Influence of Infarct-Zone Viability on Left Ventricular Remodeling After Acute Myocardial Infarction
Background The relation between residual myocardial viability after acute myocardial infarction (AMI) and ventricular remodeling has yet to be fully elucidated. We hypothesized that the presence of residual viability would favorably influence left ventricular remodeling after AMI and that serial changes in left ventricular dimensions might be related to the extent of myocardial viability in the infarct zone.
Methods and Results Ninety-three patients with a first AMI successfully treated with primary coronary angioplasty underwent two-dimensional echocardiography within 24 hours of admission and low-dose dobutamine echocardiography at a mean of 3 days after AMI. Two-dimensional echocardiography and coronary angiography were obtained in all patients 1 and 6 months after coronary angioplasty. On the basis of dobutamine echocardiography responses, patients were divided in two subsets: those with (n=48; group I) and those without (n=45; group II) infarct-zone viability. There was no difference in minimal lesion diameter and infarct-related artery patency at 1 and 6 months between the two groups. Group II patients had significantly greater end-diastolic (76±18 versus 53±14 mL/m2; P<.0003) and end-systolic (42±17 versus 22±11 mL/m2; P<.0003) volumes at 6 months than did patients in group I. The extent of infarct-zone viability was significantly inversely correlated with percent changes in end-diastolic volumes at 6 months (r=−.66; P<.000001) and was the most powerful independent predictor of late left ventricular dilation.
Conclusions After reperfused AMI, the degree of left ventricular dilation, when it occurs, is inversely related to the extent of residual myocardial viability in the infarct zone. Thus, the absence of residual infarct-zone viability discriminates patients who develop progressive left ventricular dilation after reperfused AMI from those who maintain normal left ventricular geometry.
Ventricular remodeling after acute myocardial infarction is a precursor of the development of overt heart failure and is an important predictor of mortality.1 2 Previous studies have demonstrated that infarct size3 4 and persistent occlusion of the infarct-related artery5 6 7 are two major factors that promote ventricular remodeling. However, recent studies suggest that preserved blood flow in the infarct zone independent of myocardial salvage cannot prevent remodeling when the extent of necrosis is large4 ; on the other hand, for comparable infarct size, the transmural extent of necrosis seems to be the major determinant of the occurrence of infarct expansion.8 9 10 11 Large infarcts that have only a portion of necrosis distributed completely through the wall rarely expand because the extent of expansion is inversely related to the thickness of surviving myocardium within the infarct zone.9 Moreover, recent experimental observations suggest that the benefit of reperfusion on infarct expansion is related to preservation of small islets of still-viable myocytes located mainly in the subepicardium of the scar.12
The relation between residual myocardial viability after reperfused myocardial infarction and ventricular remodeling in human beings has not yet been fully investigated. It is generally believed that only recovery in resting regional function denotes clinically relevant viability. However, although recovery in resting function is the best clinical outcome, there may be other advantages of having nonischemic viable myocardium. The presence of viable myocardium in the outer layers of the ventricular wall may in fact contribute to maintenance of left ventricular shape and size by preventing infarct expansion.13 We therefore hypothesized that the presence of residual viability would favorably influence left ventricular remodeling after acute myocardial infarction and that serial changes in left ventricular dimensions might be related to the extent of myocardial viability in the infarct zone. To test this hypothesis, we performed a prospective study of patients with acute myocardial infarction treated by primary coronary angioplasty. To avoid the confounding impact of infarct-related artery patency and residual stenosis on subsequent changes in left ventricular dimensions, only patients in whom anterograde flow was fully restored without significant residual stenosis were included in the study. Low-dose dobutamine echocardiography was used to determine the extent of infarct-zone viability because the degree of contractile reserve elicited by dobutamine provides an excellent assessment of the extent of viable myocardium in the setting of myocardial necrosis coexisting with postischemic myocardial dysfunction and no flow-limiting residual stenosis.14 15
Patients and Protocol
We prospectively studied 136 patients with acute myocardial infarction selected among 170 patients consecutively referred to the catheterization laboratory of the Division of Cardiology of Careggi Hospital for emergency primary coronary angioplasty between February 1995 and April 1996. The study inclusion criteria were as follows: (1) confirmed first acute myocardial infarction; (2) successful primary coronary angioplasty (defined as Thrombolysis In Myocardial Infarction trial (TIMI) flow grade 3 and residual stenosis <30%) within 6 hours of the onset of symptoms or between 6 and 24 hours if there was evidence of continuing ischemia; and (3) informed consent to perform dobutamine echocardiography and coronary angiography at least at two prospectively defined points in time.
