Donate Help Contact The AHA Sign In Home
American Heart Association
Circulation
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Circulation. 1996;94:286-297

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Haude, M.
Right arrow Articles by Erbel, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Haude, M.
Right arrow Articles by Erbel, R.

(Circulation. 1996;94:286-297.)
© 1996 American Heart Association, Inc.

Articles

Comparison of Myocardial Perfusion Reserve Before and After Coronary Balloon Predilatation and After Stent Implantation in Patients With Postangioplasty Restenosis

Michael Haude, MD; Guido Caspari, MD; Dietrich Baumgart, MD; Rudiger Brennecke, PhD; Jurgen Meyer, MD; Raimund Erbel, MD

the Cardiology Department, University of Essen (M.H., G.C., D.B., R.E.), and the Second Medical Clinic, Johannes Gutenberg University, Mainz (R.B., J.M.), Germany.

Correspondence to Michael Haude, MD, Cardiology Department, University of Essen, Hufelandstr 55, 45122 Essen, Federal Republic of Germany.


*    Abstract
up arrowTop
 *Abstract
down arrowIntroduction
 down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowAcknowledgment
 down arrowReferences
 
Background Stents provide a scaffold for coronary arteries after angioplasty and inhibit elastic recoil.

Methods and Results In 25 patients with postangioplasty restenosis of the left anterior descending artery, ECG-gated digital subtraction coronary angiograms were recorded at baseline and during hyperemia (12 mg papaverine IC) before and after balloon predilatation (PTCA), after implantation of a Palmaz-Schatz stent, and after 6 months. Densitometric evaluation revealed different time and density parameters to calculate two definitions of myocardial perfusion reserve (MPR1 and MPR2) and maximum flow ratio (MaxFR). Poststenotic MPR1 increased from 1.57±0.14 to 2.59±0.86 after PTCA and to 3.10±0.41 after stenting, with 2.90±0.65 at follow-up (ANOVA, P<.05), while reference MPR1 remained unchanged at 3.10±0.40. Poststenotic MPR2 increased from 1.36±0.28 to 2.50±1.20 and to 3.40±0.58, respectively, with 3.20±0.92 at follow-up (ANOVA, P<.05), while reference MPR2 remained unchanged at 3.40±0.60. MaxFR was 2.13±0.53 after PTCA, 2.83±0.35 after stenting, and 2.73±0.58 at follow-up (ANOVA, P<.05). A good correlation was found between minimal stenotic luminal diameter and MPR1 or MPR2 (r=.87 and r=.94) and between luminal gain and MaxFR (r=.75). A negative correlation was measured between recoil and MPR1, MPR2, and MaxFR (r=-.80, r=-.86, and r=-.83). At follow-up, a steeper correlation was found between MPR and minimal stenosis diameter (MPR1: slope, 0.52 versus 0.91; MPR2: slope, 1.48 versus 1.95) and between MaxFR and net lumen gain (slope, 0.78 versus 1.27).

Conclusions Coronary stent implantation in patients with postangioplasty restenosis normalized poststenotic myocardial perfusion immediately as a result of a larger postprocedural lumen and a more pronounced inhibition of elastic recoil. After 6 months this benefit was sustained despite progressive lumen loss.


Key Words: perfusion • angioplasty • stents • elasticity


*    Introduction
up arrowTop
 up arrowAbstract
 *Introduction
down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowAcknowledgment
 down arrowReferences
 
Coronary stents were designed to address two major limitations of balloon angioplasty: flow-limiting dissections or acute postprocedural vessel closure and late restenosis. Several studies documented the scaffolding properties of stents in wrapping dissections and reestablishing vessel patency in abrupt closure.1 2 3 4 5 More recently, two large-scale prospective randomized trials documented that elective stent implantation for the treatment of native coronary stenosis resulted in a significantly lower long-term restenosis rate compared with balloon angioplasty.6 7 Several angiographic and intravascular ultrasound studies were able to document the additional lumen gain after stenting compared with balloon angioplasty resulting from an inhibition of elastic recoil.8 9 10 11 Thereby, postinterventional residual stenosis can be limited to a minimum. Conversely, stents scaffold the arterial segment and thereby provide improved local flow conditions in comparison to the postangioplasty situation, with dissections of various extents protruding into the lumen. Nevertheless, less information is available as to whether this scaffolding effect subsequently improves distal coronary flow and myocardial perfusion.

Densitometric evaluation of ECG-gated digital subtraction coronary angiograms derives different parameters that provide information about coronary blood flow and myocardial perfusion.12 13 14 15 16 17 Coronary flow reserve and MPR can be calculated as the ratio of densitometric results obtained from measurements during baseline and hyperemia.14 18 19 Extensive work was performed to improve this measurement technique and the reliability of the results by introducing on-line measurements, improvement of temporal resolution, reduction of background scatter, application of quality control to the time-density curves, and semiautomatic definition of ROIs.16 17 20 21 22

The purpose of this study was to determine the effect of adjunct coronary stenting in comparison with coronary balloon angioplasty on MPR in patients with single coronary artery disease of the left anterior descending artery by x-ray densitometric techniques.


*    Methods
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
 down arrowDiscussion
 down arrowAcknowledgment
 down arrowReferences
 
Patients
The study group consisted of 25 patients with single focal restenosis of the left anterior descending artery 5.8±0.4 months after a successful balloon angioplasty procedure. Therefore, elective stenting was attempted as an alternative to repeat PTCA. All patients presented with angina pectoris and a pathological stress ECG and were treated exclusively with aspirin 100 mg/d and nitrates 60 to 120 mg/d. Patients with acute myocardial infarction or a history of Q-wave myocardial infarction, patients who demonstrated angiographically discernible thrombus formation or local spasm anytime throughout the procedure, and those who had undergone stenting as a rescue procedure for symptomatic dissections or abrupt closure were excluded from this study, primarily for optimizing measurement conditions. No patient presented angiographically discernible collateral supply to the poststenotic myocardium from the contralateral artery. Other factors contributing to the microvascular capacity, such as hypertension, diabetes, or myocardial hypertrophy, led to exclusion of the patient from this study. All patients gave informed consent for the catheterization procedure, including densitometric measurements, for balloon angioplasty and adjunct stent implantation and for recatheterization after 6 months. Coronary stenting was approved by the local institutional human research review committee in 1988. Individual baseline characteristics are presented in Table 1Down.


