This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, C.-M. Articles by Lau, C.-P. Search for Related Content PubMed PubMed Citation Articles by Yu, C.-M. Articles by Lau, C.-P. Related Collections Congestive Remodeling Pacemaker Echocardiography

(Circulation. 2002;105:438.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Tissue Doppler Echocardiographic Evidence of Reverse Remodeling and Improved Synchronicity by Simultaneously Delaying Regional Contraction After Biventricular Pacing Therapy in Heart Failure

Cheuk-Man Yu, MD, FRACP; Elaine Chau, MRCP, FHKAM; John E. Sanderson, MD; Katherine Fan, MRCP, FHKAM; Man-Oi Tang, BM; Wing-Hong Fung, MRCP, FHKAM; Hong Lin, BM, MM; Shun-Ling Kong, BN, MN; Yui-Ming Lam, MBBS, MRCP; Michael R.S. Hill, PhD; Chu-Pak Lau, MD

From the Division of Cardiology, Department of Medicine, Queen Mary Hospital (C.-M.Y., M.-O.T., H.L., S.-L.K., Y.-M.L., C.-P.L.) and Division of Cardiology, Department of Medicine, Grantham Hospital (E.C., K.F.), The University of Hong Kong; Division of Cardiology, Department of Medicine, Prince of Wales Hospital (J.E.S., W.-H.F.), The Chinese University of Hong Kong; and Medtronic Inc (M.R.S.H.), Minneapolis, Minn.

Correspondence to Dr Cheuk-Man Yu, Director of Non-Invasive Cardiac Services, Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong. E-mail cmyua{at}hkucc.hku.hk

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background— Biventricular pacing has been proposed to improve symptoms and exercise capacity in patients with advanced heart failure and wide electrocardiographic wave complexes. This study investigated the effect of biventricular pacing on reverse remodeling and the underlying mechanisms.

Methods and Results— Twenty-five patients with NYHA class III to IV heart failure and electrocardiographic wave complex duration >140 ms receiving biventricular pacing therapy were assessed serially up to 3 months after pacing and when pacing was withheld for 4 weeks. Tissue Doppler echocardiography was performed using a 6-basal, 6-mid segmental model to assess the time to peak sustained systolic contraction (T_S). There was significant improvement of ejection fraction, dP/dt, and myocardial performance index; decrease in mitral regurgitation, left ventricular (LV) end-diastolic (205±68 versus 168±67 mL, P<0.01) and end-systolic volume (162±54 versus 122±42 mL, P<0.01); and improved 6-minute hall-walk distance and quality of life score after pacing for 3 months. The mechanisms of benefits were as follows: (1) improved LV synchrony, as evident by homogeneous delay of T_S to a timing close to the latest (usually the lateral) segment abolishing the intersegmental difference in T_S and decreasing the standard deviation of T_S within the left ventricle (37.7±10.9 versus 29.3±8.3 ms, P<0.05); (2) improved interventricular synchrony; and (3) shortened isovolumic contraction time (122±57 versus 82±36 ms, P<0.05) but increased diastolic filling time. These benefits are pacing dependent, because withholding the pacing resulted in varying speeds in the loss of cardiac improvements.

Conclusions— Biventricular pacing reverses LV remodeling and improves cardiac function. Improvement of LV mechanical synchrony seems to be the predominant mechanism.

Key Words: pacing • heart failure • echocardiography • pacemakers

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Synchronous biventricular pacing is a recent advance as an adjunctive nonpharmacological therapy for patients with chronic heart failure with electromechanical delay.¹ It improves hemodynamic status acutely^2–5 and heart failure symptoms, exercise capacity, quality of life, and systolic function chronically.^6,7 Heart failure is a progressive disease that is characterized by progressive left ventricular (LV) dilatation and loss of contractile function, a condition referred to as remodeling. The severity of LV remodeling has been shown to carry independent prognostic importance.⁸ Therefore, treatments that are able to prevent or even regress LV remodeling are potentially beneficial. The use of angiotensin-converting enzyme inhibitor enalapril has been shown to prevent LV dilatation, conferring an associated survival benefit.⁹ Recently, our preliminary data have shown that biventricular pacing is effective in regressing LV remodeling and is more powerful than medical therapy alone.¹⁰ Although the benefits of biventricular pacing have been long proposed to be related to resynchronizing LV contraction, especially pre-exciting the free wall region so that it will contract as early as the septal region, this has never been demonstrated objectively. Conversely, loss of systolic synchrony has been confirmed by tagged MRI in patients with dilated cardiomyopathies and left bundle branch block.¹¹ By using echocardiography with tissue Doppler imaging (TDI), it is possible to perform serial and quantitative assessment of regional cardiac function and synchronicity both before and after pacing therapy.¹²

