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European Journal of Heart Failure 2008 10(3):273-280; doi:10.1016/j.ejheart.2008.02.007
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© 2008 European Society of Cardiology

Responders to cardiac resynchronization therapy with narrow or intermediate QRS complexes identified by simple echocardiographic indices of dyssynchrony: The DESIRE study

Serge J. Cazeaua,*, J-Claude Daubertb, Luigi Tavazzic, Gerd Frohligd and Vince Paule

a Inparys Clinical Research Group 12 rue Pasteur, 92210 — St. Cloud, France
b University Hospital Rennes, France
c IRCCS Policlinico S Matteo Pavia, Italy
d Universitätskliniken des Saarlandes Homburg, Germany
e St Peters Hospital Chertsey, United Kingdom

* Corresponding author. Tel.: +33 1 41 12 07 13; fax: +33 1 41 12 07 15. E-mail address: SergeCaz{at}aol.com (S.J. Cazeau).


   Abstract
Top
 Abstract
1. Introduction
 2. Patient population and...
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
Background: Cardiac resynchronization therapy (CRT) is recommended for patients with NYHA class III–IV refractory heart failure (HF), ejection fraction <35% and a QRS >120ms. We attempted to identify responders to CRT from echocardiographic (echo) indices of mechanical dyssynchrony in patients with QRS < 150 ms.

Methods and results: The study enrolled 51 men and 9 women (mean age: 64.5years) in NYHA class III (n=54) or IV (n=6) presenting with a mean ejection fraction: 25.7%, LV end-diastolic diameter: 69.1mm, and QRS = 121 ± 19 ms. All patients were implanted with a CRT system and followed for 1year. Implantation was preceded and followed by clinical, functional and Doppler (D)-echo evaluation. The primary combined endpoint included 1) death from any cause, 2) HF-related hospitalisations, and 3) NYHA class at 6 months. Before implant, 27 patients had ≥ 1 echo criterion of mechanical dyssynchrony (DES+ group) and 33 had no evidence of dyssynchrony (DES– group). At 12months, 8 patients (4 per group) had died, 7 from HF. As regards the primary endpoint at 6 months, 33 patients (55%) had improved, 10 (16%) were unchanged, and 17 (29%) had deteriorated. Clinical improvement was observed in 19 of 27 DES+ (70%), versus 14 of 33 DES– (42%) patients (P<0.04). Baseline QRS duration did not predict response to CRT.

Conclusions: In this population of HF patients with QRS < 150 ms, the presence of mechanical dyssynchrony at baseline D-echo examination, but not the QRS width, predicted 6-month clinical response to CRT.

Key Words: Cardiac resynchronization therapy • Cardiac mechanical dyssynchrony • QRS duration

Received November 2, 2007; Revised January 28, 2008; Accepted February 6, 2008


   1. Introduction
Top
 Abstract
 1. Introduction
2. Patient population and...
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
The implantation of a cardiac resynchronization therapy (CRT) system is recommended for heart failure patients who remain in symptomatic New York Heart Association (NYHA) Class III or IV despite optimal medical treatment with normal sinus rhythm, low left ventricular (LV) ejection fraction, LV dilatation and a QRS duration >120 ms [1-4]. Although recommendations from the European Society of Cardiology "recognize the potential superiority of mechanical dyssynchrony identification over electrical ventricular delays", its value remains to be determined in controlled trials. Mechanical dyssynchrony was initially assessed by radionuclide angiography [4]. However, because of practical limitations in its broad application, it was replaced by QRS duration, which was found to be a more convenient marker to select CRT candidates in clinical trials [5-7]. The initial cut-off value of 150 ms was shortened to 120 ms based on inclusion criteria from the most recently published studies [8,9] However, the mean duration of the QRS of patients actually enrolled in these studies was approximately 160 ms, far from the recommended 120-ms lower limit [8-10]. On the other hand, some observational studies [11-13] have shown benefits conferred by CRT in patients suffering from HF who had slightly prolonged or narrow QRS, treated on the basis of inter- or intraventricular dyssynchrony identified by Doppler-echocardiography (D-echo). Yet, no study has prospectively examined the value of D-echo to identify potential responders among patients with QRS duration<150 ms. Furthermore, simple, reproducible and expeditious techniques applicable in all echo laboratories are needed for routine applications by persons who are not echo specialists.

