Hemodynamic performance of mitroflow aortic pericardial bioprosthesis - optimizing management for the small aortic annulus.

BACKGROUND: Documentation of the hemodynamics of the Mitroflow aortic pericardial bioprosthesis has been incomplete. The aim of the study was to provide reference effective orifice areas for the implant calculation of effective orifice area indexes to avoid prosthesis-patient mismatch. METHODS: Echocardiograms were evaluated in 55 patients (39 females, 16 males), mean age 77.0 +/- 6.9 years (range 51-90 years). The mean time of the studies was 11.0 months. The prosthesis sizes and numbers evaluated were 19 mm (n = 13), 21 mm (n = 19), 23 mm (n = 13) and 25 mm (n = 10). RESULTS: Peak aortic velocities averaged from 2.2 to 2.7 m/sec, mean gradients from 10.6 to 15.1 mmHg, peak gradients from 20.7 to 29.7 mmHg, and effective orifice area (EOA) from 1.4 to 1.8 cm (2). When accounting for the subaortic velocity, mean gradients averaged from 7.5 to 10.0 mmHg, and peak gradients averaged 15.1 to 23.5 mmHg. The effective orifice area indexes ranged from 0.8 to 1.0 cm (2)/m (2). The mean postoperative left ventricular mass index was 101.6 gm/m (2). CONCLUSIONS: The IN VIVO effective orifice areas by valve size of the Mitroflow aortic pericardial bioprosthesis provide the opportunity of avoiding obstructive characteristics for all valve sizes, including optimizing the management of the small aortic annulus.

Outcome of asymptomatic patients with carotid disease. Asymptomatic Cervical Bruit Study Group.

Asymptomatic cervical atherosclerosis carries a variable risk of vascular events. We sought to identify patients with asymptomatic cervical bruits who may be at increased risk of developing ischemic events. We conducted a prospective multicenter cohort study of neurologically asymptomatic patients presenting a cervical bruit. Patients had biannual neurologic and carotid duplex evaluation. Association between ultrasonographic findings and vascular events, adjusting for common risk factors, was evaluated. Seven hundred fifteen patients were followed on average for 3.6 years. Mean age was 65 years. At initial visit, 357 subjects had a > or = 50% stenosis. Overall, 237 events occurred in 177 patients. Annual rate of all primary vascular events in patients with > or = 50% stenosis was 11.0% versus 4.2% in those with < 50% stenosis (p < 0.001). Annual rate of stroke and vascular death was 5.5% in the > or = 50% group compared with 1.9% in the < 50% group (p < 0.001). Yearly rate of unheralded ischemic stroke was 4.2% in subjects with > or = 80% stenosis and 1.4% in those with stenosis < 80% (p < 0.001). A stroke or TIA was ipsilateral to a > or = 80% stenosis in 66% of patients. Progression of carotid stenosis particularly to more than 80% was associated both with a higher rate of ipsilateral neurologic events and overall combined vascular events. Our data suggest that severity of carotid stenosis is the main risk factor predicting occurrence of neurologic and other vascular events. Yearly rate of ipsilateral stroke with > or = 50% carotid stenosis is low (1.4%) and most are nondisabling. Progression to > or = 80% or occlusion is associated with worse outcome.

Receptor imaging with atrial natriuretic peptide. Part 1: High specific activity iodine-123-atrial natriuretic peptide.

METHODS: Atrial natriuretic peptide (ANP) was labeled in high specific activity using 123I (p,2n). The biodistribution of 123I-ANP was studied in green vervet monkeys by gamma scintigraphy and in rats by dissection and gamma counting. Iodine-125-ANP was also studied in monkeys by in vitro autoradiography. RESULTS: Iodine-123-ANP showed rapid blood clearance with localization to ANP receptors in the kidneys and lungs, which accounted for 35% of total uptake. In vivo competition imaging studies using cold ANP99-126 and C-ANP102-121 proved that uptake is receptor mediated and allowed imaging of the differential biodistribution of A/B and C-ANP receptor families. Thus, it was possible through the use of selective receptor occupation to prevent uptake in certain organs and to effectively steer the labeled ANP to others. The observed biodistribution patterns were confirmed by an in vitro study using 125I-ANP in the same monkeys, which correlated the scintigraphic images with receptor distribution. An in vivo biodistribution study in rats showed a profound effect of specific activity on biodistribution, with a cutoff for receptor uptake at less than 3000 Ci/mmole. CONCLUSION: Gamma scintigraphy with 123I-ANP permits the imaging of ANP receptors in vivo. In contrast to receptor imaging with either organic molecules or antibodies, ANP provides rapid first-pass uptake and substantial accumulation (%dose/organ approximately 20% or greater) in receptors. The key to receptor imaging with peptides is high specific activity. Labeled ANP offers potential as a diagnostic tool for diabetic nephropathy, particularly for quantifying the involvement of glomerular disease.

