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European Journal of Echocardiography Advance Access originally published online on February 7, 2008
European Journal of Echocardiography 2008 9(5):594-598; doi:10.1093/ejechocard/jen005
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Published on behalf of the European Society of Cardiography. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Prognostic importance of tissue Doppler-derived diastolic function in patients presenting with acute coronary syndrome: a bedside echocardiographic study

Marjorie Richardson-Lobbedez1,{dagger}, Sylvestre Maréchaux1,{dagger}, Christophe Bauters2, Julie Darchis1, Jean Luc Auffray1, Jean Jacques Bauchart1, Jean Marc Aubert1, Thierry H. LeJemtel4, Martine Lesenne1, Eric Van Belle2, Patrick Goldstein3, Philippe Asseman2 and Pierre V. Ennezat1,*

1 Centre Hospitalier Régional et Universitaire de Lille, Intensive Care Unit, Lille F-59019, France
2 Université de Lille II, faculté de médecine, Lille F-59045, France
3 Centre Hospitalier Régional et Universitaire de Lille, Emergency Department, Lille F-59019, France
4 Division of Cardiology (THL), Tulane Medical School of Medicine, New Orleans, LA, USA

Received 4 August 2007; accepted after revision 28 October 2007; online publish-ahead-of-print 7 February 2008.

* Corresponding author. Intensive Care Unit, Cardiology Hospital, Bd Pr J. Leclercq, 59000 Lille, France. Tel: +33 03 20 44 53 30; fax: +33 03 20 44 56 04. E-mail address: ennezat{at}yahoo.com


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Conclusion
 Notes
 References
 
Aims: We sought to evaluate the prognostic value of bedside tissue Doppler derived diastolic function in patients presenting with acute coronary syndrome (ACS) on top of major clinical predictors of mortality and routine laboratory testings.

Methods and results: Bedside Doppler echocardiography and laboratory tests were prospectively performed in 239 consecutive patients (mean age 62 ± 14, 69% men) admitted for ACS. Ratio of early transmitral flow (E) to early mitral annulus velocities (e') was calculated. The study endpoint was cardiac death. The median follow-up period was 2 years. E/e' was >15 in 39 patients. Multivariate predictors of E/e' > 15 were older age, diabetes, non-ST-segment elevation ACS, and decreased LV ejection fraction (LVEF). Survival free from cardiac death was lower in patients with E/e' ratio >15 (P = 0.01). History of coronary artery disease, lower creatinine clearance, higher glycemia on admission, decreased LVEF, and E/e' >15 were independent predictors of cardiac death.

Conclusion: Bedside Doppler echocardiography provides prognostic information on top of major clinical predictors of mortality and routine laboratory testings in patients presenting with ACS.

Keywords: Tissue Doppler imaging; Acute coronary syndrome; Prognosis


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Conclusion
 Notes
 References
 
Several studies have demonstrated the prognostic importance of clinical and biological data in the risk stratification of patients with acute coronary syndrome (ACS).1–4 Clinical evidence of heart failure is a powerful predictor of worse prognosis in these patients.5 However, elevated LV filling pressure may be clinically silent. Besides its usefulness for quantification of LV systolic function, Doppler echocardiography provides useful information regarding LV filling pressure. Ommen et al.6 have previously reported that ratio of early transmitral flow (E) to early mitral annulus velocities (e') >15 indicates elevated LV enddiastolic pressure measured by cardiac catheterization. Other investigators have observed a poor outcome in a retrospective cohort of patients with ACS when E/e' ratio >15.7 However, the prognostic value of E/e' ratio >15 on top of both major clinical predictors of mortality and routine laboratory testings has not been prospectively assessed in this setting. The current study addressed this issue.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Conclusion
 Notes
 References
 
Population
The study cohort consisted of patients enrolled in a prospective observational study designed to determine the prognostic value of E/e' ratio >15 in the setting of ACS. All the patients enrolled during this period had a transthoracic echocardiogram on admission. Acute coronary syndrome was defined using the European Society of Cardiology/American College of Cardiology guidelines.8,9

