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Comparison of left ventricular–biventricular pacing on ventricular synchrony, mitral regurgitation, and global left ventricular function in patients with severe chronic heart failure
Comparison of Left Ventricular–Biventricular Pacing on Ventricular Synchrony, Mitral Regurgitation, and Global Left Ventricular Function in Patients With Severe Chronic Heart Failure Dragos Vinereanu, MD, Rob Bleasdale, MD, Mark Turner, Michael P. Frenneaux, MD, and Alan G. Fraser, MD We compared the effects of left ventricular and biventricular pacing in 16 patients (15 men and 1 woman; aged 64 ⴞ 8 years) with severe heart failure by conventional and tissue Doppler echocardiography. Intraventricular synchrony, regional and global systolic function, diastolic function and filling time, and the severity of secondary mitral regurgitation were similar between left ventricular and biventricular pacing. 䊚2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;94:519 –521)
ardiac resynchronization therapy has been shown to reduce mortality from progressive heart failure C in patients with severe left ventricular (LV) dysfunction.1 It also improves exercise capacity, symptoms, and quality of life. The mechanisms responsible for these benefits are improved synchrony of the left and right ventricle (interventricular synchrony),2,3 improved synchrony of the different segments of the left ventricle (intraventricular synchrony),4 and decreased secondary mitral regurgitation.5 LV pacing alone has exhibited comparable improvements to biventricular (BiV) pacing during acute hemodynamic or echocardiographic evaluation.6 – 8 However, no detailed comparative data on the acute effects of LV versus BiV pacing on intra- and interventricular synchrony are available. We set up a crossover study to compare the effects of LV and BiV pacing on ventricular synchrony, mitral regurgitation, and global systolic and diastolic function using conventional and tissue Doppler echocardiography. •••
Sixteen consecutive patients (aged 64 ⫾ 8 years; 15 men and 1 woman) with a BiV InSync III pacemaker (Medtronic Inc, Minneapolis, Minnesota) were studied between 1 and 6 months after transvenous implantation, with a lead placed via the coronary sinus over the free wall of the left ventricle. Right-sided cardiac leads were conventionally placed in the right atrial appendage and the right ventricular apex. All patients were in sinus rhythm when unpaced, and patients with aortic or mitral valve stenosis, pericardial disease, or cor pulmonale were excluded. Before pacing, the duration of the QRS complex was 135 From the Wales Heart Research Institute, Cardiff, United Kingdom. Dr. Fraser’s address is: Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom. E-mail: [email protected]. Manuscript received February 2, 2004; revised manuscript received and accepted April 22, 2004. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 August 15, 2004
MD,
⫾ 31 ms. Three patients (19%) were in New York Heart Association functional class II, 12 patients (75%) were in class III, and 1 patient (6%) was in class IV. Etiology of heart failure was ischemic in 11 patients (70%) and nonischemic in 5 (30%). Fifteen patients were taking an angiotensin-converting enzyme inhibitor, 2 were on a  blocker, and all were taking a loop diuretic. The protocol was approved by the local research ethics committee, and each patient gave written informed consent. The paced atrioventricular delay was optimized by conventional Doppler assessment of transmitral flow.9 The pacemaker was switched off, and after 10 minutes of rest, a detailed transthoracic echocardiographic study was performed. The pacemaker was then reprogrammed to atrio-LV mode, and the echocardiographic study was repeated after another 10-minute period of stabilization. Finally, the pacemaker was reprogrammed to BiV mode with simultaneous VV stimulation, and echocardiography was performed again after a further 10-minute period of stabilization. This sequence was used for all patients. Heart rate was measured during each stage. The electrocardiogram was recorded simultaneously. Patients were studied in the left lateral decubitus position using a commercially available ultrasound system equipped with tissue Doppler (Vingmed System 5, GE Vingmed, Horten, Norway), using a 1.5- to 2.5-MHz transducer. Digital echocardiographic data were acquired during passively held end-expiration. Standard echocardiographic studies consisted of M-mode, cross-sectional, and Doppler blood flow measurements. LV ejection fraction was calculated by the modified biplane Simpson’s method. The rate of increase in LV pressure in systole was estimated from the continuous-wave Doppler trace of the mitral regurgitant jet, between velocities of 1 and 3 m/s.10 Global diastolic function was assessed from color M-mode recordings of mitral inflow, and flow propagation velocity was measured.11 Filling time was measured from pulse-wave Doppler recording of the transmitral flow. The severity of secondary mitral regurgitation was estimated in the apical 4-chamber view by measuring the width of the vena contracta12 and by calculating the regurgitant orifice area using the proximal isovelocity surface–area method.13 Tissue Doppler echocardiography used 5 standard imaging planes: parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical long-axis views. Myocardial velocities and tim0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.04.072
519
FIGURE 1. Example of an off-line tissue Doppler myocardial trace with measurements of the peak systolic velocity (S), and of the time to peak (TTP) as the time from onset of the QRS complex to the peak systolic velocity.
