(Circulation. 1999;99:771-778.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
New Noninvasive Method for Coronary Flow Reserve Assessment
Contrast-Enhanced Transthoracic Second Harmonic Echo Doppler
From the Institute of Cardiology, University of Cagliari, Cagliari, Italy.
Correspondence to Dr Carlo Caiati, Cattedra e Divisione di Cardiologia, Ospedale S Giovanni di Dio, Via Ospedale 46, 09124, Cagliari, Italy. E-mail carlo.caiati{at}teseo.it
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Abstract |
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Background—We tested the hypothesis that blood flow velocity could be recorded in the left anterior descending coronary artery (LAD) during transthoracic echocardiography by use of second harmonic echo Doppler modality along with contrast enhancement (intravenous Levovist) at rest and after pharmacologically induced maximal vasodilation to assess coronary flow reserve (CFR) with a totally noninvasive approach.
Methods and Results—Fifty-six consecutive patients undergoing coronary angiography underwent transthoracic contrast-enhanced pulsed-wave Doppler recording of blood flow velocity in the LAD by use of harmonic color Doppler as a guide at rest and after maximal vasodilation by dipyridamole infusion. Contrast enhancement with the harmonic mode greatly improved the success rate of recording adequate pulsed-wave Doppler signal in the LAD. CFR was (mean±SD) 1.54±0.7 in patients with (group 1) and 2.79±0.9 in patients without (group 2) significant LAD stenosis (lumen narrowing >70%) (P<0.001); sensitivity and specificity in detecting significant LAD stenosis were 86% and 90%, respectively. There was close agreement between CFRs determined by this new method and intracoronary Doppler flow wire.
Conclusions—Contrast-enhanced transthoracic echo Doppler with the harmonic mode is a feasible and promising technique for assessing CFR in a totally noninvasive way.
Key Words: blood flow • coronary disease • contrast media • echocardiography
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Coronary flow reserve (CFR) assessment is a clinically useful method to assess coronary function. Several methods have been established for measuring CFR.1 However, these methods are invasive (intracoronary Doppler flow wire),2 semiinvasive (transesophageal Doppler echocardiography3 ), or extremely expensive and thus scarcely available (PET).4
The left anterior descending coronary artery (LAD) can be visualized by means of transthoracic cross-sectional echocardiography. Transthoracic blood-flow Doppler recording has been attempted in the distal part by use of high-frequency transducers.5 However, the success rate in evaluating distal LAD blood flow is so low5 that this method has never been proposed for CFR assessment.
Intravenously injected echo-contrast agents improve Doppler signal-to-noise ratio in the coronaries by enhancing signal amplitude.6 7 Second harmonic technology, a recently introduced imaging ultrasound modality, further improves the enhancing effect of echo-contrast agents by reducing noise without reducing the signal from the blood.8 Thus, we undertook this study to verify the following hypotheses: (1) coronary blood flow velocity in the LAD can be measured during a transthoracic Doppler study in baseline conditions and after pharmacologically induced maximal vasodilation with an echo-contrast agent capable of enhancing Doppler signal intensity, signal-to-noise ratio, and a nonlinear response when pulsating in an ultrasound field with second harmonic Doppler technology; (2) CFR assessed by this approach is useful in detecting significant LAD stenosis; and (3) CFR assessment is in agreement with CFR assessed by a gold-standard method, such as intracoronary Doppler flow wire.2
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Study Group
Fifty-six consecutive patients (42 men; age, 32 to 84 years; mean age, 59±11 years) scheduled for diagnostic coronary angiography were prospectively studied. The patients studied were consecutive and unselected; thus, those with large body habitus were also included. All patients underwent coronary angiography because of suspected or known coronary artery disease. Twenty-one had experienced previous myocardial infarction. All coronary active medications were withdrawn the morning of the echocardiographic study. Of the 56 patients, 23 had significant (>70% narrowing) stenosis affecting the proximal (13 patients [2 occlusions]), middle (7 patients [1 occlusion]), or distal (3 patients) portion of the LAD (group 1); the remaining 33 patients (group 2) did not have significant LAD stenosis. All patients were informed of the purpose and nature of the study and provided informed consent
Study Protocol
Each patient underwent a color-guided pulsed-wave (PW)
Doppler recording of coronary blood velocity in the
LAD in baseline condition and after dipyridamole
administration (0.54 mg/kg IV over 4 minutes, followed by 4 minutes of
no dose and then 0.28 mg/kg over 2 minutes) both before and after
contrast enhancement. Two separate infusions of the echo-contrast agent
were given: 1 for the baseline and 1 for the
dipyridamole part of the study. The second contrast
infusion was started a few seconds after the
dipyridamole administration protocol was finished.
