Relation between geometric dimensions of coronary artery stenoses and myocardial perfusion reserve in man.

To determine the relation between stenosis anatomy and perfusion in man, 31 patients had quantitative coronary arteriography and positron imaging (PET) with Rb-82 or N-13 ammonia at rest and after dipyridamole-handgrip stress. 10 patients were also studied after angioplasty (total stenoses = 41). Percent narrowing and absolute cross-sectional luminal area were related through a quadratic function to myocardial perfusion reserve determined with PET. Arteriographically determined coronary flow reserve was linearly related to relative myocardial perfusion reserve as expected, based on the derivation of equations for stenosis flow reserve. All of the correlations had considerable scatter, indicating that no single measurement derived by coronary arteriography was a good indicator of perfusion reserve by PET in individual patients. This study provides the relation between all anatomic dimensions of coronary artery stenoses and myocardial perfusion reserve in man, and suggests that PET indicates the functional significance of coronary artery stenoses for clinical purposes.

Coronary artery flow velocity is related to lumen area and regional left ventricular mass.

BACKGROUND: Coronary flow velocity varies widely between individuals, even at rest. Because of this variation, indices with less apparent deviation, such as the ratio of hyperemic to resting velocity (coronary flow reserve), have been more commonly studied. We tested the hypothesis that the flow continuity principle could be used to model resting coronary flow, and we examined the resulting velocity relationship. METHODS AND RESULTS: We studied coronary velocity in 59 patients using a Doppler wire to measure resting and hyperemic average peak velocities in the left anterior descending artery. Quantitative techniques were used to calculate lumen cross-sectional area and the lengths of all distal coronary branches. Branch lengths were used to estimate regional left ventricular mass. We then calculated the ratio of lumen area to regional mass (A/m). Regional perfusion was estimated from the double product of heart rate and systolic blood pressure. Resting velocity (V) varied inversely with A/m ratio [V=46.5/(A/m); r=0.68, P<0.001]. Disease in the left anterior descending artery was categorized as none or luminal irregularities only (n=22), mild (n=15), or moderate (n=22). The A/m ratio declined across these groups (8.7+/-4.0, 8.5+/-6.2, and 5. 6+/-3.0 mm(2)/100 g, respectively; P<0.04), and the resting average peak velocity increased (27+/-16, 33+/-11, and 37+/-20 cm/s, respectively; P=0.06). CONCLUSIONS: Resting coronary artery flow velocity is inversely related to the ratio of lumen area to regional left ventricular mass. Higher resting velocities are found when insufficient lumen size exists for the distal myocardial bed, as occurs with diffuse mild or moderate coronary atherosclerosis.

Pressure-derived fractional flow reserve to assess serial epicardial stenoses: theoretical basis and animal validation.

Background-Fractional flow reserve (FFR) is an index of stenosis severity validated for isolated stenoses. This study develops the theoretical basis and experimentally validates equations for predicting FFR of sequential stenoses separately. Methods and Results-For 2 stenoses in series, equations were derived to predict FFR (FFR(pred)) of each stenosis separately (ie, as if the other one were removed) from arterial pressure (P(a)), pressure between the 2 stenoses (P(m)), distal coronary pressure (P(d)), and coronary occlusive pressure (P(w)). In 5 dogs with 2 stenoses of varying severity in the left circumflex coronary artery, FFR(pred) was compared with FFR(app) (ratio of the pressure just distal to that just proximal to each stenoses) and to FFR(true) (ratio of the pressures distal to proximal to each stenosis but after removal of the other one) in case of fixed distal and varying proximal stenoses (n=15) and in case of fixed proximal and varying distal stenoses (n=20). The overestimation of FFR(true) by FFR(app) was larger than that of FFR(true) by FFR(pred) (0.070+/-0.007 versus 0.029+/-0.004, P<0.01 for fixed distal stenoses, and 0.114+/-0.01 versus 0.036+/-0. 004, P<0.01 for fixed proximal stenoses). This overestimation of FFR(true) by FFR(app) was larger for fixed proximal than for fixed distal stenoses. Conclusions-The interaction between 2 stenoses is such that FFR of each lesion separately cannot be calculated by the equation for isolated stenoses (P(d)/P(a) during hyperemia) applied to each separately but can be predicted by more complete equations taking into account P(a), P(m), P(d), and P(w).

