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Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation
Available online at www.sciencedirect.com
ScienceDirect Journal of Electrocardiology 51 (2018) 175 – 181 www.jecgonline.com
Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation☆,☆☆ Luigi Sciarra, MD, a Paolo Golia, MD, a Zefferino Palamà, MD, a,⁎ Antonio Scarà, MD, a Ermenegildo De Ruvo, MD, a Alessio Borrelli, MD, a Anna Maria Martino, MD, a Monia Minati, MD, a Alessandro Fagagnini, MD, a Claudia Tota, MD, a Lucia De Luca, MD, a Domenico Grieco, PhD, a Pietro Delise, MD, b Leonardo Calò, FESC a a
b
Cardiology Department, Policlinico Casilino, Rome, Italy Division of Cardiology, Hospital of Conegliano, Veneto, Italy
Abstract
Background: Left bundle branch block (LBBB) and left axis deviation (LAD) patients may have poor response to resynchronization therapy (CRT). We sought to assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony. Methods: CRT candidates with non-ischemic cardiomyopathy and LBBB were categorized as having normal QRS axis (within − 30° and + 90°) or LAD (within − 30° and − 90°). Patients underwent tissue Doppler imaging (TDI) to measure time interval between onset of QRS complex and peak systolic velocity in ejection period (Q-peak) at basal segments of septal, inferior, lateral and anterior walls, as expression of local timing of mechanical activation. Results: Thirty patients (mean age 70.6 years; 19 males) were included. Mean left ventricular ejection fraction was 0.28 ± 0.06. Mean QRS duration was 172.5 ± 13.9 ms. Fifteen patients showed LBBB with LAD (QRS duration 173 ± 14; EF 0.27 ± 0.06). The other 15 patients had LBBB with a normal QRS axis (QRS duration 172 ± 14; EF 0.29 ± 0.05). Among patients with LAD, Q-peak interval was significantly longer at the anterior wall in comparison to each other walls (septal 201 ± 46 ms, inferior 242 ± 58 ms, lateral 267 ± 45 ms, anterior 302 ± 50 ms; p b 0.0001). Conversely, in patients without LAD Q-peak interval was longer at lateral wall, when compared to each other (septal 228 ± 65 ms, inferior 250 ± 64 ms, lateral 328 ± 98 ms, anterior 291 ± 86 ms; p b 0.0001). Conclusions: Patients with heart failure, presenting LBBB and LAD, show a specific pattern of ventricular asynchrony, with latest activation at anterior wall. This finding could affect target vessel selection during CRT procedures in these patients. © 2017 Elsevier Inc. All rights reserved.
Keywords:
CRT; left blunde block; left axis deviation; Tissue doppler
Cardiac resynchronization therapy (CRT) is an established treatment for selected patients with heart failure. The main mechanism underlying CRT efficacy is deemed to be the correction of the systo-diastolic dyssynchrony occurring between the interventricular septum and the left ventricular (LV) free wall, which, to a variable extent, may be associated with intraventricular conduction disturbances, mainly left bundle branch block (LBBB) [1]. The achievement of a good ☆
Conflicts of interest: nothing to declare. The first and second author equally contributed to the design, drawing, data collection, drafting and review of the text. ⁎ Corresponding author at: via Casilina, 1049, 00100 Rome, Italy. E-mail address: [email protected] ☆☆
https://doi.org/10.1016/j.jelectrocard.2017.10.006 0022-0736/© 2017 Elsevier Inc. All rights reserved.
response to CRT depends on several factors, including among others the distance of the LV lead from the latest activated area of the left ventricle [2]. In most cases, the latter is located within the lateral or postero-lateral wall [3], that, accordingly, are preferably targeted during the implant procedure. However, a substantial variability of LV mechanical and electrical activation sequence has been described in LBBB patients [4–6]; therefore, the latest activated LV area may not be the one where the lead is more frequently positioned. Only limited data are available on the relationship between some features of the surface ECG and the LV mechanical activation sequence. It has been reported that patients with LBBB and left QRS axis deviation (LAD) may
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have a worse response to CRT than patients with normal QRS axis [7]. We sought to determine, by tissue Doppler imaging (TDI), whether the mechanical activation sequence of the left ventricle in patients with LBBB and LAD is characterized by a specific asynchrony pattern. Methods Patients population Consecutive patients undergoing CRT implant between December 2014 and April 2015 were screened for inclusion. They had been selected for CRT according to current guidelines [8]. Patients with ischemic cardiomyopathy were excluded. The patients were considered eligible for the study if they were in sinus rhythm and had complete LBBB at the surface electrocardiogram. Patients presenting with right bundle branch block or intraventricular conduction delay were excluded. LBBB was defined according to HRS recommendations for the standardization and interpretation of the electrocardiogram [9]. Subsequently, electrocardiograms were screened for the presence of LAD by two experienced electrophysiologists. Normal QRS axis was assumed to be within − 30° and 90°. LAD was diagnosed if QRS axis was between − 30° and − 90° (Fig. 1). In addition to a conventional echocardiographic evaluation, all selected patients underwent TDI, to evaluate the mechanical activation sequence of the left ventricle prior to implantation of the CRT device. LV dyssynchrony assessment Echocardiographic examinations were performed by a single, trained in imaging, cardiologist in order to avoid, in an
initial phase, inter-observer variability. He is blinded to the clinical and electrocardiographic data. A Vivid E9 (General Electric, Milwaukee, USA) was used to perform exams. Data were analyzed offline with commercial software. TDI was performed by means of pulsed-wave Doppler from two apical views (four-chamber and two-chamber) to assess LV regional timing of mechanical activation. The sample volume was placed at the basal segments of the septal, inferior, lateral and anterior walls. Gain and filters were adjusted, when required, to eliminate background noise and to obtain well defined signals. In order to optimize frame rate, sector width was narrowed to the wall of interest. Tissue Doppler signals were recorded at a sweep of 100 mm/s. In some cases, the times of aortic valve opening and closure from the pulsed-wave Doppler signals were used as a reference to correctly identify the LV ejection period. For each segment, measures were obtained in held expiration from three consecutive heart beats and the average was calculated offline. The time interval between the onset of the QRS complex and the peak of systolic velocity in the ejection period (Q-peak interval) was measured for each segment, as expression of local electromechanical delay. Subsequently, the latest mechanically activated LV segment between those examined was determined for each patient, as the one with the most prolonged Q-peak interval. In two patients with LBBB and LAD who underwent electrophysiological study and catheter ablation before the CRT procedure, the electrical activation sequence of the left ventricle was reconstructed by electroanatomical mapping (CARTO, Biosense Webster Inc., Diamond Bar, California, USA) [10].
