Cardiac CT: the trials at a glance

Trial · the question it asked · what changed afterwards. Red = nothing changed.

Trial	Question asked	What changed
Acute chest pain
CT-STAT2011	Is CCTA faster and cheaper than SPECT?	Diagnosis in 2.9 vs 6.3 h. Part of the Level A evidence pool.
ACRIN-PA2012	Is a negative CCTA safe for ED discharge?	0 events in 640 negative scans → Class 1, LOE A.
ROMICAT-II2012	Does CCTA shorten hospital stay?	−7.6 h, but more testing, more radiation, no cost saving.
CT-COMPARE2014	CCTA vs exercise ECG?	Sensitivity 100% vs 83%. Helped retire exercise ECG.
CATCH2015	Does CCTA-guided care improve outcomes?	HR 0.62 — one of few acute trials with a clinical endpoint.
BEACON2016	Any value added to hs-troponin?	Nothing. Stay identical at 6.3 h. No Class I in Europe.
RAPID-CTCA2021	Death or MI at 1 year in higher-risk ACS?	HR 0.91, not significant → ESC 2023 downgraded to Class IIa.
TARGET-CTCA2026	Any benefit once MI is already ruled out?	HR 0.95, not significant. Nothing yet — challenges Class 1.
Pooled 22 RCTs2023	What does CCTA actually deliver in the ED?	Only revascularization rose (RR 1.37). Not fewer events.
Stable chest pain
SCOT-HEART2015 / 2018 / 2025	Does CCTA change the diagnosis — then the events?	10-y HR 0.79 with revascularization identical → Class 1 A both sides of the Atlantic.
PROMISE2015 / 2025	Anatomic or functional test first?	Equivalent, not superior. 10.6-y mortality HR 0.98.
DISCHARGE2022	CT or straight to invasive angiography?	Complications 0.5% vs 1.9% → ESC 2024 Class I A gatekeeper.
CRESCENT2016	Does a calcium-gated CT protocol work?	Downstream testing 25% vs 53%. Embedded in ESC 2024 algorithm.
CAPP2015	CT vs exercise ECG for symptoms?	Inconclusive results 2.4% vs 26.9%. Used by NICE 2016.
CONSERVE2019	Selective referral after CCTA — safe?	Angiography 23% vs 89%, events identical.
PRECISE / DEFER-CTA2023	Can we defer testing in minimal-risk patients?	HR 0.35; deferral safe → ESC 2024 defer at ≤5%.
ISCHEMIA2020	Can CCTA gatekeep before randomization?	97% concordance excluding left main. Now standard trial design.
Coronary calcium
Western Denmark2022	Does CAC = 0 rule out disease at every age?	58% of under-40s with obstructive CAD had CAC = 0. No guideline caveat yet.
CONFIRM CAC = 02011	Is there plaque despite a zero score?	16% had plaque, 3.5% had ≥50% stenosis. Nothing.
CT physiology — FFR-CT and perfusion
DISCOVER-FLOW2011	Can fluid dynamics reproduce invasive FFR?	Per-vessel accuracy 84% vs 58% for stenosis alone.
DeFACTO2012	Is per-patient accuracy good enough?	Missed its endpoint (73%). Forced an algorithm rewrite.
NXT2014	Is the revised algorithm good enough?	AUC 0.90 vs 0.81 → FDA De Novo grant, Nov 2014.
PLATFORM2015	Can it prevent the empty catheterization?	Normal angiography 12% vs 73% → NICE MTG32.
ADVANCE2018	Is deferral on FFR-CT >0.80 safe?	Zero MACE in 1,592 deferred → supports COR 2a.
FORECAST2021	Does FFR-CT save money?	No (p=0.10), though angiography fell.
TARGET2023	Does on-site machine-learning CT-FFR work?	Composite 28% vs 46%. Adopted in Asia.
FUSION2026	Does it hold up without industry funding?	Unnecessary angiography 18% vs 33%. Likely lever for upgrade.
CREDENCE2020	Plaque or perfusion — which predicts FFR?	AUC 0.81 vs 0.67. Physiology depends on plaque, not just stenosis.
