Pulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation

Fibrillation

E.B. S

Introduction

Catheter ablation around the pulmonary veins (PVs) has become the treat- ment of choice for symptomatic patients with atrial fibrillation (AF) who do not respond to pharmacological therapy [1–6]. Over the past few years, a variety of strategies have been developed to achieve cure of AF [7–16]. PV stenosis is a known potential complication of radiofrequency ablation (RF) around the PVs [17–24] and its recognition is important to avoid unneces- sary workup and to initiate appropriate treatment.

Incidence and Clinical Manifestations

The incidence of PV stenosis following AF ablation has been variably reported, ranging from 0% to 42% depending on the ablative technique used and the method of assessment [7, 10, 20, 25, 26]. The latter number probably represents and overestimation since transoesophageal echocardio- graphy (TEE) instead of an anatomical imaging modality was used to estab- lish the diagnosis.

Several factors contribute to an increased risk of developing PV stenosis, such as RF delivery inside the PVs, increasing power and temperature set- tings, and a ‘learning curve’ effect [24, 27]. Recent reports have shown a trend towards a decreasing incidence of PV stenosis mainly due to limiting RF delivery at or outside the orifice of the veins, power titration based on monitoring of tissue effects of RF (as with microbubble formation on intrac-

Section of Cardiac Arrhythmias and Pacing, Center for Atrial Fibrillation, Hospital Pró-

Cardíaco, Botafogo, Rio de Janeiro, Brazil

ardiac echocardiography) and increasing operator experience [10, 27]. In centres with a high volume of AF procedures, PV stenosis is becoming a ‘dis- ease in extinction.’ However, with the widespread application of AF ablation in the electrophysiologic community more procedures are being performed by less experienced operators, increasing the chances that the incidence of PV stenosis will actually increase. In fact, a recently presented review of the European experience with AF ablation detected up to 20% of patients devel- oping PV stenosis in centres performing less than 50 procedures.

Physicians in general should thus be ready to work up patients with symptoms developing after an ablation procedure. However, PV stenosis after RF ablation is frequently asymptomatic, especially when a mild or moderate degree of stenosis is present or a single vein is involved [21, 22].

Most important is the fact that, when present, symptoms appear to be largely respiratory in origin [23], usually developing between the first and fourth month after the index procedure. The spectrum of symptoms range from persistent cough and pleuritic chest pain to more dramatic presentations, such as haemoptysis and severe exertional dyspnoea (Table 1). The severity of symptoms may be related not only to the degree of stenosis but also to the number of PVs with stenosis, with almost all patients with ≥ 2 PVs with severe stenosis being symptomatic (Fig. 1). However, given the non-specific nature of these symptoms and the frequent association with radiological evi- dence of lung consolidation, it is not surprising that many patients are ini- tially treated for other common conditions, such as pneumonia (Fig. 2) and

Table 1. Clinical presentation and CT findings in patients with severe pulmonary vein (PV) stenosis

Patients (n = 21)

Clinical presentation

Cough 8 (38.1)

Dyspnoea 11 (52.4)

Pleuritic chest pain 6 (28.6)

Haemoptysis 5 (23.8)

Asymptomatic 8 (38.1)

Spiral CT: > 70% PV stenosis (n = occluded PVs)

LSPV 14 (6)

LIPV 15 (7)

RSPV 4 (1)

RIPV 3 (1)

LSPV Left superior PV, LIPV left inferior PV, RSPV right superior PV, RIPV right inferior

PV

pulmonary embolism, before the correct diagnosis is made [21, 23, 28].

Indeed, we published a series of 18 patients developing severe PV stenosis after AF ablation who were followed by their primary-care physicians, and in Fig. 1. Correlation between the presence of respiratory symptoms and number of pul- monary veins (PVs) with severe stenosis. While less than 1/3 of patients with single-ves- sel stenosis have symptoms, the majority of patients with more than one PV involved are symptomatic. Pulmonary arterial hypertension is rare and can be documented only in patients with multi-vessel involvement

Fig. 2. CT scan of a patient with pulmonary consolidation initially attributed to pneumo-

nia. There is a clear lung infiltrate in the periphery of the left lung (arrows). The patient

did not respond to several antimicrobial regimens and was subsequently diagnosed

with PV stenosis

all patients PV stenosis was not considered in the differential diagnosis [21].

