Radiofrequency ablation using a novel insulated-tip ablation catheter can create uniform lesions comparable in size to conventional irrigated ablation catheters while using a fraction of the energy and irrigation.

INTRODUCTION: During radiofrequency ablation (RFA) using conventional RFA catheters (RFC), ~90% of the energy dissipates into the bloodstream/surrounding tissue. We hypothesized that a novel insulated-tip ablation catheter (SMT) capable of blocking the radiofrequency path may focus most of the energy into the targeted tissue while utilizing reduced power and irrigation. METHODS: This study evaluated the outcomes of RFA using SMT versus an RFC in silico, ex vivo, and in vivo. Radiofrequency applications were delivered over porcine myocardium (ex vivo) and porcine thigh muscle preparations superfused with heparinized blood (in vivo). Altogether, 274 radiofrequency applications were delivered using SMT (4-15 W, 2 or 20 ml/min) and 74 applications using RFC (30 W, 30 ml/min). RESULTS: RFA using SMT proved capable of directing 66.8% of the radiofrequency energy into the targeted tissue. Accordingly, low power-low irrigation RFA using SMT (8-12 W, 2 ml/min) yielded lesion sizes comparable with RFC, whereas high power-high irrigation (15 W, 20 ml/min) RFA with SMT yielded lesions larger than RFC (p < .05). Although SMT was associated with greater impedance drops ex vivo and in vivo, ablation using RFC was associated with increased charring/steam pop/tissue cavitation (p < .05). Lastly, lesions created with SMT were more homogeneous than RFC (p < .001). CONCLUSION: Low power-low irrigation (8-12 W, 2 ml/min) RFA using the novel SMT ablation catheter can create more uniform, but comparable-sized lesions as RFC with reduced charring/steam pop/tissue cavitation. High power-high irrigation (15 W, 20 ml/min) RFA with SMT yields lesions larger than RFC.

Use of the inverse solution guidance algorithm method for RF ablation catheter guidance.

INTRODUCTION: We previously introduced the inverse solution guidance algorithm (ISGA) methodology using a Single Equivalent Moving Dipole model of cardiac electrical activity to localize both the exit site of a re-entrant circuit and the tip of a radiofrequency (RF) ablation catheter. The purpose of this study was to investigate the use of ISGA for ablation catheter guidance in an animal model. METHODS: Ventricular tachycardia (VT) was simulated by rapid ventricular pacing at a target site in eleven Yorkshire swine. The ablation target was established using three different techniques: a pacing lead placed into the ventricular wall at the mid-myocardial level (Type-1), an intracardiac mapping catheter (Type-2), and an RF ablation catheter placed at a random position on the endocardial surface (Type-3). In each experiment, one operator placed the catheter/pacing lead at the target location, while another used the ISGA system to manipulate the RF ablation catheter starting from a random ventricular location to locate the target. RESULTS: The average localization error of the RF ablation catheter tip was 0.31 ± 0.08 cm. After analyzing approximately 35 cardiac cycles of simulated VT, the ISGA system's accuracy in locating the target was 0.4 cm after four catheter movements in the Type-1 experiment, 0.48 cm after six movements in the Type-2 experiment, and 0.67 cm after seven movements in the Type-3 experiment. CONCLUSION: We demonstrated the feasibility of using the ISGA method to guide an ablation catheter to the origin of a VT focus by analyzing a few beats of body surface potentials without electro-anatomic mapping.

Comparison of cardiovascular parameter estimation methods using swine data.

