STRA-MI-VT (STereotactic RadioAblation by Multimodal Imaging for Ventricular Tachycardia): rationale and design of an Italian experimental prospective study.

BACKGROUND: Ventricular tachycardia (VT) is a life-threatening condition, which usually implies the need of an implantable cardioverter defibrillator in combination with antiarrhythmic drugs and catheter ablation. Stereotactic body radiotherapy (SBRT) represents a common form of therapy in oncology, which has emerged as a well-tolerated and promising alternative option for the treatment of refractory VT in patients with structural heart disease. OBJECTIVE: In the STRA-MI-VT trial, we will investigate as primary endpoints safety and efficacy of SBRT for the treatment of recurrent VT in patients not eligible for catheter ablation. Secondary aim will be to evaluate SBRT effects on global mortality, changes in heart function, and in the quality of life during follow-up. METHODS: This is a spontaneous, prospective, experimental (phase Ib/II), open-label study (NCT04066517); 15 patients with structural heart disease and intractable VT will be enrolled within a 2-year period. Advanced multimodal cardiac imaging preceding chest CT-simulation will serve to elaborate the treatment plan on different linear accelerators with target and organs-at-risk definition. SBRT will consist in a single radioablation session of 25 Gy. Follow-up will last up to 12 months. CONCLUSIONS: We test the hypothesis that SBRT reduces the VT burden in a safe and effective way, leading to an improvement in quality of life and survival. If the results will be favorable, radioablation will turn into a potential alternative option for selected patients with an indication to VT ablation, based on the opportunity to treat ventricular arrhythmogenic substrates in a convenient and less-invasive manner.

Cryoballoon ablation of atrial fibrillation is effectively feasible without previous imaging of pulmonary vein anatomy: insights from the 1STOP project.

BACKGROUND: Pulmonary vein isolation by cryoablation (PVI-C) is a standard therapy for the treatment of atrial fibrillation (AF); however, PVI-C can become a challenging procedure due to the anatomy of the left atrium and pulmonary veins (PVs). Importantly, the utility of imaging before the procedure is still unknown regarding the long-term clinical outcomes following PVI-C. The aim of the analysis is to evaluate the impact of imaging before PVI-C on procedural data and AF recurrence. METHODS: Patients with paroxysmal AF underwent an index PVI-C. Data were collected prospectively in the framework of 1STOP ClinicalService® project. Patients were divided into two groups according to the utilization of pre-procedural imaging of PV anatomy (via CT or MRI) or the non-usage of pre-procedural imaging. RESULTS: Out of 912 patients, 461 (50.5%) were evaluated with CT or MRI before the PVI-C and denoted as the imaging group. Accordingly, 451 (49.5%) patients had no pre-procedural imaging and were categorized as the no imaging group. Patient baseline characteristics were comparable between the two cohorts, but the ablation centers that comprised the imaging group had fewer PVI-C cases per year than the no imaging group (p < 0.001). The procedure, fluoroscopy, and left atrial dwell times were significantly shorter in the no imaging cohort (p < 0.001). The rates of complications were significantly greater in the imaging group compared to the no imaging group (6.9% vs. 2.7%; p = 0.003); this difference was attributed to differences in transient diaphragmatic paralysis. The 12-month freedom from AF was 76.2% in the imaging group and 80.0% in the no imaging group (p = 0.390). CONCLUSIONS: In our analysis, PVI-C was effective regardless of the availability of imaging data on PV anatomy.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Histology and ultrastructure of the coenenchyme of the octocoral Swiftia exserta, a model organism for innate immunity/graft rejection.

