- Email: [email protected]
Prognostication and risk stratification by assessment of left atrioventricular plane displacement in patients with myocardial infarction
International Journal of Cardiology 83 (2002) 35–41 www.elsevier.com / locate / ijcard
Prognostication and risk stratification by assessment of left atrioventricular plane displacement in patients with myocardial infarction ¨ Brand, Erik Rydberg, Gerd Ericsson, Petri Gudmundsson, Ronnie Willenheimer* Bjorn Department of Cardiology, Malmo¨ University Hospital, Lund University, S-205 02 Malmo¨ , Sweden Received 1 June 2001; received in revised form 14 December 2001; accepted 11 January 2002
Abstract Background: Mean left atrioventricular plane displacement is strongly related to prognosis in patients with heart failure. We aimed to examine its value for prognostication and risk stratification in patients hospitalised for acute myocardial infarction. Methods and results: Left atrioventricular plane displacement was assessed by echocardiography in 271 consecutive patients with acute myocardial infarction. Mean prospective follow-up was 628 days. Atrioventricular plane displacement was readily assessed in all patients and was significantly lower in patients who died (n541, 15.1%) compared to the survivors: 8.2(5.6) v. 10.0(5.5) mm, P,0.0001. Overall mortality was 31.3% in the lowest quartile with regard to atrioventricular plane displacement (,8.00 mm) and 10.1% in the combined upper three quartiles. Thus, the hazard ratio for an atrioventricular plane displacement ,8.0 mm compared to 8 mm or more was 3.1, P50.0001. The combined mortality / heart failure hospitalisation incidence was 43.8% in the lowest and 14.6% in the combined upper three quartiles: Risk ratio 3.0, P,0.0001. In multivariate analysis, including age and history of atrial fibrillation, left atrioventricular plane displacement was an independent prognostic marker. Conclusion: In post-myocardial infarction patients, echocardiographic assessment of atrioventricular plane displacement showed a strong, independent prognostic value. Determination of left atrioventricular plane displacement can be readily performed in virtually all patients, and may in clinical practice facilitate identification of high-risk patients. 2002 Elsevier Science B.V. All rights reserved. Keywords: Myocardial infarction; Left atrioventricular plane displacement; Prognostication and risk stratification
1. Introduction The prognosis after acute myocardial infarction is related to the degree of left ventricular systolic dysfunction [1–5]. Left ventricular systolic function is often expressed as ejection fraction and most commonly measured by radionuclide ventriculography, contrast cineangiography and echocardiography. Echocardiography is the least complicated,
*Corresponding author. Tel.: 146-40-33-1000; fax: 146-40-33-6209. E-mail address: [email protected] (R. Willenheimer).
expensive and time consuming, as well as the most accessible method. Several echocardiographic techniques can be applied to evaluate global left ventricular systolic function. Traditional techniques, however, all have drawbacks. The fractional shortening and Teichholtz techniques are not reliable when left ventricular contraction is asymmetrical [6–8]. Two-dimensional echocardiography tolerates asymmetry but requires good image quality for adequate tracing of the endocardial borders [9–11], which is not always obtainable [12]. Some investigators have reported a poor agreement between left ventricular ejection fraction determined by two-dimensional echocardiog-
0167-5273 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. PII: S0167-5273( 02 )00007-4
36
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
raphy and ejection fraction evaluated by radionuclide ventriculography or contrast cineangiography [13,14]. Others have shown that two-dimensional echocardiography correlates closely with radionuclide ventriculography [15,16]. It has been reported that twodimensional echocardiographic assessment of regional wall motion correlates closely with haemodynamic status, and that it is reliable, reproducible and valuable for selecting high risk patients [17,18]. It does, however, require experienced investigators and it is somewhat time-consuming [17,18]. The left ventricular pump function has traditionally been thought to be mainly related to the action of the circumferentially oriented myocardial fibres [19]. However, the complexity of myocardial fibre orientation and the importance of longitudinal fibres was thoroughly described in man in the early 1980’s [20], and has since been further clarified [21–29]. The epicardial surface of the heart remains practically immobile during the cardiac cycle [22], and normal left ventricular ejection requires displacement of the atrioventricular plane. During cardiac systole the atrioventricular plane moves towards the apex as a result of contraction of longitudinal fibres [22]. Since the distance between the apex and the chest surface is constant during the cardiac cycle [22,23,30], the left atrioventricular plane displacement (AVPD) as measured from the surface of the thorax, using transthoracic two-dimensionally guided M-mode echocardiography, equals the intraventricular displacement [25]. Mean left AVPD reflects global left ventricular function despite left ventricular asymmetry, since it is determined in four different regions of the left ventricle—the septal, lateral, inferior and anterior regions—and since it evaluates the total shortening along the left ventricular long axis in the respective region. Demands on image quality are quite low, as the atrioventricular plane is highly echogenic, and the examination only takes a few minutes [12]. We have previously shown that the prognosis in patients with heart failure correlates closely with the degree of left AVPD impairment [12]. The aim of the present study was to investigate the prognostic value of an echocardiographic determination of the left AVPD in patients with an acute myocardial infarction. We also wanted to assess whether cardiac morbidity was related to the degree of left AVPD impairment.
2. Methods
2.1. Subjects We consecutively included all patients hospitalised with a diagnosis of acute myocardial infarction and undergoing an echocardiographic examination at our Department of Cardiology between May 1st 1997 and March 31st 1998, with a measurement of the left AVPD at the time of hospitalisation. Diagnosis of myocardial infarction was based upon at least two out of three criteria of acute myocardial infarction: typical chest symptoms, characteristic ECG changes and cardiac protein raise (CK-MB, Troponin-T or Troponin-I) characteristic of myocardial damage.