Fig. 1. Twelve‐lead surface electrocardiogram of a patient with LBBB and left QRS axis deviation.
L. Sciarra et al. / Journal of Electrocardiology 51 (2018) 175–181
Statistical analysis Continuous variables were reported as sample average ± standard deviation, binary variables as percentages. Baseline patients characteristics were compared between the groups of patients with and without deviation, by using T-student test for continuous variables and Fisher test for non parametric variables. Data relative to Q-peak intervals were analyzed hierarchically with linear mixed models having Q-peak interval as the dependent variable, septal inferior lateral and anterior wall position as independent variables, and random intercept and slope at patient level as random effect. Separate terms for presence or absence of deviation were included in the equation with block-diagonal matrix of unstructured covariance of the random effects. Post-hoc intra-individual multiple comparisons among positions were performed with the Wilcoxon Sign test with Bonferroni's correction of significance level. Statistical significance was nominally set p = 0.05 for all tests. STATA version 11SE software (StataCorp, Texas, US) was used for statistical analyses.
Results Patients population Thirty patients (mean age 70.6 ± 7.6 years; 19 males) were included. All patients had heart failure with mean NYHA class 2.8 ± 0.4; mean left ventricular ejection fraction was 0.28 ± 0.06. According to the inclusion criteria, all patients had LBBB. Mean QRS duration was 172.5 ± 13.9 ms. Fifteen patients showed LBBB with LAD (72 ± 8 years, 9 males; mean QRS duration 173 ± 14; mean NYHA class: 2.9 ± 0.5; mean EF 0.27 ± 0.06). The other 15 patients had LBBB with a normal QRS axis (mean age 70 ± 8 years, 10 males; mean QRS duration 172 ± 14; mean NYHA class 2.8 ± 0.4; mean ejection fraction (EF) 0.29 ± 0.05) at the surface ECG. Demographic, clinical and electrocardiographic data are summarized in Table 1. Echocardiographic data and LV activation sequence Among patients with LAD the mean Q-peak time at TDI was significantly longer when measured at the basal anterior wall in comparison to each of the other regions (anterior 302 ± 50 ms, septal 201 ± 46 ms, inferior 242 ± 58 ms, lateral 267 ± 45 ms, p b 0001). In all but one patients with LAD, the most delayed region was found to be the anterior wall. Conversely, among the 15 patients without LAD the mean Q-peak time was significantly longer at the lateral wall, when compared to each of the other regions (lateral 328 ± 98 ms, anterior 291 ± 86 ms, septal 228 ± 65 ms, inferior 250 ± 64 ms, p b 0.0001). The lateral wall was the latest to be mechanically activated in all the patients in the group without LAD. LV dyssynchrony data are reported in Table 2 and Fig. 2. Electrical activation mapping in the 2 patients with LBBB and LAD who underwent electroanatomic study localized
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Table 1 Patients characteristics.
Age (years) Male sex n (%) NYHA QRS (ms) LVEDV (ml) EF MR (0–3) Hypertension n (%) Diabetes n (%) Dyslipidaemia n (%) Medications Beta blockers n (%) ACE-I n (%) ARB n (%) Loop diuretics n (%) Ivabradine n (%) Aldosterone blockers n (%) Statins n (%) NOAc n (%) Aspirin n (%) Warfarin n (%) Oral hypoglycemic drugs n (%) Insulin n (%)
LBBB + LAD (15 pts)
LBBB (15 pts)
p
72 ± 8 9 (60) 2.9 ± 0.5 173 ± 14 217 ± 38 0.27 ± 0.06 1.4 ± 0.8 10 (67) 5 (33) 12 (80)
70 ± 8 10(67) 2.8 ± 0.4 172 ± 14 211 ± 39 0.29 ± 0.05 1.5 ± 0.8 11 (73) 4 (27) 12 (80)
NS NS NS NS NS NS NS NS NS NS
14 (93) 11 (73) 5 (33) 12 (80) 7 (47) 10 (67) 10 (67) 4 (27) 5 (33) 6 (40) 5 (33) 3 (20)
13 (87) 11 (73) 4 (27) 12 (80) 6 (40) 11 (73) 10 (67) 3 (20) 5 (33) 5 (33) 4 (27) 2 (13)
NS NS NS NS NS NS NS NS NS NS NS NS
LBBB + LAD: left bundle branch block with left axis deviation; LBBB: left bundle branch block without left axis deviation; NYHA: New York Heart Association functional class; LVEDV: left ventricular end-diastolic volume; EF: ejection fraction; MR: mitral regurgitation (0 = absent, 1 = mild, 2 = moderate, 3 = severe); ACE-I: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blockers; NOAc: new oral anticoagulant drugs.
the area of latest LV activation at the anterior wall in both. The CARTO map of one of these patients is shown in Fig. 3.
Discussion Main findings We found that, in patients undergoing CRT presenting with LBBB and LAD, the latest mechanically activated LV area in most cases was the anterior wall, differently from patients with normal QRS axis, in whom such area coincided with the lateral wall. This finding, which suggests the presence of a specific pattern of electro-mechanical activation in patients with LBBB and LAD, to our knowledge had not been described previously.
Table 2 Q-peak interval at four LV locations in LBBB patients with and without LAD.
