Clinical research European Heart Journal (2005) 26, 1410–1414 doi:10.1093/eurheartj/ehi279 Pulmonary haemodynamics at rest and during exercise in patients with significant pulmonary vein stenosis after radiofrequency catheter ablation for drug resistant atrial fibrillation ¨rg von Rosenthal, ¨rkle, Jo Thomas Arentz*, Reinhold Weber, Nikolaus Jander, Gerd Bu Thomas Blum, Jochem Stockinger, Laurent Haegeli, Franz Josef Neumann, and Dietrich Kalusche ¨dring 15, 79188 Bad Krozingen, Germany Abteilung Rhythmologie, Herz-Zentrum, Su Received 6 January 2005; revised 7 March 2005; accepted 18 March 2005; online publish-ahead-of-print 26 April 2005 See page 1355 for the editorial comment on this article (doi:10.1093/eurheartj/ehi313) KEYWORDS Aims Iatrogenic pulmonary vein (PV) stenosis after radiofrequency catheter ablation for atrial fibrillation (AF) is a new pathology in cardiology. The effects of PV stenosis on the pulmonary circulation are not yet known. We provide long-term follow-up data in patients with significant PV stenosis including magnetic resonance imaging (MRI) and Swan Ganz (SG) right heart catheterization. Methods and results One hundred and seventeen patients had MRI 12–24 months after the AF ablation procedure. Eleven patients (58+7 years, nine males) with significant stenosis (n ¼ 9) or occlusion of the proximal PV (n ¼ 5) at this follow-up were re-examined using MRI and SG right heart catheterization at rest and during exercise (follow-up time since PV ablation 50 + 15 months). None of these underwent previous PV angioplasty. When compared with prior MRI studies, no significant changes were noted. At rest, no patient had pulmonary hypertension. At 100 W, seven patients had elevated pulmonary artery pressures, three of them probably caused, in part, by left ventricular dysfunction. Conclusion Significant stenosis/occlusions of one or two PV do not create pulmonary hypertension at rest during long-term follow-up. However, seven of the 11 patients develop pulmonary hypertension during exercise. All three patients with stenosis/occlusions of two PV were affected. Introduction Methods The pulmonary veins (PV) had been identified as the dominant initiator or perpetuator of atrial fibrillation (AF).1–3 Current catheter ablation techniques for AF aim to isolate the PV electrically from the left atrium by radiofrequency energy (RF)4–7 or to create circumferential lesions around the PV.8–10 PV stenosis is a known potential complication of these procedures.11–15 The risk of PV stenosis had been reduced by avoiding ablations inside the vessel.14,16 However, in view of the growing number of PV ablation procedures, this complication might become more frequent in the near future. Most of the patients with significant PV stenosis have no or only few symptoms.14 In those patients, little is known about the sequela of PV stenosis/occlusion on pulmonary circulation. The aim of our study was to reveal possible long-term complications and pulmonary haemodynamics in patients with known significant PV stenosis/occlusion after PV-RF ablation. Clinical evaluation, magnetic resonance imaging (MRI), and Swan Ganz (SG) right heart catheterization at rest and during exercise were performed. Study design and patients characteristics * Corresponding author. Tel: þ49 7633 4020; fax: þ49 7633 402538. E-mail address: [email protected] In this prospective study, 117 patients had MRI 12–24 months after the AF ablation procedure. Eleven patients (9.4%) with significant stenosis (70%) or occlusion of the proximal PV at this follow-up were re-examined 27 + 12 months later (median 25, interquartile range 19–36) using MRI and SG right heart catheterization at rest and during exercise. The total follow-up time since the ablation procedure in these 11 patients was 50 + 15 months (median 49, interquartile range 43–60). Written informed consent was obtained from all patients. The ablation procedure was a focal trigger ablation in six patients (1997–98), an ostial isolation procedure without circular mapping catheter in four patients (1999–2000), and ostial isolation using a multipolar basket catheter in one patient (2002). The results of MRI of eight of the 11 patients, 2 years after the ablation procedure, including analysis of parameters predictive of PV stenosis had been published previously.14 Magnetic resonance imaging Imaging was performed using a 1.5 T imager (Magnetom Sonata, Siemens, Erlangen, Germany) and with a body array coil as a receiver. An aliquot of 18–22 mL of Gadiodiamid (Nycomed, Braunschweig, Germany) was injected intravenously at a flow rate & The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: [email protected] Downloaded from by guest on October 28, 2014 Atrial fibrillation; Pulmonary veins; Stenosis; Ablation; Pulmonary hypertension Pulmonary haemodynamics in patients with PV stenosis of 3 mL/s. The acquisition of the images was ECG-gated within a breath hold. Imaging parameters used for the series were as follows: repetition time (second)/echo time (second)/flash 3D, 1.72/0.6/208; matrix, 256 126; field of view, 400 320 mm2; and section thickness, 2 mm. Partitions of 36 images were acquired performing nine measurements repeatedly. Post-processing included maximum intensity projection. Subtraction of the arterial phase was performed. Morphology and diameter of the PV stenosis (Figure 1 ) were assessed by means of a multiplanar reconstruction algorithm as described by Kato et al. 17 MRI images at this followup were compared with those performed 2 years after the ablatsion procedure. 