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(Chest. 2003;124:1645-1651.)
© 2003 American College of Chest Physicians

Prognostic Value of Global Myocardial Performance Indices in Acute Myocardial Infarction*

Comparison to Measures of Systolic and Diastolic Left Ventricular Function

Ehud Schwammenthal, MD; Yehuda Adler, MD; Keren Amichai, MD; Alik Sagie, MD; Solomon Behar, MD; Hanoch Hod, MD and Micha S. Feinberg, MD

* From the Heart Institute (Drs. Schwammenthal, Amichai, Behar, Hod, and Feinberg) and Cardiac Rehabilitation Institute (Dr. Adler), Chaim Sheba Medical Center, Tel Hashomer, Israel; and the Department of Cardiology (Dr. Sagie), Rabin Medical Center, Petach-Tiqvah, Israel.

Correspondence to: Ehud Schwammenthal, MD, Heart Institute, Sheba Medical Center, Tel Hashomer, Israel; e-mail: sehud{at}post.tau.ac.il


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objectives: Assessment of global myocardial performance by a single index (ie, the myocardial performance index [MPI]) has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function We sought to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in acute myocardial infarction (AMI).

Patients: Four hundred seventeen consecutive patients with AMI were examined within 24 h of hospital admission.

Interventions: Doppler echocardiographic measures of systolic, diastolic, and global myocardial performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood.

Results: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%), and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to 314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) <= 40% (OR, 3.82; 95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of <= 130 ms (OR, 2.29; 95% CI, 1.0 to 5.21) as independent predictors of adverse events.

Conclusion: LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients.

Key Words: acute myocardial infarction • diastolic left ventricular function • Doppler echocardiography • myocardial performance index


   Introduction
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 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Assessment of global myocardial performance by a single index has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function.1 2 3 4 5 6 In 1995, Tei and colleagues1 2 proposed a Doppler-derived time interval index, which was defined as the sum of isovolumic contraction time and relaxation time divided by ejection time. This myocardial performance index (MPI) can be obtained easily from mitral inflow and LV outflow velocity time intervals with good reproducibility, and is independent from LV geometry and heart rate.2 It correlates well with invasive measures of systolic and diastolic LV function,3 and has been reported to correlate better with patient outcome than conventional echocardiographic parameters in various myocardial diseases.7 8 However, little information is available about the clinical value of the MPI in patients with acute myocardial infarction (AMI).9 10 Because morbidity and mortality from AMI are affected by both systolic and diastolic myocardial dysfunction, a parameter that integrates both components might be of particular value in this setting. In a small group of patients, Poulsen et al9 found the MPI to be the strongest independent predictor of the development of in-hospital congestive heart failure in patients with AMI. At the 1-year follow-up, MPI remained a significant, yet less powerful, predictor of poor outcome than restrictive LV filling.10

The purpose of the present study was to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in a large, consecutive group of patients with AMI. In addition, we sought to examine whether the assessment of global myocardial performance can be improved by relating the sum of the isovolumic time intervals to the sum of the heterovolumic time intervals (ejection time and filling time). This isovolumic time/heterovolumic time ratio (I/H) index should express the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood (ie, without performing external work).


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study Population
During the 1-year study period, 451 consecutive patients with documented AMI were admitted to the coronary care units of Sheba and Rabin Medical Centers. Myocardial infarction was diagnosed when at least two of the following criteria were present: chest pain lasting > 30 min; typical ECG changes; and elevated creatine kinase-MB fraction. Myocardial infarction location was determined using ECG criteria.11 Twelve patients died shortly after coronary care unit admission, before an echocardiographic study could be performed. Twenty-two patients could not be examined by echocardiography within 48 h of hospital admission due to logistic limitations. The remaining 417 patients constitute the study population. Patients were included in a registry that was accumulated during the screening period of the Argatroban in Acute Myocardial Infarction-2 study, a multicenter trial that was designed to assess the safety and relative efficacy of direct antithrombin therapy (ie, argatroban) compared with therapy with IV heparin in patients with AMI who are receiving thrombolytic therapy. Argatroban exerted neither a favorable nor an adverse detectable effect on outcome. Relevant data on medical history, physical examination, laboratory findings, electrocardiograms during the hospital course and 30-day follow-up were prospectively collected.