The aims of the present study were to assess the effect of biventricular pacing on LV reverse remodeling and echocardiographic parameters of cardiac function; to demonstrate the potential mechanisms of benefits objectively by echocardiography and TDI, which included the improvement of intraventricular and interventricular synchrony and possibly other mechanisms; and to confirm if continuous pacing is necessary for the reverse remodeling and other benefits.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
Twenty-five consecutive patients (mean age, 65±12 years; 18 males) with New York Heart Association (NYHA) class III (n=11) or IV (n=14) heart failure, LV ejection fraction <40%, and electrocardiographic evidence of prolonged electrocardiographic wave complex (QRS) of >140 ms received biventricular pacing therapy. The etiologies of heart failure were idiopathic dilated cardiomyopathy in 11, ischemic heart disease in 9, hypertensive cardiomyopathy in 3, alcoholic cardiomyopathy in 1, and chemotherapy-induced cardiomyopathy in 1 patient. Pharmacological management included diuretics in all patients, angiotensin-converting enzyme inhibitors in 21, angiotensin receptor antagonists in 4, ß-blockers in 17, spironolactone in 12, and digoxin in 4 patients. Serial investigations were performed before pacemaker implantation as well as 1 week, 1 month, and 3 months after biventricular pacing was instituted. The pacemakers were then changed to sensing mode (ODO), and the investigations were repeated immediately 1 week and 4 weeks afterward. Studies included echocardiography, 6-minute hall-walk test, and Minnesota Living with Heart Failure Questionnaire for quality of life assessment. The study protocol was approved by the Ethics Committee, and written informed consent was obtained from all patients.

Biventricular Pacemaker or Implantable Cardioverter Defibrillator Implantation
Atriosynchronized biventricular pacemaker was implanted as previously described.^1,10 The LV pacing lead was inserted by transvenous approach through the coronary sinus into the lateral or posterolateral cardiac vein. Nineteen patients received an Attain system (model 2187 in 14, model 4189 in 2, and model 4191 in 3 patients [side-wire lead]) (Medtronic Inc) and 6 received the Easytrak over-the-wire lead (model 4512, Guidant Inc). The biventricular devices used were InSync (model 8040, Medtronic Inc) in 19, Contak TR (model 1241, Guidant Inc) in 4, and biventricular cardioverter defibrillator (model 1823, Guidant Inc) in 2 patients. The atrioventricular interval was optimized by Doppler echocardiography.¹³

Echocardiography
Standard echocardiography, including Doppler studies, was performed (System 5, Vingmed-General Electric). The LV dimensions and ejection fraction were measured by two-dimension guided M-mode method. Change in LV volume was assessed by Simpson’s equation using the apical 4-chamber view. LV diastolic function and cardiac output were assessed by pulse-wave Doppler echocardiography.¹⁴ The rate of pressure rise in systole (dP/dt) was estimated from the continuous-wave Doppler mitral regurgitation velocity curve.¹⁵ Myocardial performance index (MPI) was also calculated.¹⁶ The severity of midsystolic mitral regurgitation was assessed by the percentage jet area relative to the left atrial size in the apical 4-chamber view. At least 3 consecutive beats of sinus rhythm were measured, and the average value was taken.

TDI was performed using apical views for the long-axis motion of the ventricles as previously described.^12,17,18 Two-dimension echocardiography with TDI-color imaging was performed with a 2.5- or 3.5-MHz phase-array transducer. Gain settings, filters, and pulse repetition frequency were adjusted to optimize color saturation, and sector size and depth were optimized for the highest possible frame rate. At least 3 consecutive beats were stored, and the images were digitized and computer analyzed offline (EchoPac 6.3.6, Vingmed-General Electric). Myocardial pulse-Doppler velocity profile signals were reconstituted offline from the TDI color images that provided regional myocardial velocity curves.¹² From the apical 4-chamber, 2-chamber, and long-axis views, a 6-basal and 6-mid segmental model was obtained in the LV, namely the septal, lateral, anteroseptal, posterior, anterior, and inferior segments at both basal and mid levels.¹² The peak myocardial sustained systolic velocity (S_M) and the time to peak S_M (T_S) were measured. For the T_S, the beginning of the QRS complex was used as the reference point.¹² The long-axis systolic displacement of the heart was calculated from the velocity-time integral of the regional velocity curve. The averages of at least 3 consecutive beats were used for comparison. The interobserver and intraobserver variabilities have been compared in 60 consecutive measurements and were 4.7% and 3.2%, respectively. Validation had been performed previously in physical models,¹⁹ animal models^17,20 and human subjects,²¹ and TDI was found to be accurate to assess regional velocity and timing of cardiac events.¹²

Statistics
For the comparison of parametric variables at different time points of assessment or among myocardial segments, paired sample t test with Bonferroni correction was used. To assess systolic synchronicity, standard deviation of T_S (T_S-SD) of the 12 LV myocardial segments in each patient was calculated. The greater the value of T_S-SD, the more severe the systolic dyssynchrony. ANOVA was used to compare the T_S of the 12 LV and the right ventricular segments at each time point. Correlation analysis was used to compare the degree of systolic dyssynchrony at baseline and improvement of reverse remodeling after pacing. All data were expressed as mean±SD. P<0.05 was considered statistically significant.

