Utility of high resolution mapping to guide ablation of ventricular arrhythmias from the aortic sinuses of Valsalva.

PURPOSE: Left ventricular outflow tract (LVOT) arrhythmias are commonly targeted from the aortic sinuses of Valsalva (SOV). Both presystolic potentials during ventricular arrhythmia (VA) and late diastolic potentials during sinus rhythm have been recognized as markers of successful ablation sites. The study aimed to evaluate the utility of high resolution mapping (HRM) with small and closely spaced electrodes for guiding ablation of VA from the SOV. METHODS: Seventeen patients with LVOT VA underwent HRM in the SOV with either PentaRay (13) or Orion (4) catheters. Ablation was guided by low amplitude high frequency potentials that were identified with HRM and tagged on the electroanatomic map. RESULTS: High frequency low amplitude potentials during sinus rhythm (late) or VA (early) were demonstrated with HRM in all 17 consecutive patients; while these potentials were either absent or usually had a far-field appearance in the recordings obtained at the same sites with a 3.5-mm standard ablation catheter. On intracardiac echocardiogram, sites with these potentials corresponded to the bases of the sinuses adjacent to the LV ostium. Ablation was acutely successful in 16 out of 17 patients. Significant reduction in VA burden (≥ 90%) was noted in 15 patients. CONCLUSIONS: High frequency low amplitude potentials during sinus rhythm (late) and VA (early) are consistently recorded using HRM in the SOV in patients with VA arising from the aortic sinuses of Valsalva. Standard ablation catheters have limited resolution for detecting these potentials. HRM may potentially improve outcomes of ablation of VA originating from the aortic SOV.

Physiology of slow pathway conduction during sinus rhythm: evidence from high density mapping within the triangle of Koch.

PURPOSE: To evaluate nature of AV nodal activation in patients with AVNRT using high density electro-anatomic mapping (HD-EAM). METHODS: HD-EAM was created in 30 patients with AVNRT from the triangle of Koch (ToK) in sinus rhythm (SR). Isochronal late activation maps (ILAM) were created. EAMs were analyzed for slow pathway (SPW) and fast pathway (FPW) activation. A pivot point (PP) was defined where FPW and SPW collided and pivoted back to the AV node (AVN). Conduction was assessed with programmed extrastimulus (PES) in 9 patients until FPW refractory period (ERP). The change in PP distance from the HIS (ΔPP) was measured in SR and PES. The ΔPP was compared to ΔAH. The PP was ablated and SR re-mapped. RESULTS: The FPW activates the His and moves inferiorly toward the coronary sinus (CS). Activation also enters the ToK near the CS and collides with the FPW which then pivots around a functional line of block (LOB) within the ToK and moves superiorly along the septal tricuspid annulus. PP electrograms are fractionated, low amplitude, and consistent with SPW potentials (Haissaguerre et al. in Circulation 85:2162-2175, 1992). During PES the PP moved superiorly until FPW ERP when only SPW activation occurs. Normalized ΔAH and ΔPR vs ΔPP was highly correlated p < 0.0001. Ablation at the PP was successful and associated with loss of SPW fusion and pivot. CONCLUSION: We conclude HD-EAM/ILAM provide a novel method for localizing the SPW in SR. This study provides further understanding of dual AV nodal physiology and may aid in targeting the SPW for ablation of AVNRT.

Coronary Spasm and Polymorphic Ventricular Tachycardia One Year After Takotsubo.

Stress cardiomyopathy is typically considered to be a disease with a favorable long-term prognosis, with malignant arrhythmias accompanying only the acute phase. We describe a 51-year-old female who presented with palpitations one year after stress cardiomyopathy and complete recovery of apical left ventricular wall motion. Coronary spasm was strongly suspected based on transient ST-segment elevations followed by sustained polymorphic ventricular tachycardia captured on ambulatory Holter. Contrast injection during coronary angiography reproduced spasm and ventricular arrhythmia that resolved with intracoronary nitroglycerine. The patient was intolerant to nitrates therefore discharged on 2 calcium channel blockers. Shared decision was made to implant cardioverter defibrillator.

Air Entrapment Causing Inappropriate Shock From a Subcutaneous Implantable Cardioverter Defibrillator.