In this study, new and existing methods of estimating stroke volume, cardiac output and total peripheral resistance from analysis of the arterial blood pressure waveform were tested over a wide range of conditions. These pulse contour analysis methods (PCMs) were applied to data obtained in six swine during infusion of volume, phenylephrine, dobutamine, isoproterenol, esmolol and nitroglycerine as well as during progressive hemorrhage. Performance of PCMs was compared using true end-ejection pressures as well as estimated end-ejection pressures. There was considerable overlap in the accuracies of the PCMs when using true end-ejection measures. However, for perhaps the most clinically relevant condition, where radial artery pressure is the input, only Wesseling's Corrected Impedance method and the Kouchoukos Correction method achieved statistically superior results. We introduced a method of estimating end-ejection by determining when the systolic pressure dropped to a value equal to the sum of the end-diastolic pressure plus a fraction of the pulse pressure. The most accurate estimation of end-ejection was obtained when that fraction was set to 60% for the central arterial pressure and to 50% for the femoral and radial arterial pressures. When the estimated end-ejection measures were used for the PCMs that depend on end-ejection measures and when radial artery pressure was used as the input, only Wesseling's Corrected Impedance method and the modified Herd's method achieved statistically superior results. This study provides a systematic comparison of multiple PCMs' ability to estimate stroke volume, cardiac output, and total peripheral resistance and introduces a new method of estimating end-systole.

Accuracy of cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm to identify sites of origin of cardiac electrical activation.

We have developed a system that could potentially be used to identify the site of origin of ventricular tachycardia (VT) and to guide a catheter to that site to deliver radio-frequency ablation therapy. This system employs the Inverse Solution Guidance Algorithm based upon Single Equivalent Moving Dipole (SEMD) localization method. The system was evaluated in in vivo swine experiments. Arrays consisting of 9 or 16 bipolar epicardial electrodes and an additional mid-myocardial pacing lead were sutured to each ventricle. Focal tachycardia was simulated by applying pacing pulses to each epicardial electrode at multiple pacing rates during breath hold at the end-expiration phase. Surface potentials were recorded from 64 surface electrodes and then analyzed using the SEMD method to localize the position of the pacing electrodes. We found a close correlation between the locations of the pacing electrodes as measured in computational and real spaces. The reproducibility error of the SEMD estimation of electrode location was 0.21 ± 0.07 cm. The vectors between every pair of bipolar electrodes were computed in computational and real spaces. At 120 bpm, the lengths of the vectors in the computational and real space had a 95% correlation. Computational space vectors were used in catheter guidance simulations which showed that this method could reduce the distance between the real space locations of the emulated catheter tip and the emulated arrhythmia origin site by approximately 72% with each movement. We have demonstrated the feasibility of using our system to guide a catheter to the site of the emulated VT origin.

Techniques for epicardial mapping and ablation with a miniature robotic walker.

BACKGROUND: Present treatments for ventricular tachycardia have significant drawbacks. To ameliorate these drawbacks, it may be advantageous to employ an epicardial robotic walker that performs mapping and ablation with precise control of needle insertion depth. This paper examines the feasibility of such a system. METHODS: This paper describes techniques for epicardial mapping and depth-controlled ablation with the robotic walker. The mapping technique developed for the current form of the system uses a single equivalent moving dipole model combined with the navigation capability of the walker. The intervention technique provides saline-enhanced radio frequency ablation, with sensing of needle penetration depth. The mapping technique was demonstrated in an artificial heart model with a simulated arrhythmia focus, followed by preliminary testing in the porcine model in vivo. The ablation technique was demonstrated in an artificial tissue model, and then in chicken breast tissue ex vivo. RESULTS: The walker located targets to within 2 mm using the SEMDM technique. No epicardial damage was found subsequent to the porcine trial in vivo. Needle insertion for ablation was controlled to within 2 mm of the target depth. Lesion size was repeatable, with diameter varying consistently in proportion to volume of saline injected. CONCLUSIONS: The experiments demonstrated the general feasibility of the techniques for mapping and depth-controlled ablation with the robotic walker.

Prospective Use of Microvolt T-Wave Alternans Testing to Guide Primary Prevention Implantable Cardioverter Defibrillator Therapy.