	Results

Top Abstract Introduction Methods Results Discussion References

 
All patients were successfully implanted and were receiving biventricular pacing at follow-up. The biventricular pacing threshold was 1.9±1.3 V at implantation and 3.2±2.3 V at 3 months at a pulse duration of 0.5 ms (P<0.05). The optimized atrioventricular interval was 92±22 ms. The QRS duration decreased from 162±30 to 142±20 ms (P=0.001). There was no change in heart failure medications, except in 2 patients who only tolerated ß-blocker therapy after implantation with biventricular pacemakers. The 1- and 4-week investigations after cessation of biventricular pacing were not performed in 3 patients. One patient with severe class IV heart failure was inotropically dependent before pacemaker implantation was considered unsafe to stop the therapy. One patient who developed acute congestive heart failure within 1 day after pacing was suspended, and therapy was turned back on. One patient was admitted for pump failure after 3 months and died.

Clinical Assessment
The New York Heart Association functional class decreased by at least one class in all but 2 patients. One of the patients subsequently died of pump failure. None of the patients experienced worsening of symptoms. In 1 patient, pulsus alternans was resolved after biventricular pacing.²² There was also progressive improvement in quality of life score (P=0.001 at 3 months) after pacing, and the benefit was relatively maintained up to 4 weeks after pacing was stopped. The 6-minute hall-walk distance was also increased early after pacing therapy, improved additionally by 3 months (all P<0.05) and was maintained after biventricular pacing was stopped (Table 1 and Figure 1).

View this table: [in this window] [in a new window]   Table 1. Serial Changes in Echocardiographic and Clinical Parameters After Biventricular Pacing in 25 Patients With Heart Failure

View larger version (24K): [in this window] [in a new window]   Figure 1. Changes in 6-minute hall-walk distance, Minnesota Living With Heart Failure quality of life score, LV end-diastolic () and end-systolic () volumes, ejection fraction, dP/dt, mitral regurgitation, isovolumic contraction time, and LV filling time before and after biventricular pacing as well as when pacing was suspended for 4 weeks. *Significant difference vs baseline. Significant difference vs biventricular pacing for 3 months. See Tables 1 and 2 for probability value. The time axis scale is not in proportion.

Left Ventricular Function
The LV fractional shortening and ejection fraction improved progressively during biventricular pacing and were significantly higher than baseline values at 1 (P<0.05) and 3 months (P<0.001). When pacing was stopped, repeating echocardiogram immediately showed a decrease in these parameters, although they were still significantly higher than prepacing values. These parameters decreased additionally 4 weeks after biventricular pacing was stopped (P<0.01 versus 3 months). The change in cardiac output followed a similar pattern to that of ejection fraction. The LV end-diastolic and end-systolic volumes were significantly smaller than baseline after pacing therapy for 1 month (P<0.05) and reduced additionally by 3 months (P<0.01). There was no change in LV volume immediately when pacing was stopped, but it was enlarged progressively over the subsequent 4 weeks (P<0.05 versus 3 months). The LV end-systolic diameter was also reduced significantly 1 and 3 months after pacing therapy (both P<0.05). The mid-systolic mitral regurgitation reduced immediately after pacing (P<0.05) and was sustained throughout the pacing period. The benefit was maintained partially during the first week after pacing was suspended. The dP/dt increased progressively and was significant after 3 months of pacing (P<0.01). The benefit was lost gradually on cessation of pacing. The isovolumic contraction time was reduced only during the period of biventricular pacing. The MPI improved gradually over the 3-month period and began to return to baseline values as soon as pacing was stopped (Tables 1 and 2 and Figure 1).

View this table: [in this window] [in a new window]   Table 2. Serial Changes in Doppler Echocardiographic Parameters After Biventricular Pacing in 25 Patients With Heart Failure

For diastolic function (Table 2), 4 patients with initial total fusion of early diastolic and atrial filling changed to an abnormal relaxation pattern (reversed early and atrial filling velocity ratio and deceleration time >240 ms) after optimization of atrioventricular interval. The LV filling time was significantly increased after optimization of atrioventricular interval (P<0.05). Cessation of biventricular pacing was associated with immediate loss of such benefit. There was no change in isovolumic relaxation time, ejection time, and deceleration time attributable to biventricular pacing (Table 2 and Figure 1).

