Comparison of relative coronary Doppler flow velocity reserve to stress myocardial perfusion imaging in patients with coronary artery disease.

To compare relative coronary artery vasodilator reserve (rCVR = CVRtarget/CVRreference) to myocardial perfusion stress imaging, 48 patients with coronary artery stenoses (61% +/- 16%; mean, +/- SD; range, 30%-91%) had measurements of target and reference vessel CVR (Doppler-tipped guidewire). rCVR was computed and compared to stress 201thallium or (99m)technetium-sestamibi myocardial tomography. Compared to 24 patients with negative stress imaging studies, 24 patients with positive stress studies had angiographically more severe stenoses (74% +/- 13% vs. 44% +/- 24%; P = 0.0005) with lower CVR(target) (1.68 +/- 0.55 vs. 2.46 +/- 0.74; P = 0.002) and lower rCVR (0.72 +/- 0.22 vs. 1.0 +/- 0.26; P < 0.003). Based on receiver-operator characteristic (ROC) cut points (CVR > 1.9; rCVR > 0.75), compared to CVR, rCVR had similar agreement (Kappa 0.54 vs. 0.50), sensitivity (63% vs. 71%), specificity (88% vs. 83%), and positive predictive value (83% vs. 81%) with myocardial perfusion tomography. A concordant CVRtarget/rCVR only slightly increased sensitivity, specificity, and positive predictive values (77%, 90%, and 87%, respectively). Although rCVR, like CVR, correlates with stress myocardial perfusion imaging results, rCVR did not have significant incremental prognostic value over CVR alone for myocardial perfusion imaging. However, rCVR does provide additional information regarding the status of the microcirculation in patients with coronary artery disease and complements the CVR for lesion assessment.

Abnormal coronary flow velocity reserve after coronary artery stenting in patients: role of relative coronary reserve to assess potential mechanisms.

BACKGROUND: Absolute coronary flow velocity reserve (CVR) after stenting may remain abnormal as a result of several different mechanisms. Relative CVR (rCVR=CVR(target)/CVR(reference)) theoretically normalizes for global microcirculatory disturbances and facilitates interpretation of abnormal CVR. METHODS AND RESULTS: To characterize potential mechanisms of poststent physiology, CVR was measured using a Doppler-tipped angioplasty guidewire in 55 patients before and after angioplasty, after stenting, and in an angiographically normal reference vessel. For the group, the percent diameter stenosis decreased from 75+/-13% to 40+/-18% after angioplasty and to 10+/-9% (all P<0.05) after stent placement. After angioplasty, CVR increased from 1.63+/-0.71 to 1.89+/-0.55 (P<0.05) and after stent placement, to 2.48+/-0.75 (P<0.05 versus pre- and postangioplasty). After angioplasty, rCVR increased from 0.64+/-0.26 to 0.75+/-0.23 and after stent placement to 1.00+/-0.34. In 17 patients with CVR(stent) < or = 2.0, increased basal coronary flow, rather than attenuated hyperemia, was responsible in large part for the lower CVR(stent) compared with patients having CVR(stent) >2.0. In 8 patients with CVR(stent) <2.0, a normal rCVR supported global microvascular disease. The subgroup of 9 patients with CVR(stent) <2.0 and abnormal rCVR (16% of the studied patients) may require a pressure-derived fractional flow reserve to differentiate persistent obstruction from diffuse atherosclerotic disease or microvascular stunning. CONCLUSIONS: Although a majority of patients after stenting normalize CVR for the individual circulation (ie, normal CVR or normal rCVR), in those with impaired CVR(stent), the analysis of coronary flow dynamics suggests several different physiological mechanisms. Additional assessment may be required to fully characterize the physiological result for such patients to exclude remediable luminal abnormalities.

Heterogeneity of coronary flow reserve in the examination of multiple individual allograft coronary arteries.

