European Heart Journal

European Heart Journal Advance Access originally published online on October 13, 2005
European Heart Journal 2006 27(2):187-192; doi:10.1093/eurheartj/ehi558

This Article Abstract Full Text (PDF) HTML Page - index.htslp All Versions of this Article: 27/2/187    most recent ehi558v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (13) Request Permissions Google Scholar Articles by Brandt, R. R. Articles by Hamm, C. W. Search for Related Content PubMed PubMed Citation Articles by Brandt, R. R. Articles by Hamm, C. W. Social Bookmarking          What's this?

© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Contractile response and mitral regurgitation after temporary interruption of long-term cardiac resynchronization therapy

Roland R. Brandt^*, Christian Reiner, Roman Arnold, Johannes Sperzel, Heinz F. Pitschner and Christian W. Hamm

Division of Cardiology, Kerckhoff Heart Center, Benekestr 2–8, 61231 Bad Nauheim, Germany

Received 17 March 2005; revised 24 August 2005; accepted 8 September 2005; online publish-ahead-of-print 13 October 2005.

^* Corresponding author. Tel: +49 6032 996 0; fax: +49 6032 996 2227. E-mail address: r.brandt{at}kerckhoff-klinik.de

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Aims Cardiac resynchronization therapy (CRT) utilizing biventricular pacing (BVP) is a promising treatment modality for symptomatic patients with chronic left ventricular (LV) systolic dysfunction and intraventricular conduction delay. Clinical studies have shown short-term improvement in contractile function and mid-term improvement in clinical status with CRT. The objective of this study was to evaluate the haemodynamic consequences of temporary interruption of CRT after long-term stimulation.

Methods and results Twenty patients (16 men, 4 women) with LV dysfunction and New York Heart Association class III or IV heart failure, despite optimal medical therapy and a QRS interval of at least 120 ms, received a transvenous BVP system at the age of 66 (interquartile range, 61–69). Patients were studied after a median duration of 427 days (interquartile range, 281–563) of continuous CRT and again 72 h after cessation of BVP. Withdrawal of CRT resulted in a significant decline in maximal rate of LV systolic pressure rise from 711 mmHg/s (interquartile range, 640–816) to 442 mmHg/s (interquartile range, 389–582) (P=0.0001) and increases in mitral effective regurgitant orifice area from 4.8 mm² (interquartile range, 0.0–7.8) to 9.1 mm² (interquartile range, 5.7–13.3) (P=0.0001), mitral regurgitant volume from 7.8 mL (interquartile range, 0.0–11.5) to 16.0 mL (interquartile range, 10.7–20.8) (P=0.0001) and fraction from 13.8% (interquartile range, 0.0–19.2) to 27.7% (interquartile range, 14.6–34.0) (P=0.0002) determined by Doppler echocardiography.

Conclusion Cessation of long-term BVP leads to a decline in LV systolic performance and an increase in functional mitral regurgitation. These results indicate a sustained benefit of long-term CRT and support the notion to maintain CRT indefinitely.

Key Words: Cardiac resynchronization therapy • Contractility • Heart failure • Mitral regurgitation

