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Europace 2007 9(2):108-112; doi:10.1093/europace/eul175
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


CRT

Acute effects of biventricular pacing on right ventricular function assessed by tissue Doppler imaging

Erwan Donal, Noëlle Vignat, Christian De Place, Emmanuelle Leray, Christophe Crocq, Philippe Mabo, Jean-Claude Daubert and Christophe Leclercq*

Department of Cardiology, University Hospital Pontchaillou, 35033 Rennes, France

Manuscript submitted 29 June 2006. Accepted after revision 3 October 2006.

* Corresponding author. Tel: +33 2 99 28 25 25; fax: +33 2 99 28 25 10. E-mail address: christophe.leclercq{at}chu-rennes.fr


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Aims The benefits of cardiac resynchronization therapy (CRT) on functional status, left ventricular (LV) remodelling and survival in patients with drug-refractory congestive heart failure (CHF), LV systolic dysfunction, and wide QRS have been demonstrated in randomized trials. However, the impact of CRT on right ventricular (RV) function, an independent prognostic factor in CHF remains questionable. This study examined the acute effects of various pacing modes on RV function in recipients of CRT systems.

Methods and results Echocardiographic examinations were performed in 15 patients (median age: 67 years, range 49–78), to compare RV function during atrial (AAI), RV and LV pacing, and biventricular (BiV) pacing, in random order. At baseline, the median LV ejection fraction was 20% (range 10–35) and the median LV end-diastolic diameter was 78 mm (range 62–85). Right ventricular function was impaired, with a median 36% fractional shortening of RV surfaces (7–59). Tissue Doppler systolic peak of velocity (Sa) recorded at the tricuspid annulus increased significantly from 9.9 cm/s (range 4.7–16.5) during AAI pacing, 10 cm/s (range 5.4–20.3) during RV pacing, and 11.7 cm/s (range 4.6–16.7) during LV pacing to 12.6 cm/s (range 6.6–19.1) during BiV pacing (P < 0.01). Trends toward improvements in other indices of RV function, particularly myocardial performance index and systolic excursion of the tricuspid annulus, were also observed.

Conclusions This short-term study showed a significant improvement in RV systolic function during BiV pacing compared with AAI, RV, or LV pacing in CRT recipients.

Key Words: Heart failure, Cardiac resynchronization therapy, Right ventricular function, Echocardiography, Doppler myocardial imaging


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Congestive heart failure (CHF) is a major disorder associated with poor quality of life and high mortality.1Go Among new therapeutic strategies, cardiac resynchronization therapy (CRT) is now well established for patients with drug-refractory symptoms, advanced left ventricular (LV) systolic dysfunction, and wide QRS.2Go–7Go However, since it was primarily developed to improve timing and function of the LV, the effects of CRT on right ventricular (RV) function, an independent prognostic factor in CHF have not been thoroughly examined.8Go–14Go Therefore, we designed an acute study to compare the effects of AAI, LV, RV, and biventricular (BiV) pacing on RV function assessed by transthoracic echocardiography in recipients of CRT systems.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Study population
The study included 15 consecutive patients who were candidates for CRT. The indication for CRT were New York Heart Association (NYHA) CHF functional class ≥III despite optimal drug therapy, a LV ejection fraction ≤35%, and presence of left bundle branch block, with a QRS duration >120 ms on surface electrocardiogram (ECG). Patients with unstable heart disease, atrial fibrillation, or absence of spontaneous atrioventricular (AV) conduction were not included in this study. The study complied with the Declaration of Helsinki, the study protocol was approved by the local ethics committee, and informed written consent was obtained from all patients.

Implanted devices
All patients had undergone implantation of CRT systems. The lead system included (i) active fixation atrial leads placed in the inter-atrial septum or in the right atrial (RA) appendage, (ii) RV leads placed in the mid inter-ventricular septum in 13, or at the apex in 2 patients, and (iii) LV leads placed in a lateral cardiac vein in 12, or in the mid-cardiac vein in 3 patients, using the technique described by Daubert et al.15Go

Study protocol
All patients were clinically stable at the time of study. Transthoracic echo-Doppler measurements were made with the pulse generator programmed, in random order, for

  1. AAI pacing from the RA with spontaneous AV conduction,
  2. DDD pacing from the RV,
  3. DDD pacing from the LV, or
  4. DDD-BiV pacing at identical heart rates.

The AV delay was individually optimized for each pacing modalities by an iterative method. It was based on measurements of the mitral inflow velocity time integral and LV filling duration. This was performed in accordance with the daily practice of pacemaker optimization in our echo-laboratory.

