Efficacy of Coronary Computed Tomography Angiography for the De Novo Detection of Chronic Total Occlusion Prior to Coronary Angiography: A Preliminary and Retrospective Study.

Coronary computed tomography angiography (CCTA) offers high-resolution anatomic characterization of the coronary vasculature but may be suboptimal for lesions dependent on real-time visualization of flow including chronic total occlusion (CTO). In CTOs, heavy calcification and distal vessel opacification from collateralization may confound luminal assessment. Several studies have examined the role of CCTA in characterizing known CTOs to guide percutaneous coronary intervention (PCI). However, the efficacy of CCTA in the de novo diagnosis of CTOs prior to coronary angiography (CAG) has not been demonstrated. A total of 233 consecutive patients who presented for CAG within a 3-month period of having CCTA were retrospectively reviewed. Those patients with prior diagnosis of CTO or prior bypass of the occluded vessels were excluded. Sensitivity and specificity analysis of CCTA in identifying CTOs using CAG as the gold standard was performed. The prevalence of CTO was 21.11% in the population that met criteria for analysis ( n = 199). The sensitivity of CCTA in predicting CTO was 57.1%, while the specificity was 96.8%. The positive predictive value and negative predictive value of CCTA in detection of CTO were 82.8 and 89.4%, respectively. Our study shows that CCTA has excellent specificity but poor sensitivity in the detection of CTO thus limiting its clinical use in de novo diagnosis. Further studies to determine the effect of de novo CTO diagnosis on clinically important procedural factors, such as radiation exposure, contrast use, and need for repeat procedures, are warranted and may implicate a role for CCTA in this setting.

Coagulation markers predicting cardiac transplant rejection.

BACKGROUND: Acute cellular rejection in cardiac allografts is a major cause of graft loss, and is associated with activation of the coagulation system. We investigated whether plasma markers of coagulation predict the presence of allograft rejection. METHODS: A total of 132 blood specimens and endomyocardial biopsies were collected from 35 patients, between February of 1997 and May of 1998. We measured plasma prothrombin fragment 1.2 (PF1.2) and p-selectin, fibrinogen, thrombomodulin, and d-dimer. Biopsies were graded according to the International Society of Heart and Lung Transplantation system, with a range of 0 to 4. Grades 0 and 1A were grouped as "no rejection," and the higher grades as "rejection." Linear and logistic regression, accounting for longitudinal data, were the principal analytic tools. RESULTS: p-Selectin level increased progressively with increasing rejection grade (P<0.001). With multivariate analysis, both p-selectin and prothrombin fragment levels significantly predicted rejection. p-Selectin levels were predictive of prothrombin fragment levels (P<0.0001) but not of d-dimer, fibrinogen, or thrombomodulin levels. This model allowed correct prediction of rejection, based on p-selectin and prothrombin fragment values, up to 85% of the time. Dichotomizing patients by a p-selectin level of 65 ng/ml resulted in an odds of rejection of 21.4 [95% C.I. 7.1-64.7] for the patients in the high- compared with the lower risk group. CONCLUSIONS: In heart transplant recipients, p-selectin levels and PF 1.2 levels are highly predictive of organ rejection. The elevation of PF 1.2 suggests that there is systemic generation of thrombin generation. These markers may be useful for noninvasively monitoring patients for organ rejection or for after response to treatment.

GPIIb-IIIa receptor inhibitors: what the interventional radiologist needs to know.

The glycoprotein IIb-IIIa (GPIIb-IIIa) receptor inhibitors have established themselves as first line therapy in the treatment of acute coronary syndromes (ACS) and percutaneous coronary intervention (PCI). The benefit of these agents rests in their ability to attenuate the deleterious effects of platelet activation, both at the site of an inflamed vessel wall (due to a ruptured plaque or PCI) and in the microcirculation as a result of embolization. Based on these results, interventional radiologists are beginning to explore the potential of using GPIIb-IIIa inhibitors during interventions in the peripheral circulation. This paper reviews the molecular biology of the GPIIb-IIIa receptor, the pharmacology of the GPIIb-IIIa receptor inhibitors, the current coronary and peripheral vascular literature as it pertains to the GPIIb-IIIa receptor inhibitors, and potential future applications of the GPIIb-IIIa receptor inhibitors in the peripheral circulation.