LBBB LBBB + LAD
Septum
Inferior
Lateral
Anterior
p
228 ± 65 201 ± 46
250 ± 64 242 ± 58
328 ± 98 267 ± 45
291 ± 86 302 ± 50
b 0.0001 b 0.0001
Mean time intervals in ms between QRS onset and peak systolic velocity in the ejection phase (Q-peak) measured in the left ventricle at the basal segment of septal, inferior, lateral and anterior wall in patients with normal QRS axis (LBBB w/o deviation) and with left axis deviation (LBBB with deviation). p values are the results of linear mixed model analysis with position as covariate and random intercept and slope at patient level as random effects. Separate terms for presence or absence of deviation were included in the equation.
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Fig. 2. Box-whisker plot (A) and panel-data line plots (B) of Q-peak interval values at different locations, in the groups with and without left axis deviation. In the upper graph, circles represent outlying points, while asterisks denote significant Bonferroni-adjusted p values of multiple comparisons: (*) p = 0.004; (**) p b 0.009, for comparisons with all other positions;
Response to CRT The presence of a substantial LV dyssynchrony at baseline has been considered a prerequisite for obtaining a response to CRT [1]. Accordingly, the reduction of LV dyssynchrony after implantation has emerged as a marker of long-term CRT response, whereas nonresponders do not obtain a significant reduction of pre-implant dyssynchrony [11]. Moreover, in patients without significant pre-implant dyssynchrony, CRT may result even in an augmentation of the dyssynchrony itself, that has been related to a less favorable long-term clinical outcome [12]. However, only the specific dyssynchrony pattern that characterizes LBBB has been associated with a favorable response to CRT. In this regard, the ability to identify a “true” LBBB pattern at the preimplant 12-lead ECG (including a QRS
duration ≥ 140 ms for men and 130 ms for women, and the presence of mid-QRS notching/slurring in at least 2 of the leads I, aVL, V1, V2, V5, V6) [13] has been strongly correlated with both the extent of LV dyssynchrony [14] as well as the response to CRT [15,16]. Other factors that have been highlighted as predictors of CRT response are the location of myocardial scar areas relative to the LV pacing site [17], the optimization of atrioventricular and interventricular pacing intervals and the proximity of the LV lead to the latest activated area of the left ventricle [2]. LBBB and left axis deviation In LBBB patients, the finding of LAD is known to be associated with more severe conduction system disease and
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Fig. 3. The bipolar CARTO mapping of the left ventricle of a patient with LBBB and LAD is displayed in right anterior oblique view (left panel) and left anterior oblique view (right panel). The earliest activation of the left ventricle is presented in red and was in the interventricular septum (see the left panel). The latest ventricular activation in presented in purple and corresponded to the anterior wall (see the right panel).
LV structural pathology, which implies a more severe prognosis [18]. Consistently, Kronborg et al. found that CRT-treated LBBB patients with LAD had lower EF and higher LV end-diastolic diameter than those with normal QRS axis; however, LAD was not a significant predictor of all-cause and cardiac mortality in that population [19]. Other studies also found no correlation between the presence of LAD and clinical outcome after CRT [20,21]. The question whether QRS axis deviation could be associated with differences in CRT results has been also addressed in a MADIT-CRT subanalysis: in contrast with previous data, the Authors found that among LBBB patients treated with CRT-D, those with LAD had a significantly higher risk of heart failure events or death than non-LAD patients. The subgroup of LBBB patients without LAD showed a trend toward greater benefit from CRT-D (versus the control group of ICD patients) compared with LAD patients. Consistently, after CRT-D LBBB patients without LAD showed significantly
larger reduction in dyssynchrony than LBBB patients with LAD. However, LAD did not affect outcome in LBBB patients treated with ICD only [7]. A more recent retrospective study of 707 LBBB patients undergoing CRT also found that left axis deviation was independent predictor of poor prognosis in patients undergoing CRT [22]. On the other hand, Garcia-Seara et al. reported a higher CRT efficacy in LBBB patients with LAD than in patients without LAD (responders were 72.7% in the LAD group vs 62.2% in the normal axis group) [23]. Notably, in the study of Garcia-Seara et al. 42% of the patients had the coronary sinus lead placed in the anterior interventricular vein, and between them, those with LAD obtained a significantly better response to CRT. In the MADIT-CRT study, where the patients with normal axis fared better, the CS lead was more often positioned in a lateral or posterolateral cardiac vein. It appears that the need of stimulating the last LV activated area to obtain effective resynchronization could
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explain these apparently conflicting results. In the setting of a LBBB + LAD pattern such area may match with the anterior wall, as evidenced in the present study. In order to evaluate the impact of the LV lead position on outcome, a subset of 799 MADIT-CRT patients was analyzed: the Authors did not find significant differences between anterior, lateral, and posterior positions, whereas apical vs basal or midventricular positions were associated with an unfavorable outcome [24]. However, in those patients the electrical or mechanical activation sequence of the left ventricle had not been assessed, nor was the QRS axis orientation at the surface ECG reported. Our results further support the finding of Garcia-Seara et al. [23], by showing that in most cases in LBBB + LAD patients the latest area of contraction in the left ventricle is the anterior wall. Since about 40% of LBBB patients undergoing CRT have LAD [7,19,23], the finding of a specific pattern of ventricular asynchrony in such patients is not devoid of clinical importance. The usefulness of determining the site of latest LV contraction before CRT, in order to optimize benefit in the single patient has been documented. However, assessment of LV contraction sequence in patients undergoing CRT may not be always feasible. The knowing of a correlation between QRS axis on surface ECG and alleged area of latest LV contraction may help in target vessel selection during CRT procedure. In particular, in patients presenting with LBBB + LAD positioning the LV lead in the anterior interventricular vein could be regarded as a valuable option. The importance of an accurate surface ECG analysis in CRT candidates is underscored by our data: along with the recognition of a “true” LBBB pattern, evaluation of QRS axis could provide a simple method to increase the number of potential responders to CRT.
