Manoj N. Obeyesekere

Risk of Arrhythmia and Sudden Death in Patients With Asymptomatic Preexcitation A Meta-Analysis

Background— The incidence of sudden cardiac death (SCD) and the management of this risk in patients with asymptomatic preexcitation remain controversial. The purpose of this meta-analysis was to define the incidence of SCD and supraventricular tachycardia in patients with asymptomatic Wolff-Parkinson-White ECG pattern. Methods and Results— We performed a systematic search of prospective, retrospective, randomized, or cohort English-language studies in EMBASE and Medline through February 2011. Studies reporting asymptomatic patients with preexcitation who did not undergo ablation were included. Twenty studies involving 1869 patients met our inclusion criteria. Participants were primarily male with a mean age ranging from 7 to 43 years. Ten SCDs were reported involving 11 722 person-years of follow-up. Seven studies originated from Italy and reported 9 SCDs. The risk of SCD is estimated at 1.25 per 1000 person-years (95% confidence interval [CI], 0.57–2.19). A total of 156 supraventricular tachycardias were reported involving 9884 person-years from 18 studies. The risk of supraventricular tachycardia was 16 (95% CI, 10–24) events per 1000 person-years of follow-up. Children had numerically higher SCD (1.93 [95% CI, 0.57–4.1] versus 0.86 [95% CI, 0.28–1.75]; P=0.07) and supraventricular tachycardia (20 [95% CI, 12–31] versus 14 [95% CI, 6–25]; P=0.38) event rates compared with adults. Conclusion— The low incidence of SCD and low risk of supraventricular tachycardia argue against routine invasive management in most asymptomatic patients with the Wolff-Parkinson-White ECG pattern.

How to Perform and Interpret Provocative Testing for the Diagnosis of Brugada Syndrome, Long-QT Syndrome, and Catecholaminergic Polymorphic Ventricular Tachycardia

Sudden cardiac death (SCD) is predominantly related to coronary artery disease and its sequelae, cardiomyopathy, and congenital or valvular heart disease. No structural abnormalities are detectable in 5–8% of SCDs.1 Identified ion channelopathies such as Brugada syndrome, long-QT syndrome (LQTS), and catecholaminergic polymorphic ventricular tachycardia (CPVT) contribute to this incidence. The diagnosis requires a high level of suspicion because of a resting ECG that is often borderline, intermittently normal, or frankly normal. Genetic testing does not provide a simple solution to this issue, as it is often neither sensitive nor specific even when the phenotype points to a specific entity and may yield results that are difficult to interpret (ie, variants of unknown significance). Pharmacological and/or exercise testing by manipulation/stressing the cardiac action potential can accentuate the desired abnormality or provoke a characteristic arrhythmia response. A systematic approach to clinical testing that includes drug provocation results in unmasking of the cause of apparently unexplained aborted SCD in >50% of patients and is very helpful in directing genetic testing of the index case and family to diagnose genetically mediated arrhythmia syndromes.2 This review will seek to highlight the clinical utility of provocative testing and describe how to perform and interpret provocative testing for the diagnosis of Brugada syndrome, LQTS, and CPVT. ### Performing Provocative Testing Pharmacological challenge should be performed in an area that has comprehensive monitoring and resuscitation equipment (including an external cardioverter-defibrillator). Testing should be performed with continuous monitoring of the patient by adequately trained/experienced personnel in an area equipped with advance resuscitation equipment (including external defibrillator) and personnel trained in advance resuscitation and an expert physician promptly available. Given the potential risk for hemodynamically compromising ventricular arrhythmias during exercise stress testing (particularly when exercise stress testing for CPVT), we advise the presence of physically capable personnel to prevent the patient …

