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International IEEE/EMBS Conference on... May 2021Validation of neural probe performance often includes implantation in live animals, to assess ability to detect and distinguish signals generated by individual neurons....
Validation of neural probe performance often includes implantation in live animals, to assess ability to detect and distinguish signals generated by individual neurons. While this method is informative, an effective alternative would streamline device development and improve ethical considerations by reducing the use of animals in the validation of neural recording devices. Here, we describe a simple system using ball electrodes to apply multiple neural waveforms to phosphate buffered saline, which are simultaneously recorded by a microelectrode probe. Using this technique, our neural probe was able to detect and distinguish spikes from multiple units of roughly physiological amplitudes (~100 microvolts peak to peak), indicating promise as an alternative to animal testing for initial validation of neural recording devices.
PubMed: 34917236
DOI: 10.1109/ner49283.2021.9441208 -
Journal of the American Heart... Dec 2021Background Unlike T-wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic...
Background Unlike T-wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM. Methods and Results Prospectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter-defibrillators underwent digital 12-lead ECG recordings during ventricular pacing (100-120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter-defibrillator therapy over 5 years of follow-up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; =0.006). Left ventricular thickness was greater in QRSA+ than in QRSA- patients (22±7 versus 20±6 mm; =0.035). Over 5 years follow-up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA- patients (5.8% versus 2.0%; =0.006), with the QRSA+/TWA- subgroup having the greatest rate (13.3% versus 2.6%; <0.001). In those with <2 risk factors, QRSA- patients had a low annual VA rate compared QRSA+ patients (0.58% versus 7.1%; =0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2-7.0]; =0.019) and QRSA+/TWA- (HR, 7.9 [95% CI, 2.9-21.7]; <0.001) as the most significant VA predictors. TWA and HCM risk factors did not predict VA. Conclusions In HCM, microvolt QRSA is a novel, rate-dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3-fold in all patients, whereas the absence of QRSA confers low VA risk in patients with <2 risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02560844.
Topics: Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Humans; Risk Factors
PubMed: 34854315
DOI: 10.1161/JAHA.121.022036 -
Sovremennye Tekhnologii V Meditsine 2021was to develop an ECG hardware and software system for monitoring electrical instability of the myocardium and to assess the diagnostic and prognostic capabilities of...
UNLABELLED
was to develop an ECG hardware and software system for monitoring electrical instability of the myocardium and to assess the diagnostic and prognostic capabilities of this setup in a cardiology clinic.
MATERIALS AND METHODS
The Intecard 7.3 software and hardware system developed in this study makes it possible to measure fluctuations of the ECG amplitude-time parameters using the beat-to-beat mode. Intecard 7.3 evaluates a number of ECG markers that reflect electrical instability of the myocardium. Among them are the fragmented QRS complex, the spatial QRS-T angle, the T-wave alternans, the duration, and dispersion of the QT interval, the turbulence and acceleration/deceleration of the heart rhythm.Clinical trials of Intecard 7.3 were carried out with 734 patients with ischemic heart disease or cardiomyopathy and 112 healthy individuals.
RESULTS
Intecard 7.3 reliably identifies fragmented QRS complexes by detecting short spikes of <25 ms in the ascending parts of the Q, R, and S waves. The QRS-T angle is determined from the reference amplitudes of the R and T waves in leads avF, V, V, and V. Digital precision processing of the ECG signal improves its accuracy to microvolts and microseconds.The software was designed to measure the T-wave amplitude in each of 300-500 cardiobeats; T-wave alternans was estimated by the moving average method. In a typical cardiobeat, the QT dispersion was calculated based on 12 ECG leads. From the sequence of RR intervals, turbulence, and deceleration of the heart rhythm were determined.During the observation period of 5.0 [2.1; 5.9] years, 90 out of 734 patients (12.3%) experienced adverse cardiovascular events (ACVE). In this period, the myocardial electrical instability was recorded in patients with ACVE more frequently than in those without ACVE. Thus, the frequency of fragmented QRS was 72.2±4.7 vs 16.8±1.5% (p<0.01), the values of the QRS-T angle were 128 [55; 101] vs 80 [53; 121]° (p<0.001), the T-wave alternans - 36.9 [15.5; 62.1] vs 21.9 [10.2; 30.7] μV (p<0.005), the QT interval - 408 [383; 438] vs 376 [351; 400] ms (p<0.001), the QT dispersion - 76 [57; 96] vs 64 [50; 92] ms (p<0.005), respectively. In patients with ACVE, the threshold that triggers pathological rhythm turbulence was higher (>0%) than that in healthy controls (p<0.001); the deceleration of the heart rhythm was reduced from 19.2 [2.2; 38.0] to 8.8 [4.0; 16.8] ms (p<0.05).A personalized model for ACVE risk stratification has been developed. In this model, the area under the ROC curve was 0.856; sensitivity - 75%; specificity - 78%; predictive accuracy - 77%.