Doppler echocardiography
Echocardiograms were carried out by staff cardiologists using HP Sonos 5500 ultrasound system (Philips, Andover, USA) with a 2–4 MHz transducer. At least three cardiac cycles were used for each measurement, and the average value was taken. LV ejection fraction (LVEF) was calculated according to the Simpson’s rule. For practical purposes, LVEF was stratified as normal (LVEF ≥ 55%), midly reduced (45–54%), moderately reduced (30–44%), or severely reduced (<30%).10 The severity of mitral regurgitation (MR) was semi-quantitatively graded from colour-flow Doppler images in the apical four- and two-chamber views. The severity of MR was classified as mild (jet area/left atrial area <20% in the absence of wall jet), moderate (jet area /left atrial area 20–40%), or severe (jet area/left atrial area >40%).11,12 Pulsed Doppler mitral inflow velocities were obtained by placing a 1–2 mm sample volume between the tips of the mitral leaflets in the apical four-chamber view. The Doppler beam was aligned parallel to the direction of flow. The following variables were measured in end expiratory apnea: peak early filling velocity (E); peak filling velocity at atrial contraction (A velocity); E/A ratio; deceleration time of the peak E velocity, defined as the slope from peak E extrapolated to the baseline value. Restrictive mitral inflow patterns were defined as a E/A ratio≥2 or an E/A ratio between 1 and 2 with a E-wave deceleration time ≤140 ms.13,14 Tissue Doppler imaging of the mitral annulus was obtained from the four apical chamber view. The sample volume was placed sequentially at the lateral and medial mitral annulus. Both velocities were averaged as previously described.15 Previous studies have demonstrated an E/e' ratio >15 to be the best Doppler predictor of an elevated mean LV diastolic pressure6 and was found valuable even in the presence of MR.16 Therefore an increased E/e' ratio was prospectively defined as >15.

Clinical data and patient follow-up
Medical history, admission heart rate, systolic blood pressure, Killip classification, medications were recorded. Laboratory tests were performed within 15 min following admission. Electrocardiographic findings were classified according to the presence or not of ST-segment elevation. Glomerular filtration rate (mL/min) was calculated using the Cockroft–Gault formula.17

After hospital discharge, the clinical status of patients was monitored by telephone calls to referring cardiologists and primary care physicians. The primary endpoint of the study was cardiac death.

Statistical analysis
Continuous variables are expressed as mean ± SD or median [25th–75th] percentiles as appropriate. Categorical variables are presented as absolute numbers and percentages. Comparisons between groups were made using Student's t-test or Mann–Whitney U test as appropriate. Categorical variables were compared using the {chi}2 test or the Fisher’s exact test as appropriate. Complete instead of stepwise multivariate logistic regression analysis was performed to determine independent predictors of E/e' > 15. Event free survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. Multivariate Cox proportional hazards modelling was used to determine the relationships between E/e' > 15 and cardiac death during follow up. An interaction between ST-segment elevation and E/e' ratio was assessed using a Cox multivariate model including E/e' > 15, presence of ST-segment elevation and the interaction between these two parameters. Clinical, biological, and echocardiographic parameters believed to have potential importance were forced into the Cox multivariate model (age, baseline heart rate, systolic blood pressure, Killip class ≥2 on admission, history of coronary events, smoking status, hypertension, diabetes mellitus, anterior infarction, creatinine clearance, coronary revascularization, and LVEF). Other variables associated with cardiac death with a P-value of <0.1 in Cox univariate analysis were entered into the multivariate Cox model. A two-tailed type I error rate <0.05 was considered for statistical significance. Analyses were conducted using SPSS 13.0 (Chicago, IL, USA) and the SAS system 9.0 for Windows (SAS Institute).