The octocoral Swiftia exserta has been utilized extensively in our laboratory to study innate immune reactions in Cnidaria such as wound healing, auto- and allo-graft reactions, and for some classical "foreign body" phagocytosis experiments. All of these reactions occur in the coenenchyme of the animal, the colonial tissue surrounding the axial skeleton in which the polyps are embedded, and do not rely on nematocysts or directly involve the polyps. In order to better understand some of the cellular reactions occurring in the coenenchyme, the present study employed several cytochemical methods (periodic acid-Schiff reaction, Mallory's aniline blue collagen stain, and Gomori's trichrome stain) and correlated the observed structures with electron microscopy (both scanning and transmission). Eight types of cells were apparent in the coenenchyme of S. exserta, exclusive of gastrodermal tissue: (i) epithelial ectoderm cells, (ii) oblong granular cells, (iii) granular amoebocytes, (iv) morula-like cells, (v) mesogleal cells, (vi) sclerocytes, (vii) axial epithelial cells, and (viii) cnidocytes with mostly atrichous isorhiza nematocysts. Several novel organizational features are now apparent from transmission electron micrographs: the ectoderm consists of a single layer of flat epithelial cells, the cell types of the mesoglea extend from beneath the thin ectoderm throughout the mesogleal cell cords, the organization of the solenia gastroderm consists of a single layer of cells, and two nematocyst types have been found. A new interpretation of the cellular architecture of S. exserta, and more broadly, octocoral biology is now possible.

Rhythm-symptom correlation in patients on continuous monitoring after catheter ablation of atrial fibrillation.

INTRODUCTION: Correlation between symptoms and atrial fibrillation (AF) episodes after catheter ablation may have clinical relevance, especially for anticoagulation usage. The aim of our project was to analyze the relationship between symptoms and AF recurrences in unselected patients following AF catheter ablation during long-term follow-up. METHODS AND RESULTS: One hundred and forty-three consecutive patients (mean age 59 ± 9 years, 85% male) were implanted with a continuous cardiac monitor (RevealXT, Medtronic Inc., Minneapolis, MN, USA) following first pulmonary vein ablation procedure. Device data were downloaded every 3 months and correlated to patients' symptom diary. AF was paroxysmal in 55% and persistent in 45%. At a mean follow-up of 14 ± 6 months, 98/143 (69%) patients had at least one AF recurrence. Among these, 53 (54%) reported AF-related symptoms while 45 (46%) were totally asymptomatic. Conversely, 13 (29%) out of 45 patients without AF recurrences reported symptoms. Globally, a significant reduction of symptoms (from 82% at baseline to 44% at last follow-up; P < 0.0001) was observed. SF-12 questionnaire showed a significant improvement of physical and mental functioning (respectively 44.5 ± 8.5 vs 51.0 ± 6.7, and 45.7 ± 9.3 vs 49.2 ± 6.1, P < 0.05 baseline vs last follow-up). At the 12-month follow-up, 80% and 77% of patients were on AAD and anticoagulant drugs, respectively. There were not differences in AAD usage in symptomatic and asymptomatic patients. CONCLUSIONS: Continuous ECG monitoring is a valuable tool for long-term follow-up after AF catheter ablation facilitating reliable assessment of symptomatic and asymptomatic AF episodes. This may have clinical implications with regards to anticoagulation therapy in high-risk patients.

Intracardiac echocardiography in electrophysiology.

Intracardiac echocardiography (ICE) is a recent, invaluable tool which can provide real-time anatomical guidance in electrophysiological procedures. By inserting intravenously an ultrasound probe and advancing it into the heart, various different views can be obtained which allow to better visualize patient anatomy, to guide the placement of electrophysiological catheters, and to detect immediately procedural complications as they occur. In atrial fibrillation ablation, ICE proves particularly useful to achieve a safer trans-septal puncture (especially in the presence of anatomical anomalies of the interatrial septum) and to help to monitor the visualization of the mapping catheters (circular, high density), or the monitoring of the balloons catheter (Cryo, Laser) position. In ventricular tachycardia ablation, on the other hand, ICE allows for continuous correlation between electrophysiological and structural findings (such as wall motion anomalies or changes in echodensity), and helps to ensure correct catheter contact and to position it, particularly around delicate structures such as the aortic cusps. In any procedure, ICE is also useful to immediately detect procedural complications, such as thrombus formation along catheters, or pericardial effusion. Thanks to its real-time morphological information, ICE provides an ideal complement to simple fluoroscopy or to more complex electroanatomic mapping techniques and is set to gain a wider role in a broad range of electrophysiological procedures.

