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 stenoses: 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.

Cardiopulmonary exercise testing identifies low risk patients with heart failure and severely impaired exercise capacity considered for heart transplantation.

OBJECTIVES: The 3-year survival rates of 500 patients with congestive heart failure (CHF) referred for heart transplantation were assessed to evaluate the clinical and exercise variables most useful for estimating prognostic risk. BACKGROUND: Detailed prognostic risk stratification of patients with a peak exercise oxygen consumption (VO2) < or = 14 ml/min per kg to identify lower risk patient subsets has been limited in earlier series by relatively small sample size. METHODS: Cardiopulmonary exercise testing was performed in 500 patients with CHF referred for heart transplantation; 154 (31%) had a peak exercise VO2 < or = 14 ml/min per kg. Univariate and multivariate analyses were performed to identify the 3-year prognostic risk. RESULTS: The 55% 3-year survival rate of the 77 patients with a peak exercise VO2 < or = 14 ml/min per kg unable to reach a peak exercise systolic blood pressure (SBP) of 120 mm Hg was significantly lower than the 83% survival rate in the 74 patients able to reach this exercise blood pressure (p = 0.004). Multivariate analysis revealed that peak exercise SBP (p = 0.0005) and percent predicted peak VO2 < or = 50% (p = 0.04) were the two most important predictors for the combined end point of death or listing as Status 1. CONCLUSIONS: Peak exercise SBP and percent predicted peak exercise VO2 are two inexpensive and easily measured noninvasive variables that can be used to further prognostically risk stratify ambulatory patients with CHF referred for heart transplantation with a peak exercise VO2 < or = 14 ml/min per kg.

Role of coronary artery lumen enlargement in improving coronary blood flow after balloon angioplasty and stenting: a combined intravascular ultrasound Doppler flow and imaging study.

OBJECTIVES: This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting. BACKGROUND: Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in > or = 50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results. METHODS: To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity. RESULTS: The percent diameter stenosis decreased from (mean +/- SD) 84 +/- 13% to 37 +/- 18% after angioplasty and to 8 +/- 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 +/- 0.79 at baseline to 1.89 +/- 0.56 (p = NS) after angioplasty but increased to 2.49 +/- 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 +/- 2.09 vs. 5.10 +/- 2.03 mm2, p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001). CONCLUSIONS: In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.

Long-term cardiopulmonary exercise performance after heart transplantation.

Functional capacity is an important outcome variable for heart transplantation, but there are few data that examine the temporal relation and duration of improvement in cardiopulmonary exercise performance after cardiac transplantation. Cardiopulmonary exercise performance was measured in 140 patients who underwent 426 treadmill exercise tests up to 9 years after cardiac transplantation. Univariate and multivariate analyses were used to predict postoperative improvement in functional capacity. Peak oxygen consumption (VO2) significantly improved from 14.2 +/- 3.7 ml/min/kg before to 21.4 +/- 5.6 ml/min/kg at a mean of 11.2 +/- 3.0 months after the transplant procedure (p < 0.001). When peak aerobic capacity was compared with a normal population, peak VO2 was < 50% of predicted in only 9 patients (12%), from 50% to 70% in 34 patients (44%), from 70% to 90% of predicted in 24 patients (31%); 10 patients (13%) were able to achieve > 90% of peak predicted VO2. The improvement seen at 6 months did not significantly change over 9 years of follow-up. Significant preoperative univariate predictors of.1-year postoperative improvement in peak VO2 were preoperative peak VO2 (p = 0.004), age (p < 0.001), ischemic cardiomyopathy (p = 0.007), and preoperative left ventricular ejection fraction (p < 0.001). Peak VO2 at 1 year in patients able to perform the test was not significantly influenced by acute rejection episodes, donor body surface area, or donor/recipient size ratio. In conclusion, exercise capacity is significantly improved within 6 months after cardiac transplantation, and maintained as long as 9 years after procedure. The magnitude of postoperative improvement is inversely related to preoperative peak VO2 and age.

Correlation of poststenotic hyperemic coronary flow velocity and pressure with abnormal stress myocardial perfusion imaging in coronary artery disease.

