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Rassegna
della Letteratura
TAXUS III Trial
In-Stent Restenosis Treated With Stent-Based Delivery of Paclitaxel Incorporated
in a Slow-Release Polymer Formulation
Kengo Tanabe; Patrick W. Serruys; Eberhard Grube; Pieter C. Smits; Guido Selbach,
Willem J. van der Giessen; Manfred Staberock; Pim de Feyter; Ralf Müller;
Evelyn Regar, Muzaffer Degertekin, Jurgen M.R. Ligthart, Clemens Disco; Bianca
Backx; Mary E. Russell
Circulation 2003; 107: 517 – 520
Background— The first clinical study of paclitaxel-eluting stent for de
novo lesions showed promising results. We performed the TAXUS III trial to evaluate
the feasibility and safety of paclitaxel-eluting stent for the treatment of
in-stent restenosis (ISR).
Methods and Results— The TAXUS III trial was a single-arm, 2-center study
that enrolled 28 patients with ISR meeting the criteria of lesion length 30
mm, 50% to 99% diameter stenosis, and vessel diameter 3.0 to 3.5 mm. They were
treated with one or more TAXUS NIRx paclitaxel-eluting stents. Twenty-five patients
completed the angiographic follow-up at 6 months, and 17 of these underwent
intravascular ultrasound (IVUS) examination. No subacute stent thrombosis occurred
up to 12 months, but there was one late chronic total occlusion, and additional
3 patients showed angiographic restenosis. The mean late loss was 0.54 mm, with
neointimal hyperplasia volume of 20.3 mm3. The major adverse cardiac event rate
was 29% (8 patients; 1 non-Q-wave myocardial infarction, 1 coronary artery bypass
grafting, and 6 target lesion revascularization [TLR]). Of the patients with
TLR, 1 had restenosis in a bare stent implanted for edge dissection and 2 had
restenosis in a gap between 2 paclitaxel-eluting stents. Two patients without
angiographic restenosis underwent TLR as a result of the IVUS assessment at
follow-up (1 incomplete apposition and 1 insufficient expansion of the stent).
Conclusions— Paclitaxel-eluting stent implantation is considered safe and
potentially efficacious in the treatment of ISR. IVUS guidance to ensure good
stent deployment with complete coverage of target lesion may reduce reintervention.
Intravascular Ultrasound Guidance Improves Angiographic and Clinical Outcome
of Stent Implantation for Long Coronary Artery Stenoses: Final Results of a
Randomized Comparison With Angiographic Guidance (TULIP Study)
Pranobe V. Oemrawsingh, Gary S. Mintz, Martin J. Schalij, Aeilko H. Zwinderman,
J. Wouter Jukema, and Ernst E.v.d. Wall
Circulation 2003; 107: 62 – 67
Background— Long coronary lesions treated with stents have a poor outcome.
This study compared the 6-month outcome of stent implantation for long lesions
in patients randomized to intravascular ultrasound (IVUS; n=73) or angiographic
guidance (n=71).
Methods and Results— Stenoses >20 mm in length and a reference diameter
that permitted a stent diameter 3 mm were eligible. Primary end points were
6-month minimal lumen diameter (MLD) and the combined end point of death, myocardial
infarction, and target-lesion revascularization (TLR). Baseline clinical and
angiographic data were comparable in both groups. At 6 months, MLD in the IVUS
group (1.82±0.53 mm) was larger than in the angiography group (1.51±0.71
mm; P=0.042). TLR and combined end-point rates at 6 months were 4% (n=3) and
6% (n=4) in the IVUS group and 14% (n=10) and 20% (n=14) in the angiography
group, respectively (P=0.037 for TLR and P=0.01 for combined events). Restenosis
(>50% diameter stenosis) was found in 23% of the IVUS group and 45% of the
angiography group (P=0.008). At 12 months, TLR and the combined end point occurred
in 10% (n=7) and 12% (n=9) of the IVUS group and 23% (n=17) and 27% (n=19) of
the angiography group (P=0.018 and P=0.026), respectively.
