Clinical/electrophysiologic characteristics of infranodal Wenckebach in patients with indication for permanent ventricular pacing: A prospective study.

BACKGROUND: Infranodal Wenckebach is rare and not well characterized. OBJECTIVE: We prospectively studied clinical and electrophysiologic characteristics of patients with atrioventricular (AV) Wenckebach with an indication for permanent ventricular pacing. METHODS: During a 2-year period, all patients with an indication for permanent ventricular pacing underwent targeted preimplantation electrophysiologic study. Clinical and electrophysiologic characteristics at presentation and ventricular pacing percentage at 6-month follow-up were evaluated. RESULTS: A total of 163 patients (median age, 68 [interquartile range, 60-74] years; male, 59%; median QRS duration, 110 [90-130] ms; complete AV block in 123 [75.5%]) were included. AV Wenckebach was noted in 22 (13.4%) patients (median age, 70 [63-76.5] years; male, 54%; median QRS duration, 120 [110-140] ms) and classified as infranodal (12/163 [7.3%]) vs AV nodal (10/163 [6.1%]). Patients with infranodal Wenckebach (infrahisian in all), compared with AV nodal Wenckebach, demonstrated higher frequency with left ventricular ejection fraction ≤40% (41.7% vs 0%; P = .04), longer median HV interval (90 vs 49 ms; P = .005), lower frequency of isolated first-degree AV block (8.3% vs 60%; P = .02), higher frequency of right bundle branch block with left anterior fascicular block (75% vs 10%; P = .003), lesser PR increment at onset of AV Wenckebach (20.5 vs 80 ms; P = .002), and onset of 2:1 AV block at longer cycle lengths (91.7% vs 20%; P = .002). CONCLUSION: Of patients referred for pacemaker implantation, infranodal Wenckebach was present in 27.5% (11/40) without complete AV block. It was as frequent as AV nodal Wenckebach and associated with characteristic electrophysiologic findings.

Phrenic Relocation by Endoscopy, Intentional Pneumothorax Using Carbon Dioxide, and Single Lung Ventilation (PHRENICS) Technique.

Strategies to prevent right phrenic nerve (PN) injury during catheter ablation can be difficult to employ, ineffective, and risky. A novel PN-sparing technique involving single lung ventilation followed by "intentional pneumothorax" was prospectively evaluated in patients with multidrug refractory periphrenic atrial tachycardia (AT). This hybrid technique, termed PHRENICS (Phrenic Relocation by Endoscopy & Intentional Pneumothorax using Carbon Dioxide & Single Lung Ventilation), resulted in effective PN relocation away from the target site in all cases, allowing successful catheter ablation of AT without procedural complication or arrhythmia recurrence. The PHRENICS hybrid ablation technique can effectively mobilize the PN, avoiding unnecessary invasion of the pericardium, and can expand the safety of catheter ablation for periphrenic AT.

Mechanically induced electrical storm as a complication of cardiac resynchronization therapy: A case report.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to improve both the functional status and mortality of heart failure patients with left bundle branch block. Multiple recent studies suggest several mechanisms for proarrhythmia associated with CRT device. CASE SUMMARY: A 51-year-old male with symptomatic non-ischemic cardiomyopathy and no previous history of ventricular arrhythmias underwent placement of a biventricular cardioverter-defibrillator. The patient developed sustained monomorphic ventricular tachycardia (VT) soon after implantation. The VT recurred despite reprogramming to right ventricular only pacing. The electrical storm resolved only after a subsequent discharge from the defibrillator caused inadvertent dislodgement of the coronary sinus lead. No recurrent VT occurred throughout 10-years follow up after urgent coronary sinus lead revision. DISCUSSION: We describe the first reported case of mechanically induced electrical storm due to the physical presence of the CS lead in a patient with a new CRT-D device. It is important to recognize mechanical proarrhythmia as a potential mechanism of electrical storm, as it may be intractable to device reprogramming. Urgent coronary sinus lead revision should be considered. Further studies on this mechanism of proarrhythmia are needed.

The Value of Programmed Ventricular Extrastimuli From the Right Ventricular Basal Septum During Supraventricular Tachycardia.

