Sachin Nayyar

Bipolar Electrogram Shannon Entropy at Sites of Rotational Activation: Implications for Ablation of Atrial Fibrillation

Background—The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results—Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles). The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions—ShEn is a mechanistically based tool that may assist AF rotor mapping.Background— The pivot is critical to rotors postulated to maintain atrial fibrillation (AF). We reasoned that wavefronts circling the pivot should broaden the amplitude distribution of bipolar electrograms because of directional information encoded in these signals. We aimed to determine whether Shannon entropy (ShEn), a measure of signal amplitude distribution, could differentiate the pivot from surrounding peripheral regions and thereby assist clinical rotor mapping. Methods and Results— Bipolar electrogram recordings were studied in 4 systems: (1) computer simulations of rotors in a 2-dimensional atrial sheet; (2) isolated rat atria recorded with a multi-electrode array (n=12); (3) epicardial plaque recordings of induced AF in hypertensive sheep (n=11); and (4) persistent AF patients (n=10). In the model systems, rotation episodes were identified, and ShEn calculated as an index of amplitude distribution. In humans, ShEn distribution was analyzed at AF termination sites and with respect to complex fractionated electrogram mean. We analyzed rotation episodes in simulations (4 cycles) and animals (rats: 14 rotors, duration 80±81 cycles; sheep: 13 rotors, 4.2±1.5 cycles). The maximum ShEn bipole was consistently colocated with the pivot zone. ShEn was negatively associated with distance from the pivot zone in simulated spiral waves, rats, and sheep. ShEn was modestly inversely associated with complex fractionated electrogram; however, there was no relationship at the sites of highest ShEn. Conclusions— ShEn is a mechanistically based tool that may assist AF rotor mapping.

Importance of the underlying substrate in determining thrombus location in atrial fibrillation: implications for left atrial appendage closure

Context The left atrial appendage (LAA) has been suggested to be the dominant location of thrombus in atrial fibrillation (AF) and has led to the development of LAA occlusion as a therapeutic modality to reduce stroke risk. However, the patient populations that would benefit most from this therapy are not well defined. Objective A systematic review was performed to better define subgroups amenable to appendage closure. Data sources The English scientific literature was searched using Pubmed through to March 1, 2011. Reference lists of relevant and review articles were screened to retrieve additional articles. Study selection Studies were only included if they described the location of thrombus in left atrium. Case reports and case series describing less than 10 thrombi were excluded. Data extraction Two reviewers independently extracted data and assessed quality of each study. Results A total of 34 studies reporting on the location of atrial thrombus in patients with AF were included: 17 in valvular AF, 10 non-valvular AF and 8 in mixed valvular and non-valvular AF. Atrial thrombi were located outside the LAA in 56% (95% CI 53, 60) of valvular AF, 22% (95% CI 19, 25) in mixed cohorts and 11% (95% CI 6, 15) non-valvular AF. In non valvular AF, the studies with higher proportion of thrombi in the left atrial cavity had non-anticoagulated patients and a greater proportion of ventricular dysfunction and history of stroke. Conclusion The location of atrial thrombus in patients with AF is dependent on the underlying substrate. In valvular AF, more than half the thrombi are located in the left atrial cavity. In the non-valvular AF group, a smaller proportion of thrombi were located outside the appendage. However, in certain subgroups (ie. non anti-coagulated, left ventricular dysfunction or prior stroke) the chances of left atrial cavity thrombus are higher.

High-density mapping of ventricular scar: a comparison of ventricular tachycardia (VT) supporting channels with channels that do not support VT.

