Frank V. Aguirre

Correlation of pharmacological 99mTc-sestamibi myocardial perfusion imaging with poststenotic coronary flow reserve in patients with angiographically intermediate coronary artery stenoses.

BACKGROUND The physiological assessment of angiographically intermediate-severity stenoses remains problematic. Functional measurements of poststenotic intracoronary Doppler coronary flow reserve can be performed in humans but have not been correlated with hyperemic myocardial perfusion imaging or angiographic data in this patient population. METHODS AND RESULTS Thirty-three patients undergoing diagnostic quantitative coronary angiography (QCA) for assessment of intermediate-severity coronary artery disease (mean QCA percent diameter stenosis, 56 +/- 14%) were studied. Proximal and distal poststenotic Doppler coronary flow velocities were measured (left anterior descending coronary artery, 16; right coronary artery, 10; left circumflex artery, 7 patients) before and during peak maximal hyperemia with intracoronary adenosine (8 to 12 micrograms). Intravenous pharmacological stress (adenosine, 20 patients; dipyridamole, 13 patients) 99mTc-sestamibi tomographic perfusion imaging was performed within 1 week of coronary flow-velocity studies. kappa statistics were calculated to measure the strength of correlation among coronary flow velocities, perfusion imaging data, and QCA results. QCA stenosis severity (abnormal, > or = 50% diameter stenosis) and poststenotic Doppler coronary flow reserve (ratio of abnormal distal hyperemic to basal flow, < or = 2.0) were correctly correlated in 20 of 27 patients (74%; kappa = .48). QCA stenosis severity and 99mTc-sestamibi imaging (abnormal if one or more reversible myocardial segments were present in the poststenotic zone) were correlated in 28 of 33 patients (85%; kappa = .63). 99mTc-sestamibi imaging results agreed with the basal (nonhyperemic) proximal-to-distal velocity ratio (normal, < 1.7) in 15 of 31 patients (48%; kappa = .17). The strongest correlation occurred between hyperemic distal flow-velocity ratio measurements and 99mTc-sestamibi perfusion imaging results in 24 of 27 patients (89%; kappa = .78). All 14 patients with abnormal distal hyperemic flow-velocity values had corresponding reversible 99mTc-sestamibi tomographic defects. More reversibly hypoperfused segments were present in patients with abnormal poststenotic hyperemic flow-velocity ratios (abnormal, 2.4 +/- 0.7 segments; normal, 0.6 +/- 1.0 segments; P < .05). The number of poststenotic myocardial 99mTc-sestamibi perfusion defects was correlated with the QCA percent cross-sectional area reduction (P < .02) and with minimal luminal diameter (P < .05) of intermediate-severity coronary artery stenoses. CONCLUSIONS Two technologically diverse functional measures of stenosis severity--Doppler-derived poststenotic hyperemic intracoronary flow reserve and vasodilator stress 99mTc-sestamibi myocardial perfusion imaging--are highly (89%) correlated. The physiological assessment of coronary stenoses of angiographically intermediate severity may be improved by the use of these techniques.

Analysis of coronary blood flow velocity dynamics in angiographicaily normal and stenosed arteries before and after endolumen enlargement by angioplasty