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Cardiac resynchronization therapy (CRT) utilizing biventricular pacing (BVP) is a promising non-pharmacological treatment option for patients with symptomatic systolic heart failure and mechanical dyssynchrony due to an intraventricular conduction abnormality. Several studies have documented an acute haemodynamic benefit^1,2 and mid-term improvement in clinical status^3,4 with the potential for improved long-term survival.⁵ Mitral regurgitation (MR) is a common finding in patients with left ventricular (LV) systolic dysfunction and an independent predictor of mortality.⁶ Several studies have shown that CRT reduces functional MR, both acutely and in trials lasting up to 6 months.^3,7–10 Altogether, there is a robust body of evidence that initiation of BVP leads to immediate beneficial haemodynamic changes. Maintenance of these improvements might be expected to result in LV reverse remodelling, which has been observed previously.^3,8–11 Nevertheless, CRT is interrupted in approximately one-third of patients in the long-run for different reasons.¹² While acute haemodynamic benefits immediately revert as soon as pacing is halted,¹ there is little information about the consequences resulting from withdrawal of long-term CRT. We hypothesized that CRT interruption after long-term BVP would lead to early haemodynamic deterioration. Therefore, the aim of this prospective clinical study was to evaluate LV systolic performance and functional MR after temporary BVP interruption in patients clinically stable on long-term CRT.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
At baseline, all patients had moderate or severe (New York Heart Association functional class III or IV) chronic heart failure due to either ischaemic or idiopathic cardiomyopathy without aortic valve disease despite optimal medical treatment, an ejection fraction of 35% or less, and a QRS interval of 120 ms or more. A total of 225 patients underwent invasive haemodynamic testing to assess eligibility for chronic CRT. Of those, 136 patients were classified as responders based on an increase in the maximal rate of LV pressure rise (dP/dt_max) of at least 20% and received a transvenous BVP device for clinical reasons with the LV pacing electrode implanted through the coronary sinus and positioned in a lateral cardiac vein. The atrioventricular delay was optimized under Doppler echocardiographic guidance to maximize LV filling time. A total of 21 patients were randomly selected for the study after long-term BVP; all of them gave informed consent before enrolment. The recruiting physician had no knowledge of the clinical history and echocardiographic data at the time of patient inclusion.

Study design
All patients were studied by echocardiography after long-term CRT. Thereafter, the BVP mode was deactivated temporarily and patients were restudied after an equilibration period of 72 h keeping all medications constant. Brachial artery blood pressure was measured in each case after completion of the echocardiographic examination with the patient still in supine position. One patient experienced intolerable congestive heart failure symptoms shortly after suspension of CRT, the BVP mode was reactivated for clinical reasons and the patient was excluded from the study. The remaining 20 patients completed the study and their data were included in the statistical analysis. Patient characteristics stratified according to the heart failure aetiology are summarized in Table 1.

View this table: [in this window] [in a new window]   Table 1 Clinical characteristics of 20 patients with severe heart failure and LV dyssynchrony

 
Echocardiography
A comprehensive two-dimensional and Doppler transthoracic echocardiographic study was performed with a phased-array system (Sonos 4500 or 5500, Philips Medical Ultrasound [Agilent], Andover, MA, USA) using second harmonic imaging (1.8–3.6 MHz) to enhance endocardial border delineation. Image acquisition was performed with the patient in the left lateral decubitus position. End-diastolic and end-systolic frames were selected from the same cardiac cycle. End-diastole was identified by the onset of the R-wave on the simultaneously recorded electrocardiogram. End-systole was identified as the smallest LV cavity size just before mitral valve opening. LV dimensions were measured by two-dimension guided M-mode method. The shape of the LV was described by the sphericity index calculated by dividing the maximum short-axis by the maximum long-axis dimension.¹⁰ LV end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated by the modified Simpson's rule utilizing the built-in quantitative programs; total stroke volume and ejection fraction were calculated as EDV–ESV and (EDV–ESV)/EDV, respectively. LV diastolic filling time was determined from the pulsed-wave Doppler tracing with the sample volume placed at the tip of the mitral leaflets. The degree of systolic MR was assessed by colour Doppler flow imaging and the proximal isovelocity surface area (PISA) method. The border of the largest regurgitant jet area in the apical four-chamber view was traced and measured by computerized planimetry. The effective regurgitant orifice area and regurgitant volume were calculated using the PISA method.¹³ The same aliasing velocity was used in individual patients for both studies. Mitral regurgitant fraction was calculated as per cent of the total LV stroke volume. The maximal rate of LV pressure rise (dP/dt_max) was estimated by measuring the time interval between 1 and 3 m/s on the MR continuous-wave Doppler spectrum.¹⁴ In case of an incomplete continuous-wave Doppler signal due to trivial MR, dP/dt_max was determined from the rising slope of the Doppler spectrum in early systole. Thereby, measurement of dP/dt_max was feasible in all patients. All measurements and calculations were performed online during the examination by the same cardiologist in triplicate from consecutive cardiac cycles and averaged for statistical analysis.

