*English version of "Langzeit-Ergebnisse der ostialen
Pulmonalvenenisolation bei paroxysmalem Vorhofflimmern", J Kardiol
2005; 12: 231-6, "Copyright 2005 by Krause & Pachernegg, Austria";
published with permission from publisher. Web link to the original
German version (pdf):
www.kup.at/kup/pdf/5370.pdf
Pürerfellner H., Aichinger J., Martinek M., Nesser H.J., Janssen
J.
†
Public Hospital Elisabethinen, Academic Teaching Hospital,
Cardiological Department, Linz, Austria
†Medtronic Inc. , Bakken Research Center, Maastricht,
Holland
Address for
correspondence: Helmut Pürerfellner, MD, KH der
Elisabethinen, II. Interne Abteilung/Kardiologie, Fadingerstr. 1,
A-4010 Linz, Austria, Europe. E-mail:
helmut.puererfellner@elisabethinen.or.at
Abstract
Introduction:
Segmental ostial pulmonary vein isolation (PVI) is considered a
potentially curative therapeutic approach in the treatment of
paroxysmal atrial fibrillation (PAF). There is only limited data
available on the long-term effect of this procedure.
Methods:
Patients (Pts) underwent a regular clinical follow up visit at 3, 6 and
24 months after PVI. Clinical success was classified as complete (i.e.
no arrhythmia recurrences, no antiarrhythmic drug), partial (i.e.
no/only few recurrences, on drug) or as a failure (no benefit). The
clinical responder rate (CRR) was determined by combining complete and
partial success.
Results:
117 patients (96 male, 21 female), aged 51±11 years (range 25 to
73) underwent a total of 166 procedures (1.4/patient) in 2-4 pulmonary
veins (PV). 115 patients (98%) had AF, 2 patients presented with
regular PV atrial tachycardia. ,109/115 patients. exhibited PAF as the
primary arrhythmia (versus persistent AF). A total of 113 patients with
PVI in the years 2001 to 2003 were evaluated for their CRR after 6 (3)
months. A single intervention was carried out in 63 patients (55.8%),
two interventions were performed in 45 patients (39.8%) and three
interventions in 5 patients (4.4%). The clinical response demonstrated
a complete success of 52% (59 patients), a partial success of 26%
(29 patients) and a failure rate of 22% (25 patients), leading to a CRR
of 78% (88 patients). Ostial PVI in all 4 PVs exhibited a tendency
towards higher curative success rates (54% versus 44% in patients with
3 PVs ablated for the 6 month follow up). Long-term clinical outcome
was evaluated in 39 patients with an ablation attempt at 3 PVs only
(excluding the right inferior PV in our early experience) and a mean
clinical follow up of 21±6 months. At this point in time
the success rate was 41% (complete, 16 patients) and 21% (partial, 8
patients), respectively, adding up to a CRR of 62% (24 patients). In
total, 20 patients (17.1%) had either a single or 2 (3 patients, 2.6%)
complications independent of the number of procedures performed with PV
stenosis as the leading cause (7.7%).
Conclusion:
The CRR of patients with medical refractory PAF in our patient cohort
is 78% at the 6 month follow up. PV stenosis is the main cause for
procedure-related complications. Ablation of all 4 PV exhibits a
tendency towards higher complete success rates despite equal CRR.
Calculation of the clinical response after a mid- to long-term follow
of 21±6 months in those patients with an ostial PVI in only 3
pulmonary veins (sparing the right inferior PV) shows a further
reduction to 62%, exclusively caused by a drop in patients with a
former partial success. To evaluate the long-term clinical
benefit of segmental ostial PVI in comparison with other ablation
techniques, more extended follow up periods are mandatory, including a
larger study cohort and a detailed description of procedural parameters.
Keywords: atrial fibrillation; pulmonary vein ablation
Introduction
Based on groundbreaking work by
Michel Haissaguerre et al. a catheter-based procedure was
recently introduced into clinical routine to treat
drug-refractory paroxysmal atrial fibrillation (PAF)1,2. During segmental
ostial pulmonary vein isolation (PVI), electrically conducting
myocardial extensions bridging the pulmonary veins (PV) with the
posterior wall of the left atrium (LA) are disconnected to prevent the
initiation (and the maintenance) of PAF.
