Acute pulmonary embolism (PE) is a major global health problem, ranking as the third leading cause of cardiovascular death, after myocardial infarction and stroke, with a mortality rate exceeding 15% within three months of diagnosis.^1,2 It is also the leading preventable cause of death among hospitalised patients.¹ In Portugal, updated data reveals an incidence of 58 cases per population of 100,000 individuals, which is higher than previously reported.^1,3,4

Classifying the severity of PE and assessing the risk of early mortality is crucial for optimal management.⁵ High-risk PE, occurring in approximately 5% of all hospitalised PE patients, is associated with a very high short-term mortality rate, ranging from 18% to 64%.⁶ The presence of right ventricular (RV) dysfunction and haemodynamic instability due to acute pressure overload are robust predictors of poor prognosis in those cases.^2,6

Most PE patients respond well to anticoagulation, but those at high-risk or intermediate-high-risk may require more advanced interventions, such as systemic thrombolysis or surgical embolectomy, which carry significant risks.¹ Recently, there has been growing interest in catheter-directed therapy (CDT), namely catheter-directed thrombolysis and pulmonary aspiration thrombectomy, due to its potential for rapid reperfusion of pulmonary arteries and improved outcomes.^7-10 However, the role of CDT in PE treatment is not yet well-defined, and current recommendations are largely based on expert consensus and non-randomized studies.^1,5

This retrospective single-centre study aims to evaluate the impact of CDT on intermediate-high-risk and high-risk acute PE at a tertiary centre in Portugal, with the goal of providing insights that could guide future clinical practice.

The main findings of this study were as follows: (1) patients with high-risk PE accounted for 75% of all individuals undergoing CDT; (2) two-thirds of the patients with high-risk PE undergoing CDT showed an absolute contraindication to systemic fibrinolysis; (3) 72% of the patients who were diagnosed with RV dysfunction upon admission, the majority of whom showed subsequent improvement after CDT; (4) in-hospital mortality was high (24%); (5) no deaths occurred within three months post-discharge (see Central Illustration).

Our cohort's mean age of 62.5 years and the predominance of females (57%) are consistent with the demographics reported in other studies on acute PE management.^2,4,14 Cardiovascular comorbidities, particularly overweight (57%), hypertension (45%), and dyslipidaemia (40%), were prevalent in our population, mirroring patterns seen in broader PE studies.^2,4,14 The frequent presence of these comorbidities underscores the importance of addressing cardiovascular risk factors in PE patients, as they significantly impact prognosis and treatment outcomes.

Acute PE can appear in a spectrum of presentations, ranging from asymptomatic to life-threatening scenarios.^2,4,14 Despite the varied clinical manifestations, dyspnoea remains the predominant symptom, as supported by studies such as PIOPED II.¹⁵ Similarly, our study found dyspnoea to be the primary symptom in the majority of cases (61%), followed by chest pain (33%) and presyncope/syncope (33%). Additionally, tachycardia (heart rate > 100/minute), tachypnoea (respiratory rate ≥ 20 breaths/min) and hypoxemia were the most frequent signs related to acute PE observed in our study.

Stratifying acute PE is important to determine the optimal approach and requires assessing specific laboratory findings, such as levels of high-sensitivity cardiac T troponin and NT-proBNP.⁵ These markers are associated with RV dysfunction, which is the most common complication and one of the most reliable predictors of poor prognosis in individuals with acute PE.⁶ The high-risk nature of our cohort is reflected in the fact that 75% of the patients presented high-risk PE, with 79% classified as PESI score class III or higher. This stratification aligns with guidelines recommending aggressive treatment in high-risk patients, where RV dysfunction plays a crucial role in determining prognosis.^5,6 In our study, 72% of the patients had RV dysfunction upon admission, supporting the assumption that RV dysfunction is the most common complication of acute PE and contributing to the high in-hospital mortality. Furthermore, the ECG findings consistent with RV overload were present in only 46% of our cohort, compared to 72% of the TTE results, confirming the greater accuracy of TTE in diagnosing RV dysfunction, when compared to ECG.

Although thrombolysis is the recommended strategy for managing high-risk PE patients, several registries, such as RIETE and ICOPER, have reported low rates (20-30%) of systemic fibrinolysis use in real-world practice, further supporting the need for alternative therapies like CDT.^2,4,5,16,17 By contrast, concerns regarding the risk of life-threatening haemorrhage have reduced enthusiasm for full-dose systemic fibrinolysis and encouraged the development of alternative treatments with a lower risk of bleeding.^8,18-20

In our study, patients with high-risk PE accounted for 75% of all patients undergoing CDT, and two-thirds of the patients with high-risk PE undergoing CDT had an absolute contraindication to systemic fibrinolysis. The remaining one-third of patients with high-risk PE were submitted to CDT after failed systemic thrombolysis. This finding resonates with the growing body of evidence suggesting that CDT is a viable alternative in high-risk patients where systemic thrombolysis is not feasible.^8,21,22

In our study population, 25% of the patients with intermediate-high-risk PE underwent CDT. Although the best approach for managing patients in the intermediate-high-risk PE group is still unclear, a combination of clinical variables, biomarkers and imaging studies may help identify those who would benefit most from close monitoring.^23,24 Currently, there are numerous treatment options available, including various thrombolysis dosages, catheter-directed therapies, surgical interventions and peripherally inserted devices to enhance cardiac output.^23,24 It is crucial to develop an improved method to identify which patients in the intermediate-high-risk category would benefit from such treatments.^23,24 Indeed, while aggressive treatment can be beneficial for patients at a significant risk of decompensation, it may well pose unnecessary risks for those not facing immediate decompensation.

In our study, a significant decrease was observed in mean PAP and RV dysfunction post-CDT, which aligns with findings from such studies as ULTIMA and SEATTLE II, which reported improved haemodynamics following CDT.^21,25-27 Furthermore, all those studies showed a low incidence of major bleeding events and no fatal intracranial haemorrhage, suggesting that CDT could be extended to patients with high-risk PE who are also at an elevated risk of bleeding, such as the elderly and those with active malignancies.^{2,4,6,9,21,25-27}

Nevertheless, the high incidence (48%) of major adverse events within 48 hours, including our 24% in-hospital mortality rate, underscores the severity of our patients’ conditions. This mortality rate is comparable to other studies, such as those by Calé et al. and Secemsky et al., which reported in-hospital mortality rates ranging from 17% to 30%.^2,14,22 It is crucial to acknowledge that we cannot categorically attribute these events to the CDT procedure itself. The observed complications highlight the need for careful patient selection and monitoring during and after CDT.

Our study's three-month follow-up revealed no deaths or symptomatic PE recurrences, which is a positive outcome when compared to previous studies that reported significant early mortality and morbidity.¹⁴ This suggests that patients who survive the critical in-hospital phase may have favourable outcomes with appropriate post-discharge care. The absence of recurrent PE and unplanned RV failure admissions further emphasizes the potential of CDT to provide durable benefits in high-risk PE patients.

Given the critical nature of the patients in our study and the complexity of their management, our findings support the broader adoption of CDT, particularly in settings where systemic thrombolysis is contraindicated or has failed. The establishment of multidisciplinary expert pulmonary embolism response teams (PERTs) and adherence to institutional and regional guidelines will be essential to optimize outcomes in this challenging patient population.⁶

Acute PE continues to be a significant cause of morbidity and mortality. Although percutaneous interventions are still in their early stages, our study found that CDT improves haemodynamic and clinical parameters with manageable bleeding complications in intermediate-high-risk and high-risk patients. Larger trials are needed to further evaluate CDT's efficacy and to identify patients who would benefit most.