Clinical Professor, Medicine - Cardiovascular Medicine
Chief, Cardiology Clinics, Cardiovascular Medicine (2009 - Present)
Clinic Advisory Council, Stanford Hospital and Clinics (2010 - Present)
Director, Electrocardiography and Stress Lab (2011 - Present)
PhD, Stanford University, Molecular Physiology (1998)
MD, Stanford University, Medicine (1998)
Current Research and Scholarly Interests
(1) Mechanisms of Arrhythmia, including Ventricular Tachycardia, Atrial Fibrillation and other arrhythmias.
(2) New technologies and devices for catheter ablation.
The precise timing of tachycardia entrainment is determined by the postpacing interval, the tachycardia cycle length, and the pacing rate: Theoretical insights and practical applications.
2016; 13 (3): 695-703
Previous observations have reported that the number of pacing stimuli required to entrain a tachycardia varies on the basis of arrhythmia type and location, but a quantitative formulation of the number needed to entrain (NNE) that unifies these observations has not been characterized.We sought to investigate the relationship between the number of pacing stimulations, the tachycardia cycle length (TCL), the overdrive pacing cycle length (PCL), and the postpacing interval (PPI) to accurately estimate the timing of tachycardia entrainment.First, we detailed a mathematical derivation unifying electrophysiological parameters with empirical confirmation in 2 patients undergoing catheter ablation of typical atrial flutter. Second, we validated our formula in 44 patients who underwent various catheter ablation procedures. For accuracy, we corrected for rate-related changes in conduction velocity.We derived the equations NNE = |(PPI - TCL)/(TCL - PCL)| + 1 and Tachycardia advancement = (NNE - 1) × (TCL - PCL) - (PPI - TCL), which state that the NNE and the amount of tachycardia advancement on the first resetting stimulation are determined using regularly measured intracardiac parameters. In the retrospective cohort, the observed PPI - TCL highly correlated with the predicted PPI - TCL (mean difference 5.8 ms; r = 0.97; P < .001), calculated as PPI - TCL = (NNE - 1) × (TCL - PCL) - tachycardia advancement.The number of pacing stimulations required to entrain a reentrant tachycardia is predictable at any PCL after correcting for cycle length-dependent changes in conduction velocity. This relationship unifies established empirically derived diagnostic and mapping criteria for supraventricular tachycardia and ventricular tachycardia. This relationship may help elucidate when antitachycardia pacing episodes are ineffective or proarrhythmic and could potentially serve as a theoretical basis to customize antitachycardia pacing settings for improved safety and effectiveness.
View details for DOI 10.1016/j.hrthm.2015.11.032
View details for PubMedID 26611239
View details for PubMedCentralID PMC4770895
- Stereotactic ablative radiotherapy for the treatment of refractory cardiac ventricular arrhythmia. Circulation. Arrhythmia and electrophysiology 2015; 8 (3): 748-750
A histological and mechanical analysis of the cardiac lead-tissue interface: implications for lead extraction.
2014; 10 (5): 2200-2208
The major risks of pacemaker and implantable cardioverter defibrillator extraction are attributable to the fibrotic tissue that encases them in situ, yet little is known about the cellular and functional properties of this response. In the present research, we performed a histological and mechanical analysis of human tissue collected from the lead-tissue interface to better understand this process and provide insights for the improvement of lead design and extraction. The lead-tissue interface consisted of a thin cellular layer underlying a smooth, acellular surface, followed by a circumferentially organized collagen-rich matrix. 51.8±4.9% of cells were myofibroblasts via immunohistochemistry, with these cells displaying a similar circumferential organization. Upon mechanical testing, samples exhibited a triphasic force-displacement response consisting of a toe region during initial tensioning, a linear elastic region and a yield and failure region. Mean fracture load was 5.6±2.1N, and mean circumferential stress at failure was 9.5±4.1MPa. While the low cellularity and fibrotic composition of tissue observed herein is consistent with a foreign body reaction to an implanted material, the significant myofibroblast response provides a mechanical explanation for the contractile forces complicating extractions. Moreover, the tensile properties of this tissue suggest the feasibility of circumferential mechanical tissue disruption, similar to balloon angioplasty devices, as a novel approach to assist with lead extraction.
