Novel algorithms improve arrhythmia detection accuracy in insertable cardiac monitors.

INTRODUCTION: Insertable cardiac monitors (ICMs) are commonly used to diagnose cardiac arrhythmias. False detections in the latest ICM systems remain an issue, primarily due to inaccurate R-wave sensing. New discrimination algorithms were developed and tested to reduce false detections of atrial fibrillation (AF), pause, and tachycardia episodes in ICMs. METHODS: Stored electrograms (EGMs) of AF, pause, and tachycardia episodes detected by Abbott Confirm Rx™ ICMs were extracted from the Merlin.net™ Patient Care Network, and manually adjudicated to establish independent training and testing datasets. New discrimination algorithms were developed to reject false episodes due to inaccurate R-wave sensing, P-wave identification, and R-R interval patterns. The performance of these new algorithms was quantified by false positive reduction (FPR) and true positive maintenance (TPM), relative to the existing algorithms. RESULTS: The new AF detection algorithm was trained on 5911 EGMs from 744 devices, resulting in 66.9% FPR and 97.8% TPM. In the testing data set of 1354 EGMs from 119 devices, this algorithm achieved 45.8% FPR and 97.0% TPM. The new pause algorithm was trained on 7178 EGMs from 1490 devices, resulting in 70.9% FPR and 98.7% TPM. In the testing data set of 1442 EGMs from 340 devices, this algorithm achieved 74.4% FPR and 99.3% TPM. The new tachycardia algorithm was trained on 520 EGMs from 204 devices, resulting in 57.0% FPR and 96.6% TPM. In the testing data set of 459 EGMs from 237 devices, this algorithm achieved 57.9% FPR and 96.5% TPM. CONCLUSION: The new algorithms substantially reduced false AF, pause, and tachycardia episodes while maintaining the majority of true arrhythmia episodes detected by the Abbott ICM algorithms that exist today. Implementing these algorithms in the next-generation ICM systems may lead to improved detection accuracy, in-clinic efficiency, and device battery longevity.

Reducing the electrogram review burden imposed by insertable cardiac monitors.

BACKGROUND: Insertable cardiac monitors (ICMs) are essential for ambulatory arrhythmia diagnosis. However, definitive diagnoses still require time-consuming, manual adjudication of electrograms (EGMs). OBJECTIVE: To evaluate the clinical impact of selecting only key EGMs for review. METHODS: Retrospective analyses of randomly selected Abbott Confirm Rx™ devices with ≥90 days of remote transmission history were performed, with each EGM adjudicated as true or false positive (TP, FP). For each device, up to 3 "key EGMs" per arrhythmia type per day were prioritized for review based on ventricular rate and episode duration. The reduction in EGMs and TP days (patient-days with at least one TP EGM), and any diagnostic delay (from the first TP), were calculated versus reviewing all EGMs. RESULTS: In 1000 ICMs over a median duration of 8.1 months, at least one atrial fibrillation (AF), tachycardia, bradycardia, or pause EGM was transmitted by 424, 343, 190, and 325 devices, respectively, with a total of 95 716 EGMs. Approximately 90% of episodes were contributed by 25% of patients. Key EGM selection reduced EGM review burden by 43%, 66%, 77%, and 50% (55% overall), while reducing TP days by 0.8%, 2.1%, 0.2%, and 0.0%, respectively. Despite reviewing fewer EGMs, 99% of devices with a TP EGM were ultimately diagnosed on the same day versus reviewing all EGMs. CONCLUSION: Key EGM selection reduced the EGM review substantially with no delay-to-diagnosis in 99% of patients exhibiting true arrhythmias. Implementing these rules in the Abbott patient care network may accelerate clinical workflow without compromising diagnostic timelines.

Effectiveness of SharpSense™ algorithms in reducing bradycardia and pause detection: real-world performance in Confirm Rx™ insertable cardiac monitor.

