Significance of low hematocrit levels in asymptomatic young adults: results of 15 years follow-up.

HYPOTHESIS: Periodic complete blood counts are not recommended for disease prevention in low-risk, non-pregnant adults. Consequently, there are few follow-up studies of the prevalence of incidentally detected anemia in asymptomatic subjects and its significance for their well-being. The objective of this survey is to determine the frequency of anemia and its predictive value for disease over a 15-yr annual follow-up of a cohort of asymptomatic young males, selected for physical fitness and intelligence. METHODS: One thousand Israeli airmen aged 18-30 yr at entry into this historical-prospective study in 1968 were used as subjects. Hematocrit (Hct) levels were examined annually. On the average each subject had 13.2 tests in the course of the 15 yr follow-up. We arbitrarily defined anemia as a Hct of 40% or less on two or more tests, and compared the prevalence of diagnosed disorders in subjects with and without anemia. RESULTS: During follow-up, anemia was found in 125 (12.5%) of the subjects. On successive annual examinations of the same individual Hct levels varied by 3% or more in 3.5% of those without anemia, and in 10.5% of those with anemia. The frequency of diagnosed disorders, excluding inter-current infections and trauma, was 25.6%, and 10.9% among those with and without anemia, respectively (OR = 2.8, 95% CI 1.8-4.6). Anemia was associated with inflammatory bowel disease (OR = 12.1, 95% CI 2.3 78.6) and malignancy (OR = 3.6, 95% CI 1.1-10.7). It preceded diagnosis only in one case with Waldenstr 246 m's macroglobulinemia, in one case of inflammatory bowel disease and two cases of myocardial infarction. CONCLUSIONS: A finding of anemia doubled the likelihood of chronic disease. However, it had a limited predictive value for subsequent morbidity and did not lead to detection of treatable disorders or to disorders that might otherwise have endangered flight safety. Fluctuations of up to 3% in Hct over time may be viewed as normal in young males.

Comparative ability of myocardial perfusion single-photon emission computed tomography to detect coronary artery disease in patients with and without diabetes mellitus.

BACKGROUND: Diabetics generally have more frequent and extensive silent myocardial ischemia than nondiabetics, increasing the importance of noninvasive detection of coronary artery disease (CAD) in this cohort. However, little is known regarding the diagnostic accuracy of myocardial perfusion single-photon emission computed tomography (SPECT) in patients with diabetes. This study was undertaken to compare the diagnostic value of rest thallium-201/stress technetium-99m sestamibi dual-isotope myocardial perfusion SPECT in patients with and without diabetes. METHODS: Of the 203 patients with diabetes and 260 patients without diabetes who underwent dual-isotope myocardial perfusion SPECT with exercise or pharmacologic stress testing, 138 diabetics (12% type 1 diabetics) and 188 nondiabetics had coronary angiography within 6 months of the nuclear test, and 65 diabetics and 72 nondiabetics had a low likelihood (<10%, mean 6% +/- 3% and 6% +/- 3%) of CAD. RESULTS: The angiographic data showed that patients with diabetes had less incidence of 1-vessel disease and a higher incidence of 3-vessel/left main artery disease than patients without diabetes (P <.05). The overall sensitivity and specificity, respectively, of SPECT for detecting CAD with the criterion of >/=50% diameter stenosis were 86% (95 of 111) and 56% (15 of 27) in diabetics, 86% (122 of 142) and 46% (21 of 46) in nondiabetics (P = not significant). With the criterion of >/=70% diameter stenosis the corresponding results were 90% (86 of 96) and 50% (21 of 42) in diabetics, and 91% (108 of 119) and 43% (30 of 69) in nondiabetics, respectively (P = not significant). The normalcy rate for low likelihood patients was 89% (58 of 65) in diabetics and 90% (65 of 72) in nondiabetics (P = not significant). The sensitivity and specificity for individual vessel detection were also similar in patients with and without diabetes (P = not significant) except for a lower sensitivity and a higher specificity for detecting left anterior descending coronary artery disease in the diabetic group (P <.05). CONCLUSION: Dual-isotope myocardial perfusion SPECT has comparable accuracy for the diagnosis of CAD in diabetic and nondiabetic patients.