The aim of this prospective multicenter study was to identify potential long-term responders to CRT on the basis of simple echo indices of dyssynchrony without reference to QRS width. We compared the clinical outcomes of CRT recipients assigned, after enrolment, to a desynchronized (DES+) versus non-desynchronized (DES–) group on baseline echo evaluation.


   2. Patient population and methods
Top
 Abstract
 1. Introduction
 2. Patient population and...
3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
The study identified 64 patients >18 years of age, in stable, chronic NYHA Class III or IV HF with a LV ejection fraction (EF) ≤40%, and LV end-diastolic diameter (EDD) ≥27 mm/m2. All were in stable sinus rhythm and selected only on the basis of QRS duration <150 ms in order to exclude patients in whom the benefits conferred by CRT have already been confirmed. Before inclusion in the study, the patients had been clinically stable for ≥3 months, and optimally treated with recommendation of at least a diuretic, beta-adrenergic blocker and angiotensin-converting inhibitor (ACE) or angiotensin receptor blocker (ARB), at the highest tolerated doses. Exclusion criteria included hypertrophic or restrictive cardiomyopathy, suspected or overt acute myocarditis, acute coronary syndrome within the last 3 months, recent (<3 months) or planned cardiac surgery or coronary angioplasty, uncontrolled hypertension, severe obstructive lung disease, inability to walk, ventricular tachyarrhythmia requiring an implantable cardioverter defibrillator, or a <1 year life expectancy for reasons other than cardiovascular disease.

This study, which complied with the Declaration of Helsinki, was reviewed and approved by the Institutional Ethics Committee of each participating centre, and all patients granted their approval to participate.

2.1. Patient evaluations and follow-up
After enrolment, patients underwent evaluations before CRT implantation (baseline), before discharge from the hospital, and at 3, 6 and 12 months of follow-up. At each evaluation, a D-echo, 6-min hall walk (6-MHW) test, evaluation of quality of life by the Minnesota Living With Heart Failure® questionnaire, and 12-lead surface electrocardiogram (ECG) were obtained. NYHA functional class was graded by a physician unaware of the study. Adverse events and number of days in hospital and reasons for hospitalisation were recorded, when applicable. A chest roentgenogram was obtained at the 6-month follow-up.

2.2. Echocardiographic examinations
The patients underwent baseline D-echo in search of 1 or more criteria of mechanical dyssynchrony. Dyssynchrony was assessed at the atrioventricular (AV), interventricular and left intraventricular levels as described previously [14]. AV dyssynchrony was defined as a LV filling time (FT) shortened to <40% of the cardiac cycle, and expressed as a percentage of the R-R interval. Interventricular dyssynchrony was defined as a >40 ms mechanical interventricular delay (IVD) calculated as the difference between left (LPEP) and right (RPEP) pre-ejection periods, measured between the onset of the QRS complex and, respectively, onset of aortic and onset of pulmonary ejection flows by pulsed wave Doppler. To define echo measurements that can be made by all caregivers, regardless of the imaging equipment available, Doppler tissue imaging was deliberately not used and intraventricular dyssynchrony was simply defined as 1) LPEP>140 ms, and/or 2) diastolic contraction of the left lateral wall (LLW), recorded in the 4-chamber apical view using M-mode colour, after closure of the aortic valve. When diastolic contraction of the LLW persisted beyond the onset of the next filling phase, the overlap of LLW contraction and ventricular filling was measured. A >50 ms overlap was a criterion of intraventricular dyssynchrony in this study. Diastolic contraction and overlap identify the presence of at least one LV segment not temporally synchronized within the cardiac cycle. The duration of LV ejection was also measured between the opening and the closure of the aortic valve, and the LPEP/LVET ratio was calculated (Fig. 1).