A Clinical Approach to Early Repolarization

The term early repolarization (ER) is defined electrocardiographically by either (1) a sharp well-defined positive deflection or notch immediately following a positive QRS complex at the onset of the ST-segment, or (2) slurring at the terminal part of the QRS complex (also termed J-waves or J-point elevation, Figure 1). Specifically, the ER pattern is present when J-point elevation of ≥0.1 mV is seen in 2 adjacent leads with either a slurred or notched morphology.1,2 Although ER was historically considered benign, this perception changed as numerous studies1–5 established an association with increased risk of death and idiopathic ventricular fibrillation (VF). The incidental discovery of early repolarization now poses numerous questions, including defining and quantitating the risk of sudden death. With the emerging reports of a genetic contribution, defining the genetic basis, inheritance, and the role of screening relatives broadens the implications of early repolarization beyond the index case. Insights into the molecular mechanism of early repolarization and therapeutic strategies continue to highlight its evolving significance. Figure 1. Prominent early repolarization manifest as inferior J-point slurring and lateral J-point notching each >2 mm in 2 contiguous leads. This review seeks to provide a concise summary of the current evidence surrounding these issues, contextualize its clinical significance, and present an approach to the clinical evaluation and management of these patients. This review will emphasize that the majority of individuals with ER are at no or minimal risk for arrhythmic events. In others the ER substrate may potentially increase arrhythmic risk associated with underlying cardiac pathology. Very rarely, clinicians will encounter individuals in whom ER is a manifestation of a primary arrhythmogenic disorder. The first study to seriously question the convention that ER is a benign phenomenon compared 206 patients with idiopathic VF with 412 healthy subjects,1 and demonstrated …

Risk of Sudden Death in Wolff-Parkinson-White Syndrome How High Is the Risk?

In 1930, Dr Louis Wolff, Sir John Parkinson, and Paul Dudley White described a case series of 11 patients with a syndrome that now bears their name.1 The first patient with a short PR interval, ventricular preexcitation, and supraventricular tachycardia was described by Cohn and Fraser in 1913.1 Wood et al postulated the accessory pathway (AP) as its anatomic substrate in 1942, and a large population series reported the prevalence of preexcitation to be 0.15% in 1962.2 Reports in 1971 and 1979 described sudden cardiac death (SCD) in patients with Wolff-Parkinson-White (WPW) syndrome related to atrial fibrillation (AF) that was conducted rapidly over the AP with a short refractory period that deteriorated into ventricular fibrillation (VF).3,4 The first operative ablation of an AP was performed by Sealy in 1967,1 whereas Weber and Schmitz described the first endocardial catheter ablation of an AP in 1983.1 The evolution of curative catheter ablation has clearly become the treatment of choice in the patient with substantive symptoms. A continuing controversy has been the use of this therapy in the asymptomatic or less symptomatic individual, and the central looming theme is the incidence of SCD as part of the natural history of this entity and our ability to predict it. The incidence of SCD in symptomatic patients with WPW syndrome was initially reported in the late 1960s and is estimated to be in the range of 0.25% per year, or 3% to 4% over a lifetime.5 Article see p 661 A number of risk factors for development of SCD have emerged,6 including (1) shortest preexcited RR interval (SPRRI) during AF4 and its surrogate, the antegrade effective refractory period (ERP) …

Tachycardia induction with ventricular extrastimuli differentiates atypical atrioventricular nodal reentrant tachycardia from orthodromic reciprocating tachycardia.