PURPOSE: SharpSense™ technology is an upgradable software enhancement introduced to the Abbott Confirm Rx™ insertable cardiac monitor (ICM). This study aims to characterize the real-world performance of SharpSense algorithms by comparing device detected pause and bradycardia episodes before and after the SharpSense upgrade. METHODS: Confirm Rx devices with at least 90 days monitoring each before and after SharpSense upgrade were included in the study. Bradycardia and pause detections and subcutaneous electrocardiograms (SECGs) within 90 days before and after the upgrade were extracted from Merlin.net™ patient care network for evaluation and adjudicated by expert adjudicators. RESULTS: A total of 197 devices were included in the analysis. Devices were implanted for syncope (35.0%), atrial fibrillation (32.5%), cryptogenic stroke (16.8%), and other indications including palpitations (15.7%). The SharpSense upgrade significantly reduced the number of bradycardia detections by 86.8% and pause detections by 93.1%. In adjudicated SECGs, the upgrade significantly reduced false positive (FP) bradycardia episodes by 91.5% and FP pause episodes by 82.8%. The percentage of devices with at least one FP episode was reduced from 39 to 20% for bradycardia and from 52 to 35% for pause. The number of devices with FP rate greater than 1 episode per week was reduced from 23 to 8% for bradycardia and from 39 to 20% for pause. CONCLUSIONS: In this real-world performance evaluation, the algorithms incorporated in SharpSense software upgrade in Confirm Rx ICMs substantially reduced false positive bradycardia and pause detections and the number of transmitted SECGs for clinic review.

Long-term reverse remodeling by cardiac resynchronization therapy with MultiPoint Pacing: A feasibility study of noninvasive hemodynamics-guided device programming.

BACKGROUND: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint Pacing [MPP]) improves acute hemodynamics and chronic outcomes in comparison to conventional biventricular pacing (BiV), though MPP programming questions persist. OBJECTIVES: In this multicenter feasibility study, we evaluated the feasibility of using noninvasive systolic blood pressure (SBP) to guide MPP programming and assessed the chronic 6-month echocardiographic CRT response. METHODS: Patients implanted with MPP-enabled CRT-defibrillator devices underwent noninvasive hemodynamic assessment (finger arterial pressure) during a pacing protocol that included atrial-only pacing and various BiV and MPP configurations. Each configuration was repeated 4 times, alternating with a reference pacing configuration, to calculate the SBP difference relative to reference (ΔSBP). CRT configurations with the greatest ΔSBP were programmed. An independent core laboratory analyzed baseline and 6-month echocardiograms, with CRT response defined as a 6-month reduction in LV end-systolic volume ≥ 15%. RESULTS: Forty-two patients (71% male; LV ejection fraction 30.3% ± 7.5%; QRS duration 161 ± 19 ms; 26% had ischemic cardiomyopathy) were enrolled in 4 European centers. Relative to atrial-only pacing, the best BiV and best MPP configurations produced significant SBP elevations of 3.1 ± 4.2 (P < .01) and 4.1 ± 4.1 mm Hg (P < .01), respectively (BiV vs MPP; P < .01). Greater SBP elevations were associated with the best MPP compared with the best BiV configurations in 29 of 37 patients completing the pacing protocol (78%). Of MPP-programmed patients completing the 6-month follow-up visit, 23 of 27 (85%) were classified as CRT responders (6-month reduction in LV end-systolic volume 37.0% ± 13.6%). CONCLUSION: Acute noninvasive hemodynamics after CRT device implantation predominantly favored MPP over BiV programming. MPP programming guided by noninvasive hemodynamics resulted in positive LV structural remodeling.

Predictive value of unipolar and bipolar electrograms in idiopathic outflow tract ventricular arrhythmia mapping and ablation.

INTRODUCTION: Radiofrequency catheter ablation is an effective therapy for focal idiopathic outflow tract ventricular arrhythmia (OTVA). However, visual inspection of the unipolar electrogram (EGM) QS morphology is subjective with a poor specificity for predicting successful ablation sites. This study aims to evaluate the predictive value of unipolar and bipolar EGMs in OTVA mapping and ablation. METHODS AND RESULTS: Twenty-two patients scheduled for idiopathic OTVA ablation were prospectively enrolled. During the procedure, unipolar and bipolar EGMs were recorded simultaneously and visually inspected by the operator to identify their values for predicting arrhythmogenic sites. Quantitative features of the unipolar EGM including the ratio of amplitude of the first positive peak versus the nadir (R-ratio), the maximum descending slope (MaxSlope), and the time interval between the initial deflection point to the MaxSlope (D-Max) were calculated for each target site in offline analysis. EGMs from 100 sites were collected in 20 patients and analyzed. The bipolar reverse polarity characteristic was not as practical for identifying successful ablation site as the unipolar QS characteristic. Successful ablation sites demonstrated smaller R-ratio and shorter D-Max than unsuccessful sites, but no significant difference in MaxSlope. A unipolar EGM-derived quantitative criterion provided significantly better specificity (0.70) than visual inspection (0.37) without compromising on the sensitivity (0.83 vs. 0.89). CONCLUSION: The bipolar reverse polarity characteristic was not a practical method for identifying target in idiopathic OTVA ablation. The unipolar EGM-derived quantitative criteria have better predictive performance than visual inspection of the QS characteristic and are likely to reduce unnecessary ablation sites.