Two-Dimensional and Pulsed-Wave Doppler Echocardiography
All patients underwent a complete echocardiographic examination (SONOS 2500 ultrasound system with a 2.5-MHz transducer; Hewlett-Packard; Andover, MA). Data were stored on high-quality videotape for subsequent analysis. The mitral inflow velocity was recorded using pulsed-wave Doppler echocardiography with the sample volume positioned between the tips of the mitral leaflets, and LV outflow velocity was measured just below the aortic valve. LV volumes and LV ejection fraction (LVEF) were determined using the modified biplane Simpson method, when >= 80% of the endocardial border could be delineated in both the four-chamber and two-chamber views, and by the single-plane method, when >= 80% of the endocardial border could be delineated only in the four-chamber view.12 13 Measurements of peak E-wave and A-wave velocity, peak E-wave velocity/peak A-wave velocity ratio (E/A), and E-wave deceleration time (EDT) were performed in a standard manner.14 15 16 17 18 19 20 21 22 Stroke distance was measured as the time-velocity integral of the systolic outflow tract velocity signal. Doppler time intervals were obtained, as demonstrated in Figure 1 , from an average of five cardiac cycles. The sum of isovolumic contraction and relaxation time was obtained by subtracting ejection time (Fig 1 , b) from the interval between two mitral inflow periods (Fig 1 , a). MPI then was determined as (a - b)/b. I/H was determined as (a - b)/(b + c), where c is the mitral filling period. All measurements were performed by an experienced observer who was blinded to the clinical data.



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  		Figure 1.. Derivation of the MPI and the I/H from Doppler tracings of mitral inflow and LV outflow. a = time between filling periods, which equals the duration of mitral regurgitation (MR), when present; b = ejection time (ET); c = filling time (FT). The sum of isovolumic contraction time (ICT) and isovolumic relaxation time (IRT) can be obtained by the subtraction of b from a.

 
Statistical Analysis
The results were expressed as the mean ± SD. The comparison of clinical characteristics was performed by {chi}2 analysis for categoric variables, and by analysis of variance for continuous variables. A p value of < 0.05 was considered to be significant. Multivariate analysis was performed to identify independent risk predictors for the combined end point of death, heart failure, and reinfarction at 30 days, using the Cox proportional hazards model.23 The end point heart failure was defined as new-onset heart failure during hospitalization (Killip classification, >= 2), or persistence or worsening of heart failure despite treatment.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
At the end of the study period, 19 patients (4.7%) had died, 96 patients (23%) were in heart failure (Killip classification, >= 2), and 20 patients (4.8%) had experienced a recurrent myocardial infarction. A total of 103 patients (25%) had reached at least one end point and were compared as group B to the 314 patients (75%) without an end point (group A).

Clinical Characteristics
Table 1 details the clinical characteristics of both groups. As expected, patients with a poor outcomes (group B) were older (p < 0.001), and a substantially higher percentage of individuals had diabetes (p < 0.001) and hypertension (p < 0.02), and had a history of myocardial infarction (p = 0.03) or a history of heart failure (p < 0.001), when compared to the patients with a favorable outcome (group A). Significantly more patients in group B were in heart failure at the time of hospital admission (p < 0.001). Anterior-wall MI occurred more frequently in group B (p < 0.001), and peak creatine phosphokinase values were significantly higher on average (p < 0.05).


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  		Table 1.. Clinical Characteristics of the Study Group*

 
Echocardiographic Parameters
Except for measures of diastolic LV size, the two groups differed in all echocardiographic parameters of LV filling and ejection, and in both indexes of global myocardial performance (Table 2 ). The parameters that discriminated best between groups A and B were LVEF (p < 0.000001)), stroke distance (p < 0.00001), EDT (p < 0.000008), and I/H (p < 0.00007). The mean percent difference ({Delta}) between the two groups was highest for I/H (0.18 ± 0.08 vs 0.22 ± 0.11, respectively; {Delta}, 20%) and LVEF (46 ± 9 vs 40 ± 10, respectively; {Delta}, 14%).


