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.

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.

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.

Factors related to end-systolic volume are important determinants of peak early diastolic transmitral flow velocity.

BACKGROUND: Three important determinants of left ventricular (LV) peak early diastolic filling rate, which is related directly to the magnitude of the transmitral pressure difference, are the rate of LV isovolumic pressure fall (T1/2), left atrial (LA) pressure at mitral valve opening (X1), and end-systolic volume (ESV). METHODS AND RESULTS: To delineate the relative degrees to which these factors contribute to the magnitude of peak early diastolic filling rate, we measured LA and regional intra-LV pressures with micromanometers, LV volume with contrast angiography, and peak transmitral flow velocity (E) with transesophageal Doppler echocardiography in 16 anesthetized closed-chest dogs. E did not correlate significantly with either X1 (r = -0.255) or T1/2 (r = -0.281). Multivariate analysis, with E entered as the dependent variable and X1 and T1/2 as independent variables, also failed to reach significance (R = 0.310). E correlated significantly with ESV (r = -0.633, p less than 0.009). Using multivariate analysis, the major determinants of ESV were found to be LV contractility (+dP/dt), afterload (aortic diastolic pressure, AOdias), and preload (end-diastolic volume, EDV) (R = 0.848, p less than 0.001). E correlated significantly with two of the determinants of ESV (+dP/dt and AOdias) (R = 0.906, p less than 0.001); however, the addition of EDV did not significantly improve the multivariate relation (R = 0.911). To determine whether X1 or T1/2 would add significantly to the above multivariate relation, these factors were entered individually along with +dP/dt and AOdias as third independent variables. Neither the addition of X1 (R = 0.906) or T1/2 (R = 0.926) resulted in a significant improvement in the prediction of E. CONCLUSIONS: Our observations confirm the importance of factors related to ESV as important determinants of early diastolic filling. These relations suggest that the process of early diastolic function is intimately related to systolic function.

Delineation of determinants of left ventricular early filling. Saline versus blood infusion.

BACKGROUND: Left atrial pressure (LAP) is often believed to play a dominant role in the determination of left ventricular (LV) early diastolic filling. In a previous study we found no significant relation between LAP and LV early filling velocity (E) but found instead a relation between E and two determinants of LV myocardial shortening (contractility and afterload). To determine if such disparate results may be related to the data ranges of the independent variables in a given population of animals, we took advantage of the differential hemodynamic effects of two modes of volume expansion: saline and whole blood. METHODS AND RESULTS: Eighteen closed-chest anesthetized dogs were instrumented with micromanometers for measurement of LV, left atrial, and aortic pressures. LV volumes were obtained with use of contrast ventriculography, pressures by micromanometry, and transmitral flow-velocity by Doppler echocardiography. After obtaining baseline measurements, group 1 (n = 9) received rapid infusion of 500 to 650 mL of saline over 10 minutes, and group 2 (n = 9) received the same volume infusion of whole blood. In terms of two known determinants of E, infusion of saline resulted in a significant increase in LAP at the moment of mitral valve opening (X1) (1.5 +/- 0.9 to 5.7 +/- 1.4 mm Hg; P < .05) and a moderate decrease in the pressure decay rate during isovolumic relaxation (tau 1/2) (22.9 +/- 2.4 to 26.3 +/- 3.5 milliseconds; P < .05). When these two factors were entered together into a multiple regression analysis with E as the dependent variable, the overall correlation was found to be significant (R = .722; P < .008), with both independent variables contributing significantly to the relation. When factors related to myocardial shortening (afterload and contractility) were added to this relation, they did not significantly improve the prediction of E. Like saline, whole blood infusion augmented X1 (1.6 +/- 2.4 to 8.8 +/- 3.2 mm Hg; P < .05) and tau 1/2 (21.5 +/- 2.6 to 32.0 +/- 6.3 milliseconds; P < .05) but also significantly increased LV afterload as measured by aortic diastolic pressure (91 +/- 10 to 110 +/- 12 mm Hg; P < .05). Multiple regression analysis of X1 and tau 1/2 with E again revealed a significant relation (R = .761; P < .002), with both independent variables contributing significantly to the relation. However, in this case, addition of contractility and afterload to the regression significantly improved the relation (R = .909; P < .001), with all four independent variables now contributing significantly to the prediction of E. CONCLUSIONS: Combined with our previous results, this study indicates the degree to which experimental methods can have an impact on the delineation of the determinants of a phenomenon as complex as LV early diastolic filling. Which independent variables emerge as primary determinants can be strongly influenced by the experimenter's choice of experimental design and manipulations. Specifically, experiments using volume infusion to delineate the responses of the cardiovascular system to variations in loading must allow for the hemodynamic changes that are inherent in the choice of infusate and infusion technique, especially when those interventions may significantly alter blood oxygen-carrying capacity and, in turn, differentially modify factors that affect the magnitude of the early diastolic transmitral pressure gradient.

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.