Variability in Postpacing Intervals Predicts Global Ventricular Activation Pattern during Tachycardia

Introduction: Assessment of ventricular activation pattern is critical to the successful ablation of ventricular tachycardia (VT). We have previously shown that the global atrial activation pattern during tachycardia can be rapidly and accurately assessed by calculating the postpacing interval variability (PPIV); PPIV was minimal in circuitous tachycardias and highly variable in centrifugal tachycardias. In the present study, we use the PPIV to determine the ventricular global activation pattern during VT. Methods: Patients with mappable VT were included. We defined global ventricular activation as either centrifugal (arising from a focus with radial expansion) or circuitous (gross macro‐reentrant circuit), based on the findings of electroanatomic mapping. PPIV was calculated as the difference in postpacing interval with right ventricular apical overdrive pacing during tachycardia at cycle lengths (CL) 10 ms and 30‐ms shorter than tachycardia, regardless of the origin of the tachycardia. We studied 20 patients with 23 VTs (11 centrifugal, mean CL 390 ± 36.1 ms; 12 circuitous, mean CL 418 ± 75.7 ms). Results: The mean PPIV was 45 ± 16 ms for patients with centrifugal VT and 6.7 ± 4.1 ms for patients with circuitous VT. Rank sum analysis of PPIV showed a significant difference between the two groups (P < 0.05). Conclusions: Our data suggest that the global ventricular activation pattern during VT can be rapidly and accurately defined by assessing the PPIV. This technique allows for a rapid confirmation of the tachycardia activation and significantly facilitates mapping and ablation. (PACE 2010; 33:129–134)     

Wide QRS Complexes: Electrophysiologic Basis of a Common Electrocardiographic Diagnosis

Wide QRS Complexes. Wide QRS complex tachycardia is a commonly encountered arrhythmia and its appropriate diagnosis often poses a challenge to most physicians. The origin of a wide QRS complex is either supraventricular with abnormal ventricular activation or ventricular. This review addresses the main electrophysiologic mechanisms involved in the genesis of a wide QRS complex and its maintenance as a sustained arrhythmia. (J Cardiovasc Electrophysiol, Vol. 3, pp. 365–393, August 1992)     

In Vitro and In Vivo Results of Transcatheter Microwave Ablation Using Forward-Firing Tip Antenna Design

This study was designed to test a microwave (MW) ablation system using approximately 2,450 MHz of energy and a deflectable catheter with forward-firing tip antenna, an early clinical prototype system. In vitro three-dimensional thermal mapping of single and double helix antenna designs was performed. Quantitative measurements of antenna radiation were recorded on tissue phantoms equipped with temperature sensors distributed radially and outwardly. In vivo testing consisted of closed-chest AV junction ablation in three dogs. Thermal mapping showed hemispherical heat distribution from the tip antenna. For the double helix design, this distribution was measured at 8,4-mm diameter with a maximum temperature of 61.62°C. As expected, the single helix design produced less heating with a measured diameter of 6.4 mm and maximum temperature of 55.90°C. The in vivo study produced lesions of geometry and size concordant with these heating patterns. MW ablation produced bundle branch block in one dog and complete AV nodal block in the remalning two, without transvalvular or other structural damage. The histopathology of the lesions was typical of a thermal burn showing hemorrhage and coagulative necrosis with clearly demarcated borders. We conclude that, using this early clinical prototype system with a deflectable catheter and a forward-firing tip antenna design, MW heating can produce a moderate-size lesion and is safe and effective for cardiac ablation.     

Radiofrequency Catheter Ablation of Ventricular Tachycardia Following Implantation of an Automatic Cardioverter Defibrillator

The present study reports on the complementary role of two nonpharmacological options of antiarrhythmic therapy. Background: Catheter ablation, antitachycardia surgery, and the implanfahie cardioverter de/ibrillator (ICD)have become important tools in the management of ventricuiar tachyarrhythmias. However, the emergence of ventricuiar tachyarrhythmias after implantation of an ICD is possihie because the arrhythmogenic suhstrate is not affected. Patients and Methods:Six of 180 patients developed frequent episodes of monomorphic ventricular tachycardia (n = 2) or incessant ventricular tachycardia (n = 4) following implantation of an ICD and underwent radio/requency (RF)catheter ablation. Catheter ablation was performed using a HF generator HAT 200. Energy was delivered between a 4-mm tip electrode of the ahiation catheter and a patch electrode. Results: Catheter ablation was done 6.8 ± 5 months following ICD implantation; 6 ± 2.2 RF impulses were delivered at the site of origin of ventricuiar tachycardia chararcterized by early endocardial activation during ventricular tachycardia, identical pace mapping and long latency between stimulus, and QRS-complex in five patients. New bundle branch reentry was the underlying mechanism of ventricular tachycardia in one patient. RF catheter ablation resulted in termination o/ incessant ventricular tachycardia. Immediately postabiation, the documented ventricular tachycardia was rendered noninducible in all patients. No ICD malfunctions have been observed. One patient died due to heart failure 24 hours after successful ablation of the incessant ventricular tachycardia. During a follow-up of 5–19 months, episodes of ventricular tachycardia recurred in four patients. All episodes could be controlled by the ICD without frequent cardioversions. Conclusion: RF catheter ablation is o complementary therapeutic option in case of frequent or incessant ventricular tachycardia after ICD implantation.     