Atypical atrial flutter: clinical features, electrophysiological characteristics and response to radiofrequency catheter ablation.

AIMS: To evaluate the clinical and electrophysiological features of atypical atrial flutter (AAF) and its response to radiofrequency catheter ablation. METHODS AND RESULTS: In 90 consecutive patients referred for sustained atrial flutter, bipolar recordings were obtained from the tricuspid annulus, coronary sinus, interatrial septum and left atrium. AAF was defined by the absence of concealed entrainment from the inferior vena cava--tricuspid annulus isthmus. Target sites were identified by early, fragmented or double potentials and by concealed entrainment. Linear lesions were created between target sites and nearby anatomical barriers in a temperature-controlled mode: 20 episodes of AAFs were documented in 19/90 (21%) patients. Mitral valve disease and surgery were significantly more frequent in patients with AAF. Target sites were identified in the right atrial free wall (n=8), interatrial septum (n=6), left atrium (n=4) and coronary sinus (n=2). Effective ablation was obtained in 15/19 patients (79%). After a 15.7 +/- 10.7 month follow-up, AAF recurred in 0/15 patients with a successful and 3/4 (75%) with a failed procedure (P<0.05). CONCLUSIONS: Conventional mapping techniques enable identification of critical sites of AAF and allow successful ablation in the majority of cases.

Non-contact mapping to guide catheter ablation of untolerated ventricular tachycardia.

AIMS: The role of a novel non-contact mapping system (ESI 3000, Endocardial Solutions) to guide radiofrequency catheter ablation of untolerated ventricular tachycardia was investigated in 17 patients; 11 with prior myocardial infarction, three with arrhythmogenic right ventricular dysplasia, and three with idiopathic dilated cardiomyopathy. METHODS: Twenty-seven monomorphic ventricular tachycardias were induced (mean cycle 320+/-60 ms, range 230-450 ms), mapped for 15-20 s, and terminated by overdrive pacing or DC shock. Off-line analysis of isopotential activation mapping was performed to identify the diastolic pathway and/or the exit point of the ventricular tachycardia reentry circuit. Radiofrequency current was applied to create a line of block across the diastolic pathway or around the exit point. RESULTS: All 27 ventricular tachycardias were mapped with the non-contact system. The endocardial exit point (-7+/-15 ms before QRS onset) was defined in 21/21 postinfarction ventricular tachycardias, in 3/3 arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated cardiomyopathy ventricular tachycardias, respectively. The diastolic pathway (earliest endocardial diastolic activity: -65+/-49 ms before QRS onset) was identified in 17/21 postinfarction ventricular tachycardias, in 1/3 arrhythmogenic right ventricular dysplasia and in 1/3 idiopathic dilated cardiomyopathy ventricular tachycardias, respectively. Catheter ablation was performed in 25/27 ventricular tachycardias (93%) in 15/17 patients (88%): 16/25 ventricular tachycardias (64%) were successfully ablated in 10/17 patients (59%). Catheter ablation was not performed in two patients or proved unsuccessful in five patients. At a follow-up of 15+/-5 months, there was no recurrence of documented ventricular tachycardia in all 10 patients with successful catheter ablation; in two of them a previously non-documented ventricular tachycardia occurred. A high recurrence of ventricular tachycardia was observed in patients with a failed procedure (5/7: 71%). No major complication or death occurred. CONCLUSIONS: Non-contact mapping can be effectively used to map and guide radiofrequency catheter ablation of untolerated ventricular tachycardias. Given the favourable acute and clinical long-term results, this approach proves to be more effective in patients with postinfarction ventricular tachycardias, in comparison to patients with arrhythmogenic right ventricular dysplasia and idiopathic dilated cardiomyopathy.

Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post-infarction ventricular tachycardia; long-term outcome in relation to acute electrophysiological findings.