Frequency and clinical implications of fluid dynamically significant diffuse coronary artery disease manifest as graded, longitudinal, base-to-apex myocardial perfusion abnormalities by noninvasive positron emission tomography.

BACKGROUND: Diffuse coronary atherosclerosis is the substrate for plaque rupture and coronary events. Therefore, in patients with mild arteriographic coronary artery disease without significant segmental dipyridamole-induced myocardial perfusion defects, we tested the hypothesis that fluid dynamically significant diffuse coronary artery narrowing is frequently manifest as a graded, longitudinal, base-to-apex myocardial perfusion abnormality by noninvasive PET. METHODS AND RESULTS: In this study, 1001 patients with documented coronary artery disease by coronary arteriography showing any visible coronary artery narrowing underwent rest-dipyridamole PET perfusion imaging. Quantitative severity of dipyridamole-induced, circumscribed, segmental PET perfusion defects was objectively measured by automated software as the minimum quadrant average relative activity indicating localized flow limiting stenoses. Quantitative severity of the graded, longitudinal, base-to-apex myocardial perfusion gradient indicating fluid dynamic effects of diffuse coronary artery narrowing was objectively measured by automated software as the spatial slope of relative activity along the cardiac longitudinal axis. CONCLUSIONS: In patients with mild arteriographic disease without statistically significant dipyridamole-induced segmental myocardial perfusion defects caused by flow-limiting stenoses compared with normal control subjects, there was a graded, longitudinal, base-to-apex myocardial perfusion gradient significantly different from normal control subjects (P=0. 001) that was also observed for moderate to severe dipyridamole-induced segmental perfusion defects (P=0.0001), indicating diffuse disease underlying segmental perfusion defects; 43% of patients with or without segmental perfusion defects demonstrated graded, longitudinal, base-to-apex perfusion abnormalities beyond +/-2 SD of normal control subjects, indicating diffuse coronary arterial narrowing by noninvasive PET perfusion imaging.

Coronary flow reserve as a physiologic measure of stenosis severity.

PART I: Coronary flow reserve indicates functional stenosis severity, but may be altered by physiologic conditions unrelated to stenosis geometry. To assess the effects of changing physiologic conditions on coronary flow reserve, aortic pressure and heart rate-blood pressure (rate-pressure) product were altered by phenylephrine and nitroprusside in 11 dogs. There was a total of 366 measurements, 26 without and 340 with acute stenoses of the left circumflex artery by a calibrated stenoser, providing percent area stenosis with flow reserve measured by flow meter after the administration of intracoronary adenosine. Absolute coronary flow reserve (maximal flow/rest flow) with no stenosis was 5.9 +/- 1.5 (1 SD) at control study, 7.0 +/- 2.2 after phenylephrine and 4.6 +/- 2.0 after nitroprusside, ranging from 2.0 to 12.1 depending on aortic pressure and rate-pressure product. However, relative coronary flow reserve (maximal flow with stenosis/normal maximal flow without stenosis) was independent of aortic pressure and rate-pressure product. Over the range of aortic pressures and rate-pressure products, the size of 1 SD expressed as a percent of mean absolute coronary flow reserve was +/- 43% without stenosis, and for each category of stenosis severity from 0 to 100% narrowing, it averaged +/- 45% compared with +/- 17% for relative coronary flow reserve. For example, for a 65% stenosis, absolute flow reserve was 5.2 +/- 1.7 (+/- 33% variation), whereas relative flow reserve was 0.9 +/- 0.09 (+/- 10% variation), where 1.0 is normal. Therefore, absolute coronary flow reserve by flow meter was highly variable for fixed stenoses depending on aortic pressure and rate-pressure product, whereas relative flow reserve more accurately and specifically described stenosis severity independent of physiologic conditions. Together, absolute and relative coronary flow reserve provide a more complete description of physiologic stenosis severity than either does alone. PART II: Coronary flow reserve directly measured by a flow meter is altered not only by stenosis, but also by physiologic variables. Stenosis flow reserve is derived from length, percent stenosis, absolute diameters and shape by quantitative coronary arteriography using standardized physiologic conditions. To study the relative merits of absolute coronary flow reserve measured by flow meter and stenosis flow reserve determined by quantitative coronary arteriography for assessing stenosis severity, aortic pressure and rate-pressure product were altered by phenylephrine and nitroprusside in 11 dogs, with 366 stenoses of the left circumflex artery by a calibrated stenoser providing percent area stenosis as described in Part I.(ABSTRACT TRUNCATED AT 400 WORDS)

Assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VII. Validation of coronary flow reserve as a single integrated functional measure of stenosis severity reflecting all its geometric dimensions.

The purpose of this study was to determine whether coronary flow reserve measured by flow meter correlated with or could be predicted by quantitative coronary arteriography accounting for all dimensions of a coronary artery stenosis. Five dogs were chronically instrumented with an inflatable stenosing cuff, a Doppler flow velocity meter, proximal and distal coronary artery catheters and aortic and pulmonary artery catheters. For 18 stenoses over a wide range of severity, orthogonal coronary arteriograms were analyzed quantitatively at rest to predict coronary flow reserve based on fluid dynamic equations. The X-ray-predicted coronary flow reserve correlated closely with that measured directly by implanted flowmeter with an r value of 0.91, a regression equation of X-ray-predicted coronary flow reserve = 1.08 (measured coronary flow reserve) - 0.08 and 95% confidence limits (+/- 2 SD) of 0.66. Neither percent diameter narrowing alone nor absolute stenosis diameter alone correlated well with measured coronary flow reserve. Results confirm that coronary flow reserve is a single integrated measure of coronary stenosis severity reflecting all its geometric dimensions. Flow reserve correlated closely with and was accurately predicted by quantitative coronary arteriography taking into account all stenosis dimensions. This study establishes the theoretical and experimental basis for using coronary flow reserve as a single, integrated functional measure of stenosis severity reflecting all of its geometric characteristics.

Measurement from arteriograms of regional myocardial bed size distal to any point in the coronary vascular tree for assessing anatomic area at risk.

OBJECTIVES: To obtain the size of regional myocardial mass for individual coronary arteries in vivo. BACKGROUND: The anatomic site of occlusion in a coronary artery does not predict the size of the risk area because location of the occlusion does not account for the size of the artery or of its dependent myocardial bed. METHODS: Intracoronary radiolabeled microspheres were injected and coronary arteriograms were quantitatively analyzed by semiautomated methods. The coronary artery lumen areas and the sum of epicardial coronary artery branch lengths distal to the points where radiomicrospheres had been injected were determined from both in vivo and postmortem coronary arteriograms. Regional myocardial mass distal to the point of each microsphere injection was correlated with corresponding distal summed coronary branch lengths and with coronary artery lumen areas. RESULTS: 1) Regional myocardial mass was closely and linearly related to sum of coronary artery branch lengths distal to any point in the coronary artery tree and therefore could be determined for any location on a coronary arteriogram. 2) The fraction of total left ventricular mass at risk distal to a stenosis could be determined from the corresponding fraction of total coronary artery tree length independently of the scale or X-ray magnification used to measure absolute branch lengths. 3) Cross-sectional lumen area at any point in the left coronary artery tree was closely related to the size of the dependent vascular bed with a curvilinear relation similar to that observed in humans with normal coronary arteriograms. CONCLUSIONS: On coronary arteriograms, the anatomic area at risk for myocardial infarction distal to any point in the coronary artery tree can be determined from the sum of distal coronary artery branch lengths. There is a curvilinear relation between coronary artery lumen area and dependent regional myocardial mass comparable to that in humans, reflecting fundamental physical principles underlying the structure of the coronary vascular tree.