CONCLUSION
Using the ECG markers of myocardial electrical instability, the Intecard 7.3 system allows one to predict life-threatening ventricular tachyarrhythmias and sudden cardiac death with an accuracy of 77%. The non-invasiveness, high productivity, and reasonable cost ensure the availability of this predictive technology in all levels of healthcare.
Topics: Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography; Humans; Myocardium; Tachycardia, Ventricular
PubMed: 34796014
DOI: 10.17691/stm2020.12.6.02 -
Hearing Research Sep 2022In the cochlea, mechano-electrical transduction is preceded by dynamic range compression. Outer hair cells (OHCs) and their voltage dependent length changes, known as... (Review)
Review
In the cochlea, mechano-electrical transduction is preceded by dynamic range compression. Outer hair cells (OHCs) and their voltage dependent length changes, known as electromotility, play a central role in this compression process, but the exact mechanisms are poorly understood. Here we review old and new experimental findings and show that (1) just audible high-frequency tones evoke an ∼1-microvolt AC receptor potential in basal OHCs; (2) any mechanical amplification of soft high-frequency tones by OHC motility would have an adverse effect on their audibility; (3) having a higher basolateral K+ conductance, while increasing the OHC corner frequency, does not boost the magnitude of the high-frequency AC receptor potential; (4) OHC receptor currents display a substantial rectified (DC) component; (5) mechanical DC responses (baseline shifts) to acoustic stimuli, while insignificant on the basilar membrane, can be comparable in magnitude to AC responses when recorded in the organ of Corti, both in the apex and the base. In the basal turn, the DC component may even exceed the AC component, lending support to Dallos' suggestion that both apical and basal OHCs display a significant degree of rectification. We further show that (6) low-intensity cochlear traveling waves, by virtue of their abrupt transition from fast to slow propagation, are well suited to transport high-frequency energy with minimal losses (∼2-dB loss for 16-kHz tones in the gerbil); (7) a 90-dB, 16-kHz tone, if transmitted without loss to its tonotopic place, would evoke a destructive displacement amplitude of 564 nm. We interpret these findings in a framework in which local dissipation is regulated by OHC motility. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.
Topics: Acoustic Stimulation; Basilar Membrane; Cochlea; Hair Cells, Auditory, Outer; Hair Cells, Vestibular
PubMed: 34686384
DOI: 10.1016/j.heares.2021.108367 -
Otolaryngology--head and Neck Surgery :... Aug 2022Electrocochleography (ECochG) is increasingly being used during cochlear implant (CI) surgery to detect and mitigate insertion-related intracochlear trauma, where a drop...
OBJECTIVE
Electrocochleography (ECochG) is increasingly being used during cochlear implant (CI) surgery to detect and mitigate insertion-related intracochlear trauma, where a drop in ECochG signal has been shown to correlate with a decline in hearing outcomes. In this study, an ECochG-guided robotics-assisted CI insertion system was developed and characterized that provides controlled and consistent electrode array insertions while monitoring and adapting to real-time ECochG signals.
STUDY DESIGN
Experimental research.
SETTING
A research laboratory and animal testing facility.
METHODS
A proof-of-concept benchtop study evaluated the ability of the system to detect simulated ECochG signal changes and robotically adapt the insertion. Additionally, the ECochG-guided insertion system was evaluated in a pilot in vivo sheep study to characterize the signal-to-noise ratio and amplitude of ECochG recordings during robotics-assisted insertions. The system comprises an electrode array insertion drive unit, an extracochlear recording electrode module, and a control console that interfaces with both components and the surgeon.
RESULTS
The system exhibited a microvolt signal resolution and a response time <100 milliseconds after signal change detection, indicating that the system can detect changes and respond faster than a human. Additionally, animal results demonstrated that the system was capable of recording ECochG signals with a high signal-to-noise ratio and sufficient amplitude.