AIMS: Radiofrequency catheter ablation is effective at terminating ventricular tachycardia, but the overall clinical role of the technique in patients with a prior myocardial infarction is still debated, due to the uncertainties of the long-term reliability of the procedure. The purpose of this study was to prospectively investigate the relationship between acute results obtained by catheter ablation and long-term outcome in a homogeneous population of patients with post-myocardial infarction ventricular tachycardia. METHODS AND RESULTS: One hundred and twenty-four consecutive patients with recurrent, drug-refractory, haemodynamically tolerated ventricular tachycardia were included in the study. This population accounted for 30% of the patients with post-myocardial infarction ventricular tachycardia admitted between April 1992 and September 1997 to the investigating centres. The ablation was successful in eliminating sustained ventricular tachycardia in 91 of them (73%); a partial result was obtained in 21 (17%) and failure in 12 (10%). Low dose amiodarone and/or beta-blockers were maintained in 86% of the patients. Over a median follow-up of 41.5 months (interquartile range 30.5-59.5 months), there were 15 deaths (12%), three of which were sudden (2.4%); the 12 remaining patients died of heart failure. Event-free survival analysis showed a significantly lower ventricular tachycardia recurrence rate in patients with a successful procedure as compared to those with failure or a partial result (19% vs 53% at one year and 27% vs 60% at 3 years, P=0.003). A repeat procedure was performed in 15 patients with early recurrences and was followed in all by long-term success. Of those who submitted to a second procedure, 93/124 patients (75%) are free of ventricular tachycardia recurrences. An implantable cardioverter-defibrillator (ICD), following procedure failure, was implanted in 13 patients (11%) of the study population. CONCLUSIONS: Radiofrequency catheter ablation is effective in a wide population of patients with recurrent tolerated ventricular tachycardia, with very low sudden death and cardiac mortality rates over the long-term. Persistent ventricular tachycardia inducibility after catheter ablation requires an ICD implant and/or repeat ablation.

Electrophysiological characteristics and outcome in patients with idiopathic right ventricular arrhythmia compared with arrhythmogenic right ventricular dysplasia.

BACKGROUND: Idiopathic right ventricular arrhythmias (IRVA) are responsive to medical and ablative treatment and have a benign prognosis. Arrhythmias caused by right ventricular dysplasia (ARVD) are refractory to treatment and may cause sudden death. It is difficult to distinguish between these two types of arrhythmia. OBJECTIVE: To differentiate patients with IRVA and ARVD by a conventional electrophysiological study. METHODS: 56 patients with a right ventricular arrhythmia were studied. They had no history or signs of any cardiac disease other than right ventricular dysplasia. They were classified as having IRVA (n = 41) or ARVD (n = 15) on the basis of family history, ECG characteristics, and various imaging techniques. They were further investigated by standard diagnostic electrophysiology. RESULTS: The two groups were clearly distinguished by the electrophysiological study in the following ways: inducibility of ventricular tachycardia by programmed electrical stimulation with ventricular extrastimuli (IRVA 3% v ARVD 93%, p < 0.0001); presence of more than one ECG morphology during tachycardia (IRVA 0% v ARVD 73%, p < 0.0001); and fragmented diastolic potentials during ventricular arrhythmia (IRVA 0% v ARVD 93%, p < 0.0001). Data from the clinical follow up in these patients supported the diagnosis derived from the electrophysiological study. CONCLUSIONS: Patients with IRVA or ARVD can be distinguished by specific electrophysiological criteria. A diagnosis of ARVD can be made reliably on the basis of clinical presentation, imaging techniques, and an electrophysiological study.

Indications for dual-chamber cardioverter defibrillators at implant and at 1 year follow-up: a retrospective analysis in the single-chamber defibrillator era.

