Credits:Jennifer A. Mears, BS3; Nirusha Lachman, PhD1; Kevin Christensen; Samuel J. Asirvatham, MD, FACC,FHRS2,3
Division of Cardiovascular Diseases and Internal
Medicine3, Department of Anatomy1, Division
of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine2, Mayo Clinic, Rochester, Minnesota
Short title: Phrenic Nerve Injury
Corresponding Author: Samuel J. Asirvatham, M.D. Division of Cardiovascular Diseases, Professor of Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905.
Radiofrequency ablation is
increasingly used as an option to optimally manage patients with symptomatic
atrial fibrillation. Presently, ablationists strive to improve success rates,
particularly with persistent atrial fibrillation, while simultaneously
attempting to reduce complications. A well-recognized complication with atrial
fibrillation ablation is injury to the phrenic nerve giving rise to
diaphragmatic paresis and patient discomfort.
Phrenic nerve damage
may occur when performing common components of atrial fibrillation ablation
including pulmonary and superior vena caval isolation. The challenge for
ablationists is to successfully target the arrhythmogenic substrate while
avoiding this complication. In order to do this, a thorough knowledge of
phrenic nerve anatomy, points in the ablation procedure where nerve damage is
more likely, and an understanding of the presently utilized techniques to avoid
this complication is required. In addition, when this complication
does arise, prompt recognition of its occurrence, knowledge of the natural
history, and available methods for management are needed.
In this review, we
discuss the underlying anatomic principles, techniques of avoiding phrenic
nerve damage, and presently available methods of diagnosing and managing this
Key words: phrenic nerve, atrial fibrillation, radiofrequency ablation, cryoablation, electroanatomic
mapping, safety, complications
Radiofrequency ablation is now well
established as an option when treating patients with symptomatic atrial
fibrillation (AF) [1, 2]. Ablation of the
AV node and placement of a permanent pacemaker as well as adjunctive atrial
flutter ablation along with antiarrhythmic therapy has been used for drug
refractory symptomatic patients for two decades. While these modalities were previously
occasionally resorted to, more recently, there has been an explosion in the
utilization of this treatment modality. The recognition that triggers for AF
are associated with the thoracic veins and subsequent understanding of the need
to circumferentially ablate atrial tissue around these veins is directly
responsible for the burgeoning use of these procedures [3-7].
While the success rates
for these procedures, particularly with paroxysmal AF, has been encouraging,
several complications relatively specific to this type of ablation have been
seen. Given the relatively benign nature of the treated arrhythmia (AF), it is
critical to be sure that the treatment (AF ablation) is of minimal risk.
Reported complications from AF ablation include stroke, pulmonary vein stenosis,
cardiac perforation, esophageal damage, and phrenic nerve injury (PNI) [8-12].
Phrenic nerve injury
had rarely been reported with ablation procedures for other arrhythmias (Figure 1) including other atrial arrhythmias , however, this complication is well recognized,
specifically with AF ablation. An integral part of most presently employed AF
ablation procedures involves circumferential ablation to electrically
disconnect the thoracic veins from the atria [14, 15]. While both right and left phrenic
nerves may be injured [16-18], most
commonly the right phrenic nerve is at risk when electrical isolation of the right
upper pulmonary vein (RUPV) or the superior vena cava (SVC) is being
Figure 1: Example of left phrenic injury with elevation of the left hemidiaphragm. Infant with ICD placed epicardially and generator over the right abdomen. The left phrenic nerve was injured during placement of the epicardial ICD lead.
When PNI occurs, patients
are sometimes severely symptomatic with shortness of breath, particularly with
exertion and when lying down [19-21].
The diagnosis is usually straightforward with right hemidiaphragmatic elevation
on routine chest radiography and further confirmation with paradoxical movement
of the diaphragm when the patient is asked to sniff (Figures 2
and 3). Since the main goal of AF ablation is to improve
patients’ symptoms, the occurrence of PNI offsets this primary goal even when
the ablation procedure is successful.
Figure 2: Anteroposterior chest radiography of PNI. Left panel is preablation and shows normal diaphragmatic height. Right panel is following ablation with phrenic nerve injury and marked elevation of the right hemidiaphragm. Ablation involved energy delivery in the vicinity of the superior vena caval ostium.
