This Article Abstract Figures Only Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stellbrink, C. Articles by Spinelli, J. Search for Related Content PubMed PubMed Citation Articles by Stellbrink, C. Articles by Spinelli, J.

CLINICAL STUDY: HEART FAILURE

Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances¹

^a Department of Cardiology, RWTH University of Technology, Aachen, Germany;
^b Department of Cardiology, University Hospital, Essen, Germany;
^c Heart Lung Institute, University Hospital, Utrecht, The Netherlands;
^d Department of Cardiology, University Hospital, Magdeburg, Germany;
^e Guidant Corporation, Brussels, Belgium
^f Guidant Corporation, St. Paul, Minnesota, USA

Manuscript received January 17, 2001; revised manuscript received August 13, 2001, accepted August 22, 2001.

^* Reprint requests and correspondence: Dr. Christoph Stellbrink, Medizinische Klinik I, RWTH Aachen, Pauwelsstrasse 30, D-52057 Aachen, Germany.
Christoph.Stellbrink{at}post.rwth-aachen.de

	Abstract

Top Abstract Methods Results Discussion References

 
OBJECTIVES: We sought to investigate the impact of six months of cardiac resynchronization therapy (CRT) on echocardiographic variables of left ventricular (LV) function.

BACKGROUND: Cardiac resynchronization therapy has recently been introduced as a new therapeutic modality in patients with advanced heart failure (HF) and conduction abnormalities. However, most studies have only investigated the early hemodynamic effects of CRT.

METHODS: Twenty-five patients (12 women and 13 men; 59.8 ± 5.1 years old) with advanced HF caused by ischemic (n = 7) or idiopathic dilated cardiomyopathy (n = 18) and a prolonged QRS complex were analyzed. All patients underwent early hemodynamic testing with a randomized testing protocol; echocardiographic measurements were compared before implantation and after six months of CRT.

RESULTS: Left ventricular end-diastolic and end-systolic diameters (LVEDD and LVESD, respectively) were significantly reduced after six months (LVEDD from 71 ± 10 to 68 ± 11 mm, p = 0.027; LVESD from 63 ± 11 to 58 ± 11 mm, p = 0.007), as were LV end-diastolic and end-systolic volumes (LVEDV from 253 ± 83 to 227 ± 112 ml, p = 0.017; LVESV from 202 ± 79 to 174 ± 101 ml, p = 0.009). Ejection fraction was significantly increased (from 22 ± 7% to 26 ± 9%, p = 0.03). "Nonresponders," with regard to LV volume reduction, had significantly higher baseline LVEDV, compared with "responders" (351 ± 52 vs. 234 ± 74 ml, p = 0.018). Overall, there was only mild mitral regurgitation at baseline, with a minor reduction by semiquantitative analysis. The results of early hemodynamic testing did not predict the volume response.

CONCLUSIONS: Cardiac resynchronization therapy may lead to a reduction in LV volumes in patients with advanced HF and conduction disturbances. Volume nonresponders have significantly higher baseline LVEDV.

Abbreviations and Acronyms   BV   biventricular   CRT   cardiac resynchronization therapy   HF   heart failure   LVEDD   left ventricular end-diastolic diameter   LVEDV   left ventricular end-diastolic volume   LVESD   left ventricular end-systolic diameter   LVESV   left ventricular end-systolic volume   EF   ejection fraction   LV   left ventricular   MR   mitral regurgitation   RV   right ventricular

