow of current across the boundary between the ischemic and nonischemic areas — the “injury current”. However, the repolarization changes observed in this study were secondary repolarization changes resulting from the altered sequence of ventricular activation. The assumption of the effect of ventricular activation slowing on transient or permanent QRS–ST changes is not new. Numerous studies have reported the association of slowed ventricular activation with changes in the QRS morphology and ST segment. 6–9,26,27,34 These associations are referred to as peri-infarction block, 35,36 peri-ischemic block, 7 arborization block 36 (however, in the case of arborization block the impaired conduction in the conduction system is only assumed). Interestingly, Surawicz 37 pointed out that the association of changes in the terminal part of the QRS complex and ST segment deviations may be caused by “the pull of ST segment”. A more recent study showed that transmural ischemia progressively increases transmural conduction time, and the apparent ST segment elevation is actually a markedly prolonged R wave, 38 and the authors concluded that markedly delayed transmural activation can be also one of mechanisms underlying the ST-segment elevation. This possibility is also stressed by Extramiana 39 in his editorial commenting different mechanisms leading to ST segment elevations. Based on our results it can be assumed that the overlapping of considerably prolonged depolarization and repolarization might be an additional mechanism to be considered in the evaluation of ST segment deviations. Slowed ventricular activation per se is usually not considered as a primary factor in pathologic QRS patterns, e.g. blocks in anterior or posterior fascicles of the left bundle, or left ventricular hypertrophy. Fascicular block causes a delay of activation in the corresponding area — analogically, the regional slowing of ventricular activation could be the primary cause of the delayed activation without necessarily assuming a block in conduction system. The increased QRS amplitude observed in our simulation study reflected the increased extent of the activation front due to altered sequence on depolarization. Our findings are consistent with findings of Wiegerinck et al. 40 Using a porcine model they showed that transmural ischemia delays ventricular activation and is associated with QRS prolongation and increase in R wave amplitude. Limitation of the study The general limitation of computer simulation is the simplification, why these models are not able to cover the complexity of a real pathophysiological problem. The
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specific limitations of our model include the analytically defined shape of the heart as well as of the areas of impaired activation. It allowed reduction of conduction velocity only in steps of 30% and 50%, respectively, while the decrease of conduction velocity in ischemic regions decreases continuously from the center to periphery. The degree of slowing in our model (50% and 30% reduction, respectively), is within reported data. 4,5 In spite of these limitations, our model helped to visualize some of the assumed processes/concepts related to the interpretation of electrocardiograms in patients with myocardial ischemia and infarction, namely the sequence of ventricular activation, the shape and extent of activation front and their relation to the electrocardiogram. Our results are consistent with the variety of QRS–ST changes that have been extensively documented in animal studies, 26,41 as well as in clinical studies in patients with Prinzmetal’s angina, 22 in patients during a stress test 42,43 or undergoing PTCA, 44,9,7,8 human studies, where myocardial ischemia and consequently altered sequence depolarization are the underlying mechanisms.
Conclusion The results of this study showed that the QRS complex and ST segment contain information about the presence and location of regional ventricular activation slowing. We showed that localized slowing in ventricular activation could be the underlying factor (pathophysiological mechanisms) of a variety of QRS and ST segment changes seen in patients with ischemic heart disease. The understanding of these ECG changes could contribute to an earlier identification of STEMI patients with severe ischemia that might favor from a more aggressive treatment since they are at a higher risk of faster progression of necrosis in the ischemic area than patients with less severe ischemia without depolarization changes in addition to ST elevation. The transient character of the ECG patterns and the broad spectrum and combinations of QRS and ST segment changes seen in patients with ischemic heart disease are probably the reasons why they are not included in the interpretation of ECG. However, there is strong evidence that localized intramyocardial conduction abnormalities play a role in the genesis of ventricular arrhythmias following myocardial infarction, 15–17,14 creating conditions for reentry as the underlying mechanisms of postinfarction tachycardia. The results of our simulation studies emphasize the importance of considering conduction alterations in the interpretation of QRS–ST patterns and create a link between understanding the role of conduction alterations/QRS-T patterns in the pathogenesis of arrhythmias.
Acknowledgment This study was supported partly by projects VEGA 2/ 0131/13 and APVV-0134-11.