OBJECTIVES This study was designed to assess whether the spectral waveform of coronary velocity on Doppler study is characteristically altered in the presence of significant stenosis with normalization of the spectral waveform after relief of endolumen obstruction. BACKGROUND Although coronary flow reserve determinations have provided physiologic information complementary to the angiographic percent diameter narrowing, flow velocity measurements have been limited to proximal arteries with inconsistent results after angioplasty. A 12-MHz Doppler guide wire permits flow velocity determination in the proximal and distal coronary artery with fast Fourier spectral analysis. METHODS With the Doppler guide wire, proximal arterial flow velocity and flow reserve measurements in 17 angiographically normal arteries were compared with measurements in 29 significantly stenosed arteries. Proximal and distal flow velocity measurements were also obtained before and after angioplasty of the 29 abnormal arteries. Velocity spectrum was digitized to compute peak diastolic velocity, peak systolic velocity, mean velocity, diastolic/systolic velocity ratio and first third and first half flow fraction. RESULTS Compared with proximal stenosed arteries, proximal normal arteries had significantly higher peak diastolic velocity (64 +/- 26 cm/s vs. 41 +/- 26 cm/s) and higher coronary vasodilator reserve (2.3 +/- 0.8 vs. 1.6 +/- 0.7). Normal arteries had higher flows in the first third and first half of the coronary cycle (46 +/- 3% vs. 39 +/- 7% and 65 +/- 2% vs. 56 +/- 10%, respectively). Before angioplasty, coronary velocity variables were significantly lower distal than proximal to the stenosis. After angioplasty, there was a greater mean increase in distal velocities (200% vs. 90% for the proximal arteries) that resulted in near equalization of proximal and distal mean velocity and a significant reduction in proximal/distal mean velocity ratio (2.4 +/- 1.7 vs. 1.2 +/- 0.4). CONCLUSIONS Before angioplasty, abnormal coronary flow velocity dynamics are more marked distal than proximal to the stenosis. Greater increase in coronary flow velocities in the distal circulation after relief of endolumen obstruction results in a significant reduction in the proximal/distal flow velocity ratio. Thus, normalization of Doppler-derived flow velocity variables with marked reduction of the proximal/distal flow velocity ratios parallels angiographic success and may prove useful as an additional end point measurement in interventional cases with questionable angiographic findings.

Bleeding Complications With the Chimeric Antibody to Platelet Glycoprotein IIb/IIIa Integrin in Patients Undergoing Percutaneous Coronary Intervention

BACKGROUND The potential for novel antiplatelet and antithrombin agents to contribute to periprocedural bleeding complications of percutaneous coronary revascularization is poorly defined. In the Evaluation of c7E3 Fab in Preventing Ischemic Complications of High-Risk Angioplasty (EPIC) trial, the periprocedural use of aspirin, heparin, and a chimeric antibody to the platelet glycoprotein IIb/IIIa integrin c7E3 Fab in 2099 patients significantly reduced postprocedural ischemic complications and 6-month clinical restenosis but was associated with increased procedural bleeding complications. We review these complications and describe clinical and procedural variables associated with increased bleeding complications in the EPIC trial. METHODS AND RESULTS Patients with high-risk clinical or lesion morphological characteristics were randomized to receive placebo bolus plus placebo infusion, c7E3 Fab bolus plus placebo infusion, or c7E3 Fab bolus plus c7E3 Fab infusion. Patients received periprocedural aspirin and intravenous heparin continued for a minimum of 12 hours after the procedure. Outcomes reflecting bleeding complications were measured: transfusions, decreased hemoglobin, and an index including both parameters. Major bleeding complications unrelated to bypass surgery occurred in 3.3%, 8.6%, and 10.6%, and blood product transfusions were used in 7.5%, 14.0%, and 16.8% of patients treated with placebo, bolus c7E3 Fab, and bolus plus infusion c7E3 Fab, respectively (both P < .001). Most major bleeding complications occurred at the femoral access site, regardless of treatment. Intracranial hemorrhage (0.3%) and death (0.09%) attributable to major bleeding complications were rare. Multivariable regression analyses identified several variables significantly and independently related to major bleeding complications or greater blood loss, including greater age, female sex, lower weight, c7E3 Fab therapy, and duration and complexity of the index procedure. Major bleeding complications and blood loss in patients receiving bolus plus infusion were not significantly greater than in those receiving bolus alone (P = .38 and P = .14, respectively). CONCLUSIONS Bleeding complications unrelated to bypass surgery were two to three times more frequent in patients receiving c7E3 Fab than in those receiving placebo, but most were transient and well tolerated. Risk-factor analysis and modification of concomitant antithrombotic and antiplatelet treatment strategies may aid in reducing bleeding complications and enhancing clinical benefit in patients receiving c7E3 Fab during percutaneous coronary revascularization.

Augmentation of coronary blood flow by intra-aortic balloon pumping in patients after coronary angioplasty.

