(Circulation. 1999;100:339-345.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Can Coronary Blood Flow Velocity Pattern After Primary Percutaneous Transluminal Coronary Angiography Predict Recovery of Regional Left Ventricular Function in Patients With Acute Myocardial Infarction?
From the Department of Cardiology, Kobe General Hospital, Kobe, Japan.
Correspondence to Kiyoshi Yoshida, MD, Department of Cardiology, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan. E-mail kyoshida{at}med.kawasaki-m.ac.jp
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Abstract |
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Background—In the era of primary percutaneous transluminal coronary angioplasty (PTCA), it is important to judge whether myocardium within acute ischemic injury is viable. This study sought to investigate parameters derived from the coronary blood flow velocity spectrum immediately after primary PTCA in patients with acute myocardial infarction and to elucidate the clinical value of coronary blood flow measurement in predicting myocardial viability.
Methods and Results—Using a Doppler guidewire, we measured
coronary blood flow velocity after successful completion of
primary PTCA in 23 consecutive patients with acute anterior myocardial
infarction. Regional wall motion was analyzed to estimate
anterior wall motion score index (A-WMSI) by
echocardiography before PTCA and 1 month after the
onset of symptoms. Average systolic peak velocity (ASV) and
deceleration time of diastolic flow velocity (DDT)
significantly correlated to 1-month A-WMSI (r=-0.54,
P=0.007 and r=-0.62,
P=0.002, respectively), and optimal cutoff values to
predict viable myocardium (defined as 1-month A-WMSI 
2.0)
were 6.5 cm/s for ASV and 600 ms for DDT (sensitivity=0.79,
specificity=0.89 and sensitivity=0.86, specificity=0.89, respectively).
ASV and DDT also correlated weakly to the change in A-WMSI
(r=0.46, P=0.03 and
r=0.49, P=0.02, respectively).
Conclusions—Low ASV and rapid DDT of coronary blood flow spectrum immediately after primary PTCA reflects a greater degree of microvascular damage in the risk area. Analysis of coronary blood flow spectrum immediately after primary PTCA by use of a Doppler guidewire is useful in predicting recovery of regional left ventricular function.
Key Words: angioplasty • microcirculation • myocardial infarction • prognosis • reperfusion
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Introduction |
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Percutaneous transluminal coronary angioplasty has been widely performed in cases of acute myocardial infarction (AMI) because of a higher rate of recanalization, better preserved left ventricular function, and a lower rate of complications compared with thrombolysis.1 2 3 4 However, patency of the infarct-related coronary artery does not always guarantee salvage of myocardium at risk of ischemia.5 Therefore, the great interest of many cardiologists is in the viability of reperfused myocardium. Assessment of regional myocardial perfusion by contrast echocardiography has revealed a no-reflow phenomenon, which is defined as a lack of enhancement of myocardium by microbubbles despite recanalization of the infarct-related coronary artery5 6 7 ; this phenomenon is thought to be established as a result of microvascular damage induced by ischemia. Some studies have shown that the no-reflow segment is not viable,5 8 and it has been shown by use of a Doppler guidewire that the coronary blood flow velocity pattern of no-reflow in patients with reperfused AMI is characterized by the appearance of systolic retrograde flow, diminished systolic antegrade flow, and rapid deceleration of diastolic flow.9 However, the relationship between the coronary blood flow velocity pattern immediately after primary PTCA and the recovery of left ventricular function has not been discussed fully. Therefore, we hypothesized that the degree of reduced systolic antegrade flow or the deceleration time of diastolic flow might reflect the degree of microvasculature damage and be predictive of residual myocardial viability. To test this hypothesis, we prospectively compared the coronary blood flow velocity pattern immediately after primary PTCA with use of a Doppler guidewire and the recovery of regional left ventricular wall motion in the risk area assessed by echocardiography in 23 consecutive patients with successfully reperfused anterior AMI.