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
Conclusions LV asynchrony pattern in patients with LBBB differs in relation to QRS axis at the surface ECG. The latest mechanically activated area was located by TDI mostly at the anterior wall in patients with LAD, whereas it was found at the lateral wall in normal axis-patients. Our results may be relevant in target vessel selection during CRT procedures. References [1] Bax JJ, Bleeker GB, Marwick TH, Molhoek SG, Boersma E, Steendijk P, et al. Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol 2004;44:1834–40. [2] Becker M, Kramann R, Franke A, Breithardt OA, Heussen N, Knackstedt C, et al. Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography. Eur Heart J 2007;28:1211–20. [3] Fung JWH, Chan JYS, Yip GWK, Chan HCK, Chan WWL, Zhang Q, et al. Effect of left ventricular endocardial activation pattern on echocardiographic and clinical response to cardiac resynchronization therapy. Heart 2007;93:432–7. [4] Ansalone G, Giannantoni P, Ricci R, Trambaiolo P, Fedele F, Santini M. Doppler myocardial imaging to evaluate the effectiveness of pacing
[14]
[15]
[16]
[17]
[18]
[19]
sites in patients receiving biventricular pacing. J Am Coll Cardiol 2002;39:489–99. Sogaard P, Egeblad H, Kim WY, Jensen HK, Pedersen AK, Kristensen BO, et al. Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 2002;40:723–30. Jia P, Ramanathan C, Ghanem RN, Ryu K, Varma N, Rudy Y. Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 2006;3:296–310. Brenyo A, Rao M, Barsheshet A, Cannom D, Quesada A, McNitt S, et al. QRS axis and the benefit of cardiac resynchronization therapy in patients with mildly symptomatic heart failure enrolled in MADITCRT. J Cardiovasc Electrophysiol 2013;24:442–8, https://doi.org/ 10.1111/jce.12057. Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt O-A, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. The task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013;34:2281–329, https://doi.org/ 10.1093/eurheartj/eht150. Surawicz B, Childers R, Deal BJ, Gettes LS, Bailey JJ, Gorgels A, 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;53:976–81, https://doi.org/10.1016/j.jacc.2008. Gepstein L, Hayan G, Ben-Haim SA. A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results. Circulation 1997;95:1611–22. Bleeker GB, Mollema SA, Holman ER, Van de Veire N, Ypenburg C, Boersma E, et al. Left ventricular resynchronization is mandatory for response to cardiac resynchronization therapy: analysis in patients with echocardiographic evidence of left ventricular dyssynchrony at baseline. Circulation 2007;116:1440–8. Auger D, Bleeker GB, Bertini M, Ewe SH, van Bommel RJ, Witkowski TG, et al. Effect of cardiac resynchronization therapy in patients without left intraventricular dyssynchrony. Eur Heart J 2012;33:913–20, https://doi.org/10.1093/eurheartj/ehr468. Strauss DG, Selvester RH, Wagner GS. Defining left bundle branch block in the era of cardiac resynchronization therapy. Am J Cardiol 2011;107:927–34, https://doi.org/10.1016/j.amjcard.2010.11.010. Andersson LG, Wu KC, Wieslander B, Loring Z, Frank TF, Maynard C, et al. Left ventricular mechanical dyssynchrony by cardiac magnetic resonance is greater in patients with strict vs. non-strict ECG criteria for left bundle branch block. Am Heart J 2013;165:956–63, https://doi.org/ 10.1016/j.ahj.2013.03.013. Mascioli G, Padeletti L, Sassone B, Zecchin M, Lucca E, Sacchi S, 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;35:927–34, https://doi.org/ 10.1111/j.1540-8159.2012.03427.x. Tian Y, Zhang P, Li X, Gao Y, Zhu T, Wang L, et al. True complete left bundle branch block morphology strongly predicts good response to cardiac resynchronization therapy. Europace 2013;15:1499–506, https://doi.org/10.1093/europace/eut049. Ypenburg C, Roes SD, Bleeker GB, Kaandorp TA, de Roos A, Schalij MJ, et al. Effect of total scar burden on contrast-enhanced magnetic resonance imaging on response to cardiac resynchronization therapy. Am J Cardiol 2007;99:657–60. Dhingra RC, Amat-Y-Leon F, Wyndham C, Sridhar SS, Wu D, Rosen KM. Significance of left axis deviation in patients with chronic left bundle branch block. Am J Cardiol 1978;42:551–6. Kronborg MB, Nielsen JC, Mortensen PT. Electrocardiographic patterns and long-term clinical outcome in cardiac resynchronization therapy. Europace 2010;12:216–22, https://doi.org/10.1093/europace/eup364.
L. Sciarra et al. / Journal of Electrocardiology 51 (2018) 175–181 [20] Gervais R, Leclercq C, Shankar A, Jacobs S, Eiskjaer H, Johannessen A, et al. Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub-analysis of the CARE-HF trial. Eur J Heart Fail 2009;11:699–705, https://doi.org/10.1093/ eurjhf/hfp074. [21] Lecoq G, Leclercq C, Leray E, Crocq C, Alonso C, de Place C, et al. Clinical and electrocardiographic predictors of a positive response to cardiac resynchronization therapy in advanced heart failure. Eur Heart J 2005;26:1094–100. [22] Perrotta L, Kandala J, Di Biase L, Valleggi A, Michelotti F, Pieragnoli P, et al. Prognostic impact of QRS axis deviation in patients treated
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with cardiac resynchronization therapy. J Cardiovasc Electrophysiol 2016;27:315–20, https://doi.org/10.1111/jce.12887. [23] Garcia-Seara J, Martinez-Sande JL, Cid B, Gude F, Bastos M, Dominguez M, et al. Influencia del eje eléctrico QRS preimplante en la respuesta a la terapia de resincronización cardiac. Rev Esp Cardiol 2008;61:1245–52. [24] Singh JP, Klein HU, Huang DT, Reek S, Kuniss M, Quesada A, et al. Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial. Circulation 2011;123:1159–66, https:// doi.org/10.1161/CIRCULATIONAHA.110.000646.