Preoperative thallium scanning, selective coronary revascularization, and long-term survival after carotid endarterectomy.

BACKGROUND AND PURPOSE: Long-term survival in patients after carotid endarterectomy (CEA) is determined mainly by their concomitant cardiac disease. We tested to determine whether preoperative thallium scanning (PTS) and subsequent selective coronary revascularization (CR), by either percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG), improve long-term survival after CEA. METHODS: Two hundred twenty-six of 255 consecutive patients (88%) undergoing CEA from 1990 to 1996 had PTS. Those with significant reversible defects on PTS were referred for coronary angiography and possible CR. Patients who had undergone PTS were divided into the following 4 groups: group 1, normal or mild defects on PTS; group 2, moderate-severe fixed and/or reversible defects in patients who did not undergo CR; group 3, patients who had CR secondary to their PTS results; and group 4, patients who had CR in the past that was not related to the PTS. Perioperative data were prospectively recorded, and data on long-term survival and cardiac and neurological complications were collected. RESULTS: Seventy-seven patients (34%) had preoperative coronary angiography, and 42 (19%) had subsequent CR: preoperative PTCA or CABG in 24, combined CEA+CABG in 10, and post-CEA CABG in 8 patients. No deaths resulted from the coronary angiography, CR, or CEA. Six patients had perioperative nonfatal myocardial infarction and 8 had stroke. During the follow-up (40+/-23 months), 47 patients (18%) died, 31 (66%) from cardiac disease and 4 (8.5%) from stroke. Independent predictors of long-term overall mortality were diabetes mellitus, preoperative T-wave inversion on ECG, lower-extremity arterial disease, and history of neurological symptoms [exp(beta)=3. 5, 3.4, 2.5, and 2.4; P=0.0003, 0.0004, 0.01, and 0.04, respectively]. In addition, preoperative moderate-severe thallium defect without CR (group 2) independently predicted long-term cardiac mortality [exp(beta)=2.8; P=0.04]. Patients with preoperative CR (group 3) had long-term survival rate similar to that of group 1 and significantly better than that of group 2 (P=0. 02). CONCLUSIONS: PTS predicts long-term survival, and selective CR based on the thallium results improves the survival rate of patients undergoing CEA.

Incremental prognostic value of adenosine myocardial perfusion single-photon emission computed tomography in women with suspected coronary artery disease.

Adenosine myocardial perfusion single-photon emission computed tomography (SPECT) is now increasingly used for risk stratification of patients with known or suspected coronary artery disease. However, the incremental prognostic value of this test over clinical and historical information in a large series of women has not been examined. Thus, we studied 923 consecutive women who underwent adenosine technetium (Tc)-99m sestamibi myocardial perfusion SPECT and were followed-up for a mean period of 26+/-8 months. During the follow-up period, 77 hard events (46 cardiac deaths and 31 nonfatal myocardial infarctions) occurred. The results of the perfusion scan significantly risk stratified the population; patients with normal scans had a low rate of nonfatal myocardial infarction and cardiac death (< 1%/year of follow up). Patients with mildly abnormal scans had low cardiac death rates (0.9%/year of follow up); these rates increased as a function of scan abnormality (4.1% and 7.5% mortality per year of follow up in moderate and severely abnormal scans). Cox proportional hazards analysis demonstrated that after adjusting for prior myocardial infarction and diabetes mellitus (the most predictive individual clinical variables [global chi-square=22.5, p <0.001]), as well as heart rate at rest (the most predictive physiologic variable [chi-square=3.8; p=0.05]), the most predictive nuclear variable (summed stress score [chi-square=48.5; p <0.0001]) added significant incremental prognostic information (global chi-square increased from 22.5 to 56.2 [p <0.0001]). In conclusion, adenosine myocardial perfusion SPECT added significant incremental prognostic information to clinical and physiologic variables in women. Normal scans were associated with an excellent prognosis. In contrast, patients with moderately to severely abnormal scans were at a higher risk for future cardiac events.

Automatic quantitation of regional myocardial wall motion and thickening from gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography.