	Methods

Top Abstract Methods Results Discussion References

 
Patient group and study design.   The PAcing THerapies in Congestive Heart Failure (PATH-CHF) study included 42 patients. All patients gave written, informed consent to take part in the study, which was performed in compliance with the Human Studies Committee of each institution. The design and inclusion and exclusion criteria of the study have been described previously (6). In brief, patients with HF of both ischemic and nonischemic origin were included if they were in New York Heart Association (NYHA) functional class III or IV HF and had sinus rhythm, a PR interval 150 ms and a QRS width >120 ms in at least two surface electrocardiographic (ECG) leads. QRS durations were automatically measured as the maximum of leads II, V₁ and V₆ and validated manually by two independent observers. All patients underwent implantation of two separate DDD pacemakers—one connected to a right atrial and right ventricular (RV) screw-in pacing lead (Sweet-Tip, Guidant Corp.) and the other connected to another right atrial and epicardial LV pacing lead (model 4316, Guidant Corp., or model 4965, Medtronic)—by a limited thoracotomy. This configuration allowed for a change of the pacing site from RV to LV and BV pacing both during implantation and at long-term follow-up. Biventricular pacing was achieved by programming one device in the VDD mode and the second device in the ventricular triggered mode (VVT).

Early hemodynamic testing
All patients underwent early hemodynamic testing during pacemaker implantation, under general anesthesia. Two 8F dual-transducer pressure catheters (model SPC-780c, Millar Instruments) were placed to measure the right atrial, RV, LV and aortic pressures. Pressure catheters and pacing leads were connected to a customized external pacing computer (FlexStim, Guidant Corp.) to acquire hemodynamic signals and execute an early pacing protocol (FlexStim protocol) (6). The FlexStim protocol is designed to measure the immediate effects of pacing, account for local baseline shifts and allow statistical comparison of multiple pacing combinations within individuals. Briefly, the RV, LV or both ventricles were stimulated in the VDD mode at one of five atrioventricular delays preset to a percentage of the patient’s intrinsic PR interval, as measured with the pacing leads. Each combination of pacing chamber and atrioventricular delay was randomly repeated five times by pacing for five beats separated by 15 nonpaced beats. The hemodynamic variables used to determine the optimized pacing mode were the changes in aortic pulse pressure and maximal upward slope of the LV systolic pressure curve (+dP/dt) (2).

Pacing protocol
For intra-individual comparisons of the primary end point of the trial—improvement of functional capacity (6)—patients were randomized to one month of optimized univentricular or BV pacing followed by one month of no pacing. During the third month, patients were crossed over to the other pacing mode. After three months, all patients were paced in the mode with the optimal early response during intra-operative testing. The functional status of the patient was assessed by a physician who had no knowledge of the pacing mode before implantation and after six months. Twenty-five patients (13 men and 12 women; 60 ± 5 years old) were analyzed; 17 patients had to be excluded for the following reasons: 4 patients died (1 due to sudden cardiac death, 1 due to nonsudden cardiac death, 1 due to liver cancer, 1 postoperatively [this patient was later classified as having an inclusion criteria violation, according to the Data Safety Monitoring Committee, because of an underestimated aortic stenosis]); 1 patient was in atrial fibrillation at the six-month follow-up; 1 patient underwent cardiac transplantation; 3 patients were not effectively paced because of an increased LV pacing threshold; and 1 patient withdrew consent. In the remaining seven patients, either one of the echocardiograms was judged as insufficient for reliable analysis by one or both independent observers.

Echocardiographic measurements
Transthoracic echocardiography was performed shortly before pacemaker implantation during intrinsic conduction and after six months when patients were paced with the optimal mode and settings. Left atrial and LV diameters were determined using M-mode echocardiography under two-dimensional guidance in the parasternal long-axis view, according to the guidelines of the American Society of Echocardiography (7). Left ventricular mass was calculated according to the Penn convention (8). The end of diastole was defined by the onset of the QRS complex in the simultaneously recorded ECG; the end of systole was defined by the smallest cavity area before mitral valve closure. For measurement of LV end-systolic and end-diastolic dimensions (LVEDD and LVESD, respectively), images were obtained in the apical two- and four-chamber views. Percent fractional shortening was calculated as: . Longitudinal and transverse LV diameters were measured in the apical four-chamber view at end diastole, and the sphericity index was calculated as the LV transverse diameter/longitudinal diameter ratio (9). Biplane LV end-systolic and end-diastolic volumes (LVESV and LVEDV, respectively) were calculated from the two-chamber and four-chamber views, according to the modified Simpson’s rule (10); measurements were averaged from three cardiac cycles. Left ventricular EF was calculated as: . Patients were classified as volume "responders" if LVESV decreased by >15%, as "stable" if LVESV changes were 15% and as "nonresponders" if LVESV increased by >15%, based on data showing a variability of 15% for repeated volume calculations derived from two-dimensional echocardiographic measurements (11). For statistical analysis, responders and stable patients were analyzed as one group, because both reduced and stable volumes were regarded as a positive clinical response to CRT. Mitral regurgitation (MR) was semiquantitatively graded on a 4-point scale (grades 0 to 3) using color-coded Doppler signals, as previously described (12), and the maximal jet area was measured in the parasternal and apical views (13). All examinations were recorded, stored on videotape and analyzed at the responsible core center (RWTH University of Technology, Aachen, Germany). Final analysis was performed off-line (from videotape) by two independent observers, after manual recalibration on a Hewlett-Packard Sonos 2500 ultrasound scanner.