Percutaneous transmyocardial laser revascularisation for severe angina: the PACIFIC randomised trial. Potential Class Improvement From Intramyocardial Channels.

BACKGROUND: Percutaneous transmyocardial laser revascularisation (PTMR) is a proposed catheter-based therapy for refractory angina pectoris when bypass surgery or angioplasty is not possible. We undertook a randomised trial to assess the safety and efficacy of this technique. METHODS: 221 patients with reversible ischaemia of Canadian Cardiovascular Society angina class III (61%) or IV (39%) and incomplete response to other therapies were recruited from 13 centres. Patients were randomly assigned PTMR with a holmium:YAG laser plus continued medical treatment (n=110) or continued medical treatment only (n=111). The primary endpoint was the exercise tolerance at 12 months. Analyses were by intention to treat. FINDINGS: 11 patients died and 19 withdrew; 92 PTMR-group and 99 medical-treatment-group patients completed the study. Exercise tolerance at 12 months had increased by a median of 89.0 s (IQR -15 to 183) with PTMR compared with 12.5 s (-67 to 125) with medical treatment only (p=0.008). On masked assessment, angina class was II or lower in 34.1% of PTMR patients compared with 13.0% of those medically treated. All indices of the Seattle angina questionnaire improved more with PTMR than with medical care only. By 12 months there had been eight deaths in the PTMR group and three in the medical treatment group, with similar survival in the two groups. INTERPRETATION: PTMR was associated with increased exercise tolerance time, low morbidity, lower angina scores assessed by masked reviewers, and improved quality of life. Although there is controversy about the mechanism of action, and the contribution of the placebo effect cannot be quantified, this unmasked study suggests that this palliative procedure provides some clinical benefits in the defined population of patients.

Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. ATLANTIC Investigators. Angina Treatments-Lasers and Normal Therapies in Comparison.

BACKGROUND: Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication. METHODS: We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months. FINDINGS: At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001). INTERPRETATION: TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options.

Factors correlating with risk of mortality after transmyocardial revascularization.

OBJECTIVES: The purpose of this study was to determine factors correlating with the risk of postoperative mortality after transmyocardial laser revascularization (TMR). BACKGROUND: Clinical studies have indicated that TMR reduces angina by an average of two classes in patients with medically refractory symptoms not treatable by coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty. Factors which correlate with mortality after TMR, however, have not been extensively investigated. METHODS: One hundred thirty-two patients with severe angina underwent TMR as sole therapy with a CO2 laser. Age, gender, ejection fraction, prior CABG, unstable angina and the severity of coronary artery disease (graded on the basis of a newly proposed Anatomic Myocardial Perfusion index, AMP) were each determined. Each vascular territory (left anterior descending artery [LAD] left circumflex artery and posterior descending artery [PDA]) was graded as either having (AMP = 1) or not having (AMP = 0) blood flow through an unobstructed major vessel in the territory. Univariate and multivariate analysis determined which factors correlated with mortality. RESULTS: Patients with at least one AMP = 1 vascular territory (overall AMP = 1) had a 5% (4/82) postoperative mortality rate (POM), compared with 25% (12/49) with overall AMP 0 (p = 0.002). Left anterior descending artery AMP (p = 0.03) and previous CABG (p = 0.04) each correlated with the risk of POM. However, multivariate analysis indicated that no factor improved the correlation obtained with overall AMP by itself. With regard to overall mortality (Kaplan-Meier curves), univariate analysis also revealed correlations with overall AMP (p < 0.001), LAD AMP (p = 0.005), previous CABG (p = 0.003) and PDA AMP (p = 0.05) each individually correlated with mortality. Multivariate analysis indicated that overall AMP = 1, female gender and previous CABG together correlated best with lower postoperative mortality. CONCLUSIONS: Patients with good blood flow to at least one region of the heart through a native artery or a patent vascular graft have a markedly reduced risk of perioperative and longer term mortality.

Modifiable risk factors for vascular access site complications in the IMPACT II Trial of angioplasty with versus without eptifibatide. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis.

OBJECTIVES: This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications. METHODS: A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5-microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75-microg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications. RESULTS: VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications. CONCLUSIONS: VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.