Figure 01
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  		Fig. 1 Temporal intraventricular dyssynchrony. Simultaneous display of the electrocardiogram, left and the right ejection flows, left ventricular filling and left lateral wall contraction. Diastolic contraction is the duration of persistent contraction of the left lateral wall (LLW) after closure of the aortic valve. Overlap is the duration of the persistent contraction after opening of the mitral valve. LPEP = left pre-ejection period; RPEP = right pre-ejection period; IVD = interventricular delay = LPEP - RPEP; LLW = left lateral wall.

 
All taped echo recording were analyzed twice in a core laboratory (Bizet Medical Centre, Paris, France), by a physician unaware of the patient's clinical status and experienced in both cardiac pacing and echo. Patients were classified as DES+ if they presented with ≥1 criterion of mechanical AV, interventricular or left intraventricular dyssynchrony, and DES — if no dyssynchrony criterion was present.

2.3. Implantation and programming of the CRT system
All DES+ and DES– patients underwent implantation of a TalentTM III MSP or TalentTM MSP 313 (ELA Medical, Sorin Group, Montrouge, France) triple chamber CRT device. All leads were implanted transvenously. Guided by a venogram, the LV lead was placed in a coronary sinus tributary, in a stable lateral position, with a <2.5 V capture threshold [15]. The right ventricular (RV) lead was placed according to the operators' preferences, with a recommendation to stay as far as possible from the LV site of stimulation. The proper lead tip positions were verified on frontal and sagittal chest X-ray. After implantation, and before discharge, all patients underwent a second D-echo examination to evaluate the same dyssynchrony criteria as at baseline.

Programming of the CRT devices was left to the investigator's discretion. It was, however, recommended that AV be optimized to allow the longest LVFT without premature interruption of the A wave.

2.4. Concomitant drug therapy
At baseline, 72% of patients were treated with beta-adrenergic blockers, 85% with ACE-inhibitors or ARB, 96% with a diuretic, and 36% of patients with a statin. All prescriptions remained stable throughout the study.

2.5. Study endpoints and study objectives
The primary study endpoint was a composite of clinical outcomes at 6 months of follow-up, including, in decreasing hierarchical order, 1) death from any cause, 2) HF-related hospitalisations, and 3) NYHA functional class. A HF-related hospitalisation was defined as a >24-h hospital stay associated with an increase in clinical manifestations consistent with HF, and requiring intravenous treatment with diuretics or an inotropic agent. The patients were classified as worsened, unchanged or improved on the basis of this primary endpoint. In case of death, the patient was classified as worsened. If the patient survived, but was hospitalised, the number of days spent in the hospital during the 6 months prior to entry into the study was compared with the number of days spent in the hospital in the 6 months following CRT system implantation. The duration of hospitalisation was considered significantly longer or shorter if the number of days in the hospital was >1/3 greater or smaller than recorded during the 6-months preceding the study period. It was, otherwise, considered unchanged. If the patient had survived and was not hospitalised, a ≥1-point change in NYHA functional class was used to classify the patient's HF status.

A patient was considered improved only if a) alive, b) not hospitalised or hospitalised for a significantly shorter duration than before CRT, and c) in a NYHA functional class at least 1 point lower than before CRT.

The primary study objective was to determine the value of simple dyssynchrony indices to predict the clinical response to CRT in this population. Other objectives were to measure the functional benefit conferred by CRT, assessed by the 6-MHW test, quality of life score by Minnesota Leaving with Heart Failure questionnaire and NYHA functional class, and the quality and safety of therapy delivery. LVEF and LV dimensions were also followed, although the study was not powered to evaluate LV reverse remodelling.