OBJECTIVES: We developed an automatic quantitative algorithm for the measurement of regional myocardial wall motion and wall thickening from three-dimensional gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomographic images. BACKGROUND: The algorithm measures the motion of the three-dimensional endocardial surface using a modification of the centerline method, as well as wall thickening using both geometry (gaussian fit) and partial volume (counts). METHODS: The algorithm was tested using a "variable thickness" heart phantom, and the quantitative results were compared with visual segmental assessment of myocardial motion and thickening in 79 clinical patients with a wide range of ejection fractions (6% to 87%). RESULTS: Phantom measurements of simulated motion and thickening were accurate regardless of the camera used (dual or triple detector), the angular span of reconstructed data (180 degrees or 360 degrees), the amount of motion (3 or 6 mm) or the amount of thickening (33%, 50% or 100%). Quantitative measurements of segmental motion and thickening in the patients were correlated with visual scores (r = 0.668, exact agreement 72.6%, kappa 0.433 and r = 0.550, exact agreement 74.7%, kappa 0.408, respectively). Significant inverse linear relations exist between the global (summed) visual motion score and the average quantitative motion, and between the global (summed) visual thickening score and the average quantitative thickening. Automatic quantitative ejection fraction measurements correlated extremely well with average quantitative motion (r = 0.929) and thickening (r = 0.959). CONCLUSIONS: Our algorithm is accurate and may be the first automatic technique for the quantitative three-dimensional assessment of regional ventricular function in cardiology.

Quantitative LVEF and qualitative regional function from gated thallium-201 perfusion SPECT.

UNLABELLED: This study investigates the feasibility of routine clinical 201Tl gated perfusion SPECT (gated Tl), and compares quantitative left ventricular ejection fraction (LVEF) and visually-assessed regional wall motion and thickening to analogous values obtained from 99mTc-sestamibi gated perfusion SPECT (gated MIBI). METHODS: We studied 121 patients with a rest gated Tl (3-3.5 mCi, 35 sec/ projection/poststress gated MIBI (25-30 mCi, 25 sec/projection) separate dual-isotope protocol on a 90 degrees dual-detector camera. Automatic quantitation of LVEFs was accomplished using previously developed and validated software, while visual scoring of motion and thickening was performed using four-point scales. RESULTS: Average myocardial counts were lower in gated Tl images (306 +/- 81 counts/pixel) compared to gated MIBI images (789 +/- 237 counts/pixel). The quality of gated Tl images was ranked as excellent, good, fair and poor in 24.0%, 42.1%, 24.8% and 9.1%, respectively, of the patients, compared to 43.0%, 43.8%, 9.1% and 4.1%, respectively, for gated MIBI images. Quantitative-gated Tl and gated MIBI LVEFs correlated well (y = 0.11 + 1.05x, r = 0.918, SEE = 6.35). Possible poststress myocardial stunning may have caused gated Tl LVEFs to overestimate gated MIBI LVEFs by a larger (p = 0.03) amount in ischemic patients (n = 47, y = -0.69 + 1.09x, r = 0.914, s.e.e. = 6.44) compared to nonischemic patients (n = 64, y = -1.58 + 1.05x, r = 0.919, s.e.e. = 5.93), the residual difference in LVEFs for this latter group being likely due to different isotope resolution in conjunction with small left ventricles. Exact agreement between gated Tl and gated MIBI segmental myocardial function in 41 nonischemic patients was 92.2% (kappa = 0.619) and 95.4% (kappa = 0.586) for motion and thickening scores, respectively. CONCLUSION: Thallium-201 gated SPECT imaging can be effectively performed on the majority of patients in our clinical environment and offers the opportunity to assess both myocardial perfusion and function using one injection and one imaging sequence, similarly to what is done with 99mTc-based agents.

An algorithm for pulmonary screening of military pilots in Israel.