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QRS complex and ST segment manifestations of ventricular ischemia: The effect of regional slowing of ventricular activation Ljuba Bacharova, MD, DSc, MBA, a, b,⁎ Vavrinec Szathmary, RNDr, PhD, c Anton Mateasik, RNDr, PhD a a International Laser Center, Bratislava, Slovak Republic Institute of Pathophysiology, Medical Faculty, Comenius University, Bratislava, Slovak Republic c Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic b
Abstract
Objective: Reduction or interruption of the blood supply to myocardium due to occlusion of coronary artery and consequent ischemia leads to changes of electrogenesis: changes in morphology and duration of action potentials and slowing of conduction velocity in the affected area. In this study we simulated the effects of localized changes in depolarization sequence on the QRS and ST segment patterns, using computer modeling. Methods: The model defines the geometry of cardiac ventricles analytically as parts of ellipsoids and allows changing the velocity of impulse propagation in the myocardium. An intramural electrically inactive area encircled by a transmural area with slowed impulse propagation velocity was introduced in anteroseptal and inferior locations. The effects on the QRS complex and the ST segment of the 12-lead electrocardiogram are presented. Results: The intramural electrically inactive area caused QRS changes typical for corresponding locations of a myocardial infarction observed in patients, which were further considerably modified by slowed impulse propagation velocity in the surrounding area. Additionally, areas of slowed impulse propagation velocity led to ST segment deviations in the “reciprocal” leads, shifting the ST segment towards the affected areas. Conclusion: Using computer modeling we showed that the localized alteration of impulse propagation not only modified the QRS complex, but produced also changes in the ST segment consistent with changes which are usually interpreted as the effect of “injury current”. © 2013 Elsevier Inc. All rights reserved.
Keywords:
Myocardial infarction; Regional ischemia; Slowed ventricular activation; QRS complex; ST segment deviation
Introduction Reduction or interruption of myocardial blood supply due to the occlusion of a coronary artery and the consequent ischemia results in changes in the active and passive electrical properties of the myocardium. At the cellular level, a decreased transmembrane resting potential, as well as changes in action potential morphology, was documented in the affected area, 1–3 with slowing of ventricular activation. 4,5 The decrease in transmembrane resting potential in the affected area leads to voltage difference between the unaffected and the ischemic area resulting in current flow – the injury current – manifested by ST segment deviation. Alterations of the action potential observed in the ischemic areas result in changes in the ST segment and T wave. However, the slowing ⁎ Corresponding author. International Laser Center, Ilkovicova 3, 841 04 Bratislava, Slovak Republic. E-mail address: [email protected] 0022-0736/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jelectrocard.2013.08.016
in ventricular activation is seldom considered in the classical interpretation of ECG changes in ischemia. The impact of slowed conduction on the QRS complex and ST segment has been repeatedly described in animal and clinical studies. 6–10 Slowed conduction is also mentioned in the recent AHA consensus report on intraventricular conduction disturbances, 11 which recommends the use of two ischemia-related terms: possible peri-infarction block characterized by the changes in QRS, and peri-ischemic block, defined as a transient increase in QRS duration accompanying the ST segment deviation observed in acute injury. However, the AHA consensus reports on ECG interpretation, considering acute ischemia/infarction, 12 as well as the report on ST segment, T and U wave 13 morphologies, do not mention this mechanism. Since there is solid evidence of increased occurrence and sustainability of ventricular tachyarrhythmias and sudden death with ventricular activation abnormalities, 14–17
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the recognition of their presence and progress is of critical clinical significance. The aim of this study was to demonstrate the effect of areas of slowed ventricular activation and of areas of electrically inactive myocardium on the resultant QRS and ST patterns using a computer simulation.