Coronary flow evaluation was performed with fundamental color
Doppler before contrast infusion and with second harmonic color
Doppler during contrast infusion.
Transthoracic Echocardiography and
Color Doppler
Echocardiography was performed with a
prototype release of the Acuson Sequoia ultrasound unit (Acuson Corp)
by use of a broadband transducer with second harmonic capability
(3V2c). B-mode and contrast-enhanced color Doppler imaging was
performed in the second harmonic mode (1.7 MHz transmitting and 3.5 MHz
receiving), whereas color-coded Doppler before contrast
enhancement and spectral Doppler were performed in fundamental
imaging at 2.5 MHz.
All studies were continuously recorded on a 0.5-in super-VHS videotape, and significant portions were also captured in a cineloop format or still frames and digitally stored to simplify off-line reviewing and measurements.
A systematic attempt was made to record flow in the distal or
middle part of the LAD. The approach for the distal part consisted
first of obtaining a short axis of the left ventricular
apex and anterior groove to search for coronary
flow.5 When a diastolic circular color-coded
blood flow was recognized in the anterior groove area, the transducer
was rotated clockwise to obtain the best long axis of color flow.
Alternatively, a modified foreshortened 2-chamber view was obtained by
sliding the transducer superiorly and medially from an apical 2-chamber
position (Figure 1
). Then, a careful
search for color-coded blood flow was made over the epicardial part of
the anterior wall with simultaneous attempts to optimize
the visualization of the anterior groove area by very slight
counterclockwise rotation and medial angling of the probe. The middle
part of the LAD was visualized by a low parasternal short-axis view of
the base of the heart modified by a slight clockwise rotation of the
transducer beam.
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If no color-coded blood flow from the LAD was visualized in the baseline condition, the same procedure was attempted again during contrast enhancement.
Spectral Doppler
PW Doppler recording was attempted with color flow
as a guide, with sample volume positioning in
diastole.3 Spectral trace of coronary
flow velocity was characterized by a biphasic flow with a prevalent
diastolic component (Figure 2). If a relatively high (>50 cm/s)
baseline velocity was recorded, probably indicating acceleration at
the stenosis site, a second Doppler recording
(reference value) was performed in a different arterial
segment. The first baseline velocity was discarded if it was 50%
higher than the reference value.6 This occurred in 2 group
1 patients.
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Echo-Contrast Enhancement
The Doppler signal enhancer used in this study was Levovist
(Schering AG).6 The echo-contrast agent was administered
by infusion with a devoted infusion pump (IVAC P4000
anesthesia syringe pump) connected over a special 50-cm
connector tubing to an in-dwelling cannula (20 to 22 gauge) inserted
into a cubital vein.
On the basis of our previous experiences, we used a concentration of 300 mg/mL.6 7 Regarding infusion rate, we started with 1 mL/min of a volume of 6 to 7 mL; this rate was increased to a maximum of 2 mL/min or decreased to a minimum of 0.5 mL/min according to the quality and entity of the Doppler signal enhancement achieved. Contrast administration was performed both before and after intravenous dipyridamole administration.
Echocardiographic Measurements
Feasibility of blood-flow-velocity Doppler recording
in the LAD (both harmonic color and spectral Doppler) was evaluated
in all protocol steps by the consensus of 2 experienced observers using
a 3-grade scoring system previously validated in our
laboratory.7 Briefly, the following scoring system was
used. For color Doppler, 1=no color Doppler signal detected in
the LAD, 2=suboptimal color Doppler signal (width <1 mm), and
3=optimal color-coded Doppler signal (width >1 mm). For
spectral Doppler, 1=no signal detection, 2=spectral signal
recognizable but with poor definition of the outline of the
diastolic and systolic waves, and 3=optimal outline
definition of at least the diastolic curve. The duration of
contrast enhancement (visually assessed) was timed by use of a built-in
chronometer of the ultrasound unit activated at the start of
contrast infusion.