BackgroundControversy exists regarding the ability of intra-aortic balloon pumping to increase coronary blood flow in patients with obstructive coronary artery disease. To assess the effects of intra-aortic balloon pumping on coronary hemodynamics, we measured coronary blood flow velocity with a 0.018-in. Doppler-tipped angioplasty guide wire in 15 patients who received an intra-aortic balloon pump for typical clinical indications. Methods and ResultsIntra-aortic balloon pumping augmented diastolic pressure 83±35%. In nine patients before angioplasty, peak diastolic coronary flow velocity beyond the stenosis (mean diameter narrowing, 95±7%) was 5.3±9.6 cm/sec and was unaffected by intra-aortic balloon pumping. After angioplasty, the improved coronary luminal diameter narrowing (n=12; mean narrowing, 18±12%) was associated with increased distal diastolic flow velocity integral and peak diastolic and mean velocities (13.3±8.4 units: 36.4±18.3 and 24.0±+11.4 cm/sec, respectively; all p<0.01 versus before angioplasty), which were further augmented (36±37%, 54±49%o, and 26+17%, respectively; allp<0.01) with intra-aortic balloon pumping. Intra-aortic balloon pumping did not significantly increase the distal systolic velocity integral (10+59%o) or peak systolic velocity (3±33%). Similar degrees of balloon pump augmentation of distal coronary flow velocity values were observed in five angiographically normal reference arteries in four patients. ConclusionThese data demonstrate lack of significant flow improvement beyond most critical stenoses with intra-aortic balloon pumping and the unequivocal restoration and intra-aortic balloon pump-mediated augmentation of both proximal and distal coronary blood flow velocities after amelioration of severe coronary obstructions in patients after successful coronary angioplasty.

Evidence for Prevention of Death and Myocardial Infarction With Platelet Membrane Glycoprotein IIb/IIIa Receptor Blockade by Abciximab (c7E3 Fab) Among Patients With Unstable Angina Undergoing Percutaneous Coronary Revascularization

OBJECTIVES We sought to evaluate whether patients with unstable angina undergoing coronary intervention derive particular clinical benefit from potent platelet inhibition. BACKGROUND Plaque rupture and platelet aggregation are pathogenetic processes common to unstable angina and ischemic complications of percutaneous coronary intervention. METHODS Of the 2,099 patients undergoing a coronary intervention in the Evaluation of 7E3 in Preventing Ischemic Complications (EPIC) trial, 489 were enrolled with the diagnosis of unstable angina and randomized to receive placebo, an abciximab (c7E3) bolus immediately before the intervention or an abciximab bolus followed by a 12-h infusion. The primary end point was a composite of death, myocardial infarction (MI) or urgent repeat revascularization within 30 days of randomization. The occurrence of death, MI or any revascularization within 6 months was also assessed. RESULTS Compared with placebo, the bolus and infusion of abciximab resulted in a 62% reduction in the rate of the primary end point (12.8% vs. 4.8%, p = 0.012) among patients with unstable angina, due primarily to a reduction in the incidences of death (3.2% vs. 1.2%, p = 0.164) and MI (9% vs. 1.8%, p = 0.004). By 6 months, cumulative death and MI were further reduced by abciximab (6.6% vs. 1.8%, p = 0.018 and 11.1% vs. 2.4%, p = 0.002, respectively). The magnitude of the risk reduction with abciximab was greater among the patients with unstable angina than among other patients in the EPIC trial without unstable angina for the end points of death (interaction: p = 0.008 at 30 days, p = 0.002 at 6 months) and MI (interaction: p = 0.004 at 30 days, p = 0.003 at 6 months). CONCLUSIONS The syndrome of unstable angina identifies patients who will experience particularly marked reductions in the risk of death and MI with abciximab during coronary intervention.

Intravenous adenosine : continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease

To assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 micrograms/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1] and 17 with [group 2] significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine. The maximal adenosine dose did not change mean arterial pressure (-10 +/- 14% and -6 +/- 12% for groups 1 and 2, respectively) but increased the heart rate (15 +/- 18% and 13 +/- 16, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 +/- 104%, 122 +/- 94% and 198 +/- 59% and 15 +/- 51%, 110 +/- 95% and 109 +/- 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 micrograms/kg of adenosine and 10 mg of intracoronary papaverine (48 +/- 25, 52 +/- 19 and 54 +/- 21 cm/s, respectively; all p less than 0.05 vs. baseline) and was significantly higher than in group 2 (37 +/- 24, 32 +/- 16, 41 +/- 23 cm/s; all p less than 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 +/- 1.50 and 2.94 +/- 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 +/- 0.81 and 2.38 +/- 0.78, respectively; both p less than 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalently to that after continuous infusion of 100 micrograms/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2 = 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p less than 0.0005). No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QT (QTc) interval from 445 +/- 44 to 501 +/- 43 ms (p less than 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements.