BACKGROUND Differentiating atypical atrioventricular nodal reentrant tachycardia (AVNRT) from septal orthodromic reentrant tachycardia (ORT(Septal)) is challenging in nonsustained tachycardia. When sustained, the postpacing interval minus tachycardia cycle length following entrainment (PPI(Entrainment) - TCL) and stimulation to atrial interval minus ventriculoatrial interval (Stim-A(Entrainment) - VA) are utilized. OBJECTIVE We hypothesized that the first tachycardia cycle after tachycardia induction with right ventricular apical extrastimulation would yield comparable information to entrainment, precluding the need for sustained tachycardia. METHODS Twenty-four patients with AVNRT (age 47 ± 18 years), 19 with ORT(Septal) (age 42 ± 17 years), and 15 with ORT over a left lateral accessory pathway (ORT(Left)) (age 41 ± 16 years) were included. The ventricular extrastimulus to atrial depolarization at tachycardia initiation (Stim-A(Initiation)) and tachycardia VA interval were measured to establish the Stim-A(Initiation) minus VA interval (Stim-A(Initiation) - VA). The ventricular extrastimulus to the subsequent right ventricular apical depolarization (postpacing interval at initiation, PPI(Initiation)) was utilized to obtain the PPI(Initiation) minus TCL (PPI(Initiation) - TCL). The AH interval associated with the PPI(Initiation) minus the AH in tachycardia was utilized to establish a corrected PPI(Initiation) minus TCL (cPPI(Initiation) - TCL). RESULTS The intervals after tachycardia initiation were longer for AVNRT than for ORT: mean PPI(Initiation) - TCL (193 ± 44 vs 91 ± 73; P <.001), cPPI(Initiation) - TCL (174 ± 44 ms vs 88 ± 50 ms; P <.001), and Stim-A(Initiation) - VA (161 ± 45 ms vs 69 ± 53 ms; P <.001). The correlation coefficient for Stim-A(Initiation) minus VA against Stim-A(Entrainment) minus VA was 0.79 and for cPPI(Initiation) minus TCL against PPI(Entrainment) minus TCL was 0.71. cPPI(Initiation) minus TCL <115 ms or Stim-A(Initiation) - VA <85 ms was observed only in ORT. The converse was observed in AVNRT but also in ORT(Septal) over decremental accessory pathways and ORT(Left). CONCLUSION Stim-A(Initiation) - VA < 85 ms or cPPI(Initiation) - TCL < 115 ms excludes AVNRT.

Management of Ventricular Arrhythmias in Suspected Channelopathies

Although structural heart disease remains the predominant substrate for ventricular arrhythmia, channelopathies including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndrome (ERS) are less common but important contributing entities. These etiologies require specific therapies potentially contrary to empirical management of arrhythmias associated with structural heart disease. Conventional therapy including antiarrhythmic drug therapy may not only fail to resolve unstable arrhythmias but worsen them. Additionally, channelopathy patients with implantable cardioverter defibrillators (ICD) and arrhythmic storms represent a major challenge, and the acute care team needs to be cognizant of unique circumstances that require specific acute therapies beyond empirical advanced life support algorithm recommendations.1 Successful and considered acute management of ventricular arrhythmias is contingent on a number of variables, including knowledge of the cardiac substrate or potential substrate; form, mechanism, and precipitants of ventricular arrhythmias; and acute effect of potential therapies. In the longer term, an understanding of the natural history of the channelopathy along with the efficacy of long-term therapy will lead to superior outcomes. This review will present the risk of ventricular arrhythmias associated with these uncommon entities, the evolving understanding of the mechanism of arrhythmia, and the mechanistic basis of therapies along with a clinical approach to summarize the evidence pertaining to acute and long-term management. Patients with a prolonged QT interval are at risk of sudden cardiac death (SCD) due to Torsade de Pointes (TdP; Figure 1). Most patients with congenital LQTS are asymptomatic and diagnosed incidentally on electrocardiogram screening or following family screening. However, syncope, aborted SCD, or SCD may be the first presentation. Most arrhythmic events in congenital LQT1 occur during physical or emotional stress, at rest or in association with sudden auditory stimulation in LQT2, and during sleep or rest in LQT3 …

Determination of inadvertent atrial capture during para-Hisian pacing.