The functional significance of coronary stenoses is frequently determined by adjunctive noninvasive myocardial perfusion imaging. Poststenotic coronary flow velocity and pressure can be measured directly during routine cardiac catheterization. The aim of this study was to correlate poststenotic (distal) flow velocity and pressure with stress perfusion imaging in patients. Quantitative angiography, basal and hyperemic transstenotic coronary flow velocities, and pressure gradients were measured in 50 patients within 1 week of exercise (n = 29) or of pharmacologic (n = 21) stress perfusion imaging. Twenty-two of 25 patients (88%) with reversible perfusion abnormalities had diminished distal coronary flow velocity reserves (CFVR) of < or = 2.0 x baseline, whereas 22 of 25 (88%) with normal perfusion imaging studies had a normal distal CFVR of > 2.0 (p = 0.000 1). Thirteen of 25 patients (52%) with reversible perfusion abnormalities had transstenotic gradients > or = 20 mm Hg, whereas 20 of 25 (80%) with normal perfusion studies had gradients <20 mm Hg (p = 0.01). Quantitative angiography did not differentiate patients with normal versus abnormal myocardial perfusion imaging. Distal CFVR was correlated more significantly with myocardial perfusion imaging results (kappa = 0.76) than with pressure gradients (kappa = 0.32). Exercise and pharmacologic stress myocardial perfusion imaging abnormalities reflect diminished post-stenotic coronary flow to a greater degree than transstenotic pressure gradients.

Successful withdrawal of corticosteroids in heart transplantation.

The ability to withdrawal corticosteroids from the maintenance immunosuppression regimen has been reported in heart transplant recipients. Most patients tested have had corticosteroids discontinued by 3 to 4 weeks after transplantation and have received perioperative administration of lymphocyte antibody therapy. To assess the importance of the additional "induction" therapy and the comparative results of delaying steroid withdrawal until after most rejections had occurred in our program, we withdrew maintenance steroids from 48 patients who were an average of 11 months (median, 8.6 months, range, 5 to 59 months) after transplantation. Mean patient age was 48 years, 95% were men, and 60% of the patients had never been treated for rejection before steroid withdrawal. Forty of the 48 patients (82%) were successfully withdrawn and remain free of steroids with an average of 25 months (range, 5 to 39 months) of follow-up off steroids. Ten episodes of rejection occurred in eight patients (82% rejection free). Six patients had a single rejection and two had more than one rejection. The average time to rejection after steroid withdrawal was 4 1/2 months, but two patients developed their first-ever rejection at 11 1/2 and 12 1/2 months after steroid withdrawal. Three of the rejections after steroid withdrawal were treated with intravenous steroids (10 mg/kg/day for 3 days) without a return to maintenance steroids. These three patients have not had a subsequent episode of rejection in 15 months of follow-up. The other three patients with rejection were returned to steroid therapy because of an inability to tolerate azathioprine, as were three patients without rejection for unrelated reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

The surgical management of allograft coronary disease: a paradigm shift.

The surgical options for heart transplant recipients who develop obstructive coronary artery disease in their allograft have historically been limited to retransplantation. Given the worse outcome in recipients of second grafts, often caused by recurrence of coronary disease, coupled with the significant increase in the number of patients on the transplantation waiting lists, has made retransplantation a limited option. However, as heart transplant recipients continue to live longer, there are an increasing number of patients who develop allograft coronary disease. Coronary bypass surgery has not been offered to these patients because of numerous pathology reports describing uniform involvement of the coronary vessel from its origin to the distal intramural branches, thereby eliminating any reasonable runoff vascular bed to handle increased flow that might be delivered with bypass conduits. However, new diagnostic techniques such as measurement of coronary flow reserve by Doppler flow wire can define the physiological vasodilating capacity or reserve which, if normal, should allow conventional bypass surgery if adequate target epicardial vessels are present. This approach would allow a more reasonable alternative to many patients who otherwise would die of this disease without any intervention. Other alternatives such as transmyocardial laser revascularization are discussed.

Assessment of transplant arteriopathy by intracoronary two-dimensional ultrasound imaging and coronary flow velocity.

Transplant coronary arteriopathy is the major impediment to the long-term survival of cardiac allografts. This report highlights two-dimensional imaging and Doppler flow to assess transplant coronary arteriopathy.

Examination of the effects of hemodynamic and pharmacologic interventions on coronary collateral flow in a patient during cardiac catheterization.