View this table:
[in this window]
[in a new window]
  		Table 1. Baseline Characteristics of 25 Patients With Stenosis of the Left Anterior Descending Coronary Artery Who Underwent Balloon Angioplasty and Coronary Stenting

Palmaz-Schatz Stent
All patients received implantation of a single second-generation Palmaz-Schatz stent 15 mm long mounted on a stent delivery system (SDS, Johnson & Johnson). The mode of implantation was described elsewhere.23 The balloon size of the SDS was identical to the balloon size used for predilatation of the target lesion. Implantation pressure was 6 atm for 30 seconds followed by a high-pressure stent dilatation at 12 atm for 30 seconds with the same noncompliant high-pressure balloon as used for predilatation of the target lesion.

Catheterization Procedure
All patients were pretreated with aspirin and nitrates. At the start of catheterization, a heparin bolus (10 000 IU), heparin infusion (1200 IU/h), and nitroglycerin infusion (3 mg/h) were administered.

Coronary angiography was performed via the femoral approach. After intracoronary injection of 0.2 mg nitroglycerin, angiograms of the right and left coronary arteries were recorded in different orthogonal projections to document coronary anatomy and the target lesion in the left anterior descending artery. Then, a 5-minute break followed to compensate for contrast medium–induced changes in coronary flow. Afterward, baseline digital angiography of the left coronary artery was performed by ECG-triggered power injection of 6 mL contrast medium (Iopromid, Ultravist 370, Schering; 4 mL/s) with a temporal delay of four cycles after start of x-ray exposure via an 8F guiding catheter. Recording time was 20 seconds. After baseline recording and after another 5-minute break, digital angiography of the left coronary artery was repeated under hyperemic conditions induced by intracoronary injection of 12 mg papaverine. Then, PTCA of the target lesion was performed with a 3.0-mm noncompliant balloon catheter in 7 patients, a 3.5-mm balloon catheter in 14, and a 4.0-mm balloon catheter in 4. In each case, insufflation pressure was 12 atm for 30 seconds, which was tolerated by all patients. The angioplasty result was documented in the same orthogonal projections as before intervention, followed by an obligatory 5-minute break. Then, digital angiograms were recorded at baseline and during hyperemia as described previously. Subsequently, stents were implanted with balloon sizes similar to those during the angioplasty procedure, followed by stent dilatation as described earlier. Finally, control angiograms were recorded after intracoronary injection of 0.2 mg nitroglycerin in the same projections as before. With a temporal delay of 5 minutes after the last angiogram, digital angiograms were recorded at baseline and during hyperemia as described above.

During 6-month angiographic follow-up, cineangiograms of the target vessel were recorded in the same projections as during the interventional procedure. Additionally, digital angiograms were recorded at baseline and during hyperemia according to the previous protocol.

Quantitative Coronary Angiography
After 2.8-fold optical magnification, selected end-diastolic cine frames with illustration of the target lesion before and after balloon angioplasty, after stent implantation, and at 6-month follow-up were digitized for quantitative evaluation by the Cardiovascular Measurement System (CMS, Medis). The matrix size of this system is 512x512x8 bits. Analysis was based on the worst-view projection. The system provides automated vessel-edge detection and calculated the following parameters using the empty catheter for calibration24 : proximal, distal, and interpolated reference diameters; proximal, distal, and interpolated reference areas assuming a circular cross-sectional area; absolute and relative MLDs; absolute and relative minimal cross-sectional areas assuming a circular cross section; lesion length; plaque area and volume; and eccentricity.

On the basis of these results, the following derived parameters were calculated: acute gain (mm) as postprocedural MLD minus preprocedural MLD, acute gain (mm2) as postprocedural minimal cross-sectional area minus preprocedural minimal lumen area, relative gain index as the gain (mm) corrected for the reference diameter (mm), relative gain index as the gain (mm2) corrected for the reference cross-sectional area (mm2), late loss (mm) as postprocedural MLD (mm) minus MLD (mm) at follow-up, late loss (mm2) as postprocedural minimal cross-sectional area (mm2) minus minimal cross-sectional area (mm2) at follow-up, relative loss index as late loss (mm) corrected for the reference diameter (mm), relative loss index as late loss (mm2) corrected for the reference cross-sectional area (mm2), net gain (mm) as MLD (mm) at follow-up minus preprocedural MLD (mm), and net gain (mm2) as minimal cross-sectional area (mm2) at follow-up minus preprocedural minimal cross-sectional area (mm2).

Digital Image Processing System
Densitometric perfusion measurements were performed by a digital image processing system controlled by a DEC PDP 11/73 control and processing computer. Data selection, acquisition, digitization, subtraction mode, interactive definition of ROIs, calculation of quality control indexes, and the determination of the densitometric parameters were performed with this computer. Live images and parametric images could be displayed simultaneously on up to three video monitors. After real-time digitization, a total of 192 frames at a matrix size of 256x256x8 bits were stored in a 12-MB acquisition buffer (VTE Picturecom). Two 90-MB magnetic disks with high transfer rates allowed digitization of several angiographic scenes per patient for repetitive measurements during interventions.

Program for Real-time ECG-Triggered Frame Digitization
To improve temporal resolution, we developed a program for ECG-triggered digitization of six frames per heart cycle. Continuous digitization of the patient's ECG allows the calculation of the mean RR time interval of the 10 heartbeats preceding the start of digitization of cineangiograms, representing the phase of trigger acquisition.16 This mean RR time interval was divided into seven equal time segments starting at the R wave. At the beginning of the first six time segments, a trigger signal is coded, while the seventh time segment is excluded as a compensation for changes in heart rate after the injection of contrast medium. After real-time digitization of the angiograms is started, six heart phase–gated frames per cycle are digitized according to the coded trigger signals, beginning at the time of each R wave. Digitization is followed by qualitative visual control using the subtraction mode to detect abnormalities caused by arrhythmia or changes in respiration.

Interactive Definition of ROIs
For the definition of ROIs, the user can define the outer contour via mouse-supported videometry to provide myocardium tangentially in the ROI and to exclude larger epicardial vessels within the ROI. After the number of ROIs and their width are defined, the program automatically computes the ROIs using a center-point method and displays them on a TV monitor superposed on a digital image depicting the coronary artery tree.20 25 In a similar way, corresponding background ROIs not superposed on myocardium were defined. In this study, we selected four poststenotic ROIs in the perfusion bed of the left anterior descending artery and four reference ROIs in the perfusion bed of the left circumflex artery.

Quality Control of the Six Heart Phase–Gated Densitograms for Each ROI
For each of the myocardial and corresponding background ROIs, six densitograms were generated according to the six phases throughout the cardiac cycle. In a next step, the heart phase–gated densitograms of the background ROIs were subtracted from the densitograms of the myocardial ROIs to compensate for changes in background noise throughout the acquisition time. Then the heart phase–gated mean density value of the four cycles before contrast medium injection was subtracted from the subsequent values. Thereby, a total of six heart phase–gated densitograms per myocardial ROI were generated from digital subtraction angiograms and after correction for background noise.