AIM: This retrospective four-centre study assessed the current indications for dual-chamber implantable cardioverter defibrillators (ICDs) at implant and during a medium-term follow-up period in a group of patients treated by single-chamber ICD in the pre dual-chamber ICD era. METHODS AND RESULTS: The study population consisted of 153 consecutive patients (127 males, mean age 58 +/- 6 years) treated by single-chamber ICD for ventricular tachycardia and/or ventricular fibrillation. Definite indications for having a dual-chamber ICD included the presence of sinus node dysfunction and of second- or third-degree atrioventricular (AV) block, while possible indications were represented by paroxysmal atrial fibrillation or flutter and first-degree AV block. At implant, dual-chamber ICD would appear definitely indicated in 10.5% of cases, and possibly indicated in an additional 17.5% of cases. During 12 +/- 10 months follow-up, such percentages remained stable (11 and 19.5%, respectively). Inappropriate ICD intervention was documented in five of 13 patients (38%), with episodes of paroxysmal atrial fibrillation or flutter. CONCLUSION: In this non-selected study population, a dual-chamber ICD would have potentially benefited approximately 30% of the patients. During medium-term follow-up, there was no progression towards increasing dual-chamber ICD indications. The 15% cumulative incidence of paroxysmal atrial tachyarrhythmias justifies the activation of dedicated detection algorithms.

Radiofrequency ablation of atrioventricular junction and pacemaker implantation versus modulation of atrioventricular conduction in drug refractory atrial fibrillation.

Modulation of atrioventricular (AV) node conduction and radiofrequency ablation of AV junction are alternative approaches to control ventricular rate in drug refractory atrial fibrillation (AF). In 2 centers, 120 patients were treated either with AV junction ablation (center 1, group 1, 60 patients [30 men, aged 64 +/- 11 years], paroxysmal AF in 24 patients) or with modulation (group 2, 60 patients [32 men, aged 58 +/- 12 years], paroxysmal AF in 43 patients). In group 1, complete AV block was achieved in all patients. In group 2, the procedure was performed in sinus rhythm (30 patients), prolonging the Wenckebach cycle length from 328 +/- 85 to 466 +/- 80 ms (p <0.01) or during AF (30 patients), decreasing ventricular rate from 178 +/- 35 to 96 +/- 35 beats/min (p <0.01), and to <100 beats/min in 17 patients (61%). Complete AV block was induced in 9 of 60 patients (15%). In groups 1 and 2, at a follow-up of 27 +/- 7 and 26 +/- 6 months, there were 2 deaths (1 cardiac, 1 sudden death) and 1 death for end-stage heart failure, respectively. Hospital readmissions decreased from 3.2 to 0.2 and from 4.2 to 0.2/year; late AF recurrences at of >120 beats/min were documented in 6% and 12%, respectively. Symptom score analysis including effort and rest dyspnea, exercise intolerance, weakness, and palpitation showed a significant improvement in both treatment groups, when acutely effective, in patients with paroxysmal and/or chronic AF. In conclusion, ablation of the AV junction shows a higher acute success rate compared with modulation of the AV node conduction in patients with drug refractory AF. Depending on the acute success, both approaches therefore were similarly effective in achieving long-term ventricular rate control and symptom score improvement.

Modulation of the atrioventricular node conduction to achieve rate control in patients with atrial fibrillation: long-term results.