Regional myocardial function is not affected by severe coronary depressurization provided coronary blood flow is maintained.

It has been suggested that vasodilation distal to a stenosis may cause a profound decrease in perfusion pressure and adversely affect regional left ventricular function. This phenomenon could explain the clinical concept of reversal of regional dysfunction by coronary revascularization. To evaluate the hypothesis that regional myocardial function parallels regional coronary blood pressure in the absence of changes in coronary flow, dogs chronically instrumented with left circumflex coronary artery flow probes, cuff occluders, pressure catheters and segmental function sonomicrometers were studied. By decreasing regional coronary vascular resistance with selective intracoronary dipyridamole and controlling blood flow with a proximal coronary cuff occluder, the mean left circumflex artery pressure was reduced from 83 +/- 3 to 38 +/- 2 mm Hg while circumflex coronary blood flow was maintained constant. Regional contractile function as measured by circumflex sonomicrometers was unchanged at constant circumflex subendocardial blood flow as measured by radioactive microspheres. These findings suggest that regional contractile function is dependent on subendocardial blood flow and is independent of coronary perfusion pressure.

Patterns in visual interpretation of coronary arteriograms as detected by quantitative coronary arteriography.

In part 1 of a three-part study, 14 novice readers and 6 experienced cardiologists interpreted phantom images of known stenosis severity. No difference between the interpretations of experienced and novice readers was detectable. Visual estimates of "moderately" severe stenosis were 30% higher than actual percent diameter stenosis. In part 2 of the study, visual interpretation of percent diameter stenosis from 212 stenoses on 241 arteriograms was compared with quantitative coronary arteriographic assessment. The visual analysis overestimated disease severity in arteries with greater than or equal to 50% diameter stenosis (except for right coronary lesions) and underestimated severity in all arteries with less than 50% diameter stenosis. Of the 241 arteriograms, 40 had quantitative and visual analysis of all three coronary arteries for assessment of significant disease. In only 62% of the cases did visual and quantitative methods agree on the presence of severe disease; visual estimates diagnosed significantly (p less than 0.05) more three-vessel disease. In part 3 of the study, comparison of percent diameter stenosis by visual estimate with quantitative coronary arteriographic assessment before and after balloon angioplasty of 38 stenoses showed that visual interpretation significantly (p less than 0.001) overestimated initial lesion severity and underestimated stenosis severity after angioplasty.

Comparison of early systolic and early diastolic regional function during regional ischemia in a chronically instrumented canine model.

Depressed left ventricular function during the early part (first third) of both systole and diastole in the resting state have been reported to be sensitive indicators of coronary artery disease in patients with normal global function at rest. To evaluate the possible mechanisms of these findings, 11 dogs were chronically instrumented with segmental function sonomicrometers in the left circumflex and left anterior descending coronary artery distribution, circumflex coronary flow probes and cuff occluders, aortic flow probes and ventricular pressure transducers. Percent segmental function during the first third of systole and diastole was measured in the control state and with graded circumflex artery flow reductions. Significant decreases in early systolic function with ischemia in the circumflex artery distribution were partially offset by compensatory augmented shortening in the left anterior descending artery distribution. With ischemia in the circumflex distribution, there was prolonged contraction into diastole manifested as impaired relaxation. Simultaneously, in the left anterior descending artery distribution, there was minimal compensatory enhanced relaxation. These results suggest that early systolic dysfunction in ischemic segments may be offset by enhanced function in nonischemic segments, rendering minimal, if any, change in global systolic function. Early diastolic dysfunction in ischemic segments exceeds compensatory changes in nonischemic areas by two-to-four-fold. Hence, early diastolic functional indexes may be more sensitive indicators of ischemia at rest than early systolic functional indexes.

Comparison of technetium-99m teboroxime tomography with automated quantitative coronary arteriography and thallium-201 tomographic imaging.

