Kevin F. Kwaku

Noninvasive Sudden Death Risk Stratification by Ambulatory ECG-Based T-Wave Alternans Analysis: Evidence and Methodological Guidelines

Extensive experimental and clinical evidence supports the utility of T‐wave alternans (TWA) as a marker of risk for ventricular fibrillation. This entity appears to reflect the fundamental arrhythmogenic property of enhanced dispersion of repolarization. This relationship probably accounts for its relative ubiquity in patients with diverse types of cardiac disease, as has been recognized with the development of analytical tools. A basic premise of this review is that ambulatory ECG monitoring of TWA as patients experience the provocative stimuli of daily activities can expose latent electrical instability in individuals at heightened risk for arrhythmias. We will discuss the literature that supports this concept and summarize the current state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA for arrhythmia risk stratification. The dynamic, nonspectral modified moving average analysis method for assessing TWA, which is compatible with ambulatory ECG monitoring, is described along with methodological guidelines for its implementation. Finally, the rationale for combined monitoring of autonomic markers along with TWA will be presented.

Effect of Ranolazine on Ventricular Vulnerability and Defibrillation Threshold in the Intact Porcine Heart

Introduction: Extensive in vitro studies and clinical evidence (MERLIN trial) indicate an antiarrhythmic potential of ranolazine, a novel antianginal agent. Programmed electrophysiologic testing was performed to quantify ranolazines effects on ventricular vulnerability and defibrillation thresholds and to gain insights into mechanisms.

T‐Wave Alternans: Does Size Matter

In the current issue, Klingenheben, Ptaszynski, and Hohnloser1 resurface an important question relevant to employing T-wave alternans (TWA) analysis for sudden death risk stratification. Specifically, they explore the possibility that quantitative assessment of the magnitude of TWA may provide complementary information beyond the results of a standardized cutpoint for a positive microvolt TWA (MTWA) test. The concept that the magnitude of TWA may be important is supported by multiple experimental studies demonstrating that higher TWA levels are associated with greater likelihood of ventricular fibrillation.2-5 Moreover, TWA undergoes an orderly progression in magnitude en route to ventricular fibrillation that includes discordant TWA, T-wave multupling, and more complex oscillatory behavior.6 The importance of TWA magnitude clinically is suggested by a prospective analysis of archived ambulatory ECG records demonstrating that patients with a recent myocardial infarction who subsequently experienced cardiac arrest or arrhythmic death exhibited higher levels of TWA at 8:00 a.m. and during periods of peak activity indicated by maximum heart rates than did matched study participants without subsequent events.7 TWA magnitude is also elevated in patients with implantable cardioverter defibrillators (ICDs) but not in normal volunteers in response to mental stress as well as to mild and maximum exercise.8 Kodama and coworkers9 recently reported that TWA was sufficiently large as to be visible in 8–10% of patients with cardiomyopathy, especially during episodes of emerging tachycardia or adrenergic stimulation with dobutamine. Raeder and coworkers10 and Hohnloser11 reported cases of spontaneous ventricular fibrillation emerging from a background of macroscopic TWA during telemetered clinical monitoring. The current practice of using a TWA cutpoint to determine risk for arrhythmic death emerged from pioneering studies of over a decade ago, which demonstrated that spectral methods used to detect subtle nonvisible levels of TWA provided predictive information equivalent to electrophysiologic testing in estimating arrhythmia-free survival in patients with a

Typical AVNRT—An Update on Mechanisms and Therapy

Typical atrioventricular reentrant tachycardia (AVNRT) is the most common paroxysmal supraventricular tachycardia among adults, and accounts for considerable morbidity. The concept of dual pathway physiology remains useful, although this physiology likely results from the functional properties of anisotropic tissue within the triangle of Koch, rather than anatomically distinct tracts of conduction. Also, there remains debate regarding whether the critical reentrant circuit path requires participation of the atrium. In our opinion, current evidence favors functional anisotropic reentry limited to the subatrial tissues as the arrhythmia mechanism. Reasons for this are reviewed. Fortunately, typical AVNRT is readily amenable to definitive therapy by catheter-based radiofrequency energy delivery at the so-called slow pathway region located at the posterior Triangle of Koch. Anterior or left-sided approaches are very rarely indicated. Results from multiple series have shown this strategy to be both safe and effective, therefore ablation therapy should now be considered as the definitive therapy of choice for the majority of patients.