BACKGROUND: The difference between the right ventricular (RV) apical stimulus-atrial electrogram (SA) interval during resetting of supraventricular tachycardia (SVT) versus the ventriculoatrial (VA) interval during SVT (ΔSA-VAapex) is an established technique for discerning SVT mechanisms but is limited by a significant diagnostic overlap. OBJECTIVES: This study hypothesized that the difference between the RV SA interval during resetting of SVTs versus the VA interval during SVTs (ΔSA-VA) would yield a more robust differentiation of atrioventricular nodal re-entrant tachycardia (AVNRT) from atrioventricular reciprocating tachycardia (AVRT) when using the RV basal septal stimulation (ΔSA-VAbase) as compared to the RV apical stimulation (ΔSA-VAapex). Moreover, it was predicted that the ΔSA-VAbase might distinguish septal from free wall accessory pathways (APs) effectively. METHODS: In this prospective study, 105 patients with AVNRTs (age 48 ± 20 years, 44% male) and 130 with AVRTs (age 26 ± 18 years, 54% male) underwent programmed ventricular extrastimuli delivered from both the RV basal septum and RV apex. The ΔSA-VA values were compared between the 2 sites. RESULTS: The ΔSA-VAbase was shorter than the ΔSA-VAapex during AVRT (44 ± 30 ms vs 58 ± 29 ms; P < 0.001), and the opposite occurred during AVNRT (133 ± 31 ms vs 125 ± 25 ms; P = 0.03). A ΔSA-VAbase of ≧85 milliseconds had a sensitivity of 97% and specificity of 96% for identifying AVNRT. Furthermore, a ΔSA-VAbase of 45-85 milliseconds identified AVRT with left free wall APs (sensitivity 86%, specificity 95%), 20-45 milliseconds for posterior septal APs (sensitivity 72%, specificity 96%), and <20 milliseconds for right free wall or anterior/mid septal APs (sensitivity 86%, specificity 98%). CONCLUSIONS: The ΔSA-VAbase during programmed ventricular extrastimuli produced a robust differentiation between AVNRT and AVRT regardless of the AP location with ≧85 milliseconds as an excellent cutoff point. This straightforward technique further allowed localizing 4 general AP sites.

Ambient circulation surrounding an ablation catheter tip affects ablation lesion characteristics.

INTRODUCTION: The association between ambient circulating environments (CEs) and ablation lesions has been largely underexplored. METHODS: Viable bovine myocardium was placed in a saline bath in an ex vivo endocardial model. Radiofrequency (RF) ablation was performed using three different ablation catheters: 3.5 mm open irrigated (OI), 4, and 8 mm. Variable flow rates of surrounding bath fluids were applied to simulate standard flow, high flow, and no flow. For in vivo epicardial ablation, 24 rats underwent a single OI ablation and performed with circulating saline (30 ml/min; n = 12), versus those immersed in saline without circulation (n = 12). RESULTS: High flow reduced ablation lesion volumes for all three catheters. In no-flow endocardial CE, both 4 mm and OI catheters produced smaller lesions compared with standard flow. However, the 8 mm catheter produced the largest lesions in a no-flow CE. Ablation performed in an in vivo model with CE resulted in smaller lesions compared with ablation performed in a no-flow environment. No statistically significant differences in steam pops were found among the groups. CONCLUSION: A higher endocardial CE flow can decrease RF effectiveness. Cardiac tissue subjected to no endocardial CE flow may also limit RF for 4 mm catheters, but not for OI catheters; these findings may have implications for RF ablation safety and efficacy, especially in the epicardial space without circulating fluid or in the endocardium under varying flow conditions.

Needle-Tipped Catheter Ablation of Papillary Muscle Results in Deeper and Larger Ablation Lesions.