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  		Table 2.. Echocardiographic Parameters

 
Independent Predictors
Multivariate regression analysis identified only the following as independent predictors of poor outcome at 30 days (Table 3 ): LVEF <= 40% (odds ratio [OR], 3.82; 95% confidence interval [CI], 2.15 to 6.87), EDT <= 130 ms (OR, 2.29; 95% CI, 1.01 to 5.21), and age (OR, 1.04 per year; 95% CI, 1.02 to 1.07). MPI was not independently related to outcome in this model (OR, 1.09; 95% CI, 0.59 to 2.14). Entering I/H instead of MPI into the model did not achieve a significant improvement (OR, 1.24; 95% CI, 0.66 to 2.30). The correlation between MPI and the two independent echocardiographic predictors of adverse outcome (ie, LVEF and EDT) was poor (r = -0.27 and r = -0.12, respectively). The corresponding correlation coefficients for I/H were r = -0.35 and r = -0.24, respectively.


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  		Table 3.. Multivariate Analysis of Predictors of Death, Congestive Heart Failure, and Reinfarction at 30 Days in 417 Patients with AMI

 

   Discussion
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The present study failed to demonstrate any incremental prognostic value of global MPIs compared to measures of systolic and diastolic LV function in a large, consecutive, and prospectively examined group of patients with AMI. Patients with poor and favorable outcomes differed significantly in most echocardiographic parameters of LV filling and ejection, and the discriminatory power of I/H was particularly high. However, only LVEF and EDT emerged as strong independent predictors of death, heart failure, and reinfarction at 30 days following AMI. These results are in accordance with the concept that combinations of different degrees of systolic and diastolic myocardial dysfunction are prevalent among patients with AMI, and that both components have a significant impact on patient outcome. The study confirms the results of previous smaller series,14 15 21 22 and reinforces the use of these two parameters of filling and ejection for risk stratification in patients with AMI.

Multiregression Analysis
If both components of myocardial function determine patient outcome, why did the global MPIs fail? Multiregression analysis may reject a parameter due to lack of a sufficiently close association to the respective end point, or despite a significant association, if this parameter is closely correlated to superior predictors of the end point. Since the correlation of both MPIs to the two strong independent echocardiographic predictors of adverse outcome was poor, it seems that the explanation is simply a low predictive accuracy of these indexes. In fact, 65 of the 103 patients (63%) with an adverse event had a favorable MPI. Almost half of the patients with a favorable MPI (48%), despite poor outcome, had an LVEF of <= 40%, and approximately one quarter of these patients (26%) had an EDT of <= 140 ms.

Pseudonormalization
One possible factor that may have confounded the diagnostic accuracy of the MPI is the phenomenon of pseudonormalization. Dujardin et al8 argued that the MPI was valuable in the risk assessment of patients with dilated cardiomyopathy, irrespective of the transmitral filling pattern, since they found that patients with similar prognoses can have similar MPI values despite having different filling patterns. With the transition from a nonrestrictive to a restrictive filling pattern, the shortening of the isovolumic relaxation time occurs but would be counterbalanced by a shortening in ejection time and the prolongation of isovolumic contraction time (Fig 2 ). Therefore, the index remained prognostically useful, whereas mitral deceleration time could be misleading, according to the authors.8



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  		Figure 2.. Diagram illustrating the pseudonormalization of the MPI, but not the I/H, with deterioration of LV function and the occurrence of a restrictive filling pattern. Left: impaired relaxation filling pattern. Right: restrictive filling pattern. With deteriorating myocardial function, isovolumic contraction time increases and ejection time shortens. Nevertheless, MPI remains unchanged due to shortening of the isovolumic relaxation time, which reflects elevated filling pressure (ie, pseudonormalization). In contrast, I/H increases, because shortening of the IRT is counterbalanced by shortening of the filling time that occurs with restrictive filling. See the legend of Figure 1 for abbreviations not used in the text.

