Invasive coronary angiography (ICA) remains the reference standard for defining coronary anatomy and enables immediate revascularization when indicated. As a luminographic technique, ICA delineates stenosis location and severity but does not visualize the arterial wall and may therefore underestimate total plaque burden and composition. Visual estimation is commonly used, although quantitative coronary angiography improves precision; foreshortening, vessel overlap, diffuse disease, and eccentric plaques can bias interpretation, and angiographic severity correlates imperfectly with ischemia or plaque vulnerability. ^,,

In stable chest pain, ICA is generally reserved for patients with very high pretest likelihood, refractory or high-risk symptoms despite guideline-directed medical therapy, or high-risk noninvasive findings when revascularization is anticipated. In acute coronary syndromes, ICA defines culprit anatomy and enables urgent PCI, while nonculprit intermediate lesions should be assessed with physiology rather than angiographic appearance alone. ^,

To overcome the limitations of anatomy alone, wirebased physiologic indices are routinely integrated during ICA. Fractional flow reserve (FFR ≤ 0.80) and instantaneous wave-free ratio (iFR ≤ 0.89) identify lesion-specific ischemia and guide revascularization, particularly for intermediate (≈40%–70%) stenoses. Randomized trials demonstrate that physiology-guided PCI reduces unnecessary stenting and improves outcomes compared with angiography-guided strategies, with iFR shown to be noninferior to FFR while avoiding pharmacologic hyperemia. ^,,,

Intravascular imaging further refines invasive assessment. Intravascular ultrasound (IVUS) quantifies plaque burden, vessel remodeling, minimal lumen area, and true vessel size and is particularly valuable in left main or diffuse disease and for stent optimization. Optical coherance tomography (OCT) provides near-microscopic resolution of plaque and stent microstructure, enabling assessment of fibrous cap thickness, thrombus, and stent pathology, and is especially useful in Acute coronary syndrome (ACS). Limitations include shallow tissue penetration and the need for contrast clearing. ^,

Radial access is preferred due to lower vascular complication rates. Overall risks of ICA include ionizing radiation, iodinated contrast exposure, access-site complications, and rare stroke or myocardial infarction.

Noninvasive imaging is central to the diagnosis and risk stratification of coronary artery disease by characterizing atherosclerotic burden, coronary anatomy, and myocardial ischemia.

Coronary artery calcium (CAC) scoring is a noncontrast CT technique that quantifies calcified plaque burden and refines cardiovascular risk prediction in primary prevention, informing statin initiation and intensity. Because CAC detects only calcified plaque and does not assess stenosis or ischemia, its role in symptomatic patients is limited. ^,

Coronary CT angiography (CCTA) provides contrast-enhanced, ECG-gated visualization of the coronary lumen and vessel wall, enabling detection of calcified and noncalcified plaque and high-risk features such as low-attenuation plaque and positive remodeling. In low–intermediate-risk stable chest pain, CCTA demonstrates high sensitivity and negative predictive value for obstructive Conronary artery disease (CAD), making it an effective rule-out test that expedites diagnosis, reduces unnecessary invasive angiography, and prompts intensified preventive therapy when high-risk plaque is identified. ^,

CT-derived fractional flow reserve (CT-FFR) augments CCTA by estimating lesion-specific ischemia using computational or machine-learning approaches, improving specificity for intermediate (40%–90%) stenoses without additional radiation exposure, although performance depends on image quality and vendor-specific algorithms. ^,,

Functional imaging complements anatomic assessment by detecting ischemia and microvascular dysfunction. Stress echocardiography identifies inducible wall-motion abnormalities without radiation but is operator dependent. Single positron emission computed tomography (SPECT) myocardial perfusion imaging is widely available with established prognostic data, though limited by spatial resolution and reduced sensitivity for balanced ischemia. Positron emission tomography (PET) myocardial perfusion imaging uniquely quantifies absolute myocardial blood flow and coronary flow reserve, enhancing detection of multivessel and microvascular disease and providing strong prognostic information, albeit with more limited availability. ^, Stress Cardiac magnetic resonance (CMR) offers high-resolution perfusion imaging and tissue characterization without ionizing radiation; in MR-INFORM, a CMR-first strategy was noninferior to FFR-guided care and reduced revascularization rates. ^,

Selection of an imaging strategy requires balancing diagnostic yield with patient safety (radiation and contrast exposure), logistics (availability, expertise, and cost), and patient-specific factors such as renal function, rhythm, body habitus, and previous revascularization.

Invasive strategies remain unmatched for lesion-level decision-making and same-sitting therapy. Pressurewire indices align PCI with ischemia and safely support deferral of nonischemic stenoses. ^, Intravascular imaging refines management by improving vessel sizing, stent optimization, and mechanistic understanding of plaque or stent pathology, particularly in left main disease, ACS, and stent failure. ^, These benefits must be weighed against contrast and radiation exposure and procedural risk, supporting guideline recommendations to reserve ICA for patients in whom revascularization is likely or noninvasive testing is high risk. ^,

Noninvasive strategies address complementary questions across anatomy, plaque biology, and physiology without catheterization. CCTA provides high sensitivity and negative predictive value for obstructive CAD and identifies high-risk plaque phenotypes that prompt intensified prevention. ^, CT-FFR improves specificity for intermediate stenoses and reduces unnecessary invasive angiography. Functional imaging adds prognostic and mechanistic insight, with PET and stress CMR offering the strongest physiologic assessment, while SPECT and stress echocardiography remain pragmatic alternatives when advanced modalities are unavailable.