Echocardiographic examination
Each transthoracic examination was performed by the same two physicians and an agreement between them was required throughout the experiment. Each measurement was performed online using a Sonos 7500 Doppler system (Philips, Andover, MA, USA).

Standard parasternal long- and short-axis and apical views were acquired with the patient in the left lateral supine position. Pulsed-waved tissue Doppler imaging (TDI) was performed from apical four-chamber views with the sample volume at the tricuspid annulus directed toward the RV free wall (Figure 1). Peak systolic (Sa), and peak early (Ea) and peak late (Aa) diastolic annular velocities were measured with lead aVF of the surface ECG at a speed of 100 mm/s. Tissue Doppler imaging measurement were performed according to the previously published methodology.16Go The scale speed and the sweep speed was systematically optimized. The electro-mechanical delay was defined as the time between the onset of the Q-wave on the surface ECG and the onset of the regional systolic motion (Sa, cm/s). The electrosystolic delay was defined as the time between onset of the Q-wave on the surface ECG and peak ‘Sa’.


Figure 1751
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Figure 1 (A) Representative example of tissue pulse Doppler tracing of the tricuspid annulus with the peak velocity ‘Sa’ (cm/s). The normal value is >11 cm/s.30Go (B) Representative example of tricuspid annulus systolic excursion recorded in M-Mode. The normal value is >14 mm.31Go (C) Representative example of MPI measured using the pulmonary outflow and the tricuspid inflow. The normal value is >0.83.27Go

 
Myocardial performance index (MPI) was calculated as the sum of isovolumic contraction and isovolumic relaxation time divided by the ejection time (Figure 1).9Go

M-mode echocardiography was used in apical four-chamber windows to measure the maximal tricuspid annulus plane systolic excursion (TAPSE, mm), as previously described (Figure 1).10Go

Two-dimensional recordings of the four-chamber view were used for measurements of the RV end-diastolic area and end-systolic area, and the calculation of the RV fractional shortening (end-diastolic–endo-systolic/end-diastolic).

Acquiring images and measuring them later proved impractical, thus two physicians, routinely practising assessment of mechanical dyssynchrony, analysed the images online and an agreement between them was required before validating the measurement for further statistical analysis.

Statistical analyses
Data are presented as medians and range in the text and as mean ± SD in the figures. Stepwise repeated measures of analysis of variance were used to compare the various pacing modes. If differences were detected, analysis of variance was completed by a Bonferroni test to adjust for multiple comparisons. All statistical analyses were performed using the SPSS version 10.0 statistical software (SPSS Inc., Chicago, IL, USA). A P value <0.05 was considered statistically significant.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Characteristics of the study population
The study included 12 men and 3 women. Their median age was 67 years (range 49–78). The underlying heart disease was ischaemic in 9 patients, and non-ischaemic in 6. All patients had received long-term therapy with furosemide and angiotensin-converting enzyme inhibitors. Furthermore, only 4 patients did not receive beta-blockers because of intolerance, and 11 received spironolactone, 25 mg daily.

The mean intrinsic QRS duration before implantation of the CRT system was 158 ± 25 (120–240) ms, and 145 ± 30 (10–180) ms with BiV pacing.

The baseline mean RV area fractional shortening in the whole study population was 36% (7–59), 9 patients had a RV area fractional shortening <40%.

The baseline median RV radial diameter measured in the two-dimensional apical four-chamber view was 41 mm (range 10–74), and the median maximal longitudinal length of the RV was 88 mm (range 68–110). No significant tricuspid regurgitation was found, preventing the estimation of increased pulmonary arterial pressure. Non-significant regurgitation was noted allowing measurement of the timing of events.

Comparison of the different pacing modalities on RV function
Median TDI ‘Sa’ was 12.6 cm/s (range 6.6–19.1) during BiV pacing (Figure 2), which is significantly higher than during LV pacing [11.7 cm/s (range 4.6–16.7)], RV pacing [10 cm/s (range 5.4–20.3)], or AAI pacing [9.9 cm/s (range 4.75–16.5)]. A trend was observed with respect to the measurements of TAPSE, and MPI, though these differences did not reach statistical significance (Table 1).


Figure 1752
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Figure 2 Diagram of mean value of systolic velocity of the tricuspid annulus recorded in tissue Doppler (Sa, cm/s) in the four pacing conditions tested.

 


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Table 1 Measurements of RV function and filling pressures during four different pacing modes

 
Likewise, RV diastolic function examined by pulsed tissue Doppler showed no significant differences among BiV and other pacing modes. Ea recorded at the tricuspid annulus was the highest during BiV pacing (8.9 cm/s; Table 1).

Patients with ischaemic heart disease showed no specific differences compared with those without ischaemia.