Relative Efficacy of Different Tilts with Biphasic Defibrillation in Humans

Objective: The goal of this study was to assess if tilt bears any impact on defibrillation efficacy of biphasic shocks. Background: Although it has been shown that hiphasic waveform may increase the defibrillation efficacy, this pulsing method has not been as extensively studied in patients, and information regarding the effect of different tilts is lacking. Methods: This study consisted of two similar but distinct protocols including 33 patients undergoing transvenous defibriilator implant. In 17 patients (Part I) defibrillation threshold was obtained delivering biphasic waveforms with 50%, 65%, and 80% tilt in random fashion. Similarly, in 16 patients (Part II) testing of biphasic waveform with 40%, 50%, and 65% tilt was performed in random order. The electrode system used consisted of two transvenous leads and a subcutaneous patch in all 33 patients. Results: In Part I, tilt of 50% demonstrated a defibrillation threshold significantly lower than 65% tilt (7.5 ± 4.3 J vs 9.7 ± 5.0 J; P = 0.04) and 80% tilt (7.5 ± 4.3) vs 11.7 ± 5.9 J; P < 0.01). Similarly, 65% tilt provided a lower defibrillation threshold than 80% tilt (9.7 ± 5.0 J vs 11.7 ± 5.9 J; P = 0.02). In Part II, no significant difference was observed in terms of defibriilation threshold between 40% tilt and the two tilts of 50% and 65%. However, as in Part I, 50% tilt provided a significant reduction of the energy to defibrillate as compared to 65% tilt (6.3 ± 3.6 J vs 9.0 ± 4.8 J; P < 0.01). The 50% tilt resulted in better defibrillation efficacy than 65% tilt independent of the lead system used for testing (Medtronic Transvene and CPI Endotak-C). Conclusions: Biphasic shocks with 50% tilt required less energy for defibrillation than 40%, 65%, and 80% tilts. However, in the clinical setting a programmable tilt may be preferable to account for some patient-to-patient variability.     

Microwave Catheter Ablation Using a Clinical Prototype System with a Lateral Firing Antenna Design

Microwave has been considered a potentially more effective and more versatile form of energy than radiofrequency. Its feasibility has been tested using various prototype systems and catheter designs. This study assessed the safety and efficacy of a clinically-suitable prototype microwave power supply and catheter system with a lateral-firing antenna design for atrioventricular (AV) junction ahlation in canines and to correlate with tissue histopathology. The system consisted of a deflectable catheter with a 6-mm antenna and a thermocouple; and a 2.45-CHz frequency generator with power, time, and temperature controls. AV junction ablations were performed using 75 W energy for up to 60 seconds. Effective heating was confirmed hy a rise in catheter temperature to 69.3 ± 8.8°C. Complete AV nodal block was accomplished in all canines after an average of 4.1 ± 2.3 applications at 66.8 ± 7.7°C, and persisted after 28 days in all chronic animals. Lesions were consistent with thermal necrosis, were hemispherical to semi linear in shape and have distinct borders. Acute lesions were 3.4 ± 1.5 mm wide, 4.8 ±2.1 long, and 2.0 ± 0.9 deep. Chronic lesions showed typical healing and were smaller in size. Ablations did not cause any transvalvular, vascular or other cardiac structural damage, and no coagulum formation was noted on the antenna or catheter tip. Microwave AV junction ablation using this clinical prototype system specifically designed for it was safe and effective. Lesion's depth was limited to 5 mm with 60-second heating while its shape corresponded to the antenna's length. Microwave energy may provide greater versatility for producing discrete or linear ablation.     

