Role of interatrial conduction in atrial fibrillation: Mechanistic insights from renewal theory-based fibrillatory dynamic analysis.

Background: Interatrial conduction has been postulated to play an important role in atrial fibrillation (AF). The pathways involved in interatrial conduction during AF remain incompletely defined. Objective: We recently showed physiological assessment of fibrillatory dynamics could be performed using renewal theory, which determines rates of phase singularity formation (λf) and destruction (λd). Using the renewal approach, we aimed to understand the role of the interatrial septum and other electrically coupled regions during AF. Method: RENEWAL-AF is a prospective multicenter observational study recruiting AF ablation patients (ACTRN 12619001172190). We studied unipolar electrograms obtained from 16 biatrial locations prior to ablation using a 16-electrode Advisor HD Grid catheter. Renewal rate constants λf and λd were calculated, and the relationships between these rate constants in regions of interatrial connectivity were examined. Results: Forty-one AF patients (28.5% female) were recruited. A positive linear correlation was observed between λf and λd (1) across the interatrial septum (λf r2 = 0.5, P < .001, λd r2 = 0.45, P < .001), (2) in regions connected by the Bachmann bundle (right atrial appendage-left atrial appendage λf r2 = 0.29, P = .001; λd r2 = 0.2, P = .008), and (3) across the inferior interatrial routes (cavotricuspid isthmus-left atrial septum λf r2 = 0.67, P < .001; λd r2 = 0.55, P < .001). Persistent AF status and left atrial volume were found to be important effect modifiers of the degree of interatrial renewal rate statistical correlation. Conclusion: Our findings support the role of interseptal statistically determined electrical disrelation in sustaining AF. Additionally, renewal theory identified preferential conduction through specific interatrial pathways during fibrillation. These findings may be of importance in identifying clinically significant targets for ablation in AF patients.

Prospective cross-sectional study using Poisson renewal theory to study phase singularity formation and destruction rates in atrial fibrillation (RENEWAL-AF): Study design.

BACKGROUND: Unstable functional reentrant circuits known as rotors have been consistently observed in atrial fibrillation and are mechanistically believed critical to the maintenance of the arrhythmia. Recently, using a Poisson renewal theory-based quantitative framework, we have demonstrated that rotor formation (λf) and destruction rates (λd) can be measured using in vivo electrophysiologic data. However, the association of λf and λd with clinical, electrical, and structural markers of atrial fibrillation phenotype is unknown. METHODS: RENEWAL-AF is a multicenter prospective cross-sectional study recruiting adult patients with paroxysmal or persistent atrial fibrillation undergoing clinically indicated catheter ablation. Patients will undergo intraprocedural electrophysiologic atrial fibrillation mapping, with λf and λd to be determined from 2-minute unipolar electrogram recordings acquired before ablation. The primary objective will be to determine the association of λf and λd as markers of fibrillatory dynamics with clinical, electrical, and structural markers of atrial fibrillation clinical phenotype, measured by preablation transthoracic echocardiogram and cardiac magnetic resonance imaging. An exploratory objective is the noninvasive assessment of λf and λd using surface ECG characteristics via a machine learning approach. RESULTS: Not applicable. CONCLUSION: This pilot study will provide insight into the correlation between λf/λd with clinical, electrophysiological, and structural markers of atrial fibrillation phenotype and provide a foundation for the development of noninvasive assessment of λf/λd using surface ECG characteristics will help expand the use of λf/λd in clinical practice.

A Randomised Controlled Trial on the Effect of Nurse-Led Educational Intervention at the Time of Catheter Ablation for Atrial Fibrillation on Quality of Life, Symptom Severity and Rehospitalisation.

BACKGROUND: Atrial Fibrillation (AF) is a common condition associated with impaired quality of life (QOL) and recurrent hospitalisation. Catheter ablation for AF is a well-established treatment for symptomatic patients despite medical therapy. We sought to examine the effect of point specific nurse-led education on QOL, AF symptomatology and readmission rate post AF ablation. METHODS: Forty-one patients undergoing AF ablation were randomised to Nurse Intervention (NI) versus Control (C), n=22 vs. 19. Both groups were well matched with respect to age, sex and AF subtype. All patients completed SF36 and AF Symptom Checklist, Frequency and Severity Scale questionnaires at baseline and six months post ablation. The NI group underwent nurse education on admission, prior to discharge, and with telephone contact. RESULTS: Baseline SF-36 and AF Symptom Checklist, Frequency and Severity scores were similar. The NI group showed significant differences compared to Control with respect to higher QOL on the SF-36 score of Physical Functioning and Vitality at six months. There were significant improvements in seven components of the AF Symptom Checklist, Frequency and Severity at six months in the NI group with a trend in a further seven. There was no difference in AF related hospital readmissions at six months between C and NI groups (10.5% vs. 13.6%, p=ns). CONCLUSION: Nurse-led education at time of AF ablation is associated with improved QOL and reduced symptom frequency and severity compared to usual care.

Assessment of oesophageal position by direct visualization with luminal contrast compared with segmentation from pre-acquired computed tomography scan-implications for ablation strategy.