Clinical Implications of Brief Device-Detected Atrial Tachyarrhythmias in a Cardiac Rhythm Management Device Population: Results from the Registry of Atrial Tachycardia and Atrial Fibrillation Episodes.

BACKGROUND: The RATE Registry (Registry of Atrial Tachycardia and Atrial Fibrillation Episodes) is a prospective, outcomes-oriented registry designed to document the prevalence of atrial tachycardia and/or fibrillation (AT/AF) of any duration in patients with pacemakers and implantable cardioverter defibrillators (ICDs) and evaluate associations between rigorously adjudicated AT/AF and predefined clinical events, including stroke. The appropriate clinical response to brief episodes of AT/AF remains unclear. METHODS: Rigorously adjudicated electrogram (EGM) data were correlated with adjudicated clinical events with logistic regression and Cox models. Long episodes of AT/AF were defined as episodes in which the onset and/or offset of AT/AF was not present within a single EGM recording. Short episodes of AT/AF were defined as episodes in which both the onset and offset of AT/AF were present within a single EGM recording. RESULTS: We enrolled 5379 patients with pacemakers (N=3141) or ICDs (N=2238) at 225 US sites (median follow-up 22.9 months). There were 359 deaths. There were 478 hospitalizations among 342 patients for clinical events. We adjudicated 37 531 EGMs; 50% of patients had at least one episode of AT/AF. Patients with clinical events were more likely than those without to have long AT/AF (31.9% vs. 22.1% for pacemaker patients and 28.7% vs. 20.2% for ICD patients; P<0.05 for both groups). Only short episodes of AT/AF were documented in 9% of pacemaker patients and 16% of ICD patients. Patients with clinical events were no more likely than those without to have short AT/AF (5.1% vs. 7.9% for pacemaker patients and 11.5% vs. 10.4% for ICD patients; P=0.21 and 0.66, respectively). CONCLUSIONS: In the RATE Registry, rigorously adjudicated short episodes of AT/AF, as defined, were not associated with increased risk of clinical events compared with patients without documented AT/AF. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00837798.

Atrial electrograms improve the accuracy of tachycardia interpretation from ICD and pacemaker recordings: The RATE Registry.

BACKGROUND: Tachycardia diagnoses from implantable device recordings ultimately depend on the analysis of captured electrograms (EGMs). The degree to which atrial EGMs improve tachycardia discrimination, dependent on the level of expertise of the medical professional involved, remains uncertain. OBJECTIVE: The purpose of this article was to determine whether atrial EGM recordings improve tachycardia discrimination and whether this improvement, if any, varies for professionals with different levels of training. METHODS: Expert-adjudicated supraventricular tachycardia (SVT) and ventricular tachycardia (VT) dual-chamber EGMs (DEGMs) from the Registry of Atrial Tachycardia and Atrial Fibrillation Episodes in the Cardiac Rhythm Management Device Population were provided to electrophysiology specialists, electrophysiology fellows (EPF), and nurse practitioners or physician assistants (NPPA). Each participant diagnosed 112 EGM episodes presented in random sequence (61 VTs and 51 SVTs) and independently categorized each as "SVT," "VT," or "uncertain" in 2 stages. First, participants analyzed ventricular EGMs (VEGMs) alone (atrial channel covered). Second, the tracings were randomized and reanalyzed with atrial EGMs exposed. The diagnostic accuracy of VEGMs alone vs DEGMs was assessed for each group. RESULTS: For all 3 groups, diagnostic accuracy improved significantly (>20% for VTs and >15% for SVTs; P < .01 for all) when DEGMs were provided. Electrophysiology specialists diagnosed VTs more accurately than did EPF and NPPA (VEGM: 73.1%±7.6% vs 58.7%±15.5% and 56.1%±14.1%; P < .01; DEGM: 98.0%±2.7% vs 90.8%±16.0% and 80.3%±7.4%; P < .01). EPF diagnosed VTs more accurately than did NPPA only when DEGMs were provided. There was no significant intergroup difference in SVT diagnoses. CONCLUSION: DEGMs are superior to VEGMs alone for tachycardia discrimination at all levels of expertise. The level of training affects diagnostic accuracy with and without atrial EGMs.