In practice, testing should be matched to pretest probability and the clinical decision at hand. For low–intermediate-risk new chest pain, CCTA is an appropriate first-line test, with CT-FFR added for intermediate lesions. For intermediate–high-risk patients or known CAD, functional imaging—preferably PET or stress CMR—should be prioritized. When anatomic and physiologic findings are discordant, physiology should adjudicate revascularization. ^,

Patient factors often determine modality choice by influencing image quality, diagnostic yield, and safety. In patients with chronic kidney disease or previous contrast-associated acute kidney injury, iodinated contrast should be avoided or minimized. When anatomy is not essential, stress echocardiography or stress CMR are preferred; when invasive assessment is required, contrast-sparing strategies and IVUS-guided minimal-contrast PCI can mitigate risk. Gadolinium-based contrast for CMR should preferentially use macrocyclic agents and be avoided in advanced CKD unless benefits clearly outweigh risks. ^,

Atrial fibrillation and high or irregular heart rates degrade CCTA image quality and specificity; when rate control is not achievable, PET or stress CMR provides a more reliable physiologic assessment. ^, Heavy coronary calcification similarly lowers CCTA specificity, favoring functional imaging or escalation to ICA with physiology when revascularization is anticipated. ^,

Body habitus and attenuation artifacts can limit stress echocardiography and SPECT, whereas PET and CMR often provide superior image quality. Previous stents or bypass grafts complicate CCTA interpretation; in patients with recurrent symptoms after PCI or CABG, functional testing is often preferred initially, with invasive assessment reserved for cases in which reintervention is contemplated.

When ischemia is suspected in the absence of obstructive epicardial disease Ischemia with non-obstructive coronary arteries, PET with absolute myocardial blood flow and coronary flow reserve or stress CMR are preferred to diagnose microvascular dysfunction and guide therapy. ^, Unstable presentations and ACS warrant direct invasive evaluation.

Radiation exposure varies by modality and protocol but is lowest with CAC scanning and PET, higher with SPECT and ICA, and absent with stress echocardiography and stress CMR. ^, Iodinated contrast increases kidney injury risk with higher cumulative doses and baseline renal dysfunction, while radiotracers are not nephrotoxic. ^,

Clinical decision-making balances the diagnostic question (anatomy, ischemic physiology, or plaque biology) against pretest probability, patient-specific constraints, and therapeutic intent.

In stable chest pain with low–intermediate likelihood of obstructive CAD, CCTA is the preferred first-line test. For intermediate stenoses, CT-FFR improves specificity and reduces unnecessary invasive angiography. Randomized trials support an anatomic-first strategy, with DISCHARGE confirming CCTA as a safer gatekeeper than routine invasive angiography. ^, When CCTA quality is limited, stress CMR or PET provides a robust physiologic assessment.

Patients with high clinical likelihood or refractory symptoms should proceed directly to ICA with physiology, supplemented by IVUS or OCT when anatomy is complex, or optimization is required. In stable ischemic heart disease, routine early revascularization does not reduce death or myocardial infarction compared with optimal medical therapy; physiology enables safe deferral of nonischemic lesions.

In ACS, invasive angiography is indicated for culprit identification and revascularization, with physiology guiding treatment of nonculprit lesions and OCT clarifying plaque morphology when it alters management.

After previous revascularization, functional testing is often preferred initially. When repeat intervention is contemplated, invasive angiography with physiology and intravascular imaging clarifies lesion significance and mechanisms of failure.

Noninvasive and invasive coronary imaging strategies are complementary rather than competitive. Contemporary pathways favor an anatomy-to-physiology sequence: CCTA provides rapid whole-tree assessment and plaque phenotyping in low–intermediate-risk patients, while CT-FFR improves specificity for intermediate lesions. In intermediate–high-risk patients or those with known CAD, functional imaging—preferably PET or stress CMR—best addresses ischemia and microvascular disease.

When revascularization is contemplated, ICA combined with lesion-specific physiology aligns PCI with ischemia, while IVUS and OCT optimize stent deployment and clarify the mechanism. Across scenarios, discordance between anatomy and ischemia is common; physiology should adjudicate revascularization, whereas extensive plaque without ischemia should prompt intensified prevention.

The central challenge moving forward is implementation: embedding these technologies into guideline-concordant, equitable, and outcome-focused pathways that prioritize physiology-guided revascularization and aggressive prevention.

Maurice Tiotsop: Writing– review & editing, Writing– original draft, Data curation, Conceptualization. Joshua K. Salabei: Writing– review & editing, Writing– original draft, Supervision, Data curation, Conceptualization.