Ventricular tachycardia associated with papillary muscle (PM) is often refractory to standard radiofrequency ablation (RFA). The needle-tipped ablation catheter (NT-AC) has been used to treat deep intramyocardial substrates, but its use for PM has not been characterized. Using an ex vivo experimental platform, both 3 mm and 6 mm NT-AC created larger ablation lesion volumes and depths than open-irrigated ablation catheter did (OI-AC; e.g., 57.12 ± 9.70mm3 and 2.42 ± 0.22 mm, respectively; p < 0.01 for all comparisons). Longer NT-AC extension (6 mm) resulted in greater ablation lesion volumes and maximum depths (e.g., 333.14 ± 29.13mm3 and 6.46 ± 0.29 mm, respectively, compared to the shorter 3 mm NT-AC extension, 143.33 ± 12.77mm3, and 4.46 ± 0.14 mm; both p < 0.001). There were no steam pops. In conclusion, for PM ablation, the NT-AC was able to achieve ablation lesions that were larger and deeper than with conventional OI-AC. Ablation of PM may be another application for needle-tip ablation. Further studies are warranted to establish long-term safety and efficacy in human studies.

Arrhythmias including atrial fibrillation and congenital heart disease in Kleefstra syndrome: a possible epigenetic link.

AIMS: Kleefstra syndrome (KS), often diagnosed in early childhood, is a rare genetic disorder due to haploinsufficiency of EHMT1 and is characterized by neuromuscular and intellectual developmental abnormalities. Although congenital heart disease (CHD) is common, the prevalence of arrhythmias and CHD subtypes in KS is unknown. METHODS AND RESULTS: Inspired by a novel case series of KS patients with atrial tachyarrhythmias in the USA, we evaluate the two largest known KS registries for arrhythmias and CHD: Radboudumc (50 patients) based on health record review at Radboud University Medical Center in the Netherlands and GenIDA (163 patients) based on worldwide surveys of patient families. Three KS patients (aged 17-25 years) presented with atrial tachyarrhythmias without manifest CHD. In the international KS registries, the median [interquartile range (IQR)] age was considerably younger: GenIDA/Radboudumc at 10/13.5 (12/13) years, respectively. Both registries had a 40% prevalence of cardiovascular abnormalities, the majority being CHD, including septal defects, vascular malformations, and valvular disease. Interestingly, 4 (8%) patients in the Radboudumc registry reported arrhythmias without CHD, including one atrial fibrillation (AF), two with supraventricular tachycardias, and one with non-sustained ventricular tachycardia. The GenIDA registry reported one patient with AF and another with chronic ectopic atrial tachycardia (AT). In total, atrial tachyarrhythmias were noted in six young KS patients (6/213 or 3%) with at least four (three AF and one AT) without structural heart disease. CONCLUSION: In addition to a high prevalence of CHD, evolving data reveal early-onset atrial tachyarrhythmias in young KS patients, including AF, even in the absence of structural heart disease.

Mapping Atrial Fibrillation After Surgical Therapy to Guide Endocardial Ablation.

BACKGROUND: Surgical ablation for atrial fibrillation (AF) can be effective, yet has mixed results. It is unclear which endocardial lesions delivered as part of hybrid therapy' will best augment surgical lesion sets in individual patients. We addressed this question by systematically mapping AF endocardially after surgical ablation and relating findings to early recurrence, then performing tailored endocardial ablation as part of hybrid therapy. METHODS: We studied 81 consecutive patients undergoing epicardial surgical ablation (stage 1 hybrid), of whom 64 proceeded to endocardial catheter mapping and ablation (stage 2). Stage 2 comprised high-density mapping of pulmonary vein (PV) or posterior wall (PW) reconnections, low-voltage zones (LVZs), and potential localized AF drivers. We related findings to postsurgical recurrence of AF. RESULTS: Mapping at stage 2 revealed PW isolation reconnection in 59.4%, PV isolation reconnection in 28.1%, and LVZ in 42.2% of patients. Postsurgical recurrence of AF occurred in 36 patients (56.3%), particularly those with long-standing persistent AF (P=0.017), but had no relationship to reconnection of PVs (P=0.53) or PW isolation (P=0.75) when compared with those without postsurgical recurrence of AF. LVZs were more common in patients with postsurgical recurrence of AF (P=0.002), long-standing persistent AF (P=0.002), advanced age (P=0.03), and elevated CHA2DS2-VASc (P=0.046). AF mapping revealed 4.4±2.7 localized focal/rotational sites near and also remote from PV or PW reconnection. After ablation at patient-specific targets, arrhythmia freedom at 1 year was 81.0% including and 73.0% excluding previously ineffective antiarrhythmic medications. CONCLUSIONS: After surgical ablation, AF may recur by several modes particularly related to localized mechanisms near low voltage zones, recovery of posterior wall or pulmonary vein isolation, or other sustaining mechanisms. LVZs are more common in patients at high clinical risk for recurrence. Patient-specific targeting of these mechanisms yields excellent long-term outcomes from hybrid ablation.

