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Balloon Angioplasty for Pulmonary Artery Stenosis After Complete Unifocalization and Repair of Tetralogy of Fallot With Major Aortopulmonary Collaterals
Abstract: Objectives. The objective of this study was to assess procedural outcomes of balloon pulmonary artery (PA) angioplasty procedures after complete repair of tetralogy of Fallot with major aortopulmonary collateral arteries (TOF/MAPCAs). Background. Our approach to patients with TOF/MAPCAs emphasizes early complete unifocalization and repair. Major PA reinterventions are relatively uncommon. Balloon PA angioplasty is often used, but the effectiveness of balloon PA angioplasty in this population is unknown. Methods. The study cohort comprised patients who underwent complete unifocalization and repair of TOF/MAPCAs at our center between 2002-2018 and underwent balloon PA angioplasty after repair. To assess immediate procedural outcomes, pre- and postintervention PA measurements were compared. Results. We reviewed 134 vessels that were dilated a median of 1.1 years after repair in 60 patients (median 2 PA branches per patient). Treated vessels included 15 central, 64 lobar, and 55 segmental branches. The median PA diameter at the level of stenosis increased from 1.9 mm to 3.3 mm (P<.001), and the median diameter increase was 50%. All but 6 treated vessels were enlarged. The stenosis-distal diameter ratio increased from a median of 64% to 89% (P<.001). The median central PA to aortic systolic pressure ratio was 47% before and 39% after intervention (P<.001). Conclusions. Balloon PA angioplasty was acutely effective at treating most stenoses of reconstructed PA branches after repair of TOF/MAPCAs. Simple angioplasty can be a useful tool in treating isolated or modest stenoses after unifocalization/PA reconstruction surgery using our approach.
J INVASIVE CARDIOL 2021;33(5):E378-E386. Epub 2021 April 29.
Key words: balloon dilation, catheterization, congenital heart disease
Patients with tetralogy of Fallot and major aortopulmonary collateral arteries (TOF/MAPCAs) are managed at our center with a programmatic approach that emphasizes early repair, usually in a single stage, with complete unifocalization and augmentation of the pulmonary circulation to the segmental level if necessary.1-3 As detailed in prior reports, this approach results in complete repair with low right ventricular (RV) pressure in the majority of patients.1 We follow patients closely with lung perfusion scintigraphy during the first year after repair,4 and recommend routine follow-up catheterization approximately 1 year after repair. These studies identify stenosis of the unifocalized pulmonary arteries (PAs) in some patients, ranging from mild and isolated to more extensive. In a previous study, we reported 43% freedom from any reintervention at 10 years after repair and 56% freedom from catheter-based reintervention.5 Patients with higher early post-repair RV to aortic pressure ratio, more complex distal PA anatomy, or a larger number of unifocalized MAPCAs had shorter freedom from reintervention. Most reinterventions were isolated in scope, consisting of balloon angioplasty of a single or few branches. In that study, detailed outcomes of the reinterventions, some of which were performed at our center and some at outside referring institutions, were not evaluated.
Studies have found balloon PA angioplasty to be effective for enlarging congenital or postoperative PA branch stenoses in patients with congenital heart disease.6-11 However, little is known about the effectiveness of angioplasty for recurrent stenosis of reconstructed PAs in patients with TOF/MAPCAs.12 Anecdotally, some interventional cardiologists believe that angioplasty is not an effective treatment for stenosis of native MAPCAs before or after unifocalization, although that impression may be derived from experience with methods of unifocalization that differ from our approach, and it may not apply to unifocalization and PA reconstruction as performed at our center.
At some centers, patients with TOF/MAPCAs are treated with a staged approach,13-26 which may favor transcatheter PA rehabilitation over surgical reconstruction. While that is not a central tenet of our approach to managing these patients, post-repair angioplasty can be an important tool for treating isolated or modest stenoses. In order to evaluate the utility of this approach, to apply interventional techniques appropriately in this context, and to counsel families most accurately, it is important to understand the technical, hemodynamic, and anatomic results of balloon angioplasty of unifocalized and reconstructed PAs. Therefore, we undertook the present study to assess acute procedural outcomes of balloon PA angioplasty procedures performed at our center after complete repair of TOF/MAPCAs.
Methods
Patients. We reviewed a subset of patients who underwent complete unifocalization and repair of TOF/MAPCAs at our center between 2002-2018 and had cardiac catheterization with balloon PA angioplasty after repair and adequate images available for review. Patients who underwent interventions at other centers were not included due to inconsistent availability of angiograms and catheterization reports. The study did not include TOF/MAPCA patients with PA stenoses that were not dilated. Patient medical records and angiograms were reviewed. Patients who had balloon angioplasty after palliative operations27,28 but before complete repair were also excluded because these patients typically underwent subsequent surgical PA revision. Available data on RV, PA, and systemic arterial blood pressures, balloon characteristics, and use of cutting balloons or stents were recorded.
Angiographic evaluation. Available angiography was reviewed, and vessel diameters were measured in the best imaging plane at the narrowest areas of stenosis and the normal vascular segment distal to the stenosis by 2 reviewers. In a few cases, measurements were calibrated by reference to catheters of known size. Stenosis to distal vessel ratio and pre to post angioplasty diameter ratios were calculated and expressed as percentages. The pre to post angioplasty ratio of the stenosis to distal vessel diameter ratio was also calculated. Due to the variety of surgical techniques and extent of surgical intervention during PA reconstruction, it is essentially impossible to determine angiographically whether stenoses are related to suture lines.
Balloon PA angioplasty. Interventions were performed at the discretion of the attending cardiologist. General criteria for intervening included a discrete angiographic stenosis (as opposed to diffuse hypoplasia), typically with a pressure gradient across the stenotic vessel. Elevated central PA pressure was a consideration in decision making, but was not necessarily present. Technical considerations, such as balloon type, size, inflation pressure, number of inflations, etc, were at the discretion of the interventional cardiologist. Because balloon inflation pressure was documented selectively, there was insufficient data for robust analysis. In general, our preference is to avoid PA stents in this population, particularly in the peripheral branches. However, in some circumstances, the operator may elect to use a cutting balloon for resistant stenosis or implant a stent for unsuccessful angioplasty or an obstructive flap. Follow-up imaging after angioplasty, including further catheterization, depended on the clinical circumstances.
Data analysis. Patient-level and vessel-level data are presented as frequency (%) or median (25th-75th percentiles). To assess immediate procedural outcomes, pre and post balloon angioplasty measurements were compared using paired t-test. The Kruskal-Wallis test was used to compare continuous data between vessel levels. Inter-rater reliability was assessed by comparing measurements performed independently by 2 authors (ZBL, GTA) at and distal to the stenosis, both before and after angioplasty, for 15 randomly selected vessels (total 60 measurements) and expressed in terms of the Pearson correlation coefficient. SPSS, version 25 (IBM) was used for statistical analysis.
Results
Patient-level data. We reviewed angiograms for 60 patients with TOF/MAPCAs who underwent balloon PA angioplasty (between March 2003 and August 2019) after complete repair performed between 2002-2018. Patient characteristics are summarized in Table 1. Native anatomy for most patients included centrally confluent PAs (n = 50; 86%), with a median of 4 MAPCAs (3-6 MAPCAs). The median age at repair was 0.5 years (0.3-1.1 years) and the median duration from repair to catheterization was 1.1 years (0.7-2.3 years). Nine patients had undergone previous catheter interventions, and 11 (20%) had other interventions performed during the same catheterization, most often conduit dilation and/or stenting (n = 6) or transcatheter pulmonary valve replacement (n = 3). The median number of vessels treated with balloon angioplasty was 2 (1-3), with 35 patients (58%) having unilateral intervention and 25 patients (42%) having bilateral intervention.
The median systolic RV and central PA pressures before intervention were 51 mm Hg (41-65 mm Hg) and 40 mm Hg (30-55 mm Hg), respectively, and the median ratio of central PA to aortic systolic pressures was 47% (37%-65%). Compared with immediate post-repair measurements (Table 1), the PA pressure and PA to aortic pressure ratios were significantly higher (P<.01 and P<.001, respectively). In patients with pressures measured and documented after all interventions, the median final RV and PA pressures were 42 mm Hg (36-50 mm Hg) (n = 34; P<.001) and 37 mm Hg (30-44 mm Hg) (n = 38; P<.01), respectively, and the median final central PA to aortic ratio was 39% (32%-50%) (P<.001). The postintervention central PA pressure and PA to aortic pressure ratios were not significantly different than in the early post-repair period (P=.13 and P=.57, respectively). Pre- and postangioplasty lung perfusion scans were not always available, but in the subset of 48 patients with postangioplasty perfusion scans, flow laterality was typically balanced, with a median of 56% (50%-60%) to the right lung and 44% (40%-50%) to the left lung. Four patients had “unbalanced” left-right flow, as defined previously, with >70% flow to the right lung.
Vessel-level data. Vessel-level outcomes are summarized in Table 2. Of the 134 PA branches treated, 81 (60%) were to the right lung and 53 (40%) were to the left lung. The branch level was typically lobar (n = 64; 48%) or segmental (n = 55; 41%), with only 15 central/proximal vessels dilated. Simple balloon angioplasty was performed in most cases, with multiple balloon sizes used in 63 vessels. Six vessels were treated with a cutting balloon, and a stent was placed in 5 (central in 2 vessels, lobar in 2 vessels, and segmental in 1 vessel). Examples of stenoses and results of balloon angioplasty are shown in Figures 1-4.
As shown in Figure 5 and Table 2, the median PA diameter at the level of stenosis increased from 1.9 mm to 3.3 mm (P<.001). All but 6 vessels were enlarged, with a 1.0 mm (0.7-1.5 mm) median increase in narrowest diameter. In 39 patients (65%), the stenosis diameter increased by 50% or more in at least 1 vessel. The stenosis to distal diameter ratio increased from a median of 64% to 89% (P<.001). Preintervention stenosis diameter (P<.01), final stenosis diameter (P<.01), and absolute diameter change (P=.04) were all larger for proximal stenoses than lobar or segmental stenoses, which were similar. The first balloon to stenosis diameter ratio was smaller for proximal than lobar or segmental stenoses (P=.03) (Figures 1 and 2). Relative change in stenosis diameter did not differ according to vessel level. There was good inter-relater reliability, with a Pearson correlation coefficient of 0.986.
Hemoptysis was reported after intervention in 3 patients, none of whom had discrete PA tears or ruptures that required closure with catheter devices or surgical intervention. There were no other major complications after catheterization and PA angioplasty in this cohort.
Discussion
The focus of this study was a selected patient population of patients who underwent balloon angioplasty for branch PA stenosis after complete repair of TOF/MAPCAs. Most of the patients in this series had been referred for catheterization for a standard 1-year post-repair assessment, and the threshold for intervention in such patients was low, even in the absence of elevated PA pressure, but a subset of patients had undergone prior PA interventions and were catheterized as follow-up in that context. In a smaller group, the primary indication for catheterization was treatment of RV-PA conduit dysfunction, and PA angioplasty was performed incidentally. The median systolic RV and central PA pressures in this patient population were 51 mm Hg and 40 mm Hg, higher than in the early post-repair period, and higher than the previously reported median RV pressure of 32 mm Hg for all patients after complete repair.1 That is not surprising, given that the study population comprised the subset of patients with PA stenoses that were determined to merit catheter intervention. Even so, a central PA systolic pressure of 40 mm Hg prior to intervention is reasonable in this complex population and is comparable to previously reported findings in repaired TOF/MAPCAs patients undergoing catheterization at our center prior to conduit replacement.29 From a clinical standpoint, 43% of patients underwent subsequent catheter interventions, which may indicate the bias of this subset of patients with more severe disease, and does not necessarily reflect broader outcomes after TOF/MAPCAs repair at our center.1,5
In this cohort, patients had varying severity, extent, and anatomic distribution of PA stenosis based on angiographic appearance and reported pressure gradients. In general, even patients with a low RV pressure often underwent PA dilation if the vessel seemed stenotic by angiography or if there was a significant pressure gradient. PA branches of all segmental levels were treated with balloon angioplasty, and only a few vessels with important stenoses that were not adequately treated with angioplasty were stented or referred for surgery. In general, balloon angioplasty was successful at enlarging stenotic branch PAs at all levels, with increases in size similar to previously reported series. Pressure gradients were not reliably recorded and can be difficult to interpret in patients undergoing multiple interventions or with multilevel stenosis. Moreover, intervention was often performed in patients with low PA pressures, and was not driven by gradient measurements per se. Thus, while it is difficult to say that there was a clear clinical benefit to the interventions performed in this series, the anatomic stenoses were usually improved, and there were no major complications.