ScienceDirect Journal of Electrocardiology 51 (2018) 175 – 181 www.jecgonline.com
Patients with left bundle branch block and left axis deviation show a specific left ventricular asynchrony pattern: Implications for left ventricular lead placement during CRT implantation☆,☆☆ Luigi Sciarra, MD, a Paolo Golia, MD, a Zefferino Palamà, MD, a,⁎ Antonio Scarà, MD, a Ermenegildo De Ruvo, MD, a Alessio Borrelli, MD, a Anna Maria Martino, MD, a Monia Minati, MD, a Alessandro Fagagnini, MD, a Claudia Tota, MD, a Lucia De Luca, MD, a Domenico Grieco, PhD, a Pietro Delise, MD, b Leonardo Calò, FESC a a
b
Cardiology Department, Policlinico Casilino, Rome, Italy Division of Cardiology, Hospital of Conegliano, Veneto, Italy
Abstract
Background: Left bundle branch block (LBBB) and left axis deviation (LAD) patients may have poor response to resynchronization therapy (CRT). We sought to assess if LBBB and LAD patients show a specific pattern of mechanical asynchrony. Methods: CRT candidates with non-ischemic cardiomyopathy and LBBB were categorized as having normal QRS axis (within − 30° and + 90°) or LAD (within − 30° and − 90°). Patients underwent tissue Doppler imaging (TDI) to measure time interval between onset of QRS complex and peak systolic velocity in ejection period (Q-peak) at basal segments of septal, inferior, lateral and anterior walls, as expression of local timing of mechanical activation. Results: Thirty patients (mean age 70.6 years; 19 males) were included. Mean left ventricular ejection fraction was 0.28 ± 0.06. Mean QRS duration was 172.5 ± 13.9 ms. Fifteen patients showed LBBB with LAD (QRS duration 173 ± 14; EF 0.27 ± 0.06). The other 15 patients had LBBB with a normal QRS axis (QRS duration 172 ± 14; EF 0.29 ± 0.05). Among patients with LAD, Q-peak interval was significantly longer at the anterior wall in comparison to each other walls (septal 201 ± 46 ms, inferior 242 ± 58 ms, lateral 267 ± 45 ms, anterior 302 ± 50 ms; p b 0.0001). Conversely, in patients without LAD Q-peak interval was longer at lateral wall, when compared to each other (septal 228 ± 65 ms, inferior 250 ± 64 ms, lateral 328 ± 98 ms, anterior 291 ± 86 ms; p b 0.0001). Conclusions: Patients with heart failure, presenting LBBB and LAD, show a specific pattern of ventricular asynchrony, with latest activation at anterior wall. This finding could affect target vessel selection during CRT procedures in these patients. © 2017 Elsevier Inc. All rights reserved.
Keywords:
CRT; left blunde block; left axis deviation; Tissue doppler
Cardiac resynchronization therapy (CRT) is an established treatment for selected patients with heart failure. The main mechanism underlying CRT efficacy is deemed to be the correction of the systo-diastolic dyssynchrony occurring between the interventricular septum and the left ventricular (LV) free wall, which, to a variable extent, may be associated with intraventricular conduction disturbances, mainly left bundle branch block (LBBB) [1]. The achievement of a good ☆
Conflicts of interest: nothing to declare. The first and second author equally contributed to the design, drawing, data collection, drafting and review of the text. ⁎ Corresponding author at: via Casilina, 1049, 00100 Rome, Italy. E-mail address: [email protected] ☆☆
https://doi.org/10.1016/j.jelectrocard.2017.10.006 0022-0736/© 2017 Elsevier Inc. All rights reserved.
response to CRT depends on several factors, including among others the distance of the LV lead from the latest activated area of the left ventricle [2]. In most cases, the latter is located within the lateral or postero-lateral wall [3], that, accordingly, are preferably targeted during the implant procedure. However, a substantial variability of LV mechanical and electrical activation sequence has been described in LBBB patients [4–6]; therefore, the latest activated LV area may not be the one where the lead is more frequently positioned. Only limited data are available on the relationship between some features of the surface ECG and the LV mechanical activation sequence. It has been reported that patients with LBBB and left QRS axis deviation (LAD) may
176
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have a worse response to CRT than patients with normal QRS axis [7]. We sought to determine, by tissue Doppler imaging (TDI), whether the mechanical activation sequence of the left ventricle in patients with LBBB and LAD is characterized by a specific asynchrony pattern. Methods Patients population Consecutive patients undergoing CRT implant between December 2014 and April 2015 were screened for inclusion. They had been selected for CRT according to current guidelines [8]. Patients with ischemic cardiomyopathy were excluded. The patients were considered eligible for the study if they were in sinus rhythm and had complete LBBB at the surface electrocardiogram. Patients presenting with right bundle branch block or intraventricular conduction delay were excluded. LBBB was defined according to HRS recommendations for the standardization and interpretation of the electrocardiogram [9]. Subsequently, electrocardiograms were screened for the presence of LAD by two experienced electrophysiologists. Normal QRS axis was assumed to be within − 30° and 90°. LAD was diagnosed if QRS axis was between − 30° and − 90° (Fig. 1). In addition to a conventional echocardiographic evaluation, all selected patients underwent TDI, to evaluate the mechanical activation sequence of the left ventricle prior to implantation of the CRT device. LV dyssynchrony assessment Echocardiographic examinations were performed by a single, trained in imaging, cardiologist in order to avoid, in an
initial phase, inter-observer variability. He is blinded to the clinical and electrocardiographic data. A Vivid E9 (General Electric, Milwaukee, USA) was used to perform exams. Data were analyzed offline with commercial software. TDI was performed by means of pulsed-wave Doppler from two apical views (four-chamber and two-chamber) to assess LV regional timing of mechanical activation. The sample volume was placed at the basal segments of the septal, inferior, lateral and anterior walls. Gain and filters were adjusted, when required, to eliminate background noise and to obtain well defined signals. In order to optimize frame rate, sector width was narrowed to the wall of interest. Tissue Doppler signals were recorded at a sweep of 100 mm/s. In some cases, the times of aortic valve opening and closure from the pulsed-wave Doppler signals were used as a reference to correctly identify the LV ejection period. For each segment, measures were obtained in held expiration from three consecutive heart beats and the average was calculated offline. The time interval between the onset of the QRS complex and the peak of systolic velocity in the ejection period (Q-peak interval) was measured for each segment, as expression of local electromechanical delay. Subsequently, the latest mechanically activated LV segment between those examined was determined for each patient, as the one with the most prolonged Q-peak interval. In two patients with LBBB and LAD who underwent electrophysiological study and catheter ablation before the CRT procedure, the electrical activation sequence of the left ventricle was reconstructed by electroanatomical mapping (CARTO, Biosense Webster Inc., Diamond Bar, California, USA) [10].
