This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Liebergen, R. A. M. Articles by Lie, K. I. Search for Related Content PubMed PubMed Citation Articles by van Liebergen, R. A. M. Articles by Lie, K. I.

(Circulation. 1998;98:2133-2140.)
© 1998 American Heart Association, Inc.

Clinical Investigation and Reports

Immediate and Long-Term Effect of Balloon Angioplasty or Stent Implantation on the Absolute and Relative Coronary Blood Flow Velocity Reserve

Rob A. M. van Liebergen, MD; Jan J. Piek, MD; Karel T. Koch, MD; Robbert J. de Winter, MD; ; Kong I. Lie, MD

From the Department of Cardiology, Academic Medical Center, Amsterdam, Netherlands.

Correspondence to Jan J. Piek, MD, Department of Cardiology, B2-108, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, PO Box 22700, 1100 DE Amsterdam, Netherlands. E-mail j.j.piek{at}amc.uva.nl

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background—There is controversy regarding the immediate and long-term effects of PTCA on the coronary flow reserve.

Methods and Results—A total of 54 patients with 1-vessel disease and normal left ventricular function were studied after balloon angioplasty (n=34) or stent implantation (n=20). Distal coronary blood flow velocity reserve (CFR) was defined as the ratio of adenosine-induced hyperemic versus baseline blood flow velocity with a 0.014-in Doppler guidewire. The relative CFR was defined as the ratio of the distal CFR and the reference CFR measured in the normal adjacent coronary artery. Hemodynamic and angiographic measurements were performed before and directly after balloon angioplasty or stent implantation and at 6-month follow-up. CFR after PTCA 2.5 was defined as an impaired CFR. Immediately after PTCA, CFR improved toward the range of the reference artery CFR. In both the balloon-treated and the stent-treated groups, initial high CFR values decreased and impaired CFR values increased at follow-up toward the values of the reference CFR in patients without restenosis. Impaired CFR after balloon angioplasty (33%) or stent implantation (58%) in patients without restenosis was related to an increased baseline flow velocity that normalized at follow-up. Patients with an increase of CFR after stenting were characterized by an unaltered baseline flow velocity and an increased adenosine-induced hyperemic flow velocity.

Conclusions—An impaired CFR (2.5) is a frequent finding after balloon angioplasty or stent implantation as a result of a high baseline flow velocity. Normalization of impaired CFR at follow-up in patients without restenosis was associated with a decline of the baseline flow velocity after both balloon angioplasty and stent implantation, supporting the contention that this phenomenon relates to a slow recovery of autoregulation of the microvascular bed.

Key Words: angioplasty • stents • blood flow

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
In a classic study, Gould et al¹ introduced the curvilinear relationship between coronary lesion severity and flow reserve distal to the narrowing. Subsequently, several clinical studies evaluated this relationship in the setting of coronary angioplasty using digital subtraction techniques,² intracoronary blood flow velocity and pressure measurements,^{3 4} or PET.⁵ A recently published large, multicenter trial (DEBATE study) demonstrated that impaired coronary flow reserve (2.5) immediately after balloon angioplasty was associated with a high incidence of recurrent angina, need for revascularization procedures, and a high restenosis rate.⁶ The hypothesis that impaired coronary flow reserve after balloon angioplasty is due to residual lumen obstruction was supported by studies showing a normalization of impaired coronary flow reserve after optimal vascular lumen enlargement by stent implantation.^{7 8} However, other studies demonstrated a spontaneous improvement of impaired coronary flow reserve after balloon angioplasty without adjunctive coronary intervention due to remodeling of the epicardial lesion⁹ and/or a slow recovery of autoregulation of the microvascular tone.^{10 11} Consequently, controversy exists regarding the mechanisms involved in the effect of coronary angioplasty on the distal coronary flow reserve. In view of its clinical relevance, we studied the immediate and long-term effects of PTCA on the distal coronary flow velocity reserve (CFR) balloon angioplasty with coronary stent implantation.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Patients
Patients (mean age, 56±9 years; range, 36 to 73 years) with single native coronary artery disease and normal left ventricular function, referred to our institution for standard balloon angioplasty (n=34) or stent implantation (n=20), were studied prospectively. Written informed consent was given according to the rules of the Institutional Ethics Committee, which approved the study.

Cardiac Catheterization
Therapy with all antianginal medication was continued until cardiac catheterization. Cardiac catheterization was performed in all patients by the percutaneous femoral approach. All patients received heparin 5000 IU IV as a bolus at the beginning of the catheterization. Additional heparin was administered if the procedure lasted >90 minutes.

Quantitative Coronary Angiography
Off-line analysis of the angiographic severity of the coronary narrowing was performed by use of an automated contour detection algorithm (QCA-CMS version 3.32, MEDIS).¹² The outer diameter of the fluid-filled guiding catheter, centered, was used as a scaling device to obtain absolute arterial dimensions. Two orthogonal projections of the coronary artery lesion during the end-diastolic phase were used to assess biplane analysis of the minimal lumen diameter (MLD) and the percent diameter stenosis of the coronary narrowing. Angiographic restenosis was defined as a diameter stenosis >50% at follow-up assessed by quantitative coronary angiography (QCA).

