Pulmonary Vein Morphology in Patients With Paroxysmal Atrial Fibrillation Initiated by Ectopic Beats Originating From the Pulmonary Veins
Implications for Catheter Ablation
Background—Successful ablation of ectopic beats originating from the pulmonary veins (PV) could eliminate paroxysmal atrial fibrillation (PAF). However, information about the structure of the PV in patients with PAF that is initiated by PV ectopic beats has not been reported.
Methods and Results—We studied the morphology of the PVs and measured their diameters in 3 groups of patients. Group I included 52 patients (aged 66±14 years; 44 men) with focal atrial fibrillation (AF) from the PVs. Group II included 8 patients (aged 50±10 years; 3 men) with focal AF from the superior vena cava or cristal terminalis. Group III included 23 control patients (aged 55±16 years; 17 men). Of the control patients, 11 had AV node and 12 had AV reentrant tachycardia. After an atrial transseptal procedure, selective PV angiography using a biplane system with a right anterior oblique view of 30 degrees, a left anterior oblique view of 60 degrees, and a cranial angle of 20 degrees was performed. The ostial and proximal portions of the right and left superior PVs (RSPV and LSPV) were significantly dilated in group I patients compared with those in groups II and III. Furthermore, the ostia of the RSPV and LSPV were significantly dilated in group II compared with group III patients. However, the mean diameters of the inferior PVs were similar between the 3 groups. Comparisons of the individual PV diameters among the 3 subgroups of group I (which was divided according to where the ectopic focus was located) showed nonselective dilatation of the PV.
Conclusions—Nonspecific dilatation of the ostia and proximal portion of superior PVs were found in patients with PAF initiated by ectopic beats from the superior PVs.
Atrial fibrillation (AF) is one of the most frequently encountered arrhythmias in the clinical setting. Jais et al1 and Haissaguerre et al2 first documented that paroxysmal AF (PAF) could be initiated by ectopic beats from the pulmonary veins (PVs) and that successful ablation of these ectopic beats could eliminate PAF. This laboratory also demonstrated similar findings.3 4 However, a lack of information about the structure of the PVs still exists.
Precise mapping of the electrical activities along the PVs requires proper delineation of PV structure, especially the atriopulmonary junction and the tributaries of the PVs. Furthermore, the design of new devices, such as an ablation balloon for circumferential isolation of the PV, requires careful evaluation of proximal PV structure and diameter.
The purposes of this study were to (1) study the structural differences of the PV between PAF patients and controls and (2) demonstrate the impact of PV structure on the ectopic beats that initiate AF and, thus, catheter ablation.
Patients were divided into 3 groups. Group I consisted of 52 patients (44 men and 8 women with a mean age of 66±14 years and an age range of 27 to 86 years) who had frequent attacks (mean, 5±2 episodes/day) of PAF initiated by atrial premature beats that were documented by 24-hour Holter monitoring. These patients were refractory to 3±1 antiarrhythmic drugs, and the electrophysiologic study and radiofrequency catheter ablation proved that the PAF originated from the PVs. Group II was composed of 8 patients (3 men and 5 women with a mean age of 50±10 years and an age range of 36 to 69 years) who had PAF; the electrophysiologic study and radiofrequency catheter ablation proved the PAF originated from the superior vena cava (SVC) or cristal terminalis. Group III was made up of 23 control subjects (17 men and 6 women with a mean age of 55±16 years and an age range of 36 to 69 years) who had AV node reentrant tachycardia (11 patients) or AV reciprocating tachycardia mediated by a concealed accessory pathway (12 patients) and who did not have documented or inducible AF. All patients gave informed consent. All antiarrhythmic drugs except amiodarone were discontinued for ≥5 half-lives before the study (Table 1⇓).
Selective PV Angiography
The details of PV angiography have been described previously.3 4 After the standard transseptal procedure, an initial intravenous bolus dose of 3000 IU of heparin was given; repeated doses of heparin were given to maintain the activated clotting time at >300 seconds. Then, 2 sheaths, 8.5-Fr SL1 and 8-Fr SR0 (Daig Co), were introduced into the left atrium (LA) in each patient. The long sheath (SL1) was used to approach the right PV, and the short sheath (SR0) was used to cannulate the left PV. A simple clockwise torque with the sheath pointing posteriorly and to the right of the spine facilitated entry into the right PV; however, a slight counterclockwise torque, again with the sheath directed posteriorly but pointing to the left of the spine, aided access to the left PV. All patients underwent selective PV angiography using a NIH or A2 multipurpose angiocatheter (Cordis) introduced through the long sheath under a biplane fluoroscopic system with a right anterior oblique view of 30 degrees, a left anterior oblique view of 60 degrees, and a cranial angle of 20 degrees.