ings were measured off-line (Echopac TVI, GE Vingmed) from 7 LV myocardial segments and 1 right ventricular segment. LV radial function was assessed from the mid-posterior wall (parasternal long-axis view), whereas longitudinal function was assessed from the basal septal and basal lateral (apical 4-chamber view), basal anterior and basal inferior (apical 2-chamber view), and basal anteroseptal and basal posterior (apical long-axis view) segments. The right ventricle was assessed from the right ventricular free wall, adjacent to the lateral tricuspid annulus, in the A4C view. Peak systolic velocity (S) was defined as the maximal velocity (centimeters per second) during systole, excluding isovolumic contraction. Time-topeak was measured from the beginning of the QRS complex to the peak systolic velocity (Figure 1). The velocities of the 6 basal segments were averaged. Intra-LV synchrony was defined as the SD of the time-to-peak systolic velocities in these 6 myocardial segments. Interventricular synchrony was defined as the difference between right ventricular and 6-site mean LV longitudinal timings. We have reported detailed studies of interobserver agreement of tissue Doppler measurements in our laboratory.14 Ten randomly selected studies were analyzed by 4 observers, and each pooled SD was divided by its corresponding mean value to give coefficients of variation (in percentages). Coefficients of variation were 8% to 13% for measurements of peak systolic velocity, and 16% to 18% for measurements of time to peak for the basal segments in the apical views. Statistical analysis was performed with SPSS software (version 11.0, SPSS Inc. Chicago, Illinois). Results are presented as mean value ⫾ SD. Differences between changes in the pacing modes from baseline were tested for significance using paired samples t 520 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 94
tests. A p value ⬍0.05 for a 2-tailed test was considered significant. We calculated and compared the changes from baseline for both pacing modalities (Table 1). Longitudinal intraventricular synchrony improved equally with both pacing modalities (Figure 2). Time-to-peak systolic velocity of the right ventricular segment increased from 150 ⫾ 42 to 238 ⫾ 31 ms during LV pacing, and to 214 ⫾ 30 ms during BiV pacing (p ⬍0.05 for LV vs BiV pacing) (Figure 2). In 63% of patients, LV pacing caused the left ventricle to reach peak systolic velocity before the right ventricle, whereas during BiV pacing, the left ventricle reached peak systolic velocity before the right ventricle in only 31% of the patients (p ⬍0.05). Regional and global systolic function, diastolic function and filling time, and the severity of secondary mitral regurgitation were all similar between LV and BiV pacing. Heart rate did not change between baseline (68 ⫾ 8 beats/min), LV pacing (69 ⫾ 12 beats/ min), and BiV pacing (69 ⫾ 11 beats/min). •••
This study shows that LV and BiV pacing provide similar improvement in the main mechanisms of benefit of cardiac resynchronization. This may be important from a technical, economic, and safety point of view, because it is easier to implant 2 rather than 3 leads. We confirm the results reported by the Guidant Congestive Heart Failure Research Group, but they used only conventional Doppler to evaluate the acute effects of cardiac resynchronization, and they did not evaluate the severity of mitral regurgitation.6 We also used tissue Doppler, which has been shown to be the best technique available for the measurement of intra- and interventricular synchrony during pacing.5,15 We separately assessed radial and longitudinal function, because these are due to different layers of myocardial fibers; circumferential, midwall fibers are responsible mainly for radial contraction, whereas longitudinal, subendocardial fibers determine long-axis function.16 Tissue Doppler measurements were obtained only from the basal segments, unlike the study reported by Yu et al,5 in which mid-segments were also