Some centers use a staged approach to treat patients with TOF/MAPCAs, during which an RV-to-PA connection is created to provide pulmonary blood flow and allow access for transcatheter interventions, and serial angioplasty procedures are undertaken to rehabilitate the pulmonary circulation.12-26,30 However, balloon angioplasty after unifocalization and PA reconstruction using the surgical methods employed at our center is a different procedure, and prior to this study, little was known about the utility to transcatheter interventions for post-repair PA stenosis. Although surgical techniques are extensive and variable in these patients, it was not possible to identify suture lines. Due to the extensive nature of the repair, it is likely that most of the treated stenoses involved anastomoses and suture lines. The anatomic effectiveness of balloon angioplasty of unifocalized MAPCAs with areas of suture lines is not well understood, but based on this preliminary study, it appears that it can be a technically successful intervention.
Most of the stenoses treated in this cohort were at the lobar or segmental PA level, reflecting the prevalence of distal abnormalities in this population and the fact that most of the complex reconstruction took place beyond the first PA branch point. During repair, the central PAs are typically amply reconstructed with pulmonary homograft patch, and proximal PA reinterventions were accordingly uncommon. In some circumstances, the geometry of unifocalized MAPCAs can make effective transcatheter intervention a challenge. Although this study did not ascertain stenotic branches that were not dilated, either based on operator discretion or because of inability to perform angioplasty for technical reasons, our anecdotal experience is that the geometry of peripheral PAs reconstructed at our center was usually amenable to selective access and intervention and was rarely a limiting factor in the ability to treat a stenosis in the catheterization lab.
Study limitations. There were a number of limitations to this study in addition to those noted above. Clinical records were reviewed retrospectively, and data were not always complete for each patient. Distal pressure measurements were inconsistently reported, and therefore were not included in the analysis. Hemodynamics may have changed during studies with each dilation and with additional interventions such as transcatheter pulmonary valve replacement. Angiographic measurements were made on available studies by 2 reviewers and were not obtained in real time by the operator during the catheterization. In a few cases, measurements were calibrated by reference to catheters of known size, but these vessels were usually small-to-medium sized. We did not always have data on balloon inflation pressure to determine whether a high- or low-pressure dilation was performed. There was a limited number of images before and after angioplasty of each vessel, and measurement accuracy may have been impacted by suboptimal images in some cases. In several instances, vessels were excluded from the study due to absence of postintervention images.
Conclusion
In this study, we found balloon angioplasty to be acutely effective at enlarging most stenoses of reconstructed PA branches after unifocalization and repair of TOF/MAPCAs at our center. These findings suggest that simple balloon angioplasty can be a useful tool in treating isolated or modest stenoses after unifocalization/PA reconstruction surgery using our approach, and should be considered as a first-line therapy in such cases, particularly when overall right-heart hemodynamics are good and/or only a few PA branches are affected. In patients with severe or multivessel residual/recurrent stenosis, or particularly high RV pressure, transcatheter reintervention may be inadequate, and based on our experience we prefer to refer for surgical revision. The subacute and chronic outcomes of these interventions were not assessed in this study, and the ultimate clinical benefit of these interventions, regardless of technical success, cannot be determined from this study.
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From the 1Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University, Stanford, California; 2Clinical and Translational Research Program, Lucile Packard Children’s Hospital, Stanford University, Stanford, California; 3Department of Anesthesiology, Lucile Packard Children’s Hospital, Stanford University, Stanford, California; and 4Department of Cardiothoracic Surgery, Lucile Packard Children's Hospital, Stanford University, Stanford, California.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
The authors report that patient consent was provided for publication of the images used herein.
Manuscript accepted August 21, 2020.
Address for corresponence: Zsofia B. Long, MD, Pediatric Cardiology, Stanford University School of Medicine, 750 Welch Road, Suite 325, Palo Alto, CA 94304-5731. Email: zlong@stanford.edu
