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Importance of defining left bundle branch block
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Journal of Electrocardiology 45 (2012) 505 – 507 www.jecgonline.com
Editorial
Importance of defining left bundle branch block The success of cardiac resynchronization therapy (CRT) has led to renewed interest in defining left bundle branch block (LBBB). Patients with LBBB have significant dyssynchrony between activation of the interventricular septum and the left ventricular (LV) lateral wall that can be potentially corrected by CRT. In contrast, patients with prolonged QRS duration due to other pathologies (eg, right bundle-branch block [RBBB], LV dilatation/hypertrophy, intramural LV conduction delay, and/or fascicular block) retain their LV myocardial activation driven by the rapidly conducting LV Purkinje system, and thus, there is minimal delay between activation of the interventricular septum and LV lateral wall. 1 However, the initial trials on CRT did not focus on dividing patients by the QRS morphologic changes that would characterize true LBBB and simply enrolled patients with prolonged QRS duration. Furthermore, in most subgroup analyses of CRT trials, the definition of LBBB was not specified, and electrocardiograms (ECGs) were not always collected at a central ECG core laboratory for rigorous analysis. More recently, evidence has accumulated that likely only patients with complete LBBB benefit from CRT and not patients with other forms of nonspecific LV conduction delay or RBBB. 2 The most definitive evidence emerged from the analysis of the Multicenter Automated Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), which enrolled patients with New York Heart Association class I and II heart failure. 3 In this study, LBBB was defined by the 1985 World Health Organization (WHO) criteria 4 that were more recently endorsed by the American Heart Association, American College of Cardiology and Heart Rhythm Society. 5 In MADIT-CRT, cardiac resynchronization therapy resulted in a 53% reduction in heart failure events or death (hazard ratio [HR], 0.47; P b .001) but a 24% increase (not statistically significant) in heart failure events or death in patients without LBBB (HR, 1.24; P = .26), and the outcome in nonspecific LV conduction delay patients was worse than patients with RBBB. 3 Analysis from prolonged follow-up in MADITCRT recently presented at the Heart Rhythm Society scientific sessions found that CRT caused a statistically significant increase in heart failure events or mortality in patients without LBBB. 6 These findings from CRT trials emphasize the importance of accurately defining LBBB. Some of the individuals classified as “LBBB” in the CRT trials may not actually have LBBB, but the observed benefit in the LBBB group is 0022-0736/$ – see front matter. Published by Elsevier Inc. doi:10.1016/j.jelectrocard.2012.06.023
“driven” by those with true complete LBBB. Recently, Strauss et al 1 reviewed the evidence for LBBB criteria and proposed strict LBBB criteria that require a QRS duration of 130 milliseconds (ms) or more in women or 140 ms or more in men, and also rS or QS morphology in lead V1 and midQRS notching/slurring in at least 2 of the leads V1, V2, V5, V6, I, or aVL. In this issue of the journal, Gettes and Kligfield 7 comment on, “Should the criteria for LBBB be revised?” Interestingly, they divide this issue into 2 questions: (1) should the criteria for LBBB be revised and (2) what should the criteria be to identify patients with LBBB who are most likely to benefit from CRT? They strongly endorse the morphologic criteria outlined in the WHO publication, 4 which require a QRS duration of 120 ms or more and all 3 of the following: 1. broad and notched or slurred R in I and V5 or V6; 2. absence of Q wave in I and V5 and V6; and 3. an R peak time of 60 ms or more in V5 or V6. However, Gettes and Kligfield 7 state that in those patients who are being considered for CRT the QRS duration threshold in LBBB should be increased to 130 ms or more, as required in MADIT-CRT. The critical aspect of the WHO LBBB criteria is the requirement for broad and notched/slurred R in I and V5 or V6. However, these criteria can be even further improved. Mid-QRS notching/slurring from LBBB can occur in the R wave in leads I, aVL, V5, or V6, and in the Q or S wave of V1 and V2 (Fig. 1). Requiring notching in 2 of the leads (I, aVL, V1, V2, V5, or V6) increases the likelihood that the notching is due to a complete LBBB, but does not require that notching be present in all 3 leads I, V5, and V6. With regard to the timing of the notch, the WHO criteria specify that R peak time (of the second part of the notch) should be 60 ms or more in V5 or V6. Alternatively, the strict LBBB criteria 1 specify that the beginning of the notch should begin after 40 ms because a notch that begins in the first 40 ms of the QRS is likely to be due to infarction/scar. 8,9 The beginning of the notch represents the time when electrical activation breaks through to the LV endocardium (Fig. 1). From computer simulations 9 and the endocardial mapping data of Auricchio et al, 10 the minimum time for the activation wavefront to proceed through the septum is 40 ms. In addition, the notch should begin in the first half of the QRS complex and end at approximately two thirds through QRS duration (Fig. 1).