Intraventricular Synchrony
Using TDI, there was marked segmental variation in T_S before pacing, being earliest in the basal anteroseptal segment and latest in the basal lateral segment (148±25 versus 216±52 ms, P<0.01). After biventricular pacing therapy, the difference in T_S between the 2 regions was abolished (191±32 versus 213±44 ms, P=NS) (Figures 2 and 3). There was also marked regional variation in the T_S among all the LV segments at baseline (ANOVA P<0.05), which was abolished after pacing therapy (ANOVA P=NS) (Figure 2). As illustrated in Figure 2, all segments had T_S delayed after biventricular pacing and were significant in the basal anteroseptal, basal posterior, basal anterior, midanteroseptal, and midlateral segments when compared with the corresponding values at baseline (all P<0.05). In some patients with left bundle branch block and paradoxical septum motion in systole, the T_S was delayed before pacing. This was corrected by abolishing the abnormal septal motion together with delaying the lateral wall contraction by pacing therapy (Figure 3). Therefore, biventricular pacing improved the synchronicity of the LV by delaying the T_S in segments with initially early peak sustained systolic contraction so that all the regions of the LV had synchronized systolic contraction, albeit slightly and simultaneously delayed.

View larger version (18K): [in this window] [in a new window]   Figure 2. Changes in the time to peak regional sustained systolic contraction (TS) before () and after () biventricular pacing. At baseline, there was marked regional variation in TS among the left ventricular segments and between the left and right ventricles. The TS was earliest in the basal anteroseptal segment and latest in the basal lateral segment. After biventricular pacing therapy, the TS was homogeneously delayed to a timing close to that of the basal lateral segment so that regional variation in TS was abolished. *P<0.05 vs basal anteroseptal segment at baseline. P<0.05 when comparing the same segment before and after pacing therapy. B indicates basal; M, mid; A, anterior; AS, anteroseptal; I, inferior; L, lateral; P, posterior; S, septal; and RV, right ventricular.

View larger version (48K): [in this window] [in a new window]   Figure 3. Regional myocardial velocity curves obtained by tissue Doppler imaging at the basal septal (yellow) and basal lateral (green) segments. In the color two-dimensional pictures, movement of the myocardium toward the probe (during contraction) is shown in red, whereas movement away from the probe (during relaxation) is shown in blue. A, In a patient with left bundle branch block, there was delay in the onset and peak sustained systolic contraction (SM) in the lateral compared with the septal wall. Regional contraction occurred in a haphazard manner in various segments as illustrated by the patchy areas of blue colors (arrowheads). B, After biventricular pacing, there was dramatic improvement in the synchronicity, as reflected by the overlapping of velocity curves in the basal septal and basal lateral segments and the homogenous red color in the two-dimensional picture. C, Another patient with left bundle branch block had systolic paradoxical septal motion resulting in significant delay in peak SM in the septal relative to the lateral wall (arrowheads). D, After biventricular pacing therapy, systolic synchronicity was achieved, as reflected by the superimposition of the myocardial velocity curves and the uniformity of red color in the two-dimensional picture.

When the T_S-SD was compared in the LV, it was significantly shorter after biventricular pacing for 3 months than baseline (37.7±10.9 versus 29.3±8.3 ms, P<0.05). When pacing was stopped and TDI was repeated immediately, the T_S-SD was increased again (41.1±11.8 ms, P<0.01 versus 3 months) and remained abnormal 4 weeks after pacing was stopped (37.8±10.6 ms, P<0.05 versus 3 months). There was no significant change in the regional S_M or the amplitude of regional long-axis displacement before and after biventricular pacing therapy (Table 3).

View this table: [in this window] [in a new window]   Table 3. Comparison of Peak Regional Sustained Systolic Velocities (SM) and Maximal Regional Long-Axis Systolic Displacement (Disp) of the Heart Before and 3 Months After Biventricular Pacing

Interventricular Synchrony
At baseline, the T_S at the basal right ventricular segment was comparable to the basal septal segment (septal, 185±33 versus right ventricular, 182±37 ms; P=NS) but was significantly earlier than the basal lateral segment (216±52 ms, P<0.05). After biventricular pacing, the difference in T_S between the 2 segments was abolished (right ventricular, 206±54 versus lateral, 214±64 ms; P=NS).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study documents the effectiveness of synchronous biventricular pacing to induce LV reverse remodeling in patients with advanced heart failure. There was also improvement of systolic function, reduction of mitral regurgitation, increase in diastolic filling time, and improvement of clinical status. Mechanistically, the benefits are attributable to an improvement in intraventricular and interventricular synchrony as well as to a shortening of isovolumic contraction time. The observed benefits were lost in various speeds when pacing was stopped.

LV Reverse Remodeling After Biventricular Pacing
Prevention of cardiac remodeling improves prognosis in heart failure.⁹ The present study confirms the previous observation that biventricular pacing can result in reverse remodeling,^10,23 and the changes are associated with improvement in cardiac function. However, it was not known how LV volume might change if pacing was withdrawn. This study found that LV volume increased gradually over 4 weeks after cessation of biventricular pacing. In addition, other echocardiographic benefits were also lost with time. The improvement in diastolic filling time, isovolumic contraction time, and MPI, which were largely dependent on the control of atrioventricular internal, were lost immediately. The benefits on ejection fraction and cardiac output were lost gradually over 4 weeks. These observations provide strong evidence that pacing is the cause of LV remodeling. The present study additionally confirmed the previous observations that systolic function and clinical status were improved, as supported by the gain in ejection fraction, dP/dt, MPI, 6-minute hall-walk distance, and quality of life score.^6,7,10 Furthermore, the improvements in quality of life score and walking distance were maintained for at least 4 weeks after pacing was suspended. This may indicate that the onset and offset of clinical benefits have a time lag, and a longer period of follow-up is needed before the loss of clinical benefit is observed.