Each of these six heart phase–gated densitograms was subsequently checked for its quality and received a quality index, Qp, which represents the product of the subindexes Q1, Q2, Q3: Qp(n)=Q1xQ2xQ3, with n=1, 2, 3, 4, 5, 6. The quality subindex Q1 compares the shape of the densitogram with a prototype densitogram, which was defined by the function t->txe1-t.20 25 After standardization on maximum intensity, two thresholds of tolerance were fixed on each side of the prototype densitogram, which were closer along the ascending part and wider along the descending part of the densitogram. The first threshold of tolerance includes the area of ±1.5 gray-scale levels along the prototype densitogram, which represents the mean value of scatter due to noise. Each measurement point of the actual densitogram within this first threshold of tolerance received a value q=1. The second threshold of tolerance represented an empirically generated area along the prototype densitogram.20 25 An actual densitogram value within this second threshold of tolerance received a quality value q with 0<q<1, with linear interpolation of the quality levels q between the borders of this second threshold of tolerance. The second lowest quality value q was assigned the quality level q1 and thereby allowed compensation for a single outlier.

Quality level Q2 checks for variation undulations in each of the six heart phase–gated densitograms.20 25 A densitogram with a single discrete maximum, defined as an intensity value larger than the two following values, received a quality value of Q2=1. More than one local maximum in the densitogram resulted in a Q2 value according to the following equation:

where max is maximum intensity value of the densitogram and m1, m2, . . . , mn are single intensity values of the densitogram.

Quality level Q3 checks the level of intensity of each of the six heart phase–gated densitograms per ROI and avoids densitograms with intensities next to the threshold of noise being assigned high quality.20 25 Densitograms within the threshold received a quality level Q3=0.

Each of the six heart phase–gated densitograms per ROI then received a weighting coefficient (Wn) according to the equation

where n=1, 2, . . . , 6. Measured densitograms were then adjusted by multiplication of the weighting coefficient W1, W2, . . . , W6, with the individual intensity values of the heart phase–gated densitograms.20 25

Finally, these six adjusted densitograms per ROI were summarized to a single new densitogram that was subsequently used for calculation of the densitometric parameters.

Definition of Densitometric Parameters
The following parameters were derived from the quality controlled densitograms.

1. According to the suggestions of Vogel et al,13 14 local mean contrast medium appearance time (MCAT), was defined as the time from the start of contrast medium injection to the time when a certain threshold of intensity is passed. This time parameter replaced mean transit time.

2. Maximum intensity of the densitogram, which was used as a substitute for vascular volume, was as outlined by Vogel and coworkers.13 14

MPR was defined as MPR=(baseline MCAT/hyperemic MCAT)x(hyperemic Imax/baseline Imax), where Imax is maximum intensity.

3. Haude et al16 26 defined rise time (RT) as the time from the start of local contrast medium–induced myocardial opacification to its maximum to replace mean transit time. Since maximum intensity was shown to poorly represent vascular volume and showed a poor reproducibility in human studies, they defined MPR to be solely related to the ratio of MPR{approx}baseline RT/hyperemic RT.

4. Pijls and coworkers17 defined mean transit time (MTT) as

Since baseline vascular volume is unpredictable but hyperemic vascular volume is uniform, they defined maximum flow ratio (MaxFR) as MaxFR=hyperemic MTT before intervention/hyperemic MTT after intervention.

Statistical Analysis
The individual data were used to calculate mean and SD. ANOVA was performed when normal distribution of data was given. Otherwise, the Kruskal-Wallis test was used to test for differences between means of several groups. If significant differences were found, the Bonferroni t test or Dunn's test was applied for multiple comparisons when appropriate. A value of P<.05 was considered statistically significant. Correlation coefficients, lines of regression, and SEEs were computed to document correlation between variables. In terms of reproducibility, we applied the technique of Bland and Altman27 to check for the agreement of repeated measurements by calculating the mean of the differences of data pairs and the corresponding SDs.


*    Results
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 *Results
down arrowDiscussion
 down arrowAcknowledgment
 down arrowReferences
 
Clinical Data
All patients had had an uncomplicated intervention. The majority of patients were in Canadian Cardiovascular Society angina classes II and III before intervention (Table 1Up), and all presented pathological stress tests. At follow-up 5.9±0.3 months after intervention, 20 patients presented no anginal complaints, 3 reported angina class I, and 2 angina class II, both presenting pathological stress tests. The remaining 23 patients did not present abnormal stress tests at follow-up.

Angiographic Results
A significant increase of minimal stenosis diameter was measured, from 0.99±0.49 to 2.04±0.33 mm after PTCA and to 3.15±0.36 mm after adjunct stenting, accounting for initial lumen gains of 1.04±0.22 and 1.11±0.32 mm, respectively (Table 2Down). Acute recoil was 0.96±0.15 mm after PTCA versus 0.07±0.17 mm after adjunct stenting (P<.001). At follow-up, a significant late loss of 0.97±0.23 mm was measured, with a residual MLD of 2.18±0.57 mm. As a result, the net luminal gain accounted for 1.18±0.13 mm. A close linear correlation was found between acute luminal gain and late luminal loss, which improved when data were corrected for vessel size (Fig 1Down). Four patients presented restenosis according to the dichotomous definition of a >50% diameter stenosis at follow-up (54%, 58%, 62%, and 64%, respectively). Table 2Down summarizes the results of quantitative coronary angiography.


View this table:
[in this window]
[in a new window]
  		Table 2. Results of Quantitative Coronary Angiography in 25 Patients With Stenosis of the Left Anterior Descending Artery Before PTCA, After PTCA, After Stenting, and at 6-Month Follow-up



View larger version (44K):
[in this window]
[in a new window]
  		Figure 1. Correlation between acute gain (AG) and late lumen loss (LL), calculated for diameter and area measurements, and after correction for reference vessel diameter as relative gain index (RGI) and relative loss index (RLI) in 25 patients with coronary stent implantation.

Densitometric Results
Densitograms of acceptable quality throughout the individual measurement sequence were obtained for 92 of 100 poststenotic ROIs in comparison to 99 of 100 reference ROIs. The average quality index of the six heart phase–gated densitograms was 0.65±0.21 for poststenotic ROIs and 0.83±0.12 for reference ROIs (P<.05).

During the sequence of densitometric measurements, mean heart rate and blood pressure did not change significantly (Table 3Down).


