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Record W4411752507 · doi:10.1101/2025.06.27.25330278

AI-Derived Splenic Response in Cardiac PET Predicts Mortality: A Multi-Site Study

2025· preprint· en· W4411752507 on OpenAlexafffund
Naga Dharmavaram, Giselle Ramirez, Aakash Shanbhag, Robert J.H. Miller, Paul Kavanagh, Jirong Yi, Mark Lemley, Valerie Builoff, Anna Marcinkiewicz, Damini Dey, Jon Hainer, Samuel Wopperer, Stacey Knight, Viet T. Le, Steve Mason, Erick Alexánderson, Isabel Carvajal-Juárez, René R. Sevag Packard, Thomas Rosamond, Mouaz H. Al‐Mallah, Leandro Slipczuk, Mark I. Travin, Wanda Acampa, Andrew J. Einstein, Panithaya Chareonthaitawee, Daniel S. Berman, Marcelo F. Di Carli, Piotr J. Slomka

Bibliographic record

VenuemedRxiv · 2025
Typepreprint
Languageen
FieldMedicine
TopicCardiac Imaging and Diagnostics
Canadian institutionsUniversity of CalgaryArtificial Intelligence in Medicine (Canada)
FundersNational Institutes of HealthNovo NordiskNational Heart, Lung, and Blood InstituteAlberta InnovatesCanon Medical Systems USAIonis PharmaceuticalsAmgenPfizerCedars-Sinai Medical CenterSun PharmaDr. Miriam and Sheldon G. Adelson Medical Research Foundation
KeywordsInternal medicineMedicineCardiology

Abstract

fetched live from OpenAlex

Abstract Background Inadequate pharmacologic stress may limit the diagnostic and prognostic accuracy of myocardial perfusion imaging (MPI). The splenic ratio (SR), a measure of stress adequacy, has emerged as a potential imaging biomarker. Objectives To evaluate the prognostic value of artificial intelligence (AI)-derived SR in a large multicenter 82 Rb-PET cohort undergoing regadenoson stress testing. Methods We retrospectively analyzed 10,913 patients from three sites in the REFINE PET registry with clinically indicated MPI and linked clinical outcomes. SR was calculated using fully automated algorithms as the ratio of splenic uptake at stress versus rest. Patients were stratified by SR into high (≥90th percentile) and low (<90th percentile) groups. The primary outcome was major adverse cardiovascular events (MACE). Survival analysis was conducted using Kaplan-Meier and Cox proportional hazards models adjusted for clinical and imaging covariates, including myocardial flow reserve (MFR ≥2 vs. <2). Results The cohort had a median age of 68 years, with 57% male patients. Common risk factors included hypertension (84%), dyslipidemia (76%), diabetes (33%), and prior coronary artery disease (31%). Median follow-up was 4.6 years. Patients with high SR (n=1,091) had an increased risk of MACE (HR 1.18, 95% CI 1.06–1.31, p=0.002). Among patients with preserved MFR (≥2; n=7,310), high SR remained independently associated with MACE (HR 1.44, 95% CI 1.24–1.67, p<0.0001). Conclusions Elevated AI-derived SR was independently associated with adverse cardiovascular outcomes, including among patients with preserved MFR. These findings support SR as a novel, automated imaging biomarker for risk stratification in 82 Rb PET MPI. Condensed Abstract AI-derived splenic ratio (SR), a marker of pharmacologic stress adequacy, was independently associated with increased cardiovascular risk in a large 82 Rb PET cohort, even among patients with preserved myocardial flow reserve (MFR). High SR identified individuals with elevated MACE risk despite normal perfusion and flow findings, suggesting unrecognized physiologic vulnerability. Incorporating automated SR into PET MPI interpretation may enhance risk stratification and identify patients who could benefit from intensified preventive care, particularly when traditional imaging markers appear reassuring. These findings support SR as a clinically meaningful, easily integrated biomarker in stress PET imaging.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.036
GPT teacher head0.347
Teacher spread0.311 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations2
Published2025
Admission routes2
Has abstractyes

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