Author + information
- Received November 17, 2015
- Revision received December 18, 2015
- Accepted January 5, 2016
- Published online March 22, 2016.
- Matthew J. Lewis, MD, MPHa,∗ (, )
- Kevin F. Kennedy, MSb,
- Jonathan Ginns, MDa,
- Matthew A. Crystal, MDc,
- Alejandro Torres, MDc,
- Julie Vincent, MDc and
- Marlon S. Rosenbaum, MDa
- aDivision of Cardiology, Department of Medicine, Schneeweiss Adult Congenital Heart Center, Columbia University Medical Center, New York, New York
- bMid-America Heart Institute, Kansas City, Missouri
- cDivision of Pediatric Cardiology, Department of Pediatrics, Columbia University Medical Center, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. Matthew J. Lewis, Division of Cardiology, Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, Suite 627, New York, New York 10032.
Background Risk factors associated with outcomes for pulmonary artery (PA) stenting remain poorly defined.
Objectives The goal of this study was to determine the effect of patient and procedural characteristics on rates of adverse events and procedural success.
Methods Registry data were collected, and 2 definitions of procedural success were pre-specified for patients with biventricular circulation: 1) 20% reduction in right ventricular pressure or 50% increase in PA diameter; and 2) 25% reduction in right ventricular pressure or 50% decrease in PA gradient or post-procedure ratio of in-stent minimum to pre-stent distal diameter >80%. A separate definition of procedural success based on normalization of PA diameter was pre-specified for patients with single ventricle palliation.
Results Between January 2011 and January 2014, a total of 1,183 PA stenting procedures were performed at 59 institutions across 1,001 admissions; 262 (22%) procedures were performed in patients with a single ventricle. The rate of procedural success was 76% for definition 1, 86% for definition 2, and 75% for single ventricle patients. In the multivariate analysis, ostial stenosis was significantly associated with procedural success for biventricular patients according to both definitions. The overall complication rate was 14%, with 9% of patients experiencing death or a major adverse event (MAE). According to multivariate analysis, weight <4 kg, having a single ventricle, and emergency status were significantly associated with death or MAEs.
Conclusions In our analysis, success was >75% across all definitions, and adverse events were relatively common. Biventricular patients with an ostial stenosis had a higher probability of a successful outcome. Patients who had a single ventricle, weight <4 kg, or who underwent an emergency procedure had a higher risk of death or MAE. These findings may help inform patient selection for PA stenting.
Pulmonary artery (PA) stenosis is common in patients with congenital heart disease, and invasive PA procedures may account for up to 20% of all catheter-based interventions in this population (1–4). Despite the relative frequency of PA interventions, little is known about how often they yield a successful outcome. Although procedural success rates remain unclear, there is increasing evidence that adverse events may be common (3,5–8). In one of the few multicenter studies of PA interventions, 22% of patients experienced an adverse event and 10% experienced a high severity event (4). Given the high rates of procedural complications and poorly defined metrics of procedural success, additional data are needed to improve patient selection.
Optimizing patient selection for PA stenting is obscured by a lack of a standardized definition of procedural success, the plurality of indications, and the paucity of multi-institutional studies. Although previous studies have classified successful outcomes of PA stenosis treatment as a >50% increase in PA diameter post-procedure and/or >20% decrease in the ratio of subpulmonic to aortic pressure, this definition has never been validated and may not apply to patients with a single ventricle (9). The heterogeneity of indications also complicates comparisons between patients, especially in the setting of small, single-center studies in which lesion location and morphological severity are not standardized. As a result, it remains challenging to define the patient parameters that provide the greatest probability of a successful outcome while minimizing the risk of complication.
The IMPACT (Improving Pediatric and Adult Congenital Treatment) Registry is a multi-institutional initiative to develop performance and quality metrics for patients with congenital heart disease undergoing diagnostic catheterizations and catheter-based interventions (10). In participation with the IMPACT Registry, the goal of the present study was to determine the rate of procedural success and adverse events for PA stenting according to indication and procedural characteristic.