recorded. However, from our experience, tissue Doppler of the basal segments has the best feasibility and reproducibility, especially in patients with heart failure and low velocities.14 Another limitation may be that velocities are load-dependent, but patients were kept in the same conditions for comparison between the 2 pacing modalities, and therefore it is unlikely that the loading changed. We evaluated mitral regurgitation by 2 independent quantitative methods; finally, we measured global systolic and diastolic function by conventional echocardiographic parameters. Resynchronization reduces the spatial and temporal heterogeneity of contraction, which was suggested by an experimental study using tagged magnetic resonance imaging to be the main mechanism by which pacing improves the efficiency of the heart.17,18 Because LV and BiV pacing decrease this asynchrony similarly, it is logical that they should have similar effects on cardiac function. We confirmed that reAUGUST 15, 2004
TABLE 1 Comparison Between Baseline, Left Ventricular (LV) Pacing, and Biventricular Pacing (BiV)
1. Bradley DJ, Bradley EA, Baughman KL, Berger RD,
Calkins H, Goodman SN, Kass DA, Powe NR. Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials. Parameter Baseline LV Pacing BiV Pacing JAMA 2003;289:730 –740. 2. Kerwin WF, Botvinick EH, O’Connell JW, Merrick Intraventricular synchrony (ms) 31 ⫾ 16 14 ⫾ 9* 12 ⫾ 7* SH, DeMarco T, Chatterjee K, Scheibly K, Saxon LA. Interventricular synchrony (ms) 65 ⫾ 95 ⫺11 ⫾ 41* 17 ⫾ 66* Ventricular contraction abnormalities in dilated cardiomyopathy: effect of biventricular pacing to correct inLongitudinal systolic velocity (cm/s) 3.5 ⫾ 1.0 3.9 ⫾ 1.0* 3.8 ⫾ 1.0* terventricular dyssynchrony. J Am Coll Cardiol 2000; Radial systolic velocity (cm/s) 3.4 ⫾ 1.0 3.5 ⫾ 1.4 3.7 ⫾ 1.0 35:1221–1227. Ejection fraction (%) 31 ⫾ 8 33 ⫾ 8* 33 ⫾ 8* 3. Verbeek XA, Vernooy K, Peschar M, Van Der Nagel dP/dt (mm Hg/s) 534 ⫾ 256 734 ⫾ 334* 658 ⫾ 241* T, Van Hunnik A, Prinzen FW. Quantification of interFlow propagation velocity (cm/s) 30 ⫾ 6 36 ⫾ 6* 36 ⫾ 6* ventricular asynchrony during LBBB and ventricular Filling time (ms) 383 ⫾ 135 429 ⫾ 130* 428 ⫾ 126* pacing. Am J Physiol Heart Circ Physiol 2002;283: 15.2 ⫾ 13 10.1 ⫾ 8* 10.5 ⫾ 9* Regurgitant orifice area (mm2) H1370 –H1378. Vena contracta diameter (mm) 5.2 ⫾ 1.7 4.1 ⫾ 1.4* 3.9 ⫾ 1.6* 4. Etienne Y, Mansourati J, Touiza A, Gilard M, Bertault-Valls V, Guillo P, Boschat J, Blanc JJ. Evaluation *p ⬍0.05, pacing (each mode) versus baseline. of left ventricular function and mitral regurgitation durdP/dt ⫽ rate of increase in LV pressure in systole. ing left ventricular-based pacing in patients with heart failure. Eur J Heart Fail 2001;3:441– 447. 5. Yu CM, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, Lin H, Kong SL, Lam YM, Hill MRS, Lau CP. Tissue Doppler echocardiography evidence of reverse remodelling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105:438 – 445. 6. Breithardt OA, Stellbrink C, Franke A, Balta O, Diem BH, Bakker P, Sack S, Auricchio A, Pochet T, Salo R. Pacing therapies for congestive heart failure study group. Guidant Congestive Heart Failure Research Group. Acute effects of cardiac resynchronization therapy on left ventricular Doppler indices in patients with congestive heart failure. Am Heart J 2002;143:34 – 44. 7. Kass DA, Chen CH, Curry C, Talbot M, Berger R, Fetics B, Nevo E. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999;99:1567–1573. 8. Puggioni E, Brignole M, Gammage M, Soldati E, Bongiorni MG, Simantirakis EN, Vardas P, Gadler F, Bergfeldt L, Tomasi C, Musso G, Gasparini G, Del Rosso A. Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation. J Am Coll Cardiol 2004;43:234 –238. 9. Ritter P, Padeletti L, Gillio-Meina L, Gaggini G. Determination of the optimal atrioventricular delay in DDD pacing. Comparison between echo and peak endocardial acceleration measurements. Europace 1999;1:126 –130. 