Conclusions— Angiographic and clinical outcome up to 12 months after long
stent placement guided by IVUS is superior to guidance by angiography.
Two-Year Angiographic
and Intravascular Ultrasound Follow-Up After Implantation of Sirolimus-Eluting
Stents in Human Coronary Arteries
J. Eduardo Sousa, Marco A. Costa, Amanda G.M.R. Sousa, Alexandre C. Abizaid,
Ana C. Seixas, Andrea S. Abizaid, Fausto Feres, Luiz A. Mattos, Robert Falotico,
Judith Jaeger, Jeffrey J. Popma, and Patrick W. Serruys
Circulation 2003; 107: 381 - 383
Background— The safety and efficacy of sirolimus-eluting stenting have
been demonstrated, but the outcome of patients treated with this novel technology
beyond the first year remains unknown. We sought to evaluate the angiographic,
intravascular ultrasound (IVUS), and clinical outcomes of patients treated with
sirolimus-eluting stents 2 years after implantation.
Methods and Results— This study included 30 patients treated with sirolimus-eluting
Bx Velocity stenting (slow release [SR], n=15, and fast release [FR], n=15)
in São Paulo, Brazil. Twenty-eight patients underwent 2-year angiographic
and IVUS follow-up. No deaths occurred during the study period. In-stent late
loss was slightly greater in the FR group (0.28±0.4 mm) than in the SR
group (- 0.09±0.23 mm, P=0.007). No patient had in-stent restenosis.
At 2-year follow-up, only 1 patient (FR group) had a 52% diameter stenosis within
the lesion segment, which required repeat revascularization. The target-vessel
revascularization rate for the entire cohort was 10% (3/30) at 2 years. All
other patients had 35% diameter stenosis. Angiographic lumen loss at the stent
edges was also minimal (in-lesion late loss was 0.33±0.42 mm [FR] and
0.13±0.29 mm [SR]). In-stent neointimal hyperplasia volume, as detected
by IVUS, remained minimal after 2 years (FR= 9.90±9 mm3 and SR=10.35±9.3
mm3).
Conclusions— This study demonstrates the safety and efficacy of sirolimus-eluting
Bx Velocity stents 2 years after implantation in humans. In-stent lumen dimensions
remained essentially unchanged at 2-year follow-up in the 2 groups, although
angiographic lumen loss was slightly higher in the FR group. Restenosis "catch-up"
was not found in our patient population.
Paclitaxel Coating Reduces In-Stent Intimal Hyperplasia in Human Coronary Arteries:
A Serial Volumetric Intravascular Ultrasound Analysis From the ASian Paclitaxel-Eluting
Stent Clinical Trial (ASPECT)
Myeong-Ki Hong, Gary S. Mintz, Cheol Whan Lee, Jong-Min Song, Ki-Hoon Han, Duk-Hyun
Kang, Jae-Kwan Song, Jae-Joong Kim, Neil J. Weissman, Neal E. Fearnot, Seong-Wook
Park, and Seung-Jung Park Circulation 2003; 107: 517 - 520
Background— The aim of this study was to use serial volumetric intravascular
ultrasound (IVUS) to evaluate the effect of a paclitaxel coating on in-stent
intimal hyperplasia (IH).
Methods and Results— Patients were randomized to placebo (bare metal stents)
or 1 of 2 doses of paclitaxel (low dose: 1.28 µg/mm2; high dose: 3.10
µg/mm2). Complete post-stent implantation and follow-up IVUS were available
in 81 patients, including 25 control patients and in 28 receiving a lowdose
and 28 receiving a high dose. Volumetric analysis of the stented segment and
of both reference segments was performed. Baseline stent measurements and both
reference measurements were similar among the groups. With increasing doses,
there was a stepwise reduction in IH accumulation within the stented segment
(31±22 mm3 in control, 18±15 mm3 in low dose, and 13±14
mm3 in high dose, P<0.001). Post hoc analysis showed less IH accumulation
when low- and high-dose patients were compared with control (P=0.009 and P<0.001,
respectively), but not when low-dose patients were compared with high-dose patients
(P=0.2). Focal late malapposition was seen in 1 high-dose patient. With increasing
doses, there was no significant change in the reference segments.