Fig. 1. Twelve‐lead surface electrocardiogram of a patient with LBBB and left QRS axis deviation.
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Statistical analysis Continuous variables were reported as sample average ± standard deviation, binary variables as percentages. Baseline patients characteristics were compared between the groups of patients with and without deviation, by using T-student test for continuous variables and Fisher test for non parametric variables. Data relative to Q-peak intervals were analyzed hierarchically with linear mixed models having Q-peak interval as the dependent variable, septal inferior lateral and anterior wall position as independent variables, and random intercept and slope at patient level as random effect. Separate terms for presence or absence of deviation were included in the equation with block-diagonal matrix of unstructured covariance of the random effects. Post-hoc intra-individual multiple comparisons among positions were performed with the Wilcoxon Sign test with Bonferroni's correction of significance level. Statistical significance was nominally set p = 0.05 for all tests. STATA version 11SE software (StataCorp, Texas, US) was used for statistical analyses.
Results Patients population Thirty patients (mean age 70.6 ± 7.6 years; 19 males) were included. All patients had heart failure with mean NYHA class 2.8 ± 0.4; mean left ventricular ejection fraction was 0.28 ± 0.06. According to the inclusion criteria, all patients had LBBB. Mean QRS duration was 172.5 ± 13.9 ms. Fifteen patients showed LBBB with LAD (72 ± 8 years, 9 males; mean QRS duration 173 ± 14; mean NYHA class: 2.9 ± 0.5; mean EF 0.27 ± 0.06). The other 15 patients had LBBB with a normal QRS axis (mean age 70 ± 8 years, 10 males; mean QRS duration 172 ± 14; mean NYHA class 2.8 ± 0.4; mean ejection fraction (EF) 0.29 ± 0.05) at the surface ECG. Demographic, clinical and electrocardiographic data are summarized in Table 1. Echocardiographic data and LV activation sequence Among patients with LAD the mean Q-peak time at TDI was significantly longer when measured at the basal anterior wall in comparison to each of the other regions (anterior 302 ± 50 ms, septal 201 ± 46 ms, inferior 242 ± 58 ms, lateral 267 ± 45 ms, p b 0001). In all but one patients with LAD, the most delayed region was found to be the anterior wall. Conversely, among the 15 patients without LAD the mean Q-peak time was significantly longer at the lateral wall, when compared to each of the other regions (lateral 328 ± 98 ms, anterior 291 ± 86 ms, septal 228 ± 65 ms, inferior 250 ± 64 ms, p b 0.0001). The lateral wall was the latest to be mechanically activated in all the patients in the group without LAD. LV dyssynchrony data are reported in Table 2 and Fig. 2. Electrical activation mapping in the 2 patients with LBBB and LAD who underwent electroanatomic study localized
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Table 1 Patients characteristics.
Age (years) Male sex n (%) NYHA QRS (ms) LVEDV (ml) EF MR (0–3) Hypertension n (%) Diabetes n (%) Dyslipidaemia n (%) Medications Beta blockers n (%) ACE-I n (%) ARB n (%) Loop diuretics n (%) Ivabradine n (%) Aldosterone blockers n (%) Statins n (%) NOAc n (%) Aspirin n (%) Warfarin n (%) Oral hypoglycemic drugs n (%) Insulin n (%)
LBBB + LAD (15 pts)
LBBB (15 pts)
p
72 ± 8 9 (60) 2.9 ± 0.5 173 ± 14 217 ± 38 0.27 ± 0.06 1.4 ± 0.8 10 (67) 5 (33) 12 (80)
70 ± 8 10(67) 2.8 ± 0.4 172 ± 14 211 ± 39 0.29 ± 0.05 1.5 ± 0.8 11 (73) 4 (27) 12 (80)
NS NS NS NS NS NS NS NS NS NS
14 (93) 11 (73) 5 (33) 12 (80) 7 (47) 10 (67) 10 (67) 4 (27) 5 (33) 6 (40) 5 (33) 3 (20)
13 (87) 11 (73) 4 (27) 12 (80) 6 (40) 11 (73) 10 (67) 3 (20) 5 (33) 5 (33) 4 (27) 2 (13)
NS NS NS NS NS NS NS NS NS NS NS NS
LBBB + LAD: left bundle branch block with left axis deviation; LBBB: left bundle branch block without left axis deviation; NYHA: New York Heart Association functional class; LVEDV: left ventricular end-diastolic volume; EF: ejection fraction; MR: mitral regurgitation (0 = absent, 1 = mild, 2 = moderate, 3 = severe); ACE-I: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blockers; NOAc: new oral anticoagulant drugs.
the area of latest LV activation at the anterior wall in both. The CARTO map of one of these patients is shown in Fig. 3.
Discussion Main findings We found that, in patients undergoing CRT presenting with LBBB and LAD, the latest mechanically activated LV area in most cases was the anterior wall, differently from patients with normal QRS axis, in whom such area coincided with the lateral wall. This finding, which suggests the presence of a specific pattern of electro-mechanical activation in patients with LBBB and LAD, to our knowledge had not been described previously.
Table 2 Q-peak interval at four LV locations in LBBB patients with and without LAD.
LBBB LBBB + LAD
Septum
Inferior
Lateral
Anterior
p
228 ± 65 201 ± 46
250 ± 64 242 ± 58
328 ± 98 267 ± 45
291 ± 86 302 ± 50
b 0.0001 b 0.0001
Mean time intervals in ms between QRS onset and peak systolic velocity in the ejection phase (Q-peak) measured in the left ventricle at the basal segment of septal, inferior, lateral and anterior wall in patients with normal QRS axis (LBBB w/o deviation) and with left axis deviation (LBBB with deviation). p values are the results of linear mixed model analysis with position as covariate and random intercept and slope at patient level as random effects. Separate terms for presence or absence of deviation were included in the equation.