Material and methods Model description Details of the model were described previously. 18 In brief, the model is defined in a three-dimensional grid of elements. The geometry of the ventricles in this model is defined analytically as segments of ellipsoids representing their inner (endocardial) and outer (epicardial) surfaces (Fig. 1). The myocardial cellular elements of the model are represented as cubiform parts of the excitable cardiac tissue, with defined model ventricular transmembrane action potentials (MAPs). The depolarization sequence in the ventricular walls from predetermined starting elements is performed by a procedure simulating the Huygens principle of wavefront propagation. After depolarization of a model cell, its consecutive repolarization is governed by its MAPs. Simulated changes The following changes, intended to represent the conditions in acute ischemic events, were simulated in the
anteroseptal and inferior locations of the left ventricle, respectively (Fig. 2): • An intramural area of electrically inactive myocardium; • A transmural area of slowed ventricular activation. The ventricular activation was slowed by one model step, i.e. about 33% in the left ventricular layers LL1and LS1 representing the model Purkinje fiber mesh of the left ventricle, and by one model step i.e. 50% in the left ventricular layers LL2–LL5 and LS2 representing the working myocardium of the left ventricle. • Superimposition of the two above described alterations simulating a combined effect of electrically inactive area surrounded by the area of slowed ventricular activation. The affected area in the anteroseptal location involved the anterior wall of the left ventricle and adjacent parts of interventricular septum and apex. The affected area in the inferior location involved a part of the inferior wall of the left ventricle. The shape and the extent of the affected areas are presented in Fig. 2. The resultant heart vectors were adjusted for the anatomical position of the model ventricles in the thorax, and vectorcardiographic vectors were calculated. The vectorcardiographic vectors were converted to 12-lead electrocardiograms, using the Dower transformation matrix. 19
Fig. 1. Long axis cross-section of the model ventricles. (A) Partition of the ventricular walls into 5 layers described in frontal cross-section of the model. LLi indicates i-th layer in the left ventricular wall; LRi, i-th layer in the right ventricular wall; LSi, i-th layer in the septum, mdu: model distance unit. (B) Simplified shape of the model action potential (MOP). APD(LXi) indicates action potential duration; AM(LXi), amplitude of action potential; DP(LXi), duration of plateau; DTR(LXi), duration of terminal repolarization of elements localized in the layer LXi.
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Fig. 2. Location and extent of simulated lesions. Long and short axes cross-sections of the model heart, dashed lines indicating the level of the sections. White: The intramural area of electrically inactive tissue (layers L2–L4 of the model), pink: the transmural area of slowed ventricular activation (layers L1–L5 of the model). The numbers indicate the volume of affected myocardium.
Results Anteroseptal location of altered ventricular activation Changes in ECG patterns due to altered ventricular activation in the anteroseptal location are presented in Fig. 3. The effect of slowed ventricular activation The duration of depolarization was prolonged by 32%. The time interval from the beginning of the depolarization to the end of repolarization was prolonged by 1%. There was no overlap between depolarization and repolarization (Table 1). Slowed ventricular activation in anteroseptal location resulted in changes of the QRS complex, namely in the amplitude of R and S waves, and in a shift of the electrical axis in the frontal plane to the left. A small Q wave was observed in aVL. The transition zone was shifted to V2. The amplitude of R wave increased in leads V3–V5, and S waves in leads V3–V6 were not present. Terminal notches of the QRS complex appeared in II and V2. The effect of electrically inactive area surrounded by an area of slowed ventricular activation The duration of depolarization was prolonged by 132%. The time interval from the beginning of the depolarization to
the end of repolarization was prolonged by 23%. As is shown in the Fig. 4, the depolarization and repolarization were overlapping for 23 model time units (mtu), i.e. about 69 ms (1 mtu is approximately equal to 3 ms). Combination of an electrically inactive area surrounded by slowed ventricular activation in the anteroseptal area resulted in changes in both QRS complex and ST segment. Low amplitude R waves were noted in the precordial leads and the transition zone was shifted to V5. Deep Q wave appeared in aVL. Slight ST segment elevations occurred in I, aVL, V5, V6 and “reciprocal” depression in III, V1. The effect of electrically inactive area The duration of depolarization was prolonged by 48%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 3%. There was a minimal overlap of depolarization and repolarization (2 mtu/6 ms). The electrically inactive area in anteroseptal location affected only the QRS complex. The electrical axis was shifted to the right and a QS configuration appeared in aVL. In the precordial leads, low amplitude R waves were observed with increased S amplitude in V4–V5, and low QRS amplitude in V5, V6. The transition zone was shifted to V6.