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Methods |
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Study Population
This study comprised 23 consecutive patients (21 men and 2 women; mean age, 61±10 years; age range, 45 to 75 years) with anterior AMI who were successfully recanalized with primary PTCA including rescue stenting within 12 hours after the onset of symptoms. The study inclusion criteria were as follows: (1) first anterior AMI, (2) successful recanalization with primary PTCA (defined as residual stenosis
25% visually) within 12 hours
after the onset of symptoms, and (3) informed consent to perform
primary PTCA and coronary blood flow measurement. The diagnosis
of AMI was based on >30 minutes of continuous chest pain, ST elevation
>2.0 mm in 
2 contiguous ECG leads, a >3-fold increase over the
normal value in serum creatine kinase, and Thrombolysis In
Myocardial Infarction (TIMI) flow grade 0, 1, or 2 at initial
coronary angiography. We excluded patients with prior
myocardial infarction, those with a cardiac event during follow-up, and
those with inadequate recording of coronary flow
velocity spectrum or poor echocardiographic image. The
study protocol was approved by the ethics committee of Kobe General
Hospital. One of the investigators obtained informed consent from all
patients before cardiac catheterization.
Study Protocol
Regional wall motion was examined in the emergency room by
use of echocardiography to determine the risk area
before angioplasty. All patients received an intravenous
bolus injection of 4000 U of heparin before angiography, and 0.5
mg · kg-1 ·
min-1 of nitroglycerin was
continuously given intravenously soon after establishment
of the diagnosis. Intracoronary isosorbide dinitrate (2 mg) was
given before coronary angiography. Diagnostic
coronary angiography was performed via the femoral approach by
use of the Judkins technique. After an additional
intravenous or intra-arterial bolus injection
of 6000 U of heparin, coronary angioplasty, including rescue
stenting, was performed. Stents were deployed by high-pressure
implantation techniques. An angiographic criterion of <25% residual
stenosis was used to determine the end point of the angioplasty
procedure. After successful angioplasty, the guidewire was exchanged
for a 0.014-in Doppler guidewire (FloWire; Cardiometrics,
Inc).10 The tip of the Doppler guidewire was placed
slightly distal to the culprit lesion, where there was neither a
significant stenosis nor a large side branch angiographically,
to assess coronary blood flow to the entire area at risk.
Phasic coronary blood flow velocity spectrum was recorded
on a Super VHS videotape (FloMap; Cardiometrics, Inc) >10 minutes
after the last balloon inflation. Serum creatine kinase was measured
serially every 3 hours after recanalization until
the peak value was obtained. Patients received conventional drug
therapy according to individual need, which was determined by the
attending physician. The stented patients received anticoagulation with
a ticlopidine and aspirin regimen (ticlopidine 100 mg twice a day and
aspirin 81 mg twice a day). All patients underwent follow-up
echocardiography to examine regional wall motion
recovery 1 month after the onset of symptoms.
Echocardiographic Wall Motion Analysis
The left ventricular wall was divided into 16
segments, and the regional wall motion of each segment was examined and
scored according to a modification of the recommendation of the
American Society of
Echocardiography,11 in which 1 is
normal, 1.5 is mild hypokinesis, 2 is hypokinesis, 2.5 is severe
hypokinesis, 3 is akinesis, and 4 is dyskinesis.12 Nine of
the 16 segments were determined to be in the vicinity of the left
anterior descending coronary artery (LAD), and the anterior
wall motion score index (A-WMSI) was calculated as an average of the
wall motion scores in these 9 segments13 (Figure 1
). The change in A-WMSI was also
estimated.
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Analysis of Coronary Blood Flow Velocity
Spectrum
The coronary blood flow velocity spectrum recorded
on a Super VHS videotape was digitized by offline computerized
planimetry. The digitized coronary blood flow velocity spectrum
provided the following parameters: time-averaged peak
velocity (cm/s; APV), average systolic peak velocity (cm/s;
ASV), average diastolic peak velocity (cm/s; ADV), maximal
peak velocity (cm/s; MPV), and deceleration time of
diastolic flow velocity (ms; DDT). Retrograde flow was
calculated as a negative value.
