|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 2000; 35:666-672 © 2000 by the American College of Cardiology Foundation |
a Duke University Medical Center, Durham, North Carolina, USA
Manuscript received August 10, 1998; revised manuscript received September 21, 1999, accepted November 15, 1999.
Reprint requests and correspondence: Dr. Akbar Shah, 1380 E. Stroop Road, Cardiology South, Inc., Kettering, Ohio 45429
Shah7865{at}aol.com
 |
Abstract |
|---|
 Top Abstract MethodsResultsDiscussionReferences |
|---|
To compare the prognostic significance of reperfusion assessment by Thrombolysis in Myocardial Infarction (TIMI) flow grade in the infarct related artery and ST-segment resolution analysis, by correlating with clinical outcomes in patients with acute myocardial infarction (AMI).
BACKGROUND
Angiographic assessment, based on epicardial coronary anatomy, has been considered the "gold standard" for reperfusion. The electrocardiogram (ECG) monitoring provides a noninvasive, real-time physiologic marker of cellular reperfusion and may better predict clinical outcomes.
METHODS
Two hundred fifty-eight AMI patients from the Thrombolytics and Myocardia Infarction phase 7 and Global Utilization of Streptokinase tPA for Occluded coronary arteries phase 1 trials were stratified based on blinded, simultaneous reperfusion assessment on the acute angiogram (divided into TIMI grades 0 & 1, TIMI grade 2 and TIMI grade 3) and ST-segment resolution analysis (divided into: <50% ST-segment elevation resolution or reelevation and 
50% ST-segment elevation resolution). In-hospital mortality, congestive heart failure (CHF) and combined mortality or CHF were compared to determine the prognostic significance of reperfusion assessment by each modality using chi-square and Fisher’s Exact tests for univariable correlation and logistic regression analysis for univariable and multivariable prediction models.
RESULTS
By logistic regression analysis, ST-segment resolution patterns were an independent predictor of the combined outcome of mortality or CHF (p = 0.024), whereas TIMI flow grade was not (p = 0.693). Among the patients determined to have failed reperfusion by TIMI flow grade assessment (TIMI flow grade 0 & 1), the ST-segment resolution of 50% identified a subgroup with relatively benign outcomes with the incidence of the combined end point of mortality or CHF 17.2% versus 37.2% in those without ST-segment resolution (p = 0.06).
CONCLUSION
Continuous 12-lead ECG monitoring can be an inexpensive and reliable modality for monitoring nutritive reperfusion status and to obtain prognostic information in patients with AMI.
| ||||||||||||||||||||
Angiographic assessment is based on the Thrombolysis in Myocardial Infarction (TIMI) flow grade determination in the epicardial infarct related artery (IRA). However, epicardial coronary patency may not mean nutritive cellular perfusion. Additionally, an angiographic "snapshot" of coronary anatomy cannot describe the fluctuations in coronary flow over time that have been reported during the acute phase of myocardial infarction in 35% to 50% of patients (2,6). In contrast, the ST-segment changes observed by electrocardiogram (ECG) monitoring can potentially provide a continuous, noninvasive, real time physiologic marker of nutritive cellular reperfusion.
We hypothesized that electrocardiographically determined reperfusion status might be more predictive of clinical outcomes than angiography. The purpose of this study was to compare the prognostic significance of simultaneous reperfusion assessment by angiographic TIMI flow grade in the IRA versus electrocardiographic ST-segment elevation resolution analysis in patients with acute myocardial infarction (AMI).
|
Methods |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
Baseline characteristics.
Data on the following baseline demographic and cardiac risk factor characteristics were provided by the cardiovascular databank at the Duke University Medical Center: time from the onset of symptoms to initiation of thrombolytic therapy, age, height, weight, history of hypertension, diabetes, myocardial infarction, angioplasty, bypass surgery and smoking. Additionally, the peak creatinine phosphokinase (CPK) levels, angiographically determined IRA, left ventricular ejection fraction (LVEF) and the number of major coronary arteries with 50% luminal stenosis were included as baseline descriptors.