Modulation of the AV node reduces the ventricular rate during AF, without affecting AV conduction during sinus rhythm. Acute and long-term results of AV node modulation in 75 patients with AF and severe related symptoms of heart failure are presented in this study. The procedure involved, in all cases, the selective ablation of the posterior inputs to the AV node; in a subgroup of 15 patients with poor modification of AV conduction properties, a sequential approach involving subsequent anterior input ablation was performed. The procedure caused acutely a prolongation of the Wenckebach cycle length (38 patients in sinus rhythm) from 334 +/- 88 to 470 +/- 80 ms (P < 0.01), and a reduction of the average ventricular rate (37 patients in AF) from 154 +/- 31 to 88 +/- 40 beats/min (P < 0.01); permanent complete AV block was induced in 9 of 75 patients (12%). Considering the "sequential" approach, an increase of the Wenckebach cycle length from 362 +/- 50 to 530 +/- 45 ms (P < 0.01) and a reduction of the average heart rate in patients with AF from 158 +/- 16 to 81 +/- 20 beats/min (P < 0.01) was obtained in this subgroup of patients, in whom the AH interval prolonged from 93 +/- 12 to 175 +/- 27 ms, and no complete AV block was observed. At a mean follow-up of 23 +/- 9 months (range 2-48), the mean number of hospital admissions per patient per year decreased from 4.2 to 0.2. Five of 49 patients with paroxysmal AF and 3 of 26 patients with chronic AF had high rate recurrences (1 > 120 beats/min) that caused severe palpitations; these patients were considered as late clinical failures (8/75; 11%). All patients reported a substantial subjective improvement and an increased exercise tolerance, as documented by a semiquantitative questionnaire. There were no episodes of late AV block or sudden cardiac deaths. In conclusion, modulation of the AV node--either by slow pathway ablation, or by a "sequential" posterior and anterior approach in refractory patients--allows a long-term control of the ventricular rate and prevents the recurrence of severe clinical symptoms in more than 75% of patients with drug refractory AF.

Incidence and clinical significance of transformation of atrial fibrillation to atrial flutter in patients undergoing long-term antiarrhythmic drug treatment.

AIMS: To investigate the rate of transformation of atrial fibrillation to atrial flutter in patients taking antiarrhythmic drugs for the prophylaxis of atrial fibrillation, we retrospectively analysed data from 305 consecutive patients with paroxysmal atrial fibrillation (155 male; mean age 63 +/- 11 years) treated with ventricular rate controlling drugs, antiarrhythmic drugs, or without drugs. METHODS AND RESULTS: At a mean follow-up of 9 months (range 1-24) all patients experienced recurrence of arrhythmia: 48 (14.6%, Group A) suffered Type 1 atrial flutter, and 257 (85.4%, Group B) atrial fibrillation. The relative rate of recurrence of atrial flutter vs atrial fibrillation was similar in patients without treatment or with ventricular rate controlling drugs (from 6.8% to 14.6%, P=ns). However, recurrence was higher (25%) in patients administered antiarrhythmic drug therapy. The relative risk in these patients was 3.02 times greater, compared with patients without treatment, or treated with rate controlling drugs (P<0.001). There were no differences between groups concerning the baseline clinical characteristics and the clinical consequences of the recurrence; patients with atrial flutter had a lower rate of conversion to sinus rhythm (42% vs 64%) and a higher rate of hospital admission (69% vs 36%) compared with those with atrial fibrillation. Six patients (8.5%) experienced 1:1 atrioventricular conduction during atrial flutter with a ventricular rate of 240-280 beats x min(-1). CONCLUSION: Our data suggest that the use of antiarrhythmic drugs for the prophylaxis of atrial fibrillation is associated with a threefold increase in the probability of Type 1 atrial flutter recurrence, as opposed to atrial fibrillation, which may have important clinical consequences, but which did not in our study.

Electrical conduction between the right atrium and the left atrium via the musculature of the coronary sinus.

BACKGROUND: The purpose of this study was to determine whether the coronary sinus (CS) musculature has electrical connections to the right atrium (RA) and left atrium (LA) and forms an RA-LA connection. METHODS AND RESULTS: Six excised dog hearts were perfused in a Langendorff preparation. A 20-electrode catheter (2-4-2-mm spacing center to center) was placed along the CS. Excision of the pulmonary veins provided access to the LA, and a second 20-electrode catheter was placed along the LA endocardium opposite the CS catheter. An incision opened the CS longitudinally, and microelectrodes were inserted into the CS musculature and adjacent LA myocardium. Continuous CS musculature was visible along a 35+/-9-mm length of the CS beginning at the ostium. During lateral LA pacing, CS electrodes recorded double potentials, a rounded, low-frequency potential followed by a sharp potential. The rounded initial potential propagated in the lateral-to-septal direction and represented "far-field" LA activation (timing coincided with adjacent LA potentials and with action potentials recorded from microelectrodes in adjacent LA cells). The sharp potential represented CS activation (timing coincided with action potentials recorded from CS musculature). A distal LA-CS connection (earliest sharp potential in the CS during lateral LA pacing) was located 26+/-7 mm from the ostium. During RA pacing posterior to the CS ostium, CS electrodes recorded septal-to-lateral activation of the high-frequency potential, with slightly later activation of the rounded potential (LA activation). Incisions surrounding the CS ostium isolating the ostium from the RA had no effect on the CS musculature and LA potentials during RA pacing within the isolated segment containing the CS ostium. RA pacing outside the isolated segment delayed activation of the CS musculature until after LA activation, confirming that the RA-CS connection was located in the region of the CS ostium as well as confirming the presence of the LA-CS connection. CONCLUSIONS: In canine hearts, the CS musculature is electrically connected to the RA and the LA and forms an RA-LA connection.