Concomitant drug treatment
Patients had to be in stable NYHA functional class III HF without a change in medication or in class IV without the need for intravenous inotropic drugs during the last month to be eligible for study inclusion. Of the 25 patients, 24 (96%) were taking angiotensin-converting enzyme inhibitors, 22 (88%) were receiving digitalis, and 11 (44%) were receiving nitrates. Of 14 patients (56%) initially taking beta-blockers, the dosage was constant in nine, reduced in two and increased in three after six months. In only one patient was a beta-blocker started during the study period. Of 24 patients (96%) taking diuretics before implantation, the dosage was kept constant in 12, reduced in 10 and increased in two. One patient began to receive diuretics during the six-month period, whereas diuretics were withdrawn in one patient.

Statistical analysis
The statistical methods used for analysis of the invasively measured hemodynamic variables have been described elsewhere (2). In brief, relative changes of +dP/dt and pulse pressure (%) in the second to fifth paced beats of each run of five paced beats were compared with the average value during the immediately preceding six nonpaced beats. A paired t test was used to evaluate the effects of pacing compared with no pacing. Cardiac dimensions and volumes were compared intra-individually by using a paired t test. Baseline volumes were compared with early changes in +dP/dt and pulse pressure by using linear regression analysis. All numeric data are expressed as the mean value ± SD. A p value <0.05 was considered significant. Inter-observer and intra-observer variabilities were defined as the difference of measurements between two observers, expressed as the percent difference (± SD) of the first observer.

	Results

Top Abstract Methods Results Discussion References

 
Baseline evaluation.   Table 1 shows the clinical data of the 25 analyzed patients. The ECG pattern of intraventricular conduction delay was classified as left bundle branch block (LBBB) type in 21 patients (84%), right bundle branch block type in one patient (4%) and intraventricular conduction delay in three patients (12%), according to previously published criteria (14). The optimal pacing site was BV in 12 (48%), LV in 10 (40%) and RV in 3 patients (12%). The mean NYHA functional class improved from 3.0 ± 0.1 at baseline to 1.9 ± 0.7 after six months of CRT, with no difference between volume responders and stable patients (n = 21; from 3.0 ± 0.2 to 1.9 ± 0.7) and volume nonresponders (n = 4; from 3.0 ± 0 to 2.1 ± 0.9; p = NS).

View larger version (97K): [in this window] [in a new window]   Figure 1 These end-diastolic echocardiographic images were obtained in the apical four-chamber view before device implantation (left) and after six months of CRT (right), where a volume reduction is demonstrated. The endocardial borders were manually delineated, and the LV cavity area surrounded by these borders was used for LV volume calculation, as explained in the text. Note the reduction in end-diastolic volume and the reduced sphericity of the LV shape in the right image.

View larger version (22K): [in this window] [in a new window]   Figure 2 A comparison of LVEDV (A) and LVESV (B) before pacemaker implantation and after six months of hemodynamically optimized pacing. There was a significant decrease in both volumes after six months.

