Despite New Tools, PE Outcomes Remain Dire for Highest-Risk Patients

Despite frequent use of advanced therapies like systemic thrombolysis and extracorporeal membrane oxygenation (ECMO), high-risk pulmonary embolism (PE) continues to be associated with very high mortality, according to data from the PERT Consortium Registry.

The American Heart Association (AHA) and the European Society of Cardiology (ESC) categorize high-risk acute PE patients as those with sustained systolic BP < 90 mm Hg, prolonged drops in systolic BP of > 40 mm Hg, vasopressor requirements, or cardiac arrest. The new analysis further broke down these patients by catastrophic (circulatory collapse) or noncatastrophic (no circulatory collapse) clinical status.

“These catastrophic patients are still dying at a rate of 42% for in-hospital mortality as compared to those that were noncatastrophic for high risk at 17%. So, it's a new category of risk that that we were able to identify,” said Taisei Kobayashi, MD (University of Pennsylvania, Philadelphia), lead author of the paper, which was published January 1, 2024, in the Journal of the American College of Cardiology.

In an accompanying editorial, Behnam N. Tehrani, MD (Inova Schar Heart and Vascular, Falls Church, VA), and colleagues, say the study offers a way forward in establishing universally accepted definitions for high-risk PE “and the pursuit of novel metrics to elucidate signals of efficacy, including durable changes in hemodynamics, metabolic measures of tissue perfusion, and echocardiographic and proteomic-based predictors of survival and myocardial recovery.”

Current PE risk-assessment models, they add, are “highly nonuniform with only modest discriminatory capacity to predict short-term outcomes.”

PERT Registry Findings

Kobayashi and colleagues analyzed data from 5,790 patients (mean age 62.5 years; 50% women) from the PERT Consortium Registry, which consists of 35 centers in the United States that have dedicated multidisciplinary pulmonary embolism response teams.

Compared with intermediate-risk patients, those in the high-risk category were less often white, had lower mean body mass index and more clinical comorbidities including diabetes and recent hospitalization, and were more likely to present with syncope and altered mental status.

The use of advanced PE therapies was 41.9% in the high-risk patients versus 30.2% for those at intermediate risk (P < 0.001). In the high-risk group, in-hospital mortality was more than five times higher than in the intermediate group and the rate of major bleeding was three times higher (P < 0.001 for both comparisons).

In multivariable analysis, factors associated with in-hospital mortality were vasopressor use, ECMO, identified clot-in-transit, and malignancy.

In addition to having higher in-hospital mortality, catastrophic high-risk PE patients had higher risk of bleeding at 24.8% compared with 8.4% in noncatastrophic high-risk patients (P < 0.001). They also had longer lengths of stay at 9 days versus 7 days (P = 0.013)

While use of advanced therapies was similar in the catastrophic and noncatastrophic groups, those with catastrophic status more often received ECMO (13.3% vs 4.8%; P < 0.001) and systemic thrombolysis (25.0% vs 11.3%; P < 0.001), but they were less likely to undergo catheter-based therapies (16.8% vs 26.2%; P < 0.01) or surgical embolectomy (0.5% vs 3.1%; P = 0.04).

A Wake-up Call

Tehrani and colleagues say the less frequent use of catheter-directed therapy and embolectomy likely reflects a selection bias toward patients “who may have been perceived as being more salvageable.”

They add that while dedicated high-risk PE registries, such as the PERT Consortium’s, aid in risk-stratifying and allow for understanding of the impact of regionalized networks and standardized treatment algorithms, much more is needed, including RCTs.

“[Defining the most effective therapies for the highest risk strata of acute PE patients who face mortality rates that rival cardiogenic shock will require carefully designed randomized clinical trials aimed at assessing the safety and efficacy of emerging catheter-based and pharmacologic therapies,” Tehrani and colleagues write.

To TCTMD, Kobayashi said a host of trials in PE patients at intermediate-high risk, like PEERLESS and HI-PEITHO, are expected to help fill evidence gaps, but that those at the highest risk are difficult to enroll in RCTs. That makes it hard to extrapolate the outcomes of such small groups of patients given what seems to be considerable heterogeneity among the high-risk substrata.

“This should be a wake-up call for us as clinicians to really think about this particular category, continue to define who makes up this high-risk category, and [consider] are there any strategies or tools in our armamentarium to use either earlier, or more selectively, to help aid in in-hospital mortality,” Kobayashi urged.