36 consecutive patients with recurrent, symptomatic, nonvalvular PAF were enrolled in the study between June 2008 and July 2009. All had failed to respond antiarrhythmic (propafenone, or amiodarone, or sotalol) or beta blocker therapy. They underwent their first catheter ablation by the cryoballoon technique.
The study was carried out in compliance with the Helsinki Declaration and was approved by the Regional and Institutional Scientific and Research Ethics Committee of the Semmelweis University Budapest (reference number: TUKEB 70/2008). All patients gave written informed consent before participating in the study.
As described in our previous report , all patients were treated with a double lumen cryoballoon (Arctic front, Cryocath, Montreal, Quebec), after local anaesthesia and under conscious sedation using boluses of midazolam and fentanyl. At first a decapolar electrophysiological catheter (Bard Electrophysiology Inc., Lowell, MA, USA) was placed in the coronary sinus through the right jugular vein, and a diagnostic quadripolar electrophysiological catheter was introduced through the right femoral vein and positioned in the right ventricle. An intracardiac echocardiography catheter (Acunave, Acuson, Mountain View, CA, USA) was introduced through the left femoral vein and positioned in the right atrium, in order to ensure safe transseptal approach. After the intracardiac echocardiography-guided single posterior transseptal puncture, a circular mapping catheter (Lasso catheter, PV Orbiter, Bard) was advanced and positioned in the antrum of each pulmonary vein to record the presence of pulmonary vein potentials. After registration, the 8 F sheath was exchanged for a 14 F steerable sheath, and the mapping catheter was exchanged for a 28 mm balloon catheter and positioned over an exchange wire to occlude the ostium of each pulmonary vein. At least two 5-minute cryo applications per vein were given to each vein, during using continuous phrenic nerve stimulation when freezing the ostium of the right superior pulmonary vein.
Antiarrhythmic drugs were stopped 5 half-lives before the ablation, and were not continued afterwards. Oral anticoagulation was before and after ablation, according to the CHADS2-score based on the valid guideline .
Comprehensive transthoracic echocardiographic examinations were performed in all patients during sinus rhythm before, and 3, 6 and 12 months after cryoballoon catheter ablation. Transoesophageal echocardiography was performed in all patients before catheter ablation, to exclude left atrial and left atrial appendage thrombus. Transthoracic and transoesophageal echocardiography were performed within 24 hours of each other.
After the ablation, follow-up examinations at 1, 3, 6 and 12 months included clinical history and examination, ECG and 24-hour Holter ECG. A 10-day transtelephonic ECG was performed before the 3-month, 6-month and 12-month follow-up visits.
Definition of success
Based on the definition of the Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation , cryoballoon catheter ablation was considered to be clinically successful, if after the initial 3-month blanking period--a time interval during which success is not evaluated--recurrent atrial arrhythmia was not recognized on clinical, or ECG or Holter ECG, or transtelephonic ECG examinations.
In order to evaluate the effect of all episodes of recurrent arrhythmia, recurrences in the blanking period were also taken into account for the final analysis. So the patients were divided into recurrent and arrhythmia-free (AF-free) groups. The recurrent group was defined as patients with recurrent atrial arrhythmia at any time during the follow-up.
Transthoracic echocardiography was performed with a General Electric Vivid S6 machine (General Electric, Milwaukee, WI, USA).
Left ventricular (LV) global systolic function was assessed by ejection fraction (EF) evaluated by the modified biplane Simpson's rule. LV longitudinal systolic function was assessed by septal and lateral systolic velocities of the mitral annulus (Sasept, Salat) using pulsed-wave tissue Doppler echocardiography (TDE).
In order to evaluate LA remodeling LA size and LA function were evaluated before and after ablation. LA volumes were calculated by two-dimensional echocardiography by the biplane area-length method. Maximal LA volume (LAVmax) was obtained at left ventricular end-systole, just before mitral valve opening. Minimal LA volume (LAVmin) was determined at left ventricular end-diastole. LA areas (A1, A2) and superoinferior longitudinal diameters were measured from apical 4- and 2-chamber views. LA volumes were calculated by the following formula : LAV = 8/3π*A1*A2/L = 0.85*A1*A2/L, where L is the shorter superoinferior diameter of the LA. LA volume index (LAVI) was calculated by dividing maximal LA volume by the body surface area (calculated by the Dubois formula, using body height and weight).
The evaluation of LA function by echocardiography is not standardized; different methods have been used to assess LA function in research and in clinical practice [20, 21]. The left atrium serves multiple functions, acts as a reservoir during left ventricular systole; as a conduit for blood transiting from the pulmonary veins to the LV during early diastole and as an active contractile pump that augments LV ventricular filling in late diastole.
In the present study four TTE methods were used in the assessment of LA function.
LA booster pump (contractile) function was assessed by:
the LA filling fraction (LAFF) which is the ratio of the velocity time integral (VTI) of the late diastolic A wave velocity of mitral inflow to the VTI of the early and late diastolic velocities of mitral inflow (LAFF = VTIA/VTIE+A) and
septal and lateral velocities of the mitral annulus during atrial contraction (Aasept, Aalat), measured by pulsed-wave TDE.
LA reservoir function was assessed by:
LA total emptying fraction (LAEF = (LAVmax-LAVmin)/LAVmax) and
the systolic fraction of pulmonary venous flow (PVSF = VTIS/VTIS+D). Pulmonary venous flow was measured within right upper pulmonary vein.
More recent methods of evaluating LA function, such as colour-coded tissue-Doppler based strain and strain-rate and two-dimensional speckle-tracking based strain and strain rate were not available in our institute during the study period.
In the detailed evaluation of left ventricular diastolic dysfunction, we used the methods described in recent recommendations [22, 23]. Septal and lateral early diastolic velocities of the mitral annulus (Easept, Ealat) were measured by TDE, which characterize left ventricular relaxation. In the assessment of mean left ventricular filling pressure E/Ea ratios were calculated, using both the lateral, septal and average Ea velocity. Early (E) and late diastolic (A) velocities of mitral inflow, and deceleration time (DT) were measured by pulsed wave Doppler echocardiography, and E/A ratio was calculated. Systolic (S) and diastolic (D) velocities of pulmonary venous flow were measured and S/D ratio was also calculated.
Data are shown as mean ± standard deviation (SD) (95% confidence interval). Unpaired t-test was used to compare means of continuous variables between unrelated groups. Chi-square analysis was used to compare patient group characteristics with discrete variables. Paired-sample Student's t-test was used to evaluate changes in echocardiographic parameters of LA size and function and of LV diastolic function during the follow-up period within groups. A p < 0.05 was considered statistically significant for all calculations. Statistical analysis was performed using SPSS (Statistical Software for Social Sciences) version 13.0.