Data for this study were obtained from the National Cardiovascular Data Registry–IMPACT Registry, which comprises data on pediatric and adult congenital heart disease catheterizations obtained from centers that have agreed to enrollment. Specific details regarding the registry have been published previously (10,11). Definitions for exposures and outcomes of interest were pre-specified and collected in accordance with a strict quality program previously described for the National Cardiovascular Data Registry (12). For the purposes of the present study, all pertinent data related to PA procedures were reviewed before formulation of the analytic plan. Endpoints were pre-specified as defined later.
Study population and exposures of interest
The study assessed IMPACT data collected during cardiac catheterizations for PA stenting in patients enrolled from January 2011 to January 2014. All patients who underwent PA stenting were eligible for inclusion. Demographic, procedural, and historical data were available for each visit. Procedure status was defined to indicate if a procedure was performed emergently, urgently, electively, or as a salvage procedure. Patients were grouped into 1 of 5 diagnostic categories. Group 1 included all patients with tetralogy of Fallot (TOF) and TOF-like anatomy (including patients with pulmonary atresia, “hemitruncus,” or a TOF-type double outlet right ventricle); group 2 comprised all patients with a primary PA abnormality; group 3 included all nongroup 1 patients with a conotruncal abnormality; group 4 comprised all patients with a single ventricle; and group 5 included all other patients. Procedural indication was defined by each patient’s treating physician and included PA gradient, PA flow discrepancy, right ventricular hypertension/dysfunction, angiographic narrowing, and pulmonary insufficiency. Procedure-specific data, including defect location and type, pre- and post-procedure proximal and distal PA systolic pressures, and pre- and postprocedure PA diameter, were also collected. Data pertaining to stent type were not standardized and incomplete, and they were not used in the analysis. Data on adverse events, including mortality, were collected per admission and subdivided into major adverse events (MAEs) based on severity (Table 1).
Outcomes and definitions of procedural success
Given the lack of a standardized definition for PA stenting procedural success, 2 definitions were pre-specified for patients with biventricular hearts, and a separate definition was pre-specified for patients with a single ventricle (Table 2). The first definition for patients with a biventricular heart was extracted from previous studies; it represented a historical definition of procedural success and consisted of improvements in subpulmonic ventricular pressure and PA diameter.
A second definition of procedural success was created and implemented to account for potential deficits in the historical definition. In addition to metrics based on changes in ventricular pressure and PA size, definition 2 also included a >50% gradient reduction across the stenosis to identify procedural success in patients with elevated pressure in the contralateral lung. In addition, the ratio of the post-procedure in-stent diameter to the pre-procedure distal diameter was used as a metric to characterize improvement in PA size. This metric was established in place of a 50% increase in stenotic diameter to clarify situations in which improvements in post-procedure PA vessel diameter may overestimate improvements in PA vessel size. Because of the low-flow state across the pulmonary arteries in patients with a single ventricle, only procedures with normalization of the vessel diameter (i.e., a ratio ≥1.0) were considered a success. To account for possible post-stenotic dilation in patients with biventricular circulation, a ratio of the post-procedure in-stent diameter to pre-procedure distal diameter >0.8 was considered a success.
Patient factors that could affect procedural success were identified based on clinical rationale and previous studies. Specific covariates pre-specified for inclusion in multivariate models of procedural success were patient weight, age, procedural indication, and procedure status. Additional covariates were included in multivariate models to include any variables that reached a p value <0.20 in the analysis (13). For multivariate models of adverse events, pre-specified variables included patient weight, age, procedural indication, procedural status, single ventricle status, and procedural success. Separate multivariate models for adverse events were made for each procedural definition of success in patients with biventricular hearts.