BACKGROUND: Epicardial and resistance vessel function in the transplanted heart has been evaluated primarily in regions supplied by a single vessel. Heterogeneity of flow among multiple perfusion fields as a marker of early endothelial dysfunction in the microcirculation has not been evaluated previously. This study tested the hypothesis that increased variability of coronary flow reserve (CFR) among multiple vascular regions would be associated with allograft coronary vasculopathy. METHODS AND RESULTS: One hundred six posttransplant patients undergoing cardiac catheterization had measurement of CFR in at least 3 major epicardial vessels. Patients were divided into those with minimal angiographic abnormalities (n=37) and those with no angiographic abnormalities (n=69). The ranges, coefficients of variation, and univariate and multivariate regression analyses of CFR were computed to determine the major clinical factors influencing the degree of variability. The abnormal angiographic group was older (54+/-11 versus 47+/-13 years; P<0.003), had older hearts (35+/-11 versus 27+/-10 years; P<0.005), and were further posttransplant (1626+/-1022 versus 931+/-984 days; P<0.0009). There was no difference in global CFR between groups (normal, 3.4+/-0.8 versus abnormal, 3.4+/-0.7; P=NS). The coefficient of variation of CFR was higher for the abnormal group (16.3+/-8.6% versus 11.0+/-5.5%; P<0. 0006). Univariate and multivariate predictors of increased variability in CFR included angiographic abnormalities, patient age, and body mass index. Both angiographic abnormalities and an elevated CV of CFR were predictive of a combined end point of death, congestive heart failure, or subsequent development of >/=50% coronary stenosis. CONCLUSIONS: These data demonstrate that increased variability of CFR is associated with discernible allograft coronary arteriopathy and is predictive of outcome in patients after heart transplantation.

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.

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.

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.

Comparison of pressure-derived fractional flow reserve with poststenotic coronary flow velocity reserve for prediction of stress myocardial perfusion imaging results.

The physiologic importance of coronary stenoses can be assessed indirectly by stress myocardial perfusion imaging or directly by translesional pressure and flow measurements. The aims of this study were to compare myocardial fractional flow reserve (FFRmyo), a recently proposed index of lesion significance derived from hyperemic translesional pressure gradients, with directly measured poststenotic flow velocity reserve for the prediction of myocardial perfusion stress imaging results in corresponding vascular beds. Poststenotic coronary flow velocity (0.018-inch guide wire) and translesional pressure gradients (2.7F fluid-filled catheter) were measured at baseline and after intracoronary adenosine (12 to 18 micrograms) in 70 arteries (diameter stenosis: mean 56% +/- 15%, range 14% to 94% by quantitative angiography). Coronary flow reserve was calculated as the ratio of hyperemic to basal mean flow velocity. FFRmyo was calculated during maximal hyperemia as equal to 1-(hyperemic gradient [mean aortic pressure-5]), where 5 is the assumed central venous pressure. Positive and negative predictive values and predictive accuracy for reversible stress myocardial perfusion abnormalities were computed. There was a significant correlation between pressure-derived FFRmyo and distal coronary flow reserve (r = 0.46; p < 0.0001). The strongest predictor of stress myocardial perfusion imaging results was the poststenotic coronary flow reserve (chi square = 33.2; p < 0.0001). The correlation between stress myocardial perfusion imaging and FFRmyo was also significant (chi square = 8.3; p < 0.005). There was no correlation between stress myocardial perfusion imaging and percentage diameter stenosis (chi square = 2.9; p = 0.10) or minimal lumen diameter (chi square = 0.47; p = 0.73). A poststenotic coronary flow reserve of < or = 2 had a positive predictive value of 89% for regionally abnormal myocardial perfusion imaging abnormalities, whereas the positive predictive values of FFRmyo and angiographic percentage diameter stenosis were only 71% and 67% respectively. In conclusion, the predictive value of poststenotic coronary flow velocity reserve for stress-induced myocardial perfusion abnormalities exceeds that of the translesional FFRmyo. These findings should be considered when applying these techniques for clinical decision making in the assessment of coronary stenosis severity.