OBJECTIVES The objective of this study was to determine the feasibility, safety and outcome of deferring angioplasty in patients with angiographically intermediate lesions that are found not to limit flow, as determined by direct translesional hemodynamic assessment. BACKGROUND The clinical importance of some coronary stenoses of intermediate angiographic severity frequently requires noninvasive stress testing. Direct translesional pressure and flow measurements may assist in clinical decision making in patients with such stenoses. METHODS Translesional spectral flow velocity (Doppler guide wire) and pressure data were obtained in 88 patients for 100 lesions (26 single-vessel and 74 multivessel coronary artery lesions) with quantitative angiographic coronary narrowings (mean +/- SD diameter narrowing 54 +/- 7% [range 40% to 74%]). Target lesion angioplasty was prospectively deferred on the basis of predetermined normal values, defined as a proximal/distal velocity ratio < 1.7 or a pressure gradient < 25 mm Hg, or both. Patients were followed up for 9 +/- 5 months (range 6 to 30). RESULTS In the deferred angioplasty group, translesional velocity ratios were similar to those of a normal reference group (mean 1.1 +/- 0.32 vs. 1.3 +/- 0.55) and significantly lower than those of a reference cohort of patients who had undergone angioplasty (2.27 +/- 1.2, p < 0.05). The mean translesional pressure gradient in the deferred angioplasty group was also lower than that in the angioplasty group (10 +/- 9 vs. 45 +/- 22 mm Hg, p < 0.001). At follow-up in the deferred angioplasty group, four, six, zero and two patients, respectively, had had subsequent angioplasty, coronary artery bypass graft surgery or myocardial infarction or had died. In one patient, death was related to angioplasty of a nontarget artery lesion, and one patient with multivessel disease had a cardiac arrest due to ventricular fibrillation 12 months after lesion assessment. Among the 10 patients requiring later angioplasty or coronary artery bypass grafting, only six procedures were performed on target arteries. No patient had a complication of translesional flow or pressure measurements. CONCLUSIONS These data demonstrate the safety, feasibility and clinical outcome of deferring angioplasty of coronary artery narrowings associated with normal translesional coronary hemodynamic variables. Given the practice of performing angioplasty without ischemic testing or when testing is inconclusive, translesional hemodynamic data obtained at diagnostic catheterization can identify patients in whom it is safe to postpone angioplasty.

Assessing the hemodynamic significance of coronary artery stenosis: Analysis of translesional pressure-flow velocity relations in patients☆

OBJECTIVES The purpose of this study was to examine the relation among the angiographic severity of coronary artery lesions, coronary flow velocity and translesional pressure gradients. BACKGROUND Determination of the clinical and hemodynamic significance of coronary artery stenoses is often difficult and inexact. Angiography has been shown to be an imperfect tool for determining the physiologic significance of eccentric or irregular coronary lumen narrowing. METHODS Using a 0.018-in. (0.046 cm) intracoronary Doppler-tipped angioplasty guide wire, spectral flow velocity data both proximal and distal to coronary stenoses were compared with translesional pressure gradient measurements and angiographic data obtained during cardiac catheterization in 101 patients. There were 17 patients with normal angiographic findings and 84 with coronary artery disease, with lesions ranging from 28% to 99% diameter narrowing. Patients with coronary disease were assigned to two groups on the basis of translesional gradients at rest. Group A (n = 56) had gradients < 20 mm Hg, and Group B (n = 28) had gradients > or = 20 mm Hg. RESULTS Proximal average peak velocity, diastolic velocity integral and total velocity integral were slightly but statistically lower in Group A; however, the distal average peak velocity and diastolic and total velocity integrals were all markedly (all p < 0.01) decreased in patients with gradients > or = 20 mm Hg (Group B). In addition, the ratio of proximal to distal total flow velocity integral was higher in Group B (2.4 +/- 1.0) than in group A (1.1 +/- 0.3, p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal to distal total flow velocity integrals (r = 0.8, p < 0.001), with a weaker relation between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). In angiographically intermediate stenoses (range 50% to 70%), angiography was a poor predictor of translesional gradients (r = 0.2, p = NS), whereas the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.001). Only two patients with a proximal/distal total flow velocity ratio < 1.7 had a translesional gradient > 30 mm Hg. Both patients had a very proximal lesion in a nonbranching right coronary artery. CONCLUSIONS These data demonstrate that in branching human coronary arteries, a close relation exists between translesional hemodynamics and distal coronary flow velocity. Translesional coronary flow velocity is a new and easily applicable method for determining the hemodynamic significance of coronary artery stenoses that is superior to angiography and can be applied at the time of diagnostic catheterization. These data will provide a rational approach to making decisions on the use of coronary interventional techniques when angiographic findings are questionable.