Cardiac Resynchronization by Biventricular Pacing
Prolongation of QRS duration has been described in patients with heart failure and is an indicator of increased mortality.²⁴ This is likely attributable to dyssynchronous LV systolic movement, as demonstrated by a tagged MRI study in patients with dilated cardiomyopathy.¹¹ However, improvement of cardiac synchronicity has not been demonstrated objectively after pacing therapy. Using TDI, we demonstrated the presence of LV systolic dyssynchrony in patients before pacing therapy by the significant regional difference in T_S and the marked increase in T_S-SD among the 12 LV segments. The improvement of intraventricular synchronicity after biventricular pacing was reflected by the loss of regional difference in T_S as well as the significant reduction in T_S-SD. Interestingly, biventricular pacing improves LV synchronicity by homogeneously delaying those sites with early peak systolic contraction, in particular in the anteroseptal, septal, inferior, and posterior segments, causing all segments to contract late with respect to the QRS onset but simultaneously with respect to each other. Nonetheless, as illustrated in Figure 3, some patients actually had paradoxical septal motion so that sustained systolic contraction is earlier in the lateral wall. In this situation, biventricular pacing helps by abolishing the abnormal septal motion together with delaying the T_S in the lateral wall so that synchronicity was successfully achieved. Therefore, biventricular pacing improves LV synchronicity not by early preexcitation of the lateral wall but by ensuring a delayed, yet synchronous, contraction. In the right ventricle, there was also delay in the T_S to a magnitude similar to that of the septum during biventricular pacing, resulting in simultaneous peak contraction with the LV; ie, interventricular synchrony is also achieved. Because the segmental peak systolic velocities and the regional long-axis systolic displacement were not changed during biventricular pacing, this finding suggests that biventricular pacing has no direct inotropic effect on the failing heart. This is consistent with the recent finding that biventricular pacing did not increase the energy consumption of the heart²⁵; rather, it ensures improved ejection fraction through a more efficiently contracting ventricle.

Other Mechanisms of Benefit by Biventricular Pacing
One of the findings in this study was the shortening of isovolumic contraction time during biventricular pacing, without change in ejection time and isovolumic relaxation time. More precisely, this is actually the wasted presystolic time after atrial filling is completed but before mitral valve closure. With atrioventricular interval optimized by Doppler echocardiography, there was forced closure of the mitral valve immediately after atrial filling was completed, hence the presystolic time was abolished.¹³ As a result, diastolic filling time was increased and the fusion of early and late diastolic filling was reduced. The midsystolic mitral regurgitation was also improved, probably as a result of improved synchronicity that reduced the distortion of mitral apparatus during contraction.

The proposed mechanisms of improvement in intraventricular synchrony, atrioventricular synchrony, and interventricular synchrony are summarized in Figure 4. As this study was conducted in a relatively short duration, the long-term benefits need to be prospectively assessed by additional studies. In addition, whether reverse remodeling induced by biventricular pacing therapy will improve the prognosis of heart failure, as is seen in pharmacological therapy, needs to be addressed by large-scale, multicenter studies.

View larger version (27K): [in this window] [in a new window]   Figure 4. Proposed mechanisms of benefit of biventricular pacing. The major mechanism is by delaying the TS in the left ventricular (LV) segments so that intraventricular synchrony is improved. As a result of improved synchrony, systole becomes more effective, and ejection fraction (EF), cardiac output (CO), and other parameters of cardiac function are improved. Left ventricular end-systolic volume (LVESV) is reduced. By synchronizing the contraction, mechanical mitral regurgitation (MR) attributable to distortion of mitral apparatus in the presence of dyssynchrony and left atrial (LA) pressure is reduced. As a result, LV end-diastolic pressure and volume (LVEDV) are decreased. A second mechanism is the shortening of isovolumic contraction time (IVCT) after optimization of atrioventricular delay. The effective diastolic filling time is increased, which, in turn, increases the stroke volume. A less important mechanism is the improvement of interventricular synchrony between the left and right (RV) ventricles. This benefit may mediate through ventricular interdependence. This results in the gain in RV cardiac output and, hence, the LV filling is augmented. The end effect of reverse remodeling will additionally improve cardiac synchrony and decrease secondary mitral regurgitation, forming a positive feedback loop.

	Acknowledgments

 
The work was supported by a research grant from Medtronic, Inc.