BACKGROUND: Medical screening is used routinely to qualify and classify candidates for pilot training. The respiratory system assumes even greater importance owing to the increased stress of flying high-performance aircraft in a hostile environment characterized by high altitude, varying acceleration ("G" forces), and the possibility of rapid decompression. Any respiratory dysfunction may threaten the pilot's health, flight safety, and completion of the mission. Only those candidates with the highest psychophysical score are accepted to undergo special aeromedical screening. Physical suitability is an important factor in the selection and classification of candidates for flight training programs, and pulmonary function testing is central within this screening protocol. METHODS: We developed a respiratory algorithm for this unique screening process. The algorithm represents a practical and efficient approach for large-scale screening of healthy candidates for flight training. The algorithm deals with the major pulmonary health problems encountered in a previously screened healthy population aged 17 to 25 years. If by anamnesis, physical examination results, or baseline spirometry findings there is reason to suspect a respiratory problem that could emerge to endanger the pilot's life, a specially designed evaluation is performed according to the algorithm. We explain, step by step, the basis for each suggested test in order to reach a decision (operational specifications). The pulmonary function studies we recommend are reasonably priced and can be easily and reliably performed by regular medical staff technicians. The major justification for performing pulmonary function studies in a healthy population that has already gone through a preliminary medical screening and has been found fit is to identify occult or latent abnormalities. These abnormalities may have no or minimal clinical expression under ordinary circumstances but, under the stress of flight during the ensuing 5 to 10 years, may produce serious limitation in function. RESULTS: Two cases, seen in the Air Force Medical Center, are presented to illustrate how the algorithm is implemented. The algorithm has been in use for more than 5 years, and has been applied to the screening of several thousand candidates. Follow-up of the accepted candidates has not revealed any significant defects in the decision-making process. CONCLUSION: Use of the algorithm is highly cost-effective since it allows for nonspecialist physicians to carry out pulmonary screening and involves the pulmonary specialist only infrequently, ie, when a particularly complicated and/or borderline case is encountered. It is our contention that a similar algorithm would be useful in many other settings where large-scale screening is required.

Analysis of high frequency QRS potential during exercise testing in patients with coronary artery disease and in healthy subjects.

High resolution ECG waveforms from leads V3, V4, V5, and V6 were analyzed in two groups of male subjects before, during, and following treadmill exercise testing. Group A included 32 coronary artery disease (CAD) patients, with arteriographically proven > 75% obstruction of at least two main coronary arteries, and group B included 30 healthy subjects, without history or symptoms of CAD. Signal averaging and filtering techniques were used in order to enhance the signal-to-noise ratio of the recorded ECG. The averaged QRS waveforms were filtered between 150 and 250 Hz. QRS complexes of the four leads were combined to form a "precordial average complex" (PAC). The PAC signals were examined for each subject at different stages of the exercise test and two parameters were computed: the root mean square (RMS) voltage; and the peak amplitude. The values of RMS and peak amplitudes measured at each stage of the exercise test were normalized to the values at rest. Normalized RMS (NRMS) values at peak exercise, immediately after peak exercise, and during the recovery phase were found to be higher for the healthy subjects than for the CAD group (1.17 +/- 0.31 vs 0.94 +/- 0.26, P < 0.008 at peak exercise, 1.13 +/- 0.24 vs 0.84 +/- 0.19, P < 0.001 after peak exercise, 1.08 +/- 0.22 vs 0.94 +/- 0.17, P < 0.007 during recovery). Cut-off NRMS value of one had a sensitivity of 81.3% and a specificity of 70.0% in differentiating CAD patients from healthy subjects in the examined groups. Normalized peak amplitude (NAMP) values exhibited similar behavior, with higher values for the healthy subjects than for the CAD group (1.23 +/- 0.48 vs 0.94 +/- 0.36, P < 0.03 at peak exercise, 1.20 +/- 0.34 vs 0.83 +/- 0.28, P < 0.001 after peak exercise, 1.10 +/- 0.29 vs 0.94 +/- 0.23, P < 0.02 during recovery). Specificity of 73.3% and sensitivity of 71.8% were found using a postpeak NAMP cut-off value of 1. In conclusion, the present study shows that using high frequency ECG may contribute to identifying patients with CAD. Further studies in larger groups of patients are required to better define the true predictive value of the method described for the diagnosis of CAD.

Repeatability of treadmill exercise ejection fraction and wall motion using technetium 99m-labeled sestamibi first-pass radionuclide ventriculography.

