Comparing phase and electrographic flow mapping for persistent atrial fibrillation.

BACKGROUND: An increasing number of methods are being used to map atrial fibrillation (AF), yet the sensitivity of identifying potential localized AF sources of these novel methods are unclear. Here, we report a comparison of two approaches to map AF based upon (1) electrographic flow mapping and (2) phase mapping in a multicenter registry of patients in whom ablation terminated persistent AF. METHODS: Fifty-three consecutive patients with persistent AF in whom ablation terminated AF in an international multicenter registry were enrolled. Electrographic flow mapping (EGF) and phase mapping were applied to the multipolar simultaneous electrograms recorded from a 64-pole basket catheter in the chamber (left vs right atrium) where AF termination occurred. We analyzed if the mapping methods were able to detect localized sources at the AF termination site. We also analyzed global results of mapping AF for each method, patterns of activation of localized sources. RESULTS: Patients were 64.3 ± 9.4 years old and 69.8% were male. EGF and phase mapping identified localized sources at AF termination sites in 81% and 83% of the patients, respectively. Methods were complementary and in only n = 2 (3.7%) neither method identified a source. Globally, EGF identified more localized sources than phase mapping (5.3 ± 2.8 vs 1.8 ± 0.5, P < 0.001), with a higher prevalence of focal (compared to rotational) activation pattern (49% vs 2%, P < 0.01). CONCLUSIONS: EGF is a novel vectorial-based AF mapping method, which can detect sites of AF termination, agreeing with, and complementary to, an alternative AF mapping method using phase analysis.

Mechanisms linking electrical alternans and clinical ventricular arrhythmia in human heart failure.

BACKGROUND: Mechanisms of ventricular tachycardia (VT) and ventricular fibrillation (VF) in patients with heart failure (HF) are undefined. OBJECTIVE: The purpose of this study was to elucidate VT/VF mechanisms in HF by using a computational-clinical approach. METHODS: In 53 patients with HF and 18 control patients, we established the relationship between low-amplitude action potential voltage alternans (APV-ALT) during ventricular pacing at near-resting heart rates and VT/VF on long-term follow-up. Mechanisms underlying the transition of APV-ALT to VT/VF, which cannot be ascertained in patients, were dissected with multiscale human ventricular models based on human electrophysiological and magnetic resonance imaging data (control and HF). RESULTS: For patients with APV-ALT k-score >1.7, complex action potential duration (APD) oscillations (≥2.3% of mean APD), rather than APD alternans, most accurately predicted VT/VF during long-term follow-up (+82%; -90% predictive values). In the failing human ventricular models, abnormal sarcoplasmic reticulum (SR) calcium handling caused APV-ALT (>1 mV) during pacing with a cycle length of 550 ms, which transitioned into large magnitude (>100 ms) discordant repolarization time alternans (RT-ALT) at faster rates. This initiated VT/VF (cycle length <400 ms) by steepening apicobasal repolarization (189 ms/mm) until unidirectional conduction block and reentry. Complex APD oscillations resulted from nonstationary discordant RT-ALT. Restoring SR calcium to control levels was antiarrhythmic by terminating electrical alternans. CONCLUSION: APV-ALT and complex APD oscillations at near-resting heart rates in patients with HF are linked to arrhythmogenic discordant RT-ALT. This may enable novel physiologically tailored, bioengineered indices to improve VT/VF risk stratification, where SR calcium handling and spatial apicobasal repolarization are potential therapeutic targets.

Demonstration of the proarrhythmic preconditioning of single premature extrastimuli by use of the magnitude, phase, and distribution of repolarization alternans.