Criteria of exclusion were clinical signs of heart failure or cardiogenic shock in the first week after myocardial infarction, postinfarction angina, life-limiting noncardiac disease, and conditions precluding cardiac catheterization. No upper age limit was used.
Of the 136 patients selected for the study, 10 (7%) were excluded because of inadequate image quality on the baseline echocardiogram and 11 because of normalization of left ventricular regional function at the time of dobutamine echocardiography. Later, further exclusions were due to reinfarction (2 patients) and death (5 patients); an additional 15 patients did not adhere to the follow-up protocol. Thus, 93 patients (71 men, 22 women; mean age, 61±12 years; range, 36 to 86 years) completed the study protocol. The research protocol was approved by the hospital’s Ethics Committee. Patients received conventional drug therapy according to individual needs, which therapy remained the responsibility of the attending physician. All patients underwent two-dimensional echocardiography within 24 hours of admission. Low-dose dobutamine echocardiography was performed at a mean of 3 days (range, 2 to 5 days) after admission. Two-dimensional echocardiography and coronary angiography were obtained in all patients 1 and 6 months after primary coronary angioplasty.
Two-dimensional echocardiographic studies were performed with commercially available imaging systems (Aloka model SSD-830; 2.5- and 3.5-MHz transducers). Complete two-dimensional echocardiograms were performed on three consecutive examinations on each patient (within 24 hours of the onset of symptoms and 1 and 6 months after the first examination). Patient angulation, respiratory phases, and the transducer position were recorded to guarantee return to the same echocardiographic view in subsequent studies.
Patients underwent dobutamine echocardiography at a mean of 3 days (range, 2 to 5 days) after the onset of myocardial infarction while taking all prescribed medications. Images were displayed in real time and were recorded on a videotape by a 0.5-in VHS cassette recorder (Sony SVO-140PA). During continuous electrocardiographic and two-dimensional echocardiographic monitoring, an intravenous infusion of dobutamine (5 μg/kg body weight per minute) was started with an infusion pump and continued for 5 minutes and then increased to 10 μg/kg per minute for another 5 minutes. The criteria for stopping dobutamine infusion included the occurrence of hypotension, angina, or significant ventricular arrhythmias.
Two investigators blinded to the clinical and angiographic data analyzed the baseline, dobutamine, and follow-up echocardiograms. Discrepancies were resolved by consensus.
Two-dimensional echocardiographic images were transferred to the hard disk of a TomTec P90 (TomTec Imaging Systems, Inc) medical off-line computer analysis system and digitized. Left ventricular volumes were then measured by use of the modified Simpson’s rule algorithm from orthogonal apical long-axis projections.16 The mean values of three measurements of the technically best cardiac cycles were taken from each examination. Ten random study echocardiograms were reanalyzed to measure intraobserver and interobserver variabilities. The volume indexes were obtained by dividing the volume by the body surface area at each time point. The ejection fraction was obtained by the following equation: (End-Diastolic Volume−End-Systolic Volume)/End-Diastolic Volume.