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The main finding of the present study was that Sa, an index of RV function and of prognosis in chronic CHF10Go,11Go was significantly improved by BiV pacing during an acute comparison vs. atrial, RV- and LV-pacing. Many studies have highlighted the beneficial effects of BiV pacing on LV function and dimensions.4Go,5Go,7Go,17Go–20Go Despite the predictive role of RV dysfunction on mortality and non-fatal cardiac events, the impact of CRT on RV function has not been widely studied.13Go Most studies have used RVEF measured by radionuclide ventriculography or thermo-dilution techniques as an index of RV function.9Go–13Go Echocardiography has been used less frequently probably on account of the relative complexity of the RV geometry.21Go,22Go The RV is composed of two main chambers, and its systolic function is determined by two components. The first, related to circular fibres shortening, is particularly challenging to assess with Doppler-echocardiographic techniques.23Go Therefore, echocardiography has mostly focused on the longitudinal component of RV systolic function,16Go–18Go and a fairly close correlation between the magnitude of TAPSE and radionuclide ventriculography has been reported.21Go More recently, an equivalent correlation was reported for Sa measured using pulsed-wave TDI.12Go,24Go Furthermore, Sa was closely correlated with prognosis in patients with CHF. As demonstrated by Meluzin et al. with a cut-off value of 10.8 cm/s, the RV peak systolic velocity (Sa, cm/s) has also been shown to be sensitive in the early detection of RV dysfunction in Chagas' disease, in contrast to conventional parameters.17Go,25Go Our study confirms the sensitivity of Sa in a pacing CHF-population. Myocardial performance index has also been proposed as a non-geometric measurement of RV function, and its clinical value and correlation with patient survival has been demonstrated.26Go,27Go However, MPI appears less sensitive than Sa. The trends of these two variables were parallel, but only Sa variations were significant (Sa, cm/s).

A significant increase in RV peak systolic velocity (Sa, cm/s) during BiV pacing might be of clinical importance since, to the best of our knowledge, this study is the first to demonstrate a significant increase in this parameter. We may hypothesize, from these acute results, that only BiV-pacing provides a significant beneficial effect on RV function.1Go However, further studies in large groups of patient are necessary. As a matter of fact, the RV is highly sensitive to pre-load and pulmonary arterial pressures.10Go,24Go The beneficial effects of BiV pacing on the LV, as previously demonstrated acutely, might have influenced these results. Nevertheless, in our study, increase in RV peak systolic velocity (Sa, cm/s) was not observed during LV pacing despite its positive impact on LV haemodynamics.28Go,29Go Thus, at least acutely, BiV appears preferable to LV pacing by the beneficial effect it exerts on RV function, which is known to be critically important in the functional status and survival of patients with CHF.

Study limitations
This was an acute study, performed in a small population.

The quantitative echocardiographic evaluation was performed online by two physicians. No testing of the reproducibility of echocardiographic parameters was performed.

The global echocardiographic assessment of RV-function in the different modes of pacing implied a too prolonged examination to consider in routine practice.

Despite these limitations, we believe that our findings might be of clinical interest. However, further large studies are needed to confirm these results.

Conclusions
This acute study showed that RV systolic function was significantly improved by BiV pacing compared with AAI, RV and LV pacing in CRT recipients, with a significant increase in the peak systolic velocity (Sa, cm/s).


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
[1] Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, et al. Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 2005; 26: 1115–40.[Free Full Text]

[2] Hunt SA, Abraham TW, Chin MH, Feldman AM, Francis GS, Ganiats TG, et al. ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult—summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society. Circulation 2005; 112: 1825–52.

[3] Leclercq C and Kass DA. Retiming the failing heart: principles and current clinical status of cardiac resynchronization. J Am Coll Cardiol 2002; 39: 194–201.[Abstract/Free Full Text]

[4] Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, et al. Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 2001; 344: 873–80.[Abstract/Free Full Text]

[5] Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Multicenter InSync Randomized Clinical Evaluation. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002; 346: 1845–53.[Abstract/Free Full Text]

[6] Bradley DJ, Bradley EA, Baughman KL, Berger RD, Calkins H, Goodman SN, et al. Cardiac resynchronization and death from progressive heart failure a meta-analysis of randomized controlled trials. JAMA 2003; 289: 730–40.[Abstract/Free Full Text]

[7] Cleland JGF, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization therapy on morbidity and mortality in heart failure [the Cardiac Resynchronization-Heart Failure (CARE-HF) Trial]. N Eng J Med 2005; 352: 1539–49.[Abstract/Free Full Text]

[8] Yu CM, Bleeker GB, Fung JW, Schalij MJ, Zhang Q, van der Wall EE, et al. Left ventricular reverse remodeling but not clinical improvement predicts long-term survival after cardiac resynchronization therapy. Circulation 2005; 112: 1580–6.