Success rates reported in recent
literature differ to a big extent (between 50 and 90%)3,4 and are not always
comparable, as applied techniques may vary considerably and are
changing with growing experience in the same group. Moreover,
evaluation of success is not consistent within published reports, as
clinical judgement of ablation outcome may be difficult to determine
(missing ECG documentation in symptomatic periods, asymptomatic
episodes). In addition, follow up periods are rarely comparable and
sometimes are rather short, so that there is still a lack of data
addressing the long-term outcome in ablation of the PV ostia to treat
PAF nowadays.
We have reported on our early
experience in the past5. In
this paper we report on our own short and long-term results with
special consideration of distinct procedural parameters which have been
developed in a time period of three years from 2001 to 2004.
Patients and
Methods
Lasso
Procedure
Briefly, after puncture of one
(or both) femoral and the left subclavian (in case the coronary sinus
can not be entered by a femoral access) vein(s) a multipolar electrode
catheter is introduced in the coronary sinus to record left atrial
activity. Thereafter, a (usually double) transseptal puncture is
performed followed by pulmonary venography. Next, two electrode
catheters are placed in the LA via two long sheaths, one for
ablation (Celsius THERMOCOOL 7F, Biosense Webster, Inc.) and one
circular decapolar catheter (“Lasso”, Biosense Webster, Inc.) to record
electrical activity of myocardial extensions connecting the LA
with a PV. The lasso catheter is situated as proximal as possible
inside the PV whereas the ablations catheter is positioned at the very
os to segmentally isolate the PV, thereby preventing stenosis
which may occur when delivering energy deep inside a PV. Electrical
entrance block from the LA to the PV is considered as the endpoint of
the procedure which is documented by the elimination of PV potentials
on the Lasso catheter. We have been using irrigated ablation catheters
from the very beginning of our PV ablation experience, delivering up to
30 Watts of energy in the superior PVs (left superior, LSPV and right
superior, RSPV) and a maximum of 20-25 Watts in the inferior PVs (left
inferior, LIPV and right inferior, RIPV). The approach of targeting a
PV for ablation is “empiric” i.e. independent of its arrhythmic
activity during the time of the procedure. In the time period from 2001
to the first half of 2002, 3 PVs were routinely isolated, whereas since
then all 4 PVs (including the RIPV which is sometimes more difficult to
reach) were targeted during a single procedure.
Follow
up
In the following we report on our
experience in ostial PVI in the time period between 12/2000 and
02/2004. The last follow up visit was performed in 04/2004. After the
procedure, patients were monitored on an outpatient basis after one
month and on an inpatient basis after 3, 6 and approximately 24 months.
The following tests were routinely performed: Clinical examination,
Holter-ECG, evaluation of quality of life using a standardized
questionnaire, in addition (on an inpatient basis) transthoracic
and transesophageal echocardiography, stress test, spiral computed
tomography (CT) of the PVs, and (only in case of significant PV
stenosis) magnetic resonance imaging of the PV and a lung scan.
Success
criteria
Two distinct time periods were
analyzed in order to evaluate the clinical outcome: a short term follow
up period of 6 months (3 months for the last patients in this series)
and a long-term follow up of approximately 24 months. The clinical
outcome was classified as complete success (CS) if patients were
without any documented arrhythmias and free of antiarrythmic
medication. A partial success (PS) was defined by an absence of
clinical symptoms while patients being still on an antiarrhythmic drug.
These two groups comprised the patient cohort for which the clinical
response rate (CRR) was calculated. A clinical failure (CF) was
classified as such in the rest of patients who showed no benefit while
usually still on drug.
Results
Demographics
117 patients (96 male, 21 female)
aged 51±11 years (range 25-73 years) were included for chronic
follow up. 26 patients (22%) had an underlying heart disease
(hypertension n=18, coronary artery disease n=4, diabetes n=4); 2
patients had a history of a transient ischemic cerebral attack.
Patients had used a mean number of 3.1±1.4 antiarrhythmic drugs.
In most instances several class I, II and class III drugs had been
administered previously (propafenone 70%, betablocker 65%, amiodarone
56%, sotalol 51%, flecainide 26%); uncommonly, class IV drugs
(verapamil in 18% and digoxin in 14%).
