Psychosocial stress and atherosclerosis: family and work stress accelerate progression of coronary disease in women. The Stockholm Female Coronary Angiography Study.

OBJECTIVE: To examine the impact of psychosocial stress, experienced in the family and work life, on the progression of coronary atherosclerosis in women cardiac patients. DESIGN: Longitudinal follow-up study. The mean luminal diameter change over 3 years was averaged over 10 predefined coronary segments, representing the entire coronary tree. Stress in family life was measured by using the Stockholm Marital Stress Scale and that of work life by the demand-control questionnaire. SUBJECTS: Amongst patients enrolled in the Stockholm Female Coronary Angiography Study, 80 women were evaluated for stress exposure and coronary atherosclerosis progression using serial quantitative coronary angiography. RESULTS: Multi-variable-controlled mixed models anova analyses revealed that women with high stress from either family or work had significant disease progression over 3 years, whereas those with low stress had only slight progression. In women who were free of stress from either family or work life, i.e. they were satisfied with both of these life domains, the coronary artery changes had regressed. Their mean coronary luminal diameter increased by 0.22 mm (95% CI: 0.10; 0.35 mm) when compared with women who experienced stress from both sources, whose luminal diameter decreased by 0.20 mm (95% CI: -0.14; -0.25). These associations were independent of baseline luminal diameter and standard cardiovascular risk factors, including age smoking, hypertension and HDL at baseline. CONCLUSIONS: Stress from family or work life may accelerate coronary disease processes in women, whereas relative protection may be obtained from a satisfactory job and a happy marriage.

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.

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.

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).

Social relations and extent and severity of coronary artery disease. The Stockholm Female Coronary Risk Study.

AIMS: Social relations have been repeatedly linked to coronary heart disease in men, even after careful control for standard risk factors. Women have rarely been studied and results have not been conclusive. We investigated the role of social support in the severity and extent of coronary artery disease in women. METHODS AND RESULTS: One hundred and thirty-one women, aged 30 to 65 years, who were hospitalized for an acute coronary event and were included in the Stockholm Female Coronary Risk Study, were examined with computer assisted quantitative coronary angiography. Angiographic measures included presence of stenosis greater than 50% in at least one coronary artery (severity) and the number of stenoses greater than 20% within the coronary tree (extent). Social factors included two measures of social support, which were previously shown to predict coronary disease in prospective studies of men. After adjustment for age, lack of social support was associated with both measures of coronary artery disease. With further adjustment for smoking, education, menopausal status, hypertension, high density lipoprotein and body mass index, the risk ratio for stenosis greater than 50% in women with poor as compared to those with strong social support was 2.5 (95% confidence interval 1.2 to 5.3; P=0.003). Also, women with poor social support had more stenoses obstructing at least 20% of the coronary lumen with multivariate adjustment, but the difference from women with strong support was only of borderline significance (P=0.09). CONCLUSION: The findings suggest that lack of social support contributes to the severity of coronary artery disease in women, independent of standard risk factors.

Intensive lifestyle changes for reversal of coronary heart disease.

CONTEXT: The Lifestyle Heart Trial demonstrated that intensive lifestyle changes may lead to regression of coronary atherosclerosis after 1 year. OBJECTIVES: To determine the feasibility of patients to sustain intensive lifestyle changes for a total of 5 years and the effects of these lifestyle changes (without lipid-lowering drugs) on coronary heart disease. DESIGN: Randomized controlled trial conducted from 1986 to 1992 using a randomized invitational design. PATIENTS: Forty-eight patients with moderate to severe coronary heart disease were randomized to an intensive lifestyle change group or to a usual-care control group, and 35 completed the 5-year follow-up quantitative coronary arteriography. SETTING: Two tertiary care university medical centers. INTERVENTION: Intensive lifestyle changes (10% fat whole foods vegetarian diet, aerobic exercise, stress management training, smoking cessation, group psychosocial support) for 5 years. MAIN OUTCOME MEASURES: Adherence to intensive lifestyle changes, changes in coronary artery percent diameter stenosis, and cardiac events. RESULTS: Experimental group patients (20 [71%] of 28 patients completed 5-year follow-up) made and maintained comprehensive lifestyle changes for 5 years, whereas control group patients (15 [75%] of 20 patients completed 5-year follow-up) made more moderate changes. In the experimental group, the average percent diameter stenosis at baseline decreased 1.75 absolute percentage points after 1 year (a 4.5% relative improvement) and by 3.1 absolute percentage points after 5 years (a 7.9% relative improvement). In contrast, the average percent diameter stenosis in the control group increased by 2.3 percentage points after 1 year (a 5.4% relative worsening) and by 11.8 percentage points after 5 years (a 27.7% relative worsening) (P=.001 between groups. Twenty-five cardiac events occurred in 28 experimental group patients vs 45 events in 20 control group patients during the 5-year follow-up (risk ratio for any event for the control group, 2.47 [95% confidence interval, 1.48-4.20]). CONCLUSIONS: More regression of coronary atherosclerosis occurred after 5 years than after 1 year in the experimental group. In contrast, in the control group, coronary atherosclerosis continued to progress and more than twice as many cardiac events occurred.