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Editorial / Journal of Electrocardiology 45 (2012) 505–507
Fig. 1. QRS morphology in complete LBBB. The LBBB activation sequence and representative QRS-T waveforms are depicted in their anatomical locations for the sagittal (A), transverse (B), and frontal (C) planes. The key LBBB QRS morphology feature shown is the mid-QRS notching that occurs at 50 and 90 ms, with slurring in between. The beginning of the notch represents the time when the electrical depolarization wavefront reaches the endocardium of the LV (after proceeding through the septum). The end of the notch occurs when the depolarization wavefront begins to reach the epicardium of the lateral wall. These notches are best seen in leads I, aVL, V1, V2, V5, and V6. Reprinted with permission from Strauss et al.1
Finally, with regard to the absence of Q waves in I and V5 and V6 that are specified in the WHO criteria, this is valid in uncomplicated LBBB; however, in the presence of anteroapical infarction, Q waves can be present in these leads, even in the presence of complete LBBB. 8 In addition to the morphology criteria requiring mid-QRS notching/slurring, Strauss et al 1 recommended that the QRS duration be 130 ms or more in women or 140 ms or more in men. The increase in QRS duration threshold beyond the conventional criteria of 120 ms or more is because QRS duration should increase by 60 ms with the onset of complete LBBB (40 ms to reach the LV endocardium and 20 additional milliseconds beyond normal to reenter the LV Purkinje network and proceed to the LV lateral wall). In the endocardial mapping study by Auricchio et al 10 of patients with LBBB by conventional ECG criteria, the QRS duration in patients with endocardial activation consistent with complete LBBB was 170 ± 16 ms, whereas QRS duration was 133 ± 28 ms in other patients. Furthermore, in the study of Grant and Dodge 11 (discussed extensively by Gettes and Kligfield 7), the authors note that although it had been believed that QRS duration prolongs by 40 ms with the onset of LBBB based on canine studies, the QRS duration prolongation in humans was often more than 70 to 80 ms. Grant and Dodge 11 state that the average QRS duration prolongation with the onset of supposed LBBB was 50 to 60 ms; however, this average included the one third of patients that they concluded did not have true LBBB. This supports that QRS prolongation should be more than 60 ms with the onset of true LBBB. The strict LBBB criteria 1 include different QRS duration thresholds by sex because women have smaller ventricles and a shorter QRS duration of more than 5 ms at baseline compared with men (87.1 ± 8.7 ms vs 92.7 ± 9.3 ms, respectively), 12 which doubles with LBBB because activation of the interventricular septum and LV lateral walls uncoupled. Even in a woman with a QRS duration 2 SDs below average at baseline (QRS duration, 70 ms), her QRS duration would be 130 ms with the onset of LBBB. Gettes and Kligfield 7 present one case of a woman with a QRS duration of 80 ms at baseline prolonged by 44 ms to reach 124 ms with the onset of potential LBBB. However, this paper ECG is of relatively poor quality, and the authors note that these measurements were unconfirmed by their evaluation of superimposed waveforms or the points identified to represent the onset or offset of the QRS complex. In contrast, Strauss et al 1 presented a series of cases where digital 12-lead ECGs were analyzed; one case included a woman that presented with a QRS duration of 76 ms at baseline that was prolonged by 72 ms to reach 148 ms with LBBB. 1 Moving forward, it is critical to validate LBBB criteria in comparison of endocardial activation mapping, as previously performed by Auricchio et al. 10 Currently, databases for validating conduction abnormality automated algorithms for commercial use only involve a reference standard of physician visual interpretation. In addition, any modified LBBB criteria should be analyzed to predict CRT benefit. A very recent study by Mascioli et al 13 did investigate the