Angiography. In accordance with the TAMI-7 and GUSTO-1 protocols, all patients had acute coronary angiography performed (after informed consent) 90–180 min after the start of thrombolytic therapy (7,9). Infarct related artery TIMI flow grade for TAMI-7 patients was determined at the angiographic core laboratory at the University of Michigan Hospital; that for GUSTO-1 patients was determined at the angiographic core laboratory at George Washington University Hospital. For the purposes of our study, patients were divided into three groups: 1) TIMI grade flow 0 & 1, 2) TIMI flow grade 2, and 3) TIMI flow grade 3.
Continuous 12-lead ECG monitoring.
All patients in this study had continuous 12-lead ECG monitoring using a portable digital instrument (ST100, Mortara Instrument, Milwaukee, Wisconsin) (2). Monitoring was initiated at median (25th, 75th percentiles) of 3.46 min (–9.33 min, 21.22 min) after the start of thrombolytic therapy and continued for median (25th, 75th percentiles) of 25.17 (12.19, 41.48) hours. All ST-segment monitoring data were analyzed at the Ischemia Monitoring Laboratory, Duke University Medical Center by a single experienced physician, blinded to all clinical and angiographic data. Assessment of each patient’s ST-segment resolution at the time of protocol angiography was performed using the previously published continuous ST-segment resolution analysis method (10). Patients were divided into two groups: 1) those with either less than 50% resolution of the ST-segment elevation from the peak ST-segment elevation in the lead showing the greatest ST-segment elevation, or 150 µV or , and 2) those with 50% or more ST-segment elevation resolution (without reelevation). In order to determine reperfusion status simultaneous with angiography, all analyses were based on continuous ECG data until within 5 min of the initial angiographic contrast injection. The 5 min window was allowed for any possible clock discrepancy. The physician analyzing the ST-segment data was kept blinded to all the continuous ECG data subsequent to the time of initial angiographic contrast injection.
Outcomes. Data for the outcomes were provided by the coordinating center for TAMI-7 and GUSTO-1 trials at Duke University Medical Center. For the purpose of this study, the following parameters were analyzed as outcomes: in-hospital all-cause mortality, the incidence of new congestive heart failure (CHF), and the "combined end point" of mortality or CHF.
Statistical analyses. Data for baseline and clinical outcome parameters are reported using percentages for categorical variables and 50th (25th, 75th) percentiles for continuous variables. To determine possible univariate correlates of adverse cardiac outcomes and ST-segment/TIMI flow grade category, we applied the chi-square and Fisher’s exact test for categorical variables. A p value of <0.05 was considered statistically significant. The sample sizes and events rates were small in some subgroups; thus, 95% confidence intervals were also given for the event to show how much variability exists. We used exact binomial distribution to find the 95% confidence intervals. A family of comparisons was not used since we were not comparing multiple TIMI flow grades subgroups to one another. We were comparing two ST-segment resolution categories within each TIMI flow grade subgroup. We thought that utilizing 95% confidence intervals was more informative. A logistic regression model was used to determine if ST-segment resolution analysis, rather than TIMI flow grade determination, more accurately predicts the combined end point. Stepwise regression was not used. Multicollinearity was not a factor since TIMI flow was not an independent predictor and stepwise regression was not used.
|
Results |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
|
|
|
|
|
Discussion |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
The results of our study support the hypothesis that ST-segment resolution as a continuous, physiologic marker of reperfusion predicts outcomes better than a transient, anatomic marker such as angiographic TIMI flow grade in the IRA. Outcomes in our study population did not differ significantly when grouped according to TIMI flow grade although there were trends toward better outcomes in patients with TIMI 3 flow grade compared with those with TIMI grades 
2 flow. Conversely, when grouped according to ST-segment elevation resolution characteristics, patients whose ST-segment elevation resolved had significantly lower incidence of the combined end point than those whose ST-segment elevation persisted. Similarly, logistic regression analysis indicated ST-segment resolution to be an independent predictor of the combined end point; TIMI grade flow was not an independent predictor and did not add to the information from ST-segment resolution analysis. These results become more significant when one considers that the continuous ECG data for the time after the TIMI flow grade determination were not allowed to be used for patient prognostic stratification. This censoring of available data provided myocardial reperfusion by angiography and ECG, based only on the data obtained until a specific point in time. However, in clinical settings, the continuous ECG monitoring can describe dynamic ST-segment changes even after angiographic determination of coronary anatomy.