Received October 3, 2001; revision received November 2, 2001; accepted November 6, 2001.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Daubert JC, Ritter P, Le Breton H, et al. Permanent left ventricular pacing with transvenous leads inserted into the coronary veins. Pacing Clin Electrophysiol. 1998; 21: 239–245.[CrossRef][Medline] [Order article via Infotrieve]
   
2. Gibson DG, Chamberlain DA, Coltart DJ, et al. Effect of changes in ventricular activation on cardiac haemodynamics in man: comparison of right ventricular, left ventricular, and simultaneous pacing of both ventricles. Br Heart J. 1971; 33: 397–400.[Free Full Text]
   
3. Leclercq C, Cazeau S, Le Breton H, et al. Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol. 1998; 32: 1825–1831.[Abstract/Free Full Text]
   
4. Auricchio A, Stellbrink C, Block M, et al. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure: the Pacing Therapies for Congestive Heart Failure Study Group. The Guidant Congestive Heart Failure Research Group. Circulation. 1999; 99: 2993–3001.[Abstract/Free Full Text]
   
5. Kass DA, Chen CH, Curry C, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation. 1999; 99: 1567–1573.[Abstract/Free Full Text]
   
6. Gras D, Mabo P, Tang T, et al. Multisite pacing as a supplemental treatment of congestive heart failure: preliminary results of the Medtronic Inc in sync study pacing. Clin Electrophysiol. 1998; 21: 2249–2255.
   
7. Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med. 2001; 344: 873–880.[Abstract/Free Full Text]
   
8. Lee TH, Hamilton MA, Stevenson LW, et al. Impact of left ventricular cavity size on survival in advanced heart failure. Am J Cardiol. 1993; 72: 672–676.[CrossRef][Medline] [Order article via Infotrieve]
   
9. Konstam MA, Rousseau MF, Kronenberg MW, et al. Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dysfunction in patients with heart failure: SOLVD Investigators. Circulation. 1992; 86: 431–438.[Abstract/Free Full Text]
   
10. Lau CP, Yu CM, Chau E, et al. Reversal of left ventricular remodeling by synchronous biventricular pacing in heart failure. Pacing Clin Electrophysiol. 2000; 23: 1722–1725.[Medline] [Order article via Infotrieve]
    
11. Nelson GS, Curry CW, Wyman BT, et al. Predictors of systolic augmentation from left ventricular preexcitation in patients with dilated cardiomyopathy and intraventricular conduction delay. Circulation. 2000; 101: 2703–2709.[Abstract/Free Full Text]
    
12. Pai RG, Gill KS. Amplitudes, durations, and timings of apically directed left ventricular myocardial velocities, I: their normal pattern and coupling to ventricular filling and ejection. J Am Soc Echocardiogr. 1998; 11: 105–111.[CrossRef][Medline] [Order article via Infotrieve]
    
13. Kindermann M, Frohlig G, Doerr T, et al. Optimizing the AV delay in DDD pacemaker patients with high degree AV block: mitral valve Doppler versus impedance cardiography. Pacing Clin Electrophysiol. 1997; 20: 2453–2462.[CrossRef][Medline] [Order article via Infotrieve]
    
14. Yu CM, Sanderson JE, Shum IO, et al. Diastolic dysfunction and natriuretic peptides in systolic heart failure: higher ANP and BNP levels are associated with the restrictive filling pattern. Eur Heart J. 1996; 17: 1694–1702.[Abstract/Free Full Text]
    
15. Bargiggia GS, Bertucci C, Recusani F, et al. A new method for estimating left ventricular dP/dt by continuous wave Doppler-echocardiography: validation studies at cardiac catheterization. Circulation. 1989; 80: 1287–1292.[Abstract/Free Full Text]
    
16. Tei C, Ling LH, Hodge DO, et al. 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.[Medline] [Order article via Infotrieve]
    
17. Miyatake K, Yamagishi M, Tanaka N, et al. New method for evaluating left ventricular wall motion by color-coded tissue Doppler imaging: in vitro and in vivo studies. J Am Coll Cardiol. 1995; 25: 717–724.[Abstract]
    
18. Yu CM, Wang Q, Lau CP, et al. Reversible impairment of left and right ventricular systolic and diastolic function during short-lasting atrial fibrillation in patients with an implantable atrial defibrillator: a tissue Doppler imaging study. Pacing Clin Electrophysiol. 2001; 24: 979–988.[CrossRef][Medline] [Order article via Infotrieve]
    
19. Fleming AD, McDicken WN, Sutherland GR, et al. Assessment of colour Doppler tissue imaging using test-phantoms. Ultrasound Med Biol. 1994; 20: 937–951.[CrossRef][Medline] [Order article via Infotrieve]
    
20. Naito J, Masuyama T, Mano T, et al. Validation of transthoracic myocardial ultrasonic tissue characterization: comparison of transthoracic and open-chest measurements of integrated backscatter. Ultrasound Med Biol. 1995; 21: 33–40.[CrossRef][Medline] [Order article via Infotrieve]
    
21. Rodriguez L, Garcia M, Ares M, et al. Assessment of mitral annular dynamics during diastole by Doppler tissue imaging: comparison with mitral Doppler inflow in subjects without heart disease and in patients with left ventricular hypertrophy. Am Heart J. 1996; 131: 982–987.[CrossRef][Medline] [Order article via Infotrieve]
    
22. Yu CM, Lau CP, Tang AS. Case report: resolution of pulsus alternans by synchronous atrio-biventricular pacing. J Interven Cardiol Electrophysiol. 2000; 4: 595–597.
    