The vasomotor response of native human collateral vessels to pharmacologic or hemodynamic vasodilatory stimuli is not well known. We describe a case where retrograde collateral flow velocity was measured both at baseline and following selected hemodynamic and pharmacologic interventions. This index case represents the first in a series of potential human physiologic studies designed to address questions pertaining to control of collateral blood supply in humans.

Intraaortic balloon pump support during high-risk coronary angioplasty.

Intraaortic balloon pump support has been demonstrated to be of clinical benefit when used therapeutically and prophylactically in high-risk patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Afterload reduction and post-PTCA-enhanced coronary blood flow afforded by diastolic augmentation during intraaortic balloon pumping provides hemodynamic stabilization, attenuates clinical perturbations of myocardial ischemia, and may provide an important 'bridge' to emergent coronary bypass surgery following abrupt vessel closure complicating PTCA. Recent studies demonstrate a reduction in cardiac morbidity and improved coronary artery patency among patients receiving prophylactic intraaortic balloon pumping after establishing infarct artery reperfusion during acute cardiac catheterization for acute myocardial infarction. A modest increase in cardiac output (20-30%), the requirement of a stable, regular cardiac rhythm, peripheral vascular disease and aortic insufficiency limits the use of intraaortic balloon pump support in relatively few patients. These studies demonstrate that intraaortic balloon counterpulsation provides an effective and safe form of mechanical support in many high-risk patients undergoing PTCA.

Quantification of collateral blood flow during PTCA by intravascular Doppler.

The assessment of flow velocity using the Doppler guidewire provides a means of investigating both antegrade and retrograde blood flow in the coronary artery distal to obstructive lesions and occluding PTCA balloons. This has yielded unique qualitative and quantitative information regarding coronary collateral blood flow, and the responses of collaterals to pharmacological and haemodynamic perturbations. The current study analysed collateral flow velocity recordings obtained during coronary interventions in 46 patients in our laboratory. The mean collateral peak velocity integral distal to the occluding PTCA balloon was 9 +/- 7 units, while antegrade distal coronary peak velocity integral following stenosis relief by PTCA was 27 +/- 12 units. Thus, during PTCA balloon occlusion collaterals were able to supply a mean of 30 +/- 18% of the flow provided antegrade by successful PTCA. Variability in collateral flow velocity was not accounted for by differences in the PTCA artery assessed, the supply artery, the direction of collateral filling, the severity of coronary stenosis, or the angiographic grade of collaterals, and the magnitude of collateral flow velocity did not correlate with preserved left ventricular regional wall motion. The measurement of collateral flow velocity by intravascular Doppler provides unique and quantitative information regarding the coronary collateral circulation.

Patterns of phasic coronary collateral flow velocity in patients.

Antegrade or retrograde collateral flow velocity Doppler signals, acquired with the flowire, permit the quantitation of collateral blood flow and its phasic patterns. The velocity spectra are easily visualized, and reproducible alterations during balloon occlusion may be directly related to coronary collateral flow-dependent variables of ischemia and left ventricular wall motion. The effects of pharmacologic stimulation on collateral flow remain under study.

Assessment of blood flow distal to coronary artery stenoses. Correlations between myocardial positron emission tomography and poststenotic intracoronary Doppler flow reserve.

BACKGROUND: Previous studies have correlated quantitative coronary angiographic stenosis severity with positron emission tomography (PET) myocardial perfusion and proximal measurements of intracoronary flow velocities in normal and diseased coronary arteries. The aim of this study was to correlate regional myocardial blood flow (RMBF) derived from [15O]H2O PET with directly measured poststenotic intracoronary Doppler flow velocity data acquired under basal conditions and dipyridamole-induced hyperemia. METHODS AND RESULTS: Eleven consecutive patients 53 +/- 13 years old with ischemic chest pain and isolated proximal left coronary artery stenoses (left anterior descending, 9; left circumflex, 2; mean, 59 +/- 23% diameter stenosis) underwent [15O]H2O myocardial PET and intracoronary Doppler flow velocity studies within 1 week. PET RMBF (mL.g-1.min-1) and myocardial perfusion reserve (MPR) were calculated in poststenotic and normal reference vascular beds. Poststenotic Doppler average peak flow velocities (APV; cm/s) and coronary flow velocity reserve (CFR) were compared with corresponding PET data and quantitative angiographic lesional parameters. PET RMBF and Doppler APV were linearly correlated (r = .60; P < .001), as were poststenotic PET MPR and Doppler CFR (r = .76; P < .0002). Relative coronary flow velocity and MPR ratios between poststenotic and angiographically normal vascular beds were comparably reduced (0.83 +/- 0.25 versus 0.86 +/- 0.21, respectively; P = NS). CONCLUSIONS: Intracoronary Doppler flow velocities acquired distal to isolated left coronary artery stenoses correlated with [15O]H2O PET regional myocardial perfusion and are useful for assessment of the physiological significance of coronary stenoses in humans.