CFR assessment was performed by 1 experienced operator blinded to the clinical and angiographic data. Measurements were made off-line by use of the built-in calculation package of the ultrasound unit. The following coronary flow velocity parameters were measured before and after dipyridamole: peak and mean diastolic velocity and peak and mean systolic velocity. For each parameter, the highest 3 (in case of sinus rhythm; n=52) or 6 (in case of atrial fibrillation; n=2) cycles were averaged. CFR was calculated as the ratio of hyperemic to basal peak (peak CFR) and mean (mean CFR) diastolic flow velocity.
Left ventricular mass was calculated by use of the modified formula of Devereux et al.9
Interobserver measurement variability was determined by having a second independent observer measure Doppler velocity recordings in 10 patients. Intraobserver variability was assessed by having 1 observer remeasure spectral curves 1 month apart in 10 patients as well. Intraoperator and interoperator reproducibility of velocity data acquisition was assessed by repeating measurements in 13 and 9 LAD segments, respectively. For this purpose, evaluations were performed by the same operator and by 2 different operators, respectively, 2 times, 2 hours apart.
Reproducibility of the angle between LAD flow direction and the ultrasound spectral Doppler beam in baseline conditions and during dipyridamole vasodilation was assessed in the first 33 patients enrolled in the study for both the rest and dipyridamole parts of the study.
Coronary Angiography
All coronary angiograms were blindly read, and calipers
were used in cases of questionable findings. Any LAD angiographic
obstruction >70% was considered a significant stenosis.
Doppler Flow Wire
In a subgroup of 16 patients (17 cases overall because 1 patient
was studied before and after coronary angioplasty),
intravascular velocity measurement in the LAD, distal to the eventual
stenosis, was attained by means of a 0.014-in, 14-MHz
Doppler guide wire (Flow Wire Cardiometrics, Inc) at rest and after
hyperemic stimulus as previously described. Care was taken to
avoid placement in a side branch or poststenotic velocity jet.
Spectral Doppler signal was then recorded at baseline and after
an 18-µg IC bolus of adenosine.2
Hyperemic stimulus was repeated at least twice. In most cases,
premedication with either intracoronary (200 µg) or
sublingual (0.4 mg) nitroglycerin was performed. CFR
was computed as the ratio of hyperemic to basal average peak
velocity.
All intravascular Doppler studies except 1 (postangioplasty case) were performed within 48 hours of transthoracic Doppler examinations by a researcher blinded to the transthoracic Doppler results.
Statistical Analysis
Continuous data are expressed as mean±SD. Differences in
Doppler score before and after contrast enhancement were tested by
use of a 
2 analysis (contingency
table, 3 rows times 2 columns). The differences between the 2 groups
for the parametric and categorical data were tested by use of
an unpaired 2-tailed t test and a 2
test, respectively. Differences between baseline and hyperemic
data were tested overall by use of an unpaired 2-tailed t
test and within groups by use of a paired 2-tailed t test.
Sensitivity and specificity for CFR as a predictor of significant LAD
stenosis were calculated in the traditional manner.
Intraobserver interobserver measurement variability and reproducibility and comparison of CFR evaluated by the 2 methods were evaluated by use of both a linear regression analysis expressed as the correlation of coefficients (r) and SEE and the Bland-Altman10 method for assessing the limits of agreement between the repeated measurements.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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No significant difference was found between the 2 study groups in terms of demographic and clinical characteristics and left ventricular mass.
Blood flow velocity in baseline conditions and after dipyridamole vasodilation was attempted first in the distal LAD. If no (3 patients) or an unsatisfactory (9 patients) recording was obtained in the distal segment, recording was attempted in the middle portion (12 patients). In 1 patient (from group 1), blood flow velocity recording during dipyridamole vasodilation was not achieved, so this patient was excluded from CFR evaluation (CFR feasibility, 98%).
Effect of Contrast Enhancement on Color and Spectral
Doppler
The use of contrast agent greatly improved both second harmonic
color (Figure 1
) and PW Doppler recording
feasibility (Figure 2) in the LAD (Table 1).
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The contrast-enhancing effect peaked at 
3 minutes after the
infusion was begun and remained constant until the end of the infusion.