BACKGROUND: We hypothesized that single premature extrastimuli (S(2)) insufficient to induce reentry produce proarrhythmic effects (proarrhythmic preconditioning) that are measurable by use of the magnitude, phase, and temporal distribution of repolarization alternans (RPA; alternate-beat fluctuations in ECG repolarization). METHODS AND RESULTS: Before programmed electrical stimulation (PES), surface ECG leads I, aVF, and V(1) were recorded in 30 patients during simultaneous atrial and ventricular pacing at 500 ms with S(2) coupling intervals (CIs) decreasing from 400 to 240 ms in 20-ms steps. We determined RPA magnitude (V(alt)) as the 0.5-cycle/beat peak after spectral decomposition of consecutive STU intervals over 64 beats immediately preceding and following each S(2), RPA phase reversals as discontinuities in the even/odd phase of STU alternation, and RPA distribution as the time point of median RPA magnitude within repolarization. Eighteen patients were induced into ventricular tachycardia (VT), whereas 12 were not. Extrastimuli dynamically modulated each characteristic of RPA. S(2) augmented V(alt) in inducible (8.2+/-2.3 versus 6.2+/-1.6 microV; P=0.003) but not noninducible patients. S(2) reversed RPA phase more in inducible than in noninducible patients (56.7% versus 45.3%; P=0.02 by chi(2)), particularly when CI was < or =300 ms (66.3% versus 46.5%; P=0.006). Finally, S(2) redistributed RPA significantly later within repolarization in inducible patients. Each effect was more marked for CI < or =300 ms. CONCLUSIONS: A single S(2) increases RPA magnitude, reverses its phase, and redistributes it later in repolarization in patients with the substrates for VT. These effects become more pronounced with shorter coupling intervals. These results suggest that it is possible to track the dynamic proarrhythmic preconditioning of single premature depolarizations.

Exploiting rate-related hysteresis in repolarization alternans to improve risk stratification for ventricular tachycardia.

OBJECTIVES: We sought to study the effect of heart rate acceleration and deceleration on the ability of repolarization alternans (RPA) to stratify ventricular tachycardia (VT) risk. BACKGROUND: Heart rate fluctuations alter arrhythmic propensity, yet it is unclear whether fluctuations, as well as absolute rate, dynamically increase VT risk. We hypothesized that repolarization heterogeneity reflected by RPA would exhibit hysteresis during rising and falling heart rate, which may reflect arrhythmic propensity. METHODS: The RPA magnitude (absolute voltage of alternation [V(alt)] and T-wave alternans ratio [TWAR]) and temporal distribution were determined from the electrocardiogram (ECG) in 60 patients during paced heart rate acceleration from 100 to 150 beats/min, then deceleration to 100 beats/min at electrophysiologic study (EPS). The V(alt) and TWAR thresholds were varied prospectively to generate receiver-operating characteristics (ROC) for the prediction of inducible VT at EPS. RESULTS: Thirty-six patients were induced into VT and 24 were not. Hysteresis of RPA was seen. The V(alt) reached steady-state within 60 beats of each rate transition and was higher in deceleration than in acceleration at matched heart rates. In induced patients, V(alt) rose then fell with heart rate. In noninduced patients, V(alt) was insensitive to acceleration, but rose on initial deceleration. The RPA distributed later within repolarization in induced patients but, on deceleration, moved earlier in both groups. By ROC analysis, V(alt) = 2.6 microV in late repolarization at 120 beats/min provided optimal sensitivity and specificity for VT in acceleration (87.5% and 88.7%, respectively) versus deceleration (80% and 62.5%, respectively; p = 0.004, chi-square test). CONCLUSIONS: 1) Physiologic fluctuations in heart rate may affect the clinical utility of RPA for VT risk stratification; and 2) repolarization dispersion measured by RPA is more exaggerated during deceleration than acceleration at matched heart rates (rate hysteresis).

Stimulus parameters influence characteristics of optical intrinsic signal responses in somatosensory cortex.