Technetium-99m (Tc-99m) teboroxime is a new perfusion tracer that is highly extracted and rapidly cleared by the myocardium. To determine the feasibility of Tc-99m teboroxime imaging in the diagnosis of patients with suspected coronary artery disease, 30 patients underwent single photon emission computed tomography imaging with Tc-99m teboroxime (25.2 +/- 1 mCi) at peak exercise and again 60 min later at rest. All patients underwent either a thallium stress test (n = 26) or automated quantitative coronary arteriography (n = 25), or both, without intervening revascularization or infarction. Images were reviewed by two investigators who had no knowledge of clinical data. Coronary lesions with greater than or equal to 50% diameter narrowing by quantitative coronary arteriography were considered significant. Both thallium and Tc-99m teboroxime detected disease in all patients with two or three vessel disease. One vessel disease was detected with Tc-99m teboroxime in 9 of 10 patients and with thallium in 8 of 10 (p = NS). In patients without angiographically significant disease. Tc-99m teboroxime demonstrated normal perfusion in six of eight patients and thallium in three of five (p = NS). Overall, when presence or absence of disease detected by Tc-99m teboroxime or thallium was compared with quantitative coronary arteriography, there was no difference between Tc-99m teboroxime and thallium. These results suggest that Tc-99m teboroxime is comparable to thallium as an imaging agent. The rapid biologic half-life, 5.3 min, allows studies to be completed in 60 to 90 min.

Cyclic flow variations after coronary angioplasty in humans: clinical and angiographic characteristics and elimination with 7E3 monoclonal antiplatelet antibody.

OBJECTIVES: We tested the hypothesis that cyclic alterations in coronary artery blood flow that occurred after coronary angioplasty could be attenuated or abolished by a monoclonal antibody to the platelet surface membrane GP IIb/IIIa receptor. BACKGROUND: Coronary artery cyclic flow variations may occur after coronary angioplasty in experimental animal models and humans. In animal models of coronary thrombosis, cyclic alterations in flow often have preceded thrombotic occlusion or reocclusion. Several agents that inhibit platelet function have been shown to attenuate or eliminate cyclic flow variations in these models. METHODS: We monitored coronary artery flow in 27 patients for 30 min after coronary angioplasty, using 0.018-in. (0.046 cm) coronary guide wires with pulsed wave Doppler ultrasound transducers on the distal tips. Clinical data were collected and quantitative analyses performed on coronary arteriograms made before and after the angioplasty procedures. We compared findings in patients with and without cyclic flow variations detected. RESULTS: There were 20 men and 7 women. Mean age was 58 years, and 63% had unstable angina. They received standard doses of nitrates, aspirin, heparin, calcium channel antagonists and other medications clinically indicated. Nevertheless, we detected cyclic flow variations in five patients (19%). Four of these patients had stable flow restored with intravenous injection of 0.25 mg/kg normal body weight of monoclonal antibody c7E3 Fab to the platelet GP IIb/IIIa receptor. In one patient, stable flow was restored by repeat dilation when an immediate angiogram revealed renarrowing. Patients developing cyclic alterations in flow had longer lesions (18.7 +/- 7.5 mm vs. 13.1 +/- 5.7 mm, p < 0.05) that had responded less well to angioplasty (stenosis postangioplasty 47 +/- 13% vs. 33 +/- 15%, p < 0.05). CONCLUSIONS: Cyclic alterations in coronary artery blood flow may occur in some patients after coronary angioplasty, despite the use of standard antiplatelet, antithrombotic and antivasospastic medications. We found that they could be eliminated by this monoclonal antibody that blocks the final common event of platelet aggregation.

Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VIII. Clinical feasibility of positron cardiac imaging without a cyclotron using generator-produced rubidium-82.