Figure 3: Lateral chest radiography of phrenic nerve injury. Corresponding lateral radiographic images to those shown in Figure 2. Right panel is postablation and the marked elevation of the right diaphragm (no elevation of cardiac silhouette as would occur if this was the left hemidiaphragm) is noted.
For ablationists to
avoid this complication and yet successfully target the arrhythmogenic
substrate for AF, significant background knowledge is required. First, a
detailed understanding of the anatomical course and variation of the phrenic
nerve is needed. In addition, appreciating the parts of the AF ablation
procedure, which particularly pose a risk for PNI, and the available techniques
to prevent this complication must be thoroughly understood.
Along with esophageal
damage, PNI shares the difficulty with avoidance as a result of the highly
variable and difficult to visualize the course of these anatomic structures.
In this review, we
discuss the regional anatomy of the phrenic nerve, reports of specific parts of
the AF ablation procedure where PNI has occurred, and critically analyze the
pros and cons of presently utilized techniques to avoid this troublesome
should be thoroughly cognizant with the anatomic course and relations of both
the right and left phrenic nerve (Figure 4). Importantly,
the variations that occur with the nerve course and with congenital and other
structural heart disease must be appreciated. Specifically, the regional
anatomy of the nerve in relation to the pulmonary veins, SVC, lateral right
atrium, and the left atrial appendage must be well understood prior to the
delivery of radiofrequency energy at these locations.
Figure 4: Anatomic dissection showing typical course of the phrenic nerve. Solid arrow points to the right phrenic nerve immediately adjacent to the SVC. As it courses posteriorly, the nerve becomes related to the RUPV (see text). Hatched arrow points to the left phrenic nerve. The dissection has lifted the nerve away from its typical adjacent location to the left atrial appendage. LV - left ventricle
Right and Left Phrenic Nerve Course
nerve is a mixed somatic nerve that arises mainly from the anterior ramus of
the fourth with contributions from the third and fifth cervical segments
(although the 5th cervical nerve root is often seen to join the
phrenic trunk on the anterior surface of the scalenus anterior, it may descend
into the thorax before it joins the nerve). The phrenic trunk forms at the
upper lateral border of the scalenus anterior muscle and descends along its
anterior surface, behind the prevertebral fascia [22-24]. In its decent, it passes behind the
sternocleidomastoid, inferior belly of omohyoid, transverse cervical and
suprascapular arteries, internal jugular vein, and thoracic duct on the left.
the phrenic nerve enters the thorax, it crosses medially in front of the
internal thoracic artery [25, 26].
However, this relationship may not always be consistent as upon entering the
thorax, the phrenic nerve has been recorded to cross the internal thoracic
artery either superiorly, lie between the internal thoracic artery and the
first rib, or cross it inferiorly where it is held against the artery by the
adjacent lung and pleura as it passes into the mediastinum. In a study
conducted by Owens et al , the phrenic nerve conformed to the standard description of
its course in only 64% of specimens dissected. This relationship was found to
be asymmetric in 46%.
the thorax, the phrenic nerve passes downward and in front of the hilum of the
lung between the fibrous pericardium and mediastinal pleura and is accompanied
by the pericardiophrenic vessels towards the thoracic diaphragm.
phrenic nerve is said to originate from displaced fibers of the 5th
cervical ventral ramus (sometimes 4th or 6th cervical
segments), which runs within a branch of the nerve to subclavius. In its
course, it lies lateral to the phrenic nerve as it passes inferiorly posterior
to the subclavian vein. In most cases, it joins the phrenic nerve near the
first rib but may also join the nerve at the level of the pulmonary hilum or
beyond [22, 27].
recent incidental finding by Prakash et al  is that the phrenic nerve was seen to give off a
communicating branch to C5 root of the brachial plexus and was located in front
of the subclavian vein just as it entered the thorax.
The Right Phrenic Nerve and the Superior Vena Cava
The right phrenic nerve is covered
by mediastinal pleura as it descends along the brachiocephalic vein and then
along the right anterolateral border of the SVC (Figure 5).
The nerve is separated from the SVC at its right atrial junction by
pericardium. It continues inferiorly along the same line over the right atrial
wall. Histological reports have shown a close relationship between the right
phrenic nerve and the SVC, separated by variable amount of fatty tissue . The right phrenic nerve appears to be closest to the SVC
superiorly and as it curves posteriorly approaching the superior cavo-atrial
Figure 5: Anatomic dissection showing the adjacent and very close relationship of the right phrenic nerve (arrow) with the SVC close to the ostium. Attempts at circumferential isolation of the SVC often is limited because of this relationship.