Subcutaneous implantable cardioverter defibrillator (S-ICD) is an accepted alternative to conventional transvenous devices. Their efficacy in arrhythmia management is comparable to ICDs. However, those devices also have limitations such as lack of anti-tachycardia pacing capability or higher occurrence of device oversensing associated with inappropriate shocks. Air entrapment inside one or more of subcutaneous pockets has been reported as one of uncommon causes of device malfunction. It is important to recognize the wandering or drifting baseline signals during device interrogation for timely diagnosis and appropriate treatment.

"2 for 1 Phenomenon" on Implantable Cardioverter Defibrillator Intracardiac Tracing.

"2 for 1 phenomenon" is simultaneous anterograde conduction over the fast and slow pathways of the atrioventricular (AV) nodal pathway, leading to a double ventricular response from each atrial beat. This phenomenon can initiate AV nodal reentrant tachycardia (AVNRT). The unique induction of AVNRT was observed in a patient with an implantable cardioverter defibrillator in our case. Minimal to no retrograde invasion of the slow pathway from the anterogradely conducted fast pathway depolarization is the most accepted explanation.

Device therapy in the setting of long QT syndrome.

Congenital long QT syndrome (LQTS) is an inherited disorder of myocardial repolarization characterized by prolongation of the QT interval associated with life-threatening polymorphic ventricular tachycardia. The treatment of congenital LQTS involves antiadrenergic therapies: ß-blockers and surgical left cardiac sympathetic denervation (LCSD) to decrease sympathetic input to the heart, cardiac pacing, and implantable cardioverter-defibrillator (ICDs). Although this article focuses on the role of device therapy for the treatment of LQTS, it also discusses the role of ß-blockers and LCSD because they are concomitant with device therapy. After implantation, programming should be optimized to minimize the risk for inappropriate ICD therapies.

QTc compared to JTc for monitoring drug-induced repolarization changes in the setting of ventricular pacing.

BACKGROUND: QT prolongation is a risk factor for proarrhythmia when beginning antiarrhythmic drug therapy (AAD). However, there are no data regarding monitoring repolarization changes during a ventricular paced (VP) rhythm. OBJECTIVE: The purpose of this study was to compare serial changes in corrected QT and JT intervals, during native conduction (NC) and VP rhythms when initiating Class III AADs. METHODS: Twenty-two patients (73% men; mean age 65 ± 11 years) with an implantable device and with <10% VP were monitored during AAD initiation (16 sotalol, 6 dofetilide). QTc and JTc were measured from ECGs obtained during NC and VP at baseline (pre-AAD) and then after each AAD dose. RESULTS: During AAD loading, mean QTc increased significantly during NC (431 ± 28 ms to 463 ± 33 ms, P = .002) but not with VP (520 ± 48 ms to 538 ± 45 ms, P = .07). Mean percent increase in peak QTc during NC was significantly greater than during VP (12% vs 7%, P = .003). In contrast, peak JTc during AAD loading was not significantly different between NC and VP (P = .67). CONCLUSION: When initiating AAD, the change in QTc during VP does not correlate with the change in QTc during NC; thus, the VP QTc is inadequate for monitoring repolarization changes. However, VP JTc correlates well with JTc during NC. When initiating Class III AADs in patients with VP rhythms, the JTc, and not the QTc, interval is the useful marker for assessing repolarization.

Ibandronate and ventricular arrhythmia risk.

