A total of 253 consecutive patients were included in the registry from 2014 to 2022, representing all CDT procedures performed at the 13 centers (an average of 5.86 procedures per year per million population, see table 1 of the supplementary data and figure 1 of the supplementary data). Ninety-three (36.8%) were HR-PE patients at the time of CDT, and 160 (63.2%) were IHR-PE patients. Baseline characteristics are shown in table 1. The mean age was 62.3±15.1 years, with a wide range between 16 and 86 years, and 45.5% were female. HR-PE patients were of similar age and had similar cardiovascular risk factors but more had frequently active cancer, recent surgery, or recent immobilization.

At admission, 74 (29.2%) patients were classified as HR-PE and 179 (70.8%) patients as IHR-PE. Of the 179 IHR-PE patients at admission, 19 (10.6%) had clinical deterioration meeting HR-PE criteria before undergoing CDT (figure 1A). For the purposes of this study, high-risk patients were considered those with HR-PE criteria as per the 2019 ESC guidelines before the CDT procedure: 93 (36.8%) patients (figure 1B), and 160 (63.2%) patients were classified as IHR-PE. Other risk stratification parameters are shown in table 2.

Figure 1.

Pulmonary embolism risk stratification. CDT, catheter-directed therapy; PE, pulmonary embolism.

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CDT was the elective reperfusion strategy in 90.9% of patients, and was a rescue therapy after failed thrombolysis in the remaining 9.1%. Anticoagulation was initiated before CDT in most patients, but unfractionated heparin was more frequently used in HR-PE than IHR-PE (table 3). Local thrombolysis was the most frequent method of CDT in the overall cohort (70.8%), followed by aspiration thrombectomy (51.8%), with 23.3% of patients receiving both therapies. However, aspiration thrombectomy was favored in HR-PE patients compared with IHR-PE patients (80.6% vs 35%, P<.001), as shown in table 3, figure 2, and figure 3. Most procedures (77.3%) were considered urgent (< 24hours from hospital admission), although 20.5% of HR-PE patients were treated<2hours from hospital admission. Median [interquartile range] procedural time was 60 [40-90minutes].

Figure 2.

Central illustration. Summary of the study findings. CDT, catheter-directed therapy; HR-PE, high-risk pulmonary embolism; IHR-PE, intermediate-high-risk pulmonary embolism.

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Figure 3.

Catheter-directed therapy strategy. CDT, catheter-directed therapy.

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Treatment strategy details are summarized in table 3. The access site was mostly femoral in HR-PE patients (78.5%), and nonfemoral (mainly antecubital veins) in IHR-PsE patients (58.7%). In our registry, only 51 patients (20.2%) underwent CDT with specific devices: 30.1% in HR-PE procedures and 14.4% in IHR-PE procedures (P<.003). The use of PE dedicated devices increased over time and reached 73% in 2022 (figure 1 of the supplementary data). The local thrombolysis strategy used mostly alteplase with a mean dose of 20.7±8mg over a mean of 18.6±6.6hours. Ultrasound-assisted thrombolysis was infrequent (2.8%) and used the EKOS system (Boston Scientific, USA). The aspiration thrombectomy strategy used specific PE devices in only 35.1% of patients, and most frequently (42%) used coronary guide catheters (6-Fr to 8-Fr). In the HR-PE subgroup, the need for cardiorespiratory support was frequent (72% vasopressors, 42% mechanical ventilation, 7.5% extracorporeal membrane oxygenator) but the need for support was rare in IHR-PE procedures.