Optical imaging of intrinsic signals was performed in the barrel cortex of the rat during whisker deflections of varying frequencies (1 to 20 Hz) and durations (0.1 to 5 s). A dose-response relationship was shown between these stimuli and the characteristics of the optically recorded intrinsic signal response. At constant frequencies, longer stimulus durations increased response magnitude, as defined by mean pixel value in statistically determined regions of interest. At constant durations, higher stimulus frequencies increased response magnitude. Response magnitude was also increased by greater numbers of deflections. When stimulus number was constant, there were no differences in response magnitude, regardless of stimulus frequency and duration. Spatial extent of responses, as defined by number of pixels in regions of interest, did not differ between stimulus frequencies, durations, or numbers. Comparison of the time to reach peak intrinsic signal response after stimulus onset ("time-to-peak") suggested that higher frequencies were associated with faster time-to-peak. Registration of intrinsic signal responses with cytochrome oxidase-stained whisker barrels demonstrated that responses were located over the barrel corresponding to the stimulated whisker. In summary, we have shown that the absolute number of stimuli delivered to the system is, at least for short stimulus periods (< or = 5 s), a determining factor for the magnitude of these responses, whereas stimulus frequency appears to influence time-to-peak response.

Functional increases in cerebral blood volume over somatosensory cortex.

We have examined the relationship between cerebral blood volume (CBV) and electrophysiology over primary somatosensory cortex (S-I) in the rat. We did this by comparing the spatial characteristics and time course of activity-related changes in plasma fluorescence, intrinsic optical reflectance signals, and single unit electrophysiology in S-I to identical stimuli. S-Is of urethane-anesthetized male Sprague-Dawley rats were exposed, and fluorescent Texas Red dextran dye (MW 70,000) was administered intravenously. Subsequently, foredigit electroshock or vibrissal deflection was associated with fluorescence increases over contralateral forelimb or posteromedial barrel subfield cortex. Fluorescence was delayed and prolonged, indicating that CBV increases at 1-1.5 s and peaks 2-2.5 s after the onset of stimulation in both regions. When stimulus intensity was adjusted to produce barely detectable fluorescence foci (10% above back-ground), significant electrophysiologic spiking was seen. At these parameters, fluorescence change overlay areas of increased cortical layer III cell firing on single unit recordings. However, surface boundaries of the smallest observable fluorescence foci at their peak spatial extents consistently overspilled electrophysiologic center receptive fields. Corresponding intrinsic optical reflectance decreases were seen at 610 and 850 nm, exhibiting similar timing and colocalizing closely with fluorescence increase at both wavelengths after identical stimuli. These signals similarly overspilled electrophysiologic activity. Thus, we observed delayed increases in vascular fluorescence (related to CBV) over activated cortex. The smallest detectable fluorescence changes overspilled the center receptive field boundaries and were associated with appreciable electrophysiologic firing. In addition, the striking spatial and temporal similarity between intrinsic optical reflectance and fluorescence activity suggests that changes in intrinsic cortical reflectance are strongly related to changes in CBV.

Spectral analysis of periodic fluctuations in electrocardiographic repolarization.

Repolarization alternans (RPA) indicates alternate-beat fluctuations in the temporal or spatial characteristics of the echocardiogram (ECG) STU segment which may represent dispersion in repolarization. Spectral decomposition has revealed microvolt-level RPA which has been found to correlate with ventricular tachycardia (VT) and fibrillation, and is increasingly being used for clinical risk stratification. However, while interruptions in periodicity are known to affect spectral decomposition, their quantitative impact on RPA and its clinical utility have been poorly described. We therefore studied the effect of variable alignment, extrasystoles, dissimilar beats and beat exclusion on RPA magnitude in simulations and on the sensitivity and specificity of RPA for VT in a pilot clinical study. RPA magnitude was exquisitely sensitive to QRS alignment such that +/- 1 ms random beat misalignment reduced it by 68% in simulations. Correspondingly, suboptimal QRS alignment in clinical ECG's caused the sensitivity of RPA for inducible VT to fall from 93% to as low as 63%; while JT alignment was also less effective for RPA recovery. As an experiment in minimizing morphometric irregularities in clinical ECG's, we found that RPA magnitude actually fell when replacing either measurably dissimilar or ectopic beats with more representative beats. In addition, inserting or deleting beats also reduced RPA magnitude in clinical sequences and simulations. These statistical analyses suggest that the precision of beat alignment and interruptions to ECG periodicity, which may occur physiologically, may greatly reduce the clinical utility of RPA for VT. Dynamic alterations in RPA in response to sequence irregularities require further study before RPA may be optimally applied to screen for ventricular arrhythmias.