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 Conclusion
 Notes
 References
 
Patient characteristics
Between 1 June and 1 October 2004, 239 patients presenting with ACS were enrolled in this prospective observational study. Patients with atrio-ventricular block (n = 3), primary valve disease (n = 7), mechanical ventilation (n = 9), or poor echocardiographic window (n = 6) were ineligible for the study. The clinical characteristics of the 239 patients are shown in Table 1. One hundred sixty five men and 74 (31%) women were included. Mean age was 62 ± 14 years. Nineteen patients (8%) had unstable angina. Three patients presented with atrial fibrillation. History of previous myocardial infarction or coronary revascularization was reported in 28% of the patients. The use of glycoprotein 2b3a receptor blocker, clopidogrel, and aspirin was 54, 92, and 97%, respectively. Coronary angiography was performed in 224 patients. One hundred seventy seven patients underwent percutaneous coronary interventions with stenting and 17 coronary artery bypass graft surgery. The mean length of hospital stay was 4 ± 5 days. Index echocardiograms were obtained 3.7 ± 0.4 h after admission and all before cardiac catheterism. E/e' ratio was more than 15 in 39 patients (16%). Univariate predictors of E/e' ratio > 15 are depicted in Table 1. Multivariate predictors of E/e' > 15 were older age, diabetes, non-ST segment elevation ACS and decreased LVEF (Table 2).


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  		Table 1 Patients characteristics according to the E/e' ratio

 


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  		Table 2 Independent predictors of E/e' ratio >15 in patients with acute coronary syndrome

 
At hospital discharge, 87% of the patients received a beta-blocker, 97% aspirin, 93% clopidogrel, 93% a statin, 95% an angiotensin-converting enzyme inhibitor, or an angiotensin II receptor blocker.

Follow-up
Follow-up data were available for 235 patients. During follow-up, a median of 706 [615–773] days later, 40 patients died. Thirty-two patients died from cardiac causes. Survival free from cardiac death was significantly lower in patients with a E/e' ratio >15 (log- rank = 6.36, P = 0.01, Figure 1). There was no interaction between the presence of ST-segment elevation and a E/e' ratio >15 (P = 0.80), so that no further analysis was carried out according to the presence or absence of ST-segment elevation. As depicted in Table 3, age, a history of previous coronary events, diabetes mellitus, hypertension, current smoking, a lower systolic blood pressure and a higher heart rate on admission, a Killip class ≥2, a lower creatinine clearance, a lower hemoglobin level and a higher glycemia on admission, a lower LVEF, the presence of moderate or severe MR, and a higher E/e' ratio were the univariate predictors of cardiac death. Survival free from cardiac death according to LVEF as a categorical variable is depicted in Figure 2. By Cox multivariate analysis, history of previous coronary events, creatinine clearance, glycemia on admission, LVEF, and E/e' > 15 were independent predictors of cardiac death (Table 2). E/e' ratio >15 added independent and incremental prognostic information to that provided by clinical and biological parameters (Figure 3).


Figure 1
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  		Figure 1 Cumulative survival curves (follow-up in days) according to E/e' ratio below and above 15.

 


Figure 2
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  		Figure 2 Cumulative survival curves (follow-up in days) according to LV ejection fraction.

 


Figure 3
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  		Figure 3 Incremental prognostic value of Doppler echocardiography over clinical data and routine blood test: {chi}2= 58 for clinical variables (age, gender, hypertension, smoking status, history of previous coronary events, systolic blood pressure, heart rate, and Killip class ≥2 on admission); {chi}2= 80 (P < 0.0001 vs. clinical variables alone) for clinical variables plus routine blood tests (creatinine clearance, glycemia, hemoglobin); {chi}2 = 91 (P = 0.004 vs. clinical plus biological variables) for clinical variables plus blood tests plus echocardiographic parameters including LV ejection fraction, moderate to severe mitral regurgitation and E/e' > 15.

