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Qualitative Observation of Left Ventricular Multiphasic Septal Motion and Septal-to-Lateral Apical Shuffle Predicts Left Ventricular Reverse Remodeling After Cardiac Resynchronization Therapy
Qualitative Observation of Left Ventricular Multiphasic Septal Motion and Septal-to-Lateral Apical Shuffle Predicts Left Ventricular Reverse Remodeling After Cardiac Resynchronization Therapy Annemieke H.M. Jansen, MDa,*, Jan melle van Dantzig, MD, PhDa, Franck Bracke, MD, PhDa, Albert Meijer, MD, PhDa, Kathinka H. Peels, MDa, Renee B.A. van den Brink, MD, PhDb, Emile C. Cheriex, MD, PhDc, Ben J.M. Delemarre, MD, PhDd, Pol A. van der Wouw, MDe, Hendrikus H.M. Korsten, MD, PhDa, and Norbert M. van Hemel, MD, PhDf A multiphasic septal motion and typical septal-to-lateral apical shuffle of the left ventricle can be observed echocardiographically in some patients with left branch bundle block. The relation of both with left ventricular (LV) dyssynchrony according to tissue Doppler and LV reverse remodeling after cardiac resynchronization therapy was investigated. Fiftythree patients (37 men; age 68 ⴞ 8 years) with ischemic (n ⴝ 26) or idiopathic (n ⴝ 27) cardiomyopathy, baseline QRS duration 171 ⴞ 30 ms, LV ejection fraction 21 ⴞ 7%, and LV end-diastolic volume 257 ⴞ 91 ml were studied. LV dyssynchrony using tissue Doppler was considered present if the SD of the interval between QRS and onset of systolic velocity of 6 basal LV segments was >20 ms. Shuffle was evaluated visually independently by 5 cardiologists and considered present if observed in >1 view. LV reverse remodeling, defined as LV end-systolic volume decrease >10%, was observed in 37 patients (70%) after 3 months of CRT. Sensitivity and specificity of either shuffle or multiphasic septal motion for all 5 observers (range 90% to 97% and 67% to 83%, respectively) were found to predict LV dyssynchrony. To predict LV reverse remodeling, sensitivity and specificity from 87% to 92% and 69% to 81% were observed, respectively. In conclusion, the qualitative observation of a typical shuffle or multiphasic septal motion predicts LV dyssynchrony and LV reverse remodeling adequately. © 2007 Elsevier Inc. All rights reserved. (Am J Cardiol 2007;99:966 –969)
Multiphasic septal motion (Figure 1) is observed in some patients with left branch bundle block (LBBB).1 In addition, a typical abnormal septal-to-lateral apical motion (Figure 1), also known as the “shuffle” (or “hula hoop”), can be observed in some patients with LBBB. Whether the multiphasic septal pattern or shuffle of the apex is an expression of left ventricular (LV) dyssynchrony is not known. Because simple visual inspection of 2-dimensional echocardiography is far less cumbersome then tissue Doppler, the correlation between these 2 echocardiographic phenomena with LV dyssynchrony assessed using tissue Doppler and the therapeutic response to cardiac resynchronization therapy (CRT) assessed using LV reverse remodeling was investigated.
a
Catharina Ziekenhuis, Eindhoven; bAcademisch Medisch Centrum, Amsterdam; cAcademisch Ziekenhuis, Maastricht; dZiekenhuis Leyenburg, Den Haag; eOnze Lieve Gasthuis, Amsterdam; and fUtrecht University, Utrecht, The Netherlands. Manuscript received August 18, 2006; revised manuscript received and accepted November 7, 2006. Dr. Jansen was supported by an unrestricted educational grant from Medtronic Netherlands BV and foundation “Vrienden van het Hart”, Eindhoven, The Netherlands. Dr. van Dantzig has received lecture fees from Medtronic, Inc., The Netherlands. *Corresponding author: Tel: 31-40-239-7004; fax: 31-40-244-7885. E-mail address: [email protected] (A.H.M. Jansen). 0002-9149/07/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.11.044
Methods Patients: Fifty-three consecutive patients (37 men; mean age 68 ⫾ 8 years) in New York Heart Association class III or IV heart failure despite optimal medication, LV ejection fraction ⬍35%, sinus rhythm, and LBBB, underwent CRT. Patients with mitral valve replacement or severe valvular disease other than mitral regurgitation were excluded. Divided according to cause based on cardiovascular history (coronary artery bypass grafting, percutaneous coronary intervention, or myocardial infarction) and coronary angiography, 27 patients were diagnosed with dilated cardiomyopathy and 26 with ischemic cardiomyopathy. Baseline QRS duration was 171 ⫾ 30 ms with a PR interval of 189 ⫾ 30 ms. Diuretics were prescribed for 94% of patients, angiotensin-converting enzyme inhibitors for 79%,  blockers for 72%, spironolactone for 51%, and digoxin for 21%. Informed consent was obtained from all patients. Changes in medication were avoided unless clinically mandatory. Biventricular pacemaker implantation: The coronary sinus lead (Medtronic 4193, Minneapolis, Minnesota) was positioned in a posterior or posterolateral branch of the coronary sinus, the right ventricular lead was positioned in the apical or mid-septal region, and the right atrial lead was positioned in the atrial appendage. All leads were connected to a Medtronic InSync 8042 pulse generator. www.AJConline.org
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Figure 1. Example of multiphasic septal motion (open arrow) and septal-to-lateral apical shuffle of the left ventricle (apical arrow). (A) End of diastole (mitral valve open), septum in outward position. (B) Start of systole, inward moving of septum (open arrow), apical motion (shuffle) from septal to lateral (apical arrow). (C) Late systole: late outward movement of septum (open arrow), apical motion (shuffle) from septal to lateral (apical arrow). (D) End of systole, apical motion lateral to septal (apical arrow), return to initial position.