Analysis of Coronary Angiogram
Percent diameter stenosis and minimum lumen
diameter of the culprit lesion were quantitatively analyzed
offline by auto edge detection with a validated technique (CMS; Medical
Imaging Systems, Inc)14 from a cineangiogram
taken before and after primary PTCA. Contrast flow through the
infarct-related coronary artery was graded by the standard TIMI
flow scale of 0 to 3 from the final coronary
angiogram.15 Collateral flow was graded according to the
Rentrop classification of 0 to 3 from the initial coronary
angiogram.16
Statistics
Results are reported as mean±SD unless otherwise indicated. The
difference between A-WMSI before recanalization and
A-WMSI at 1 month after symptom onset was evaluated by paired
Student's t test. Comparisons of continuous variables
between 2 groups were made by unpaired Student's t test.
The 
2 test was used to compare categorical
variables. Linear regression analysis was applied to
estimate the relation between parameters obtained from
coronary blood flow velocity spectrum recordings and
1-month A-WMSI or the change in A-WMSI. Statistical differences were
considered significant at a value of P<0.05. The ability of
the coronary blood flow parameters to predict
viable myocardium was analyzed by use of receiver
operating characteristic (ROC) curves, ie, plots of sensitivity versus
1-specificity.17 18
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Results |
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Patient Characteristics and Clinical Results
Thirteen patients (57%) had a history of hypertension, 7 (30%) had diabetes mellitus, 12 (52%) had a cholesterol level >220 mg/dL, and 16 (70%) were smokers. Mean time from the onset of symptoms to coronary reperfusion was 250±129 minutes. Peak creatine kinase level was 5116±3849 IU/L. Nineteen patients developed Q-wave infarction, whereas the other 4 manifested non–Q-wave infarction. There was no clinical, ECG, or enzymatic evidence of reinfarction in any patient during the 1-month follow-up. In-hospital medications were as follows: nitrate (n=23; 100%), ACE inhibitor (n=19; 83%), ß-adrenergic blocking agent (n=14; 61%), calcium antagonist (n=3; 13%), and diuretics (n=3; 13%). (See Table 1
.)
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Angiographic Results
Primary PTCA, including rescue stenting, was successfully
performed in all patients. The culprit lesion was the proximal LAD
(segment 6) in 17 patients and mid LAD (segment 7) in 6. Eighteen
patients had single-vessel disease, 4 had double-vessel disease, and 1
had triple-vessel disease. No patient showed good collateral flow
(Rentrop grade 3), 4 showed fair collateral flow (Rentrop grade 2), and
the remaining 19 showed poor or no collateral flow (Rentrop grade 1 or
0) on the initial coronary angiogram. Rescue stenting was
performed in 10 patients, and the reasons for rescue stenting were as
follows: suboptimal result after repeat balloon inflation (n=5), large
dissection (n=2), and haziness or recurrent thrombus (n=3). Percent
diameters of stenosis before and after angioplasty were
89±15% and 26±15%, respectively. Minimum lumen diameter after
angioplasty was 2.4±0.7 mm. Three patients showed TIMI 2 reflow,
and the remaining 20 patients showed TIMI 3 reflow. Only 2 patients had
insignificant stenosis distal to the culprit lesion. (See Table 1
.)
Baseline and Follow-Up Echocardiography
Baseline and follow-up echocardiography
examinations were performed in all 23 patients. A-WMSI decreased
significantly from baseline to follow-up (from 2.49±0.45 to
1.93±0.54; P<0.0001; Figure 2), and the change in A-WMSI was
0.56±0.42.
