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Background: Although risk stratification is an important goal of cardiac noninvasive tests (NITs), few contemporary data exist on the prognostic value of different NITs according to patient sex., Objectives: The goal of this study was to compare the results and prognostic information derived from anatomic versus stress testing in stable men and women with suspected coronary artery disease., Methods: In 8,966 patients tested at randomization (4,500 to computed tomography angiography [CTA], 52% female; 4,466 to stress testing, 53% female), we assessed the relationship between sex and NIT results and between sex and a composite of death, myocardial infarction, or unstable angina hospitalization., Results: In women, a positive CTA (≥70% stenosis) was less likely than a positive stress test result (8% vs. 12%; adjusted odds ratio: 0.67). Compared with negative test results, a positive CTA was more strongly associated with subsequent clinical events than a positive stress test result (CTA-adjusted hazard ratio of 5.86 vs. stress-adjusted hazard ratio of 2.27; adjusted p = 0.028). Men were more likely to have a positive CTA than a positive stress test result (16% vs. 14%; adjusted odds ratio: 1.23). Compared with negative test results, a positive CTA was less strongly associated with subsequent clinical events than a positive stress test result in men, although this difference was not statistically significant (adjusted p = 0.168). Negative CTA and stress test results were equally likely to predict an event in both sexes. A significant interaction between sex, NIT type, and test result (p = 0.01) suggests that sex and NIT type jointly influence the relationship between test result and clinical events., Conclusions: The prognostic value of an NIT result varies according to test type and patient sex. Women seem to derive more prognostic information from a CTA, whereas men tend to derive similar prognostic value from both test types., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We studied whether assessment of endothelium-dependent vasomotion (EDV) with brachial artery ultrasound (BAUS) imaging predicts the presence or absence of coronary artery disease (CAD) as defined by exercise myocardial perfusion imaging (ExMPI)., Background: Abnormalities in EDV can be detected in arteries before the development of overt atherosclerosis, and its presence may predict poor long-term prognosis. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral EDV., Methods: Clinically-indicated ExMPI along with BAUS were performed in 94 subjects (43 women, 51 men). Coronary artery disease was defined by myocardial ischemia or infarction on single photon emission computed tomography images. Flow-mediated dilation (FMD) after upper arm occlusion was defined as the percent change in arterial diameter during reactive hyperemia relative to the baseline., Results: Subjects with CAD by ExMPI (n = 23) had a lower FMD (6.3 +/- 0.7%) than those without CAD by ExMPI (n = 71) (10.5 +/- 0.6%; p = 0.0004). Flow-mediated dilation was highly predictive for CAD with an odds ratio of 1.32 for each percent decrease in FMD (p = 0.001). Based on a receiver-operator analysis, an FMD of 10% was used as a cut-point for further analysis. Twenty-one of 23 subjects who were positive for ExMPI had an FMD < 10% (sensitivity 91%), whereas only two of 40 subjects with an FMD > or =10% were ExMPI-positive (negative predictive value: 95%). There was a correlation between the number of cardiac risk factors and FMD. Individuals with an FMD < 10% exercised for a shorter duration than those with an FMD > or =10% (456 +/- 24 vs. 544 +/- 31 s, respectively; p = 0.02)., Conclusions: Assessment of EDV with BAUS has a high sensitivity and an excellent negative predictive value for CAD and, thus, has the potential for use as a screening tool to exclude CAD in low-risk subjects. Further standardization of BAUS is required, however, before specific cut-points for excluding CAD can be established.

Objectives: We prospectively compared dipyridamole single-photon emission computed tomography (SPECT) imaging with Tc-99m sestamibi and Tc-99m tetrofosmin for the detection of reversible perfusion defects in patients with mild-to-moderate coronary artery disease., Background: Tc-99m tetrofosmin has a lower first-pass myocardial extraction fraction compared to Tc-99m sestamibi and thus could underestimate mild perfusion defects., Methods: Eighty-one patients with 50% to 90% stenosis in one or two major epicardial vessels without previous myocardial infarction, and seven with <5% probability of coronary artery disease underwent dipyridamole SPECT imaging with both agents. The SPECT data were analyzed quantitatively., Results: Tc-99m sestamibi detected reversible perfusion defects in a greater number of segments (total 363 and 285, p < 0.001, and mean +/- SD, 2.2 +/- 3.0 and 1.8 +/- 2.5 per patient, p = 0.008, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively), demonstrated a larger extent of perfusion defect (mean +/- SD, 15.8% +/- 12.3% and 12.0% +/- 11.4%, p < 0.03, for Tc-99m sestamibi and Tc-99m tetrofosmin, respectively) and more often correctly identified patients with disease in more than one coronary artery (p = 0.02). There was better defect contrast with Tc-99m sestamibi (defect/normal wall count ratios were 0.60 +/- 0.15 vs. 0.73 +/- 0.14 for Tc-99m sestamibi and Tc99m tetrofosmin, respectively, p = 0.01, for reversible defects seen in identical segments with both agents; and 0.73 +/- 0.16 vs 0.79 +/- 0.17, respectively, p <0.01, for reversible defects detected with either agent alone). There was no significant difference in diagnostic sensitivity or image quality., Conclusions: These differences between two commonly used tracers may have significant diagnostic and prognostic implications.