Background— Inadvertent capture of the atrium will lead to spurious results during para-Hisian pacing. We sought to establish whether the stimulation-to-atrial electrogram interval at the proximal coronary sinus (stim-PCS) or high right atrium (stim-HRA) could signal inadvertent atrial capture. Methods and Results— Para-Hisian pacing with and without intentional atrial capture was performed in 31 patients. Stim-HRA and stim-PCS intervals were measured with atrial capture, His plus para-Hisian ventricular (H+V) capture, and para-Hisian ventricular (V) capture alone. The mean stim-HRA interval was significantly shorter with atrial capture (66±18 ms) than with H+V (121±27 ms, P<0.001) or V capture alone (174±38 ms, P<0.001). The mean stim-PCS interval was significantly shorter with atrial capture (51±16 ms) than with H+V (92±22 ms, P<0.001) or V capture alone (146±33 ms, P<0.001). A stim-PCS <60 ms (stim-HRA <70 ms) was observed only with atrial capture. A stim-PCS >90 ms (stim-HRA >100 ms) was observed only in the absence of atrial capture. A stim-HRA of <85 ms was highly specific and stim-PCS of <85 ms highly sensitive at identifying atrial capture. Stim-HRA intervals of 75 to 97 ms and stim-PCS intervals of 65 to 88 ms were observed with either atrial, His, or para-Hisian ventricular capture without atrial capture. In this overlap zone, all patients demonstrated a stim-PCS or stim-HRA interval prolongation of at least 20 ms when the catheter was advanced to avoid deliberate atrial pacing. The QRS morphology was of limited value in distinguishing atrial capture due to concurrent ventricular or H+V capture, as observed in 20 of 31 (65%) patients. Conclusions— Stim-PCS and stim-HRA intervals can be used to monitor for inadvertent atrial capture during para-Hisian pacing. A stim-PCS <60 ms (or stim-HRA <70 ms) and stim-PCS >90 ms (or stim-HRA >100 ms) were observed only with and without atrial capture, respectively, but there was significant overlap between these values. Deliberate atrial capture and loss of capture reliably identifies atrial capture regardless of intervals.

Further evidence for the "muscle bundle" hypothesis of cavotricuspid isthmus conduction: physiological proof, with clinical implications for ablation.

Two Line Flutter Ablation. Introduction: It has been suggested that the cavotricuspid isthmus (CTI) is composed of discrete muscle bundles with preferred paths of conduction. An ablation technique targeting high‐voltage local electrograms (maximum voltage guided or MVG technique) has been described with the aim of preferentially targeting the muscle bundles. We hypothesized that the MVG technique could provide isthmus block even if the high voltage targets were clearly separated on different ablation lines. In contrast, conduction over a continuous sheet of muscle would require a single continuous ablation line.

KCNJ2 variant of unknown significance reclassified as long QT syndrome causing ventricular fibrillation.

KCNJ2 is the only gene implicated in Andersen-Tawil syndrome. Sudden cardiac arrest is rare in Andersen-Tawil syndrome. However, sudden cardiac arrest is often the index presentation in other forms of long QT syndrome. We present an unreported variant in the KCNJ2 gene, associated with long QT syndrome, that presented with ventricular fibrillation. Exercise testing and adrenaline infusion were useful in assigning pathogenicity to this variant of unknown significance.

Intermittent Preexcitation and the Risk of Sudden Death: The Exception That Proves the Rule?

The prevalence of preexcitation is reported to be 0.1– 0.3%.1 The most contentious issue is the management of the asymptomatic individual found to have the Wolff–Parkinson– White (WPW) ECG pattern. Crucial to this issue is the incidence of sudden cardiac death (SCD), which is fortunately exceptionally low—estimated at 0.1% per year in the asymptomatic patient and 0.3% in the symptomatic.2,3 Despite their sensitivity, both invasive and noninvasive variables lack specificity for identifying patients at risk of SCD.4,5 In addition to inherent limitations of these variables, the key limitation relates to the very low incidence of SCD, which poses immense challenges to the specificity and positive predictive value of any measure, and to a lesser extent, the limited number of patients with long follow up who undergo testing without ablation.2,3,6 Intermittent loss of the delta wave during sinus rhythm relates to failure of conduction over the accessory pathway (AP) and would intuitively suggest a narrow window of conduction over the AP and hence inability to provide a rapid preexcited ventricular response during atrial fibrillation (AF).7,8 Intermittent preexcitation has been equated with a long AP anterograde effective refractory period (ERP) and shortest preexcited RR intervals (SPRRI) in AF that are long and, therefore, a low risk for SCD.5,7,8 The striking paucity of SCD among patients with intermittent preexcitation also supports this position, despite the rare occurrence of short SPRRIs.2,3,9-11 In fact, 15% of patients with intermittent preexcitation reportedly demonstrate SPRRI of less than 250 ms.7 However, in a series of patients resuscitated from ventricular fibrillation (VF), a SPRRI of ≤200 ms was the norm (mean SPRRI 180+/–29 ms) in the absence of isoproterenol, with few over 220 and none >250 ms (Fig. 1).13