PDF: ENCLOSE
(2023)Objective
To evaluate the diagnostic yield of admission nongated cardiac CTA, including spectral reconstructions, for detecting cardioembolic sources in patients with acute ischemic stroke or TIA.
Study Summary
• Nongated cardiac CTA extended from standard stroke imaging identified cardiac thrombi in 12% of patients and significantly improved diagnostic certainty of cardioembolic stroke.
Intervention
Admission spectral nongated head-to-heart CTA as part of the acute stroke protocol, reconstructed with iodine maps and spectral imaging.
Inclusion Criteria
Patients ≥18 years with suspected TIA or AIS, admitted within 9 hours of symptom onset, undergoing standard NCCT, CTP, and nongated head-to-heart CTA.
Study Design
Arms: Single-arm prospective imaging study (cardiac CTA compared with clinical and echocardiographic follow-up).
Patients per Arm: 370 patients with assessable cardiac CTA; 271 had spectral reconstructions.
Outcome
• Cardiac thrombus detected in 12%: 9% in LAA, 4% in LV. • LAA thrombus found in 6% of patients without AF and 7% not on anticoagulation. • Spectral iodine maps significantly improved diagnostic certainty for thrombus (p<0.001). • Presence of thrombus associated with more severe stroke, higher clot burden, and more frequent EVT. • Expert panel changed etiology to cardioembolic in 68% after reviewing cardiac CTA vs 0% before (p<0.001). • Nongated CTA added <5s scan time with no extra contrast and acceptable radiation dose.
Bottom Line
Admission nongated cardiac CTA identified cardiac thrombi in 12% of patients and increased diagnostic certainty of a cardioembolic stroke mechanism; iodine spectral maps provided additional diagnostic value, especially for left atrial appendage thrombus.
Major Points
- ENCLOSE demonstrated that nongated cardiac CTA — performed as a simple EXTENSION of routine acute stroke CTA (no additional contrast, no ECG gating) — can detect cardiac thrombus in 12% of stroke patients.
- Left atrial appendage (LAA) thrombus was found in 9%, left ventricular (LV) thrombus in 4% — these are immediately actionable findings that mandate anticoagulation.
- Spectral iodine mapping (dual-energy CT technique) significantly improved diagnostic certainty for LAA thrombus vs standard CTA — the iodine map distinguishes slow-flow (stasis) from true thrombus.
- Expert panel review showed cardiac CTA data increased the likelihood of diagnosing cardioembolic stroke etiology from 0% 'certainly present' to 68% 'certainly present' — dramatically changing management decisions.
- Patients with cardiac thrombus had higher NIHSS (median 10 vs 4), more frequent AF (43% vs 13%), and higher rates of endovascular treatment — consistent with cardioembolic strokes being more severe.
- Clinical implication: extending the CTA scan field inferiorly to cover the heart adds ~10 seconds of scan time and no additional contrast — virtually zero incremental cost or risk for a high-yield diagnostic finding.
- Challenges the traditional stroke workup paradigm where cardiac imaging (TTE/TEE) is done days later — cardiac CTA provides the same information (thrombus detection) at the time of acute stroke imaging.
- Limitations: nongated CT has lower sensitivity than ECG-gated cardiac CT or TEE for small LAA thrombi. Some findings may be false positives (slow-flow artifact mimicking thrombus).
- Single-center Dutch study (n=370) — needs multicenter validation and comparison with TEE (the gold standard for LAA thrombus detection).
- Aligns with the growing 'one-stop-shop' CT approach to acute stroke workup: head CT → CTA brain + neck + heart → CT perfusion, all in a single session.
Study Design
- Study Type
- Prospective observational cohort study
- Randomization
- No
- Blinding
- Imaging interpretation blinded to clinical data; expert panel blinded in staged fashion
- Sample Size
- 370
- Follow-up
- 90 days for selected clinical outcomes
- Centers
- 1
- Countries
- Netherlands
Primary Outcome
Definition: Presence of cardiac thrombus on admission nongated cardiac CTA
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 0% (no thrombus) | 12% had cardiac thrombus; 9% LAA, 4% LV | - |
Limitations & Criticisms
- Single-center study (University Medical Center Utrecht) — imaging protocols, scanner technology (spectral CT), and radiologist expertise may not be available at all stroke centers.
- No gold standard comparison with TEE — cannot determine false positive/negative rates of cardiac CTA for LAA thrombus. TEE remains the reference standard.
- Nongated CT cannot reliably measure cardiac chamber dimensions, wall motion, or ejection fraction — it detects thrombus but misses other cardioembolic risk factors (PFO, valvular disease, low EF).
- Observational design with no clinical outcomes endpoint — detecting thrombus is informative, but the study did not demonstrate that cardiac CTA-guided management improved stroke outcomes.
- Expert panel review was not fully blinded — panel members may have been influenced by knowing the study hypothesis, potentially inflating the reported diagnostic value.
- Small sample size (n=370) with only 44 thrombus-positive patients — subgroup analyses are underpowered and associations may be chance findings.
- Selection bias: only patients with assessable cardiac CTA were included — those with poor image quality or incomplete scans were excluded, potentially enriching the sample for higher-quality studies.
- Spectral CT (dual-energy) technology is not available at all centers — standard single-energy CTA may have lower sensitivity for LAA thrombus, limiting generalizability.
- No assessment of inter-rater reliability for cardiac CTA thrombus detection — reproducibility across different radiologists is unknown.
Citation
Stroke. 2023;54:821–830. doi:10.1161/STROKEAHA.122.041018