Women's approaches to decision making about mammography.

Health professionals have an obligation to understand women's decision making about mammography and to advocate for their active participation in health care decision making. Although mammography is a major screening measure for the second largest cancer killer of women, only approximately half of women older than age 50 years, and fewer older than age 70 years, undergo mammography in accordance with American Cancer Society (ACS) guidelines. Therefore, the purpose of this study was to identify women's overall decision-making approaches when considering mammography. Subjects were a purposive, convenience sample of 50 women in the community who had made a decision about mammography; they included those who chose to have mammograms and those who decided not to have mammograms according to the pre-1997 ACS guidelines. Subjects participated in audiotaped interviews. Results indicated that women approached the mammography decision differently, regardless of the decision they made. Three overall decision-making approaches to addressing risk factors, issues about mammography, or other factors before their decision were evident. The approaches were (1) thoughtful consideration; (2) cursory consideration; and (3) little or no consideration. Each approach has implications for nurses who assist women in making decisions about mammography.

Line of reasoning as a representation of nurses' clinical decision making.

Line of reasoning (LOR) is offered as an alternative representation of clinical decision making for studies using protocol analysis. A LOR is defined as an argument or set of arguments leading to a conclusion. Because LOR combines both knowledge and cognitive processes, it provides a more complete representation of how a person uses knowledge to make a decision in a particular situation than do other representations. Operationalization of LOR in the form of templates and narratives enhances systematic data interpretation and coding. The use of LOR as a representation is illustrated in a study of critical care nurses' clinical decision making, specifically the determination of a patient's readiness to wean from mechanical ventilation.

Differing rate dependence and temporal distribution of repolarization alternans in patients with and without ventricular tachycardia.

INTRODUCTION: Repolarization alternans (RPA) may reflect repolarization heterogeneities underlying VT, yet its temporal dynamics are poorly understood. We hypothesized that RPA occurring late, rather than early, within repolarization reflects a temporal variation in recovery that may predispose to wavefront fractionation and the initiation of reentrant VT, and that this temporal distribution may vary with heart rate. METHODS AND RESULTS: ECG leads I, aVF, and V1 were recorded in 40 patients during electrophysiologic study. RPA across the JT interval was computed spectrally for 64-beat sequences at paced cycle lengths (CLs) of 600, 500, and 400 msec, and expressed as the T wave alternans ratio (TWAR) on the vector ECG lead. Significant RPA (TWAR > or = 3) was reconstructed into the time domain, and its center of area used to represent its temporal distribution. Twenty-two patients were inducible into VT and 18 were not. RPA was of larger magnitude in inducible than noninducible patients (TWAR = 11.1 vs 4.42, P = 0.035; 38.3 vs 5.74, P = 0.004; and 88.8 vs 4.28, P = 0.001 in each, respectively), and was distributed later (P < 0.02; CL 600 msec). Applying TWAR > or = 3 to the distal half of the JT segment produced greater specificity for inducible VT (88.9%, 66.7%, and 69.2% at each CL, respectively) than did RPA of the entire JT segment (77.8%, 53.3%, and 69.2%). CONCLUSION: RPA is more specific for inducible VT when distributed late rather than elsewhere in repolarization, and this temporal distribution is heart rate sensitive. Further study is required to interpret these findings in the context of temporal dispersion of refractoriness.

Mapping functional activity in rodent cortex using optical intrinsic signals.