View details for DOI 10.1016/j.actbio.2014.01.008
View details for PubMedID 24434537
- Is the wearable cardioverter-defibrillator the answer for early post-myocardial infarction patients at risk for sudden death?: mind the gap. Journal of the American College of Cardiology 2013; 62 (21): 2008-2009
- How insensitive ... How a mutation in the SCN5A voltage sensor leads to clinical arrhythmia HEART RHYTHM 2012; 9 (10): 1689-1690
Incidence and clinical predictors of low defibrillation safety margin at time of implantable defibrillator implantation
JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY
2012; 34 (1): 93-100
Determination of the defibrillation safety margin (DSM) is the most common method of testing device effectiveness at the time of implantation of implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRTD). Low DSM remains a problem in clinical practice.The purpose of this study is to ascertain the incidence and clinical predictors of low DSM and the treatment strategies for low DSM in ICD or CRTD recipients.Selected ICD or CRTD recipients from January 2006 to May 2008 who underwent DSM test at the time of implantation were included. Low DSM patients were defined as patients who had a DSM within 10 J of the maximum delivered energy of the device. These patients were compared to patients who had DSM > 10 J.This study included 243 patients. Of these, 13 (5.3%) patients had low DSM, and 230 patients had adequate DSM. Patients with low DSM had a high prevalence of amiodarone use (69% vs 13%, p < 0.01), secondary prevention indications (69% vs 30%, p < 0.01), and a trend toward younger age (51 ± 18 vs 58 ± 15 years, p = 0.08). After adjustment for age and sex, amiodarone use was significantly associated with low DSM. All low DSM patients except one obtained adequate DSM after taking additional steps, including discontinuing amiodarone and starting sotalol, RV lead repositioning, adding a subcutaneous array or shock coil, changing single-coil to dual-coil lead, and upgrading to a high output device.The incidence of low DSM patients is low with high-energy devices. Amiodarone use is associated with low DSM, and its discontinuation or substitution with sotalol is one of a variety of available options for low DSM patients.
View details for DOI 10.1007/s10840-011-9648-z
View details for Web of Science ID 000303541200013
View details for PubMedID 22391960
Electroanatomic localization of a slowly conducting atrioventricular (Mahaim) accessory pathway
JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY
2011; 31 (2): 119-124
We present a case of a 34-year-old female with Ebstein's anomaly and symptomatic wide complex tachyarrhythmia. Electrophysiologic evaluation demonstrated antidromic tachycardia utilizing a right-sided decremental, slowly conducting atrioventricular pathway. Distinct accessory pathway potentials along the length of the bypass tract were sequentially recorded to define the anatomic course of the pathway, as uniquely represented on a three-dimensional electroanatomic map, and to successfully guide catheter ablation.
View details for DOI 10.1007/s10840-009-9440-5
View details for Web of Science ID 000293026800003
View details for PubMedID 19943099
Visualizing ablation gaps in vitro using a deflectable fiber optic endocardial visualization catheter
JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY
2009; 25 (2): 107-110
The efficacy of pulmonary vein isolation for the treatment of atrial fibrillation may be limited by the ability to make continuous and transmural lesions utilizing an ablation catheter. Gaps often persist between ablation lesions leading to failed electrical isolation and thus failed ablation. Recently, a deflectable fiberoptic endocardial visualization catheter has been introduced for use in imaging the coronary sinus using light in the visible spectrum. We utilize this catheter to visualize the endocardial surface and examine radiofrequency ablation lesions in porcine endocardium to determine the presence of gaps between radiofrequency lesions.Videos were taken of the lesions and shown to two readers who were asked to identify the gaps ranging from less than 0.1 mm-9.8 mm.Ninety-four lesion gaps were reviewed. The readers demonstrated a combined accuracy of 98.4% at identifying gaps.Gaps between ablation lesions can be accurately identified down to less than 1 mm distances in vitro using a direct visualization catheter. Further studies are warranted to confirm these finding in vivo.
