Heat‐Stress Responses Modulate Beta‐Adrenergic Agonist and Angiotensin II Effects on the Arrhythmogenesis of Pulmonary Vein Cardiomyocytes

Effect of Heat Stress on Pulmonary Vein Cardiomyocytes. Introduction: Heat stress‐induced responses reduce the occurrence of atrial fibrillation (AF). Pulmonary vein (PV) cardiomyocytes with pacemaker activity play a critical role in the pathophysiology of AF. In this study, we examined whether heat‐stress responses alter the electrophysiological characteristics of PV cardiomyocytes and protect the PV against angiotensin II‐ or isoproterenol‐induced arrhythmogenesis. Methods and Results: We used whole‐cell patch clamp techniques to investigate the spontaneous activity and ionic currents in single isolated rabbit PV pacemaker cardiomyocytes with or without (control) exposure to heat stress (43°C, 15 minutes) 5 ± 1 hours before the experiments. Compared to control cardiomyocytes, heat‐stressed PV cardiomyocytes had slower beating rates. Heat‐stressed PV cardiomyocytes had larger L‐type calcium currents, transient outward currents, smaller inward rectifier potassium currents, but similar sodium‐calcium exchanger currents_. Additionally, heat‐stressed PV cardiomyocytes had a lower incidence of pacemaker currents than control PV cardiomyocytes. Moreover, isoproterenol increased the beating rate of control cardiomyocytes but not heat‐stressed PV cardiomyocytes. Similarly, angiotensin II also increased the beating rate of control cardiomyocytes, but not heat‐stressed PV cardiomyocytes, in association with decreased expression of the angiotensin II type 1 receptor. Conclusion: Heat‐stress responses altered the electrophysiological characteristics of PV cardiomyocytes and attenuated the effects of isoproterenol and angiotensin II on PV arrhythmogenesis, which may play a role in the protective potential of heat‐stress responses. (J Cardiovasc Electrophysiol, Vol. 22, pp. 183‐190, February 2011)     

Incidence and Electrophysiologic Properties of Dissociated Pulmonary Vein Activity Following Pulmonary Vein Isolation During Catheter Ablation of Atrial Fibrillation

Dissociated PV Activity During AF Ablation. Introduction: Pulmonary veins (PV) play an important role in the arrhythmogenesis of atrial fibrillation (AF). Catheter‐based PV isolation is one of the primary treatments for symptomatic drug refractory AF. Following electrical isolation, isolated rhythms in the PV are encountered. The aim of this study was to assess the frequency of postisolation PV activity and classify the different rhythms observed. Methods and Results: This single center prospective study sought to assess the dissociated activity in the PVs following their isolation during AF ablation. In 100 consecutive patients (60 paroxysmal, 40 persistent) undergoing AF ablation, dissociated PV activity was recorded using a multielectrode mapping catheter following antral PV isolation. The dissociated PV activity was classified as (1) silent, (2) isolated ectopic beats, (3) ectopic rhythm, and (4) PV fibrillation. All the PVs were successfully isolated in all the patients. In 91 of 100 patients, there was dissociated activity in at least 1 isolated ipsilateral PV group. There was no significant difference in spontaneous PV activity between patients with paroxysmal and persistent AF (91.7% vs 90%, P = 1.0). Among the 200 isolated ipsilateral PV groups, 64 of 200 (32%) were silent, 86 of 200 (43%) demonstrated isolated ectopic beats, 41 of 200 (20.5%) had ectopic rhythms and 9 of 200 (4.5%) had PV fibrillation. The average cycle length of the PV ectopic rhythm was 2594 ± 966 ms (range 1193–4750 ms). Conclusions: Following PV isolation, a majority of patients demonstrate dissociated activity in at least 1 PV. This finding was evident in patients with both paroxysmal and persistent AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1338‐1343, December 2010)     

Cryoballoon Pulmonary Vein Isolation with Real-Time Recordings from the Pulmonary Veins

