Prediction of episode of hemodynamic instability using an electrocardiogram based analytic: a retrospective cohort study.

BACKGROUND: Predicting the onset of hemodynamic instability before it occurs remains a sought-after goal in acute and critical care medicine. Technologies that allow for this may assist clinicians in preventing episodes of hemodynamic instability (EHI). We tested a novel noninvasive technology, the Analytic for Hemodynamic Instability-Predictive Indicator (AHI-PI), which analyzes a single lead of electrocardiogram (ECG) and extracts heart rate variability and morphologic waveform features to predict an EHI prior to its occurrence. METHODS: Retrospective cohort study at a quaternary care academic health system using data from hospitalized adult patients between August 2019 and April 2020 undergoing continuous ECG monitoring with intermittent noninvasive blood pressure (NIBP) or with continuous intraarterial pressure (IAP) monitoring. RESULTS: AHI-PI's low and high-risk indications were compared with the presence of EHI in the future as indicated by vital signs (heart rate > 100 beats/min with a systolic blood pressure < 90 mmHg or a mean arterial blood pressure of < 70 mmHg). 4,633 patients were analyzed (3,961 undergoing NIBP monitoring, 672 with continuous IAP monitoring). 692 patients had an EHI (380 undergoing NIBP, 312 undergoing IAP). For IAP patients, the sensitivity and specificity of AHI-PI to predict EHI was 89.7% and 78.3% with a positive and negative predictive value of 33.7% and 98.4% respectively. For NIBP patients, AHI-PI had a sensitivity and specificity of 86.3% and 80.5% with a positive and negative predictive value of 11.7% and 99.5% respectively. Both groups performed with an AUC of 0.87. AHI-PI predicted EHI in both groups with a median lead time of 1.1 h (average lead time of 3.7 h for IAP group, 2.9 h for NIBP group). CONCLUSIONS: AHI-PI predicted EHIs with high sensitivity and specificity and within clinically significant time windows that may allow for intervention. Performance was similar in patients undergoing NIBP and IAP monitoring.

Detection of Hemodynamic Status Using an Analytic Based on an Electrocardiogram Lead Waveform.

OBJECTIVES: Delayed identification of hemodynamic deterioration remains a persistent issue for in-hospital patient care. Clinicians continue to rely on vital signs associated with tachycardia and hypotension to identify hemodynamically unstable patients. A novel, noninvasive technology, the Analytic for Hemodynamic Instability (AHI), uses only the continuous electrocardiogram (ECG) signal from a typical hospital multiparameter telemetry monitor to monitor hemodynamics. The intent of this study was to determine if AHI is able to predict hemodynamic instability without the need for continuous direct measurement of blood pressure. DESIGN: Retrospective cohort study. SETTING: Single quaternary care academic health system in Michigan. PATIENTS: Hospitalized adult patients between November 2019 and February 2020 undergoing continuous ECG and intra-arterial blood pressure monitoring in an intensive care setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One million two hundred fifty-two thousand seven hundred forty-two 5-minute windows of the analytic output were analyzed from 597 consecutive adult patients. AHI outputs were compared with vital sign indications of hemodynamic instability (heart rate > 100 beats/min, systolic blood pressure < 90 mm Hg, and shock index of > 1) in the same window. The observed sensitivity and specificity of AHI were 96.9% and 79.0%, respectively, with an area under the curve (AUC) of 0.90 for heart rate and systolic blood pressure. For the shock index analysis, AHI's sensitivity was 72.0% and specificity was 80.3% with an AUC of 0.81. CONCLUSIONS: The AHI-derived hemodynamic status appropriately detected the various gold standard indications of hemodynamic instability (hypotension, tachycardia and hypotension, and shock index > 1). AHI may provide continuous dynamic hemodynamic monitoring capabilities in patients who traditionally have intermittent static vital sign measurements.

Competitive Drivers of Atrial Fibrillation: The Interplay Between Focal Drivers and Multiwavelet Reentry.