The purpose of this study was to determine the clinical feasibility of diagnosing significant coronary artery disease by positron imaging of myocardial perfusion without a cyclotron, using generator-produced rubidium-82 (82Rb). Fifty patients underwent positron emission tomography of the entire heart using a multislice positron camera and intravenous 82Rb or nitrogen-13 ammonia (13NH3) before and after intravenous dipyridamole combined with handgrip stress. Images were read by two observers blinded as to clinical or arteriographic data. Automated quantitative coronary arteriography was obtained for the arteriographic determination of coronary flow reserve, previously demonstrated to be a single integrated measure of stenosis severity accounting for all its geometric dimensions of length, absolute diameter, percent narrowing and asymmetry by quantitative analysis of cine films. Significant coronary artery disease was defined as an arteriographically determined coronary flow reserve of less than 3.0 based on all stenosis dimensions. Any single geometric measure of stenosis severity alone was an inadequate reference standard for comparison with perfusion images. Sensitivity of identifying patients with coronary artery disease having an arteriographically determined coronary flow reserve of less than 3.0 was 95% by positron imaging with a specificity of 100%. The single case that was missed, studied with 13NH3, had a 43% diameter narrowing of a small ramus intermedius off the left coronary artery with no significant narrowing of the major coronary arteries. Positron emission tomography of myocardial perfusion before and after intravenous dipyridamole combined with handgrip stress utilizing generator-produced 82Rb provides sensitive and specific diagnosis of reduced coronary flow reserve due to coronary artery disease in humans.

Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients.

OBJECTIVES: The purpose of this study was to identify qualitative or quantitative variables present on angioscopy, intravascular ultrasound imaging or quantitative coronary arteriography that were associated with adverse clinical outcome after coronary intervention in high risk patients. BACKGROUND: Patients with acute coronary syndromes and complex lesion morphology on angiography are at increased risk for acute complications after coronary angioplasty. Newer devices that primarily remove atheroma have not improved outcome over that of balloon angioplasty. Intravascular imaging can accurately identify intraluminal and intramural histopathologic features not adequately visualized during coronary arteriography and may provide mechanistic insight into the pathogenesis of abrupt closure and restenosis. METHODS: Sixty high risk patients with unstable coronary syndromes and complex lesions on angiography underwent angioscopy (n = 40) and intravascular ultrasound imaging (n = 46) during interventional procedures. In 26 patients, both angioscopy and intravascular ultrasound were performed in the same lesion. All patients underwent off-line quantitative coronary arteriography. Coronary interventions included balloon (n = 21) and excimer laser (n = 4) angioplasty, directional (n = 19) and rotational (n = 6) atherectomy and stent implantation (n = 11). Patients were followed up for 1 year for objective evidence for recurrent ischemia. RESULTS: Patients whose clinical presentation included rest angina or acute myocardial infarction or who received thrombolytic therapy within 24 h of procedure were significantly more likely to experience recurrent ischemia after intervention. Plaque rupture or thrombus on preprocedure angioscopy or angioscopic thrombus after intervention were also significantly associated with adverse outcome. Qualitative or quantitative variables on angiography, intravascular ultrasound or off-line quantitative arteriography were not associated with recurrent ischemia on univariate analysis. Multivariate predictors of recurrent ischemia were plaque rupture on preprocedure angioscopy (p < 0.05, odds ratio [OR] 10.15) and angioscopic thrombus after intervention (p < 0.05, OR 7.26). CONCLUSIONS: Angioscopic plaque rupture and thrombus were independently associated with adverse outcome in patients with complex lesions after interventional procedures. These features were not identified by either angiography or intravascular ultrasound.

Noninvasive assessment of coronary collaterals in man by PET perfusion imaging.

At present, coronary collateralization cannot be identified or assessed noninvasively in patients. In animal studies, coronary collaterals are associated with coronary steal, defined as a regional fall in perfusion during coronary arteriolar vasodilation. To determine the effect of coronary arteriolar vasodilation on collateral bed perfusion in man, myocardial perfusion imaging was performed before and after pharmacologic coronary vasodilation in patients with coronary artery disease (CAD). Regional myocardial activity of 82Rb or 13N ammonia was measured by positron emission tomography (PET) at rest and with intravenous dipyridamole/handgrip stress in 28 patients with angiographic collaterals and in 25 control patients with similar CAD severity by quantitative arteriography. Regional myocardial activity decreased after dipyridamole, indicating coronary steal, in 25 of 28 patients with angiographic collaterals and in only 4 of 25 control patients without angiographic collaterals. These findings suggest that developed collaterals are associated with myocardial steal in patients with CAD, allowing potential use of PET for non-invasive identification of coronary collateralization.