The duration of the enhancement at rest and after
dipyridamole was 8±5 and 6±5 minutes, respectively,
depending on the total injected volume and infusion rate.
Dipyridamole Infusion
No major adverse reactions occurred after
dipyridamole infusion. Slight modifications of heart
rate and systolic blood pressure were observed after
dipyridamole infusion. Heart rate and systolic
blood pressure increased 17±10 bpm (from 65±13 to 81±14 bpm
[P<0.01]) and 5±15 mm Hg (from 128±19 to
133±23 mm Hg [P<0.05]). Diastolic
blood pressure did not change at all. This response was similar in the
2 groups.
Transthoracic CFR Versus Angiography
Blood flow velocity was similar in the 2 groups in the baseline
conditions (Table 2). After
dipyridamole infusion, blood flow velocity increased
much more in group 2 (Figure 2) than in group 1 (Figures 3 and 4 and
Table 2). Consequently, peak and mean diastolic CFRs
were much higher in group 2 than in group 1 (Figure 4). A CFR
for peak diastolic volume <2.0 had a sensitivity of
86% and a specificity of 90% for the presence of significant LAD
stenosis. Notably, the 2 patients from group 2 with the lowest
hyperemic-to-normal-flow-velocity ratio (1.57 and 1.53) had
60% stenosis of the mid-LAD, a positive exercise
201Tl scan for moderate apical and anterior
ischemia, and a normal LAD with typical effort angina. This
last patient underwent intracoronary Doppler flow wire in
the LAD (Table 3, patient 5) that
confirmed the abnormal CFR value in the absence of coronary
stenosis. Of the 3 false-negative patients in group 1 (Figure 4), 2 had distal LAD stenoses and the other had a LAD
proximal occlusion.
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Of the 3 patients with LAD occlusion, 1 had a middle occlusion, and CFR was evaluated in the midportion of the vessel (proximal to the stenosis) because no flow was detected in the distal part; the other 2 showed proximal occlusion immediately after a stenotic and a normal, respectively, diagonal branch leading to the apex. The CFRs for these 2 patients, very likely obtained in the diagonals, were blunted and normal, respectively.
Transthoracic Versus Intracoronary CFR
CFR as assessed with this new method closely agreed with
intracoronary Doppler flow wire CFR (r=0.88). In
all but 2 cases, the difference between intracoronary and
transthoracic CFR was a maximum of 0.3 (Figure 5). Overall, the upper and lower limits
of agreement between the 2 approaches were 0.83 (95% CI, 0.43 to 1.25)
and -0.8 (95% CI, -1.21 to -0.39), respectively.
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Intraobserver and Interobserver Variability and Reproducibility and
Angle Variability
Intraobserver and interobserver variabilities in tracing curve
outlines were low (Table 4).
Intraobserver and interobserver reproducibility of blood flow velocity
recording was high (Table 4). There was no significant
variation of 
angle between baseline (11.6±12 grades) and
dipyridamole (11.4±13 grades [P=NS])
recordings.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This study demonstrates that transthoracic harmonic color Doppler and PW Doppler, in conjunction with intravenous injection of an echo-contrast agent with appropriate ultrasound characteristics,8 allows detection of LAD blood flow and, more importantly, its accurate measurement in baseline conditions and during dipyridamole vasodilation, thus providing a totally noninvasive assessment of CFR. PW Doppler recording of optimal quality (score 3) was achieved in 96% of patients at baseline and in 89% during dipyridamole infusion after contrast enhancement and in only 7% and 4%, respectively, before contrast enhancement (P<0.001). CFR assessed with this new method can accurately predict the presence of a significant (>70% narrowing) LAD stenosis (sensitivity, 86%; specificity, 90%) and is in strict agreement with CFR as assessed by intracoronary Doppler flow wire (r=0.88), a highly reliable and reproducible method for assessing CFR2 (Figures 2
and 5 and Table 3).
Echo Doppler Assessment of Coronary Flow and
Reserve
A semiinvasive approach to CFR with ultrasound was first
proposed by Iliceto et al3 some years ago. However, this
approach required transesophageal intubation of an
ultrasound probe to be obtained.7 In the last few years,
scattered reports5 have indicated that the distal LAD can
be visualized by a transthoracic approach by use of a
high-frequency transducer. However, the success rate of visualizing the
artery and the flow, especially in unselected populations, was
extremely low (between 18% and 56%). Interestingly, our precontrast
feasibility data (Table 1) parallel those of these reports.