Evidence for multiple atrio-AV nodal inputs in the normal dog heart.

INTRODUCTION: Complete AV block after combined fast pathway (FP) and slow pathway (SP) ablation is uncommon. The purpose of this study was to interrupt activation of these and additional inputs by placing a radiofrequency lesion across the interatrial septum between the FP and SP ablation sites. METHODS AND RESULTS: In eight anesthetized open chest dogs, FP ablation induced significant A-H prolongation (deltaA-H: 51 +/- 14 msec; P < 0.001) and a shift of earliest retrograde atrial activation from the anterior septum to the region of the coronary sinus (CS) os. Subsequently, ablation of the interatrial septum across the fossa ovalis was successful in 5 of 8 dogs, changing the sequence of atrial activation (A) so that A at the His-bundle electrogram, which initially preceded A at the CS os (18 +/- 4 msec vs 46 +/- 7 msec, P < 0.01), now followed CS os A (81 +/- 31 msec vs 59 +/- 20 msec, P < 0.05). Additional ablation of the SP caused a type II Mobitz AV block or complete AV block in 5 of 8 dogs. The four dogs with complete AV block showed a stable, high junctional escape rhythm at a rate of 64 +/- 16 beats/min. Pacing between the ablation lesions and the AV node in one dog showed 1:1 AV conduction and Wenckebach-type AV block indicating preserved AV nodal function. Histology showed necrotic changes in the FP and SP transitional cell zones and in the atrial tissue of the interatrial septum. However, the compact AV node, His bundle, and adjacent atria and transitional cells were undamaged. CONCLUSION: There are additional AV nodal inputs in the interatrial septum in addition to the anterior FP and posterior SP inputs. Ablation of all of these may be required, if the aim is production of complete AV block proximal to the AV node with a high junctional escape rhythm.

Why a large tip electrode makes a deeper radiofrequency lesion: effects of increase in electrode cooling and electrode-tissue interface area.

INTRODUCTION: Increasing electrode size allows an increase in radiofrequency lesion depth. The purpose of this study was to examine the roles of added electrode cooling and electrode-tissue interface area in producing deeper lesions. METHODS AND RESULTS: In 10 dogs, the thigh muscle was exposed and superfused with heparinized blood. An 8-French catheter with 4- or 8-mm tip electrode was positioned against the muscle with a blood flow of 350 mL/min directed around the electrode. Radiofrequency current was delivered using four methods: (1) electrode perpendicular to the muscle, using variable voltage to maintain the electrode-tissue interface temperature at 60 degrees C; (2) same except the surrounding blood was stationary; (3) perpendicular electrode position, maintaining tissue temperature (3.5-mm depth) at 90 degrees C; and (4) electrode parallel to the muscle, maintaining tissue temperature at 90 degrees C. Electrode-tissue interface temperature, tissue temperature (3.5- and 7.0-mm depths), and lesion size were compared between the 4- and 8-mm electrodes in each method. In Methods 1 and 2, the tissue temperatures and lesion depth were greater with the 8-mm electrode. These differences were smaller without blood flow, suggesting the improved convective cooling of the larger electrode resulted in greater power delivered to the tissue at the same electrode-tissue interface temperature. In Method 3 (same tissue current density), the electrode-tissue interface temperature was significantly lower with the 8-mm electrode. With parallel orientation and same tissue temperature at 3.5-mm depth (Method 4), the tissue temperature at 7.0-mm depth and lesion depth were greater with the 8-mm electrode, suggesting increased conductive heating due to larger volume of resistive heating because of the larger electrode-tissue interface area. CONCLUSION: With a larger electrode, both increased cooling and increased electrode-tissue interface area increase volume of resistive heating and lesion depth.