Arrhythmia
characteristics
Arrhythmia history showed a wide
inter-individual variation and lasted for 73±67 months (median
48 months), the maximal episode duration within the last 3 months had a
median of 390 min, the mean number of arrhythmia recurrences acccounted
for n=2/week. Table 1
illustrates the classification of the preexisting arrhythmia as defined
by the surface ECG. 115/117 patients (98%) exhibited AF as their
primary clinical atrial tachyarrhythmia with 86 presenting only with
PAF, 10 showing additional regularized atrial tachycardias, 14 typical
atrial flutter and 5 patients presenting both types, respectively. The
majority of patients (109/115, 94.7%) presented with PAF, 6/115 (5.3%)
showed only persisting AF . Two patients (1.6%) exhibited nearly
incessant “P on T” atrial runs suggesting a pulmonary venous origin
which was reconfirmed during the ablation procedure. These 2
patients underwent pulmonary venous segmental ostial ablation and
therefore were both included in this analysis.
Table 1: Classification of the preexisting
arrhythmia (AF=atrial fibrillation)
Procedures
166 procedures (1.42/patient) in
2-4 PVs were performed in total, consisting of 117 (71%) primary, 44
(27%) secondary und 5 (2%) tertiary procedures. Figure 1 illustrates the respective
numbers of primary, secondary and tertiary procedures per patient and
year (of first procedure) between 2001 and 2003. In 63 patients (55.8%)
a single procedure was carried out, as opposed to 45 patients (39.8%)
with a second and 5 patients (4.4%) with a third ablation procedure.
The duration of the primary procedure lasted for 228±55 min and
was significantly longer in comparison with the secondary
(206±56 min, p=0.004). The fluoroscopic time duration for the
primary and secondary procedure accounted for 62±15min, and
53±20min, respectively.
Figure 1: Relative percentage of
primary, scondary and teriary procedures per patient and per year of
ablation (of
the
primary procedure)
In most of the patients the LSPV
(96%), LIPV (96%) and the RSPV (95%) were isolated ostially, whereas
the RIPV was targeted in only 55%. The reason for this is that this PV
is usually more difficult to reach and was spared in our early ablation
experience from 2001 to the first half of the year 2002. Consequently,
the number of patients with PVI in 3PVs, 4 PVs or 2 PVs accounted
for 40 % (n=47), 54% (n=63) and 6% (n=7), respectively.
Success
rates
113 patients were evaluated for
the determination of the clinical outcome after 6 months (after 3
months only in 8/113 patients with a limited follow up). CRR accounted
for 78% (88 patients) consisting of 52% CS (59 patients), 26% PS
(29 patients) und 22% CF (25 patients), respectively (Figure 2). CS was higher in patients
undergoing PVI in 4 PVs versus PVI in 3 PVs (54% versus 44%) (Figure 3). However, the CRR was
similar in both groups (77% in 4 PVs and 78% in 3 PVs, respectively).
Figure 2: Success rates in
the short- and longterm follow up period
Figure 3: Success rates in
a 3 versus a 4 PV approach (including the RIPV)
For the determination of
the long term succes rate after a mean of 21±6 months only those
patients with PVI in 3 PVs (sparing the RIPV) were evaluated. For a
total of 39 patients the CS, PS and CF rates accounted for 41% (n=16),
21% (n=8), 38% (n=15), respectively, leading to a CRR of 62% (n=24).
Considering only this group of 39 patients for their specific clinical
course after 6 months separately, CS, PS and CF rates account for
41% (n=16), 33% (n=13) and 26% (n=10), respectively, leading to a CRR
of 74% (n=29) (Figure 2). From these results one may conclude
that CRR in the longterm follow up is reduced by a reduction in PS,
however, the CS rate seems stable even in the long run.
The clinical success rates per
year of experience are depicted in Figure
4. As patients had to have all procedures performed within a
single year for this analysis, the number of patients evaluated
decreases to n=103.
Figure 4: Success rates per
year of ablation performed
Complications
Significant PV stenoses are the
leading cause of side effects in the longterm follow up ranging up to
7.7% (n=9), all other complications account for less than 1.5%, such as
pericardial tamponade (n=2), pericardial effusion (n=2), stroke (n=2),
pneumo-/hemothorax (n=2), groin hematoma (n=2) and pericarditis (n=1).
In total, 20 patients (17.1%) had either a single or 2 (3
patients, 2.6%) complications independent of the number of procedures
performed.
Discussion
We have reported repeatedly on
our experience in ostial PVI recently, in particular on the occurence
of PV stenosis6,7
, quality of life8 and the
evaluation of procedural success by use of longterm implantable
monitoring provided by special implantable pacemakers with extended
storage capabilities in chronically paced patients9.
