Faculty Bibliography

Therapeutic anticoagulation is the mainstay therapy in acute pulmonary embolism (PE), however, select patients benefit from emergent reperfusion to prevent or rescue acute right ventricular failure and haemodynamic collapse. Compared to other leading causes of cardiovascular mortality such as myocardial infarction and stroke, there is a substantial paucity of literature informing on advanced therapies in PE. Recent years have seen significant evolution in the armamentarium available for PE care with the uptake of several endovascular treatment modalities and increased use of mechanical circulatory support. While several ongoing randomised controlled trials may alter the therapeutic landscape and approach to PE management, at present, we are left with multiple selections with limited guidance. In this review, we discuss the latest therapeutic options available for acute PE and offer an approach to their implementation.

BACKGROUND:Despite the increasing use of catheter-based therapies (CBTs) for acute pulmonary embolism (PE), evidence is limited regarding the long-term outcome. OBJECTIVES/OBJECTIVE:We aimed to investigate the efficacy of CBT for high- and intermediate-risk PE in older adults. METHODS:We included Medicare fee-for-service beneficiaries aged 65 to 99 years admitted for PE from 2017 to 2020 and compared in-hospital and long-term outcomes between patients treated with and without CBT. Propensity score matching weight and instrumental variable analyses were implemented. RESULTS:We included 6,742 and 23,750 patients with high-risk and intermediate-risk PE, of which 11.4% and 15.1% patients were treated with CBT. In high-risk PE, patients treated with CBT, compared with those without, experienced lower in-hospital death (29.0% vs 43.9%; adjusted OR [aOR]: 0.73; 95% CI: 0.61-0.87) and 3-year mortality (45.7% vs 65.5%; adjusted HR: 0.76; 95% CI: 0.67-0.85) but higher intracranial hemorrhage (2.1% vs 1.0%; aOR: 2.29; 95% CI: 1.18-4.44). In intermediate-risk PE, we found no evidence that the incidence of in-hospital death differed between the 2 groups (3.1% vs 4.1%; aOR: 0.93; 95% CI: 0.75-1.16), but patients treated with CBT experienced lower 3-year mortality (14.9% vs 30.3%; adjusted HR: 0.69; 95% CI: 0.63-0.75) and higher incidence of intracranial hemorrhage (0.5% vs 0.3%; aOR: 2.04; 95% CI: 1.17-3.55). The association between the use of CBT and lower 3-year mortality was consistent in the instrumental variable analysis. CONCLUSIONS:Among older adults with high-risk or intermediate-risk PE, patients treated with CBT experienced lower mortality over the follow-up of up to 3 years, but higher risk of in-hospital bleeding complications.

BACKGROUND:In the ISCHEMIA Trial, 5179 patients with stable coronary disease were randomized to initial invasive or conservative management. METHODS:PCI was recommended with a SYNTAX score 0-22 (low) and CABG with a SYNTAX score ≥33 (high). Either could be recommended for intermediate scores. The composite primary outcome was cardiovascular death, MI, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. There were two cohorts in this analysis. The descriptive cohort included patients who underwent CABG or PCI within 180 days of randomization and had no primary outcome before revascularization. The comparative cohort excluded participants with prior CABG, single vessel disease, SYNTAX score ≥ 45, and without core laboratory assessment. We focused on the intermediate (23-32) SYNTAX comparative group for which either CABG or PCI could be recommended. RESULTS:For 1935 patients in the descriptive cohort (485 CABG, 1450 PCI), the SYNTAX score was 27.3 ± 11.0 in the CABG group and 15.3 ± 8.6 in the PCI group, p<0.0001. Most patients with low SYNTAX scores underwent PCI (87.1%), while most with high SYNTAX scores underwent CABG (72.6%). For the 1203 patients (385 CABG, 818 PCI) in the entire comparative cohort, the adjusted 4-year primary event rate was 14.5% for CABG and 13.2% for PCI (difference 1.3%, 95% CI, -4.9% to 7.7%). For the 346 patients (163 CABG, 183 PCI) in the intermediate SYNTAX group, the adjusted 4-year primary event rate was 10.6% for CABG and 18.3% for PCI (difference -7.6%, 95% CI, -16.1% to 0.9%). CONCLUSIONS:Selection of revascularization method resulted in more PCI in the low SYNTAX group and more CABG in the high SYNTAX group. There was no statistical evidence of a difference between PCI and CABG in the intermediate SYNTAX group but the CIs are broad, reflecting uncertainty. GOV IDENTIFIER/UNASSIGNED:NCT01471522; https://clinicaltrials.gov/ct2/show/NCT01471522.