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Relation Between Coronary Blood Flow Velocity Pattern and
Late Results
In accordance with a previous report on low-dose
dobutamine
echocardiography,13 we defined viable
myocardium as 1-month A-WMSI 2.00. We divided our
patients into 2 groups: viable myocardium group (1-month
A-WMSI 2.00) and nonviable myocardium group (1-month
A-WMSI >2.00). The viable group showed a higher rate of TIMI 3 reflow
(14 of 14 versus 6 of 9; P=0.02), a lower peak creatine
kinase value (3445±3054 versus 7716±3617 IU/L; P=0.006),
and a lower 1-month A-WMSI (1.58±0.33 versus 2.48±0.24;
P<0.0001). However, there was no significant difference in
baseline characteristics, residual stenosis, or A-WMSI before
recanalization (Table 2). Doppler velocimetry data showed
significantly higher ASV (12±6 versus 2±8 cm/s; P=0.004),
lower MPV (28±11 versus 56±24 cm/s; P=0.0009), and longer
DDT (954±326 versus 470±181 ms; P=0.0006) in the viable
group compared with the nonviable group (Table 3). Figures 3 and 4
show a typical coronary blood flow velocity spectrum in
patients from the viable and nonviable groups, respectively. The
coronary blood flow velocity pattern with viable
myocardium seems almost normal and that with nonviable
myocardium shows reduced ASV caused by systolic
retrograde flow and rapid deceleration of diastolic flow
velocity. ASV and DDT imme1diately after primary PTCA were compared
with 1-month A-WMSI. ASV and DDT significantly correlated with 1-month
A-WMSI (y=-8.5x+24.4, r=-0.54,
P=0.007 and y=-420x+1576,
r=-0.62, P=0.002, respectively; Figure 5), with substantial scatter. On the
basis of ROC curve analysis,17 18 optimal
cutoff values of 6.5 cm/s for ASV and 600 ms for DDT were chosen to
predict viable myocardium (sensitivity=0.79,
specificity=0.89 and sensitivity=0.86, specificity=0.89, respectively).
There was also a weak correlation between ASV and DDT and the change in
A-WMSI (y=9.2x+2.8, r=0.46,
P=0.03 and y=428x+524,
r=0.49, P=0.02, respectively).
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Although stented patients showed significantly lower percent diameter stenosis (17±14% versus 34±13%; P=0.005) and larger minimum lumen diameter (2.7±0.6 versus 2.1±0.6 mm; P=0.03), there was no significant difference in 1-month A-WMSI (1.87±0.59 versus 1.97±0.51; P=NS) or in coronary blood flow parameters (APV, 18±8 versus 17±8 cm/s; ASV, 9±10 versus 7±7 cm/s; ADV, 24±10 versus 23±11 cm/s; DDT, 709±293 versus 808±418 ms; all P=NS) between stented and nonstented patients.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We directly measured coronary blood flow velocity after successful primary PTCA and investigated the relationship of the parameters derived from coronary blood flow velocity spectrum at reperfusion and preserved myocardial viability at late stage. Our major finding was that the higher the ASV and the longer the DDT of the coronary blood flow velocity pattern after primary PTCA, the more the myocardium within a region of acute ischemic injury would recover. We conclude that a low ASV and short DDT can represent characteristics of coronary blood flow with severe microvascular damage, given no significant residual stenosis in the epicardial coronary artery and given that ASV and DDT at reperfusion are predictive of the recovery of regional left ventricular function. To the best of our knowledge, this is the first report to directly compare the coronary blood flow velocity pattern immediately after primary PTCA with the recovery of regional left ventricular function.
Coronary Blood Flow Velocity Pattern and Microvascular
Damage
In the present study, patients with low ASV showed poorer
regional recovery of left ventricular function. Early
systolic retrograde flow has previously been reported to be
observed frequently in patients with no reflow in case of AMI after
successful recanalization.9 In that
previous report, early systolic retrograde flow was explained
by an occluded coronary microvasculature, which is thought to
cause backflow during systole by contraction of the
myocardium. We believe the degree of backflow during
systole reflects ASV and that the higher percentage of occluded
coronary microvasculature in the infarct-related
coronary bed reflects a lower ASV.