Within each TIMI flow grade category (0/1, 2 and 3), patients with ST-segment elevation resolution had trends toward lower incidence of all outcome parameters compared with those with persistent ST-segment elevation. However, due to small numbers in patient subgroups, any concrete conclusions are not possible. These results suggest that when clinical outcomes are used as the standard, TIMI grade 3 flow is a specific, though not a sensitive, marker for successful reperfusion. In our study, angiography failed to distinguish patients with good outcomes among those with TIMI grades <3 flow. However, continuous ECG monitoring was both a specific and a sensitive predictor of clinical outcomes.
It is noteworthy that in our study the in-hospital mortality rate in patients with TIMI flow grade 3 was 6.4%—higher than the 4.4% rate reported in the GUSTO angiographic substudy (9). The reasons for this difference cannot be fully explained but could be due to a smaller sample size or due to the fact that patients from both TAMI-7 and GUSTO-1 trials were included. However, it is important to point out that both mortality rate and the incidence of CHF were always concordant in prognostication of every patient group, emphasizing the validity of outcome data in our population. Similarly, as opposed to our study, GUSTO angiographic study showed TIMI flow grade to correlate with in-hospital mortality. We are unable to fully explain the difference in findings of the two studies. Smaller sample size and inclusion of TAMI-7 patients in our study could, at least in part, explain the difference. It is noteworthy that even in our study, TIMI flow grade 3 was a specific marker for "good outcomes." However, it was not a sensitive marker, whereas, the resolution of ST-segment was a sensitive as well as specific predictor of "good outcomes."
TIMI flow grade 2. At the time of the TAMI-7 and GUSTO-1 trials, TIMI flow grade 2 was clinically considered a marker of successful reperfusion. This study considered these patients as a separate group, based on several reports of outcomes in patients with TIMI grade flow 2 intermediate between those with TIMI flow grades 0/1 and 3 and significantly worse than those with TIMI flow grade 3 (13–18). The results of our study suggest that TIMI flow grade 2 is a marker of high risk in some and low risk in others. Although pathophysiology is not considered in this study, in some patients with TIMI flow grade 2, benefits from partial reperfusion may be outweighed by possible risks, such as reperfusion injury. In others, TIMI flow grade 2 would actually be associated with nutritive cellular reperfusion. ST-segment elevation resolution characteristics may help ascertain the true clinical significance of TIMI flow grade 2 in an individual. However, these results regarding TIMI grade 2 flow should be viewed with consideration of the small number of such patients in this population.
Results of our study suggest that "angiographic reperfusion" may not be synonymous with nutritive cellular reperfusion. Angiography does not provide any physiologic markers of cellular reperfusion and only provides brief visualization of epicardial anatomy. Additionally, the invasive and expensive nature of the acute angiography places practical limits on its routine applicability for patients with AMI, especially in the current era of healthcare economics. Obviously, electrocardiographic monitoring is not a substitute for the angiographic data in every patient with AMI. However, in many patients, information obtained through electrocardiographic monitoring can potentially be used to identify patients who need an acute angiogram instead of conservative observation, and in other patients, this information could supplement angiographic data, in acute care and risk stratification.
Study limitations. Although our study was retrospective, it was based on blinded analysis of predefined angiographic, electrocardiographic and clinical variables. The study population was relatively small to address all the issues discussed, characterize other subtle bias and multivariate analysis regarding baseline characteristics. Additionally, collateral blood flow information was unavailable for consideration while making angiography-based decisions. Only 50% level of ST-segment elevation resolution was evaluated in this study. Other degrees of ST-segment resolution may indeed have prognostic values. Because of these limitations, validation of our findings in a larger prospective study will be required.