Introduction: Cryoballoon (CB) ablation represents a novel technology for pulmonary vein isolation (PVI). We investigated feasibility and safety of CB-PVI, utilizing a novel spiral catheter (SC), thereby obtaining real-time PV potential registration.
Methods: Following double transseptal puncture, a Lasso catheter (Biosense Webster, Diamond Bar, CA, USA) and the 28 mm CB were positioned within the left atrium. A novel SC (Promap, ProRhythm Inc., Ronkonkoma, NY, USA) was inserted through the lumen of the CB allowing PV signal registration during treatment. Time to PV conduction block was analyzed. If no stable balloon position was obtained, the SC was exchanged for a regular guide wire and PV conduction was assessed after treatment by Lasso catheter.
Results: In 18 patients, 39 of 72 PVs (54%) were successfully isolated using the SC. The remaining 33 PVs were isolated switching to the regular guide wire. Time to PV conduction block was significantly shorter in PVs in which sustained PVI was achieved as compared to PVs in which PV conduction recovered within 30 minutes (33 ± 21 seconds vs 99 ± 65 seconds). In 40 PVs, time to PV conduction block was not obtained because of: (1) PVI not being achieved during initial treatment; (2) a distal position of the SC; or (3) isolation with regular guide wire. No procedural complications occurred.
Conclusion: Visualization of real-time PV conduction during CB PVI is safe, feasible, and allows accurate timing of PVI onset in a subset of PVs. Time to PV conduction block predicts sustained PVI. However, mechanical properties of the SC need to be improved to further simplify CB PVI.     

Pulmonary Vein Bigeminy: Electrophysiological Characteristics and Results of Catheter Ablation

Pulmonary vein bigeminy is the pair of a second, late and ectopic pulmonary vein potential following atrial far-field activation and a first passive pulmonary vein potential during sinus rhythm. The aim of this study was to determine the electrophysiological characteristics of pulmonary vein bigeminy and to evaluate its relevance as a trigger for paroxysmal atrial fibrillation. Methods and Results: Pulmonary vein bigeminy was recorded in 8 of 45 patients (18%) who underwent mapping of pulmonary veins for ablation of focal atrial fibrillation. The premature ectopic pulmonary vein potentials were conducted to the atria in 5 patients and were not conducted (concealed bigeminy) in 3 patients. The coupling interval of the ectopic pulmonary vein potential to the preceding atrial signal during sinus rhythm was significantly longer in patients with conducted bigeminy (375 ± 25 ms) than with concealed bigeminy (230 ± 17 ms). The pulmonary vein bigeminy was driven by coronary sinus pacing with the pacing cycle length at lower stimulation rates and was suppressed by overdrive pacing. Coronary sinus pacing led to a separation of the first pulmonary vein potential from the atrial signal but the interval between the atrial signal and the second pulmonary vein potential remained unchanged. Focal ablation at the site of earliest ectopic pulmonary vein activity in 5 patients induced rapid repetitive firing before elimination of the pulmonary vein bigeminy. Ostial disconnection of the arrhythmogenic pulmonary vein in 3 patients was associated with elimination of the pulmonary vein bigeminy. During the follow-up of 9 ± 5 months after ablation of the pulmonary vein bigeminy, 5 of the 8 patients (63%) were free of atrial fibrillation without antiarrhythmic medication. Conclusions: The response of pulmonary vein bigeminy to atrial pacing and ostial ablation suggests that pulmonary vein bigeminy depends on an intact electrophysiological breakthrough between the left atrium and the pulmonary vein. Ablation targeting the pulmonary vein bigeminy is a possible limited approach for this subgroup of patients with paroxysmal atrial fibrillation.     

Role of Right Middle Pulmonary Vein in Patients with Paroxysmal Atrial Fibrillation

INTRODUCTION: Elimination of the ectopic foci from pulmonary veins (PVs) has proved to be a curative therapy for focal atrial fibrillation (AF). However, information about the importance of the right middle PV (RMPV) in initiation of AF and radiofrequency ablation of AF is limited. METHOD AND RESULTS: Forty-three patients (34 men and 9 women; age 65+/-12 years) with drug-refractory paroxysmal AF underwent electrophysiologic study and catheter ablation for treatment of AF. Three-dimensional magnetic resonance angiography (MRA) of the PVs and left atrium (LA) was performed to determine the anatomic patterns of RMPV. Diameter of PV ostium was measured at the junction of the LA and each PV. MRA findings showed the following: (1) 36 (84%) of 43 patients had a discrete RMPV; (2) there are three drainage patterns of RMPV, including joining the proximal part (<1 cm from the ostium) of the right superior PV (RSPV), joining the right inferior PV (RIPV), and a separate RMPV ostium in the LA wall; and (3) the ostial diameter of RMPV was significantly smaller than RSPV and RIPV (P < 0.01). Electrophysiologic studies demonstrated that five AF foci arose from RMPV. The coupling interval between the ectopic beat of AF and sinus beat was longer in RMPV than RSPV (262+/-45 msec vs 212+/-47 msec; P = 0.043). All AFs from RMPV were ablated successfully. PV stenosis or AF recurrence from RMPV was not found during follow-up of 10+/-4 months. CONCLUSION: RMPV was detected by MRA in >80% of paroxysmal AF patients. Ectopy from RMPV can initiate AF, and radiofrequency ablation of RMPV foci is feasible and safe.     