The success of CDT (defined as technical procedure completed without procedural complications or 48-hour death) was 90.9% (98.1% of IHR-PE patients vs 78.5% of HR-PE patients, P<.001). The investigators reported pre- and postinvasive measurements in 179 patients and pre- and postechocardiogram measurements in 67 patients (table 2 of the supplementary data). Hemodynamics improved significantly after the procedure, with a mean rise in systolic pressure of 10.5±20mmHg and a mean decrease in systolic pulmonary pressure of 11.8±11mmHg. Right ventricle diameter decreased by a mean of 6.1mm, and tricuspid annulus systolic excursion increased by 5.5mm (table 2 of the supplementary data). During CDT, there were 7 complications (2.8%), 4 of them in HR-PE patients (4.3% of CDT in HR-PE) and 3 in IHR-PE (1.9% of CDT in IHR-PE) but only 2 were definitely related to CDT device or procedure (table 3 of the supplementary data). There were 2 fatal complications, of which 1 was definitely related to CDT (cardiac tamponade due to direct injury from the catheter) and another was possibly related to CDT (atrioventricular block possibly traumatic but in the setting of profound obstructive shock).

In-hospital adverse events are shown in table 4 and were considerably higher in the HR-PE patients (59.1%) than in the IHR-PE patients (16.3%), P<.001. In-hospital mortality was 15.5% and was significantly higher in HR-PE patients (37.6%) than in IHR-PE patients (2.5%), P<.001. The causes of in-hospital death were PE-related shock/cardiac arrest in 21 patients (51.3%), fatal bleeding in 3 patients (7.7%), cancer in 3 patients (7.7%), other, non-PE-related causes in 10 patients (25.6%), cardiac tamponade plus PE-related shock in 1 patient (2.6%), and unknown in 1 patient (2.6%). The median [interquartile range] length of stay was 10 [8-16.5] days.

Follow-up data were available for 250 patients (98.8%) with a mean follow-up of 19.4±20 months. One-month survival was significantly higher in the IHR-PE group than in the HR-PE group: 1-month mortality was 1.3% vs 29.3% (P<.001). Long-term (24-month) mortality was lower at 8.2% vs 40.2% (P<.001), and Kaplan-Meier curves showed that most deaths occurred in the first month (figure 4A). Interestingly, estimation of long-term survival among patients alive at discharge showed that there were no differences in 24-month mortality between IHR-PE and HR-PE: 5.8% vs 5.3% (P<.001) (figure 4B), suggesting there was no late mortality burden after surviving a higher risk PE presentation.

Figure 4.

Kaplan-Meier survival curves for the overall population (A) and for patients discharged alive (B). PE, pulmonary embolism.

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Contemporary studies show an in-hospital mortality rate of 6.5% in unselected PE patients (stable throughout 2016-2019 in a large United States administrative database).18 HR-PE in the same cohort, which includes several reperfusion strategies, including CDT, showed an in-hospital mortality decrease from 48.1% to 38.9%, similar to our HR-PE mortality (37.6%).18 Mortality in HR-PE patients is multifactorial and frequently derives from postcardiac arrest syndrome or multiorgan failure facilitated by obstructive shock.3 To improve these appalling figures, emergency services and in-hospital PERTs should coordinate to provide patients with prompt diagnosis and rapid access to reperfusion and supportive critical care.19,20 Evidence supporting CDT in this setting remains scarce, and our study is one of the largest series (n=93) of CDT in HR-PE. When dealing with unstable patients, time is a critical factor; consequently CDT timing and strategy should be discussed in detail. If CDT is to compete with systemic thrombolysis, which can virtually be administered seconds after decision, it must be provided promptly. In our study, only 20.5% of HR-PE patients underwent CDT in the first 2hours from admission (80%). A recent European consensus statement recommends that CDT should be initiated 60 to 90minutes after decision, or 2 to 4hours after completion of systemic thrombolysis (if considered failed); however, this was an expert consensus with little or no supporting evidence, and the issue should be clarified by further studies.5 In addition, time to benefit should be considered when choosing a CDT strategy. Local thrombolysis usually requires at least 12hours of infusion (although some faster protocols have been tested)21 but aspiration thrombectomy can provide hemodynamic improvement in<60minutes.13,14 Indeed, a preference for aspiration thrombectomy over local thrombolysis was present in our study (figure 3).