Perpendicular catheter orientation during papillary muscle ablation results in larger, deeper lesions.

INTRODUCTION: Ablation of papillary muscles (PMs) for refractory ventricular arrhythmias can often be challenging. The catheter approach and orientation during ablation may affect optimal radiofrequency (RF) delivery. Yet, no previous study investigated the association between catheter orientation and PM lesion size. We evaluated ablation lesion characteristics with various catheter orientations relative to the PM tissue during open irrigated ablation, using a standardized, experimental setting. METHODS: Viable bovine PM was positioned on a load cell in a circulating saline bath. RF ablation was performed over PM tissue at 50 W, with the open irrigated catheter positioned either perpendicular or parallel to the PM surface. Applied force was 10 g. Ablation lesions were sectioned and underwent quantitative morphometric analysis. RESULTS: A catheter position oriented directly perpendicular to the PM tissue resulted in the largest ablation lesion volumes and depths compared with ablation with the catheter parallel to PM tissue (75.26 ± 8.40 mm3 vs. 34.04 ± 2.91 mm3 , p < .001) and (3.33 ± 0.18 mm vs. 2.24 ± 0.10 mm, p < .001), respectively. There were no significant differences in initial impedance, peak voltage, peak current, or overall decrease in impedance among groups. Parallel catheter orientation resulted in higher peak temperature (41.33 ± 0.28°C vs. 40.28 ± 0.24°C, p = .003), yet, there were no steam pops in either group. CONCLUSION: For PM ablation, catheter orientation perpendicular to the PM tissue achieves more effective and larger ablation lesions, with greater lesion depth. This may have implications for the chosen ventricular access approach, the type of catheter used, consideration for remote navigation, and steerable sheaths.

Sinus node sparing novel hybrid approach for treatment of inappropriate sinus tachycardia/postural sinus tachycardia: multicenter experience.

BACKGROUND: The ideal treatment of inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) still needs to be defined. Medical treatments yield suboptimal results. Endocardial catheter ablation of the sinus node (SN) may risk phrenic nerve damage and open-heart surgery may be accompanied by unjustified invasive risks. METHODS: We describe our first multicenter experience of 255 consecutive patients (235 females, 25.94 ± 3.84 years) having undergone a novel SN sparing hybrid thoracoscopic ablation for drug-resistant IST (n = 204, 80%) or POTS (n = 51, 20%). As previously described, the SN was identified with 3D mapping. Surgery was performed through three 5-mm ports from the right side. A minimally invasive approach with a bipolar radiofrequency clamp was used to ablate targeted areas while sparing the SN region. The targeted areas included isolation of the superior and the inferior caval veins, and a crista terminalis line was made. All lines were interconnected. RESULTS: Normal sinus rhythm (SR) was restored in all patients at the end of the procedure. All patients discontinued medication during the follow-up. After a blanking period of 6 months, all patients presented stable SR. At a mean of 4.07 ± 1.8 years, normal SN reduction and chronotropic response to exercise were present. In the 51 patients initially diagnosed with POTS, no syncope occurred. During follow-up, pericarditis was the most common complication (121 patients: 47%), with complete resolution in all cases. Pneumothorax was observed in 5 patients (1.9%), only 3 (1.1%) required surgical drainage. Five patients (1.9%) required a dual-chamber pacemaker due to sinus arrest > 5 s. CONCLUSIONS: Preliminary results of this multicenter experience with a novel SN sparing hybrid ablation of IST/POTS, using surgical thoracoscopic video-assisted epicardial ablation combined with simultaneous endocardial 3D mapping may prove to be an efficient and safe therapeutic option in patients with symptomatic drug-resistant IST and POTS. Importantly, in our study, all patients had a complete resolution of the symptoms and restored normal SN activity.