View this table:
[in this window]
[in a new window]
  		Table 3. Results on Heart Rate and Mean Blood Pressure Measured During Digital Subtraction Coronary Angiograms Before Intervention, After PTCA, After Stenting, and at Follow-up in 25 Patients With Stenosis of the Left Anterior Descending Artery

The results for the different densitometric parameters derived at baseline and during hyperemia before and after intervention, after adjunct stenting, and at follow-up are listed in Table 4Down. Baseline densitometric results for poststenotic ROIs were similar, whereas hyperemic results changed significantly in comparison to preinterventional results.


View this table:
[in this window]
[in a new window]
  		Table 4. Results of Densitometric Parameters

Poststenotic MPR, defined as the ratio of baseline rise time divided by hyperemic rise time, increased from 1.57±0.14 before intervention to 2.59±0.86 after PTCA and to 3.10±0.41 after stenting (P<.05, Fig 2Down). At follow-up, poststenotic MPR was 2.90±0.65 (P<.05 versus before intervention). MPR in reference ROIs did not change significantly throughout the measurement sequences.



View larger version (43K):
[in this window]
[in a new window]
  		Figure 2. Results on two definitions of MPR and maximum flow ratio (Max. FR) before intervention after PTCA, after adjunct stenting, and at 6-month follow-up (FU), obtained from 92 poststenotic ROIs and from 98 reference ROIs in 25 patients with stent implantation. Results are presented as mean±SD. b indicates baseline; h, hyperemia; Imax, maximum intensity; MCAT, mean contrast medium appearance time; MTT, mean transit time; and RT, rise time.

Similar results were measured when MPR was defined as the ratio of baseline mean contrast medium appear-ance time divided by hyperemic mean contrast medium appearance time multiplied by the ratio of hyperemic maximal intensity divided by baseline maximal intensity. Poststenotic MPR increased from 1.36±0.28 before intervention to 2.50±1.2 after PTCA and to 3.40±0.87 after stenting, with a nonsignificant drop to 3.20±0.92 at follow-up (Fig 2Up). Again, MPR did not change significantly for reference ROIs throughout the measurements (Fig 2Up).

Poststenotic maximal flow ratio, defined as the ratio of hyperemic mean transit time before and after intervention, was 2.13±0.53 after PTCA, 2.83±0.35 after stenting, and 2.73±0.58 at follow-up (Fig 2Up). Results for reference ROIs did not change significantly (Fig 2Up).

Reproducibility of Densitometric Measurements
A good reproducibility was found for both definitions of MPR and for maximal flow ratio (Fig 3Down). Accuracy and precision were better for measurements after stenting compared with measurements before and after PTCA and for measurements in reference ROIs compared with poststenotic ROIs (Table 5Down).



View larger version (22K):
[in this window]
[in a new window]
  		Figure 3. Reproducibility results for two definitions of MPR and maximum flow ratio (Max FR) obtained in five patients with stenosis of the left anterior descending artery before intervention ({bullet}), after balloon angioplasty ({blacktriangleup}), and after stenting ({diamondsuit}). Closed symbols represent poststenotic ROIs; open circles represent reference ROIs. Solid lines represent lines of regression; dotted lines represent 95% confidence intervals. Other abbreviations as in Fig 2Up.


View this table:
[in this window]
[in a new window]
  		Table 5. Results on Accuracy and Precision of Densitometric Reproducibility Measurements in Five Patients Before PTCA, After PTCA, and After Stenting

Correlation Between Densitometric Perfusion Measurements and Results of Quantitative Coronary Angiography
A linear correlation was documented between MPR and minimal stenosis diameter independent of the definition of MPR and between maximal flow ratio and luminal gain measured before and after PTCA and after stenting (Fig 4Down). A curvilinear correlation was found when results of densitometric perfusion measurements were compared with area stenosis measurements (Fig 4Down). A negative correlation was documented between MPR or maximal flow ratio and recoil (Fig 5Down).



View larger version (44K):
[in this window]
[in a new window]
  		Figure 4. Correlation between stenosis dimensions and two definitions of MPR and maximum flow ratio (Max FR) obtained before intervention ({bullet}), after balloon angioplasty ({triangleup}), and after stenting ({diamondsuit}) in 25 patients with stenosis of the left anterior descending artery. Upper panels represent diameter measurements; lower panels represent area measurements. Solid lines represent lines of regression; broken lines represent 95% confidence intervals. MCA indicates minimal cross-sectional area; other abbreviations as in Fig 2Up.



View larger version (47K):
[in this window]
[in a new window]
  		Figure 5. Correlation between recoil and two definitions of MPR and maximum flow ratio (Max FR) obtained after balloon angioplasty ({triangleup}) and after stenting ({diamondsuit}) in 25 patients with stenosis of the left anterior descending artery. Upper panels represent diameter measurements; lower panels represent area measurements. Solid lines represent lines of regression; broken lines represent 95% confidence intervals. Other abbreviations as in previous figures.

At follow-up, the close correlation between residual stenosis dimensions and MPR or maximal flow ratio persisted, but the slopes of the regression lines were steeper in all measurements compared with the acute results (Fig 6Down).



View larger version (40K):
[in this window]
[in a new window]
  		Figure 6. Correlation between stenosis dimensions and two definitions of MPR and maximum flow ratio (Max FR) obtained at 6-month follow-up in 25 patients after balloon angioplasty and adjunct stenting of a stenosis of the left anterior descending artery. Upper panels represent diameter measurements; lower panels represent area measurements. Solid lines represent lines of regression; broken lines represent 95% confidence intervals. Other abbreviations as in previous figures.


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowAcknowledgment
 down arrowReferences
 
In this study, we wanted to evaluate the impact of postangioplasty residual stenosis on poststenotic MPR and whether adjunct coronary stenting, which limits residual stenosis to a minimum, provides additional improvement. Since others have shown that poststenotic MPR was not restored to normal levels immediately after an angiographically successful balloon angioplasty procedure in the majority of patients,28 29 residual stenosis with an irregular shape would be an explanation, because postinterventional tears fill with contrast medium and thereby result in an angiographic overestimation of the true lumen size despite limited flow conditions.