View larger version (20K): [in this window] [in a new window]   Figure 3 A comparison of echocardiographically determined EF before pacemaker implantation and after six months of hemodynamically optimized pacing. There was a small but significant increase in EF after six months.

Comparison of pre-implantation volumes, early hemodynamic responses and long-term volume responses
No correlation between baseline volumes and the early increase in either aortic pulse pressure or +dP/dt induced by CRT was observed (Fig. 4, A and B). Volume nonresponders were found among those with very large and only minimal early hemodynamic response.

View larger version (14K): [in this window] [in a new window]   Figure 4 Percent changes in +dP/dt (A) and pulse pressure (PP) (B), plotted against the baseline LVESV values, as determined by echocardiography. There was no correlation between early hemodynamic improvement in PP or +dP/dt and baseline LV volume. Moreover, long-term volume nonresponders (open circles) were found among high and low early hemodynamic responders (solid diamonds), both for PP and +dP/dt. Three volume nonresponders were among those patients with the highest early hemodynamic response.

	Discussion

Top Abstract Methods Results Discussion References

Effect on MR
Some investigators have speculated that LV-based pacing leads to a reduction in MR (19), which can be explained by 1) a reduction in presystolic MR by optimizing atrioventricular delay and 2) a reduction in systolic MR by improved coaptation of the valve leaflets, which may be impaired by delayed contraction of the anterolateral papillary muscle. The sphericity associated with LV dilation leads to functional MR (20); thus, reversal of this process may reduce MR. However, the degree of baseline MR in our study was low; thus, despite the fact that some reduction was noted, it seems unlikely that this was the prevailing mechanism for LV volume reduction.

Prediction of volume response
Some patients did not respond to CRT with a reduction in LV volumes, and the extent of the early hemodynamic response was not a good predictor of volume effects. In fact, three of four volume nonresponders were among those with the largest early hemodynamic improvement. Thus, other factors are involved in the reverse remodeling response to CRT, such as baseline geometry and LV size. The fact that volume nonresponders had a higher mean LVEDV is in concordance with data from drug trials indicating that nonresponders to pharmacologic therapy had higher baseline LVEDD values (21). However, our data do not yet allow for the conclusion that CRT is not indicated in very dilated hearts, because the positive early hemodynamic effects of CRT can still lead to symptomatic improvement despite the lack of volume reduction, as shown by a similar improvement in NYHA functional class in volume nonresponders. Moreover, we could not define a cut-off value above which a reduction in LV volumes can no longer be expected.

Interaction with drug treatment
A dose-related "reverse remodeling effect" in HF has been described for beta-blocker treatment (22,23). An additive effect of beta-blockers on volumes in our study cannot be completely ruled out, because there were more volume responders than nonresponders receiving beta-blocker therapy. However, patients were receiving stable drug therapy before study inclusion, and dose adjustments during the study were minor, as indicated by the lack of a significant change in heart rate. Moreover, recent data suggest that patients with a QRS width >120 ms, as in our study, are less likely to respond to beta-blocker therapy with an improvement in EF, compared with patients with a narrow QRS width (24). It is also noteworthy that 5 of 16 volume responders were not taking beta-blockers. We believe that CRT is complementary to beta-blockers because: 1) it leads to an improvement in exercise capacity (4), which has not been consistently shown for beta-blockers; 2) it minimizes the risk of bradyarrhythmias; and 3) it can be useful in the early treatment phase to overcome the initial negative inotropy and hypotension associated with beta-blockers. Cardiac resynchronization therapy is an attractive alternative to positive inotropic drug therapy for this purpose, because the hemodynamic benefit achieved by CRT is associated with a reduction in myocardial oxygen demand (25). The reason for this is a more efficient systolic contraction, which leads to a reduction in regional wall stress, because areas of delayed activation, such as the LV free wall in LBBB, are known to have greater regional wall stress (26). A reduction in both wall stress and oxygen demand with CRT can lead to a decrease in sympathetic nervous activation (27), which may contribute to a reduction in LV size.