2.2. Echocardiography Two-dimensional echocardiography were performed 4.2 (6.4) days after the myocardial infarction by an experienced investigator. The equipment used was a Hewlett-Packard (Andover, MA, USA) Sonos 2000 or 2500 echocardiography system and a 2.5 MHz transducer. Apical views were obtained with the patient in a left lateral recumbent position. Measurements were acquired during silent respiration or endexpiratory apnoea. Left AVPD was determined in two-dimensionallyguided M-mode in the four and two chamber views, as described previously [12,31,32]. The regional AVPD (mm) was the distance covered by the atrioventricular plane between the position most remote from the apex (corresponding to the onset of contraction) and the location closest to the apex (corresponding to the end of contraction, including any post-ejection shortening), i.e. the full extent of the displacement. AVPD was measured in the septal, lateral, inferior and anterior regions of the left ventricle, and was calculated from an average of two heart cycles at each site in patients with regular rhythm, and four in patients with irregular rhythm. The mean of the average AVPD in the four regions was calculated and is expressed as left AVPD. No patients had to be excluded from this study due to poor image quality, and all four regions of left AVPD was measured in all patients. The mean inter-observer variability in our laboratory between two investigators examining each pa-
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
tient immediately after one another was 4.8% (AVPD difference range 0–1.2 mm) in a series of 53 consecutive patients with an average left AVPD of 7.8 mm (range 3.3–15.5 mm) [12]. The intra-observer variability of the determination of left AVPD was mean 2.0% (range 0–6%), corresponding to 0.23 mm (range 0–0.95 mm), in 39 randomly examined patients with an average left AVPD of 11.2 mm (range 5.6–17.5 mm) [33]. The average left AVPD in 15 controls (mean age 65 years, range 54 to 77 years, eight (53%) women) was 13.561.1 mm, and a left AVPD ,10.0 mm is considered abnormal [33]. Assessment of the echocardiograms was performed blinded to patient follow-up and other clinical data. Investigations were in accordance with the Declaration of Helsinki.
2.3. Follow-up Patients were followed-up with respect to mortality and cardiac hospitalisations for an average of 628 days following inclusion. All hospitalisations and deaths in Malmo¨ are registered in a central database. ¨ Since all patients included were residents of Malmo, cardiac morbidity, expressed as cardiac hospitalisations, and all cause mortality were reliably assessed from this database. The causes of hospitalisations were categorised into heart failure and ischemic (myocardial infarction and unstable angina pectoris). Other causes of hospitalisation were not subject to assessment in this study.
2.4. Statistics Differences between two groups regarding continuous variables were tested by Student’s unpaired t-test. To evaluate differences between groups with respect to nominal values the x 2 (for more than 232) and Fischer’s exact (for 232) tests were used. To compare multiple groups regarding continuous variables the Kruskal–Wallis test was performed. Simple and multiple linear regression analysis and analysis of variance were used to analyse correlations between continuous variables. Logistic regression analysis was used to assess the relation between left AVPD and mortality risk. Multiple logistic regression analysis was used to assess the independent prognostic value
37
of left AVPD. Data are expressed as mean (S.D.), and a P-value of ,0.05 was considered significant. In analysing the endpoints we combined the endpoints into ‘morbid and mortal’ events consisting of events that in previous studies have been shown to be associated with a worsened prognosis (hospitalisation due to myocardial re-infarction, heart failure and unstable angina pectoris).
3. Results A total of 271 patients were included into the study. Baseline characteristics are displayed in Table 1. The patients were followed up for 628 (199) days. The average left AVPD in all patients (n5271) was 9.7 (2.4) mm, and was significantly lower in the patients who died (n541, 15.1%) compared to the survivors: 8.2 (5.6) mm v. 10.0 (5.5) mm, P, 0.0001. The relation between left AVPD and mortality is shown in Fig. 1. The patients were divided into quartiles with respect to left AVPD. In the quartiles left AVPD was ,8.00, 8.00–9.75, 9.76–11.05 and .11.05 mm, respectively. The quartiles were compared regarding mortality (Fig. 2) and combined death or heart failure hospitalisation (Fig. 3). In both analyses we found that the patients in the lowest quartile had a substantially higher event rate compared with those in the combined upper three quartiles. Mortality was 31.3% v. 10.1%: Hazard ratio (HR) 3.10, P50.0001. The frequency of death or heart failure hospitalisation was 43.8% v. 14.6%: Risk ratio (RR) 3.00, P,0.0001. The incidence of the combined morbid and mortal events (mortality and hospitalisation due to heart failure, myocardial infarction and unstable angina pectoris) also differed significantly between the patients in the lowest quartile and those in the combined upper three quartiles: 48.4% v. 30.4%, RR 1.59, P50.0082 (Fig. 4). Baseline characteristics comparing patients in the lowest and the upper three AVPD quartiles are shown in Table 1. Mean age was higher and there was a non-significant 40% greater proportion of women in the lowest quartile. Patients in the lowest AVPD quartile had a higher prevalence of prior myocardial infarctions and pre-existing atrial fibrillation, heart failure, diabetes and hypertension. The rate of other
38
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
Table 1 Baseline characteristics comparing the lowest (Q 1) and the combined upper three (Q 2–4) AVPD quartiles
Age, years (S.D.) Females, n (%) Current smoking, n (%) AMI / echo-time, days (S.D.) Q-wave infarction, n (%) Anterior AMI, n (%) Prior AMI, n (%) Prior angina pectoris, n (%) Prior PTCA / CABG, n (%) Prior atrial fibrillation, n (%) Prior heart failure, n (%) Prior diabetes mellitus, n (%) Prior hypertension, n (%) Obstructive lung disease, n (%) Malignancy, n (%) Kidney disease, n (%) Collagenosis, n (%)
All
Q1
Q 2–4
P
69.1 (11.8) 83 (30.6) 82 (30.5) 4.2 (6.4) 121 (45.7) 107 (41.5) 83 (30.9) 113 (40.0) 17 (6.3) 19 (7.0) 20 (7.5) 56 (20.7) 86 (31.9) 29 (10.8) 17 (6.3) 9 (3.3) 12 (4.5)
74.5 (8.7) 25 (39.1) 16 (25.4) 4.0 (3.2) 26 (42.6) 23 (39.0) 27 (42.2) 28 (44.4) 5 (7.9) 13 (20.3) 9 (14.3) 19 (29.7) 28 (43.8) 8 (12.7) 5 (7.9) 2 (3.2) 4 (6.3)
67.5 (12.2) 58 (28.0) 66 (32.0) 4.3 (7.2) 95 (46.6) 84 (42.2) 56 (27.3) 85 (41.3) 12 (5.9) 6 (2.9) 11(5.4) 37 (18.0) 58 (28.2) 21(10.2) 12 (5.8) 7 (3.4) 8 (3.9)
,0.0001 NS NS NS NS NS 0.0246 NS NS ,0.000 1 0.0185 0.0433 0.0193 NS NS NS NS
AVPD, atrioventricular plane displacement; AMI, acute myocardial infarction; AMI / echo-time, time from acute myocardial infarction to echocardiographic examination; PTCA / CABG, percutaneouos transluminal coronary angioplasty or coronary bypass surgery.