Data are presented as mean ± SD for continuous data and number (%) for categorical data. Given the nature of the database, procedures were used as the unit of analysis. Unadjusted comparisons were made with either the chi-square test or the Student t test. Modified hierarchical Poisson regression was used to estimate the risk ratio (RR) of covariates predicting the adverse events or success endpoints. We used a random intercept model to account for the clustering of patients in hospitals, with no additional corrections for multiple procedures within patients or admissions. A p value of 0.05 was used to determine statistical significance. SAS version 9.3 (SAS Institute, Inc., Cary, North Carolina) was used for all analyses.
Between January 2011 and January 2014, data were collected on 1,183 PA stenting procedures at 59 institutions across 1,001 unique admissions and 974 patients. Table 3 presents demographic data and baseline characteristics. Mean patient age was 8.6 ± 9.8 years, and mean patient weight was 28.7 ± 26.2 kg. Twenty patients (2%) had planned cardiac surgery during their admission. Overall, 211 (18%) procedures were performed in patients with TOF or TOF-like diagnoses (group 1); 182 (15%) procedures were performed in patients with a primary PA stenosis (group 2); 110 (9%) procedures were performed in patients with conotruncal abnormalities (group 3); 262 (22%) procedures were performed in patients with a single ventricle (group 4); and 234 (20%) procedures were performed in patients with a different diagnosis (group 5). Diagnoses were not available for 184 patients.
Data on PA stenting location were available for 1,182 procedures with PA stenting in the right PA in 395 lesions (33%) and in the left PA in 787 lesions (67%). A total of 510 (43%) procedures were performed on an ostial PA stenosis, whereas a distal obstruction was present in 188 (16%) procedures. The mean pre-procedure PA diameter of the stenotic segment was 5.4 ± 3.4 mm, and the mean pre-procedure distal diameter was 9.0 ± 4.0 mm. The mean post-procedure PA in-stent diameter was 9.5 ± 4.0 mm.
The overall rate of procedural success for procedures in biventricular hearts was 76% (95% confidence interval [CI]: 73% to 79%) for definition 1 and 84% (95% CI: 82% to 86%) for definition 2. There was a significant difference in the number of procedures classified as successful for each definition (p < 0.001). Patients with a single ventricle had a successful intervention in 75% (95% CI: 70% to 80%) of cases. Procedural success rates according to definition and indication are shown in Figure 1. Notably, there was no significant difference in procedural success by indication. Table 4 illustrates univariate associations between specific variables of interest and each definition of success. Pre-procedure distal diameter was the only variable in the univariate single ventricle model significantly associated with procedural success. No variable in the multivariate single ventricle model was associated with success.
Multivariable models of procedural success by definition are illustrated in Table 5. For biventricular hearts, the only variables significantly associated with both definitions of procedural success were the presence of an ostial stenosis (definition 1, RR: 1.12; p = 0.007; definition 2, RR: 1.08; p = 0.02) and the pre-procedure distal diameter (definition 1, RR: 0.93; p = 0.009; definition 2, RR: 0.99; p = 0.002). No variable in the multivariate single ventricle model was significantly associated with procedural success.
In our study, 14% (95% CI: 12% to 16%) of all procedures involved a complication, and 9% (95% CI: 7 to 11) of all procedures had an MAE (Figure 2). Nineteen deaths (1.7%) occurred, including 2 intraprocedural deaths. Of the 17 non-intraprocedural deaths reported per patient admission, 10 (59%) were associated with an urgent or emergent procedure, and none occurred in patients who had associated cardiac surgery. Univariate associations between specific variables and rates of adverse events were determined before the multivariate analysis. Table 6 illustrates multivariate models of any adverse event and MAEs for all patients. Weight <4 kg, emergency procedures, and single ventricle status were significantly associated with the risk of any adverse event and MAE. Patients undergoing PA stenting secondary to PA flow abnormalities or angiographic narrowing had a lower risk of events than patients with right ventricular hypertension. Two models utilizing each definition of success, but otherwise identical covariates, were used to assess the relationship between procedural success and MAEs in biventricular patients (Table 7). Procedures categorized as successful according to the second definition were associated with a lower risk of MAEs. There was no significant association between procedures categorized as successful according to the first definition and MAEs.