BACKGROUND: There is debate whether human atrial fibrillation is driven by focal drivers or multiwavelet reentry. We propose that the changing activation sequences surrounding a focal driver can at times self-sustain in the absence of that driver. Further, the relationship between focal drivers and surrounding chaotic activation is bidirectional; focal drivers can generate chaotic activation, which may affect the dynamics of focal drivers. METHODS AND RESULTS: In a propagation model, we generated tissues that support structural micro-reentry and moving functional reentrant circuits. We qualitatively assessed (1) the tissue's ability to support self-sustaining fibrillation after elimination of the focal driver, (2) the impact that structural-reentrant substrate has on the duration of fibrillation, the impact that micro-reentrant (3) frequency, (4) excitable gap, and (5) exposure to surrounding fibrillation have on micro-reentry in the setting of chaotic activation, and finally the likelihood fibrillation will end in structural reentry based on (6) the distance between and (7) the relative lengths of an ablated tissue's inner and outer boundaries. We found (1) focal drivers produced chaotic activation when waves encountered heterogeneous refractoriness; chaotic activation could then repeatedly initiate and terminate micro-reentry. Perpetuation of fibrillation following elimination of micro-reentry was predicted by tissue properties. (2) Duration of fibrillation was increased by the presence of a structural micro-reentrant substrate only when surrounding tissue had a low propensity to support self-sustaining chaotic activation. Likelihood of micro-reentry around the structural reentrant substrate increased as (3) the frequency of structural reentry increased relative to the frequency of fibrillation in the surrounding tissue, (4) the excitable gap of micro-reentry increased, and (5) the exposure of the structural circuit to the surrounding tissue decreased. Likelihood of organized tachycardia following termination of fibrillation increased with (6) decreasing distance and (7) disparity of size between focal obstacle and external boundary. CONCLUSION: Focal drivers such as structural micro-reentry and the chaotic activation they produce are continuously interacting with one another. In order to accurately describe cardiac tissue's propensity to support fibrillation, the relative characteristics of both stationary and moving drivers must be taken into account.

Atmospheric Deposition of Coal-Related Pollutants in the Pacific Northwest of the United States from 1950 to 2016.

Coal-related elements are toxic and persistent pollutants that have spread globally since the industrial revolution, mainly from point-source emissions. A sediment core was collected from Deep Lake in northeastern Washington State (USA) by the Washington State Department of Ecology, with the aim of assessing recent changes in atmospheric deposition in the US Pacific Northwest. The core was divided into depth intervals and dated by lead-210. A sample from each cross section was digested and analyzed for toxic metals and metalloids using inductively coupled plasma-mass spectrometry. Data show recent increases in the concentrations of arsenic, barium, selenium, and mercury. Comparison with 1993 US Geological Survey ice core data from the Upper Fremont Glacier in Wyoming (USA), Asian coal consumption data, and weather patterns suggests that pollutant inputs to Deep Lake sediments are the result of coal-burning activities in the Asia-Pacific region. Most notably, mercury deposition in Deep Lake has increased from approximately 20 ppb in 1996 to 9470 ppb in 2014 (an ~400-fold increase), and since 1993 when the ice core was analyzed. Environ Toxicol Chem 2020;39:335-342. © 2019 SETAC.

Prospective, Tissue-Specific Optimization of Ablation for Multiwavelet Reentry: Predicting the Required Amount, Location, and Configuration of Lesions.