Statistical analysis
The sample size for this prospective study was estimated on the basis of two preceding studies that evaluated the acute haemodynamic effect of CRT initiation.^1,7 Assuming that temporary cessation of CRT would exert a converse effect of the same magnitude and standard deviation, 20 patients would yield 80% power to detect a significant difference with the use of a two-sided alpha level of 0.05. Data are presented as median values and interquartile range for continuous variables and absolute frequencies for categorical variables unless specified otherwise. For continuous variables, the paired Wilcoxon test was used to compare data during and after withdrawal of CRT. The relation between the change in echocardiographic parameters was analysed by linear regression analysis. A two-sided probability value of P<0.05 was considered statistically significant. The intraobserver variability of echocardiographic measurements was assessed by the primary reader performing a second analysis of 10 randomly selected studies on stored video images. Interobserver variability was tested by a second blinded observer for the same randomly selected studies. Intra- and interobserver variabilities were calculated as percentage difference. The percentage difference was calculated for each pair of measurements as |measurement 1–measurement 2|/[0.5x(measurement 1+measurement 2)]x100 and expressed as mean±standard deviation.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Study population
Twenty patients were studied after a median duration of 427 days (interquartile range, 281–563) of continuous CRT and again 72 h after cessation of BVP. Seventeen patients reported worsening of their functional status 72 h after CRT withdrawal, while the remaining three patients noted no change.

Echocardiographic measurements
LVESV and LVEDV increased significantly after CRT withdrawal and there was also a trend towards a decrease in total stroke volume (Table 2). Significant decreases were observed in LV ejection fraction and diastolic filling time. In contrast, neither LV end-diastolic diameter nor sphericity index showed significant change. Likewise, left atrial size remained unchanged. Importantly, systolic and diastolic blood pressure decreased significantly. Nevertheless, MR measured by two different methods worsened significantly after CRT interruption (Table 3). Furthermore, LV contractility as assessed by Doppler-derived dP/dt_max decreased significantly from 711 mmHg/s (interquartile range, 640–816) to 442 mmHg/s (interquartile range, 389–582) (P=0.0001) after withdrawal of CRT. The decrease in contractility was uniform in all but one patient, in whom no change in dP/dt_max was noted (Figure 1). Worsening of MR did not correlate with any change in echocardiographic geometric parameters. However, a correlation was observed between the decrease in dP/dt_max and the increase in mitral effective regurgitant orifice area (P=0.045). Individual examples are depicted in Figures 2 and 3.

View this table: [in this window] [in a new window]   Table 2 Echocardiographic and haemodynamic variables of 20 patients during long-term CRT and 72 h after CRT discontinuation (Off)

 

View this table: [in this window] [in a new window]   Table 3 MR in 20 patients during long-term CRT and 72 h after CRT discontinuation (Off)

 

View larger version (15K): [in this window] [in a new window]   Figure 1 Individual changes in maximal rate of LV pressure rise (LV dP/dtmax) during long-term CRT and 72 h after CRT discontinuation (Off).

 

View larger version (96K): [in this window] [in a new window]   Figure 2 Example of change in LV pressure rise (dP/dtmax) during CRT (A) and 72 h after discontinuation (B).

 

View larger version (104K): [in this window] [in a new window]   Figure 3 Example of change in PISA method during CRT (A) and 72 h after discontinuation (B). Please note the identical aliasing velocity of 13 cm/s. See online supplementary material for a colour version of this figure.

 
Repeatability of measurements
Intraobserver variability was as follows: 4.5±4.2% for dP/dt_max, 10.7±8.7% for MR jet area, and 10.2±12.3% for mitral regurgitant volume. For interobserver variability, the corresponding values were 6.5±4.9%, 12.2±11.3%, and 12.2±8.4%, respectively.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
CRT using BVP has an established role in the management of drug-refractory systolic heart failure in patients with LV dyssynchrony.^{3–5,8,10,11} However, most clinical studies have a relatively short follow-up period of 3–6 months, and there is little information about the consequences resulting from withdrawal of long-term CRT. The main result of the current study is that CRT termination after prolonged treatment has detrimental effects on patient haemodynamics. This study is the first to comprehensively investigate the haemodynamic consequences of CRT withdrawal after long-term stimulation and supports the notion to maintain CRT indefinitely.