2.6. Statistical analysis
The data were analyzed on an intention-to-treat principle. Patients with missing value for the main analysis were omitted. All patients enrolled were included in the safety analysis. Continuous variables were compared by Student's t-test, according to respect of model hypothesis (normality of residuals, homogeneity of variances). If an assumption was not verified, a non-parametric Kruskal-Wallis test was performed. Non-continuous variables were analyzed using the Fisher's exact test for dichotomous and non-ordered categorical variables. All statistical tests were two-sided. A P value≤0.05 was considered statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Patient population and...
 3. Results
4. Discussion
 5. Conclusions
 Acknowledgments
 References
 
3.1. Study population
The mean age of the 64 patients, 54 men and 10 women enrolled by the investigator centres (Appendix A) was 64.2±12.5 years. Mean LVEF and mean LVEDD were 27±8% and 69±9 mm, respectively. 56 patients were in NYHA functional class III and 8 in Class IV. An ischaemic cardiomyopathy was diagnosed in 27 patients, and 37 presented with a dilated cardiomyopathy of other aetiology. All patients were in sinus rhythm, with a mean R-R interval of 825±184 ms and intrinsic QRS width of 121±19 ms (range 80-150 ms). Four patients were excluded due to unsuccessful LV lead implantation (n=1) and unsatisfactory baseline echo (n=3), therefore 60 patients underwent complete follow-up and had echo recordings of high enough quality for detailed analyses.

In the overall population, the mean baseline measurements showed significant dyssynchrony neither at the AV (LVFT=47±9%), nor interventricular (IVD=20±24 ms), nor left intraventricular (LPEP=134±24 ms) levels. No overlapping contraction of the LLW with the filling phase of the next cardiac cycle was observed, such that this mean measurement was negative (–75±102 ms) suggesting the persistence of isovolumic relaxation of the LLW. Global isovolumic relaxation, calculated as the difference between aortic valve closure and mitral valve opening was 104±105 ms. However, a mean 34±51 ms post-systolic diastolic contraction of the LLW was observed during isovolumic relaxation. The mean LVET measured 248±46 ms, isovolumic contraction duration 75±87 ms, and the LPEP/LVET ratio was 0.56±0.14. The mitral regurgitation area ratio, reported to the left atrial area in the 4-chamber apical view, was 23±16%.

3.2. Implantation procedure and biventricular stimulation
The LV lead was successfully implanted in 93.5% with the tip-electrode placed in a lateral position in 29 patients, postero-lateral in 15, antero-lateral in 12, posterior in 3, and infero-apical in 1 patient. No lead was implanted in the great cardiac vein. The RV lead position was apical in 18 patients, septal in 36, at the RV outflow tract in 1, the RV anterior wall in 1, the mid-inferior wall in 1, and was not specified in 3 patients.

Despite individual changes in QRS width and axis between intrinsic and paced QRS complexes, the mean values did not differ significantly from baseline, in the overall study population. Mean QRS width increased from 121±19 ms to 140±28 ms and mean QRS axis from 1±59° to 14±82°. These non-significant differences were observed in both DES+ and DES– patients.

3.3. Desynchronized versus non-desynchronized patients
Among the 60 patients, 27 (mean age 62±15 years) were classified DES+, as they had ≥1 criterion of mechanical dyssynchrony. A single criterion was fulfilled in 16 patients (LPEP>140 ms in 7, LVFT<40% in 5, IVD>40 ms in 3, and overlapping of diastolic contraction with LV filling in 1 patient), 2 criteria in 9 patients, and 3 criteria in 2 patients. The DES– group included 33 patients whose mean age was 67±11 years (ns versus the DES+ group). The baseline clinical and echo characteristics of the 2 study groups are shown in Table 1. Compared with DES+, DES– patients had a significantly higher LVEF and were more likely to suffer from ischaemic heart disease. As expected, they had a longer LVFT, shorter IVD and LPEP, and shorter mean duration of diastolic contraction. Since their mean LVET was longer and LPEP shorter, the LPEP/LVET ratio was significantly lower.