1411 19–36) ago, no significant changes were noted. The minimal mean diameter of the stenosis was 6.0 + 1.6 mm, 2 years after the ablation procedure and 6.2 + 1.6 mm at this follow-up (P ¼ 0.83). The linear correlation analysis excluded an effect of time between first and second follow-up examination on change in minimal stenosis diameter (P ¼ 0.63). No late progression of stenosis to occlusion was observed. SG catheter right heart catheterization Eleven patients (58+7 years, nine males) with known significant PV stenosis were examined, and five of them had organic heart disease (Table 1 ) as reported subsequently: Discussion All medications of the patients were stopped more than five halftimes before haemodynamic testing. SG right heart catheterization was performed from the antecubital vein using a balloon floating catheter. Right heart, pulmonary artery (PA), and pulmonary capillary wedge pressures (PCP) were measured and compared with normal values at rest and during exercise established in our institution.18 Cardiac output was calculated using the Fick’s equation. Exercise was a supine bicycle ergometric starting at 50 W, with 25–50 W increments for every 5 min. Exercise was stopped at maximal exertion, for severe dyspnoea or angina, or if the patients were unable to maintain a cycling frequency .40 r.p.m. Statistical analysis Parametric data are presented as mean + SD; the duration of follow-up time as median and interquartile range. The paired twosided t-test was used to compare continuous variables. A linear regression analysis was performed between the follow-up time and the change of the minimal diameter of stenosis. Statistical significance was defined as P , 0.05. Data were analysed by use of BMDP Statistical software, 1993. Results . . . arterial hypertension (n ¼ 3), one with left ventricular hypertrophy; VVIR pacemaker after AV nodal ablation, chronic AF, and left ventricular dysfunction with an ejection fraction (EF) of 45% (n ¼ 1); coronary heart disease, chronic AF (n ¼ 1); Only three patients had dyspnoea during moderate or vigorous exercise. No patient had pneumonia during follow-up. None of these underwent previous PV angioplasty. Magnetic resonance imaging Eight patients had a single PV stenosis (Figure 1 ) or occlusion, two patients had two stenosis of the upper PV, and one patient had occlusion of both upper PV (Table 1 ), as reported subsequently: . . . . ostial PV occlusion (n ¼ 4); distal PV occlusion (2 cm from the ostium) (n ¼ 1); .70% ostial stenosis (n ¼ 2) (Figure 1 ); .70% distal stenosis of the main vessel (n ¼ 7). When compared with prior MRI studies performed on these patients 27 + 12 months (median 25, interquartile range PV stenosis after RF catheter ablation of AF is a new problem in cardiology. Recurrent and drug resistant pneumonia or dyspnoea due to pulmonary hypertension may be the subacute complication necessitating intervention in the form of angioplasty or stenting.19–21 However, the question remains how to deal with the majority of patients with significant PV stenosis who have no or only discrete symptoms. Saad et al. 16 recommended PV dilation for patients with luminal narrowing of 70%, irrespective of the presence of symptoms.16 The rationale for intervening in these patients was the unknown risk of developing pulmonary hypertension as well as the risk of lesion progression to total occlusion. However, the results of PV angioplasty or stenting reported by Quereshi et al. 21 are disappointing. First, angioplasty was associated with a high restenosis rate of 45%, a problem not completely resolved by stenting. Secondly, major adverse events occurred in 29%, including pulmonary haemorrhage, PV tear requiring immediate surgery, and cerebral embolic event.21 To our knowledge, we report for the first time long-term follow-up data in patients with significant PV stenosis but no or only few clinical symptoms. Our study describes morphologic changes of PV stenosis revealed by MRI and Downloaded from by guest on October 28, 2014 Study patients At rest, no patient had pulmonary arterial hypertension. The maximum work load achieved was 100 + 37 W. Stable PCP position during exercise was recorded in 10 of the 11 patients. At 50 W four patients and at the maximum power level of 100 + 37 W seven patients had elevated mean PA pressures when compared with normal values (Figure 2 ). However, three of these seven patients had elevated PCP (Figure 3 ), which may be due to left ventricular dysfunction [one patient with arterial hypertension and left ventricular hypertrophy, one with reduced left ventricular function (EF of 45%) and VVIR pacemaker after AV nodal ablation, and one with coronary heart disease and chronic AF]. The remaining four patients, three with stenosis/occlusions of two PV, had elevated PA pressures, while PCP were normal. Two patients showed an inadequate increase of cardiac index (CI) during exercise: one patient with VVIR pacemaker after HIS bundle ablation who was unable to increase the heart rate and one patient with stenosis of both upper PV (Figure 4 ). Ten patients had a normal increase of heart rate during exercise. Normally, pulmonary vascular resistance decreases during exercise. In our patient