Accurate monitoring of intravascular fluid volume: A novel application of intrathoracic impedance measures for the guidance of volume reduction therapy.

BACKGROUND: A significant proportion of patients admitted for acute decompensated heart failure (ADHF) that undergo volume reduction therapy are discharged with unchanged or increased bodyweight suggesting that the endpoints for these therapies are not optimally defined. We aimed to identify vectors that can help monitor changes in intravascular fluid volume, that in turn may more accurately guide volume reduction therapy. METHODS: Data from six different impedance vectors and corresponding changes in intravascular volume derived from changes in hematocrit were obtained from 132 clinical congestion events in 56 unique patients enrolled in a multisite trial of early detection of clinical congestion events (DEFEAT PE). Mixed effects regression models were used to determine the relation between changes in impedance derived from six different vectors and changes in intravascular plasma volume. RESULTS: Changes in impedance were negatively associated with changes in plasma volume. Two vectors, the right atrial ring to left ventricular ring and the left ventricular ring to the right ventricular ring, were most closely associated with changes in intravascular plasma volume. CONCLUSION: Impedance vectors derived from a multivector monitoring system reflect changes in intravascular plasma volume. Two of these vectors most closely track changes in plasma volume and may be used to more accurately guide and optimize volume reduction therapy.

Thoracic impedance measures tissue characteristics in the vicinity of the electrodes, not intervening lung water: implications for heart failure monitoring.

The rationale for intrathoracic impedance (Z) detection of worsening heart failure (HF) presupposes that changes in Z reflect changes in pulmonary congestion, but is confounded by poor specificity in clinical trials. We therefore tested the hypothesis that Z is primarily affected by tissue/water content in proximity to electrodes rather than by lung water distribution between electrodes through the use of a new computational model for deriving the near-field impedance contributions from the various electrodes. Six sheep were implanted with a left atrial pressure (LAP) monitor and a cardiac resynchronization therapy device which measured Z from six vectors comprising of five electrodes. The vector-based Z was modelled as the summation of the near-field impedances of the two electrodes forming the vector. During volume expansion an acute increase in LAP resulted in simultaneous reductions in the near-field impedances of the intra-cardiac electrodes, while the subcutaneous electrode showed several hours of lag (all p<0.001). In contrast, during the simulated formation of device-pocket edema (induced by fluid injection) the near-field impedance of the subcutaneous electrode had an instantaneous response, while the intra-cardiac electrodes had a minimal inconsistent response. This study suggests that the primary contribution to the vector based Z is from the tissue/water in proximity to the individual electrodes. This novel finding may help explain the limited utility of Z for detecting worsening HF.

Analysis of different device-based intrathoracic impedance vectors for detection of heart failure events (from the Detect Fluid Early from Intrathoracic Impedance Monitoring study).

Detect Fluid Early from Intrathoracic Impedance Monitoring (DEFEAT-PE) is a prospective, multicenter study of multiple intrathoracic impedance vectors to detect pulmonary congestion (PC) events. Changes in intrathoracic impedance between the right ventricular (RV) coil and device can (RVcoil→Can) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs (CRT-Ds) are used clinically for the detection of PC events, but other impedance vectors and algorithms have not been studied prospectively. An initial 75-patient study was used to derive optimal impedance vectors to detect PC events, with 2 vector combinations selected for prospective analysis in DEFEAT-PE (ICD vectors: RVring→Can + RVcoil→Can, detection threshold 13 days; CRT-D vectors: left ventricular ring→Can + RVcoil→Can, detection threshold 14 days). Impedance changes were considered true positive if detected <30 days before an adjudicated PC event. One hundred sixty-two patients were enrolled (80 with ICDs and 82 with CRT-Ds), all with ≥1 previous PC event. One hundred forty-four patients provided study data, with 214 patient-years of follow-up and 139 PC events. Sensitivity for PC events of the prespecified algorithms was as follows: ICD: sensitivity 32.3%, false-positive rate 1.28 per patient-year; CRT-D: sensitivity 32.4%, false-positive rate 1.66 per patient-year. An alternative algorithm, ultimately approved by the US Food and Drug Administration (RVring→Can + RVcoil→Can, detection threshold 14 days), resulted in (for all patients) sensitivity of 21.6% and a false-positive rate of 0.9 per patient-year. The CRT-D thoracic impedance vector algorithm selected in the derivation study was not superior to the ICD algorithm RVring→Can + RVcoil→Can when studied prospectively. In conclusion, to achieve an acceptably low false-positive rate, the intrathoracic impedance algorithms studied in DEFEAT-PE resulted in low sensitivity for the prediction of heart failure events.