AIMS: Atrio-oesophageal fistula is a rare but often fatal complication of catheter ablation for atrial fibrillation (AF). Various strategies are employed to evaluate the oesophageal position in relation to the posterior left atrium (LA). These include segmentation of the oesophagus from a pre-acquired computed tomography (CT) scan and direct, real-time assessment of the oesophageal position using contrast at the time of the procedure. METHODS AND RESULTS: One hundred and fourteen patients with drug-refractory AF underwent CT scanning prior to AF ablation. The LA and oesophagus were segmented from this scan. The oesophagus was deemed midline, ostial if it crossed directly behind any of the pulmonary vein (PV) ostia, or antral if it passed within 5 mm of a PV ostium. Under general anaesthesia at the time of ablation, the same patients were administered contrast via an oro-gastric tube to outline the oesophagus. Catheters were placed at the PV ostia and oesophageal position in relation to the PVs was established radiographically using a postero-anterior view. Oesophageal position assessed by real-time assessment correlated with the CT scan in only 59% of patients. In 34% the oesophagus was more right sided on direct visualization, while in 7% it was more left sided. CONCLUSION: Segmentation of the oesophagus from the CT scan did not correlate the real-time oesophageal position at the time of the procedure in over 40% of patients under general anaesthesia. Reliance on the determination of oesophageal position by previously acquired CT may be misleading at best and provide a false sense of security when ablating in the posterior LA.

Vertebral artery dissection secondary to defibrillation threshold testing.

We report a case of vertebral artery dissection presenting 2 days after ICD implantation with defibrillation threshold testing in a 57-year-old man with ischemic cardiomyopathy. The association between vertebral artery dissection and neck trauma and the role of DFT testing in ICD implantation are discussed.

Pulmonary venous isolation versus additional substrate modification as treatment for paroxysmal atrial fibrillation.

BACKGROUND: Pulmonary vein isolation alone is ineffective in maintaining sinus rhythm in up to one third of patients with paroxysmal atrial fibrillation (AF). We compared pulmonary vein antral isolation plus additional limited ablation along the inferoposterior left atrium and epicardially within the adjacent coronary sinus (PVAI + CS) to pulmonary vein antral isolation (PVAI) alone in patients with paroxysmal AF. METHODS: Forty-two consecutive patients with paroxysmal AF were prospectively randomized to PVAI vs. PVAI + CS. All patients were seen 3, 6, 12, and 18 months after ablation and underwent 24-h ambulatory Holter monitoring. RESULTS: Following a single procedure, 17 out of 22 patients (77%) remained arrhythmia free off antiarrhythmic medication after PVAI at 18 months vs. 10 out of 20 (50%) after PVAI + CS (p < 0.01). After PVAI, three patients had recurrent paroxysmal AF, and two had atrial tachycardia, whereas after PVAI + CS, three patients had recurrent paroxysmal AF, and seven had atrial tachycardia. All patients in the PVAI + CS group with atrial tachycardia who underwent a second procedure were found to have peri-mitral macro-reentry as the underlying mechanism. Eighty-one percent of patients remained arrhythmia free off medication after 1.09 procedures in the PVAI group vs. 80% after 1.35 procedures in the PVAI + CS group (p < 0.01). CONCLUSION: The addition of limited ablation along the inferoposterior left atrium and within the adjacent coronary sinus to PVAI alone did not reduce the recurrence rate of paroxysmal atrial fibrillation and was associated with an increased rate of peri-mitral macro-reentrant atrial tachycardia.

Left ventricular outflow tract ventricular tachycardia originating from the noncoronary cusp: electrocardiographic and electrophysiological characterization and radiofrequency ablation.

Noncoronary cusp (NCC) ventricular tachycardia is a rare form of monomorphic outflow tract tachycardia, and its electrocardiographic and electrophysiological characteristics have not been well described previously. The NCC should be considered for catheter ablation if attempts to eliminate ventricular tachyarrhythmia were unsuccessful in the other common anatomical sites of the left ventricular outflow tract.

Effects of components of ischemia on the Kv4.3 current stably expressed in Chinese hamster ovary cells.

We investigated the effects of three components of ischemia: external acidosis (pH=6.0), extracellular hyperkalemia ([K(+)]=20 mmol/l), and resting membrane depolarization to -60 mV, on Kv4.3 current stably expressed in Chinese Hamster Ovary cells. We used single electrode whole cell patch clamp techniques to study changes in the current elicited. External acidosis caused a positive shift in the steady state activation curve from -13.4 +/- 2.1 mV to -3.3 +/- 1.5 mV (n=8, P=0.004) and the steady state inactivation curve from -56.5 +/- 0.4 mV to -46.7 +/- 0.5 mV (n=14, P<0.0001). Acidosis also caused an acceleration of recovery from inactivation with the t(1/2) decreasing from 306 ms (95% CI 287-327 ms) to 194 ms (95% CI 182-207 ms), (n=14, P<0.05). Hyperkalemia did not affect any of these parameters. Combined acidosis and hyperkalemia produced effects similar to those seen with acidosis. Changing the holding potential from -90 mV to -60 mV with test potentials of +5 and +85 mV decreased the peak currents by 34.1% and 32.4% respectively (n=14). However, in the presence of external acidosis the decrease in peak currents induced by changing the holding potential was less marked. In acidotic bath the peak current at -60 mV was reduced by only 13.6% at a test potential of +5 mV and 12.3% at a test potential of +85 mV (n=14). Taken together our data suggest that the membrane depolarization and changes in pH which occur under ischemic conditions would be accompanied by relative preservation of Kv4.3 currents and provide a molecular basis for the observation of preserved epicardial I(to) and epicardial action potential duration (APD) shortening in ischemia.