Mitral regurgitation
Functional MR occurs, despite a structurally normal valve, as a consequence of spatial or functional alterations.¹⁵ MR was evaluated in our study by two different methods and increased significantly after temporary suspension of CRT. Systolic blood pressure is a major determinant of mitral regurgitant volume.¹⁶ MR is expected to worsen in the setting of elevated blood pressure and improve with lower blood pressure. However, MR severity increased in our study in spite of a lower systemic arterial pressure. Our results nicely mirror the findings of Breithardt et al.,⁷ who have elegantly demonstrated that the effective mitral regurgitant orifice area decreased immediately after first-time initiation of CRT. Apparently, some of the mechanisms responsible for amelioration of functional MR with CRT also result in renewed worsening of MR after termination of long-term CRT. Intraventricular conduction delay, particularly with left bundle-branch block pattern, adversely influences ventricular function by dyssynchronous LV wall motion.¹⁷ It is conceivable, that delayed electrical activation of the LV lateral wall also adversely affects the timing of force development in the anterolateral papillary muscle and worsens MR. Indeed, functional MR is strongly associated with prolongation of the QRS complex in general, and with left bundle-branch block in particular.¹⁸ Conversely, CRT could significantly improve the efficacy of mitral valve closure by concomitant stimulation of the LV lateral wall with the adjacent anterolateral papillary muscle and explain the immediate decrease in MR with initiation of CRT.⁷ Functional MR can also be a consequence of a modified LV geometry affecting the mitral valve apparatus.¹⁹ We did not find any relation between changes in echocardiographic geometric parameters and worsening of MR. This may indicate that the predominant mechanism for worsening of MR after CRT withdrawal is not the result of simple distortion of the mitral valve, but rather related to discoordinate papillary muscle contraction. Indeed, a shortened interpapillary muscle time delay with initiation of CRT was significantly correlated with reductions in MR.²⁰ This increase in MR severity in our study cannot be accounted for by other factors because all other parameters, in particular cardiac medication, remained unchanged during the 72 h time interval between measurements.

Yu et al.⁹ have evaluated 25 patients after 3 months of CRT and could demonstrate an immediate increase MR severity when the pacemaker was turned off. However, MR was assessed only by the change in jet area relative to left atrial area. Colour Doppler flow imaging represents a rather crude measure of MR severity that is dependent on jet direction and machine settings. Our study confirms and extends the observation of Yu et al.⁹ First, the more sophisticated PISA method used in our study allows reliable measurement of the instantaneous regurgitant flow and regurgitant orifice area and is preferable for accurate quantitative assessment of MR severity.¹³ Second, most studies have a relatively short follow-up period of 3–6 months,^3,8–11 while our patients were studied after prolonged CRT. Worsening MR after discontinuation of CRT may also contribute to the increase in BNP levels observed by Sinha et al.²¹

The degree of MR observed in our patients after CRT withdrawal was in the mild to moderate range. However, even mild MR in patients with LV dysfunction is associated with reduced survival⁶ and MR tends to progress over time.²² Some^3,8–10 but not all investigators¹¹ have reported a significant reduction in MR in response to chronic CRT, regardless of whether the cause was idiopathic or ischaemic. The improvement in MR severity was paralleled by LV reverse remodelling.^3,8–11 The degree to which the reduction in MR plays a role in LV reverse remodelling is currently unclear.