Feasibility of using multivector impedance to monitor pulmonary congestion in heart failure patients.

PURPOSE: Pulmonary edema (PE) is associated with fluid accumulation in the lungs. Device-based impedance measurements have been used to detect fluid overload prior to hospitalization. However, studies have reported a high false positive rate (FPR). The objective of this study was to develop and test a new multivector impedance-based algorithm that reliably tracks PE clinical events. METHODS: We enrolled patients with implanted CRT-Ds in 23 US centers within 2 weeks of device implant. Six-vector impedance data was collected automatically by the CRT-Ds every 30 min during emergency department visits/hospitalizations and every 2 h at all other times. Detection algorithms for cardiac resynchronization therapy defibrillator (CRT-D) and implantable cardiac defibrillator (ICD) devices were developed using those impedance vectors that would be available in corresponding devices and retrospectively evaluated. RESULTS: There were 75 patients (69 % male), mean age 66 ± 12 years, with a LVEF of 23 ± 6 % and QRS of 149 ± 25 ms. Twenty-one major clinical events occurred over 8.2 ± 2.6 months of follow-up time. CRT-D vector combinations resulted in a sensitivity of 71.4 % (95 % confidence interval 47.8-88.7) and a FPR of 0.56 (0.30-0.94) false positives per patient-year (FPs/pt-yr); ICD vector combinations resulted in a sensitivity of 61.9 % (38.4-81.9) and a FPR of 0.63 (0.36-0.90) FPs/pt-yr. In comparison, the single-vector RVCoil-Can implementation of this algorithm resulted in a sensitivity of 57.1 % (34.0-78.2) and a FPR of 0.74 (0.44-1.12) FPs/pt-yr. CONCLUSIONS: This multivector impedance algorithm was effective in tracking PE clinical events in this patient population. Additional studies are needed to prospectively evaluate the performance of this algorithm in a larger population.

Monitoring of heart failure: comparison of left atrial pressure with intrathoracic impedance and natriuretic peptide measurements in an experimental model of ovine heart failure.

Monitoring of HF (heart failure) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aimed to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may have an impact on the potential for early therapeutic intervention. Six sheep were implanted with a LAP (left atrial pressure) sensor and a CRT-D (cardiac resynchronization therapy defibrillator) capable of monitoring impedance along six lead configuration vectors. An estimate of ALAP (LAP from admittance) was determined by linear regression. HF was induced by rapid ventricular pacing at 180 and 220 bpm (beats/min) for a week each, followed by a third week with daily pacing suspensions for increasing durations (1-5 h). Incremental pacing induced progressively severe HF reflected in increases in LAP (5.9 ± 0.4 to 24.5 ± 1.6 mmHg) and plasma atrial (20 ± 3 to 197 ± 36 pmol/l) and B-type natriuretic peptide (3.7 ± 0.7 to 32.7 ± 5.4 pmol/l) (all P<0.001) levels. All impedance vectors decreased in proportion to HF severity (all P<0.001), with the LVring (left ventricular)-case vector correlating best with LAP (r2=0.63, P<0.001). Natriuretic peptides closely paralleled rapid acute changes in LAP during alterations in pacing (P<0.001), whereas impedance changes were delayed relative to LAP. ALAP exhibited good agreement with LAP. In summary, impedance measured with an LV lead correlates significantly with changes in LAP, but exhibits a delayed response to acute alterations. Natriuretic peptides respond rapidly to acute LAP changes. Direct LAP, impedance and natriuretic peptide measurements all show promise as early indicators of worsening HF. ALAP provides an estimate of LAP that may be clinically useful.

The role of photon scattering in optical signal distortion during arrhythmia and defibrillation.