concomitant diseases was the same when comparing the lowest and the upper three AVPD quartiles. Left AVPD was an independent prognostic marker (P5 0.0225), in multiple logistic regression analysis including the other two most powerful prognostic markers, age and history of atrial fibrillation. Thrombolytic treatment and medication at discharge is shown in Table 2.
4. Discussion
Fig. 1. Mortality risk plotted against the mean left atrioventricular plane displacement (AVPD) by logistic regression analysis. Dotted lines show 95% confidence interval.
Fig. 2. Mortality in relation to quartiles of mean left atrioventricular plane displacement. P50.0002 for between quartile difference tested by the x 2 test. 1, Quartile with lowest AVPD; 4, quartile with highest AVPD.
In the present study, all cause mortality in patients after myocardial infarction was strongly related to left AVPD. We have previously found a strong relation between left AVPD and mortality in heart failure patients [12]. In the present study, the mortality risk curve in relation to left AVPD had the same appearance as in the heart failure patients in that study [12].
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
Fig. 3. Event rate of combined death or heart failure hospitalisation by quartiles of mean left atrioventricular plane displacement. P,0.0001 for between quartile difference tested by the x 2 test. 1, Quartile with lowest AVPD; 4, quartile with highest AVPD.
The only obvious difference was that left AVPD was higher and the mortality rate lower compared with the heart failure patients. We also found a higher rate of hospitalisation for heart failure in patients with low left AVPD. This is to be expected given the known relationship between heart failure morbidity and left ventricular systolic dysfunction. There was, however, no such difference regarding hospitalisation due to ischemic events, i.e. myocardial infarction and unstable angina pectoris. There were some important differences in baseline characteristics between the patients in the lowest and those in the combined upper three AVPD quartiles. Thus, the mean age was substantially higher and a history of atrial fibrillation was considerably more
39
Fig. 4. Rates of combined ‘morbid and mortal’ events (myocardial infarction, mortality, heart failure and unstable angina pectoris). Between quartile difference tested by the x 2 test: morbid and mortal, P50.0382. 1, Quartile with lowest AVPD; 4, quartile with highest AVPD.
common in the lowest quartile. However, the multiple logistic regression analysis showed that the prognostic value of left AVPD was independent of these variables. It is well known that assessment of left ventricular systolic function provides important prognostic information. However, as opposed to most other methods for the evaluation of left ventricular systolic function, determination of left AVPD is easy, highly reliable and reproducible, and can be performed in virtually all patients. Left AVPD has a high discriminative value, which is indicated by the considerable differences in mortality and heart failure hospitalisation rates, despite the small differences in left AVPD between AVPD quartiles of patients. As the frequency of autopsies performed in Malmo¨
Table 2 Thrombolytic treatment and medication at hospital discharge comparing the lowest (Q 1) and the combined upper three (Q 2–4) AVPD quartiles
Thrombolysis, n (%) b-Blockers Calcium-blockers Nitrates Diuretics RAAS inhibitors Digitalis glycosids Aspirin / antiplatelet drugs Anti-coagulants
All
Q1
Q 2–4
P
71(26.5) 66.4% 13.8% 40.3% 38.8% 33.2% 7.8% 88.0% 16.8%
7(11.1) 44.4% 20.6% 34.9% 74.6% 58.7% 20.6% 85.7% 17.5%
64(31.2) 73.2% 11.7% 42.0% 27.8% 25.4% 3.9% 88.8% 16.6%
0.0015 ,0.000 1 NS NS ,0.0001 ,0.0001 ,0.0001 NS NS
AVPD, atrioventricular plane displacement; RAAS, renin–angiotensin–aldesterone system.
40
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
has dropped in the last decades, and the determination of the cause of death without an autopsy being performed is subject to a high degree of subjectivity, we choose not to assess cause of death but only to register total mortality. This may be regarded as a limitation to the study. Another possible limitation is that we did not assess non-cardiac reasons for hospitalisation.
5. Conclusions In conclusion, echo cardiographic assessment of left AVPD is a powerful independent clinical tool for prognostication and risk stratification in patients with acute myocardial infarction. Left AVPD is easily and readily assessed in all patients, which is an advantage compared to many other prognostic methods. By using risk stratification based on assessment of left AVPD in clinical practice high-risk patients may be readily and correctly identified.