Rapid identification of the course of anomalous coronary arteries in adults: The “dot and eye” method

It is often difficult to delineate the true course of anomalous coronary arteries by angiography because it only provides a 2-dimensional view of a complex 3-dimensional structure. The purpose of this study was to confirm morphologically the radiographic appearance of anomalous coronary arteries and to construct a protocol for rapid determination of their true course. Twenty-one adults who had anomalous origin of coronary arteries without other evidence of congenital heart disease were reviewed. Using an anatomically correct model of the heart, solder wire was placed in the pathologically described anomalous positions and radiographed. With this model the pathologically described courses could be easily recognized and separated radiographically. These courses were confirmed in the operating room in 2 patients and a rare anomaly of posterior origin of a coronary artery was also confirmed by autopsy.

Variations in normal coronary vasodilatory reserve stratified by artery, gender, heart transplantation and coronary artery disease

OBJECTIVES The purpose of the study was to assess the spectrum of coronary vasodilatory reserve values in patients with angiographically normal arteries who had atypical chest pain syndromes or remote coronary artery disease or were heart transplant recipients. BACKGROUND The measurement of post-stenotic coronary vasodilatory reserve, now possible in a large number of patients in the cardiac catheterization laboratory, is increasingly used for decision making. Controversy exists regarding the range of normal values obtained in angiographically normal coronary arteries in patients with different clinical presentations. METHODS Quantitative coronary arteriography was performed in 214 patients classified into three groups: 85 patients with chest pain syndromes and angiographically normal arteries (group 1); 21 patients with one normal vessel and at least one vessel with > 50% diameter lumen narrowing (group 2); and 108 heart transplant recipients (group 3). Coronary vasodilatory reserve (the ratio of maximal to basal average coronary flow velocity) was measured in 416 arteries using a 0.018-in. (0.04 cm) Doppler-tipped angioplasty guide wire. Intracoronary adenosine (8 to 18 micrograms) was used to produce maximal hyperemia. RESULTS Coronary vasodilatory reserve was higher in angiographically normal arteries in patients with chest pain syndromes (group 1:2.80 +/- 0.6 [group mean +/- SD]) than in normal vessels in patients with remote coronary artery disease (group 2: 2.5 +/- 0.95, p = 0.04); both values were significantly higher than those in the post-stenotic segment of the diseased artery (1.8 +/- 0.6, p < 0.007). Coronary vasodilatory reserve in transplant recipients (group 3) was higher than that in the other groups (3.1 +/- 0.9, p < 0.05 vs. groups 1 and 2) as a group and for individual arteries. When stratified by vessel, coronary vasodilatory reserve was similar among the left anterior descending, left circumflex and right coronary arteries. There were no differences between coronary vasodilatory reserve values on the basis of gender for patients with coronary artery disease and transplant recipients. In group 1 (chest pain), there was a trend toward higher coronary vasodilatory reserve in men than in women (2.9 +/- 0.6 vs 2.7 +/- 0.6, p = 0.07). CONCLUSIONS These findings identify a normal reference range for studies assessing the coronary circulation and post-stenotic coronary vasodilatory reserve in patients with and without coronary artery disease encountered in the cardiac catheterization laboratory.