Fig. 3. Derived 12-lead electrocardiograms, resulted from electrical changes in anteroseptal location. (A) The effect of transmural area of slowed ventricular activation; (B) the effect of intramural electrically inactive area surrounded by area of slowed ventricular activation; (C) the effect of intramural electrically inactive area. Blue: the reference ECG, red: pathological ECG.
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Table 1 Time intervals of depolarization and repolarization.
Reference Slowing AS Slowing Inf Comb AS Comb Inf MI AS MI Inf
Depolarization mtu (ms) delta%
Depolarization onset–repolarization offset interval mtu (ms) delta %
Overlap mtu (ms)
25 33 38 58 57 37 34
104 (312) 0 106 (318) 1 111 (333) 6 128 (384) 23 128 (384) 23 108 (324) 3 108 (324) 3
0 0 2 (6) 23 (69) 22 (66) 2 (6) 0
(75) 0 (99) 32 (114) 52 (174) 132 (171) 128 (111) 48 (102) 36
Slowing: slowed ventricular activation; Comb: combination of electrically inactive area surrounded by the area of slowed ventricular activation; MI: electrically inactive area. AS: Anteroseptal location; Inf: Inferior location. mtu: model time units; ms: milliseconds. Overlap: the duration of overlapping depolarization and repolarization.
Inferior location of altered ventricular activation The changes in ECG patterns due to altered ventricular activation in the inferior location are presented in Figs. 5. The effect of slowed ventricular activation The duration of depolarization was prolonged by 52%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 3%. Depolarization and repolarization overlapped for 2 mtu (6 ms) (Table 1). In the inferior location, major changes were observed in QRS amplitudes: small Q waves in III and aVF, increased R wave amplitude in II, III, aVF and deep S waves in aVL, V2–V4. The effect of electrically inactive area surrounded by an area of slowed ventricular activation The duration of depolarization was prolonged by 128%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 23%. Depolarization and repolarization overlapped 22 mtu, i.e. about 66 ms. Fig. 6 shows the overlapping of depolarization and repolarization and its effects in the QRS-T pattern.
The combination of an electrically inactive area surrounded by slowed ventricular activation in the inferior area resulted in changes in both QRS complex and ST segment. Remarkable Q waves appeared in leads II, III, aVF, the electrical axis in the frontal plane was shifted to the left. ST segment elevations were seen in II, III and aVF, with “reciprocal” ST segment depression in aVL, and V1–V4. The effect of electrically inactive area The duration of depolarization was prolonged by 36%. The time interval from the beginning of depolarization to the end of repolarization was prolonged by 3%. There was no overlap between depolarization and repolarization. The electrically inactive area in the inferior location produced deep Q waves in leads III, aVF, and increased R wave amplitude in aVL, the electrical axis was shifted to the left. Terminal QRS notches were present in II, III, and aVF. Discussion Computer simulation has shown that the modification of depolarization sequence resulted in changes of both QRS
Fig. 4. Leads III and V1 with ST segment deviation observed in the case of the combination of intramural electrically inactive area surrounded by area of slowed ventricular activation in the anteroseptal location. Arrows indicate the duration of depolarization and repolarization. Blue: the reference ECG, red: pathological ECG. depol: depolarization. The units are model time units (mtu).
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Fig. 5. Derived 12-lead electrocardiograms, resulted from electrical changes in inferior location. (A) The effect of transmural area of slowed ventricular activation; (B) the effect of intramural electrically inactive area surrounded by area of slowed ventricular activation; (C) the effect of intramural electrically inactive area. Blue: the reference ECG, red: pathological ECG.