Study limitations
The number of patients analyzed was small, and the changes observed need to be verified in larger patient cohorts. Because no control group was studied, a positive effect of the close medical follow-up, rather than CRT, cannot be ruled out. The cross-over period during the first three months after implantation may have affected the results because different pacing modes were used and patients were not paced during the second month. However, the differences in the early hemodynamic response between optimal univentricular (LV in most cases) and BV pacing were minor (2), and patients were constantly paced for the last four months before echocardiographic re-evaluation. Thus, we believe that the data are not invalidated by the cross-over period. The study was not designed to assess the impact of CRT on the severity of MR. Thus, no systematic, prospective evaluation of MR severity was performed. The modified Simpson’s rule was used for LV volume calculation, which may not be optimal for the spherical shape and asymmetrical contraction in the hearts examined. With the disco-ordinated contraction in LBBB, the smallest cavity area may not truly represent the end of systole, as late activated areas may still be contracting. Finally, echocardiographic data have not been correlated to functional variables.

Conclusions
The data of this study indicate that long-term CRT leads to a reduction in LV volumes in the majority of patients with advanced HF and ventricular conduction disturbances. Patients with higher baseline volumes are less likely to show a decrease in volume. The mechanisms leading to this "reverse remodeling" effect are incompletely understood, but may involve a reduction in regional wall stress, myocardial oxygen demand and functional MR. Further studies in larger patient cohorts are needed to more clearly define the clinical characteristics of patients who show reverse remodeling by CRT.

	Acknowledgments

 
The following centers and investigators participated in the PATH-CHF study (in alphabetical order of centers): University Hospital, Aachen, Germany: C. Stellbrink, B. Diem, O. A. Breithardt, F. A. Schöndube; University Hospital Skejky Sygehus Aarhus, Denmark: P. T. Mortensen, A. K. Pedersen; University Hospital, Essen, Germany: S. Sack, F. Heinzel, U. Wolfhard; University Hospital, Magdeburg, Germany: A. Auricchio (Principal Investigator), H. Klein, M. Kloss, T. Welte, C. Huth; University Hospital, Münster, Germany: M. Block, B. Lamp; Heart and Diabetes Center, Bad Oeynhausen, Germany: J. Vogt; University Hospital, Utrecht, The Netherlands: H. Kirkels, P. Bakker.

We are indebted to the patients who participated in this trial. We would also like to thank the nurses and technicians of the Heart Failure Program, Intensive Care Unit, Surgery and Pacemaker/ICD Clinic of each institution, without whose support this study would not have been possible.

	Footnotes

 
¹ The PAcing THerapies in Congestive Heart Failure (PATH-CHF) study was supported by a grant from the Guidant Corporation (St. Paul, Minnesota). Drs. Pochet, Salo, Kramer and Spinelli have corporate appointments with Guidant Corp.

² On behalf of the CPI Guidant Congestive Heart Failure Research Group.

³ On behalf of the PATH-CHF Investigators.

	References

Top Abstract Methods Results Discussion References

 