Importance of the Activation Sequence of the His or Right Bundle for Diagnosis of Complex Tachycardia Circuits.

In this review, we emphasize the unique value of recording the activation sequence of the His bundle or right bundle branch (RB) for diagnoses of various supraventricular and fascicular tachycardias. A close analysis of the His to RB (H-RB) activation sequence can help differentiate various forms of supraventricular tachycardias, namely atrioventricular nodal reentry tachycardia from concealed nodofascicular tachycardia, a common clinical dilemma. Furthermore, bundle branch reentry tachycardia and fascicular tachycardias often are included in the differential diagnosis of supraventricular tachycardia with aberrancy, and the use of this technique can help the operator make the distinction between supraventricular tachycardias and these other forms of ventricular tachycardias using the His-Purkinje system. We show that this technique is enhanced by the use of multipolar catheters placed to span the proximal His to RB position to record the activation sequence between proximal His potential to the distal RB potential. This allows the operator to fully analyze the activation sequence in sinus rhythm as compared to that during tachycardia and may help target ablation of these arrhythmias. We argue that 3 patterns of H-RB activation are commonly identified-the anterograde H-RB pattern, the retrograde H-RB (right bundle to His bundle) pattern, and the chevron H-RB pattern (simultaneous proximal His and proximal RB activation)-and specific arrhythmias tend to be associated with specific H-RB activation sequences. We show that being able to record and categorize this H-RB relationship can be instrumental to the operator, along with standard pacing maneuvers, to make an arrhythmia diagnosis in complex tachycardia circuits. We highlight the importance of H-RB activation patterns in these complex tachycardias by means of case illustrations from our groups as well as from prior reports.

Substrate Characterization and Outcomes of Ventricular Tachycardia Ablation in TTN (Titin) Cardiomyopathy: A Multicenter Study.

[Figure: see text].

Generation of three heterozygous KCNH2 mutation-carrying human induced pluripotent stem cell lines for modeling LQT2 syndrome.

Congenital long QT syndrome type 2 (LQT2) results from KCNH2 mutations that cause loss of Kv11.1 channel function which can lead to arrhythmias, syncope, and sudden death. Here, we generated three human-induced pluripotent stem cell (iPSC) lines from peripheral blood mononuclear cells (PBMCs) of two LQT2 patients carrying pathogenic variants (c.1714G > A and c.2960del) and one LQT2 patient carrying a variant of uncertain significance (c.1870A > T) in KCNH2. All lines show typical iPSC morphology, high expression of pluripotent markers, normal karyotype, and differentiate into three germ layers in vitro. These lines are valuable resources for studying the pathological mechanisms of LQTS caused by caused by KCNH2 mutations.

The Role of the Left Septal Fascicle in Fascicular Arrhythmias: Clinical Presentation and Laboratory Evaluation.

OBJECTIVES: This study describes a series of cases best explained by invoking the left septal fascicle (LSF) as a critical component of the arrhythmia circuit. BACKGROUND: Numerous anatomic studies have shown evidence of the LSF, but its precise role in the onset of arrhythmia is unclear. METHODS: This paper presents 5 cases that implicated the LSF as a critical component of arrhythmogenesis. RESULTS: The first case had ventricular fibrillation repeatedly documented after a single premature atrial complex, produced left-sided conduction delay and simultaneous earliest activation of the left anterior fascicle (LAF) and left posterior fascicle (LPF). The LSF was ablated, resulting in an arrhythmia cure. The second case showed narrow QRS morphology during fascicular re-entrant tachycardia. The earliest mid-septal diastolic potentials had distal-to-proximal activation suggesting an LSF as a retrograde common pathway. The third case, with multiple ectopic Purkinje-related premature complexes exhibited earliest Purkinje potentials in the mid-septum, with subsequent anterograde activation of the LAF and LPF. Ablation of the LSF eliminated the premature ventricular complexes (PVCs). The fourth case demonstrated LPF and LAF PVCs. The His-left bundle activation showed earliest potentials at the proximal insertion of the left bundle during LPF PVCs, as well as a distal-to-proximal activation pattern during LAF PVC, suggestive of LSF involvement. The fifth case had focal non-re-entrant fascicular beats successfully ablated over the LSF. CONCLUSIONS: Involvement of the LSF is suspected with presentation of multiform fascicular and narrow QRS complex ventricular episodes of arrhythmia. Diagnoses and ablation require detailed mapping of the entire left sided conduction system.