Management of patients with carotid bruit undergoing cardiopulmonary bypass.

During a 31 month period, 1,433 consecutive patients undergoing cardiac procedures were screened for carotid bruit. A total of 94 patients with carotid bruit were identified who had ultrasonic carotid duplex scans. Nine patients had a history of transient ischemic attack, carotid bruit, and reduction in internal carotid artery diameter by greater than or equal to 50% according to ultrasonic carotid duplex scanning. All nine patients underwent carotid angiography followed by thromboendarterectomy prior to or simultaneous with cardiopulmonary bypass. There was one neurological complication leading to death in this subset. Sixteen patients with asymptomatic carotid bruit had ultrasonic carotid duplex scanning revealing an internal carotid artery lesion of greater than or equal to 50% but did not undergo arteriography or thromboendarterectomy prior to the cardiac procedure. Perfusion pressure was maintained at greater than or equal to 70 mm Hg during bypass. There were no focal neurological events in this subset. Sixty-six patients with internal carotid artery stenosis of less than 50% diameter reduction and asymptomatic bruits had no further work-up or modification in perfusion technique, and there were no focal neurological events in this group. Thus there were no focal neurological events in any of the 82 patients with asymptomatic carotid bruit. An additional group of three patients with a previous stroke and internal carotid artery occlusion by ultrasonic carotid duplex scanning had transient exacerbation of neurological symptoms after cardiopulmonary bypass. The remaining 1,339 patients without carotid bruit had nine (0.7%) focal neurological events postoperatively. We believe that asymptomatic patients with or without hemodynamically significant stenosis can safely undergo cardiopulmonary bypass procedures without carotid thromboendarterectomy. Patients with asymptomatic bruits can be safely screened with ultrasonic carotid duplex scanning and do not require arteriography prior to cardiopulmonary bypass.

In vivo measurement of atrial natriuretic peptide receptors using nuclear imaging.

We have successfully visualized atrial natriuretic peptide (ANP) receptors in vivo using nuclear imaging. 123I-Labelled ANP, injected in green vervet monkeys, was rapidly bound to ANP receptors in the kidneys and lungs. That the observed uptake was receptor mediated was demonstrated with competition studies using simultaneous injection of unlabelled ANP 99-126. It was possible to distinguish between the ANP receptor subtypes by the use of selective antagonists. Thus coinjection of ANP 102-121-des[Gln, Ser, Gly, Leu, Gly] (C-ANP), an ANP analog that selectively binds to the ANP C-receptor, decreased uptake in the kidneys by 50% but increased relative uptake in the lungs and soft tissues. This method permits for the first time, the dynamic in vivo analysis of ANP receptors and their interaction with endogenous ligand. Differences and changes in local ANP receptor concentrations and occupancy could be detected. Since ANP receptor density and affinity are influenced by various physiological and pathological conditions, clinical and diagnostic applications seem possible.

Effect of prolonged infusion of ANF in normotensive and hypertensive monkeys.

It is now recognized that bolus and short-term infusions of atrial natriuretic factor (ANF) into different species lead to a slight and transient decrease of blood pressure, while prolonged infusions cause a significant blood pressure reduction in hypertensive but not in normotensive rats. The present study was designed to evaluate the effects of prolonged ANF infusions on blood pressure and humoral parameters in normotensive and hypertensive African green monkeys (Cercopithecus aethiops). Human-ANF infusions (100 ng/kg.hr) in conscious, normotensive vervets for a period of 48 hours evoked highly significant decreases of blood pressure (from 124/65 to 104/53 mm Hg), plasma renin activity, aldosterone, and hematocrit. This fall in blood pressure was not accompanied by an increase of plasma cGMP levels at the end of the infusion. Forty-eight hours after the infusion was terminated, the decrease in blood pressure was still significant (97/46 mm Hg), as was the drop in aldosterone. In hypertensive monkeys, systolic blood pressure declined from 175 +/- 8 to 130 +/- 8 mm Hg, while diastolic pressure fell from 117 +/- 10 to 88 +/- 4 mm Hg. These data demonstrate that the chronic infusion of ANF in both normotensive and hypertensive vervets has more profound effects than does acute bolus administration, effects that persist for a prolonged period of time after discontinuation of the infusion.