1. 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]
2. Auricchio A, Stellbrink C, Block M, et al. The effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation. 1999;99:2993–3001[Abstract/Free Full Text]
3. Blanc JJ, Etienne Y, Gilard M, et al. Evaluation of different ventricular pacing sites in patients with severe heart failure: Results of an acute hemodynamic study. Circulation. 1997;96:3273–3277[Abstract/Free Full Text]
4. the MUltisite Stimulation In Cardiomyopathies (MUSTIC) Study InvestigatorsCazeau 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]
5. St. John Sutton M, Pfeffer MA, Plappert T, et al. Quantitative echocardiographic measurements are major predictors of cardiovascular events after acute myocardial infarction: The protective effects of captopril. Circulation. 1994;89:68–75[Abstract/Free Full Text]
6. Auricchio A, Stellbrink C, Sack S, et al. The PAcing THerapies for Congestive Heart Failure (PATH CHF) Study: Rationale, design, and endpoints of a prospective randomized multicenter study. Am J Cardiol. 1999;83:130D–135D[CrossRef][Medline]
7. Sahn DJ, DeMaria AN, Kisslo J, Weyman AE. Recommendations regarding quantitation in M-mode echocardiography: Results of a survey of echocardiogrpahic measurements. Circulation. 1978;58:1072–1083[Abstract/Free Full Text]
8. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: Anatomic validation of the method. Circulation. 1977;55:613–618[Abstract/Free Full Text]
9. Douglas P, Morrow R, Ioli A, Reichek N. Left ventricular shape, afterload and survival in idiopathic dilated cardiomyopathy. J Am Coll Cardiol. 1989;13:311–315[Abstract]
10. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr. 1989;2:358–367[Medline]
11. Himelman RB, Cassidy MM, Landzberg JS, Schiller NB. Reproducibility of quantitative two-dimensional echocardiography. Am Heart J. 1988;115:425–431[CrossRef][Medline]
12. Miyatake K, Izumi S, Okamoto M, et al. Semiquantitative grading of severity of mitral regurgitation by real-time two-dimensional Doppler flow imaging technique. J Am Coll Cardiol. 1986;7:82–88[Abstract]
13. Spain MG, Smith MD, Grayburn PA, Harlamert EA, DeMaria AN. Quantitative assessment of mitral regurgitation by Doppler color flow imaging: Angiographic and hemodynamic correlations. J Am Coll Cardiol. 1989;3:585–590
14. the World Health Organizational/International Society and Federation for Cardiology Task Force Ad HocWillems JL, Robles de Medina EO, Bernard R, et al. Criteria for intraventricular conduction disturbances and pre-excitation. J Am Coll Cardiol. 1985;5:1261–1275[Abstract]
15. AbrahamWTReport from the MIRACLE (Multicenter Insync Randomnized Clinical Evaluation) study. Presented at the 22nd Annual Scientific Session of the North American Society of Pacing and Electrophysiology (NASPE) 2001 in Boston, USA
16. Dujardin KS, Enriquez-Sarano M, Rossi A, Bailey KR, Seward JB. Echocardiographic assessment of left ventricular remodeling: Are left ventricular diameters suitable tools? J Am Coll Cardiol. 1997;30:1534–1541[Abstract]
17. Laskey W, St. John Sutton M, Zeevi G, Hirshfeld J, Reichek N. Left ventricular mechanisms in dilated cardiomyopathy. Am J Cardiol. 1984;54:620–625[CrossRef][Medline]
18. Tischler MD, Niggel J, Borowski DT, LeWinter M. Relation between left ventricular shape and exercise capacity in patients with left ventricular dysfunction. J Am Coll Cardiol. 1993;22:751–757[Abstract]
19. Kim WY, Sogaard P, Mortensen PT, et al. Three-dimensional echocardiography documents haemodynamic improvement by biventricular pacing in patients with severe heart failure. Heart. 2001;85:514–520[Abstract/Free Full Text]
20. Kono T, Sabbah HN, Stein PD, Brymer JF, Khaja F. Left ventricular shape as a determinant of functional mitral regurgitation in patients with severe heart failure secondary to either coronary artery disease or idiopathic dilated cardiomyopathy. Am J Cardiol. 1991;68:355–359[CrossRef][Medline]
21. Levine TB, Levine AB, Bolenbaugh J, et al. Impact of left ventricular size on pharmacologic reverse remodeling in heart failure. Clin Cardiol. 2000;23:355–358[Medline]
22. Bristow MR, Gilbert EM, Abraham WT, et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. Circulation. 1996;94:2807–2816[Abstract/Free Full Text]
23. the Australia–New Zealand Heart Failure Research Collaborative GroupDoughty RN, Whalley GA, Gamble G, MacMahon S, Sharpe N. Left ventricular remodeling in patients with congestive heart failure due to ischemic heart disease. J Am Coll Cardiol. 1997;29:1060–1066[Abstract]
24. Baker C, Book WM, Martin R, Klein L, Causey RL, Smith AL. Narrow QRS diuration predicts improved ejection fraction on carvedilol. (abstr)J Card Failure. 2000;6(3 Suppl 2):228
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]
26. Prinzen FW, Hunter WC, Wyman BT, McVeigh ER. Mapping of regional myocardial strain and work during ventricular pacing: Experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol. 1999;33:1735–1742[Abstract/Free Full Text]
27. Hamdan MH, Zagrodzky JD, Joglar JA, et al. Biventricular pacing decreases sympathetic activity compared with right ventricular pacing in patients with reduced ejection fraction. Circulation. 2000;102:1027–1032[Abstract/Free Full Text]