The PV ostium was defined as the junction of the PV with the LA. The diameter of the PV ostium was measured in each of the 2 projections (left and right anterior oblique views), and the mean value was obtained. Similar measurements were made 5, 10, 15, 20, 25, and 30 mm inside the PVs; the locations of the venous tributaries were also determined. All measurements were corrected for the degree of magnification of the angiographic image by relating the diameter of the long sheath in each projection to its true diameter. Measurements were made in the still frame that best showed the PV ostium. The diameter of PV ostium was the distance between 2 points: 1 point was the junction between the upper wall of the PV and the wall of the LA, and the other point was the junction between the lower wall of the PV and the wall of the LA. While measurements were made, the patients were in sinus rhythm; the mean heart rates in the 3 groups were 70±10, 66±10, and 68±9 beats/min (P>0.05), respectively.
Pulmonary venous flow is phasic: the first phase of flow occurs during ventricular systole and the second phase of flow during ventricular diastole; it reaches a maximum at the beginning of atrial contraction. At this point, reversed flow occurs.5 To minimize the variations in the diameter of the PVs that occur because of this phasic flow, all measurements were made at the end of ventricular systole. Furthermore, PV diameters were rechecked by 2 cardiologists who were not aware of the diagnosis.
Electrophysiological Study and Radiofrequency Catheter Ablation
Two multipolar, closely spaced (interelectrode space, 2 mm; distance between each bipolar pair, 5 mm) electrode catheters with a deflectable tip (Mansfield Division, Boston Scientific Inc) were introduced from the right and left femoral veins and placed in the anterolateral high right atrium and the His bundle area for recording and pacing. A 7-Fr, deflectable, decapolar catheter (Daig Co), which had a 2-mm interelectrode distance within each pair and 5 mm of space between each electrode pair, was also inserted into the coronary sinus via the internal jugular vein. Two 6-Fr, deflectable, decapolar catheters (same electrode spacing as coronary sinus catheter) were put into the superior PVs (or inferior PVs if the P wave of the ectopic beat initiating the AF was not positive in the inferior leads) through the 2 long transseptal sheaths, with the first pair of electrodes straddling the ostium of the PVs. For patients with a possibility of right atrial ectopic foci, one duodecapolar catheter (1–2-1 mm spacing, Daig Co) was put in the SVC and one Crista catheter (Cordis-Webster Co) was put along the cristal terminalis for detailed mapping.
A programmed digital stimulator (DTU-210 or 215, Bloom Associate Ltd) was used to deliver electrical impulses of 2.0 ms for a interval of twice the diastolic threshold. Intracardiac bipolar electrograms (filter was set from 30 to 500 Hz) were displayed simultaneously with ECG leads V1, I, and II on a multichannel recorder (CardioLab System, Prucka Engineering, Inc), and were recorded on paper at a speed of 100 or 200 mm/s. The methods used to provoke spontaneous AF are standardized in our laboratory.3 4
The presumed ablation site was chosen on the basis of the earliest bipolar activity and/or a local unipolar QS pattern of the ectopic beats that initiated AF. Among the patients with ≥2 ectopic foci initiating AF, the ectopic foci were sequentially ablated. The protocols used to provoke spontaneous AF before ablation were repeated to confirm the procedural success.3 4
Quantitative data are expressed as mean±SD, and they were compared using unpaired t tests. P<0.05 was considered significant. One-way ANOVA was used to analyze the differences among the 3 groups.
Right and Left Superior PVs
The mean ostial diameters of the right and left superior PVs (RSPV and LSPV) in group I patients were significantly greater than those in the other 2 groups (Figures 1 through 3⇓⇓⇓). At distances of 5, 10, and 15 mm inside the ostium, the mean diameters of group I patients were still greater than those in control patients. However, the mean diameters of group I patients were similar to those of group II patients and control patients at distances of 20, 25, and 30 mm from the ostium. This proximal dilatation was seen consistently in the left and right anterior oblique view projections. Furthermore, the ratio of superior PV ostium diameter to LA size was similar between the 3 groups (Table 2⇓⇓).