References [1] Taylor GJ, Humphries JO, Mellits ED et al. Predictors of clinical course, coronary anatomy and left ventricular function after recovery from acute myocardial infarction. Circulation 1980;62:960–70. [2] The Multicenter Post-infarction Research Group. Risk stratification and survival after myocardial infarction. New Engl J Med 1983;309:331–6. [3] Madsen EB, Hougaard P, Gilpin E. Dynamic evaluation of prognosis from time-dependent variables in acute myocardial infarction. Am J Cardiol 1983;51:1579–83. [4] Silverman KJ, Grossman W. Natural history and strategies for evaluation management. New Engl J Med 1984;310:1712–7. [5] Shah PK, Maddahi J, Staniloff HM et al. Variable spectrum and prognostic implications of left and right ventricular ejection fractions in patients with and without clinical heart failure after acute myocardial infarction. Am J Cardiol 1986;58:387–93. [6] Fortuin NJ, Hood WPJ, Sherman ME et al. Determination of left ventricular volumes by ultrasound. Circulation 1971;44:575–84. [7] Teichholtz LE, Kreulen T, Herman MV et al. Problems in echocardiographic volume determinations; echocardiographic–angiographic correlations in the presence or absence of asynergy. Am J Cardiol 1976;37:7–11. [8] Starling MR, Crawford MH, O’Rourke RA et al. Accuracy of subxiphoid echocardiography for assessing left ventricular size and performance. Circulation 1980;61:367–73. [9] Carr KW, Engler RL, Forsythe JR et al. Measurement of left ventricular ejection fraction by mechanical cross-sectional echocardiography. Circulation 1979;59:1196–206.
[10] Schiller NB, Acquatella H, Ports TA et al. Left ventricular volume from paired biplane two-dimensional echocardiography. Circulation 1979;60:547–55. [11] Parisi AF, Moynihan PF, Feldman CL et al. Approaches to determination of left ventricular volume and ejection fraction by real-time two-dimensional echocardiography. Clin Cardiol 1979;2:257–63. [12] Willenheimer R, Cline C, Erhardt L et al. Left ventricular atrioventricular plane displacement: An echocardiographic technique for rapid assessment of prognosis in heart failure. Heart 1997;78:230–6. [13] Folland ED, Parisi AF, Moynihan PF et al. Assessment of left ventricular ejection fraction and volumes by real time two-dimensional echocardiography. Circulation 1979;60:760–6. [14] Starling MR, Crawford MH, Sorensen SG et al. Comparative accuracy of apical biplane cross-sectional echocardiography and gated equilibrium radionuclide angiography for estimating left ventricular size and performance. Circulation 1981;63:1075–84. [15] Senior R, Sridhara BS, Basu S et al. Comparison of radionuclide ventriculography and 2D echocardiography for the measurement of left ventricular ejection fraction following acute myocardial infarction. Eur Heart J 1994;15:1235–9. [16] Naik M, Diamond G, Pai T et al. Correspondence of left ventricular ejection fraction determinations from two-dimensional echocardiography, radionuclide angiography and contrast cineangiography. J Am Coll Cardiol 1995;25:937–42. [17] Fisher JP, Picard MH, Mikan JS et al. Quantitation of myocardial dysfunction in ischeamic heart disease by echocardiographic endocardial surface mapping: correlation with hemodynamic status. Am Heart J 1995;129:1114–21. [18] Køber L, Torp-Pedersen C, Carlsen J et al. On behalf of the TRACE study group. An echocardiographic method for selecting high risk patients shortly after acute myocardial infarction, for inclusion in multicentre studies (as used in the TRACE study). Eur Heart J 1994;15:1616–20. [19] Rushmer RF, editor, Cardiovascular dynamics, 4th edition, Philadelphia: WB Saunders, 1976, p. 93. [20] Greenbaum RA, Ho SY, Gibson DG et al. Left ventricular fibre architecture in man. Br Heart J 1981;45:248–63. [21] Jones CJH, Raposo L, Gibson DG. Functional importance of the long axis dynamics of the human left ventricle. Br Heart J 1990;63:215–20. ¨ S. Cardiac pumping and the function of the ventricular [22] Lundback septum. Acta Physiol Scand 1986;550(suppl):1–101. [23] Pai RG, Bodenheimer MM, Pai SM et al. Usefulness of systolic excursion of the mitral annulus as an index of left ventricular systolic function. Am J Cardiol 1991;67:22–4. [24] Simonson JS, Schiller NB. Descent of the base of the left ventricle: an echocardiographic index of the left ventricular function. J Am Soc Echocardiogr 1989;2:25–35. ¨ [25] Hoglund C, Alam M, Thorstrand C. Atrioventricular valve plane displacement in healthy persons. Acta Med Scand 1988;224:557–62. ¨ [26] Alam M, Hoglund C. Serial echocardiographic studies following thrombolytic treatment in myocardial infarction with special reference to the atrioventricular valve plane displacement. Clin Cardiol 1992;15:30–6. ¨ [27] Alam M, Hoglund C, Thorstrand C. Londitudinal systolic shortening of the left ventricle: an echocardiographic study in subjects with and without preserved global function. Clin Physiol 1992;12:443–52. ¨ [28] Alam M, Hoglund C, Thorstrand C et al. Atrioventricular plane displacement in severe congestive heart failure following dilated cardiomyopathy or myocardial infarction. J Intern Med 1990;228:569–75.
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41 ¨ [29] Alam M, Hoglund C, Thorstrand C et al. Haemodynamic significance of the atrioventricular plane displacement in patients with coronary artery disease. Eur Heart J 1992;13:194–200. [30] McDonald IG. The shape and movements of the human left ventricle during systole. A study by cineangiography and by cineradiography of epicardial markers. Am J Cardiol 1970;26:221–30. [31] Willenheimer R, Erhardt L, Cline C et al. Prognostic significance of changes in left ventricular systolic function in elderly patients with congestive heart failure. Coronary Artery Dis 1997;8:711–7.
41
[32] Willenheimer R, Israelsson B, Cline C et al. Left atrioventricular plane displacement (AVPD) is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure. Eur Heart J 1999;20:612–8. [33] Willenheimer R. Assessment of left ventricular dysfunction and remodeling by determination of atrioventricular plane displacement and simplified echocardiography. Scand Cardiovasc J 1998;32(suppl 48).