complex as well as ST segment patterns, namely in QRS duration and amplitude, in a shift of electrical axis, as well as in notching in the terminal portion of QRS and changes of repolarization. The areas of slowed ventricular activation represented myocardium with slowed conduction velocity during ischemia. Slowing of myocardial ventricular conduction was recorded in experimental studies, 4,10,14 and hypothetically considered to be present in areas of acute or chronic ischemia, and/or scattered fibrosis. 6–9,16,17,14,20,21 In our study simulation the MI was defined as an electrically inactive region. The location of affected areas represented occlusion of left anterior descending artery (LAD) for the anteroseptal location, and of left circumflex artery (LCx) and right coronary artery (RCA), respectively, for the inferior location. QRS complex prolongation As expected, the areas of slowed ventricular activation, as well as the areas of electrically inactive tissue increased the
duration of depolarization resulting in prolongation of QRS complex duration, but resulted in a slight prolongation of the interval from the onset of depolarization to the end of repolarization (the interval is analogical to the QT interval). A considerable prolongation of the depolarization was observed when the area of inactive myocardium was surrounded by an area of slowed ventricular activation, i.e. in the combination of “ischemic” and MI areas, and the interval from the onset of depolarization to the end of repolarization (“QT interval”) was significantly prolonged. Since our simulation allowed determining the duration of both depolarization and repolarization, it could be observed that their overlapping created patterns imitating ST segment deviations without changed QRS duration in the leads with expected ST segment deviations. In the studies considering slowed ventricular activation in ischemic heart disease, the prolongation is considered to be characteristic for a peri-ischemic block. 6,7 According to our results, the QRS duration depends on the interplay between the site, extent and severity of myocardial impairment that
Fig. 6. Leads III and V1 with ST segment deviation observed in the case of the combination of intramural electrically inactive area surrounded by area of slowed ventricular activation in the inferior location. Arrows indicate the duration of depolarization and repolarization. Blue: the reference ECG, red: pathological ECG. depol: depolarization. The units are model time units (mtu).
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could lead to overlapping of depolarization and repolarization processes.
complex can imitate patterns of early repolarization, however it was also caused by the prolonged depolarization.
QRS complex morphology
Interpretation of the QRS complex and ST segment changes in ischemic heart disease
The spectrum of changes in the QRS complex morphology due to slowed ventricular activation alone or in combination with MI was wide, including Q deflections, decrease or/increase of QRS amplitude, shift of the electrical axis, fascicular block patterns, as well as terminal notching of QRS. Anteroseptal slowing of ventricular activation led to Q waves in aVL, and slowing in inferior location to Q waves in III and aVF. While Q waves are expected in myocardial necrosis, transient Q waves have been observed also in patients with Prinzmetal’s angina, 22,23 or during a treadmill test. 24,25 It is possible that slowed ventricular activation due to transient regional ischemia could be considered in these cases. Changes in R and S wave amplitudes occurred in the case of simulated slowed ventricular activation in both anteroseptal and inferior locations. Reference to changes in R and S wave amplitudes can be found in both animal 26 and human studies. 6–8,27,28 The QRS complex changes in addition to conventional ST segment deviations indicate severe ischemia, a faster progression of irreversible myocardial necrosis and more serious prognosis. These changes include the increase in the R wave amplitude in inferior leads, and disappearance of S waves in leads V1–V3. 29–31 The combination of changes in R and S wave amplitudes in limb leads resulted in changes in electrical axis comparable with a fascicular block pattern. This finding is consistent with clinical studies, fascicular-block-like patterns were previously reported by Selvester et al. 21 in patients undergoing percutaneous transluminal angioplasty of the left anterior descending coronary artery. Transient “septal fascicular blocks” were reported also by others. 23,32 The tissue of the conduction system is relatively more resistant to ischemia as compared to myocardium, 33 therefore the delayed ventricular activation due to regional ischemia can produce ECG patterns consistent with fascicular block also in cases with unaffected conduction system. 21 ST segment deviations and notching in terminal part of QRS In this simulation study we observed ST segment changes imitating visually ST segment deviation if the area of slowed ventricular activation surrounded the electrically inactive area, i.e. in a combination of “ischemia” and “myocardial infarction”. Moreover, the ST segment deviations were present in leads known to occur in patients with known location of ischemia: in the anteroseptal location in leads I, aVL and in lateral precordial leads, with “reciprocal” depression in lead III, and in the inferior location the ST segment elevations in III and aVF with “reciprocal” ST segment depressions in anterior precordial leads. These changes were observed during overlapping of the prolonged depolarization and the regular onset of repolarization. Our simulations did not include changes in the action potential, therefore the concept of the “injury current” cannot be applied. The observed notching in the terminal part of QRS