Optical mapping of arrhythmias and defibrillation provides important insights; however, a limitation of the technique is signal distortion due to photon scattering. The goal of this experimental/simulation study is to investigate the role of three-dimensional photon scattering in optical signal distortion during ventricular tachycardia (VT) and defibrillation. A three-dimensional realistic bidomain rabbit ventricular model was combined with a model of photon transport. Shocks were applied via external electrodes to induce sustained VT, and transmembrane potentials (V(m)) were compared with synthesized optical signals (V(opt)). Fluorescent recordings were conducted in isolated rabbit hearts to validate simulation results. Results demonstrate that shock-induced membrane polarization magnitude is smaller in V(opt) and in experimental signals as compared to V(m). This is due to transduction of potentials from weakly polarized midmyocardium to the epicardium. During shock-induced reentry and in sustained VT, photon scattering, combined with complex wavefront dynamics, results in optical action potentials near a filament exhibiting i), elevated resting potential, ii), reduced amplitude relative to pacing, and iii), dual-humped morphologies. A shift of up to 4 mm in the phase singularity location was observed in V(opt) maps when compared to V(m). This combined experimental/simulation study provides an interpretation of optical recordings during VT and defibrillation.

Three-dimensional panoramic imaging of cardiac arrhythmias in rabbit heart.

Cardiac fluorescent optical imaging provides the unique opportunity to investigate the dynamics of propagating electrical waves during ventricular arrhythmias and the termination of arrhythmias by strong electric shocks. Panoramic imaging systems using charge-coupled device (CCD) cameras as the photodetector have been developed to overcome the inability to monitor electrical activity from the entire cardiac surface. Photodiode arrays (PDAs) are known to have higher temporal resolution and signal quality, but lower spatial resolution compared to CCD cameras. We construct a panoramic imaging system with three PDAs and image Langendorff perfused rabbit hearts (n=18) during normal sinus rhythm, epicardial pacing, and arrhythmias. The recorded spatiotemporal dynamics of electrical activity is texture mapped onto a reconstructed 3-D geometrical heart model specific to each heart studied. The PDA-based system provides sufficient spatial resolution (1.72 mm without interpolation) for the study of wavefront propagation in the rabbit heart. The reconstructed 3-D electrical activity provides us with a powerful tool to investigate the fundamental mechanisms of arrhythmia maintenance and termination.

Direct measurements of membrane time constant during defibrillation strength shocks.

BACKGROUND: Defibrillation shocks impose significant energy demand on implantable cardioverter-defibrillators (ICDs). Several modeling studies have been devoted to optimizing shock parameters, and a large number of these studies treat the heart as a simplified lumped network. The time constant of membrane polarization (tau(m)) is a key variable for such modeling efforts. OBJECTIVE: The purpose of this study was to perform direct measurements of transmembrane potential (V(m)) during defibrillation strength shocks and estimate tau(m) of membrane polarization. METHODS: A portion of the left ventricular epicardial surface of Langendorff-perfused rabbit hearts was stimulated using uniform electric fields produced by two parallel line electrodes. The V(m)s were recorded from di-4-ANEPPS-stained hearts using a multisite optical mapping system. The hearts were paced with 20 S1 pulses from the apex, and shocks (S2: 5, 10, 20 V/cm) were applied via the line electrodes during the action potential of the 20th S1 at two different coupling intervals (S1S2: 120 and 180 ms). Residual responses were obtained by subtracting responses to the 19th S1 from the responses to the 20th S1S2 pair and used for time-constant analysis by fitting a monoexponential function. RESULTS: tau(m) exhibited a large variation and ranged from approximately 1 to 30 ms. Furthermore, tau(m) varied with electric field strength, S1S2 interval, position of the tissue from stimulating electrodes, and polarity of the response. To a large extent, the effects of all these factors were captured in a single parameter-the change in transmembrane voltage (DeltaV(m)) in response to the applied field (E). tau(m) showed a monotonically decreasing trend with DeltaV(m) for all Es and S1S2s. CONCLUSION: Time constant of membrane polarization varies significantly during defibrillation strength shocks and shows a strong dependence on DeltaV(m).

Fluorescence imaging for real-time monitoring of high-intensity focused ultrasound cardiac ablation.