Coronary Blood Flow Velocity Analysis
All coronary blood flow velocity measurements with the Doppler angioplasty guidewire (FloWire, EndoSonics) were performed as previously described.¹³ After on-line assessment of the baseline average peak velocity (APV), hyperemia was induced by administration of an intracoronary bolus of adenosine (12 µg in the right coronary artery; 18 µg in the left coronary artery). CFR was defined as the ratio of the adenosine-induced hyperemic/baseline APV. The reference CFR was determined in an adjacent angiographically normal coronary artery. The relative CFR (rCFR) was defined as the ratio of the distal/reference CFR. An impaired CFR after PTCA was defined as a CFR 2.5.⁶

Study Protocol
Nitroglycerin (0.1 mg IC) was administered every 30 minutes throughout the procedure. A Doppler guidewire was inserted across the coronary narrowing before the first balloon inflation to obtain optimal and stable baseline and adenosine-induced hyperemic coronary blood flow velocity signals. The balloon catheter was advanced over the Doppler guidewire at the site of the coronary narrowing. Consecutive balloon inflations of 1 to 2 minutes' duration were performed until an angiographically satisfactory result was achieved after a waiting time of 10 minutes. A successful balloon angioplasty was defined as a diameter stenosis <50% by visual assessment. Coronary stents (Palmaz-Schatz, Johnson & Johnson) were implanted under guidance by intravascular ultrasound imaging for optimal deployment against the vascular wall. Angiography was performed after successful balloon angioplasty or stent implantation and at follow-up in the same directions as before balloon angioplasty. Baseline and adenosine-induced hyperemic coronary blood flow velocity measurements were performed at the same location distal to the dilated segment and in an angiographically normal reference coronary artery as well.

Statistical Analysis
Continuous data are presented as mean±SD. ² analysis was used to detect a difference in categorical patient characteristics. A 2-tailed paired t test (or Wilcoxon test for nonparametric data) was used to identify variation within subjects. A 2-tailed unpaired t test (or Mann-Whitney test for nonparametric data) was used to assess differences in continuous variables. Forward stepwise linear regression analysis was used to assess the independent explanatory variables for the alterations of the absolute and relative CFRs at follow-up in both the balloon-treated and stent-treated patients. Potential explanatory variables having an association after univariate analysis (P<0.1) were included. A value of P<0.05 was considered statistically significant.

	Results

Top Abstract Introduction Methods Results Discussion References

 
QCA at follow-up (6.7±1.9 months) revealed an absence of restenosis in 27 of the 34 patients enrolled in the balloon-treated group and 19 of the 20 patients included in the stent-treated group. The baseline characteristics of the 46 patients without restenosis at follow-up are shown in Table 1. In both patient groups, heart rate and mean aortic pressure did not change in individual patients during the procedure (Table 2).

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics of the Study Patients Without Restenosis at Follow-Up

View this table: [in this window] [in a new window]   Table 2. QCA and Coronary Blood Flow Velocity Data in Patients Without Restenosis at Follow-Up

QCA Data in Patients Without Restenosis at Follow-Up
Standard balloon angioplasty and high-pressure stent implantation (14±3 bar) resulted in a direct improvement of the angiographic variables (Table 2). Follow-up in the stent-treated patient group revealed a reduction of the arterial dimensions. However, all angiographic luminal dimensions were larger at follow-up in the stent-treated group than in the balloon-treated group (Table 2).

Blood Flow Velocity Data in Patients Without Restenosis
The reference CFR of the normal coronary artery after PTCA was 3.3±0.4 in the balloon-treated patients and 3.2±0.7 in the stent-treated patients and did not change at follow-up in either of the patient groups (3.2±0.6 and 3.0±0.4, respectively).

CFR and rCFR increased after standard balloon angioplasty (Table 2). Stent implantation resulted in a significant increase in adenosine-induced hyperemic blood flow velocity but did not yield an increase in CFR and rCFR as a result of a nonsignificant increase in baseline blood flow velocity (Table 2).

When the pooled data before balloon angioplasty and at follow-up were used, the overall linear relationship between CFR and rCFR in the both patient groups, including patients with restenosis, was strong (r=0.93, Figure 1). An absolute CFR cutoff value of 2.5 was in accordance with a relative CFR cutoff value of 0.80 (Figure 1).

View larger version (30K): [in this window] [in a new window]   Figure 1. Overall linear relationship between absolute CFR and rCFR of both balloon-treated (BA) and stent-treated (stent) patient groups, including patients with restenosis, using pooled data before PTCA and at follow-up. CFR value of 2.5 was in accordance with rCFR value of 0.80.