View details for DOI 10.1007/s10840-008-9338-7
View details for Web of Science ID 000267683500004
View details for PubMedID 19148727
Direct Visualization of Cardiac Radiofrequency Ablation Lesions
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
2009; 2 (2): 198-201
Effective ablation of atrial fibrillation and other cardiac arrhythmias requires precise catheter navigation and controlled delivery of energy to cardiac tissue. In this study, we summarize our initial experience using a fiber optic direct visualization catheter to evaluate and guide placement of endocardial radiofrequency (RF) ablation lesions. RF lesions were created in cadaveric porcine hearts and examined in a blood-filled field using a direct visualization catheter. Direct visualization of RF lesions was repeated in vivo using an ovine model. Lesions and interlesion gaps were clearly identifiable using the direct visualization catheter. It was possible to place lesions in proximity to anatomical landmarks and in relation to one another. Catheter-generated images correlated well with lesion appearance on gross examination. Direct catheter-based visualization is a feasible technique for guiding RF lesion placement, estimating lesion size, and identifying interlesion gaps. Future work is needed to correlate surface appearance with transmurality and electrical isolation.
View details for DOI 10.1007/s12265-009-9094-9
View details for Web of Science ID 000284690100010
View details for PubMedID 20559988
The Efficacy of Implantable Cardioverter-Defibrillators in Heart Transplant Recipients Results From a Multicenter Registry
2009; 2 (3): 197-201
Sudden cardiac death among orthotopic heart transplant recipients is an important mechanism of death after cardiac transplantation. The role for implantable cardioverter-defibrillators (ICDs) in this population is not well established. This study sought to determine whether ICDs are effective in preventing sudden cardiac death in high-risk heart transplant recipients.We retrospectively analyzed the records of all orthotopic heart transplant patients who had ICD implantation between January 1995 and December 2005 at 5 heart transplant centers. Thirty-six patients were considered high risk for sudden cardiac death. The mean age at orthotopic heart transplant was 44+/-14 years, the majority being male (n=29). The mean age at ICD implantation was 52+/-14 years, whereas the average time from orthotopic heart transplant to ICD implant was 8 years +/-6 years. The main indications for ICD implantation were severe allograft vasculopathy (n=12), unexplained syncope (n=9), history of cardiac arrest (n=8), and severe left ventricular dysfunction (n=7). Twenty-two shocks were delivered to 10 patients (28%), of whom 8 (80%) received 12 appropriate shocks for either rapid ventricular tachycardia or ventricular fibrillation. The shocks were effective in terminating the ventricular arrhythmias in all cases. Three (8%) patients received 10 inappropriate shocks. Underlying allograft vasculopathy was present in 100% (8 of 8) of patients who received appropriate ICD therapy.Use of ICDs after heart transplantation may be appropriate in selected high-risk patients. Further studies are needed to establish an appropriate prevention strategy in this population.
View details for DOI 10.1161/CIRCHEARTFAILURE.108.814525
View details for Web of Science ID 000269161600007
View details for PubMedID 19808340
A New Approach for ICD Rhythm Classification based on Support Vector Machines
Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2009: 2478–2481
Inappropriate shocks due to misclassification of supraventricular and ventricular arrhythmias remain a major problem in the care of patients with Implantable Cardioverter Defibrillators (ICDs). The purpose of this study was to investigate the ability of a new covariance-based support vector machine classifier, to distinguish ventricular tachycardia from other rhythms such as supraventricular tachycardia. The proposed algorithm is applicable on both single and dual chamber ICDs and has a low computational demand. The results demonstrate that suggested algorithm has considerable promise and merits further investigation.
View details for Web of Science ID 000280543601357
View details for PubMedID 19964965
Optimal Programming of ICDs for Prevention of Appropriate and Inappropriate Shocks.