The left ventricle was divided according to a 16-segment model.17 For each segment, wall motion was scored as 1 (normal), 2 (hypokinetic), 3 (akinetic), or 4 (dyskinetic). In evaluating regional wall-motion abnormalities, attention was also paid to the systolic thickening in the central portion of each segment. Anterior and inferior infarct zones were constructed, and in each patient, both global and infarct-zone wall-motion score indexes were derived for all stages of dobutamine echocardiography and follow-up two-dimensional echocardiograms.18
Infarct-zone viability was defined as an improvement of resting asynergy ≥1 grade at any dose of dobutamine in >2 contiguous infarct-zone segments and a decrease of 0.22 in infarct-zone wall-motion score index.18
In all patients, coronary angiography was performed at admission and 1 and 6 months after the index infarction. All angiograms were analyzed in a random sequence by two experienced observers blinded to dobutamine echocardiography and two-dimensional echocardiography results. Discrepancies were resolved by consensus. The infarct-related artery was analyzed by use of a quantitative computer-assisted, edge-detection system (Siemens Hicor II) that compared the stenotic segment defined by the observer with a “normal” segment defined in the same vessel and expressed the result as percent stenosis. The minimal lesion diameter was also used for subsequent analysis. In all patients, the infarct-related artery was analyzed both before and after primary coronary angioplasty to assess residual stenosis. Contrast flow through the epicardial vessel was graded by use of the standard TIMI trial flow scale of 0 to 3,19 and retrograde collateral flow was scored according to the classification of Rentrop et al.20 The presence of grade 2 or 3 collateral flow was considered significant. The same views of coronary arteries were used at follow-up to assess arterial patency and restenosis rate.
Continuous data are expressed as mean±SD. Baseline data were compared by means of the χ2 test for categorical variables and unpaired t test for continuous variables. ANOVA with the Tukey post hoc test was used to analyze repeated measures of global and infarct-zone wall-motion score index, ejection fraction, and end-systolic and end-diastolic volumes. Simple linear regression analysis was used to correlate infarct-zone viability, peak creatine kinase, and infarct-zone wall-motion index with the changes in left ventricular end-diastolic volume index. Linear regression analysis was also used to determine intraobserver and interobserver variabilities. Univariate and multivariate regression analyses were performed to determine the association between clinical two-dimensional echocardiography, dobutamine echocardiography, and coronary angiography variables and changes in left ventricular end-diastolic volume index. A value of P<.05 was considered statistically significant. Statistical analyses were performed with Statistica 4.5 for Windows (StatSoft, Inc, 1993).
Baseline Patient Characteristics
Patients were divided into two groups based on the presence or absence of infarct-zone viability. Forty-eight patients showed contractile reserve during dobutamine infusion and were assigned to an infarct-zone viability group (group I), and 45 did not (group II). Table 1⇓ summarizes patient characteristics of these two subsets. There were no significant differences in age, sex, culprit lesion, time from the onset of symptoms to reperfusion, infarct location, angiographic collateral grade, multivessel disease, and frequency of coronary risk factors between the two groups. Patients in group I had a lower peak creatine kinase than patients in group II (2279±1627 versus 4154±3030 U/L; P<.005) and were less frequently treated with ACE inhibitors (28 versus 37 patients; P<.03).
In the majority of patients, the infarct-related vessel was totally or subtotally occluded with TIMI 0 or 1 flow. By design, all patients achieved an optimal angiographic result after primary coronary angioplasty (residual stenosis <30% and TIMI 3 flow). Twenty-eight patients received stent implantation in the infarct-related artery (17 patients in group I and 11 in group II; P=.25). Lesion minimal lumen diameter increased from 0.10±0.23 at baseline to 2.99±0.54 mm after coronary angioplasty in group I and from 0.07±0.29 to 2.9±0.56 mm in group II. (See Table 2⇓.)
At 1-month follow-up, the angiographic patency rate was 98% in group I and 100% in group II (P=.51). Lesion minimal diameter was 2.76±0.79 in group I and 2.9±0.63 mm in group II (P=.39).
At 6-month follow-up, the angiographic patency rate of the infarct-related artery was 98% in group I and 96% in group II (P=.48). No significant difference was found in minimal lumen diameter and restenosis rate (>50%) between the two groups (Table 2⇑).
Changes in Regional and Global Ventricular Function and Left Ventricular Volumes
At baseline, there was no significant difference in left ventricular ejection fraction between the two groups (45±11% versus 44±10%; P=.99), whereas regional contractile function (expressed as wall-motion score index) was slightly better in group I than in group II (1.99±0.4 versus 2.16±0.4; P=.053). According to ANOVA, a significant improvement in left ventricular global function was observed in group I from baseline to 1-month follow-up (45±11 to 56±8; P<.0003) and from baseline to 6-month follow-up (45±11 to 61±8; P<.0003), whereas no significant improvement was found in patients in group II (baseline to 1-month follow-up, 44±10 to 47±15; P<.84; baseline to 6-month follow-up, 44±10 to 46±13; P<.97) (Fig 1A⇓). Comparison between groups by ANOVA revealed that patients with infarct-zone viability (group I) had significantly higher improvement of global ventricular function at 6 months than patients without infarct-zone viability (group II) (Fig 1A⇓). Similarly, the regional contractile function in the infarct zone showed a higher improvement in patients in group I than in those in group II (group I, 1.99±0.4 to 1.4±0.4 from baseline to 6-month follow-up, P<.0005; group II, 2.16±0.4 to 2.02±0.5, P<.05) (Fig 1B⇓).
