Peter Spector

Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: two systematic literature reviews and meta-analyses

Background—Although radiofrequency catheter ablation (RFA) has evolved from an experimental procedure to an important treatment option for atrial fibrillation, the relative safety and efficacy of catheter ablation relative to that of antiarrhythmic drug (AAD) therapy has not been established. Methods and Results—Two separate systematic reviews were conducted: one on RFA and the other on AAD to provide accurate and broadly representative estimates of the clinical efficacy and safety of both therapies in the treatment of atrial fibrillation. Electronic searches were conducted in EMBASE and MEDLINE from 1990 to 2007. For the RFA review, all study designs were accepted. For the AAD review, articles were limited to prospective studies on the following drugs of interest: amiodarone, dofetilide, sotalol, flecainide, and propafenone. Data were extracted by 1 reviewer, with a second reviewer performing independent confirmation of extracted data. Sixty-three RFA and 34 AAD studies were included in the reviews. Patients enrolled in RFA studies tended to be younger (mean age, 55 versus 62 years), had longer duration of atrial fibrillation (6.0 versus 3.1 years), and had failed a greater number of prior drug trials (2.6 versus 1.7). The single-procedure success rate of ablation off AAD therapy was 57% (95% CI, 50% to 64%), the multiple procedure success rate off AAD was 71% (95% CI, 65% to 77%), and the multiple procedure success rate on AAD or with unknown AAD usage was 77% (95% CI, 73% to 81%). In comparison, the success rate for AAD therapy was 52% (95% CI, 47% to 57%). A major complication of catheter ablation occurred in 4.9% of patients. Adverse events for AAD studies, although more common (30% versus 5%), were less severe. Conclusions—Studies of RFA for treatment of atrial fibrillation report higher efficacy rates than do studies of AAD therapy and a lower rate of complications.Background— Although radiofrequency catheter ablation (RFA) has evolved from an experimental procedure to an important treatment option for atrial fibrillation, the relative safety and efficacy of catheter ablation relative to that of antiarrhythmic drug (AAD) therapy has not been established. Methods and Results— Two separate systematic reviews were conducted: one on RFA and the other on AAD to provide accurate and broadly representative estimates of the clinical efficacy and safety of both therapies in the treatment of atrial fibrillation. Electronic searches were conducted in EMBASE and MEDLINE from 1990 to 2007. For the RFA review, all study designs were accepted. For the AAD review, articles were limited to prospective studies on the following drugs of interest: amiodarone, dofetilide, sotalol, flecainide, and propafenone. Data were extracted by 1 reviewer, with a second reviewer performing independent confirmation of extracted data. Sixty-three RFA and 34 AAD studies were included in the reviews. Patients enrolled in RFA studies tended to be younger (mean age, 55 versus 62 years), had longer duration of atrial fibrillation (6.0 versus 3.1 years), and had failed a greater number of prior drug trials (2.6 versus 1.7). The single-procedure success rate of ablation off AAD therapy was 57% (95% CI, 50% to 64%), the multiple procedure success rate off AAD was 71% (95% CI, 65% to 77%), and the multiple procedure success rate on AAD or with unknown AAD usage was 77% (95% CI, 73% to 81%). In comparison, the success rate for AAD therapy was 52% (95% CI, 47% to 57%). A major complication of catheter ablation occurred in 4.9% of patients. Adverse events for AAD studies, although more common (30% versus 5%), were less severe. Conclusions— Studies of RFA for treatment of atrial fibrillation report higher efficacy rates than do studies of AAD therapy and a lower rate of complications. Received October 6, 2008; accepted April 28, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

The temporal variability of dominant frequency and complex fractionated atrial electrograms constrains the validity of sequential mapping in human atrial fibrillation