Acute effects of conjugated estrogens on coronary blood flow response to acetylcholine in men.

Estrogen therapy is associated with a 50% reduction in the clinical manifestations of coronary artery disease in postmenopausal women. Attenuation of coronary vasomotor dysfunction may contribute to estrogen's cardioprotective effects. We hypothesized that conjugated estrogens, which contain several vasoactive estrogenic compounds, may favorably influence the vasomotor response to acetylcholine in men. Twenty men, 56 +/- 5 years of age, referred for clinically indicated coronary angiography, participated in this study. Acetylcholine-induced changes in coronary flow were measured by quantitative coronary angiography and intracoronary Doppler ultrasonography before and 15 minutes after intravenous administration of conjugated estrogens (0.625 mg) in 12 men and placebo in 8 men. Initial acetylcholine infusion resulted in no significant increase in coronary blood flow. However, 15 minutes after estrogen administration repeat acetylcholine infusion caused a mean 32% increase in coronary blood flow from 41 +/- 5 to 54 +/- 8 ml/min (p = 0.02). Acetylcholine-induced change in flow after estrogen was significantly different from that before estrogen (p = 0.03). Placebo administration did not affect acetylcholine-induced changes in coronary flow. Thus, intravenous conjugated estrogens favorably modulate acetylcholine-induced changes in coronary hemodynamics in men. This suggests that novel nonfeminizing estrogenic compounds may have anti-ischemic effects in men.

Long-term estrogen therapy abolishes acute estrogen-induced coronary flow augmentation in postmenopausal women.

Postmenopausal estrogen replacement therapy (ERT) may reduce the clinical manifestations of coronary heart disease by favorably modulating coronary vasoreactivity. Intravenous ethinyl estradiol acutely increases coronary flow in postmenopausal women not receiving ERT. Because several vasoactive agents induce vasomotor tolerance when administered on a long-term basis, we hypothesized that long-term ERT attenuates the acute coronary vasomotor effects of intravenous ethinyl estradiol. To test this hypothesis, coronary hemodynamics were determined before and 15 minutes after intravenous ethinyl estradiol (35 micrograms) in 10 postmenopausal women who were receiving long-term conjugated ERT (group 1) and 10 who had never received ERT (group 2). Estradiol administration in group 1 was not associated with significant changes in coronary flow or resistance. However, women in group 2 exhibited a 28.6% +/- 6.5% (p < 0.001) increase in coronary flow and a 19.9% +/- 3.5% (p = 0.008) decrease in resistance. These results demonstrate that long-term ERT significantly attenuates the response of coronary arteries to the acute vasomotor effects of a high dose of estradiol. This response may be caused by long-term estrogen-induced coronary flow augmentation or to the development of vasomotor tolerance to estrogen.

Clinical evaluation of a microsample coagulation analyzer, and comparison with existing techniques.

A new microsample coagulation analyzer (Hemochron Jr.) has recently been developed which performs a modified activated clotting time (ACT+) and an aPTT by using different reagents. The Hemochron Jr. measures the clotting time of a 5-microliter whole-blood sample by an optical detector and extrapolates the results to the activated clotting time (ACT+) or the plasma-activated partial thromboplastin time by using a validated regression analysis. We compared 124 simultaneous ACT+ and Hemochron ACTs, and 53 paired Hemochron Jr. aPTTs and hospital laboratory aPTTs, in 44 patients during coronary intervention. The Hemochron Jr. aPTT closely correlated with the lab aPTT (r = .79, P < .0001), and the test results were available much more rapidly than the lab aPTT (3.5 +/- 1.1 vs. 56.3 +/- 25.5 min, P = 0.0029). A comparison of duplicate ACT+ measurements did not identify a significant difference in the means (292 +/- 115 sec vs. 293 +/- 112 sec, P = 0.72). The ACT+ closely correlated with the Hemochron ACTs (r = .85, P < .0001). At baseline, the mean ACT+ (175 +/- 43 sec) exceeded the Hemochron ACT (144 +/- 36 sec) by 22% (P < .001). After heparin administration, the mean ACT+ (378 +/- 74 sec) exceeded the Hemochron ACT (332 +/- 65) by 12% (P < .001). The Hemochron Jr. provides a fast and reproducible methodology for measuring ACT and aPTT, using a small blood volume. Further studies are required to determine the optimal anticoagulation range when using the Hemochron Jr. during or after interventional procedures.