The Right Phrenic Nerve and the Right Upper Pulmonary Vein
The right phrenic nerve shares an
anatomically close relationship with the RUPV  with a minimal distance of about 2.1mm between them . However, it must be noted that this relationship and the
distance between the right phrenic nerve and the RUPV is highly variable (Figure 6). From a technical standpoint, therefore, this puts
the phrenic nerve at high risk for injury during RUPV isolation.
Figure 6: Schematic representation of one technique to avoid diaphragmatic injury. A pacing catheter is placed deep into the SVC. With high output stimulation, persistent phrenic nerve stimulation occurs. Cryoablation is then done close to the ostium. If diaphragmatic movement stops, then cryoenergy delivery is immediately discontinued. If diaphragmatic movement continues, then cooling to an ablative level -70 – (-)80°C is done, thus allowing completion of the SVC isolation procedure. Reproduced with permission from: Bruce CJ et al, J Interv Card Electrophysiol 2008; 22:211-219.
The right and left
phrenic nerve receive its blood supply from the internal thoracic artery
(ITA). A pericardiophrenic branch descends along each phrenic nerve within a
fascial sheath to form a neurovascular bundle that adheres to the fibrous
pericardium. Around 70% of blood supply is received from the pericardiophrenic
branch of the ITA with the remainder from pericardial and pleural branches
arising from the upper segment of the ITA .
The ITA and the phrenic
nerve share an anatomically important relationship. The ITA has been recorded
to cross the nerve obliquely from lateral to medial and sometimes anterior to
posterior . A study by Puri et al recorded both phrenic nerves
crossing the ITA anteriorly in 54%, posteriorly in 14%, the left phrenic nerve
crossing anteriorly in 12%, and the right phrenic nerve crossing posteriorly in
12% with this position switched in 20% of cases .
Division of the phrenic
nerve in the neck leads to paralysis of the corresponding half of the
diaphragm. In its proximal course, the phrenic nerve may be impaired as a
result of brachial plexus injuries. However, cardiac surgery remains one of
the most common causes of damage to the phrenic nerves. Other causes of
phrenic nerve damage include tumors of the lung, associated mediastinal
structures, and infections [34, 35].
Left Phrenic Nerve and Cardiac
The left phrenic nerve continues
over the aortic arch, pulmonary trunk, and left pericardial wall over the left
atrial appendage as it continues along the underlying left ventricular
surface. The left phrenic nerve may be separated from the pericardium by a
variable layer of adipose tissue. In about 80% of individuals, the left
phrenic nerve is closely related to the underlying left oblique marginal vein
and the left marginal artery. It may also pass close to the left main stem,
left anterior descending artery, or the great cardiac vein .
Prior to the advent of thoracic
vein-related ablation for AF, rare reports of PNI with ablation for other
arrhythmias existed. These typically involved ablation in the right atrium
close to the superior vena caval junction as was performed to modify the sinus
node (inappropriate sinus tachycardia), atrial tachycardias arising from the
superior crista terminalis [13, 36-38], and ablation of right atrial flutters [23, 25, 26].
isolation targeting the triggers in the thoracic veins became an integral part
of AF ablation, PNI was increasingly recognized. Lee et al describe a
61-year-old woman with a 7-year history of paroxysmal AF . Radiofrequency ablation was performed. Isolation of the
left superior, left inferior, and the right inferior pulmonary veins was
completely achieved without difficulty. However, 25 radiofrequency pulses with
a total duration of 1,297 seconds were required to isolate the right superior
pulmonary vein. The procedure was well tolerated except for complaints of
chest pain radiating to her back. One day after the ablation, the patient
complained of shortness of breath and orthopnea, and chest radiography revealed
right diaphragmatic elevation. Three days later, the patient’s symptoms
improved somewhat, and by day four, chest x-ray revealed a significant
resolution of right hemidiaphragmatic elevation. Four weeks later, she was
asymptomatic and the right diaphragmatic elevation disappeared completely.