LV contractility
LV contractility indexed by Doppler-derived dP/dt_max decreased significantly after termination of CRT. This observation provides strong evidence that dP/dt_max is particularly sensitive to re-occurrence of LV dyssynchrony generating regions of both early and delayed contraction. Contraction of the early activated myocardium occurs before LV ejection and largely serves to increase pre-load on the late activated regions, which in turn stretches the already relaxing early activated territory resulting in a decline in LV systolic performance. The remarkable decline in dP/dt_max provides direct evidence of the magnitude by which CRT assists LV function even after prolonged treatment. The present study is consistent with a previous observation that LV systolic function deteriorates after termination of 12 weeks of CRT.⁹ Importantly, dP/dt_max is a strong predictor of survival in patients with LV dysfunction.²³ Whether improvement in LV contractility with CRT also translates into improved survival remains to be established. Our data do not permit firm conclusions about the observed relation between the decrease in dP/dt_max and worsening of MR. However, an in vitro experimental study has suggested that an increased transmitral pressure acting to close the mitral leaflets also decreases the regurgitant orifice area.²⁴ Conversely, a decrease in LV systolic performance would be expected to increase functional MR.

Study limitations
The current study examined the haemodynamic consequences of CRT termination after long-term treatment. We did not systematically perform baseline measurements at the time of pacemaker implantation. Our results consistently demonstrated a highly significant change in haemodynamic parameters with CRT interruption, while all medications of the study patients were kept constant between measurements. Although no control group was studied, it would be most unlikely, that the observed results were due to any other effect rather than CRT interruption alone. On the basis of the known benefit, CRT could not be withheld from patients longer than 72 h for ethical reasons in order to document serial changes over a longer period without CRT. We did not perform echocardiographic measurements after re-institution of CRT, which could have re-inforced our hypothesis by showing a returning beneficial haemodynamic effect. However, it is reasonable to predict this very effect based on previously published studies.^1,2 The sample size (n=20) was rather small, but provided sufficient data for a reliable statistical analysis.

Clinical relevance
The clinical relevance of our findings comes from the fact that CRT is interrupted in a substantial number of patients after successful implantation.¹² A decline in LV systolic function and worsening of MR after interruption of CRT would be expected to exacerbate LV dilatation and further depress LV function. Moreover, even mild MR in patients with LV dysfunction is associated with reduced survival.⁶ Our study indicates that patients derive continuous haemodynamic benefit from CRT after long-term stimulation. Therefore, every effort should be made to maintain CRT indefinitely. Indeed, preliminary results indicate that CRT is well tolerated after 2 years of ongoing treatment.²⁵

Supplementary material: Supplementary material is available at European Heart Journal online.