Editorial / Journal of Electrocardiology 45 (2012) 505–507 1
ability of the new strict LBBB criteria to predict benefit from CRT. In multivariable analysis, the presence of “false LBBB” (meeting conventional LBBB criteria, but not the new strict LBBB criteria) predicted a 4-fold (HR, 3.98) increase in heart failure hospitalization or death compared with “true LBBB,” and “true LBBB” was the only variable significantly related to a greater increase in LV ejection fraction (HR, 4.57). 13 This was, however, a small single center study, and the results should be confirmed in a larger population. In addition, future trials should prospectively save patient digital ECGs to allow for automated analysis, and QRS duration thresholds to diagnose LBBB might be normalized to LV size or morphology. 14 David G. Strauss, MD, PhD Office of Science and Engineering Laboratories Center for Devices and Radiological Health US Food and Drug Administration Silver Spring, MD, USA E-mail address: [email protected]
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References 1. Strauss DG, Selvester RH, Wagner GS. Defining left bundle branch block in the era of cardiac resynchronization therapy. Am J Cardiol 2011;107:927. 2. Sipahi I, Chou JC, Hyden M, et al. Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: metaanalysis of randomized controlled trials. Am Heart J 2012;163: 260.e263. 3. Zareba W, Klein H, Cygankiewicz I, et al. Effectiveness of cardiac resynchronization therapy by QRS morphology in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT). Circulation 2011;123:1061. 4. Willems JL, Robles de Medina EO, Bernard R, et al. Criteria for intraventricular conduction disturbances and pre-excitation. World
11. 12.
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14.
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Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc. J Am Coll Cardiol 1985;5:1261. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009;53:976. Haigney MC, Goldstein RE, Krone RD, et al. Cardiac resynchronization therapy in MADIT-CRT patients with non–left bundle branch block conduction disturbances. Heart Rhythm 2012;9:S65. Gettes LS, Kligfield P. Should electrocardiogram criteria for the diagnosis of left bundle-branch block be revised? J Electrocardiol 2012;45:500. Strauss DG, Selvester RH, Lima JA, et al. ECG quantification of myocardial scar in cardiomyopathy patients with or without conduction defects: correlation with cardiac magnetic resonance and arrhythmogenesis. Circ Arrhythm Electrophysiol Dec 2008;1:327. Strauss DG, Selvester RH. The QRS complex—a biomarker that “images” the heart: QRS scores to quantify myocardial scar in the presence of normal and abnormal ventricular conduction. J Electrocardiol 2009;42:85. Auricchio A, Fantoni C, Regoli F, et al. Characterization of left ventricular activation in patients with heart failure and left bundlebranch block. Circulation 2004;109:1133. Grant RP, Dodge HT. Mechanisms of QRS complex prolongation in man; left ventricular conduction disturbances. Am J Med 1956;20:834. Macfarlane P, Lawrie TDV. Appendix 1: normal limits. In: Macfarlane P, Lawrie TDV, editors. Comprehensive electrocardiology: theory and practice in health and disease, Vol 3. New York: Pergammon Press; 1989. p. 1441. Mascioli G, Padeletti L, Sassone B, et al. Electrocardiographic criteria of true left bundle branch block: a simple sign to predict a better clinical and instrumental response to CRT. Pacing Clin Electrophysiol 2012 [Epub ahead of print]. Hakacova N, Steding K, Engblom H, et al. Aspects of left ventricular morphology outperform left ventricular mass for prediction of QRS duration. Ann Noninvasive Electrocardiol 2010;15:124.