10. Bargiggia GS, Bertucci C, Recusani F, Raisaro A, de Servi S, Valdes-Cruz LM, Sahn DJ, Tronconi L. A new method for estimating left ventricular dp/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization. Circulation 1989;80:1287–1292. FIGURE 2. Mean time-to-peak of the 6 LV basal segments and of 11. Brun P, Tribouilloy C, Duval AM, Iserin L, Meguira A, Pelle G, Dubois-Rande JL. Left ventricular flow propagation during early filling is related to wall relaxation: the right ventricular (RV) free wall segment during baseline, LV a color M-mode Doppler analysis. J Am Coll Cardiol 1992;20:420 – 432. pacing, and BiV. BA ⴝ basal anterior; BAS ⴝ basal anterosep12. Hall SA, Brickner ME, Willett DL, Irani WN, Afridi I, Grayburn PA. tal; BI ⴝ basal inferior; BL ⴝ basal lateral; BP ⴝ basal posterior; Assessment of mitral regurgitation severity by Doppler color flow mapping of the BS ⴝ basal septal. vena contracta. Circulation 1997;95:636 – 642. 13. Enriquez-Sarano M, Miller FA Jr, Hayes SN, Bailey KR, Tajik AJ, Seward JB. Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol 1995;25:703–709. 14. Fraser AG, Payne N, Madler CF, Janerot-Sjoberg B, Lind B, Grocott-Mason gional and global systolic parameters were improved RM, Ionescu AA, Florescu N, Wilkenshoff U, Lancellotti P, Wutte M, Brodin Feasibility and reproducibility of off-line tissue Doppler measurement of to the same degree by both pacing modes. Both pacing LA. regional myocardial function during dobutamine stress echocardiography. Eur J modes also changed the diastolic inflow pattern sim- Echocardiogr 2003;4:43–53. Sogaard P, Egeblad H, Pedersen AK, Kim WY, Kristensen BO, Hansen PS, ilarly, increasing the filling time and decreasing esti- 15. Mortensen PT. Sequential versus simultaneous biventricular resynchronization mated LV filling pressure. We studied a relatively for severe heart failure: evaluation by tissue Doppler imaging. Circulation 2002; small number of patients, and therefore a type II 106:2078 –2084. 16. Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick EH. Fiber statistical error cannot be excluded, but all the data orientation in the canine left ventricle during diastole and systole. Circ Res were consistently similar between the 2 pacing mo- 1969;24:339 –347. 17. Wyman BT, Hunter WC, Prinzen FW, Faris OP, McVeigh ER. Effects of dalities. Our data are also supported by recent mid- singleand biventricular pacing on temporal and spatial dynamics of ventricular term studies showing that LV pacing alone results in contraction. Am J Physiol Heart Circ Physiol 2002;282:H372–H379. significant improvement in exercise tolerance and pa- 18. Leclercq C, Faris O, Tunin R, Johnson J, Kato R, Evans F, Spinelli J, Halperin H, McVeigh E, Kass DA. Systolic improvement and mechanical resynrameters of LV function,19,20 but this should now be chronization does not require electrical synchrony in the dilated failing heart with left bundle-branch block. Circulation 2002;106:1760 –1763. tested in long-term comparative studies. 19. Touiza A, Etienne Y, Gilard M, Fatemi M, Mansourati J, Blanc JJ. Long-term left We have reported elsewhere21 in a detailed analy- ventricular pacing: assessment and comparison with biventricular pacing in patients sis that similar benefits from LV and BiV pacing can with severe congestive heart failure. J Am Coll Cardiol 2001;38:1966 –1970. 20. Blanc JJ, Bertault-Valls V, Fatemi M, Gilard M, Pennec PY, Etienne Y. be observed whether patients have a prolonged QRS Midterm benefits of left univentricular pacing in patients with congestive heart duration on the surface electrocardiogram or a normal failure. Circulation 2004;109:1741–1744. QRS duration. Thus, the benefits of LV pacing alone 21. Turner MS, Bleasdale RA, Vinereneau D, Mumford CE, Paul V, Fraser AG, MP. Electrical and mechanical components of dyssychrony in heart may be applicable to all patients who currently receive Frenneaux failure patients with normal QRS duration and left bundle-branch block. Impact resynchronization therapy. of left and biventricular pacing. Circulation 2004;109:2544 –2549.
