In cardiac catheterizations involving PV interventions at a high-volume referral center, we found serious AEs were common (12%) and major/catastrophic AEs, including one patient death, were uncommon (1.8%). On a patient level, as most patients underwent multiple transcatheter interventions, 32% of patients experienced a serious AE and 6% experienced a major/catastrophic event. Most of the serious AEs were short lived and non-life threatening and their incidence should be balanced against the high mortality of aggressive disease. Young patients, patients with low systemic arterial saturations and patients with severely elevated mean pulmonary artery pressure at the time of catheterization were particularly vulnerable. Additionally, analysis of a smaller, more recent sample of this cohort found that hospitalized patients, younger patients, and patients with significant RV dysfunction were more likely to require high-level cardiorespiratory support 48 hours after the catheterization. Both the large sample size predictive analysis for the primary outcome and the 48-hour high-level support outcome are, to our knowledge, the first to be performed in patients with PVS. These data may assist clinicians in anticipating peri-catheterization care needs and counseling families on the potential risks and expectations of the treatment plan for patients with PVS.
The incidence of all level AEs of 25% is similar to a previous study from our institution analyzing a cohort of patients receiving PV interventions between 2005 and 2014 (28%; 114/406 cases, excluding access-related issues not accounted for by the authors)[11]. Notably, the incidence of stroke in our cohort (0.36% [3/841] of cases, 1.25% [3/240] of patients) was lower than that reported in this earlier, non-overlapping cohort from our center (2.5% [10/406] of cases, 6.25% [9/144] of patients)[11]. While not assessed prospectively, the findings of the prior study drove a change in institutional practice to continue anticoagulation 18 to 24 hours post catheterization using heparin or enoxaparin in the absence of bleeding; in theory to prevent post-intervention thrombus formation within the pulmonary veins. Further, all patients with PVS were managed with aspirin therapy with dosing continued through catheterization. There was only one stroke in the last five years (0.15% [1/648] of cases) following these institutional changes.
Younger age at the time of intervention was associated with both study outcomes. Prior studies have identified younger age at the time of diagnosis as a risk factor for mortality in patients with PVS[4, 16, 17], suggesting this may be a higher risk cohort. In addition, lower weight and smaller PVs in younger patients likely contribute to a more technically demanding procedure, potentially increasing the chances of serious AEs. It is reported that higher complexity surgical or transcatheter interventions are associated with a higher likelihood of AEs [18, 19]. Lastly, more patients in this age group were admitted to the ICU or had a longer LOS prior to catheterization suggesting higher severity of illness that was not captured in this study.
Low systemic arterial saturation, a marker of severity of lung disease in PVS, was associated with serious AEs. Pulmonary venous obstruction precipitates capillary remodeling, flow redistribution, and pulmonary edema, leading to impaired oxygenation and V/Q mismatch[20, 21]. All of these factors can worsen at the time of catheterization. Though we did not find an association between low systemic arterial saturation and need for high-level support after PV interventions, PVS patients with hypoxemia may require closer monitoring after interventions as suggested by a recent study reporting higher ICU admission in this population[12].
Severely elevated PA pressures were also associated with a higher frequency of serious AEs. Pulmonary hypertension is an independent risk factor for mortality in PVS[22] and increases the risk of AEs during anesthesia, especially in younger patients undergoing interventional catheterizations[23]. Elevated PA pressures can additionally place patients at risk of pulmonary hemorrhage after balloon angioplasty due to increased pressure in the lung segment with balloon inflation. Notably, pulmonary hemorrhage was the most common serious AE in this cohort, occurring in 2.3% of cases and accounting for 17% (20/120) of the serious AEs.
Contrary to our hypothesis, the number of PVs undergoing intervention and the number of balloon and stent angioplasties were not predictors of serious AEs. Our findings may suggest that multiple interventions on a higher number of PVs are safe to pursue, further supported by the lack of association between longer case duration and serious AEs. It should be considered that longer-term risks associated with longer PVS cases, including exposure to higher doses of radiation and contrast, remain unexplored.
High-level cardiorespiratory support at 48 hours after PV intervention was required in 9% of cases. A recent study from our institution using an overlapping cohort of patients found that ICU admission and mechanical ventilation immediately post-catheterization was as high as 50% in a cohort of patients from 2011 to 2021[12]. However, the authors noted a significant decrease in recent years, coinciding with the period captured in our analysis (2019–2021). We found that younger age and worse RV dysfunction were predictors of high-level cardiorespiratory support 48 hours after catheterization. In patients with severe PVS and biventricular circulation, longstanding pulmonary hypertension can lead to RV dysfunction, significantly increasing the risk of cardiorespiratory failure and death in patients with PVS[22]. This is especially true in patients that are ill enough to require hospitalization, as suggested by the strong association of pre-catheterization hospital LOS of one day or greater with need for high-level support. Patients that require inpatient therapy and monitoring may have advanced-stage PVS and/or additional comorbidities contributing to their illness severity that were not captured in this study.
The strengths of our study include the use of a comprehensive dataset from a referral center specialized in PVS management with a large sample size for a relatively rare disease. The limitations of this study include the use of an institutional catheterization database with retrospectively collected data, which limited available variables to those entered into the database. This also limited the sample size for the secondary outcome analysis of higher-level cardiorespiratory support after catheterization. The single-center design may limit the generalizability of results. Patient outcomes may be influenced by operator-related factors and advancement of catheterization techniques over time. Need for mechanical ventilation, vasoactive support, and ECMO were relatively rare outcomes in our cohort, and this may have limited identification of risk factors. Future studies should aim to include multicenter data to consider variation in center practices.