CONCLUSION
An ECochG-guided robotics-assisted CI insertion system can detect real-time drops in ECochG signals during electrode array insertions and immediately alter the insertion motion. The system may provide a surgeon the means to monitor and reduce CI insertion-related trauma beyond manual insertion techniques for improved CI hearing outcomes.
Topics: Animals; Audiometry, Evoked Response; Cochlea; Cochlear Implantation; Cochlear Implants; Craniocerebral Trauma; Hearing; Humans; Labyrinth Diseases; Sheep
PubMed: 34609909
DOI: 10.1177/01945998211049210 -
International Archives of... Jul 2021Mismatch negativity (MMN) is a promising instrument for the investigation of different auditory disorders, as it does not need behavioral responses. To analyze...
Mismatch negativity (MMN) is a promising instrument for the investigation of different auditory disorders, as it does not need behavioral responses. To analyze the influence of the ear, gender and age variables in the MMN in children with typical development; and to compare the different measures of this potential, using verbal and nonverbal stimuli in the sample studied, providing reference values. Observational, descriptive, cross-sectional, quantitative study, with 23 children, aged from 5 to 11 years and 11 months old, divided by age group. Mismatch negativity was performed using verbal and nonverbal stimuli, and the data was analyzed by means of the statistical Student -test. No significant differences were noted for the ear, gender and age variables in the MMN with both stimuli. There were significant differences for the latency, duration and area variables when the stimuli were compared. The reference values established for nonverbal stimuli were: latency 249.8 milliseconds, amplitude 2.28 µv, duration 82.97 milliseconds, and area 137.3 microvolt x microseconds (μVx μs); as for the verbal stimuli, they were: latency 265.3 milliseconds, amplitude - 2.82 µv, duration 110.5 milliseconds, and area 225.5 microvolt x microseconds (μVx μs). The variables studied did not influence the recordings of the MMN. Latency, duration and area of the MMN with verbal stimuli were higher. It was possible to furnish reference values for children with typical development in the age group studied.
PubMed: 34377175
DOI: 10.1055/s-0040-1713590 -
Frontiers in Physiology 2021Microvolt T-wave alternans (TWA), an oscillation in T-wave morphology of the electrocardiogram (ECG), has been associated with increased susceptibility to ventricular...
Microvolt T-wave alternans (TWA), an oscillation in T-wave morphology of the electrocardiogram (ECG), has been associated with increased susceptibility to ventricular tachy-arrhythmias, while vagus nerve stimulation has shown promising anti-arrhythmic effects in and animal studies. We aimed to examine the effect of non-invasive, acute low-level tragus stimulation (LLTS) on TWA in patients with ischemic cardiomyopathy and heart failure. 26 patients with ischemic cardiomyopathy (left ventricular ejection fraction <35%) and chronic stable heart failure, previously implanted with an automatic implantable cardioverter defibrillator (ICD) device with an atrial lead (dual chamber ICD or cardiac resynchronization therapy defibrillator), were enrolled in the study. Each patient sequentially received, (1) Sham LLTS (electrode on tragus, but no stimulation delivered) for 5 min; (2) Active LLTS at two different frequencies (5 and 20 Hz, 15 min each); and (3) Active LLTS, during concomitant atrial pacing at 100 bpm at two different frequencies (5 and 20 Hz, 15 min each). LLTS was delivered through a transcutaneous electrical nerve stimulation device (pulse width 200 μs, frequency 5/20 Hz, amplitude 1 mA lower than the discomfort threshold). TWA burden was assessed using continuous ECG monitoring during sham and active LLTS in sinus rhythm, as well as during atrial pacing. Right atrial pacing at 100 bpm led to significantly heightened TWA burden compared to sinus rhythm, with or without LLTS. Acute LLTS at both 5 and 20 Hz, during sinus rhythm led to a significant rise in TWA burden in the precordial leads ( < 0.05). Acute LLTS results in a heart-rate dependent increase in TWA burden.