Journal of Electrocardiology 45 (2012) 505 – 507 www.jecgonline.com
Editorial
Importance of defining left bundle branch block The success of cardiac resynchronization therapy (CRT) has led to renewed interest in defining left bundle branch block (LBBB). Patients with LBBB have significant dyssynchrony between activation of the interventricular septum and the left ventricular (LV) lateral wall that can be potentially corrected by CRT. In contrast, patients with prolonged QRS duration due to other pathologies (eg, right bundle-branch block [RBBB], LV dilatation/hypertrophy, intramural LV conduction delay, and/or fascicular block) retain their LV myocardial activation driven by the rapidly conducting LV Purkinje system, and thus, there is minimal delay between activation of the interventricular septum and LV lateral wall. 1 However, the initial trials on CRT did not focus on dividing patients by the QRS morphologic changes that would characterize true LBBB and simply enrolled patients with prolonged QRS duration. Furthermore, in most subgroup analyses of CRT trials, the definition of LBBB was not specified, and electrocardiograms (ECGs) were not always collected at a central ECG core laboratory for rigorous analysis. More recently, evidence has accumulated that likely only patients with complete LBBB benefit from CRT and not patients with other forms of nonspecific LV conduction delay or RBBB. 2 The most definitive evidence emerged from the analysis of the Multicenter Automated Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT), which enrolled patients with New York Heart Association class I and II heart failure. 3 In this study, LBBB was defined by the 1985 World Health Organization (WHO) criteria 4 that were more recently endorsed by the American Heart Association, American College of Cardiology and Heart Rhythm Society. 5 In MADIT-CRT, cardiac resynchronization therapy resulted in a 53% reduction in heart failure events or death (hazard ratio [HR], 0.47; P b .001) but a 24% increase (not statistically significant) in heart failure events or death in patients without LBBB (HR, 1.24; P = .26), and the outcome in nonspecific LV conduction delay patients was worse than patients with RBBB. 3 Analysis from prolonged follow-up in MADITCRT recently presented at the Heart Rhythm Society scientific sessions found that CRT caused a statistically significant increase in heart failure events or mortality in patients without LBBB. 6 These findings from CRT trials emphasize the importance of accurately defining LBBB. Some of the individuals classified as “LBBB” in the CRT trials may not actually have LBBB, but the observed benefit in the LBBB group is 0022-0736/$ – see front matter. Published by Elsevier Inc. doi:10.1016/j.jelectrocard.2012.06.023
“driven” by those with true complete LBBB. Recently, Strauss et al 1 reviewed the evidence for LBBB criteria and proposed strict LBBB criteria that require a QRS duration of 130 milliseconds (ms) or more in women or 140 ms or more in men, and also rS or QS morphology in lead V1 and midQRS notching/slurring in at least 2 of the leads V1, V2, V5, V6, I, or aVL. In this issue of the journal, Gettes and Kligfield 7 comment on, “Should the criteria for LBBB be revised?” Interestingly, they divide this issue into 2 questions: (1) should the criteria for LBBB be revised and (2) what should the criteria be to identify patients with LBBB who are most likely to benefit from CRT? They strongly endorse the morphologic criteria outlined in the WHO publication, 4 which require a QRS duration of 120 ms or more and all 3 of the following: 1. broad and notched or slurred R in I and V5 or V6; 2. absence of Q wave in I and V5 and V6; and 3. an R peak time of 60 ms or more in V5 or V6. However, Gettes and Kligfield 7 state that in those patients who are being considered for CRT the QRS duration threshold in LBBB should be increased to 130 ms or more, as required in MADIT-CRT. The critical aspect of the WHO LBBB criteria is the requirement for broad and notched/slurred R in I and V5 or V6. However, these criteria can be even further improved. Mid-QRS notching/slurring from LBBB can occur in the R wave in leads I, aVL, V5, or V6, and in the Q or S wave of V1 and V2 (Fig. 1). Requiring notching in 2 of the leads (I, aVL, V1, V2, V5, or V6) increases the likelihood that the notching is due to a complete LBBB, but does not require that notching be present in all 3 leads I, V5, and V6. With regard to the timing of the notch, the WHO criteria specify that R peak time (of the second part of the notch) should be 60 ms or more in V5 or V6. Alternatively, the strict LBBB criteria 1 specify that the beginning of the notch should begin after 40 ms because a notch that begins in the first 40 ms of the QRS is likely to be due to infarction/scar. 8,9 The beginning of the notch represents the time when electrical activation breaks through to the LV endocardium (Fig. 1). From computer simulations 9 and the endocardial mapping data of Auricchio et al, 10 the minimum time for the activation wavefront to proceed through the septum is 40 ms. In addition, the notch should begin in the first half of the QRS complex and end at approximately two thirds through QRS duration (Fig. 1).