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Fig. 2. Box-whisker plot (A) and panel-data line plots (B) of Q-peak interval values at different locations, in the groups with and without left axis deviation. In the upper graph, circles represent outlying points, while asterisks denote significant Bonferroni-adjusted p values of multiple comparisons: (*) p = 0.004; (**) p b 0.009, for comparisons with all other positions;
Response to CRT The presence of a substantial LV dyssynchrony at baseline has been considered a prerequisite for obtaining a response to CRT [1]. Accordingly, the reduction of LV dyssynchrony after implantation has emerged as a marker of long-term CRT response, whereas nonresponders do not obtain a significant reduction of pre-implant dyssynchrony [11]. Moreover, in patients without significant pre-implant dyssynchrony, CRT may result even in an augmentation of the dyssynchrony itself, that has been related to a less favorable long-term clinical outcome [12]. However, only the specific dyssynchrony pattern that characterizes LBBB has been associated with a favorable response to CRT. In this regard, the ability to identify a “true” LBBB pattern at the preimplant 12-lead ECG (including a QRS
duration ≥ 140 ms for men and 130 ms for women, and the presence of mid-QRS notching/slurring in at least 2 of the leads I, aVL, V1, V2, V5, V6) [13] has been strongly correlated with both the extent of LV dyssynchrony [14] as well as the response to CRT [15,16]. Other factors that have been highlighted as predictors of CRT response are the location of myocardial scar areas relative to the LV pacing site [17], the optimization of atrioventricular and interventricular pacing intervals and the proximity of the LV lead to the latest activated area of the left ventricle [2]. LBBB and left axis deviation In LBBB patients, the finding of LAD is known to be associated with more severe conduction system disease and
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Fig. 3. The bipolar CARTO mapping of the left ventricle of a patient with LBBB and LAD is displayed in right anterior oblique view (left panel) and left anterior oblique view (right panel). The earliest activation of the left ventricle is presented in red and was in the interventricular septum (see the left panel). The latest ventricular activation in presented in purple and corresponded to the anterior wall (see the right panel).
LV structural pathology, which implies a more severe prognosis [18]. Consistently, Kronborg et al. found that CRT-treated LBBB patients with LAD had lower EF and higher LV end-diastolic diameter than those with normal QRS axis; however, LAD was not a significant predictor of all-cause and cardiac mortality in that population [19]. Other studies also found no correlation between the presence of LAD and clinical outcome after CRT [20,21]. The question whether QRS axis deviation could be associated with differences in CRT results has been also addressed in a MADIT-CRT subanalysis: in contrast with previous data, the Authors found that among LBBB patients treated with CRT-D, those with LAD had a significantly higher risk of heart failure events or death than non-LAD patients. The subgroup of LBBB patients without LAD showed a trend toward greater benefit from CRT-D (versus the control group of ICD patients) compared with LAD patients. Consistently, after CRT-D LBBB patients without LAD showed significantly
larger reduction in dyssynchrony than LBBB patients with LAD. However, LAD did not affect outcome in LBBB patients treated with ICD only [7]. A more recent retrospective study of 707 LBBB patients undergoing CRT also found that left axis deviation was independent predictor of poor prognosis in patients undergoing CRT [22]. On the other hand, Garcia-Seara et al. reported a higher CRT efficacy in LBBB patients with LAD than in patients without LAD (responders were 72.7% in the LAD group vs 62.2% in the normal axis group) [23]. Notably, in the study of Garcia-Seara et al. 42% of the patients had the coronary sinus lead placed in the anterior interventricular vein, and between them, those with LAD obtained a significantly better response to CRT. In the MADIT-CRT study, where the patients with normal axis fared better, the CS lead was more often positioned in a lateral or posterolateral cardiac vein. It appears that the need of stimulating the last LV activated area to obtain effective resynchronization could
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explain these apparently conflicting results. In the setting of a LBBB + LAD pattern such area may match with the anterior wall, as evidenced in the present study. In order to evaluate the impact of the LV lead position on outcome, a subset of 799 MADIT-CRT patients was analyzed: the Authors did not find significant differences between anterior, lateral, and posterior positions, whereas apical vs basal or midventricular positions were associated with an unfavorable outcome [24]. However, in those patients the electrical or mechanical activation sequence of the left ventricle had not been assessed, nor was the QRS axis orientation at the surface ECG reported. Our results further support the finding of Garcia-Seara et al. [23], by showing that in most cases in LBBB + LAD patients the latest area of contraction in the left ventricle is the anterior wall. Since about 40% of LBBB patients undergoing CRT have LAD [7,19,23], the finding of a specific pattern of ventricular asynchrony in such patients is not devoid of clinical importance. The usefulness of determining the site of latest LV contraction before CRT, in order to optimize benefit in the single patient has been documented. However, assessment of LV contraction sequence in patients undergoing CRT may not be always feasible. The knowing of a correlation between QRS axis on surface ECG and alleged area of latest LV contraction may help in target vessel selection during CRT procedure. In particular, in patients presenting with LBBB + LAD positioning the LV lead in the anterior interventricular vein could be regarded as a valuable option. The importance of an accurate surface ECG analysis in CRT candidates is underscored by our data: along with the recognition of a “true” LBBB pattern, evaluation of QRS axis could provide a simple method to increase the number of potential responders to CRT.