BACKGROUND: Peak treadmill exercise radionuclide ventriculography (RVG) with technetium 99m has recently been validated for determination of left ventricular ejection fraction (LVEF). However, the repeatability of this technique for determination of both LVEF and regional wall motion has not been reported. METHODS AND RESULTS: Each of 27 clinically stable patients underwent two treadmill exercise RVG studies within 40 +/- 51 days. The level of exercise achieved in the two tests was similar (double product: 26,357 +/- 3877 vs 26,621 +/- 4287), and there was no change in clinical or treatment status between the studies. Acquisition and processing were accomplished with a mobile multicrystal camera and a new version of a commercial software (Scinticor SIM 400 V. 4.1 BETA, Milwaukee, Wis.) that uses two left ventricular regions of interest. The two tests were compared to assess agreement (repeatability) on both an automatically calculated LVEF and wall motion in five left ventricular segments (basal anterior, distal anterior, apical, distal inferior, and basal inferior), with a 3-point semiquantitative visual score. Intraobserver and interobserver agreements (reproducibility) also were assessed on quantitative exercise LVEF derived from the same RVG test from a separate group of 20 patients with a broad range of exercise LVEF. The first and second treadmill exercise LVEFs were highly correlated (r = 0.92, SEE = 3.96, y = 0.97x + 0.58; and r = 0.99, SEE = 1.32, y = 0.99x + 0.25, respectively). Results of segmental visual score agreement between the first and the second treadmill first-pass studies were as follows: overall, 86% (116/135, kappa = 0.74); basal anterior, 85% (23/27, kappa = 0.72); distal anterior, 85% (23/27, kappa = 0.84); apical, 93% (25/27, kappa = 0.85); distal inferior, 93% (25/27, kappa = 0.80); and basal inferior, 67% (18/27, kappa = 0.64). CONCLUSION: Treadmill exercise first-pass RVG is a highly repeatable and reproducible test for quantitative LVEF and visual regional wall motion analysis. Our results imply the procedure may be useful for serial follow-up of patients with coronary artery disease and for the evaluation of the efficacy of medical or interventional treatment.

Postural control in pilots and candidates for flight training.

Postural control may reflect the pilot's ability to deal successfully with the stresses of spatial orientation. In this study, we hypothesized that fighter pilots would have better performance on the "tetra-axiametric posture test" than would helicopter pilots (less rigorously selected) and candidates for flight training. We tested 28 fighter pilots, 23 helicopter pilots and 43 candidates by tetra-axiametric posturography. Fighter pilots were found on the level position to have significantly more compensatory anterior-posterior sway (moving anterior-posterior rather than laterally, p = 0.02) and required less movements to maintain balance (p = 0.02) than did candidates. Helicopter pilots had intermediate values. In stressed positions, fighter pilots demonstrated relatively more slow movements (p = 0.018) than did the candidates, which may be related to increased labyrinth control. In the stressed positions, helicopter pilots had postural profiles similar to the candidates. We conclude that there are significant differences in postural control as tested by tetraaxiametric posturography between fighter pilots, helicopter pilots, and candidates for flight training. This could be due to either innate ability, which could be used in the selection process, or to training. A prospective study is planned in order to determine if posturography can predict a candidate's ability to complete flight training.

Perioperative myocardial ischemia in carotid endarterectomy under cervical plexus block and prophylactic nitroglycerin infusion.

Perioperative myocardial ischemia was evaluated in 36 consecutive carotid endarterectomy procedures carried out on patients with a high (72.2%) prevalence of ischemic heart disease. The procedures were performed under cervical plexus block plus a prophylactic intravenous nitroglycerin infusion. Findings of myocardial ischemia on perioperative (48 hours) continuous electrocardiogram recordings were correlated with preoperative cardiac status, perioperative continuous intra-arterial blood pressure measurements, and postoperative cardiac outcome. In two patients, ST segment analysis was un-interpretable because of bundle-branch blocks. Altogether, 64 episodes of significant ST segment depression were detected in 18 (52.9%) of the remaining procedures. In 8 (23.5%) procedures, ST segment depressions occurred either during carotid artery clamping at the time of the largest rise in blood pressure or within 2 hours of declamping, when blood pressure tended to decline. There were four (11.7%) postoperative cardiac events: three myocardial infarctions (one Q wave and two non-Q wave) and one episode of unstable angina pectoris. All four patients with cardiac events had early signs of myocardial ischemia either at the time of cross-clamping, or soon after declamping of the carotid artery. All myocardial infarctions developed following prolonged (> 10 hours) myocardial ischemia, starting with the first 20 hours after surgery. Thus, ST segment depression occurring during clamping or soon after carotid declamping was associated with cardiac complications (sensitivity 100% and specificity 86.6%) and suggests the possible usefulness of on-line ST segment trend monitoring.