Prognostication and risk stratification by assessment of left atrioventricular plane displacement in patients with myocardial infarction ¨ Brand, Erik Rydberg, Gerd Ericsson, Petri Gudmundsson, Ronnie Willenheimer* Bjorn Department of Cardiology, Malmo¨ University Hospital, Lund University, S-205 02 Malmo¨ , Sweden Received 1 June 2001; received in revised form 14 December 2001; accepted 11 January 2002
Abstract Background: Mean left atrioventricular plane displacement is strongly related to prognosis in patients with heart failure. We aimed to examine its value for prognostication and risk stratification in patients hospitalised for acute myocardial infarction. Methods and results: Left atrioventricular plane displacement was assessed by echocardiography in 271 consecutive patients with acute myocardial infarction. Mean prospective follow-up was 628 days. Atrioventricular plane displacement was readily assessed in all patients and was significantly lower in patients who died (n541, 15.1%) compared to the survivors: 8.2(5.6) v. 10.0(5.5) mm, P,0.0001. Overall mortality was 31.3% in the lowest quartile with regard to atrioventricular plane displacement (,8.00 mm) and 10.1% in the combined upper three quartiles. Thus, the hazard ratio for an atrioventricular plane displacement ,8.0 mm compared to 8 mm or more was 3.1, P50.0001. The combined mortality / heart failure hospitalisation incidence was 43.8% in the lowest and 14.6% in the combined upper three quartiles: Risk ratio 3.0, P,0.0001. In multivariate analysis, including age and history of atrial fibrillation, left atrioventricular plane displacement was an independent prognostic marker. Conclusion: In post-myocardial infarction patients, echocardiographic assessment of atrioventricular plane displacement showed a strong, independent prognostic value. Determination of left atrioventricular plane displacement can be readily performed in virtually all patients, and may in clinical practice facilitate identification of high-risk patients. 2002 Elsevier Science B.V. All rights reserved. Keywords: Myocardial infarction; Left atrioventricular plane displacement; Prognostication and risk stratification
1. Introduction The prognosis after acute myocardial infarction is related to the degree of left ventricular systolic dysfunction [1–5]. Left ventricular systolic function is often expressed as ejection fraction and most commonly measured by radionuclide ventriculography, contrast cineangiography and echocardiography. Echocardiography is the least complicated,
*Corresponding author. Tel.: 146-40-33-1000; fax: 146-40-33-6209. E-mail address: [email protected] (R. Willenheimer).
expensive and time consuming, as well as the most accessible method. Several echocardiographic techniques can be applied to evaluate global left ventricular systolic function. Traditional techniques, however, all have drawbacks. The fractional shortening and Teichholtz techniques are not reliable when left ventricular contraction is asymmetrical [6–8]. Two-dimensional echocardiography tolerates asymmetry but requires good image quality for adequate tracing of the endocardial borders [9–11], which is not always obtainable [12]. Some investigators have reported a poor agreement between left ventricular ejection fraction determined by two-dimensional echocardiog-
0167-5273 / 02 / $ – see front matter 2002 Elsevier Science B.V. All rights reserved. PII: S0167-5273( 02 )00007-4
36
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
raphy and ejection fraction evaluated by radionuclide ventriculography or contrast cineangiography [13,14]. Others have shown that two-dimensional echocardiography correlates closely with radionuclide ventriculography [15,16]. It has been reported that twodimensional echocardiographic assessment of regional wall motion correlates closely with haemodynamic status, and that it is reliable, reproducible and valuable for selecting high risk patients [17,18]. It does, however, require experienced investigators and it is somewhat time-consuming [17,18]. The left ventricular pump function has traditionally been thought to be mainly related to the action of the circumferentially oriented myocardial fibres [19]. However, the complexity of myocardial fibre orientation and the importance of longitudinal fibres was thoroughly described in man in the early 1980’s [20], and has since been further clarified [21–29]. The epicardial surface of the heart remains practically immobile during the cardiac cycle [22], and normal left ventricular ejection requires displacement of the atrioventricular plane. During cardiac systole the atrioventricular plane moves towards the apex as a result of contraction of longitudinal fibres [22]. Since the distance between the apex and the chest surface is constant during the cardiac cycle [22,23,30], the left atrioventricular plane displacement (AVPD) as measured from the surface of the thorax, using transthoracic two-dimensionally guided M-mode echocardiography, equals the intraventricular displacement [25]. Mean left AVPD reflects global left ventricular function despite left ventricular asymmetry, since it is determined in four different regions of the left ventricle—the septal, lateral, inferior and anterior regions—and since it evaluates the total shortening along the left ventricular long axis in the respective region. Demands on image quality are quite low, as the atrioventricular plane is highly echogenic, and the examination only takes a few minutes [12]. We have previously shown that the prognosis in patients with heart failure correlates closely with the degree of left AVPD impairment [12]. The aim of the present study was to investigate the prognostic value of an echocardiographic determination of the left AVPD in patients with an acute myocardial infarction. We also wanted to assess whether cardiac morbidity was related to the degree of left AVPD impairment.
2. Methods
2.1. Subjects We consecutively included all patients hospitalised with a diagnosis of acute myocardial infarction and undergoing an echocardiographic examination at our Department of Cardiology between May 1st 1997 and March 31st 1998, with a measurement of the left AVPD at the time of hospitalisation. Diagnosis of myocardial infarction was based upon at least two out of three criteria of acute myocardial infarction: typical chest symptoms, characteristic ECG changes and cardiac protein raise (CK-MB, Troponin-T or Troponin-I) characteristic of myocardial damage.