Objectives: The goal of this study was to examine the effect of heart failure etiology on peripheral vascular endothelial function in cardiac transplant recipients., Background: Peripheral vascular endothelial dysfunction occurs in patients with heart failure of either ischemic or nonischemic etiology. The effect of heart failure etiology on peripheral endothelial function after cardiac transplantation is unknown., Methods: Using brachial artery ultrasound, endothelium-dependent, flow-mediated dilation (FMD) was assessed in patients with heart failure with either nonischemic cardiomyopathy (n = 10) or ischemic cardiomyopathy (n = 7), cardiac transplant recipients with prior nonischemic cardiomyopathy (n = 10) or prior ischemic cardiomyopathy (n = 10) and normal controls (n = 10)., Results: Patients with heart failure with either ischemic cardiomyopathy or nonischemic cardiomyopathy had impaired FMD (3.6 +/- 1.0% and 5.1 +/- 1.2%, respectively, p = NS) compared with normal subjects (13.9 +/- 1.3%, p < 0.01 compared with either heart failure group). In transplant recipients with antecedent nonischemic cardiomyopathy, FMD was markedly higher than that of heart failure patients with nonischemic cardiomyopathy (13.0 +/- 2.4%, p < 0.001) and similar to that of normal subjects (p = NS). However, FMD remained impaired in transplant recipients with prior ischemic cardiomyopathy (5.5 +/- 1.5%, p = 0.001 compared with normal, p = 0.002 vs. transplant recipients with previous nonischemic cardiomyopathy)., Conclusions: Peripheral vascular endothelial function is normal in cardiac transplant recipients with antecedent nonischemic cardiomyopathy, but remains impaired in those with prior ischemic cardiomyopathy. In contrast, endothelial function is uniformly abnormal for patients with heart failure, regardless of etiology. These findings indicate that cardiac transplantation corrects peripheral endothelial function for patients without ischemic heart disease, but not in those with prior atherosclerotic coronary disease.

Objectives: Evaluate the safety, tolerability and preliminary efficacy of intracoronary (IC) basic fibroblast growth factor (bFGF, FGF-2)., Background: FGF-2 is a heparin-binding growth factor capable of inducing functionally significant angiogenesis in animal models of myocardial ischemia., Methods: Phase I, open-label dose-escalation study of FGF-2 administered as a single 20-min infusion in patients with ischemic heart disease not amenable to treatment with CABG or PTCA., Results: Fifty-two patients enrolled in this study received IC FGF-2 (0.33 to 48 microg/kg). Hypotension was dose-dependent and dose-limiting, with 36 microg/kg being the maximally tolerated dose. Four patients died and four patients had non-Q-wave myocardial infarctions. Laboratory parameters and retinal examinations showed mild and mainly transient changes during the 6-month follow-up. There was an improvement in quality of life as assessed by Seattle Angina Questionnaire and improvement in exercise tolerance as assessed by treadmill exercise testing (510+/-24 s at baseline, 561+/-26 s at day 29 [p = 0.023], 609+/-26 s at day 57 (p < 0.001), and 633+/-24 s at day 180 (p < 0.001), overall p < 0.001). Magnetic resonance (MR) imaging showed increased regional wall thickening (baseline: 34+/-1.7%, day 29: 38.7+/-1.9% [p = 0.006], day 57: 41.4+/-1.9% [p < 0.001], and day 180: 42.0+/-2.3% [p < 0.001], overall p = 0.001) and a reduction in the extent of the ischemic area at all time points compared with baseline., Conclusions: Intracoronary administration of rFGF-2 appears safe and is well tolerated over a 100-fold dose range (0.33 to 0.36 microk/kg). Preliminary evidence of efficacy is tempered by the open-label uncontrolled design of the study.

Objectives: We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction., Background: Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial., Methods: We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome., Results: On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology., Conclusions: In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.

Objectives: This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction., Background: APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown., Methods: We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome., Results: APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users., Conclusions: In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.