INTRODUCTION: Bisphosphonates, including ibandronate, are used in the prevention and treatment of osteoporosis. METHODS AND RESULTS: We report a case of suspected ibandronate-associated arrhythmia, following a single dose of ibandronate in a 55-year-old female. ECG at presentation revealed frequent ectopy and QT/QTc interval prolongation; at follow-up 9 months later the QT/QTc intervals were normalized. Proarrhythmic potential of ibandronate was assessed with a combination of in vivo and in vitro approaches in canines and canine ventricular myocytes. We observed late onset in vivo repolarization instability after ibandronate treatment. Myocytes superfused with ibandronate exhibited action potential duration (APD) prolongation and variability, increased early afterdepolarizations (EADs) and reduced Ito (P < 0.05), with no change in IKr . Ibandronate-induced APD changes and EADs were prevented by inhibition of intracellular calcium cycling. Ibandronate increased sarcoplasmic reticulum calcium load; during washout there was an increase in calcium spark frequency and spontaneous calcium waves. Computational modeling was used to examine the observed effects of ibandronate. While reductions in Ito alone had modest effects on APD, when combined with altered RyR inactivation kinetics, the model predicted effects on APD and SR Ca(2+) load consistent with observed experimental results. CONCLUSION: Ibandronate may increase the susceptibility to ventricular ectopy and arrhythmias. Collectively these data suggest that reduced Ito combined with abnormal RyR calcium handling may result in a previously unrecognized form of drug-induced proarrhythmia.

Impact of international normalized ratio and activated clotting time on unfractionated heparin dosing during ablation of atrial fibrillation.

BACKGROUND: For ablation of atrial fibrillation, it is unclear how baseline international normalized ratio (INR) affects the dosing of unfractionated heparin (UFH). METHODS AND RESULTS: A retrospective review of 170 consecutive patients undergoing atrial fibrillation ablation with baseline activated clotting time (ACT) and INR values was performed. Patients were grouped according to INR <2.0 (G<2; n=129) and INR ≥2.0 (G≥2; n=41). Clinical variables, UFH doses, and ACT values were recorded. An equation was derived to calculate the first bolus of UFH required to achieve an ACT ≥300 seconds, and this was subsequently assessed in 168 patients. For the initial 170 patients, the baseline INR (2.47±0.31 versus 1.53±0.31) and ACT (185±26 versus 153±30 seconds) were significantly greater in G≥2 (P<0.001). The amount of UFH to achieve the first ACT ≥300 seconds was significantly higher for G<2 versus G≥2 (9701±2390 versus 8268±2366 U; P=0.0001). Baseline INR, ACT, and weight were predictors of the UFH dosage to achieve an ACT ≥300 seconds. An equation derived to achieve an ACT ≥300 seconds after a single bolus of UFH met this end point in 160 of 168 patients (95%). CONCLUSIONS: Baseline INR and ACT, in addition to weight, are the only predictors of UFH dosage needed to achieve an ACT ≥300 seconds. A derived equation predicted the UFH dosage to achieve an ACT ≥300 seconds.

A rare case of permanent junctional reciprocating tachycardia ablated on the roof of the left atrium.

Left-sided anteroseptal accessory pathways that course through the aortomitral fibrous continuity are some of the rarest types of accessory pathways. At this region the atrium and ventricle are separated by their greatest distance because of the intervening aortic valve. These pathways often have a long circuitous course that may involve the root and cusps of the aortic valve. Prior reports have demonstrated the feasibility of ablating these pathways along the anteroseptal mitral annulus, the left ventricular outflow tract, or in the left or noncoronary cusps of the aortic valve. We describe a case of a concealed decremental anteroseptal accessory pathway that was ablated on the roof of the left atrium remote from the mitral or aortic valve annuli. This report indicates that when an appropriate site for ablation of a left-sided anteroseptal accessory pathway is not found close to a valve annulus, these pathways may be amenable to ablation by targeting their atrial insertion site.

The Management of Vasovagal Syncope in a Patient with Brugada Syndrome.

Vasovagal syncope is the most common cause of the neurally mediated reflex syncopes. A higher susceptibility to vasovagal syncope has been reported in patients with Brugada syndrome (BrS) and may be caused by associated autonomic dysfunction. It is unclear what risk vasovagal syncope confers to patients with BrS. This article reviews the pathophysiology of vasovagal syncope and autonomic dysfunction in patients with BrS and its association with BrS, treatment options for patients with BrS with vasovagal syncope, specific therapies and those that may be harmful in patients with BrS, and potential therapies and monitoring for patients with BrS with vasovagal syncope.

Management of sudden cardiac death risk in the very early postmyocardial infarction period.