Coronary angiography using 4 Fr catheters with acisted power injection: A randomized comparison to 6 Fr manual technique and early ambulation.

Coronary angiography using 4 Fr catheters may reduce access site complications, promote better utilization of outpatient facilities, but at a cost of suboptimal image quality. To determine whether 4 Fr diagnostic angiography with power injection (Acist, Minneapolis, MN) was equivalent to 6 Fr manual technique, 101 unselected patients were randomized to transfemoral coronary angiography with 4 or 6 Fr catheters. Procedural characteristics, angiographic quality scores, and results of 90 min ambulation were analyzed. Coronary angiographic quality scores using 4 Fr and 6 Fr catheters were equivalent (left coronary artery 4.73 +/- 0.6 vs. 4.80 +/- 0.65, P = 0.28; right coronary artery 4.98 +/- 90.13 vs. 4.97 +/- 0.16, P = 0.48). However, 4 Fr left ventriculographic image score was lower (4.53 +/- 0.68 vs. 4.83 +/- 0.42, P = 0.0002), attributed, in part, to a smaller injected contrast volume (32 +/- 11 vs. 37 +/- 4 mL, P = 0.001). The total study contrast volume was significantly less in the 4 Fr group (119 +/- 35 vs. 159 +/- 52 mL, P = 0.001). Complications related to early ambulation at 90 min were similar and minimal in both groups. Compared to 6 Fr manual contrast injection technique, diagnostic angiography through 4 Fr catheters with power contrast injection resulted in equivalent coronary angiographic image quality, slightly reduced but diagnostic left ventricular image quality, and significantly less contrast volume. Four Fr angiography facilitates early ambulation without compromising safety and image quality.

Superior accuracy of anatomic positioning with echocardiographic- over fluoroscopic-guided endomyocardial biopsy.

To assess the superior anatomic positioning of echocardiographic-guided endomyocardial biopsy compared to traditional fluoroscopic-guided technique, these two modalities were compared in a blinded fashion during femoral sheath endomyocardial biopsy in 21 patients, 19 being evaluated after orthotopic cardiac transplantation. The simultaneous fluoroscopic and echocardiographic imaging indicated that traditional fluoroscopic positioning of the bioptome against the septum is inaccurate in over half of patients undergoing biopsy. This finding should be considered in cardiomyopathy patients or those at high risk for biopsy-related complications.

Quantitative demonstration of dipyridamole-induced coronary steal and alteration by angioplasty in man: analysis by simultaneous, continuous dual Doppler spectral flow velocity.

In the course of studying the effects of coronary angioplasty on branch vessel flow using two Doppler flow velocity guidewires, we quantitated simultaneous blood flow responses proximal and distal to a stenosis. The alterations of flow documented a horizontal epicardial steal induced during dipyridamole hyperemia, hyperemic flow reversal by intravenous aminophylline, and subsequent normalization of distal hyperemia after endoluminal enlargement by successful angioplasty. The quantitative physiology of the patient described here confirms one postulated mechanism of abnormal myocardial perfusion stress scintigraphy. Continuous dual flowire spectral coronary flow determinations appear to be a valuable method in verifying postulated mechanisms of various pharmacologic and mechanical stimuli influencing coronary blood flow in patients with atherosclerotic coronary artery disease.

Continuous coronary flow velocity monitoring during coronary interventions: velocity trend patterns associated with adverse events.