Atrioventricular delay and interventricular pacing interval were optimized within 1 day after implantation using invasive LV dP/dtmax measurements with a sensor-tipped pressure guide wire (PW-4, RADI Medical Systems, Uppsala, Sweden) and Doppler echocardiography using maximal transmitral flow as previously described.2
Table 1 Baseline characteristics
Echocardiography: Echocardiography was performed using a Sonos 7500 S3 transducer (Philips Medical Systems, Andover, Massachusetts) ⬍1 week before and 3 months after pacemaker implantation. The nomenclature of LV segments and measurements of LV dimensions were according to recommendations of the American Society of Echocardiography.3 LV volumes and ejection fraction were obtained in the apical 4- and 2-chamber views (biplane method). Degree of mitral regurgitation (grades I to IV) was measured as the mid-systolic percentage of jet area relative to the left atrial area in the apical 4-chamber view. Measurements were averaged for ⱖ3 consecutive beats. Cardiac index was assessed using pulse-wave Doppler of the LV outflow tract. Myocardial performance index was calculated as the sum of isovolumic contraction and relaxation time divided by ejection time.4,5 LV reverse remodeling was considered present with a LV end-systolic volume decrease ⱖ10% after 3 months of CRT.6
New York Heart Association class (0/1/2/3/4) 6-Minute walking test (m) QRS (ms) Ischemic/dilated cardiomyopathy LV ejection fraction (%) LV end-diastolic volume (ml) Mitral regurgitation/left atrium (area) SD-TsO-6 (ms)
LV dyssynchrony: LV dyssynchrony was calculated using tissue Doppler as previously described.7,8 Briefly, spectral displays of 6 basal LV segments with pulse-wave tissue Doppler were obtained in the 4-, 3-, and 2-chamber apical views and stored digitally for off-line analysis. The interval from onset of QRS to onset of systolic velocity (TsO) was measured in 4 end-expiratory beats and averaged. We previously showed that LV reverse remodeling can be well predicted by the SD of TsO of 6 LV segments (SD-TsO-6): SD-TsO-6 ⬎20 ms had sensitivity of 96%, specificity of 92%, and positive and negative predictive values of 96% and 92% to predict LV reverse remodeling after CRT.7 The multiphasic septal motion pattern is characterized by an early systolic inward motion followed by a late systolic outward movement. The shuffle is an abnormal systolic septal-to-lateral apical motion of the left ventricle. The
Variable
LV Reverse Remodeling Yes (n ⫽ 37)
No (n ⫽ 16)
0/0/0/36/1
0/0/0/15/1
p Value
NS
403 ⫾ 128 170 ⫾ 30 14/23
378 ⫾ 98 164 ⫾ 24 12/4
NS NS 0.02
22 ⫾ 7 269 ⫾ 94 0.35 ⫾ 0.2
21 ⫾ 7 221 ⫾ 68 0.28 ⫾ 0.2
NS NS NS
36.7 ⫾ 15
13.0 ⫾ 5
⬍0.0001
presence of both echocardiographic phenomena was evaluated in the 4-, 2-, and 3-chamber views and considered present if seen in ⱖ1 view. The digitally stored images (mean frame rate 50 Hz) were evaluated independently by 5 experienced echocardiologists from different institutions, blinded to results of tissue Doppler and LV reverse remodeling. The observed multiphasic septal motion and shuffle were related to LV dyssynchrony measured using SDTsO-6 and LV reverse remodeling after 3 months of CRT. Statistical analysis: Paired-sample t test was used for comparison of parametric variables before and after CRT. Unpaired t test was used for the comparison between patients with and without LV reverse remodeling. Sensitivity and specificity of both echocardiographic phenomena for all 5 observers to predict LV dyssynchrony and LV reverse remodeling were calculated. All tests were performed using Medcalc Statistical Analysis program (Medcalc, Mariakerke, Belgium). Results After 3 months of CRT, 37 patients (70%) had LV reverse remodeling, whereas LV volumes and ejection fraction
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Table 2 Differences between baseline and 3 months cardiac resynchronization therapy in patients divided according to left ventricular (LV) reverse remodeling Variable
LV Reverse Remodeling
New York Heart Association class at 3 mo ⌬ 6-Minute walking test (%) (n ⫽ 41) ⌬ LV ejection fraction (%) ⌬ LV end-systolic volume (%) ⌬ Mitral regurgitation/left atrium (area) ⌬ Cardiac index (L/min/m2)
Yes
No
0/0/35/2/0
0/0/8/8/0
p Value
0.04
25 ⫾ 36
22 ⫾ 30
8.2 ⫾ 5 26 ⫾ 14 ⫺0.15 ⫾ 0.2
1.5 ⫾ 2 0.3 ⫾ 6 ⫺0.02 ⫾ 0.1
⬍0.0001 ⬍0.0001 0.006
0.21 ⫾ 0.3
⫺0.06 ⫾ 0.3