Importance of long-duration postoperative ST-segment depression in cardiac morbidity after vascular surgery.

Major vascular surgery is associated with a high incidence of cardiac ischaemic complications. By means of continuous perioperative electrocardiographic recording, we studied 151 consecutive patients undergoing major vascular surgery to find out the characteristics of any myocardial ischaemia and the relation to outcome. 13 (8.6%) patients had postoperative cardiac events (6 myocardial infarctions, 2 unstable angina, and 5 congestive heart failure). There were 342 perioperative ischaemic episodes shown by ST-segment depression; 164 (48%) occurred postoperatively. Postoperative ischaemic episodes were significantly longer than episodes before or during operations (3.2 vs 1.7 and 1.5 min per h monitored, respectively, p < 0.001). Both Detsky's cardiac risk index and long-duration (> 2 h) preoperative ischaemia were predictive of postoperative cardiac complications (odds ratios in univariate analysis 3.3, p = 0.03, and 7.2, p = 0.009, respectively). However, long-duration (> 2 h) postoperative ischaemia was the only factor significantly associated with cardiac morbidity in multivariate logistic regression analysis (odds ratio 21.7, p = 0.001). Long-duration ST-segment depression preceded most (84.6%) postoperative cardiac events, including myocardial infarctions, and no cardiac event was preceded by ST-segment elevation. 5 of the 6 postoperative myocardial infarctions were non-Q-wave infarctions. We conclude that long-duration subendocardial ischaemia, rather than acute coronary artery occlusion, may bring about postoperative myocardial injury and complications.

The incidence of myopia in the Israel Air Force rated population: a 10-year prospective study.

It is important to define the risk in pilots of becoming myopic in order to determine the need for yearly screening, and to predict pilot eligibility in environments where the use of corrective lenses may present problems. We conducted a prospective study of 1400 air force personnel followed for 10 years, who could be divided into three major groups; those with 20/20 vision in both eyes, those with 20/25 in one eye only and whose vision was 20/20 using both eyes together, and those who were accepted despite the fact that they required corrective lenses. Over the 10-year period, 23.1% of those with 20/25 visual acuity in one eye needed corrective lenses, significantly more than the 7.4% observed in those with 20/20 vision in both eyes (relative risk 3.1, 95% confidence interval 2.2-4.3, p less than 0.0000). The prevalence of corrective lenses increased until age 26. We conclude that 7.4% of pilots will become myopic over a 10-year period if accepted with 20/20 vision in both eyes. The risk, however, is much higher in those with incipient growth myopia starting in one eye at entry. Therefore, the annual screening of visual acuity in air force personnel is essential.

Cardiovascular risk factor clustering and ratio of total cholesterol to high-density lipoprotein cholesterol in angiographically documented coronary artery disease.

High levels of cardiac risk factors tend to cluster together and act synergistically. To develop a suitable and practical marker for clustering, we evaluated 380 consecutive patients at the time of coronary angiography. Analyses of lipid, rheologic, clinical and arteriographic profiles indicated a variety of interwoven relations. Because the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol (total/HDL cholesterol) was closely related to both the presence and extent of greater than or equal to 50% diameter reduction of greater than or equal to 1 coronary arteries, it was used to divide patients into quartiles. Clustering of high- and low-level risk factors was demonstrated in the highest and lowest quartiles of total/HDL cholesterol, respectively (p less than 0.001). The highest quartile may be characterized by an only moderately elevated total cholesterol level but patients in this quartile may have a very low HDL cholesterol level, high triglycerides, a tendency toward high hemoglobin and fibrinogen levels, a history of smoking, previous myocardial infarction and multivessel disease. These results suggest that total/HDL cholesterol serves as a marker not only for obstructive coronary disease but also for a cluster of potentially modifiable risk factors.