BACKGROUND It has been proposed that sequential mapping of dominant frequency (DF) and complex fractionated atrial electrograms (CFAE) can identify target sites for ablation of atrial fibrillation (AF). These mapping strategies are valid only if DF and CFAE are temporally stable on the timescale of the mapping procedure. We postulate that DF and CFAE are temporally variable; consequently, sequential mapping can be misleading. OBJECTIVE To make prolonged spatially stable multielectrode recordings to assess the temporal stability of DF and CFAE. METHODS We recorded electrical activity for 5 minutes with the use of a 64-electrode basket catheter placed in the left atrium of 18 patients presenting for AF ablation. DF and CFAE were determined off-line, and their temporal variability was quantified. Maps created from simultaneous versus sequentially acquired data were compared. RESULTS DF was temporally variable: the average temporal coefficient of variation was 22.7% +/- 5.4%. DF sites were transient, meeting criteria for only 22.1 seconds out of 5 minutes. Similarly, CFAEs were transient (average duration of CFAE 8.8 +/- 11.3 seconds). DF and CFAE sequential maps failed to identify 93.0% +/- 12.4% and 35.9% +/- 14.9% of DF and CFAE sites, respectively. CONCLUSION Because of temporal variability, sequential DF and CFAE maps do not accurately reflect the spatial distribution of excitation frequency during any given sampling interval. The spatial distribution of DF and CFAE sites on maps created with sequential point acquisition depends upon the time at which each site is sampled.

Emergence of complex behavior: an interactive model of cardiac excitation provides a powerful tool for understanding electric propagation.

We have developed a straightforward, physiologically based mathematical in silico model of cardiac electric activity to facilitate understanding of the fundamental principles that determine how excitation propagates through the heart. Despite its simplicity, the model provides a very powerful teaching tool. In fact, its simplicity is integral to the models utility. The contrast between the minimal set of rules that govern the models function and the widely varied complex behaviors it can manifest offers insight into the nature of emergent behavior in wave propagation. Emergence in this context refers to the richness of the tissue activation patterns that arise from the aggregate behavior of the simple cells that comprise the tissue. Each cell can be active, inactive, or refractory and interacts only with its immediate neighbors. From these simple building blocks, very elaborate global behaviors emerge. From the perspective of the electrophysiology student, the notion of emergent properties can act as a Rosetta stone for deciphering electrophysiological behavior. The spread of electric excitation through the intricate 3D structure of the heart can take widely varied forms, ranging from the orderly propagation seen during sinus rhythm to the marked disorganization seen during ventricular fibrillation. Observation of the diverse and sometimes complex patterns of conduction (eg, unidirectional block, reentry, spiral waves) as well as the responses to pacing maneuvers (eg, entrainment) suggests to the electrophysiology student a nearly infinite array of possibilities, the mastery of which can be daunting. However, with study, it becomes apparent that one need not memorize every possible cardiac behavior. Instead, there are overarching principles of cardiac excitation and propagation1 from which these varied phenomena emerge and through which one can understand and predict rather than memorize electrophysiological behavior. Understanding these fundamental principles is integral to mastering electrophysiology. A framework for interpreting clinical observations predicated on these …

Ablation of multi-wavelet re-entry: general principles and in silico analyses

AIMS Catheter ablation strategies for treatment of cardiac arrhythmias are quite successful when targeting spatially constrained substrates. Complex, dynamic, and spatially varying substrates, however, pose a significant challenge for ablation, which delivers spatially fixed lesions. We describe tissue excitation using concepts of surface topology which provides a framework for addressing this challenge. The aim of this study was to test the efficacy of mechanism-based ablation strategies in the setting of complex dynamic substrates. METHODS AND RESULTS We used a computational model of propagation through electrically excitable tissue to test the effects of ablation on excitation patterns of progressively greater complexity, from fixed rotors to multi-wavelet re-entry. Our results indicate that (i) focal ablation at a spiral-wave core does not result in termination; (ii) termination requires linear lesions from the tissue edge to the spiral-wave core; (iii) meandering spiral-waves terminate upon collision with a boundary (linear lesion or tissue edge); (iv) the probability of terminating multi-wavelet re-entry is proportional to the ratio of total boundary length to tissue area; (v) the efficacy of linear lesions varies directly with the regional density of spiral-waves. CONCLUSION We establish a theoretical framework for re-entrant arrhythmias that explains the requirements for their successful treatment. We demonstrate the inadequacy of focal ablation for spatially fixed spiral-waves. Mechanistically guided principles for ablating multi-wavelet re-entry are provided. The potential to capitalize upon regional heterogeneity of spiral-wave density for improved ablation efficacy is described.

