Estimating the real-world performance of the PROMISE minimal-risk tool.

BACKGROUND: Stable chest pain is a common indication for cardiac catheterization. We assessed the prognostic value of the Prospective Multicenter Imaging Study for Evaluation (PROMISE) Minimal-Risk Tool in identifying patients who are at very low risk of obstructive coronary artery disease (CAD) or downstream cardiovascular adverse outcomes. METHODS: We applied the PROMISE Minimal-Risk Tool to consecutive patients without known CAD who underwent elective cardiac catheterization for stable angina from January 1, 2000 to December 31, 2014 in the Duke Databank for Cardiovascular Disease (DDCD). Patients with scores >0.46 (top decile of lowest-risk from the PROMISE cohort) were classified as low-risk. Logistic regression modeling compared likelihood of freedom from obstructive coronary artery disease on index angiography, 2-year survival, and 2-year survival free of myocardial infarction (MI) and MI/revascularization between low- and non low-risk patients. Alternative cut points to define low- risk patients were also explored. RESULTS: Among 6251 patients undergoing cardiac catheterization for stable chest pain, 1082 (17.3%) were low-risk per the PROMISE minimal-risk tool. Among low risk patients, obstructive coronary artery disease was observed in 14.9% and left main disease (≥ 50% Stenosis) was rare (0.9%). Compared with other patients, low risk patients had a higher likelihood of freedom from obstructive coronary disease on index catheterization (85.1% vs. 44.2%, OR 4.84, 95% CI 4.06-5.77). Low risk patients had significantly higher survival (98.2% vs. 94.4%, OR 3.18, 95% CI 1.99-5.08), MI-free survival (97.2% vs. 91.9%, OR 3.03, 95% CI 2.07-4.45), and MI/revascularization-free survival (86.2 vs. 59.9%, OR 4.19, 95% CI 3.48-5.05) at 2 years than non-low risk patients. Operating characteristics for predicting the outcomes of interest varied modestly depending on the low-risk cut-point used but the positive predictive value for 2 year freedom from death was >98% regardless. CONCLUSION: The PROMISE minimal-risk tool identifies 17% of stable chest pain patients referred to cardiac catheterization as low risk. These patients have a low prevalence of obstructive CAD and better survival than non-low risk patients. While this suggests that these patients are unlikely to benefit from catheterization, further research is needed to confirm a favorable downstream prognosis with medical management alone.

Delayed tension pneumocephalus complicating orbital exenteration.

A 43-year-old woman with a recurrent adenoid cystic carcinoma of the lacrimal gland was treated by orbital exenteration and reconstruction. Eight days later she developed symptoms of cerebral irritation and a computed tomogram showed intracerebral and subarachnoid air. She recovered with conservative treatment.

Early cardioversion of atrial fibrillation facilitated by transesophageal echocardiography: short-term safety and impact on maintenance of sinus rhythm at 1 year.

BACKGROUND: For patients presenting with atrial fibrillation of only a few weeks duration, the use of transesophageal echocardiography offers the opportunity to markedly abbreviate the duration of atrial fibrillation before cardioversion. We sought to determine if the shorter duration of atrial fibrillation allowed by a transesophageal echocardiography strategy had an impact on the recurrence of atrial fibrillation and prevalence of sinus rhythm during the first year following cardioversion. METHODS: Transesophageal echocardiography was attempted in 539 patients (292 men, 247 women; 71.6 +/- 13.0 years.) with atrial fibrillation > or =2 days (66.1% <3 weeks) or of unknown duration before elective cardioversion of atrial fibrillation. Therapeutic anticoagulation at the time of transesophageal echocardiography was present in 94.6% of patients, and 73.4% of subjects were discharged on warfarin. RESULTS: Atrial thrombi were identified in 70 (13.1%) patients. Successful cardioversion in 413 patients without evidence of atrial thrombi was associated with clinical thromboembolism in 1 patient (0.24%, 95% confidence interval: 0.0--0.8%). In patients with atrial fibrillation <3 weeks at the time of cardioversion (a duration incompatible with conventional therapy of 3 to 4 weeks of warfarin before cardioversion), the 1-year atrial fibrillation recurrence rate was lower (41.1% vs. 57.9%, P <0.01), and the prevalence of sinus rhythm at 1 year was increased (65.8% vs. 51.3%, P <0.03). No other clinical or echocardiographic index was associated with recurrence of atrial fibrillation or sinus rhythm at 1 year. CONCLUSIONS: Early cardioversion facilitated by transesophageal echocardiography has a favorable safety profile and provides the associated benefit of reduced recurrence of atrial fibrillation for patients in whom the duration of atrial fibrillation is <3 weeks.

Patient motion compensation during transthoracic 3-D echocardiography.