IHR-PE is an entirely different category that emerged in the 2014 ESC guidelines and attempted to encompass stable PE patients who merit special attention due to their risk of deterioration.22 Indeed, 7.2% of IHR-PE patients might die at 30 days,23 and 10.6% have an in-hospital adverse outcome (defined as PE-related death, cardiopulmonary resuscitation, or vasopressor treatment).24 Our study shows that CDT could help to reduce mortality: in-hospital mortality was 2.5% in the overall IHR cohort and was 0% in the PE dedicated devices subgroup. A randomized clinical trial with a medical treatment arm is warranted in this setting. However, in its absence, contemporary single-arm studies of CDT for IHR show very low mortality: 0.8% 30-day mortality in the FLASH registry,13 and 2.5% 30-day mortality in the Extract-PE study.14 Moreover, a meta-analysis comparing CDT vs systemic anticoagulation alone for submassive pulmonary embolism (n=9789) reported a significant decrease in in-hospital mortality, which was 2.4% with CDT vs 6.3% with medical treatment (relative risk, 0.41, 95% confidence interval (95%CI), 0.30-0.56, P<.00001)9; similarly, in a meta-analysis including 65 589 IHR and HR patients, CDT showed a 30-day mortality decrease compared with systemic thrombolysis 7.3 vs 13.6%; odds ratio, 0.51, 95%CI, 0.38–0.69, P<.001.10

Follow-up of our patients showed that long-term prognosis of HR-PE patients who survived to hospital discharge was no worse than that in patients with hemodynamic stability at admission (figure 4). This finding is markedly different to other major thrombotic syndromes such as myocardial infarction, in which infarct size correlates with 1-year all-cause mortality in patients discharged alive,25 myocardial infarction presenting with cardiogenic shock, which is also associated with higher 1-year and 5-year mortality in patients surviving beyond 30 days or hospital discharge,26 and stroke, in which stroke severity is independently associated with 1-year readmission.27 This finding supports the need to optimize the acute management of PE through dedicated in-hospital pathways (including, but not limited to, PERTs) and out-of-hospital local and regional networks such as stroke or myocardial infarction networks.

Any new interventional technique requires time to develop successive iterations in the toolset and procedural planning. Access to pulmonary arteries requires safe crossing of the right heart and navigating through anatomical tortuosity. In this registry, 3 out of 253 patients (1.2%) had potential direct cardiac injury related to the catheters or devices themselves, 2 of them with fatal consequences (only one of those with a definite relationship). These adverse events should be adequately reported and closely monitored.

In addition, the size and frequent high level of organization of embolized thrombi do not facilitate extraction. Contemporary dedicated devices such as FlowTriever (Inari Medical, USA)28 or the Indigo System (Penumbra, USA)14,29 are specifically designed for this task, but were not available until 2022 (FlowTriever) and 2018 (Indigo 8-Fr). Our registry also shows a limited (but increasing) uptake of PE dedicated devices, likely related to incremental cost and the low number of cases per hospital, which limits the progression of the learning curve of these devices. Whether the overall increase in CDT procedures or the use of dedicated PE devices has impacted the outcomes of patients with PE remains unclear and warrants specific randomized clinical trials.

The registry has all the potential inherent biases of observational studies. However, we complied with STROBE standards, and the primary outcome was all-cause mortality, which is an outcome with a lower risk of bias. The potential selection bias might have been mitigated by including consecutive patients. However, we have no information on the total number of PE patients evaluated or admitted in the study period, and therefore a survival bias should be acknowledged because the registry represents only patients who survived to PERT evaluation and to the CDT procedure. To increase the number of patients included, the study period was long, which might have add heterogeneity to the treatment strategies. Although there was an open invitation for participation, the initiative originated from the Spanish Interventional Cardiology Association, and therefore interventional radiology is likely under-represented. The registry contained self-reported data and no external monitoring and so local investigators were responsible for the integrity of the data. Finally, the number of patients with dedicated PE devices was low (n=51). Therefore, this registry does not allow for interdevice comparisons.