Le et al demonstrate a
similar case with a 61-year-old male with a 6-year history of paroxysmal AF . He underwent 41 radiofrequency pulses for duration of
2080 seconds. He was symptomatic on post-procedure day one, and a chest x-ray
revealed right hemidiaphragmatic elevation. Post-procedure day six, his symptoms
had improved but the elevation persisted. Five months later, he was
asymptomatic, but chest x-ray, fluoroscopy, and pulmonary function test
revealed persistent right hemidiaphragm paralysis and restrictive pulmonary
Between 1997 and 2004,
Sacher et al studied 3755 consecutive patients who underwent AF ablation at
five centers . Eighteen (0.48%) patients demonstrated PNI. Right PNI
occurred during right superior pulmonary vein ablation or SVC disconnection,
and left PNI occurred during left atrial appendage ablation. After a mean
follow-up (36 +/- 33 months), 12 patients had complete recovery, 3 had partial
recovery, and 3 had no recovery of diaphragmatic function.
Swallow et al present a
50-year-old man with recurrent AF that had undergone radiofrequency ablation to
the ostia of the pulmonary veins . The procedure was prolonged because of a large right
superior pulmonary vein. The following day he was breathless, and a chest
radiograph showed an elevated right hemidiaphragm. Six weeks after ablation,
magnetic phrenic nerve stimulation showed right hemidiaphragm weakness.
However, 9 months following ablation, a diaphragm function test showed full recovery [40, 41].
Data from 17 patients
with PNI caused by varying ablation techniques performed between December 1999
and December 2005 at 3 centers were reviewed by Bai and colleagues . Thirteen of these patients underwent an ablation for AF. Radiofrequency
ablation was done in 9/13, cryoablation in 1/13, ultrasound ablation in 2/13,
and laser ablation in 1/13. Bai et al concluded that PNI caused by catheter
ablation regardless of the energy source appears to functionally recover over
Right Upper Pulmonary Vein
Because of the relationship
described above between the phrenic nerve and the right upper vein, this is a
common location wherein PNI has been reported. Because the phrenic nerve has a
closer relationship to the mid and distal portions of this vein, ablation that
is performed entirely in the left atrium circumferentially isolating the vein
≥5 mm from the ostium of the pulmonary vein is recommended. Because of
anatomic variation in the phrenic nerve, no ablation site or technique is
foolproof and thus requires the adjunctive use of techniques to identify phrenic
nerve location described below.
Superior Vena Cava
The most common site where phrenic
nerve-related issues arise when ablating is the SVC. This vein is a
well-established site for triggers of AF initiators [42-45]. Unlike the situation with the right
upper vein, the phrenic nerve crosses the ostium of the SVC, thus, a
generalizable approach of ablation proximal or distal to the ostium cannot be
recommended. Perhaps more so than ablation at any other site, precise
knowledge on the course of this nerve is essential to avoid injury when
attempting to electrically isolate this vein.
Other Locations for Potential
Phrenic Nerve Injury with AF Ablation
Occasionally, ablation is required
in or around the left atrial appendage to treat AF. Triggers of AF, if found
to arise within this structure, may require isolation of a portion of the
appendage to avoid energy delivery with the attendant risk of cardiac
perforation deeper in the appendage. Because of the proximity of the left
phrenic nerve with the lateral wall of the left atrial appendage, injury to
this nerve may occur.
pulmonary vein isolation, occasionally, triggers from other veins such as the
vein of Marshall may continue to occur. Ablation in the vein of Marshall itself is unlikely to result in PNI, but if isolation of this vein in the lateral
coronary sinus is contemplated, left PNI is possible [3, 46]
Phrenic nerve injury is a
significant limitation to the use of ultrasound-based approaches to ablation in
or around the thoracic veins [47, 48].
Cryoablation both in
the experimental canine model and with clinical ablation has been associated
with PNI as well [16, 49-51].
Okumura et al conducted a study that examined tissue temperatures around
pulmonary veins during high intensity focused ultrasound balloon ablation for
AF in the canine model . Tissue temperatures in eight dogs undergoing 51 right
superior pulmonary vein high intensity focused ultrasound ablations were
recorded from epicardial thermocouples at right superior pulmonary vein orifice
and phrenic nerve. This study disclosed the direct high intensity focused
ultrasound ablation effect as the mechanism of PNI occurring within 4-7 mm from
the balloon surface.