Branching Pattern of Proximal PV
In group I, the first PV branch occurred within the first 10 mm in 14 patients (26.9%); in 10 patients (19.2%), it occurred 10 to 20 mm inside the PV ostia. In group II, 1 patient (12.5%) had the first branch within the first 10 mm, and 2 patients (25%) had it 10 to 20 mm inside the PV ostia. Of the control population, 3 subjects (13%) demonstrated an early vessel within the first 10 mm, and 4 subjects (17.4%) had the branch 10 to 20 mm inside the PV ostia.
Relationship Between the Ectopic Foci Initiating AF and the Dilatation of the PVs
Group I patients were further divided into 3 subgroups on the basis of the location of the ectopic foci. In group IA, the ectopic focus was in the LSPV only (20 patients; mean age, 64±12 years; 17 men); in group IB, the ectopic focus was in the RSPV only (15 patients; mean age, 66±17 years; 11 men); and in group IC, the ectopic foci were from both the RSPV and LSPV (17 patients; mean age, 67±14 years; 16 men). These ectopic foci initiated spontaneous AF, and they were eliminated after successful ablation. The results of comparing the individual PV diameters among the subgroups (IA, IB, and IC) showed a nonselective dilatation of the PVs (Table 2⇑). Furthermore, the dilatation of the PV ostia showed a positive relation between RSPV and LSPV (Figure 4⇓). The sites with successful ablation of the ectopic foci were further divided into proximal or distal lesions (<20 mm or ≥20 mm inside the PV, respectively); the diameters of proximal or distal lesions were not related to the ectopic foci of AF. Group II patients had ectopic foci in the SVC (n=5) or the upper portion of the cristal terminalis (n=3).
Relationship Between PV Diameters and Other Parameters
In all 3 groups, no pressure gradient existed between the proximal PVs and LA pressure. The diameters of the superior PVs were not related to LA size (Figure 5⇓), LA pressure (<12 mm Hg: RSPV ostium diameter [O]=13.6±1.6 mm, LSPV-O=13.8±1.4 mm; ≥12 mm Hg: RSPV-O= 13.6±1.4 mm, LSPV-O=13.9±1.3 mm), historical duration of PAF (<2 years: RSPV-O=13.4±1.7 mm, LSPV-O=13.9±1.7 mm; ≥2 years: RSPV-O=13.7±1.4 mm, LSPV-O=13.7±1.3 mm), or the presence of other structural heart diseases (with heart disease: RSPV-O=13.4±1.6 mm, LSPV-O=13.6±1.6 mm; without heart disease: RSPV-O=13.6±1.4 mm, LSPV-O=13.9±1.3 mm). The diameters of the RSPVs were not related to the patient’s age (r=0.21, P=0.13), body weight (r=0.16, P=0.26), height (r=−0.05, P=0.73), or body mass index (r=0.18, P=0.19). The diameters of the LSPVs were also not related to the patient’s age (r=0.2, P=0.15), body weight (r=0.02, P=0.92), height (r=−0.21, P=0.13), or body mass index (r=0.14, P=0.98).
This is the first study that measures the size of the PVs and relates it to arrhythmia. We showed that the patients who had PAF that was initiated by ectopic beats from the superior PVs had greater superior PV diameters than did either control subjects or the patients who had PAF that originated from the SVC or cristal terminalis. However, the dilatation of the PV was not related to the site of the ectopic beats that initiated PAF.
Relation Between PV Diameter/Structure and AF
In the present study, we found that the superior PVs were significantly dilated and that most of the ectopic beats initiating PAF originated from the superior PVs. However, site-specific dilatation of the PVs was not evident. Furthermore, the similar ratios of PV ostium diameter to LA size between the 3 groups suggests simultaneous dilatation of the PVs and LA. However, the nonlinear relationship between PV diameter and LA size suggests that the extent of the dilation of the LA and PV ostia was different; this may be due to the different compliance of the PV vascular wall and LA wall among individuals. Thus, some patients had a greater dilatation of the PVs and less enlargement of the LA, whereas others had greater enlargement of the LA and less dilatation of the PVs.