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  		Table 1 Baseline clinical and echocardiographic characteristics of the study groups

 
No significant difference was found in echo variables between baseline and pre-discharge measurements in the overall population and within each group. LPEP increased from 134±24 ms to 161±34 ms, a 20% difference, LVFT increased from 47±9 to 48±10%, IVD decreased from 20±24 to 9±40 ms, and no change was observed in the mean overlap value, which remained negative at –87±84 ms. No significant difference was observed between DES+ and DES– patients after CRT system implantation.

3.4. Adverse events
At the end of the 12-month follow-up, 8 patients (13% of the overall population) had died, 4 in the DES+ and 4 in the DES– group. HF was the cause of death in 7 patients, and septicaemia of intestinal origin unrelated to the procedure/device in 1 patient. No patient died of a ventricular arrhythmia. The study was terminated prematurely in 7 patients in the DES+, versus 2 patients in the DES– group (ns). In the DES+ group, 2 patients were lost to follow-up, 1 developed a ventricular tachyarrhythmia requiring upgrade to a CRT-D system, 1 patient suffered a stroke, 2 patients developed congestive HF and 1 patient developed a pulse generator pocket infection. The 2 DES– patients who exited the study prematurely underwent emergent heart transplantation. No device malfunction or lead-related complication was observed.

3.5. Clinical end-points at 6 months
Evaluation at 6 months revealed that 33 patients (55%) had improved, 10 (16%) were unchanged, and 17 (29%) had deteriorated (8 deaths and 9 increases in number of hospitalisations). Among the unchanged patients, 8 were not hospitalised and had no change in NYHA functional class, and 2, who had no change in the number of hospitalisations, were classified as unchanged despite a 1 point decrease in NYHA functional class.

The implantation of CRT systems conferred a greater benefit to DES+ than to DES– patients. A clinical improvement was observed in 19 of 27 DES+ (70%), versus 14 of 33 DES– (42%) patients (P<0.04). Baseline QRS duration did not predict the response to CRT. Among patients with a QRS≤120 ms, 42% were improved, versus 57% of patients with QRS>120 ms (P<0.2). No QRS cut-off value between 120 and 150 was predictive of clinical outcome.

3.6. Predictors of clinical improvement
Comparisons between patients who did versus patients who did not manifest significant clinical improvements at 6 months are shown in Table 2. The two groups are compared at baseline. At 6 months, changes from baseline are compared within each group. The patients who did not improve were significantly older, had a significantly slower sinus rate, shorter IVD, and less overlap than the patients who did improve.


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  		Table 2 Baseline and 6-month clinical and echocardiographic characteristics of patients who improved versus patients who did not improve clinically during the study

 
Before discharge and at 6 months, all measurements pertaining to dyssynchrony were similar in both groups and had not changed significantly from baseline. At 6 months, non-improved patients had a significantly longer LPEP and a higher LPEP/LVET ratio compared to baseline, which was not observed in improved patients. The difference in LPEP/LVET ratio evolution between the two groups was significant (P<0.004).


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Patient population and...
 3. Results
 4. Discussion
5. Conclusions
 Acknowledgments
 References
 
4.1. "Narrow" QRS and cardiac resynchronization therapy
The objective of the DESIRE study was not to assess the value of CRT in a "narrow" QRS population but to examine whether the presence of mechanical dyssynchrony prior to the implantation of the system might predict a more favourable clinical outcome. It evaluated the pertinence of ECG and simple echo variables involved in the decision process. The rationale for enrolling patients with a QRS<150 ms was to select patients in whom the value of CRT was not clearly established in current guidelines. DESIRE suggests a positive response to CRT in a population with a QRS near 120 ms. The response rate was higher in patients who presented with than in patients presenting without mechanical dyssynchrony (70% versus 42%) and the success rate in the DES– group was comparable to the 46% CRT success rate of the RethinQ study that included narrow-QRS patients without mechanical dyssynchrony according to the DESIRE criteria [16].