Bulk patient motion during transthoracic 3-D echocardiography (3DE) produces image plane misregistration and errors in left ventricular (LV) volume and ejection fraction (EF). To correct for patient motion, we used a magnetic locating system to track both the ultrasound transducer and the chest wall of the patient, so images could be registered in a patient-centered coordinate system ("correction"). Fourteen subjects each underwent 3DE, with deliberate patient motion, to measure LV volume and EF. Results were compared to magnetic resonance imaging (MRI). Without correction, 3DE differed significantly from MRI (EF: r = 0.78, SEE = 5.8%). Application of correction increased 3DE accuracy, despite patient motion (EF: r = 0.91, SEE = 3.7%), to a level comparable to that of 3DE in the absence of motion (EF: r = 0.93, SEE = 3.5%). Patient motion during 3DE examination can be corrected using a magnetic spatial location system.

Gender differences in exercise-induced changes in sex hormone levels and lipid peroxidation in athletes participating in the Hawaii Ironman triathlon. Ginsburg-gender and exercise-induced lipid peroxidation.

BACKGROUND: Exercise reduces the risk of coronary heart disease in men and women but paradoxically, may promote free-radical formation, lipid peroxidation and vascular tissue injury. In this study, we assessed whether exercise-induced oxidative stress similarly affected men and women who participated in the Hawaii Ironman triathlon. METHODS AND RESULTS: Fifty-seven athletes (38 males) who completed the triathlon (3.9 km swim, 180.2 km bike, 42.2 km run) participated in this study. Blood samples were obtained 2 days before and immediately after the triathlon for the measurement of lipids, antioxidants and sex hormones and for the assessment of the susceptibility of plasma lipids to peroxidation. Lipid changes after exercise were similar for men and women. However, the susceptibility of plasma lipids to peroxidation was reduced by 61% (P < 0.001) in men and only 14% (P = NS) in women postrace. These changes were not associated with the supplemental use or levels of antioxidants. In addition, in men there was an increase of 58% in the antioxidant sex hormone estradiol and a decrease of 58% in testosterone (P < 0.001) postrace. No significant changes were noted for these two hormones in women. CONCLUSIONS: There are significant gender-specific differences in the susceptibility of lipids to peroxidation and in changes in estradiol and testosterone levels as a result of ultra-endurance exercise. These changes may in part explain the salutary effect of exercise on the development of vascular disease.

Effect of increased body mass index on accuracy of two-dimensional echocardiography for measurement of left ventricular volume, ejection fraction, and mass.

We used 2- and 3-dimensional echocardiography to determine left ventricular volume, mass, and ejection fraction in overweight (body mass index [BMI] > or = 25 kg/m2), obese (BMI > or = 30 kg/m2), and control (BMI < 25 kg/m2) subjects. Compared with corresponding magnetic resonance imaging measurements, 3-dimensional echocardiography is more accurate than 2-dimensional echocardiography in all patients, but particularly in overweight and obese subjects.

Importance of an intact growth hormone/insulin-like growth factor 1 axis for normal post-infarction healing: studies in dwarf rats.

Treatment with GH attenuates remodeling and improves left ventricular function in the setting of experimental heart failure following coronary ligation. This study was designed to test the hypothesis that an intact GH/insulin-like growth factor 1 (IGF-1) axis is required for normal myocardial infarction healing. Myocardial infarction was induced by coronary ligation in GH-deficient dwarf rats and in age-matched controls. In dwarf rats, serum IGF-1 levels were reduced by 50%, and grow rate was 50% less than normal littermates, although no differences in myocardial IGF-1 messenger RNA levels were observed compared with controls. All rats underwent transthoracic echocardiography at baseline, 2 weeks, and 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure was obtained by in vivo closed chest catheterization. At 6 weeks, both infarcted groups exhibited similar myocardial infarction size at transthoracic echocardiography and at morphometric histology. In both groups with myocardial infarction, there was significant left ventricular dilation and reduced systolic function. However, the extent of remodeling as assessed by the increase in end-diastolic dimension (%Delta + 36 +/- 5 vs. +19 +/- 4; P: < 0.01) and depression of function (%Delta fractional shortening -12 +/- 2 vs. -7 +/- 1; P: < 0.01) were both greater in the dwarf group. Furthermore, dwarf rats failed to develop compensatory hypertrophy of noninfarcted posterior wall (%Delta posterior wall +5 +/- 1 vs. +15 +/- 3; P: < 0.01). Therefore, pathologic left ventricular remodeling and functional loss following myocardial infarction is more marked in conditions of GH deficiency. An intact GH/IGF-1 axis appears necessary for a normal response to myocardial infarction injury in the rat.

Echocardiographic assessment of cardiac morphology and function in mutant dwarf rats.