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Alcohol to Assess Changes in Atrial Electrophysiology.

OBJECTIVES: This study sought to identify acute changes in human atrial electrophysiology during alcohol exposure. BACKGROUND: The mechanism by which a discrete episode of atrial fibrillation (AF) occurs remains unknown. Alcohol appears to increase the risk for AF, providing an opportunity to study electrophysiologic effects that may render the heart prone to arrhythmia. METHODS: In this randomized, double-blinded, placebo-controlled trial, intravenous alcohol titrated to 0.08% blood alcohol concentration was compared with a volume and osmolarity-matched, masked, placebo in patients undergoing AF ablation procedures. Right, left, and pulmonary vein atrial effective refractory periods (AERPs) and conduction times were measured pre- and post-infusion. Isoproterenol infusions and burst atrial pacing were used to assess AF inducibility. RESULTS: Of 100 participants (50 in each group), placebo recipients were more likely to be diabetic (22% vs. 4%; p = 0.007) and to have undergone a prior AF ablation (36% vs. 22%; p = 0.005). Pulmonary vein AERPs decreased an average of 12 ms (95% confidence interval: 1 to 22 ms; p = 0.026) in the alcohol group, with no change in the placebo group (p = 0.98). Whereas no statistically significant differences in continuously assessed AERPs were observed, the proportion of AERP sites tested that decreased with alcohol (median: 0.5; interquartile range: 0.6 to 0.6) was larger than with placebo (median: 0.4; interquartile range: 0.2 to 0.6; p = 0.0043). No statistically significant differences in conduction times or in the proportion with inducible AF were observed. CONCLUSIONS: Acute exposure to alcohol reduces AERP, particularly in the pulmonary veins. These data demonstrate a direct mechanistic link between alcohol, a common lifestyle exposure, and immediate proarrhythmic effects in human atria. (How Alcohol Induces Atrial Tachyarrhythmias Study [HOLIDAY]; NCT01996943).

Long-term outcomes of ablation for ventricular arrhythmias in mitral valve prolapse.

PURPOSE: Prior studies reporting efficacy of radiofrequency catheter ablation for complex ventricular ectopy in mitral valve prolapse (MVP) are limited by selective inclusion of bileaflet MVP, papillary muscle only ablation, or short-term follow-up. We sought to evaluate the long-term incidence of hemodynamically significant ventricular tachycardia (VT) or fibrillation (VF) in patients with MVP after initial ablation. METHODS: We studied consecutive patients with MVP undergoing ablation for complex ventricular ectopy between 2013 and 2017 at our institution. Of 580 patients with MVP, we included 15 (2.6%, 10 women; mean age 50 ± 14 years, 53% bileaflet) with complex ventricular ectopy treated with initial ablation. RESULTS: Over a median follow-up of 3406 (1875-6551) days or 9 years, 5 of 15 (33%) patients developed hemodynamically significant VT/VF after their initial ablation and underwent placement of an implantable cardioverter defibrillator (ICD). Three of 5 also underwent repeat ablations. Sustained VT was inducible prior to index ablation in all 5 who developed VT/VF, compared to none of the 10 patients who did not develop VT/VF after index ablation (p = 0.002). Complex ventricular ectopy at index ablation was multifocal in all 5 patients who underwent repeat intervention versus 4 of 10 patients (40%) who did not (p = 0.04). All 3 patients with subsequent VT/VF who underwent repeat ablation had a new clinically dominant focus of ventricular arrhythmia and 3 of the patients with ICD had appropriate VT/VF therapies. CONCLUSIONS: In the long term, a subset of MVP patients treated with ablation for ventricular arrhythmias, all with multifocal ectopy on initial EP study, develop hemodynamically significant VT/VF. Our findings suggest the progressive nature of ventricular arrhythmias in patients with MVP and multifocal ectopy.