Misdiagnoses lead to improper diagnostic and therapeutic procedures, such as prolonged antibiotic treatment (5 patients), treatment for possible asth- matic syndrome and bronchitis (3 patients), placement of a vena cava filter (1 patient), and lung resection surgery (1 patient). Therefore, if a high degree of alertness and awareness is not present, this diagnosis can remain unknown.

Diagnostic Methods and Therapeutic Interventions

Strong suspicion is required to promptly diagnose PV stenosis, not only because it can mimic more prevalent respiratory and cardiovascular syn- dromes but also because diagnostic tests can be misleading, as we and others previously described [21–23, 28]. A number of imaging modalities have been used in the evaluation of PV stenosis. CT scanning is probably the most helpful since it can reliably identify the location and extension of the lesions (Fig. 3), while providing assessment of concomitant lung (e.g. consolidation or haemorrhage), mediastinal, and hilar (e.g. enlarged nodes) abnormalities

Fig. 3. Spiral CT scan at the level of the inferior PVs demonstrating a severe narrowing

(arrow) of the proximal portion of the left inferior PV (LIPV). This location probably

indicates that radiofrequency (RF) lesions were in fact placed inside the vein. RIPV

Right inferior PV, LA left atrium

(Fig. 2). The only caveat is that some vessels that appear totally occluded on CT scanning are in fact patent when evaluated by PV angiography [29], the gold-standard diagnostic modality. Magnetic resonance angiography can also be performed with comparable results and has the advantage of avoid- ing iodine contrast injection [30–33].

Echocardiography has also been used to detect and predict the develop- ment of PV stenosis. TEE can provide accurate views of the superior PVs, and increased flow velocity on Doppler has been used as a surrogate for decreased luminal diameter. However, experience with intracardiac echocar- diography (ICE) has demonstrated that even vessels with markedly increased flow velocities may not show significant stenosis when evaluated by CT or angiography [34]. As such, we believe that significant overestimation of the degree of stenosis may occur with an echo-based assessment.

Ventilation/perfusion (V/Q) scanning is a simple and accurate method to detect and evaluate the haemodynamic consequences of PV stenosis, the most common finding being a segmental perfusion abnormality in the pres- ence of normal ventilation (similar to findings seen in pulmonary arterial embolism). In our experience, perfusion defects occur mainly when the degree of PV luminal narrowing is ≥ 70% [22], indicating that mild and moderate degrees of narrowing have minimal, if any, consequence on the physiology of the pulmonary circulation. Severe PV stenosis, in contrast, is associated with significant reduction in the pulmonary flow, which is only partially reversible even after successful treatment with PV dilatation. In our series evaluating 18 patients with severe PV stenosis, average pulmonary flow to the left lung increased from 11.7 ± 10.2% to 22.3 ± 10.8% after PV intervention [21].

Percutaneous PV dilatation is currently the treatment of choice for

patients with symptoms attributable to severe PV stenosis, and it is associat-

ed with significant improvement in pressure gradients, venous diameter,

lung perfusion, and symptoms [23, 29]. In a recent study involving 19

patients undergoing interventional procedures in 30 PVs, functional classifi-

cation improved dramatically from a mean NYHA score of 3.1 to 1.7, with

most patients able to perform their usual activities with no or only minimal

limitation [29]. Unfortunately, the short-term results are not maintained,

with approximately 50% of patients developing restenosis and necessitating

repeat interventions [23, 29]. PV stenting does not appear to provide better

results than simple balloon dilatation, at least when bare-metal stents are

used. Currently, there is no published experience regarding the use of drug-

coated stents, but better results are expected based on their successful use in

the coronary arteries and in saphenous vein grafts.

Prognosis and Importance of Preventive Strategies

Progression of PV stenosis beyond the third month after ablation is rare but can occur in up to 10% of patients [22], indicating the need to repeat imag- ing evaluation every 3–6 months or if symptoms develop or worsen. More commonly, the degree of narrowing remains stable or improves (up to 30%

of patients), probably reflecting the inflammatory nature of PV pathology.