Although the mutant dwarf rat has been proposed as a model of growth hormone (GH) deficiency, few studies have addressed its cardiovascular abnormalities. Therefore, the aim of the present study was to investigate cardiac structure and function in mutant dwarf rats in vivo before and after chronic GH administration, by means of transthoracic Doppler echocardiography. To this purpose, forty 90-day-old female dwarf rats were randomized to receive either GH treatment or placebo. Twenty age-and sex-matched Lewis rats (200-250 g) served as the control group. All rats underwent echocardiograms before receiving any drug and after 3 weeks of therapy. Echocardiographically detected left ventricular mass indexed to tibial length was reduced by 41% in dwarf rats compared to the control group. Such relative cardiac atrophy was also evident at the myocyte level, and was fully reversible after GH therapy. In contrast to the control group, dwarf rats also showed a reduction of left ventricular diastolic volumes normalized to tibial length and impaired cardiac performance as suggested by the reduction of cardiac index, abnormal stress-shortening relations, and a significant elevation of total peripheral vascular resistance. All these abnormalities were reversible upon GH therapy for 3 weeks. In conclusion, GH plays an important role in maintaining a normal cardiac structure and function. Since the observed changes are similar to those seen in GH-deficient men, the mutant dwarf rat represents a faithful animal model of GH deficiency.

Accuracy of three-dimensional echocardiography with unrestricted selection of imaging planes for measurement of left ventricular volumes and ejection fraction.

BACKGROUND: Accurate, reproducible, noninvasive determination of left ventricular (LV) volumes and ejection fraction (EF) is important for clinical assessment, risk stratification, selection of therapy, and serial monitoring of patients with cardiovascular disease. Three-dimensional echocardiography (3DE) approaches have demonstrated significantly greater accuracy than current clinical 2DE, but the clinical utility of 3DE has been limited because of the need for substantial modifications to scanning technique (eg, all image acquisition from a single acoustic window) or cumbersome additional hardware. We describe a novel 3DE system without these limitations and its application to patients. METHODS AND RESULTS: Twenty-five patients were examined by 3DE, 2DE, and magnetic resonance imaging (MRI). The 3DE system used a magnetic scanhead tracking device, and volumes were computed with a novel deformable shell model. End-diastolic volumes and EF by MRI ranged from 96 to 375 mL and 18% to 73%, respectively. There was excellent correlation, without statistically significant differences, between MRI and 3DE for end-systolic volume (ESV) (r(2) = 0.99) and end-diastolic volume (EDV) (r(2) = 0.98), ventricular stroke volume (SV) (r(2) = 0.93), and EF (r(2) = 0.97), with standard error estimates less than 10 mL for volumes and 3% for EF. Conventional 2DE consistently underestimated volumes (EDV, P <.01; ESV, P <.01; SV, P <.05); correlations with MRI were r(2) = 0.91 for ESV, r(2) = 0.88 for EDV, r(2) = 0.62 for SV, and r(2) = 0.72 for EF. Standard error estimates ranged from 16 to 20 mL for ventricular volumes and 9% for EF. Interobserver variability was reduced 3-fold with use of 3DE. CONCLUSIONS: The novel 3DE system allows unrestricted selection and combination of acoustic windows in a single examination, improves accuracy of estimates of LV volumes and EF 3-fold compared with 2DE, and is practical for routine clinical assessment of LV size and function in patients with a wide range of cardiac pathology.

Enrollment of women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute.

BACKGROUND: With the recognition that certain aspects of cardiovascular disease are specific to sex, the government has sought to ensure that federally funded clinical research yields adequate high-quality information about heart disease in women. METHODS: We tabulated the numbers of men and women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1965 and 1998, recording both total numbers and the numbers for each type of cardiovascular disease. We analyzed the data according to the sex-specific prevalence of disease and assessed changes in enrollment over time. We performed a similar analysis after excluding all single-sex trials. RESULTS: A total of 398,801 subjects (215,796 women and 183,005 men) were enrolled in NHLBI-funded studies of cardiovascular disease. The overall enrollment rate for women (54 percent) exceeded the prevalence of cardiovascular disease in women in the general population (49 percent) and increased over time (P=0.002). With single-sex trials excluded, the enrollment rate for women was 38 percent, which did not change significantly over time. In studies of coronary artery disease and hypertension the rates of enrollment of women were similar to or exceeded the prevalence of these disorders in women. The enrollment rate increased significantly over time in studies of coronary artery disease (P<0.001) but not in studies of hypertension or arrhythmia. Women were under-enrolled in studies of heart failure, and the rate of enrollment did not change significantly over time. When single-sex trials were excluded from the analysis of enrollment rates according to the prevalence of disease, the results were similar. There was no change in enrollment rates overtime for any category of disease. CONCLUSIONS: Federal efforts to increase the representation of women in clinical trials have been moderately successful primarily because of the institution of a small number of large, single-sex trials involving coronary artery disease. There has been no change in the sex composition of cohorts in the majority of studies of cardiovascular disease.