0.02
NS
⌬ ⫽ Change between baseline and 3-month follow-up. Table 3 Accuracy of shuffle and shuffle or multiphasic septal motion to predict left ventricular (LV) dyssynchrony assessed using SD of to onset of systolic velocity ␣ six basal LV segments (cut-off value ⬎20 ms) Sensitivity Specificity (%) (%) Shuffle Observer 1 Observer 2 Observer 3 Observer 4 Observer 5 Shuffle ⫹ Multiphasic septal motion Observer 1 Observer 2 Observer 3 Observer 4 Observer 5
Table 4 Accuracy of shuffle and shuffle or multiphasic septal motion to predict left ventricular reverse remodeling after 3 months’ cardiac resynchronization therapy
Positive Negative Predictive Predictive Value (%) Value (%)
77 83 89 83 86
89 72 78 89 89
93 85 89 94 94
67 69 78 73 76
90 94 94 91 97
83 67 72 67 83
91 85 87 84 92
82 86 87 80 94
were unchanged in the remaining 16 patients. Baseline characteristics were similar in patients with versus without LV reverse remodeling except for a significantly higher presence of mechanical LV dyssynchrony assessed using SD-TsO-6 in the LV reverse remodeling group (Table 1). Baseline LV dyssynchrony was also significantly higher in the dilated versus ischemic cardiomyopathy group (35 ⫾ 18 vs 25 ⫾ 15 ms, p ⫽ 0.03), explaining the fewer volume responders in patients with an ischemic cause (p ⫽ 0.02; Table 1). Changes after 3 months of CRT are listed in Table 2. Clinically, volume responders showed more improvement in New York Heart Association classification than patients without LV reverse remodeling. As defined, LV end-systolic volume and subsequently, LV ejection fraction were improved in only patients with LV reverse remodeling. In addition, reverse remodeling was accompanied by a decrease in mitral regurgitation severity and an increase in cardiac index, whereas such beneficial changes were absent in patients in whom CRT did not cause regression of LV volume.
Sensitivity Specificity (%) (%) Shuffle Observer 1 Observer 2 Observer 3 Observer 4 Observer 5 Shuffle ⫹ multiphasic septal motion Observer 1 Observer 2 Observer 3 Observer 4 Observer 5
Positive Negative Predictive Predictive Value (%) Value (%)
73 81 86 78 81
88 75 81 88 88
93 88 91 94 94
58 63 72 64 67
87 92 92 92 92
81 69 75 75 81
91 87 89 89 92
72 79 80 80 81
Shuffle: In 27 patients, all 5 cardiologists observed a shuffle, whereas in 14 patients, no one observed a shuffle (Figure 1). Therefore, observations were unanimous in 41 patients (77%). A shuffle was found by 4, 3, 2, or 1 cardiologists in 0, 6, 3, and 3 patients, respectively. Visual inspection of the shuffle by the 5 observers had a sensitivity of 77% to 89% for LV dyssynchrony measured using tissue Doppler, whereas specificity ranged from 72% to 89% (Table 3). In the 27 patients with a shuffle observed by all 5 observers, 96% had an SD-TsO-6 ⬎20 ms, whereas this was 35% (p ⬍0.0001) in the 14 patients with no shuffle. Visual inspection of the shuffle by the 5 observers had a sensitivity of 73% to 87% for LV reverse remodeling, whereas specificity ranged from 75% to 88% (Table 4). Shuffle and multiphasic pattern: Five cardiologists unanimously observed a shuffle or multiphasic septal motion in 32 patients, whereas in 9 patients, both phenomena were not seen (Figure 1). Therefore, observations were unanimous in 41 patients (77%). A shuffle or multiphasic pattern was observed by 4, 3, 2, or 1 cardiologists in 1, 6, 1, and 4 patients, respectively. Mean intraobserver variability of both 2-dimensional echocardiographic phenomena assessed in 36 views (12 patients) by 5 cardiologists with a time delay of 3 months was 6 ⫾ 2%. Interobserver variability of both 2-dimensional echocardiographic phenomena assessed in all 53 patients among all 5 observers was 11 ⫾ 4%. Lack of consensus was probably caused by the presence of limited dyssynchrony. This was the only item that was significantly different among images. In the 12 patients for whom observers disagreed about the presence of a shuffle or multiphasic septal motion, the degree of LV dyssynchrony was significantly less than in patients with agreement about the shuffle or multiphasic pattern (SD-TsO-6 18.2 ⫾ 11 vs 40.0 ⫾ 14 ms, respectively, p ⬍0.0001), although compared with patients for whom it was agreed no shuffle or multiphasic pattern was seen, there was a small, albeit not significant, difference (SD-TsO-6 18.2 ⫾ 11 vs 12.6 ⫾ 6 ms, p ⫽ NS).