Current treatment options in cardiovascular medicine
2008; 10 (5): 408-416
Expansion of indications for implantable cardioverter-defibrillators (ICDs) has led to a significant increase in the number of patients receiving ICDs and the number of lives saved because of ICD therapy. However, appropriate or inappropriate shocks are frequent and may result in a significant decrease in quality of life in patients with ICDs. Atrial fibrillation with rapid ventricular response, sinus tachycardia, atrial tachycardia or atrial flutter with rapid conduction, and other supraventricular tachycardias are the most common arrhythmias causing inappropriate therapy. Other causes include oversensing of diaphragmatic potentials or myopotentials, T-wave oversensing, double or triple counting of intracardiac signals, lead fractures or header connection problems, lead chatter or noise, and electromagnetic interference. Strategies to reduce inappropriate therapy using device programming rely on the ability to distinguish supraventricular and atrial arrhythmias from ventricular tachycardia. Avoiding therapy for nonsustained ventricular arrhythmias and increasing the role of antitachycardia pacing to terminate ventricular tachycardia are key approaches to reducing shocks for ventricular arrhythmias. Optimal programming holds great promise for decreasing the overall incidence of shock therapy and increasing ICD acceptance.
View details for PubMedID 18814830
Time-resolved three-dimensional imaging of the left atrium and pulmonary veins in the interventional suite - A comparison between muttisweep gated rotational three-dimensional reconstructed fluoroscopy and multislice computed tomography
2008; 5 (4): 513-519
Cardiac computed tomography (CT) is commonly used to visualize left atrial (LA) anatomy for ablation of atrial fibrillation. We have developed a new imaging technique that allows acquisition and visualization of three-dimensional (3D) cardiac images in the catheter lab.We sought to compare LA and pulmonary vein (PV) dimensions acquired using gated multisweep rotational fluoroscopy (C-arm CT) system and multislice computed tomography (MSCT) in an in vivo porcine model.A Siemens AXIOM Artis dTA C-arm system (Siemens AG, Medical Solutions) was modified to allow acquisition of four bidirectional sweeps during synchronized acquisition of the electrocardiogram signal to allow retrospective gating. C-arm CT image volumes were then reconstructed. Gated MSCT (SOMATOM Sensation 16 and 64, Siemens AG, Medical Solutions) and C-arm CT images were acquired in six animals. The two main PV diameters were measured in orthogonal axes. LA volumes were calculated. C-arm CT measurements were compared with the MSCT measurements.The average PV diameters using the C-arm CT were 2.24 x 1.35 cm, versus 2.27 x 1.38 cm for CT. The average difference was 0.034 cm (1.9%) between the C-arm CT and standard CT. The average LA volume using MSCT was 49.1 +/- 12.7 cm(3), as compared with 51.0 +/- 8.7 cm(3) obtained by the C-arm CT. The average difference between the C-arm CT and the MSCT was 1.9 cm(3) (3.7%). There were no significant differences in either the PV or LA measurements.Visualization of 3D cardiac anatomy during ablation procedures is possible and highly accurate. The 3D cardiac reconstructions acquired during ablation procedures will be valuable for procedural planning and guidance.
View details for DOI 10.1016/j.hrthm.2007.12.027
View details for Web of Science ID 000254596600003
View details for PubMedID 18362018
A Covariance-Based Algorithm: A Novel Technique for Rhythm Discrimination in ICDs
30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society
IEEE. 2008: 5478–5481
Inappropriate shocks due to misclassification of supraventricular and ventricular arrhythmias remain a major problem in the care of patients with Implantable Cardioverter defibrillators (ICDs). In this study we have investigated the ability of a new covariance-based algorithm, to distinguish Ventricular Tachycardia from other rhythms such as Supraventricular Tachycardia. The proposed algorithm has a low computational demand and with a small adjustment is applicable on both single-chamber and dual-chamber ICDs. The results are promising and suggest that the new covariance-based algorithm may be an effective method for ICD rhythm classification and may decrease inappropriate shocks.