Conflict of interest: none declared.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Aurrichio A, Stellbrink C, Block M, Sack S, Vogt J, Bakker P, Klein H for the Pacing Therapies for Congestive Heart Failure Study Group; Kramer A, Ding J, Salo R, Tockman B, Pochet T, Spinelli J for the Guidant Congestive Heart Failure Research Group. Effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 1999;99:2993–3001.[Medline]
2. Leclercq C, Cazeau S, Le Breton H, Ritter P, Mabo P, Gras D, Pavin D, Lazarus A, Daubert JC. Acute haemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol 1998;32:1825–1831.[Abstract/Free Full Text]
3. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, Kocovic DZ, Packer M, Clavell AL, Hayes DL, Ellestad M, Messenger J for the MIRACLE Study Group. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845–1853.[Abstract/Free Full Text]
4. Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, Garrigue S, Kappenberger L, Haywood GA, Santini M, Bailleul C, Daubert JC for the Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Group. 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. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, Carson P, DiCarlo L, DeMets D, White BG, DeVries DW, Feldman AM for the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators. Cardiac resynchronization therapy with and without an implantable defibrillator in advanced chronic heart failure. N Engl J Med 2004;350:2140–2150.[Abstract/Free Full Text]
6. Tichon BH, Felker GM, Shaw LK, Cabell CH, O'Connor CM. Relation of frequency and severity of mitral regurgitation to survival among patients with left ventricular systolic dysfunction and heart failure. Am J Cardiol 2003;91:538–543.[CrossRef][ISI][Medline]
7. Breithardt OA, Sinha AM, Schwammenthal E, Bidaoui N, Markus KU, Franke A, Stellbrink C. Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol 2003;41:765–770.[Abstract/Free Full Text]
8. St John Sutton MG, Plappert T, Abraham WT, Smith AL, DeLurgio DB, Leon AR, Loh E, Kocovic DZ, Fisher WG, Ellestad M, Messenger J, Kruger K, Hilpisch KE, Hill MRS for the Multicenter InSync Ramdomized Clinical Evaluation (MIRACLE) Study Group. Effect of cardiac resynchronization therapy on left ventricular size and function in chronic heart failure. Circulation 2003;107:1985–1990.[Abstract/Free Full Text]
9. Yu CM, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, Lin H, Kong SL, Lam YM, Hill MRS, Lau CP. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105:438–445.[Abstract/Free Full Text]
10. Saxon LA, De Marco T, Schafer J, Chatterjee K, Kumar UN, Foster E for the VIGOR Congestive Heart Failure Investigators. Effects of long-term biventricular stimulation for resynchronization on echocardiographic measures of remodeling. Circulation 2002;105:1304–1310.[Abstract/Free Full Text]
11. Stellbrink CS, Breithardt OA, Franke A, Sack S, Bakker P, Auricchio A on behalf of the PATH-CHF Investigators; Pochet T, Salo R, Kramer A, Spinelli J on behalf of the CPI Guidant Congestive Heart Failure Research Group. Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances. J Am Coll Cardiol 2001;38:1957–1965.[Abstract/Free Full Text]
12. Knight BP, Desai A, Coman J, Faddis M, Yong P. Long-term retention of cardiac resynchronization therapy. J Am Coll Cardiol 2004;44:72–77.[Abstract/Free Full Text]
13. Enriquez-Sarano M, Miller FA, 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.[Abstract]
14. 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. Circulation 1989;80:1287–1292.[Abstract/Free Full Text]
15. Brandt RR, Sperzel J, Pitscher HF, Hamm CW. Echocardiographic assessment of mitral regurgitation in patients with heart failure. Eur Heart J 2004;6(Suppl. D):D25–D28.
16. Levine HJ, Gaasch WH. Vasoactive drugs in chronic regurgitant lesions of the mitral and aortic valves. J Am Coll Cardiol 1996;28:1083–1091.[Abstract]
17. Nelson GS, Curry CW, Wyman BT, Kramer A, Declerck J, Talbot M, Douglas MR, Berger RD, McVeigh ER, Kass DA. 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]
18. Erlebacher JA, Barbarash S. Intraventricular conduction delay and functional mitral regurgitation. Am J Cardiol 2001;88:83–86.[ISI]
19. Yiu SF, Enriquez-Sarano M, Tribouilloy C, Seward JB, Tajik AJ. Determinants of the degree of functional mitral regurgitation in patients with systolic left ventricular dysfunction: a quantitative clinical study. Circulation 2000;102:1400–1406.[Abstract/Free Full Text]
20. Kanzaki H, Bazaz R, Schwartzman D, Dohi K, Sade LE, Gorcsan J III. A mechanism for immediate reduction in mitral regurgitation after cardiac resynchronization therapy: insights from mechanical activation strain mapping. J Am Coll Cardiol 2004;44:1619–1625.[Abstract/Free Full Text]
21. Sinha AM, Filzmaier K, Breithardt OE, Kunz D, Graf J, Markus KU, Hanrath P, Stellbrink C. Usefulness of brain natriuretic peptide release as a surrogate marker of the efficacy of long-term cardiac resynchronization therapy in patients with heart failure. Am J Cardiol 2003;91:755–758.[CrossRef][ISI][Medline]
22. Enriquez-Sarano M, Basmadjian AJ, Rossi A, Bailey KR, Seward JB, Tajik AJ. Progression of mitral regurgitation: a prospective Doppler echocardiographic study. J Am Coll Cardiol 1999;34:1137–1144.[Abstract/Free Full Text]
23. Kolias TJ, Aaronson KD, Armstrong WF. Doppler-derived dP/dt and –dP/dt predict survival in congestive heart failure. J Am Coll Cardiol 2000;36:1594–1599.[Abstract/Free Full Text]
24. He S, Fontaine AA, Schwammenthal E, Yoganathan AP, Levine RA. Integrated mechanism for functional mitral regurgitation: leaflet restriction versus coapting force: in vitro studies. Circulation 1997;96:1826–1834.[Abstract/Free Full Text]
25. Leclercq C, Linde C, Cazeau S, Kappenberger L, Sutton R, Bailleul C, Daubert C. Sustained clinical efficacy of biventricular pacing in patients with advanced heart failure and stable sinus rhythm: 2 years follow-up from the MUSTIC study. (Abstract). Pacing Clin Electrophysiol 2002;24:601.