Tse et al used the
CryoCor cryoablation system (CryoCor Inc., San Diego, California) in 52
patients with paroxysmal or persistent AF to isolate the pulmonary vein . Cryoablation was applied twice at each targeted site (2.5
to 5 min/application). Of these 52 patients, one had transient phrenic nerve
paresis during cryoablation in the right superior pulmonary vein, which
resulted in premature procedure termination. The diaphragmatic movement
resumed immediately after cryoablation was terminated, and there was no damage
or loss of diaphragmatic or pulmonary function at 12-month follow-up.
In another study done
by Van Belle et al, a cryo-thermal balloon approach was used for all
consecutive patients who were selected for circumferential pulmonary vein
isolation because of paroxysmal AF between August 2005 and August 2007 . There were 141 patients included in this study. Of these
141 patients, 4 patients had asymptomatic right PNI persisting at discharge.
All 4 patients had recovery of their diaphragmatic movement at 6-month
The exact reason why
circumferential ablation catheters appear to have a higher propensity to damage
the phrenic nerve is unknown. Most likely, however, is that these devices need
to be placed slightly into the pulmonary vein for stability. Specifically,
when placed deeper into the right upper pulmonary vein, the risk of phrenic
nerve damage would then increase. Other possibilities include resonant
frequency ablation occurring with ultrasound systems where energy delivery and
heating may occur at a significant distance from where the device has been
placed. Future design of pulmonary vein ablation devices will need to incorporate
these possibilities, specifically by positioning the energy delivery system
outside the pulmonary vein, targeting the perivenous atrial myocardium.
Phrenic stimulation as well as
injury may occur during device implantation. This may be particularly relevant
with epicardial device implantation and combined pacing and ablation procedures
in patients with a Mustard/Senning procedure with congenital d-transposition of
the great arteries [52-54].
With some complications associated
with AF ablation, there appears to be definite ways of avoiding their occurrence.
For example, pulmonary vein stenosis likely does not occur if ablation is
performed in the atrium, avoiding the vein altogether. Other feared
complications have no established method to affect the possibility of
occurrence at all. An example of this situation is stroke resulting from
coagulum formation on electrodes during ablation. Phrenic nerve injury does
not clearly fit in either category. Although there is no foolproof method of
avoiding PNI, several methods have been developed and clinically used that
significantly decrease the likelihood of its occurrence.
Pacing Maneuvers to Identify the Phrenic Nerve Course
The phrenic nerve can be stimulated
when pacing close to the nerve from an endocardial site. Testing for unwanted
phrenic nerve stimulation when placing permanent pacemaker leads is routine,
and electrophysiologists are familiar with recognizing the characteristic jerky
diaphragmatic stimulation when the nerve is captured (Figure 7).
Figure 7: RAO and LAO radiographs with technique of cryoablation exemplified. The circumferential mapping catheter is in the SVC. The pacing catheter (solid arrow) is deep in the SVC at a site where consistent phrenic nerve stimulation is achieved. With continued pacing, cryoenergy is delivered via a catheter placed at the ostium (hatched arrow). Entrance and exit block was achieved in this vein following the procedure.
In the setting of
radiofrequency ablation, the premise behind this maneuver is that if bipolar
pacing done just prior to radiofrequency energy delivery results in phrenic
nerve stimulation, then ablation at that site is likely to damage the nerve.
Conversely, if with pacing output, no diaphragmatic stimulation is seen, it is
considered safe to deliver radiofrequency energy.
This maneuver has as
its advantages - its simplicity, reproducibility, and the fact that the entire
course of the nerve can be mapped out and visualized with three-dimensional
mapping systems . Schmidt et al performed three-dimensional electroanatomic
mapping in the left and right atriums, SVC, and right pulmonary veins and
combined it with a pace mapping technique in order to reconstruct the anatomic
course of the right phrenic nerve. Pacing was performed at maximum output with
a cycle length of 800 ms, and phrenic nerve capture was defined as either a
fluoroscopically visible or a palpable movement of the right diaphragm. As soon
as capture of the phrenic nerve was obtained, the mapping catheter was moved until
capture was lost. Each pacing location was marked with a different color
according to the pacing response in the electroanatomic map. Hence, a
delineation of the phrenic nerve’s anatomic course was obtained. From this
study, they concluded that pace mapping of the phrenic nerve using three-dimensional
mapping can be done in a timely manner and can provide important information on
the exact location of the phrenic nerve, which in turn can help prevent PNI.