Experimental study has demonstrated that microvascular ischemic damage after epicardial coronary artery occlusion affects coronary vascular resistance,19 20 and perivascular edema and capillary leukocyte plugging after myocardial ischemia contribute to prevention of full restoration of myocardial perfusion.21 Short DDT may be explained by an increase in coronary vascular resistance caused by such ischemic microvascular damage. The high ratio of perfused myocardium per functioning coronary microvasculature might reflect the coronary blood flow and would be observed as a short DDT.
Although much better correlation would be expected between ASV, DDT, and the change in A-WMSI, only weak correlations were obtained. This might be related to the fact that good wall motion segments before recanalization, which could be out of the substantial area at risk, were included.
Coronary Blood Flow and TIMI Flow Grade
The TIMI study group grading system has been widely used to assess
coronary perfusion,15 and some studies have shown
worse outcome with TIMI grade 2 reflow than with TIMI grade 3
reflow.22 23 24 25 Because the TIMI criterion is based on
visual judgment of radiocontrast media runoff in coronary
angiography and is thought to be affected by various factors, such as
injection speed, injection volume, and diameter and size of the
coronary artery, an accurate assessment of coronary
blood flow is quite difficult.26 We demonstrated that more
quantitative assessment of coronary blood flow was possible in
patients with reperfused AMI by use of a Doppler guidewire, as
previously reported.26
Study Limitations
First, we assumed A-WMSI at 1 month to be an indicator of
myocardial viability. This parameter is considered to
represent myocardial viability but to be semiquantitative.
Further examination should be done in comparison with a single-photon
emission CT (SPECT) or PET study to assess the degree of myocardial
damage more quantitatively.27
Second, the coronary blood flow velocity pattern may alter with the stenosis. In the present study, there was no significant difference in coronary blood flow parameters between stented and nonstented subjects, and therefore the effect of residual stenosis of the epicardial coronary artery should be minimal. The routine use of stents could decrease residual stenosis to almost 0%; thus, the effect of stenosis in the epicardial coronary artery should not be considered.28 29
Third, coronary blood flow measurements were performed 10
minutes after the last balloon inflation in the present study. Some
studies have documented that the hyperemic response continues
for several hours and that coronary perfusion dynamically
alters within a few hours after prolonged coronary occlusion in
animals.30 31 These dynamic coronary flow changes
after reperfused AMI may be the reason for the substantial scatter in
plots of ASV and DDT versus 1-month A-WMSI demonstrated in Figure 5. The continuous observation of coronary blood flow
alternation for several hours after recanalization
could resolve these issues.
Clinical Implications
In the present study, we revealed the characteristics of
coronary blood flow with effective reperfusion and demonstrated
that ASV and DDT after reperfused coronary artery were
predictive of the recovery of regional left ventricular
function. Analysis of coronary blood flow velocity
pattern by use of a Doppler guidewire can be used to predict the
regional recovery of left ventricular function at the time
of recanalization. This should be helpful in
treating patients with reperfused acute myocardial infarction.
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Acknowledgments |
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The authors gratefully acknowledge the excellent assistance of all medical personnel of the coronary care unit and catheterization laboratory.
Received November 20, 1998; revision received April 21, 1999; accepted April 30, 1999.
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Circulation. 1989;80:1846–1861.We measured
coronary blood flow velocity immediately after primary PTCA in
23 consecutive patients with acute anterior myocardial infarction by
use of a Doppler guidewire. Averaged systolic peak velocity
(ASV) and deceleration time of diastolic flow velocity
(DDT) significantly correlated with 1-month anterior wall motion score
index (A-WMSI) (r=-0.54, P=0.007;
r=-0.62, P=0.002, respectively). Optimal
cutoff values to predict viable myocardium, defined as
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