BRIEF REPORTS
521
ardiac resynchronization therapy has been shown to reduce mortality from progressive heart failure C in patients with severe left ventricular (LV) dysfunction.1 It also improves exercise capacity, symptoms, and quality of life. The mechanisms responsible for these benefits are improved synchrony of the left and right ventricle (interventricular synchrony),2,3 improved synchrony of the different segments of the left ventricle (intraventricular synchrony),4 and decreased secondary mitral regurgitation.5 LV pacing alone has exhibited comparable improvements to biventricular (BiV) pacing during acute hemodynamic or echocardiographic evaluation.6 – 8 However, no detailed comparative data on the acute effects of LV versus BiV pacing on intra- and interventricular synchrony are available. We set up a crossover study to compare the effects of LV and BiV pacing on ventricular synchrony, mitral regurgitation, and global systolic and diastolic function using conventional and tissue Doppler echocardiography. •••
Sixteen consecutive patients (aged 64 ⫾ 8 years; 15 men and 1 woman) with a BiV InSync III pacemaker (Medtronic Inc, Minneapolis, Minnesota) were studied between 1 and 6 months after transvenous implantation, with a lead placed via the coronary sinus over the free wall of the left ventricle. Right-sided cardiac leads were conventionally placed in the right atrial appendage and the right ventricular apex. All patients were in sinus rhythm when unpaced, and patients with aortic or mitral valve stenosis, pericardial disease, or cor pulmonale were excluded. Before pacing, the duration of the QRS complex was 135 From the Wales Heart Research Institute, Cardiff, United Kingdom. Dr. Fraser’s address is: Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom. E-mail: [email protected]. Manuscript received February 2, 2004; revised manuscript received and accepted April 22, 2004. ©2004 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 94 August 15, 2004
MD,
⫾ 31 ms. Three patients (19%) were in New York Heart Association functional class II, 12 patients (75%) were in class III, and 1 patient (6%) was in class IV. Etiology of heart failure was ischemic in 11 patients (70%) and nonischemic in 5 (30%). Fifteen patients were taking an angiotensin-converting enzyme inhibitor, 2 were on a  blocker, and all were taking a loop diuretic. The protocol was approved by the local research ethics committee, and each patient gave written informed consent. The paced atrioventricular delay was optimized by conventional Doppler assessment of transmitral flow.9 The pacemaker was switched off, and after 10 minutes of rest, a detailed transthoracic echocardiographic study was performed. The pacemaker was then reprogrammed to atrio-LV mode, and the echocardiographic study was repeated after another 10-minute period of stabilization. Finally, the pacemaker was reprogrammed to BiV mode with simultaneous VV stimulation, and echocardiography was performed again after a further 10-minute period of stabilization. This sequence was used for all patients. Heart rate was measured during each stage. The electrocardiogram was recorded simultaneously. Patients were studied in the left lateral decubitus position using a commercially available ultrasound system equipped with tissue Doppler (Vingmed System 5, GE Vingmed, Horten, Norway), using a 1.5- to 2.5-MHz transducer. Digital echocardiographic data were acquired during passively held end-expiration. Standard echocardiographic studies consisted of M-mode, cross-sectional, and Doppler blood flow measurements. LV ejection fraction was calculated by the modified biplane Simpson’s method. The rate of increase in LV pressure in systole was estimated from the continuous-wave Doppler trace of the mitral regurgitant jet, between velocities of 1 and 3 m/s.10 Global diastolic function was assessed from color M-mode recordings of mitral inflow, and flow propagation velocity was measured.11 Filling time was measured from pulse-wave Doppler recording of the transmitral flow. The severity of secondary mitral regurgitation was estimated in the apical 4-chamber view by measuring the width of the vena contracta12 and by calculating the regurgitant orifice area using the proximal isovelocity surface–area method.13 Tissue Doppler echocardiography used 5 standard imaging planes: parasternal long-axis, parasternal short-axis, apical 4-chamber, apical 2-chamber, and apical long-axis views. Myocardial velocities and tim0002-9149/04/$–see front matter doi:10.1016/j.amjcard.2004.04.072
519
FIGURE 1. Example of an off-line tissue Doppler myocardial trace with measurements of the peak systolic velocity (S), and of the time to peak (TTP) as the time from onset of the QRS complex to the peak systolic velocity.