Pulmonary Vein Antral Isolation and Nonpulmonary Vein Trigger Ablation without Additional Substrate Modification for Treating Longstanding Persistent Atrial Fibrillation

PV Ablation for Persistent Atrial Fibrillation. Introduction: Effectiveness of antral pulmonary vein isolation (PVAI) and ablation of non‐PV triggers (non‐PVTA) in controlling longstanding persistent atrial fibrillation (AF) has not been reported. We sought to describe clinical outcomes with this ablation strategy in patients (pts) followed for at least 1 year. Methods: Two hundred pts underwent PVAI for longstanding persistent AF and were followed for recurrence. Thirty‐three pts with <1‐year follow‐up and 37 pts with additional RF atrial ablation were excluded, leaving 130 pts for analysis. Results: All 130 pts (108 men, mean LA 4.7 ± 0.6 cm, mean AF duration of 38 ± 44 months) underwent PVAI with entrance/exit block. In addition, 24 pts (15 pts during the initial procedure and 9 additional pts at repeat ablations) had 40 non‐PVTA, including 3 with AVNRT. During follow‐up, atrial flutter (AFL) was noted in 7 (5%) pts. The AF‐free survival after single procedure without antiarrhythmic drugs (AAD) was 38%. Repeat AF or AFL ablation was performed in 37 pts (28%) with PV reconnection uniformly identified (3.7 ± 0.5 veins/pt). During mean follow‐up of 41.1 ± 23.8 months (range 12–103 months), 85/130 pts (65%) were in sinus rhythm with 65 pts (50%) off AAD, 20 pts (15%) on AAD. Additionally, 9 pts (7%) have had rare episodes of AF such that 72% of pts have had good long‐term clinical outcome. Of the 36 pts with recurrent AF, 20 pts have not had a repeat procedure. Conclusions: PVAI with non‐PVTA for longstanding persistent AF provides good long‐term AF control in over 70% of patients with infrequent (5%) AFL. AAD therapy and repeat PVAI may be required for this optimal outcome. (J Cardiovasc Electrophysiol, Vol. 23, pp. 806‐813, August 2012)     

肺静脉前庭的组织解剖学特点与心房颤动

肺静脉前庭是肺静脉和左房相延续的区域，胚胎发育中由肺静脉与左房融合、吸收逐渐形成，该处肌纤维走行复杂，可呈环形、纵行或斜行排列，不同肌纤维相互交错、各向异性明显，激动在此处传导时存在明显延缓或阻滞。肺静脉及其前庭组织与心房颤动的发生、维持密切相关，深入认识肺静脉前庭区域的组织解剖学特点，对理解心房颤动发生、维持机制，进而指导临床治疗具有重要意义。     

Lobectomy for Pulmonary Vein Occlusion Secondary to Radiofrequency Ablation

Pulmonary Vein Occlusion After RF Ablation . Pulmonary vein stenosis, a recognized complication of transcatheter radiofrequency ablation in the left atrium, is often asymptomatic. Significant stenosis is commonly treated with percutaneous balloon dilation with or without stenting. We encountered a case of complete pulmonary vein occlusion that caused lobar thrombosis, pleuritic pain, and persistent cough. Imaging studies revealed virtually no perfusion to the affected lobe. A lobectomy was performed, resolving the persistent cough and pain. Pulmonary vein occlusion should be suspected in patients who present with pulmonary symptoms after having undergone ablative procedures for atrial fibrillation. This condition may necessitate surgical intervention if interventions such as balloon dilation or stenting are not possible or are ineffective. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1055‐1058, September 2010)     

Pulmonary Vein Stenting for the Treatment of Acquired Severe Pulmonary Vein Stenosis after Pulmonary Vein Isolation: Clinical Implications after Long-Term Follow-Up of 4 Years