Critical atrial site for ablation of pacing-induced atrial fibrillation in the normal dog heart.

INTRODUCTION: Radiofrequency catheter ablation (RFA) has been used recently to treat atrial fibrillation (AF). The purpose of this study was to investigate a new approach to preventing AF by RFA. METHODS AND RESULTS: In open chest, anesthetized dogs, AF (lasting > 30 sec) was induced after burst stimulation, and electrophysiologic parameters were recorded before and after RFA. In group 1 (9 dogs) we performed selective and combined slow and fast pathway RFA, whereas in group 2 (11 dogs) RFA was applied as a linear lesion at the mid-atrial septum between the inferior vena cava and the fossa ovalis. After ablation, the Wenckebach cycle length was significantly prolonged only in group 1 (194 +/- 23 vs 282 +/- 35 msec, P = 0.002), whereas the interval between the stimulus (S) artifact applied at the high right atrium to the His bundle (H) (SH interval) prolonged to the same extent in both groups (162 +/- 14 vs 146 +/- 45 msec, P = NS); group 1 due to an A-H prolongation whereas in group 2 it was due to an intra-atrial conduction delay. In group 1 AF still remained inducible, although with a longer mean R-R interval (215 +/- 16 vs 433 +/- 88 msec, P < 0.05). No instance of complete AV block developed. In group 2, sustained AF was noninducible in 10 dogs and its duration was markedly shorter in the remaining one (8 sec). Gross anatomy and histology did not reveal any damage inside of Koch's triangle, and particularly to the compact AV node. CONCLUSION: These findings suggest that RFA at the mid-atrial septum prevents AF in the normal dog heart. This approach might also be successful in those clinical settings in which the atrial septum plays a critical role in the maintenance of sustained AF.

Electrophysiology of the atrio-AV nodal inputs and exits in the normal dog heart: radiofrequency ablation using an epicardial approach.

INTRODUCTION: We studied the effects of selective and combined ablation of the fast (FP) and slow pathway (SP) on AV and VA conduction in the normal dog heart using a novel epicardial ablation technique. METHODS AND RESULTS: For FP ablation, radiofrequency current (RFC) was applied to a catheter tip that was held epicardially against the base of the right atrial wall. SP ablation was performed epicardially at the crux the heart. Twenty-three dogs were assigned to two ablation protocols: FP/SP ablation group (n = 17) and SP/FP ablation group (n = 6). In 12 of 17 dogs, FP ablation prolonged the PR interval (97 +/- 10 to 149 +/- 22 msec, P < 0.005) with no significant change in anterograde Wenckebach cycle length (WBCL). Subsequent SP ablation performed in 8 dogs further prolonged the PR interval and the anterograde WBCL (117 +/- 22 to 193 +/- 27, P < 0.005). Complete AV block was seen in 1 of 8 dogs, whereas complete or high-grade VA block was seen in 6 of 8 dogs. In the SP/FP ablation group, SP ablation significantly increased WBCL with no PR changes. Combined SP/FP ablation in 6 dogs prolonged the PR interval significantly, but no instance of complete AV block was seen. VA block was found in 50% of these cases. Histologic studies revealed that RFC ablation affected the anterior and posterior atrium adjacent to the undamaged AV node and His bundle. CONCLUSION: Using an epicardial approach, combined ablation of the FP and SP AV nodal inputs can be achieved with an unexpectedly low incidence of complete AV block, although retrograde VA conduction was significantly compromised.