There are several
disadvantages and pitfalls to avoid when utilizing this technique to avoid
phrenic nerve damage.
- The optimal pacing output to
perform this maneuver is unknown. In one study, high output pacing at 10
V at 2.9 msec  was used and in another at 10 mA at 0.5 msec . If too low an output is used, phrenic nerve stimulation
may not occur despite the proximity of the nerve, and on the other hand,
if too high an output is used, ablation may be avoided at multiple sites
- The propensity to damage the
phrenic nerve at any given location likely varies with the type of
catheter (irrigation vs non-irrigation), power delivery, temperature
reached, duration of energy delivery, and other factors that affect lesion
size. Thus, at a given site in a particular patient, phrenic nerve
stimulation at 5 V at 4.5 msec may in fact signify the likelihood of PNI
when ablating at 60 W for 120 sec but perhaps not at 30 W for 30 sec. The
latter seconds may have been sufficient to complete circumferential
isolation of the SVC.
- If the patient is under general
anesthesia, a skeletal muscle paralytic agent cannot be used since phrenic
stimulation then cannot be recognized whether or not capture occurs with
- Deep respiration and other
movement may cause phrenic nerve stimulation to be absent at one point in
the respiratory cycle, and if ablation energy is delivered at another
point, PNI may occur. Thus, care to avoid movement and continued pacing
stimulation for at least two full respiratory cycles is required.
- In some instances, the operator
may not wish to stimulate the atrial myocardium at the site of planned
ablation. For example, ablation may be performed during a tachyarrhythmia
to assess the effect of exit block on isolation of a thoracic vein.
Pacing may terminate the arrhythmia, and asynchronous pacing may be
required when tachycardia rates are high that may result in changing the
arrhythmia to AF.
- Finally, the actual etiology of
phrenic nerve damage with ablation is not known. While it is presumed
that it is a result of direct heating of the nerve, another possibility is
that the blood supply (pericardial phrenic arteries) is damaged, giving
rise to ischemic injury to the nerve. In this case, pacing at a site
where the arterial supply exists will not result in diaphragmatic
stimulation, but ablation at that site will nonetheless damage the nerve.
In summary, because of the above
reasons, pacing to identify the phrenic nerve location is not foolproof.
Damage to the surrounding artery supplying the phrenic nerve, changes in
position, and inappropriately low pacing outputs may all mislead the operator
into thinking a particular site of ablation is safe, and yet, PNI results.
Although cryo energy can result in
PNI and, by itself, does not enhance the safety of ablation, a technique has
been described with cryo-mapping to avoid PNI  (Figure 8). The key to this maneuver
is the characteristic of cryo energy where cooling tissue to a certain level
provides a bioelectric effect (slowing of conduction, etc.) that is temporary
and can be made permanent if cooled to a more significant level. This
technique of cryo-mapping is widely used in electrophysiology, particularly
when ablating near the conduction system [57, 58].
For example, when ablating mid septal or anteroseptal accessory pathways, once
a suitable site for ablation has been defined (pathway potential, etc.) , cooling to -30 - (-)35°C is first done. If pathway
conduction is lost but AV nodal conduction is still present, then further
cooling to -70 – (-)75°C is performed with the aim of permanently destroying
the accessory pathway. In contradistinction, if AV block occurs at -35°C, then
cooling is turned off and AV node conduction allowed to return and that site
not chosen for further energy delivery.
Figure 8: Diagrammatic representation of the typical course of the right phrenic nerve in relation to the SVC and the right superior pulmonary vein (RSPV). Inset shows that while typically (solid circle) the phrenic nerve is in proximity to the distal RSPV, marked variation with no proximity or proximity relatively closer to the base also occurs.
An analogous maneuver
can be done to assess phrenic nerve risk at a given ablation site. Here, a
standard electrode catheter is placed high in the SVC and the catheter moved
until consistent phrenic nerve stimulation at all stages of the respiratory
cycle noted. Cryoablation is then performed at a site where radiofrequency
energy delivery was considered high risk to cause phrenic damage. If, when
cooling to -35°C, diaphragmatic stimulation that had up to that point been
observed consistently when pacing within the SVC occurs, then cooling is
stopped and ablation not performed. However, if phrenic nerve stimulation
continues despite cooling at the questionable site at -35°C, then further
cooling to -70 – (-)75°C is undertaken to ablate the tissue and enable the
obtaining of entrance block into the SVC (Figure 9).