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				E. Donal, C. De Place, G. Kervio, F. Bauer, R. Gervais, C. Leclercq, P. Mabo, and J.-C. Daubert Mitral regurgitation in dilated cardiomyopathy: value of both regional left ventricular contractility and dyssynchrony Eur J Echocardiogr, June 26, 2008; (2008) jen188v1. [Abstract] [Full Text] [PDF]

				E. Agricola, M. Oppizzi, M. Pisani, A. Meris, F. Maisano, and A. Margonato Ischemic mitral regurgitation: mechanisms and echocardiographic classification Eur J Echocardiogr, March 1, 2008; 9(2): 207 - 221. [Abstract] [Full Text] [PDF]

				C. Ypenburg, P. Lancellotti, L. F. Tops, G. B. Bleeker, E. R. Holman, L. A. Pierard, M. J. Schalij, and J. J. Bax Acute Effects of Initiation and Withdrawal of Cardiac Resynchronization Therapy on Papillary Muscle Dyssynchrony and Mitral Regurgitation J. Am. Coll. Cardiol., November 20, 2007; 50(21): 2071 - 2077. [Abstract] [Full Text] [PDF]

				L. A. Pierard Echocardiographic Monitoring Throughout Exercise: Better Than the Post-Treadmill Approach? J. Am. Coll. Cardiol., November 6, 2007; 50(19): 1864 - 1866. [Full Text] [PDF]

				G. B Bleeker, C.-M. Yu, P. Nihoyannopoulos, J. de Sutter, N. Van de Veire, E. R Holman, M. J Schalij, E. E van der Wall, and J. J Bax Optimal use of echocardiography in cardiac resynchronisation therapy Heart, November 1, 2007; 93(11): 1339 - 1350. [Abstract] [Full Text] [PDF]

				L. A. Pierard and P. Lancellotti When and how does cardiac resynchronization therapy reduce dynamic mitral regurgitation? Eur. Heart J., September 1, 2007; 28(17): 2055 - 2056. [Full Text] [PDF]

				F. Cabrera-Bueno, J. M. Garcia-Pinilla, J. Pena-Hernandez, M. Jimenez-Navarro, J. J. Gomez-Doblas, A. Barrera-Cordero, J. Alzueta-Rodriguez, and E. de Teresa-Galvan Repercussion of functional mitral regurgitation on reverse remodelling in cardiac resynchronization therapy Europace, September 1, 2007; 9(9): 757 - 761. [Abstract] [Full Text] [PDF]

				L. A. Pierard Left ventricular dyssynchrony and functional mitral regurgitation: two dynamic conditions Eur. Heart J., April 12, 2007; (2007) ehm079v1. [Full Text] [PDF]

				J J Bax and D Poldermans Mitral regurgitation and left ventricular dyssynchrony: implications for treatment Heart, October 1, 2006; 92(10): 1363 - 1364. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) HTML Page - index.htslp All Versions of this Article: 27/2/187    most recent ehi558v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (13) Request Permissions Google Scholar Articles by Brandt, R. R. Articles by Hamm, C. W. Search for Related Content PubMed PubMed Citation Articles by Brandt, R. R. Articles by Hamm, C. W. Social Bookmarking          What's this?

Online ISSN 1522-9645 - Print ISSN 0195-668x

Copyright © 2008 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics