percutaneous pulmonary vein stenting for the treatment of severe stenosis after pulmonary vein...

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Percutaneous Pulmonary Vein Stenting for the Treatment ofSevere Stenosis After Pulmonary Vein Isolation

THOMAS NEUMANN, M.D.,∗ JOHANNES SPERZEL, M.D.,∗ THORSTEN DILL, M.D.,∗

ALEXANDER KLUGE, M.D.,† ALI ERDOGAN, M.D.,∗ HARALD GREIS, M.D.,∗

JOCHEN HANSEL, M.D.,∗ ALEXANDER BERKOWITSCH, PH.D.,∗ KLAUS KURZIDIM, M.D.,∗

MALTE KUNISS, M.D.,∗ CHRISTIAN W. HAMM, M.D., F.E.S.C., F.A.C.C.,∗

and HEINZ-F. PITSCHNER, M.D., F.E.S.C.∗

From the ∗Department of Cardiology, and †Department of Radiology, Kerckhoff Heart Center, Bad Nauheim, Germany

Percutaneous Pulmonary Vein Stenting. Introduction: Pulmonary vein stenosis (PVS) is a potentialcomplication of pulmonary vein isolation (PVI) using radiofrequency energy. The aim of our study was theevaluation of the severity and long-term outcome of primary angioplasty and angioplasty with pulmonaryvein stenting for PVS.

Methods and Results: Twelve patients with 15 PVS (greater than 70% stenosis) were prospectively eval-uated. Primary dilation of the stenosis was performed because of clinical symptoms (10 patients) and/orthe lung perfusion scans showed a significant perfusion defect (11 patients). Magnetic resonance imagingand lung perfusion scans performed before, directly after, during 3-month, and 6-month follow-up. In thestenting group additional multislice CT-scans directly after, during 6-month, and 12-month follow-up wereperformed.

Within 2 months after primary balloon angioplasty, the PV size parameters were significantly reduced(P < 0.001) with recurrence of PVS in 11 of 15 PVs (73%). Pulmonary vein stenting in 8 patients and 11PVs resulted in no vein stenosis during 12-month follow-up. Normalization of lung perfusion was noted in8 of 12 patients. We observed 2 patients with hemoptysis during PV dilation, as severe complications withpotential life-threatening character.

Conclusion: PVS stenting seems to be superior to balloon angioplasty and effective at least over a periodof 12 months in treating acquired PVS after pulmonary vein isolation. (J Cardiovasc Electrophysiol, Vol. 16,pp. 1180-1188, November 2005)

catheter ablation, atrial fibrillation, MRI, stenosis, stents

Introduction

Radiofrequency catheter ablation (RFCA) of the pul-monary veins (PV) has been shown to be curative in 50–80%of patients with drug refractory atrial fibrillation.1-4 However,certain life-threatening complications can arise after the pro-cedure.5,6 One potential complication is severe pulmonaryvein stenosis (PVS),7-11 defined as a diameter reduction ofthe original PV diameter >70%.12,13

The clinical presentation of patients with severe PVSvaries from asymptomatic to highly symptomatic with re-current pneumonia, hemoptysis, cough, dyspnea, and chestpain.9,12,14,15

Several approaches tried to reduce the occurrence of PVstenosis after pulmonary vein isolation (PVI). One of the mosteffective seems to be the limitation of energy amount duringRFCA application and consistent energy application outsidethe PVs.11,12,16 The use of new energy sources may also beeffective in preventing PV stenosis.17-19

Address for correspondence: Thomas Neumann, M.D., Kerckhoff HeartCenter, Department of Cardiology, Benekestrasse 2-8, 61231 Bad Nauheim,Germany. Fax: +49 6003-828990; E-mail: [email protected]

Manuscript received 3 February 2005; Revised manuscript 18 April 2005;Accepted for publication 20 April 2005.

doi: 10.1111/j.1540-8167.2005.50073.x

However, only a few data are available regarding the treat-ment options for patients with acquired severe PVS afterPVI.9,12,14,15

The aim of our study was to test a stepwise approach,beginning with one or two dilations of the stenosis and ifnecessary stenting of stenosis after unsuccessful dilation.

Methods

Study Population with PVI

In total we performed PVI in 139 patients (female n =53) with a mean follow-up of 26 ± 11 months. The meanage of patients was 53.2 ± 9.9 years. Structural heart diseasewas observed in 69 patients (hypertensive cardiomyopathy,n = 53; slight reduction of left ventricular function, n =16). In total we treated 503 pulmonary veins. We performedmagnetic resonance imagings (MRIs) in all patients each 3months after PVI, independently of clinical symptoms.

Study Population with Angioplasty/Stenting

The subjects of this prospective single-center study con-sisted of 12 patients consecutively enrolled, mean age 59 ±8.5 years (male, n = 7). As a result of systematic follow-up we detected all patients with severe PV stenosis re-gardless of the presence of symptoms. We only performed

Neumann et al. Percutaneous Pulmonary Vein Stenting 1181

angioplasty/stenting in patients with severe stenosis and clin-ical symptoms or reduced perfusion scans. Asymptomatic pa-tients without reduced perfusion scans were excluded fromthe study.

Four patients had mild heart disease, including cardiomy-opathy (n = 1) or CAD (n = 3) with normal ejection fractionand normal atrial dimensions.

Clinical evaluation and qualitative perfusion scan usingMRI20 were performed before each dilation or stenting pro-cedure and every 3 months.

Prior to PV stenting we tried to enlarge the PVS at leastonce using balloon dilation in all patients.

The study was approved by our local institutional reviewcommittee.

EP Study

All patients were studied after placement of two transsep-tal 8F sheaths in the left atrium. One sheath was used tointroduce a multipolar mapping catheter (LassoTM Catheter,10 Polar, Biosense Webster, Diamond Bar, CA, USA) intothe PVs for mapping purposes. The second was used for theablation catheter. The ablation catheter was positioned on theangiographically identified atrial site of the PV ostium. Theaim of the chosen ablation strategies was the electrical dis-connection of the PVs and the left atrium. The procedure wassuccessful when pacing near the PV ostial site could not pen-etrate into the PV or isolated spontaneous activity in the PVwas not conducted to the atrial site. Radiofrequency energywas delivered at the PV ostium with a power output of 15–50W for 40–60 seconds. All ablations were carried out using acooled tip catheter (Chilli�). Applied power during ablationwas regulated to achieve a temperature at the electrode tipbetween 24◦C and 30◦C. Energy delivery was interrupted iftemperature measurement on the catheter tip showed morethan 30◦C.

Percutaneous Pulmonary Vein Dilation and Stenting

Before the procedure patients were orally anticoagulatedto a therapeutic international normalized ratio of 2–3 for atleast 1 month. During procedure intravenous heparin wasadministered to achieve an activated clotting time of 250–300 seconds. A loading dose of aspirin and clopidogrel wasgiven directly after procedure.

A conventional x-ray angiography of the target PV steno-sis was performed by a power injection of 20 mL of a contrastagent (Imeron�, 350 mg iodine/mL, Byk Gulden) before andafter dilation.

Directly before and after PV dilation, we performed in-vasive measurements of pulmonary artery pressure and pul-monary capillary wedge pressure.

A percutaneous transluminal coronary angioplastyguidewire (Emerald Guide, CordisTM) was introducedthrough the narrowed PV as far distally as possible. If thestenosis could not be crossed, a different guidewire (HighTorque Floppy II, GuidantTM) was used. A 2–6 mm ballooncatheter (Powerflex P3, CordisTM) was initially inflated todilate the stenosis using up to 12 atm pressure. After thatwe dilated the remaining stenosis using 10–12 mm balloonsfrom the same company with maximal pressures up to 14atms. The inflation times ranged between 10 and 40 seconds.

For the pulmonary vein stenting we used the same inter-ventional strategy. First, a percutaneous transluminal coro-

nary angioplasty guidewire was introduced through the nar-rowed PV as far distally as possible. A 2–6 mm ballooncatheter was initially inflated to dilate the stenosis using upto 12 atm pressure. In general, lesions were at least graduallydilated with a goal final diameter ≥7 mm.

Secondly, we implanted a 10–12 mm stent (Palmaz Gen-esis Stent-large, CordisTM) into the remaining narrowing in-flating the balloon up to 12 atm for 30–60 seconds.

Clinical Follow-Up of the Patients

A successful outcome was defined as no recurrence of PVnarrowing at the treated area of more than 70% of the orig-inal PV lumina observed before PVI. Late luminal loss wasdefined as the difference between the minimal diameter atthe completion of the interventional procedure and that mea-sured during follow-up. After dilation and stent implantationwe performed MRI with perfusion scans (Fig. 2) and evalu-ation of the PV diameter proximal and distal to the stent andmultislice CT scans (Fig. 1). The use of MRI for evaluationof in-stent thrombosis is not practicable because of magneticabsorption inside the stent. Furthermore, the patients weresystematically asked if clinical symptoms occurred beforeand after the dilation and stenting procedure and at everyfollow-up.

Patients were discharged on combination therapy withclopidogrel (75 mg twice per day) and 100 mg aspirin perday.

MRI Protocol

For MRI, the patient was positioned supine in a 1.5 Teslascanner (SONATA�, Siemens). After defining the correct im-age planes TrueFISP-cine images (Fast Precession SteadyState-sequence; TR 32 msec, TE 1.6 msec, SLT 5 mm) wereobtained for functional and anatomic evaluation in long-axisviews (2- and 4-chamber view) and in selected planes ad-justed to the individual course of the PV.

For three-dimensional (3D)-MRA data acquisition andfurther image processing, a contrast-enhanced nongatedFISP-3D sequence (effective SLT typically ≤2 mm, slabthickness: 80 mm, FOV 280 × 320 mm, matrix 160× 256, pixel size: 1.75 × 1.25 mm) was positioned ina para-coronal orientation and after injection of contrastagent (0.1 mmol/kg body weight, Magnevist�, Gd-DTPA,Schering) two consecutive breath-hold measurements wereobtained.

Multislice CT

For CT the patient was positioned supine in the scan-ner (SENSATION CARDIAC�, Siemens). Contrast agent(IMERON 400, ALTANA Pharma) was administered intra-venously at an injection rate of 4 mL/sec adjusted to the body-weight (1 mL/kg bw). To improve the evaluation of stents inthe PV, contrast and brightness of the images were individu-ally adjusted to achieve the best quality.

Statistical Analysis

Results are presented as median and interquartile ranges(IQRs) for continuous variables and as percentages for cate-gorical data. Wilcoxon were used to compare measurementsof different treatments.

1182 Journal of Cardiovascular Electrophysiology Vol. 16, No. 11, November 2005

Figure 1. Angiograms of a left upper pulmonary vein before (A) and after pulmonary vein stenting (B). Spiral CT scans of the same patient (C–D). Secondarypulmonary vein stenting resulted in reestablishment of the blood flow in this vein. The stent was implanted at the ostial site of the PV. There was no evidenceof in-stent thrombosis 6 months later.

For univariate analysis we used the log rank test. The cut-offs of continuous variables were defined and predictive ac-curacy was estimated using receiver operating characteris-tics (ROC) analysis. The predictive value of parameters wastested using multivariate Cox regressions model. A proba-bility value of <0.05 was considered statistically significant.

Figure 2. MRI perfusion scans; normal lung perfusion (A), slight decrease in pulmonary perfusion within the left lung (B), severe decrease in pulmonaryperfusion within the left lung (C).

Results

Clinical Success Rate of PVI

We found a clinical success rate of 61.9% (n = 86). Thesepatients had neither documented nor subjectively sensedepisodes of atrial fibrillation lasting longer than 30 seconds


TABLE 1

Primary Dilation, Redilation, and Secondary Stenting Data

Results of Quantitative MRI and Multislice CT Dilation Stenting P Value

Luminal diameter (mm)Before procedure 1 (1–2) 3 (2–4) 0.061 day after procedure 8 (7.5–9) 10 (9–10) 0.0053 months after procedure 6 (5–6.5) 10 (9–10) 0.0016 months after procedure 3 (2–4) 9 (8.5–10) 0.003

Stenosis (% of luminal diameter)Before procedure 91.7 (90.2–92.7) 74.2 (67.3–84.9) <0.021 day after procedure 39.7 (27.1–46.9) 28.2 (16.7–38.8) 0.0073 months after procedure 59.9 (51.1–64.7) 27.9 (16.7–39.8) 0.0026 months after procedure 75 (65.9–88.2) 37.1 (18.8–45.3) <0.001

Late luminal loss (mm)6 months after procedure 4.5 (4–5) 1 (0–1) <0.0001

Values are presented as medians and interquartile ranges (IQRs). Stenosis was defined as the percentage decrease of the luminal PV diameter at the time offollow-up in comparison to the original PV diameter before catheter ablation. Late luminal loss was defined as the difference between the minimal diameter1 day after dilation or stenting and the minimal diameter at the 6-month follow-up.

after PVI. Furthermore, 46 patients (33.1%) had a drastic re-duction of AF episodes without taking any antiarrhythmicdrugs (including class-I, class-III agents, and β-blockers).But we also found in 7 patients (5%) no clear clinical successafter PVI.

Incidence of Pulmonary Vein Stenosis

The incidence of severe pulmonary vein stenosis was 4.2%(21 severe PVS of 503 treated PVs). Presented as a percentageof the total number of patients treated the incidence was 8.6%(12 of 139).

Results of Angioplasty

A total of 12 patients with 15 severe PV stenoses wereincluded in the study. Severe PVS were first treated by balloondilation after a median follow-up of 12 months (IQR = 11–16) after PVI. The median diameter at the PV ostium of thevessels was 13 mm (IQR = 12–15), measured by MRI 1 daybefore PVI. We observed a median percentage decrease ofthe luminal diameter before PVI up to 1 day before primaryballoon dilation of 91.7% (IQR = 90.2–92.7). The median PVdiameter 1 day before balloon dilation was 1 mm (IQR = 1–2). The final goal diameter at primary dilation was achieved in93.3 % (14 of 15 PVs). One day after primary balloon dilationwe measured a median diameter of 8 mm (IQR = 7.5–9) at thetarget dilated segment, documenting a percentage decreaseof the luminal diameter before PVI up to 1 day after primaryballoon dilation of 39.7% (IQR = 27.1–46.9).

Two months after primary balloon dilation the PV diam-eters were already significantly reduced in comparison to 1day after dilation (P < 0.001). After a median follow-up of7 months (IQR = 6–7), a severe restenosis after at least oneballoon dilation was observed in 11 of 15 of the treated PVs(8/12 patients). These patients had a median PV diameter of3 mm prior to stenting (IQR = 2–4).

In a total of 6 PVs (4 patients), repeated balloon dilationswere performed during follow-up. Subsequently, PV stentingwas performed in all of these patients because of recurrentstenosis despite multiple primary balloon dilations. None ofthe patients without PV stenting had more than one dilation.

Results of Stenting

The luminal diameter before dilation or stenting was notsignificantly different. However, we measured significant dif-ferences between the luminal diameters 1 day, 3, and 6 monthsafter dilation versus stenting (Table 1). Furthermore, we ob-served a significant difference in late luminal loss duringfollow-up between dilation and stenting (P < 0.0001).

The percentage decrease of the luminal diameter beforePVI up to 1 day before stenting was 74.2 (IQR = 67.3–84.9).The remaining four PVs (4 patients) had no severe recurrentstenosis or patients refused a further intervention due to alack of clinical symptoms.

We performed pulmonary vein stenting in 11 PVs (8 pa-tients). After median follow-up of 12 months (IQR = 10.5–12.5) we did not observe any severe restenosis in the treatedPV (Fig. 3). We did not observe a relevant reduction of theluminal diameter at the distal edge of the stent. Furthermore,performance of multislice CT scans excluded acute and sub-acute in-stent thrombosis or restenosis inside the stent.

The size of the dilation balloons used was 2–12 mm. Thediameter of the implanted stents varied from 8 to 10 mm.In 1 patient we used a 5 mm stent to manage a distal PVdissection (see “Adverse Events”). The length of the balloonswas always 20 mm. Concerning the size and length of thestents used, we observed no differences in the outcome.

Clinical Data, Results of Perfusion Scans, andHemodynamic Data After Angioplasty/Stenting

The results of the perfusion scans and the clinical symp-toms of the patients in each treated PV are given in detail inTable 2 (A–D). The most frequent symptoms in patients withPV stenosis was dyspnea. We observed no patients with theNew York Heart Association (NYHA) grade IV. Neverthe-less, all of our patients with dyspnea had a NYHA grade ≥II. We also observed completely asymptomatic patients withsevere stenosis and severe loss of perfusion. After primarydilation we observed a short-term improvement in clinicalsymptoms and perfusion scans, which typically worsenedduring the follow-up of 6 months. After stenting there wasan improvement in clinical symptoms and results of perfu-sion scans, which then remained stable. During follow-up,


Figure 3. Time course of each pulmonaryvein diameter evaluated by MRI every 3months. After pulmonary vein isolation (A),after angioplasty (B), and after pulmonaryvein stenting (C). PV number 3,4,7 at (B) hada second angioplasty between day 90 and 180.PV number 5,8,9 at (B) had a second angio-plasty between day 1 and 90.

we observed a complete restoration of the lung perfusion in>50% of the cases.

We noticed a significant difference in pulmonary capil-lary wedge pressure (PCP) before and after intervention atthe affected lung side, at the contralateral side, and at theaffected lung segment. We also observed a significant dif-ference of PCP between stenosed segment and not affectedlung segments (Table 3B). Mean pulmonary artery pressuresdecreased after intervention at both lung sides (Table 3A).

Adverse Events

Three adverse events occurred during the procedures. Onepatient had hemoptysis immediately after dilation of the leftupper PV. The hemoptysis stopped 10 minutes after therapeu-tic administration of protamin intravenous (i.v.). One patienthad a slight dissection of the left upper PV during dilationdirectly before stenting with hemoptysis. This adverse eventwas resolved by additionally stenting the vein distal to theoriginal stenosis at the site of dissection. One patient had anallergic reaction to the contrast agent used.

Discussion

In comparison with previous studies of pulmonary veindilation or stenting9,11,12,14,15 our prospective trial enrolledpatients with severe PV stenosis with either clinical symp-toms or a decrease of MRI lung perfusion, which we treatedin a stepwise approach. After dilation alone, we observed agood short-term improvement of clinical symptoms and per-fusion scans, which subsequently worsened during follow-upof 6 months.

In contrast to high recurrence rate of PV stenosis afterballoon dilation of severe stenosis, we found no restenosisafter pulmonary vein stenting after a median follow-up of 12months. Therefore, we conclude that pulmonary vein stentingmight be an alternative to surgery in treating severe PVS afterPVI. The results are based on acute and long-term follow-up.

Our results are similar to others,12,21 in particular compa-rable to the study of Qureshi and coworkers.14 In contrast totheir study, we performed our study in a prospective manner

and performed MRIs every 3 months already at the beginning.Nevertheless, there exist some comparable results betweenthe two studies, which should be noted. We found a resteno-sis rate after primary angioplasty alone of 66.7%, Qureshi etal. found 47%. The most important difference compared tothe study of Qureshi et al. and a recent published study ofPacker et al.22 is the absence of in-stent restenosis in our pa-tients. One explanation for the high in-stent restenosis rate inthe latter working group is the use of partial very small stents.As already shown in the study of Kluge et al.20 6 mm is anabsolutely critical diameter for low PV flow and correlatedwith perfusion defects. Qureshi et al. used in nine treated PVsstents with a diameter <10 mm (minimal 4 mm Bx velocitystent, table 2 of their manuscript). Packer et al. described 14stent procedures in their series. Of the 14 stent procedures,8 veins were stented at the time of the original procedure.Four of these latter veins showed in-stent restenosis. In con-trast, we used a stepwise approach. All patients were initiallytreated by dilation alone and only at the time of restenosiswe implanted stents. At the time of stenting we predilatedall stenosis with balloon dilation to the planed diameter ofthe stent, which we proposed to implant. We did not performa primary stent implantation as a first-line therapy for thetreatment for PV stenosis.

We observed minor procedure-related complications and2 patients with hemoptysis as severe complications. Qureshiand coworkers also reported about four serious adverse eventsof 19 treated patients (hemoptysis requiring ventilation, pul-monary hemorrhage, emergent surgical repair of pulmonaryvein, and an embolic cerebral event). Three of their four ad-verse events occurred during their early experience.

Due to observations of restenosis on the edges of stents incoronary arteries,23 we attached importance in our study tothe distal edge of the stent region but found no restenosis atthis “critical region” of the stent.

We observed a wide range of clinical symptoms, predomi-nantly dyspnea, as well as asymptomatic patients with severePVS and severe perfusion defects. The rationale for balloondilation/stenting of these patients lies in the unknown like-lihood of developing pulmonary hypertension as well as therisk of lesion progression.9,12,14 Nevertheless, the results of


TABLE 2

Clinical Symptoms and Perfusion Scans After Dilation (A, B) and After Stenting (C, D)

A PV Stenosis Symptoms Before Lung Perfusion Mismatch Symptoms 1 Day Lung Perfusion MismatchPatient Localization Dilation 1 Day Before Dilation After Dilation 1 Day After Dilation

1 LUPV Dyspnea, hemoptysis Severe decrease of perfusion Asymptomatic Slight decrease of perfusion1 LLPV Dyspnea, hemoptysis Severe decrease of perfusion Asymptomatic Slight decrease of perfusion2 LUPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion2 LLPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion3 LUPV Dyspnea, cough Severe decrease of perfusion Asymptomatic Slight decrease of perfusion4 LUPV Dyspnea, wheezing Severe decrease of perfusion Asymptomatic Slight decrease of perfusion5 LLPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion6 LUPV Dyspnea Normal perfusion Dyspnea Normal perfusion6 LLPV Dyspnea Normal perfusion Dyspnea Normal perfusion7 LLPV Wheezing Severe decrease of perfusion Asymptomatic Slight decrease of perfusion8 LLPV Asymptomatic Severe decrease of perfusion Asymptomatic Severe decrease of perfusion9 SUPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion10 LLPV Dyspnea Slight decrease of perfusion Asymptomatic Slight decrease of perfusion11 SLPV Dyspnea, cough, pneumonia, hemoptysis Severe decrease of perfusion Cough, pleuritic chest pain Slight decrease of perfusion12 LLPV Asymtomatic Slight decrease of perfusion Asymptomatic Slight decrease of perfusion

B PV Stenosis Symptoms After Lung Perfusion Mismatch Symptoms After Lung Perfusion MismatchPatient Localization 3 Months 3 Months After Dilation 6 Months 6 Months After Dilation

1 LUPV Asymptomatic Slight decrease of perfusion Dyspnea Severe decrease of perfusion1 LLPV Asymptomatic Normal perfusion Dyspnea Severe decrease of perfusion2 LUPV Dyspnea Slight decrease of perfusion Dyspnea Severe decrease of perfusion2 LLPV Dyspnea Slight decrease of perfusion Dyspnea Slight decrease of perfusion3 LUPV Asymptomatic Slight decrease of perfusion Asymptomatic Severe decrease of perfusion4 LUPV Dyspnea Slight decrease of perfusion Dyspnea, wheezing Severe decrease of perfusion5 LLPV Dyspnea Slight decrease of perfusion Dyspnea Slight decrease of perfusion6 LUPV Dyspnea Slight decrease of perfusion Dyspnea Severe decrease of perfusion6 LLPV Dyspnea Slight decrease of perfusion Dyspnea Severe decrease of perfusion7 LLPV Asymptomatic Slight decrease of perfusion Dyspnea Slight decrease of perfusion8 LLPV Dyspnea Servere decrease of perfusion Dyspnea Severe decrease of perfusion9 SUPV Asymptomatic Slight decrease of perfusion Asymptomatic Slight decrease of perfusion10 LLPV Asymptomatic Slight decrease of perfusion Dyspnea Severe decrease of perfusion11 SLPV Asymptomatic Slight decrease of perfusion Asymptomatic Slight decrease of perfusion12 LLPV Asymptomatic Slight decrease of perfusion Asymptomatic Slight decrease of perfusion

C PV Stenosis Symptoms Before Lung Perfusion Mismatch Symptoms 1 Day Lung Perfusion MismatchPatient Localization Stenting 1 Day Before Stenting After Stenting 1 Day After Stenting

1 LUPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion1 LLPV Dyspnea Severe decrease of perfusion Asymptomatic Normal perfusion2 LUPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion2 LLPV Dyspnea Slight decrease of perfusion Asymptomatic Normal perfusion3 LUPV Asymptomatic Severe decrease of perfusion Asymptomatic Normal perfusion4 LUPV Dyspnea; wheezing Severe decrease of perfusion Asymptomatic Slight decrease of perfusion5 LLPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion6 LUPV Dyspnea Severe decrease of perfusion Dyspnea Slight decrease of perfusion6 LLPV Dyspnea Severe decrease of perfusion Dyspnea Slight decrease of perfusion7 LLPV Cough; wheezing Severe decrease of perfusion Asymptomatic Slight decrease of perfusion8 LLPV Dyspnea Severe decrease of perfusion Asymptomatic Slight decrease of perfusion

Symptoms Lung Perfusion Symptoms Lung Perfusion Symptoms Lung PerfusionD After Mismatch 3 Months After Mismatch 6 Months After Mismatch 12 MonthsPatient 3 Months after Stenting 6 Months After Stenting 12 Months After Sterting

1 Asymptomatic Slight Asymptomatic Slight Asymptomatic Slight1 Asymptomatic No Asymptomatic No Asymptomatic No2 Asymptomatic Slight Asymptomatic Slight Asymptomatic Slight2 Asymptomatic No Asymptomatic No Asymptomatic No3 Asymptomatic No Asymptomatic No Asymptomatic No4 Asymptomatic Slight Asymptomatic Slight Asymptomatic Slight5 Asymptomatic Slight Asymptomatic No Asymptomatic No6 Asymptomatic Slight Asymptomatic Slight Asymptomatic Slight6 Dyspnea Slight Dyspnea Slight Asymptomatic No7 Asymptomatic Slight Asymptomatic No Asymptomatic No8 Asymptomatic No Asymptomatic No Asymptomatic No

(A–D): Individual symptoms and MRI perfusion scans of patients undergoing primary pulmonary vein dilation are listed (A, B). Symptoms and results ofMRI perfusion scans are described qualitatively. The perfusion defect refers to the lung segment that is drained by the treated pulmonary vein. Symptomsand perfusion scans of patients undergoing pulmonary vein stenting (C, D) are also listed.


TABLE 3

Hemodynamic Data, Mean Pulmonary Artery Pressure [mmHg] of Affected, Contralateral Lung Sides Before and After Intervention (A), Mean PulmonaryCapillary Wedge Pressures [mmHg] of the Affected, Contralateral, and Affected Lung Segment Before and After Intervention (B)

mPAP Affected Side mPAP Affected Side mPAP Contralateral Side mPAP ContralateralA Before Intervention After Intervention Before Intervention After InterventionPatient No. Treated PV [mmHg] [mmHg] [mmHg] [mmHg]

1 LUPV 22 17 18 172 LLPV 22 17 18 171 LUPV∗ 18 15 16 142 LLPV∗ 18 15 16 143 LUPV 22 12 25 194 LLPV 22 12 25 193 LUPV∗ 15 9 18 74 LLPV∗ 15 9 18 75 LUPV 11 11 11 125 LUPV∗ 15 16 16 1.a.6 LUPV 16 13 14 146 LUPV∗ 12 13 15 147 LLPV 22 17 21 98 LUPV 23 14 22 1.a.9 LLPV 23 13 22 1.a.8 LUPV∗ 29 16 32 1.a.9 LLPV∗ 29 16 32 1.a.8 LUPV† 18 15 15 129 LLPV† 18 15 15 1210 LLPV 27 24 26 2511 LLPV 18 14 18 13Median (IQR 25/75) 18 (16/22) 15 (13/16) 18 (16/22) 14 (12/17)

P < 0.001 P < 0.001

ns

ns

mPCP Affected mPCP Affected mPCP mPCP mPCP mPCP AffectedSide Side Contralateral Contralateral Affected Segment

Before After Side Before Side After Segment Before After theB Intervention Intervention Intervention Intervention Intervention InterventionPatient No. Treated PV [mm Hg] [mm Hg] [mm Hg] [mm Hg] [mm Hg] [mm Hg]

1 LUPV 22 17 11 11 25 112 LLPV 22 17 11 11 26 141 LUPV∗ 12 9 9 9 21 132 LLPV∗ 12 9 9 9 17 103 LUPV 15 9 13 11 19 104 LLPV 15 9 13 11 21 123 LUPV∗ 8 9 9 7 18 114 LLPV∗ 8 9 9 7 17 115 LUPV 7 7 8 9 13 35 LUPV∗ 9 8 8 8 15 96 LUPV 12 8 5 6 12 86 LUPV∗ 9 6 8 7 13 97 LLPV 21 16 10 10 20 178 LUPV 18 11 13 3 19 109 LLPV 18 11 13 5 23 98 LUPV∗ 27 13 21 16 29 159 LLPV∗ 27 13 21 16 22 178 LUPV† 16 8 7 7 8 69 LLPV† 16 8 7 6 18 910 LLPV 22 16 13 13 15 1111 LLPV 8 5 8 7 19 10Median (IQR 25/75) 15 (9/21) 9 (8/13) 9 (8/13) 9 (7/11) 19 (15/2 1) 10 (9/12)

P < 0.001 P = 0.002 P < 0.001

P < 0.001 P < 0.001

P = 0.009

ns

(A, B): Hemodynamic data. Mean pulmonary artery pressures (mPAP) of lung sides with PV stenosis, mPAP of contralateral lung side before and after PVdilation/stenting (A). Mean pulmonary capillary wedge pressures (mPCP) of the affected and contralateral lung sides (B); additionally, values of mPCP ofthe affected lung segments before and after intervention. Value used for pressure measurement is mmHg.∗, † values of a further dilation procedure or before/after stenting.


our study demonstrate an improvement in clinical symptomsand results of perfusion scans, which remained stable over thefollow-up. Over this period, we observed a complete restora-tion of the lung perfusion in >50% of the cases.

The published Cleveland Clinic experience12 describedthat patients with pulmonary vein stenosis do not have symp-toms unless more than one pulmonary vein has a severe steno-sis. This was not the case in our patients. We have no expla-nation for these different results.

To the best of our knowledge, there exist no publishedsystematic hemodynamic data of acquired pulmonary veinstenosis. In our study, we could show that the effects of in-tervention on hemodynamic parameters were pronounced onmean pulmonary capillary wedge pressures (mPCP) in theaffected segments (Table 3b). This fact clearly demonstratesthat changes were related to the postcapillary pulmonary veinsegment with stenosis. We observed that the median of PVpressures was 15 mmHg (above the 12 mmHg in a physio-logical range) and decreased to normal on the affected sidein total. Two explanations seems to be suitable for this ob-servation. Measurements were taken by technical limitationof catheter approach in a pulmonary artery segment not pro-jected at the anatomical segment of the stenosed PV, but injunction with the segment. The second explanation may bethe assumption that a reflectory spastic component is causal,which involves more vessels than given at the stenotic seg-ment. The pathophysiologic base for the second assumptionis unclear. The medians of mPAP observed in our study, wereat the upper end of the normal ranges on the affected and con-tralateral sides. Nevertheless, the changes after interventionseems to support the second assumption.

Clinical Implications

The study has some important clinical implications forpatients undergoing PV isolation. First, our study underlinesthe importance of repeated clinical and imaging investiga-tions after PVI in all patients. The time period may need tobe extended to more than 1 year because the time course forthe development of severe stenosis is not restricted to thefirst months if any significant narrowing has been noted ear-lier after PVI. The clinical symptoms of patients with severestenosis ranged from asymptomatic to highly symptomaticand are not always coincident with changes in the functionalstate as indexed by lung perfusion scanning. Additional in-vestigation with lung perfusion appears to facilitate the deci-sion for potential angioplasty/stenting. The indication for PVintervention should be a combination of clinical symptoms,the degree of the PV narrowing, and the result of the lungperfusion scan.

Pulmonary vein stenting of severe stenosis after balloonangioplasty appears to be superior to angioplasty alone.

Study Limitations

The limitations of the study are its small sample size andlack of randomization in the treatment of vein stenosis strate-gies. The clinical follow-up for patients undergoing stentplacement is only 1 year and long-term follow-up over yearswill be required to confirm the ultimate clinical utility of PVstenting.

Acknowledgments: We thank Mary K. Steen-Miller M.D., Justus LiebigUniversity of Giessen as a native speaker, Peter Reinisch, Kerckhoff Heart

Center for technical support, and Hassan Bahavar, Kerckhoff Heart Centerfor their assistance.

References

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percutaneous pulmonary vein stenting for the treatment of severe stenosis after pulmonary vein...

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