Oxazoline N-oxide-mediated [2+3] cycloadditions. Application to a synthesis of (-)-tetrahydrolipstatin.

[reaction: see text] A [2+3] cycloaddition of camphor-derived oxazoline N-oxide to alpha,beta-unsaturated ester afforded adduct 8. Tetrahydrolipstatin 1 was prepared from this compound in a nine-step sequence of reactions.

Oxazoline N-oxide mediated [2 + 3] cycloadditions. Application to a formal synthesis of (+)-carpetimycin A.

[formula: see text] Cycloaddition between gamma,delta-unsaturated beta-enamino ester 9 and camphor-derived oxazoline N-oxide 8 afforded a single adduct, 14. Dipolarophile 9 proved to be very reactive despite the substitution on the double bond. Stereoselective sodium cyanoborohydride reduction of the imminium intermediate 14a gave rise stereoselectively to beta-amino ester derivative 15a. Oxidative acidic hydrolysis, oxidation of the resulting aldehyde 18, deprotection, and cyclization afforded the beta-lactam 23, a direct precursor of (+)-carpetimycin A.

Is siphon disease important in predicting outcome of carotid endarterectomy?

The prevalence of atherosclerosis at the carotid bifurcation and in the siphon was reviewed in 141 patients who underwent 149 endarterectomies. The relationship between the presence and severity of siphon lesions and focal neurologic symptoms, both before and after operation, was also examined. Siphon disease was found in 84% of the 282 sides. Most lesions (42%) were in the 20% to 49% diameter-reduction category. Only 9% were stenoses greater than 50%, and 10% were occlusions. The majority (65%) were smooth. No relationship was found between the severity of disease at the carotid bifurcation and in the siphon. No pattern of siphon disease could be related to the occurrence of symptoms. Furthermore, no relation was found between the severity of siphon disease and recurrent symptoms after endarterectomy.

Change in amplitude distributions of Doppler spectrograms recorded below the aortic valve in patients with a valvular aortic stenosis.

Amplitude distributions of Doppler spectrograms were characterized in a group of 22 patients having no aortic pressure gradient and another group of 26 patients having a stenotic aortic valve. Specifically, for each patient, the ratios of the mean amplitude in three normalized frequency bands (low, middle and high) to the mean amplitude of the Doppler spectrogram computed in selected portions of the systolic period were considered. Pulsed-wave Doppler spectrograms were recorded by positioning the sample volume in the left ventricular outflow tract, approximately 1 cm below the aortic valve. Statistically significant differences were found between the middle (p = 0.041) and high (p = 0.028) frequency bands of Doppler signals recorded from the two groups of patients. The differences observed are believed to be attributed to blood flow eddies generated below the stenotic aortic heart valve and to changes in blood flow orientation.

Flow velocity patterns in the carotid bifurcations of young, presumed normal subjects.

Spectral analysis of pulsed Doppler velocity waveforms has been found useful as a diagnostic technique in the assessment of carotid artery disease. While spectral broadening of the velocity waveform obtained at center stream sites is usually associated with arterial disease, the present study describes spectral patterns resulting from disturbed blood flow in the proximal branches of the carotid bifurcation in young, presumed normal human subjects. In those studied, spectral patterns in the bifurcation region exhibit characteristics similar to those occurring in zones of flow separation in model studies under conditions of steady flow. It is important to distinguish the spectral patterns due to arterial disease from those occurring in the normal bifurcation. This paper describes the types of flow disturbances noted in presumed normal arteries and points out the need to understand the flow velocity patterns that may be found at specific anatomical sites across the carotid bifurcation.

Computer evaluation of Doppler spectral envelope area in patients having a valvular aortic stenosis.

The reliability of three algorithms to estimate the maximal and minimal frequency contours of Doppler spectrograms was evaluated in a group of 48 patients. Two algorithms had previously been used in the literature. These are the Modified Threshold Crossing Method and the Hybrid method. The third algorithm is new and is the Maximal Background Noise Threshold Crossing Method. A new approach was also proposed in the present study to estimate the background noise level of Doppler spectrograms. This level was used as a threshold in the computation of the spectral envelopes. Two diagnostic spectral parameters (the spectral envelope area and the systolic velocity integral) extracted from Doppler spectrograms recorded in the left ventricular outflow tract were also evaluated and tested to discriminate between 23 patients having no aortic pressure gradient and 25 patients with a stenotic aortic valve. Results describe the influence of the threshold level used in the Modified Threshold Crossing Method and the Hybrid method on the variability of the spectral contours. It is clearly demonstrated that the variability of minimal frequency contours is higher than that of maximal frequency contours. All three algorithms provided similar diagnostic performances with the spectral envelope area (71% to 73% of correct classifications) while the Maximal Background Noise Threshold Crossing Method and the Hybrid method provided the best results for the systolic velocity integral (69% of correct classifications). Because the systolic velocity integral combined with the continuity equation is used in the literature to evaluate noninvasively the aortic valve area, these results suggest the use of the spectral envelope area instead of the systolic velocity integral.