Coronary artery spasm in the transplanted human heart. A case report.

This report describes a patient manifesting spontaneous and catheter-induced coronary artery spasm in a transplanted, denervated heart. This diagnosis should be considered in patients undergoing posttransplant coronary angiography. Intracoronary nitroglycerin should routinely be administered prior to coronary artery injections during posttransplant angiography.

Comparison of bedside and hospital laboratory coagulation studies during and after coronary intervention.

The activated clotting time is routinely used to monitor anticoagulation during coronary intervention, whereas the hospital laboratory APTT guides pre- and postprocedure heparin therapy. An optimal coagulation test for patients undergoing percutaneous revascularization would provide a rapid and accurate assessment of anticoagulation throughout a broad range of heparin therapy. We studied the relationships of the bedside whole blood APTT, ACT, and the laboratory APTT in 166 patients undergoing coronary intervation. The whole blood APTT correlated closely with the laboratory APTT (range 18-80 sec) (r = .75), whereas the ACT and laboratory APTT had only a fair correlation (r = .42). Also, the whole blood APTT demonstrated a strong correlation with the ACT throughout the range of heparin therapy for intervention (r = .81). The diagnostic accuracy of the whole blood APTT, based on the receiver operating characteristic curve, was significantly better than that for the ACT in determining the anticoagulation status. The whole blood APTT obtained by bedside monitoring provides a rapid and accurate assessment of anticoagulation throughout the range of heparin dosing associated with coronary intervention. In situations in which an adequate assessment of residual anticoagulation is necessary, the whole blood APTT is superior to the ACT and probably should be the method of choice.

Heat-induced changes in the mechanical behavior of passive coronary arteries.

We performed in vitro pressure-diameter and axial force-length experiments on nondiseased, passive bovine coronary arteries subjected to bath temperatures from 21 to 80 degrees C for 90 s to 4 hr. Over the strain ranges studied, we found that: (a) vessel behavior remained the same over 20 min of testing at 21 to 55 degrees C, (b) vessels stiffened multiaxially after 5 min of exposure to 60 degrees C and continued to stiffen over 20 min of testing, (c) dramatic multiaxial vessel stiffening and shrinkage occurred after 90 s of exposure to 70 and 80 degrees C, and (d) heat-induced changes at 70 degrees C depended on the intraluminal pressure during heating. Thus, passive bovine coronary arteries exhibit a complex thermomechanical behavior that depends on the temperature, duration of thermal exposure, and the mechanical loads applied during heating.

Coronary angioplasty through a new 6 French guiding catheter.

Coronary angioplasty through smaller-diameter guiding catheters using predominantly fixed-wire balloon systems has been possible, but has had some limitations. The purpose of this prospective, nonrandomized study was to investigate the results of percutaneous transluminal coronary angioplasty using a new 6F guiding catheter with over-the-wire balloon systems. Coronary angioplasty using over-the-wire balloon systems through a new 6F guiding catheter was evaluated in 79 lesions in 70 patients and then compared to randomly selected procedures using 7F guiding catheters in 70 patients performed over the same time period. Coronary angioplasty through 6F guiding catheters and over-the-wire balloons including 8 long (30-mm) and 3 perfusion balloons was successful in 94.9% of lesions and in 94% of patients. Coronary angioplasty through 7F guiding catheters was successful in 97.5% of lesions and in 97.1% of patients, respectively. Success rates between 6F and 7F guiding catheter groups were similar overall and for proximal, mid, distal, or complex (total, subtotal, or length > 10-mm) lesions. There were no failures to withdraw the deflated balloon into the 6F guiding catheter. Vessel opacification after dilatation with the guidewire across the lesion was similar between the 6F and 7F guiding catheter groups. The mean change in hematocrit for the 6F procedures (-1.4 +/- 3.7%) was significantly lower than for the 7F procedures (-3.3 +/- 3.2%, P < 0.001). Coronary angioplasty using a variety of over-the-wire balloon catheters through a new 6F guiding catheter is feasible with success rates comparable to 7F guiding catheters. Angioplasty with this 6F guiding catheter reduces procedural blood loss compared to larger-lumen guiding catheters.