CLINICAL STUDIES
Determinants of coronary blood flow after thrombolytic administration
C. Michael Gibson, MS, MD, FACC*,
Sabina Murphy, MPH*,
Ian B. A. Menown, MD, MRCP ,
Rafael F. Sequeira, MD, FACC ,
Robert Greene, MD, FACC ,
Frans Van de Werf, MD||,
Marc J. Schweiger, MD, FACC¶,
Magdi Ghali, MD, FACC#,
Martin J. Frey, MD, FACC**,
Kathryn A. Ryan, BS*,
Susan J. Marble, RN, MS*,
Robert P. Giugliano, MD, SM,
Elliott M. Antman, MD, FACC,
Christopher P. Cannon, MD, FACC,
Eugene Braunwald, MD, FACC for the TIMI Study Group
* Cardiovascular Division of the Department of Medicine, the University of California San Francisco, San Francisco, California, USA
Royal Victoria Hospital, Belfast, Northern Ireland, Ireland
Jackson Memorial Hospital, Miami, Florida, USA
Alta Bates Medical Center, Berkeley, California, USA
|| UZ Gasthuisberg, Leuven, Belgium
¶ Baystate Medical Center, Springfield, Massachusetts, USA
# Iowa Heart Center/Mercy Hospital, Des Moines, Iowa, USA
** Sarasota Memorial Hospital, Sarasota, Florida, USA
Brigham & Women’s Hospital, Boston, Massachusetts, USA
Manuscript received October 28, 1998;
revised manuscript received June 8, 1999,
accepted July 19, 1999.
Reprint requests and correspondence: C. Michael Gibson, Associate Chief of Cardiology, University of San Francisco, 3333 California Street, Suite 430, San Francisco, California 94118
OBJECTIVES
This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients.
BACKGROUND
Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored.
METHODS
The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow.
RESULTS
The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 ± 17.2, n = 181) remained significantly slower than normal (21.0 ± 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003).
CONCLUSIONS
Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.
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Abbreviations and Acronyms
| | AMI | = acute myocardial infarction | | ANOVA | = analysis of variance | | CTFC | = corrected Thrombolysis in Myocardial Infarction frame count. (Number of frames required for dye to reach a standardized distal landmark) | | LAD | = left anterior descending artery | | PAMI | = Primary Angioplasty in Myocardial Infarction | | PTCA | = percutaneous transluminal coronary angioplasty | | RCA | = right coronary artery | | rt-PA | = recombinant tissue plasminogen activator | | TIMI | = Thrombolysis in Myocardial Infarction | | TNK | = a mutant of recombinant tissue plasminogen activator |
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