Conclusions— Paclitaxel-coated stents are effective in reducing in-stent
neointimal tissue proliferation in humans. They are not associated with edge
restenosis or significant late malapposition.
Heparin-Coated Stent Placement for the Treatment of Stenoses in Small Coronary
Arteries of Symptomatic Patients
Michael Haude, Thomas F.M. Konorza, Uldis Kalnins, Andrejs Erglis, Kari Saunamäki,
Helmut D.Glogar, Eberhard Grube, Robert Gil, Antonio Serra, Hans G. Richardt,
Peter Sick, and Raimund Erbel
Circulation 2003; 107: 1265 – 1270
Background— The role of stents, especially of heparin-coated stents for
the treatment of stenoses in small coronary arteries, is still unclear. Therefore,
we performed this prospective, randomized trial to evaluate the angiographic
and clinical outcome after treatment of stenoses in small coronary arteries
(2.0 to 2.6 mm) of symptomatic patients.
Methods and Results— We randomly assigned 588 patients to angioplasty (n=195),
bare stenting (n=196), or heparin-coated stenting (n=197). The primary end point
was minimal lumen diameter (MLD) at 6 months. With comparable baseline parameters,
the two stent arms showed a larger postinterventional MLD, larger acute gain,
and smaller residual percent diameter stenosis, although a residual stenosis
of 12±16% was achieved in the angioplasty arm, including a 27% crossover
rate to stenting. Eighty percent of patients had follow-up angiography, which
documented a borderline significantly larger MLD and smaller percent diameter
stenosis for the two stent groups (1.34±0.48 mm and 42±20% after
angioplasty, 1.47±0.48 mm and 36±20% after bare stenting, and
1.45±0.54 mm and 38±23% after heparin-coated stenting; P=0.049
and P=0.038, respectively), but restenosis rates were not different (32%, 25%,
and 30%). Thrombotic events occurred in 1.0% after angioplasty and 0.5% after
bare or heparin-coated stenting. Survival without myocardial infarction or target
vessel revascularization at 250 days was 84.6% (angioplasty), 88.3% (bare stenting),
and 88.3% (heparin-coated stenting; logrank P=0.39).
Conclusion— Compared with angioplasty with provisional stenting, bare and
heparin-coated stenting confer superior angiographic results and a nonsignificant
24% reduction in clinical events, with no difference between bare and heparin-coated
stenting in the treatment of stenoses in small coronaryarteries.
Adjunctive Platelet Glycoprotein IIb/IIIa Receptor Inhibition With Tirofiban
Before Primary Angioplasty Improves Angiographic Outcomes: Results of the TIrofiban
Given in the Emergency Room before Primary Angioplasty (TIGER-PA) Pilot Trial
David P. Lee, Niall A. Herity, Bonnie L. Hiatt, William F. Fearon, Mehrdad Rezaee,
Andrew J. Carter, Michelle Huston, Donald Schreiber, Peter M. DiBattiste, and
Alan C. Yeung
Circulation 2003; 107: 1497 - 1501
Background— Previous work has suggested that platelet glycoprotein IIb/IIIa
receptor blockade may confer benefit in the treatment of acute myocardial infarction.
The TIGER-PA pilot trial was a singlecenter randomized study to evaluate the
safety, feasibility, and utility of early tirofiban administration before planned
primary angioplasty in patients presenting with acute myocardial infarction.
Methods and Results— A total of 100 patients presenting with acute myocardial
infarction were randomized to either early administration of tirofiban in the
emergency room or later administration in the catheterization laboratory. The
primary outcome measures were initial TIMI grade flow, corrected TIMI frame
counts, and TIMI grade myocardial perfusion ("blush"). Thirty-day
major adverse cardiac events were also assessed. Angiographic outcomes demonstrate
a significant improvement in initial TIMI grade flow, corrected TIMI frame counts,
and TIMI grade myocardial perfusion when patients are given tirofiban in the
emergency room before primary angioplasty. The rate of 30-day major adverse
cardiac events suggests that early administration may be beneficial.