Principles of Cardiac Electric Propagation and Their Implications for Re-entrant Arrhythmias

The study of clinical electrophysiology essentially comprises examining how electric excitation develops and spreads through the millions of cells that constitute the heart. Given the enormous number of cells in a human heart, there is an extremely large number of possible ways that the heart can behave. We encounter rhythms across the spectrum from the organized and orderly behavior of sinus rhythm through repetitive continuous excitation (via reentry) in structurally defined circuits like atrial flutter and, finally, the complex, dynamic, and disorganized behavior of fibrillation. Despite these myriad possibilities, one can apply a basic understanding of the principles of propagation to predict how cardiac tissue will behave under varied circumstances and in response to various manipulations. In this article, we review the principles of propagation and how these can be used to understand reentry of all degrees of complexity. We use these principles to explain the mechanisms by which antiarrhythmic medications and ablation can terminate and prevent reentry. This article is not intended to be an exhaustive description of the physiology of cardiac propagation, rather, it is meant to capture the essence of propagation with sufficient detail to provide an intuitive feel for the interplay of the physiological features relevant to propagation. The figures and videos used in this article were created using a computational model of cardiac propagation (VisibleEP LLC, Colchester, VT). It is a hybrid between a physics-based and cellular automaton model. The model incorporates the fundamental features of propagation without modeling individual ion channels.1 The model manifests several relevant emergent properties, for example, electrotonic interactions, restitution of action potential duration, and conduction velocity as well as source–sink balance–dependent propagation. ### Cell Excitation A cell becomes excited when the balance of inward and outward currents passes a critical point after which inward currents exceed outward and an action potential ensues. …

Ablation of Multiwavelet Re-entry Guided by Circuit-Density and Distribution Maximizing the Probability of Circuit Annihilation

Background—A key mechanism responsible for atrial fibrillation is multiwavelet re-entry (MWR). We have previously demonstrated improved efficiency of ablation when lesions were placed in regions of high circuit-density. In this study, we undertook a quantitative assessment of the relative effect of ablation on the probability of MWR termination and the inducibility of MWR, as a function of lesion length and circuit-density overlap. Methods and Results—We used a computational model to simulate MWR in tissues with (and without) localized regions of decreased action potential duration and increased intercellular resistance. We measured baseline circuit-density and distribution. We then assessed the effect of various ablation lesion sets on the inducibility and duration of MWR as a function of ablation lesion length and overlap with circuit-density. Higher circuit-density reproducibly localized to regions of shorter wavelength. Ablation lines with high circuit-density overlap showed maximum decreases in duration of MWR at lengths equal to the distance from the tissue boundary to the far side of the high circuit-density region (high-overlap, −43.5% [confidence interval, −22.0% to −65.1%] versus low-overlap, −4.4% [confidence interval, 7.3% to −16.0%]). Further ablation (beyond the length required to cross the high circuit-density region) provided minimal further reductions in duration and increased inducibility. Conclusions—Ablation at sites of high circuit-density most efficiently decreased re-entrant duration while minimally increasing inducibility. Ablation lines delivered at sites of low circuit-density minimally decreased duration yet increased inducibility of MWR.Background— A key mechanism responsible for atrial fibrillation is multiwavelet re-entry (MWR). We have previously demonstrated improved efficiency of ablation when lesions were placed in regions of high circuit-density. In this study, we undertook a quantitative assessment of the relative effect of ablation on the probability of MWR termination and the inducibility of MWR, as a function of lesion length and circuit-density overlap. Methods and Results— We used a computational model to simulate MWR in tissues with (and without) localized regions of decreased action potential duration and increased intercellular resistance. We measured baseline circuit-density and distribution. We then assessed the effect of various ablation lesion sets on the inducibility and duration of MWR as a function of ablation lesion length and overlap with circuit-density. Higher circuit-density reproducibly localized to regions of shorter wavelength. Ablation lines with high circuit-density overlap showed maximum decreases in duration of MWR at lengths equal to the distance from the tissue boundary to the far side of the high circuit-density region (high-overlap, −43.5% [confidence interval, −22.0% to −65.1%] versus low-overlap, −4.4% [confidence interval, 7.3% to −16.0%]). Further ablation (beyond the length required to cross the high circuit-density region) provided minimal further reductions in duration and increased inducibility. Conclusions— Ablation at sites of high circuit-density most efficiently decreased re-entrant duration while minimally increasing inducibility. Ablation lines delivered at sites of low circuit-density minimally decreased duration yet increased inducibility of MWR.