Side effects and limitations of radio-frequency ablation of cardiac arrhythmias prompted search for alternative energy sources and means of their application. High-intensity focused ultrasound (HIFU) is becoming an increasingly attractive modality for ablation because of its unique ability for non-invasive or minimally invasive, non-contact focal ablation in 3D volume without affecting intervening and surrounding cells. The purpose of this study is to develop a real-time monitoring technique to elucidate HIFU-induced modifications of electrical conduction in cardiac tissues and to investigate the HIFU cardiac ablation process to help to achieve optimal HIFU ablation outcome. We conducted experimental studies applying HIFU at 4.23 MHz to ablate the atrio-ventricular (AV) node and ventricular tissue of Langendorff-perfused rabbit hearts. We employed fluorescent voltage-sensitive dye imaging and surface electrodes to monitor the electrical conduction activity induced by HIFU application in real time. In ventricular epicardium HIFU ablation, fluorescent imaging revealed gradual reduction of the plateau phase and amplitude of the action potential. Subsequently, conduction block and cell death were observed at the site of ablation. When HIFU was applied to the AV node, fluorescent imaging and electrograms revealed the development of the AV block. The study establishes that real-time fluorescent imaging provides novel monitoring and assessment to study HIFU cardiac ablation, which may be able to provide improved understanding of HIFU cardiac ablation process and mechanism useful for development of successful clinical applications.

The Gurvich waveform has lower defibrillation threshold than the rectilinear waveform and the truncated exponential waveform in the rabbit heart.

Implantable cardioverter defibrillator studies have established the superiority of biphasic waveforms over monophasic waveforms. However, external defibrillator studies of biphasic waveforms are not as widespread. Our objective was to compare the defibrillation efficacy of clinically used biphasic waveforms, i.e., truncated exponential, rectilinear, and quasi-sinusoidal (Gurvich) waveforms in a fibrillating heart model. Langendorff-perfused rabbit hearts (n = 10) were stained with a voltage-sensitive fluorescent dye, Di-4-ANEPPS. Transmembrane action potentials were optically mapped from the anterior epicardium. We found that the Gurvich waveform was significantly superior (p < 0.05) to the rectilinear and truncated exponential waveforms. The defibrillation thresholds (mean +/- SE) were as follows: Gurvich, 0.25 +/- 0.01 J; rectilinear-1, 0.34 +/- 0.01 J; rectilinear-2, 0.33 +/- 0.01 J; and truncated exponential, 0.32 +/- 0.02 J. Using optically recorded transmembrane responses, we determined the shock-response transfer function, which allowed us to predict the cellular response to waveforms at high accuracy. The passive parallel resistor-capacitor model (RC-model) predicted polarization superiority of the Gurvich waveform in the myocardium with a membrane time constant (taum) of less than 2 ms. The finding of a lower defibrillation threshold with the Gurvich waveform in an in vitro model of external defibrillation suggests that the Gurvich waveform may be important for future external defibrillator designs.

Mechanisms of superiority of ascending ramp waveforms: new insights into mechanisms of shock-induced vulnerability and defibrillation.

Monophasic ascending ramp (AR) and descending ramp (DR) waveforms are known to have significantly different defibrillation thresholds. We hypothesized that this difference arises due to differences in mechanisms of arrhythmia induction for the two waveforms. Rabbit hearts (n = 10) were Langendorff perfused, and AR and DR waveforms (7, 20, and 40 ms) were randomly delivered from two line electrodes placed 10 mm apart on the anterior ventricular epicardium. We optically mapped cellular responses to shocks of various strengths (5, 10, and 20 V/cm) and coupling intervals (CIs; 120, 180, and 300 ms). Optical mapping revealed that maximum virtual electrode polarization (VEP) was reached at significantly different times for AR and DR of the same duration (P < 0.05) for all tested CIs. As a result, VEP for AR were stronger than for DR at the end of the shock. Postshock break excitation resulting from AR generated faster propagation and typically could not form reentry. In contrast, partially dissipated VEP resulting from DR generated slower propagation; the wavefront was able to propagate into deexcited tissue and thus formed a shock-induced reentry circuit. Therefore, for the same delivered energy, AR was less proarrhythmic compared with DR. An active bidomain model was used to confirm the electrophysiological results. The VEP hypothesis explains differences in vulnerability associated with monophasic AR and DR waveforms and, by extension, the superior defibrillation efficacy of the AR waveform compared with the DR waveform.