Conclusions— This pilot study suggests that early administration of tirofiban
improves angiographic outcomes and is safe and feasible in patients undergoing
primary angioplasty for acute myocardial infarction.
Detection of Coronary Artery Stenoses With Thin-Slice Multi-Detector Row
Spiral Computed Tomography and Multiplanar Reconstruction
Dieter Ropers, Ulrich Baum, Karsten Pohle, Katharina Anders, Stefan Ulzheimer,
Bernd Ohnesorge, Christian Schlundt, Werner Bautz, Werner G. Daniel, and Stephan
Achenbach Circulation 2003; 107: 664 – 666
Background— We analyzed the accuracy of multi-detector row spiral computed
tomography (MDCT) using a 16-slice CT scanner with improved spatial and temporal
resolution, as well as routine premedication with ß-blockers for detection
of coronary stenoses.
Methods and Results— Seventy-seven patients with suspected coronary disease
were studied by MDCT (12x0.75-mm cross-sections, 420 ms rotation, 100 mL contrast
agent IV at 5 mL/s). Patients with a heart rate above 60/min received 50 mg
atenolol before the scan. In axial MDCT images and multiplanar reconstructions,
all coronary arteries and side branches with a diameter of 1.5 mm or more were
assessed for the presence of stenoses exceeding 50% diameter reduction. In comparison
to invasive coronary angiography, MDCT correctly classified 35 of 41 patients
(85%) as having at least 1 coronary stenosis and correctly detected 57 of 78
coronary lesions (73%). After excluding 38 of 308 coronary arteries (left main,
left anterior descending, left circumflex, and right coronary artery in 77 patients)
classified as unevaluable by MDCT (12%), 57 of 62 lesions were detected, and
absence of stenosis was correctly identified in 194 of 208 arteries (sensitivity:
92%; specificity: 93%; accuracy: 93%; positive and negative predictive values:
79% and 97%).
Conclusions— MDCT coronary angiography with improved spatial resolution
and premedication with oral ß-blockade permits detection of coronary artery
stenoses with high accuracy and a low rate of unevaluable arteries.
Intracardiac Echocardiography Is Superior to Conventional Monitoring for
Guiding Device Closure of Interatrial Communications
Thomas Bartel, Thomas Konorza, Jawed Arjumand, Tiko Ebradlidze, Holger Eggebrecht,
Guido Caspari, Ulrich Neudorf, and Raimund Erbel Circulation 2003; 107: 795
- 797
Background— This study sought to test whether intracardiac echocardiography
(ICE) is superior to conventional monitoring in guiding device closure of interatrial
communications (atrial septal defect [ASD] and patent foramen ovale [PFO]).
Methods and Results— Forty-four patients undergoing device closure of ASD
(n=6) or PFO (n=38) were randomized to have the procedure guided by either ICE
(group 1; n=22) or by transesophageal echocardiography (TEE) (group 2; n=22).
All interventions were completed successfully. In 1 patient from group 2, atrial
fibrillation occurred 1 day after device implantation; the patient was successfully
cardioverted on the next day. There were no other complications. Fluoroscopy
time (FT) (6.0±1.7 minutes versus 9.5±1.6 minutes; P<0.0001)
as well as procedure time (PT) (33.4±4.7 minutes versus 37.8±5.6
minutes; P<0.01) were shorter in group 1 than in group 2. Group 2 patients
required general anesthesia without (n=19) or with endotracheal intubation (n=3).
In contrast, ICE allowed continuous monitoring of the whole procedure, including
balloon sizing before device closure, without sedation.
Conclusions— ICE is a safe tool to guide device closure of PFO and ASD.
Supine patients tolerate ICE better than TEE. ICE reduces FT and PT. ICE seems
to be advantageous, especially when long continuous or repeated echocardiographic
viewing is required.