2.2. Echocardiography Two-dimensional echocardiography were performed 4.2 (6.4) days after the myocardial infarction by an experienced investigator. The equipment used was a Hewlett-Packard (Andover, MA, USA) Sonos 2000 or 2500 echocardiography system and a 2.5 MHz transducer. Apical views were obtained with the patient in a left lateral recumbent position. Measurements were acquired during silent respiration or endexpiratory apnoea. Left AVPD was determined in two-dimensionallyguided M-mode in the four and two chamber views, as described previously [12,31,32]. The regional AVPD (mm) was the distance covered by the atrioventricular plane between the position most remote from the apex (corresponding to the onset of contraction) and the location closest to the apex (corresponding to the end of contraction, including any post-ejection shortening), i.e. the full extent of the displacement. AVPD was measured in the septal, lateral, inferior and anterior regions of the left ventricle, and was calculated from an average of two heart cycles at each site in patients with regular rhythm, and four in patients with irregular rhythm. The mean of the average AVPD in the four regions was calculated and is expressed as left AVPD. No patients had to be excluded from this study due to poor image quality, and all four regions of left AVPD was measured in all patients. The mean inter-observer variability in our laboratory between two investigators examining each pa-
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
tient immediately after one another was 4.8% (AVPD difference range 0–1.2 mm) in a series of 53 consecutive patients with an average left AVPD of 7.8 mm (range 3.3–15.5 mm) [12]. The intra-observer variability of the determination of left AVPD was mean 2.0% (range 0–6%), corresponding to 0.23 mm (range 0–0.95 mm), in 39 randomly examined patients with an average left AVPD of 11.2 mm (range 5.6–17.5 mm) [33]. The average left AVPD in 15 controls (mean age 65 years, range 54 to 77 years, eight (53%) women) was 13.561.1 mm, and a left AVPD ,10.0 mm is considered abnormal [33]. Assessment of the echocardiograms was performed blinded to patient follow-up and other clinical data. Investigations were in accordance with the Declaration of Helsinki.
2.3. Follow-up Patients were followed-up with respect to mortality and cardiac hospitalisations for an average of 628 days following inclusion. All hospitalisations and deaths in Malmo¨ are registered in a central database. ¨ Since all patients included were residents of Malmo, cardiac morbidity, expressed as cardiac hospitalisations, and all cause mortality were reliably assessed from this database. The causes of hospitalisations were categorised into heart failure and ischemic (myocardial infarction and unstable angina pectoris). Other causes of hospitalisation were not subject to assessment in this study.
2.4. Statistics Differences between two groups regarding continuous variables were tested by Student’s unpaired t-test. To evaluate differences between groups with respect to nominal values the x 2 (for more than 232) and Fischer’s exact (for 232) tests were used. To compare multiple groups regarding continuous variables the Kruskal–Wallis test was performed. Simple and multiple linear regression analysis and analysis of variance were used to analyse correlations between continuous variables. Logistic regression analysis was used to assess the relation between left AVPD and mortality risk. Multiple logistic regression analysis was used to assess the independent prognostic value
37
of left AVPD. Data are expressed as mean (S.D.), and a P-value of ,0.05 was considered significant. In analysing the endpoints we combined the endpoints into ‘morbid and mortal’ events consisting of events that in previous studies have been shown to be associated with a worsened prognosis (hospitalisation due to myocardial re-infarction, heart failure and unstable angina pectoris).
3. Results A total of 271 patients were included into the study. Baseline characteristics are displayed in Table 1. The patients were followed up for 628 (199) days. The average left AVPD in all patients (n5271) was 9.7 (2.4) mm, and was significantly lower in the patients who died (n541, 15.1%) compared to the survivors: 8.2 (5.6) mm v. 10.0 (5.5) mm, P, 0.0001. The relation between left AVPD and mortality is shown in Fig. 1. The patients were divided into quartiles with respect to left AVPD. In the quartiles left AVPD was ,8.00, 8.00–9.75, 9.76–11.05 and .11.05 mm, respectively. The quartiles were compared regarding mortality (Fig. 2) and combined death or heart failure hospitalisation (Fig. 3). In both analyses we found that the patients in the lowest quartile had a substantially higher event rate compared with those in the combined upper three quartiles. Mortality was 31.3% v. 10.1%: Hazard ratio (HR) 3.10, P50.0001. The frequency of death or heart failure hospitalisation was 43.8% v. 14.6%: Risk ratio (RR) 3.00, P,0.0001. The incidence of the combined morbid and mortal events (mortality and hospitalisation due to heart failure, myocardial infarction and unstable angina pectoris) also differed significantly between the patients in the lowest quartile and those in the combined upper three quartiles: 48.4% v. 30.4%, RR 1.59, P50.0082 (Fig. 4). Baseline characteristics comparing patients in the lowest and the upper three AVPD quartiles are shown in Table 1. Mean age was higher and there was a non-significant 40% greater proportion of women in the lowest quartile. Patients in the lowest AVPD quartile had a higher prevalence of prior myocardial infarctions and pre-existing atrial fibrillation, heart failure, diabetes and hypertension. The rate of other
38
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
Table 1 Baseline characteristics comparing the lowest (Q 1) and the combined upper three (Q 2–4) AVPD quartiles
Age, years (S.D.) Females, n (%) Current smoking, n (%) AMI / echo-time, days (S.D.) Q-wave infarction, n (%) Anterior AMI, n (%) Prior AMI, n (%) Prior angina pectoris, n (%) Prior PTCA / CABG, n (%) Prior atrial fibrillation, n (%) Prior heart failure, n (%) Prior diabetes mellitus, n (%) Prior hypertension, n (%) Obstructive lung disease, n (%) Malignancy, n (%) Kidney disease, n (%) Collagenosis, n (%)
All
Q1
Q 2–4
P
69.1 (11.8) 83 (30.6) 82 (30.5) 4.2 (6.4) 121 (45.7) 107 (41.5) 83 (30.9) 113 (40.0) 17 (6.3) 19 (7.0) 20 (7.5) 56 (20.7) 86 (31.9) 29 (10.8) 17 (6.3) 9 (3.3) 12 (4.5)
74.5 (8.7) 25 (39.1) 16 (25.4) 4.0 (3.2) 26 (42.6) 23 (39.0) 27 (42.2) 28 (44.4) 5 (7.9) 13 (20.3) 9 (14.3) 19 (29.7) 28 (43.8) 8 (12.7) 5 (7.9) 2 (3.2) 4 (6.3)
67.5 (12.2) 58 (28.0) 66 (32.0) 4.3 (7.2) 95 (46.6) 84 (42.2) 56 (27.3) 85 (41.3) 12 (5.9) 6 (2.9) 11(5.4) 37 (18.0) 58 (28.2) 21(10.2) 12 (5.8) 7 (3.4) 8 (3.9)
,0.0001 NS NS NS NS NS 0.0246 NS NS ,0.000 1 0.0185 0.0433 0.0193 NS NS NS NS
AVPD, atrioventricular plane displacement; AMI, acute myocardial infarction; AMI / echo-time, time from acute myocardial infarction to echocardiographic examination; PTCA / CABG, percutaneouos transluminal coronary angioplasty or coronary bypass surgery.