ings were measured off-line (Echopac TVI, GE Vingmed) from 7 LV myocardial segments and 1 right ventricular segment. LV radial function was assessed from the mid-posterior wall (parasternal long-axis view), whereas longitudinal function was assessed from the basal septal and basal lateral (apical 4-chamber view), basal anterior and basal inferior (apical 2-chamber view), and basal anteroseptal and basal posterior (apical long-axis view) segments. The right ventricle was assessed from the right ventricular free wall, adjacent to the lateral tricuspid annulus, in the A4C view. Peak systolic velocity (S) was defined as the maximal velocity (centimeters per second) during systole, excluding isovolumic contraction. Time-topeak was measured from the beginning of the QRS complex to the peak systolic velocity (Figure 1). The velocities of the 6 basal segments were averaged. Intra-LV synchrony was defined as the SD of the time-to-peak systolic velocities in these 6 myocardial segments. Interventricular synchrony was defined as the difference between right ventricular and 6-site mean LV longitudinal timings. We have reported detailed studies of interobserver agreement of tissue Doppler measurements in our laboratory.14 Ten randomly selected studies were analyzed by 4 observers, and each pooled SD was divided by its corresponding mean value to give coefficients of variation (in percentages). Coefficients of variation were 8% to 13% for measurements of peak systolic velocity, and 16% to 18% for measurements of time to peak for the basal segments in the apical views. Statistical analysis was performed with SPSS software (version 11.0, SPSS Inc. Chicago, Illinois). Results are presented as mean value ⫾ SD. Differences between changes in the pacing modes from baseline were tested for significance using paired samples t 520 THE AMERICAN JOURNAL OF CARDIOLOGY姞
VOL. 94
tests. A p value ⬍0.05 for a 2-tailed test was considered significant. We calculated and compared the changes from baseline for both pacing modalities (Table 1). Longitudinal intraventricular synchrony improved equally with both pacing modalities (Figure 2). Time-to-peak systolic velocity of the right ventricular segment increased from 150 ⫾ 42 to 238 ⫾ 31 ms during LV pacing, and to 214 ⫾ 30 ms during BiV pacing (p ⬍0.05 for LV vs BiV pacing) (Figure 2). In 63% of patients, LV pacing caused the left ventricle to reach peak systolic velocity before the right ventricle, whereas during BiV pacing, the left ventricle reached peak systolic velocity before the right ventricle in only 31% of the patients (p ⬍0.05). Regional and global systolic function, diastolic function and filling time, and the severity of secondary mitral regurgitation were all similar between LV and BiV pacing. Heart rate did not change between baseline (68 ⫾ 8 beats/min), LV pacing (69 ⫾ 12 beats/ min), and BiV pacing (69 ⫾ 11 beats/min). •••
This study shows that LV and BiV pacing provide similar improvement in the main mechanisms of benefit of cardiac resynchronization. This may be important from a technical, economic, and safety point of view, because it is easier to implant 2 rather than 3 leads. We confirm the results reported by the Guidant Congestive Heart Failure Research Group, but they used only conventional Doppler to evaluate the acute effects of cardiac resynchronization, and they did not evaluate the severity of mitral regurgitation.6 We also used tissue Doppler, which has been shown to be the best technique available for the measurement of intra- and interventricular synchrony during pacing.5,15 We separately assessed radial and longitudinal function, because these are due to different layers of myocardial fibers; circumferential, midwall fibers are responsible mainly for radial contraction, whereas longitudinal, subendocardial fibers determine long-axis function.16 Tissue Doppler measurements were obtained only from the basal segments, unlike the study reported by Yu et al,5 in which mid-segments were also recorded. However, from our experience, tissue Doppler of the basal segments has