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Editorial / Journal of Electrocardiology 45 (2012) 505–507
Fig. 1. QRS morphology in complete LBBB. The LBBB activation sequence and representative QRS-T waveforms are depicted in their anatomical locations for the sagittal (A), transverse (B), and frontal (C) planes. The key LBBB QRS morphology feature shown is the mid-QRS notching that occurs at 50 and 90 ms, with slurring in between. The beginning of the notch represents the time when the electrical depolarization wavefront reaches the endocardium of the LV (after proceeding through the septum). The end of the notch occurs when the depolarization wavefront begins to reach the epicardium of the lateral wall. These notches are best seen in leads I, aVL, V1, V2, V5, and V6. Reprinted with permission from Strauss et al.1
Finally, with regard to the absence of Q waves in I and V5 and V6 that are specified in the WHO criteria, this is valid in uncomplicated LBBB; however, in the presence of anteroapical infarction, Q waves can be present in these leads, even in the presence of complete LBBB. 8 In addition to the morphology criteria requiring mid-QRS notching/slurring, Strauss et al 1 recommended that the QRS duration be 130 ms or more in women or 140 ms or more in men. The increase in QRS duration threshold beyond the conventional criteria of 120 ms or more is because QRS duration should increase by 60 ms with the onset of complete LBBB (40 ms to reach the LV endocardium and 20 additional milliseconds beyond normal to reenter the LV Purkinje network and proceed to the LV lateral wall). In the endocardial mapping study by Auricchio et al 10 of patients with LBBB by conventional ECG criteria, the QRS duration in patients with endocardial activation consistent with complete LBBB was 170 ± 16 ms, whereas QRS duration was 133 ± 28 ms in other patients. Furthermore, in the study of Grant and Dodge 11 (discussed extensively by Gettes and Kligfield 7), the authors note that although it had been believed that QRS duration prolongs by 40 ms with the onset of LBBB based on canine studies, the QRS duration prolongation in humans was often more than 70 to 80 ms. Grant and Dodge 11 state that the average QRS duration prolongation with the onset of supposed LBBB was 50 to 60 ms; however, this average included the one third of patients that they concluded did not have true LBBB. This supports that QRS prolongation should be more than 60 ms with the onset of true LBBB. The strict LBBB criteria 1 include different QRS duration thresholds by sex because women have smaller ventricles and a shorter QRS duration of more than 5 ms at baseline compared with men (87.1 ± 8.7 ms vs 92.7 ± 9.3 ms, respectively), 12 which doubles with LBBB because activation of the interventricular septum and LV lateral walls uncoupled. Even in a woman with a QRS duration 2 SDs below average at baseline (QRS duration, 70 ms), her QRS duration would be 130 ms with the onset of LBBB. Gettes and Kligfield 7 present one case of a woman with a QRS duration of 80 ms at baseline prolonged by 44 ms to reach 124 ms with the onset of potential LBBB. However, this paper ECG is of relatively poor quality, and the authors note that these measurements were unconfirmed by their evaluation of superimposed waveforms or the points identified to represent the onset or offset of the QRS complex. In contrast, Strauss et al 1 presented a series of cases where digital 12-lead ECGs were analyzed; one case included a woman that presented with a QRS duration of 76 ms at baseline that was prolonged by 72 ms to reach 148 ms with LBBB. 1 Moving forward, it is critical to validate LBBB criteria in comparison of endocardial activation mapping, as previously performed by Auricchio et al. 10 Currently, databases for validating conduction abnormality automated algorithms for commercial use only involve a reference standard of physician visual interpretation. In addition, any modified LBBB criteria should be analyzed to predict CRT benefit. A very recent study by Mascioli et al 13 did investigate the