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Relations between both 2-dimensional echocardiographic phenomena and LV dyssynchrony are listed in Table 3. If a shuffle or multiphasic septal motion was present according to all 5 cardiologists, 97% had an SDTsO-6 ⬎20 ms, whereas in patients with no shuffle or multiphasic pattern, this was 24% (p ⬍0.0001). Visual inspection of the 2-dimensional echocardiographic phenomena by the 5 observers had sensitivity of 90% to 97% for LV dyssynchrony, whereas specificity ranged from 67% to 83% (Table 3). For LV reverse remodeling, sensitivity and specificity ranged from 87% to 92% and specificity ranged from 69% to 81% (Table 4).
tion of the delay between 2 opposite LV segments, but observation of an abnormal septal-to-lateral systolic apical motion or multiphasic septal motion pattern of the left ventricle. This study is limited by the small number of patients, although applicability of both signs is supported because in the present study, 5 different observers from 5 different institutions were able to independently accurately predict either LV dyssynchrony or LV reverse remodeling. Therefore, visualization of both signs is well within the realm of most experienced echocardiographers and applicable on routine echocardiograms.
Discussion
1. Feigenbaum H, Armstrong WH, Ryan T. Evaluation of systolic and diastolic function of the left ventricle. In: Weinberg R, Murphy J, Jackson A, eds. Echocardiography. Sixth edition. Philadelphia: Lippincott Williams & Wilkins, 2005:154 –156. 2. Jansen AH, Bracke FA, van Dantzig JM, Meijer A, van der Voort PH, Aarnoudse W, Van Gelder BM, Peels KH. Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 2006;97:552–557. 3. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358 –367. 4. John Sutton MG, Plappert T, Abraham WT, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Fisher WG, Ellestad M, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation 2003;107:1985–1990. 5. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, Tajik AJ, Seward JB. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function—a study in normals and dilated cardiomyopathy. J Cardiol 1995;26:357–366. 6. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, Chan YS, Kong SL, Bax JJ. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 2005;112:1580 –1586. 7. Jansen AH, Bracke F, van Dantzig JM, Meijer A, Korsten EH, Peels KH, van Hemel NM. Optimization of pulsed wave tissue Doppler to predict left ventricular reverse remodeling after cardiac resynchronization therapy. J Am Soc Echocardiogr 2006;19:185–191. 8. Garcia MJ, Rodriguez L, Ares M, Griffin BP, Klein AL, Stewart WJ, Thomas JD. Myocardial wall velocity assessment by pulsed Doppler tissue imaging: characteristic findings in normal subjects. Am Heart J 1996;132:648 – 656. 9. Kapetanakis S, Kearney MT, Siva A, Gall N, Cooklin M, Monaghan MJ. Real-time three-dimensional echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony. Circulation 2005;112:992–1000. 10. Penicka M, Bartunek J, De Bruyne B, Vanderheyden M, Goethals M, De Zutter M, Brugada P, Geelen P. Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography. Circulation 2004;109:978 –983. 11. Yu CM, Fung JW, Zhang Q, Chan CK, Chan YS, Lin H, Kum LC, Kong SL, Zhang Y, Sanderson JE. Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy. Circulation 2004;110:66 –73. 12. Kvitting JP, Wigstrom L, Strotmann JM, Sutherland GR. How accurate is visual assessment of synchronicity in myocardial motion? An in vitro study with computer-simulated regional delay in myocardial motion: clinical implications for rest and stress echocardiography studies. J Am Soc Echocardiogr 1999;12:698 –705. 13. Sutherland GR, Kukulski T, Kvitting JE, D’hooge J, Arnold M, Brandt E, Hatle L, Wranne B. Quantitation of left-ventricular asynergy by cardiac ultrasound. Am J Cardiol 2000;86:4G–9G.