the best feasibility and reproducibility, especially in patients with heart failure and low velocities.14 Another limitation may be that velocities are load-dependent, but patients were kept in the same conditions for comparison between the 2 pacing modalities, and therefore it is unlikely that the loading changed. We evaluated mitral regurgitation by 2 independent quantitative methods; finally, we measured global systolic and diastolic function by conventional echocardiographic parameters. Resynchronization reduces the spatial and temporal heterogeneity of contraction, which was suggested by an experimental study using tagged magnetic resonance imaging to be the main mechanism by which pacing improves the efficiency of the heart.17,18 Because LV and BiV pacing decrease this asynchrony similarly, it is logical that they should have similar effects on cardiac function. We confirmed that reAUGUST 15, 2004
TABLE 1 Comparison Between Baseline, Left Ventricular (LV) Pacing, and Biventricular Pacing (BiV)
1. Bradley DJ, Bradley EA, Baughman KL, Berger RD,
Calkins H, Goodman SN, Kass DA, Powe NR. Cardiac resynchronization and death from progressive heart failure: a meta-analysis of randomized controlled trials. Parameter Baseline LV Pacing BiV Pacing JAMA 2003;289:730 –740. 2. Kerwin WF, Botvinick EH, O’Connell JW, Merrick Intraventricular synchrony (ms) 31 ⫾ 16 14 ⫾ 9* 12 ⫾ 7* SH, DeMarco T, Chatterjee K, Scheibly K, Saxon LA. Interventricular synchrony (ms) 65 ⫾ 95 ⫺11 ⫾ 41* 17 ⫾ 66* Ventricular contraction abnormalities in dilated cardiomyopathy: effect of biventricular pacing to correct inLongitudinal systolic velocity (cm/s) 3.5 ⫾ 1.0 3.9 ⫾ 1.0* 3.8 ⫾ 1.0* terventricular dyssynchrony. J Am Coll Cardiol 2000; Radial systolic velocity (cm/s) 3.4 ⫾ 1.0 3.5 ⫾ 1.4 3.7 ⫾ 1.0 35:1221–1227. Ejection fraction (%) 31 ⫾ 8 33 ⫾ 8* 33 ⫾ 8* 3. Verbeek XA, Vernooy K, Peschar M, Van Der Nagel dP/dt (mm Hg/s) 534 ⫾ 256 734 ⫾ 334* 658 ⫾ 241* T, Van Hunnik A, Prinzen FW. Quantification of interFlow propagation velocity (cm/s) 30 ⫾ 6 36 ⫾ 6* 36 ⫾ 6* ventricular asynchrony during LBBB and ventricular Filling time (ms) 383 ⫾ 135 429 ⫾ 130* 428 ⫾ 126* pacing. Am J Physiol Heart Circ Physiol 2002;283: 15.2 ⫾ 13 10.1 ⫾ 8* 10.5 ⫾ 9* Regurgitant orifice area (mm2) H1370 –H1378. Vena contracta diameter (mm) 5.2 ⫾ 1.7 4.1 ⫾ 1.4* 3.9 ⫾ 1.6* 4. Etienne Y, Mansourati J, Touiza A, Gilard M, Bertault-Valls V, Guillo P, Boschat J, Blanc JJ. Evaluation *p ⬍0.05, pacing (each mode) versus baseline. of left ventricular function and mitral regurgitation durdP/dt ⫽ rate of increase in LV pressure in systole. ing left ventricular-based pacing in patients with heart failure. Eur J Heart Fail 2001;3:441– 447. 5. Yu CM, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, Lin H, Kong SL, Lam YM, Hill MRS, Lau CP. Tissue Doppler echocardiography evidence of reverse remodelling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105:438 – 445. 6. Breithardt OA, Stellbrink C, Franke A, Balta O, Diem BH, Bakker P, Sack S, Auricchio A, Pochet T, Salo R. Pacing therapies for congestive heart failure study group. Guidant Congestive Heart Failure Research Group. Acute effects of cardiac resynchronization therapy on left ventricular Doppler indices in patients with congestive heart failure. Am Heart J 2002;143:34 – 44. 7. Kass DA, Chen CH, Curry C, Talbot M, Berger R, Fetics B, Nevo E. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999;99:1567–1573. 8. Puggioni E, Brignole M, Gammage M, Soldati E, Bongiorni MG, Simantirakis EN, Vardas P, Gadler F, Bergfeldt L, Tomasi C, Musso G, Gasparini G, Del Rosso A. Acute comparative effect of right and left ventricular pacing in patients with permanent atrial fibrillation. J Am Coll Cardiol 2004;43:234 –238. 9. Ritter P, Padeletti L, Gillio-Meina L, Gaggini G. Determination of the optimal atrioventricular delay in DDD pacing. Comparison between echo and peak endocardial acceleration measurements. Europace 1999;1:126 –130. 