Based on these data, we recommend routine imaging evaluation with either CT or MRI 3 months after the procedure, irrespective of the presence of symptoms. If no stenosis is detected, no further evaluation is needed unless compatible symptoms develop. In the presence of luminal narrowing, repeat evaluation is undertaken at 6 and 12 months.

Development of pulmonary arterial hypertension appears to be extreme- ly rare and occurs only in the presence of severe stenosis of several PVs (Fig. 1). Importantly, it is almost always associated with severe symptoms and appears to be reversible when PV dilatation is performed.

Risk factors for the development of PV stenosis, although yet to be com- pletely defined, include energy delivery inside the veins [18, 24, 32], vein size, and use of excessive power during RF applications [22, 24]. As such, reliable and precise delineation of the PV–left atrium (LA) junction appears to be important. Our initial experience with ostial isolation based on elec- troanatomical mapping to delineate the PVs proved to be disappointing, with isolation observed in only 31% of treated veins and with severe stenosis developing in 15.5% of patients, comparable to the 20% severe stenosis rate obtained when we performed distal PV isolation based on a circular catheter in a selected group of patients.

Once it became clear that we had to avoid lesions inside the veins, selec- tive PV angiography was utilised to determine the ostia. This approach decreased the incidence of severe stenosis to about 3%. However, in our experience the use of ICE was associated with the most considerable decrease in the occurrence of stenosis. When used to guide ostial positioning of the circular catheter (Fig. 4), it reduced severe stenosis to 1.4%. It is likely that angiography in not always reliable for adequate ostial visualisation because of the streaming effect of the contrast in the vein and the frequent gradual funnelling of the PV junction into the left atrial cavity.

Traditional methods for titration of energy delivery, such as tip tempera-

ture and impedance measures, may not be accurate [35]. This is especially

true for left-side procedures, during which the use of excessive power may

result in thromboembolic complications. Thus, the development of a reliable

method to achieve more accurate energy delivery is needed and visualisation

of microbubbles by ICE is a suitable option, being associated with a signifi-

cantly reduced incidence of severe PV stenosis. Indeed, it is remarkable that

none of our patients have developed severe stenosis since this strategy was introduced.

The rationale for microbubble-guided power titration lies in the premise that adequate tissue heating cannot be predicted simply by monitoring impedance and temperature. Instead, the formation of scattered microbub- bles is believed to reflect significant tissue overheating [10, 36–38]. When this occurs, energy deliver has to be interrupted. However, if this phenome- non cannot be controlled, tissue desiccation will result, creating the milieu for coagulum formation and PV stenosis.

Other experienced groups also reported avoidance of PV stenosis just by performing circumferential ablation well outside the PVs [7, 12, 15, 39], usu- ally up to 1 cm away from the PV–LA junction, a strategy that does not nec- essarily aim for PV isolation [39, 40].

Conclusions

Albeit almost an extinct complication in high-volume and experienced cen-

tres, PV stenosis most likely will continue to be a feared complication of AF

ablative procedures, as they are more often performed in community set-

Fig. 4. Example of the use of intracardiac echocardiography (ICE) to guide ostial posi-

tioning of a circular mapping catheter in the right inferior PV (RIPV). The circular

catheter is placed on the atrial side of the PV–LA junction, allowing real-time monitor-

ing and avoiding the need for PV angiography. LA Left atrium, RA right atrium

tings by less-experienced operators. Severe PV stenosis is associated with a variety of respiratory symptoms that frequently mimic more common heart and lung diseases. A high degree of suspicion is necessary to avoid mislead- ing diagnostic procedures and allow proper and prompt management of these patients.

PV dilatation is the treatment of choice for symptomatic patients but is still associated with a frequent need for repeat interventions due to resteno- sis. It remains to be seen whether the use of drug-coated stents will provide long-lasting results. Emphasis should be placed on prevention and imaging modalities that help to accurately delineate the PV–LA junction and guide power titration, both of which appear to provide the best means to avoid PV injury by RF energy.

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