End-diastolic and end-systolic volume indexes were similar in both groups at baseline. Patients in group I showed an evident although not significant trend toward a decrease in end-diastolic volume index during the study period (baseline to 1-month follow-up, 63±18 to 57±14 mL/m2, P=.87; baseline to 6-month follow-up, 63±18 to 53±14 mL/m2, P=.18). In contrast, end-diastolic volume index significantly increased in patients in group II (baseline to 1-month follow-up, 64±13 to 74±18 mL/m2, P<.05; baseline to 6-month follow-up, 64±13 to 76±18 mL/m2, P<.03) and was significantly larger than in group I patients 6 months after infarction (Fig 1C⇑). Fig 1D⇑ shows the time course of end-systolic volume index in the two groups. In group I, end-systolic volume index significantly decreased between baseline, 1-month follow-up, and 6-month follow-up, whereas it remained substantially unchanged in group II. In group II, end-systolic volume index was significantly larger than in patients in group I at the 1- and 6-month follow-ups.
Relation of Infarct-Zone Viability to Change in Left Ventricular End-Diastolic Volume Index
In Fig 2⇓, the change in left ventricular end-diastolic volume index from baseline to 6 months was plotted against the dobutamine-induced change in infarct-zone wall-motion score index. A significant inverse correlation was found between the two variables (r=−.66; P<.000001). A significant correlation was also found between peak creatine kinase and change in left ventricular end-diastolic volume index (r=.51; P<.00001).
To evaluate the independent contribution of infarct-zone viability to late left ventricular dilation, multiple regression analysis was performed. Variables used for analysis were as follows: age, ejection fraction, peak creatine kinase, global and infarct-zone wall-motion score indexes, dobutamine-induced changes in wall-motion score index, infarct location, onset of reperfusion, collaterals, culprit lesion, and ACE inhibitor therapy. For multiple regression analysis, factors showing a value of P<.1 in univariate analysis were selected. Only dobutamine-induced change in infarct-zone wall-motion score index (an estimate of infarct-zone viability) and peak creatine kinase (an estimate of infarct size) were found to be significant independent predictors of end-diastolic volume index change at 6 months (Table 3⇓). Of the two variables, dobutamine-induced change in infarct-zone wall-motion score index had a higher partial correlation coefficient (r=.48; P<.00001) than did peak creatine kinase (r=.36; P<.003).
ACE Inhibitor Therapy
Table 1⇑ shows that ACE inhibitor therapy was used more often in group II patients. Patients in group II treated with ACE inhibitors had a worse baseline ejection fraction (41±8% versus 52±8%; P=.003) and a higher infarct-zone wall-motion score index (2.24±0.4 versus 1.84±0.55; P=.024) than patients who were not treated with ACE inhibitors. Among patients of group II treated with ACE inhibitors, end-diastolic volume index increased from 65±12 at baseline to 73±18 at follow-up (P=.088). When patients were characterized in terms of the presence or absence of left ventricular dilation, no significant difference in frequency of ACE inhibitor administration was observed. Eighteen of 22 patients (82%) with an increase in left ventricular end-diastolic volume index of ≥20% and 47 of 71 patients (66%) without left ventricular dilation were treated with ACE inhibitor therapy (P=.13).
Safety of Low-Dose Dobutamine Echocardiography
No patient showed hemodynamic derangement, complex ventricular or supraventricular arrhythmias, or angina during or immediately after low-dose dobutamine echocardiography. Heart rate increased from 78±12 bpm at rest to 87±14 bpm at peak dobutamine infusion (P<.05), and systolic blood pressure increased from 116±11 mm Hg at rest to 134±12 mm Hg at peak dobutamine infusion (P<.05).