PubMed: 34366894
DOI: 10.3389/fphys.2021.707724 -
International Journal of Molecular... May 2021Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and... (Review)
Review
Non-ischemic dilated cardiomyopathy encompasses a wide spectrum of myocardial disorders, characterized by left ventricular dilatation with systolic impairment and increased risk of sudden cardiac death. In spite of all the therapeutic progress that has been made in recent years, dilated cardiomyopathy continues to be an important cause of cardiac transplant, being associated with an enormous cost burden for health care systems worldwide. Predicting the prognosis of patients with dilated cardiomyopathy is essential to individualize treatment. Late gadolinium enhancement-cardiac magnetic resonance imaging, microvolt T-wave alternans, and genetic testing have emerged as powerful tools in predicting sudden cardiac death occurrence and maximizing patient's selection. Despite all these new diagnostic modalities, additional tests to complement or replace current tools are required for better risk stratification. Therefore, biomarkers are an easy and important tool that can help to detect patients at risk of adverse cardiovascular events. Additionally, identifying potential biomarkers involved in dilated cardiomyopathy can provide us important information regarding the diagnostic, prognostic, risk stratification, and response to treatment for these patients. Many potential biomarkers have been studied in patients with dilated cardiomyopathy, but only a few have been adopted in current practice. Therefore, the aim of our review is to provide the clinicians with an update on the well-known and novel biomarkers that can be useful for risk stratification of patients with non-ischemic dilated cardiomyopathy.
Topics: Biomarkers; Cardiomyopathy, Dilated; Contrast Media; Gadolinium; Humans; Magnetic Resonance Imaging; Risk Assessment
PubMed: 34073616
DOI: 10.3390/ijms22115688 -
Journal of Arrhythmia Apr 2021Early detection of cardiac involvement in patients with sarcoidosis is important but currently unresolved. The aim of this study was to elucidate the utility of...
BACKGROUND
Early detection of cardiac involvement in patients with sarcoidosis is important but currently unresolved. The aim of this study was to elucidate the utility of frequency domain microvolt T-wave alternans (TWA), signal-averaged ECG (SAECG), and heart rate turbulence (HRT) using 24-hour Holter ECG for detecting cardiac involvement in patients with pulmonary sarcoidosis.
METHODS
This study consisted of consecutive 40 pulmonary sarcoidosis patients (11 males, 62 ± 13 years) who underwent 24-hour Holter monitoring with and without cardiac involvement. All patients underwent frequency domain TWA, SAECG, and HRT using 24-hour Holter monitoring. Patients with atrial fibrillation pacing or wide QRS electrocardiogram were excluded.
RESULTS
After 14 patients were excluded, a total of 26 patients (six males, 59 ± 14 years) were evaluated. Seven patients had cardiac involvement (cardiac sarcoidosis [CS] group). On the Holter SAECG, duration of low-amplitude signals <40 μV in the terminal filtered QRS complex (LAS40) was significantly higher, and root mean square voltage of the terminal 40 ms of the filtered QRS complex (RMS40) was significantly lower in the CS group compared with the non-CS group (LAS40: 61.4 ± 35.9 vs 37.6 ± 9.2 ms; = .018, RMS40: 11.4 ± 10.3 vs 23.6 ± 13.2 ms; = .023). Prevalence of positive late potential (LP) was also significantly higher in the CS group than that in the non-CS group (85.7% vs 31.5%; = .026). The sensitivity, specificity, positive, and negative predictive values of LP for identifying patients with cardiac involvement were 85.7%, 68.4%, 50.0%, and 92.8%, respectively.
CONCLUSION
Holter SAECG may be useful for detecting cardiac involvement in patients with pulmonary sarcoidosis.
PubMed: 33850586
DOI: 10.1002/joa3.12501 -
Science Advances Mar 2021The transverse voltage generated by a temperature gradient in a perpendicularly applied magnetic field, termed the Nernst effect, has promise for thermoelectric...
The transverse voltage generated by a temperature gradient in a perpendicularly applied magnetic field, termed the Nernst effect, has promise for thermoelectric applications and for probing electronic structure. In magnetic materials, an anomalous Nernst effect (ANE) is possible in a zero magnetic field. We report a colossal ANE in the ferromagnetic metal UCoRuAl, reaching 23 microvolts per kelvin. Uranium's 5 electrons provide strong electronic correlations that lead to narrow bands, a known route to producing a large thermoelectric response. In addition, uranium's strong spin-orbit coupling produces an intrinsic transverse response in this material due to the Berry curvature associated with the relativistic electronic structure. Theoretical calculations show that in UCoRuAl at least 148 Weyl nodes, and two nodal lines, exist within 60 millielectron volt of the Fermi level. This work demonstrates that magnetic actinide materials can host strong Nernst and Hall responses due to their combined correlated and topological nature.
PubMed: 33771869
DOI: 10.1126/sciadv.abf1467