Introduction: Severe pulmonary vein stenosis (PVS) after catheter ablation of atrial fibrillation (AF) is a well-recognized complication with a further reported incidence of 1.3%. The preferred therapy for symptomatic PVS is pulmonary vein (PV) angioplasty, but this treatment modality is followed by restenosis in 44–70%. Whether there is additional long-term benefit from PVS stenting is uncertain. The aim of this study was the evaluation of the long-term success after PV stenting of severe stenosis.
Methods and Results: Ten patients (pts) with 13 PVS were prospectively evaluated. PV stenting was performed with Palmaz Genesis stents. Magnetic resonance imaging (MRI), lung perfusion scans, and CT-scans were performed before, directly after, and every 12 months thereafter. Primary endpoint of the study was the occurrence of restenosis after PV stenting. After a median follow-up of 47.7 (IQRs 25/75 47.2–48.5) months, the primary endpoint was achieved in 3 out of 13 PVs (23% of the treated PVs). We observed two in-stent restenosis 2 and 4 years after PV stenting. These pts experienced onset of dyspnea some weeks before. After an additional balloon angioplasty, the in-stent restenosis was resolved. In one asymptomatic patient, we observed an occlusion of the PV stent 13 months poststenting. Normalization of lung perfusion was noted 4 years after PV stenting versus directly poststenting in all pts without in-stent restenosis (n = 7).
Conclusion: PVS stenting with stent sizes ≥10 mm seems to be an adequate therapy modality for treatment of severe acquired PVS. Late in-stent restenosis after PVS stenting can occur. The normalization of the initially disturbed lung perfusion scan is possible and remains stable, even 4 years after PVS stenting.     

Spontaneous Transition from Atrial Fibrillation to Typical Atrial Flutter during Catheter Ablation of the Pulmonary Vein

A 71-year-old male patient was admitted for catheter ablation of the pulmonary veins to treat paroxysmal atrial fibrillation. Atrial fibrillation originating from the left superior pulmonary vein was induced after a pause of atrial pacing under isoproterenol infusion and became sustained. Spontaneous transition from atrial fibrillation to typical atrial flutter was noted after complete isolation of the pulmonary vein focus from the left atrium. Subsequently linear ablation of the cavotricuspid isthmus was created with completely bi-directional isthmus conduction block. We hypothesized that ectopic pulmonary vein focus played an important role in the spontaneous conversion of atrial fibrillation to typical atrial flutter, and complete isolation of the pulmonary vein could stop the spontaneous transition between the two atrial tachyarrhythmias.     

肺静脉隔离术后心房颤动复发的原因和机制

节段性肺静脉电隔离术后心房颤动复发率较高,限制了该项技术的临床应用,现对其复发的原因与机制作一综述。     

Initial Experience with a Novel Focused Ultrasound Ablation System for Ring Ablation Outside the Pulmonary Vein

Introduction: Atrial fibrillation has been shown to initiate from triggers within pulmonary veins. Several studies have documented that electrical isolation of those triggers can lead to maintenance of sinus rhythm. The complication of pulmonary vein stenosis has limited the utility of delivering ablation energy within the pulmonary vein. We utilize a focused ultrasound catheter ablation system for delivery of transmural ablation lines proximal to the pulmonary vein ostium. Methods: Nine dogs (weight 30–39 kg) were anesthetized and ventilated. Through a transseptal approach, pulmonary veins were engaged with the focused balloon ultrasound catheter. Ultrasound power was delivered at 40 acoustic watts outside the pulmonary vein ostium, focused 2 mm off the balloon surface, with a depth of approximately 6 mm, for 30–120 seconds. Following ablation, lesions were histopathologically analyzed. Results: Of nine animals studied, fourteen pulmonary veins were ablated. We found successful delivery of near circumferential and transmural ablation lines in 6/14 pulmonary veins. In each of the six circumferential ablations, successful alignment of the ultrasound transducer along the longitudinal axis of the parabolic balloon occurred. The final four ablations were conducted with an enhanced catheter design that assured axial alignment. Of these ablations, all four were circumferential. The remaining 8 pulmonary veins had incomplete delivery of lesions. In each of these veins the ultrasound transducer was misaligned with the balloon axis when therapy was delivered. Conclusion: Focused ultrasound ablation is a new means of performing pulmonary vein isolation. This method provides delivery of lesions outside the vein, limiting the risk of pulmonary vein stenosis for the treatment of atrial fibrillation.