Computer analysis and pattern recognition of Doppler blood flow spectra for disease classification in the lower limb arteries.

In the present study, a computer processing method was developed to objectively classify disease in the lower limb arteries evaluated by noninvasive ultrasonic duplex scanning. This method analyzes Doppler blood flow signals, extracts diagnostic features from Doppler spectrograms and classifies the severity of the disease into three categories of diameter reduction (0-19%, 20-49% and 50-99%). The features investigated were based on frequency features obtained at peak systole, spectral broadening indices and normalized amplitudes of the power spectrogram computed in various positive and negative frequency bands. A total of 379 arterial segments studied from the aorta to the popliteal artery were classified using a pattern recognition method based on the Bayes model. Two classification schemes using a two-node decision rule were tested. Both schemes gave similar results, the first one provided an overall accuracy of 83% (Kappa = 0.42) and the second an overall accuracy of 81% (Kappa = 0.35) when compared with conventional biplane contrast arteriography. These performances, especially for the 0 to 19% lesion category, are better than the one obtained by the technologist (accuracy = 76% and Kappa = 0.33), based on visual interpretation of the Doppler spectrograms. To recognize hemodynamically significant stenoses (50-99% lesions), the pattern recognition system has a sensitivity and a specificity of 50% and 99%, respectively, using classification scheme I. With classification scheme II, the sensitivity and the specificity are 50% and 98%, respectively. Visual interpretation of the Doppler spectrograms leads to a sensitivity and a specificity of 50% and 98%, respectively. These results are the first to be obtained by a pattern recognition system in classifying lower limb arterial stenoses.

Variability in measurement of specific parameters for carotid duplex examination.

The variability of four carotid artery frequency parameters used for classifying disease with duplex scanning was prospectively studied. Forty-eight patients (94 patent carotid arteries) were each examined by two technologists. Measured parameters were the peak systolic frequency (PSF) and the first zero slope from the common carotid artery, and the PSF and end diastolic frequency (EDF) from the internal carotid artery. Measurements from all the examinations were made twice by each technologist. Interobserver, intraobserver, and interpatient variability in measurement of the first zero slope was so great that we have abandoned its use. Measurement of variability for PSF and EDF was much less (correlation coefficients 0.68 to 0.92). These parameters were measured with sufficient precision to warrant their continued use for important decision steps in classifying carotid artery disease. Interpatient differences in PSF sufficient to cause disagreement regarding the hemodynamic significance of carotid disease occurred in only three instances. In each of these cases the differences were due to examination technique (failure to identify a very distal internal carotid artery stenosis, difficulty distinguishing between a kink and a stenosis, and failure to recognize an improper Doppler angle). We conclude that the variability of PSF and EDF is within clinically acceptable levels and is mainly due to examination technique rather than measurement of waveform parameters or changes in patient hemodynamics.

Evaluating carotid artery disease. The concordance between pulsed Doppler/spectrum analysis and angiography.

The results of ultrasonic pulsed Doppler duplex scanning with spectral analysis and computer pattern recognition are compared with the results of contrast arteriography in patients screened for extracranial carotid artery disease. The intraangiographer variability (one radiologist reading the same films twice) and the interangiographer variability (two radiologists reading the same film independently) were also studied. To calculate degrees of agreement corrected for chance, the Kappa statistic was computed for all the evaluation methods employed. At the present time, the concordance between spectral analysis and cerebral contrast angiography reaches a Kappa value of 0.682 +/- 0.064. This level of agreement compares favorably with the interangiographer agreement level (K = 0.568 +/- 0.058) and the intraangiographer agreement (K = 0.711 +/- 0.054). The computer pattern recognition program predicted the degree of stenosis by angiography with an agreement of K = 0.721 +/- 0.059. This concordance compares favorably to that observed when the radiologists are compared with themselves and is greater than that reached by two different radiologists. The continuous improvement in precision and accuracy of duplex scanning offers the promise of its usefulness in clinical and epidemiological studies.

Post-endarterectomy carotid ultrasonic duplex scanning concordance with contrast angiography.