Normalization of the CFR and rCFR at Follow-Up in Patients Without Restenosis
Balloon-treated patients demonstrated similar CFR and rCFR at follow-up, as measured directly after balloon angioplasty (Table 2). However, a correlation between the CFR of the dilated vessel and the CFR of the normal reference vessel was absent after balloon angioplasty (Figure 2A). This correlation improved at follow-up (r=0.63, Figure 2B) as a result of alterations of the CFR of the dilated vessel. When all patient characteristics, angiographic and hemodynamic variables, and their changes at follow-up were used, stepwise regression analysis revealed the CFR after balloon angioplasty (r=-0.74, P<0.0001; Figure 3) and the alterations of the reference CFR at follow-up (r=0.39, P=0.07) to be the only independent explanatory variables for the alterations of the CFR at follow-up (y=2.1-0.70xCFR after balloon angioplasty+0.67xalterations of the reference CFR at follow-up, r²=0.79, P<0.0001). The rCFR immediately after balloon angioplasty was the sole independent variable for the alterations of the rCFR at follow-up (r=-0.82, P<0.0001; Figure 3). The CFR after stent implantation was lower than the reference CFR (3.2±0.7), whereas it was in the range of the reference CFR at follow-up. The relationship between CFR and reference CFR was moderate after stent placement (Figure 2C) and slightly improved at follow-up (Figure 2D). After stepwise regression analysis, alterations of the CFR during follow-up were explained by the CFR immediately after stent implantation (r=-0.93, P<0.0001; Figure 3). The rCFR after stent implantation was the only explanatory variable for the alterations of the rCFR during follow-up after stepwise regression analysis. The regression lines of the CFR and rCFR were similar in stent-treated and balloon-treated patient groups (Figure 3).

View larger version (24K): [in this window] [in a new window]   Figure 2. Top, Relationship between absolute CFR and reference CFR (CFRref) immediately after balloon angioplasty (BA; A) and at follow-up (B). Bottom, Relationship between same variables immediately after stent implantation (C) and at follow-up (D).

View larger version (15K): [in this window] [in a new window]   Figure 3. Left, Relationship between CFR immediately after PTCA and alterations of CFR at follow-up (CFR at follow-up) in both balloon-treated (BA; r=-0.74, P<0.0001) and stent-treated (stent; r=-0.92, P<0.0001) patients without restenosis. Right, Relationship between rCFR and alterations of rCFR at follow-up (rCFR) in both balloon-treated (r=-0.82, P<0.0001) and stent-treated (r=-0.85, P<0.0001) patients without restenosis.

Impaired CFR After Balloon Angioplasty
Of all 54 patients, 23 (43%) demonstrated impaired CFR (2.5) immediately after balloon angioplasty; of these 23 patients, 14 did not receive adjunct stent implantation. Five of these 14 patients of the balloon-treated group developed angiographic restenosis at late follow-up. The 9 patients without restenosis at follow-up demonstrated a nonsignificant increase of CFR (P=0.07) and a significant increase of rCFR during follow-up (P<0.05; Table 3). Baseline APV after balloon angioplasty in the balloon-treated patient group was higher in patients with impaired CFR than in patients without impaired CFR after balloon angioplasty (Figure 4, Table 3). There were no other angiographic or hemodynamic differences (Table 3) between the two groups.

View this table: [in this window] [in a new window]   Table 3. Differences Between Patients With Impaired CFR (2.5) and Without Impaired CFR (>2.5) After PTCA in the Balloon-Treated Patient Group Without Restenosis

View larger version (23K): [in this window] [in a new window]   Figure 4. Baseline blood flow velocity (left) and adenosine-induced hyperemic blood flow velocity (right) measured before balloon angioplasty, after balloon angioplasty (BA), after stenting (stent), and at follow-up are illustrated in both balloon-treated patients (top) and stent-treated patients (bottom) without restenosis. Significant differences in baseline blood flow velocity were present between patients with impaired CFR and without impaired CFR after PTCA in both balloon-treated patient group and stent-treated patient group.

In the stent-treated group, 8 of 19 patients demonstrated impaired CFR after balloon angioplasty. After stent implantation, impaired CFR and rCFR improved toward values within the range of the reference coronary artery (from 2.0±0.2 to 2.7±0.9 and from 0.68±0.19 to 0.89±0.21, respectively; both P=0.07). These alterations were related to a nonsignificant increase of the hyperemic blood flow velocity (45±14 to 54±23 cm/s; P=0.18), whereas the baseline blood flow velocity remained unchanged after stent implantation (23±7 to 23±14 cm/s).

Impaired CFR After Stent Implantation
Immediately after stent implantation, 11 patients demonstrated an impaired CFR (2.0±0.3; Table 4, Figure 3A). None of these patients developed restenosis at follow-up. Impaired CFR after stent implantation improved at follow-up toward values documented in patients without impaired CFR after stent implantation (Table 4). Impaired CFR was related to a transient increase of the baseline APV after stent implantation compared with patients without impaired CFR (Figure 4, Table 4). In patients with impaired CFR after stent implantation, the angiographic variables and adenosine-induced hyperemic APV were similar to those values in patients without impaired CFR and remained similar at follow-up (Figure 4, Table 4).