23. Porciani MC, Puglisi A, Colella A, et al. Echocardiographic evaluation of the effect of biventricular pacing: the InSync Italian Registry. Eur Heart J. 2000; 2 (suppl J): J23–J30.
    
24. Aaronson KD, Schwartz JS, Chen TM, et al. Development and prospective validation of a clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation. Circulation. 1997; 95: 2660–2667.[Abstract/Free Full Text]
    
25. Nelson GS, Berger RD, Fetics BJ, et al. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation. 2000; 102: 3053–3059.[Abstract/Free Full Text]
    

This article has been cited by other articles:

				P. Lim, A. Buakhamsri, Z. B. Popovic, N. L. Greenberg, D. Patel, J. D. Thomas, and R. A. Grimm Longitudinal Strain Delay Index by Speckle Tracking Imaging: A New Marker of Response to Cardiac Resynchronization Therapy Circulation, September 9, 2008; 118(11): 1130 - 1137. [Abstract] [Full Text] [PDF]

				S-A Chang, H-K Kim, H-Y Lee, S-Y Choi, B-K Koo, Y-J Kim, D-W Sohn, B-H Oh, Y-B Park, Y-S Choi, et al. Restoration of left ventricular synchronous contraction after acute myocardial infarction by stem cell therapy: new insights into the therapeutic implication of stem cell therapy for acute myocardial infarction Heart, August 1, 2008; 94(8): 995 - 1001. [Abstract] [Full Text] [PDF]

				M Marciniak, B Bijnens, A Baltabaeva, A Marciniak, C Parsai, P Claus, and G R Sutherland Interventricular interaction as a possible mechanism for the presence of a biphasic systolic velocity profile in normal left ventricular free walls Heart, August 1, 2008; 94(8): 1058 - 1064. [Abstract] [Full Text] [PDF]

				N R Van de Veire, J De Sutter, J J Bax, and J R T C Roelandt Technological advances in tissue Doppler imaging echocardiography Heart, August 1, 2008; 94(8): 1065 - 1074. [Abstract] [Full Text] [PDF]

				C. Miyazaki, G. Lin, B. D. Powell, R. E. Espinosa, C. J. Bruce, F. A. Miller Jr, B. L. Karon, R. F. Rea, D. L. Hayes, and J. K. Oh Strain Dyssynchrony Index Correlates With Improvement in Left Ventricular Volume After Cardiac Resynchronization Therapy Better Than Tissue Velocity Dyssynchrony Indexes Circ Cardiovasc Imaging, July 1, 2008; 1(1): 14 - 22. [Abstract] [Full Text] [PDF]

				S. De Castro, F. Faletra, E. Di Angelantonio, C. Conca, A. Marcantonio, M. Francone, D. Cartoni, F. Mirabelli, C. Gaudio, S. Caselli, et al. Tomographic Left Ventricular Volumetric Emptying Analysis by Real-Time 3-Dimensional Echocardiography: Influence of Left Ventricular Dysfunction With and Without Electrical Dyssynchrony Circ Cardiovasc Imaging, July 1, 2008; 1(1): 41 - 49. [Abstract] [Full Text] [PDF]

				F. W. Prinzen and A. Auricchio Is echocardiographic assessment of dyssynchrony useful to select candidates for cardiac resynchronization therapy?: Echocardiography Is Not Useful Before Cardiac Resynchronization Therapy if QRS Duration Is Available Circ Cardiovasc Imaging, July 1, 2008; 1(1): 70 - 78. [Full Text] [PDF]

				J. W H Fung, G. W K Yip, and C.-M. Yu Does atrial fibrillation preclude biventricular pacing? Heart, July 1, 2008; 94(7): 826 - 827. [Full Text] [PDF]

				A. H.M. Jansen, F. Bracke, J. m. van Dantzig, K. H. Peels, J. C. Post, H. C.M. van den Bosch, B. van Gelder, A. Meijer, H. H.M. Korsten, J. de Vries, et al. The influence of myocardial scar and dyssynchrony on reverse remodeling in cardiac resynchronization therapy Eur J Echocardiogr, July 1, 2008; 9(4): 483 - 488. [Abstract] [Full Text] [PDF]

				S. Y. Hayashi, A. Seeberger, B. Lind, J. Nowak, M. M. do Nascimento, B. Lindholm, and L.-A. Brodin A single session of haemodialysis improves left ventricular synchronicity in patients with end-stage renal disease: a pilot tissue synchronization imaging study Nephrol. Dial. Transplant., June 13, 2008; (2008) gfn311v1. [Abstract] [Full Text] [PDF]