The results of this study document that poststenotic MPR can be restored immediately to normal reference values of >3.0 on an average only after stent implantation but not after balloon predilatation with the same balloon size in carefully selected patients with a single postangioplasty coronary restenosis excluding other factors that affect vascular capacity, such as angiographically discernible collaterals, myocardial infarction of the target area, hypertension, diabetes, or myocardial hypertrophy. This supports previously published data obtained in a small number of unselected patients with stent implantation by use of densitometric or intracoronary Doppler techniques.29 30 Since baseline perfusion conditions remained constant throughout the measurement sequences, as could be documented by the different densitometric parameters, the subsequent improvement of poststenotic MPR after balloon angioplasty and after stenting is induced primarily by an improvement of hyperemic perfusion. The intraindividual comparison between poststenotic and reference MPRs at each step is of major importance for the interpretation of the functional improvement after balloon angioplasty and adjunct stenting. Since diffuse, nonstenotic atherosclerosis of the reference vessel may be present even in patients with single coronary artery disease, which could be documented angiographically and even more clearly by intravascular ultrasound,31 this may have an impact on the intraindividual target goal in improving poststenotic MPR. Therefore, we selected patients with a single stenosis of the left anterior descending coronary artery, allowing for simultaneous estimation of the reference MPR in the perfusion bed of the left circumflex artery during the same injection.

Metabolic (lactate), humoral (endothelin, thromboxane), or myogenic (vasodilatation, spasm) factors have been shown to affect flow conditions in complicated angioplasty procedures with prolonged ischemia, but it seems unlikely that they affect the additional improvement of MPR after stenting compared with balloon angioplasty in the elective and uncomplicated procedures reported here, although they cannot be ruled out completely.32 33 34 Since the study protocol fixed the duration of balloon insufflation to 30 seconds with sufficient time to recover from ischemia, a preconditioning effect during repeat balloon inflations, as is known from longer insufflations, cannot be assumed as an explanation for the improvement of MPR after stenting compared with balloon angio-plasty.35 36 37 Hemodynamic parameters such as blood pressure and heart rate were within the range of 10% changes throughout the individual densitometric measurements.

There was a close relationship between angiographically measured stenosis dimensions and related poststenotic MPR, supporting the important role of residual stenosis in the functional result. The measured stenosis dimensions before and after balloon predilatation and after adjunct stent implantation and postinterventional elastic recoil were comparable to those reported by others.8 38 39 40

Long-term follow-up documented a substantial lumen loss at the stented vessel site, but MPR of the supplied area remained in the range of the normal reference MPR, as was shown by a steeper relationship between morpho-metric and functional results, suggesting some long-term recovery of microvascular capacity. Similar results were reported by Zijlstra et al,28 who documented, in contrast to the immediate postangioplasty result, a long-term recovery of poststenotic MPR to the normal range 5 months after the procedure. They found larger epicardial dimensions in the target vessel at follow-up compared with the immediate postangioplasty result in 10 of 15 patients, which was interpreted as a contribution to the functional improvement. Johnson et al41 reported a late increase in cross-sectional obstruction area after balloon angioplasty in one third of their patients. Nevertheless, in our study we could not document a late improvement of residual stenosis after stenting. Therefore, recovery of the microvascular capacity contributes more to the persisting normalization of MPR after 6 months.

Densitometric evaluation of digital subtraction angiocardiograms provides information about coronary flow by analyzing the contrast medium propagation through epicardial vessels, the capillary bed, and the coronary venous system and by generating time-density curves similar to indicator dilution curves.12 13 14 15 16 17 It was shown that intra-coronary injections of papaverine or adenosine induced maximum hyperemia most reliably and, because of their shorter half-life compared with dipyridamole, allowed for a repetition of measurements during cardiac catheterization.42 43 Maximum dilatation of the vascular bed is achieved {approx}25 to 60 seconds after intracoronary injection of 8 to 12 mg papaverine. This time period is sufficient to provide steady-state hyperemic conditions during the acquisition of the time-density curves.16 17

Alternative techniques that provide information about the functional effect of coronary interventions on poststenotic flow or perfusion include visual estimation of contrast medium propagation according to the TIMI classification,44 which is popular but not very precise. Coronary sinus thermodilution techniques were used to estimate coronary blood flow45 but never gained wide acceptance in clinical practice, primarily because of difficulties encountered with instrumentation of the coronary sinus. Second, measurements reflect flow mainly within the myocardial territory supplied by the left anterior descending artery. Doppler techniques via intracoronary catheters or more recently available Doppler wires allow the recording of epicardial flow velocity.46 47 48 Kirkeeide et al49 and Gould et al50 defined stenosis flow reserve as a single measure of severity derived from all integrated stenosis geometry by fluid dynamic equations using quantitative coronary angiography. Nevertheless, these techniques do not reflect myocardial perfusion within the precapillaries and capillaries.

Limitations of the Study
In general, the results of this study are obtained from a carefully selected patient population with a single postangioplasty restenosis of the left anterior descending artery, excluding other factors that could influence vascular capacity as described before. Therefore, these results should not be extrapolated to an unselected patient population, as was outlined by others, who documented an improvement in poststenotic MPR after balloon angioplasty in selected but not in unselected patients.51 Assuming the exclusion of other factors influencing microvascular capacity, the results obtained in patients with postangioplasty restenosis are likely to be expanded to individuals undergoing primary angioplasty and stenting. This is supported by quantitative angiographic studies, which have shown similar results on acute gain and elastic recoil after balloon angioplasty for primary and restenotic lesions.8 40 An average 30% loss of the maximum achievable diameter and an average 50% loss of the maximum achievable cross-sectional area immediately after balloon deflation is reported for both primary and restenotic lesions.8 39 40

Furthermore, this study is not intended to directly compare balloon angioplasty and stenting with respect to their impact on long-term myocardial perfusion reserve. The importance of early improvement of myocardial perfusion reserve after stenting to normal reference values on long-term outcome has not yet been established in comparison to balloon angioplasty. Therefore, a randomized trial is mandatory comparing the results on myocardial perfusion reserve in two groups of patients with balloon angioplasty or predilatation and stent implantation.

Densitometric Measurements
Densitometric evaluation of digital subtraction coronary angiograms requires excellent angiographic recordings free of motion artifacts and arrhythmia. This could be obtained in the majority of our patients after careful instruction to withhold breath in deep inspiration for about 20 seconds. In two patients, extrasystoles throughout the recordings required repetition of the digital subtraction coronary angiograms. Atrial fibrillation will not allow these kinds of measurements.