Echo-Doppler Enhancement: Methodological
Considerations
The high success rate in detecting coronary flow in the
LAD relies on the combination of contrast enhancement and second
harmonic technology. Contrast enhancement has been proved useful in
increasing Doppler signal-to-noise ratio in coronaries by
increasing signal amplitude.6 7 In addition, harmonic
Doppler imaging with echo-contrast agents capable of nonlinear
emission of harmonics can further increase the signal-to-noise ratio by
eliminating flashing and clutter artifacts coming from the tissue
without significantly reducing the signal from blood.8 In
the harmonic mode, the echoes in second harmonic frequency coming from
the resonant contrast agent are received, whereas echoes from the solid
tissue and red blood cells in fundamental frequency (containing noise)
are suppressed or attenuated. Thus, a contrast-dependent image is
produced.
Color Doppler recording of coronary blood flow is of crucial importance because it allows more appropriate PW sample volume positioning. We administered contrast by infusion and not by bolus because infusion has the advantage of maintaining the enhancing effect of the agent over several minutes.
CFR and Stenosis Severity
The good separation of the 2 patient groups (with and without
significant LAD stenosis) with CFR as assessed with this new
method (Figure 4) was related mainly to the
homogeneously reduced hyperemic blood flow response
in the group with significant LAD stenosis (except for the 3
false-negative). This was likely determined by measurement of CFR in
the poststenotic segment. Coronary flow velocity and
CFR measured distal rather than proximal to a coronary
stenosis is a more precise index of flow response not being
influenced by nonnarrowed branching arteries11 whose
presence can pseudonormalize flow response to a vasodilating agent.
Study Limitations
CFR assessment can be invalidated if measurements are performed at
the stenosis site. In our study, however, to circumvent this
problem, a second Doppler sampling (reference value) was obtained
in a different portion of the artery6 in patients with
relatively high baseline velocity (>50 cm/s), possibly indicating
acceleration at the stenosis site.
In a certain number of cases, the angle was quite large (>30°),
causing underestimation of the true velocity. However, for the purpose
of the CFR evaluation, the absolute velocity value was not needed
because CFR is a quotient of 2 velocities. In our study, there was no
significant difference between the angle at baseline and during
dipyridamole recording.
We measured a CFR index using a simple ratio of 2 velocities. This, as previously pointed out by others,12 is a reliable indicator of CFR.
In patients with coronary occlusion and distal LAD stenosis, false-negative studies may arise. Erroneous sampling in a LAD branch (occlusion) or in a prestenotic segment (distal stenosis) is a likely explanation.
In some of our patients without significant LAD stenosis, CFR
individual values show a certain scatter, with an average value that
appears to be lower than the normal CFR values already reported in
other animal and human studies that used a variety of
techniques.13 This can be explained by taking in account
the fact that our "control group" included patients scheduled for
coronary angiography because of chest pain. In these patients,
CFR can theoretically be impaired because of several causes, such as X
syndrome, that can increase resistance to coronary blood flow
(see patient 5 in Table 3).
Methodological limitations could explain some discrepancies with
intravascular Doppler flow wire. In particular, in the 2 patients
with the largest CFR discrepancy, sampling proximal to the LAD
stenosis by transthoracic Doppler (Table 3, patient 8) and a lower vasodilator effect of
dipyridamole with respect to
adenosine14 (Table 3, patient 9) could very
likely explain the difference in CFR measurements.
Clinical Implications
This totally noninvasive method to assess CFR has potentially
interesting clinical applications. It may provide additional
information to cardiac catheterization in the
assessment of LAD coronary stenoses, especially those
of intermediate anatomic severity whose functional impact can be
precisely assessed only with the poststenotic CFR
evaluation.11 It may also be useful in the noninvasive
detection of LAD stenosis in situations, such as a left
bundle-branch block, in which stress tests (both
scintigraphy and echocardiography) are
not reliable because of the high number of the false-positive studies;
in assessing microcirculation impairment in conditions affecting CFR in
the absence of coronary artery disease; and because of the
possible serial evaluation, for exploring short- and long-term effects
of various therapeutic interventions, such as coronary
angioplasty, on CFR.