Early and Late Effects of Clopidogrel in Patients With Acute Coronary Syndromes
Salim Yusuf, Shamir R. Mehta, Feng Zhao, Bernard J. Gersh, Patrick J. Commerford,
Mel Blumenthal, Andrzej Budaj, Thomas Wittlinger, and Keith A.A. Fox
Circulation 2003; 107: 966 – 972
Background— The risk of ischemic events is high, both early and late after
acute coronary syndromes (ACS). We examine the benefits and risks associated
with the use of adding clopidogrel to aspirin within the first 30 days and later
(31 days to 12 months) in 12 562 patients with ACS.
Methods and Results— A total of 12 562 ACS patients were randomized to
receive clopidogrel (300 mg initially followed by 75 mg/d) or placebo for 3
to 12 mo nths. The proportion of patients experiencing cardiovascular death,
myocardial infarction, or strokes (primary outcome) at 30 days was 5.4% in the
placebo group and 4.3% in the active group (relative risk 0.79, 95% CI 0.67
to 0.92). Beyond 30 days, the corresponding rates were 6.3% versus 5.2% (relative
risk 0.82, 95% CI 0.70 to 0.95). There was no significant excess in life-threatening
bleeds in each period (0.97% versus 1.28%, relative risk 1.32, 95% CI 0.95 to
1.84 for 0 to 30 days; 0.83% versus 0.91%, relative risk 1.09, 95% CI 0.75 to
1.59 for 31 days to 12 months). Further subdivision of the early data indicates
benefits within 24 hours with consistently lower rates of the primary outcome
in combination with refractory or severe ischemia.
Conclusions— Clopidogrel reduces the risk of ischemic vascular events,
with the benefits emerging within 24 hours of initiation of treatment and continuing
throughout the 12 months (mean 9 months) of the study.
Pilot Trial of Oral Rapamycin for Recalcitrant Restenosis
Prabhtej S. Brara, Mehran Moussavian, Mark A. Grise, John P. Reilly, Mindy Fernandez,
Richard A. Schatz, and Paul S. Teirstein
Circulation 2003; 107: 1722 – 1724
Background— Sirolimus-coated stents are a promising new therapy for restenosis.
We treated a select group of patients at especially high risk for restenosis
with oral sirolimus.
Methods and Results— Patients were treated with an oral sirolimus-loading
dose of 6 mg after coronary angioplasty, followed by 2 mg/d for 4 weeks. Serum
electrolytes, lipid profile, renal panel, and complete blood cell count were
measured at 1, 3, and 5 weeks after drug initiation. Oral sirolimus was prescribed
to 22 patients who had a total of 28 lesions and were at high risk for restenosis.
Of the 22 study patients, 11 (50%) discontinued oral sirolimus early because
of side effects or laboratory abnormalities. Hypertriglyceridemia and leukopenia
were the most frequent adverse events, occurring in 3 patients each. All adverse
drug effects were reversible after discontinuation. Follow-up was obtained in
100% of patients at a mean of 9.9±1.8 months, ranging from 6.5 to 11.8
months. Target lesion revascularization (TLR) occurred in 15 of 28 lesions (53.6%)
and 13 of 22 patients (59.1%). There was no difference in TLR for patients receiving
a complete course of sirolimus (n=8; 72.7%) compared with patients who terminated
treatment prematurely (n=5; 45.5%; P=NS). Clinically driven repeat cardiac catheterization
was obtained in 15 (68.2%) patients; restenosis (>50% diameter stenosis at
follow-up) was present in 13 (86.7%).
Conclusion— Oral sirolimus does not appear to provide benefit to patients
with recalcitrant restenosis. Adverse drug effects are frequent, underscoring
the importance of local drug delivery to achieve high tissue concentrations
without systemic adverse drug effects.