Two separate analyses were performed to confirm these results. First, death was removed from both “all” and “major” adverse events, with no significant change in the predictors or rate of MAEs for all patients. Separately, to assess for possible confounding, all patients who underwent planned cardiac surgery during their admission were removed. Similarly, no significant change was observed in predictors or the absolute rate of MAEs.
In our cohort of 1,183 proximal PA stenting procedures, success rates across each definition exceeded 75%, with a 14% rate of any adverse event and 9% rate of MAEs (Central Illustration). The presence of an ostial stenosis was associated with a greater rate of procedural success for patients with biventricular circulation; a single ventricle, weight <4 kg, and emergency procedure were associated with death or MAEs. This study is the first to report rates of procedural success in a large, multi-institutional cohort of patients undergoing PA stenting with concordant rates of procedural adverse events according to indication and patient characteristic.
Definitions of procedural success
Classically, procedural success in PA stenting has been defined by an improvement in PA diameter, a decrease in right ventricular pressure, or an improvement in pulmonary blood flow (7,9,14). These criteria may not apply equally to all patients with congenital heart disease undergoing PA rehabilitation. In patients with a single ventricle, for example, the goal of PA stenting is generally normalization of the PA diameter relative to nonstenotic segments. In addition, by failing to include a change in PA gradient, the standard definition might not account for lesions stented to diminish pulmonary hypertension in the contralateral lung. In such cases, treating improvements in vessel diameter as a ratio relative to the unaffected segment or as an improvement in pressure gradient may provide a more accurate assessment of post-procedure success. Because the optimal definition of procedural success is not known, we added an additional definition of success to account for these considerations. In so doing, we were able to select for covariates that met both definitions of success, minimizing the contribution of procedures that increased PA diameter but failed to improve PA gradient, the ratio of the stenotic segment to the distal segment, or the subpulmonic ventricular pressure.
The majority of covariates did not have a significant association with procedural success according to either definition. Although certain metrics of PA vessel size, such as pre-procedure distal diameter, were significant, the magnitude of the effect was sufficiently small that it is unlikely that these results were clinically meaningful. The presence of an ostial stenosis was significantly associated with higher odds of a successful procedure according to both definitions. Because an ostial lesion may affect a larger vascular bed, successful stenting may have a more pronounced effect on reducing elevated right ventricular pressures. Ostial lesions are also generally easier to access, and operators may feel more comfortable using higher pressures during dilation and stent deployment. As a result, successful stenting of ostial lesions may be simpler technically and therefore less affected by the heterogeneity of this cohort. Finally, because vessel angulation contributes to narrowing in ostial lesions, they may be intrinsically more amenable to stenting than mid- and distal-PA lesions, which are more likely to be scar related.
Indication was not a statistically significant predictor of procedural success; however, patients who underwent stenting secondary to an angiographic narrowing or PA flow discrepancy were at lower risk for an MAE. Unfortunately, the lack of a clear, standardized definition for indication complicates interpretation of these findings and may have led to misclassification bias. In addition, the unequal distribution of patients in each category and the heterogeneous nature of each group increase the probability of confounding, further limiting our ability to infer associations between indication and outcome. Therefore, although these results were the first to suggest a possible association between indication and adverse events in PA stenting, future studies with standardized indications are needed to validate our findings.
Predictors of adverse events and procedural success
In our cohort of patients undergoing PA stenting, 14% of procedures were associated with an adverse event, and 9% were associated with either death or an MAE. These rates are similar to those reported in previous studies of outcomes in PA rehabilitation (4) but are the first to confirm such high rates for PA stenting alone. Similar to earlier studies, we found that low patient weight and nonelective status were associated with a higher rate of adverse events. However, our study was the first to identify single ventricle status as an independent risk factor. We found that patients with a single ventricle were 2.3 times more likely to have an MAE than patients with biventricular circulation, even after controlling for procedure status, patient age, and patient weight. These results suggest that additional measures should be used to mitigate risk in patients with a palliated single ventricle. Prospective studies designed to identify modifiable risk factors and the impact of balloon type, stent type, operator experience, and center volume are needed in this population.