View details for Web of Science ID 000262404503170
View details for PubMedID 19163957
Characterization of human coronary sinus valves by direct visualization during biventricular pacemaker implantation
PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY
2008; 31 (1): 78-82
The precise reasons for failure to cannulate the coronary sinus during biventricular device implantation are unknown. Visualization of the coronary sinus ostium during electrophysiology procedures may enhance understanding of how unusual anatomy can affect successful cannulation of the coronary sinus.The aim of this study was to describe the morphology of valves at the coronary sinus ostium (CSO) visualized directly with an illuminated fiberoptic endoscope during implantation of biventricular devices.The coronary sinus anatomy of one hundred consecutive patients undergoing implantation of biventricular devices was investigated using a fiberoptic endocardial visualization catheter (EVC).The CSO was clearly visualized in 98 patients using the EVC. A Thebesian valve was seen in 54% of these. Almost all Thebesian valves were positioned at the inferior (61%) or posterior (33%) aspect of the CSO. Only six patients had Thebesian valves that covered more than 70% of the CSO, but all were successfully implanted with a transvenous left ventricular pacing lead after cannulating the coronary sinus under direct visualization.Over half of patients undergoing biventricular device implantation have identifiable Thebesian valves. Even valves covering the majority of the ostial area may be traversed using direct visualization and modern catheterization techniques.
View details for Web of Science ID 000253373400015
View details for PubMedID 18181913
Cardiac device infections complicated by erosion
JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY
2007; 19 (2): 133-137
Implantation of pacemakers and implantable cardioverter-defibrillators (ICDs) can be complicated by infection and device erosion. It is unclear if the clinical features of patients who have device erosion differ from those without erosion.We retrospectively examined the records of all patients referred for explantation of a pacemaker or defibrillator from January 2000 to May 2005. We examined demographic variables including age, gender, and body mass index (BMI) as well as clinical variables related to erosion and procedural variables.Seventy-two patients with infected pacemakers or ICDs were identified. Of these cases, 30 (42%) developed infection complicated by erosion, of which 8/28 (29%) were related to ICDs, and 22/44 (50%) were related to pacemakers.Device erosion was significantly associated with the presence of a non-systemic infection as opposed to cases without erosion. This finding may have implications in the timing of device re-implantation.
View details for DOI 10.1007/s10840-007-9143-8
View details for Web of Science ID 000249009800008
View details for PubMedID 17668305
- Epicardial ablation of postinfarction ventricular tachycardia with an externally irrigated catheter in a patient with mechanical aortic and mitral valves HEART RHYTHM 2007; 4 (5): 651-654
- VF and fatal cardiac arrest following ICD therapy delivery: What is the cause? PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY 2007; 30 (4): 551-553
Large radiofrequency ablation lesions can be created with a retractable infusion-needle catheter
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
2006; 17 (6): 657-661
Radiofrequency (RF) catheter ablation of ventricular tachycardia is sometimes limited by inadequate lesion depth. We report the use of a novel retractable needle-tipped electrode catheter with intramyocardial (IM) saline infusion and IM RF energy delivery to create large myocardial ablation lesions.The left ventricle was entered via the femoral artery in 6 and 11 anesthetized goats and swine (32-90 kg) with an 8-F electrode catheter with an extendable 27-gauge needle at the tip (modified for RF ablation by making the needle electrically active). The needle was advanced 5-7 mm intramyocardially and 0.9% saline was infused 1 mL/min x 60 seconds prior to, and throughout a 120-second application of RF via the active needle, with power titrated to 12 W for 9 lesions, and 30-40 W for 37 lesions, followed by a 120-second RF application using the 4-mm-tip electrode, with power titrated to achieve a 10-Omega decrease in impedance. Needle/saline lesions were compared to 18 standard 4-mm-tip control lesions (power titrated to < or =50 W, to achieve a 10-Omega impedance decrease or limited to 60 degrees Celsius) and to 17 irrigated 3.5-mm-tip lesions (power titrated to < or =50 W, temperature limited to 50 degrees Celsius, 30 mL/min infusion rate). Lesions were identified in the excised heart, fixed, serially sectioned from the endocardium, and digitally analyzed to calculate volume.Lesions were homogeneous and had distinct borders. Compared to 4-mm-tip and irrigated-tip lesions, high-power needle/saline lesions were significantly deeper (13 +/- 2 vs 5 +/- 1 and 8 +/- 3 mm, P < 0.001), had significantly larger volumes (1,700 +/- 750 vs 240 +/- 170 and 750 +/- 650 mm(3), P < 0.001), and had larger cross-sectional area at each millimeter depth beyond the 1 mm (P < 0.01).IM saline infusion and IM RF energy delivery markedly increase RF lesion size as compared to standard RF ablation and is feasible with a percutaneous catheter. This method warrants further investigation because of its potential clinical utility.