In this paper our data highlight
the potentially curative therapeutic approach of segmental ostial PVI
over a short- and longterm follow up in a patient cohort with highly
symptomatic and medically drug-refractory recurrent PAF and
without significant underlying heart disease. In total, 78% of patients
show a clinical benefit over a follow up period of 6 months, which is
reduced to 62% in the long-term after approximately 24 months in a
patient cohort that underwent PVI in 3 PVs (sparing the RIPV). An
ablation procedure that includes PVI in the RIPV as well exhibits a
higher curative success rate after 6 months of follow up (54% versus
44%).
Segmental
ostial PVI
According to current knowledge, a
segmental ostial ablation approach at the PV-LA junction represents a
predominant trigger elimination of ectopic foci from within the PVs
capable of initiating PAF by rapid focal discharges. To which extent an
ongoing fibrillatory process in the LA may be maintained by such PV
discharges remains an open issue at this point in time10. In addition, ectopic activity that
may trigger PAF may also be generated at different sites in both atria
(posterior and anterior LA, coronary sinus, terminal crest, superior
caval vein). This may well explain why a 100% cure rate is unlikely
when applying radiofrequency ablation at the ostial level of the PVs
solely.
Procedural
parameters
Despite the fact that the
arrhythmogenic potential of the RIPV was somewhat in doubt years ago,
our results are in accordance with other more recent reports in the
literature demonstrating the importance of implementing this PV in the
ablation procedure. As illustrated in figure
3 the CS is higher when isolating all 4 PVs (versus 3 PVs). The
RIPV is sometimes more difficult to reach technically, however, with
improved catheter steerability this problems is solved most of
the time nowadays. Other procedural parameters do not seem crucial in
our series as our approach of isolating the PVs did not change over the
years using the same diagnostic catheter (Lasso catheter) within the PV
ostium and a stable energy source for ablation (radiofrequency ablation
with irrigated catheters) with unchanged energy settings (30 Watts for
the superior PVs and 20-25 Watts for the inferior PVs).
Longterm
success rate
Our longterm success rates after
approximately 24 months may be limited by the fact that these results
represent the outcome in patients having undergone ostial PVI in 3 PVs
exclusively. If we compare the longterm success rate of this separted
group with its 6 month follow up data, it is obvious that the CS is
literally idenitical (41%) whereas the PS and the CRR seem to be
somewhat higher on a short term basis (33% versus 21% and 74% versus
62%, respectively). Our results demonstrating a stable cure rate over
an extendend period are confirmed in a previously published larger
report11.
However, it remains interesting to reconfirm those data by our own
series of patients having undergone a 4 PV ablation approach from the
second half ot the year 2002 onwards.
Learning
curve
To find an appropriate measure
for our learning curve we have analyzed the number of secondary
procedures and the success rates . As depicted in figure 1 there is a constant
decrease of secondary procedures per patient with growing experience :
The percentage decreases from about 50% in patients with their primary
procedure in the year 2001 to 40% and 25%, respectively in patients who
underwent PVI in the year 2002 and 2003. The reason for this is based
on the growing knowledge about the nature of early recurrences (within
the first days after the primary procedure): As those recurrences may
merely represent transient effects of leason healing we tended to treat
those arrhythmias conservatively with growing experience by
administering antiarrhythmic drugs instead of performing an early redo
procedure. In addition , we were able to exactly quantify and publish
the decrease of arrhythmic burden of PAF within the first 3 months
after PVI in 12 patients who were previously implanted with a last
generation implantable pacemaker offering extended storage capabilities
(Medtronic Inc, AT 500)9.
Figure 4 demonstrates the success rate based on the year of the
primary procedure. It shows an increase in the CS from 40% in the year
2001 to about 50% in the next two years. The most likely cause for this
is the fact that the procedure changed from a 3 PV to a 4 PV isolation
approach (including the RIPV) . The CRR, however, remains fairly
constant, reaching 70 to 80%.
Redo
procedures
In general, concomitant atrial
tachycardias or atrial flutter were not a primary target for ablation
during the first ablation session. In case of a recurrence of PAF, one
or more PVs were usually reconnected and had to be reisolated. In
addition, sustained atrial tachycardias as well as right or left atrial
flutter circuits were mapped as appropriate. However, no detailed
ablation results for these substrates are available in this reported
patient series.