PURPOSE OF REVIEW: The purpose of this review is to summarize the numerous recent studies assessing the strategies to manage the increased risk of sudden cardiac death (SCD) early after a myocardial infarction (MI). RECENT FINDINGS: Early after a MI, the risk of SCD is high. Several trials have been completed in attempt to identify and treat patients at increased risk for SCD early post-MI. These trials have evaluated QT interval, cardiac autonomic modulation, signal-averaged ECG, microvolt T-wave alternans, electrophysiology testing and early measurement of the left-ventricular ejection fraction (LVEF). Although some of these parameters were associated with increased total mortality, no parameter provided adequate predictive accuracy of increased risk for SCD that could guide use of an implantable cardiac defibrillator (ICD). SUMMARY: Other than LVEF measured more than 40 days post-MI (consistent with current ICD guidelines), there is no noninvasive or invasive test that reliably predicts the risk for SCD or that can guide empiric ICD implantation soon after a MI. In the early post-MI period, therefore, the goal is to maximize medical therapy and revascularization. The LVEF should then be measured no sooner than 40 days post-MI and, if the LVEF is 35% or less, the patient should be considered for ICD implantation.

Cardiac potassium channel dysfunction in sudden infant death syndrome.

Life-threatening arrhythmias have been suspected as one cause of the sudden infant death syndrome (SIDS), and this hypothesis is supported by the observation that mutations in arrhythmia susceptibility genes occur in 5-10% of cases. However, the functional consequences of cardiac potassium channel gene mutations associated with SIDS and how these alleles might mechanistically predispose to sudden death are unknown. To address these questions, we studied four missense KCNH2 (encoding HERG) variants, one compound KCNH2 genotype, and a missense KCNQ1 mutation all previously identified in Norwegian SIDS cases. Three of the six variants exhibited functional impairments while three were biophysically similar to wild-type channels (KCNH2 variants V279M, R885C, and S1040G). When co-expressed with WT-HERG, R273Q and K897T/R954C generated currents resembling the rapid component of the cardiac delayed rectifier current (I(Kr)) but with significantly diminished amplitude. Action potential modeling demonstrated that this level of functional impairment was sufficient to evoke increased action potential duration and pause-dependent early afterdepolarizations. By contrast, KCNQ1-I274V causes a gain-of-function in I(Ks) characterized by increased current density, faster activation, and slower deactivation leading to accumulation of instantaneous current upon repeated stimulation. Action potential simulations using a Markov model of heterozygous I274V-I(Ks) incorporated into the Luo-Rudy (LRd) ventricular cell model demonstrated marked rate-dependent shortening of action potential duration predicting a short QT phenotype. Our results indicate that certain potassium channel mutations associated with SIDS confer overt functional defects consistent with either LQTS or SQTS, and further emphasize the role of congenital arrhythmia susceptibility in this syndrome.

Prevalence of long-QT syndrome gene variants in sudden infant death syndrome.

BACKGROUND: The hypothesis that some cases of sudden infant death syndrome (SIDS) could be caused by long-QT syndrome (LQTS) has been supported by molecular studies. However, there are inadequate data regarding the true prevalence of mutations in arrhythmia-susceptibility genes among SIDS cases. Given the importance and potential implications of these observations, we performed a study to more accurately quantify the contribution to SIDS of LQTS gene mutations and rare variants. METHODS AND RESULTS: Molecular screening of 7 genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CAV3) associated with LQTS was performed with denaturing high-performance liquid chromatography and nucleotide sequencing of genomic DNA from 201 cases diagnosed as SIDS according to the Nordic Criteria, and from 182 infant and adult controls. All SIDS and control cases originated from the same regions in Norway. Genetic analysis was blinded to diagnosis. Mutations and rare variants were found in 26 of 201 cases (12.9%). On the basis of their functional effect, however, we considered 8 mutations and 7 rare variants found in 19 of 201 cases as likely contributors to sudden death (9.5%; 95% CI, 5.8 to 14.4%). CONCLUSIONS: We demonstrated that 9.5% of cases diagnosed as SIDS carry functionally significant genetic variants in LQTS genes. The present study demonstrates that sudden arrhythmic death is an important contributor to SIDS. As these variants likely modify ventricular repolarization and QT interval duration, our results support the debated concept that an ECG would probably identify most infants at risk for sudden death due to LQTS either in infancy or later on in life.