[9] Di Salvo TG, Mathier M, Semigran MJ, Dec GW. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol 1995; 25: 1143–53.[Abstract]

[10] Ghio S, Gavazzi A, Campana C, Inserra C, Klersy C, Sebastiani R, et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol 2001; 37: 183–8.[Abstract/Free Full Text]

[11] De Groote P, Millaire A, Foucher-Hossein C, Nuque O, Marchandise X, Ducloux G, et al. Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure. J Am Coll Cardiol 1998; 32: 948–54.[Abstract/Free Full Text]

[12] Juillière Y, Barbier G, Feldmann L, Grentzinger A, Danchin N, Cherrier F. Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy. Eur Heart J 1997; 18: 276–80.[Abstract/Free Full Text]

[13] Meluzin J, Spinarova L, Dusek L, Toman J, Hude P, Krejci J. Prognostic importance of the right ventricular function assessed by Doppler tissue imaging. Eur J Echocardiogr 2003; 4: 262–71.[CrossRef][Medline]

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[17] Leclercq C, Cazeau S, Le Breton H, Ritter P, Mabo P, Gras D, et al. Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure. J Am Coll Cardiol 1998; 32: 1825–31.[Abstract/Free Full Text]

[18] Sogaard P, Egeblad H, Kim WY, Jensen HK, Pedersen AK, Kristensen BO, et al. Tissue Doppler imaging predicts improved systolic performance and reversed left ventricular remodeling during long-term cardiac resynchronization therapy. J Am Coll Cardiol 2002; 40: 723–30.[Abstract/Free Full Text]

[19] Duncan A, Wait D, Gibson D, Daubert JC. MUSTIC (Multisite Stimulationin Cardiomyopathies) Trial. Left ventricular remodelling and haemodynamic effects of multisite biventricular pacing in patients with left ventricular systolic dysfunction and activation disturbances in sinus rhythm: sub-study of the MUSTIC (Multisite Stimulation in Cardiomyopathies) trial. Eur Heart J 2003; 24: 430–41.[Abstract/Free Full Text]

[20] Breithardt OA, Claus P, Sutherland GR. Do we understand who benefits from resynchronisation therapy? Eur Heart J 2004; 25: 535–6.[Free Full Text]

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[22] Burgess MI, Mogulkoc N, Bright-Thomas RJ, Bishop P, Egan JJ, Ray SG. Comparison of echocardiographic markers of right ventricular function in determining prognosis in chronic pulmonary disease. J Am Soc Echocardiogr 2002; 15: 63–9.[CrossRef][Web of Science][Medline]

[23] Lopez-Candales A, Dohi K, Bazaz R, Edelman K. Relation of right ventricular free wall mechanical delay to right ventricular dysfunction as determined by tissue Doppler imaging. Am J Cardiol 2005; 96: 602–6.[CrossRef][Web of Science][Medline]

[24] Meluzin J, Spinarova L, Hude P, Krejci J, Kinci V, Panovsky R, et al. Prognostic importance of various echocardiographic right ventricular functional parameters in patients with symptomatic heart failure. J Am Soc Echocardiogr 2005; 18: 435–44.[CrossRef][Web of Science][Medline]

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[27] Yeo TC, Dujardin KS, Tei C, Mahoney DW, McGoon MD, Seward JB. Value of a Doppler-derived index combining systolic and diastolic time intervals in predicting outcome in primary pulmonary hypertension. Am J Cardiol 1998; 81: 1157–61.[CrossRef][Web of Science][Medline]

[28] Blanc JJ, Etienne Y, Gilard M, Mansourati J, Munier S, Boschat J, et al. Evaluation of different ventricular pacing sites in patients with severe heart failure: results of an acute hemodynamic study. Circulation 1997; 96: 3273–7.

[29] Kass DA, Chen CH, Curry C, Talbot M, Berger R, Fetics B, et al. Improved left ventricular mechanics from acute VDD pacing in patients with dilated cardiomyopathy and ventricular conduction delay. Circulation 1999; 99: 1567–73.

[30] Nageh MF, Kopelen HA, Zoghbi WA, Quinones MA, Nagueh SF. Estimation of mean right atrial pressure using tissue Doppler imaging. Am J Cardiol 1999; 84: 1448–51.[CrossRef][Web of Science][Medline]

[31] Ghio S, Recusani F, Klersy C, Sebastiani R, Laudisa ML, Campana C, et al. Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy. Am J Cardiol 2000; 85: 837–842.[CrossRef][Web of Science][Medline]


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