Background—Surviving myocytes within scar may form channels that support ventricular tachycardia (VT) circuits. There are little data on the properties of channels that comprise VT circuits and those that are non-VT supporting channels. Methods and Results—In 22 patients with ischemic cardiomyopathy and VT, high-density mapping was performed with the PentaRay catheter and Ensite NavX system during sinus rhythm. A channel was defined as a series of matching pace-maps with a stimulus (S) to QRS time of ≥40 ms. Sites were determined to be part of a VT channel if there were matching pace-maps to the VT morphology. This was confirmed with entrainment mapping when possible. Of the 238 channels identified, 57 channels corresponded to an inducible VT. Channels that were part of a VT circuit were more commonly located within dense scar than non-VT channels (97% versus 82%; P=0.036). VT supporting channels were of greater length (mean±SEM, 53±5 versus 33±4 mm), had higher longest S-QRS (130±12 versus 82±12 ms), longer conduction time (103±14 versus 43±13 ms), and slower conduction velocity (0.87±0.23 versus 1.39±0.21 m/s) than non-VT channels (P<0.001). Of all the fractionated, late, and very late potentials located in scar, only 21%, 26%, and 29%, respectively, were recorded within VT channels. Conclusions—High-density mapping shows substantial differences among channels in ventricular scar. Channels supporting VT are more commonly located in dense scar, longer than non-VT channels, and have slower conduction velocity. Only a minority of scar-related potentials participate in the VT supporting channels.

Autonomic modulation of repolarization instability in patients with heart failure prone to ventricular tachycardia

QT variability (QTV) signifies repolarization lability, and increased QTV is a risk predictor for sudden cardiac death. The aim of the present study was to investigate the role of autonomic nervous system activity on QTV. This study was performed in 29 subjects: 10 heart failure (HF) patients with spontaneous ventricular tachycardia [HFVT(+)], 10 HF patients without spontaneous VT [HFVT(-)], and 9 subjects with structurally normal hearts (HNorm). The beat-to-beat QT interval was measured on 3-min records of surface ECGs at baseline and during interventions (atrial pacing and esmolol, isoprenaline, and atropine infusion). Variability in QT intervals was expressed as the SD of all QT intervals (SDQT). The ratio of the SDQT to SD of RR intervals (SDRR) was calculated as an index of QTV normalized to heart rate variability. There was a trend toward a higher baseline SDQT-to-SDRR ratio in the HFVT(+) group compared with the HFVT(-) and HNorm groups (P = 0.09). SDQT increased significantly in the HFVT(+) and HFVT(-) groups compared with the HNorm group during fixed-rate atrial pacing (P = 0.008). Compared with baseline, isoprenaline infusion increased SDQT in HNorm subjects (P = 0.02) but not in HF patients. SDQT remained elevated in the HFVT(+) group relative to the HNorm group despite acute β-adrenoceptor blockade with esmolol (P = 0.02). In conclusion, patients with HF and spontaneous VT have larger fluctuations in beat-to-beat QT intervals. This appears to be a genuine effect that is not solely a consequence of heart rate variation. The effect of acute autonomic nervous system modulation on QTV appears to be limited in HF patients.

Mapping and Ablation of the Pulmonary Veins and Cavo-Tricuspid Isthmus With a Magnetic Resonance Imaging-Compatible Externally Irrigated Ablation Catheter and Integrated Electrophysiology System

Background— Magnetic resonance imaging (MRI)–guided interventional electrophysiology (EP) has rapidly emerged as a promising alternative to x-ray–guided ablation. We aimed to evaluate an externally irrigated MRI-compatible ablation catheter and integrated EP pacing and recording system, testing the feasibility of pulmonary vein and cavo-tricuspid isthmus ablation. Methods and Results— Externally irrigated MRI-compatible ablation and diagnostic EP catheters and an integrated EP recording system (Imricor Medical Systems, Burnsville, MN) were tested in n=11 sheep in a 1.5-T MRI scanner. Power-controlled (40 W, 120-second duration) lesions were formed at the pulmonary vein and cavo-tricuspid isthmus. Real-time intracardiac electrograms were recorded during MRI. Steady-state free precession non–breath-hold images were repeatedly acquired to guide catheter navigation. Lesion visualization was performed using noncontrast (T2-weighted turbo spin echo pulse sequence) and gadolinium-diethylene triamine pentaacetic acid–enhanced T1-weighted imaging (inversion-recovery gradient echo pulse sequence). Catheters were able to be visualized and navigated under cardiovascular magnetic resonance guidance. In total, 8±2.5 lesions (radiofrequency time, 16±4.2 minutes) were formed at the pulmonary vein ostia, and 6.5±1.3 lesions (radiofrequency time, 13±2.2 minutes) were formed at the cavo-tricuspid isthmus, with the end point of bidirectional block. The mean procedure time was 150±55 minutes. Lesion visualization with both T2W imaging and contrast-enhanced imaging correlated with sites of injury at autopsy. Conclusions— These data demonstrate the feasibility of using multiple catheters, an integrated EP pacing and recording system, and externally irrigated ablation with cardiovascular magnetic resonance guidance to undertake clinically relevant biatrial mapping and ablation.