There was excellent agreement between left ventricular volume index measurements made by a single observer at two time points (intraobserver variability; r=.96) and between measurements made by two independent observers (interobserver variability; r=.94). We have previously described the high intraobserver and interobserver agreement with diagnosis of viability by means of dobutamine echocardiography achieved in our laboratory.15
This prospective study demonstrates that left ventricular dilation occurs after primary coronary angioplasty in patients with acute myocardial infarction despite the persistence of patency of the infarct-related artery and the absence of significant residual stenosis. The degree of left ventricular dilation is related to the extent of residual myocardial viability in the infarct zone, which represents a major independent contributor to subsequent changes in left ventricular geometry and performance. Thus, our results suggest that the absence of residual infarct-zone viability discriminates patients who develop progressive left ventricular dilation after an index infarction from those who maintain normal left ventricular geometry.
Mechanisms of Left Ventricular Remodeling: The Role of Infarct-Zone Viability
Dilation of the left ventricle may play an important active role in the development of chronic heart failure, and left ventricular volume is a well-recognized prognostic factor in patients recovering from myocardial infarction.1 2 Left ventricular dilation is the result of chronic changes of left ventricular shape and structure (remodeling) and is characterized by cavity enlargement disproportionate to changes in filling pressure.21 Among factors that influence left ventricular dilation, the final infarct size3 4 and the perfusional status of the infarct-related artery5 6 7 are considered to be two major determinants of left ventricular remodeling in postinfarction patients. Although a large myocardial infarction generally triggers left ventricular remodeling, the estimation of the infarct size might not be sufficient to predict left ventricular dilation because transmural extent of myocardial necrosis is necessary for expansion. The extent of expansion is in fact inversely related to the thickness of surviving myocardium within the infarct zone.9 Islands of residual viable subepicardial myocytes that are salvaged by anterograde flow may prevent left ventricular dilation, as recent studies of late reperfusion in rats have suggested.12 The present study confirms these experimental observations in that residual myocardial viability in the infarct zone is an important and independent contributor to subsequent changes in left ventricular geometry and performance. In our series, the extent of asynergy and peak creatine kinase (as estimates of infarct size) were significantly higher in patients without residual myocardial viability in the infarct zone. Obviously, this may account at least in part for the difference in left ventricular volumes. However, the correlations between the change in left ventricular end-diastolic volume index and peak creatine kinase and infarct-zone wall-motion score index were weaker than that between end-diastolic volume index and infarct-zone viability, and after controlling for infarct size, infarct-zone viability was the most powerful independent predictor of left ventricular dilation.
Counterbalancing the effect of infarct size on the subsequent left ventricular remodeling is the presence of preserved blood flow to the infarct zone5 6 7 and the absence of residual stenosis (<1.5 mm).22 By design, to avoid the confounding impact of these two variables on subsequent changes in left ventricular dimensions, we chose to enroll in the study only patients with patent infarct-related arteries and without significant residual stenosis. In addition, the follow-up patency and restenosis rate of patients with infarct-zone viability compared with those without were similar. The inverse linear relation between left ventricular end-diastolic volume index change and infarct-zone viability, as shown in the current study, demonstrates that left ventricular dilation decreases dramatically with an increase in the extent of residual viability and suggests that preserved flow to the infarct zone cannot prevent remodeling when infarct-zone viability is absent. These results also confirm and expand the previous observation by Ito et al,23 who found that microvascular integrity in the infarct zone, a sensitive marker of myocardial viability, prevents left ventricular remodeling in reperfused patients. The consistency between our results and those of Ito et al using different techniques to explore different aspects of myocardial viability further enhance the strength of the tested hypothesis.