				M. O. Sweeney and F. W. Prinzen Ventricular Pump Function and Pacing: Physiological and Clinical Integration Circ Arrhythmia Electrophysiol, June 1, 2008; 1(2): 127 - 139. [Full Text] [PDF]

				V. Delgado, C. Ypenburg, R. J. van Bommel, L. F. Tops, S. A. Mollema, N. A. Marsan, G. B. Bleeker, M. J. Schalij, and J. J. Bax Assessment of Left Ventricular Dyssynchrony by Speckle Tracking Strain Imaging: Comparison Between Longitudinal, Circumferential, and Radial Strain in Cardiac Resynchronization Therapy J. Am. Coll. Cardiol., May 20, 2008; 51(20): 1944 - 1952. [Abstract] [Full Text] [PDF]

				C. Miyazaki, B. D. Powell, C. J. Bruce, R. E. Espinosa, M. M. Redfield, F. A. Miller, D. L. Hayes, Y.-M. Cha, and J. K. Oh Comparison of Echocardiographic Dyssynchrony Assessment by Tissue Velocity and Strain Imaging in Subjects With or Without Systolic Dysfunction and With or Without Left Bundle-Branch Block Circulation, May 20, 2008; 117(20): 2617 - 2625. [Abstract] [Full Text] [PDF]

				A. K. Bilge, B. Ozben, T. Ozyigit, D. Acar, D. Hunerel, K. Adalet, and Y. Nisanci Assessment of Early Changes in the Segmental Functions of the Left and the Right Ventricles After Biventricular Pacing in Heart Failure: A Study With Tissue Doppler Imaging Angiology, May 1, 2008; 59(2): 179 - 184. [Abstract] [PDF]

				F. Zanon, E. Bacchiega, L. Rampin, S. Aggio, E. Baracca, G. Pastore, T. Marotta, G. Corbucci, L. Roncon, D. Rubello, et al. Direct His bundle pacing preserves coronary perfusion compared with right ventricular apical pacing: a prospective, cross-over mid-term study Europace, May 1, 2008; 10(5): 580 - 587. [Abstract] [Full Text] [PDF]

				L. J. Anderson, C. Miyazaki, G. R. Sutherland, and J. K. Oh Patient Selection and Echocardiographic Assessment of Dyssynchrony in Cardiac Resynchronization Therapy Circulation, April 15, 2008; 117(15): 2009 - 2023. [Full Text] [PDF]

				M. Brignole, D. Oddone, R. Maggi, G. Lupi, R. Bollini, S. Corallo, S. Robotti, A. Solano, P. Donateo, and F. Croci Resynchronization of the left ventricular contraction by tailored programming of right and left ventricular pacing Europace, April 1, 2008; 10(4): 489 - 495. [Abstract] [Full Text] [PDF]

				K. Chakir, S. K. Daya, R. S. Tunin, R. H. Helm, M. J. Byrne, V. L. Dimaano, A. C. Lardo, T. P. Abraham, G. F. Tomaselli, and D. A. Kass Reversal of Global Apoptosis and Regional Stress Kinase Activation by Cardiac Resynchronization Circulation, March 18, 2008; 117(11): 1369 - 1377. [Abstract] [Full Text] [PDF]

				N R Van de Veire, C-M Yu, N Ajmone-Marsan, G B Bleeker, C Ypenburg, J De Sutter, Q Zhang, J W H Fung, J Y S Chan, E R Holman, et al. Triplane tissue Doppler imaging: a novel three-dimensional imaging modality that predicts reverse left ventricular remodelling after cardiac resynchronisation therapy Heart, March 1, 2008; 94(3): e9 - e9. [Abstract] [Full Text] [PDF]

				T. Inage, T. Yoshida, T. Hiraki, M. Ohe, T. Takeuchi, Y. Nagamoto, Y. Fukuda, T. Gondo, and T. Imaizumi Chronic cardiac resynchronization therapy reverses cardiac remodelling and improves invasive haemodynamics of patients with severe heart failure on optimal medical treatment Europace, March 1, 2008; 10(3): 379 - 383. [Abstract] [Full Text] [PDF]

				J. G. Delfino, K. R. Johnson, R. L. Eisner, S. Eder, A. R. Leon, and J. N. Oshinski Three-directional Myocardial Phase-Contrast Tissue Velocity MR Imaging with Navigator-Echo Gating: In Vivo and in Vitro Study Radiology, March 1, 2008; 246(3): 917 - 925. [Abstract] [Full Text] [PDF]

				P. Bordachar, L. Labrousse, J.-B. Thambo, P. Reant, S. Lafitte, M. D. O'Neill, P. Jais, M. Haissaguerre, J. Clementy, and P. Dos Santos Haemodynamic impact of the left ventricular pacing site during graded ischaemia in an open-chest pig model Europace, February 1, 2008; 10(2): 242 - 248. [Abstract] [Full Text] [PDF]

D. A. Kass An epidemic of dyssynchrony: but what does it mean? J. Am. Coll. Cardiol., January 1, 2008; 51(1): 12 - 17.