Editorial / Journal of Electrocardiology 45 (2012) 505–507 1
ability of the new strict LBBB criteria to predict benefit from CRT. In multivariable analysis, the presence of “false LBBB” (meeting conventional LBBB criteria, but not the new strict LBBB criteria) predicted a 4-fold (HR, 3.98) increase in heart failure hospitalization or death compared with “true LBBB,” and “true LBBB” was the only variable significantly related to a greater increase in LV ejection fraction (HR, 4.57). 13 This was, however, a small single center study, and the results should be confirmed in a larger population. In addition, future trials should prospectively save patient digital ECGs to allow for automated analysis, and QRS duration thresholds to diagnose LBBB might be normalized to LV size or morphology. 14 David G. Strauss, MD, PhD Office of Science and Engineering Laboratories Center for Devices and Radiological Health US Food and Drug Administration Silver Spring, MD, USA E-mail address: [email protected]
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References 1. Strauss DG, Selvester RH, Wagner GS. Defining left bundle branch block in the era of cardiac resynchronization therapy. Am J Cardiol 2011;107:927. 2. Sipahi I, Chou JC, Hyden M, et al. Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: metaanalysis of randomized controlled trials. Am Heart J 2012;163: 260.e263. 3. Zareba W, Klein H, Cygankiewicz I, et al. Effectiveness of cardiac resynchronization therapy by QRS morphology in the Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy (MADIT-CRT). Circulation 2011;123:1061. 4. Willems JL, Robles de Medina EO, Bernard R, et al. Criteria for intraventricular conduction disturbances and pre-excitation. World
11. 12.
13.
14.
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Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc. J Am Coll Cardiol 1985;5:1261. Surawicz B, Childers R, Deal BJ, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part III: intraventricular conduction disturbances: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. J Am Coll Cardiol 2009;53:976. Haigney MC, Goldstein RE, Krone RD, et al. Cardiac resynchronization therapy in MADIT-CRT patients with non–left bundle branch block conduction disturbances. Heart Rhythm 2012;9:S65. Gettes LS, Kligfield P. Should electrocardiogram criteria for the diagnosis of left bundle-branch block be revised? J Electrocardiol 2012;45:500. Strauss DG, Selvester RH, Lima JA, et al. ECG quantification of myocardial scar in cardiomyopathy patients with or without conduction defects: correlation with cardiac magnetic resonance and arrhythmogenesis. Circ Arrhythm Electrophysiol Dec 2008;1:327. Strauss DG, Selvester RH. The QRS complex—a biomarker that “images” the heart: QRS scores to quantify myocardial scar in the presence of normal and abnormal ventricular conduction. J Electrocardiol 2009;42:85. Auricchio A, Fantoni C, Regoli F, et al. Characterization of left ventricular activation in patients with heart failure and left bundlebranch block. Circulation 2004;109:1133. Grant RP, Dodge HT. Mechanisms of QRS complex prolongation in man; left ventricular conduction disturbances. Am J Med 1956;20:834. Macfarlane P, Lawrie TDV. Appendix 1: normal limits. In: Macfarlane P, Lawrie TDV, editors. Comprehensive electrocardiology: theory and practice in health and disease, Vol 3. New York: Pergammon Press; 1989. p. 1441. Mascioli G, Padeletti L, Sassone B, et al. Electrocardiographic criteria of true left bundle branch block: a simple sign to predict a better clinical and instrumental response to CRT. Pacing Clin Electrophysiol 2012 [Epub ahead of print]. Hakacova N, Steding K, Engblom H, et al. Aspects of left ventricular morphology outperform left ventricular mass for prediction of QRS duration. Ann Noninvasive Electrocardiol 2010;15:124.