Contrast medium was used as the indicator, an agent that itself has hyperemic properties that might influence the time-density curves, especially during the second part representing contrast medium washout. Furthermore, the requirement of complete substitution of blood by the contrast medium bolus cannot be fulfilled in every situation under clinical conditions in the catheterization laboratory. Nevertheless, reproducibility measurements, performed in a subset of patients under baseline and hyperemic conditions before and after balloon angioplasty and after stenting showed good results. A general limitation of the applied densitometric approach is the poor temporal resolution of the time-density curves resulting from the R wave–triggered image acquisition. In vivo studies pointed out that up to 40% changes of flow reserve using the technique proposed by Vogel et al13 14 account for inaccuracy related to the poor temporal resolution.19 Furthermore, the quality of the densitograms is rarely taken into account. Pijls et al17 fitted the time-density curve to a gamma function and calculated a relative fitting error, which should be <10% to accept the fit and to calculate mean transit time. In our series, we improved temporal resolution by generating not only one but six time-density curves per ROI throughout the cardiac cycle. In addition, we applied sophisticated quality controls to these time-density curves, which have been validated previously.20 25 Thereby, we were able to improve accuracy and precision of the densitometric parameters and of the derived MPR and maximum flow ratio.20 25

There is an ongoing discussion as to which densitometric parameter best represents mean transit time and vascular volume. Several authors pointed out that maximum intensity of the time-density curves does not precisely reflect vascular volume.17 19 25 Therefore, Pijls et al17 calculated maximum flow ratio by comparing hyperemic mean transit time before and after coronary interventions, ruling out the problem of differences in vascular volume at baseline and during hyperemia, since vascular volume is uniform during maximum hyperemia. Therefore, we applied two definitions of MPR. One was defined by Vogel et al,13 14 applying mean contrast medium appearance time and maximum intensity to substitute for mean transit time and vascular volume. Another description of MPR, defined by our group, uses only the ratio of baseline and hyperemic rise time and does not use maximum intensity for reasons listed above.16 Rise time is reported to have a better reproducibility and representation of epicardial electromagnetic flow compared with mean contrast medium appearance time.17 Furthermore, we applied maximum flow ratio as defined by Pijls et al.17 All these definitions came up with the same results, that adjunct stenting improves MPR and maximum flow ratio in comparison to balloon angioplasty.

Quantitative Coronary Angiography
Despite use of an extensively validated quantitative coronary angiography system, there are some general problems with the detection of luminal dimensions from subsequent angiograms before and after balloon angioplasty, after stenting, and at late follow-up. Especially in the postangioplasty setting, a substantial overestimation of the vascular lumen can occur, since postangioplasty tears, slits, and dissections can be filled by contrast medium. Intravascular ultrasound imaging provides a better delineation in this situation. Changes in epicardial vasomotor tone were eliminated by repeat intracoronary injection of nitroglycerin. As a result, reference vessel dimensions were similar throughout the measurements. Nevertheless, quantitative angiographic results of this study are comparable to those of other studies.6 7 8 23 39 In particular, incomplete dilatation as the reason for the postangioplasty angiographic and subsequent functional result can be ruled out, since the average acute gain of 1.04 mm after balloon angioplasty was comparable to that reported for PTCA arms of large-scale, randomized trials, with an acute gain ranging from 0.79 to 1.24 mm.6 7 52 53 54 55

In conclusion, coronary stenting is able to restore MPR within the normal range immediately compared with predilatation using the same balloon size and inflation pressure in selected patients with a single postangioplasty restenosis of the left anterior descending artery. A pronounced inhibition of elastic recoil resulting in a smaller residual stenosis after stenting seems to be primarily responsible. At 6 months, this improvement was sustained despite progressive luminal renarrowing at the stented vessel site, suggesting recovery of microvascular capacity.


*    Acknowledgment
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 *Acknowledgment
down arrowReferences
 
This work was supported by a grant from the Verband der Lebensversicherungs-Unternehmer eV, Bonn, Germany.


*    Selected Abbreviations and Acronyms
 
MLD = minimal lumen diameter
MPR = myocardial perfusion reserve
PTCA = percutaneous transluminal coronary balloon angioplasty
ROI = region of interest

Received October 19, 1995; revision received December 27, 1995; accepted January 4, 1996.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 up arrowAcknowledgment
 *References
 