BACKGROUND: We hypothesized that a negative microvolt T-wave alternans (MTWA) test would identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillator (ICD) therapy in a prospective cohort. METHODS AND RESULTS: Data were pooled from 8 centers where MTWA testing was performed specifically for the purpose of guiding primary prevention ICD implantation. Cohorts were included if the ratio of ICDs implanted in patients who were MTWA "non-negative" to patients who were MTWA negative was >2:1, indicating that MTWA testing had a significant impact on the decision to implant an ICD. The pooled cohort included 651 patients: 371 MTWA non-negative and 280 MTWA negative. Among non-negative patients, 62% underwent ICD implantation whereas only 13% of MTWA-negative patients received an ICD (P<0.01). Despite a substantially lower prevalence of ICDs, long-term survival (6.9 years) was significantly better among MTWA-negative patients (68.2% non-negative vs. 87.1% negative, P=0.026). CONCLUSIONS: MTWA-negative patients had significantly better survival than MTWA non-negative patients, the majority of whom had ICDs. Despite a very low prevalence of ICDs, long-term survival among patients with left ventricular ejection fraction ≤40% and a negative MTWA test was better than in the ICD arm of any study to date that has demonstrated a benefit of ICDs. This provides further evidence that MTWA-negative patients are unlikely to benefit from primary prevention ICD therapy.

A method to noninvasively identify cardiac bioelectrical sources.

BACKGROUND: We have introduced a method to guide radiofrequency catheter ablation (RCA) procedures that estimates the location of a catheter tip used to pace the ventricles and the target site for ablation using the single equivalent moving dipole (SEMD). OBJECTIVE: To investigate the accuracy of this method in resolving epicardial and endocardial electrical sources. METHODS: Two electrode arrays, each of nine pacing electrodes at known distances from each other, sutured on the left- and right-ventricular (LV and RV) epicardial surfaces of swine, were used to pace the heart at multiple rates, while body surface potentials from 64 sites were recorded and used to estimate the SEMD location. A similar approach was followed for pacing from catheters in the LV and RV. RESULTS: The overall (RV & LV) error in estimating the interelectrode distance of adjacent epicardial electrodes was 0.38 ± 0.45 cm. The overall endocardial (RV & LV) interelectrode distance error, was 0.44 ± 0.26 cm. Heart rate did not significantly affect the error of the estimated SEMD location (P > 0.05). The guiding process error became progressively smaller as the SEMD approached an epicardial target site and close to the target, the overall absolute error was ∼ 0.28 cm. The estimated epicardial SEMD locations preserved their topology in image space with respect to their corresponding physical location of the epicardial electrodes. CONCLUSION: The proposed algorithm suggests one can efficiently and accurately resolve epicardial electrical sources without the need of an imaging modality. In addition, the error in resolving these sources is sufficient to guide RCA procedures.

The single equivalent moving dipole model does not require spatial anatomical information to determine cardiac sources of activation.

Radio-frequency catheter ablation (RCA) is an established treatment for ventricular tachycardia (VT). A key feature of the RCA procedure is the need for a mapping approach that facilitates the identification of the target ablation site. In this study, we investigate the effect of the location of the reference potential and spatial anatomical constraints on the accuracy of an algorithm to identify the target site for ablation therapy of VT. This algorithm involves processing body surface potentials using the single equivalent moving dipole (SEMD) model embedded in an infinite homogeneous volume conductor to model cardiac electrical activity. We employed a swine animal model and an electrode array of nine electrodes that was sutured on the epicardial surface of the right ventricle. We identified two potential reference electrode locations: at an electrode most far away from the heart (R1) and at the average of all 64 body surface electrode potentials (R2). Also, we developed three spatial "constraining" schemes of the algorithm used to obtain the SEMD location: one that does not impose any constraint on the inverse solution (S1), one that constrains the solution into a volume that corresponds to the heart (S2), and one that constrains the solution into a volume that corresponds to the body surface (S3). We have found that R2S1 is the most accurate approach (p < 0.05 versus R1S1 at earliest activation time-EAT) for localizing epicardial electrical sources of known locations in vivo. Although the homogeneous volume conductor introduces systematic error in the estimated compared to the true dipole location, we have observed that the overall error of the estimated interelectrode distance compared to the true one was 0.4 ± 0.4 cm and 0.4 ± 0.1 cm for the R1S1 and R2S1 combinations, respectively, at the EAT (p = N.S.) and 1.0 ± 0.6 and 0.5 ± 0.4 cm, respectively, at the pacing spike time (PST, ). In conclusion, our algorithm to estimate the SEMD parameters from body surface potentials can potentially be a useful method to rapidly and accurately guide the catheter tip to the target site during a RCA procedure without the need for spatial anatomical information obtained by conventional imaging modalities.

Cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm.

BACKGROUND: We developed and evaluated a novel system for guiding radiofrequency catheter ablation therapy of ventricular tachycardia. This guidance system employs an inverse solution guidance algorithm (ISGA) using a single equivalent moving dipole (SEMD) localization method. The method and system were evaluated in both a saline tank phantom model and in vivo animal (swine) experiments. METHODS: A catheter with two platinum electrodes spaced 3 mm apart was used as the dipole source in the phantom study. A 40-Hz sinusoidal signal was applied to the electrode pair. In the animal study, four to eight electrodes were sutured onto the right ventricle. These electrodes were connected to a stimulus generator delivering 1-ms duration pacing pulses. Signals were recorded from 64 electrodes, located either on the inner surface of the saline tank or on the body surface of the pig, and then processed by the ISGA to localize the physical or bioelectrical SEMD. RESULTS: In the phantom studies, the guidance algorithm was used to advance a catheter tip to the location of the source dipole. The distance from the final position of the catheter tip to the position of the target dipole was 2.22 ± 0.78 mm in real space and 1.38 ± 0.78 mm in image space (computational space). The ISGA successfully tracked the locations of electrodes sutured on the ventricular myocardium and the movement of an endocardial catheter placed in the animal's right ventricle. CONCLUSION: In conclusion, we successfully demonstrated the feasibility of using an SEMD inverse algorithm to guide a cardiac ablation catheter.

Sympathetic withdrawal is associated with hypotension after hepatic reperfusion.

OBJECTIVE: Post-reperfusion syndrome (PRS), severe hypotension after graft reperfusion during liver transplantation, is an adverse clinical event associated with poorer patient outcomes. The purpose of this study was to determine whether alterations in autonomic control in liver transplant recipients prior to graft reperfusion are associated with the subsequent development of PRS. METHODS: Heart rate variability (HRV), systolic arterial blood pressure (SBP) variability, and baroreflex sensitivity of 218 liver transplant recipients were evaluated using 5 min of ECG and arterial blood pressure signals 10 min before graft reperfusion along with other clinical parameters. Logistic regression analyses were performed to assess predictors of PRS occurrence. RESULTS: Seventy-seven patients (35 %) developed PRS while 141 did not. There were significant differences in SBP (110 ± 16 vs. 119 ± 16 mmHg, P < 0.001) and the ratio of low frequency power to high frequency power (LF/HF) of HRV (1.0 ± 1.4 vs. 2.1 ± 3.7, P = 0.003) between the PRS group and No-PRS group. In multivariate logistic regression analysis, predictors were LF/HF (odds ratio 0.817, P = 0.028) and SBP (odds ratio 0.966, P < 0.001). INTERPRETATION: Low LF/HF and SBP measured before hepatic graft reperfusion were significantly correlated with subsequent PRS occurrence, suggesting that sympathovagal imbalance and depressed SBP may be key factors predisposing to reperfusion-related severe hypotension in liver transplant recipients.

Estimation of changes in instantaneous aortic blood flow by the analysis of arterial blood pressure.

The purpose of this study was to introduce and validate a new algorithm to estimate instantaneous aortic blood flow (ABF) by mathematical analysis of arterial blood pressure (ABP) waveforms. The algorithm is based on an autoregressive with exogenous input (ARX) model. We applied this algorithm to diastolic ABP waveforms to estimate the autoregressive model coefficients by requiring the estimated diastolic flow to be zero. The algorithm incorporating the coefficients was then applied to the entire ABP signal to estimate ABF. The algorithm was applied to six Yorkshire swine data sets over a wide range of physiological conditions for validation. Quantitative measures of waveform shape (standard deviation, skewness, and kurtosis), as well as stroke volume and cardiac output from the estimated ABF, were computed. Values of these measures were compared with those obtained from ABF waveforms recorded using a Transonic aortic flow probe placed around the aortic root. The estimation errors were compared with those obtained using a windkessel model. The ARX model algorithm achieved significantly lower errors in the waveform measures, stroke volume, and cardiac output than those obtained using the windkessel model (P < 0.05).