Since the inception of CRT, QRS width has been used as a convenient marker of dyssynchrony, as it is easily applicable in multicenter trials and in the real world. The initial 150-ms cut-off value was determined experimentally. However, the presently recommended 120-ms value is based on the inclusion criterion chosen in CARE-HF and COMPANION [8,9], although the mean QRS of the patients ultimately enrolled in these trials was considerably longer. The absence of QRS narrowing after implant is generally considered ineffective delivery of therapy [17]. In concordance with the initial observations [11] this study found a 55% improvement according to a robust clinical composite criterion in a population enrolled on the basis of a QRS<150 ms despite QRS widening after implant. In the study by Achilli et al. [11] and the RethinQ study [16], patients were selected according to the presence of mechanical dyssynchrony at echo, whereas, in the present study, the echocardiographic evaluation of dyssynchrony was performed after enrolment, in order to separate DES– from DES+ and compare their outcomes. A significantly greater improvement was observed in DES+ patients, confirming that a pre-operative assessment was important in this specific population. In contrast, the ECG was non-contributory. The deliberate choice of simple indices of dyssynchrony in this study should enable their reproducible application as pointed out by the PROSPECT trial [18] on a large-scale with standard echo instrumentation.

CRT was introduced in 1994, from the working hypothesis that an improvement might be expected by correcting interventricular dyssynchrony, after optimization of AV synchrony [19]. Several authors later focused their attention on intraventricular dyssynchrony [20-23], defined as differences in contraction delays among various LV segments. However, in patients with a wide QRS and marked dyssynchrony, the timing of septum and lateral wall contractions might not be asynchronous [24]; and furthermore this method does not describe the amount of LV mass contracting after the end of systole, marked by the closure of the aortic valve. In the present study, intraventricular dyssynchrony was not detected by measuring differences in the timing of LV segments [20-23], but by temporal dyssynchrony of at least one LV segment between diastole and systole. It was expressed as a prolonged systole, identified locally by a diastolic contraction of the LLW after aortic valve closure, globally by LPEP prolongation, or both. A prolongation of systole shortens the filling period, justifying the choice of LVFT as a diagnostic criterion of cardiac dyssynchrony. While this choice might be challenged, we believe that a marked increase in the AV temporal sequence in patients with advanced ventricular dysfunction might strongly interfere with ventricular filling and, ultimately, with cardiac performance. The cut-off values for LVFT, IVD, LPEP and LLW overlap were suggested by preliminary observations made in candidates for CRT who had a wide QRS [25]. The present population, who had a narrower QRS, had a lesser degree of dyssynchrony. However, DES+ patients enrolled on the basis of ≥1 criterion had a significantly longer mean LPEP, IVD, and diastolic contraction, and shorter LVFT than DES– patients. This observation supports the hypothesis of a relationship between these variables which is also suggested by PROSPECT data that shows that no single parameter presently describes dyssynchrony. Diastolic contraction of the LLW was not prolonged enough, in this population, to cause overlap with the next filling phase, and further patient selections based on this simple methodology should probably also include an evaluation of the septum to sharpen the discrimination between DES+ and DES– patients. The identification process in the present study may therefore be incomplete as some desynchronized intraventricular segments may have been missed, perhaps explaining the clinical improvement observed in some DES– patients.

Finally, the post-implant measurements revealed no improvement, as judged from the criteria of dyssynchrony used in the study, in contrast to the initial experience in patients with wide QRS [25]. This suggests that standard biventricular stimulation did not deliver optimal therapy in this "narrow QRS" population, an observation that warrants further evaluation which is also supported by the RethinQ study. The only difference observed was the change in LPEP/LVET ratio, a variable correlated with cardiac output and LVEF [26,27]. At 6 months, it increased in non-responders and decreased non-significantly in responders. The difference in the evolution of this variable was significant, despite a small number of observations. Its prognostic value after implant warrants further evaluation.