Clinical implications. The findings of our study must be considered preliminary. Assuming validation in a larger patient population, continuous ST-segment monitoring could provide a noninvasive, inexpensive and reliable method for monitoring nutritive reperfusion status in AMI patients. ST-segment monitoring could be utilized for real-time acute patient care and to obtain highly sensitive and specific prognostic information independent of TIMI flow grade in the IRA.
|
References |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  M. Majidi, A. S. Kosinski, S. M. Al-Khatib, M. E. Lemmert, L. Smolders, A. van Weert, J. H.C. Reiber, D. Tzivoni, F. W.H.M. Bar, H. J.J. Wellens, et al. Reperfusion ventricular arrhythmia 'bursts' in TIMI 3 flow restoration with primary angioplasty for anterior ST-elevation myocardial infarction: a more precise definition of reperfusion arrhythmias Europace, August 1, 2008; 10(8): 988 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. McDonald, Y. Fu, U. Zeymer, G. Wagner, S. G. Goodman, A. Ross, C. B. Granger, F. Van de Werf, P. W. Armstrong, and for the ASSENT-4 PCI Investigators Adverse outcomes in fibrinolytic-based facilitated percutaneous coronary intervention: insights from the ASSENT-4 PCI electrocardiographic substudy Eur. Heart J., April 1, 2008; 29(7): 871 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S G Foussas, M N Zairis, S S Makrygiannis, S J Manousakis, F A Anastassiadis, C S Apostolatos, N G Patsourakos, M P Glyptis, J K Papadopoulos, D C Xenos, et al. The significance of circulating levels of both cardiac troponin I and high-sensitivity C reactive protein for the prediction of intravenous thrombolysis outcome in patients with ST-segment elevation myocardial infarction Heart, August 1, 2007; 93(8): 952 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Johanson, Y. Fu, S. G. Goodman, M. Dellborg, P. W. Armstrong, M. W. Krucoff, L. Wallentin, and G. S. Wagner A dynamic model forecasting myocardial infarct size before, during, and after reperfusion therapy: an ASSENT-2 ECG/VCG substudy Eur. Heart J., September 1, 2005; 26(17): 1726 - 1733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Lefevre, E. Garcia, B. Reimers, I. Lang, C. di Mario, A. Colombo, F.-J. Neumann, M. V. Chavarri, P. Brunel, E. Grube, et al. X-Sizer for Thrombectomy in Acute Myocardial Infarction Improves ST-Segment Resolution: Results of the X-Sizer in AMI for Negligible Embolization and Optimal ST Resolution (X AMINE ST) Trial J. Am. Coll. Cardiol., July 19, 2005; 46(2): 246 - 252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sorajja, B. J. Gersh, C. Costantini, M. G. McLaughlin, P. Zimetbaum, D. A. Cox, E. Garcia, J. E. Tcheng, R. Mehran, A. J. Lansky, et al. Combined prognostic utility of ST-segment recovery and myocardial blush after primary percutaneous coronary intervention in acute myocardial infarction Eur. Heart J., April 1, 2005; 26(7): 667 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Borjesson and M. Dellborg Exercise testing post-MI: still worthwhile in the interventional era Eur. Heart J., January 2, 2005; 26(2): 105 - 106. [Full Text] [PDF]
|
|
|
|
|
|
M. G. McLaughlin, G. W. Stone, E. Aymong, G. Gardner, R. Mehran, A. J. Lansky, C. L. Grines, J. E. Tcheng, D. A. Cox, T. Stuckey, et al. Prognostic utility of comparative methods for assessment of ST-segment resolution after primary angioplasty for acute myocardial infarction: The controlled abciximab and device investigation to lower late angioplasty complications (CADILLAC) trial J. Am. Coll. Cardiol., September 15, 2004; 44(6): 1215 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Zairis, A. G. Lyras, S. S. Makrygiannis, P. K. Psarogianni, E. N. Adamopoulou, S. M. Handanis, A. Papantonakos, S. K. Argyrakis, A. A. Prekates, and S. G. Foussas Type 2 Diabetes and Intravenous Thrombolysis Outcome in the Setting of ST Elevation Myocardial Infarction Diabetes Care, April 1, 2004; 27(4): 967 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Roe, C. L. Green, R. P. Giugliano, C. M. Gibson, K. Baran, M. Greenberg, S. T. Palmeri, S. Crater, K. Trollinger, K. Hannan, et al. Improved speed and stability of st-segment recovery with reduced-dose tenecteplase and eptifibatide compared with full-dose tenecteplase for acute st-segment elevation myocardial infarction J. Am. Coll. Cardiol., February 18, 2004; 43(4): 549 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Bjorklund, B. Lindahl, P. Johanson, T. Jernberg, A.