The results of ultrasonic duplex scanning combined with spectral analysis are compared with the results of contrast angiography in patients after endarterectomy in which recurrence of carotid arterial disease was suspected. Thirty-six patients underwent a duplex scan study within 3 months of their post-operative angiogram, performed at their physician's discretion (44 studies). The overall accuracy of the method was 80%. Our ability to predict a greater than 50% diameter reduction along with total occlusion was 94%. The measure of agreement corrected for chance between arteriography and duplex scanning as expressed by the Kappa statistic was 0.675 +/- SE (K) 0.096. This level of agreement compared favorably to that of inter- and intra-observer variability in reading cerebral angiograms. The accuracy reported justifies the clinical use of ultrasonic duplex scanning in the detection of recurrent stenosis after carotid endarterectomy.

Noninvasive mapping of lower limb arterial lesions.

Thirty patients with peripheral arterial disease were evaluated using an ultrasonic duplex scanner. A total of 338 arterial segments from the level of the iliac to the popliteal artery were studied and compared with the results of arteriography read independently by two radiologists who were unaware of the results with the scanner. The results demonstrate that this method is not only suitable for clinical use but is as good as arteriography in defining both the location and extent of the arterial involvement.

Sources of variability in carotid duplex examination: a prospective study.

Interobserver and intraobserver variability of ultrasonic, duplex carotid artery examinations was studied in a prospective, randomized, and blinded clinical trial. Forty-eight patients were examined by two technologists, yielding 96 carotid artery examinations. The kappa statistic was calculated to determine the degree of agreement corrected for chance. The kappa value between examinations by different technologists was 0.476. Variability occurred at both steps in the examination procedure: (1) obtaining the velocity waveforms (kappa = 0.536); and (2) using these waveforms to classify the extent of carotid disease (kappa = 0.609 for interobserver variability in reading waveforms). Minimal to moderate disease categories accounted for most of the variability. There was little disagreement in categorizing lesions as greater than or less than 50% diameter reduction. Intraobserver variability in rereading spectral waveforms was minimal (kappa = 0.842 and 0.894). Recognition of disturbed flow patterns in normal carotid bulbs may reduce variability.

Computer based pattern recognition of carotid artery Doppler signals for disease classification: prospective validation.

A computer based pattern recognition method has been developed to classify the percent diameter reduction in nonoccluded internal carotid arteries. Using a combined B-mode/pulsed Doppler unit, the system utilizes spectral waveforms obtained from the low common and proximal internal carotid artery locations. The ECG-R wave is used as a time reference to synchronize the averaging of Doppler spectra from 20 heart cycles. An averaged waveform is generated and represents the spectral data from which features are extracted for analysis. A stepwise selection algorithm identifies a feature subset for partitioning the entire range of disease into two states, less than and greater than a decision point. Three such partitions are made, leading to the following categories: Normal, 1-20, 21-50 and 51-99% dia. reduction. A classifier was trained, tested prospectively against unknown data and the results compared to angiography. Of the 170 vessels tested, 141 (82%) were classified in the same category by angiography and the computer system. Agreement for each category was 93% (27/29) for the normals, 81.5% (44/54) for the 1-20% lesions, 78% (29/37) for the 21-50% lesions and 82% (41/50) for the 51-99% lesions. The computer method and angiography differed by more than one category in only one of the 170 tests. The level of agreement corrected for chance (Kappa +/- SE(K] was 0.769 +/- 0.039. Future efforts will be directed toward dividing classification of disease further (especially in the 51-99% category), developing a dedicated microprocessor for on-line analysis of the signals and using the system for prospective epidemiological studies of various populations.

The use of common carotid waveform analysis in the diagnosis of carotid occlusive disease.

Duplex scanning with spectral analysis of the pulsed Doppler signal are currently used to detect and classify disease at the carotid bifurcation. Although the sensitivity of the test exceeds 90%, the method has a lower specificity which ranges between 8 and 50%. The poor specificity is due to the difficulty in distinguishing flow disturbances normally present at the carotid bifurcation from those produced by minimal amount of disease. In order to improve the ability of the method to predict normalcy, new features measured from the low common carotid waveform are evaluated on 150 sides. The difference of frequency from the systolic peak (a) to the point of first zero slope after peak systole (b) was used to define the ratio (a-b)/a. A ratio greater than 0.5 was associated with 76% of the normal sides and only 7% of the diseased sides. A ratio below 0.5 was associated with 83% of the diseased sides. This ratio, when used alone, can improve the specificity of the method to 76%.