BACKGROUND: Treatment of multiwavelet reentry (MWR) remains difficult. We previously developed a metric, the fibrillogenicity index, to assess the propensity of homogeneous, 2-dimensional tissues to support MWR. In this study, we demonstrate a method by which fibrillogenicity index can be generalized to heterogeneous tissues and validate an algorithm for prospective, tissue-specific optimization of ablation to reduce MWR burden. METHODS AND RESULTS: We used a computational model to simulate and measure the duration of MWR in tissues with heterogeneously distributed action potential durations and then assessed the relative efficacy of a variety of ablation strategies for reducing tissues' ability to support MWR. We then derived and tested a strategy in which multiple linear lesions partially divided a fibrillogenic tissue into functionally equivalent subsections. The composite action potential duration of heterogeneous tissue was well approximated by an inverse sum of cellular action potential durations (R(2)=0.82). Linear ablation more efficiently reduced MWR duration than branching ablation patterns and optimally reduced disease burden when positioned at a tissue's functional (rather than geometric) center. The duration of MWR after application of prospective, individually optimized ablation sets fell within 4.4% (95% confidence interval, 3-5.8) of the predicted target. CONCLUSIONS: We think that this study presents a novel approach for (1) quantifying the extent of a tissue's electric derangement, (2) prospectively determining the amount of ablation required to minimize the burden of MWR, and (3) predicting the most efficient distribution of these ablation lesions in tissue refractory to standard ablation strategies.

Prospectively quantifying the propensity for atrial fibrillation: a mechanistic formulation.

The goal of this study was to determine quantitative relationships between electrophysiologic parameters and the propensity of cardiac tissue to undergo atrial fibrillation. We used a computational model to simulate episodes of fibrillation, which we then characterized in terms of both their duration and the population dynamics of the electrical waves which drove them. Monte Carlo sampling revealed that episode durations followed an exponential decay distribution and wave population sizes followed a normal distribution. Half-lives of reentrant episodes increased exponentially with either increasing tissue area to boundary length ratio (A/BL) or decreasing action potential duration (APD), resistance (R) or capacitance (C). We found that the qualitative form of fibrillatory activity (e.g., multi-wavelet reentry (MWR) vs. rotors) was dependent on the ratio of resistance and capacitance to APD; MWR was reliably produced below a ratio of 0.18. We found that a composite of these electrophysiologic parameters, which we term the fibrillogenicity index (Fb = A/(BL*APD*R*C)), reliably predicted the duration of MWR episodes (r2 = 0.93). Given that some of the quantities comprising Fb are amenable to manipulation (via either pharmacologic treatment or catheter ablation), these findings provide a theoretical basis for the development of titrated therapies of atrial fibrillation.

Mapping multi-wavelet reentry without isochrones: an electrogram-guided approach to define substrate distribution.

AIMS: A key mechanism responsible for atrial fibrillation is multi-wavelet reentry (MWR). We have previously demonstrated that ablation in regions of increased circuit density reduces the duration of, and decreases the inducibility of MWR. In this study, we demonstrate a method for identifying local circuit density using electrogram frequency and validated its effectiveness for map-guided ablation in a computer model of MWR. METHODS AND RESULTS: We simulated MWR in tissues with variation of action potential duration and intercellular resistance. Electrograms were calculated using various electrode sizes and configurations. We measured and compared the number of circuits to the tissue activation frequency and electrogram frequency using three recording configurations [unipolar, contact bipolar, orthogonal closed unipolar (OCU)] and two frequency measurements (dominant frequency, centroid frequency). We then used the highest resolution electrogram frequency map (OCU centroid frequency) to guide the placement of lesions to high frequency regions. Map-guided ablation was compared with no ablation and random/blind ablation lesions of equal length. Electrogram frequency correlated with tissue frequency and circuit density as a function of electrode spatial resolution. Map-guided ablation resulted in a significant reduction in MWR duration (142 ± 174 vs. 41 ± 63 s). CONCLUSION: Electrogram frequency correlates with circuit density in MWR provided electrodes have high spatial resolution. Map-guided ablation is superior to no ablation and to blind/random ablation.

Improved spatial resolution and electrogram wave direction independence with the use of an orthogonal electrode configuration.