This study investigates the accuracy of 2 echocardiographic LV motion characteristics: first, a typical LV shuffle motion, and second, a multiphasic septal motion pattern in predicting LV dyssynchrony and LV reverse remodeling after CRT. Shuffle is an abnormal septal-to-lateral apical LV systolic motion, whereas multiphasic septal motion pattern is characterized by early systolic inward and late systolic outward movement of the septum and is a known echocardiographic feature of LBBB (Figure 1). Observation of the shuffle by 5 independent cardiologists predicted LV dyssynchrony detected using tissue Doppler with a sensitivity range of 77% to 89% and specificity range of 72% to 89% (Table 3). Results improved if the presence of either the shuffle or multiphasic septal motion pattern was taken into account. LV dyssynchrony could then be predicted with sensitivity of 90% to 97% and specificity of 67% to 83% (Table 3). More important than the capability to predict dyssynchrony is the prediction of LV reverse remodeling itself, because it was shown to be related to improved survival.6 In the present study, simple visual observation of either a shuffle or multiphasic septal motion performed almost as well to predict LV reverse remodeling as the SD of the activation time of 6 basal LV segments acquired using pulse tissue Doppler (Table 4). LV reverse remodeling could be predicted with sensitivity and specificity ranging from 87% to 92% and 69% to 81%, respectively. Pulse-wave tissue Doppler to establish LV mechanical dyssynchrony is a time-consuming method because ⱖ6 basal LV segments need to be investigated and calculated. Decreasing the number of investigated segments to 2 provides inferior results in detecting LV dyssynchrony and predicting reverse remodeling.6 Color tissue Doppler and volume analysis using 3-dimensional echocardiography may provide an accurate prediction of dyssynchrony, but are also labor-intensive methods and not widely available.7,9 –11 All these methods therefore are less suitable for screening purposes, and visual interpretation of LV dyssynchrony using 2-dimensional echocardiography, as in the present study, would increase the clinical applicability and feasibility to select patients for CRT in daily practice. Previous reports of visual estimation of LV dyssynchrony are limited and concluded that intraventricular activation delays ⬍70 ms cannot be detected with the human eye.12,13 However, the principle of the shuffle is not detec-
Multiphasic septal motion (Figure 1) is observed in some patients with left branch bundle block (LBBB).1 In addition, a typical abnormal septal-to-lateral apical motion (Figure 1), also known as the “shuffle” (or “hula hoop”), can be observed in some patients with LBBB. Whether the multiphasic septal pattern or shuffle of the apex is an expression of left ventricular (LV) dyssynchrony is not known. Because simple visual inspection of 2-dimensional echocardiography is far less cumbersome then tissue Doppler, the correlation between these 2 echocardiographic phenomena with LV dyssynchrony assessed using tissue Doppler and the therapeutic response to cardiac resynchronization therapy (CRT) assessed using LV reverse remodeling was investigated.
a
Catharina Ziekenhuis, Eindhoven; bAcademisch Medisch Centrum, Amsterdam; cAcademisch Ziekenhuis, Maastricht; dZiekenhuis Leyenburg, Den Haag; eOnze Lieve Gasthuis, Amsterdam; and fUtrecht University, Utrecht, The Netherlands. Manuscript received August 18, 2006; revised manuscript received and accepted November 7, 2006. Dr. Jansen was supported by an unrestricted educational grant from Medtronic Netherlands BV and foundation “Vrienden van het Hart”, Eindhoven, The Netherlands. Dr. van Dantzig has received lecture fees from Medtronic, Inc., The Netherlands. *Corresponding author: Tel: 31-40-239-7004; fax: 31-40-244-7885. E-mail address: [email protected] (A.H.M. Jansen). 0002-9149/07/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.11.044
Methods Patients: Fifty-three consecutive patients (37 men; mean age 68 ⫾ 8 years) in New York Heart Association class III or IV heart failure despite optimal medication, LV ejection fraction ⬍35%, sinus rhythm, and LBBB, underwent CRT. Patients with mitral valve replacement or severe valvular disease other than mitral regurgitation were excluded. Divided according to cause based on cardiovascular history (coronary artery bypass grafting, percutaneous coronary intervention, or myocardial infarction) and coronary angiography, 27 patients were diagnosed with dilated cardiomyopathy and 26 with ischemic cardiomyopathy. Baseline QRS duration was 171 ⫾ 30 ms with a PR interval of 189 ⫾ 30 ms. Diuretics were prescribed for 94% of patients, angiotensin-converting enzyme inhibitors for 79%,  blockers for 72%, spironolactone for 51%, and digoxin for 21%. Informed consent was obtained from all patients. Changes in medication were avoided unless clinically mandatory. Biventricular pacemaker implantation: The coronary sinus lead (Medtronic 4193, Minneapolis, Minnesota) was positioned in a posterior or posterolateral branch of the coronary sinus, the right ventricular lead was positioned in the apical or mid-septal region, and the right atrial lead was positioned in the atrial appendage. All leads were connected to a Medtronic InSync 8042 pulse generator. www.AJConline.org
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Figure 1. Example of multiphasic septal motion (open arrow) and septal-to-lateral apical shuffle of the left ventricle (apical arrow). (A) End of diastole (mitral valve open), septum in outward position. (B) Start of systole, inward moving of septum (open arrow), apical motion (shuffle) from septal to lateral (apical arrow). (C) Late systole: late outward movement of septum (open arrow), apical motion (shuffle) from septal to lateral (apical arrow). (D) End of systole, apical motion lateral to septal (apical arrow), return to initial position.