concomitant diseases was the same when comparing the lowest and the upper three AVPD quartiles. Left AVPD was an independent prognostic marker (P5 0.0225), in multiple logistic regression analysis including the other two most powerful prognostic markers, age and history of atrial fibrillation. Thrombolytic treatment and medication at discharge is shown in Table 2.
4. Discussion
Fig. 1. Mortality risk plotted against the mean left atrioventricular plane displacement (AVPD) by logistic regression analysis. Dotted lines show 95% confidence interval.
Fig. 2. Mortality in relation to quartiles of mean left atrioventricular plane displacement. P50.0002 for between quartile difference tested by the x 2 test. 1, Quartile with lowest AVPD; 4, quartile with highest AVPD.
In the present study, all cause mortality in patients after myocardial infarction was strongly related to left AVPD. We have previously found a strong relation between left AVPD and mortality in heart failure patients [12]. In the present study, the mortality risk curve in relation to left AVPD had the same appearance as in the heart failure patients in that study [12].
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
Fig. 3. Event rate of combined death or heart failure hospitalisation by quartiles of mean left atrioventricular plane displacement. P,0.0001 for between quartile difference tested by the x 2 test. 1, Quartile with lowest AVPD; 4, quartile with highest AVPD.
The only obvious difference was that left AVPD was higher and the mortality rate lower compared with the heart failure patients. We also found a higher rate of hospitalisation for heart failure in patients with low left AVPD. This is to be expected given the known relationship between heart failure morbidity and left ventricular systolic dysfunction. There was, however, no such difference regarding hospitalisation due to ischemic events, i.e. myocardial infarction and unstable angina pectoris. There were some important differences in baseline characteristics between the patients in the lowest and those in the combined upper three AVPD quartiles. Thus, the mean age was substantially higher and a history of atrial fibrillation was considerably more
39
Fig. 4. Rates of combined ‘morbid and mortal’ events (myocardial infarction, mortality, heart failure and unstable angina pectoris). Between quartile difference tested by the x 2 test: morbid and mortal, P50.0382. 1, Quartile with lowest AVPD; 4, quartile with highest AVPD.
common in the lowest quartile. However, the multiple logistic regression analysis showed that the prognostic value of left AVPD was independent of these variables. It is well known that assessment of left ventricular systolic function provides important prognostic information. However, as opposed to most other methods for the evaluation of left ventricular systolic function, determination of left AVPD is easy, highly reliable and reproducible, and can be performed in virtually all patients. Left AVPD has a high discriminative value, which is indicated by the considerable differences in mortality and heart failure hospitalisation rates, despite the small differences in left AVPD between AVPD quartiles of patients. As the frequency of autopsies performed in Malmo¨
Table 2 Thrombolytic treatment and medication at hospital discharge comparing the lowest (Q 1) and the combined upper three (Q 2–4) AVPD quartiles
Thrombolysis, n (%) b-Blockers Calcium-blockers Nitrates Diuretics RAAS inhibitors Digitalis glycosids Aspirin / antiplatelet drugs Anti-coagulants
All
Q1
Q 2–4
P
71(26.5) 66.4% 13.8% 40.3% 38.8% 33.2% 7.8% 88.0% 16.8%
7(11.1) 44.4% 20.6% 34.9% 74.6% 58.7% 20.6% 85.7% 17.5%
64(31.2) 73.2% 11.7% 42.0% 27.8% 25.4% 3.9% 88.8% 16.6%
0.0015 ,0.000 1 NS NS ,0.0001 ,0.0001 ,0.0001 NS NS
AVPD, atrioventricular plane displacement; RAAS, renin–angiotensin–aldesterone system.
40
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41
has dropped in the last decades, and the determination of the cause of death without an autopsy being performed is subject to a high degree of subjectivity, we choose not to assess cause of death but only to register total mortality. This may be regarded as a limitation to the study. Another possible limitation is that we did not assess non-cardiac reasons for hospitalisation.
5. Conclusions In conclusion, echo cardiographic assessment of left AVPD is a powerful independent clinical tool for prognostication and risk stratification in patients with acute myocardial infarction. Left AVPD is easily and readily assessed in all patients, which is an advantage compared to many other prognostic methods. By using risk stratification based on assessment of left AVPD in clinical practice high-risk patients may be readily and correctly identified.
