Pulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation

Pulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation E.B. SAAD Introduction Catheter ablation around the pulmonary veins (PVs) has become the treatment 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 unnecessary 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 echocardiography (TEE) instead of an anatomical imaging modality was used to establish the diagnosis. Several factors contribute to an increased risk of developing PV stenosis, such as RF delivery inside the PVs, increasing power and temperature settings, 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

242 E.B. Saad ardiac echocardiography) and increasing operator experience [10, 27]. In centres with a high volume of AF procedures, PV stenosis is becoming a disease 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 developing 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 evidence of lung consolidation, it is not surprising that many patients are initially 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) n (%) 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 Vein Stenosis After Catheter Ablation of Atrial Fibrillation 243 Fig. 1. Correlation between the presence of respiratory symptoms and number of pulmonary veins (PVs) with severe stenosis. While less than 1/3 of patients with single-vessel 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 pneumonia. 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 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

244 E.B. Saad 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 asthmatic 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 syndromes 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

Pulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation 245 (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 avoiding iodine contrast injection [30 33]. Echocardiography has also been used to detect and predict the development 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 echocardiography (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 presence 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 associated 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 classification 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 drugcoated stents, but better results are expected based on their successful use in the coronary arteries and in saphenous vein grafts.

246 E.B. Saad 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 imaging 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 extremely 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 completely 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 electroanatomical 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, selective 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 temperature 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 significantly reduced incidence of severe PV stenosis. Indeed, it is remarkable that

Pulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation 247 Fig. 4. Example of the use of intracardiac echocardiography (ICE) to guide ostial positioning 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 monitoring and avoiding the need for PV angiography. LA Left atrium, RA right atrium 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 microbubbles is believed to reflect significant tissue overheating [10, 36 38]. When this occurs, energy deliver has to be interrupted. However, if this phenomenon 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], usually up to 1 cm away from the PV LA junction, a strategy that does not necessarily aim for PV isolation [39, 40]. Conclusions Albeit almost an extinct complication in high-volume and experienced centres, PV stenosis most likely will continue to be a feared complication of AF ablative procedures, as they are more often performed in community set-

248 E.B. Saad 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 misleading 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 restenosis. 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. References 1. Haïssaguerre M, Jaïs P, Shah DC et al (1998) Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 339:659 666 2. Marrouche NF, Dresing T, Cole C et al (2002) Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies. J Am Coll Cardiol 40:464 474 3. Pappone C, Oreto G, Rosanio S et al (2001) Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation 104:2539 2544 4. Chen SA, Tai CT, Tsai CF et al (2000) Radiofrequency catheter ablation of atrial fibrillation initiated by pulmonary vein ectopic beats. J Cardiovasc Electrophysiol 11:218 227 5. Oral H, Knight BP, Tada H et al (2002) Pulmonary vein isolation for paroxysmal and persistent atrial fibrillation. Circulation 105:1077 1081 6. Gerstenfeld EP, Guerra P, Sparks PB et al (2001) Clinical outcome after radiofrequency catheter ablation of focal atrial fibrillation triggers. J Cardiovasc Electrophysiol 12:900 908 7. Pappone C, Rosanio S, Oreto G et al (2000) Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation. Circulation 102:2619 2628 8. Natale A, Pisano E, Shewchik J et al (2000) First human experience with pulmonary vein isolation using a through-the-balloon circumferential ultrasound ablation system for recurrent atrial fibrillation. Circulation 102:1879 1882 9. Jaïs P, Hocini M, Macle L et al (2002) Distinctive electrophysiological properties of pulmonary veins in patients with atrial fibrillation. Circulation 106:2479 2485 10. Marrouche NF, Martin DO, Wazni O et al (2003) Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications. Circulation 107(21):2710 2716 11. Kanagaratnam L, Tomassoni G, Schweikert R et al (2001) Empirical pulmonary vein isolation in patients with chronic atrial fibrillation using a three-dimensional

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