View this table: [in this window] [in a new window]   Table 4. Differences Between Patients With Impaired CFR (2.5) and Without Impaired CFR (>2.5) After Stent Implantation in Stent-Treated Patient Group

Impaired rCFR After PTCA
The rCFR cutoff value was determined to be 2.5/3.1=0.80 (Figure 1). Patients with an impaired rCFR (0.80) after PTCA demonstrated results similar to those of patients with impaired CFR (2.5) after PTCA; ie, a transient increase of the baseline blood flow velocity compared with those patients without impaired rCFR (>0.80) in the balloon-treated patient group (26±20 cm/s, n=9, versus 14±4 cm/s, n=18; P<0.05) and in the stent-treated patient group (33±18 cm/s, n=10, versus 18±9 cm/s, n=9; P<0.05).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study demonstrates an overall immediate improvement of absolute and relative CFR toward normal values after balloon angioplasty. Despite the additional lumen enlargement as determined by angiographic variables, there was no further improvement of the absolute and relative CFR after stent implantation. Impaired CFR immediately after successful balloon angioplasty or stent implantation was related to an increase in baseline blood flow velocity. Individual values of distal CFR changed at follow-up in patients without restenosis; ie, at follow-up, initial high values decreased and low values increased toward values of the reference CFR. Normalization of impaired CFR at follow-up in patients without restenosis after balloon angioplasty or stenting was associated with a decline of the baseline blood flow velocity toward values seen in patients without impaired CFR, supporting the contention that this phenomenon is predominantly related to a slow recovery of autoregulation of the microvascular bed.

Immediate Effect on CFR After Balloon Angioplasty or Stent Implantation
In this study, the average CFR improved immediately after balloon angioplasty to a value that was within the range of the CFR of the normal reference coronary artery. This improvement after balloon angioplasty is in accordance with the findings of several other studies evaluating myocardial or coronary flow reserve using digital subtraction angiography,¹⁴ PET,¹⁵ or distal blood flow velocity measurements.^{3 6}

Impaired CFR After PTCA
In the balloon-treated patients as well as in the stent-treated patient group, an impaired CFR was related to a higher baseline blood flow velocity, whereas the adenosine-induced hyperemic response was similar to that of patients without impaired CFR. These findings are in accordance with other studies that demonstrated an impaired coronary flow reserve immediately after balloon angioplasty, compared with normal values of the control group, due to an increased baseline coronary blood flow.^{10 16} Several mechanisms have been postulated for the observed increase in baseline flow velocity after PTCA, such as (1) failure of the peripheral arterial vascular bed to vasoconstrict appropriately on the sudden increase in distal coronary pressure produced by coronary angioplasty, (2) epicardial vasoconstriction at the site of the Doppler guidewire tip mediated by a myogenic response and/or neural mechanisms,^{17 18} or (3) the influence of drug therapy.^{19 20} However, all patients were treated with nitroglycerin during the procedure, and there was no difference in drug therapy (nitrates, calcium antagonists, ß-blockers, or ACE inhibitors) between patients with and without impaired CFR after PTCA. Finally, baseline blood flow velocity can still be elevated by the hyperemic response after balloon occlusion. The hyperemic effect of balloon occlusion should be minimal after the 10 minutes that we used as the time period between the balloon occlusion and the blood flow velocity measurements. Nevertheless, the precise mechanism responsible for the elevated baseline blood flow velocity immediately after PTCA remains unelucidated and requires further investigation.

The similar adenosine-induced hyperemic response in patients with impaired CFR, as in patients without impaired CFR after balloon angioplasty or stent implantation (Tables 3 and 4), eliminates several potential mechanisms affecting the CFR immediately after PTCA, ie, residual lumen obstruction, diffuse coronary artery disease undetectable by angiography, differences in drug therapy, platelet activation, microembolization of platelet aggregates, and release of platelet-mediated vasomotor products that occur after angioplasty-induced medial injury.²¹

A residual epicardial stenosis may be responsible for an impaired CFR after balloon angioplasty due to a reduction in adenosine-induced hyperemic blood flow velocity. This is illustrated in patients with impaired CFR after balloon angioplasty in the stent-treated patient group. High-pressure stent implantation resulted in augmentation of the angiographic lumen in conjunction with an immediate increase of the absolute and relative CFRs. This improvement in CFR was achieved by an increase of the adenosine-induced hyperemic response after stent implantation while the baseline flow velocity remained unchanged. This phenomenon was also reported by other studies, suggesting an important role of residual lumen obstruction for impaired CFR after balloon angioplasty.^{7 8} Nevertheless, the mean CFR for the whole patient group remained unchanged after stent implantation as a result of a variable response in CFR, ie, 9 of 19 patients showed an increase and 10 patients showed a decrease.

Long-Term Effect of Balloon Angioplasty and Stent Implantation
Several studies reported a delayed recovery of impaired coronary flow reserve at follow-up toward the higher reference values of control subjects.^{9 11 22} Improvement of the impaired myocardial or coronary flow reserve was considered to be related to a temporarily increased baseline value or a temporarily impaired hyperemic blood flow immediately after angioplasty²² or potentially related to an improvement of the stenosis geometry at follow-up.⁹ Our results described a long-term response after balloon angioplasty similar to that found after stent implantation (Figure 3). This indicates that the long-term adaptation of the CFR toward normal reference values is not due to epicardial remodeling at the site of the lesion. In this respect, our findings are not in agreement with the findings of Zijlstra et al,⁹ who reported that an increase of CFR was associated with an improvement in arterial luminal dimensions. Furthermore, patients with impaired CFR after PTCA demonstrated a decrease of the high baseline blood flow velocity at follow-up toward the baseline values of patients without impaired CFR (Figure 4). These findings emphasize the important role of the slow recovery of autoregulation in explaining the transiently impaired CFR immediately after PTCA.