4.2. Study limitations
The size of the population enrolled in the study was smaller than planned by the protocol. "Narrow QRS" patients are currently not commonly viewed as potential candidates for CRT despite suffering from severe HF, and are infrequently referred to pacemaker centres. The use of CRT pacemakers in DESIRE could be criticised, especially for ischaemic patients. There is however no current evidence of the superiority of CRT-D devices over CRT-P at least in primary prevention patients [28]. Actually, no ventricular arrhythmic death was observed at 1 year in DESIRE, and a single patient underwent upgrade of the system to a CRT-D device.

Since the small size of the study population precluded the strict application of the composite endpoint proposed by Packer, [29] we assigned a hierarchy to our study endpoints. The subjective NYHA functional class endpoint was considered last and, when decreased along with an increase in the number of hospitalisations, was not viewed as a clinical improvement. In an attempt to document the changes in clinical status, the duration of hospitalisation before versus after CRT implant was compared. While we acknowledge the softness of this criterion, a marked difference was, nevertheless, observed between clinically improved and non-improved patients at 6 months of follow-up.


   5. Conclusions
Top
 Abstract
 1. Introduction
 2. Patient population and...
 3. Results
 4. Discussion
 5. Conclusions
Acknowledgments
 References
 
In this study of patients presenting with chronic HF and a QRS width <150 ms, the presence of one or more simple indices of mechanical dyssynchrony at baseline D-echo examination, but not QRS duration, predicted the response to CRT at 6 months of follow-up.

The following investigators and institutions participated in the DESIRE study:

Principal investigator: Dr. Serge Cazeau, Inparys, St Cloud, France.

Co-investigators: Pr. Jean Claude Daubert, CHRU Pontchaillou, Rennes, France; Dr. Vince Paul, St Peter's Hospital, Chertsey, UK; Pr. Gerd Fröhlig, Medizinische Universität, Homburg, Germany; Pr. Luigi Tavazzi, Policlinico San Matteo, Pavia, Italy; Dr. Frédéric Anselme, Hopital Charles Nicolle, Rouen, France; Dr. Jean Pierre Cebron, Nouvelles Cliniques Nantaises, Nantes, France; Dr. Ralph Mletzko, Herz-Kreislauf-Kliniken, Bad Bevensen, Germany; Dr. Pascal Defaye, CHRU Albert Michalon, Grenoble, France; Dr. Robert Franck, Hopital Pitié Salpétrière, Paris, France; Pr. Nadir Saoudi, Centre Hospitalier Princesse Grace, Monaco; Pr. Pierre Djiane, Hopital Sainte Marguerite, Marseille, France; Dr. Thomas Lavergne, HEGP, Paris, France; Dr. Marc Delay, Centre Hospitalier Rangueil, Toulouse, France; Pr. Jean Marc Davy, CHU Arnaud de Villeneuve, Montpellier, France; Dr. Ludwig Binner, Universitätsklinik, Ulm, Germany; Pr. Nicholas Sadoul, CHU Brabois, Nancy, France.

Echocardiography core laboratory: Dr. Gael Jauvert, Clinique Bizet, Paris, France.


   Acknowledgments
Top
 Abstract
 1. Introduction
 2. Patient population and...
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
References
 
This study was supported by the Research Department of ELA Medical, Sorin Group, Montrouge, France.

The authors express their gratitude to Professor Michel Komajda, Groupe hospitalier Pitie-Salpetriere, Paris, France, for his assistance in the development of the protocol, Mr Emanuel Prades, Sorin Group, for his contributions to the data collection, Pierre Henri Siot, Sorin Group, for his help in the statistical analysis, and Dr Gael Jauvert, for supervising the core echocardiographic laboratory of Bizet Medical Centre.


   References
Top
 Abstract
 1. Introduction
 2. Patient population and...
 3. Results
 4. Discussion
 5. Conclusions
 Acknowledgments
 References
 

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