This article has been cited by other articles:

				S. Gelsomino, R. Lorusso, C. Rostagno, S. Caciolli, G. Bille, G. De Cicco, S. Romagnoli, C. Porciani, P. Stefano, and G. F. Gensini Prognostic value of Doppler-derived mitral deceleration time on left ventricular reverse remodelling after undersized mitral annuloplasty Eur J Echocardiogr, September 1, 2008; 9(5): 631 - 640. [Abstract] [Full Text] [PDF]

				S. H. Lim, G. Y.H. Lip, and J. E. Sanderson Ventricular optimization of biventricular pacing: a systematic review Europace, August 1, 2008; 10(8): 901 - 906. [Abstract] [Full Text] [PDF]

				B. Kirn, A. Jansen, F. Bracke, B. van Gelder, T. Arts, and F. W. Prinzen Mechanical discoordination rather than dyssynchrony predicts reverse remodeling upon cardiac resynchronization Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H640 - H646. [Abstract] [Full Text] [PDF]

				A. E. Epstein, J. P. DiMarco, K. A. Ellenbogen, N.A. M. Estes III, R. A. Freedman, L. S. Gettes, A. M. Gillinov, G. Gregoratos, S. C. Hammill, D. L. Hayes, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons J. Am. Coll. Cardiol., May 27, 2008; 51(21): e1 - e62. [Full Text] [PDF]

				A. E. Epstein, J. P. DiMarco, K. A. Ellenbogen, N.A. M. Estes III, R. A. Freedman, L. S. Gettes, A. M. Gillinov, G. Gregoratos, S. C. Hammill, D. L. Hayes, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons Circulation, May 27, 2008; 117(21): e350 - e408. [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]

				S. Gelsomino, R. Lorusso, I. Capecchi, C. Rostagno, S. Romagnoli, G. Bille, G. De Cicco, C. Tetta, P. Stefano, and G. F. Gensini Left Ventricular Reverse Remodeling After Undersized Mitral Ring Annuloplasty in Patients With Ischemic Regurgitation Ann. Thorac. Surg., April 1, 2008; 85(4): 1319 - 1330. [Abstract] [Full Text] [PDF]

				S. Gelsomino, R. Lorusso, G. De Cicco, I. Capecchi, C. Rostagno, S. Caciolli, S. Romagnoli, U. Da Broi, P. Stefano, and G. F. Gensini Five-year echocardiographic results of combined undersized mitral ring annuloplasty and coronary artery bypass grafting for chronic ischaemic mitral regurgitation Eur. Heart J., January 2, 2008; 29(2): 231 - 240. [Abstract] [Full Text] [PDF]

				Authors/Task Force Members, P. E. Vardas, A. Auricchio, J.-J. Blanc, J.-C. Daubert, H. Drexler, H. Ector, M. Gasparini, C. Linde, F. B. Morgado, et al. Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association Europace, October 1, 2007; 9(10): 959 - 998. [Full Text] [PDF]