To improve spatial resolution in recordings of intra-cardiac electrograms we characterized the utility of a novel configuration of two recording electrodes arranged perpendicularly to the endocardial surface. We hypothesized that this configuration denoted as orthogonal close unipolar (OCU) would combine advantages of conventional unipolar and contact bipolar (CBP) configurations. Electrical excitation was simulated in a computational model as arising from dipole current or from multi-wavelet reentry sources. Recordings were calculated for electrode tips 1 mm above the plane of the heart. Analogous recordings were obtained from swine hearts. Electrograms recorded with CBP showed strong dependence on orientation of the electrode pair with respect to the direction of spread of tissue excitation. By contrast, OCU recordings exhibited no directional dependence. OCU was significantly superior to CBP with respect to avoidance of far-field confounding of local tissue activity; the average far-field/near-field ratios for CBP and OCU were 0.09 and 0.05, respectively, for the simulated dipole current sources. In the swine hearts the ratios of ventricular to atrial signals for CBP and OCU were 0.15 ± 0.07 and 0.08 ± 0.09, respectively (p < 0.001). The difference between the actual dominant frequency in the tissue and that recorded by the electrodes was 0.44 ± 0.33 Hz for OCU, 0.58 ± 0.40 Hz for unipolar, and 0.62 ± 0.46 Hz for CBP. OCU confers improved spatial resolution compared with both unipolar and CBP electrode configurations. Unlike the case with CBP, OCU recordings are independent of excitation wave-front direction.

Ablation of multiwavelet re-entry guided by circuit-density and distribution: maximizing the probability of circuit annihilation.

BACKGROUND: A key mechanism responsible for atrial fibrillation is multiwavelet re-entry (MWR). We have previously demonstrated improved efficiency of ablation when lesions were placed in regions of high circuit-density. In this study, we undertook a quantitative assessment of the relative effect of ablation on the probability of MWR termination and the inducibility of MWR, as a function of lesion length and circuit-density overlap. METHODS AND RESULTS: We used a computational model to simulate MWR in tissues with (and without) localized regions of decreased action potential duration and increased intercellular resistance. We measured baseline circuit-density and distribution. We then assessed the effect of various ablation lesion sets on the inducibility and duration of MWR as a function of ablation lesion length and overlap with circuit-density. Higher circuit-density reproducibly localized to regions of shorter wavelength. Ablation lines with high circuit-density overlap showed maximum decreases in duration of MWR at lengths equal to the distance from the tissue boundary to the far side of the high circuit-density region (high-overlap, -43.5% [confidence interval, -22.0% to -65.1%] versus low-overlap, -4.4% [confidence interval, 7.3% to -16.0%]). Further ablation (beyond the length required to cross the high circuit-density region) provided minimal further reductions in duration and increased inducibility. CONCLUSIONS: Ablation at sites of high circuit-density most efficiently decreased re-entrant duration while minimally increasing inducibility. Ablation lines delivered at sites of low circuit-density minimally decreased duration yet increased inducibility of MWR.

Ablation of multi-wavelet re-entry: general principles and in silico analyses.

AIMS: Catheter ablation strategies for treatment of cardiac arrhythmias are quite successful when targeting spatially constrained substrates. Complex, dynamic, and spatially varying substrates, however, pose a significant challenge for ablation, which delivers spatially fixed lesions. We describe tissue excitation using concepts of surface topology which provides a framework for addressing this challenge. The aim of this study was to test the efficacy of mechanism-based ablation strategies in the setting of complex dynamic substrates. METHODS AND RESULTS: We used a computational model of propagation through electrically excitable tissue to test the effects of ablation on excitation patterns of progressively greater complexity, from fixed rotors to multi-wavelet re-entry. Our results indicate that (i) focal ablation at a spiral-wave core does not result in termination; (ii) termination requires linear lesions from the tissue edge to the spiral-wave core; (iii) meandering spiral-waves terminate upon collision with a boundary (linear lesion or tissue edge); (iv) the probability of terminating multi-wavelet re-entry is proportional to the ratio of total boundary length to tissue area; (v) the efficacy of linear lesions varies directly with the regional density of spiral-waves. CONCLUSION: We establish a theoretical framework for re-entrant arrhythmias that explains the requirements for their successful treatment. We demonstrate the inadequacy of focal ablation for spatially fixed spiral-waves. Mechanistically guided principles for ablating multi-wavelet re-entry are provided. The potential to capitalize upon regional heterogeneity of spiral-wave density for improved ablation efficacy is described.