Objectives: This prospective study was conducted in 115 women to directly compare the sensitivity and specificity of thallium-201 (Tl-201), technetium-99m (Tc-99m) sestamibi perfusion and Tc-99m sestamibi electrocardiographic (ECG)-gated single-photon emission computed tomographic (SPECT) studies for detection of coronary artery disease (CAD)., Background: Data on the comparative diagnostic accuracy of Tl-201 and Tc-99m sestamibi perfusion imaging for the detection of CAD, specifically in women, are very limited., Methods: Eighty-five patients with suspected CAD, scheduled for coronary angiography, and 30 volunteers with a pretest likelihood of < or = 5% for CAD were evaluated. Within 1 week, each patient underwent Tl-201 and Tc-99m sestamibi SPECT imaging procedures (both perfusion and gated SPECT imaging). Treadmill stress testing was used in 78 patients and dipyridamole in the remaining 37 patients. All images were interpreted by three observers in a blinded manner (consensus reading). Technetium-99m sestamibi SPECT studies were read without and then with ECG gating. Technetium-99m sestamibi gated SPECT studies were used to differentiate scar tissue from soft tissue attenuation artifact., Results: The overall sensitivities for detecting > or = 50% and > or = 70% stenoses were 75.0% and 84.3%, respectively, for Tl-201, and 71.9% and 80.4%, respectively, for Tc-99m sestamibi perfusion studies (p = 0.48). The specificity for lesions > or = 50% was 61.9% for Tl-201 and 85.7% for Tc-99m sestamibi perfusion (p = 0.07), whereas for lesions > or = 70% it was 58.8% for Tl-201 and 82.4% for Tc-99m sestamibi perfusion (p = 0.01). When the 34 patients with a normal coronary angiogram were added to the group of 30 normal volunteers, the "specificity" for lesions > or = 70% was 67.2% for Tl-201, 84.4% for Tc-99m sestamibi SPECT perfusion (p = 0.02) and 92.2% for Tc-99m sestamibi gated SPECT (p = 0.0004)., Conclusions: Both Tl-201 SPECT and Tc-99m sestamibi SPECT perfusion studies had a similar sensitivity for the detection of CAD in women. However, Tc-99m sestamibi SPECT perfusion imaging shows a significantly better specificity, which is further enhanced by the use of ECG gating.

Objectives: The aim of this study was to determine whether persistent coronary aneurysms in patients with Kawasaki disease are associated with altered myocardial perfusion and function., Background: Some patients with Kawasaki disease have died suddenly because of severe coronary artery stenosis; others have chronic coronary aneurysms., Methods: Eleven patients with chronic coronary aneurysms were enrolled in the study. The size of the aneurysms and the degree of associated stenosis were determined by angiography in nine patients and by echocardiography in two. All patients underwent simultaneous function and myocardial perfusion assessment during symptom-limited exercise by echocardiography and technetium-99m sestamibi imaging, respectively., Results: Of 33 vascular territories, 18 contained coronary aneurysms measuring 3.5 to 10 mm. Three aneurysms were associated with significant stenosis as detected by angiography. Of the 18 vascular territories, 13 were normal, and 5 manifested stress-induced perfusion defects; of the latter 5 areas, 4 had associated wall motion abnormalities. The three territories supplied by stenotic coronary arteries had both abnormal regional function and perfusion demonstrated during exercise., Conclusions: Patients with chronic coronary aneurysms may have associated stenosis, as detected by angiography, with a subjacent myocardium that is subject to abnormal perfusion and function. However, the majority of coronary aneurysms are associated with normal regional coronary flow reserve, as assessed by myocardial perfusion imaging, and even giant coronary aneurysms may be associated with normal coronary flow reserve and preserved regional myocardial function during stress.

To assess the long-term changes in cardiac function in asymptomatic patients with severe left ventricular dysfunction, left ventricular (cineangiography) and right ventricular (radionuclide angiography) function were assessed at baseline in 49 patients enrolled in the prevention arm of the Studies of Left Ventricular Dysfunction. After an average follow-up period of 12.4 months, 30 patients (11 randomized to the placebo group and 19 to the enalapril group) could be restudied to assess the progression of ventricular dysfunction. After 1 year of follow-up, the changes in heart rate, left ventricular end-diastolic and systolic pressure and right ventricular volumes were comparable in both groups. However, there were modest but opposite changes in left ventricular end-diastolic volume (+9 ml/m2 with placebo vs. -10 ml/m2 with enalapril, p < 0.05) and end-systolic volume (+5 ml/m2 with placebo vs. -13 ml/m2 with enalapril, p < 0.05). Mean systolic wall stress increased insignificantly in both groups, whereas ejection fraction increased from 29% to 31% in the placebo group and from 28% to 32% with enalapril (p = NS, placebo vs. enalapril). Even in asymptomatic patients with severe left ventricular dysfunction, there was a slow progression of left ventricular dilation. Enalapril administration appeared to slow this progression, but wall stress was not normalized by the treatment at the doses used in the study, indicating that at least one of the stimuli for further remodeling remained present.

The effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 +/- 16 to 70 +/- 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 +/- 4 to 13 +/- 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 +/- 9% to 46 +/- 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p less than 0.005), suggesting that the increase in end-diastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 +/- 8 to 34 +/- 7 mm Hg.min.m2/liter (p less than 0.05). In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 +/- 16 to 41 +/- 10 ml/m2 (p less than 0.05), cardiac index from 3.2 +/- 0.7 to 2.8 +/- 0.6 liters/min per m2 (p less than 0.05) and stroke volume index from 28 +/- 6 to 24 +/- 5 ml/m2 (p less than 0.01), with no change in systemic vascular resistance index (40 +/- 10 mm Hg.min.m2).(ABSTRACT TRUNCATED AT 250 WORDS)