The proximal portion of the PV has a sleeve of myocardium that is a direct extension from the adjacent atrial tissue and that is electrically coupled to the atrium.6 The electrical activity in the PVs was presumed to be a result of this cardiac musculature because the smooth muscles were noted to be electrically quiescent.7 It is possible that disorganized contraction of the muscle sphincters at the atriopulmonary venous junction as a result of rapid and chaotic firing of the ectopic focus in addition to the delayed changes of structure similar to the LA may account for an increase in the dimensions of the atriopulmonary venous junction.
Dilatation of PVs in patients with PAF caused by the PVs may stretch the proximal portion of the PVs to a greater degree than in control patients; thus, the ectopic beats might be initiated by the stretch mechanism. Previous studies have demonstrated that increased stretch may modify the electrophysiological characteristics of cardiac tissue and induce triggered activity resulting in arrhythmia.8 9 In the patients with PAF originating from the SVC/cristal terminalis, PV dilatation was also demonstrated. It is possible that these patients may have ectopic beats from PVs in the late follow-up period. Although the dilatation of PV diameters did not show a site-specific relationship, the possibility of pathological changes in the PVs may explain the spontaneous onset of ectopic beats from the PVs. Previous studies also showed significant dilatation of the coronary sinus ostium in patients with AV nodal reentrant tachycardia and speculated that the tissue around the ostium was closely related to the slow pathways in patients with this disease.10 Furthermore, diverticulum in the proximal portion of the coronary sinus was also demonstrated to be related to the accessory pathway in the posteroseptal space.11 12
Implications for Catheter Ablation
The assessment of PV anatomy and the measurement of PV diameters during the venophase of pulmonary arterial angiography has several shortcomings; for example, the margins of the PVs were not accurately delineated, and the inferior PVs were often overlapped by several structures, resulting in inadequate visualization.13 14 Thus, selective PV angiography following a transseptal procedure would be better to delineate PV structure and to guide accurate mapping along the PVs. Therefore, we selectively cannulated individual PVs.
The most commonly used method of radiofrequency ablation of ectopic beats from the PVs is the application of energy to the source or exit site of the ectopic beats. However, a risk of PV stenosis with subsequent pulmonary hypertension has been reported with this method.15 16 The new device for circumferential balloon isolation of the PV ostium using radiofrequency or ultrasound energy blocks the conduction between the PVs and LA and prevents AF initiated by ectopic beats from the PVs. Thus, the diameters of the PVs become very important for selecting the optimal size of the balloon for the ablation of the PVs. Furthermore, the diameters of the PVs would be very important in the follow-up study to determine stenosis. For this reason, strict adherence to limited sites of application assigned to the region for successful ablation may result in a lower risk of PV stenosis.
This study had several limitations. (1) It did not include patients who had PAF that was initiated by ectopic beats from the inferior PVs. However, the incidence of ectopic beats from inferior PVs is very low.2 3 Thus, dilatation of the right inferior PV ostium in patients with PAF from superior PVs needs further study. (2) Because PV angiography is an invasive procedure and the group II patients had definite foci in the right atrium, inferior PV angiography was not routinely performed in these patients. (3) We did not routinely perform PV angiography at follow-up; thus, we did not determine whether PV diameters decreased after long-term sinus rhythm (without the occurrence of PAF after radiofrequency ablation). (4) Only 4 patients underwent additional procedures for recurrent PAF, and their PV angiographic assessment did not show any significant narrowing or stenosis. However, our routine follow-up transesophageal echocardiographic examination found ≈40% of patients had an increase of PV flow velocity after the ablation of PV lesions, but none of these patients had significant stenosis of the PV.16 (5) Ways to measure the diameter of the PV ostium still need further investigation to improve accuracy. However, we usually injected contrast media in the distal PVs, proximal PVs, and the PV branches to see the details of the PV trunk, PV branches, and the junction of the PV and LA; thus, we could clearly identify the PV ostium.
Nonspecific dilatation of superior PVs occurred in patients who had PAF that was initiated by ectopic beats from superior PVs. The structure and diameters of the proximal portions of the superior PVs were different between PAF and control patients.
Supported in part by grants from the National Science Council (NSC 88-2314-B-010-094, 88-2314-B-010-093) and Tzou 146s Medical Foundation (VTY88-P5-45; VGH-23, 47, 61, 65, 254, and 301), Taipei, Taiwan, Republic of China.
- Received July 30, 1999.
- Revision received September 17, 1999.
- Accepted October 11, 1999.
- Copyright © 2000 by American Heart Association
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