Continuous measurement of blood flow velocity during interventional procedures has the potential to provide an early warning of coronary flow instability, which can lead to abrupt closure or other adverse events before angiography. The magnitude and fluctuations of the average velocity over time (trend) was studied by using a 0.018-inch Doppler-tipped angioplasty guide wire in 32 patients after coronary angiography (n = 20), atherectomy (n = 2), urgent stent (n = 6), urgent vein graft thrombolysis (n = 4), or acute myocardial infarction (n = 2). The patients (mean age 60 +/- 11 years) had postprocedural in-laboratory flow monitoring for a mean of 19 +/- 11 (range 8 to 36) minutes. The coronary artery monitored was the left anterior descending in 13, circumflex in 6, right coronary artery in 9, and saphenous vein graft in 4. Seven patients had flow-related events during continuous flow velocity monitoring before serial angiographic study. These events included coronary vasospasm (abrupt flow acceleration), vasovagal flow cessation, cyclical flow variations resulting from accumulation of intraluminal thrombus, and rapid decline of flow velocity. The last two patterns were associated with abrupt vessel closure during angioplasty. Continuous flow velocity monitoring is easily incorporated into routine interventional procedures and provides an early indication of unstable flow and the potential for abrupt vessel closure and other adverse events.

Influence of intimal thickening on coronary blood flow responses in orthotopic heart transplant recipients. A combined intravascular Doppler and ultrasound imaging study.

BACKGROUND: Intravascular ultrasound imaging detects epicardial intimal thickening in the majority of heart transplant recipients with angiographically normal epicardial coronary arteries. Although coronary artery vasoreactivity is abnormal after cardiac transplantation, intimal thickening does not appear to affect conduit vessel responses. However, the effect of intimal thickening on both conduit and resistance vessel responses, as measured by changes in volumetric coronary blood flow (CBF), is unknown. METHODS AND RESULTS: Epicardial coronary artery conductance and microvascular resistance vessel responses were studied after intracoronary adenosine and nitroglycerin administration in 36 orthotopic heart transplant recipients 1 month to 7 years after transplantation. Sequentially measured coronary flow average peak velocity ([APV, cm/s] 0.018 in Doppler guide wire) and epicardial luminal cross-sectional area ([CSA, mm2] 4.3F 30-MHz ultrasound catheter) data were obtained at baseline and during peak hyperemia after administration of 12 to 18 micrograms IC adenosine and 150 to 200 micrograms IC nitroglycerin. Volumetric CBF (mL/min) was calculated as CBF = APV (cm/s) x CSA (mm2) x 60 seconds/1 min x 1 cm2/100 mm2 x 0.5. Measurements were made from a discrete position in the proximal left anterior descending (LAD) artery (n = 22), mid-LAD artery (n = 7), proximal circumflex artery (n = 6), and proximal right coronary artery (n = 1). Intimal thickening was present in 19 of 32 patients (60%). Both adenosine and nitroglycerin increased APV (from 18.9 +/- 4.9 to 56.0 +/- 11.5 cm/s for adenosine and from 20.2 +/- 5.3 to 49.1 +/- 11.5 cm/s for nitroglycerin; both P < .05). Coronary flow velocity reserve was significantly higher for adenosine compared with nitroglycerin (3.1 +/- 0.6 versus 2.5 +/- 0.7, respectively; P < .001). Epicardial luminal CSA was unchanged during adenosine hyperemia compared with baseline (17.4 +/- 3.8 versus 17.3 +/- 4.0 mm2, respectively; P = NS) but was significantly greater during nitroglycerin hyperemia compared with baseline (18.7 +/- 3.8 versus 17.3 +/- 4.0 mm2, 6.2 +/- 3.6% change; P < .05). Baseline CBF was similar before drug administration. Hyperemic adenosine and nitroglycerin CBF responses (297 +/- 99 and 276 +/- 87 mL/min, respectively; P = NS) and CBF reserve (3.0 +/- 0.7 and 2.7 +/- 0.7, respectively; P = NS) were not significantly different. Importantly, intimal thickening did not diminish resting or hyperemic APV, coronary flow velocity reserve, luminal CSA, CBF, or CBF reserve responses. CONCLUSIONS: In this study of angiographically normal heart transplant recipients, epicardial intimal thickening does not diminish conduit and resistance vessel responses during endothelial-independent vasodilator administration.