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
Conclusions LV asynchrony pattern in patients with LBBB differs in relation to QRS axis at the surface ECG. The latest mechanically activated area was located by TDI mostly at the anterior wall in patients with LAD, whereas it was found at the lateral wall in normal axis-patients. Our results may be relevant in target vessel selection during CRT procedures. References [1] Bax JJ, Bleeker GB, Marwick TH, Molhoek SG, Boersma E, Steendijk P, et al. Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy. J Am Coll Cardiol 2004;44:1834–40. [2] Becker M, Kramann R, Franke A, Breithardt OA, Heussen N, Knackstedt C, et al. Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography. Eur Heart J 2007;28:1211–20. [3] Fung JWH, Chan JYS, Yip GWK, Chan HCK, Chan WWL, Zhang Q, et al. Effect of left ventricular endocardial activation pattern on echocardiographic and clinical response to cardiac resynchronization therapy. Heart 2007;93:432–7. [4] Ansalone G, Giannantoni P, Ricci R, Trambaiolo P, Fedele F, Santini M. Doppler myocardial imaging to evaluate the effectiveness of pacing
[14]
[15]
[16]
[17]
[18]
[19]
sites in patients receiving biventricular pacing. J Am Coll Cardiol 2002;39:489–99. Sogaard P, Egeblad H, Kim WY, Jensen HK, Pedersen AK, Kristensen BO, et al. Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 2002;40:723–30. Jia P, Ramanathan C, Ghanem RN, Ryu K, Varma N, Rudy Y. Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses. Heart Rhythm 2006;3:296–310. Brenyo A, Rao M, Barsheshet A, Cannom D, Quesada A, McNitt S, et al. QRS axis and the benefit of cardiac resynchronization therapy in patients with mildly symptomatic heart failure enrolled in MADITCRT. J Cardiovasc Electrophysiol 2013;24:442–8, https://doi.org/ 10.1111/jce.12057. Brignole M, Auricchio A, Baron-Esquivias G, Bordachar P, Boriani G, Breithardt O-A, et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy. The task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA). Eur Heart J 2013;34:2281–329, https://doi.org/ 10.1093/eurheartj/eht150. Surawicz B, Childers R, Deal BJ, Gettes LS, Bailey JJ, Gorgels A, 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;53:976–81, https://doi.org/10.1016/j.jacc.2008. Gepstein L, Hayan G, Ben-Haim SA. A novel method for nonfluoroscopic catheter-based electroanatomical mapping of the heart: in vitro and in vivo accuracy results. Circulation 1997;95:1611–22. Bleeker GB, Mollema SA, Holman ER, Van de Veire N, Ypenburg C, Boersma E, et al. Left ventricular resynchronization is mandatory for response to cardiac resynchronization therapy: analysis in patients with echocardiographic evidence of left ventricular dyssynchrony at baseline. Circulation 2007;116:1440–8. Auger D, Bleeker GB, Bertini M, Ewe SH, van Bommel RJ, Witkowski TG, et al. Effect of cardiac resynchronization therapy in patients without left intraventricular dyssynchrony. Eur Heart J 2012;33:913–20, https://doi.org/10.1093/eurheartj/ehr468. Strauss DG, Selvester RH, Wagner GS. Defining left bundle branch block in the era of cardiac resynchronization therapy. Am J Cardiol 2011;107:927–34, https://doi.org/10.1016/j.amjcard.2010.11.010. Andersson LG, Wu KC, Wieslander B, Loring Z, Frank TF, Maynard C, et al. Left ventricular mechanical dyssynchrony by cardiac magnetic resonance is greater in patients with strict vs. non-strict ECG criteria for left bundle branch block. Am Heart J 2013;165:956–63, https://doi.org/ 10.1016/j.ahj.2013.03.013. Mascioli G, Padeletti L, Sassone B, Zecchin M, Lucca E, Sacchi S, 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;35:927–34, https://doi.org/ 10.1111/j.1540-8159.2012.03427.x. Tian Y, Zhang P, Li X, Gao Y, Zhu T, Wang L, et al. True complete left bundle branch block morphology strongly predicts good response to cardiac resynchronization therapy. Europace 2013;15:1499–506, https://doi.org/10.1093/europace/eut049. Ypenburg C, Roes SD, Bleeker GB, Kaandorp TA, de Roos A, Schalij MJ, et al. Effect of total scar burden on contrast-enhanced magnetic resonance imaging on response to cardiac resynchronization therapy. Am J Cardiol 2007;99:657–60. Dhingra RC, Amat-Y-Leon F, Wyndham C, Sridhar SS, Wu D, Rosen KM. Significance of left axis deviation in patients with chronic left bundle branch block. Am J Cardiol 1978;42:551–6. Kronborg MB, Nielsen JC, Mortensen PT. Electrocardiographic patterns and long-term clinical outcome in cardiac resynchronization therapy. Europace 2010;12:216–22, https://doi.org/10.1093/europace/eup364.
L. Sciarra et al. / Journal of Electrocardiology 51 (2018) 175–181 [20] Gervais R, Leclercq C, Shankar A, Jacobs S, Eiskjaer H, Johannessen A, et al. Surface electrocardiogram to predict outcome in candidates for cardiac resynchronization therapy: a sub-analysis of the CARE-HF trial. Eur J Heart Fail 2009;11:699–705, https://doi.org/10.1093/ eurjhf/hfp074. [21] Lecoq G, Leclercq C, Leray E, Crocq C, Alonso C, de Place C, et al. Clinical and electrocardiographic predictors of a positive response to cardiac resynchronization therapy in advanced heart failure. Eur Heart J 2005;26:1094–100. [22] Perrotta L, Kandala J, Di Biase L, Valleggi A, Michelotti F, Pieragnoli P, et al. Prognostic impact of QRS axis deviation in patients treated
181
with cardiac resynchronization therapy. J Cardiovasc Electrophysiol 2016;27:315–20, https://doi.org/10.1111/jce.12887. [23] Garcia-Seara J, Martinez-Sande JL, Cid B, Gude F, Bastos M, Dominguez M, et al. Influencia del eje eléctrico QRS preimplante en la respuesta a la terapia de resincronización cardiac. Rev Esp Cardiol 2008;61:1245–52. [24] Singh JP, Klein HU, Huang DT, Reek S, Kuniss M, Quesada A, et al. Left ventricular lead position and clinical outcome in the multicenter automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) trial. Circulation 2011;123:1159–66, https:// doi.org/10.1161/CIRCULATIONAHA.110.000646.