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.

Lipoprotein(a) as a determinant of coronary heart disease in young women.

BACKGROUND: Lipoprotein(a) [Lp(a)] appears to be a risk factor for coronary heart disease (CHD) in men. The role of Lp(a) in women, however, is less clear. METHODS AND RESULTS: We examined the ability of Lp(a) to predict CHD in a population-based case-control study of women 65 years of age or younger who lived in the greater Stockholm area. Subjects were all patients hospitalized for an acute CHD event between February 1991 and February 1994. Control subjects were randomly selected from the city census and were matched to patients by age and catchment area. Lp(a) was measured 3 months after hospitalization by use of an immunoturbidometric method (Incstar) calibrated to the Northwest Lipid Research Laboratories (coefficient of variation was < 9%). Of the 292 consecutive patients, 110 (37%) were hospitalized for an acute myocardial infarction, and 182 were hospitalized (63%) for angina pectoris. The mean age for both patients and control subjects was 56 +/- 7 years. Of participants, 74 patients (25%) and 84 control subjects (29%) were premenopausal. The distributions of Lp(a) were highly skewed in both patients and control subjects, with a range from 0.001 to 1.14 g/L. Age-adjusted odds ratio for CHD in the highest versus the lowest quartile of Lp(a) was 2.3 (95% confidence interval [CI], 1.4 to 3.7). After adjustment for age, smoking, education, body mass index, systolic blood pressure, total cholesterol, triglycerides, and HDL, the odds ratio was 2.9 (95% CI, 1.6 to 5.0). The odds ratios were similar when myocardial infarction and angina patients were compared with their respective control subjects. The odds ratios were 5.1 (95% CI, 1.4 to 18.4) and 2.4 (95% CI, 1.3 to 4.5) in premenopausal and postmenopausal women, respectively. CONCLUSIONS: These results suggest that Lp(a) is a determinant of CHD in both premenopausal and postmenopausal women.

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.

Rotational atherectomy with a new device: initial clinical experience.

The Bard Atherectomy Catheter is a new rotational atherectomy device that consists of a flexible, hollow, thin-walled cutting catheter that, while rotated at 1,500 revolutions per minute, is advanced across the lesion over a special spiral guidewire system. We report the initial clinical experience with this device in 20 peripheral lesions in ten patients. The majority of patients were treated for limb salvage. All lesions were successfully intervened on by atherectomy followed by adjunctive balloon angioplasty. A reduction to less than 50% stenosis was achieved in 13 of the 20 lesions (65%) after atherectomy but in all 20 lesions (100%) after adjunctive angioplasty for all lesions and stenting for dissections in two. Baseline minimal lesion lumen diameter was 0.8 +/- 0.7 mm with a reference vessel diameter of 4.2 +/- 1.7 mm (75 +/- 21% stenosis). The lumen improved to 2.0 +/- 0.8 mm (45 +/- 19% stenosis) (P < 0.001) following atherectomy and to 3.9 +/- 1.9 mm (13 +/- 16% stenosis) (P < 0.001) after adjunctive angioplasty. The average weight of removed atheroma was 45 +/- 58 mg. All ten patients had initial improvement in symptoms. At 6 months follow-up there was persistent improvement in eight patients and two subjects had undergone amputations. Our early clinical experience with this low profile, flexible atherectomy device, that enables extraction of a large amount of atheroma, suggests that it will become a valuable addition to current atherectomy technologies in small- and medium-sized vessels. The value of this device in coronary vessels is under investigation.