Ventricular Fibrillation and Polymorphic Ventricular Tachycardia with Critical Coronary Artery Stenosis:

ICD Therapy and CABG for Sudden Death. Introduction: Previous studies have suggested that coronary artery bypass surgery is sufficient to prevent recurrence of sudden death in patients with critical coronary artery stenosis presenting with ventricular fibrillation or polymorphic ventricular tachycardia. We present our experience in patients with one or more episodes of sudden death associated with documented ventricular fibrillation or polymorphic ventricular tachycardia and severe operable coronary artery disease who underwent defibrillator implant at the time of bypass surgery. Methods and Results: Fifty-eight consecutive patients (age 63 ± 8 years) were included in this study. Eighteen of the 58 patients had no evidence of previous myocardial infarction. The mean ejection fraction was 37 ± 13%. All patients underwent electrophysiologic study before and after revascularization. At the time of first defibrillator discharge, each patient was reevaluated to exclude the presence of ischemia. The benefits of defibrillator implant were estimated comparing the projected survival based upon defibrillator discharge preceded by syncope or presyncope with survival curves generated including total death and sudden plus cardiac death. After a mean follow-up of 4.6 ± 2 years, 22 patients received appropriate shocks preceded by syncope or presyncope, and an additional 19 patients received asymptomatic shocks. At 4 years, survival free of total death was 71.2%, and the projected survival was 58.8% (P < 0.05). Multivariate analysis showed that ejection fraction lower than 30% and induction of arrhythmia with one or two extrastimuii (S2, S3) were independent predictors for defibrillator discharge. None of the remaining variables including age, gender, number of bypasses, history of myocardial infarction, and type of arrhythmias induced were predictive for death and occurrence of shocks. Conclusions: In patients with ventricular fibrillation and polymorphic ventricular tachycardia, bypass surgery does not protect from recurrence of life-threatening arrhythmias, and, as in our population, defibrillator implant may have significant impact on survival.     

Functional Bundle Branch Block as a Delayed Manifestation of Retrograde Concealment in the His-Purkinje System

Delayed Manifestation of Retrograde HPS Concealment. Introduction: The mechanism of functional bundle branch block induced at the onset of supraventricular tachycardia (SVT) is well established. However, no data exist to address the underlying mechanism of functional bundle branch block occurring in the second beat of SVT, when the first beat is conducted with a narrow QRS morphology and preceded by ventricular stimulation. Methods and Results: Two patients showing such a phenomenon form the basis of this report. Patient 1 with AV nodal reentrant tachycardia of the common variety persistently demonstrated functional right bundle branch block in the second SVT complex when a short train of ventricular pacing was introduced during SVT. This occurred without any discernible change in the SVT cycle length. Patient 2 bad a manifest posteroseptal accessory pathway and inducible orthodromic reentrant tachycardia. Functional bundle branch block during propagation of the second SVT complex invariably occurred either in the left bundle when SVT was induced by a bundle branch reentrant complex during premature ventricular stimulation, or in the right bundle when SVT was induced with a short train of ventricular pacing. The development of functional bundle branch block was preceded by minimal or no cycle length variations in the His-bundle inputs. Conclusion: These observations suggest that the type of functional bundle branch block occurring in the second SVT complex as a de novo phenomenon may be related to the relative timing of the retrograde penetration of the right versus left bundle during ventricular pacing or bundle branch reentrant complex. Therefore, due to its longest cycle length of activation and refractoriness, the earliest site of retrograde penetration is the most likely site of functional block during propagation of the second SVT complex. This delayed manifestation of retrograde concealment may provide new information regarding the electrophysiologic behavior of the His-Purkinje system.     

Suppression of human papillomavirus type 16 E5 oncoprotein: A promising step in fostering the treatment of cervical cancer

Cervical cancer is a growing global disease in developing countries. Persistent infection with humanpapillomaviruses (HPV) is an essential causative agent in this type of cancer. Several studies demonstrate HPV E5oncoprotein can impress the normal life cycle of HPV-infected cells by targeting some pivotal cellular signalingpathways, such as the epidermal growth factor receptor (EGFR) signaling pathway. In this study, we used E5-siRNAto knockdown that essential oncogene and considered the effect of E5 silencing on proliferation, apoptosis, cell cycle,apoptosis-related gene expression, and the initiator of the EGFR signaling pathway in cervical cancer cells. The resultsdemonstrate that E5 plays an essential role in the proliferation and inhibited apoptosis in cervical cancer.Furthermore, silencing E5 reduces proliferation, increases apoptosis, and elevates related-genes expression of thesemalignant cells. Overall, E5 suppression may be appropriate for ameliorating cervical cancer progression.