The conserved phosphoinositide 3-kinase pathway determines heart size in mice.

Phosphoinositide 3-kinase (PI3K) has been shown to regulate cell and organ size in Drosophila, but the role of PI3K in vertebrates in vivo is not well understood. To examine the role of PI3K in intact mammalian tissue, we have created and characterized transgenic mice expressing constitutively active or dominant-negative mutants of PI3K in the heart. Cardiac- specific expression of constitutively active PI3K resulted in mice with larger hearts, while dominant-negative PI3K resulted in mice with smaller hearts. The increase or decrease in heart size was associated with comparable increase or decrease in myocyte size. Cardiomyopathic changes, such as myocyte necrosis, apoptosis, interstitial fibrosis or contractile dysfunction, were not observed in either of the transgenic mice. Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals.

Left ventricular hypertrophy in ascending aortic stenosis mice: anoikis and the progression to early failure.

BACKGROUND: To determine potential mechanisms of the transition from hypertrophy to very early failure, we examined apoptosis in a model of ascending aortic stenosis (AS) in male FVB/n mice. METHODS AND RESULTS: Compared with age-matched controls, 4-week and 7-week AS animals (n=12 to 16 per group) had increased ratios of left ventricular weight to body weight (4.7+/-0.7 versus 3.1+/-0.2 and 5. 7+/-0.4 versus 2.7+/-0.1 mg/g, respectively, P<0.05) with similar body weights. Myocyte width was also increased in 4-week and 7-week AS mice compared with controls (19.0+/-0.8 and 25.2+/-1.8 versus 14. 1+/-0.5 microm, respectively, P<0.01). By 7 weeks, AS myocytes displayed branching with distinct differences in intercalated disk size and staining for beta(1)-integrin on both cell surface and adjacent extracellular matrix. In vivo left ventricular systolic developed pressure per gram as well as endocardial fractional shortening were similar in 4-week AS and controls but depressed in 7-week AS mice. Myocyte apoptosis estimated by in situ nick end-labeling (TUNEL) was extremely rare in 4-week AS and control mice; however, a low prevalence of TUNEL-positive myocytes and DNA laddering were detected in 7-week AS mice. The specificity of TUNEL labeling was confirmed by in situ ligation of hairpin oligonucleotides. CONCLUSIONS: Our findings indicate that myocyte apoptosis develops during the transition from hypertrophy to early failure in mice with chronic biomechanical stress and support the hypothesis that the disruption of normal myocyte anchorage to adjacent extracellular matrix and cells, a process called anoikis, may signal apoptosis.

Physicians' recommendations to patients for use of antibiotic prophylaxis to prevent endocarditis.

CONTEXT: The American Heart Association recommendations for infectious endocarditis (IE) prophylaxis, published in June 1997, sought to improve patient and physician compliance by simplifying the dosing regimen and clarifying endocarditis risk. Adherence to these updated recommendations in patients with echocardiographic verification of their endocarditis risk profile is unknown. OBJECTIVE: To determine the recommended and actual use of IE prophylaxis as reported by patients undergoing echocardiography. DESIGN, SETTING, AND PARTICIPANTS: All patients who underwent outpatient transthoracic echocardiography at a university-based tertiary hospital in Boston, Mass, during December 1997 were contacted 6 to 9 months later to respond to a survey, completed by 218 (80%) eligible subjects. MAIN OUTCOME MEASURE: Patients' report of their physicians' instructions on actual use of IE prophylaxis in accordance with patient risk category, determined by echocardiographic data. RESULTS: One hundred eight patients (49.5%) had clinical or echocardiographic findings for which prophylaxis was indicated. Of these 108 patients, 71 (65.7%) reported that they were instructed to take IE prophylaxis. Sixteen high-risk patients (88. 9%) but only 55 moderate-risk patients (61.1%) reported that they were instructed to take prophylaxis. Among the 110 negligible-risk patients, 29 (26.4%) reported that they had been instructed to take IE prophylaxis. Overall, 100 patients (45.9%) reported that they received physician instructions to take IE prophylaxis. Of those who subsequently underwent a procedure for which IE prophylaxis was indicated (n=68), 9 (13.2%) elected not to follow their physician's advice to take prophylaxis. CONCLUSIONS: We found that although most patients reported receiving instructions for IE prophylaxis use consistent with American Heart Association guidelines, IE prophylaxis overuse among negligible-risk patients and underuse among moderate-risk patients was common. Continued physician and patient education may lead to improved adherence to the current American Heart Association recommendations. JAMA. 2000;284:68-71