Noninvasive Determination of Coronary Blood Flow Velocity With Cardiovascular
Magnetic Resonance in Patients After Stent Deployment
Eike Nagel, Thomas Thouet, Christoph Klein, Simon Schalla, Axel Bornstedt, Bernhard
Schnackenburg, Jürgen Hug, Ernst Wellnhofer, and Eckart Fleck
Circulation 2003; 107: 1738 – 1743
Background— In patients with coronary artery stents, no direct noninvasive
coronary artery imaging is possible with magnetic resonance (MR). A well-established
method for the assessment of the functional significance of a coronary lesion
is the measurement of coronary flow reserve by invasive intracoronary Doppler.
The purpose of the study was to determine coronary flow velocity reserve (CFVR)
with MR after stent deployment.
Methods and Results— Thirty-eight patients after successful PTCA and stent
deployment were included. CFVR was measured perpendicular to the artery distal
to the stent using phase-contrast velocity quantification at rest and during
adenosine-stimulated hyperemia with a 1.5T MR tomograph (ACS NT, Philips). Measurements
were repeated after 3 months and compared with invasive coronary angiography.
In 18 patients, additional invasive Doppler flow measurements were obtained.
CFVR could be determined in 29 of 38 (76%) of the patients. After 3 months,
significant differences were obtained between coronary arteries with and without
restenosis. Using a threshold of 1.2, a sensitivity of 83% with a specificity
of 94% was achieved for 75% stenoses. CFVR with CMR was similar to Doppler results
(r=0.87), with a mean relative difference of 7.5%.
Conclusions— In patients with preserved coronary microcirculating vasoreactivity
that are suitable for MR coronary angiography and flow assessments, CMR measures
of coronary blood flow velocities reserve may be used to detect in-stent restenosis.
Relation of Inflammation and Benefit of Statins After Percutaneous Coronary
Interventions
Albert W. Chan, Deepak L. Bhatt, Derek P. Chew, Joel Reginelli, Jakob P. Schneider,
Eric J. Topol, and Stephen G. Ellis
Circulation 2003; 107: 1750 – 1756
Background— Beyond lipid lowering, statins are known to possess antiinflammatory
and antithrombotic properties. Recent studies suggested an association between
statins and early reduction in death or myocardial infarction (MI) after percutaneous
coronary interventions (PCIs). We sought to examine the interrelationship between
inflammation, statin use, and PCI outcomes.
Methods and Results— In the year 2000, 1552 consecutive United States residents
underwent elective or urgent PCI at the Cleveland Clinic and were prospectively
followed for 1 year. Preprocedural serum high-sensitivity C-reactive protein
(hsCRP) levels were routinely measured. Patients who had statins initiated before
the procedure (39.6%) had a lower median hsCRP level (0.40 versus 0.50 mg/dL,
P=0.012) independent of the baseline cholesterol levels and had less frequent
periprocedural MI (defined by CKMB 3xupper limit of normal, 5.7% versus 8.1%,
P=0.038). At 1 year, statin pretreatment was predictive of survival predominantly
among patients within the highest hsCRP quartile (mortality rate with statin
pretreatment versus no pretreatment when hsCRP 1.11 mg/dL, 5.7% versus 14.8%,
P=0.009). Using multivariate analysis, preprocedural hsCRP level remained an
independent predictor for 1-year death or MI only in patients without statin
therapy (hazard ratio, 1.32/quartile; P=0.001). After adjusting for the propensity
of receiving statins, statin pretreatment was an independent predictor for 1-year
survival within the highest hsCRP quartile (hazard ratio, 0.44; P=0.039).
Conclusions— Statin therapy before PCI is associated with a marked reduction
in mortality among patients with high hsCRP levels. A hsCRP-guided strategy
may improve targeting of statin therapy and clinical outcome among patients
undergoing PCI.