Figure 9: Isolation of the SVC using the cryoablation mapping technique discussed in the text. A circumferential mapping catheter (Lasso 1,2 - LASSO 10) was placed in the SVC. Repeated initiations of AF as well as atrial flutter from this vein were noted. Because of phrenic nerve proximity in the posterolateral portion of the SVC ostium, the cryomapping technique was utilized. Following completion of the ablation, continued rapid tachycardia (arrows) in the SVC occurred intermittently; however, exit block (no conduction to the atrium) was no evident.
There are several
potential disadvantages with this maneuver.
- It is possible that long-term
phrenic nerve damage will occur even when cooling to -35°C.
- If phrenic nerve stimulation
stops when ablating at -35°C, cryo energy is simply stopped and no
solution of how to isolate the vein is offered. Dib et al developed a new
method using cryo-mapping to successfully ablate at the SVC/right atrium
junction despite phrenic nerve proximity . Between January 2001 and January 2007, 110 patients
had partial or circumferential radiofrequency ablation at or near the
SVC/right atrium junction. Of these 110 patients, 66 had phrenic nerve
proximity as ascertained by pacing at 10 mA output. In all but 7, the
junction was ablated at points where phrenic nerve proximity was not
present. In the remaining 7 patients who had continued arrhythmogenicity
despite attempts to modify the substrate, they paced 4 cm into the SVC
where consistent phrenic nerve stimulation was obtained. In 1 patient,
diaphragmatic stimulation ceased at -30°C, and the energy delivery was
stopped. In 6 of 7 patients, with continued diaphragmatic capture, cryoablation
at -70/-80°C was then performed.
- Meticulous attention is required
to be sure that the pacing site is cephalad to where cryo energy is being
delivered. This is because diaphragmatic stimulation will still occur if
the phrenic nerve is paced caudal (lower) then where complete transection
of the phrenic nerve had occurred.
mapping is a frequently employed technique during mapping and ablation
procedures [60, 61]. Typically, the
local electrogram voltage and activation times relative to a standard reference
are tagged using this system and a three-dimensional color-coded map rendered.
Pacing maneuvers as
described above are performed to identify sites for phrenic nerve stimulation
as seen. These points are then tagged on the system as phrenic nerve location
sites, and the course of the nerve can be traced out. The ablationist may now
be able to design a set of ablation lesions that is likely to result in
electrical disconnection of the SVC (or right superior pulmonary vein) without
damaging the phrenic nerve (Figures 10 and 11).
Figure 10: Electroanatomic map of the right atrium, posterior view. The black dots represent areas of phrenic nerve stimulation noted when pacing endocardially with the catheter. The red dots are ablation lesions placed with attempts to avoid proximity to the phrenic nerve while completing an AF procedure (endocardial right atrial maze).
Figure 11: Electroanatomic map of the left atrium and the SVC. Following ablation in the left atrium, the SVC continued to trigger arrhythmia. Isolation of this vein was attempted. Care was required to avoid ablation energy delivery near sites of phrenic nerve stimulation (pink dots). Ablation dots are tagged red.
Since this maneuver is
an extension of the pacing maneuvers to identify phrenic nerve stimulation, the
same limitations apply.
Online Imaging of the Phrenic Nerve
Ideally, reliable realtime imaging
of the phrenic nerve would allow beat-to-beat assessment of the likelihood of
damaging this structure with ablation. Intracardiac ultrasound can
occasionally be used to define phrenic nerve location; however, careful imaging
is located, and validation with pacing is still needed because of the lack of
surety of knowing that another structure is not being imaged.
and MRI have been used as diagnostic tools in the assessment of peripheral
nerve lesions . Although conventional CT visualization of the phrenic
nerves, even with high resolution is difficult , studies in the past have attempted to identify them based
on characteristic clues and by structures within its field [34, 62]. However, more recently, the use of
64-slice MDCT has enabled clearer visualization and assessment of the phrenic
nerves and other mediastinal structures related to cardiac anatomy .
proximity of the pericardiophrenic artery and vein to the phrenic nerve has
been a useful anatomical indicator in the delineation of the phrenic nerve.