Atrioventricular delay and interventricular pacing interval were optimized within 1 day after implantation using invasive LV dP/dtmax measurements with a sensor-tipped pressure guide wire (PW-4, RADI Medical Systems, Uppsala, Sweden) and Doppler echocardiography using maximal transmitral flow as previously described.2
Table 1 Baseline characteristics
Echocardiography: Echocardiography was performed using a Sonos 7500 S3 transducer (Philips Medical Systems, Andover, Massachusetts) ⬍1 week before and 3 months after pacemaker implantation. The nomenclature of LV segments and measurements of LV dimensions were according to recommendations of the American Society of Echocardiography.3 LV volumes and ejection fraction were obtained in the apical 4- and 2-chamber views (biplane method). Degree of mitral regurgitation (grades I to IV) was measured as the mid-systolic percentage of jet area relative to the left atrial area in the apical 4-chamber view. Measurements were averaged for ⱖ3 consecutive beats. Cardiac index was assessed using pulse-wave Doppler of the LV outflow tract. Myocardial performance index was calculated as the sum of isovolumic contraction and relaxation time divided by ejection time.4,5 LV reverse remodeling was considered present with a LV end-systolic volume decrease ⱖ10% after 3 months of CRT.6
New York Heart Association class (0/1/2/3/4) 6-Minute walking test (m) QRS (ms) Ischemic/dilated cardiomyopathy LV ejection fraction (%) LV end-diastolic volume (ml) Mitral regurgitation/left atrium (area) SD-TsO-6 (ms)
LV dyssynchrony: LV dyssynchrony was calculated using tissue Doppler as previously described.7,8 Briefly, spectral displays of 6 basal LV segments with pulse-wave tissue Doppler were obtained in the 4-, 3-, and 2-chamber apical views and stored digitally for off-line analysis. The interval from onset of QRS to onset of systolic velocity (TsO) was measured in 4 end-expiratory beats and averaged. We previously showed that LV reverse remodeling can be well predicted by the SD of TsO of 6 LV segments (SD-TsO-6): SD-TsO-6 ⬎20 ms had sensitivity of 96%, specificity of 92%, and positive and negative predictive values of 96% and 92% to predict LV reverse remodeling after CRT.7 The multiphasic septal motion pattern is characterized by an early systolic inward motion followed by a late systolic outward movement. The shuffle is an abnormal systolic septal-to-lateral apical motion of the left ventricle. The
Variable
LV Reverse Remodeling Yes (n ⫽ 37)
No (n ⫽ 16)
0/0/0/36/1
0/0/0/15/1
p Value
NS
403 ⫾ 128 170 ⫾ 30 14/23
378 ⫾ 98 164 ⫾ 24 12/4
NS NS 0.02
22 ⫾ 7 269 ⫾ 94 0.35 ⫾ 0.2
21 ⫾ 7 221 ⫾ 68 0.28 ⫾ 0.2
NS NS NS
36.7 ⫾ 15
13.0 ⫾ 5
⬍0.0001
presence of both echocardiographic phenomena was evaluated in the 4-, 2-, and 3-chamber views and considered present if seen in ⱖ1 view. The digitally stored images (mean frame rate 50 Hz) were evaluated independently by 5 experienced echocardiologists from different institutions, blinded to results of tissue Doppler and LV reverse remodeling. The observed multiphasic septal motion and shuffle were related to LV dyssynchrony measured using SDTsO-6 and LV reverse remodeling after 3 months of CRT. Statistical analysis: Paired-sample t test was used for comparison of parametric variables before and after CRT. Unpaired t test was used for the comparison between patients with and without LV reverse remodeling. Sensitivity and specificity of both echocardiographic phenomena for all 5 observers to predict LV dyssynchrony and LV reverse remodeling were calculated. All tests were performed using Medcalc Statistical Analysis program (Medcalc, Mariakerke, Belgium). Results After 3 months of CRT, 37 patients (70%) had LV reverse remodeling, whereas LV volumes and ejection fraction
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Table 2 Differences between baseline and 3 months cardiac resynchronization therapy in patients divided according to left ventricular (LV) reverse remodeling Variable
LV Reverse Remodeling
New York Heart Association class at 3 mo ⌬ 6-Minute walking test (%) (n ⫽ 41) ⌬ LV ejection fraction (%) ⌬ LV end-systolic volume (%) ⌬ Mitral regurgitation/left atrium (area) ⌬ Cardiac index (L/min/m2)
Yes
No
0/0/35/2/0
0/0/8/8/0
p Value
0.04
25 ⫾ 36
22 ⫾ 30
8.2 ⫾ 5 26 ⫾ 14 ⫺0.15 ⫾ 0.2
1.5 ⫾ 2 0.3 ⫾ 6 ⫺0.02 ⫾ 0.1
⬍0.0001 ⬍0.0001 0.006
0.21 ⫾ 0.3
⫺0.06 ⫾ 0.3
0.02
NS
⌬ ⫽ Change between baseline and 3-month follow-up. Table 3 Accuracy of shuffle and shuffle or multiphasic septal motion to predict left ventricular (LV) dyssynchrony assessed using SD of to onset of systolic velocity ␣ six basal LV segments (cut-off value ⬎20 ms) Sensitivity Specificity (%) (%) Shuffle Observer 1 Observer 2 Observer 3 Observer 4 Observer 5 Shuffle ⫹ Multiphasic septal motion Observer 1 Observer 2 Observer 3 Observer 4 Observer 5
Table 4 Accuracy of shuffle and shuffle or multiphasic septal motion to predict left ventricular reverse remodeling after 3 months’ cardiac resynchronization therapy
Positive Negative Predictive Predictive Value (%) Value (%)
77 83 89 83 86
89 72 78 89 89
93 85 89 94 94
67 69 78 73 76
90 94 94 91 97
83 67 72 67 83
91 85 87 84 92
82 86 87 80 94
were unchanged in the remaining 16 patients. Baseline characteristics were similar in patients with versus without LV reverse remodeling except for a significantly higher presence of mechanical LV dyssynchrony assessed using SD-TsO-6 in the LV reverse remodeling group (Table 1). Baseline LV dyssynchrony was also significantly higher in the dilated versus ischemic cardiomyopathy group (35 ⫾ 18 vs 25 ⫾ 15 ms, p ⫽ 0.03), explaining the fewer volume responders in patients with an ischemic cause (p ⫽ 0.02; Table 1). Changes after 3 months of CRT are listed in Table 2. Clinically, volume responders showed more improvement in New York Heart Association classification than patients without LV reverse remodeling. As defined, LV end-systolic volume and subsequently, LV ejection fraction were improved in only patients with LV reverse remodeling. In addition, reverse remodeling was accompanied by a decrease in mitral regurgitation severity and an increase in cardiac index, whereas such beneficial changes were absent in patients in whom CRT did not cause regression of LV volume.