Relative CFR
The present study shows the long-term effect of PTCA on the distal CFR, revealing "normalization" toward values of the reference coronary artery in patients without restenosis. At present, the literature regarding the effect of PTCA on CFR is restricted to the analysis of the dilated coronary artery. Nevertheless, CFR measurements are subject to a high interpatient variability that is related to a variety of physiological^{23 24} and pathophysiological conditions.^{25 26 27} The absolute CFR 2.5 as a definition of impaired CFR after PTCA is based on data obtained in a selected patient population. A CFR >2.5 after successful PTCA is in accordance with a rCFR >0.80 (Figure 1). This value is in agreement with a study by Kern et al²⁸ yielding rCFR of >0.81 after stent implantation in all patients, including a subset with impaired CFR of the reference vessel. The use of rCFR may be important in those patients with an impaired CFR related to the aforementioned (patho-)physiological conditions.^{8 29} The present study suggests that a CFR of 2.0, used as a cutoff value for diagnostic purposes in several studies, is in accordance with an rCFR of 0.60 (Figure 1). Nevertheless, the role of the rCFR for diagnostic and therapeutic purposes is at present the subject of study in multicenter trials.

Limitations of the Study
Intracoronary blood flow velocity assessment is a sensitive technique for the detection of alterations in coronary blood flow, but this method is also prone to technical failures, and accurate measurements depend on the time, skill, and experience of the cardiologist.

The site of the repeated blood flow velocity measurements was determined by angiography, although this method for making repeated measurements may have been a contributing factor in the variations noted. Moreover, these single-center results were obtained in a uniform selected group of patients, which limits extrapolation to other patient categories or other institutions.

The reference CFR was measured only immediately after PTCA and at late follow-up to calculate the relative CFR. The reference CFR was not measured before PTCA, although recent studies indicate that this limitation is not a major drawback of the present study.^{9 30}

In the present study, the role of remodeling in the normalization process of the CFR was limited, on the basis of long-term normalization effects in patients treated with balloon angioplasty similar to those treated with stent implantation (Figure 4). However, complete evaluation of remodeling cannot be judged without intravascular ultrasound, which was not performed in the present study.³¹

Furthermore, this study was not designed to evaluate the time period of improvement of the distal CFR after PTCA. Several studies implied a normalization of the average coronary vasodilatory reserve within 3 months.^{22 32}

Clinical Implications
Patients with impaired CFR after balloon angioplasty may benefit from additional stent implantation instead of omitting adjunct intervention; ie, better long-term angiographic and hemodynamic results and less restenosis at follow-up. For this reason, assessment of the CFR and/or CFR directly after angiographically satisfactory balloon angioplasty can be a cost-effective tool for decision making regarding adjunctive stenting. However, the limited number of patients studied precludes conclusions regarding the selection of patients with impaired CFR after balloon angioplasty who may benefit from additional stent implantation. This clinically relevant issue is currently being evaluated in multicenter studies involving larger cohorts of patients (DEBATE 2 and DESTINI study).

	Acknowledgments

 
This study was supported by the Netherlands Heart Foundation, the Hague, Netherlands (grant 95.179). Dr Piek is a clinical investigator for the Netherlands Heart Foundation (grant D96.020). We gratefully acknowledge the technical and nursing staff of our Cardiac Catheterization Laboratory (chief: Peter J. Belgraver, RN) for skilled assistance. We thank Morton J. Kern, MD (J.G. Mudd Cardiac Catheterization Laboratory, St Louis University Hospital) for his helpful suggestions during the conduct of this study.

Received January 14, 1998; revision received June 25, 1998; accepted July 11, 1998.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis: instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol. 1974;33:87–94.[Medline] [Order article via Infotrieve]
   
2. Zijlstra F, Fioretti P, Reiber JH, Serruys PW. Correlations between quantitative cineangiography, coronary flow reserve measured with digital subtraction cineangiography and exercise thallium perfusion scintigraphy. Int J Card Imaging. 1988;3:133–139.[Medline] [Order article via Infotrieve]
   
3. Di Mario C, Gil R, Serruys PW. Long-term reproducibility of coronary flow velocity in patients with coronary artery disease. Am J Cardiol. 1995;75:1177–1180.[Medline] [Order article via Infotrieve]
   
4. Bartunek J, Sys SU, Heyndrickx GR, Pijls NHJ, De Bruyne B. Quantitative coronary angiography in predicting functional significance of stenoses in unselected patient cohort. J Am Coll Cardiol. 1995;26:328–334.[Abstract]
   
5. Di Carli M, Czernin J, Hoh CK, Gerbaudo VH, Brunken RC, Huang SC, Phelps ME, Schelbert HR. Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease. Circulation. 1995;91:1944–1951.[Abstract/Free Full Text]
   
6. Serruys PW, Di Mario C, Piek J, Schroeder E, Vrints C, Probst P, De Bruyne B, Hanet C, Fleck E, Haude M, Verna E, Voudris V, Geschwind H, Emanuelsson H, Mühlberger V, Danzi G, Peels HO, Ford AJ, Boersma E, for the DEBATE Study Group. Prognostic value of intracoronary flow velocity and diameter stenosis in assessing the short- and long-term outcomes of coronary balloon angioplasty: the DEBATE Study (Doppler Endpoints Balloon Angioplasty Trial Europe). Circulation. 1997;96:3369–3377.[Abstract/Free Full Text]
   