Coronary artery flow monitoring: the value of intravascular Doppler for detection of complications after interventions.

Ultrasound transducer-tipped guidewires can be used for coronary interventions, and they permit the monitoring of coronary flow before, during, and after the interventions. The flow signal contains valuable information regarding the quality and stability of the final result. Restoration of typical phasic flow patterns with diastolic predominance is one guide to final result. Monitoring the trend in average velocity over several minutes after completion of the procedure can detect subtle alterations in flow that may presage abrupt closure. These flow alterations might also help predict active plaques with heavy thrombus involvement that may undergo recurrence in the weeks and months after successful procedures.

Coronary artery flow monitoring following coronary interventions.

Coronary guidewires with ultrasound transducer tips are commercially available and are appropriately sized for use in coronary interventions. These guidewires permit monitoring of coronary flow before, during and after the interventions. The measured flow signal contains valuable information regarding the quality and the stability of the final result. After completion of the procedure, monitoring the trend in average velocity over several minutes can reveal subtle alterations in flow that may presage abrupt closure. Abnormal or unstable flow patterns also may help predict lesions that might develop recurrences in the weeks and months after successful procedures.

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.

Analytic isocenter calibration. A new approach for accurate x-ray gantries.

Isocenter calibration transforms cardiac structures in digitized biplane angiograms to absolute dimensions, calculating their radiological magnification and video transformation. Since a scaling device is not required, isocenter calibration yields to more accurate measurements than the widely used reference object calibration. Both isocenter methods reported so far, regarding geometrically inaccurate x-ray gantries, yield to different and complex computational formulas. Since these formulas are hard to understand, isocenter calibration is less widely used. To facilitate the implementation of the isocenter calibration, the basic formulas for accurate x-ray gantries are derived. Shifting virtually one x-ray system onto the other, basic isocenter calibration is derived geometrically in three simple steps. The radiological magnification of an object is illustrated as a ratio of planes. The calculation of all parameters entering the computations is demonstrated geometrically, by use of the isocenter of the x-ray gantry. The derivation gives a clear idea of isocenter calibration. It is simple to derive and facilitates the understanding of the error regarding developments. When geometrical inaccuracies vanish, all formulas become equivalent. However, even if the inaccuracies increase, all methods provide nearly identical results, indicating the robustness of isocenter calibration.

Comparative validation of quantitative coronary angiography systems. Results and implications from a multicenter study using a standardized approach.

BACKGROUND: Computerized quantitative coronary angiography (QCA) has fundamentally altered our approach to the assessment of coronary interventional techniques and strategies aimed at the prevention of recurrence and progression of stenosis. It is essential, therefore, that the performance of QCA systems, upon which much of our scientific understanding has become integrally dependent, is evaluated in an objective and uniform manner. METHODS AND RESULTS: We validated 10 QCA systems at core laboratories in North America and Europe. Cine films were made of phantom stenoses of known diameter (0.5 to 1.9 mm) under four experimental conditions: in vivo (coronary arteries of pigs) calibrated at the isocenter or by use of the catheter as a scaling device and in vitro with 50% contrast and 100% contrast. The cine films were analyzed by each automated QCA system without observer interaction. Accuracy and precision were taken as the mean and SD of the signed differences between the phantom stenoses, and the measured minimal luminal diameters and the correlation coefficient (r), the SEE, the y intercept, and the slope were derived by their linear regression. Performance of the 10 QCA systems ranged widely: accuracy, +0.07 to +0.31 mm; precision, +/- 0.14 to +/- 0.24 mm; correlation (r), .96 to .89; SEE, +/- 0.11 to +/- 0.16 mm; intercept, +0.08 to +0.31 mm; and slope, 0.86 to 0.64. CONCLUSIONS: There is a marked variability in performance between systems when assessed over the range of 0.5 to 1.9 mm. The range of accuracy, intercept, and slope values of this report indicates that absolute measurements of luminal diameter from different multicenter angiographic trials may not be directly comparable and additionally suggests that such absolute measurements may not be directly applicable to clinical practice using an on-line QCA system with a different edge detection algorithm. Power calculations and study design of angiographic trials should be adjusted for the precision of the QCA system used to avoid the risk of failing to detect small differences in patient populations. This study may guide the fine-tuning of algorithms incorporated within each system and facilitate the maintenance of high standards of QCA for scientific studies.