Sensitivity Specificity (%) (%) Shuffle Observer 1 Observer 2 Observer 3 Observer 4 Observer 5 Shuffle ⫹ multiphasic septal motion Observer 1 Observer 2 Observer 3 Observer 4 Observer 5
Positive Negative Predictive Predictive Value (%) Value (%)
73 81 86 78 81
88 75 81 88 88
93 88 91 94 94
58 63 72 64 67
87 92 92 92 92
81 69 75 75 81
91 87 89 89 92
72 79 80 80 81
Shuffle: In 27 patients, all 5 cardiologists observed a shuffle, whereas in 14 patients, no one observed a shuffle (Figure 1). Therefore, observations were unanimous in 41 patients (77%). A shuffle was found by 4, 3, 2, or 1 cardiologists in 0, 6, 3, and 3 patients, respectively. Visual inspection of the shuffle by the 5 observers had a sensitivity of 77% to 89% for LV dyssynchrony measured using tissue Doppler, whereas specificity ranged from 72% to 89% (Table 3). In the 27 patients with a shuffle observed by all 5 observers, 96% had an SD-TsO-6 ⬎20 ms, whereas this was 35% (p ⬍0.0001) in the 14 patients with no shuffle. Visual inspection of the shuffle by the 5 observers had a sensitivity of 73% to 87% for LV reverse remodeling, whereas specificity ranged from 75% to 88% (Table 4). Shuffle and multiphasic pattern: Five cardiologists unanimously observed a shuffle or multiphasic septal motion in 32 patients, whereas in 9 patients, both phenomena were not seen (Figure 1). Therefore, observations were unanimous in 41 patients (77%). A shuffle or multiphasic pattern was observed by 4, 3, 2, or 1 cardiologists in 1, 6, 1, and 4 patients, respectively. Mean intraobserver variability of both 2-dimensional echocardiographic phenomena assessed in 36 views (12 patients) by 5 cardiologists with a time delay of 3 months was 6 ⫾ 2%. Interobserver variability of both 2-dimensional echocardiographic phenomena assessed in all 53 patients among all 5 observers was 11 ⫾ 4%. Lack of consensus was probably caused by the presence of limited dyssynchrony. This was the only item that was significantly different among images. In the 12 patients for whom observers disagreed about the presence of a shuffle or multiphasic septal motion, the degree of LV dyssynchrony was significantly less than in patients with agreement about the shuffle or multiphasic pattern (SD-TsO-6 18.2 ⫾ 11 vs 40.0 ⫾ 14 ms, respectively, p ⬍0.0001), although compared with patients for whom it was agreed no shuffle or multiphasic pattern was seen, there was a small, albeit not significant, difference (SD-TsO-6 18.2 ⫾ 11 vs 12.6 ⫾ 6 ms, p ⫽ NS).
Heart Failure/2D Echo Phenomena Predict Response to CRT
969
Relations between both 2-dimensional echocardiographic phenomena and LV dyssynchrony are listed in Table 3. If a shuffle or multiphasic septal motion was present according to all 5 cardiologists, 97% had an SDTsO-6 ⬎20 ms, whereas in patients with no shuffle or multiphasic pattern, this was 24% (p ⬍0.0001). Visual inspection of the 2-dimensional echocardiographic phenomena by the 5 observers had sensitivity of 90% to 97% for LV dyssynchrony, whereas specificity ranged from 67% to 83% (Table 3). For LV reverse remodeling, sensitivity and specificity ranged from 87% to 92% and specificity ranged from 69% to 81% (Table 4).
tion of the delay between 2 opposite LV segments, but observation of an abnormal septal-to-lateral systolic apical motion or multiphasic septal motion pattern of the left ventricle. This study is limited by the small number of patients, although applicability of both signs is supported because in the present study, 5 different observers from 5 different institutions were able to independently accurately predict either LV dyssynchrony or LV reverse remodeling. Therefore, visualization of both signs is well within the realm of most experienced echocardiographers and applicable on routine echocardiograms.