7. Haude M, Caspari G, Baumgart D, Brennecke R, Meyer J, Erbel R. Comparison of myocardial perfusion reserve before and after coronary balloon predilatation and after stent implantation in patients with postangioplasty restenosis. Circulation. 1996;94:286–297.[Abstract/Free Full Text]
   
8. Kern MJ, Dupouy P, Drury JH, Aguirre FV, Aptecar E, Bach RG, Caracciolo EA, Donohue TJ, Dubois Rande JL, Geschwind HJ, Mechem CJ, Kane G, Teiger E, Wolford TL. Role of coronary artery lumen enlargement in improving coronary blood flow after balloon angioplasty and stenting: a combined intravascular ultrasound Doppler flow and imaging study. J Am Coll Cardiol. 1997;29:1520–1527.[Abstract]
   
9. Zijlstra F, Reiber JHC, Juilliere Y, Serruys PW. Normalization of coronary flow reserve by percutaneous transluminal coronary angioplasty. Am J Cardiol. 1988;61:55–60.[Medline] [Order article via Infotrieve]
   
10. Nanto S, Kodama K, Hori M, Mishima M, Hirayama A, Inoue M, Kamada T. Temporal increase in resting coronary blood flow causes an impairment of coronary flow reserve after coronary angioplasty. Am Heart J. 1992;123:28–36.[Medline] [Order article via Infotrieve]
    
11. Wilson RF, Johnson MR, Marcus ML, Aylward PEG, Skorton DJ, Collins S, White CW. The effect of coronary angioplasty on coronary flow reserve. Circulation. 1988;77:873–885.[Abstract/Free Full Text]
    
12. van der Zwet PMJ, Reiber JHC. A new approach for the quantification of complex lesion morphology: the gradient field transform: basic principles and validation results. J Am Coll Cardiol. 1994;24:216–224.[Abstract]
    
13. Doucette JW, Corl PD, Payne HM, Flynn AE, Goto M, Nassi M, Segal J. Validation of a Doppler guide wire for intravascular measurement of coronary artery flow velocity. Circulation. 1992;85:1899–1911.[Abstract/Free Full Text]
    
14. Hodgson JMcB, Riley RS, Most AS, Williams DO. Assessment of coronary flow reserve using digital angiography before and after successful percutaneous transluminal coronary angiography. Am J Cardiol. 1987;60:61–65.[Medline] [Order article via Infotrieve]
    
15. Walsh MN, Geltman EM, Steele RL, Kenzora JL, Ludbrook PA, Sobel BE, Bergmann SR. Augmented myocardial perfusion reserve after coronary angioplasty quantified by positron emission tomography with H₂¹⁵O. J Am Coll Cardiol. 1990;15:119–127.[Abstract]
    
16. Kern MJ, Deligonul U, Vandormael M, Labovitz AJ, Gudipati CV, Gabliani G, Bodet J, Shah Y, Kennedy HL. Impaired coronary vasodilator reserve in the immediate postcoronary angioplasty period: analysis of coronary artery flow velocity indexes and regional cardiac venous efflux. J Am Coll Cardiol. 1989;13:860–872.[Abstract]
    
17. Fischell TA, Bausback KN, McDonald TV. Evidence for altered epicardial coronary artery autoregulation as a cause of distal coronary vasoconstriction after successful percutaneous transluminal coronary angioplasty. J Clin Invest. 1990;86:575–584.
    
18. Gregorini L, Fajadet J, Robert G, Cassagneau B, Bernis M, Marco J. Coronary vasoconstriction after percutaneous transluminal coronary angioplasty is attenuated by antiadrenergic agents. Circulation. 1994;90:895–907.[Abstract/Free Full Text]
    
19. Bache RJ. Effects of calcium entry blockade on myocardial blood flow. Circulation. 1989;80(suppl IV):IV-40–IV-46.
    
20. Schwartz JS, Bache RJ. Pharmacologic vasodilators in the coronary circulation. Circulation. 1987;75(suppl I):I-162–I-167.
    
21. Bates ER, McGillem MJ, Beals TF, DeBoe SF, Mikelson JK, Mancini GBJ, Vogel RA. Effect of angioplasty-induced endothelial denudation compared with medial injury on regional coronary blood flow. Circulation. 1987;76:710–716.[Abstract/Free Full Text]
    
22. Uren NG, Crake T, Lefroy DC, de Silva R, Davies GJ, Maseri A. Delayed recovery of coronary resistive vessel function after coronary angioplasty. J Am Coll Cardiol. 1993;21:612–621.[Abstract]
    
23. Hoffman JIE. A critical view of coronary reserve. Circulation. 1987;75:6–11.
    
24. McGinn AL, White CW, Wilson RF. Interstudy variability of coronary flow reserve: influence of heart rate, arterial pressure, and ventricular preload. Circulation. 1990;81:1319–1330.[Abstract/Free Full Text]
    