 
In view of the pathophysiology of myocardial dysfunction, and supported by the findings of this study, a more appropriate interpretation is the following one: with deteriorating myocardial function (indicated by a prolongation of isovolumic contraction time, a shortening of ejection time, and the appearance of a restrictive filling pattern) an increase in MPI is prevented by a shortening of the isovolumic relaxation time. The shortened isovolumic relaxation time reflects, of course, an increase in left atrial pressure and not an improvement in relaxation. The lack of increase in MPI, not the shortening of the EDT, is therefore misleading. The behavior of MPI can be accurately termed pseudonormalization (Fig 2) , since it has the same pathophysiologic basis as pseudonormalization of the LV filling pattern.

The I/H was specifically designed to (partially) solve the problem of pseudonormalization (Fig 2) . In patients with severe LV dysfunction, the shortening of the isovolumic relaxation time is accompanied by a shortening in filling time,24 25 26 which is taken into consideration by the I/H index. Therefore, in contrast to MPI, the I/H index increases, more truthfully reflecting myocardial deterioration (Fig 2) . Although pseudonormalization could explain the high proportion of patients who had a favorable MPI despite a poor prognosis, it cannot be the only reason for the low predictive value of the MPI, because the I/H index also was rejected by the multivariate analysis.

Assessment of LV Function
The comprehensive assessment of LV function requires information about cardiac pressure and volumes, and their change over time. It appears that this cannot be achieved by a simple ratio of isovolumic time intervals and ejection time alone. The MPI neglects whether the LV ejects a large or a small portion of its filling volume during systole, yet LVEF is a powerful measure of systolic ventricular function (and outcome), for which the mere duration of systole is a poor substitute. With the deterioration of LV diastolic function, filling pressure will increase (and EDT will decrease), yet the associated shortening of isovolumic relaxation time will prevent an increase in MPI and will mask diastolic dysfunction just when it becomes clinically relevant. An elevated filling pressure, which is mirrored by a restrictive filling pattern,16 17 18 may reflect more extensive myocardial damage, or more extensive ischemia, and therefore defines independently a high-risk subset of patients, as was shown in this study. Consequently, the assessment of LV function and risk stratification is incomplete without an assessment of the transmitral filling pattern.

Limitations
The quality of a model depends on the cutoff values chosen. For LVEF, EDT, and E/A, established and published cutoff values were used for comparability.18 19 20 For MPI, for which less data are available in the setting of AMI, and I/H (a so-far untested index), the border between the third and fourth quartile of data distribution was used. The cutoff value for MPI obtained by this method was 0.52, which turned out to be almost the exact arithmetic mean of the cutoff values for MPI chosen in the two studies by Poulsen et al9 10 (0.6 and 0.45, respectively). Although all data collection was prospective and consecutive, the original purpose of the data gathered was to assess the effect of argatroban on patients with AMI. Twelve patients died shortly after hospital admission, before an echocardiographic study could be performed (< 2.7% of all eligible patients, and 10% of all eligible patients who had experienced an event), and 22 patients could not be examined by echocardiography within 48 h of hospital admission due to logistic limitations. It is highly unlikely that these limitations have significantly affected the results of the study.

The present article deals with acute LV dysfunction in patients who were examined within 48 h of an AMI. It is possible that indexes of global myocardial performance are better suited to reflect chronic myocardial disease, such as in dilated cardiomyopathy.8

In summary, LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients.


   Acknowledgements
 
We would like to thank Valentina Boyko, MSc, and Miriam Cohen, BSc, for their expert statistical assistance.


   Footnotes
 
Abbreviations: AMI = acute myocardial infarction; CI = confidence interval; E/A = peak E-wave velocity/peak A-wave velocity ratio; EDT = E-wave deceleration time; I/H = isovolumic time/heterovolumic time ratio; LV = left ventricle, ventricular; LVEF = left ventricular ejection fraction; MPI = myocardial performance index; OR = odds ratio

Received for publication May 23, 2002. Accepted for publication March 20, 2003.


   References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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