 


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  		Table 3 Clinical, laboratory, and echocardiographic variables associated with cardiac death in Cox univariate and multivariate analysis

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Conclusion
 Notes
 References
 
The present data indicate that (i) bedside Doppler echocardiography obtained on admission provides prognostic information in patients with ACS receiving a modern therapeutic strategy and (ii) the association between E/e' ratio >15 and the long-term risk of cardiac death was independent of clinical evidence of heart failure, as well as of renal dysfunction, blood glucose level, LV systolic dysfunction, and MR.

Prognosis, clinical, and biological data in acute coronary syndrome
Both history of previous coronary events and lower glomerular-filtration rate correlated with poor prognosis in the present cohort of patients with ACS. Such observation is not unexpected since previous studies demonstrated the importance of these parameters in patients presenting with ACS.1,3 Interestingly, higher glycemia on admission correlated with poor outcome independently from previous diabetes, as previously reported.18 Of note, hyperglycemia on admission predicts LV remodelling after first anterior myocardial infarction in non-diabetic patients.19

Prognosis and Doppler echocardiography in acute coronary syndrome
Besides its usefulness for quantification of LV systolic function, Doppler echocardiography provides useful information for the assessment of diastolic function and LV filling pressures. The E/e' ratio has been well validated to assess LV filling pressures.6 The threshold of E/e' > 15 identifies at best patients with mean LV diastolic pressures above 12 mmHg measured by micromanometer-tipped catheters.6 Raised LV filling pressures indicate a relatively load intolerant myocardium. This may results from major myocardial damage due to coronary occlusion or conversely from minor damage associated with a previous stiff LV chamber due to aging, hypertension, diabetes, or coronary atherosclerosis. These patients with increased LV filling pressures show poor outcome in our cohort as in other.7

The analysis of mitral inflow using pulsed Doppler signal recorded at the tips of the leaflets has a prognostic value in various cardiac diseases. Higher mitral E/A ratios and shorter deceleration times that define the restrictive pattern indicate an increased risk of adverse events after myocardial infarction.20 Similarly Temporelli et al.21 have also observed a poor outcome in 571 patients enrolled in the GISSI-3 trial when mitral deceleration time is shortened. The propagation velocity of mitral inflow measured on M-mode colour Doppler echocardiography has also prognostic significance.22 However, reproducibility and quality of measurement of a colour M-mode slope that requires to carefully adjust the colour scale, in acute condition may be questionable in routine clinical practice. By contrast, the direct recording of mitral annulus motion using tissue Doppler is easily obtained. The E/e' ratio gives a reasonable estimate of LV filling pressures6 and remains valid in the presence of sinus tachycardia,23 functional MR,16 and preserved or depressed LV systolic function.24

Interestingly, MR was associated with cardiac death in univariate analysis. However, MR was not an independent predictor of poor outcome in contrast to Perez de Isla et al.25 findings. LV dilation and dysfunction affect mitral leaflet competence thereby leading to functional MR.26 Functional MR in ACS might be the harbinger of LV dysfunction and could explain why the association was not found after adjustment on LV function parameters as previously suggested by Hillis et al.27

Current guidelines do not recommend index echocardiogram for patients admitted for unequivocal ACS.9 However, bedside Doppler echocardiography may provide valuable diagnostic and prognostic information in the management of patients with acute chest pain who are admitted in intensive care.

When the present investigation was initiated, B-type natriuretic peptide measurement was not routinely performed.28 Because of the time-dependent changes in E/e', discharge E/e' may provide further additional information. MR was not quantified using the flow convergence method.29 For these reasons, other community-based studies with ACS will be valuable.


   Conclusion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
Notes
 References
 
Bedside Doppler echocardiography provides additional prognostic information over clinical and biological parameters that are routinely determined in patients presenting with ACS. The present study advocates to perform index bedside Doppler echocardiography in the modern era of ACS management.

Conflict of interest: none declared.


   Notes
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Notes
References
 
{dagger} M. R.-L. and S. M. both contributed equally to the preparation of the manuscript. Back


   References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 Notes
 References
 

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