25. Nahser PJ, Brown RE, Oskarsson H, Winniford MD, Rossen JD. Maximal coronary flow reserve and metabolic coronary vasodilation in patients with diabetes mellitus. Circulation. 1995;91:635–640.[Abstract/Free Full Text]
    
26. Kyriakidis MK, Dernellis JM, Androulakis AE, Kelepeshis GA, Barbetseas J, Anastasakis AN, Trikas AG, Tentolouris CA, Gialafos JE, Toutouzas PK. Changes in phasic coronary blood flow velocity profile and relative coronary flow reserve in patients with hypertrophic obstructive cardiomyopathy. Circulation. 1997;96:834–841.[Abstract/Free Full Text]
    
27. Claeys MJ, Vrints CJ, Bosmans J, Krug B, Blockx PP, Snoeck JP. Coronary flow reserve during coronary angioplasty in patients with a recent myocardial infarction: relation to stenosis and myocardial viability. J Am Coll Cardiol. 1996;28:1712–1719.[Abstract]
    
28. Kern MJ, Puri S, Donohue TJ, Bach RG, Aguirre FV, Caracciolo EA, Wolford TL. Role of relative flow velocity reserve in determining an endpoint for coronary artery stenting. Circulation. 1997;96(suppl I):I-702. Abstract.
    
29. Gould KL, Kirkeeide RL, Buchi M. Coronary flow reserve as a physiologic measure of stenosis severity. J Am Coll Cardiol. 1990;15:459–474.[Abstract]
    
30. Foley JB, Watson KR, Chisholm RJ. Impact of coronary angioplasty on coronary vasodilator response of normal nondilated coronary arteries in patients with stable angina. Am J Cardiol. 1995;75:1070–1071.[Medline] [Order article via Infotrieve]
    
31. Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Wong SC, Hong MK, Kovach JA, Leon MB. Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study. Circulation. 1996;94:35–43.[Abstract/Free Full Text]
    
32. Zijlstra F, den Boer A, Reiber JHC, van Es GA, Lubsen J, Serruys PW. Assessment of immediate and long-term functional results of percutaneous transluminal coronary angioplasty. Circulation. 1988;78:15–24.Patients with 1-vessel disease were studied to evaluate the immediate and long-term effects of balloon angioplasty (n=34) or stent implantation (n=20) on the coronary flow velocity reserve (CFR). In both patient groups, high CFR values after PTCA decreased and impaired CFR (2.5) values after PTCA increased at follow-up toward the values of the reference CFR in patients without restenosis. A transiently impaired CFR after PTCA was a frequent finding and was a result of a high baseline flow velocity after PTCA that normalized at follow-up, supporting the contention that this phenomenon relates to a slow recovery of the microvascular autoregulation.[Abstract/Free Full Text]
    

This article has been cited by other articles:

				J. B. Selvanayagam, A. S.H. Cheng, M. Jerosch-Herold, K. Rahimi, I. Porto, W. van Gaal, K. M. Channon, S. Neubauer, and A. P. Banning Effect of Distal Embolization on Myocardial Perfusion Reserve After Percutaneous Coronary Intervention: A Quantitative Magnetic Resonance Perfusion Study Circulation, September 25, 2007; 116(13): 1458 - 1464. [Abstract] [Full Text] [PDF]

				M. Fenchel, A. Franow, N. I. Stauder, U. Kramer, U. Helber, C. D. Claussen, and S. Miller Myocardial Perfusion after Angioplasty in Patients Suspected of Having Single-Vessel Coronary Artery Disease: Improvement Detected at Rest-Stress First-Pass Perfusion MR Imaging--Initial Experience Radiology, October 1, 2005; 237(1): 67 - 74. [Abstract] [Full Text] [PDF]

				B.-J. Verhoeff, M. Siebes, M. Meuwissen, B. Atasever, M. Voskuil, R. J. de Winter, K. T. Koch, J. G.P. Tijssen, J. A.E. Spaan, and J. J. Piek Influence of Percutaneous Coronary Intervention on Coronary Microvascular Resistance Index Circulation, January 4, 2005; 111(1): 76 - 82. [Abstract] [Full Text] [PDF]

				P. Voci, F. Pizzuto, and F. Romeo Coronary flow: a new asset for the echo lab? Eur. Heart J., November 1, 2004; 25(21): 1867 - 1879. [Full Text] [PDF]

				G S Werner, U Emig, P Bahrmann, M Ferrari, and H R Figulla Recovery of impaired microvascular function in collateral dependent myocardium after recanalisation of a chronic total coronary occlusion Heart, November 1, 2004; 90(11): 1303 - 1309. [Abstract] [Full Text] [PDF]

				M. Siebes, B.-J. Verhoeff, M. Meuwissen, R. J. de Winter, J. A.E. Spaan, and J. J. Piek Single-Wire Pressure and Flow Velocity Measurement to Quantify Coronary Stenosis Hemodynamics and Effects of Percutaneous Interventions Circulation, February 17, 2004; 109(6): 756 - 762. [Abstract] [Full Text] [PDF]

				S. E. Langerak, H. W. Vliegen, J. W. Jukema, A. H. Zwinderman, H. J. Lamb, A. de Roos, and E. E. van der Wall Vein Graft Function Improvement after Percutaneous Intervention: Evaluation with MR Flow Mapping Radiology, September 1, 2003; 228(3): 834 - 841. [Abstract] [Full Text] [PDF]