BACKGROUND:Acute pulmonary embolism (PE) is a common cause of cardiovascular morbidity and mortality. Catheter-based therapies (CBT) are emerging technologies that provide reperfusion for patients with PE. However, the optimal timing of these interventions from initial presentation is unknown. AIMS/OBJECTIVE:This study aimed to determine whether the timing of CBT affects outcomes among patients with acute PE managed with CBT. METHODS:This was a retrospective cohort study of patients with PE who underwent CBT and were included in the Nationwide Readmissions Database between January 2017 and December 2020. Patients who underwent early CBT (≤1 day from admission) were compared with those who underwent delayed CBT (>1 day). The primary outcome was death at 90 days, and secondary outcomes included 90-day readmissions. Propensity scores were estimated using logistic regression, and propensity score weighting (PSW) was utilised to compare outcomes between early and delayed CBT. Cox proportional hazards modelling was used to estimate the risk of primary and readmission outcomes. RESULTS:A total of 12,137 patients were included: 1,992 (16.4%) had high-risk PE, and 1,856 (15.3%) were treated with delayed CBT. After PSW, early CBT was associated with a lower risk of 90-day death in both intermediate-risk (hazard ratio [HR] 0.55, 95% confidence interval [CI]: 0.46-0.66) and high-risk (HR 0.89, 95% CI: 0.80-0.99) PE. Early CBT was associated with lower rates of all-cause readmission in patients with intermediate-risk PE (HR 0.86, 95% CI: 0.78-0.95) and in those with high-risk PE (HR 0.84, 95% CI: 0.69-1.05). CONCLUSIONS:Among patients with intermediate- or high-risk PE, early CBT was associated with a lower risk of 90-day death and readmission. A further prospective study on the optimal timing for reperfusion using CBT is needed.

BACKGROUND:Evidence is limited regarding the comparative effectiveness and safety of mechanical thrombectomy (MT) vs catheter-directed thrombolysis (CDT) for high-risk pulmonary embolism (PE). OBJECTIVES/OBJECTIVE:This observational study aimed to compare the outcomes of older adults with high-risk PE treated with MT vs CDT using a target trial emulation framework. METHODS:We included Medicare fee-for-service beneficiaries aged 65 to 99 years admitted with high-risk PE (defined by cardiac arrest, shock, and vasopressor use) who underwent MT/CDT from 2017 to 2020. We evaluated 1-year mortality using an inverse probability of treatment weighting approach, controlling for 62 baseline covariates. We also evaluated readmissions and in-hospital outcomes, including intracranial hemorrhage. Patients were followed from the date of the index procedure to the outcomes of interest, 1 year, or December 2020. RESULTS:We included 235 and 484 patients in the MT and CDT groups, respectively. The absolute risk of 1-year mortality was 48.4% (95% CI: 34.1%-63.3%) in the MT group and 45.4% (95% CI: 37.8%-55.8%) in the CDT group, with an adjusted HR of 1.16 (95% CI: 0.84-1.59). We found no evidence that all-cause readmission (MT vs CDT; subdistribution HR: 0.89; 95% CI: 0.56-1.40), intracranial hemorrhage (adjusted OR: 0.36; 95% CI: 0.07-1.77), or transfusions (adjusted OR: 0.96; 95% CI: 0.52-1.76) differed significantly between the 2 groups. CONCLUSIONS:Among older adults with high-risk PE treated with catheter-based therapies, the clinical outcomes were similar between the patients treated with MT vs CDT. Randomized trials are needed to confirm our findings.

Pulmonary embolism response teams (PERTs) are being increasingly used for the management of patients admitted with acute pulmonary embolism (PE) and are endorsed by societal guidelines. Whether PERT improves outcomes remains unknown. The objective of this meta-analysis was to compare the outcomes of patients with acute PE treated by a PERT versus no PERT.A systematic review and study level meta-analysis was conducted by searching PubMed and EMBASE databases from inception until November 10, 2024 and included studies evaluating efficacy of PERT vs no PERT in patients admitted for acute PE. Outcomes included all-cause mortality (in-hospital and 30-day mortality), major and clinically relevant bleeding, advanced therapies utilization, length of stay (LOS), and 30-day readmission. Twenty-four retrospective observational studies met the inclusion criteria, comprising 15,809 patients (mean age 61.6 years with 49% male) with acute PE of which 6228 were treated with a PERT and 9,581 without a PERT. Lower all-cause mortality (in-hospital or 30-day mortality) [odds ratio (OR)= 0.72; 95% CI: 0.56 to 0.93; 24 studies], major or clinically relevant bleeding (OR= 0.60; 95% CI: 0.42 to 0.86; 15 studies), higher utilization of advanced therapies (OR= 3.16; 95% CI: 1.81 to 5.49; 19 studies), and lower hospital LOS (MD= -1.49; 95% CI: -2.59 to -0.39; 14 studies) were seen in the patients treated by a PERT compared to those not treated by a PERT. In this large meta-analysis of observational studies comparing outcomes in patients treated by PERT versus not treated by PERT, there were significantly lower short-term mortality, lower major or clinically relevant bleeding, higher utilization of advanced therapies and lower hospital length of stay with the existence of PERT. PERT should be the standard of care for the management of patients with acute PE.

BACKGROUND:Patients with intermediate-risk pulmonary embolism (PE) have outcomes worse than uncomplicated ST elevation myocardial infarction. Yet, no large-scale study has compared the outcomes of large-bore mechanical thrombectomy (LBMT) with anticoagulation alone (AC). The aim of this study was to compare the clinical outcomes among patients receiving LBMT vs AC alone. METHODS:This was a two-center retrospective study that included patients with intermediate-risk PE from October 2016 - October 2023 from the institution's Pulmonary Embolism Response Team (PERT) database. The primary outcome was a composite of 30-day mortality, resuscitated cardiac arrest or hemodynamic decompensation. Inverse probability of treatment weighting (IPTW) was used to balance covariates; Kaplan Meir curves and IPTW multivariable Cox regression were used to assess the relationship between treatment groups and outcomes. RESULTS:Of the 273 patients included in the analysis, 192 (70 %) patients received AC alone and 81 (30 %) patients received LBMT and AC. A total of 30 (10.9 %) patients experienced the primary composite outcome over a median follow-up of 30 days. The primary composite outcome was significantly lower in the group that received LBMT compared to those on AC alone (1.2 % vs 15.1 %, log-rank p < 0.001; adjusted HR: 0.02; 95 % CI: 0.002-0.17, p < 0.001) driven by a lower rate of 30-day all-cause mortality (0 % vs 7.3 %, log-rank p = 0.01), resuscitated cardiac arrest (0 % vs 6.8 %, log-rank p = 0.016) and new or worsening hemodynamic instability (4 % vs 11.1 %, log-rank p = 0.007). CONCLUSION/CONCLUSIONS:In this largest cohort to date comparing LBMT versus AC alone in acute intermediate-risk PE, LBMT had a significantly lower rate of the primary composite outcome including a lower rate of all-cause mortality when compared to AC alone. Ongoing randomized trials will test these associations.