In conclusion, the combined use of echo-contrast agents and second harmonic technology can succeed in detecting coronary blood flow and measuring flow and reserve in humans in a totally noninvasive way. Because of its noninvasive nature, this new method has potential in both pathophysiological and clinical studies. Larger studies are needed to investigate its potential in various diseases with possible CFR impairment.
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Acknowledgments |
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We would like to thank Maria Domenica Gaias, RN, for her technical assistance and Tracy Primm and Hetty Lewis for their assistance in the preparation of this manuscript.
Received July 2, 1998; revision received October 14, 1998; accepted October 26, 1998.
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References |
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A Hagendorff, A Werner, D Pfeiffer, and H Becher Estimation of vasodilator response by analysis of Doppler intensity kinetics with myocardial contrast echocardiography using an intravenous standardized bolus administration Eur J Echocardiogr, August 1, 2004; 5(4): 272 - 283. [Abstract] [Full Text] [PDF]
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S. Lee, Y. Otsuji, S. Minagoe, S. Hamasaki, K. Toyonaga, M. Negishi, M. Tsurugida, H. Toda, and C. Tei Noninvasive Evaluation of Coronary Reperfusion by Transthoracic Doppler Echocardiography in Patients With Anterior Acute Myocardial Infarction Before Coronary Intervention Circulation, December 2, 2003; 108(22): 2763 - 2768. [Abstract] [Full Text] [PDF]
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H. Lethen, H. P. Tries, S. Kersting, and H. Lambertz Validation of noninvasive assessment of coronary flow velocity reserve in the right coronary artery: A comparison of transthoracic echocardiographic results with intracoronary Doppler flow wire measurements Eur. Heart J., September 1, 2003; 24(17): 1567 - 1575. [Abstract] [Full Text] [PDF]
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A Auriti, C Cianfrocca, C Pristipino, S Greco, M Galeazzi, V Guido, and M Santini Improving feasibility of posterior descending coronary artery flow recording by transthoracic Doppler echocardiography Eur J Echocardiogr, September 1, 2003; 4(3): 214 - 220. [Abstract] [Full Text] [PDF]
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R Montisci, A Vacca, P Garau, P Colonna, M Ruscazio, G Passiu, S Iliceto, and A Mathieu Detection of early impairment of coronary flow reserve in patients with systemic sclerosis Ann Rheum Dis, September 1, 2003; 62(9): 890 - 893. [Abstract] [Full Text] [PDF]
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S. Hiraishi, H. Hirota, Y. Horiguchi, N. Takeda, N. Fujino, N. Ogawa, and Y. Nakahata Transthoracic Doppler assessment of coronary flow velocity reserve in children with Kawasaki disease: Comparison with coronary angiography and thallium-201 imaging J. Am. Coll. Cardiol., November 20, 2002; 40(10): 1816 - 1824. [Abstract] [Full Text] [PDF]
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M. Ruscazio, R. Montisci, P. Colonna, C. Caiati, L. Chen, G. Lai, M. Cadeddu, R. Pirisi, and S. Iliceto Detection of coronary restenosis aftercoronary angioplasty by contrast-enhanced transthoracic echocardiographic Doppler assessment of coronary flow velocity reserve J. Am. Coll. Cardiol., September 4, 2002; 40(5): 896 - 903. [Abstract] [Full Text] [PDF]
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M Teragaki, I Toda, M Takagi, S Fukuda, K Ujino, K Takeuchi, and J Yoshikawa New applications of intracardiac echocardiography: assessment of coronary blood flow by colour and pulsed Doppler imaging in dogs Heart, September 1, 2002; 88(3): 283 - 288. [Abstract] [Full Text] [PDF]
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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]
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M. Bonacchi, E. Prifti, G. Giunti, and A. Salica Right Y-graft, a new surgical technique using mammary arteries for total myocardial revascularization Ann. Thorac. Surg., September 1, 2000; 70(3): 820 - 823. [Abstract] [Full Text] [PDF]
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C. Caiati, N. Zedda, C. Montaldo, R. Montisci, and S. Iliceto Contrast-enhanced transthoracic second harmonic echo doppler with adenosine: A noninvasive, rapid and effective method for coronary flow reserve assessment J. Am. Coll. Cardiol., July 1, 1999; 34(1): 122 - 130. [Abstract] [Full Text] [PDF]
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