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.

Restenosis revisited: insights provided by quantitative coronary angiography.

In this editorial, the problem of restenosis after coronary balloon angioplasty and other transluminal interventions is reviewed from the perspective of quantitative coronary angiography. The review is largely based on the experience of the Thoraxcentre in the application of quantitative angiography to the study of restenosis over the past decade, with incorporation and discussion of relevant and significant contributions from other groups. Current discrepancies in the angiographic definition of restenosis are highlighted and the use of percent diameter stenosis or MLD as the measurement parameter of choice is objectively addressed. Perspectives on the pathologic paradigm of restenosis are briefly reviewed as a basis from which to evaluate quantitative angiographic information provided by various studies. Particular attention is then paid, in chronologic fashion, to discussion and elaboration of insights to the restenosis process provided by quantitative angiographic studies, which have led to the introduction of some new methodological approaches to the comparison of short- and long-term angiographic luminal changes after various interventions. A word of caution on the potential pitfalls of quantitative angiographic studies is provided and counterbalanced with a discussion of clinical correlations of quantitative angiographic measurements. Finally, a proposal is made for the application of quantitative angiographic measurements to randomized clinical trials for the purpose of comparing new interventional devices.

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)

Experimental basis of determining maximum coronary, myocardial, and collateral blood flow by pressure measurements for assessing functional stenosis severity before and after percutaneous transluminal coronary angioplasty.

BACKGROUND: Severity of coronary artery stenosis has been defined in terms of geometric dimensions, pressure gradient-flow relations, resistance to flow and coronary flow reserve, or maximum flow capacity after maximum arteriolar vasodilation. A direct relation between coronary pressure and flow, however, may only be presumed if the resistances in the coronary circulation are constant (and minimal) as theoretically is the case during maximum arteriolar vasodilation. In that case, pressure measurements theoretically can be used to predict maximum flow and assess functional stenosis severity. METHODS AND RESULTS: A theoretical model was developed for the different components of the coronary circulation, and a set of equations was derived by which the relative maximum flow or fractional flow reserve in both the stenotic epicardial artery and the myocardial vascular bed and the proportional contribution of coronary arterial and collateral flow to myocardial blood flow are calculated from measurements of arterial, distal coronary, and central venous pressures during maximum arteriolar vasodilation. To test this model, five dogs were acutely instrumented with an epicardial, coronary Doppler flow velocity transducer. Distal coronary pressures were measured by an ultrathin pressure-monitoring guide wire (0.015 in.) with minimal influence on transstenotic pressure gradient. Fractional flow reserve was calculated from the pressure measurements and compared with relative maximum coronary artery flow measured directly by the Doppler flowmeter at three different levels of arterial pressure for each of 12 different severities of stenosis at each pressure level. Relative maximum blood flow through the stenotic artery (Qs) measured directly by the Doppler flowmeter showed an excellent correlation with the pressure-derived values of Qs (r = 0.98 +/- 0.01, intercept = 0.02 +/- 0.03, slope = 0.98 +/- 0.04), of the relative maximum myocardial flow (r = 0.98 +/- 0.02, intercept = 0.26 +/- 0.07, slope = 0.73 +/- 0.08), and of the collateral blood flow (r = 0.96 +/- 0.04, intercept = 0.24 +/- 0.07, slope = -0.24 +/- 0.06). Moreover, the theoretically predicted constant relation between mean arterial pressure and coronary wedge pressure, both corrected for venous pressure, was confirmed experimentally (r = 0.97 +/- 0.03, intercept = 9.5 +/- 13.3, slope = 4.4 +/- 1.2). CONCLUSIONS: These results provide the experimental basis for determining relative maximum flow or fractional flow reserve of both the epicardial coronary artery and the myocardium, including collateral flow, from pressure measurements during maximum arteriolar vasodilation. With a suitable guide wire for reliably measuring distal coronary pressure clinically, this method may have potential applications during percutaneous transluminal coronary angioplasty for assessing changes in the functional severity of coronary artery stenoses and for estimating collateral flow achievable during occlusion of the coronary artery.

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.