Hestia criteria for outpatient management of pulmonary embolism

Clinical background

Pulmonary embolism has traditionally been managed with admission and parenteral anticoagulation, but a substantial proportion of patients have a risk of complications low enough for outpatient treatment to be both safe and economical with resources. The difficulty lies in identifying these patients reliably without missing those who later deteriorate at home. The Hestia criteria were developed for precisely this purpose: a structured exclusion checklist that determines whether a patient with confirmed pulmonary embolism can be sent home, rather than a scoring scale that estimates probable risk. The instrument serves the same function as PESI and sPESI but rests on a different principle, in which each individual criterion constitutes an absolute barrier to outpatient treatment.

Applying the Hestia criteria

The Hestia criteria form a checklist of 11 exclusion criteria, not an additive score. The principle is binary: if any criterion is present the patient is not suitable for outpatient treatment; if all are absent, outpatient treatment can be considered.

The criteria are:

1. Haemodynamic instability (e.g. marked hypotension, need for thrombolysis or vasopressors)
2. Need for thrombolysis or embolectomy
3. Active bleeding or a high bleeding risk
4. Need for oxygen for more than 24 hours to maintain an SpO₂ >90%
5. Pulmonary embolism diagnosed during ongoing anticoagulant treatment
6. Severe pain requiring intravenous treatment for more than 24 hours
7. A medical or social reason for hospital care for more than 24 hours (e.g. concurrent infection, malignancy requiring admission, lack of support at home)
8. Creatinine clearance <30 mL/min
9. Severe hepatic impairment
10. Pregnancy
11. A documented history of heparin-induced thrombocytopenia (HIT)

The derivation study was a prospective cohort study in 12 Dutch hospitals between 2008 and 2010 [1]. A total of 297 patients with objectively confirmed acute pulmonary embolism were triaged with the criteria. Those meeting no exclusion criterion were sent home immediately or within 24 hours, on nadroparin with transition to a vitamin K antagonist. During three months of follow-up, 2.0% (95% CI 0.8 to 4.3) had recurrent venous thromboembolism, 1.0% (95% CI 0.2 to 2.9) died (none from pulmonary embolism), and 0.7% (95% CI 0.08 to 2.4) had a major bleed, one of which was a fatal intracranial haemorrhage [1].

Interpretation in practice

Because the Hestia criteria form an exclusion checklist, there are only two outcomes:

The subjective criterion "a medical or social reason for hospital care" is the only one requiring clinical judgement without an objective threshold. In a post hoc analysis of the combined Hestia and Vesta cohorts, this criterion was the sole reason for admission in 38% of the admitted patients, and the commonest objective reason for admission overall was a need for oxygen (45%) [3]. When the subjective criterion was used as the sole reason for admission, the clinicians had taken account of right ventricular strain and haemodynamic response, not only the RV/LV ratio on imaging [3].

Validation and performance

The Hestia criteria have been validated in several prospective studies since their derivation. The most important is the Vesta study, a randomised non-inferiority trial in 17 Dutch hospitals with 550 patients, in which Hestia without biomarkers was compared with Hestia combined with NT-proBNP [4]. The primary endpoint was fatal pulmonary embolism or bleeding, cardiopulmonary resuscitation or intensive care admission within 30 days. In the group sent home directly on the basis of Hestia alone, the primary endpoint occurred in 1.1% (95% CI 0.2 to 3.2), compared with 0% in the NT-proBNP group (P = 0.25), within the predefined non-inferiority margin of 3.4% [4]. The study could not draw firm conclusions about whether NT-proBNP added anything, since few patients had a raised value, but it confirmed that Hestia alone was safe [4].

In a comparative study of Hestia and sPESI in 468 patients from the same cohort, both methods selected more than half of the patients as suitable for outpatient treatment, but they identified partly different patients [5]. Both showed good sensitivity and negative predictive value for 30-day mortality. Hestia identified a proportion of patients whom sPESI classified as high risk but who could nonetheless be treated safely at home, suggesting that Hestia may be less restrictive [5].

A particular question has been whether right ventricular dysfunction on CT, defined as an RV/LV ratio >1.0, should be a barrier to outpatient treatment. In an analysis of 496 patients, 35% of those treated at home according to Hestia had right ventricular dysfunction and were classified as intermediate-high risk by the ESC, without any complications occurring [2]. This supports the view that Hestia works irrespective of right ventricular function demonstrated on imaging, which is also reflected in the pitfalls described for this calculator.

A Cochrane review from 2022 identified only two randomised trials, with a total of 453 participants, comparing outpatient with inpatient treatment of low-risk pulmonary embolism [6]. The strength of the evidence was judged to be low, with wide confidence intervals including effects in both directions for mortality, bleeding and recurrence. The review found no clear difference between outpatient and inpatient treatment, but it should be noted that the studies were small and few [6].

A recent review from 2023 concludes that both sPESI and the Hestia criteria are safe decision aids for identifying patients who can be managed as outpatients, provided that they are combined with the clinician's overall judgement of the need for hospital care [7].

Limitations

The Hestia criteria are intended for patients who are already haemodynamically stable. They form a suitability checklist, not a mortality risk score, and give no information about the prognosis of those who cannot be sent home.

All the validation studies were conducted in Dutch hospitals with established thrombosis services and good access to outpatient follow-up. Generalisability to health systems organised differently, particularly where rapid outpatient follow-up cannot be guaranteed, has not been systematically evaluated.

The subjective criterion "a medical or social reason for hospital care" is both a strength and a weakness. It allows the clinician to weigh in patient-specific factors not captured by the objective criteria, but it also means that interobserver reliability is lower and that the decision may vary between clinicians. In practice this criterion is often used to ensure that patients with appreciable right ventricular strain or haemodynamic compromise are not sent home, even though the RV/LV ratio alone is not a formal criterion [3].

The criteria were validated with LMWH and vitamin K antagonists as the anticoagulant regimen. Direct oral anticoagulants (DOACs) are now first-line treatment for pulmonary embolism in many countries, and although the principle of patient selection should be the same, the data from the original studies come from a different treatment context.

Pregnancy and documented HIT are exclusion criteria not because outpatient treatment is contraindicated in itself, but because these patients require particular monitoring and a choice of anticoagulant that cannot be standardised within an outpatient model.

References

1. Zondag W et al. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost 2011. PMID: 21645235
2. Zondag W et al. Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function. J Thromb Haemost 2013. PMID: 23336721
3. Hendriks SV et al. Reasons for Hospitalization of Patients with Acute Pulmonary Embolism Based on the Hestia Decision Rule. Thromb Haemost 2020. PMID: 32594509
4. den Exter PL et al. Efficacy and Safety of Outpatient Treatment Based on the Hestia Clinical Decision Rule with or without N-Terminal Pro-Brain Natriuretic Peptide Testing in Patients with Acute Pulmonary Embolism. A Randomized Clinical Trial. Am J Respir Crit Care Med 2016. PMID: 27030891
5. Zondag W et al. Comparison of two methods for selection of out of hospital treatment in patients with acute pulmonary embolism. Thromb Haemost 2013. PMID: 23138355
6. Yoo HH et al. Outpatient versus inpatient treatment for acute pulmonary embolism. Cochrane Database Syst Rev 2022. PMID: 35511086
7. de Wit K, D'Arsigny CL. Risk stratification of acute pulmonary embolism. J Thromb Haemost 2023. PMID: 37187357