ACE Therapy and Infarct-Zone Viability
By design, our study could not adequately assess the effects of ACE inhibitor therapy on left ventricular remodeling. Patients received drug therapy according to individual need, which remained the responsibility of the attending physician. Fewer patients with than without infarct-zone viability were treated with ACE inhibitors, and therefore the difference between the two groups in terms of left ventricular volumes cannot be explained on that basis. Patients without infarct-zone viability treated with ACE inhibitors had a worse baseline ejection fraction and a higher infarct-zone wall-motion score than patients without infarct-zone viability who were not treated with ACE inhibitors. This reflects the current physician’s preference to treat patients with left ventricular dysfunction and larger infarcts with ACE inhibitors. In spite of ACE inhibitor therapy, these patients showed an increase, although not significant, in end-diastolic left ventricular volume from baseline to follow-up. When patients were characterized in terms of the presence or absence of left ventricular dilation, no significant difference in frequency of ACE inhibitor administration was observed. These data are not surprising. In all the studies on the antiremodeling effect of ACE inhibitors, the benefit on chamber volume was very small and of borderline significance.24 In the Captopril And Thrombolysis Study (CATS), dilation was not prevented by captopril in the large-infarct group.25 Interestingly, the incidence of heart failure showed the same pattern as the occurrence of ventricular dilation during the 1-year follow-up. The treatment effect on progression to heart failure, compared with the occurrence of dilation, was confined to the patients with medium infarcts. As in the CATS trial, our study population comprised patients with small and large infarcts and thus patients with low and high risks of subsequent dilation. In patients with large infarcts and an absence of myocardial viability, the effect of ACE inhibitors on dilation is probably offset by the magnitude of myocardial damage.
Left Ventricular Dilation and Cardiac Performance
Left ventricular dilation, as an important feature of remodeling, is progressive over time and is associated with an increase of end-systolic volume and deterioration of cardiac performance and survival.1 2 3 In the present study, progressive diastolic dilation observed among patients without infarct-zone viability was accompanied by a consensual but not equivalent elevation of end-systolic volume, indicating preservation of ventricular ejection over time. This is not surprising because left ventricular dilation in its early phase appears to be the major compensatory mechanism after loss of contractile myocardium, resulting in restoration of initially depressed stroke volume.3 21 26 Therefore, at least in the early phase of left ventricular remodeling, ejection fraction remains unchanged. Gaudron et al3 showed that ejection fraction among patients with progressive dilation significantly decreases only 1 to 3 years after infarction. Thus, dilation of the left ventricle precedes any detectable deterioration of global cardiac performance at rest by 6 months. Moreover, development of left ventricular dysfunction might have been postponed in our series by the persistent patency of the infarct-related artery.
The results of the present study should be considered in light of some limitations. First, the analysis of regional function at rest and during dobutamine infusion was semiquantitative. However, this qualitative approach has been widely adopted for clinical studies with stress echocardiography in ischemic heart disease.27 Similarly, echocardiographic assessment of cardiac volumes was based on several geometric assumptions that are not necessarily met in the setting of myocardial infarction. However, over the past several years, echocardiography has become a useful and established tool for serial measurements of left ventricular volumes, and “routine measurements of two-dimensional echocardiography elevates the practice of echocardiography from a highly subjective, qualitative examination to an objective quantitative clinical tool.”16
Second, the performance of dobutamine echocardiography was tested in a setting in which no patient had significant residual stenosis. Therefore, the results of the present study may not be directly applicable to clinical situations in which residual stenosis is present.
Third, the presence of both anterior and inferior infarctions might be considered a limitation because it has been reported that expansion is more common in patients with anterior infarction. However, many other studies7 9 28 have also reported expansion and left ventricular enlargement in patients with an inferior infarction, and in our series, multiple regression analysis showed that infarct location was not an independent predictor of subsequent left ventricular dilation. Moreover, by including patients with inferior infarction, the results of our study are representative of a wide population with acute myocardial infarction.
Finally, serial echocardiographic measurements of left ventricular volumes were not extended beyond 6 months, and prognostic information was not designed to be obtained within the short-term format. Left ventricular dilation after infarction is not necessarily progressive and does not necessarily portend a poor outcome.3 Previous studies have shown that dilation occurs in ≈45% of patients3 29 30 31 32 but is progressive in only 16% within 6 months32 and in only 20% within 3 years after infarction.3 Although progressive deterioration of cardiac performance is highly probable among patients with progressive left ventricular dilation, we cannot establish how many patients from our series are actually destined to have progressive disease.