				M. G. Stoel, F. Zijlstra, and C. A. Visser Frame Count Reserve Circulation, June 24, 2003; 107(24): 3034 - 3039. [Abstract] [Full Text] [PDF]

				S. Mohlenkamp, P. E Beighley, E. A Pfeifer, T. R Behrenbeck, P. F Sheedy II, and E. L Ritman Intramyocardial blood volume, perfusion and transit time in response to embolization of different sized microvessels Cardiovasc Res, March 1, 2003; 57(3): 843 - 852. [Abstract] [Full Text] [PDF]

				L. Gregorini, J. Marco, B. Farah, M. Bernies, C. Palombo, M. Kozakova, I. M. Bossi, B. Cassagneau, J. Fajadet, C. Di Mario, et al. Effects of Selective {alpha}1- and {alpha}2-Adrenergic Blockade on Coronary Flow Reserve After Coronary Stenting Circulation, December 3, 2002; 106(23): 2901 - 2907. [Abstract] [Full Text] [PDF]

				M. Voskuil, R. A. M. van Liebergen, M. Albertal, E. Boersma, J. G. P. Tijssen, P. W. Serruys, J. J. Piek, and the DEBATE II Investigators Coronary hemodynamics of stent implantation after suboptimal and optimal balloon angioplasty J. Am. Coll. Cardiol., May 1, 2002; 39(9): 1513 - 1517. [Abstract] [Full Text] [PDF]

				T. Nishida, C. Di Mario, M.J. Kern, T.J. Anderson, I. Moussa, R. Bonan, T. Muramatsu, A.C. Jain, J. Suarez de Lezo, S.Y. Cho, et al. Impact of final coronary flow velocity reserve on late outcome following stent implantation Eur. Heart J., February 2, 2002; 23(4): 331 - 340. [Abstract] [Full Text] [PDF]

				M. Albertal, E. Regar, G. Van Langenhove, S.G. Carlier, P. Serrano, E. Boersma, B. Bruyne, C. Di Mario, J. Piek, and P.W. Serruys Flow velocity and predictors of a suboptimal coronary flow velocity reserve after coronary balloon angioplasty Eur. Heart J., January 2, 2002; 23(2): 133 - 138. [Abstract] [Full Text] [PDF]

				G. S. Werner, M. Ferrari, B. M. Richartz, O. Gastmann, and H. R. Figulla Microvascular Dysfunction in Chronic Total Coronary Occlusions Circulation, September 4, 2001; 104(10): 1129 - 1134. [Abstract] [Full Text] [PDF]

				R. Seabra-Gomes Is there a future for coronary physiological evaluation in clinical decision making? Eur. Heart J., September 2, 2001; 22(18): 1633 - 1635. [PDF]

				F. Pizzuto, P. Voci, E. Mariano, P. Emilio Puddu, G. Sardella, and A. Nigri Assessment of flow velocity reserve by transthoracic Doppler echocardiography and venous adenosine infusion before and after left anterior descending coronary artery stenting J. Am. Coll. Cardiol., July 1, 2001; 38(1): 155 - 162. [Abstract] [Full Text] [PDF]

				J. Herrmann, M. Haude, A. Lerman, R. Schulz, L. Volbracht, J. Ge, A. Schmermund, H. Wieneke, C. von Birgelen, H. Eggebrecht, et al. Abnormal Coronary Flow Velocity Reserve After Coronary Intervention Is Associated With Cardiac Marker Elevation Circulation, May 15, 2001; 103(19): 2339 - 2345. [Abstract] [Full Text] [PDF]

				S. A. J. Chamuleau, M. Meuwissen, B. L. F. van Eck-Smit, K. T. Koch, A. de Jong, R. J. de Winter, C. E. Schotborgh, M. Bax, H. J. Verberne, J. G. P. Tijssen, et al. Fractional flow reserve, absolute and relative coronary blood flow velocity reserve in relation to the results of technetium-99m sestambi single-photon emission computed tomography in patients with two-vessel coronary artery disease J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1316 - 1322. [Abstract] [Full Text] [PDF]

				M. Haude, D. Baumgart, E. Verna, J. J. Piek, C. Vrints, P. Probst, and R. Erbel Intracoronary Doppler- and Quantitative Coronary Angiography-Derived Predictors of Major Adverse Cardiac Events After Stent Implantation Circulation, March 6, 2001; 103(9): 1212 - 1217. [Abstract] [Full Text] [PDF]

				H. V. Anderson and B. A. Carabello Provisional Versus Routine Stenting : Routine Stenting Is Here To Stay Circulation, December 12, 2000; 102(24): 2910 - 2914. [Full Text] [PDF]

				E. Verna, L. Ceriani, L. Giovanella, G. Binaghi, and S. Garancini "False-Positive" Myocardial Perfusion Scintigraphy Findings in Patients with Angiographically Normal Coronary Arteries: Insights from Intravascular Sonography Studies J. Nucl. Med., December 1, 2000; 41(12): 1935 - 1940. [Abstract] [Full Text] [PDF]