Promiscuous binding of extracellular peptides to cell surface class I MHC protein.

Algorithms derived from measurements of short-peptide (8-10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K(b), can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide-MHC complexes that form on cells exposed to extracellular (exogenous) peptides.

Clinical utility of microvolt T-wave alternans testing in identifying patients at high or low risk of sudden cardiac death.

BACKGROUND: Previous studies have demonstrated that microvolt T-wave alternans (MTWA) testing is a robust predictor of ventricular tachyarrhythmias and sudden cardiac death (SCD) in at-risk patients. However, recent studies have suggested that MTWA testing is not as good a predictor of "appropriate" implantable cardioverter-defibrillator (ICD) therapy as it is a predictor of SCD in patients without ICDs. OBJECTIVE: To evaluate the utility of MTWA testing for SCD risk stratification in patients without ICDs. METHODS: Patient-level data were obtained from 5 prospective studies of MTWA testing in patients with no history of ventricular arrhythmia or SCD. In these studies, ICDs were implanted in only a minority of patients and patients with ICDs were excluded from the analysis. We conducted a pooled analysis and examined the 2-year risk for SCD based on the MTWA test result. RESULTS: The pooled cohort included 2883 patients. MTWA testing was positive in 856 (30%), negative in 1627 (56%), and indeterminate in 400 (14%) patients. Among patients with a left ventricular ejection fraction (LVEF) of ≤35%, annual SCD event rates were 4.0%, 0.9%, and 4.6% among groups with MTWA positive, negative, and indeterminate test results. The SCD rate was significantly lower among patients with a negative MTWA test result than in patients with either positive or indeterminate MTWA test results (P <.001 for both comparisons). In patients with an LVEF of >35%, annual SCD event rates were 3.0%, 0.3%, and 0.3% among the groups with MTWA positive, negative, and indeterminate test results. The SCD rate associated with a positive MTWA test result was significantly higher than that associated with either negative (P <.001) or indeterminate MTWA test results (P = .003). CONCLUSIONS: In patients without ICDs, MTWA testing is a powerful predictor of SCD. Among patients with an LVEF of ≤35%, a negative MTWA test result is associated with a low risk for SCD. Conversely, among patients with an LVEF of >35%, a positive MTWA test result identifies patients at significantly heightened SCD risk. These findings may have important implications for refining primary prevention ICD treatment algorithms.

Cardiac output and stroke volume estimation using a hybrid of three Windkessel models.

Cardiac output (CO) and stroke volume (SV) are the key hemodynamic parameters to be monitored and assessed in ambulatory and critically ill patients. The purpose of this study was to introduce and validate a new algorithm to continuously estimate, within a proportionality constant, CO and SV by means of mathematical analysis of peripheral arterial blood pressure (ABP) waveforms. The algorithm combines three variants of the Windkessel model. Input parameters to the algorithm are the end-diastolic pressure, mean arterial pressures, inter-beat interval, and the time interval from end-diastolic to peak systolic pressure. The SV estimates from the three variants of the Windkessel model were weighted and integrated to provide beat-to-beat SV estimation. In order to validate the new algorithm, the estimated CO and SV were compared to those obtained through surgically implanted Transonic™ aortic flow probes placed around the aortic roots of six Yorkshire swine. Overall, estimation errors in CO and SV derived from radial ABP were 10.1% and 14.5% respectively, and 12.7% and 16.5% from femoral ABP. The new algorithm demonstrated statistically significant improvement in SV estimation compared with previous methods.

A method for guiding ablation catheters to arrhythmogenic sites using body surface electrocardiographic signals.

Treatment of hemodynamically unstable ventricular arrhythmias requires rapid and accurate localization of the reentrant circuit. We have previously described an algorithm that uses the single-equivalent moving dipole model to rapidly identify both the location of cardiac sources from body surface electrocardiographic signals and the location of the ablation catheter tip from current pulses delivered at the tip. However, during catheter ablation, in the presence of sources of systematic error, even if the exit site and catheter tip dipole are superposed in real space, their calculated positions may be separated by as much as 5 mm if their orientations are not exactly matched. In this study, we present a method to compensate for the effect of dipole orientation and examine the method's ability to guide a dipole at a catheter tip to an arrhythmogenic dipole corresponding to the exit site. In computer simulations, we show that the new method enables the user to guide the catheter tip to within 1.5 mm of the arrhythmogenic dipole using a realistic number of movements of the ablation catheter. These results suggest that this method has the potential to greatly facilitate RF ablation procedures, especially in the significant patient population with hemodynamically unstable arrhythmias.