Changes in myocardial perfusion reserve after PTCA: noninvasive assessment with positron tomography.

The effect of percutaneous transluminal coronary angioplasty (PTCA) on myocardial perfusion reserve has not been previously determined. Accordingly, 11 patients underwent positron imaging with [13N]ammonia or 82Rb at rest and following dipyridamole + handgrip stress before and after PTCA. The ratio of stress to rest activity (S:R) was determined for each region of interest. Relative myocardial perfusion reserve by positron tomography (RMPR) was calculated by dividing S:R of the stenotic area by a corresponding value from a normal reference area of the same patient. Automated quantitative coronary arteriography was used to objectively measure the percent diameter (%D) and the percent area narrowing (%A) of the stenoses. In nine patients with successful PTCA, %D and %A improved (68 +/- 10 to 49 +/- 15% and 92 +/- 3 to 72 +/- 5%) and RMPR increased from 0.79 +/- 0.07 to 0.96 +/- 0.05. In the two patients in whom PTCA was unsuccessful, RMPR was unchanged. Changes in RMPR correlated inversely with changes in %D (r = -0.68) and %A (r = -0.92) and directly with improved coronary flow reserve derived from all stenosis measurements (r = 0.73, p less than 0.001 for each). This study suggests that dipyridamole + handgrip stress imaging with PET can be used to assess changes in myocardial perfusion reserve before and after PTCA with the potential for determining restenosis noninvasively.

Coronary artery flow monitoring following coronary interventions.

Technologic innovations have made it possible to measure coronary artery blood flow in awake patients. Both flow velocity as well as flow reserve can be assessed. In particular, the period of time immediately following coronary interventions offers a unique opportunity to study important features of coronary flow behavior. In 22 patients, coronary flow reserve was measured before and after an intervention, either angioplasty or atherectomy, using a 0.018-in Doppler guidewire (Flowire). The minimum lumen diameter (MLD) was increased from 1.0 +/- 0.4 to 1.7 +/- 0.4 mm, while coronary flow velocity increased significantly, rising from 29 +/- 13 to 39 +/- 14 cm/sec (p < 0.025). The maximum hyperemic velocity also increased, from 44 +/- 16 to 69 +/- 21 cm/sec. Using only the preintervention or postintervention values, the flow reserve ratio was 1.53 +/- 0.4 prior to intervention and 1.84 +/- 0.5 after intervention (p = nonsignificant). However, the post-intervention value may have been artifactually reduced by the fact that both resting as well as hyperemic velocities increased. When the post-intervention flow reserve ratio was recalculated, using the preintervention resting value, flow reserve ratio was seen in increase from 1.53 +/- 0.4 to 2.73 +/- 1.2 (p < 0.001). Measurements of coronary flow in the postintervention period also revealed several interesting phenomena. Spasm of a coronary artery was documented, and its resolution in response to intracoronary nitroglycerin was observed. Elastic recoil following angioplasty was documented by gradual decline in coronary flow over 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved stenosis geometry by quantitative coronary arteriography after vigorous risk factor modification.

This study is a randomized, controlled, blinded, arteriographic trial to determine the effects of a low-cholesterol, low-fat, vegetarian diet, stress management and moderate aerobic exercise on geometric dimensions, shape and fluid dynamic characteristics of coronary artery stenoses in humans. Complex changes of different primary stenosis dimensions in opposite directions or to different degrees cause stenosis shape change with profound effects on fluid dynamic severity, not accounted for by simple percent narrowing. Accordingly, all stenosis dimensions were analyzed, including proximal, minimal, distal diameter, integrated length, exit angles and exit effects, determining stenosis shape and a single integrated measure of stenosis severity, stenosis flow reserve reflecting functional severity. In the control group, complex shape change and a stenosis-molding characteristic of statistically significant progressing severity occurred with worsening of stenosis flow reserve. In the treated group, complex shape change and stenosis molding characteristic of significant regressing severity was observed with improved stenosis flow reserve, thereby documenting the multidimensional characteristics of regressing coronary artery disease in humans.