  1. Sigwart U, Puel J, Mirkovitch V, Joffre F, Kappenberger L. Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. N Engl J Med. 1987;316:701-706.[Abstract]
  2. Roubin GS, Cannon AD, Agrawal SK, Macander PJ, Dean LS, Baxley WA, Breland J. Intracoronary stenting for acute and threatened closure complicating percutaneous transluminal coronary angioplasty. Circulation. 1992;85:916-927.[Abstract/Free Full Text]
  3. Haude M, Erbel R, Straub U, Dietz U, Schatz R, Meyer J. Results on intracoronary stents for management of coronary dissection after balloon angioplasty. Am J Cardiol. 1991;67:691-696.[Medline] [Order article via Infotrieve]
  4. De Feyter PJ, De Scheerder I, van den Brand M, Laarman GJ, Suryapranata H, Serruys PW. Emergency stenting for refractory acute coronary artery occlusion during coronary angioplasty. Am J Cardiol. 1990;66:1147-1150.[Medline] [Order article via Infotrieve]
  5. Herman HC, Buchbinder M, Cleman MW, Fishman D, Goldberg S, Leon MB, Schatz RA, Teirstein P, Walker CM, Hirshfeld JW Jr. Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty. Circulation. 1992;86:812-819.[Abstract/Free Full Text]
  6. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi J, Sigwart U, Colombo A, Goy JJ, van den Heuvel P, Delcan J, Morel MA, for the Benestent study group. A comparison of balloon expandable stent implantation with balloon angioplasty in patients with coronary artery disease. N Engl J Med. 1994;331:489-495.[Abstract/Free Full Text]
  7. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, Cleman M, Heuser R, Almond D, Teirstein PS, Fish D, Colombo A, Brinker J, Moses J, Shaknovich A, Hirshfeld S, Bailey S, Ellis S, Rake R, Goldberg S, for the Stent Restenosis Study Investigators. A randomized comparison of coronary stent placement and balloon angioplasty in the treatment of coronary artery disease. N Engl J Med. 1994;331:496-501.[Abstract/Free Full Text]
  8. Haude M, Erbel R, Issa H, Meyer J. Quantitative analysis of elastic recoil after balloon angioplasty and after intracoronary implantation of balloon expandable Palmaz-Schatz stents. J Am Coll Cardiol. 1993;21:26-34.[Abstract]
  9. Hermans WR, Rensing BJ, Strauss BH, Serruys PW. Methodological problems related to the quantitative assessment of stretch, elastic recoil, and balloon artery ratio. Cathet Cardiovasc Diagn. 1992;25:174-185.[Medline] [Order article via Infotrieve]
  10. Macaya C, Alfonso F, Iniguez A, Coicolea J, Hernandez R, Zarco P. Stenting for elastic recoil during coronary angioplasty of the left main coronary artery. Am J Cardiol. 1992;70:105-107.[Medline] [Order article via Infotrieve]
  11. Painter JA, Mintz GS, Wong SC, Popma JJ, Pichard AD, Kent KM, Satler LF, Leon MB. Serial intravascular ultrasound studies fail to show evidence of chronic Palmaz-Schatz stent recoil. Am J Cardiol. 1995;75:398-400.[Medline] [Order article via Infotrieve]
  12. Rutishauser W, Noseda G, Bussmann WD, Preter B. Blood flow measurement through single coronary arteries by roentgen densitometry, part II: right coronary artery flow in conscious man. Am J Roentgenol. 1970;109:21-24.[Abstract]
  13. Vogel RA. The radiographic assessment of coronary blood flow parameters. Circulation. 1985;72:460-465.[Free Full Text]
  14. Vogel RA, Lefree MT, Bates ER, O'Neill W, Foster R, Kirlin P, Smith D, Robb B. Application of digital techniques to selective coronary arteriography: use of myocardial contrast appearance time to measure coronary flow reserve. Am Heart J. 1984;107:153-164.[Medline] [Order article via Infotrieve]
  15. Hodgson JM, LeGrand V, Bates ER, Mancini J, Aueron FM, O'Neill W, Simon SB, Beauman GJ, LeFree MT, Vogel RA. Validation in dogs of a rapid digital angiographic technique to measure relative coronary blood flow during routine cardiac catheterization. Am J Cardiol. 1985;55:188-193.[Medline] [Order article via Infotrieve]
  16. Haude M, Brennecke R, Erbel R, Jung D, Kiefer E, Schmidt T, Meyer J. Computerized determination of the densitometric parameter `mean rise time': a tool in the analysis of myocardial perfusion. Comput Cardiol. 1987;14:19-22.
  17. Pijls NHJ, Uijen GJH, Hoevelaken A, Arts T, Aengevaeren WRM, Bos HS, Fast JH, van Leeuwen KL, van der Werf T. Mean transit time for the assessment of myocardial perfusion by videodensitometry. Circulation. 1990;81:1331-1340.[Abstract/Free Full Text]
  18. Cusma JT, Toggart EJ, Folts JD, Pepler WW, Hangiandreou NJ, Lee CS, Mistretta CA. Digital subtraction angiographic imaging of coronary flow reserve. Circulation. 1987;75:461-472.[Abstract/Free Full Text]
  19. Hess OM, McGillem MJ, DeBoe SF, Pinto IMF, Gallagher KP, Mancini GBJ. Determination of coronary flow reserve by parametric imaging. Circulation. 1990;82:1438-1448. Comment in Circulation. 1990;82:1533-1535.[Abstract/Free Full Text]
  20. Lang M, Brennecke R, Haude M, Renneisen U, Erbel R, Meyer J. Improving the applicability of myocardial densitometry and parametric imaging by extended automated densogram analysis. Int J Card Imaging. 1995;11:105-115.[Medline] [Order article via Infotrieve]
  21. Eigler NL, Pfaff JM, Zeiher AM, Whiting JS, Forrester JS. Digital angiographic impulse response analysis of regional myocardial perfusion: linearity, reproducibility, accuracy, and comparison with conventional indicator dilution curve parameters in phantom and canine models. Circ Res. 1988;64:853-866.[Abstract/Free Full Text]
  22. Eigler NL, Schuhlen H, Whiting JS, Pfaff JM, Zeiher AM, Gu S. Digital angiographic impulse response analysis of regional myocardial perfusion: estimation of coronary flow, flow reserve, and distribution volume by compartmental transit time measurement in a canine model. Circ Res. 1991;68:870-880.[Abstract/Free Full Text]
  23. Haude M, Erbel R, Hafner G, Heublein B, Hoepp HW, Franzen D, Prellwitz W, Lichtlen P, Hilger HH, Meyer J. Multi-center results after intracoronary implantation of balloon-expandable Palmaz-Schatz stents. Z Kardiol. 1993;82:77-86.
  24. Reiber JHC, Serruys PW, Kooijman CJ, Wijns W, Slager CJ, Gerbrands JJ, Schuurbiers JCH, den Boer A, Hugenholtz PG. Assessment of short-, medium-, and long-term variations in arterial dimensions from computer-assisted quantification of coronary cineangiograms. Circulation. 1985;71:280-288.[Abstract/Free Full Text]
  25. Haude M, Brennecke R, Erbel R, Renneisen R, Lang M, Deutsch HP, Meyer J. Computerized estimation of quality standards for the X-ray densitometric assessment of myocardial perfusion. Comput Cardiol. 1990;17:317-320.
  26. Haude M, Brennecke R, Erbel R, Renneisen R, Lang M, Eißner D, Hahn K, Meyer J. Parametric assessment of myocardial perfusion by densitometric evaluation of digital subtraction coronary angiograms: a comparison with tomographic TI-201 scintigraphy results. Comput Cardiol. 1991;18:141-144.
  27. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurements. Lancet. 1986;327:307-310.
  28. 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.[Abstract/Free Full Text]
  29. Ge J, Erbel R, Zamorano J, Haude M, Kearney P, Gorge G, Meyer J. Improvement of coronary morphology and blood flow after stenting: assessment by intravascular ultrasound and intracoronary Doppler. Int J Card Imaging. 1995;11:81-87.[Medline] [Order article via Infotrieve]