Ablation using irrigated radiofrequency: A hands-on guide

t t e p e e ntroduction he advent of irrigated radiofrequency (RF) catheters has ed to the common misconception that irrigation somehow akes ablation both safer and more effective. In fact, this is ot true. Irrigation (or any other means of cooling the atheter tip) results in the ability to deliver greater energy nd as such can lead to steam pops, collateral damage, and hrombus formation. It is important to recognize that irrigaion allows greater energy delivery; it does not mandate it. he operator must determine the appropriate power settings, rrigant flow rates, and lesion duration for each ablation site. his requires balancing the competing demands of efficacy transmural tissue destruction) against those of safety avoidance of catheter or tissue overheating and/or collatral tissue heating). Current technological limitations reuire that these decisions be based on incomplete informaion about the tissue effects of ablation. We will review the iophysics of RF ablation and the role of irrigation to rovide a context for making rational decisions about the se of irrigated RF catheters.

The Impact of Pharmacologic Sympathetic and Parasympathetic Blockade on Atrial Electrogram Characteristics in Patients with Atrial Fibrillation

Background:  Ablation of atrial autonomic inputs exerts antifibrillatory effects. However, because ablation destroys both myocardium and nerve cells, the effect of autonomic withdrawal alone remains unclear. We therefore examined the effects of pharmacologic autonomic blockade (PAB) on frequency and fractionation in patients with atrial fibrillation (AF).

Pulmonary vein encircling ablation alters the atrial electrophysiologic response to autonomic stimulation

ObjectivePulmonary vein encircling ablation is often effective in the treatment of atrial fibrillation (AF). The success of the procedure does not depend upon creation of continuous lines of block. Thus mechanisms by which pulmonary vein encircling can cure AF remain unclear. Stimulation of cardiac autonomic ganglia alters atrial refractoriness and potentiates AF. We hypothesized that pulmonary vein encircling alters atrial autonomic function and that these alterations account in part for prevention of AF recurrences following ablation.MethodsAtrial effective refractory periods (ERP) and AF inducibility were quantified in ten dogs before and during central autonomic nerve stimulation. Pulmonary vein encircling ablation was then performed and electrophysiologic testing repeated. In two dogs subjected to sham procedures measurements were repeated without performance of ablation. Hearts were examined histologically.ResultsAutonomic nerve stimulation led to decreased atrial refractoriness and increased AF inducibility and duration. Each of these effects were attenuated following pulmonary vein encircling (e.g., mean ERP decreased before (−23.7 ± 1.8, p < 0.001) but not after ablation (−2.3 ± 1.9, p = 0.25); AF inducibility increased by 26% before vs. 5% after ablation). No attenuation was seen in the sham operated animals. Histologic analysis following pulmonary vein encircling demonstrated destruction of some but not all autonomic ganglia.ConclusionAutonomic stimulation shortens atrial refractory periods and potentiates AF. Pulmonary vein encircling ablation partially destroys atrial autonomic inputs, attenuates the refractory period shortening effect of autonomic stimulation and decreases AF inducibility. Destruction of autonomic ganglia may contribute to the anti-fibrillatory effects of pulmonary vein encircling and warrants further investigation.

On the ill-conditioned nature of the intracardiac inverse problem

Multi-electrode catheters can be placed transvenously and positioned on the atrial endocardial surface in order to sample the chaotic electrical activity taking place during atrial fibrillation. We consider here the possibility of placing an array of electrodes over a relatively small, and hence roughly planar, region of the atrial surface in order to examine local activity patterns. This provides a spatially coarse but temporally fine sampling of electrical activity that can be expressed at each point in time as the convolution of the true electrical excitation of the tissue with a hyperbolic point spread function. We demonstrate the deconvolution of sampled signals using a polynomial approximation of the true electrical activity. When the deconvolution is unconstrained the inverse problem is poorly conditioned, showing that a high spatial sampling rate is required for accurate reconstructions of atrial activity in the vicinity of the electrode array. We discuss ways in which the conditioning of the problem might be improved through the application of constraints on the solution.