10. Bargiggia GS, Bertucci C, Recusani F, Raisaro A, de Servi S, Valdes-Cruz LM, Sahn DJ, Tronconi L. A new method for estimating left ventricular dp/dt by continuous wave Doppler-echocardiography. Validation studies at cardiac catheterization. Circulation 1989;80:1287–1292. FIGURE 2. Mean time-to-peak of the 6 LV basal segments and of 11. Brun P, Tribouilloy C, Duval AM, Iserin L, Meguira A, Pelle G, Dubois-Rande JL. Left ventricular flow propagation during early filling is related to wall relaxation: the right ventricular (RV) free wall segment during baseline, LV a color M-mode Doppler analysis. J Am Coll Cardiol 1992;20:420 – 432. pacing, and BiV. BA ⴝ basal anterior; BAS ⴝ basal anterosep12. Hall SA, Brickner ME, Willett DL, Irani WN, Afridi I, Grayburn PA. tal; BI ⴝ basal inferior; BL ⴝ basal lateral; BP ⴝ basal posterior; Assessment of mitral regurgitation severity by Doppler color flow mapping of the BS ⴝ basal septal. vena contracta. Circulation 1997;95:636 – 642. 13. Enriquez-Sarano M, Miller FA Jr, Hayes SN, Bailey KR, Tajik AJ, Seward JB. Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol 1995;25:703–709. 14. Fraser AG, Payne N, Madler CF, Janerot-Sjoberg B, Lind B, Grocott-Mason gional and global systolic parameters were improved RM, Ionescu AA, Florescu N, Wilkenshoff U, Lancellotti P, Wutte M, Brodin Feasibility and reproducibility of off-line tissue Doppler measurement of to the same degree by both pacing modes. Both pacing LA. regional myocardial function during dobutamine stress echocardiography. Eur J modes also changed the diastolic inflow pattern sim- Echocardiogr 2003;4:43–53. Sogaard P, Egeblad H, Pedersen AK, Kim WY, Kristensen BO, Hansen PS, ilarly, increasing the filling time and decreasing esti- 15. Mortensen PT. Sequential versus simultaneous biventricular resynchronization mated LV filling pressure. We studied a relatively for severe heart failure: evaluation by tissue Doppler imaging. Circulation 2002; small number of patients, and therefore a type II 106:2078 –2084. 16. Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick EH. Fiber statistical error cannot be excluded, but all the data orientation in the canine left ventricle during diastole and systole. Circ Res were consistently similar between the 2 pacing mo- 1969;24:339 –347. 17. Wyman BT, Hunter WC, Prinzen FW, Faris OP, McVeigh ER. Effects of dalities. Our data are also supported by recent mid- singleand biventricular pacing on temporal and spatial dynamics of ventricular term studies showing that LV pacing alone results in contraction. Am J Physiol Heart Circ Physiol 2002;282:H372–H379. significant improvement in exercise tolerance and pa- 18. Leclercq C, Faris O, Tunin R, Johnson J, Kato R, Evans F, Spinelli J, Halperin H, McVeigh E, Kass DA. Systolic improvement and mechanical resynrameters of LV function,19,20 but this should now be chronization does not require electrical synchrony in the dilated failing heart with left bundle-branch block. Circulation 2002;106:1760 –1763. tested in long-term comparative studies. 19. Touiza A, Etienne Y, Gilard M, Fatemi M, Mansourati J, Blanc JJ. Long-term left We have reported elsewhere21 in a detailed analy- ventricular pacing: assessment and comparison with biventricular pacing in patients sis that similar benefits from LV and BiV pacing can with severe congestive heart failure. J Am Coll Cardiol 2001;38:1966 –1970. 20. Blanc JJ, Bertault-Valls V, Fatemi M, Gilard M, Pennec PY, Etienne Y. be observed whether patients have a prolonged QRS Midterm benefits of left univentricular pacing in patients with congestive heart duration on the surface electrocardiogram or a normal failure. Circulation 2004;109:1741–1744. QRS duration. Thus, the benefits of LV pacing alone 21. Turner MS, Bleasdale RA, Vinereneau D, Mumford CE, Paul V, Fraser AG, MP. Electrical and mechanical components of dyssychrony in heart may be applicable to all patients who currently receive Frenneaux failure patients with normal QRS duration and left bundle-branch block. Impact resynchronization therapy. of left and biventricular pacing. Circulation 2004;109:2544 –2549.
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