group, the mean value of pulmonary resistance (PVR) remained unchanged during exercise (Figure 5 ). Only the patient with occlusion of both upper PV had an important increase of PVR during exercise. SG right heart catheterization 1412 T. Arentz et al. Downloaded from by guest on October 28, 2014 Figure 1 Angio-MRI of a stenosed left upper PV. (A, B ) Definition of the long axis in coronal and axial orientations after multiplanar reconstruction. The diameter will be determined by the mean of two perpendicular measurements of the cross-sectional view of the minimal diameter (C ). (D ) A 3D reconstruction in anterior–posterior view. haemodynamic evaluation of pulmonary circulation at rest and during exercise. Progression of PV stenosis has been observed during the first 6 months after ablation.15,16,22 We have reported one case of progression of stenosis to occlusion between the 12 and the 15 month follow-up.14 In this current study, no significant changes in degree or morphology of stenosis was noted between the 2 years follow-up, and the current late follow-up was reported 50 + 15 months (median 49, interquartile range 43–60) after the ablation procedure. None of the 11 patients had pulmonary hypertension at rest. However, during exercise seven patients had pulmonary hypertension. Three of these seven patients had simultaneous augmentation of PA and PCP pressures, likely caused by left ventricular dysfunction. All three patients with stenosis/occlusion in two PVs had augmentation of PA pressures during exercise, while PCP remained normal and all these patients had clinical symptoms in form of dyspnoea. The mean pulmonary vascular resistance in our patient group did not decrease during exercise as normally expected. This may indicate that the pulmonary vascular capacity to dilate during exercise was used, in part, at rest to compensate PV stenosis. The potential long-term effects of exercise induced pulmonary hypertension in this patient population are not yet known. On the basis of our data, invasive therapy in form of PV angioplasty or PV stenting might be considered in patients with two or more stenosed PV to prevent pulmonary hypertension during exercise. Whether patients with one stenosed PV and no or only few clinical symptoms need invasive therapy to prevent pulmonary hypertension may be answered by prospective randomized studies. Limitations . The sample size of the study including 11 patients with 14 PV stenosis is small. In addition, there were eight distal luminal narrowing of the main vessel, a finding, that becomes rarer nowadays as RF lesions are applied more ostially. Pulmonary haemodynamics in patients with PV stenosis 1413 Table 1 Demographic and clinical characteristics of the 11 patients with PV stenosis Age (years) Sex 1 2 3 4 5 6 7 8 9 10 11 52 63 39 55 56 56 63 62 63 63 62 M F M M M M M M F M M Average/Total 58 + 7 9 male Heart disease AH, Hypertrophy AF, Coronary heart disease AH AH EF 45%, AF, VVIR Type of ablation PV affected Degree of stenosis (%) Changes in PV diameter (mm) Distal Ostial Ostial Ostial Distal Distal Distal Distal Ostial Distal Ostial LU LU LL RU RU LU LU, RU LU, RU LU, RU RU LU 80 100 70 100 100 90 70,80 80,70 100,100 80 80 20.1 — 20.2 — — 20.1 0/20.5 þ0.1/þ0.1 — þ0.1 þ0.8 6 distal, 5 ostial 14 PVs þ0.2 M, male; F, female; AH, arterial hypertension; LU, left upper PV; RU, right upper; LL, left lower. Downloaded from by guest on October 28, 2014 Figure 2 Mean PA pressures (PAm) of 11 patients with PV stenosis at rest, at 50 W, and at the mean maximum exercise level of 100 + 37 W. Normal values are indicated by the grey line. The dotted lines represent the three patients with elevated PCP during exercise (Figure 3 ). Figure 3 PCP of 10 patients at rest, at 50 W, and at the mean maximum exercise level of 100 + 37 W. Normal values are indicated by the grey line. Figure 4 CI at rest, at 50 W, and at the mean maximum exercise level of 100 + 37 W. The values of the 11 patients and the mean values are shown. Figure 5 Pulmonary resistance at rest, at 50 W, and at the mean maximum exercise level of 100 + 37 W. The values of 10 patients in whom a PCP position was reached and the mean values are shown. 1414 . . No SG right heart catheterization was performed in a control group of AF patients without significant stenosis after PV ablation or after successful dilation of a PV stenosis. Lung scanning to assess the functional consequence of PV stenosis was not performed in this study. Conclusions One or two significant PV stenosis/occlusions do not create pulmonary hypertension at rest during long-term followup. However, seven of the 11 patients develop pulmonary hypertension during exercise. All three patients with stenosis/occlusions of two PV were affected. No progression of PV stenosis was observed .2 years after the ablation procedure. T. Arentz et al. 9. 10. 11. 12. 13. Acknowledgements The authors thank Dr Peter Ott from Sarver Heart Centre, University of Arizona, for his excellent work to revise the manuscript and Professor E. Weitzenblum from the Department of Pneumology, University of Strasbourg, France, to help us to discuss the haemodynamic results. 14. 15. 1. Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrique S, Le Mouroux A, LeMetayer P, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins. N Engl J Med 1998;339:659–666. 2. 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