Complications
With regard to diagnosis,
management and outcome in PV stenosis follwing ostial PVI we may refer
to our previously published results6,7. Despite the fact that there may be
multiple factors operational for the occurence of PV stenosis (energy
source, amount of delivered energy, localisation of the affected PV)
the exact site of energy delivery at the ostial level seems to be of
highest importance: The more energy delivered within a PV (versus
ostial) the higher the chance of developing significant PV stenosis. In
general, the symptom threshold (including dyspnea, hemoptysis and
pneumonia) for significant PV narrowing exceeds 60% of luminal
narrowing, however, not every single significant PV narrowing produces
symptoms. Lung scanning is a useful diagnostic test to document
hemodynamically significant PV stenosis by detecting a segmental
perfusion deficit. Interventions in significant PV stenosis including
PV dilatation and/or stenting may lead to a high reocclusion rate. In
our published series of 6 patients with predominant single PV stenosis
the clinical outcome is beneficial despite reocclusion in 2 patients
during a longterm follow up.
Limitations
Longterm success is based on the
results in patients with a 3 PV ostial isolation approach (sparing the
RIPV). It may well be that chronic results in patients with a 4 PV
(including the RIPV) approach are superior .
Although routine longterm ECG
monitoring was performed at prespecified points in time during follow
up, clinical success is primarily based on symptomatic episodes
of PAF. It remains unclear who often and to what extent silent episodes
of PAF may have changed the clinical results of PVI in our
patient subgroups.
Future
outlook
According to many other working
groups worldwide we have changed our ablation strategy recently: Using
a 3 dimensional mapping system (CARTO, Biosense Webster Inc.) an
electroanatomic map of the LA including the mitral valve annulus and
the PVs is reconstructed pre ablation. Thereafter, periostial
circumferential atrial lesions are deployed around the septal and
lateral PVs in order to modify the substrate of PAF (Figure 5). In addition, an ablation
line in between the LIPV and the mitral valve is drawn (socalled
„mitral isthmus“), which is at times accompanied by a roof line in the
LA connecting the superior PVs. It seems critical to attain complete
lesion sets designed to prevent the spread of focal discharges from
withhin the PV to the rest of the LA (Pappone approach12). At this point in time we are
still using a multipolar circular catheter to be located at the ostial
level to monitor and guide PV isolation at the LA-PV junction. Recently
published reports demonstrate higher success rates using
circumferential PV atrial ablation in contrast to segmental ostial PVI
both in PAF13 and (even
more) in persistent to permanent forms of AF. An additional advantage
of this technique is based on the diminished occurence of PV stenoses
by applying energy >1cm away from the ostial level. However,
additional point lesions at the ostial level of a PV are often required
to accomplish complete LA-PV block.
a
b
Figure 5: Elecroanatomical
Mapping (CARTO): the red dots are representing ablation spots
a) Anteroposterior projection, b) posteroranterior projection
In the meantime a multislice CT
imaging modality is available in our institution which enables the 3
dimensional representation of a patient´s individual cardiac
anatomy (Figure 6). In
addition, worldwide intensive collaboration within different
manufacturers of cardiac visualization systems is ongoing to enable "3
D image integration" which will allow a direct transfer of
imaging files to the mapping system at work. By this, a direct transfer
of the individual electrical activation to the individual
patient´s anatomy seems feasible ("image guiding“).
Moreover, interesting and
promising efforts are made by one manufacturer (Stereotaxis, Inc) to
conduct an ablation procedure by remote navigation of the ablation
catheter which is directed by a strong magnetic field around the
patient´s body.
Figure 6:
Multislice CT demonstrating aortic (above), pulmonary arterial (mid)
and pulmonary venous vasculature (posterioanterior projection)
Conclusion
The CRR in patients with
medically refractory PAF undergoing ostial PVI accounts for 78% after a
short term follow up of 6 months. A 4 PV procedure (including the RIPV)
warrants a higher CS. In patients with a 3 PV procedure (sparing the
RIPV) the CRR in the longterm follow up is reduced to 62%. However, the
CS rate seems to be constant, whereas the PS is reduced. PV stenosis is
the main cause for complications. In addition to an exact analysis of
procedural parameters a longer follow up period seems necessary to
better quantify the clinical benefit to risk ratio of segmental ostial
PVI in contrast to other strategies in the treatment of atrial
fibrillation.