Suppression of calcium-induced repolarization heterogeneity as a mechanism of nitroglycerin's antiarrhythmic action

Abstract: This study examined whether the antifibrillatory action of nitroglycerin (NTG) is attributable to reduction in calcium-induced heterogeneity of repolarization independent of autonomic and coronary vasodilatory influences. The effects of intrapericardial (IPC) NTG on coronary blood flow, contractility, repolarization, and arrhythmia susceptibility were measured in anesthetized pigs (N = 43). Autonomic influences were minimized by vagotomy and β-adrenergic blockade (metoprolol, 1.25 mg/kg, intravenous). Electrophysiological parameters were tested at 30 min, a time when coronary hemodynamics had returned to baseline. Intracoronary calcium chloride (CaCl2, 50-mg bolus) injection augmented contractility (dP/dtmax, 1760 ± 144 to 2769 ± 274 mmHg/s, and following NTG, 1531 ± 384 to 2138 ± 242 mmHg/s, P < 0.0002), reflecting increased myocardial intracellular calcium. Calcium increased repolarization heterogeneity (interlead precordial T-wave heterogeneity, 95 ± 15 to 264 ± 33 μV, P < 0.006; Tpeak−Tend, an index of transmural dispersion of repolarization, 37 ± 3 to 76 ± 6 ms, P < 0.05) and lowered repetitive extrasystole threshold (RET; 24 ± 2 to 13 ± 1 mA, and following NTG, 32 ± 4 to 18 ± 1 mA, P < 0.0001). IPC NTG raised the RET from baseline by 33% and blunted calcium-induced contractility (dP/dtmax by 23%, P < 0.05), repolarization changes (T-wave heterogeneity by 24%, P < 0.006; Tpeak−Tend by 18%, P = 0.04), and arrhythmia vulnerability (RET by 39%, P < 0.003). Thus, the capacity of NTG to suppress calcium-induced repolarization heterogeneity is an important mechanism of its antiarrhythmic action, which is independent of autonomic and vasodilatory actions.

Delayed occurrence of unheralded phase IV complete heart block after ethanol septal ablation for symmetric hypertrophic obstructive cardiomyopathy.

Ethanol septal ablation has emerged as a less invasive alternative to surgical myomectomy for treatment of asymmetric hypertrophic obstructive cardiomyopathy (ASH). The procedure has very low mortality, but high‐degree AV conduction block is a frequent complication. Prior studies have documented baseline left bundle branch block and high volume of ethanol injection (greater than 4 mL) as risk factors. Complete heart block is often preceded by postprocedure conduction abnormalities and generally develops within 48 hours after ethanol ablation. We present a unique case of a patient with symmetric hypertensive hypertrophic obstructive cardiomyopathy (SHOCM) who developed phase IV complete heart block >96 hours postprocedure without preceding conduction abnormalities or other classic risk factors. 3

Atrioventricular Nodal Reentrant Tachycardia in Two Siblings with Wolfram Syndrome

This is a case of two siblings with the autosomal recessive Wolfram syndrome who both have documented atrioventricular nodal reentrant tachycardia (AVNRT). This is the first report to our knowledge that links AVNRT to a syndrome in which the putative gene has been identified.

Cell Therapy for Rate Control in Atrial Fibrillation A New Approach to an Old Problem

Physicians and patients alike have long sought ways by which to tame the rapid and irregular heartbeats that typically accompany atrial fibrillation (AF). In addition to offering symptomatic relief from palpitations, this goal has gained further importance since the recognition that sustained rapid, and perhaps also irregular, ventricular rates can lead to adverse structural cardiac remodeling and the development of a tachycardia-induced cardiomyopathy.1 In many instances, maintenance of sinus rhythm is either impractical or unachievable, and in addition to therapeutic anticoagulation, most patients will require some strategy to control their ventricular rate during AF. Article p 2485 The mainstays of pharmacological rate control for AF have remained unchanged for decades and consist of digoxin, β-blockers, and the nondihydropyridine calcium channel antagonists verapamil and diltiazem alone or in combination.2,3 However, medical treatment often is limited by a lack of efficacy or intolerance of side effects. Research involving novel agents such as selective A1 adenosine agonists4,5 remains in early stages and is unlikely to overcome the drawbacks of currently available drugs. A nearly 100% efficacious approach to ventricular rate control in AF is catheter-based radiofrequency ablation of the AV junction (AVJ).6,7 Experimentally, the same result is achievable with cryoablation,8 laser energy,9 or ethanol infusion into the AV nodal artery.10 Although appropriate in selected patients,6,11–13 radiofrequency AVJ ablation has the distinct disadvantage of rendering them permanently pacemaker dependent. An increased risk of tachyarrhythmic sudden death after AVJ ablation may be countered by pacing at higher rates early after the procedure; however, concerns exist over the potential long-term hemodynamic consequences of obligate right ventricular pacing, particularly in the presence of preexisting heart failure.14–17 A notionally more appealing procedure is catheter-based radiofrequency AVJ modification18; however, a high rate of unintended AV implantation …