  30. Haude M, Lang M, Issa H, Renneisen U, Brennecke R. Additional improvement of stenosis dimensions and coronary flow after intracoronary implantation of Palmaz-Schatz stents. Circulation. 1991;84(suppl II):II-196. Abstract.
  31. Mintz GS, Painter JA, Pichard AD, Kent KM, Satler LF, Popma JJ, Chuang YC, Bucher TA, Sokolowicz LE, Leon MB. Atherosclerosis in angiographically `normal' coronary artery reference segments: an intravascular ultrasound study with clinical correlation. J Am Coll Cardiol. 1995;25:1479-1485.[Abstract]
  32. Serruys PW, van den Brand M, Meij S, Slager C, Schuurbiers JCH, Hugenholtz PG, Brower RW. Left ventricular performance, regional blood flow, wall motion, and lactate metabolism during transluminal angioplasty. Circulation. 1984;70:25-36.[Abstract/Free Full Text]
  33. Rothman MT, Baim DS, Simplon JB, Harrison DC. Coronary hemodynamics during percutaneous transluminal coronary angioplasty. Am J Cardiol. 1982;49:1615-1622.[Medline] [Order article via Infotrieve]
  34. Machay V, Block PC, Palacios I, Philbin D, Watkins WD. Thromboxane release during percutaneous transluminal coronary angioplasty. Am Heart J. 1986;1:111-119.
  35. Bauer B, Simkhovich BZ, Kloner RA, Przyklenk K. Does preconditioning protect the coronary vasculature from subsequent ischemia/reperfusion injury? Circulation. 1993;88:659-672.[Abstract/Free Full Text]
  36. Deutsch E, Berger M, Kussmaul WG, Hirshfeld JW Jr, Herrmann HC, Laskey WK. Adaptation to ischemia during percutaneous transluminal coronary angioplasty: clinical, hemodynamic, and metabolic features. Circulation. 1990;82:2044-2051.[Abstract/Free Full Text]
  37. Reimer KA, Murry CE, Jennings RB. Cardiac adaptation to ischemia: ischemic preconditioning increases myocardial tolerance to subsequent ischemic episodes. Circulation. 1990;82:2266-2268.[Free Full Text]
  38. Hanet C, Wijns W, Michel X, Schroeder E. Influence of balloon size and stenosis morphology on immediate and delayed elastic recoil after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol. 1991;18:506-511.[Abstract]
  39. Rensing BJ, Hermans WR, Strauss BH, Serruys PW. Regional differences in elastic recoil after percutaneous transluminal coronary angioplasty: a quantitative angiographic study. J Am Coll Cardiol. 1991;17(6 suppl B):34B-38B.
  40. Rensing BJ, Hermans WR, Beatt KJ, Laarman GJ, Suryapranata H, van den Brand M, de Feyter PJ, Serruys PW. Quantitative angiographic assessment of elastic recoil after percutaneous transluminal coronary angioplasty. Am J Cardiol. 1990;66:1039-1044.[Medline] [Order article via Infotrieve]
  41. Johnson MR, Brayden GP, Ericksen EE, Collins SM, Skorton DJ, Harrison DG, Marcus ML, White CW. Changes in cross-sectional area of the coronary lumen in the six months after angioplasty: a quantitative analysis of the variable response to percutaneous transluminal angioplasty. Circulation. 1986;73:467-475.[Abstract/Free Full Text]
  42. Wilson RF, White CW. Intracoronary papaverine: an ideal coronary vasodilator for studies of the coronary circulation in conscious humans. Circulation. 1986;73:444-451.[Abstract/Free Full Text]
  43. Wilson RF, Wyche K, Christensen BV, Laxson DD. Effects of adenosine on human coronary arterial circulation. Circulation. 1990;82:1595-1606.[Abstract/Free Full Text]
  44. TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial: phase I findings. N Engl J Med. 1985;312:932-936.[Medline] [Order article via Infotrieve]
  45. Ganz W, Tamura K, Marcus HS, Donos R, Yoshida S, Swan HJC. Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation. 1971;44:181-195.[Abstract/Free Full Text]
  46. Sibley DH, Millar HD, Hartley CJ, Whitlow PL. Subselective measurement of coronary blood flow velocity using a steerable Doppler catheter. J Am Coll Cardiol. 1986;8:1332-1340.[Abstract]
  47. Wilson RF, Laughlin DE, Ackell PH, Chilian WM, Holida MD, Hartley CJ, Armstrong ML, Marcus ML, White CW. Transluminal subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man. Circulation. 1985;72:82-89.[Abstract/Free Full Text]
  48. Kern MJ, Donohue TJ, Aguirre FV, Bach RG, Caracciolo EA, Ofilli E, Labovitz AJ. Assessment of angiographically intermediate coronary artery stenosis using the Doppler wire. Am J Cardiol. 1993;71:26D-33D.[Medline] [Order article via Infotrieve]
  49. Kirkeeide R, Gould KL, Parsel L. Assessment of coronary stenoses by myocardial imaging during coronary vasodilatation, VII: validation of coronary flow reserve as a single integrated measure of stenosis severity accounting for all its geometric dimensions. J Am Coll Cardiol. 1986;7:103-113.[Abstract]
  50. Gould KL, Kirkeeide R, Buchi M. Coronary flow reserve as a physiological measure of stenosis severity, I: relative and absolute coronary flow reserve during changing aortic pressure; II: determination from angiographic stenosis dimensions under standardized conditions. J Am Coll Cardiol. 1990;15:459-474.[Abstract]
  51. Laarman GJ, Serruys PW, Suryapranata H, van den Brand M, Jonkers PR, de Feyter PJ, Roelandt JRTC. Inability of coronary blood flow reserve measurements to assess the efficacy of coronary angioplasty in the first 24 hours in unselected patients. Am Heart J. 1991;122:631-639.[Medline] [Order article via Infotrieve]
  52. Topol EJ, Leya F, Pinkerton CA, Whitlow PL, Hofling B, Simonton CA, Masden RR, Serruys PW, Leon MB, Williams DO, King SB, Mark DB, Isner JM, Holmes DR, Ellis SG, Lee KL, Keeler GP, Berdan LG, Hinohara T, Califf RM. A comparison of directional atherectomy with coronary angioplasty in patients with coronary angioplasty. N Engl J Med. 1993;329:221-227.[Abstract/Free Full Text]
  53. Adelmann AG, Cohen M, Kimball BP, Bonan R, Ricci DR, Webb JG, Larame L, Barbeau G, Traboulsi M, Corbett BN, Schwartz L, Logan AG. Canadian atherectomy trial: a comparison of directional coronary atherectomy and percutaneous transluminal coronary angioplasty for lesions of the proximal left anterior descending artery. N Engl J Med. 1993;329:228-234.[Abstract/Free Full Text]
  54. Foley DP, Melkert R, Serruys PW, on behalf of the CARPORT, MERCATOR, MARCATOR, and PARK Investigators. Influence of coronary vessel size on renarrowing process and late angiographic outcome after successful balloon angioplasty. Circulation. 1994;90:1239-1251.[Abstract/Free Full Text]
  55. Weintraub WS, Boccuzzi SJ, Klein JL, Kosinski ASK, King SB, Ivanhoe R, Cedarholm JC, Stillabower ME, Talley MD, DeMario SJ, O'Neill WW, Frazier JE II, Cohen-Bernstein CL, Robbins DC, Brown CL, Alexander RW, and the Lovastatin Restenosis Trial Study Group. Lack of effect of lovastatin on restenosis after coronary angioplasty. N Engl J Med. 1994;331:1331-1337.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J Am Coll CardiolHome page
K. Leineweber, D. Bose, M. Vogelsang, M. Haude, R. Erbel, and G. Heusch
Intense Vasoconstriction in Response to Aspirate From Stented Saphenous Vein Aortocoronary Bypass Grafts
J. Am. Coll. Cardiol., March 7, 2006; 47(5): 981 - 986.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
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]

Home page
 CirculationHome page
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,