The traditional interpretation of QRS complex changes in ischemic heart disease/myocardial infarction is focused on identifying the presence of Q wave, assuming necrosis or fibrotic scar in the affected area. The ST segment deviations are usually interpreted as a manifestation of the flow of current across the boundary between the ischemic and nonischemic areas — the “injury current”. However, the repolarization changes observed in this study were secondary repolarization changes resulting from the altered sequence of ventricular activation. The assumption of the effect of ventricular activation slowing on transient or permanent QRS–ST changes is not new. Numerous studies have reported the association of slowed ventricular activation with changes in the QRS morphology and ST segment. 6–9,26,27,34 These associations are referred to as peri-infarction block, 35,36 peri-ischemic block, 7 arborization block 36 (however, in the case of arborization block the impaired conduction in the conduction system is only assumed). Interestingly, Surawicz 37 pointed out that the association of changes in the terminal part of the QRS complex and ST segment deviations may be caused by “the pull of ST segment”. A more recent study showed that transmural ischemia progressively increases transmural conduction time, and the apparent ST segment elevation is actually a markedly prolonged R wave, 38 and the authors concluded that markedly delayed transmural activation can be also one of mechanisms underlying the ST-segment elevation. This possibility is also stressed by Extramiana 39 in his editorial commenting different mechanisms leading to ST segment elevations. Based on our results it can be assumed that the overlapping of considerably prolonged depolarization and repolarization might be an additional mechanism to be considered in the evaluation of ST segment deviations. Slowed ventricular activation per se is usually not considered as a primary factor in pathologic QRS patterns, e.g. blocks in anterior or posterior fascicles of the left bundle, or left ventricular hypertrophy. Fascicular block causes a delay of activation in the corresponding area — analogically, the regional slowing of ventricular activation could be the primary cause of the delayed activation without necessarily assuming a block in conduction system. The increased QRS amplitude observed in our simulation study reflected the increased extent of the activation front due to altered sequence on depolarization. Our findings are consistent with findings of Wiegerinck et al. 40 Using a porcine model they showed that transmural ischemia delays ventricular activation and is associated with QRS prolongation and increase in R wave amplitude. Limitation of the study The general limitation of computer simulation is the simplification, why these models are not able to cover the complexity of a real pathophysiological problem. The
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specific limitations of our model include the analytically defined shape of the heart as well as of the areas of impaired activation. It allowed reduction of conduction velocity only in steps of 30% and 50%, respectively, while the decrease of conduction velocity in ischemic regions decreases continuously from the center to periphery. The degree of slowing in our model (50% and 30% reduction, respectively), is within reported data. 4,5 In spite of these limitations, our model helped to visualize some of the assumed processes/concepts related to the interpretation of electrocardiograms in patients with myocardial ischemia and infarction, namely the sequence of ventricular activation, the shape and extent of activation front and their relation to the electrocardiogram. Our results are consistent with the variety of QRS–ST changes that have been extensively documented in animal studies, 26,41 as well as in clinical studies in patients with Prinzmetal’s angina, 22 in patients during a stress test 42,43 or undergoing PTCA, 44,9,7,8 human studies, where myocardial ischemia and consequently altered sequence depolarization are the underlying mechanisms.
Conclusion The results of this study showed that the QRS complex and ST segment contain information about the presence and location of regional ventricular activation slowing. We showed that localized slowing in ventricular activation could be the underlying factor (pathophysiological mechanisms) of a variety of QRS and ST segment changes seen in patients with ischemic heart disease. The understanding of these ECG changes could contribute to an earlier identification of STEMI patients with severe ischemia that might favor from a more aggressive treatment since they are at a higher risk of faster progression of necrosis in the ischemic area than patients with less severe ischemia without depolarization changes in addition to ST elevation. The transient character of the ECG patterns and the broad spectrum and combinations of QRS and ST segment changes seen in patients with ischemic heart disease are probably the reasons why they are not included in the interpretation of ECG. However, there is strong evidence that localized intramyocardial conduction abnormalities play a role in the genesis of ventricular arrhythmias following myocardial infarction, 15–17,14 creating conditions for reentry as the underlying mechanisms of postinfarction tachycardia. The results of our simulation studies emphasize the importance of considering conduction alterations in the interpretation of QRS–ST patterns and create a link between understanding the role of conduction alterations/QRS-T patterns in the pathogenesis of arrhythmias.
Acknowledgment This study was supported partly by projects VEGA 2/ 0131/13 and APVV-0134-11.
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