Validation of a novel catheter guiding method for the ablative therapy of ventricular tachycardia in a phantom model.

Accurate guidance of an ablation catheter is critical in the RF ablation (RFA) of ventricular tachycardia (VT). With current technologies, it is challenging to rapidly and accurately localize the site of origin of an arrhythmia, often restricting treatment to patients with hemodynamically stable arrhythmias. We investigated the effectiveness of a new guidance method, the inverse solution guidance algorithm (ISGA), which is based on a single-equivalent dipole representation of cardiac electrical activity and is suitable for patients with hemodynamically unstable VT. Imaging was performed in homogeneous and inhomogeneous saline-filled torso phantoms in which a catheter tip was guided toward a stationary electrical dipole source over distances of more than 5 cm. Using ISGA, the moving catheter tip was guided to within 0.61 +/-0.43 and 0.55 +/-0.39 mm of the stationary source in the homogeneous and inhomogeneous phantoms, respectively. This accuracy was achieved with less than ten movements of the catheter. These results suggest that ISGA has potential to provide accurate and efficient guidance for RFA procedures in the patient population with hemodynamically unstable arrhythmias.

Evidence regarding clinical use of microvolt T-wave alternans.

BACKGROUND: Microvolt T-wave alternans (MTWA) testing in many studies has proven to be a highly accurate predictor of ventricular tachyarrhythmic events (VTEs) in patients with risk factors for sudden cardiac death (SCD) but without a prior history of sustained VTEs (primary prevention patients). In some recent studies involving primary prevention patients with prophylactically implanted cardioverter-defibrillators (ICDs), MTWA has not performed as well. OBJECTIVE: This study examined the hypothesis that MTWA is an accurate predictor of VTEs in primary prevention patients without implanted ICDs, but not of appropriate ICD therapy in such patients with implanted ICDs. METHODS: This study identified prospective clinical trials evaluating MTWA measured using the spectral analytic method in primary prevention populations and analyzed studies in which: (1) few patients had implanted ICDs and as a result none or a small fraction (< or =15%) of the reported end point VTEs were appropriate ICD therapies (low ICD group), or (2) many of the patients had implanted ICDs and the majority of the reported end point VTEs were appropriate ICD therapies (high ICD group). RESULTS: In the low ICD group comprising 3,682 patients, the hazard ratio associated with a nonnegative versus negative MTWA test was 13.6 (95% confidence interval [CI] 8.5 to 30.4) and the annual event rate among the MTWA-negative patients was 0.3% (95% CI: 0.1% to 0.5%). In contrast, in the high ICD group comprising 2,234 patients, the hazard ratio was only 1.6 (95% CI: 1.2 to 2.1) and the annual event rate among the MTWA-negative patients was elevated to 5.4% (95% CI: 4.1% to 6.7%). In support of these findings, we analyzed published data from the Multicenter Automatic Defibrillator Trial II (MADIT II) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) trials and determined that in those trials only 32% of patients who received appropriate ICD therapy averted an SCD. CONCLUSION: This study found that MTWA testing using the spectral analytic method provides an accurate means of predicting VTEs in primary prevention patients without implanted ICDs; in particular, the event rate is very low among such patients with a negative MTWA test. In prospective trials of ICD therapy, the number of patients receiving appropriate ICD therapy greatly exceeds the number of patients who avert SCD as a result of ICD therapy. In trials involving patients with implanted ICDs, these excess appropriate ICD therapies seem to distribute randomly between MTWA-negative and MTWA-nonnegative patients, obscuring the predictive accuracy of MTWA for SCD. Appropriate ICD therapy is an unreliable surrogate end point for SCD.