Mapping and Ablation of the Pulmonary Veins and Cavo-Tricuspid Isthmus with an MRI Compatible Externally-Irrigated Ablation Catheter and Integrated Electrophysiology System

Background— Magnetic resonance imaging (MRI)–guided interventional electrophysiology (EP) has rapidly emerged as a promising alternative to x-ray–guided ablation. We aimed to evaluate an externally irrigated MRI-compatible ablation catheter and integrated EP pacing and recording system, testing the feasibility of pulmonary vein and cavo-tricuspid isthmus ablation. Methods and Results— Externally irrigated MRI-compatible ablation and diagnostic EP catheters and an integrated EP recording system (Imricor Medical Systems, Burnsville, MN) were tested in n=11 sheep in a 1.5-T MRI scanner. Power-controlled (40 W, 120-second duration) lesions were formed at the pulmonary vein and cavo-tricuspid isthmus. Real-time intracardiac electrograms were recorded during MRI. Steady-state free precession non–breath-hold images were repeatedly acquired to guide catheter navigation. Lesion visualization was performed using noncontrast (T2-weighted turbo spin echo pulse sequence) and gadolinium-diethylene triamine pentaacetic acid–enhanced T1-weighted imaging (inversion-recovery gradient echo pulse sequence). Catheters were able to be visualized and navigated under cardiovascular magnetic resonance guidance. In total, 8±2.5 lesions (radiofrequency time, 16±4.2 minutes) were formed at the pulmonary vein ostia, and 6.5±1.3 lesions (radiofrequency time, 13±2.2 minutes) were formed at the cavo-tricuspid isthmus, with the end point of bidirectional block. The mean procedure time was 150±55 minutes. Lesion visualization with both T2W imaging and contrast-enhanced imaging correlated with sites of injury at autopsy. Conclusions— These data demonstrate the feasibility of using multiple catheters, an integrated EP pacing and recording system, and externally irrigated ablation with cardiovascular magnetic resonance guidance to undertake clinically relevant biatrial mapping and ablation.

Brugada Pattern in Toxic Myocarditis due to Severe Aluminum Phosphide Poisoning

Brugada pattern electrocardiogram (ECG) unmasking can occur due to various drugs. There are old reports of the acute infarction pattern in aluminum phosphide (rodenticide)‐related toxic myocarditis. The given case illustrates the Brugada pattern and various other ECG abnormalities in a patient with this poisoning. The old reported cases of the acute infarction pattern are also likely the Brugada pattern.

Results of Radiofrequency Ablation of Permanent Atrial Fibrillation of > 2 Years Duration and Left Atrial Size >5 cm Using 2-mm Irrigated Tip Ablation Catheter and Targeting Areas of Complex Fractionated Atrial Electrograms

Complex fractionated atrial electrograms (CFAEs) have shown promise as target sites for ablation of atrial fibrillation (AF); however, the data are limited with regard to patients with a large left atrium (LA) (>5 cm), and/or a permanent AF duration of >2 years. We tested the hypothesis that ablation of user-defined, computer-generated CFAE and pulmonary vein isolation, without additional lines would help long-term maintenance of sinus rhythm (SR). A total of 21 patients, 9 men and 12 women, aged 32 to 78 years (mean 44 +/- 3.3) were selected. All had chronic AF for >2 years (range 2 to 20; mean 3.8) and a LA of 5.3 to 11.3 cm (mean 6.4 cm). The underlying structural heart disease was rheumatic mitral valve disease in 18, aortic stenosis in 1, and hypertension in 2. Mapping and ablation was done using the NAVx Ensite system and a 2-mm-tip IBI Therapy Cool Path ablation catheter. The target included circumferential pulmonary vein ablation and elimination of areas in the LA and proximal coronary sinus showing CFAEs. During ablation, 3 patients converted to SR. In 15 others, significant organization of the atrial activity occurred. They then underwent successful electrical cardioversion. Three patients showed no change in atrial activity nor had electrical cardioversion. No procedural complications occurred. Patients took oral amiodarone for 3 months after the procedure. At 3 to 12 months (mean 9.8) of follow-up, 3 patients who were in AF at the end of the ablation procedure continued to be in AF. Of the rest, all but 3 were able to maintain SR without antiarrhythmic drugs. In conclusion, ablation using a 2-mm tip irrigation catheter, targeting user-defined CFAEs and pulmonary vein isolation facilitated maintenance of SR in most patients with a LA >5 cm and an AF duration of >2 years.