Dan-NICAD 1 & 22018 / 2023	Does stress testing after an abnormal CCTA work?	Sensitivity only 36–64%. A negative stress test does not exclude ischemia.
CORE3202014	Does CT perfusion add to CCTA?	AUC 0.87 vs 0.84. Nothing — CTP never entered guidelines.
Plaque, inflammation and AI
CONFIRM2011	Does non-obstructive disease carry risk?	Predicts mortality. Broke the stenosis-only model.
ICONIC2018	What did the culprit look like beforehand?	75% were <50% stenosis at baseline. Nothing.
PROMISE high-risk plaque2018	Does high-risk plaque predict events?	aHR 1.72 overall, 4.31 if non-obstructive → CAD-RADS 2.0 modifier only.
SCOT-HEART LAP2020	Does low-attenuation plaque predict MI?	>4%: HR 4.65 — beats calcium score and stenosis. No treatment trigger.
PARADIGM2018	Do statins change plaque?	Calcified up, non-calcified down. No serial-CT recommendation.
EVAPORATE2020	Does icosapent ethyl change plaque?	LAP −17% vs +109%. Labeling rests on REDUCE-IT, not this.
CRISP-CT / ORFAN2018 / 2024	Does perivascular inflammation predict death?	HR up to 29.8 → FDA De Novo, July 2026. No CPT code, no guideline.
CLARIFY / CERTAIN / CONFIRM22021–2026	Does AI match — or beat — the reader?	AUC 0.81 vs 0.79 → CPT 75577, Jan 2026. ACC still declines routine use.
TRANSFORMongoing	Does plaque-directed therapy improve outcomes?	Has not reported. The trial that settles the field.
Structural heart CT
Jilaihawi / Binder2012 / 2013	CT or TEE for TAVR annular sizing?	Paravalvular leak 21.9% → 7.5%. Practice changed worldwide — still no Class or Level.
VIVID registry2018	Can CT predict coronary obstruction?	VTC ≤4 mm, AUC 0.943. Consensus-level only.
BASILICA2019 / 2021	Can leaflet laceration prevent obstruction?	100% freedom at 30 days. CT selects who gets it.
Redo-TAVR CT2020	Will the coronaries stay reachable?	Access impossible in 27% vs 10% by valve type. Drives lifetime planning.
Yoon neo-LVOT2019	Can CT predict LVOT obstruction in TMVR?	<170 mm²: sensitivity 96%. Expert recommendation.
LAMPOON2019	Can laceration prevent LVOT obstruction?	100% technical success, 93% 30-day survival.
SCAI / HRS LAAO2025	CT or TEE before appendage occlusion?	Either — conditional, very low certainty. CT not preferred.
Prosthetic valves
Makkar2015	Does 4D CT reveal leaflet abnormality?	Reduced motion in 13–40%. Created a new clinical entity.
RESOLVE / SAVORY2017	How common is leaflet thrombosis?	12% overall; TIA link but not stroke.
GALILEO-4D2020	Does rivaroxaban fix it?	Yes on CT — but the parent trial stopped for harm.
ADAPT-TAVR2022	Does leaflet thrombosis cause emboli?	No association found.
NOTION-4 / ACASA-TAVI2026	Is the benefit durable?	Gone once the drug stops; safety favoured aspirin.
Gündüz2015	Pannus or thrombus?	≥145 HU: sensitivity 87.5%, specificity 95.5%. Predicts thrombolysis response.
Heart Team, cath lab, operating room
SYNTAX III2018	Same revascularization decision from CT?	~93% agreement, κ 0.82.
FASTTRACK CABG2024	Can surgeons operate from CT alone?	99.1% feasible without angiography. No guideline change.
P32022	Can CT predict the result of PCI?	Post-PCI FFR predicted to 0.02 ± 0.07.
P4ongoing	Can CT-guided PCI compete with angiography?	Has not reported. Stent sizing still unvalidated.
CorMicA2018	What does a normal CCTA miss?	89% had abnormal coronary function → ESC 2024 Class I B for function testing.

Full detail, with every reference linked, is in the companion manuscript.