After reperfused myocardial infarction, the presence of a relatively large amount of viable myocardium in the infarct zone strongly contributes to maintenance of left ventricular wall shape and size by preventing infarct expansion independently of infarct size and patency of the infarct-related artery. Thus, by using a rather simple technique such as dobutamine echocardiography in a very early phase of recovery (mean of 3 days after the index infarction), it is possible for one to identify reperfused patients at high risk for progressive left ventricular enlargement.
- Received May 14, 1997.
- Revision received July 9, 1997.
- Accepted July 15, 1997.
- Copyright © 1997 by American Heart Association
Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction: experimental observations and clinical implications. Circulation. 1990;81:1161-1172.
St. John Sutton M, Pfeffer MA, Plappert T, Rouleau JL, Moye LA, Dagenais GR, Lamas GA, Klein M, Sussex B, Goldman S, Menapace FJ, Parker JO, Lewis S, Sestier F, Gordon DF, McEwan P, Bernstein V, Braunwald E, for the SAVE Investigators. Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. Circulation. 1994;89:68-75.
Gaudron P, Eilles C, Kugler I, Ertl G. Progressive left ventricular dysfunction and remodeling after myocardial infarction: potential mechanisms and early predictors. Circulation. 1993;87:755-763.
Hochman JS, Choo H. Limitation of myocardial infarct expansion by reperfusion independent of myocardial salvage. Circulation. 1987;75:299-306.
Kaul S. There may be more to myocardial viability than meets the eye! Circulation. 1995;92:2790-2793. Editorial.
Sklenar J, Camarano G, Goodman NC, Ismail S, Kaul S. Dobutamine echocardiography for the determining the extent of myocardial salvage after reperfusion: an experimental evaluation. Circulation. 1994;90:1503-1512.
Bolognese L, Antoniucci D, Rovai D, Buonamici P, Cerisano G, Santoro GM, Marini C, L’Abbate A, Fazzini PF. Myocardial contrast echocardiography versus dobutamine echocardiography for predicting functional recovery after acute myocardial infarction treated with primary coronary angioplasty. J Am Coll Cardiol. 1996;28:1677-1683.
Schiller NB. Two-dimensional echocardiographic determination of left ventricular volume, systolic function, and mass. Circulation. 1991;84(suppl I):I-280-I-287.
Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik AJ. Recommendations for quantification of the left ventricle by two dimensional echocardiography: American Society of Echocardiography Committee on Standards Subcommittee. J Am Soc Echocardiogr. 1989;2:358-367.
Smart SC, Sawada S, Ryan T, Segar D, Atherton L, Berkovitz K, Bourdillon PDV, Feigenbaum H. Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction. Circulation. 1993;88:405-411.
Gaudron P, Eilles C, Ertl G, Kochsiek K. Adaptation to cardiac dysfunction after myocardial infarction. Circulation. 1993;87(suppl IV):IV-83-IV-89.
Ito H, Maruyama A, Iwakura K, Takiuchi S, Masuyama T, Hori M, Higashino Y, Fujii K, Minamino T. Clinical implications of the ‘no reflow’ phenomenon: a predictor of complications and left ventricular remodeling in reperfused anterior wall myocardial infarction. Circulation. 1996;93:223-228.
Cohn JN. Structural basis of heart failure: ventricular remodeling and its pharmacological inhibition. Circulation. 1995;91:2504-2507.
Kingma JH, van Gilst WH, Peels KH, Dambrink JHE, Verheugt FWA, Wielenga RP, for the CATS Investigators. Acute intervention with captopril during thrombolysis in patients with first anterior myocardial infarction. Eur Heart J. 1994;15:898-907.
Grossman W, Lorell BH. Hemodynamic aspects of left ventricular remodeling after myocardial infarction. Circulation. 1993;87(suppl VII):VII-28-VII-30.
Jugdutt BI, Warnica W. Intravenous nitroglycerin therapy to limit infarct size, expansion, and complications: effect of timing, dosage, and infarct location. Circulation. 1988;78:906-919.
McKay RG, Pfeffer MA, Pasternak RC, Markis J, Come PC, Nakao S, Alderman JD, Ferguson JJ, Safian RD, Grossman W. Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion. Circulation. 1986;74:693-702.