Matsumoto uses this consistent relationship to define the right and left
pericardiophrenic bundles (RPCB and LPCB) . The LPCB was visible in 74% of patients with frequent
contact on the left atrial appendage. The LPCB was identified most effectively
on axial images at the level of the lateral left ventricular wall as a rounded
structure with variable density. The RPCB, on the other hand, was detected in
only 47% of patients in this study. Visualization of the right and left PCBs
are said to be dependent on the amount of adipose tissue within the bundles,
flow in the pericardiophrenic vessels, pleural folds, age, sex, and related
technical challenges such as minimal contrast differential between RPCB and
mediastinal structures [62, 63].
In a more recent study,
the phrenic nerve has been identified by means of electroanatomic mapping . In almost 90% of patients, the phrenic nerve was
successfully captured. This technique uses 3D mapping and pace mapping over a
craniocaudal distance of around 40 mm to trace the anatomic course of the
nerve. In addition to being able to identify the course of the right phrenic
nerve in a reasonable timeframe in patients, the phrenic nerve relationship
with the SVC and the RUPV is also possible with electroanatomic mapping .
However, to date, no
direct phrenic nerve visualization using imaging technology is available. The
high degree of variability in the course of the phrenic nerves, especially the
right phrenic nerve, remains a challenge to the effective characterization of
these nerves through imaging.
Even with the highest degree of
caution and the use of all available maneuvers to identify the phrenic nerve,
ablationists must be prepared to manage this condition should it occur. Prompt
diagnosis is important despite the lack of availability of any specific
treatment since unnecessary evaluation for shortness of breath may otherwise
occur. An understanding of the natural history of PNI along with the
availability of certain therapeutic interventions that may be considered in
specific instances is required. Unfortunately, accurate knowledge for the
likelihood and timing of phrenic nerve function recovery and selecting patients
for specific interventions is unknown.
Phrenic nerve injury is suspected
when a patient complains of shortness of breath, often described as difficulty
in taking in a deep breath, following ablation. The diagnosis is also often
picked up on routine chest x-rays in otherwise asymptomatic individuals. The
characteristic finding is elevation of the affected hemidiaphragm (usually
right) that was not present prior to ablation. A similar radiologic appearance
may result from subdiaphragmatic fluid collections, subpulmonic effusions, or
atelectasis following ablation. When doubt exists, a sniff test with cine
fluoroscopy is performed when the patient is asked to sniff. Normally, the
diaphragm will move down with sniffing, but a paralyzed diaphragm will move
paradoxically upward while the normal diaphragm moves down [19, 20, 64, 65].
Natural History of PNI
Although exact timing of recovery
and whether recovery is certain is not presently known, most patients appear to
recover phrenic nerve function (following ablation-induced damage) before a
6-12-month timeframe [16, 38, 50, 51].
Treatment of Persisting
At present, there is no widely
available simple method of restoring phrenic nerve or diaphragmatic function. In
certain cases, plication of the diaphragm to avoid elevation of the diaphragm
and adverse mechanical impact on respiration can be considered. However, the
role of this procedure in adults is not clear as only isolated case reports or
small series have been reported [66-69].
stimulators placed surgically can also be considered in rare cases. Diaphragmatic
pacing is the stimulation of the phrenic nerves with electrical current via an
implanted pacemaker, resulting in the contraction of the diaphragm . Dr. Surani and colleagues present a case report of a
60-year-old female with confirmed right hemidiaphragm paralysis. She underwent
successful placement of a right diaphragmatic pacemaker, and her symptoms
rapidly abated . Lue et al sought to evaluate the long-term complications
of phrenic nerve pacemakers to see if they were beneficial to patients or not . They studied three patients who had had phrenic nerve
pacemakers for over 20 years. Although pulmonary complications and the surgery
itself are a hindrance, the patients’ independence and quality of life were
greatly improved due to these devices.
Phrenic nerve injury is a
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High-risk locations include the ostium of the SVC and within the RUPV. An
accurate knowledge of the anatomy of this nerve, its propensity for a variable
course, and knowledge of maneuvers that can identify nerve proximity will allow
ablationists to perform successful venous isolation with low risk of nerve injury.
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