View details for DOI 10.1111/j.1540-8167.2006.00439.x
View details for Web of Science ID 000237740000018
View details for PubMedID 16836718
- Modified temporary cardiac pacing using transvenous active fixation leads and external re-sterilized pulse generators JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2006; 47 (7): 1487-1489
Epicardial catheter mapping and ablation of ventricular tachycardia
2006; 3 (3): 360-363
Percutaneous entry into the pericardial space allows epicardial catheter mapping and ablation in the electrophysiology laboratory, opening a perspective on cardiac electrophysiology that previously was limited largely to the operating room. Scar-related reentry after myocardial infarction usually involves the subendocardium but in some patients can only be ablated from the epicardium. Epicardial, scar-related reentry also is an important cause of ventricular tachycardia in nonischemic cardiomyopathies. Rare supraventricular tachycardias and idiopathic ventricular tachycardia that cannot be defined from the endocardium sometimes can be ablated from the epicardium. With appropriate precautions the procedural risks are low. Epicardial catheter techniques expand the options for investigating cardiac electrophysiology and treating arrhythmias in humans and may lead to insights into transmural properties influencing repolarization and the genesis of arrhythmias.
View details for DOI 10.1016/j.hrthm.2005.10.022
View details for Web of Science ID 000235779600020
View details for PubMedID 16500312
- Effects on ion permeation with hydrophobic substitutions at a residue in shaker S6 that interacts with a signature sequence amino acid Conference on Molecular and Functional Diversity of Ion Channels and Receptors NEW YORK ACAD SCIENCES. 1999: 458–464
Voltage-dependent gating of single wild-type and S4 mutant KAT1 inward rectifier potassium channels
JOURNAL OF GENERAL PHYSIOLOGY
1998; 112 (6): 679-713
The voltage-dependent gating mechanism of KAT1 inward rectifier potassium channels was studied using single channel current recordings from Xenopus oocytes injected with KAT1 mRNA. The inward rectification properties of KAT1 result from an intrinsic gating mechanism in the KAT1 channel protein, not from pore block by an extrinsic cation species. KAT1 channels activate with hyperpolarizing potentials from -110 through -190 mV with a slow voltage-dependent time course. Transitions before first opening are voltage dependent and account for much of the voltage dependence of activation, while transitions after first opening are only slightly voltage dependent. Using burst analysis, transitions near the open state were analyzed in detail. A kinetic model with multiple closed states before first opening, a single open state, a single closed state after first opening, and a closed-state inactivation pathway accurately describes the single channel and macroscopic data. Two mutations neutralizing charged residues in the S4 region (R177Q and R176L) were introduced, and their effects on single channel gating properties were examined. Both mutations resulted in depolarizing shifts in the steady state conductance-voltage relationship, shortened first latencies to opening, decreased probability of terminating bursts, and increased burst durations. These effects on gating were well described by changes in the rate constants in the kinetic model describing KAT1 channel gating. All transitions before the open state were affected by the mutations, while the transitions after the open state were unaffected, implying that the S4 region contributes to the early steps in gating for KAT1 channels.
View details for Web of Science ID 000077357400003
View details for PubMedID 9834140