Successful interventions did not increase the risk for adverse events. Instead, we found that patients who had a procedural success according to the second definition were significantly less likely to have an MAE. Anatomic factors that decrease the probability of a successful outcome may also play a role in defining which patients are at highest risk for an MAE. Long-term follow-up is necessary to validate these results and to further inform how successful PA interventions are classified in this population.
In this study, current practice standards for PA stenting resulted in successful procedures 75% to 84% of the time. These findings are consistent with those reported in previous studies, in which success rates have varied from 70% to 98% (14–17). We also found an associated rate of 9% for death or MAE. Because our results did not account for adverse events that occur after the index hospitalization, the relative rate of successful procedures to adverse events may be even lower. Although long-term follow-up is necessary to refine these data, our results suggest that PA stenting is associated with significant risk. Furthermore, given that PA stenting can complicate subsequent cardiac surgery, an improved understanding of optimal patient selection is needed. Although lesion location seemed to play a larger role than demographic, clinical, or historical covariates in defining which patients were mostly likely to benefit from PA stenting, the presence of an ostial stenosis was associated with only a modest improvement in the rate of procedural success. These results highlight the need for additional, prospective research powered to ascertain modifiable risk factors in patients undergoing PA stenting.
This study did not address long-term outcomes of PA stenting. In addition, we were limited to data made available through the registry and were unable to risk-stratify patients based on pre-procedure indices of ventricular and pulmonary function. Given the nature of the registry, limited data were available regarding stent and balloon type, and data pertaining to MAEs could not be further adjudicated. Furthermore, we were unable to assess for changes in pulmonary blood flow for defining successful interventions and were unable to discern between mortality from procedures and the hospitalization. Nonetheless, this study is the largest to assess the rates of procedural success and adverse events exclusively in patients with congenital heart disease undergoing PA stenting.
In our study, PA stenting had a success rate >75% with a 14% risk of any adverse event and a 9% risk of death or MAE. Biventricular patients with an ostial stenosis have a higher probability of a successful outcome; patients with a single ventricle, weight <4 kg, or emergency procedure have a higher risk of death or MAE. In addition, patients with a post-procedure ratio of in-stent minimum to distal PA diameter ≥0.8, a >50% decrease in gradient across the stenosis, or >25% decrease in subpulmonic ventricular pressure were less likely to incur an MAE. These findings should inform referring physicians and operators regarding patient selection before PA stenting. Given the high rate of adverse events, further study is necessary to elucidate mechanisms to minimize patient risk and further validate definitions of procedural success.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: PA stenting can be successfully achieved in most cases, but adverse events are common. Patients with ostial PA stenosis have a higher probability of successful outcomes than those with more distal PA lesions, and patients undergoing emergency procedures, those with a single ventricle, and those with low weight will face a higher risk of MAEs.
TRANSLATIONAL OUTLOOK: Additional research is necessary to define the rate of late adverse events after PA stenting and the influence of stent type on procedural outcomes.
This research was supported by the American College of Cardiology’s National Cardiovascular Data Registry. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. The views expressed in this paper represent those of the authors and do not necessarily represent the official views of the National Cardiovascular Data Registry or its associated professional societies identified at www.CVQuality.ACC.org/NCDR.
- Abbreviations and Acronyms
- confidence interval
- major adverse event
- pulmonary artery
- risk ratio
- tetralogy of Fallot
- Received November 17, 2015.
- Revision received December 18, 2015.
- Accepted January 5, 2016.
- American College of Cardiology Foundation
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