				D. A. Kass Highlighting the R in CRT Circulation, September 25, 2007; 116(13): 1434 - 1436. [Full Text] [PDF]

				Authors/Task Force Members, P. E. Vardas, A. Auricchio, J.-J. Blanc, J.-C. Daubert, H. Drexler, H. Ector, M. Gasparini, C. Linde, F. B. Morgado, et al. Guidelines for cardiac pacing and cardiac resynchronization therapy: The Task Force for Cardiac Pacing and Cardiac Resynchronization Therapy of the European Society of Cardiology. Developed in Collaboration with the European Heart Rhythm Association Eur. Heart J., September 2, 2007; 28(18): 2256 - 2295. [Full Text] [PDF]

				K. Vernooy, R. N.M. Cornelussen, X. A.A.M. Verbeek, W. Y.R. Vanagt, A. van Hunnik, M. Kuiper, T. Arts, H. J.G.M. Crijns, and F. W. Prinzen Cardiac resynchronization therapy cures dyssynchronopathy in canine left bundle-branch block hearts Eur. Heart J., September 1, 2007; 28(17): 2148 - 2155. [Abstract] [Full Text] [PDF]

				J. N. Kirkpatrick, M. A. Vannan, J. Narula, and R. M. Lang Echocardiography in Heart Failure: Applications, Utility, and New Horizons J. Am. Coll. Cardiol., July 31, 2007; 50(5): 381 - 396. [Abstract] [Full Text] [PDF]

				M. Becker, R. Kramann, A. Franke, O.-A. Breithardt, N. Heussen, C. Knackstedt, C. Stellbrink, P. Schauerte, M. Kelm, and R. Hoffmann Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography Eur. Heart J., May 2, 2007; 28(10): 1211 - 1220. [Abstract] [Full Text] [PDF]

				M. M. Henneman, J. Chen, C. Ypenburg, P. Dibbets, G. B. Bleeker, E. Boersma, M. P. Stokkel, E. E. van der Wall, E. V. Garcia, and J. J. Bax Phase Analysis of Gated Myocardial Perfusion Single-Photon Emission Computed Tomography Compared With Tissue Doppler Imaging for the Assessment of Left Ventricular Dyssynchrony J. Am. Coll. Cardiol., April 24, 2007; 49(16): 1708 - 1714. [Abstract] [Full Text] [PDF]

				M S. J. Sutton and M G Keane Reverse remodelling in heart failure with cardiac resynchronisation therapy Heart, February 1, 2007; 93(2): 167 - 171. [Abstract] [Full Text] [PDF]

				C M C van Campen, F C Visser, C C de Cock, H S Vos, O Kamp, and C A Visser Comparison of the haemodynamics of different pacing sites in patients undergoing resynchronisation treatment: need for individualisation of lead localisation Heart, December 1, 2006; 92(12): 1795 - 1800. [Abstract] [Full Text] [PDF]

				M. Rivero-Ayerza, D. A.M.J. Theuns, H. M. Garcia-Garcia, E. Boersma, M. Simoons, and L. J. Jordaens Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials Eur. Heart J., November 2, 2006; 27(22): 2682 - 2688. [Abstract] [Full Text] [PDF]

				H.-F. Tse and C.-P. Lau Selection of Permanent Ventricular Pacing Site: How Far Should We Go? J. Am. Coll. Cardiol., October 17, 2006; 48(8): 1649 - 1651. [Full Text] [PDF]

				C-M Yu, Q Zhang, Y-S Chan, C-K Chan, G W K Yip, L C C Kum, E B Wu, P-W Lee, Y-Y Lam, S Chan, et al. Tissue Doppler velocity is superior to displacement and strain mapping in predicting left ventricular reverse remodelling response after cardiac resynchronisation therapy Heart, October 1, 2006; 92(10): 1452 - 1456. [Abstract] [Full Text] [PDF]

				M. C. Porciani, A. Lilli, R. Macioce, F. Cappelli, G. Demarchi, A. Pappone, G. Ricciardi, and L. Padeletti Utility of a new left ventricular asynchrony index as a predictor of reverse remodelling after cardiac resynchronization therapy Eur. Heart J., August 1, 2006; 27(15): 1818 - 1823. [Abstract] [Full Text] [PDF]