-M. Svensson, P. Venge, L. Wallentin, M. Dellborg, and the ASSENT-2 and ASSENT-PLUS study groups Admission Troponin T and measurement of ST-segment resolution at 60 min improve early risk stratification in ST-elevation myocardial infarction Eur. Heart J., January 2, 2004; 25(2): 113 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. W. Armstrong, G. Wagner, S. G. Goodman, F. Van de Werf, C. Granger, L. Wallentin, Y. Fu, and for the ASSENT 3 Investigators ST segment resolution in ASSENT 3: insights into the role of three different treatment strategies for acute myocardial infarction Eur. Heart J., August 2, 2003; 24(16): 1515 - 1522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L Galiuto, A Lombardo, A Maseri, L Santoro, I Porto, D Cianflone, A G Rebuzzi, and F Crea Temporal evolution and functional outcome of no reflow: sustained and spontaneously reversible patterns following successful coronary recanalisation Heart, July 1, 2003; 89(7): 731 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Johanson, T. Jernberg, G. Gunnarsson, B. Lindahl, L. Wallentin, and M. Dellborg Prognostic value of ST-segment resolution--when and what to measure Eur. Heart J., February 2, 2003; 24(4): 337 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-K. Wong, J.K. French, M.W. Krucoff, W. Gao, P.E. Aylward, and H.D. White Slowed ST segment recovery despite early infarct artery patency in patients with Q waves at presentation with a first acute myocardial infarction. Implications of initial Q waves on myocyte reperfusion Eur. Heart J., September 2, 2002; 23(18): 1449 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Poli, R. Fetiveau, P. Vandoni, G. del Rosso, M. D'Urbano, G. Seveso, F. Cafiero, and S. De Servi Integrated Analysis of Myocardial Blush and ST-Segment Elevation Recovery After Successful Primary Angioplasty: Real-Time Grading of Microvascular Reperfusion and Prediction of Early and Late Recovery of Left Ventricular Function Circulation, July 16, 2002; 106(3): 313 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Jernberg, B. Lindahl, and L. Wallentin Continuous multilead ST-segment monitoring should be a part of the clinical routine Eur. Heart J., June 2, 2002; 23(12): 918 - 921. [Full Text] [PDF]
|
|
|
|
|
|
Y. Fu, S. Goodman, W.-C. Chang, F. Van de Werf, C. B. Granger, and P. W. Armstrong Time to Treatment Influences the Impact of ST-Segment Resolution on One-Year Prognosis: Insights From the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) Trial Circulation, November 27, 2001; 104(22): 2653 - 2659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. de Lemos and E. Braunwald ST segment resolution as a tool for assessing the efficacy of reperfusion therapy J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1283 - 1294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Kazerooni Population and Sample Am. J. Roentgenol., November 1, 2001; 177(5): 993 - 999. [Full Text] [PDF]
|
|
|
|
|
|
E. Giannitsis, M. Muller-Bardorff, S. Lehrke, U. Wiegand, R. Tolg, B. Weidtmann, F. Hartmann, G. Richardt, and H. A. Katus Admission Troponin T Level Predicts Clinical Outcomes, TIMI Flow, and Myocardial Tissue Perfusion After Primary Percutaneous Intervention for Acute ST-Segment Elevation Myocardial Infarction Circulation, August 7, 2001; 104(6): 630 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Widimsky Pharmacological versus catheter-based reperfusion: What is present state of the art? Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C47 - C54. [Abstract] [PDF]
|
|
|
|
|
|
J. Lopez-Sendon Coronary reperfusion in the clinical setting: antithrombotic support to thrombolysis in the coronary care unit Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C55 - C61. [Abstract] [PDF]
|
|
|
|
|
|
M. T. Roe, E. M. Ohman, A. C. P. Maas, R. H. Christenson, K. W. Mahaffey, C. B. Granger, R. A. Harrington, R. M. Califf, and M. W. Krucoff Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion J. Am. Coll. Cardiol., January 1, 2001; 37(1): 9 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Trial of Abciximab With and Without Low-Dose Reteplase for Acute Myocardial Infarction Circulation, June 20, 2000; 101(24): 2788 - 2794. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 ST-Segment Resolution: A Better Predictor Than Angiography? Journal Watch Emergency Medicine, June 1, 2000; 2000(601): 9 - 9. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