Discussion
1. Feigenbaum H, Armstrong WH, Ryan T. Evaluation of systolic and diastolic function of the left ventricle. In: Weinberg R, Murphy J, Jackson A, eds. Echocardiography. Sixth edition. Philadelphia: Lippincott Williams & Wilkins, 2005:154 –156. 2. Jansen AH, Bracke FA, van Dantzig JM, Meijer A, van der Voort PH, Aarnoudse W, Van Gelder BM, Peels KH. Correlation of echo-Doppler optimization of atrioventricular delay in cardiac resynchronization therapy with invasive hemodynamics in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 2006;97:552–557. 3. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358 –367. 4. John Sutton MG, Plappert T, Abraham WT, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Fisher WG, Ellestad M, et al. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation 2003;107:1985–1990. 5. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, Tajik AJ, Seward JB. New index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function—a study in normals and dilated cardiomyopathy. J Cardiol 1995;26:357–366. 6. Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, Chan YS, Kong SL, Bax JJ. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 2005;112:1580 –1586. 7. Jansen AH, Bracke F, van Dantzig JM, Meijer A, Korsten EH, Peels KH, van Hemel NM. Optimization of pulsed wave tissue Doppler to predict left ventricular reverse remodeling after cardiac resynchronization therapy. J Am Soc Echocardiogr 2006;19:185–191. 8. Garcia MJ, Rodriguez L, Ares M, Griffin BP, Klein AL, Stewart WJ, Thomas JD. Myocardial wall velocity assessment by pulsed Doppler tissue imaging: characteristic findings in normal subjects. Am Heart J 1996;132:648 – 656. 9. Kapetanakis S, Kearney MT, Siva A, Gall N, Cooklin M, Monaghan MJ. Real-time three-dimensional echocardiography: a novel technique to quantify global left ventricular mechanical dyssynchrony. Circulation 2005;112:992–1000. 10. Penicka M, Bartunek J, De Bruyne B, Vanderheyden M, Goethals M, De Zutter M, Brugada P, Geelen P. Improvement of left ventricular function after cardiac resynchronization therapy is predicted by tissue Doppler imaging echocardiography. Circulation 2004;109:978 –983. 11. Yu CM, Fung JW, Zhang Q, Chan CK, Chan YS, Lin H, Kum LC, Kong SL, Zhang Y, Sanderson JE. Tissue Doppler imaging is superior to strain rate imaging and postsystolic shortening on the prediction of reverse remodeling in both ischemic and nonischemic heart failure after cardiac resynchronization therapy. Circulation 2004;110:66 –73. 12. Kvitting JP, Wigstrom L, Strotmann JM, Sutherland GR. How accurate is visual assessment of synchronicity in myocardial motion? An in vitro study with computer-simulated regional delay in myocardial motion: clinical implications for rest and stress echocardiography studies. J Am Soc Echocardiogr 1999;12:698 –705. 13. Sutherland GR, Kukulski T, Kvitting JE, D’hooge J, Arnold M, Brandt E, Hatle L, Wranne B. Quantitation of left-ventricular asynergy by cardiac ultrasound. Am J Cardiol 2000;86:4G–9G.
This study investigates the accuracy of 2 echocardiographic LV motion characteristics: first, a typical LV shuffle motion, and second, a multiphasic septal motion pattern in predicting LV dyssynchrony and LV reverse remodeling after CRT. Shuffle is an abnormal septal-to-lateral apical LV systolic motion, whereas multiphasic septal motion pattern is characterized by early systolic inward and late systolic outward movement of the septum and is a known echocardiographic feature of LBBB (Figure 1). Observation of the shuffle by 5 independent cardiologists predicted LV dyssynchrony detected using tissue Doppler with a sensitivity range of 77% to 89% and specificity range of 72% to 89% (Table 3). Results improved if the presence of either the shuffle or multiphasic septal motion pattern was taken into account. LV dyssynchrony could then be predicted with sensitivity of 90% to 97% and specificity of 67% to 83% (Table 3). More important than the capability to predict dyssynchrony is the prediction of LV reverse remodeling itself, because it was shown to be related to improved survival.6 In the present study, simple visual observation of either a shuffle or multiphasic septal motion performed almost as well to predict LV reverse remodeling as the SD of the activation time of 6 basal LV segments acquired using pulse tissue Doppler (Table 4). LV reverse remodeling could be predicted with sensitivity and specificity ranging from 87% to 92% and 69% to 81%, respectively. Pulse-wave tissue Doppler to establish LV mechanical dyssynchrony is a time-consuming method because ⱖ6 basal LV segments need to be investigated and calculated. Decreasing the number of investigated segments to 2 provides inferior results in detecting LV dyssynchrony and predicting reverse remodeling.6 Color tissue Doppler and volume analysis using 3-dimensional echocardiography may provide an accurate prediction of dyssynchrony, but are also labor-intensive methods and not widely available.7,9 –11 All these methods therefore are less suitable for screening purposes, and visual interpretation of LV dyssynchrony using 2-dimensional echocardiography, as in the present study, would increase the clinical applicability and feasibility to select patients for CRT in daily practice. Previous reports of visual estimation of LV dyssynchrony are limited and concluded that intraventricular activation delays ⬍70 ms cannot be detected with the human eye.12,13 However, the principle of the shuffle is not detec-