Development of Time- and Voltage-Domain Mapping (V-T-Mapping) to Localize Ventricular Tachycardia Channels During Sinus Rhythm

Background—In ventricular scar, impulse spread is slow because it traverses split and zigzag channels of surviving muscle. We aimed to evaluate scar electrograms to determine their local delay (activation time) and inequality in voltage splitting (entropy), and their relationship to channels. We reasoned that unlike innocuous channels, which are often short with multiple side branches, ventricular tachycardia (VT) supporting channels have very slow impulse spread and possess low entropy because of their longer protected length and relative lack of side-branching. Methods and Results—Patients with ischemic cardiomyopathy and multiple VT were studied. In initial mapping stage (16 patients and 58 VTs), left ventricular endocardial mapping was performed in sinus rhythm. Detailed pace mapping was used to identify VT channels and confirmed, when feasible, by entrainment. Scar electrograms were analyzed in time and voltage domains to determine mean activation time, dispersion in activation time, and entropy. Predictive performances of these properties to detect VT channels were tested. In the application stage (7 patients and 20 VTs), these properties were prospectively tested to guide catheter ablation. A mean number of 763±203 sampling points were taken. From 1770 pace maps, 47 channels corresponded to VTs. A combination of scar electrograms with the latest mean activation time and minimum entropy, in a high activation dispersion region, accurately recognized regions containing VT channels (&kgr;=0.89, sensitivity=86%, specificity=100%, positive predictive value=93%, and negative predictive value=100%). Finally, focused ablation within 5-mm rim of the prospective channel regions eliminated 18 of 20 inducible VTs. Conclusions—Activation time and entropy mapping in the scar accurately identify VT channels during sinus rhythm. The method integrates principles of reentry formation to recognize VT channels without pace mapping or mapping during VT.

Interactive real-time mapping and ablation of the pulmonary veins and cavotricuspid isthmus in an ovine model with an externally-irrigated MRI-compatible ablation catheter

Summary In recent years MRI-guided interventional electrophysiology (EP) has rapidly emerged as a promising alternative to conventional X-ray guided ablation. We present a novel MRI-compatible electrophysiologic ablation and recording system, performing realistic biatrial simulated procedures. Background To date, preclinical studies evaluating MRI-guided ablation have used non-irrigated catheters limited to test lesions in the right heart. Modern complex EP procedures require externally irrigated catheters to produce adequate lesion depth. We present the first feasibility study of an externally-irrigated MRI-compatible ablation catheter, and integrated EP pacing and recording system. We demonstrate the feasibility of pulmonary vein (PV) and cavotricuspid isthmus (CTI) ablation, the targets of ablation in atrial fibrillation and typical atrial flutter respectively. Methods An externally irrigated MRI-compatible ablation and diagnostic electrophysiology catheters and integrated EP recording system (Imricor Medical Systems, Burnsville, MN) were tested in n=11 sheep, in a 1.5T MRI scanner. The diagnostic catheters were placed in the coronary sinus, and right ventricula ra pex. Power controlled (40W, 120 second duration) lesions were formed at the pulmonary veins and cavotricuspid isthmus with the ablation catheter. Real-time intracardiac electrograms were recorded during MR imaging. Steady state free precession (SSFP) non-breath-hold images were repeatedly acquired to guide the catheter to the target region using passive catheter tracking. Markers in the catheter were used to ensure adequate visualization of the catheter. Lesion visualization was performed using both noncontrast (T2-weighted turbo spin echo pulse sequence) and gadolinium-DTPA enhanced T1-weighted imaging (inversion-recovery gradient echo pulse sequence).