References [1] Taylor GJ, Humphries JO, Mellits ED et al. Predictors of clinical course, coronary anatomy and left ventricular function after recovery from acute myocardial infarction. Circulation 1980;62:960–70. [2] The Multicenter Post-infarction Research Group. Risk stratification and survival after myocardial infarction. New Engl J Med 1983;309:331–6. [3] Madsen EB, Hougaard P, Gilpin E. Dynamic evaluation of prognosis from time-dependent variables in acute myocardial infarction. Am J Cardiol 1983;51:1579–83. [4] Silverman KJ, Grossman W. Natural history and strategies for evaluation management. New Engl J Med 1984;310:1712–7. [5] Shah PK, Maddahi J, Staniloff HM et al. Variable spectrum and prognostic implications of left and right ventricular ejection fractions in patients with and without clinical heart failure after acute myocardial infarction. Am J Cardiol 1986;58:387–93. [6] Fortuin NJ, Hood WPJ, Sherman ME et al. Determination of left ventricular volumes by ultrasound. Circulation 1971;44:575–84. [7] Teichholtz LE, Kreulen T, Herman MV et al. Problems in echocardiographic volume determinations; echocardiographic–angiographic correlations in the presence or absence of asynergy. Am J Cardiol 1976;37:7–11. [8] Starling MR, Crawford MH, O’Rourke RA et al. Accuracy of subxiphoid echocardiography for assessing left ventricular size and performance. Circulation 1980;61:367–73. [9] Carr KW, Engler RL, Forsythe JR et al. Measurement of left ventricular ejection fraction by mechanical cross-sectional echocardiography. Circulation 1979;59:1196–206.
[10] Schiller NB, Acquatella H, Ports TA et al. Left ventricular volume from paired biplane two-dimensional echocardiography. Circulation 1979;60:547–55. [11] Parisi AF, Moynihan PF, Feldman CL et al. Approaches to determination of left ventricular volume and ejection fraction by real-time two-dimensional echocardiography. Clin Cardiol 1979;2:257–63. [12] Willenheimer R, Cline C, Erhardt L et al. Left ventricular atrioventricular plane displacement: An echocardiographic technique for rapid assessment of prognosis in heart failure. Heart 1997;78:230–6. [13] Folland ED, Parisi AF, Moynihan PF et al. Assessment of left ventricular ejection fraction and volumes by real time two-dimensional echocardiography. Circulation 1979;60:760–6. [14] Starling MR, Crawford MH, Sorensen SG et al. Comparative accuracy of apical biplane cross-sectional echocardiography and gated equilibrium radionuclide angiography for estimating left ventricular size and performance. Circulation 1981;63:1075–84. [15] Senior R, Sridhara BS, Basu S et al. Comparison of radionuclide ventriculography and 2D echocardiography for the measurement of left ventricular ejection fraction following acute myocardial infarction. Eur Heart J 1994;15:1235–9. [16] Naik M, Diamond G, Pai T et al. Correspondence of left ventricular ejection fraction determinations from two-dimensional echocardiography, radionuclide angiography and contrast cineangiography. J Am Coll Cardiol 1995;25:937–42. [17] Fisher JP, Picard MH, Mikan JS et al. Quantitation of myocardial dysfunction in ischeamic heart disease by echocardiographic endocardial surface mapping: correlation with hemodynamic status. Am Heart J 1995;129:1114–21. [18] Køber L, Torp-Pedersen C, Carlsen J et al. On behalf of the TRACE study group. An echocardiographic method for selecting high risk patients shortly after acute myocardial infarction, for inclusion in multicentre studies (as used in the TRACE study). Eur Heart J 1994;15:1616–20. [19] Rushmer RF, editor, Cardiovascular dynamics, 4th edition, Philadelphia: WB Saunders, 1976, p. 93. [20] Greenbaum RA, Ho SY, Gibson DG et al. Left ventricular fibre architecture in man. Br Heart J 1981;45:248–63. [21] Jones CJH, Raposo L, Gibson DG. Functional importance of the long axis dynamics of the human left ventricle. Br Heart J 1990;63:215–20. ¨ S. Cardiac pumping and the function of the ventricular [22] Lundback septum. Acta Physiol Scand 1986;550(suppl):1–101. [23] Pai RG, Bodenheimer MM, Pai SM et al. Usefulness of systolic excursion of the mitral annulus as an index of left ventricular systolic function. Am J Cardiol 1991;67:22–4. [24] Simonson JS, Schiller NB. Descent of the base of the left ventricle: an echocardiographic index of the left ventricular function. J Am Soc Echocardiogr 1989;2:25–35. ¨ [25] Hoglund C, Alam M, Thorstrand C. Atrioventricular valve plane displacement in healthy persons. Acta Med Scand 1988;224:557–62. ¨ [26] Alam M, Hoglund C. Serial echocardiographic studies following thrombolytic treatment in myocardial infarction with special reference to the atrioventricular valve plane displacement. Clin Cardiol 1992;15:30–6. ¨ [27] Alam M, Hoglund C, Thorstrand C. Londitudinal systolic shortening of the left ventricle: an echocardiographic study in subjects with and without preserved global function. Clin Physiol 1992;12:443–52. ¨ [28] Alam M, Hoglund C, Thorstrand C et al. Atrioventricular plane displacement in severe congestive heart failure following dilated cardiomyopathy or myocardial infarction. J Intern Med 1990;228:569–75.
B. Brand et al. / International Journal of Cardiology 83 (2002) 35 – 41 ¨ [29] Alam M, Hoglund C, Thorstrand C et al. Haemodynamic significance of the atrioventricular plane displacement in patients with coronary artery disease. Eur Heart J 1992;13:194–200. [30] McDonald IG. The shape and movements of the human left ventricle during systole. A study by cineangiography and by cineradiography of epicardial markers. Am J Cardiol 1970;26:221–30. [31] Willenheimer R, Erhardt L, Cline C et al. Prognostic significance of changes in left ventricular systolic function in elderly patients with congestive heart failure. Coronary Artery Dis 1997;8:711–7.
41
[32] Willenheimer R, Israelsson B, Cline C et al. Left atrioventricular plane displacement (AVPD) is related to both systolic and diastolic left ventricular performance in patients with chronic heart failure. Eur Heart J 1999;20:612–8. [33] Willenheimer R. Assessment of left ventricular dysfunction and remodeling by determination of atrioventricular plane displacement and simplified echocardiography. Scand Cardiovasc J 1998;32(suppl 48).