We have investigated the dynamic response of rodent posteromedial barrel subfield (PMBSF) cortex to mechanical whisker deflection, using optical intrinsic signal imaging. While electrophysiologic response in barrel cortex has been well studied, dynamic metabolic changes affecting activity-related perfusion or oxidative enzymes are not well understood. Male Sprague-Dawley rats were anesthetized. Contralateral single and multiple vibrissae were deflected while images of somatosensory cortex were acquired with a charge-coupled-device camera. Intrinsic signals were observed over PMBSF as stimulus-related reflectance decreases (10(-3) of baseline) comprising two distinct spatiotemporal components. At 610 nm the first, diffuse, component begins 0.5-1 sec after stimulus onset, peaks at 2.5-3 sec, and returns to baseline by 4-5 sec. The second component is macrovascular, beginning at 1-1.5 sec, peaking at 3 sec, and dissipating by 5-6 sec. Similar patterns were observed at 550 nm and 850 nm. Signal size and location varied with the stimulus. Evoked potentials were found to have maximal amplitude in the region of maximal optical signals, diminishing toward the optical periphery. We have demonstrated PMBSF response to vibrissal deflection using optical reflectance methods. These intrinsic signals overlie regions of maximal electrophysiologic response, but commence, peak, and extinguish over a time scale of seconds from stimulus onset. They most likely indicate activity-related microvascular recruitment and chromophore redox changes.

Coronary care nurses' clinical decision making.

Increasing acuity of hospitalized persons with cardiac disease places great demands on nurses' decision-making abilities. Yet nursing lags in knowledge-based system development because of limited understanding about how nurses use knowledge to make decisions. The two research questions for this study were: how do the lines of reasoning used by experienced coronary care nurses compare with those used by new coronary care nurses in a representative sample of hypothetical patient cases, and are the predominant lines of reasoning used by coronary care nurses in hypothetical situations similar to those used for comparable situations in clinical practice? Line of reasoning was defined as a set of arguments in which knowledge is embedded within decision-making processes that lead to a conclusion. Sixteen subjects (eight experienced and eight new nurses) from coronary care and coronary step-down units in a large, private, teaching hospital in Minnesota, USA, were asked to think aloud while making clinical decisions about six hypothetical cases and comparable actual case. One finding was that most subjects in both groups used multiple lines of reasoning per case; but they used only one predominantly. This finding highlighted the non-linear nature of clinical decision making. Subjects used 25 predominant lines of reasoning, with intergroup differences on six of them. Where there were differences, experienced nurses used lines of reasoning of lower quality than did new subjects. The type variability in lines of reasoning suggested that multiple pathways should be incorporated into knowledge-system design. One implication of the variability in subjects' line of reasoning quality is that nurses at all levels of expertise are fallible and could benefit from decision support. The finding that subjects tended to use similar lines of reasoning for comparable hypothetical and actual cases was modest validation of subjects' performance on hypothetical cases as representing their decision making in practice. Consequently, there was support for using simulations and case studies in teaching and studying clinical decision making.

Imaging optical reflectance in rodent barrel and forelimb sensory cortex.

Novel neuroimaging techniques are extending the scope for studying dynamic brain function. We have developed a system which enables the repeatable imaging of rapid function in rodent primary somatosensory cortex (S-I), based on activity-related changes in its optical reflectance (intrinsic signals). The S-I cortices of anesthetized male Sprague-Dawley rats were exposed. Images were acquired with a slow-scan, cooled, charge-coupled device camera (CCD) through filters at 550, 610, and 850 nm before, during, and after contralateral stimulation (vibrissal deflection or forepaw stimulation). Images were divided by prestimulus controls and then averaged across 9-27 trials to produce maps of stimulus-related reflectance change. Optical activity had magnitude 10(-3) of baseline reflectance and consistently comprised two distinct spatiotemporal components over cortex, depending on paradigm. The diffuse signal at 610 nm begins 0.5-1 s after stimulus onset and has a duration of 4-5 s. The second signal is macrovenous and is delayed by 1 s. Similar response patterns were observed at 550 and 850 nm. Evoked potentials, recorded at sites inside and outside the zone of optical activity, confirmed the functional nature of these signals. Using a CCD we have imaged functional reflectance changes over rodent S-I which commence, peak, and extinguish over a time scale of seconds. This optical activity is consistent with the etiologies of microvascular recruitment and chromophore redox change.