Estrogen replacement therapy and outcome of coronary balloon angioplasty in postmenopausal women.

Estrogen replacement therapy (ERT) in women after menopause is associated with prevention of clinical coronary artery disease. However, few studies have investigated possible benefits from ERT in postmenopausal women undergoing treatment for established coronary disease. We therefore retrospectively reviewed the clinical outcomes of 428 postmenopausal women undergoing percutaneous transluminal coronary balloon angioplasty (PTCA) to test the hypothesis that ERT has a beneficial effect in this setting. The women were divided into 2 groups based on ERT status at the time of the procedure. Estrogen users were younger (60 +/- 10 vs 68 +/- 9 years, p <0.001), more commonly had family histories of coronary heart disease (54% vs 41%, p = 0.04), had less incidence of hypertension (63% vs 76%, p = 0.02), and had slightly fewer diseased vessels per patient (1.3 +/- 0.5 vs 1.5 +/- 0.7, p = 0.03) compared with nonusers. No in-hospital deaths occurred in estrogen users compared with 5% hospital mortality in nonusers (p = 0.01). The combined outcome of death or myocardial infarction (MI) also was lower in estrogen users (4% vs 12%, p = 0.04). Of 348 women discharged after successful PTCA, 336 (97%) were able to be contacted at an average follow-up interval of 22 +/- 17 months (range 5 to 82). Estrogen users had superior event-free survival both for death as well as for death or nonfatal MI. Repeat revascularizations were similar in both groups (32% vs 24%, p = 0.15). In a Cox proportional-hazards model, nonusers had 4 times the likelihood of death after angioplasty compared with estrogen users (OR = 4.025, 95% CI = 1.3 to 13.4, p = 0.02). We conclude that estrogen replacement may offer protection against clinical coronary events in postmenopausal women who already have established coronary disease and are undergoing balloon angioplasty. The benefit was independent of age, smoking, presence of diabetes mellitus, or the number of diseased coronary vessels. However, it did not include a reduction in repeat revascularization procedures, suggesting no reduction in restenosis.

Changes in proximal and distal coronary artery diameter during atrial pacing-induced myocardial ischemia.

BACKGROUND: The present study was designed to evaluate the role of tachycardia-induced dynamic coronary artery diameter changes in the development of myocardial ischemia. METHODS: Coronary angiography at rest and during atrial pacing-induced myocardial ischemia was performed in 22 patients. The diameter of the proximal and the corresponding distal coronary artery segments at rest and during pacing was measured using quantitative coronary angiography. Plasma levels of noradrenaline, adrenaline, dopamine and endothelin were determined in a subset of 14 patients in blood drawn from aorta and coronary sinus at rest and during pacing. RESULTS: Luminal diameter in normal proximal and distal segments increased, respectively, from 2.93 +/- 0.34 and 1.40 +/- 0.04 mm at rest to 3.03 +/- 0.25 and 1.58 +/- 0.07 mm during atrial pacing. The diameter of the proximal coronary artery segments with significant concentric stenosis decreased from 1.28 +/- 0.4 mm at rest to 0.95 +/- 0.34 mm during pacing, whereas segments with either significant eccentric or non-significant stenosis did not change significantly. A correlation was found between the noradrenaline level in the coronary sinus and the distal coronary artery diameter. CONCLUSIONS: A decrease in diameter of coronary artery segments with concentric stenosis during tachycardia might contribute to the development of myocardial ischemia. Some of the dynamic coronary artery changes may be influenced by the plasma level of noradrenaline. No evidence was found to suggest that dynamic changes in the diameter of proximal segments are related to the changes in diameter of the corresponding distal segments.