Reduction of Major Adverse Cardiac Events With Intracoronary Compared With Intravenous
Bolus Application of Abciximab in Patients With Acute Myocardial Infarction
or Unstable Angina Undergoing Coronary Angioplasty
Jochen Wöhrle, Olaf C. Grebe, Thorsten Nusser, Eyas Al-Khayer, Stefan Schaible,
Matthias Kochs, Vinzenz Hombach, and Martin Höher
Circulation 2003; 107: 1840 – 1843
Background— In patients with acute myocardial infarction or unstable angina
undergoing coronary angioplasty, abciximab reduces major adverse cardiac events
(MACE). Clinical trials have studied intravenous administration only. Intracoronary
bolus application of abciximab causes very high local drug concentrations and
may be more effective. We studied whether intracoronary bolus administration
of abciximab is associated with a reduced MACE rate compared with the standard
intravenous bolus application.
Methods and Results— We stratified 403 consecutive patients with acute
myocardial infarction or unstable angina undergoing coronary angioplasty according
to the type of application of abciximab. A 20-mg bolus of abciximab was given
intravenously in 109 patients and intracoronarily in 294 patients. There were
no differences between the groups with regard to diabetes mellitus, cardiogenic
shock, successful intervention, or preprocedural and postprocedural TIMI flow.
At 30 days, the incidence of MACE (death, myocardial infarction, urgent revascularization)
was significantly lower in the patients with intracoronary compared with intravenous
administration of abciximab (10.2% versus 20.2%; P<0.008), which was independent
from stenting in multivariate analysis. The effect was most pronounced in patients
with preprocedural TIMI 0/1 flow (MACE: intracoronary 11.8% versus intravenous
27.5%, P<0.002; n=273).
Conclusions— In patients with acute myocardial infarction or unstable angina
undergoing emergency coronary angioplasty, intracoronary bolus application of
abciximab is associated with a reduction of MACE compared with the standard
intravenous bolus application of abciximab. Prospective, randomized trials are
warranted to further assess intracoronary application of abciximab.
Intracoronary and Intravenous Adenosine 5'-Triphosphate, Adenosine, Papaverine,
and Contrast Medium to Assess Fractional Flow Reserve in Humans
Bernard De Bruyne, Nico H.J. Pijls, Emanuele Barbato, Jozef Bartunek, Jan-Willem
Bech, William Wijns, and Guy R. Heyndrickx
Circulation 2003; 107: 1877 – 1883
Background— Inducing both maximal and steady-state coronary hyperemia is
of clinical importance to take full advantage of fractional flow reserve measurements.
The present study compares different dosages and routes of administration of
adenosine 5'-triphosphate (ATP), adenosine, contrast medium, and papaverine
regarding their potential to achieve both maximal and steady-state hyperemia.
Methods and Results— In 21 patients with an isolated coronary stenosis,
coronary vasodilation was induced successively by papaverine (20 mg intracoronary),
adenosine (20 and 40 µg intracoronary), ATP (20 and 40 µg intracoronary),
iohexol (6 mL intracoronary), adenosine or ATP through an antecubital vein (140
and 180 µg · kg-1 · min-1), or adenosine or ATP through
a femoral vein (140 and 180 µg · kg-1 · min-1). Because
vessel dimensions did not change, the ratio of distal coronary pressure (Pd)
to aortic pressure (Pa) was used as an index of myocardial resistance. Pd/Pa
was 0.77±0.21 at rest and decreased to 0.61±0.21 after papaverine.
Pd
/Pa decreased to a similar level with all other vasodilators, except with contrast
medium (0.68±0.21; P<0.01 versus papaverine). Steady-state hyperemia
could only be obtained by intracoronary papaverine and by intravenous ATP or
adenosine. In another 23 patients, an intravenous infusion of ATP was varied
from 0 to 280 µg · kg-1 · min-1. At doses >140 µg
· kg-1 · min-1, there was neither a further decrease in Pd/Pa
ratio nor a further increase in coronary flow velocities.
Conclusion— Provided sufficient dosages are used, ATP, adenosine, and papaverine
(but not contrast medium) induce maximal hyperemia and are therefore suitable
to assess fractional flow reserve. Only intracoronary papaverine and intravenous
ATP or adenosine induce steady-state hyperemia enabling a pressure pullback
maneuver that is useful in assessing diffuse coronary atherosclerosis.